bluuebunny/crossref_metadata_2025 huggingface dataset:
Occupational stress: evidence from industries affected by COVID-19 in Japan
Authors: Piao Xiangdan , Xie Jun , Managi Shunsuke
Published: May 2022

Background

This study provides objective evidence on the impact of COVID-19 based on employee occupational stress reported from 13 different industries, and examines the determinants of employee psychological well-being. As the economic and social impacts of the COVID-19 pandemic continue, governments should consider industry-level differences when making support decisions concerning public resource allocation to corporations. However, little evidence exists regarding the differences in occupational stress across industries.

Methods

Employee occupational stress data (N = 673,071) was derived from workers in Japan from 2018 to 2020. The sample comprises workers from 13 industries, including civil services, service industry (other), real estate, medical/welfare, wholesale/retail, academic research, and accommodation/restaurant business. A logit model is employed to investigate the differences in employees’ psychological well-being before and during the pandemic.

Results

In 2020, 11 out of 12 industries had significantly worse occupational stress compared to employees engaged in civil services. Over 23% of employees from the wholesale/retail and accommodation/restaurant industries were observed as high-stress employees. Improved compensation policies supporting these industries are suggested. In contrast, reduced occupational stress was found among employees in the transportation/postal and information/communication industries. Among the 13 industries, aside from high job demands, tough inter-person relationships in the workplace became the most significant stressors during the pandemic.

Conclusions

The results confirm that the pandemic has had a heterogeneous effect on employee occupational stress across industries, thus suggesting that the level of compensation given to different industries during the COVID-19 pandemic should be discussed and approved by the Japanese government. Additionally, support for the wholesale/retail and accommodation/restaurant industries during the pandemic should be improved.
Tooth retention, health, and quality of life in older adults: a scoping review
Authors: Atanda Adejare Jay , Livinski Alicia A. , London Steven D. , Boroumand Shahdokht , Weatherspoon Darien , Iafolla Timothy J. , Dye Bruce A.
Published: May 2022

Objective

This scoping review describes the relationship between tooth retention, health, and quality of life in older adults.

Methods

Seven databases were searched for English language articles for subjects ≥ 65 y from 1981 to 2021. Exposure was tooth retention (≥ 20), and outcomes were general/systemic health and quality of life. Methodological quality was assessed using the Newcastle–Ottawa Scale and Cochrane Risk of Bias 2.0 tool.

Results

140 articles were included, only four were randomized trials. Inter-rater agreement (κ) regarding study inclusion was 0.924. Most were assessed with low risk of bias (n = 103) and of good quality (n = 96). Most studies were conducted in Japan (n = 60) and Europe (n = 51) and only nine in the US. Tooth retention was referred to as “functional dentition” in 132 studies and “shortened dental arch” in 19 studies. Study outcomes were broadly synthesized as (1) cognitive decline/functional dependence, (2) health status/chronic diseases, (3) nutrition, and (4) quality of life.

Discussion

There is a positive relationship between tooth retention, overall health, and quality of life. Older adults retaining ≥ 20 teeth are less likely to experience poorer health. Having < 20 teeth increases the likelihood for functional dependence and onset of disability, and may affect successful ageing. This review supports the general finding that the more teeth older adults retain as they age, the less likely they are to have adverse health outcomes. However, significant knowledge gaps remain which can limit decision-making affecting successful ageing for many older adults. This review highlights the need to consider, as an important marker of oral health and function, the retention of a functional minimum of a natural dentition, rather than a simple numeric score of missing teeth.
Compassion in healthcare: an updated scoping review of the literature
Authors: Malenfant Sydney , Jaggi Priya , Hayden K. Alix , Sinclair Shane
Published: May 2022

Background

A previous review on compassion in healthcare (1988-2014) identified several empirical studies and their limitations. Given the large influx and the disparate nature of the topic within the healthcare literature over the past 5 years, the objective of this study was to provide an update to our original scoping review to provide a current and comprehensive map of the literature to guide future research and to identify gaps and limitations that remain unaddressed.

Methods

Eight electronic databases along with the grey literature were searched to identify empirical studies published between 2015 and 2020. Of focus were studies that aimed to explore compassion within the clinical setting, or interventions or educational programs for improving compassion, sampling clinicians and/or patient populations. Following title and abstract review, two reviewers independently screened full-text articles, and performed data extraction. Utilizing a narrative synthesis approach, data were mapped onto the categories, themes, and subthemes that were identified in the original review. Newly identified categories were discussed among the team until consensus was achieved.

Results

Of the 14,166 number of records identified, 5263 remained after removal of duplicates, and 50 articles were included in the final review. Studies were predominantly conducted in the UK and were qualitative in design. In contrast to the original review, a larger number of studies sampled solely patients (n = 12), and the remainder focused on clinicians (n = 27) or a mix of clinicians and other (e.g. patients and/or family members) (n = 11). Forty-six studies explored perspectives on the nature of compassion or compassionate behaviours, traversing six themes: nature of compassion, development of compassion, interpersonal factors related to compassion, action and practical compassion, barriers and enablers of compassion, and outcomes of compassion. Four studies reported on the category of educational or clinical interventions, a notable decrease compared to the 10 studies identified in the original review.

Conclusions

Since the original scoping review on compassion in healthcare, while a greater number of studies incorporated patient perspectives, clinical or educational interventions appeared to be limited. More efficacious and evidence-based interventions or training programs tailored towards improving compassion for patients in healthcare is required.
A prognostic model using the neutrophil-albumin ratio and PG-SGA to predict overall survival in advanced palliative lung cancer
Authors: Feng Changyan , Yu Huiqing , Lei Haike , Cao Haoyang , Chen Mengting , Liu Shihong
Published: May 2022

Objective

Inflammation and malnutrition are common in patients with advanced lung cancer undergoing palliative care, and their survival time is limited. In this study, we created a prognostic model using the Inflam-Nutri score to predict the survival of these patients.

Methods

A retrospective cohort study was conducted on 223 patients with advanced, histologically confirmed unresectable lung cancer treated between January 2017 and December 2018. The cutoff values of the neutrophil-albumin ratio (NAR) and Patient-Generated Subjective Global Assessment (PG-SGA) score were determined by the X-tile program. Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analysis were performed to identify prognostic factors of overall survival (OS). We then established a nomogram model. The model was assessed by a validation cohort of 72 patients treated between January 2019 and December 2019. The predictive accuracy and discriminative ability were assessed by the concordance index (C-index), a plot of the calibration curve and risk group stratification. The clinical usefulness of the nomogram was measured by decision curve analysis (DCA).

Results

The nomogram incorporated stage, supportive care treatment, the NAR and the PG-SGA score. The calibration curve presented good performance in the validation cohorts. The model showed discriminability with a C-index of 0.76 in the training cohort and 0.77 in the validation cohort. DCA demonstrated that the nomogram provided a higher net benefit across a wide, reasonable range of threshold probabilities for predicting OS. The survival curves of different risk groups were clearly separated.

Conclusions

The NAR and PG-SGA scores were independently related to survival. Our prognostic model based on the Inflam-Nutri score could provide prognostic information for advanced palliative lung cancer patients and physicians.
The emotional impact of urinary tract infections in women: a qualitative analysis
Authors: Grigoryan Larissa , Mulgirigama Aruni , Powell Marcy , Schmiemann Guido
Published: May 2022

Background

While many studies address the clinical management of participants with uncomplicated urinary tract infection (uUTI), the emotional impact of uUTIs has been investigated less often. The aim of this qualitative study was to understand the emotional experience of women with uUTIs.

Methods

This was a qualitative, exploratory, in-depth interview-based study conducted among women in the United States (US) and Germany. Women aged ≥ 18 years with at least one uUTI treated with antibiotics in the past year were recruited through a patient community panel and physician referrals. Participants were recruited using purposive sampling to include an equal split of those with 1 or ≥ 2 antibiotics, and an equal split of those treated for a single or recurrent uUTIs (≥ 2 uUTIs in the past year). A structured telephone interview included questions about symptoms, diagnosis, treatment, and retreatment (if any). Each participant was queried about her emotions and the impact of the uUTI on life activities. Thematic analysis of responses was carried out to identify common themes.

Results

A total of 65 participants completed the interview, 40 (61.5%) from the US and 25 (38.5%) from Germany. Major themes that emerged from the analyses included (1) a wide range of negative emotions were experienced due to uUTI symptoms, interference with activities of daily life, and effects on relationships and sleep; (2) varied emotions and understanding related to uUTI treatment and management approaches; (3) treatment failure caused frustration, worry, and anger; and (4) the prospect of recurrent uUTIs provoked dread and helplessness.

Conclusion

Our research uncovered emotions of helplessness and dread experienced by women in the context of uUTI clinical treatment failure and recurrent uUTIs. Knowing patients’ perspectives on UTI management will help guide the development of patient education and improve shared decision-making.
Shared meditation involving cancer patients, health professionals and third persons is relevant and improves well-being: IMPLIC pilot study
Authors: Prevost Virginie , Lefevre-Arbogast Sophie , Leconte Alexandra , Delorme Claire , Benoit Sandrine , Tran Titi , Clarisse Bénédicte
Published: May 2022

Background

Alleviating suffering and improving quality of life are universally shared goals. In this context, we implemented a pilot study to assess the feasibility and acceptability of a mindfulness intervention in the form of meditation involving together cancer patients, health professionals, and third persons.

Methods

Two groups of 15 participants equally composed of patients, health professionals and third persons were constituted. A dedicated programme on mindfulness and compassion was constructed, including 12 weekly sessions of 1.5 h and a half-day retreat. Adherence and satisfaction with the programme were evaluated. All participants completed questionnaires on perceived stress, quality of life, mindfulness, empathy, and self-efficacy. Burnout was assessed in health professionals.

Results

Shared meditation was feasible as 70% of participants attended ≥ 80% of the 13 meditation sessions. Satisfaction with the programme was high (median satisfaction score: 9.1 out of 10) and all participants expressed positive attitudes towards shared meditation and a benefit on their global quality of life. Participants reported significant improvement in stress (p < 0.001), global quality of life (p = 0.004), self-efficacy (p < 0.001), and mindfulness skills (p < 0.001) from baseline to post-programme.

Conclusions

This study demonstrated the feasibility of a shared dedicated meditation programme in terms of participation and acceptability of participants. The measured benefits observed among participants furthermore justify the interest of a subsequent randomized study aiming to demonstrate the potential added value of shared meditation by promoting bridge-building between cancer patients, health professionals and others.

Trial Registration

ClinicalTrials.gov. NCT04410185. Registered on June 1, 2020.
Do programme coordinators contribute to the professional development of residents? an exploratory study
Authors: Aono Mayumi , Obara Haruo , Kawakami Chihiro , Imafuku Rintaro , Saiki Takuya , Barone Michael A. , Suzuki Yasuyuki
Published: May 2022

Background

With the development of training programmes for health professions, the role of programme coordinators has become increasingly important. However, their role in providing educational support for the professional development of resident trainees has not been investigated well. This study aimed to qualitatively analyse the involvement of programme coordinators in educational support for residents.

Methods

Semi-structured reflective writing on ‘support for residents’ was collected from programme coordinators in teaching hospitals in Japan in 2017–18 using a web-based questionnaire. Descriptions were qualitatively analysed thematically, using the professional identity formation (PIF) framework.

Results

A total of 39 cases of “support for residents” by 31 coordinators were analysed. We found that residents most commonly faced prior personal problems, including mental health issues and insufficient social skills/unprofessional behaviour. A thematic analysis revealed that coordinators played a variety of educational roles: 1) requesting supervisors to reconsider their teaching; 2) protecting residents from the negative influence of clinical experiences; 3) facilitating residents’ self-assessment and confidence; 4) creating a safer learning environment; 5) providing support for prior personal problems through 5–1) fostering a better atmosphere for the mental health of residents, and 5–2) intervening for residents with insufficient social skills/unprofessional behaviour; 6) providing support for isolated residents; and 7) preventing problems with peers.

Conclusions

This study identified seven educational roles of programme coordinators for residents from a standpoint of PIF of residents. Based on these findings, four valuable attributes for coordinators were established: non-hierarchical relationships with residents, parenting attitudes, sensitivity to residents’ changes, and the perspective of the citizen and a member of the public. These attributes would underpin coordinators’ educational roles and facilitate the professional development of residents. This study provides a basis for defining and revising the role profiles of programme coordinators, and for improving staff development.
Automatic recognition of micronucleus by combining attention mechanism and AlexNet
Authors: Wei Weiyi , Tao Hong , Chen Wenxia , Wu Xiaoqin
Published: May 2022

Background

Micronucleus (MN) is an abnormal fragment in a human cell caused by disorders in the mechanism regulating chromosome segregation. It can be used as a biomarker for genotoxicity, tumor risk, and tumor malignancy. The in vitro micronucleus assay is a commonly used method to detect micronucleus. However, it is time-consuming and the visual scoring can be inconsistent.

Methods

To alleviate this issue, we proposed a computer-aided diagnosis method combining convolutional neural networks and visual attention for micronucleus recognition. The backbone of our model is AlexNet without any dense layers and it is pretrained on the ImageNet dataset. Two attention modules are applied to extract cell image features and generate attention maps highlighting the region of interest to improve the interpretability of the network. Given the problems in the data set, we leverage data augmentation and focal loss to alleviate the impact.

Results

Experiments show that the proposed network yields better performance with fewer parameters. The AP value, F1 value and AUC value reach 0.932, 0.811 and 0.995, respectively.

Conclusion

In conclusion, the proposed network can effectively recognize micronucleus, and it can play an auxiliary role in clinical diagnosis by doctors.
Comparison of cardiovascular outcomes between SGLT2 inhibitors in diabetes mellitus
Authors: Suzuki Yuta , Kaneko Hidehiro , Okada Akira , Itoh Hidetaka , Matsuoka Satoshi , Fujiu Katsuhito , Michihata Nobuaki , Jo Taisuke , Takeda Norifumi , Morita Hiroyuki , Kamiya Kentaro , Matsunaga Atsuhiko , Ako Junya , Node Koichi , Yasunaga Hideo , Komuro Issei
Published: May 2022

Background

There have been scarce data comparing cardiovascular outcomes between individual sodium-glucose cotransporter-2 (SGLT2) inhibitors. We aimed to compare the subsequent cardiovascular risk between individual SGLT2 inhibitors.

Methods

We analyzed 25,315 patients with diabetes mellitus (DM) newly taking SGLT2 inhibitors (empagliflozin: 5302, dapagliflozin: 4681, canagliflozin: 4411, other SGLT2 inhibitors: 10,921). We compared the risks of developing heart failure (HF), myocardial infarction (MI), angina pectoris (AP), stroke, and atrial fibrillation (AF) between individual SGLT2 inhibitors.

Results

Median age was 52 years, and 82.5% were men. The median fasting plasma glucose and HbA1c levels were 149 (Q1-Q3:127–182) mg/dL and 7.5 (Q1-Q3:6.9–8.6) %. During a mean follow-up of 814 ± 591 days, 855 HF, 143 MI, 815 AP, 340 stroke, and 139 AF events were recorded. Compared with empagliflozin, the risk of developing HF, MI, AP, stroke, and AF was not significantly different in dapagliflozin, canagliflozin, and other SGLT inhibitors. For developing HF, compared with empagliflozin, hazard ratios of dapagliflozin, canagliflozin, and other SGLT2 inhibitors were 1.02 (95% confidence interval [CI] 0.81–1.27), 1.08 (95% CI 0.87–1.35), and 0.88 (95% CI 0.73–1.07), respectively. Wald tests showed that there was no significant difference in the risk of developing HF, MI, AP, stroke, and AF among individual SGLT2 inhibitors. We confirmed the robustness of these results through a multitude of sensitivity analyses.

Conclusion

The risks for subsequent development of HF, MI, AP, stroke, and AF were comparable between individual SGLT2 inhibitors. This is the first study comparing the wide-range cardiovascular outcomes of patients with DM treated with individual SGLT2 inhibitors using large-scale real-world data.
Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations
Authors: Zou Jiale , Wang Shuang , Chai Ningli , Yue Hua , Ye Peng , Guo Peilin , Li Feng , Wei Bo , Ma Guanghui , Wei Wei , Linghu Enqiang
Published: May 2022

Background

Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal.

Results

Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route.

Conclusions

This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy.

Graphical Abstract
Predictors of health-related quality of life after cardiac surgery: a systematic review
Authors: Sanders Julie , Bowden Tracey , Woolfe-Loftus Nicholas , Sekhon Mandeep , Aitken Leanne M.
Published: May 2022

Background

Health-related quality of life (HRQoL) is important in determining surgical success, particularly from the patients’ perspective.

Aims

To identify predictors for HRQoL outcome after cardiac surgery in order to identify potentially modifiable factors where interventions to improve patient outcomes could be targeted.

Methods

Electronic databases (including MEDLINE, CINAHL, Embase) were searched between January 2001 and December 2020 for studies determining predictors of HRQoL (using a recognised and validated tool) in adult patients undergoing cardiac surgery. Data extraction and quality assessments were undertaken and data was summarised using descriptive statistics and narrative synthesis, as appropriate.

Results

Overall, 3924 papers were screened with 41 papers included in the review. Considerable methodological heterogeneity between studies was observed. Most were single-centre (75.6%) prospective observational studies (73.2%) conducted in patients undergoing coronary artery bypass graft (CABG) (n = 51.2%) using a version of the SF-36 (n = 63.4%). Overall, 103 independent predictors (62 pre-operative, five intra-operative and 36 post-operative) were identified, where 34 (33.0%) were reported in more than one study. Potential pre-operative modifiable predictors include alcohol use, BMI/weight, depression, pre-operative quality of life and smoking while in the post-operative period pain and strategies to reduce post-operative complications and intensive care and hospital length of stay are potential therapeutic targets.

Conclusion

Despite a lack of consistency across studies, several potentially modifiable predictors were identified that could be targeted in interventions to improve patient or treatment outcomes. This may contribute to delivering more person-centred care involving shared decision-making to improve patient HRQoL after cardiac surgery.
Thrombin generation capacity is enhanced by low antithrombin activity and depends on the activity of the related coagulation factors
Authors: Tsuchida Takumi , Hayakawa Mineji , Kawahara Shota , Kumano Osamu
Published: May 2022

Background

Supplementation with antithrombin (AT) concentrates is now common in the treatment of congenital and acquired AT deficiency. However, there is no established consensus on the target and timing of supplementation. We aimed to elucidate the effects of AT deficiency on the balance between coagulation activation and inhibition using a thrombin generation assay as in vitro global assay.

Methods

Samples were prepared by admixing commercially acquired AT-deficient plasma with < 1% AT activity with pooled normal plasma. The AT activity in each sample was adjusted to 100, 90, 70, 50, 40, 30, 10, 5, and < 1%. A thrombin generation assay was performed in each sample. AT concentrate-spiked samples were also prepared by adjusting the AT activities in four types of the concentrates: one recombinant and three plasma-derived AT concentrates. The final targeted AT activities in the samples were adjusted to 100, 50, 30, and 5% by spiking each concentrate into the AT-deficient plasma. We also prepared samples with five levels of prothrombin time (PT) % in coagulation factors with the AT activity fixed at 30% by dilution by mixing AT-deficient plasma and normal plasma with Owren’s veronal buffer to adjust the coagulation factor activities in several proportions. The theoretical target PT% values were 100, 66, 50, 40, and 30%. A thrombin generation assay was performed on all samples.

Results

The ability to generate thrombin depended on the AT activity, and the amount of thrombin generation was increased as AT was decreased. Additionally, the amount of thrombin generation was changed significantly when AT activity was ≤ 50%, indicating that AT suppressed thrombin generation. In particular, thrombin generation was remarkable when AT activity was < 30%, and it can be assumed that the prognosis is poor due to organ failure from thrombotic tendency.

Conclusions

The results presented in this basic research were found to be consistent with the clinical findings to date. The mechanism by which 30–50% of AT activity is set as the clinical boundary was elucidated by the thrombin generation assay.
Optogenetic control of NOTCH1 signaling
Authors: Kałafut Joanna , Czapiński Jakub , Przybyszewska-Podstawka Alicja , Czerwonka Arkadiusz , Odrzywolski Adrian , Sahlgren Cecilia , Rivero-Müller Adolfo
Published: May 2022

The Notch signaling pathway is a crucial regulator of cell differentiation as well as tissue organization, whose deregulation is linked to the pathogenesis of different diseases. NOTCH1 plays a key role in breast cancer progression by increasing proliferation, maintenance of cancer stem cells, and impairment of cell death. NOTCH1 is a mechanosensitive receptor, where mechanical force is required to activate the proteolytic cleavage and release of the Notch intracellular domain (NICD). We circumvent this limitation by regulating Notch activity by light. To achieve this, we have engineered an optogenetic NOTCH1 receptor (optoNotch) to control the activation of NOTCH1 intracellular domain (N1ICD) and its downstream transcriptional activities. Using optoNotch we confirm that NOTCH1 activation increases cell proliferation in MCF7 and MDA-MB-468 breast cancer cells in 2D and spheroid 3D cultures, although causing distinct cell-type specific migratory phenotypes. Additionally, optoNotch activation induced chemoresistance on the same cell lines. OptoNotch allows the fine-tuning, ligand-independent, regulation of N1ICD activity and thus a better understanding of the spatiotemporal complexity of Notch signaling.
Associations of neighborhood walkability with moderate to vigorous physical activity: an application of compositional data analysis comparing compositional and non-compositional approaches
Authors: Bird Madeleine , Datta Geetanjali D , Chinerman Deanna , Kakinami Lisa , Mathieu Marie-Eve , Henderson Mélanie , Barnett Tracie A
Published: May 2022

Background

We compared the relation between neighborhood features and moderate to vigorous physical activity (MVPA) using linear regression analysis and the more novel compositional data analysis (CoDA). Compositional data analysis allows us to take the time children allocate to different movement behaviours during a 24-hour time period into account.

Methodology

Data from youth participants (n = 409) in the QUALITY (QUebec Adipose and Lifestyle InvesTigation in Youth) cohort were included. Time spent in MVPA, light physical activity, sedentary behavior, and sleep (“24-hour movement behaviours”) was measured using accelerometers. Neighborhood data were collected using a geographic information system and through direct observation. In CoDA models, we used orthogonal logratio coordinates, which allows for the association of neighbourhood walkability with MVPA to be estimated with respect to the average composition of all other behaviours within a 24-hour time frame. In baseline linear regression models, MVPA was regressed cross-sectionally on neighborhood walkability. All models were stratified by sex, and controlled for BMI z-scores, pubertal development, seasonal variation, parental education, and neighbourhood safety.

Results

Based on CoDA, girls who lived in more walkable neighborhoods had 10% higher daily MVPA (95% CI: 2%, 19%), taking into account all other movement behaviours. Based on linear regression, girls who resided in more walkable neighborhoods engaged in 4.2 (95% confidence interval [CI]: 1.2, 6.6) more minutes of MVPA per day on average than girls residing in less walkable neighborhoods.

Conclusions

Unlike with traditional linear models, all movement behaviours were included in a single model using CoDA, allowing for a more complete picture of the strength and direction of the association between neighbourhood Walkability and MVPA. Application of CoDA to investigate determinants of physical activity provides additional insight into potential mechanisms and the ways in which people allocate their time.
No evidence of bovine leukemia virus proviral DNA and antibodies in human specimens from Japan
Authors: Yamanaka Meripet Polat , Saito Susumu , Hara Yukiko , Matsuura Ryosuke , Takeshima Shin-nosuke , Hosomichi Kazuyoshi , Matsumoto Yasunobu , Furuta Rika A. , Takei Masami , Aida Yoko
Published: May 2022

Background

The potential risk and association of bovine leukemia virus (BLV) with human remains controversial as it has been reported to be both positive and negative in human breast cancer and blood samples. Therefore, establishing the presence of BLV in comprehensive human clinical samples in different geographical locations is essential.

Result

In this study, we examined the presence of BLV proviral DNA in human blood and breast cancer tissue specimens from Japan. PCR analysis of BLV provirus in 97 Japanese human blood samples and 23 breast cancer tissues showed negative result for all samples tested using long-fragment PCR and highly-sensitive short-fragment PCR amplification. No IgG and IgM antibodies were detected in any of the 97 human serum samples using BLV gp51 and p24 indirect ELISA test. Western blot analysis also showed negative result for IgG and IgM antibodies in all tested human serum samples.

Conclusion

Our results indicate that Japanese human specimens including 97 human blood, 23 breast cancer tissues, and 97 serum samples were negative for BLV.
Non-linear transformation of enzyme-linked immunosorbent assay (ELISA) measurements allows usage of linear models for data analysis
Authors: Lange Thomas M. , Rotärmel Maria , Müller Dominik , Mahone Gregory S. , Kopisch-Obuch Friedrich , Keunecke Harald , Schmitt Armin O.
Published: May 2022

Background

In research questions such as in resistance breeding against theBeet necrotic yellow vein virusit is of interest to compare the virus concentrations of samples from different groups. The enzyme-linked immunosorbent assay (ELISA) counts as the standard tool to measure virus concentrations. Simple methods for data analysis such as analysis of variance (ANOVA), however, are impaired due to non-normality of the resulting optical density (OD) values as well as unequal variances in different groups.

Methods

To understand the relationship between the OD values from an ELISA test and the virus concentration per sample, we used a large serial dilution and modelled its non-linear form using a five parameter logistic regression model. Furthermore, we examined if the quality of the model can be increased if one or several of the model parameters are defined beforehand. Subsequently, we used the inverse of the best model to estimate the virus concentration for every measured OD value.

Results

We show that the transformed data are essentially normally distributed but provide unequal variances per group. Thus, we propose a generalised least squares model which allows for unequal variances of the groups to analyse the transformed data.

Conclusions

ANOVA requires normally distributed data as well as equal variances. Both requirements are not met with raw OD values from an ELISA test. A transformation with an inverse logistic function, however, gives the possibility to use linear models for data analysis of virus concentrations. We conclude that this method can be applied in every trial where virus concentrations of samples from different groups are to be compared via OD values from an ELISA test. To encourage researchers to use this method in their studies, we provide an R script for data transformation as well as the data from our trial.
Medical nutrition therapy and clinical outcomes in critically ill adults: a European multinational, prospective observational cohort study (EuroPN)
Authors: Matejovic Martin , Huet Olivier , Dams Karolien , Elke Gunnar , Vaquerizo Alonso Clara , Csomos Akos , Krzych Łukasz J. , Tetamo Romano , Puthucheary Zudin , Rooyackers Olav , Tjäder Inga , Kuechenhoff Helmut , Hartl Wolfgang H. , Hiesmayr Michael
Published: May 2022

Background

Medical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European intensive care units (ICU) and their importance for clinical outcomes.

Methods

Prospective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low: < 10 kcal/kg, < 0.8 g/kg; moderate: 10–20 kcal/kg, 0.8–1.2 g/kg, high: > 20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV).

Results

A total of 1172 patients with median [Q1;Q3] APACHE II score of 18.5 [13.0;26.0] were included, and 24% died within 90 days. Median length of ICU stay was 10.0 [7.0;16.0] days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% [59;107] and 65% [41;91] of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 [95% CI: 1.60;3.25] for calorie intake, 0.14 [0.09;0.20] for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (− 2.74 [− 3.28; − 2.21] and − 0.12 [− 0.15; − 0.09], respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 [95% CI: 1.5;14.09] on day 12; for protein: maximum HR 2.60 [1.09;6.23] on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, [0.05;0.39] on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements.

Conclusions

Calorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes.

Trial registrationNCT04143503, registered on October 25, 2019.

Graphical abstract
Modeling zero inflation is not necessary for spatial transcriptomics
Authors: Zhao Peiyao , Zhu Jiaqiang , Ma Ying , Zhou Xiang
Published: May 2022

Background

Spatial transcriptomics are a set of new technologies that profile gene expression on tissues with spatial localization information. With technological advances, recent spatial transcriptomics data are often in the form of sparse counts with an excessive amount of zero values.

Results

We perform a comprehensive analysis on 20 spatial transcriptomics datasets collected from 11 distinct technologies to characterize the distributional properties of the expression count data and understand the statistical nature of the zero values. Across datasets, we show that a substantial fraction of genes displays overdispersion and/or zero inflation that cannot be accounted for by a Poisson model, with genes displaying overdispersion substantially overlapped with genes displaying zero inflation. In addition, we find that either the Poisson or the negative binomial model is sufficient for modeling the majority of genes across most spatial transcriptomics technologies. We further show major sources of overdispersion and zero inflation in spatial transcriptomics including gene expression heterogeneity across tissue locations and spatial distribution of cell types. In particular, when we focus on a relatively homogeneous set of tissue locations or control for cell type compositions, the number of detected overdispersed and/or zero-inflated genes is substantially reduced, and a simple Poisson model is often sufficient to fit the gene expression data there.

Conclusions

Our study provides the first comprehensive evidence that excessive zeros in spatial transcriptomics are not due to zero inflation, supporting the use of count models without a zero inflation component for modeling spatial transcriptomics.
Reducing the risk of Plasmodium vivax after falciparum infections in co-endemic areas—a randomized controlled trial (PRIMA)
Authors: Thriemer Kamala , Degaga Tamiru Shibru , Christian Michael , Alam Mohammad Shafiul , Ley Benedikt , Hossain Mohammad Sharif , Kibria Mohammad Golam , Tego Tedla Teferi , Abate Dagimawie Tadesse , Weston Sophie , Karahalios Amalia , Rajasekhar Megha , Simpson Julie A. , Rumaseb Angela , Mnjala Hellen , Lee Grant , Anose Rodas Temesgen , Kidane Fitsum Getahun , Woyessa Adugna , Baird Kevin , Sutanto Inge , Hailu Asrat , Price Ric N.
Published: May 2022

Background

Plasmodium vivax forms dormant liver stages that can reactivate weeks or months following an acute infection. Recurrent infections are often associated with a febrile illness and can cause a cumulative risk of severe anaemia, direct and indirect mortality, and onward transmission of the parasite. There is an increased risk of P. vivax parasitaemia following falciparum malaria suggesting a rationale for universal use of radically curative treatment in patients with P. falciparum malaria even in the absence of detectable P. vivax parasitaemia in areas that are co-endemic for both species.

Methods

This is a multicentre, health care facility-based, randomized, controlled, open-label trial in Bangladesh, Indonesia and Ethiopia. Patients with uncomplicated falciparum malaria, G6PD activity of ≥70% of the adjusted male median (AMM) and haemoglobin levels ≥8g/dl are recruited into the study and randomized to either receive standard schizonticidal treatment plus 7-day high dose primaquine (total dose 7mg/kg) or standard care in a 1:1 ratio. Patients are followed up weekly until day 63. The primary endpoint is the incidence risk of any P. vivax parasitemia on day 63. Secondary endpoints include incidence risk on day 63 of symptomatic P. vivax malaria and the risk of any P. falciparum parasitaemia. Secondary safety outcomes include the proportion of adverse events and serious adverse events, the incidence risk of severe anaemia (Hb<5g/dl and <7g/dl) and/or the risk for blood transfusion, the incidence risk of ≥ 25% fall in haemoglobin with and without haemoglobinuria, and the incidence risk of ≥ 25% fall in haemoglobin to under 7g/dl with and without haemoglobinuria.

Discussion

This study evaluates the potential benefit of a universal radical cure for both P. vivax and P. falciparum in different endemic locations. If found safe and effective universal radical cure could represent a cost-effective approach to clear otherwise unrecognised P. vivax infections and hence accelerate P. vivax elimination.

Trial registration

NCT03916003. Registered on 12 April 2019.
Structural and functional specificity of H3K36 methylation
Authors: Lam Ulysses Tsz Fung , Tan Bryan Kok Yan , Poh John Jia Xin , Chen Ee Sin
Published: May 2022

The methylation of histone H3 at lysine 36 (H3K36me) is essential for maintaining genomic stability. Indeed, this methylation mark is essential for proper transcription, recombination, and DNA damage response. Loss- and gain-of-function mutations in H3K36 methyltransferases are closely linked to human developmental disorders and various cancers. Structural analyses suggest that nucleosomal components such as the linker DNA and a hydrophobic patch constituted by histone H2A and H3 are likely determinants of H3K36 methylation in addition to the histone H3 tail, which encompasses H3K36 and the catalytic SET domain. Interaction of H3K36 methyltransferases with the nucleosome collaborates with regulation of their auto-inhibitory changes fine-tunes the precision of H3K36me in mediating dimethylation by NSD2 and NSD3 as well as trimethylation by Set2/SETD2. The identification of specific structural features and various cis-acting factors that bind to different forms of H3K36me, particularly the di-(H3K36me2) and tri-(H3K36me3) methylated forms of H3K36, have highlighted the intricacy of H3K36me functional significance. Here, we consolidate these findings and offer structural insight to the regulation of H3K36me2 to H3K36me3 conversion. We also discuss the mechanisms that underlie the cooperation between H3K36me and other chromatin modifications (in particular, H3K27me3, H3 acetylation, DNA methylation and N6-methyladenosine in RNAs) in the physiological regulation of the epigenomic functions of chromatin.
RETRACTED ARTICLE: Association of cord blood asprosin concentration with atherogenic lipid profile and anthropometric indices
Authors: Hussein Hanan Khudhair , Aubead Nassrin Malik , Kzar Hamzah H. , Karim Yasir Salam , Amin Ali H. , Al-Gazally Moaed E. , Ahmed Tousief Irshad , Jawad Mohammed Abed , Hammid Ali Thaeer , Jalil Abduladheem Turki , Mustafa Yasser Fakri , Saleh Marwan Mahmood , Heydari Hafez
Published: May 2022

Background

Elevated lipids in umbilical cord blood affect fetal programming, leading to a higher risk of developing cardiovascular disease in later life. However, the causes of changes in the lipid profile of umbilical cord blood are not clear yet. This study aimed for the first time to determine the association of asprosin concentration with TAG, TC, HDL-C, LDL-C concentrations and TAG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C/HDL-C ratio in umbilical cord blood as well as newborn anthropometric indices. This cross-sectional study was based on 450 mother- newborn pairs of a birth cohort study in Sabzevar, Iran. Multiple linear regression was used to estimate the association of lipid concentration and lipid ratios as well as birth weight (BW), birth length (BL), head circumference (HC) and chest circumference (CC) with asprosin in cord blood samples controlled for the relevant covariates.

Result

In fully adjusted models, each 1 ng/mL increase in asprosin was associated with 0.19 (95% CI 0.06, 0.31, P < 0.01), 0.19 (95% CI 0.10, 0.29, P < 0.01), 0.17 (95% CI 0.09, 0.25, P < 0.01), 0.17 (95% CI 0.09, 0.25, P < 0.01), 0.01 (95% CI 0.00, 0.013, P < 0.01), 0.01 (95% CI 0.01, 0.01, P < 0.01), 0.01 (95% CI 0.01, 0.01, P < 0.01) and 0.01 (95% CI 0.01, 0.01, P < 0.01) increase in TAG, TC, LDL-C, TAG/HDL-C, TC/HDL-C, LDL-C/HDL-C and non-HDL-C/HDL-C ratio respectively. Moreover, higher asprosin levels was positively associated with newborn BW, BL, HC and CC; however, these associations were not statistically significant.

Conclusion

Overall, our findings support the positive association between cord asprosin concentration and the development of atherogenic lipid profile in newborns. Further studies are needed to confirm the findings of this study in other populations.
RNA-Seq analysis of duck embryo fibroblast cells gene expression during duck Tembusu virus infection
Authors: Pan Yuhong , Wu Xuedong , Cai Wenjun , Cheng Anchun , Wang Mingshu , Chen Shun , Huang Juan , Yang Qiao , Wu Ying , Sun Di , Mao Sai , Zhu Dekang , Liu Mafeng , Zhao Xinxin , Zhang Shaqiu , Gao Qun , Ou Xumin , Tian Bin , Yin Zhongqiong , Jia Renyong
Published: May 2022

Duck Tembusu virus (DTMUV), a member of the family Flaviviridae and an economically important pathogen with a broad host range, leads to markedly decreased egg production. However, the molecular mechanism underlying the host-DTMUV interaction remains unclear. Here, we performed high-throughput RNA sequencing (RNA-Seq) to study the dynamic changes in host gene expression at 12, 24, 36, 48 and 60 h post-infection (hpi) in duck embryo fibroblasts (DEF) infected with DTMUV. A total of 3129 differentially expressed genes (DEG) were identified after DTMUV infection. Gene Ontology (GO) category and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these DEG were associated with multiple biological functions, including signal transduction, host immunity, virus infection, cell apoptosis, cell proliferation, and pathogenicity-related and metabolic process signaling pathways. This study analyzed viral infection and host immunity induced by DTMUV infection from a novel perspective, and the results provide valuable information regarding the mechanisms underlying host-DTMUV interactions, which will prove useful for the future development of antiviral drugs or vaccines for poultry, thus benefiting the entire poultry industry.
Single cell transcriptomic analysis of human amnion identifies cell-specific signatures associated with membrane rupture and parturition
Authors: Wang Wang-Sheng , Lin Yi-Kai , Zhang Fan , Lei Wen-Jia , Pan Fang , Zhu Ya-Nan , Lu Jiang-Wen , Zhang Chu-Yue , Zhou Qiong , Ying Hao , Sun Kang
Published: May 2022

Background

The human amnion is an intrauterine tissue which is involved in the initiation of parturition. In-depth understanding of gene expression signatures of individual cell types in the amnion with respect to membrane rupture at parturition may help identify crucial initiators of parturition for the development of specific strategies to prevent preterm birth, a leading cause of perinatal mortality.

Results

Six major cell types were revealed in human amnion including epithelial cells, fibroblasts and immunocytes as well as three other cell types expressing dual cell markers including epithelial/fibroblast, immune/epithelial and immune/fibroblast markers. The existence of cell types expressing these dual cell markers indicates the presence of epithelial-mesenchymal (EMT), epithelial-immune (EIT) and mesenchymal-immune (MIT) transitions in amnion at parturition. We found that the rupture zone of amnion exhibited some specific increases in subcluster proportions of immune and EMT cells related to extracellular matrix remodeling and inflammation in labor. The non-rupture zone exhibited some common changes in subcluster compositions of epithelial and fibroblast cells with the rupture zone in labor, particularly those related to oxidative stress and apoptosis in epithelial cells and zinc ion transport in fibroblasts. Moreover, we identified that C–C motif chemokine ligand 20 (CCL20) was among the top up-regulated genes in amnion epithelial cells, fibroblasts and immunocytes in the rupture zone at parturition. Studies in pregnant mice showed that administration of CCL20 induced immunocytes infiltration to tissues at the maternal–fetal interface and led to preterm birth.

Conclusions

Apart from the conventional epithelial, fibroblast and immunocytes, human amnion cells may undergo EMT, EIT and FIT in preparation for parturition. Intense inflammation and ECM remodeling are present in the rupture zone, while enhanced apoptosis and oxidative stress in epithelial cells and zinc ion transport in fibroblasts are present in amnion regardless of the rupture zones at parturition. CCL20 derived from the major cell types of the amnion participates in labor onset.