bluuebunny/crossref_metadata_2025 huggingface dataset:
RUNX3 pathway signature predicts clinical benefits of immune checkpoint inhibition plus tyrosine kinase inhibition in advanced renal cell carcinoma
Authors: Wang Jiajun , Zhang Sihong , Wang Ying , Zhu Yanjun , Xu Xianglai , Guo Jianming
Published: January 2024

Background

Checkpoint inhibitor immunotherapy plus tyrosine kinase inhibitor (IO/TKI) have been recently recommended as standard first-line therapy for advanced renal cell carcinoma, while no clinical-available biomarker has been applied. This study aimed to investigate the associations between RUNX3 pathway signature and IO/TKI benefits in renal cell carcinoma (RCC).

Methods

Two IO/TKI cohorts (ZS-MRCC, JAVELIN-101) and one high-risk localized RCC cohort (ZS-HRRCC) were included. All samples were evaluated by RNA-sequencing, and RUNX Family Transcription Factor 3 (RUNX3) pathway were determined by single sample gene set enrichment analysis. Flow cytometry were applied for immune cell infiltration and function.

Results

RUNX3 signature was elevated in RCC samples, compared non-tumor tissues (P < 0.001). High-RUNX3 signature was associated with shorter progression-free survival (PFS) in both IO/TKI cohorts (ZS-MRCC cohort, P = 0.025; JAVELIN-101 cohort, P = 0.019). RUNX3 signature also predicted IO/TKI benefit in advanced RCC, compared with TKI monotherapy (interaction p = 0.027). RUNX3 signature was associated with decreased number of GZMB + CD8 + T cells (Spearman’s ρ=-0.42, P = 0.006), and increased number of PD1 + CD8 + T cells (Spearman’s ρ = 0.29, P = 0.072). Moreover, the integration of RUNX3 signature and GZMB expression showed predictive potential for TKI/IO (log-rank P < 0.001). In addition, the predictive value of RUNX3 signature for IO/TKI benefit was restricted in SETD2-wild type patients (log-rank P < 0.001). Finally, a risk score was established by random forest for IO/TKI benefit, showing remarkable predictive potency (Log-rank P < 0.001).

Conclusions

RUNX3 pathway signature could be a potential predictive biomarker for IO/TKI treatment in advanced RCC, for both prognosis and treatment selection between IO/TKI and TKI monotherapy.
The prevalence of probable overactive bladder and associated risk factors among medical students in Jordan: a cross-sectional study
Authors: Abuorouq Saleh , Al-Zubi Mohammad , Al-Ali Abdullah M. , Aloqaily Laith H. , Talafha Malek A. , Migdadi Azmi M. , Serhan Hashem Abu
Published: January 2024

Background

To discuss the impact of overactive bladder (OAB) on medical students. overactive bladder. is a chronic condition that causes sudden and intense urges to urinate, which can have significant physical and psychological effects on patients’ lives. The prevalence of OAB among medical students is relatively high, with some studies reporting rates as high as 35.4%. This research aims to shed light on the prevalence rates and risk factors associated with OAB among medical students in Jordan.

Methods

A cross-sectional study was conducted using an online self-reported questionnaire as the study tool. The questionnaire collected the sociodemographic, health, and academic characteristics of medical students, as well as the new 7-item OABSS score.

Results

Out of the total sample of medical students surveyed (n = 525), 44.5% reported experiencing symptoms of OAB. Furthermore, the analysis also revealed that there was a significant difference in the prevalence of OAB between the ages of medical students. In addition, the study also found that there was a significant association between OAB symptoms and basic years, positive history of diagnostic UTI, positive history of recent trauma, high stress, and taking certain medications.

Conclusions

The study highlights the need for further research in this area and emphasizes the possible implications of OAB for medical students, including the need for additional support and resources to manage the condition.
Predicting stone composition via machine-learning models trained on intra-operative endoscopic digital images
Authors: Zhu Guanhua , Li Chengbai , Guo Yinsheng , Sun Lu , Jin Tao , Wang Ziyue , Li Shiqing , Zhou Feng
Published: January 2024

Objectives

The aim of this study was to use deep learning (DL) of intraoperative images of urinary stones to predict the composition of urinary stones. In this way, the laser frequency and intensity can be adjusted in real time to reduce operation time and surgical trauma.

Materials and methods

A total of 490 patients who underwent holmium laser surgery during the two-year period from March 2021 to March 2023 and had stone analysis results were collected by the stone laboratory. A total of 1658 intraoperative stone images were obtained. The eight stone categories with the highest number of stones were selected by sorting. Single component stones include calcium oxalate monohydrate (W1), calcium oxalate dihydrate (W2), magnesium ammonium phosphate hexahydrate, apatite carbonate (CH) and anhydrous uric acid (U). Mixed stones include W2 + U, W1 + W2 and W1 + CH. All stones have intraoperative videos. More than 20 intraoperative high-resolution images of the stones, including the surface and core of the stones, were available for each patient via FFmpeg command screenshots. The deep convolutional neural network (CNN) ResNet-101 (ResNet, Microsoft) was applied to each image as a multiclass classification model.

Results

The composition prediction rates for each component were as follows: calcium oxalate monohydrate 99% (n = 142), calcium oxalate dihydrate 100% (n = 29), apatite carbonate 100% (n = 131), anhydrous uric acid 98% (n = 57), W1 + W2 100% (n = 82), W1 + CH 100% ( n = 20) and W2 + U 100% (n = 24). The overall weighted recall of the cellular neural network component analysis for the entire cohort was 99%.

Conclusion

This preliminary study suggests that DL is a promising method for identifying urinary stone components from intraoperative endoscopic images. Compared to intraoperative identification of stone components by the human eye, DL can discriminate single and mixed stone components more accurately and quickly. At the same time, based on the training of stone images in vitro, it is closer to the clinical application of stone images in vivo. This technology can be used to identify the composition of stones in real time and to adjust the frequency and energy intensity of the holmium laser in time. The prediction of stone composition can significantly shorten the operation time, improve the efficiency of stone surgery and prevent the risk of postoperative infection.
Characteristics and influencing factors of the first dental visit among children in Bangkok, Thailand: a cross-sectional study
Authors: Kasemkhun Pornpailin , Jirarattanasopha Varangkanar , Lertsooksawat Wannee
Published: January 2024

Background

The first dental visit (FDV) is fundamental to good oral health. This study aimed to investigate the characteristics of FDV, including the influencing factors, in children attending the government dental hospital in Bangkok.

Methods

This study included 289 pairs of new patients (aged 0–12 years) and their parents. The questionnaires, consisting of three parts: socio-demographic, reasons for the child’s FDV and for not having FDV earlier, and the children’s oral health knowledge and attitude, were completed by parents. The Chi-square and Kruskal-Wallis tests were used to compare variables among age groups. The level of statistical significance was set atp < 0.05. A multiple linear regression analysis was performed to identify the factors that influence the age at FDV. The variables included in the analysis were the child’s characteristics, the family’s socio-demographic background, the presence of symptoms, and the parents’ knowledge and attitude towards their child’s oral health.

Results

The mean ages of children at FDV were 5.57 ± 2.88 (age range of 0.58–11.92) years. There were 2.42% who had FDV ≤ 12 months of age, and 76.5% of all children already had dental caries. A low attitude score among parents was significantly found in the older age group of children (p = 0.001). The influencing factors with the age at FDV were the parental age (p < 0.001), the presence of symptoms or chief complaints (p = 0.016), and the presence of dental caries (p < 0.001).

Conclusions

Children in Bangkok had seriously delayed FDV compared to the recommended guidelines. The parental age strongly influenced the proper age at FDV, together with the presence of symptoms or chief complaints, and the presence of dental caries. Thus, an effective campaign to raise awareness about FDV is still needed, especially in advanced maternal age.
The effectiveness of educational intervention based on the Health Action Model (HAM) in improving breast cancer screening behaviors
Authors: Mahboobighazaani Fahimeh , Karimi Masoud , Azadbakht Mojtaba , Ghahremani Leila
Published: January 2024

Introduction

Breast cancer disease is known as the most common cancer among women. Lack of knowledge and awareness is a leading cause of breast cancer, and since nearly all women are increasingly susceptible to this disease, training screening behaviors for early detection is proven essential in order to reduce breast cancer mortality. Therefore, the present study was designed to determine the effect of educational intervention based on the Health Action Model in improving breast cancer screening behaviors in women aged 30 to 69 in Kashan, Iran.

Methods

This quasi-experimental study was conducted on 162 women aged 30–69 years old among the clients of Comprehensive health service centers in Kashan, Iran and they were assigned to intervention and control groups. The research instrument included a questionnaire assessed within three phases: baseline, 3-months, and 6-months, containing Health Action Model (HAM) structures and also three screening behaviors. The intervention consisted of a model-based education package and was carried out over 2 months. To evaluate the effect of the intervention, the mean of model structures and proportion screening behaviors in the third and sixth months were compared with the baseline phase. All analyses were carried out using SPSS, version 22.

Results

The intervention and control groups were homogeneous regarding the structures of the HAM and the proportion of screening behaviors in the baseline phase (p > 0.05). In the 3-month (p < 0.05) and 6-month (p < 0.05) phases, the mean scores of the HAM constructs in the intervention group were found higher compared with the control group. Moreover, the proportion of clinical breast examinations in the intervention group was statistically higher than in the control group in the 3-month (p < 0.001) and 6-month (p < 0.001) phases. In addition, the proportion of mammography performed in the 3-month (p = 0.002) and 6-month (p < 0.001) phases were reported to be higher in the intervention group compared with the control group.

Conclusion

Overall, these results provide important insight into the effectiveness of the interventions based on the Health Action Model in promoting breast cancer screening behaviors and the determinants of such behaviors.
The unbroken chain of female genital mutilation: a qualitative assessment of high school girls’ perspectives
Authors: Hemmeda Lina , Anwer Lena , Abbas Marwa , Elfaki Lina , Omer Maram , Khalid Maab , Hassan Mushrega , Mostafa Mihrab , Hamza Lina , Mahmoud Maab , Osman Maram Mohamed , Mohamed Mozan , Bakheet Lamees , Omer Alaa T.
Published: January 2024

Background

Female Genital Mutilation (FGM) is defined as any procedure that involves damage to the female external genitalia. This practice is majorly prevalent in Sudan, as it is estimated that over 12 million Sudanese women are circumcised. This study uncovers rural females’ knowledge and insights about FGM domestically.

Methods

A qualitative, deductive study with thematic analysis was conducted. A total of 42 female high school students were recruited and divided into five focus groups, each of which included girls from four different high school classes in the main school of the study area. A topic guide was prepared and used to lead the focus groups. Thematic analysis was used, and the study data had been categorized into four themes: knowledge, procedure and performance, experience, and practice. The condensed meaning units of each theme were identified, then classified to formulate sub-themes.

Results

All the participants indicated that FGM is a traditional practice in the village. The vast majority have heard about it from family members, mainly mothers and grandmothers. Regarding the procedure, all the participants agreed that midwives perform FGM, but most of them don’t know what exactly is being removed. According to all participants, mothers and grandmothers are the decision-makers for FGM. The majority of the participants stated that they do not discriminate between the circumcised and uncircumcised women and most of them agreed that circumcision has negative side effects. They have mentioned pain, difficult urination, and walking as early side effects, while psychological impacts and labor obstruction as late ones. Generally, the majority of the participants agreed that circumcision is not beneficial and should stop.

Conclusion

Knowledge regarding the dangers of FGM among high school girls is better than expected given the high prevalence of the practice. Generally, the process is well understood, the performers are known, the experience is universal, and the side effects are acknowledged. Nevertheless, a majority still showed an intent to circumcise their daughters in the future.
The impact of diabetes, anemia, and renal function in the relationship between osteoporosis and fasting blood glucose among Taiwanese women: a cross-sectional study
Authors: Chuang Tzyy-Ling , Koo Malcolm , Wang Yuh-Feng
Published: January 2024

Background

The aim of this study was to investigate the association between fasting blood glucose and osteoporosis in women with diabetes, anemia, and renal function.

Methods

The medical records of women who underwent a general health examination at a regional hospital in southern Taiwan were retrospectively reviewed. Logistic regression analysis was performed to assess the association between osteoporosis and fasting blood glucose separately for the eight subgroups (diabetes or non-diabetes, anemia or non-anemia, normal or decreased renal function), adjusting for other clinical characteristics and laboratory findings.

Results

A total of 11,872 women were included in the study. Among women with diabetes, anemia, and decreased renal function, an increment of 10 mg/dL in fasting blood glucose was associated with an increased risk of osteoporosis (adjusted odds ratio [aOR] = 1.57, p = 0.004). Among women without diabetes, fasting blood glucose was significantly associated with an increased risk of osteoporosis in those with anemia and normal renal function (OR = 1.14, p = 0.023) and those without anemia and normal renal function (OR = 1.04, p = 0.015), but these associations were not significant after adjusting for other covariates.

Conclusions

Higher fasting blood glucose levels in women with diabetes, anemia, and decreased renal function were associated with an increased risk of osteoporosis. Clinicians should be vigilant about glucose control in patients with diabetes to reduce the risk of fracture.
Team-based learning (TBL) in clinical disciplines for undergraduate medical students—a scoping review
Authors: Sterpu Irene , Herling Lotta , Nordquist Jonas , Rotgans Jerome , Acharya Ganesh
Published: January 2024

Background

Team-based learning (TBL) is an evidence-based pedagogical method that has been used in undergraduate medical education since 2001. However, its use in clinical disciplines is rarely reported, and the impact of its implementation is not known. The aim of this study was to explore and map the published literature on the impact of implementing TBL in clinical disciplines in undergraduate medical education.

Methods

A comprehensive search of Medline, Education Resources Information Center (ERIC), and Web of Science databases was performed on November 24, 2021 and updated April 6, 2023, using relevant Medical Subject Headings (MeSH) and free-text terms. Original research studies reporting on the implementation of TBL in clinical disciplines in undergraduate medical education published in peer-reviewed English language journals were included irrespective of their methodological design.

Results

The initial search identified 2,383 records. Of these, 49 met the inclusion criteria. Most of the studies (n = 44, 90%) described the implementation of a modified version of TBL in which one or more TBL steps were missing, and one study had undefined protocol for the implementation. The most reported outcomes were knowledge acquisition (n = 38, 78%) and students’ satisfaction or attitudes toward TBL (n = 34, 69%). Despite some differences in their results, the studies found that implementing TBL is associated with increased knowledge acquisition (n = 19, 39%), student engagement (n = 6, 12%), and student satisfaction (n = 31, 63%).

Conclusions

Most of the studies reported positive results in students’ satisfaction and students’ engagement, whilst the results on knowledge acquisition and retention were more contradictory. In most of the studies, TBL was implemented in a modified form and diverse comparators were used. The methodological quality also varied. Thus, no unequivocal conclusions could be drawn regarding the value of implementing TBL in clinical disciplines. More studies with rigorous methodologies are needed in this field.
The impact of moulage on learners’ experience in simulation-based education and training: systematic review
Authors: DCosta Stacia , Zadow Grace , Reidlinger Dianne P. , Cox Gregory R. , Hudson Carly , Ingabire Ale , Stokes-Parish Jessica
Published: January 2024

Background

Moulage is a technique used to simulate injury, disease, aging and other physical characteristics specific to a scenario, often used in health and emergency worker training, predominantly for simulation-based learning activities. Its use in allied health fields is unclear. Previous work has explored moulage as an adjunct for authentic simulations, however there is opportunity for broadening its scope.

Aim

To explore the effects of moulage interventions in simulation-based education and training, for learner experience. A secondary aim was to understand which pedagogical frameworks were embedded in moulage interventions.

Method

Four electronic databases (PubMed, CINAHL, EmBase, Proquest Central) were systematically searched to December 2022 for studies utilising moulage in simulation-based education experiences. Outcomes were focused on learner satisfaction, confidence, immersion, engagement, performance, or knowledge. Study quality was assessed using the Mixed Methods Appraisal Tool.

Results

Twenty studies (n = 11,470) were included. Studies were primarily conducted in medicine (n = 9 studies) and nursing (n = 5 studies) and less frequently across other health disciplines. The findings demonstrated greater learner satisfaction, confidence, and immersion when moulage was used against a comparator group. Minimal improvements in knowledge and performance were identified. One study underpinned the intervention with a pedagogical theory.

Conclusion

Moulage improves learner experience in simulation-based education or training, but not knowledge or clinical performance. Further research utilising moulage across a broader range of professions is needed. Interventions using moulage should be underpinned by pedagogical theories.
Pathology and solutions for activities of medical education development offices
Authors: Gazki Parvin Rezaei , Hekmat Somayeh Noori , Salajegheh Mahla
Published: January 2024

Background and aim

Education development offices are one of the main branches of medical education centers for directing the educational performance of medical sciences universities to achieve educational goals. Due to their close presence and communication with educational environments, these offices are highly important. To effectively guide and empower these offices, it is necessary to analyze their current situation, identify the challenges, and provide solutions to address them. This study was conducted to identify the challenges and provide solutions for the activities of medical education development offices.

Methods

This qualitative study was conducted in two stages, including 29 semi-structured interviews and a focus group discussion with experts in 2022 at Kerman University of Medical Sciences. The sampling method was purposive. The content analysis of data was performed based on conventional qualitative content analysis.

Results

Data analysis resulted in the emergence of two main categories including challenges facing the activities of medical education development offices and solutions for improving the activities of these offices, and comprising some categories containing organizational structure factors, cognitive factors, communication factors, and motivational factors.

Conclusion

Education development offices are one of medical universities’ main policymaking and quality control institutions. Efforts are being made to establish EDOs structures within the university. The formation of a clear and performance-based reward system for faculty members who are the managers of the EDOs is proposed. Improving interactions between EDOs and other parts of the university to coordinate activities, and exchange of experiences are highlighted.
Hooked on technology: examining the co-occurrence of nomophobia and impulsive sensation seeking among nursing students
Authors: El-Ashry Ayman Mohamed , El-Sayed Mona Metwally , Elhay Eman Sameh Abd , Taha Samah Mohamed , Atta Mohamed Hussein Ramadan , Hammad Heba Abdel-Hamid , Khedr Mahmoud Abdelwahab
Published: January 2024

Background

Nomophobia, the crippling fear of being disconnected from mobile devices, is a burgeoning global concern. Given the critical nature of the profession of nursing students, understanding nomophobia’s prevalence and potential impacts on patient care and professional conductors becomes even more crucial.

Aim

This study explores the relationship between nomophobia and impulsive sensation-seeking among nursing students in Egypt.

Design and methods

A multicenter cross-sectional survey was conducted with 1626 nursing students randomly selected from three universities across Egypt.

Tools

The Arabic versions of the Nomophobia and Impulsive Sensation Seeking Questionnaires were employed to gather data.

Results

Our findings revealed that 40.3% of the surveyed nursing students exhibited severe nomophobia, indicating a substantial dependence on their mobile devices. Notably, this high prevalence was accompanied by a strong tendency towards impulsive sensation-seeking behaviors. Furthermore, a stepwise regression analysis identified several significant predictors of nomophobia (p < 0.001). Impulsive sensation-seeking, year of study, average daily smartphone usage, and age emerged as key factors, explaining 27.5% of the variability in nomophobia scores.

Conclusion

The prevalence of nomophobia among Egyptian nursing students is undeniable, highlighting their substantial reliance on mobile devices. A significant association with impulsive sensation-seeking behavior further compounds this dependence. Factors such as impulsive sensation seeking, year of study, average daily smartphone usage, and age were identified as significant predictors of nomophobia. Recognizing these factors as key predictors of nomophobia is crucial for designing effective interventions and psychotherapies. Prioritizing such interventions can promote future nurses’ well-being and ensure they deliver the highest quality care to their patients.
Legal issues in digital oral health: a scoping review
Authors: Mariño Rodrigo J. , Zaror Carlos
Published: January 2024

Background

This scoping review aims to systematically and critically describe the numerous legal challenges brought about by the utilization of digital oral health in the delivery of oral healthcare.

Methods

A systematic search was conducted. The following electronic databases were reviewed from inception up to March 2023: MEDLINE, Embase, Scopus, and LILACS. The search included any scientific document and paper in English, Spanish, or Portuguese on legal issues raised using digital health in oral healthcare delivery. Two reviewers conducted the selection process and data extraction. Legal issues raised concerning the adoption of digital health technology were analysed using the modified Mars’ framework.

Results

Seventeen studies were included. Most of the documents identified and covered generic aspects of delivering digital oral healthcare (n = 11) without explicitly referring to any dental specialty. The most mentioned legal issues were data security (n = 15); liability and malpractice (n = 14); consent (n = 12); and confidentiality (n = 12). To a lower extent, patient-practitioner relationship (n = 11); and license and jurisdiction (n = 11) were also covered. These were followed by privacy of information (n = 10); adequacy of records (n = 9); and e-referrals (n = 8). On the other hand, fewer studies commented on social media use (n = 3), authentication (n = 2); or e-prescriptions (n = 2). Before implementing any digital health solution, practitioners need to be aware of the many legal issues that the introduction of these technologies involves, be clear where the responsibility lies, and apply extreme caution in following national guidelines. Current literature concentrates on a few well-known legal issues. Issues around authentication, use of social media, and e-prescriptions received less attention.
Camel filariasis (Dipetalonema evansi) and its association with clinical balanoposthitis with reference to prominent changes in clinical findings, serum testosterone, semen analysis, and testicular histopathology
Authors: Khalphallah Arafat , Al-Daek Taher , Abdelhamid Mahmoud , Elmeligy Enas , El-Hawari Sayed Fathi , Khesruf Khaled A. , Nasr Heba A. , Mohamed Ragab H.
Published: January 2024

Background

Camel filariasis induced variable clinical syndromes characterized by fever, lethargy, localized dermal lesions, loss of condition, and testicular and scrotal swelling. The objective of the present work focused on clarifying the diagnostic importance of clinical findings, serum testosterone, and semen analysis as well as blood smear and testicular histopathology as a differential tool between only balanoposthitis without filariasis male camels group (OnlyBpgr) and balanoposthitis-filariasis infected male camels group (BpFlgr). The study also monitored the associations between the severity of ticks’ infestations in investigated male camels and the occurrence of balanoposthitis only or balanoposthitis with filariasis.

Results and conclusions

The study reported significant correlation between serum testosterone, serum cortisol, and sperm vitality and abnormalities percentages. The study included male camels (n = 250) classified into three groups: healthy control group (Contgr; n = 30), OnlyBpgr (n = 210), and BpFlgr (n = 10). These male camels were clinically and laboratory examined, and skin scraping tests and testicular histopathology were conducted. The study confirmed the association of the changes in clinical findings, whole blood picture, serum testosterone, serum cortisol, and semen analysis, with OnlyBpgr and BpFlgr. These changes were more prominent in BpFlgr than in OnlyBpgr. Skin scraping test results revealed a higher severity of live ticks’ infestation in BpFlgr than in OnlyBpgr because, unlike OnlyBpgr, all camels in BpFlgr (n = 10) were suffering from live ticks’ infestation. It also concluded the higher efficacy of histopathology of testicular tissues in male camels as a diagnostic tool for adult filaria in balanoposthitis-affected male camels than blood smear because all cases of camel filariasis in the current work were negative for microfilaria on microscopic examination of diurnal blood smear as well as testicular histopathology revealed detection of adult filaria in all camel filariasis associated with balanoposthitis. Strong correlation relationships were demonstrated between serum testosterone, serum cortisol, and semen analysis results. Positive correlations were reported between serum testosterone levels and sperm vitality percentages. However, negative correlations were stated between serum testosterone and each of serum cortisol and sperm abnormalities either in Contgr, OnlyBpgr, or BpFlgr.
Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes
Authors: González-Lleó Ana M. , Sánchez-Hernández Rosa M. , Plana Núria , Ibarretxe Daiana , Rehues Pere , Ribalta Josep , Llop Dídac , Wägner Ana M. , Masana Lluís , Boronat Mauro
Published: January 2024

Background

The diabetogenic effect of statins has been well established by clinical trials, Mendelian randomisation studies and meta-analyses. According to large clinical trials, PCSK9 inhibitors (PCSK9i) have no deleterious impact on glucose metabolism. However, few real-life studies have yet evaluated the long-term effects of these drugs on glucose homeostasis and their impact on new-onset diabetes (NODM).

Methods

We studied 218 patients treated with either alirocumab or evolocumab (70% with familial hypercholesterolemia) for at least three years (PCSK9iG). We studied the NODM rate in the nondiabetic group at baseline (168) and overall glucose metabolism control in the whole group. Incidental DM was compared with two groups. The first was a propensity score matching (PSM)-selected group (n = 168) from the database of patients attending the Reus lipid unit (Metbank, n = 745) who were not on PCSK9i (PSMG). The second was a subgroup with a similar age range (n = 563) of the Di@bet.es study (Spanish prospective study on diabetes development n = 5072) (D@G). The incidence was reported as the percentage of NODM cases per year.

Results

The fasting glucose (FG) level of the subjects with normoglycaemia at baseline increased from 91 (86-95.5) to 93 (87–101) mg/dL (p = 0.014). There were 14 NODM cases in the PCSK9i group (2.6%/y), all among people with prediabetes at baseline. The incidence of NODM in PSMG and D@G was 1.8%/y (p = 0.69 compared with the PCSK9iG). The incidence among the subjects with prediabetes was 5.1%/y in the PCSK9iG, 4.8%/y in the PSMG and 3.9%/y in the D@G (p = 0.922 and p = 0.682, respectively). In the multivariate analysis, only the FG level was associated with the development of NODM in the PCSK9iG (OR 1.1; 95% CI: 1.0-1.3; p = 0.027). Neither FG nor A1c levels changed significantly in patients with DM at baseline.

Conclusion

A nonsignificant increase in NODM occurred in the PCSK9iG, particularly in patients with prediabetes, compared with the PSMG and D@G groups. Baseline FG levels were the main variable associated with the development of DM. In the subjects who had DM at baseline, glucose control did not change. The impact of PCSK9i on glucose metabolism should not be of concern when prescribing these therapies.
Three new LmbU targets outside lmb cluster inhibit lincomycin biosynthesis in Streptomyces lincolnensis
Authors: Mao Yue , Zhang Xianyan , Zhou Tianyu , Hou Bingbing , Ye Jiang , Wu Haizhen , Wang Ruida , Zhang Huizhan
Published: January 2024

Background

Antibiotics biosynthesis is usually regulated by the cluster-situated regulatory gene(s) (CSRG(s)), which directly regulate the genes within the corresponding biosynthetic gene cluster (BGC). Previously, we have demonstrated that LmbU functions as a cluster-situated regulator (CSR) of lincomycin. And it has been found that LmbU regulates twenty non-lmb genes through comparative transcriptomic analysis. However, the regulatory mode of CSRs’ targets outside the BGC remains unknown.

Results

We screened the targets of LmbU in the whole genome of Streptomyces lincolnensis and found fourteen candidate targets, among which, eight targets can bind to LmbU by electrophoretic mobility shift assays (EMSA). Reporter assays in vivo revealed that LmbU repressed the transcription of SLINC_0469 and SLINC_1037 while activating the transcription of SLINC_8097. In addition, disruptions of SLINC_0469, SLINC_1037, and SLINC_8097 promoted the production of lincomycin, and qRT-PCR showed that SLINC_0469, SLINC_1037, and SLINC_8097 inhibited transcription of the lmb genes, indicating that all the three regulators can negatively regulate lincomycin biosynthesis.

Conclusions

LmbU can directly regulate genes outside the lmb cluster, and these genes can affect both lincomycin biosynthesis and the transcription of lmb genes. Our results first erected the cascade regulatory circuit of LmbU and regulators outside lmb cluster, which provides the theoretical basis for the functional research of LmbU family proteins.
Bioelectricity in dental medicine: a narrative review
Authors: Min Qingqing , Gao Yajun , Wang Yao
Published: January 2024

Background

Bioelectric signals, whether exogenous or endogenous, play crucial roles in the life processes of organisms. Recently, the significance of bioelectricity in the field of dentistry is steadily gaining greater attention.

Objective

This narrative review aims to comprehensively outline the theory, physiological effects, and practical applications of bioelectricity in dental medicine and to offer insights into its potential future direction. It attempts to provide dental clinicians and researchers with an electrophysiological perspective to enhance their clinical practice or fundamental research endeavors.

Methods

An online computer search for relevant literature was performed in PubMed, Web of Science and Cochrane Library, with the keywords “bioelectricity, endogenous electric signal, electric stimulation, dental medicine.”

Results

Eventually, 288 documents were included for review. The variance in ion concentration between the interior and exterior of the cell membrane, referred to as transmembrane potential, forms the fundamental basis of bioelectricity. Transmembrane potential has been established as an essential regulator of intercellular communication, mechanotransduction, migration, proliferation, and immune responses. Thus, exogenous electric stimulation can significantly alter cellular action by affecting transmembrane potential. In the field of dental medicine, electric stimulation has proven useful for assessing pulp condition, locating root apices, improving the properties of dental biomaterials, expediting orthodontic tooth movement, facilitating implant osteointegration, addressing maxillofacial malignancies, and managing neuromuscular dysfunction. Furthermore, the reprogramming of bioelectric signals holds promise as a means to guide organism development and intervene in disease processes. Besides, the development of high-throughput electrophysiological tools will be imperative for identifying ion channel targets and precisely modulating bioelectricity in the future.

Conclusions

Bioelectricity has found application in various concepts of dental medicine but large-scale, standardized, randomized controlled clinical trials are still necessary in the future. In addition, the precise, repeatable and predictable measurement and modulation methods of bioelectric signal patterns are essential research direction.

Graphical abstract
Changes in tuberculosis risk after transplantation in the setting of decreased community tuberculosis incidence: a national population-based study, 2008–2020
Authors: Hyun JongHoon , Lee Myeongjee , Jung Inkyung , Kim Eunhwa , Hahn Seung Min , Kim Yu Ri , Lim Sungmin , Ihn Kyong , Kim Min Young , Ahn Jong Gyun , Yeom Joon-Sup , Jeong Su Jin , Kang Ji-Man
Published: January 2024

Background

Transplant recipients are immunocompromised and vulnerable to developing tuberculosis. However, active tuberculosis incidence is rapidly declining in South Korea, but the trend of tuberculosis infection among transplant recipients has not been elucidated. This study aimed to evaluate the risk of active tuberculosis after transplantation, including risk factors for tuberculosis and standardized incidence ratios, compared with that in the general population.

Methods

This retrospective study was conducted based on the South Korean health insurance review and assessment database among those who underwent transplantation (62,484 recipients) between 2008 and 2020. Tuberculosis incidence was compared in recipients treated during higher- (2010–2012) and lower-disease burden (2016–2018) periods. Standardized incidence ratios were analyzed using the Korean Tuberculosis Surveillance System. The primary outcome was the number of new tuberculosis cases after transplantation.

Results

Of 57,103 recipients analyzed, the overall cumulative incidence rate 1 year after transplantation was 0.8% (95% confidence interval [CI]: 0.7–0.8), significantly higher in the higher-burden period than in the lower-burden period (1.7% vs. 1.0% 3 years after transplantation, P < 0.001). Individuals who underwent allogeneic hematopoietic stem cell transplantation had the highest tuberculosis incidence, followed by those who underwent solid organ transplantation and autologous hematopoietic stem cell transplantation (P < 0.001). The overall standardized incidence ratio was 3.9 (95% CI 3.7–4.2) and was the highest in children aged 0–19 years, at 9.0 (95% CI 5.7–13.5). Male sex, older age, tuberculosis history, liver transplantation, and allogeneic hematopoietic stem cell transplantation were risk factors for tuberculosis.

Conclusions

Transplant recipients are vulnerable to developing tuberculosis, possibly influenced by their immunocompromised status, solid organ transplant type, age, and community prevalence of tuberculosis. Tuberculosis prevalence by country, transplant type, and age should be considered to establish an appropriate tuberculosis prevention strategy for high-risk groups.

Graphical Abstract
The progression of inorganic nanoparticles and natural products for inflammatory bowel disease
Authors: Li Qingrong , Lin Liting , Zhang Cong , Zhang Hengguo , Ma Yan , Qian Haisheng , Chen Xu-Lin , Wang Xianwen
Published: January 2024

There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract).

Graphical Abstract
M2 microglia-derived exosome-loaded electroconductive hydrogel for enhancing neurological recovery after spinal cord injury
Authors: Guan Pengfei , Fan Lei , Zhu Zhaobo , Yang Qinfeng , Kang Xinchang , Li Junji , Zhang Zuyu , Liu Shencai , Liu Can , Wang Xuelian , Xu Jing , Wang Kun , Sun Yongjian
Published: January 2024

Electroconductive hydrogels offer a promising avenue for enhancing the repair efficacy of spinal cord injuries (SCI) by restoring disrupted electrical signals along the spinal cord’s conduction pathway. Nonetheless, the application of hydrogels composed of diverse electroconductive materials has demonstrated limited capacity to mitigate the post-SCI inflammatory response. Recent research has indicated that the transplantation of M2 microglia effectively fosters SCI recovery by attenuating the excessive inflammatory response. Exosomes (Exos), small vesicles discharged by cells carrying similar biological functions to their originating cells, present a compelling alternative to cellular transplantation. This investigation endeavors to exploit M2 microglia-derived exosomes (M2-Exos) successfully isolated and reversibly bonded to electroconductive hydrogels through hydrogen bonding for synergistic promotion of SCI repair to synergistically enhance SCI repair. In vitro experiments substantiated the significant capacity of M2-Exos-laden electroconductive hydrogels to stimulate the growth of neural stem cells and axons in the dorsal root ganglion and modulate microglial M2 polarization. Furthermore, M2-Exos demonstrated a remarkable ability to mitigate the initial inflammatory reaction within the injury site. When combined with the electroconductive hydrogel, M2-Exos worked synergistically to expedite neuronal and axonal regeneration, substantially enhancing the functional recovery of rats afflicted with SCI. These findings underscore the potential of M2-Exos as a valuable reparative factor, amplifying the efficacy of electroconductive hydrogels in their capacity to foster SCI rehabilitation.
Clinical impact of ampulla of Vater cancer subtype classification based on immunohistochemical staining
Authors: Kwon Chae Hwa , Ahn Ji Hyun , Seo Hyung Il , Kim Dong Uk , Han Sung Yong , Kim Suk , Lee Nam Kyung , Hong Seung Baek , Park Young Mok , Noh Byeong Gwan
Published: January 2024

Background

The histological subtype is an important prognostic factor for ampulla of Vater (AoV) cancer. This study proposes a classification system for the histological subtyping of AoV cancer based on immunohistochemical (IHC) staining and its prognostic significance.

Methods

Seventy-five AoV cancers were analyzed for cytokeratin 7 (CK7), CK20, and causal-type homeobox transcription factor 2 (CDX2) expression by IHC staining. We differentiated the subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) into classification I: CK7/CK20, classification II: CK7/CK20 or CDX2, classification III: CK7/CDX2 and examined their associations with clinicopathological factors.

Results

Classifications I, II, and III subtypes were INT (7, 10, and 10 cases), PB (43, 37, and 38 cases), MIX (13, 19, and 18 cases), and NOS (12, 9, and 9 cases). Significant differences in disease-free survival among the subtypes were observed in classifications II and III using CDX2; the PB and NOS subtype exhibited shorter survival time compared with INT subtype. In classification III, an association was revealed between advanced T/N stage, poor differentiation, lymphovascular invasion (LVI), the PB and NOS subtypes, and recurrence risk. In classification III, the subtypes differed significantly in T/N stage and LVI. Patients with the PB subtype had advanced T and N stages and a higher incidence of LVI.

Conclusions

Classification using CDX2 revealed subtypes with distinct prognostic significance. Combining CK7 and CDX2 or adding CDX2 to CK7/CK20 is useful for distinguishing subtypes, predicting disease outcomes, and impacting the clinical management of patients with AoV cancer.
Prognostic and clinicopathological significance of C-reactive protein in patients with ovarian cancer: a meta-analysis
Authors: Zhang Wei , Zhang Zongxin , Qian Lihong
Published: January 2024

Background

Many studies have explored the relationship between C-reactive protein (CRP) levels and survival outcomes in patients with ovarian cancer (OC); however, consistent results have not been reported. As such, this meta-analysis was performed to accurately assess the prognostic and clinicopathological roles of CRP in OC.

Methods

The PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched for relevant studies published from inception to April 7, 2023. The effect of CRP level(s) and OC prognostic outcomes was analyzed by computing the combined hazard ratio (HR) and corresponding 95% confidence interval (CI). Thereafter, the association between CRP level(s) and clinicopathological factors was evaluated using a combined odds ratio (OR) and corresponding 95% CI.

Results

The present meta-analysis included 15 studies comprising 3202 subjects. According to the combined data, higher CRP levels were markedly associated with unfavorable overall survival (OS) (HR 1.23 [95% CI 1.11–1.37]; p < 0.001) and progression-free survival (PFS) (HR 1.55 [95% CI 1.30–1.84]; p < 0.001) in patients with OC. Furthermore, the results indicated that high CRP levels were significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stages III–IV (p < 0.001), residual tumor size ≥ 1 cm (p < 0.001), histological grade 3 (p = 0.040), and ascites volume ≥ 500 mL (p < 0.001).

Conclusion

The results of this meta-analysis demonstrated that higher serum CRP levels were strongly associated with dismal OS and PFS in subjects with OC. High CRP levels were also significantly associated with clinical factors implicated in tumor aggressiveness and the development of OC.
Brief communications: changes in inflammatory biomarkers and lipid profiles after switching to long-acting cabotegravir plus rilpivirine
Authors: Adachi Eisuke , Saito Makoto , Otani Amato , Koga Michiko , Yotsuyanagi Hiroshi
Published: January 2024

We assessed whether the impact of cabotegravir plus rilpivirine on inflammation reduction differs from that of oral antiretrovirals, using real-world data. Inflammatory biomarkers and lipid profiles were followed from baseline to 8 months after switching. Seventy-eight participants were analyzed. The CD4/CD8 ratio and C-reactive protein did not change. There were transient decreases in CD8 and CD4 counts in the group that switched from the dolutegravir-based regimen, but not in the tenofovir alafenamide-based regimen group. High-density lipoprotein (HDL) cholesterol increased, resulting in a decrease in the total-cholesterol to HDL cholesterol ratio, whereas there was no significant change in low-density lipoprotein cholesterol.