bluuebunny/crossref_metadata_2025 huggingface dataset:
Recommendations for Improving Oral Pre-exposure Prophylaxis Implementation and Social Marketing in Ugandan Fisherfolk Communities: A Qualitative Exploration
Authors: Bogart Laura M , Musoke William , Mayatsa Jimmy , Marsh Terry , Naigino Rose , Banegura Anchilla , Mukama Christopher Semei , Allupo Stella , Odiit Mary , Kadama Herbert , Mukasa Barbara , Wanyenze Rhoda K
Published: October 2022

Background: HIV is hyperendemic among fisherfolk in Sub-Saharan Africa, especially around Lake Victoria, Uganda. Purpose/Research Design: We conducted cross-sectional semi-structured interviews about oral pre-exposure prophylaxis (PrEP) implementation with 35 Ugandan fisherfolk (15 women, 20 men) and 10 key stakeholders (healthcare providers, policymakers, community leaders). We used a directed content analysis approach based on implementation science and social marketing frameworks. Results: Participants showed high acceptability for PrEP. Anticipated barriers among fisherfolk included stigma (due to similar medications/packaging as HIV treatment); misconceptions; mobility, competing needs, poverty, and partner conflict. Anticipated provider barriers included insufficient staffing and travel support. Recommendations included: change PrEP packaging; integrate PrEP with other services; decrease PrEP refill frequency; give transportation resources to providers; train more healthcare workers to provide PrEP to fisherfolk; and use positively framed messages to promote PrEP. Conclusions: Results can inform policymakers and healthcare organizations on how to overcome barriers to PrEP scale-up in most at-risk populations with poor healthcare access.
The Case for Offering Paid Leave: Benefits to the Employer, Employee, and Society
Authors: Davison H. Kristl , Blackburn Adam Scott
Published: October 2022

The COVID-19 pandemic has highlighted numerous problems in the labor market in the U.S., including high and low unemployment rates, burnout of employees in many industries, and inadequate time off for caregiving and medical issues. In this manuscript, we propose that employer-sponsored paid leave is increasingly important given that the U.S. lags behind most other nations in its leave policies, and many employees, particularly those in lower-wage, part-time, or front-line occupations do not have paid leave from their employers. We first discuss the common types of paid leave. Then, we make the case that paid leave is advantageous for both employees and employers, as well as society. We conclude with specific recommendations on how to implement paid leave in organizations.
Human Resources Analytics: Leveraging Human Resources for Enhancing Business Performance
Authors: Madhani Pankaj M.
Published: October 2022

Human resources (HR) analytics enables managers to replace decision-making based on anecdotal experience, hierarchy, and risk avoidance with higher-quality data-driven decisions based on data analysis, prediction, and experimental research. Human Resources analytics underscores the value of HR data by emphasizing how people create value for the organization, so that value can be captured and leveraged. The research discusses transition of HR analytics with a linear three-stage maturity model and explains progression from traditional HR analytics to new age HR analytics. Research provides various key requirements for successful deployment of HR analytics in the organizations. Human Resources analytics focus on various HRM activities including selection, appraisal, compensation, rewards, and development to maximize their impact on organizational performance. Research also provides various illustrations of HR analytics deployment across various industries.
Wage Theft and the Struggle over the Working Day in Hospitality Work: A Typology of Unpaid Labour Time
Authors: Cole Matthew , Stuart Mark , Hardy Kate , Spencer David
Published: October 2022

Drawing on Marxist political economy, this article examines wage theft in hospitality work. Through a detailed, qualitative study of workers’ experiences in London hotels, a novel typology is developed that reveals how managers extract additional unpaid labour time through wage theft. The article argues that both the legal definition and existing academic formulations of wage theft fail to encompass the full range of ways that employers extract unpaid labour time. They also overlook the systemic dimension of unpaid labour time under capitalism. The article contributes new insights into the sociological dimensions of exploitation by proposing an alternative conceptualisation of wage theft that incorporates both formal violations of the law and the more subtle, informal means by which the theft of wages is secured.
Measuring Efficiency Performance in Primary Public Health Clinics, Sarawak, Malaysia
Authors: Ting Siew King , Suhaimi Rosita , Yong Sze Wei , Dollery Brian
Published: October 2022

The health care system in Malaysia has undergone various reforms in order to improve its performance. In Malaysia, secondary and tertiary care services are provided by hospitals, while primary care services are supplied by health clinics. Health clinics are constrained with limited resources in providing health services to the public. The optimum utilization of resources in health clinics is thus critical and warrants empirical investigation. Using data envelopment analysis (DEA) by employing three inputs and three outputs of 32 decision-making units (DMUs), this study aims to measure the technical efficiency and scale efficiency of health clinics in Samarahan District, Sarawak. Data was drawn from 16 public health clinics in the district over 2 years from 2015 to 2016. Our results show that only 34.37% of health clinics are operating at the efficient scale of production within the most productive scale size (MPSS), while the remaining 65.63% of health clinics either experience increasing returns to scale (37.50%) or diminishing returns to scale (28.13%). 68.75% of health clinics are technically efficient while only 31.25% are technically inefficient. The article advances several public policy recommendations for improving the performance of the health clinics.
The Effect of Financial Development on Unemployment in Emerging Market Countries
Authors: Raifu Isiaka Akande , Afolabi Joshua Adeyemi
Published: October 2022

This study examined the effect of financial development on unemployment in 19 emerging market countries, considering their age groups and gender dichotomy. The data covers the period from 1991–2019. Pooled Ordinary Least Square (OLS), Dynamic OLS, and quantile regression via moments were employed as the estimation methods. Robustness was tested with Fully Modified OLS and Canonical Cointegration Regression (CCR) estimation methods. Our results show that financial development has a conditional mean reducing effect on unemployment and a reducing effect on the distribution of unemployment. However, the reducing effect of financial development on the distribution of unemployment varies across the working-age population and youths. Thus, there is a need to formulate and implement a long-term financial policy to ensure economic growth and guarantee employment for the working-age population and the youths irrespective of gender.
Adam Smith on Education as a Means to Political Judgment
Authors: Frame Edward , Schwarze Michelle
Published: October 2022

Even the most zealous interpreters of Adam Smith as an advocate of free markets and commercial progress have long acknowledged his support for public education. Yet the comparatively little scholarship on Smith’s educational theory never fully articulates his defense of public education, often framing it as a corrective to economic and moral problems generated by the market while ignoring its political importance. We argue here that Smith saw public education as much more than anesthesia to treat the wounds inflicted by the market. For Smith, compulsory public education not only promotes distributive justice, develops moral judgment, and cultivates good citizenship—it is vital for securing all three. A compulsory education affords citizens the opportunity to sympathize with others and be objects of sympathy while teaching them how to be skeptical of the rhetorical efforts of others. As such, this paper argues that Smith’s major works offer a potent defense of public education as a precondition for political judgment rather than a mere program “needed to offset the social costs of the division of labor.”
A combined review of vibration control strategies for high-speed trains and railway infrastructures: Challenges and solutions
Authors: Zhang Chunwei , Kordestani Hadi , Shadabfar Mahdi
Published: October 2022

People use trains as a means of transportation to travel to various nearby and distant destinations, resulting in an increasing amount of time spent inside such vehicles. Consequently, railway transportation sectors are focusing significantly more on enhancing passengers’ demand and level of satisfaction, including but not limited to high-speed travel, safety, and riding comfort. This paper provides a state-of-the-art review of available solutions for reducing undesired vibrations that have a substantial impact on improving the critical velocity limits of trains, maintaining the quality of riding comfort, and resolving safety concerns. In this regard, the solutions proposed for train vibration control are divided into two main categories: direct and indirect solutions. The direct solutions are those methods that are applied directly to trains’ bodies or bogies to attenuate the undesired vibrations, for example, improving the suspension/damper system, implementing active/semi-active control strategies, or applying various carriage optimization design modifications. Indirect solutions, on the other hand, are those that could indirectly affect trains’ vibrations, for example, controlling vibrations in railway bridge structures during train passages. Since the identification of vibration characteristics is assumed to be the first step in choosing proper solutions, particularly for active or semi-active control implementations, this review has examined the literature pertinent to modal identification of trains and railway infrastructures. Additionally, despite the installation of dampers between the bogie and suspension, the train’s equation of motion, and consequently, the vibration control of the bogie, has relied on the sky-hook model for decades. The fundamental problem for systems whose control strategies are based on the sky-hook concept is that the ‘sky’ does not actually exist. A solution to solve the sky-hook logic issue is using tuned rotatory inertia dampers and active rotatory inertia drivers which is addressed in this paper as well. Finally, it is concluded that these three solutions – employing a suspension/damper system in the bogie, an elastic connection for the train’s under-chassis-suspended equipment, and a ballastless railway – can practically mitigate vibration and noise in a train.
Association between the IL-6 polymorphisms and coal workers’ pneumoconiosis in a Chinese Hui population
Authors: Xu Xiangzhao , Yin Jun , Zhang Junlong , Xu Shulan , Yang Yaowen , Hai Xiaoyu , Yu Yongsheng , Lu Ruirui , Liu Mingzhou
Published: October 2022

Objective

To determine whether polymorphisms in IL-6 and IL-12 contribute to the etiology of coal workers’ pneumoconiosis (CWP) in a Chinese Hui population, and to evaluate the efficacy and safety of high frequency oscillatory ventilation (HFOV) in the treatment of CWP.

Introduction

Genes and the environments interplay in the development of CWP, and the association between the potential functional polymorphisms in many genes and CWP have been reported.

Methods

We genotyped the IL-6-634C/G (rs1800796) and IL-12B-1188A/C (rs3212227) polymorphisms in a case-control study including 160 CWP patients and 150 dust-exposed control subjects of Chinese Hui population, and analyzed the associations between these genetic variants and CWP risk. We also evaluated the efficacy and safety of HFOV for whole lung lavage (WLL) in the treatment of CWP.

Results

Carrying the C allele of IL-6-634C/G (rs1800796) was associated with decreased risk of CWP ( p < 0.05). No significant differences in allele or genotype frequencies of IL-12B-1188A/C was found between the CWP cases and control subjects ( p > 0.05). Compared with CWP patients with routine WLL, CWP patients received HFOV showed better pulmonary functions. HFOV treatment also yield a significant higher efficient rate (97.50%) than WLL treatment (81.25%, p = 0.001). CWP patients receiving HFOV and WLL treatment both showed significantly increased serum contents of Clara cell protein 16 (CC16) and superoxide dismutase (SOD), and decreased serum contents of serum malonaldehyde (MDA). While the increasing of CC16 and SOD, and decreasing of MDA in patients receiving HFOV was more noticeable than patients receiving WLL.

Conclusions

Taking together, the −634C/G polymorphisms in IL-6 play a role in the etiology of CWP. HFOV, when applied in CWP patients, significant improves their pulmonary functions.
Does affirming Black and Latino people as American weaken racial solidarity? A surprising “no” from two pre-registered experiments
Authors: Pérez Efrén O. , Ramos Alisson , Vicuña Bianca V.
Published: October 2022

Drawing on social identity theory, we predicted that affirming Black and Latino individuals as American would undermine solidarity between people of color (PoC), who are broadly stereotyped by society as un-American. We tested this prediction in two pre-registered experiments with Black and Latino adults ( N = 1,880), where participants read about another minoritized group’s contribution to U.S. culture (i.e., Latino people: reggaetón and hip hop; Black people: jazz and hip hop). Reading about Latinos’ musical contributions to U.S. culture insignificantly reduced Black solidarity with PoC, although an increase in Black solidarity with PoC unexpectedly boosted support for pro-Latino policies. In turn, reading about Black contributions to U.S. culture surprisingly increased Latino solidarity with PoC, which then substantially heightened pro-Black policy support. This unanticipated mediation effect is statistically robust and substantively meaningful. We explain how these contradictory results help advance research on the conditions that catalyze solidarity between PoC.
Technology Adoption and Human Resource Management Practices: The Use of Artificial Intelligence for Recruitment in Bangladesh
Authors: Islam Muhaiminul , Mamun Abdullah Al , Afrin Samina , Ali Quaosar G. M. Azmal , Uddin Md. Aftab
Published: October 2022

Artificial intelligence (AI) is now considered indispensable in undertaking operational activities, especially in the area of human resource analytics. However, in practice, the rate of the adoption of such modern algorithms in organisations is still in its early stages. Consequently, the primary objective of this study is to identify the main antecedents of the adoption of AI-based technologies in recruitment, using the lens of the unified theory of acceptance and use of technology (UTAUT) model, alongside perceived credibility and moderating variables, in the context of an emerging nation in South Asia, namely Bangladesh. Data were collected from 283 human resource professionals employed in different manufacturing and service firms in Bangladesh through the administration of a questionnaire, which was analysed by applying PLS-SEM. The outcomes of the study show that all the direct hypothesised relationships were found to be significant, apart from the extended variable of perceived credibility. However, no moderating effect of gender or firm size was found in any of the hypothesised propositions. Finally, policy implications and recommendations for future researchers are proposed.
Tricuspid Atresia with Double Outlet Right Ventricle and L Malposed Great Arteries
Authors: Singhi Anil Kumar , Mohapatra Soumya Kanti , Bari Ejaz Ahmad
Published: October 2022

Double outlet right ventricle is a very rare association in a patient with tricuspid atresia. The anomaly has been documented in a young boy with illustrative echocardiogram, angiographic images and cardiac computed tomographic imaging. The images describing the rare anomaly would be good to understand the importance of segmental analysis in a complex heart disease.
Proteomic alterations associated with residual disease in neoadjuvant chemotherapy treated ovarian cancer tissues
Authors: Penick Emily R. , Bateman Nicholas W. , Rojas Christine , Magana Cuauhtemoc , Conrads Kelly , Zhou Ming , Hood Brian L. , Wang Guisong , Parikh Niyati , Huang Ying , Darcy Kathleen M. , Casablanca Yovanni , Mhawech-Fauceglia Paulette , Conrads Thomas P. , Maxwell G. Larry
Published: October 2022

Background

Optimal cytoreduction to no residual disease (R0) correlates with improved disease outcome for high-grade serous ovarian cancer (HGSOC) patients. Treatment of HGSOC patients with neoadjuvant chemotherapy, however, may select for tumor cells harboring alterations in hallmark cancer pathways including metastatic potential. This study assessed this hypothesis by performing proteomic analysis of matched, chemotherapy naïve and neoadjuvant chemotherapy (NACT)-treated HGSOC tumors obtained from patients who had suboptimal (R1, n = 6) versus optimal (R0, n = 14) debulking at interval debulking surgery (IDS).

Methods

Tumor epithelium was harvested by laser microdissection from formalin-fixed, paraffin-embedded tissues from matched, pre- and post-NACT treated tumors for twenty HGSOC patients and analyzed by quantitative mass spectrometry-based proteomics.

Results

Differential analysis of patient matched pre- and post-NACT treated tumors revealed proteins associated with cell survival and metabolic signaling to be significantly altered in post-NACT treated tumor cells. Comparison of pre-NACT treated tumors from suboptimal (R1) versus optimally (R0) debulked patients identified proteins associated with tumor cell viability and invasion signaling enriched in R1 patients. We identified five proteins altered between R1 and R0 patients in pre- NACT treated tumors that significantly correlated with PFS in an independent cohort of HGSOC patients, including Fermitin family homolog 2 (FERMT2), a protein elevated in R1 that correlated with disease progression in HGSOC patients (multivariate Cox HR = 1.65, Wald p = 0.022) and increased metastatic potential in solid-tumor malignancies.

Conclusions

This study identified distinct proteome profiles in patient matched pre- and post-NACT HGSOC tumors that correlate with NACT resistance and that may predict residual disease status at IDS that collectively warrant further pre-clinical investigation.
A novel semiautomatic Chinese keywords instrument screening delirium based on electronic medical records
Authors: Chen Ling , Li Nan , Zheng Yuxia , Gao Langli , Ge Ning , Xie Dongmei , Yue Jirong
Published: October 2022

Background

Delirium is frequently unrecognized due to the absence of regular screening. In addition to validated bedside tools, the computer-assisted instrument based on clinical notes from electronic medical records may be useful.

Aims

To assess the psychometric properties of a Chinese-chart-based keyword instrument for semiautomatically screening delirium using Natural language processing (NLP) based on clinical notes from electronic medical records.

Methods

The patients were admitted to West China Hospital from January 2015 to December 2017. Grouping patients based on the medical notes, those with accessible physician documents but no nurse documents were classified as the physician & no-nurse (PNN) group, while those with accessible physician and nurse documents were classified as the physician & nurse (PN) group. The psychometric properties, test–retest reliability, internal consistency reliability (Cronbach's α), and criterion validity were calculated. Using receiver operating characteristic (ROC) analysis, the criterion validity of delirium was evaluated in comparison to the results of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

Results

A total of 779 patients were enrolled in the study. Their ages ranged from 65 to 103 years (82.5 ± 6.5), with men accounting for 71.9% of the total. A total of 312 patients had access to only physician documents in the physician & no-nurse (PNN) group, whereas 467 patients had access to both physician and nurse documents in the physician & nurse (PN) group. All 779 patients had a Cronbach's alpha of 0.728 in terms of reliability, with 100% test–retest reliability. The area under the ROC curve (AUC) values of the delirium screening instrument for criterion validity were 0.76 (all patients, n = 779), 0.72 (PNN, n = 312), and 0.79 (PN, n = 467), respectively.

Conclusion

A delirium screening instrument composed of Chinese keywords that can be easily and quickly obtained from electronic medical records was developed, which improved delirium detection in older people.

Trial registration

Not applicable.
Early essential newborn care in national tertiary hospitals in Cambodia and Lao People’s Democratic Republic: a cross-sectional study
Authors: Kitamura Tomomi , Obara Hiromi , Honda Mari , Mori Tomoko , Ito Tomoo , Nagai Mari , Rattana Sommana , Rathavy Tung , Sugiura Yasuo
Published: October 2022

Background

Ministries of health in collaboration with the World Health Organization Regional Office for the Western Pacific (WPRO) have been scaling up early essential newborn care (EENC). This study was carried out to understand current EENC practices at hospitals in two priority countries: the Kingdom of Cambodia (Cambodia) and Lao People’s Democratic Republic (Lao PDR).

Methods

EENC is subdivided into 79 checkpoints, referencing the self-monitoring checklist developed by the WPRO. Each checkpoint is rated using a 0 to 2-point scale, and a percentage was calculated for the rate of practice of each checkpoint by dividing the total scores by the maximum possible scores.

Results

In total, 55 and 56 deliveries were observed in Cambodia and Lao PDR, respectively, and 35 and 34 normal deliveries were included in the analysis. The overall rates of the practices within the first 15 minutes after birth were high in both countries. The rates of the practices before birth and 15 minutes after birth were lower than the rates of the practices performed within the first 15 minutes after birth, especially “hand wash before preparation”, “preparation for newborn resuscitation”, and “monitoring of postpartum mothers and babies”. A detailed analysis revealed that the quality of the practices differed between the two countries regarding skin-to-skin contact and breastfeeding support.

Conclusions

The high rates of the practices within the first 15 minutes after birth suggest that the EENC coaching sessions supported by ministries of health and the WPRO have been effective. Differences in the quality of practices performed at a high rate between the two countries appeared to be related to factors such as the timing of the study, the perception of the staff, and the situation at the health facilities. These differences and identified practices with lower rates should be improved according to the situation in each country or health facility. Therefore, determining the quality of the practices in a country or a health facility is important. To further improve the quality of EENC, interventions tailored to the specific situation are necessary.
Interaction of miR-200a-3p with YAP regulates cell proliferation and metastasis differentially in HPV-positive and HPV-negative cervical cancer cells
Authors: Chen Hong , Gu Lingling , Zhang Min , Chen Huifen , Liao Hong , Cao Xueping , Yu Lu , Zhang Jun
Published: October 2022

Background

Although evidence has revealed that miR-200a-3p is involved in the malignant progression of various tumors, the regulatory mechanism of miR-200a-3p in the development of cervical cancer (CC) cells with different HPV statuses remains unknown. The present study was to investigate the differential effects of either miR-200a-3p or YAP on tumorous cells’ fate in vitro in HPV-negative and HPV-positive cervical cancer cell models, and to explore if the changes in proliferation, migration, and invasion of the CC cells with different HPV statuses could be attributed to the differential interactions between miR-200a-3p and YAP.

Methods

The colony formation assays, EDU assays and Transwell assays were performed for CC cell proliferation, migration and invasion capacities analysis. The prediction of downstream targets of miR-200a-3p was performed by bioinformatical databases. The dual-luciferase reporter assays were used to validate the binding sites of miR-200a-3p and YAP. The qRT-PCR assays were performed to quantify the mRNA expression of miR-200a-3p and YAP, and the protein levels of YAP were examined by Western blot analysis.

Results

The results demonstrated that miR-200a-3p overexpression suppressed proliferation, migration, and invasion of the HPV-negative C33A cells but promoted the growth and metastasis of HPV-positive CC cells, while YAP promoted the cell growth and metastasis not only in HPV-negative but also in the HPV-positive CC cells. The suppressive role of miR-200a-3p in C33A cells appeared to be mediated partially by direct interaction with YAP, and YAP might participate in miR-200a-3p-mediated cellular changes in CC cells differing from not only the presence or absence of HPV but even also the subtypes of HPV of CC cells. Meanwhile, we preliminarily revealed that the expression level of miR-200a-3p was significantly decreased in HPV-negative, but not in HPV16-positive cervical neoplasm mucus samples.

Conclusion

miR-200a-3p-mediated functional changes of YAP exhibited regulatory effects on cells’ fate differentially in HPV-negative and HPV-positive cervical cancer cells.
Designing physical activity interventions for women aged 50+: a qualitative study of participant perspectives
Authors: Wallbank Geraldine , Haynes Abby , Tiedemann Anne , Sherrington Catherine , Grunseit Anne C.
Published: October 2022

Background

TheActive Women over 50trial tested a scalable program for increasing physical activity among women aged 50+. The program included information, activity tracker and email support. This study sought to describe the participant perspectives of theActive Women over 50program and considerations for designing physical activity interventions for this demographic.

Methods

Women who completed theActive Women over 50trial were purposively recruited for maximum variation in age, employment, carer responsibility, medical conditions and physical activity. Individual semi-structured interviews explored their perspectives on physical activity,Active Women over 50program components and suggestions for future iterations. Data were thematically analysed.

Results

Participants’ capacity to be physically active was shaped by an interplay of factors. Our analysis generated four main themes relating to physical activity in general and to the program: Age and gender matters, Physical activity is social, Strategising for physical activity and the Self-responsibility discourse. At this midlife stage, physical activity participation was challenged by personal, life-stage and cultural factors, alongside a tension of the self-responsibility discourse which also impacted the program experience. Social factors and finding a suitable strategy for motivation were deemed integral aspects of being active. Future programs could consider facilitation of social networks and accountability, life-stage health information and positive framing to support self-responsibility.

Conclusion

A range of strategies is key to supporting women over 50 to be more physically active due to the variety of circumstances and levels of agency experienced. We offer suggestions that do not need to be resource intensive but could be incorporated into a scaled program.
Qualitative study of barriers and facilitators encountered by individuals with physical diseases in returning and continuing to work
Authors: Inoue Shunsuke , Tateishi Seiichiro , Harada Arisa , Oginosawa Yasushi , Abe Haruhiko , Saeki Satoru , Tsukada Junichi , Mori Koji
Published: October 2022

Background

The number of employees with physical diseases is increasing, and there is a need for support to help them return and continue to work. To provide effective support, it is important to identify barriers and facilitators for individuals in returning and continuing to work. Previous studies have reported barriers and facilitators for specific diseases. However, few reports have dealt with these issues across various diseases. To identify a range of barriers and facilitators that may apply to different physical diseases, we conducted a qualitative analysis by interviewing patients with diverse characteristics being treated for diseases.

Methods

We conducted semi-structured interviews based on the criteria for qualitative research. We investigated three disease groups to obtain details of barriers and facilitators: impairments that were visible to other people (mainly stroke); impairments invisible to others (mainly heart disease); and impairments that changed over time (mainly cancer). Interview transcripts were analyzed and the results reported using systematic text condensation.

Results

We extracted 769 meaning units from 28 patient interviews. We categorized barriers and facilitators that were generalizable to various diseases into three themes (personal factors, workplace factors, and inter-sectoral collaboration and social resources) and 10 sub-themes (work ability, psychological impacts, health literacy, social status, family background, workplace structure, workplace system, workplace support, inter-sectoral collaboration, and social resources).

Conclusions

This study identified 10 sub-themes that can be applied for workers with physical diseases; those sub-themes may be used as a basis for communicating with those individuals about returning and continuing to work. Our results suggest that various barriers and facilitators for workers with physical diseases should be understood and addressed at medical institutions, workplaces, and support sites.
Silver-Silica nanoparticles induced dose-dependent modulation of histopathological, immunohistochemical, ultrastructural, proinflammatory, and immune status of broiler chickens
Authors: Khafaga Asmaa F. , Fouda Moustafa M. G. , Alwan Ali B. , Abdelsalam Nader R. , Taha Ayman E. , Atta Mustafa S. , Dosoky Waleed M.
Published: October 2022

Silver nanoparticles (AgNPs) are a powerful disinfectant, but little information is available on their potential use as a growth promoter and the safety margin of this. In this study, 480 1-day-old Cobb chicks were assigned to one control and three treated groups. The treated groups were supplemented with silver-doped silica nanoparticles (SiO2@AgNPs) at three dietary levels (8, 16, and 20 mg/kg diet) for 35 days. The results revealed no significant changes in the growth performance and oxidative parameters, and in most of the hematological and biochemical parameters among the control and treated groups. In contrast, dose-dependent adverse effects were exerted on the histopathological structure and immunohistochemical expression of CD45 in liver, kidneys, and lymphoid organs (spleen, bursa, and thymus). In addition, the relative weight of lymphoid organs and the serum levels of immunoglobulins M and G were significantly diminished. Moreover, the gene expression of proinflammatory cytokines (IL-β1 and TNF-α) and the ultrastructural morphology in breast muscle showed significant dose-dependent alterations. It could be concluded that the dietary supplementation of SiO2@AgNPs at a level of 8 mg/kg diet or more has dose-dependent proinflammatory and immunosuppressive effects on broiler chickens.
Novel prokaryotic system employing previously unknown nucleic acids-based receptors
Authors: Tetz Victor , Tetz George
Published: October 2022

The present study describes a previously unknown universal system that orchestrates the interaction of bacteria with the environment, named the Teazeled receptor system (TR-system). The identical system was recently discovered within eukaryotes. The system includes DNA- and RNA-based molecules named “TezRs”, that form receptor’s network located outside the membrane, as well as reverse transcriptases and integrases. TR-system takes part in the control of all major aspects of bacterial behavior, such as intra cellular communication, growth, biofilm formation and dispersal, utilization of nutrients including xenobiotics, virulence, chemo- and magnetoreception, response to external factors (e.g., temperature, UV, light and gas content), mutation events, phage-host interaction, and DNA recombination activity. Additionally, it supervises the function of other receptor-mediated signaling pathways. Importantly, the TR-system is responsible for the formation and maintenance of cell memory to preceding cellular events, as well the ability to “forget” preceding events. Transcriptome and biochemical analysis revealed that the loss of different TezRs instigates significant alterations in gene expression and proteins synthesis.
Quality of life in patients with non-small cell lung cancer treated with PD-1/PD-L1 inhibitors: a systematic review and meta-analysis
Authors: Liu Wei , Zhang Qian , Zhang Tiantian , Li Li , Xu Chunhua
Published: October 2022

Background

Immune checkpoint inhibitors (ICIs) have dramatically prolonged survival in non-small cell lung cancer (NSCLC) patients, but little research had focused on its impact on quality of life (QoL). The purpose of our study was to compare the QoL in patients with NSCLC treated with programmed cell death protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors versus chemotherapy.

Methods

We searched for randomized controlled trials utilizing the Quality of Life Questionnaire Core 30 items (QLQ-C30) and the EuroQol Five Dimensions Questionnaire-3L (EQ-5D-3L) to assess the QoL of NSCLC treated with PD-1/PD-L1 inhibitors versus chemotherapy. We collected hazard ratios (HRs) for the time from baseline to the first clinically significant deterioration (TTD) and effect size as the difference in mean change between and within treatment groups in patients’ reported outcomes (PROs). (PROSPERO registration number: CRD42022296680).

Results

In the five trials reported by QLQ-C30, TTD was longer in PD-1/PD-L1 inhibitors compared with control groups (HR = 0.86; 95% CI = 0.76, 0.97; P = 0.013), with similar results in terms of physical function, role function, and pain. The difference in mean change between the PD-1/PD-L1 inhibitors group and the chemotherapy group in QLQ-C30 and EQ-5D VAS was 3.64 (95% CI = 1.62, 5.66; P = 0.001) and 4.74 (95% CI = 2.65, 6.83; P = 0.001), which supported PD-1/PD-L1 inhibitors. However, for the EQ-5D utility index, there was no statistically significant difference between the two groups, with a mean change difference of 0.03 (95% CI = −0.01, 0.07; P = 0.094). The mean change from baseline to follow-up in PD-1/PD-L1 inhibitors group was 2.57 (95% CI = 0.43, 4.71; P = 0.019), and chemotherapy group was −1.31 (95% CI = −3.71, 1.09; P = 0.284), correspondingly. The subgroup analysis showed that no difference was observed between open-label and double-blind trials in patients treated with chemotherapy or PD-1/PD-L1 inhibitors.

Conclusion

In conclusion, PD-1/PD-L1 inhibitors could improve the QoL of patients with NSCLC compared to chemotherapy and reduce unfavorable symptoms during treatment.
Omentin1 ameliorates myocardial ischemia-induced heart failure via SIRT3/FOXO3a-dependent mitochondrial dynamical homeostasis and mitophagy
Authors: Hu Jingui , Liu Tao , Fu Fei , Cui Zekun , Lai Qiong , Zhang Yuanyuan , Yu Boyang , Liu Fuming , Kou Junping , Li Fang
Published: October 2022

Background

Adipose tissue-derived adipokines are involved in various crosstalk between adipose tissue and other organs. Omentin1, a novel adipokine, exerts vital roles in the maintenance of body metabolism, insulin resistance and the like. However, the protective effect of omentin1 in myocardial ischemia (MI)-induced heart failure (HF) and its specific mechanism remains unclear and to be elucidated.

Methods

The model of MI-induced HF mice and oxygen glucose deprivation (OGD)-injured cardiomyocytes were performed. Mice with overexpression of omentin1 were constructed by a fat-specific adeno-associated virus (AAV) vector system.

Results

We demonstrated that circulating omentin1 level diminished in HF patients compared with healthy subjects. Furthermore, the fat-specific overexpression of omentin1 ameliorated cardiac function, cardiac hypertrophy, infarct size and cardiac pathological features, and also enhanced SIRT3/FOXO3a signaling in HF mice. Additionally, administration with AAV-omentin1 increased mitochondrial fusion and decreased mitochondrial fission in HF mice, as evidenced by up-regulated expression of Mfn2 and OPA1, and downregulation of p-Drp1(Ser616). Then, it also promoted PINK1/Parkin-dependent mitophagy. Simultaneously, treatment with recombinant omentin1 strengthened OGD-injured cardiomyocyte viability, restrained LDH release, and enhanced the mitochondrial accumulation of SIRT3 and nucleus transduction of FOXO3a. Besides, omentin1 also ameliorated unbalanced mitochondrial fusion-fission dynamics and activated mitophagy, thereby, improving the damaged mitochondria morphology and controlling mitochondrial quality in OGD-injured cardiomyocytes. Interestingly, SIRT3 played an important role in the improvement effects of omentin1 on mitochondrial function, unbalanced mitochondrial fusion-fission dynamics and mitophagy.

Conclusion

Omentin1 improves MI-induced HF and myocardial injury by maintaining mitochondrial dynamical homeostasis and activating mitophagy via upregulation of SIRT3/FOXO3a signaling. This study provides evidence for further application of omentin1 in cardiovascular diseases from the perspective of crosstalk between heart and adipose tissue.
Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patients
Authors: Zhang Ran , Liu Feng
Published: October 2022

Background

Cancer-associated fibroblasts (CAFs) play multiple roles in regulating tumor metastasis and treatment response. Current clinical indicators are insufficient to accurately assess disease risk and radiotherapy response, emphasizing the urgent need for additional molecular prognostic markers.

Methods

In order to investigate CAF-related genes associated with radiotherapy and construct prognostic CAF-related gene signatures for prostate cancer, we firstly established a radio-resistant prostate CAF cell subline (referred to as CAFR) from Mus-CAF (referred to as CAF) through fractionated irradiation using X-rays. Transcriptome sequencing for CAF and CAFR was conducted, and 2626 CAF-related differentially expressed genes (DEGs) associated with radiotherapy were identified. Human homologous genes of mouse CAF-related DEGs were then obtained.

Results

Functional enrichment analysis revealed that these CAF-related DEGs were significantly enriched ECM- and immune-related functions and pathways. Based on GSE116918 dataset, 186 CAF-related DEGs were correlated with biochemical recurrence-free survival (BCRFS) of prostate cancer patients, 16 of which were selected to construct a BCRFS-related CAF signature, such as ACPP, THBS2, and KCTD14; 142 CAF-related DEGs were correlated with metastasis-free survival (MFS), 16 of which were used to construct a MFS-related CAF signature, such as HOPX, TMEM132A, and ZNF467. Both Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets confirmed that the two CAF signatures accurately predicted BCRFS and MFS of prostate cancer patients. The risk scores were higher in patients with higher gleason grades and higher clinical T stages. Moreover, the BCRFS-related CAF signature was an independent prognostic factor and a nomogram consisting of BCRFS-related CAF signature and various clinical factors accurately predicted 2-, 3-, and 5-year survival time of prostate cancer patients. Furthermore, the risk score was positively correlated with multiple immune checkpoints.

Conclusions

Our established CAF signatures could accurately predict BCRFS and MFS in prostate cancer patients undergoing radiotherapy.
Artificial intelligence for quantifying immune infiltrates interacting with stroma in colorectal cancer
Authors: Yang Jing , Ye Huifen , Fan Xinjuan , Li Yajun , Wu Xiaomei , Zhao Minning , Hu Qingru , Ye Yunrui , Wu Lin , Li Zhenhui , Zhang Xueli , Liang Changhong , Wang Yingyi , Xu Yao , Li Qian , Yao Su , You Dingyun , Zhao Ke , Liu Zaiyi
Published: October 2022

Background

We proposed an artificial intelligence-based immune index, Deep-immune score, quantifying the infiltration of immune cells interacting with the tumor stroma in hematoxylin and eosin-stained whole-slide images of colorectal cancer.

Methods

A total of 1010 colorectal cancer patients from three centers were enrolled in this retrospective study, divided into a primary (N = 544) and a validation cohort (N = 466). We proposed the Deep-immune score, which reflected both tumor stroma proportion and the infiltration of immune cells in the stroma region. We further analyzed the correlation between the score and CD3+ T cells density in the stroma region using immunohistochemistry-stained whole-slide images. Survival analysis was performed using the Cox proportional hazard model, and the endpoint of the event was the overall survival.

Result

Patients were classified into 4-level score groups (score 1–4). A high Deep-immune score was associated with a high level of CD3+ T cells infiltration in the stroma region. In the primary cohort, survival analysis showed a significant difference in 5-year survival rates between score 4 and score 1 groups: 87.4% vs. 58.2% (Hazard ratio for score 4 vs. score 1 0.27, 95% confidence interval 0.15–0.48, P < 0.001). Similar trends were observed in the validation cohort (89.8% vs. 67.0%; 0.31, 0.15–0.62, < 0.001). Stratified analysis showed that the Deep-immune score could distinguish high-risk and low-risk patients in stage II colorectal cancer (P = 0.018).

Conclusion

The proposed Deep-immune score quantified by artificial intelligence can reflect the immune status of patients with colorectal cancer and is associate with favorable survival. This digital pathology-based finding might advocate change in risk stratification and consequent precision medicine.
CTRP1 prevents high fat diet-induced obesity and improves glucose homeostasis in obese and STZ-induced diabetic mice
Authors: Ren Mingzhi , Pan Jianfei , Yu Xueying , Chang Kaile , Yuan Xiaopeng , Zhang Chunbo
Published: October 2022

Background

C1q/tumor necrosis factor-related protein 1 (CTRP1) is an adipokine secreted by adipose tissue, related to chondrocyte proliferation, inflammation, and glucose homeostasis. However, the therapeutic effects on metabolic disorders and the underlying mechanism were unclear. Here, we investigated the functions and mechanisms of CTRP1 in treating obesity and diabetes.

Methods

The plasmid containing human CTRP1 was delivered to mice by hydrodynamic injection, which sustained expression of CTRP1 in the liver and high protein level in the blood. High-fat diet (HFD) fed mice and STZ-induced diabetes model were used to study the effects of CTRP1 on obesity, glucose homeostasis, insulin resistance, and hepatic lipid accumulation. The lipid accumulation in liver and adipose tissue, glucose tolerance, insulin sensitivity, food intake, and energy expenditure were detected by H&E staining, Oil-Red O staining, glucose tolerance test, insulin tolerance test, and metabolic cage, respectively. The metabolic-related genes and signal pathways were determined using qPCR and western blotting.

Results

With high blood circulation, CTRP1 prevented obesity, hyperglycemia, insulin resistance, and fatty liver in HFD-fed mice. CTRP1 also improved glucose metabolism and insulin resistance in obese and STZ-induced diabetic mice. The metabolic cage study revealed that CTRP1 reduced food intake and enhanced energy expenditure. The mechanistic study demonstrated that CTRP1 upregulated the protein level of leptin in blood, thermogenic gene expression in brown adipose tissue, and the gene expression responsible for lipolysis and glycolysis in white adipose tissue (WAT). CTRP1 also downregulated the expression of inflammatory genes in WAT. Overexpression of CTRP1 activated AMPK and PI3K/Akt signaling pathways and inhibited ERK signaling pathway.

Conclusion

These results demonstrate that CTRP1 could improve glucose homeostasis and prevent HFD-induced obesity and fatty liver through upregulating the energy expenditure and reducing food intake, suggesting CTRP1 may serve as a promising target for treating metabolic diseases.
Inhibition of Schwann cell pannexin 1 attenuates neuropathic pain through the suppression of inflammatory responses
Authors: Wang Qian , Li Han-yang , Ling Zhuo-min , Chen Gang , Wei Zhong-Ya
Published: October 2022

Background

Neuropathic pain is still a challenge for clinical treatment as a result of the comprehensive pathogenesis. Although emerging evidence demonstrates the pivotal role of glial cells in regulating neuropathic pain, the role of Schwann cells and their underlying mechanisms still need to be uncovered. Pannexin 1 (Panx 1), an important membrane channel for the release of ATP and inflammatory cytokines, as well as its activation in central glial cells, contributes to pain development. Here, we hypothesized that Schwann cell Panx 1 participates in the regulation of neuroinflammation and contributes to neuropathic pain.

Methods

A mouse model of chronic constriction injury (CCI) in CD1 adult mice or P0-Cre transgenic mice, and in vitro cultured Schwann cells were used. Intrasciatic injection with Panx 1 blockers or the desired virus was used to knock down the expression of Panx 1. Mechanical and thermal sensitivity was assessed using Von Frey and a hot plate assay. The expression of Panx 1 was measured using qPCR, western blotting, and immunofluorescence. The production of cytokines was monitored through qPCR and enzyme-linked immunosorbent assay (ELISA). Panx1 channel activity was detected by ethidium bromide (EB) uptake.

Results

CCI induced persistent neuroinflammatory responses and upregulation of Panx 1 in Schwann cells. Intrasciatic injection of Panx 1 blockers, carbenoxolone (CBX), probenecid, and Panx 1 mimetic peptide (10Panx) effectively reduced mechanical and heat hyperalgesia. Probenecid treatment of CCI-induced mice significantly reduced Panx 1 expression in Schwann cells, but not in dorsal root ganglion (DRG). In addition, Panx 1 knockdown in Schwann cells with Panx 1 shRNA-AAV in P0-Cre mice significantly reduced CCI-induced neuropathic pain. To determine whether Schwann cell Panx 1 participates in the regulation of neuroinflammation and contributes to neuropathic pain, we evaluated its effect in LPS-treated Schwann cells. We found that inhibition of Panx 1 via CBX and Panx 1-siRNA effectively attenuated the production of selective cytokines, as well as its mechanism of action being dependent on both Panx 1 channel activity and its expression.

Conclusion

In this study, we found that CCI-related neuroinflammation correlates with Panx 1 activation in Schwann cells, indicating that inhibition of Panx 1 channels in Schwann cells reduces neuropathic pain through the suppression of neuroinflammatory responses.