bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing an interprofessional decision support tool for diabetic foot ulcers management in primary care within the family medicine group model: a Delphi study in Canada
Authors: Brousseau-Foley Magali , Blanchette Virginie , Houle Julie , Trudeau François
Published: April 2024

Background

Primary care professionals encounter difficulties coordinating the continuum of care between primary care providers and second-line specialists and adhere to practice guidelines pertaining to diabetic foot ulcers management. Family medicine groups are providing primary care services aimed to improve access, interdisciplinary care, coordination and quality of health services, and reduce emergency department visits. Most professionals working in family medicine groups are primary care physicians and registered nurses. The aim of this study was to develop and validate an interprofessional decision support tool to guide the management of diabetic foot ulcers for primary care professionals working within the family medicine group model.

Methods

A one-page decision tool developed by the research team was validated by an expert panel using a three-round Delphi protocol held between December 2019 and August 2021. The tool includes 43 individual actions and a care pathway from initial presentation to secondary prevention. Data collection was realized with both paper and electronic questionnaires, and answers were compiled in an electronic spreadsheet. Data was analyzed with use of descriptive statistics, and consensus for each item was defined as ≥ 80% agreement.

Results

Experts from 12 pre-identified professions of the diabetic foot ulcer interdisciplinary care team were included, 39 participants out of the 59 invited to first round (66.1%), 34 out of 39 for second (87.2%) and 22 out of 34 for third (64.7%) rounds. All items included in the final version of the decision support tool reached consensus and were deemed clear, relevant and feasible. One or more professionals were identified to be responsible for every action to be taken.

Conclusions

This study provided a comprehensive decision support tool to guide primary care professionals in the management of diabetic foot ulcers. Implementation and evaluation in the clinical setting will need to be undertaken in the future.
Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer
Authors: Choi Yonghwa , Lee Jangwoo , Shin Keewon , Lee Ji Won , Kim Ju Won , Lee Soohyeon , Choi Yoon Ji , Park Kyong Hwa , Kim Jwa Hoon
Published: April 2024

Background

Paclitaxel is commonly used as a second-line therapy for advanced gastric cancer (AGC). The decision to proceed with second-line chemotherapy and select an appropriate regimen is critical for vulnerable patients with AGC progressing after first-line chemotherapy. However, no predictive biomarkers exist to identify patients with AGC who would benefit from paclitaxel-based chemotherapy.

Methods

This study included 288 patients with AGC receiving second-line paclitaxel-based chemotherapy between 2017 and 2022 as part of the K-MASTER project, a nationwide government-funded precision medicine initiative. The data included clinical (age [young-onset vs. others], sex, histology [intestinal vs. diffuse type], prior trastuzumab use, duration of first-line chemotherapy), and genomic factors (pathogenic or likely pathogenic variants). Data were randomly divided into training and validation sets (0.8:0.2). Four machine learning (ML) methods, namely random forest (RF), logistic regression (LR), artificial neural network (ANN), and ANN with genetic embedding (ANN with GE), were used to develop the prediction model and validated in the validation sets.

Results

The median patient age was 64 years (range 25–91), and 65.6% of those were male. A total of 288 patients were divided into the training (n = 230) and validation (n = 58) sets. No significant differences existed in baseline characteristics between the training and validation sets. In the training set, the areas under the ROC curves (AUROC) for predicting better progression-free survival (PFS) with paclitaxel-based chemotherapy were 0.499, 0.679, 0.618, and 0.732 in the RF, LR, ANN, and ANN with GE models, respectively. The ANN with the GE model that achieved the highest AUROC recorded accuracy, sensitivity, specificity, and F1-score performance of 0.458, 0.912, 0.724, and 0.579, respectively. In the validation set, the ANN with GE model predicted that paclitaxel-sensitive patients had significantly longer PFS (median PFS 7.59 vs. 2.07 months, P = 0.020) and overall survival (OS) (median OS 14.70 vs. 7.50 months, P = 0.008). The LR model predicted that paclitaxel-sensitive patients showed a trend for longer PFS (median PFS 6.48 vs. 2.33 months, P = 0.078) and OS (median OS 12.20 vs. 8.61 months, P = 0.099).

Conclusions

These ML models, integrated with clinical and genomic factors, offer the possibility to help identify patients with AGC who may benefit from paclitaxel chemotherapy.
Comparative characteristics of early-onset vs. late-onset advanced colorectal cancer: a nationwide study in China
Authors: Liu Hongwei , Xu Huifang , Liu Yin , Zhao Yuqian , Zhang Xi , Yu Yanqin , Du Lingbin , Liu Yunyong , Wang Wenjun , Cao Helu , Ma Li , Huang Juanxiu , Cao Ji , Li Li , Fan Yanping , Gu Xiaofen , Feng Changyan , Zhu Qian , Wang Xiaohui , Du Jingchang , Zhang Shaokai , Qiao Youlin
Published: April 2024

Background

The incidence of early-onset colorectal cancer (EOCRC, diagnosed in patients under the age of 50 years) has been increasing around the world. Here, we aimed to systematically identify distinctive features of EOCRC.

Methods

From 2020 to 2021, we conducted a nationwide survey in 19 hospitals, collecting data on advanced CRC patients’ demographics, clinical features, disease knowledge, medical experiences, expenditures, and health-related quality of life (HRQOL). We compared these features between EOCRC and late-onset colorectal cancer (LOCRC, ≥ 50 years old) groups and analyzed the association between EOCRC and HRQOL using multivariate linear regression.

Findings

In total, 991 patients with EOCRC and 3581 patients with LOCRC were included. Compared to the LOCRC group, the EOCRC group had higher levels of education, were more informed about the risk factors for CRC, were more likely to have widespread metastases throughout the body, were more inclined to undergo gene testing, and were more likely to opt for targeted therapy, radiotherapy, and chemotherapy. However, HRQOL in the EOCRC group was similar to that of the LOCRC group, and no significant association was observed between EOCRC and HRQOL (beta: -0.753, P value: 0.307).

Interpretation

In Chinese patients, EOCRC patients had more aggressive features. Despite undergoing more intensified treatments and gene testing, they had similar HRQOL compared with LOCRC. These findings advocate for a more tailored approach to treatment, especially for young CRC patients with advanced TNM stages and metastasis.
The impact of combined administration of surfactant and intratracheal budesonide compared to surfactant alone on bronchopulmonary dysplasia (BPD) and mortality rate in preterm infants with respiratory distress syndrome: a single-blind randomized clinical trial
Authors: Marzban Asghar , Mokhtari Samira , Tavakkolian Pouria , Mansouri Reza , Jafari Nahid , Maleki Azam
Published: April 2024

Background

Respiratory distress syndrome (RDS) is one of the most important and common disorders among premature infants.

Objective

This study aimed to compare the effect of the combination of surfactant and budesonide with surfactant alone on Bronchopulmonary dysplasia (BPD) and mortality rate among premature infants with RDS.

Method

An outcome assessor-blind randomized clinical trial was conducted on 134 premature infants with RDS who were born in Ayatollah Mousavi Hospital, Zanjan, Iran in 2021. The covariate adaptive randomization method was utilized to allocate participants into two groups (surfactant alone and a combination of surfactant and budesonide). The primary outcomes were BPD and Mortality rate from admission to hospital discharge. The data in this study were analyzed using SPSS software version 18.

Results

Overall the comparison of mortality rate and BPD between the two groups did not show a significant difference(p > 0.05). The subgroup results showed that administering surfactant with budesonide to infants under 30 weeks of age significantly reduced the number of deaths compared to using surfactant alone (5 vs. 17). Similar positive effects were observed for the occurrence of Pulmonary Hemorrhage, the need for a second dose of surfactant, oxygen index, mean blood pressure and mean arterial pressure (MAP) in infants under 34 weeks of age compared to more than 34 weeks (p < 0.05).

Conclusion

These findings suggest that the combination therapy of surfactant and budesonide may be beneficial, particularly in preterm infants with less than 34 weeks gestational age and 1500 birth weight. However, further studies with larger sample sizes and longer follow-up periods are needed to confirm these results and assess long-term outcomes.

Trial registration

The study was registered at the Iranian Registry of Clinical Trials website under the code IRCT20201222049802N1. https://en.irct.ir/user/trial/48117/view.

Registration date

28/02/2021.

Public repository: Data set

This research data set link is displayed on the Zanjan-Iran Medical Sciences website: https://repository.zums.ac.ir/cgi/users/login? target=https%3 A%2 F/repository.zums.ac.ir/id/eprint.
Diet and lifestyle behaviours simultaneously act on frailty: it is time to move the threshold of frailty prevention and control forward
Authors: Yang Shan-lan , Wu Lei , Huang He-lang , Zhang Lang-lang , Chen Yi-xin , Zhou Sheng , Chen Xiu-xiu , Wang Jiao-feng , Zhang Chao-bao , Bao Zhi-jun
Published: April 2024

Background

To analyse the association among the simultaneous effects of dietary intake, daily life behavioural factors, and frailty outcomes in older Chinese women, we predicted the probability of maintaining physical robustness under a combination of different variables.

Methods

The Fried frailty criterion was used to determine the three groups of “frailty”, “pre-frailty”, and “robust”, and a national epidemiological survey was performed. The three-classification decision tree model was fitted, and the comprehensive performance of the model was evaluated to predict the probability of occurrence of different outcomes.

Results

Among the 1,044 participants, 15.9% were frailty and 50.29% were pre-frailty; the overall prevalence first increased and then decreased with age, reaching a peak at 70–74 years of age. Through univariate analysis, filtering, and embedded screening, eight significant variables were identified: staple food, spices, exercise (frequency, intensity, and time), work frequency, self-feeling, and family emotions. In the three-classification decision tree, the values of each evaluation index of Model 3 were relatively average; the accuracy, recall, specificity, precision, and F1 score range were between 75% and 84%, and the AUC was also greater than 0.800, indicating excellent performance and the best interpretability of the results. Model 3 takes exercise time as the root node and contains 6 variables and 10 types, suggesting the impact of the comprehensive effect of these variables on robust and non-robust populations (the predicted probability range is 6.67–93.33%).

Conclusion

The combined effect of these factors (no exercise or less than 0.5 h of exercise per day, occasional exercise, exercise at low intensity, feeling more tired at work, and eating too many staple foods (> 450 g per day) are more detrimental to maintaining robustness.
Factors affecting safe pesticide-use behaviors among farm plant agriculturists in northeastern Thailand
Authors: Suphim Bunliang , Songthap Archin
Published: April 2024

Background

Pesticide poisoning is a major public health problem in Thailand and is the result of intensive inappropriate and unsafe use of pesticides. This analytical cross-sectional study aimed to determine the factors affecting safe pesticide-use behaviors among farm plant agriculturists in northeastern Thailand.

Methods

The study sample included 427 farm plant agriculturists in Loei Province, northeastern Thailand. Individuals were randomly selected by a multistage random sampling technique. The following data were collected via a self-administered questionnaire consisting of 8 parts: (1) sociodemographic characteristics, (2) knowledge about pesticide use, (3) perceived severity of impact from pesticide use among farm plant agriculturists, (4) perceived susceptibility to pesticide use, (5) perceived self-efficacy in the modification of safe pesticide-use behaviors, (6) perceived outcome of the modification of safe pesticide-use behaviors, (7) social support, and (8) safe pesticide-use behaviors. Frequencies, percentages, means, standard deviations, and multiple regression analyses were employed for data analysis.

Results

The majority of participants (79.4%) had high scores for safe pesticide-use behaviors among farm plant agriculturists (scores of 112–150). Factors that significantly affected safe pesticide-use behaviors included knowledge about pesticide use (β = 0.282), social support (β = 0.217), reading information from pesticide labels before pesticide use (β = 0.207), perceived self-efficacy (β = 0.186), female sex (β = -0.140), rice farmer status (β = 0.129), corn farmer status (β = 0.127), perceived susceptibility (β = 0.126), having received information from the internet (β = -0.124), and perceived severity (β = -0.098). Together, these 10 factors were found to explain 32.5% of the safe pesticide-use behaviors among farm plant agriculturists.

Conclusions

Our findings indicate that there is a need to increase the number of promotional activities related to the safe use of pesticides through social support and training, with the aim of increasing the overall level of knowledge, perceived self-efficacy, perceived susceptibility, and modification of the perceived impact severity of pesticide use. Thus, relevant agencies should promote and support the safe use of pesticides by farm plant agriculturists.

This study revealed that the factors affecting safe pesticide-use behaviors among farm plant agriculturists included knowledge about pesticide use, social support, reading pesticide container labels, perceived self-efficacy in the modification of pesticide-use behaviors, sex, rice farmer status, corn farmer status, perceived susceptibility to pesticide use, having received information from the internet, and perceived severity of impact from pesticide use.
The effects of different positions on lower extremity hemodynamics during robot-assisted laparoscopic radical prostatectomy for prostate cancer
Authors: Wang Zheng , Wang Xinyu , Yu Xiaofen
Published: April 2024

Purpose

This study aimed to investigate the effects of two different positions on lower extremity hemodynamics during robot-assisted laparoscopic radical prostatectomy (RARP) for prostate cancer.

Methods

A total of 196 patients who underwent RARP in our hospital from February 2020 to March 2022 were included in this study. Among them, 98 patients who underwent surgery with the Trendelenburg position and split-leg position with calf reverse arch from March 2021 to March 2022 were assigned to the observation group, while 98 patients who underwent surgery with the Trendelenburg position and low lithotomy position from February 2020 to February 2021 were assigned to the control group. Using an ultrasound diagnostic instrument to detect the internal diameter, mean blood flow velocity, and mean blood flow volume of the left deep femoral vein at different times, such as the supine position (T0), after 5 minutes of placing the patient in the leg spilt or low lithotomy position (T1), after 5 minutes of pneumoperitoneum (T2), after 5 minutes of head-down tilt or head-down tilt and calf reverse arch (T3), 1.5 hours after the start of surgery (T4), before the removal of CO2 gas (T5), and before the patient left the operating room (T6). As well as the patency of deep venous blood flow in both lower extremities before leaving the operating room,

Results

After establishment of pneumoperitoneum, the internal diameter of the deep femoral vein increased significantly, while the mean blood flow velocity and mean blood flow volume decreased significantly in both groups(T0) (P<0.001). With the prolongation of surgical time, the impact on lower extremity hemodynamics in the observation group was smaller than that in the control group. From T2 to T6, the internal diameter of the femoral vein in the observation group was smaller than that in the control group, while the mean blood flow velocity and mean blood flow volume were increased compared to the control group (P<0.05). Before leaving the operating room, the patency of deep venous blood flow in the observation group was better than that in the control group (P=0.003).

Conclusion

Placing patients in the Trendelenburg position and split-leg position with calf reverse arch during RARP for prostate cancer has a smaller impact on lower extremity hemodynamics than the low lithotomy position, and can relatively reduce the risk of postoperative deep vein thrombosis.
Postoperative pain after single-visit root canal treatments in necrotic teeth comparing instruments’ kinematics and apical instrumentation limits – a prospective randomized multicenter clinical trial
Authors: Machado Ricardo , Moreira Guilherme , Comparin Daniel , Barroso Arthur Pimentel , Nascimento Jaqueline , Ferraz Caio Cézar Randi , Ignácio Sérgio Aparecido , da Fonseca Roberti Garcia Lucas , Amaral Rodrigo Rodrigues , Shadid David , da Silva Neto Ulisses Xavier
Published: April 2024

Objectives

This prospective randomized multicenter clinical trial (PRMCT) investigated postoperative pain after single-visit root canal treatments in teeth affected by pulp necrosis (PN), and asymptomatic apical periodontitis (AAP) (with apical radiolucent areas) or normal periradicular tissues (without apical radiolucent areas) comparing different instruments' kinematics and apical instrumentation limits.

Methods

Before chemomechanical preparation, 240 patients/teeth were randomly distributed into four groups (n = 60) according to the instruments' kinematics (rotary or reciprocating) and apical instrumentation limits (with or without intentional foraminal enlargement [IFE]). After that, specimens were submitted to the same irrigation and obturation techniques, and the patients were referred to undergo the definitive restorations. No medication was prescribed, but the patients were instructed to take either paracetamol (750 mg every 6 h for three days) or ibuprofen (600 mg every 6 h for three days) in pain cases. Postoperative pain incidence and levels were assessed at 24-, 48-, and 72 h following treatment completion according to a verbal rating scale (VRS) following a score. The Kolmogorov–Smirnov test was applied to assess the normality of the data. Mann–Whitney U, Chi-square, Friedman's ANOVA, and Friedman's multiple 2 to 2 comparison tests were employed to identify potential significant statistical differences among the variables in the study groups (P < .05).

Results

Significant statistical differences were only observed among the groups considering tooth, periradicular status, and the occurrence of overfilling (sealer extrusion) (P < 0.00). Patients with teeth instrumented through rotary kinematics and without IFE experienced lower rates of postoperative pain; however, this difference was relevant only at 24 h (P < 0.05).

Conclusions

Postoperative pain was lower after using a rotary file system (Profile 04) inserted up to the apical constriction (AC). However, this finding was just statistically meaningful at 24 h.

Trial registration

This PRMCT was approved by the Human Research Ethics Committee of the Paranaense University – UNIPAR, Francisco Beltrão, PR, Brazil (CAAE. 46,774,621.6.0000.0109) on 02/09/2021. It was registered at The Brazilian Registry of Clinical Trials – ReBEC (RBR-3r967t) on 01/06/2023, was performed according to the Principles of the Helsinki Declaration and is reported following the Consolidated Standards of Reporting Trials Statement.
Micro-computed tomographic evaluation on the quality of single-cone obturation using a modified passive-deflation sealer injection needle: an in vitro study
Authors: Chen Zhuo , Chen Nuo , Yang Yanling , Fan Wei
Published: April 2024

Objectives

This study aimed to design a modified passive-deflation sealer injection needle and investigate its ability to improve obturation quality of single-cone technique through assessing the distribution of voids in root canals using micro-computed tomography (micro-CT).

Materials and methods

Forty-eight mandibular incisors were divided into eight groups (n = 6), according to the taper of root canal preparation (0.06 or 0.04), the needle used for sealer injection (modified or commercial iRoot SP injection needle), and the obturation method (iRoot SP sealer-only or single-cone obturation). After obturation, each specimen was scanned by micro-CT. The volumetric percentage and distribution of all voids were first analyzed and compared among groups, then the open and closed voids were separately analyzed and compared among single-cone obturation groups.

Results

Compared to commercial needle groups, modified needle groups showed much less voids, especially in the apical root canal part (P < 0.05). Besides, the modified needle groups produced much less open voids than commercial needle groups despite the root canal taper (P < 0.05).

Conclusions

The modified passive deflation sealer injection needle could effectively improve the quality of single-cone obturation through reducing intra-canal voids, especially open voids throughout the root canal, thus might possibly be developed as an effective intra-canal sealer delivering instrument.
Orthodontists’ use of remote monitoring platforms pre-, amid, and post-COVID-19: a survey study
Authors: Logan Sophie , Riedy Christine A. , Hargett Kadriye , Katebi Negin
Published: April 2024

Background

Did the COVID-19 pandemic affect orthodontists’ use of remote monitoring platforms? The goal of this research was to examine orthodontists’ experiences implementing remote monitoring platforms before, during, and after the initial COVID-19 lockdown.

Methods

In this descriptive cross-sectional survey study, an electronic, anonymous questionnaire consisting of a series of 31 short-answer and multiple-choice questions was administered to an international sampling of practicing orthodontists. The target population in the study included currently practicing orthodontists who were graduates of an accredited orthodontic residency program. Participants were recruited in 2021 through collaboration with the American Association of Orthodontists (AAO) Partners in Research Program and the Harvard School of Dental Medicine Orthodontic Alumni Association. Descriptive analysis was conducted, reporting frequency (N and %) distributions for each question. The questionnaire aimed to describe whether orthodontists incorporated remote monitoring platforms into their practices, their experiences doing so, and if the COVID-19 pandemic influenced their use of these resources.

Results

Orthodontists’ use of remote monitoring platforms was negligible prior to the pandemic; however, a quarter of surveyed orthodontists began using a remote monitoring platform during COVID-19 and nearly all respondents plan to continue using remote monitoring for the foreseeable future. Approximately half of orthodontists believe most patients’ treatment progress can be monitored to the standard of care between in-person orthodontic appointments using remote monitoring platforms. Half of the orthodontists who do not currently use a remote monitoring platform in their practice are interested in learning more about how to implement one.

Conclusions

The COVID-19 pandemic led to an increase in the interest and adoption of remote monitoring platforms in orthodontic practices. Most orthodontists had not incorporated remote monitoring platforms into their practices prior to the COVID-19 pandemic. However, this study revealed that a subset of orthodontists utilized the pandemic as motivation to incorporate remote monitoring into their practices and an additional group of orthodontists were interested in incorporating one in the future. Remote monitoring platforms garnered interest and importance with the arrival of the COVID-19 pandemic and may only have an increasing role in the field in years to come.
Skeletal, dentoalveolar and soft tissue changes after stabilization splint treatment for patients with temporomandibular joint disorders
Authors: Al-hadad Saba Ahmed , Ahmed Madiha Mohammed Saleh , Zhao Yunshan , Wang Lu , Hu Wanqing , Li Chushen , Chen Xi , Alhammadi Maged Sultan
Published: April 2024

Background

Temporomandibular disorder (TMD) is a grouping of heterogeneous disorders with multifactorial origins. Stabilization splints (SS) have demonstrated an acceptable treatment effect in TMD. The possible changes at the skeletal, dental, and soft tissue levels need to be addressed to evaluate the benefit/risk ratio of this therapeutic procedure. Accordingly, this study aimed to three‑dimensionally evaluate skeletal, dentoalveolar and soft tissue changes after SS treatment for patients with TMD.

Methods

This retrospective study included 74 adult patients with myofascial and/or intra-articular disorders (25 males and 49 females), with an average age of 22.88 ± 4.8 years, who underwent SS treatment. Pre- and post-treatment Cone beam computed tomography were analysed using Invivo 6.0.3 software. The primary outcome was the vertical skeletal and dentoalveolar changes, while the secondary outcomes were the anteroposterior skeletal, dentoalveolar and soft tissue changes. Paired t-test and Wilcoxon rank sum test were used for statistical analyses.

Results

For the primary outcome; skeletally, there was a significant increase in mandibular plane inclination (difference: 0.82°±1.37), decrease facial height ratio (difference: 0.45%±1.07) and at the dentoalveolar level, the inclination of the functional (FOP-SN, FOP-FH) and bisecting (BOP-SN, BOP-FH) occlusal planes exhibited a significant increase too (difference: 0.38 ± 1.43°, 0.49 ± 1.62°, 0.44 ± 1.29° and 0.41 ± 1.17°, respectively) and also a decrease in the overbite (difference: -0.54 ± 0.83). For the secondary outcomes; there was a significant decrease in mandibular position (SNB) (difference: 1.60 ± 1.36°) and increase in the overjet (difference: 0.93 ± 1.04, p < 0.001) and a significant lower lip retrusion (difference: 0.33 ± 1.01 mm p < 0.01), was observed too.

Conclusions

SS therapy resulted in significant vertical skeletal and dentoalveolar changes that were manifested mainly by facial height ratio, mandibular and occlusal plane changes, and to a lesser extent, significant anteroposterior skeletal, dentoalveolar, and soft tissue changes in the form of mandibular position, increased overjet and a more retrusive lower lip. These changes should be considered during patients’ selection prior to initiating SS therapy.
Sleep pattern and disorders among pregnant women in Ibadan, Southwest Nigeria
Authors: Ojelere Blessing O , Adeoye Ikeola A.
Published: April 2024

Background

Sleep is essential for pregnant women’s and the offspring’s health and wellbeing. Poor sleep and disorders have been linked with adverse fetal outcomes and delivery conditions. However, pregnant women often experience several forms of sleep disruption, which has been scarcely reported in low and middle-income countries (LMIC), including Nigeria where the influence of lifestyle factors has also been lacking. We investigated sleep patterns and disorders and the associated factors among pregnant women in Southwest, Nigeria.

Method

A cross-sectional study was conducted among five hundred (500) pregnant women attending Adeoyo Maternity Teaching Hospital. A semi-structured questionnaire was used to examine different domains of sleep and associated disorders, namely sleep quality (Pittsburgh Sleep Quality Index (> 5 and ≤ 5)), insomnia (Insomnia Severity Index (> 8 and ≤ 8)), restless leg syndrome (Restless Leg Syndrome Rating Scale (> 10 and ≤ 10). Significant covariates such as physical activity, minimum dietary diversity, smoking and alcohol intake were also assessed. We conducted bivariate and multivariate analysis at p < 0.05 significance level.

Results

The mean age of participants was 30.4 ± 4.8 years. The pattern of sleep disorder in pregnant were poor sleep quality (50%), restless leg syndrome (58.2%) and insomnia (33.4%). Being currently married (AOR = 6.13; 95% CI: (1.65–22.23)), increasing gestational age: second trimester (AOR = 8.25;95% CI: (1.78–38.17)) to third trimester (AOR = 10.98; 95% CI: (2.44–49.48)) increased the odds of poor sleep quality. Factors associated with restless leg syndrome were marital status [AOR = 3.60; 95% CI; (1.25–10.35)], religion, rigorous physical activities [AOR = 1.52; 95% CI: (1.05–2.21)] and alcohol consumption [AOR = 3.51; 95% CI: (1.00–12.27)]. Factors associated with insomnia were maternal age [AOR = 1.83; 95% CI: (1.11–3.01)], income [AOR = 2.99 (1.26–7.16)] and rigorous physical activity [AOR = 2.55 (1.61–4.02)].

Conclusion

Poor sleep quality, restless leg syndrome and insomnia were typical among pregnant women in Ibadan, Southwest Nigeria. Thus, awareness and education on the importance of sleep and its risk and protective factors, such as alcohol consumption, smoking, rigorous activity and spousal and family support, should be increased to reduce poor sleep quality and sleep disorders (restless leg syndrome and insomnia) during the pregnancy period.
Pharmacokinetic/pharmacodynamic evaluation of gamithromycin against rabbit pasteurellosis
Authors: Wei Xin-Yi , Zhang Jing , Zhang Yin , Fu Wen-Zhen , Zhong Long-Gen , Pan Yi-Duo , Sun Jian , Liao Xiao-Ping , Liu Ya-Hong , Zhou Yu-Feng
Published: April 2024

Background

Gamithromycin is an effective therapy for bovine and swine respiratory diseases but not utilized for rabbits. Given its potent activity against respiratory pathogens, we sought to determine the pharmacokinetic profiles, antimicrobial activity and target pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with therapeutic effect of gamithromycin against Pasteurella multocida in rabbits.

Results

Gamithromycin showed favorable PK properties in rabbits, including high subcutaneous bioavailability (86.7 ± 10.7%) and low plasma protein binding (18.5–31.9%). PK analysis identified a mean plasma peak concentration (Cmax) of 1.64 ± 0.86 mg/L and terminal half-life (T1/2) of 31.5 ± 5.74 h after subcutaneous injection. For P. multocida, short post-antibiotic effects (PAE) (1.1–5.3 h) and post-antibiotic sub-inhibitory concentration effects (PA-SME) (6.6–9.1 h) were observed after exposure to gamithromycin at 1 to 4× minimal inhibitory concentration (MIC). Gamithromycin demonstrated concentration-dependent bactericidal activity and the PK/PD index area under the concentration-time curve over 24 h (AUC24h)/MIC correlated well with efficacy (R2 > 0.99). The plasma AUC24h/MIC ratios of gamithromycin associated with the bacteriostatic, bactericidal and bacterial eradication against P. multocida were 15.4, 24.9 and 27.8 h in rabbits, respectively.

Conclusions

Subcutaneous administration of 6 mg/kg gamithromycin reached therapeutic concentrations in rabbit plasma against P. multocida. The PK/PD ratios determined herein in combination with ex vivo activity and favorable rabbit PK indicate that gamithromycin may be used for the treatment of rabbit pasteurellosis.
PPARγ attenuates cellular senescence of alveolar macrophages in asthma-COPD overlap
Authors: Wan Rongjun , Srikaram Prakhyath , Xie Shaobing , Chen Qiong , Hu Chengping , Wan Mei , Li Yuanyuan , Gao Peisong
Published: April 2024

Background

Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a complex condition characterized by shared clinical and pathophysiological features of asthma and COPD in older individuals. However, the pathophysiology of ACO remains unexplored. We aimed to identify the major inflammatory cells in ACO, examine senescence within these cells, and elucidate the genes responsible for regulating senescence.

Methods

Bioinformatic analyses were performed to investigate major cell types and cellular senescence signatures in a public single-cell RNA sequencing (scRNA-Seq) dataset derived from the lung tissues of patients with ACO. Similar analyses were carried out in an independent cohort study Immune Mechanisms Severe Asthma (IMSA), which included bulk RNA-Seq and CyTOF data from bronchoalveolar lavage fluid (BALF) samples.

Results

The analysis of the scRNA-Seq data revealed that monocytes/ macrophages were the predominant cell type in the lung tissues of ACO patients, constituting more than 50% of the cells analyzed. Lung monocytes/macrophages from patients with ACO exhibited a lower prevalence of senescence as defined by lower enrichment scores of SenMayo and expression levels of cellular senescence markers. Intriguingly, analysis of the IMSA dataset showed similar results in patients with severe asthma. They also exhibited a lower prevalence of senescence, particularly in airway CD206 + macrophages, along with increased cytokine expression (e.g., IL-4, IL-13, and IL-22). Further exploration identified alveolar macrophages as a major subtype of monocytes/macrophages driving cellular senescence in ACO. Differentially expressed genes related to oxidation-reduction, cytokines, and growth factors were implicated in regulating senescence in alveolar macrophages. PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) emerged as one of the predominant regulators modulating the senescent signature of alveolar macrophages in ACO.

Conclusion

The findings suggest that senescence in macrophages, particularly alveolar macrophages, plays a crucial role in the pathophysiology of ACO. Furthermore, PPARγ may represent a potential therapeutic target for interventions aimed at modulating senescence-associated processes in ACO.Key words ACO, Asthma, COPD, Macrophages, Senescence, PPARγ.
High LGALS3 expression induced by HCP5/hsa-miR-27b-3p correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma
Authors: Ren Yinghui , Qian Yongmei , Zhang Qicheng , Li Xiaoping , Li Mingjiang , Li Wei , Yang Pan , Ren Hengchang , Li Hongxia , Weng Yiqi , Li Dengwen , Xu Ke , Yu Wenli
Published: April 2024

Background

Hepatocellular carcinoma (HCC) is widely recognized for its unfavorable prognosis. Increasing evidence has revealed that LGALS3 has an essential function in initiating and developing several malignancies in humans. Nevertheless, thorough analysis of the expression profile, clinical prognosis, pathway prediction, and immune infiltration of LGALS3 has not been fully explored in HCC.

Methods

In this study, an initial pan-cancer analysis was conducted to investigate the expression and prognosis of LGALS3. Following a comprehensive analysis, which included expression analysis and correlation analysis, noncoding RNAs that contribute to the overexpression of LGALS3 were subsequently identified. This identification was further validated using HCC clinical tissue samples. TIMER2 and GEPIA2 were employed to examine the correlation between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration in HCC. The R program was applied to analyze the expression distribution of immune score in in HCC patients with high and low LGALS3 expression. The expression profiles of immune checkpoints were also analyzed. Use R to perform GSVA analysis in order to explore potential signaling pathways.

Results

First, we conducted pan-cancer analysis for LGALS3 expression level through an in-depth analysis of public databases and found that HCC has a high LGALS3 gene and protein expression level, which were then verified in clinical HCC specimens. Meanwhile, high LGALS3 gene expression is related to malignant progression and poor prognosis of HCC. Univariate and multivariate analyses confirmed that LGALS3 could serve as an independent prognostic marker for HCC. Next, by combining comprehensive analysis and validation on HCC clinical tissue samples, we hypothesize that the HCP5/hsa-miR-27b-3p axis could serve as the most promising LGALS3 regulation mechanism in HCC. KEGG and GO analyses highlighted that the LGALS3-related genes were involved in tumor immunity. Furthermore, we detected a significant positive association between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration. In addition, high LGALS3 expression groups had significantly higher immune cell scores and immune checkpoint expression levels. Finally, GSVA analysis was performed to predict potential signaling pathways linked to LGALS3 and HCP5 in immune evasion and metabolic reprogramming of HCC.

Conclusions

Our findings indicated that the upregulation of LGALS3 via the HCP5/hsa-miR-27b-3p axis is associated with unfavorable prognosis and increased tumor immune infiltration in HCC.
An exosomal strategy for targeting cancer-associated fibroblasts mediated tumors desmoplastic microenvironments
Authors: Xue Xiaoxia , Wang Xiangpeng , Pang Mingshi , Yu Liuchunyang , Qian Jinxiu , Li Xiaoyu , Tian Meng , Lu Cheng , Xiao Cheng , Liu Yuanyan
Published: April 2024

Tumors desmoplastic microenvironments are characterized by abundant stromal cells and extracellular matrix (ECM) deposition. Cancer-associated fibroblasts (CAFs), as the most abundant of all stromal cells, play significant role in mediating microenvironments, which not only remodel ECM to establish unique pathological barriers to hinder drug delivery in desmoplastic tumors, but also talk with immune cells and cancer cells to promote immunosuppression and cancer stem cells-mediated drug resistance. Thus, CAFs mediated desmoplastic microenvironments will be emerging as promising strategy to treat desmoplastic tumors. However, due to the complexity of microenvironments and the heterogeneity of CAFs in such tumors, an effective deliver system should be fully considered when designing the strategy of targeting CAFs mediated microenvironments. Engineered exosomes own powerful intercellular communication, cargoes delivery, penetration and targeted property of desired sites, which endow them with powerful theranostic potential in desmoplastic tumors. Here, we illustrate the significance of CAFs in tumors desmoplastic microenvironments and the theranostic potential of engineered exosomes targeting CAFs mediated desmoplastic microenvironments in next generation personalized nano-drugs development.

Graphical Abstract
Hydralazine loaded nanodroplets combined with ultrasound-targeted microbubble destruction to induce pyroptosis for tumor treatment
Authors: Huang Shuting , Shang Mengmeng , Guo Lu , Sun Xiao , Xiao Shan , Shi Dandan , Meng Dong , Zhao Yading , Wang Xiaoxuan , Liu Rui , Li Jie
Published: April 2024

Pyroptosis, a novel type of programmed cell death (PCD), which provides a feasible therapeutic option for the treatment of tumors. However, due to the hypermethylation of the promoter, the critical protein Gasdermin E (GSDME) is lacking in the majority of cancer cells, which cannot start the pyroptosis process and leads to dissatisfactory therapeutic effects. Additionally, the quick clearance, systemic side effects, and low concentration at the tumor site of conventional pyroptosis reagents restrict their use in clinical cancer therapy. Here, we described a combination therapy that induces tumor cell pyroptosis via the use of ultrasound-targeted microbubble destruction (UTMD) in combination with DNA demethylation. The combined application of UTMD and hydralazine-loaded nanodroplets (HYD-NDs) can lead to the rapid release of HYD (a demethylation drug), which can cause the up-regulation of GSDME expression, and produce reactive oxygen species (ROS) by UTMD to cleave up-regulated GSDME, thereby inducing pyroptosis. HYD-NDs combined with ultrasound (US) group had the strongest tumor inhibition effect, and the tumor inhibition rate was 87.15% (HYD-NDs group: 51.41 ± 3.61%, NDs + US group: 32.73%±7.72%), indicating that the strategy had a more significant synergistic anti-tumor effect. In addition, as a new drug delivery carrier, HYD-NDs have great biosafety, tumor targeting, and ultrasound imaging performance. According to the results, the combined therapy reasonably regulated the process of tumor cell pyroptosis, which offered a new strategy for optimizing the therapy of GSDME-silenced solid tumors.
“Everything is kind of the same except my mind is with me”: exploring cannabis substitution in a sample of adults in early recovery from an opioid or stimulant addiction
Authors: Beaugard Corinne A. , Walley Alexander Y. , Amodeo Maryann
Published: April 2024

Background

Recovery from addiction is frequently equated with abstinence. However, some individuals who resolve an addiction continue to use substances, including via substitution (i.e., increased use of one substance after eliminating/ reducing another). Substitution may play a distinct role during early recovery (≤ 1 year), as this period is marked by dramatic change and adjustment. Cannabis is one of the most used substances and is legal for medical and recreational use in an increasing number of states. Consequently, cannabis an increasingly accessible substitute for substances, like fentanyl, heroin, cocaine and methamphetamine, with higher risk profiles (e.g., associated with risk for withdrawal, overdose, and incarceration).

Methods

Fourteen participants reported that they had resolved a primary opioid or stimulant addiction and subsequently increased their cannabis use within the previous 12 months. Using grounded theory, the interviewer explored their experiences of cannabis use during early recovery. Data were analyzed in three stages: line by line coding for all text related to cannabis use and recovery, focused coding, and axial coding to generate a theory about recovery with cannabis substitution. The motivational model of substance use provided sensitizing concepts.

Results & discussion

The final sample included eight men and six women ranging in age from 20 to 50 years old. Three participants resolved an addiction to methamphetamine and the remaining 11, an addiction to opioids. Participants explained that cannabis was appealing because of its less harmful profile (e.g., no overdose risk, safe supply, few side effects). Participants’ primary motives for cannabis use included mitigation of psychiatric symptoms, withdrawal/ cravings, and boredom. While cannabis was effective toward these ends, participants also reported some negative side effects (e.g., decreased productivity, social anxiety). All participants described typical benefits of recovery (e.g., improved self-concept, better relationships) while continuing to use cannabis. Their experiences with and beliefs about substitution suggest it can be an effective strategy for some individuals during early recovery.

Conclusions

Cannabis use may benefit some adults who are reducing their opioid or stimulant use, especially during early recovery. The addiction field’s focus on abstinence has limited our knowledge about non-abstinent recovery. Longitudinal studies are needed to understand the nature of substitution and its impact on recovery over time.
GDF9His209GlnfsTer6/S428T and GDF9Q321X/S428T bi-allelic variants caused female subfertility with defective follicle enlargement
Authors: Duan Yuwei , Cai Bing , Guo Jing , Wang Chen , Mai Qingyun , Xu Yan , Zeng Yang , Shi Yue , Wang Boyan , Ding Chenhui , Chen Minghui , Zhou Canquan , Xu Yanwen
Published: April 2024

Background

Antral follicles consist of an oocyte cumulus complex surrounding by somatic cells, including mural granulosa cells as the inner layer and theca cells as the outsider layer. The communications between oocytes and granulosa cells have been extensively explored in in vitro studies, however, the role of oocyte-derived factor GDF9 on in vivo antral follicle development remains elusive due to lack of an appropriate animal model. Clinically, the phenotype of GDF9 variants needs to be determined.

Methods

Whole-exome sequencing (WES) was performed on two unrelated infertile women characterized by an early rise of estradiol level and defect in follicle enlargement. Besides, WES data on 1,039 women undergoing ART treatment were collected. A Gdf9Q308X/S415T mouse model was generated based on the variant found in one of the patients.

Results

Two probands with bi-allelic GDF9 variants (GDF9His209GlnfsTer6/S428T, GDF9Q321X/S428T) and eight GDF9S428T heterozygotes with normal ovarian response were identified. In vitro experiments confirmed that these variants caused reduction of GDF9 secretion, and/or alleviation in BMP15 binding. Gdf9Q308X/S415T mouse model was constructed, which recapitulated the phenotypes in probands with abnormal estrogen secretion and defected follicle enlargement. Further experiments in mouse model showed an earlier expression of STAR in small antral follicles and decreased proliferative capacity in large antral follicles. In addition, RNA sequencing of granulosa cells revealed the transcriptomic profiles related to defective follicle enlargement in the Gdf9Q308X/S415T group. One of the downregulated genes, P4HA2 (a collagen related gene), was found to be stimulated by GDF9 protein, which partly explained the phenotype of defective follicle enlargement.

Conclusions

GDF9 bi-allelic variants contributed to the defect in antral follicle development. Oocyte itself participated in the regulation of follicle development through GDF9 paracrine effect, highlighting the essential role of oocyte-derived factors on ovarian response.
High glucose-induced p66Shc mitochondrial translocation regulates autophagy initiation and autophagosome formation in syncytiotrophoblast and extravillous trophoblast
Authors: Ji Lulu , Zhang Xiaoli , Chen Zhiguo , Wang Yuexiao , Zhu Hengxuan , Nai Yaru , Huang Yanyi , Lai Rujie , Zhong Yu , Yang Xiting , Wang Qiongtao , Hu Hanyang , Wang Lin
Published: April 2024

Background

p66Shc, as a redox enzyme, regulates reactive oxygen species (ROS) production in mitochondria and autophagy. However, the mechanisms by which p66Shc affects autophagosome formation are not fully understood.

Methods

p66Shc expression and its location in the trophoblast cells were detected in vivo and in vitro. Small hairpin RNAs or CRISPR/Cas9, RNA sequencing, and confocal laser scanning microscope were used to clarify p66Shc’s role in regulating autophagic flux and STING activation. In addition, p66Shc affects mitochondrial-associated endoplasmic reticulum membranes (MAMs) formation were observed by transmission electron microscopy (TEM). Mitochondrial function was evaluated by detected cytoplastic mitochondrial DNA (mtDNA) and mitochondrial membrane potential (MMP).

Results

High glucose induces the expression and mitochondrial translocation of p66Shc, which promotes MAMs formation and stimulates PINK1-PRKN-mediated mitophagy. Moreover, mitochondrial localized p66Shc reduces MMP and triggers cytosolic mtDNA release, thus activates cGAS/STING signaling and ultimately leads to enhanced autophagy and cellular senescence. Specially, we found p66Shc is required for the interaction between STING and LC3II, as well as between STING and ATG5, thereby regulates cGAS/STING-mediated autophagy. We also identified hundreds of genes associated several biological processes including aging are co-regulated by p66Shc and ATG5, deletion either of which results in diminished cellular senescence.

Conclusion

p66Shc is not only implicated in the initiation of autophagy by promoting MAMs formation, but also helps stabilizing active autophagic flux by activating cGAS/STING pathway in trophoblast.