bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic accuracy of pleural fluid to serum carcinoembryonic antigen ratio and delta value for malignant pleural effusion: findings from two cohorts
Authors: Jiang Meng-Ping , Wen Jian-Xun , Hai Ling , Jiang Ting-Wang , Huang Jin-Hong , Chen Hong , Wang Ya-Fei , Zheng Wen-Qi , Hu Zhi-De , Yan Li
Published: March 2023

Background:

Pleural fluid (PF) carcinoembryonic antigen (CEA) is a widely used diagnostic marker for malignant pleural effusion (MPE). Recent studies revealed that PF to serum CEA was also a promising diagnostic parameter for MPE.

Objective:

We aimed to investigate whether PF to serum CEA ratio and delta CEA (PF minus serum CEA) provided added value to PF CEA in diagnosing MPE.

Methods:

Patients with pleural effusion in a retrospective cohort (BUFF) and a prospective cohort (SIMPLE) were included. The clinical characteristics of the patients were extracted from their medical records. The diagnostic value of CEA ratio and delta CEA was estimated by a receiver operating characteristics (ROC) curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Results:

A total of 148 patients in the BUFF cohort and 164 patients in the SIMPLE cohort were enrolled. The BUFF cohort had 46 MPE patients and 102 benign pleural effusion (BPE) patients, and the SIMPLE cohort had 85 MPE patients and 79 BPE patients. In both cohorts, MPE patients had significantly higher PF CEA, serum CEA, CEA ratio, and delta CEA. The area under ROC curves (AUCs) of PF CEA, CEA ratio, and delta CEA were 0.78 (95% CI: 0.67–0.88), 0.80 (95% CI: 0.72–0.89) and 0.83 (95% CI: 0.75–0.91) in the BUFF cohort, and 0.89 (95% CI: 0.83–0.94), 0.86 (95% CI: 0.80–0.92), and 0.84 (95% CI: 0.78–0.91) in the SIMPLE cohort. The differences between the AUCs of PF CEA, CEA ratio, and delta CEA did not reach statistical significance. The continuous NRI and IDI of CEA ratio and delta CEA were <0.

Conclusion:

CEA ratio and delta value cannot provide added diagnostic value to PF CEA. The simultaneous determination of serum and PF CEA should not be adopted in clinical practice.
Incompressible versus compressible large eddy simulation for the identification of premixed flame dynamics
Authors: Eder Alexander J , Silva Camilo F , Haeringer Matthias , Kuhlmann Johannes , Polifke Wolfgang
Published: March 2023

The present work compares the respective advantages and disadvantages of compressible and incompressible computational fluid dynamics (CFD) formulations when used for the estimation of the acoustic flame response. The flame transfer function of a turbulent premixed swirl-stabilized burner is determined by applying system identification (SI) to time series data extracted from large eddy simulation (LES). By analyzing the quality of the results, the present study shows that incompressible simulations exhibit several advantages over their compressible counterpart with equal prediction of the flame dynamics. On the one hand, the forcing signals can be designed in such a way that desired statistical properties can be enhanced, while maintaining optimal values in the amplitude. On the other hand, computational costs are reduced and the implementation is fundamentally simpler due to the absence of acoustic wave propagation and corresponding resonances in the flame response or even self-excited acoustic oscillations. Such an increase in efficiency makes the incompressible CFD/SI modeling approach very appealing for the study of a wide variety of systems that rely on premixed combustion. In conclusion, the present study reveals that both methodologies predict the same flame dynamics, which confirms that incompressible simulation can be used for thermoacoustic analyses of acoustically compact velocity-sensitive flames.
The Nature of Rehabilitation Programs to Improve Musculoskeletal, Biomechanical, Functional, and Patient-Reported Outcomes in Athletes With ACL Reconstruction: A Scoping Review
Authors: Poretti Kelly , Ghoddosi Navid , Martin Joel , Eddo Oladipo , Cortes Nelson , Clark Nicholas C.
Published: March 2023

Context:

After anterior cruciate ligament (ACL) reconstruction (ACLR), athletes commonly undergo prolonged rehabilitation (eg, 9-12 months), but few actually return to preinjury sports activities. The nature (composition, configuration) of an ACL rehabilitation program (ACL-RP) is an important factor in determining rehabilitation outcomes; however, details about the nature of ACL-RPs are reported inconsistently in research studies. To guide future research reporting to support clinical translation and implementation of ACL-RPs, it is necessary to describe the nature, reporting, and outcomes of ACL-RPs in the current literature.

Objective:

The purpose of this scoping review was to understand the nature and reporting of various ACL-RPs that address musculoskeletal, biomechanical, functional, or patient-reported outcome measures in adult and pediatric athletes with ACLR.

Data Sources:

Articles were selected from searches in 5 electronic databases (PubMed, EbscoHost [MEDLINE, SportDiscus, CINAHL Plus], PROQuest, Cochrane, and Embase).

Study Selection:

Studies were included if they evaluated a post-ACL-RP that implemented strength, balance, plyometric, change of direction running, and/or agility running and included self-reported physical function, quality of life, or pain outcomes.

Study Design:

Scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines.

Level of Evidence:

Level 4.

Data Extraction:

Data were extracted and synthesized to evaluate the reporting of acute program variables (APVs) and exercise descriptors (EDs); 17 studies were included in the final synthesis.

Results:

Studies reported between 0% and 67% of the APVs and EDs combined. Only 2 studies were considered to have adequate reporting of both APVs and EDs.

Conclusion:

Inadequate reporting of APVs and EDs in past studies restricts the translation and implementation of existing research-based ACL-RPs to present-day clinical contexts.
Does NPTEL enhance E-learning in India? A case study on status and deterrents
Authors: Bargavi R , Shanmugam Kavitha
Published: March 2023

The foundation of our educational system today is technology-based. Over time, technology has transformed how students learn and how teachers impart knowledge. Further, technology provides a platform for everyone to study and learn throughout their lives. Many platforms and options are available to expand one’s knowledge in a particular area of interest. National Technology Programme for Enhanced Learning (NPTEL) is one such venture. This teaching case will give detailed information about NTPEL, its initiatives and its progress. The case study also elucidates the challenges that are deterrents to the usage of NPTEL.
Pattern of anti-epileptic medications nonadherence and associated factors at ambulatory clinic of Jimma Medical Center, Southwestern Ethiopia: A prospective observational study
Authors: Bayane Yadeta Babu , Senbeta Birbirsa Sefera
Published: March 2023

Objective:

This study is designed to assess the pattern of nonadherence, and associated factors among ambulatory patients with epilepsy at Jimma Medical Center, Southwestern Ethiopia, from November 2020 to April 2021.

Methods:

A hospital-based prospective observational study was employed. A consecutive sampling method was used to recruit study participants. Nonadherence was assessed by the Hill–Bone compliance to the high blood pressure therapy scale. A threshold of 18 scores was used to classify adherence status. Epi-Data manager version 4.6 was used for data entry and all statistical analysis was performed by Statistical Package for Social Science 25.0. Multivariable logistic regression was performed to explore associated factors.

Results:

A survey included 334 patients with epilepsy. One hundred twenty-two (36.52%) of the study participants were found to be non-adherent. The factors associated with nonadherence were poor involvement of the patient in the therapeutic decision (adjusted odds ratio = 1.74; 95% confidence interval: 1.04–2.90; p = 0.034), per month income of lesser than1000 Ethiopian birr (adjusted odds ratio = 2.66; 95% confidence interval: 1.03–6.84; p = 0.042), recent seizure episodes (adjusted odds ratio = 1.97; 95% confidence interval: 1.20–3.23; p = 0.007), adverse drug reaction (AOR = 2.13; 95% confidence interval: 1.31–3.47; p = 0.002), and negative medication belief (adjusted odds ratio = 1.28; 95% confidence interval: 1.53–2.25; p = 0.043).

Conclusions:

In our setting, the magnitude of nonadherence was substantially high. Hence, providing regular health-related information about the disease and treatment, supplying free antiepileptic drugs, routine assessment of adverse drug reactions, and a multidisciplinary approach involving patients may improve adherence.
Magnitude of chronic osteomyelitis and its associated factors in children as diagnosed on X-ray visiting at Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia: A cross-sectional study
Authors: Mulualem Biruk , Belay Genetu , Bogale Eyob Ketema
Published: March 2023

Objectives:

To assess the magnitude of chronic osteomyelitis and its associated factors in children at Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar, Ethiopia, in 2022.

Methods:

A hospital-based cross-sectional study was done between April 15, 2022 and August 15, 2022, in children with an age of 18 years or below, who visited Felege Hiwot Comprehensive Specialized Hospital. A total sample size of 168 participants was involved in the study. The random sampling technique was applied to select the study participants. The data were collected from the patients, their charts, and X-ray requests. The data were cleaned, stored, checked for completeness, and entered into EpiData Version 3.1, which were then exported to SPSS Version 23 for analysis. Descriptive analysis was done, and bivariable and multivariable logistic regression were used for analysis.

Results:

The prevalence of chronic osteomyelitis was found to be 86.3%. The tibia and femur were the most commonly involved bones, and metaphyseal involvement was very common. The most common radiological findings were sequestrum (56%) and involucrum (53%). Of the total patients with radiological evidence of chronic osteomyelitis, 16.6% had complications, the most common of which was a pathologic fracture (12.4%). Being male (adjusted odds ratio = 6.162, 95% confidence interval: 1.12–34.147), being over 10 years old (adjusted odds ratio = 4.048, 95% confidence interval: 1.032–15.886), living in a rural area (adjusted odds ratio = 4.046, 95% confidence interval: 1.236–13.364), having a discharging sinus (adjusted odds ratio = 5.237, 95% confidence interval: 1.393–19.693), having a clinical complaint lasting more than 1 year (adjusted odds ratio = 5.189, 95% confidence interval: 1.247–21.588), and a preceding event of trauma (adjusted odds ratio = =10.363, 95% confidence interval: 1.101–97.509) were the factors associated with chronic osteomyelitis.

Conclusion:

The prevalence of chronic osteomyelitis is high. In this study, being male, being in the age group above 10 years, having rural residency, having a discharging sinus, having a clinical complaint duration of more than 1 year, and having a preceding event of trauma were the factors associated with chronic osteomyelitis. Therefore, healthcare providers should have a high index of suspicion of chronic osteomyelitis in older male children from rural areas with a chronic discharging sinus following trauma.
Atypical Vancouver B1 Periprosthetic Fractures: The Unsolved Problem
Authors: Vicenti Giovanni , Solarino Giuseppe , Ottaviani Guglielmo , Carrozzo Massimiliano , Simone Filippo , Zavattini Giacomo , Zaccari Domenico , Buono Claudio , Bizzoca Davide , Maccagnano Giuseppe , Moretti Biagio
Published: March 2023

Atypical femoral fractures (AFF) are stress or insufficiency fractures induced by low energy trauma or no trauma, frequently correlated with prolonged bisphosphonate therapy. The diagnosis follows major and minor criteria, originally described by the Task Force of the American Society for Bone and Mineral Research in 2010 and updated in 2014. However, the definition of AFFs in the report excluded periprosthetic fractures. When atypical fractures occur close to a prosthetic implant the situation become critical, the surgical treatment is often demolitive and supported by medical treatment. Moreover, acute ORIF as a first line treatment is frequently burdened by a high failure rate , and often a stem revision is required as second line treatment. The healing process is long and difficult with poor functional results and impairing outcomes. We present a case treated at our institution of a 78 year old woman with a history of a femoral atypical periprosthetic fracture, complicated by multiple surgical revisions. Its arduous management reflects all the difficulties that these type of fractures could present to the surgeon, while its good final result may teach us how to approach them in a correct way.
An Untold Saga of the Politics of Identity: The Struggle for Recognition of the Naths of Bengal
Authors: Debnath Kunal
Published: March 2023

The Naths of Bengal belong to the Yogi caste which can be seen from the perspective of ‘a struggle for recognition’. The Naths of Bengal have been asserting their identity and showing resistance against the Brahmanical caste order since the mid-nineteenth century through breaking the monopoly of the Brahmans over priestcraft, sacred thread, and the apex position of the caste hierarchy. All of these monopolies were challenged by the Naths and they contested their position in the system of hierarchy through the popular ‘origin myth’ of their caste. However, the question of the Naths is still unaddressed in the academic realm. Despite their social resistance against their ascribed status, the Naths are lagging in the arena of politics in post-colonial West Bengal since they are unenthusiastic to politicise themselves.
Liquidity Impact of Novel Market Surveillance Measures—An Evidence from India
Authors: Inamdar Mohd Merajuddin , Chari Latha
Published: March 2023

Stock price manipulation can be defined as trading behaviour that distorts stock prices with the intent of personal gains. Securities market regulators around the world undertake market surveillance to prevent market manipulation protect investors and ensure market integrity. The Securities Exchange Board of India along with stock exchanges has implemented a novel additional surveillance measure (ASM) which tracks stocks on a daily basis for abnormal price and volume activity accompanied by the participation of market-dominating investors in trading activity. Stocks that breach predefined limits of the above parameters are categorized as ASM category and subject to overall additional margins and selective additional margins for the dominating investor. There are mainly two types of ASM, Long term additional surveillance measures (LTASM) and short-term additional surveillance measures (STASM). STASM consider a shorter duration time (5/15 days) for share price observation LTASM considers a longer duration (1 month/1 year) for screening of the stock for surveillance measures as per ASM criteria. This study is based on STASM. The mechanism, on the one hand, is expected to deter manipulators and on the other, warn investors about suspicious activity in the stock, which is not supported by fundamentals. This article analyses the impact of surveillance actions on a price return and liquidity. The article also looks at the degree of speculative activity surrounding the event. This study used regression analysis for impact assessment. The study results show that the prices of the stock stabilize after inclusion and there is an overall fall in liquidity post-inclusion. However, the liquidity impact is different for stocks with positive abnormal returns as compared to those with negative abnormal returns. The result of the study gives insight into the effectiveness of STASM which will be useful for regulators and investors to prevent market manipulations.
The Experience of Being Male Nurse: Exploring the Enhancing Factors and Barriers of Jordanian Nursing Students
Authors: Shudifat Raed , Algunmeeyn Abdullah , Shoqirat Noordeen , Alja'afreh Mahmoud
Published: March 2023

Introduction

Despite advances in health care and education, males continue to be considered a minority in nursing programs. Little is known about the decision of Jordanian male nursing students to become nurses.

Objective

The purpose of this research was to explore the factors that encourage or discourage Jordanian male nursing students from pursuing a career in nursing.

Methods

A qualitative narrative approach was used for this study. Data were collected using semi-structured individual interviews. Purposive sampling was used in the research. In this study, interviews were conducted with a sample of 28 male college students.

Results

The current study discovered that the following six themes exemplified the male nursing students’ lives: “helping and caring,” “job security and economic stability,” “parents and peer influence,” “level of autonomy,” “social stigma,” and “long working hours.”

Conclusion

The study's findings highlighted the importance of researching male nursing students’ motivating and inhibiting factors.
Visualizing Underemployment Dynamics in Australia: Combining Sankey and Sequence Analysis Plots
Authors: Fauser Sophia , Mooi-Reci Irma
Published: March 2023

This visualization uses annual data from the Household, Income and Labour Dynamics in Australia (HILDA) Survey to illustrate the dynamics of underemployment for Australian men and women in their early careers (ages 25–34 years). Visualizing the dynamics of underemployment reveals that it is a persistent and gender-biased issue. Women are more likely to experience underemployment in their early careers compared with men. Additionally, women are more likely to become trapped in a cycle of underemployment and inactivity, leading to unfavorable long-term work experiences. This disparity highlights the need for policies that improve women’s human capital and productivity by addressing underemployment in their early careers.
FOXP1 regulates oxidative stress, SIRT1 expression, and resistance to chemotherapies in acute myeloid leukemia cells
Authors: Levavasseur Francoise , Oussous Samia , Zubaidan Tuerdi , Kosmider Olivier , Pendino Frédéric , Rombaut David , Bouscary Didier , Fontenay Michaela , Lauret Evelyne , Dusanter-Fourt Isabelle
Published: March 2023

Transcription factor Forkhead box P1 (FOXP1) belongs to the same protein family as the FOXOs that are well-known regulators of murine hematopoietic stem progenitor cell (HSPC) maintenance via dampening oxidative stress. FOXP1 and FOXOs can play opposite, or similar, roles depending on cell context; they can crossregulate each other’s expression. In a previous study, we have shown that FOXP1 contributes to healthy human HSPC and acute myeloid leukemia (AML) cell growth. Here, we investigated the role of FOXP1 in HSPCs and AML cell oxidative stress defense in a human context. FOXP1 expression level was associated with an inferior survival outcome in patients with cytogenetically normal AML. FOXP1 knockdown enhanced superoxide anion levels of human-committed CD34+CD38+ cells but not stem cell–enriched CD34+CD38− HSPCs or AML cells in vitro. FOXP1 knockdown triggered enhanced NRF2 activity and increased cell oxidative stress. FOXP1 had no impact on FOXO1/3/4 expression in these cells; genetic and pharmacological inhibition of FOXOs did not change superoxide anion levels of human HSPCs or AML cells. Moreover, FOXP1 antioxidant activity was independent of changes in expression of superoxide dismutase 1 and 2 or catalase. Instead, FOXP1 upregulated expression of the stress sensor SIRT1 by stabilizing SIRT1 protein. FOXP1 loss sensitized AML cells to chemotherapy. Together, this study identified FOXP1 as a new safeguard against myeloid progenitor oxidative stress, which works independently of FOXOs but through SIRT1 and contributes to AML chemoresistance. It proposes FOXP1 expression/activity as a promising target to overcome drug resistance of AML HSPCs.
Barriers and facilitators of integration of pharmacists in the provision of clinical pharmacy services in Tanzania
Authors: Kilonzi Manase , Mutagonda Ritah F. , Mlyuka Hamu J. , Mwakawanga Dorkasi L. , Mikomangwa Wigilya P. , Kibanga Wema A. , Marealle Alphonce Ignace , Mallya Bertha , Katabalo Deogratias , Sanga Sofia , Kalokola Fredrick , Rwegasha John , Magambo Rose , Mmassy John , Kabissi Sungwa , Balati Josephine A. , Maduki Peter , OmaryMashikuMinzi  , Kamuhabwa Appolinary A. R.
Published: March 2023

Background

Collaboration between medical doctors and nurses in the provision of healthcare services has been there for decades. The concept of clinical pharmacy services as a main goal for pharmacy practice is relatively new and is yielding more positive results for healthcare providers (HCPs), patients, and the health system. This study assessed barriers and facilitators toward the integration of pharmacists in the provision of CPS in Tanzania.

Methods

A qualitative study was conducted in five tertiary hospitals representing Tanzania mainland. Ten (10) focus group discussions (FGDs) with 83 HCPs and 14 in-depth interviews (IDIs) with hospital administrators in referral hospitals were conducted between August and September 2021. The experienced qualitative researchers moderated the IDIs and FGDs, and all discussions were audio-recorded. Finally, the audios were transcribed verbatim, and analysis was done using a thematic approach.

Results

Limited skills, lack of confidence, poor communication, inferiority, and superiority behaviors among HCPs were among the mentioned barriers. Shortage of pharmacists, lack of in-job training, standard operating procedures (SOPs), and guidelines were also mentioned. The study noted the high acceptability of CPS by other HCPs, the positive perception of pharmacists, and the recognition of CPS by the Tanzania Pharmacy Act and regulation.

Conclusion

The facilitators and barriers to the integration of pharmacists in the provision of CPS lie at the individual, health facility, and health system levels. Therefore, the study recommends in-job pharmacists training, fostering teamwork among HCPs, and development of CPS SoPs, and guidelines.
Examining the relationship between health literacy and quality of life: evidence from older people admitted to the hospital
Authors: Mehralian Gholamhossein , Yusefi Ali Reza , Davarani Esmat Rezabeigi , Ahmadidarrehsima Sudabeh , Nikmanesh Parnian
Published: March 2023

Introduction

Literacy has become an increasingly serious problem, especially as it relates to health care. In this regard, health literacy (HL), as a cognitive skill, has proven to be an influential factor to improve of the quality of life (QOL). This study aimed to examine the level of HL and its relationship with the QOL of older people at the time of discharge from the hospital in the south of Iran.

Methods

This descriptive-analytical cross-sectional study included 300 older people admitted and treated in 10 teaching-therapeutic hospitals affiliated with the Shiraz University of Medical Sciences in 2021. The standard Health Literacy for Iranian Adults (HELIA) questionnaire and the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) were used to collect the required data. Data were analyzed with SPSS software version 23 software using descriptive and inferential statistics, Pearson’s correlation coefficient, T-test, ANOVA, and multiple linear regression at p = 0.05.

Results

The mean scores of Hl and QOL for older people were 48.22 ± 9.63 (out of 100) and 61.59 ± 12.43 (out of 120), respectively. Moreover, there was a significant direct correlation between the participants’ HL and their QOL (r=0.388, p<0.001). All dimensions of HL, including comprehension (β=0.461, p<0.001), decision-making and behavior (β=0.434, p<0.001), access (β=0.397, p<0.001), reading skill (β=0.362, p=0.002), and assessment (β=0.278, p=0.004), were significant relationship with QOL. A statistically significant difference was revealed between the mean scores of HL regarding the participants’ gender (p=0.04) and level of education (p=0.001). Furthermore, the mean scores of QOL were significantly different with regard to older people’s gender (p=0.02), marital status (p=0.03), level of education (p=0.002), and income (p=0.01).

Conclusion

The findings revealed the participants’ inadequate HL and average QOL. Considering the relationship of HL with QOL, it is recommended to develop comprehensive programs and effective interventions to develop HL skills and subsequently improve QOL among older people.
Does telehealth affect the adherence to ART among patients with HIV? A systematic review and meta-analysis
Authors: Esmaeili Elham Davtalab , Azizi Hosein , Dastgiri Saeed , Kalankesh Leila R.
Published: March 2023

Background

Several studies have shown different effects of telehealth interventions on adherence to Antiretroviral therapy (ART) among people living with HIV. This study conducted a meta-analysis of Randomized Controlled Trials (RCTs) to estimate the pooled effect of telehealth interventions on the treatment adherence of HIV patients.

Methods

The researchers conducted literature searches in Scopus, PubMed, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials databases. In addition, open grey was systematically searched until January 2022 for RCTs around the effects of telehealth on adherence to treatment ART among patients with HIV. Each study’s methodological quality was assessed using the Cochrane Collaboration tool. Pooled Standard Mean Differences (SMD) and Risk Ratio (RR) with 95% CI were calculated using the random effects model.

Results

In total, 12 eligible articles were considered in the present systematic review. A random-effects meta-analysis using 5 RCTs yielded the pooled RR estimate of 1.18 (95% CI: 1.03 to 1.35, p < 0.05); I2 = 0, suggesting the adherence to treatment among patients with HIV who received telehealth intervention was significantly 18% upper than control groups. Moreover, the random effects analysis of SMD showed a positive effect for telehealth with SMR = 0.36 (95% CI: 0.22 to 0.49, p < 0.05); I2 = 91.9%, indicating that telehealth intervention increased ART adherence to the treatment group compared to the control group.

Conclusion

Telehealth intervention as a new modality of health care service delivery could be a valuable strategy to improve ART adherence among patients with HIV. It can strengthen the capacity of HIV care services. On a large scale, telehealth can be utilized as a supplementary component for ART delivery and retention toward successful adherence to the therapy.
Politics of COVID-19 vaccination in Japan: how governing incumbents’ representation affected regional rollout variation
Authors: Kikuchi M. , Ishihara S. , Kohno M.
Published: March 2023

Background

Despite initial delay, Japan’s COVID-19 vaccination accelerated remarkably from May to September 2021 under the leadership of Prime Minister Yoshihide Suga. His “campaign” for vaccination, however, did not yield uniform results nationwide.

Methods

To highlight political determinants for the regional variation, we employ ordinary least squares regression analyses to investigate how the share/presence of incumbent politicians belonging to the governing parties, the Liberal Democratic Party and Komei Party, influenced the varying progress of rollouts across prefectures as well as across cities/towns/villages. The data on the vaccination rate for all 47 prefectures was obtained from Government Chief Information Officer (CIO)’s Portal, Japan (GCPJ) approximately one month prior to the anticipated general election, the national election for the more important House of Representatives of Japan’s bicameral parliament (Diet). The data for lower administrative units, though its availability was limited to only three prefectures, was obtained from the respective governments of Kagawa and Ehime and from a local newspaper in Gifu.

Results

The findings reveal that at both prefectural and sub-prefectural administrative levels, the share/presence of the governing parties’ representation in the national parliament had a positive and statistically significant effect on the region’s vaccination progress, after controlling for the local proliferation of COVID-19 and demographic characteristics.

Conclusion

Our findings contribute insights into the understudied area of the contemporary COVID-19 health environment, namely how the political dynamics of democracy affect the pattern of vaccine dissemination in Japan.

Trial registration

: Not applicable.
Identification of immune cells infiltrating in hippocampus and key genes associated with Alzheimer’s disease
Authors: Liu Chenming , Xu Sutong , Liu Qiulu , Chai Huazhen , Luo Yuping , Li Siguang
Published: March 2023

Alzheimer’s disease (AD) is the most prevalent cause of dementia and is primarily associated with memory impairment and cognitive decline, but the etiology of AD has not been elucidated. In recent years, evidence has shown that immune cells play critical roles in AD pathology. In the current study, we collected the transcriptomic data of the hippocampus from gene expression omnibus database, and investigated the effect of immune cell infiltration in the hippocampus on AD, and analyzed the key genes that influence the pathogenesis of AD patients. The results revealed that the relative abundance of immune cells in the hippocampus of AD patients was altered. Of all given 28 kinds of immune cells, monocytes were the important immune cell associated with AD. We identified 4 key genes associated with both AD and monocytes, including KDELR1, SPTAN1, CDC16 and RBBP6, and they differentially expressed in 5XFAD mice and WT mice. The logistic regression and random forest models based on the 4 key genes could effectively distinguish AD from healthy samples. Our research provided a new perspective on immunotherapy for AD patients.
Laboratory evaluation of the miniature direct-on-blood PCR nucleic acid lateral flow immunoassay (mini-dbPCR-NALFIA), a simplified molecular diagnostic test for Plasmodium
Authors: van Dijk Norbert J. , Menting Sandra , Wentink-Bonnema Ellen M. S. , Broekhuizen-van Haaften Patricia E. , Withycombe Elen , Schallig Henk D. F. H. , Mens Petra F.
Published: March 2023

Background

Point-of-care diagnosis of malaria is currently based on microscopy and rapid diagnostic tests. However, both techniques have their constraints, including poor sensitivity for low parasitaemias. Hence, more accurate diagnostic tests for field use and routine clinical settings are warranted. The miniature direct-on-blood PCR nucleic acid lateral flow immunoassay (mini-dbPCR-NALFIA) is an innovative, easy-to-use molecular assay for diagnosis of malaria in resource-limited settings. Unlike traditional molecular methods, mini-dbPCR-NALFIA does not require DNA extraction and makes use of a handheld, portable thermal cycler that can run on a solar-charged power pack. Result read-out is done using a rapid lateral flow strip enabling differentiation of Plasmodium falciparum and non-falciparum malaria infections. A laboratory evaluation was performed to assess the performance of the mini-dbPCR-NALFIA for diagnosis of pan-Plasmodium and P. falciparum infections in whole blood.

Methods

Diagnostic accuracy of the mini-dbPCR-NALFIA was determined by testing a set of Plasmodium-positive blood samples from returned travellers (n = 29), and Plasmodium-negative blood samples from travellers with suspected malaria (n = 23), the Dutch Blood Bank (n = 19) and intensive care patients at the Amsterdam University Medical Centers (n = 16). Alethia Malaria (LAMP) with microscopy for species differentiation were used as reference. Limit of detection for P. falciparum was determined by 23 measurements of a dilution series of a P. falciparum culture. A fixed sample set was tested three times by the same operator to evaluate the repeatability, and once by five different operators to assess the reproducibility.

Results

Overall sensitivity and specificity of the mini-dbPCR-NALFIA were 96.6% (95% CI, 82.2%–99.9%) and 98.3% (95% CI, 90.8%–100%). Limit of detection for P. falciparum was 10 parasites per microlitre of blood. The repeatability of the assay was 93.7% (95% CI, 89.5%–97.8%) and reproducibility was 84.6% (95% CI, 79.5%–89.6%).

Conclusions

Mini-dbPCR-NALFIA is a sensitive, specific and robust method for molecular diagnosis of Plasmodium infections in whole blood and differentiation of P. falciparum. Incorporation of a miniature thermal cycler makes the assay well-adapted to resource-limited settings. A phase-3 field trial is currently being conducted to evaluate the potential implementation of this tool in different malaria transmission areas.
Using antenatal care as a platform for malaria surveillance data collection: study protocol
Authors: Gutman Julie R. , Mwesigwa Julia Nanteza , Arnett Kyra , Kangale Chabu , Aaron Sijenunu , Babarinde Dele , Buekens Julie , Candrinho Baltazar , Debe Siaka , Digre Peder , Drake Mary , Gansané Adama , Gogue Christelle , Griffith Kevin S. , Hicks Joseph , Kinda Réné , Koenker Hannah , Lemwayi Ruth , Munsey Anna , Obi Emmanuel , Ogouyèmi-Hounto Aurore , Okoko Okefu Oyale , Onikpo Faustin , Onoja Ali , Porter Travis , Savaio Binete , Tynuv Kenzie , Uhomoibhi Perpetua , Wagman Joseph , Wolf Katherine , Zulliger Rose , Walker Patrick , Miller John M. , Robertson Molly
Published: March 2023

Background

While many malaria-endemic countries have health management information systems that can measure and report malaria trends in a timely manner, these routine systems have limitations. Periodic community cross-sectional household surveys are used to estimate malaria prevalence and intervention coverage but lack geographic granularity and are resource intensive. Incorporating malaria testing for all women at their first antenatal care (ANC) visit (i.e., ANC1) could provide a more timely and granular source of data for monitoring trends in malaria burden and intervention coverage. This article describes a protocol designed to assess if ANC-based surveillance could be a pragmatic tool to monitor malaria.

Methods

This is an observational, cross-sectional study conducted in Benin, Burkina Faso, Mozambique, Nigeria, Tanzania, and Zambia. Pregnant women attending ANC1 in selected health facilities will be tested for malaria infection by rapid diagnostic test and administered a brief questionnaire to capture key indicators of malaria control intervention coverage and care-seeking behaviour. In each location, contemporaneous cross-sectional household surveys will be leveraged to assess correlations between estimates obtained using each method, and the use of ANC data as a tool to track trends in malaria burden and intervention coverage will be validated.

Results

This study will assess malaria prevalence at ANC1 aggregated at health facility and district levels, and by gravidity relative to current pregnancy (i.e., gravida 1, gravida 2, and gravida 3 +). ANC1 malaria prevalence will be presented as monthly trends. Additionally, correlation between ANC1 and household survey–derived estimates of malaria prevalence, bed net ownership and use, and care-seeking will be assessed.

Conclusion

ANC1-based surveillance has the potential to provide a cost-effective, localized measure of malaria prevalence that is representative of the general population and useful for tracking monthly changes in parasite prevalence, as well as providing population-representative estimates of intervention coverage and care-seeking behavior. This study will evaluate the representativeness of these measures and collect information on operational feasibility, usefulness for programmatic decision-making, and potential for scale-up of malaria ANC1 surveillance.
Effects of adverse fertility-related factors on mitochondrial DNA in the oocyte: a comprehensive review
Authors: Zhang Wenying , Wu Fuju
Published: March 2023

The decline of oocyte quality has profound impacts on fertilization, implantation, embryonic development, and the genetic quality of future generations. One factor that is often ignored but is involved in the decline of oocyte quality is mitochondrial DNA (mtDNA) abnormalities. Abnormalities in mtDNA affect the energy production of mitochondria, the dynamic balance of the mitochondrial network, and the pathogenesis of mtDNA diseases in offspring. In this review, we have detailed the characteristics of mtDNA in oocytes and the maternal inheritance of mtDNA. Next, we summarized the mtDNA abnormalities in oocytes derived from aging, diabetes, obesity, and assisted reproductive technology (ART) in an attempt to further elucidate the possible mechanisms underlying the decline in oocyte health. Because multiple infertility factors are often involved when an individual is infertile, a comprehensive understanding of the individual effects of each infertility-related factor on mtDNA is necessary. Herein, we consider the influence of infertility-related factors on the mtDNA of the oocyte as a collective perspective for the first time, providing a supplementary angle and reference for multi-directional improvement strategies of oocyte quality in the future. In addition, we highlight the importance of studying ART-derived mitochondrial abnormalities during every ART procedure.
Honokiol acts as an AMPK complex agonist therapeutic in non-alcoholic fatty liver disease and metabolic syndrome
Authors: Tian Ruifeng , Yang Jinjie , Wang Xiaoming , Liu Shuaiyang , Dong Ruixiang , Wang Zhenya , Yang Zifeng , Zhang Yingping , Cai Zhiwei , Yang Hailong , Hu Yufeng , She Zhi-Gang , Li Hongliang , Zhou Junjie , Zhang Xiao-Jing
Published: March 2023

Background

Non-alcoholic fatty liver (NAFLD) and its related metabolic syndrome have become major threats to human health, but there is still a need for effective and safe drugs to treat these conditions. Here we aimed to identify potential drug candidates for NAFLD and the underlying molecular mechanisms.

Methods

A drug repositioning strategy was used to screen an FDA-approved drug library with approximately 3000 compounds in an in vitro hepatocyte model of lipid accumulation, with honokiol identified as an effective anti-NAFLD candidate. We systematically examined the therapeutic effect of honokiol in NAFLD and metabolic syndrome in multiple in vitro and in vivo models. Transcriptomic examination and biotin-streptavidin binding assays were used to explore the underlying molecular mechanisms, confirmed by rescue experiments.

Results

Honokiol significantly inhibited metabolic syndrome and NAFLD progression as evidenced by improved hepatic steatosis, liver fibrosis, adipose inflammation, and insulin resistance. Mechanistically, the beneficial effects of honokiol were largely through AMPK activation. Rather than acting on the classical upstream regulators of AMPK, honokiol directly bound to the AMPKγ1 subunit to robustly activate AMPK signaling. Mutation of honokiol-binding sites of AMPKγ1 largely abolished the protective capacity of honokiol against NAFLD.

Conclusion

These findings clearly demonstrate the beneficial effects of honokiol in multiple models and reveal a previously unappreciated signaling mechanism of honokiol in NAFLD and metabolic syndrome. This study also provides new insights into metabolic disease treatment by targeting AMPKγ1 subunit-mediated signaling activation.
Tumor cell integrin β4 and tumor stroma E-/P-selectin cooperatively regulate tumor growth in vivo
Authors: Genduso Sandra , Freytag Vera , Schetler Daniela , Kirchner Lennart , Schiecke Alina , Maar Hanna , Wicklein Daniel , Gebauer Florian , Bröker Katharina , Stürken Christine , Milde-Langosch Karin , Oliveira-Ferrer Leticia , Ricklefs Franz L. , Ewald Florian , Wolters-Eisfeld Gerrit , Riecken Kristoffer , Unrau Ludmilla , Krause Linda , Bohnenberger Hanibal , Offermann Anne , Perner Sven , Sebens Susanne , Lamszus Katrin , Diehl Linda , Linder Stefan , Jücker Manfred , Schumacher Udo , Lange Tobias
Published: March 2023

Background

The immunological composition of the tumor microenvironment has a decisive influence on the biological course of cancer and is therefore of profound clinical relevance. In this study, we analyzed the cooperative effects of integrin β4 (ITGB4) on tumor cells and E-/P-selectin on endothelial cells within the tumor stroma for regulating tumor growth by shaping the local and systemic immune environment.

Methods

We used several preclinical mouse models for different solid human cancer types (xenograft and syngeneic) to explore the role of ITGB4 (shRNA-mediated knockdown in tumor cells) and E-/P-selectins (knockout in mice) for tumor growth; effects on apoptosis, proliferation and intratumoral signaling pathways were determined by histological and biochemical methods and 3D in vitro experiments; changes in the intratumoral and systemic immune cell composition were determined by flow cytometry and immunohistochemistry; chemokine levels and their attracting potential were measured by ELISA and 3D invasion assays.

Results

We observed a very robust synergism between ITGB4 and E-/P-selectin for the regulation of tumor growth, accompanied by an increased recruitment of CD11b+ Gr-1Hi cells with low granularity (i.e., myeloid-derived suppressor cells, MDSCs) specifically into ITGB4-depleted tumors. ITGB4-depleted tumors undergo apoptosis and actively attract MDSCs, well-known to promote tumor growth in several cancers, via increased secretion of different chemokines. MDSC trafficking into tumors crucially depends on E-/P-selectin expression. Analyses of clinical samples confirmed an inverse relationship between ITGB4 expression in tumors and number of tumor-infiltrating leukocytes.

Conclusions

These findings suggest a distinct vulnerability of ITGB4Lo tumors for MDSC-directed immunotherapies.

Graphical Abstract
Effects of n-3 polyunsaturated fatty acid on metabolic status in women with polycystic ovary syndrome: a meta-analysis of randomized controlled trials
Authors: Zhou Jie , Zuo Wenting , Tan Yong , Wang Xudong , Zhu Meihong , Zhang Huili
Published: March 2023

This meta-analysis was conducted to summarize the effects of n-3 polyunsaturated fatty acid (n-3 PUFA) on metabolic status including insulin metabolism and lipid metabolism in women with polycystic ovary syndrome (PCOS) by randomized controlled trials (RCTs). Four mainstream databases including PubMed, Cochrane Library, Embase and Web of Science were searched from their inception to October 2021. The registration number of this study was CRD42021285233. The quality assessment was performed referring the Cochrane Risk of Bias Tool. Mean differences (MD) and 95% confidence intervals (CIs) were generated for continuous variables by meta-analysis. Subgroup analyses were performed based on study duration (≤ 8 weeks or > 8 weeks), the source of n-3 PUFA (marine derived or plant origins) and dosage of n-3 PUFA (≤ 1000 mg/d or > 1000 mg/d). Eventually, 11 RCTs reporting 816 patients were enrolled. Compared with control group, n-3 PUFA treatment decreased waist circumference (MD = -2.76, 95% CI: -3.82 to -1.69; p < 0.00001), fasting plasma glucose (MD = -3.91, 95% CI: -5.69 to -2.13; p < 0.0001), fasting insulin (MD = -2.45, 95% CI: -3.19 to -1.71; p < 0.00001), homeostatic model assessment of insulin resistance (MD = -0.45, 95% CI: -0.80 to -0.11; p = 0.01), triglyceride (MD = -9.33, 95% CI: -10.56 to -8.10; p < 0.00001), total cholesterol (MD = -12.32, 95% CI: -19.15 to -5.50; p = 0.0004), low-density lipoprotein cholesterol (MD = -10.53, 95% CI: -19.31 to -1.75; p = 0.02), and increase quantitative insulin sensitivity check index (MD = 0.01, 95% CI: 0.01 to 0.02; p < 0.00001), Adiponectin (MD = 1.46, 95% CI: 1.12 to 1.80; p < 0.00001) in PCOS patients. However, n-3 PUFA failed to change body weight, body mass index, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and hs-CRP in the overall analysis. Further subgroup analyses showed that supplements of n-3 PUFA for more than 8 weeks is more conducive to improve the metabolic status in insulin resistance and lipid profiles. The meta-analysis demonstrates that n-3 PUFA may be an effective intervention for alleviating metabolic status in PCOS. Hence, we recommend PCOS patients replenish n-3 PUFA with duration > 8 weeks regardless of the source and the dosage to retard the pathogenesis of PCOS related metabolic diseases.
Relationships between circulating metabolites and facial skin aging: a Mendelian randomization study
Authors: Liu Zhengye , Mi Jiarui , Wu Huiling
Published: March 2023

Background

Blood metabolites are important to various aspects of our health. However, currently, there is little evidence about the role of circulating metabolites in the process of skin aging.

Objectives

To examine the potential effects of circulating metabolites on the process of skin aging.

Method

In the primary analyses, we applied several MR methods to study the associations between 249 metabolites and facial skin aging risk. In the secondary analyses, we replicated the analyses with another array of datasets including 123 metabolites. MR Bayesian model averaging (MR-BMA) method was further used to prioritize the metabolites for the identification of predominant metabolites that are associated with skin aging.

Results

In the primary analyses, only the unsaturation degree of fatty acids was found significantly associated with skin aging with the IVW method after multiple testing (odds ratio = 1.084, 95% confidence interval = 1.049–1.120, p = 1.737 × 10−06). Additionally, 11 out of 17 unsaturation-related biomarkers showed a significant or suggestively significant causal effect [p < 0.05 and > 2 × 10−4 (0.05/249 metabolites)]. In the secondary analyses, seven metabolic biomarkers were found significantly associated with skin aging [p < 4 × 10−4 (0.05/123)], while six of them were related to the unsaturation degree. MR-BMA method validated that the unsaturation degree of fatty acids plays a dominant role in facial skin aging.

Conclusions

Our study used systemic MR analyses and provided a comprehensive atlas for the associations between circulating metabolites and the risk of facial skin aging. Genetically proxied unsaturation degree of fatty acids was highlighted as a dominant factor correlated with the risk of facial skin aging.
Collaborative learning, scaffolding-based instruction, and self-assessment: impacts on intermediate EFL learners’ reading comprehension, motivation, and anxiety
Authors: Ahmed Abdel-Al Ibrahim Khaled , Cuba Carbajal Nestor , Zuta Manuel Enrique Chenet , Bayat Sania
Published: March 2023

This research set to examine the impacts of collaborative learning (CL), scaffolding instruction, and self-assessment on reading anxiety, reading motivation, and reading comprehension of Iranian EFL learners. Based on Preliminary English Test (PET) results, a sample of 58 students was chosen to represent the study’s sample subject out of a total of 71 participants. Running a convenience sampling technique, two equal groups (the control and experimental) were chosen at random from among them. Afterward, both groups completed pretests to gauge their reading motivation, anxiety, and comprehension. Two groups were then treated with a variety of treatments. Learners in the experimental group got scaffolding instruction, self-assessment, and CL as treatment, whereas the control group received typical instructor-based teaching and assessment. Later, both groups took the post-test for reading anxiety, reading comprehension, and reading motivation after the treatment. According to the one-way ANCOVA analysis, the post-test results for the two groups were different. Based on the data analysis, the experimental group outdid the control group in reading anxiety, reading motivation, and reading comprehension. It was concluded that Iranian EFL learners were able to develop both their reading comprehension and reading motivation while experiencing less reading anxiety thanks to CL, self-assessment, and scaffolding instruction. Finally, the conclusions, implications, limitations, and suggestions for further studies were provided.