bluuebunny/crossref_metadata_2025 huggingface dataset:
Spiritual Leadership and Organizational Citizenship Behavior: A Meta-Analysis
Authors: Göçen Ahmet , Şen Sedat
Published: August 2021

There have been many studies on spiritual leadership (SL) and its effects on organizational outcomes, ranging from commitment to organizational citizenship behaviors (OCBs). Precisely, researches regarding SL and OCB were conducted in different regions, cultures, and industries. These topics attracted a growing interest in the second half of the last decade. To clarify the SL–OCB relationship with regard to varied regions and industries, a meta-analysis was needed. Thus, the purpose of this study was to systematically analyze the quantitative studies exploring SL and OCB and to determine whether region, school, or other variables have any moderating effects on the link between SL and OCB. Upon a thorough analysis of the papers on the relationship between both SL and OCB in the literature, 43 studies met the search terms, but only 17 of them were included in this study. The results revealed a mean effect size of [Formula: see text] = .465, which displayed a statistically significant and positive relationship at the medium level between SL and OCB. The research also explored the effects of both Middle Eastern and Far Eastern samples, along with the factors of schools and other industries, on the link between SL and OCB. Neither different regions nor type of institutions had a significant effect on the link between SL and OCB.
Auditor’s Income Taxation and Audit Quality
Authors: Steller Marcel , Pummerer Erich
Published: August 2021

We use an analytical research model to analyze the effect of the auditor’s personal income tax on audit effort. We show that the auditor’s level of care crucially depends on the tax rate and amount of loss recognition. Taxes may cause paradoxical effects on the auditor’s effort, audit quality, and marginal audit fee if profits and losses are taxed differently or in case of risk-averse decision-makers. Therefore, compared with the pretax setting, taxes have distortional effects. Thus, common auditing standards (e.g., International Standards on Auditing framework) will imply diverse audit quality and marginal audit fees depending on the respective national tax law. Our results are relevant for standard setters, auditors, and financial statements’ addressees.
Developing the Process and Tracking the Implementation and Evaluation of the National Institutes of Health Strategic Plan for Women’s Health Research
Authors: Noursi Samia , Clayton Janine Austin , Shieh Ching-yi , Sharon Laura , Hopkins Dawnkimberly , Simms Dana , Sinclair Amber
Published: August 2021

Background

The National Institutes of Health (NIH) released Advancing Science for the Health of Women: The Trans-NIH Strategic Plan for Women’s Health Research, 2019–2023 (Strategic Plan) in February 2019. The NIH Office of Research on Women’s Health (ORWH) engaged staff members from across NIH to develop recommendations on the implementation and evaluation of the Strategic Plan. Objective: This paper describes the process used to develop recommendations for tools and approaches that NIH Institutes, Centers, and Offices (ICOs) could apply when implementing and evaluating the Strategic Plan. Methods: A Trans-NIH Strategic Plan Implementation and Evaluation Guidance Development Team conducted meetings and individual interviews with 69 NIH staff members knowledgeable about research on the health of women and sex and gender differences and met with 11 Advisory Committee on Research on Women’s Health Strategic Plan Evaluation Working Group members. The purpose of these stakeholder meetings and interviews was to obtain recommendations for implementing the Strategic Plan and identify measures for evaluating implementation success. A thematic analysis was performed to synthesize and map the recommendations to the Strategic Plan goals and objectives. Results: The process resulted in the Guide for Implementing and Evaluating the 2019–2023 Trans-NIH Strategic Plan for Women’s Health Research Across NIH Institutes, Centers, and Offices (the Guide), which includes both a conceptual and logic model for implementation and evaluation. Conclusions: The Guide offers methods, tools, and suggestions that ICO planning and evaluation staff, as well as national and international entities, can choose from when determining how to implement the Strategic Plan through ICO activities, programs, and research initiatives and how to evaluate their efforts in the context of their unique mission.
“When did I Stop being a Child?” The Subjective Feeling of Adulthood of Mexican and Central American Unaccompanied 1.25 Generation Immigrants
Authors: Diaz-Strong Daysi Ximena
Published: August 2021

Employing narrative inquiry, this paper examines how 30 Mexican and Central American young adults (ages 21 to 34) who immigrated without a parent as teenagers—the unaccompanied 1.25 generation— experienced the subjective feeling of adulthood. Structural realities pushed the unaccompanied 1.25 generation into early adult roles, independence, and social responsibility. In many cases, attainment of “adult” roles, independence, and even social responsibility was not followed by the subjective feeling of adulthood. Instead, the feeling of adulthood emerged in gendered ways, was gradual, and resulted from seeing themselves as competent, mature, and capable of thoughtful decision-making. Moreover, in some cases, traumatic events led some to early identification with adult status or disrupted their identification with adulthood. Their experiences support the idea that becoming an adult is an internal process, and raises questions on how independence and social responsibility are experienced by marginalized youth and incorporated into their sense of adulthood.
Renal lymphomatous infiltration by mantle cell lymphoma: Treatment with chemoradiation and initiation of angiotensin converting enzyme (ACE) inhibitor for renal protection
Authors: Damron Ethan P , Gunther Jillian R , Kala Jaya
Published: August 2021

Background:

Mantle Cell Lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma (NHL) that often takes an aggressive course. Rarely, MCL may cause acute kidney injury (AKI) either by direct lymphomatous invasion or by paraneoplastic processes.

Case presentation:

We present a rare case of a 64-year-old-man with AKI caused by recurrent MCL infiltrating into the bilateral renal collecting systems who was treated with renal-directed low-dose radiation therapy (RT; 4 Gy) and concurrent systemic chemotherapy. In order to prevent possible radiation-induced damage to the kidneys, he was started on captopril prior to start of RT. After RT, his renal function continued to improve until returning to baseline.

Conclusion:

Renal-directed RT with a low-dose of radiation (4 Gy) was used successfully to treat renal MCL infiltration and reverse the effects of AKI. We would also like to highlight the potential use of angiotensin converting enzyme (ACE) inhibitors to decrease the chances of radiation-induced kidney injury.
A pipeline for RNA-seq based eQTL analysis with automated quality control procedures
Authors: Wang Tao , Liu Yongzhuang , Ruan Junpeng , Dong Xianjun , Wang Yadong , Peng Jiajie
Published: August 2021

Background

Advances in the expression quantitative trait loci (eQTL) studies have provided valuable insights into the mechanism of diseases and traits-associated genetic variants. However, it remains challenging to evaluate and control the quality of multi-source heterogeneous eQTL raw data for researchers with limited computational background. There is an urgent need to develop a powerful and user-friendly tool to automatically process the raw datasets in various formats and perform the eQTL mapping afterward.

Results

In this work, we present a pipeline for eQTL analysis, termed eQTLQC, featured with automated data preprocessing for both genotype data and gene expression data. Our pipeline provides a set of quality control and normalization approaches, and utilizes automated techniques to reduce manual intervention. We demonstrate the utility and robustness of this pipeline by performing eQTL case studies using multiple independent real-world datasets with RNA-seq data and whole genome sequencing (WGS) based genotype data.

Conclusions

eQTLQC provides a reliable computational workflow for eQTL analysis. It provides standard quality control and normalization as well as eQTL mapping procedures for eQTL raw data in multiple formats. The source code, demo data, and instructions are freely available at https://github.com/stormlovetao/eQTLQC.
RSAtrace3D: robust vectorization software for measuring monocot root system architecture
Authors: Teramoto Shota , Tanabata Takanari , Uga Yusaku
Published: August 2021

Background

The root distribution in the soil is one of the elements that comprise the root system architecture (RSA). In monocots, RSA comprises radicle and crown roots, each of which can be basically represented by a single curve with lateral root branches or approximated using a polyline. Moreover, RSA vectorization (polyline conversion) is useful for RSA phenotyping. However, a robust software that can enable RSA vectorization while using noisy three-dimensional (3D) volumes is unavailable.

Results

We developed RSAtrace3D, which is a robust 3D RSA vectorization software for monocot RSA phenotyping. It manages the single root (radicle or crown root) as a polyline (a vector), and the set of the polylines represents the entire RSA. RSAtrace3D vectorizes root segments between the two ends of a single root. By utilizing several base points on the root, RSAtrace3D suits noisy images if it is difficult to vectorize it using only two end nodes of the root. Additionally, by employing a simple tracking algorithm that uses the center of gravity (COG) of the root voxels to determine the tracking direction, RSAtrace3D efficiently vectorizes the roots. Thus, RSAtrace3D represents the single root shape more precisely than straight lines or spline curves. As a case study, rice (Oryza sativa) RSA was vectorized from X-ray computed tomography (CT) images, and RSA traits were calculated. In addition, varietal differences in RSA traits were observed. The vector data were 32,000 times more compact than raw X-ray CT images. Therefore, this makes it easier to share data and perform re-analyses. For example, using data from previously conducted studies. For monocot plants, the vectorization and phenotyping algorithm are extendable and suitable for numerous applications.

Conclusions

RSAtrace3D is an RSA vectorization software for 3D RSA phenotyping for monocots. Owing to the high expandability of the RSA vectorization and phenotyping algorithm, RSAtrace3D can be applied not only to rice in X-ray CT images but also to other monocots in various 3D images. Since this software is written in Python language, it can be easily modified and will be extensively applied by researchers in this field.
The influence of a gluten-free diet on health-related quality of life in individuals with celiac disease
Authors: Al-sunaid Fahdah F. , Al-homidi Maha M. , Al-qahtani Rawan M. , Al-ashwal Reema A. , Mudhish Ghada A. , Hanbazaza Mahitab A. , Al-zaben Abeer S.
Published: August 2021

Background

Adherence to a gluten-free diet (GFD) and food insecurity (FI) may influence health-related quality of life (HRQOL) in individuals with celiac disease (CD). This study aimed to investigate the association between adherence to a GFD, FI, and HRQOL in individuals with CD.

Methods

This cross-sectional study included 97 adults (mean age: 34 ± 9 years) diagnosed with CD. The participants were on a GFD for more than 6 months. Sociodemographic characteristics and medical history were assessed. Adherence to a GFD, FI, and HRQOL were assessed using validated questionnaires.

Results

Most participants (73%) adhered to a GFD, and 62% were experiencing FI. Individuals with CD faced difficulty in accessing GF foods due to the high cost (90%) and limited availability (79%). The mean overall HRQOL score was 60. Scores on the physical and mental health domains were 69 and 47, respectively. Adherence to a GFD was significantly associated with FI (P = 0.02), while there was no association between adherence to a GFD and HRQOL measures (P > 0.05). Participants facing FI had lower scores in emotional well-being and mental health domains, and overall HRQOL (P < 0.05).

Conclusions

The findings of the present study demonstrate that FI influences adherence to a GFD, and that FI is associated with HRQOL in terms of both emotional well-being and mental health.
Carers’ experiences of assistive technology use in dementia care: a cross sectional survey
Authors: Sriram Vimal , Jenkinson Crispin , Peters Michele
Published: August 2021

Background

Assistive Technology (AT) supports persons with dementia and their carers (family, friends and neighbours), yet little is known about experiences and the impact of AT on carers. We report on an exploratory survey that examined the types, uses, costs and impact of AT on carers as well as their quality of life.

Methods

A cross-sectional survey using the Carers Assistive Technology Experience Questionnaire collected data from carers in the UK, who used at least one AT in the previous year and provided more than 10 h of care for a person with dementia, living at home. Carers completed the questionnaire online or on paper and information on AT, socio-demographic details, and Short-Form Health Survey (SF-12) data were collected. Descriptive and inferential statistics were used to report results and draw conclusions.

Results

Data from 201 carers was analysed. Smartphones and tablet computers were the most frequently used AT. AT were used predominantly for safety, communication, and reminders. Carers usually make decisions on buying and continued use of AT. Multiple AT devices were used in the care of persons with dementia and number of AT used was associated with perceived satisfaction. Satisfaction with AT was not related to age, living arrangements and relationship of carers. From the SF-12, Mean Physical Component Score was 49.19 (95%CI- 47.75 to 50.63) and Mental Component Score was 45.37 (95%CI- 43.93 to 46.80). Women, carers in the 46–65 age group and carers who were not extremely satisfied with AT had lower MCS scores. Carers who lived with the person with dementia and older carers had lower PCS scores.

Conclusions

Carers report that AT has a beneficial impact. Carers use multiple ATs, perceive AT to be satisfactory and recommend AT use to others. To support carers, we recommend establishment of centrally funded information sources and a loan store for AT. Further research on incremental addition of AT and changes to formal/paid care because of using AT should be undertaken. Practitioners, academics, manufactures and policy makers should consider the experiences of carers in research, development and use of AT to facilitate improved community living of people with dementia.
Evaluation of asymptomatic bacteruria management before and after antimicrobial stewardship program implementation: retrospective study
Authors: Alghamdi Ahlam , Almajid Majid , Alalawi Raneem , Alganame Amjad , Alanazi Shorooq , Alghamdi Ghaida , Alharthi Salman , Alghamdi Isra
Published: August 2021

Background

The Infectious Diseases Society of America (IDSA) recommends against screening for and/or treating asymptomatic bacteriuria (ASB). This study aims to evaluate the inappropriate use of antibiotics in ASB before and after Antimicrobial Stewardship Program (ASP) implementation and advance towards its appropriate use.

Method

We performed a retrospective study of patients diagnosed with ASB from 2016 to 2019 at a tertiary hospital in Saudi Arabia. This study included hospitalized patients ≥ 18 years old who had a positive urine culture with no documented signs or symptoms of urinary tract infection We excluded pregnant women, solid organ transplant patients, patient on active chemotherapy, and patients about to undergo urological surgery.

Results

A total of 716 patients with a positive urine culture were screened. Among these, we identified 109 patients with ASB who were included in our study. The rate of inappropriate antibiotic use was 95% during the study period. The implementation of the ASP Program was associated with a significant reduction in the use of carbapenems (P = 0.04) and an increase in the use of cephalosporins (P = 0.01). However, overprescribing antimicrobial agents was a concern in both eras. Approximately 90% of the microorganisms identified were gram-negative bacteria. Of those, 38.7% were multidrug-resistant strains.

Conclusion

The urine culture order in ASB is considered relatively small number; however, it showed a high rate of the inappropriate use of antibiotics when there is an order of urine culture in both era. ASP ought to focus on targeting the ordering physician, promoting awareness and/or organizational interventions that appear to reduce the incidence of overtreatment.
Risk factors, clinical features and outcome of new-onset acute kidney injury among critically ill patients: a database analysis based on prospective cohort study
Authors: Jiang Yi-Jia , Xi Xiu-Ming , Jia Hui-Miao , Zheng Xi , Wang Mei-Ping , Li Wen , Li Wen-Xiong
Published: August 2021

Background

Acute kidney injury (AKI) newly-emerged in intensive care unit (ICU), has not been thoroughly studied in previous researches, is likely to differ from AKI developed before ICU admission. This study aimed to evaluate the incidence, risk factors, clinical features and outcome of new-onset AKI in critically ill patients.

Methods

The data of present study derived from a multicenter, prospective cohort study in17 Chinese ICUs (January 2014 - August 2015). The incidence, risk factors, clinical features and survival analysis of new-onset AKI were assessed.

Results

A total of 3374 adult critically ill patients were eligible. The incidence of new-onset AKI was 30.0 % (n = 1012). Factors associated with a higher risk of new-onset AKI included coronary heart disease, hypertension, chronic liver disease, use of nephrotoxic drugs, sepsis, SOFA score, APACHEII score and use of vasopressors. The new-onset AKI was an independent risk factor for 28-day mortality (adjusted hazard ratio, 1.643; 95 % CI, 1.370–1.948;P < 0.001). 220 (21.7 %) patients received renal replacement therapy (RRT), 71 (32.3 %) of them were successfully weaning from RRT. More than half of the new-onset AKI were transient AKI (renal recovery within 48 h). There was no statistical relationship between transient AKI and 28-day mortality (hazard ratio, 1.406; 95 % CI, 0.840–1.304;P = 0.686), while persistent AKI (non-renal recovery within 48 h) was strongly associated with 28-day mortality (adjusted hazard ratio, 1.486; 95 % CI, 1.137–1.943;P < 0.001).

Conclusions

New-onset AKI is common in ICU patients and is associated with significantly higher 28-day mortality. Only persistent AKI, but not transient AKI is associated with significantly higher 28-day mortality.
Risk factors of endometrial cancer in patients with endometrial hyperplasia: implication for clinical treatments
Authors: Zhao Jie , Hu Yongting , Zhao Yanan , Chen Dongmei , Fang Tingfeng , Ding Miao
Published: August 2021

Background

Endometrial hyperplasia (EH) is commonly-seen in the patients with endometrial cancer (EC), we aimed to evaluated the risk factors of EC in patients with EH, to provide evidence to the clinical prevention and treatment of EC.

Methods

This study was a retrospective study design. EH patients confirmed by pathological examinations and treated with hysterectomy in our hospital from June 1, 2018 to February 28, 2021 were included. The clinical characteristics of EC and no-EC patients were compared and analyzed. Logistics regression analyses were conducted to evaluate the risk factors of EC in patients with EH.

Results

A total of 228 EH patients were included, the incidence of EC in the EH patients was 31.58%. There were significant differences in the age, BMI, diabetes, hypertension and pathology of EH between EC and no EC groups (all P < 0.05), no significant differences in the hyperlipidemia, preoperative CA125, number of deliveries, menopause and endometrial thickness between EC and no EC groups were found (all P > 0.05). Logistic regression analyses indicated that age > 50 y (OR 3.064, 95% CI 1.945–5.931), BMI ≥ 25 kg/m2 (OR 2.705, 95% CI 1.121–3.889), diabetes (OR 3.049, 95% CI 1.781–5.114), hypertension (OR 2.725, 95% CI 1.108–3.431) and severe hyperplasia (OR 3.181, 95% CI 1.496–4.228) were the risk factors of EC in patients with EH (all P < 0.05).

Conclusions

The risk of EC in EH patients is high, especially for those patients with age > 50 y, BMI ≥ 25 kg/m2, diabetes, hypertension and severe hyperplasia, special attentions should be paid for occurrence of EC and early diagnosis and early treatment are needed for those patients.
Patient connectivity with healthcare professionals and health insurer using digital health technologies during the COVID-19 pandemic: a German cross-sectional study
Authors: Hannemann Niels , Götz Nina-Alexandra , Schmidt Lisa , Hübner Ursula , Babitsch Birgit
Published: August 2021

Background

Digital health technologies enable patients to make a personal contribution to the improvement of their health by enabling them to manage their health. In order to exploit the potential of digital health technologies, Internet-based networking between patients and health care providers is required. However, this networking and access to digital health technologies are less prevalent in sociodemographically deprived cohorts. The paper explores how the use of digital health technologies, which connect patients with health care providers and health insurers has changed during the COVID-19 pandemic.

Methods

The data from a German-based cross-sectional online study conducted between April 29 and May 8, 2020, were used for this purpose. A total of 1.570 participants were included in the study. Accordingly, the influence of sociodemographic determinants, subjective perceptions, and personal competencies will affect the use of online booking of medical appointments and medications, video consultations with providers, and the data transmission to health insurers via an app.

Results

The highest level of education (OR 1.806) and the presence of a chronic illness (OR 1.706) particularly increased the likelihood of using online booking. With regard to data transmission via an app to a health insurance company, the strongest increase in the probability of use was shown by belonging to the highest subjective social status (OR 1.757) and generation Y (OR 2.303). Furthermore, the results show that the higher the subjectively perceived restriction of the subjects' life situation was due to the COVID-19 pandemic, the higher the relative probability of using online booking (OR 1.103) as well as data transmission via an app to a health insurance company (OR 1.113). In addition, higher digital literacy contributes to the use of online booking (OR 1.033) and data transmission via an app to the health insurer (OR 1.034).

Conclusions

Socially determined differences can be identified for the likelihood of using digital technologies in health care, which persist even under restrictive conditions during the COVID-19 pandemic. Thus, the results indicate a digital divide with regard to the technologies investigated in this study.
Successful implementation of a trans-jurisdictional, primary care, anticipatory care planning intervention for older adults at risk of functional decline: interviews with key health professionals
Authors: Corry Dagmar Anna S. , Carter Gillian , Doyle Frank , Fahey Tom , Gillespie Patrick , McGlade Kieran , O’Halloran Peter , O’Neill Nina , Wallace Emma , Brazil Kevin
Published: August 2021

Background

Aging populations present a challenge to health systems internationally, due to the increasing complexity of care for older adults living with functional decline. This study aimed to elicit expert views of key health professionals on effective and sustainable implementation of a nurse-led, person-centred anticipatory care planning (ACP) intervention for older adults at risk of functional decline in a primary care setting.

Methods

We examined the feasibility of an ACP intervention in a trans-jurisdictional feasibility cluster randomized controlled trial consisting of home visits by research nurses who assessed participants’ health, discussed their health goals and devised an anticipatory care plan following consultation with participants’ GPs and adjunct clinical pharmacist. As part of the project, we elicited the views and recommendations of experienced key health professionals working with the target population who were recruited using a ‘snowballing technique’ in cooperation with older people health networks in the Republic of Ireland (ROI) and Northern Ireland (NI), United Kingdom [n = 16: 7 ROI, 9 NI]. Following receipt of written information about the intervention and the provision of informed consent, the health professionals were interviewed to determine their expert views on the feasibility of the ACP intervention and recommendations for successful implementation. Data were analyzed using thematic analysis.

Results

The ACP intervention was perceived to be beneficial for most older patients with multimorbidity. Effective and sustainable implementation was said to be facilitated by accurate and timely patient selection, GP buy-in, use of existing structures within health systems, multidisciplinary and integrated working, ACP nurse training, as well as patient health literacy. Barriers emerged as significant work already undertaken, increasing workload, lack of time, funding and resources, fragmented services, and geographical inequalities.

Conclusions

The key health professionals perceived the ACP intervention to be highly beneficial to patients, with significant potential to prevent or avoid functional decline and hospital admissions. They suggested that successful implementation of this primary care based, whole-person approach would involve integrated and multi-disciplinary working, GP buy in, patient health education, and ACP nurse training. The findings have potential implications for a full trial, and patient care and health policy.

Trial registration

Clinicaltrials.gov, ID: NCT03902743. Registered on 4 April 2019.
Comparison of a single-access glove port with a SILS™ port in a surgical simulator model using MISTELS
Authors: Strohmeier Ulrike , Dupré Gilles , Bockstahler Barbara , Tichy Alexander , Liehmann Lea
Published: August 2021

Background

Recent advances in laparoscopy both in human and veterinary medicine have looked at means of being less invasive by using single-port access surgery as opposed to multiport access surgery. The glove port has gained popularity as a cost-effective alternative to commercially available single-port access devices. The primary aim of this study was to compare the glove port to the SILS™ port in a simulator model using the first two MISTELS (McGill inanimate system for training and evaluation of laparoscopic skills) tasks (peg transfer and pattern cutting).

Methods

Twenty-two novices were enrolled in this experimental study. Each participant had 60 min to practise both MISTELS tasks using two-port laparoscopy. Thereafter participants performed both tasks using the glove and SILS™ port with scores being calculated based on task completion time and errors. Higher scores were indicative of better performance. Participants were assigned into two groups with the starting order of the single ports being randomly selected. A self-evaluation questionnaire with three questions was completed by each participant after testing, rating each port.

Results

Significantly (p < 0.05) higher scores were achieved using the glove port compared to the SILS™ port when performing both tasks. The glove port was subjectively evaluated as easier to use with more manoeuvrability of the instruments than the SILS™ port.

Implications of the study

The glove port’s improved manoeuvrability and ease of use make it a cost-effective alternative to the SILS™ port, for use in single-port laparoscopic veterinary surgery.
Milk lymphocyte profile and macrophage functions: new insights into the immunity of the mammary gland in quarters infected with Corynebacterium bovis
Authors: Silva Vitória M. , Souza Marina T. , Blagitz Maiara G. , Souza Fernando N. , Batista Camila F. , Alves Alexandre J. , Fernandes Artur C. C. , Sanchez Eduardo M. R. , Ordinola-Ramirez Carla M. , da Costa Luciana , Della Libera Alice M. M. P.
Published: August 2021

Backgrounds

The present study explored the viability of bovine milk macrophages, their intracellular production of reactive oxygen and nitrogen species (RONS), and their phagocytosis of Staphylococcus aureus, as well as the profile of lymphocytes, from healthy udder quarters and udder quarters infected by Corynebacterium bovis. The study included 28 healthy udder quarters from 12 dairy cows and 20 udder quarters infected by C. bovis from 10 dairy cows. The percentages of macrophages and lymphocytes were identified by flow cytometry using monoclonal antibodies. Macrophage viability, RONS production, and S. aureus phagocytosis were evaluated by flow cytometry.

Results

Milk samples from quarters infected with C. bovis showed a lower percentage of macrophages but an increased number of milk macrophages per mL and a higher percentage of macrophages that produced intracellular RONS and phagocytosed S. aureus. No effect of C. bovis infection on macrophage viability was found. Udder quarters infected by C. bovis showed a higher percentage of T cells and CD4+ T lymphocytes, but no effect was found on the percentage of CD8+ CD4− T, CD8− CD4− T, or B lymphocytes.

Conclusions

Thus, our results corroborate, at least in part, the finding that intramammary infections by C. bovis may offer protection against intramammary infections by major pathogens.
The experience of life events and body composition in middle childhood: a population-based study
Authors: Derks Ivonne P. M. , Hannani Sara , Vehmeijer Florianne O. L. , Tiemeier Henning , Jansen Pauline W.
Published: August 2021

While studies suggest potential influences of childhood adversities on obesity development in adulthood, less is known about the short-term association in children. We examined the association between a wide range of life events experienced in the first ten years of life (including maltreatment and milder adversities) and body composition in 5333 ten-year old Dutch children. In structured interviews, mothers retrospectively reported on their children’s experience of 24 events. BMI was calculated, and fat mass index and fat free mass index were determined by dual-x-ray absorptiometry scanning. Linear regressions showed that, unadjusted, a higher number of life events was associated with higher BMI and body composition. However, associations attenuated to non-significance after adjustment for covariates. Similar findings were observed for maltreatment and milder life events. Thus, the number of experienced life events was not associated with body composition in middle childhood. Rather, other factors, like socioeconomic conditions, accounted for the relationship between life events and weight development in children.
Functional genomics atlas of synovial fibroblasts defining rheumatoid arthritis heritability
Authors: Ge Xiangyu , Frank-Bertoncelj Mojca , Klein Kerstin , McGovern Amanda , Kuret Tadeja , Houtman Miranda , Burja Blaž , Micheroli Raphael , Shi Chenfu , Marks Miriam , Filer Andrew , Buckley Christopher D. , Orozco Gisela , Distler Oliver , Morris Andrew P. , Martin Paul , Eyre Stephen , Ospelt Caroline
Published: August 2021

Background

Genome-wide association studies have reported more than 100 risk loci for rheumatoid arthritis (RA). These loci are shown to be enriched in immune cell-specific enhancers, but the analysis so far has excluded stromal cells, such as synovial fibroblasts (FLS), despite their crucial involvement in the pathogenesis of RA. Here we integrate DNA architecture, 3D chromatin interactions, DNA accessibility, and gene expression in FLS, B cells, and T cells with genetic fine mapping of RA loci.

Results

We identify putative causal variants, enhancers, genes, and cell types for 30–60% of RA loci and demonstrate that FLS account for up to 24% of RA heritability. TNF stimulation of FLS alters the organization of topologically associating domains, chromatin state, and the expression of putative causal genes such as TNFAIP3 and IFNAR1. Several putative causal genes constitute RA-relevant functional networks in FLS with roles in cellular proliferation and activation. Finally, we demonstrate that risk variants can have joint-specific effects on target gene expression in RA FLS, which may contribute to the development of the characteristic pattern of joint involvement in RA.

Conclusion

Overall, our research provides the first direct evidence for a causal role of FLS in the genetic susceptibility for RA accounting for up to a quarter of RA heritability.
Microarray-based analysis of renal complement components reveals a therapeutic target for lupus nephritis
Authors: Liu Tao , Yang Mingyue , Xia Ying , Jiang Chuan , Li Chenxu , Jiang Zhenyu , Wang Xiaosong
Published: August 2021

Background

Screening abnormal pathways and complement components in the kidneys of patients with lupus nephritis (LN) and NZB/W mice may help to identify complement-related therapeutic targets for LN.

Methods

KEGG and GO enrichment assays were used to analyze kidney microarray data of LN patients and NZB/W mice. Immunohistochemistry and immunofluorescence assays were used to measure renal expression of complement-related proteins and TGFβ1. Cytokines were measured using RT-qPCR and ELISA.

Results

We screened the renal pathogenic pathways present in LN patients and NZB/W mice and selected the complement activation pathway for further study. The results indicated greater renal expression of C1qa, C1qb, C3, C3aR1, and C5aR1 at the mRNA and protein levels. C3 appeared to be a key factor in LN and the renal signaling downstream of C1 was inhibited. There were significant correlations between the expression of TGFβ1 and C3. Analysis of primary cell cultures indicated that TGFβ1 promoted the expression of C3 and that a TGFβ1 antagonist decreased the levels of C3 and C3aR. TGFβ1 inhibition significantly inhibited the deposition of complement-related factors in the kidneys of NZB/W mice.

Conclusions

At the onset of LN, there are significant increases in the renal levels of C3 and other complement pathway-related factors in patients with LN and NZB/W mice. C3 may lead to albuminuria and participate in the pathogenesis of LN. TGFβ1 promotes C3 synthesis, and TGFβ1 inhibition may block the progression of LN by inhibiting the synthesis of C3 and other complement components.
Screening, assessment and management of perioperative malnutrition: a survey of UK practice
Authors: Matthews L. S. , Wootton S. A. , Davies S. J. , Levett D. Z. H.
Published: August 2021

Background

Perioperative malnutrition is common and is associated with increased mortality, complications and healthcare costs. Patients having surgery for cancer and gastro-intestinal disease are at particular risk. It is a modifiable pre-operative risk factor and perioperative clinicians are well placed to identify those at risk and instigate interventions shown to improve outcome. Thus, we conducted a survey of Perioperative Medicine Leads with the aim of assessing the current provision of nutritional screening and intervention pathways in the UK.

Methods

Perioperative Medicine Leads registered with the Royal College of Anaesthetists were asked to complete an online survey exploring current practice in screening, assessment and management of malnutrition in the perioperative period. The survey included a mixture of open and closed questions, graded response questions and options for free text. Where a response was not received, departments were phoned directly and e-mails sent to non-responders.

Results

We received 121 completed questionnaires from 167 Perioperative Medicine Leads (response rate of 72.5%). Seventy respondents (57.9%) reported using the Malnutrition Universal Screening Tool to screen patients; however, only 61 (50.4%) referred patients at nutritional risk onto a dietitian. Sixty (49.6%) lacked confidence in local ability to identify and manage malnutrition perioperatively, with 28 (23.1%) reporting having a structured pathway for managing malnourished patients. One hundred eleven respondents (91.7%) agreed that malnutrition impacts on quality of life after surgery and 105 (86.8%) felt adopting a standard protocol would improve outcomes for patients. Those reporting a lack of confidence in dealing with malnutrition perioperatively cited a lack of organisational support, patients being seen too close to surgery and lack of clarity around responsibility as key reasons for difficulties in managing this group of patients.

Conclusions

Malnutrition in the perioperative period is a modifiable risk factor which is common and results in increased morbidity for patients and increased cost to healthcare systems. This survey highlights areas of practice where perioperative clinicians can improve the assessment and management of patients at nutritional risk prior to elective surgery.
Characterization of Non–Small-Cell Lung Cancers With MET Exon 14 Skipping Alterations Detected in Tissue or Liquid: Clinicogenomics and Real-World Treatment Patterns
Authors: Lee Jessica K. , Madison Russell , Classon Anthony , Gjoerup Ole , Rosenzweig Mark , Frampton Garrett M. , Alexander Brian M. , Oxnard Geoffrey R. , Venstrom Jeffrey M. , Awad Mark M. , Schrock Alexa B.
Published: August 2021

PURPOSE

MET exon 14 ( METex14) skipping alterations are oncogenic drivers in non–small-cell lung cancer (NSCLC). We present a comprehensive overview of METex14 samples from 1,592 patients with NSCLC, associated clinicogenomic characteristics, potential mechanisms of acquired resistance, treatment patterns, and outcomes to MET inhibitors.

METHODS

Hybrid capture–based comprehensive genomic profiling (CGP) was performed on samples from 69,219 patients with NSCLC. For treatment patterns and outcomes analysis, patients with advanced METex14-altered NSCLC were selected from the Flatiron Health-Foundation Medicine clinicogenomic database, a nationwide deidentified electronic health record–derived database linked to Foundation Medicine CGP for patients treated between January 2011 and March 2020.

RESULTS

A total of 1,592 patients with NSCLC (2.3%) were identified with 1,599 METex14 alterations spanning multiple functional sites (1,458 of 60,244 tissue samples and 134 of 8,975 liquid samples). Low tumor mutational burden and high programmed death ligand 1 expression were enriched in METex14-altered samples. MDM2, CDK4, and MET coamplifications and TP53 mutations were present in 34%, 19%, 11%, and 42% of tissue samples, respectively. Comparing tissue and liquid cohorts, coalteration frequency and acquired resistance mechanisms, including multiple MET mutations, EGFR, ERBB2, KRAS, and PI3K pathway alterations, were generally similar. Positive percent agreement with the tissue was 100% for METex14 pairs collected within 1 year (n = 7). Treatment patterns showed increasing adoption of MET inhibitors in METex14-altered NSCLC after receipt of CGP results; the real-world response rate to MET inhibitors was 45%, and time to treatment discontinuation was 4.4 months.

CONCLUSION

Diverse METex14 alterations were present in 2%-3% of NSCLC cases. Tissue and liquid comparisons showed high concordance and similar coalteration profiles. Characterizing common co-occurring alterations and immunotherapy biomarkers, including those present before or acquired after treatment, may be critical for predicting responses to MET inhibitors and informing rational combination strategies.
LLF580, an FGF21 Analog, Reduces Triglycerides and Hepatic Fat in Obese Adults With Modest Hypertriglyceridemia
Authors: Rader Daniel J , Maratos-Flier Eleftheria , Nguyen Amanda , Hom Doug , Ferriere Michael , Li Yifang , Kompa Jill , Martic Miljen , Hinder Markus , Basson Craig T , Yowe David , Diener John , Goldfine Allison B ,   CLLF580X2102 Study Team, Bajaj Archna , Escalon Maricer , Fein Melanie , Hunt Allen , Kankam Martin K , Koren Michael , Rader Daniel J , Wilson Jessica
Published: August 2021

Purpose

To evaluate the safety and potential efficacy of LLF580, a genetically engineered variant of human fibroblast growth factor-21, for triglyceride lowering, weight loss, and hepatic fat reduction.

Methods

A multicenter, double-blind, parallel design trial in obese, mildly hypertriglyceridemic adults randomized (1:1) to LLF580 300 mg or placebo subcutaneously every 4 weeks for 3 doses.

Results

Of 64 randomized study participants, 61 (mean ± SD: age 45 ± 11 years, 49% male, 80/15/5% Caucasian/African American/other, body mass index 36.1 ± 3.8 kg/m2) received LLF580 (n = 30) or placebo (n = 31) at 7 research sites in the United States. LLF580 lowered serum triglycerides by 54% (least square mean placebo adjusted change from baseline), total cholesterol 7%, low-density lipoprotein cholesterol 12%, and increased high-density lipoprotein cholesterol 36% compared with placebo (all P < 0.001) over 12 weeks. Substantial reduction of liver fat of 52% over placebo (P < 0.001) was also demonstrated in the setting of improved liver function tests including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, the composite enhanced liver fibrosis score, and N-terminal type III collagen propeptide (all P < 0.05). Insulin and C-peptide levels and insulin resistance by homeostatic model assessment for insulin resistance were all lower, and adiponectin higher with LLF580 treatment compared with placebo, whereas fasting glucose and glycated hemoglobin were unchanged. Reductions in biomarkers of bone formation without differences in markers of bone resorption were observed. LLF580 was generally safe and well tolerated, except for higher incidence of generally mild to moderate gastrointestinal adverse effects.

Conclusions

In obese, mildly hypertriglyceridemic adults, LLF580 was generally safe and demonstrated beneficial effects on serum lipids, liver fat, and biomarkers of liver injury, suggesting it may be effective for treatment of select metabolic disorders including hypertriglyceridemia and nonalcoholic fatty liver disease. Assessments of longer term safety and efficacy are warranted.

ClinicalTrials.gov Identifier

NCT03466203
LH Induces De Novo Cholesterol Biosynthesis via SREBP Activation in Granulosa Cells During Ovulation in Female Mice
Authors: Nakanishi Tomoya , Tanaka Risa , Tonai Shingo , Lee Joo Yeon , Yamaoka Manami , Kawai Tomoko , Okamoto Asako , Shimada Masayuki , Yamashita Yasuhisa
Published: August 2021

In the liver, the sterol response element binding protein (SREBP) and the SREBP cleavage-activated protein (SCAP) complex upregulate cholesterol biosynthesis by gene induction of de novo cholesterol synthetic enzymes (Hmgcr, Cyp51, and Dhcr7). Insulin induced gene 1 (INSIG1) negatively regulates cholesterol biosynthesis by the inhibition of de novo cholesterol biosynthetic gene expression. In the ovary, cholesterol is de novo synthesized; however, the roles of SREBP and its regulators (SCAP and INSIG1) are not well understood. In this study, when immature mice were treated with gonadotropins (eCG followed by hCG), eCG induced and hCG maintained the expression of SREBP-1a, -2, and SCAP granulosa cells, whereas INSIG1 expression was dramatically downregulated after hCG injection. Downregulation of INSIG1 led to generate the SREBPs active form and translocate the SREBPs active form to nuclei. Inhibition of generation of the SREBPs active form by fatostatin or Scap siRNA in both in vivo and in vitro significantly decreased the expressions of de novo cholesterol biosynthetic enzymes, cholesterol accumulation, and progesterone (P4) production compared with the control group. Fatostatin treatment inhibited the ovulation and increased the formation of abnormal corpus luteum which trapped the matured oocyte in the corpus luteum; however, the phenomenon was abolished by P4 administration. The results showed that decreasing INSIG1 level after hCG stimulation activated SREBP-induced de novo cholesterol biosynthesis in granulosa cells of preovulatory follicles, which is essential for P4 production and the rupture of matured oocyte during ovulation process.
On the “Spiritual” in Aesthetic Experience; or, The “Nonfactual in Facticity”
Authors: de Vries Hent
Published: August 2021

This article revisits the original meaning of “spiritual” as distinct from “intellectual” experience in Theodor W. Adorno’s late work. It does so through the implicitly Hegelian motifs in Wassily Kandinsky’s manifesto “On the Spiritual in Art,” a text that Adorno engages in passing in his Aesthetic Theory and that was, in turn, deeply influenced by the thought of Kandinsky’s nephew Alexandre Kojève, who also wrote an essay on his uncle’s paintings. This genealogy of motifs is of more than mere historical and anecdotal significance. At stake is nothing less than an accurate understanding of “spiritual experience [geistige Erfahrung]” as a more than merely theoretical matrix for what Adorno, in Negative Dialectics and the lecture courses, calls his materials studies. Rather than indicating largely esoteric or theosophical elements in Kandinsky’s influence on modernist aesthetic discourse, “spiritual experience,” in part read through the eyes of Kojève and, via him, Vladimir Soloviev, is thereby distinguished from what Adorno sees as an irrepressible tendency toward “spiritualization” in contemporary culture and the philosophy that reflects on it. Instead, it reveals a dimension of depth that the reception of Critical Theory has all too often ignored or disparaged.
Transforming growth factor β3 deficiency promotes defective lipid metabolism and fibrosis in murine kidney
Authors: Escasany Elia , Lanzón Borja , García-Carrasco Almudena , Izquierdo-Lahuerta Adriana , Torres Lucía , Corrales Patricia , Rodríguez Rodríguez Ana Elena , Luis-Lima Sergio , Martínez Álvarez Concepción , Javier Ruperez Francisco , Ros Manuel , Porrini Esteban , Rydén Mikael , Medina-Gómez Gema
Published: August 2021

Glomerulosclerosis and tubulointerstitial fibrosis are pathological features of chronic kidney disease. Transforming growth factor β (TGFβ) is a key player in the development of fibrosis. However, of the three known TGFβ isoforms, only TGFβ1 has an established role in fibrosis, and the pathophysiological relevance of TGFβ2 and TGFβ3 is unknown. Because Tgfb3 deficiency in mice results in early postnatal lethality, we analyzed the kidney phenotype of heterozygous Tgfb3-knockout mice (Tgfb3+/−) and compared it with that of matched wild-type mice. Four-month-old Tgfb3+/− mice exhibited incipient renal fibrosis with epithelial–mesenchymal transition, in addition to glomerular basement membrane thickening and podocyte foot process effacement associated with albuminuria. Also evident was insulin resistance and oxidative stress at the renal level, together with aberrant renal lipid metabolism and mitochondrial function. Omics analysis revealed toxic species, such as diacylglycerides and ceramides, and dysregulated mitochondrial metabolism in Tgfb3+/− mice. Kidneys of Tgfb3+/− mice showed morphological alterations of mitochondria and overactivation of non-canonical MAPK ERK1/2 and JNK cascades. Our study indicates that renal TGFβ3 might have antifibrotic and renoprotective properties, opposing or counteracting the activity of TGFβ1.

This article has an associated First Person interview with the first author of the paper.