bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Optimism on Cognitive Performance of People Living in Rural Area: Findings From a 20-Year Study in US Adults
Authors: Bhattacharyya Kallol Kumar , Molinari Victor
Published: March 2024

Objectives: Mid- or early-late-life cognitive function is an indicator for developing late-life dementia. However, it is still unclear whether rural/urban living contexts provide cognitive benefits across adulthood. Further, higher optimism serves as a general protective factor for many health outcomes. The present study examines associations between rurality/urbanicity, optimism, and change in mid/late-life cognitive functions over time. Methods: Data were from waves 1 to 3 (1995–2015) of the Midlife in the United States (MIDUS) study ( N = 2,507). Structural equation models examine whether long-term rural living across both waves (1–2) or intermittent rural living at one wave is associated with better cognitive function over 20 years, compared to no rural living, while controlling for prior cognitive function and covariates (baseline socio-demographics, health, and functional status). Additionally, we assessed if optimism mediates the above associations. Results: After controlling for covariates, long-term rural living (waves 1–2) was indirectly (through less optimism) associated with significantly lower levels of cognitive executive function and episodic memory in wave 3. Conclusions: While long-term rural living and cognitive outcomes have no direct association for MIDUS middle-aged and older adults, mediating roles of optimism in these associations were evident. Future investigations could examine mechanisms that underlie these risk/protective factors on late-life cognition.
Depression in Final-Year Medical Students in Ho Chi Minh City, Vietnam: The Role of Career-Choice Motivation
Authors: Uyen Binh Pham Duong , Vo Thi Minh Tam , Hoai Do Thuong Thi , Huynh Giao , Tran Mai Hoang , Phung Hai Ngoc , An Pham Le
Published: March 2024

OBJECTIVES

Depression in medical students is concerning, potentially fueled by many stressors including career choice-relating stress. Choosing Medicine is a life-long commitment, and low intrinsic motivation or excessive dependence on family can complicate this decision and adding stress throughout their training. This stress intensifies in the final year, as students lacking personal drive struggle to see themselves continuing the career. Given limited studies on this crucial topic in Asia and Vietnam, we explored direct linkage between career choice motivation and depression in final-year medical students.

METHODS

A cross-sectional study was conducted with 569 final-year students between June and July 2020. The Vietnamese Patient Health Questionnaire 9 (PHQ-9) and 16-item CCM questionnaire were used as survey tools. Univariate analysis was used for descriptive statistics (absolute and relative frequency, mean (M), standard deviation (SD). Multinomial logistic regression models were used to explore the relationship between variables using STATA 5.1.

RESULTS

The depression among participants was about 24.6% (PHQ-9 cut-off ≥ 12). No difference in gender was found regarding depression. The most acknowledged motivator is securing employment (M = 4.14, SD = 1.02) and the least is parental wishes (M = 3.17, SD = 1.32). Familial influence on career choice significantly increased odds of having “ moderately-severe depression” (OR = 1.17, 95% CI 1.04-1.32) and “ severe depression” (OR = 1.36, 95% CI 1.10-1.68), whereas, career-choice motivators including satisfaction (OR = .76, 95% CI .60-.97), self-competence (OR = .80, 95% CI .66-.97) and career success (OR = .84, 95% CI .71-.99) were found to be protective factors for depression.

CONCLUSIONS

Roughly a quarter of final-year medical students encountered depression. Occupational security ranked as the primary motivator, with parental wish being the least. Familial influence heightened depression risk, while career prospects, satisfaction and self-efficacy acted as protective factors. Medical career paths should align with intrinsic motivations and personal interests for better mental health outcomes.
Shared Medical Appointment: A Novel Model for Incorporating Group Visits Into Residency Training for Substance Use Disorders
Authors: Cavallo Dana A. , Salwan Jasleen K. , Doernberg Molly , Tetrault Jeanette M. , Holt Stephen R.
Published: March 2024

Background:

Shared medical appointments (SMAs) are a novel modality for treating patients with similar conditions, together, by a team of interdisciplinary providers. SMAs benefit patients with substance use disorder (SUD), but no research has focused on the feasibility of implementation of SMAs in a teaching clinic.

Methods:

Primary care residents rotated in a half-day ambulatory addiction clinic for 4 weeks where a third-year resident co-facilitated 4 SMAs. Confidence, knowledge, and attitudes about SUD care were assessed using web-based surveys at weeks 0, 4, and 8. Pre- and post-intervention scores were compared using a t test for paired samples.

Results:

Ten residents were included in the analyses. Using a 10-point Likert scale, confidence in SUD knowledge (7.0-8.3, P = .003), confidence in counseling patients with SUD (7.1-8.2, P = .023), and confidence in facilitating an SMA (5.7-8.3, P = .007) showed statistically significant increases from baseline following exposure to the SMAs. Confidence that counseling and other treatments will make a difference for patients with illicit drug use increased (7.1-8.0, P = .142), but did not differ statistically. Furthermore, on a 4-point Likert scale, understanding of behavioral therapies for treating and preventing the relapse of SUD (2.9-3.2, P = .180) showed a similar increase. Attitudes toward patients with SUD (42.4-42.1, P = .303) and physician empathy (119.3-119.2, P = .963) did not change from pre- to post-intervention.

Conclusions:

SMAs are a feasible training tool in the education of primary care residents on an addiction medicine rotation. Residents develop confidence co-facilitating SMAs after 4 weeks. Overall, exposure to SMAs during residency can provide an opportunity to increase confidence in treating patients with SUD, as well as provide a training modality that may shift the way residents interact with patients receiving SUD treatment.
Model Parameters Identification and Backstepping Control of Lower Limb Exoskeleton Based on Enhanced Whale Algorithm
Authors: Shi Yan , Kou Jiange , Chen Zhenlei , Wang Yixuan , Guo Qing
Published: March 2024

Exoskeletons generally require accurate dynamic models to design the model-based controller conveniently under the human-robot interaction condition. However, due to unknown model parameters such as the mass, moment of inertia and mechanical size, the dynamic model of exoskeletons is difficult to construct. Hence, an enhanced whale optimization algorithm (EWOA) is proposed to identify the exoskeleton model parameters. Meanwhile, the periodic excitation trajectories are designed by finite Fourier series to input the desired position demand of exoskeletons with mechanical physical constraints. Then a backstepping controller based on the identified model is adopted to improve the human-robot wearable comfortable performance under cooperative motion. Finally, the proposed Model parameters identification and control are verified by a two-DOF exoskeletons platform. The knee joint motion achieves a steady-state response after 0.5 s. Meanwhile, the position error of hip joint response is less than 0.03 rad after 0.9 s. In addition, the steady-state human-robot interaction torque of the two joints is constrained within 15 $${\text{N}\cdot\text{m}}$$

N
·
m

. This research proposes a whale optimization algorithm to optimize the excitation trajectory and identify model parameters. Furthermore, an enhanced mutation strategy is adopted to avoid whale evolution's unsatisfactory local optimal value.
A comparative study on biosynthesized silver nanoparticles from H. undatus fruit peel and their therapeutic applications
Authors: Anguraj Aswini , Michael Helan Soundra Rani , Sugumaran Sathish , Madhusudhanan Gogul Ramnath , Sivaraman Rathish Kumar
Published: March 2024

The green synthesis of nanoparticles (NPs) gained significant impacts in various fields due to the use of eco-friendly approaches. In this study, silver nanoparticles (AgNPs) were synthesized from the aqueous extract of Hylocereus undatus fruit peel. The presence of AgNPs was analysed using characterization methods such as UV‒Vis, FTIR, GCMS, XRD, EDAX, and FESEM. The synthesized AgNPs showed greater antibacterial activity against Escherichia coli than against Streptococcus pneumoniae. The antifungal activity against Candida albicans was greater than that against Candida tropicalis. The IC50 value for the antibiofilm activity of the AgNPs was 2.81 µg/mL, whereas that of the H. undatus peel extract was 1.34 µg/mL. The invitro antioxidant activity of the AgNPs was evaluated using two different methods. The DPPH radical scavenging activity of the AgNPs and fruit peel extract was observed with IC50 values of 3.8 and 2.03 µg/mL respectively. On the other hand, nitric oxide radical scavenging activities were recorded and the IC50 values were calculated to be 2.8 and 2.3 µg/mL. The AgNPs demonstrated thrombolytic activity in human blood with 10, 32.36, and 56.25% lysis. The cytotoxicity of the AgNPs was minimal, with an IC50 of 0.2 µg/mL and the peel extract had the greatest cytotoxicity with an IC50 of 0.3 µg/mL. The findings of this study demonstrated that the synthesized AgNPs from H. undatus peel extract could be potential candidates for treating prostate cancer.

Graphical abstract
Fitness difference between two synonymous mutations of Phytophthora infestans ATP6 gene
Authors: Nkurikiyimfura Oswald , Waheed Abdul , Fang Hanmei , Yuan Xiaoxian , Chen Lixia , Wang Yan-Ping , Lu Guodong , Zhan Jiasui , Yang Lina
Published: March 2024

Background

Sequence variation produced by mutation provides the ultimate source of natural selection for species adaptation. Unlike nonsynonymous mutation, synonymous mutations are generally considered to be selectively neutral but accumulating evidence suggests they also contribute to species adaptation by regulating the flow of genetic information and the development of functional traits. In this study, we analysed sequence characteristics of ATP6, a housekeeping gene from 139 Phytophthora infestans isolates, and compared the fitness components including metabolic rate, temperature sensitivity, aggressiveness, and fungicide tolerance among synonymous mutations.

Results

We found that the housekeeping gene exhibited low genetic variation and was represented by two major synonymous mutants at similar frequency (0.496 and 0.468, respectively). The two synonymous mutants were generated by a single nucleotide substitution but differed significantly in fitness as well as temperature-mediated spatial distribution and expression. The synonymous mutant ending in AT was more common in cold regions and was more expressed at lower experimental temperature than the synonymous mutant ending in GC and vice versa.

Conclusion

Our results are consistent with the argument that synonymous mutations can modulate the adaptive evolution of species including pathogens and have important implications for sustainable disease management, especially under climate change.
Biodiversity and distribution patterns of blooming jellyfish in the Bohai Sea revealed by eDNA metabarcoding
Authors: Ye Lijing , Peng Saijun , Ma Yuanqing , Zhang Wenjing , Wang Lei , Sun Xiyan , Zhang Chen , Yeasmin Munjira , Zhao Jianmin , Dong Zhijun
Published: March 2024

Background

The mass occurrence of scyphozoan jellyfish severely affects marine ecosystems and coastal economies, and the study of blooming jellyfish population dynamics has emerged in response. However, traditional ecological survey methods required for such research have difficulties in detecting cryptic life stages and surveying population dynamics owing to high spatiotemporal variations in their occurrence. The environmental DNA (eDNA) technique is an effective tool for overcoming these limitations.

Results

In this study, we investigated the biodiversity and spatial distribution characteristics of blooming jellyfish in the Bohai Sea of China using an eDNA metabarcoding approach, which covered the surface, middle, and bottom seawater layers, and sediments. Six jellyfish taxa were identified, of which Aurelia coerulea, Nemopilema nomurai, and Cyanea nozakii were the most dominant. These three blooming jellyfish presented a marked vertical distribution pattern in the offshore regions. A. coerulea was mainly distributed in the surface layer, whereas C. nozakii and N. nomurai showed a upper-middle and middle-bottom aggregation, respectively. Horizontally, A. coerulea and C. nozakii were more abundant in the inshore regions, whereas N. nomurai was mainly distributed offshore. Spearman’s correlation analysis revealed a strong correlation between the eDNA of the three dominant blooming jellyfish species and temperature, salinity, and nutrients.

Conclusions

Our study confirms the applicability of the eDNA approach to both biodiverstiy evaluation of blooming jellyfish and investigating their spatial distribution, and it can be used as a supplementary tool to traditional survey methods.
Chalkiness and premature controlled by energy homeostasis in OsNAC02 Ko-mutant during vegetative endosperm development
Authors: Yan Mei , Jiao Guiai , Shao Gaoneng , Chen Ying , Zhu Maodi , Yang Lingwei , Xie Lihong , Hu Peisong , Tang Shaoqing
Published: March 2024

Background

Chalkiness is a common phenotype induced by various reasons, such as abiotic stress or the imbalance of starch synthesis and metabolism during the development period. However, the reason mainly for one gene losing its function such as NAC (TFs has a large family in rice) which may cause premature is rarely known to us.

Results

The Ko-Osnac02 mutant demonstrated an obviously early maturation stage compared to the wild type (WT) with 15 days earlier. The result showed that the mature endosperm of Ko-Osnac02 mutant exhibited chalkiness, characterized by white-core and white-belly in mature endosperm. As grain filling rate is a crucial factor in determining the yield and quality of rice (Oryza sativa, ssp. japonica), it's significant that mutant has a lower amylose content (AC) and higher soluble sugar content in the mature endosperm. Interestingly among the top DEGs in the RNA sequencing of N2 (3DAP) and WT seeds revealed that the OsBAM2 (LOC_Os10g32810) expressed significantly high in N2 mutant, which involved in Maltose up-regulated by the starch degradation. As Prediction of Protein interaction showed in the chalky endosperm formation in N2 seeds (3 DAP), seven genes were expressed at a lower-level which should be verified by a heatmap diagrams based on DEGs of N2 versus WT. The Tubulin genes controlling cell cycle are downregulated together with the MCM family genes MCM4 ( ↓), MCM7 ( ↑), which may cause white-core in the early endosperm development. In conclusion, the developing period drastically decreased in the Ko-Osnac02 mutants, which might cause the chalkiness in seeds during the early endosperm development.

Conclusions

The gene OsNAC02 which controls a great genetic co-network for cell cycle regulation in early development, and KO-Osnac02 mutant shows prematurity and white-core in endosperm.
Change in cardiovascular health and rate of cognitive decline in older adults: a 15-year population-based study
Authors: Speh Andreja , Kramberger Milica G. , Winblad Bengt , Bäckman Lars , Qiu Chengxuan , Laukka Erika J.
Published: March 2024

Background

Previous research on associations between cardiovascular health, measured at a single timepoint, and rate of age-related cognitive decline shows divergent findings dependent on the participants’ age and the health metric studied. The aim of this study was to add to the knowledge in this field by investigating whether change in cardiovascular health, assessed with Life’s Simple 7 (LS7) score, is associated with rate of cognitive change in young-old and old-old adults.

Methods

The study included 1022 participants aged ≥ 60 years from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic memory, semantic memory, verbal fluency, and perceptual speed) across up to 15 years. LS7, composed of seven cardiovascular health metrics (smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure), was assessed at baseline and at the 6-year follow-up. Change in LS7 was calculated as the difference between baseline and 6 years (range − 5 to 8 points) and categorised into worse (−5 to −2 points), stable (−1 to 1 points), and improved (2 to 8 points). Change in cognitive performance as a function of LS7 change categories was estimated using linear mixed-effects models.

Results

Participants were classified as stable (67.1%), improved (21.0%), or worse (11.8%) according to changes in LS7 score. Both the worse and improved categories were associated with faster cognitive decline. Age-stratified analyses revealed that worsening of LS7 was clearly associated with faster cognitive decline in the old-old (≥ 78 years), whereas improvement tended be associated with faster cognitive decline in the young-old (< 78 years) group.

Conclusions

Change in cardiovascular health in old age may lead to accelerated cognitive decline, particularly in late senescence. These results suggest that it is important to monitor and maintain cardiovascular health status in very old adults.
Does HIV index testing bring patients into treatment at earlier stages of HIV disease? Results from a retrospective study in Ukraine
Authors: Secor Andrew M. , Ihnatiuk Alyona , Shapoval Anna , McDowell Misti , Hetman Larisa , Wagner Anjuli D. , Pintye Jillian , Beima-Sofie Kristin , Golden Matthew R. , Puttkammer Nancy
Published: March 2024

Background

Over one-third of people living with HIV (PLH) in Ukraine are not on treatment. Index testing services, which link potentially exposed partners (named partners) of known PLH (index patients) with testing and treatment services, are being scaled in Ukraine and could potentially close this gap.

Methods

This retrospective study included patient data from 14,554 adult PLH who initiated antiretroviral treatment (ART) between October 2018 and May 2021 at one of 35 facilities participating in an intervention to strengthen index testing services. Mixed effects modified Poisson models were used to assess differences between named partners and other ART initiators, and an interrupted time series (ITS) analysis was used to assess changes in ART initiation over time.

Results

Compared to other ART initiators, named partners were significantly less likely to have a confirmed TB diagnosis (aRR = 0.56, 95% CI = 0.40, 0.77, p < 0.001), a CD4 count less than 200 cells/mm3 (aRR = 0.84, 95% CI = 0.73, 0.97, p = 0.017), or be categorized as WHO HIV stage 4 (aRR = 0.68, 9% CI = 0.55, 0.83, p < 0.001) at the time of ART initiation, and were significantly more likely to initiate ART within seven days of testing for HIV (aRR = 1.36, 95% CI = 1.22, 1.50, p < 0.001). Our ITS analysis showed a modest 2.34% (95% CI = 0.26%, 4.38%; p = 0.028) month-on-month reduction in mean ART initiations comparing the post-intervention period to the pre-intervention period, although these results were likely confounded by the COVID epidemic.

Conclusion

Our findings suggest that index testing services may be beneficial in bringing PLH into treatment at an earlier stage of HIV disease and decreasing delays between HIV testing and ART initiation, potentially improving patient outcomes and retention in the HIV care cascade.
Combining radiomics with thyroid imaging reporting and data system to predict lateral cervical lymph node metastases in medullary thyroid cancer
Authors: Liu Zhiqiang , Zhang Xiwei , Zhao Xiaohui , Guo Qianqian , Li Zhengjiang , Wei Minghui , Niu Lijuan , An Changming
Published: March 2024

Background

Medullary Thyroid Carcinoma (MTC) is a rare type of thyroid cancer. Accurate prediction of lateral cervical lymph node metastases (LCLNM) in MTC patients can help guide surgical decisions and ensure that patients receive the most appropriate and effective surgery. To our knowledge, no studies have been published that use radiomics analysis to forecast LCLNM in MTC patients. The purpose of this study is to develop a radiomics combined with thyroid imaging reporting and data system (TI-RADS) model that can use preoperative thyroid ultrasound images to noninvasively predict the LCLNM status of MTC.

Methods

We retrospectively included 218 MTC patients who were confirmed from postoperative pathology as LCLNM negative (n=111) and positive (n=107). Ultrasound features were selected using the Student’s t-test, while radiomics features are first extracted from preoperative thyroid ultrasound images, and then a two-step feature selection approach was used to select features. These features are then used to establish three regularized logistic regression models, namely the TI-RADS model (TM), the radiomics model (RM), and the radiomics-TI-RADS model (RTM), in 5-fold cross-validation to determine the likelihood of the LCLNM. The Delong’s test and decision curve analysis (DCA) were used to evaluate and compare the performance of the models.

Results

The ultrasound features of margin and TI-RADS level, and a total of 12 selected radiomics features, were significantly different between the LCLNM negative and positive groups (p<0.05). The TM, RM, and RTM yielded an averaged AUC of 0.68±0.05, 0.78±0.06, and 0.82±0.05 in the 5-fold cross-validation dataset, respectively. RM and RTM are statistically better than TM (p<0.05 and p<0.001) according to Delong test. DCA demonstrates that RTM brings more benefit than TM and RM.

Conclusions

We have developed a joint radiomics-based model for noninvasive prediction of the LCLNM in MTC patients solely using preoperative thyroid ultrasound imaging. It has the potential to be used as a complementary tool to help guide treatment decisions for this rare form of thyroid cancer.
Global, regional, and national burden of non-communicable diseases attributable to occupational asbestos exposure 1990–2019 and prediction to 2035: worsening or improving?
Authors: Miao Xinlu , Yao Teng , Dong Chenxian , Chen Zuhai , Wei Wanting , Shi Zhengyang , Xu Tongtong , Shao Jianjiang , Niu Qiang , Rui Dongsheng , Hu Yunhua , Yan Yizhong
Published: March 2024

Understanding the burden associated with occupational asbestos exposure on a global and regional scale is necessary to implement coordinated prevention and control strategies. By the GBD Study 2019, we conducted a comprehensive assessment of the non-communicable diseases burden attributable to occupational asbestos exposure. In 2019, 239,330 deaths and 4,189,000 disability-adjusted life years (DALYs) worldwide due to occupational asbestos exposure occurred. 1990–2019, deaths and DALYs attributed to occupational asbestos exposure increased by 65.65% and 43.66%, respectively. Age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) decreased, with the most rapid declines in high Socio-Demographic Index (SDI) regions, with average annual percent change (AAPC) of − 1.05(95%CI: −1.2, −0.89) and −1.53(95%CI: −1.71, −1.36), respectively. Lung cancer, mesothelioma and ovarian cancer were the top three contributors to the increase in deaths and DALYs, accounting for more than 96%. AAPCs of ASMR and ASDR were positively associated with SDI. Global deaths from occupational asbestos exposure were predicted to increase and ASMR to decrease by 2035, mostly in males. Due consideration should be given to the susceptibility of the elderly, the lag of asbestos onset, and the regional differences, and constantly improve the prevention and control measures of occupational asbestos exposure and related diseases.
Different methods of determining centric relation – comparison with a digital mandibular motion analyser
Authors: Jász Bálint , Ambrus Szilvia , Garay Tamás , Schmidt Péter , Hermann Péter , Körmendi Szandra , Jász Máté
Published: March 2024

Background

Finding and registering the maxillary–mandibular jaw relation is crucial in dental practice. Several comparative studies have been conducted to investigate the reproducibility and accuracy of techniques for determining the centric relation (CR) position of the mandible. The aim of our study was to determine which of seven different CR determination methods had the smallest deviation from the theoretical zero with the help of a digital mandibular motion analyser. The chosen theoretical zero position, the maximal intercuspal position (MIP), is the most reproducible and widely used position.

Methods

Thirty-four volunteers (24 females and 10 males) with a mean (SD) age of 29.1 (± 7.3) years with a negative history of temporomandibular disorder (TMD) participated in the study. A digital mandibular motion analyser was used to register the condylar position after the use of each technique for the determination of CR. The calibration was performed to the maximal intercuspal position (MIP) for each volunteer. The investigated techniques were (A) the gothic arch tracer, (B) the adduction field method, (C) Dawson’s bimanual manipulation, (D) the patient placing the tongue tip on the palatal rugae, (E) the patient placing the tongue tip to the border of the hard and soft palate, (F) the patient actively pulling the chin backwards, and (G) the examiner pushing the patient’s chin back.

Results

The position of the mandibular condyle was illustrated in a three-dimensional coordinate system, where the origin represented the MIP. Among the seven methods examined, five showed significant deviations compared to the MIP. Among these, two methods resulted in posterior deviation of the condyles. Methods C and E coincided with the MIP in all directions.

Conclusions

Within the limitations of our study, we found that the smallest deviations from our theoretical zero (MIP) among the investigated centric relation determining methods were obtained with the bimanual mandibular manipulation technique derived from Dawson and the placement of the tongue tip on the border of the hard and soft palate (linguomandibular homotrophy theory).
Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study
Authors: Wu Tong-Tong , Chen Yu-Yi , Yuan Zi-Chun , Yang Guo-Wang , Zhang Gan-Lin
Published: March 2024

Background

Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant.

Method/design

A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12.

Trial registration

China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.
Protective effect of Tao Hong Si Wu Decoction against inflammatory injury caused by intestinal flora disorders in an ischemic stroke mouse model
Authors: Zhang Lijuan , Xue Sujun , Fei Changyi , Yu Chao , Li Jingjing , Li Yumeng , Wang Ni , Chu Furui , Pan Lingyu , Duan Xianchun , Peng Daiyin
Published: March 2024

Background and aims

Recent studies have shown that intestinal flora are involved in the pathological process of ischemic stroke (IS). The potential protective effect of the traditional Chinese prescription, Tao Hong Si Wu Decoction (THSWD), against inflammatory injury after IS and its underlying mechanisms of action were investigated in the current study.

Methods

Fifty SPF(Specefic pathogen Free) male C57 mice were randomly assigned to sham operation, model, THSWD low-dose (6.5 g/kg), medium-dose (13 g/kg) and high-dose (26 g/kg) groups (10 mice per group). Mouse models of transient middle cerebral artery occlusion were prepared via thread embolism. Neurological function score, hematoxylin-eosin (HE) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), 16S ribosomal DNA (rDNA) sequencing, quantitative reverse transcription PCR (qRT-PCR) and other methods were employed to elucidate the underlying molecular mechanisms.

Results

Notably, THSWD induced a reduction in the neurological function score (P < 0.01) and neuronal injury in brain tissue, increase in protein expression of Claudin-5 and zonula occludens-1 (ZO-1) in brain tissue(P < 0.01), and decrease in serum lipopolysaccharide (LPS)(P < 0.01), diamine oxidase (DAO)(P < 0.01) and D-lactic acid(P < 0.01, P < 0.05) levels to a significant extent. THSWD also inhibited the levels of tumor necrosis factor-α (TNF-α)(P < 0.01) and interleukin − 1β (IL-1β)(P < 0.01) in brain tissue, and increased alpha and beta diversity in ischemic stroke mice, along with a certain reversal effect on different microflora. Finally, THSWD inhibited the polarization of microglia cells(P < 0.01) and decreased the protein and gene expression of toll-like receptor-4 (TLR-4)(P < 0.01, P < 0.05) and nuclear factor kappa B (NF-κB)(P < 0.01) in brain tissue.

Conclusion

Our data indicate that THSWD may interfere with inflammatory response in ischemic stroke by regulating intestinal flora and promoting intestinal barrier repair.
Exploring advanced clinical practitioner perspectives on training, role identity and competence: a qualitative study
Authors: Kuczawski Maxine , Ablard Suzanne , Sampson Fiona , Croft Susan , Sutton-Klein Joanna , Mason Suzanne
Published: March 2024

Background

Advanced Clinical Practitioners (ACPs) are a new role that have been established to address gaps and support the existing medical workforce in an effort to help reduce increasing pressures on NHS services. ACPs have the potential to practice at a similar level to mid-grade medical staff, for example independently undertaking assessments, requesting and interpreting investigations, and diagnosing and discharging patients. These roles have been shown to improve both service outcomes and quality of patient care. However, there is currently no widespread formalised standard of training within the UK resulting in variations in the training experiences and clinical capabilities of ACPs. We sought to explore the training experiences of ACPs as well as their views on role identity and future development of the role.

Methods

Five online focus groups were conducted between March and May 2021 with trainee and qualified advanced clinical practitioners working in a range of healthcare settings, in the North of England. The focus groups aimed to explore the experiences of undertaking ACP training including supervision, gaining competence, role identity and career progression. Thematic analysis of the focus group transcripts was performed, informed by grounded theory principles.

Results

Fourteen advanced clinical practitioners participated. Analysis revealed that training was influenced by internal and external perceptions of the role, often acting as barriers, with structural aspects being significant contributory factors. Key themes identified (1) clinical training lacked structure and support, negatively impacting progress, (2) existing knowledge and experience acted as both an enabler and inhibitor, with implications for confidence, (3) the role and responsibilities are poorly understood by both advanced clinical practitioners and the wider medical profession and (4) advanced clinical practitioners recognised the value and importance of the role but felt changes were necessary, to provide security and sustainability.

Conclusions

Appropriate structure and support are crucial throughout the training process to enable staff to have a smooth transition to advanced level, ensuring they obtain the necessary confidence and competence. Structural changes and knowledge brokering are essential, particularly in relation to role clarity and its responsibilities, sufficient allocated time to learn and practice, role accreditation and continuous appropriate supervision.
New improvements in grapevine genome editing: high efficiency biallelic homozygous knock-out from regenerated plantlets by using an optimized zCas9i
Authors: Villette Jérémy , Lecourieux Fatma , Bastiancig Eliot , Héloir Marie-Claire , Poinssot Benoit
Published: March 2024

Background

For ten years, CRISPR/cas9 system has become a very useful tool for obtaining site-specific mutations on targeted genes in many plant organisms. This technology opens up a wide range of possibilities for improved plant breeding in the future. In plants, the CRISPR/Cas9 system is mostly used through stable transformation with constructs that allow for the expression of the Cas9 gene and sgRNA. Numerous studies have shown that site-specific mutation efficiency can vary greatly between different plant species due to factors such as plant transformation efficiency, Cas9 expression, Cas9 nucleotide sequence, the addition of intronic sequences, and many other parameters. Since 2016, when the first edited grapevine was created, the number of studies using functional genomic approaches in grapevine has remained low due to difficulties with plant transformation and gene editing efficiency. In this study, we optimized the process to obtain site-specific mutations and generate knock-out mutants of grapevine (Vitis vinifera cv. ‘Chardonnay’). Building on existing methods of grapevine transformation, we improved the method for selecting transformed plants at chosen steps of the developing process using fluorescence microscopy.

Results

By comparison of two different Cas9 gene and two different promoters, we increased site-specific mutation efficiency using a maize-codon optimized Cas9 containing 13 introns (zCas9i), achieving up to 100% biallelic mutation in grapevine plantlets cv. ‘Chardonnay’. These results are directly correlated with Cas9 expression level.

Conclusions

Taken together, our results highlight a complete methodology for obtaining a wide range of homozygous knock-out mutants for functional genomic studies and future breeding programs in grapevine.
Bone cement reinforcement improves the therapeutic effects of screws in elderly patients with pelvic fragility factures
Authors: Gao Lecai , Xing Baorui
Published: March 2024

Background

Pelvic fragility fractures in elderly individuals present significant challenges in orthopedic and geriatric medicine due to reduced bone density and increased frailty associated with aging.

Methods

This study involved 150 elderly patients with pelvic fragility fractures. The patients were divided into two groups, the observation group (Observation) and the control group (Control), using a random number table. Artificial intelligence, specifically the Tianji Orthopedic Robot, was employed for surgical assistance. The observation group received bone cement reinforcement along with screw fixation using the robotic system, while the control group received conventional screw fixation alone. Follow-up data were collected for one-year post-treatment.

Results

The observation group exhibited significantly lower clinical healing time of fractures and reduced bed rest time compared to the control group. Additionally, the observation group experienced less postoperative pain at 1 and 3 months, indicating the benefits of bone cement reinforcement. Moreover, patients in the observation group demonstrated significantly better functional recovery at 1-, 3-, and 6-months post-surgery compared to the control group.

Conclusion

The combination of bone cement reinforcement and robotic technology resulted in accelerated fracture healing, reduced bed rest time, and improved postoperative pain relief and functional recovery.
Cardioprotective role of royal jelly in the prevention of celecoxib-mediated cardiotoxicity in adult male albino rats
Authors: Eleiwa Naglaa Z. H. , Khalifa Hesham A. M. I. , Nazim Heba A.
Published: March 2024

Background

Celecoxib, a cyclooxygenase-2 selective inhibitor non-steroidal anti-inflammatory drugs, is used for the management of short- and long-term pain as well as in other inflammatory conditions. Unfortunately, its chronic use is highly associated with serious abnormal cardiovascular events. The current study was designed to explore the effect of long-term administration of celecoxib on the cardiac tissues of male albino rats. The study also examined the alleged cardioprotective effect of royal jelly.

Methods

Thirty, male albino rats were randomly divided into 3 equal groups; 10 each: (1) rats served as the control group and received no drug; (2) rats received celecoxib (50 mg/kg/day, orally), for 30 consecutive days; (3) rats received celecoxib (50 mg/kg/day, orally) plus royal jelly (300 mg/kg/day, orally) for 30 consecutive days. Sera were collected to assay cardiac enzymes and oxidant/antioxidant status. Rats were euthanatized and cardiac tissues were dissected for quantitative estimation of apoptotic genes (Bax) and anti-apoptotic gene (Bcl-2).

Results

Long-term celecoxib administration caused cardiotoxicity in male albino rats as manifested by significant elevation of serum levels of creatine phosphokinase (CPK), creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH), with ameliorative effects of royal jelly against celecoxib-induced cardiotoxicity as manifested by significantly decrease in serum CPK, CK-MB, and LDH levels. It also showed a significant decrease in the oxidative stress indicator malondialdehyde (MDA) levels and the bax gene. Additionally, it demonstrated significant increases in the bcl-2 gene and superoxide dismutase (SOD) levels, which contribute to its therapeutic effects against celecoxib-induced cardiotoxicity.

Conclusion

Long-term celecoxib administration caused cardiotoxicity in male albino rats with protective effect of royal jelly being given together. It could be concluded that royal jelly may prove a useful adjunct in patients being prescribed celecoxib.

Trial registration

Not applicable.
Engineering Escherichia coli for high-yielding 2,5-Dimethylpyrazine synthesis from L-Threonine by reconstructing metabolic pathways and enhancing cofactors regeneration
Authors: Liu Xin-Xin , Wang Yao , Zhang Jian-Hui , Lu Yun-Feng , Dong Zi-Xing , Yue Chao , Huang Xian-Qing , Zhang Si-Pu , Li Dan-Dan , Yao Lun-Guang , Tang Cun-Duo
Published: March 2024

2,5-Dimethylpyrazine (2,5-DMP) is important pharmaceutical raw material and food flavoring agent. Recently, engineering microbes to produce 2,5-DMP has become an attractive alternative to chemical synthesis approach. In this study, metabolic engineering strategies were used to optimize the modified Escherichia coli BL21 (DE3) strain for efficient synthesis of 2,5-DMP using L-threonine dehydrogenase (EcTDH) from Escherichia coli BL21, NADH oxidase (EhNOX) from Enterococcus hirae, aminoacetone oxidase (ScAAO) from Streptococcus cristatus and L-threonine transporter protein (EcSstT) from Escherichia coli BL21, respectively. We further optimized the reaction conditions for synthesizing 2,5-DMP. In optimized conditions, the modified strain can convert L-threonine to obtain 2,5-DMP with a yield of 2897.30 mg/L. Therefore, the strategies used in this study contribute to the development of high-level cell factories for 2,5-DMP.

Graphical Abstract
Estimating COVID-19 vaccine acceptance in pregnant and lactating women: a cross-sectional study in Lebanon
Authors: Zayoud Dana , Haddad Chadia , Khachman Dalia , Ajrouche Roula , Lahoud Nathalie
Published: March 2024

Background

The COVID-19 pandemic highlights vaccination’s critical role in reducing morbidity and mortality, depending on public attitude. This study aims to identify the estimates of COVID-19 vaccine acceptance in pregnant and lactating women, as well as associated potential factors.

Methods

A cross-sectional study was conducted between August and September 2021, through an online survey and with a paper survey distributed in gynecology and pediatric clinics. Pregnant and breastfeeding women aged 18 years and above were recruited. The attitude scale was created specifically for evaluating attitudes towards the COVID-19 vaccine.

Results

In total, 207 women participated, with 132 breastfeeding, 74 pregnant and 1 experiencing both conditions. Of these, one hundred and twenty women (58%) considered themselves at risk for COVID-19 infection. In addition, 51.7% (n = 107) of women expressed the intent to receive the vaccine once available. A multivariable linear regression was conducted taking the COVID-19 vaccination attitude scale as a dependent variable. The results revealed an R-squared value of 0.558, indicating that approximately 55.8% of the variance in the attitude scale was accounted for by the included predictors. The results showed that preventive measures (ß=2.25, 95% Confidence Interval (CI) [1.02; 3.48], p < 0.001), preference for vaccines made in Europe and America (ß=1.23; 95% CI [0.69–1.77], p < 0.001), protect yourself for getting sick (ß=4.22, 95% Confidence Interval (CI) [2.83; 5.61], p < 0.001) and belief in the importance of vaccination for themselves and their baby (ß=3.49; 95% CI [2.01; 4.98], p < 0.001) were associated with a positive attitude towards vaccination. Conversely, experiencing a previous bad reaction to a vaccine (ß= -1.35; 95% CI [0.85–1.85], p < 0.001) and concerns regarding COVID-19 vaccine safety (ß= -4.09; 95% CI [-5.98; -2.21], p < 0.001) were associated with a negative attitude towards vaccination.

Conclusion

Our findings reveal that COVID-19 vaccine acceptability among pregnant and breastfeeding women, amidst the pandemic was insufficient to meet community immunity. The identified reasons for vaccine reluctance, notably concerns about safety for both personal health and the health of their pregnancy or newborns, along with insufficient information about the vaccine, underscore the pressing need to address these factors to improve immunization rates.
Anti-reflux mucosectomy (ARMS) for refractory gastroesophageal reflux disease
Authors: Zhu Xian , Shen Jianwei
Published: March 2024

Gastroesophageal reflux disease (GERD) is one of the most common diseases seen by gastroenterologists worldwide. A significant proportion of patients have a suboptimal response to acid inhibitors, especially proton pump inhibitors and potassium-competitive acid blockers. Due to concerns regarding the safety of long-term medication, many patients are unwilling to take lifelong medication. Endoscopic antireflux management offers a minimally invasive option for GERD patients. In recent decades, there have been several endoscopic antireflux therapies, including radiofrequency therapy, transoral fundoplication, and mucosal resection or mucosal ablation. Of these, antireflux mucosectomy (ARMS) is an effective and safe therapy for refractory GERD. This review provides an updated summary of antireflux mucosectomy.
Molecular and clinicopathologic characteristics of CNS embryonal tumors with BRD4::LEUTX fusion
Authors: Andreiuolo Felipe , Ferrone Christina K. , Rajan Sharika , Perry Arie , Guney Ekin , Cham Elaine , Giannini Caterina , Toland Angus , Willard Nicholas , de Souza Andrea Silveira , Dazelle Karen , Chung Hye-Jung , Singh Omkar , Conway Kyle , Coley Nicholas , Dampier Christopher , Abdullaev Zied , Pratt Drew , Cimino Patrick J. , Quezado Martha , Aldape Kenneth
Published: March 2024

Central nervous system (CNS) embryonal tumors are a heterogeneous group of high-grade malignancies, and the increasing clinical use of methylation profiling and next-generation sequencing has led to the identification of molecularly distinct subtypes. One proposed tumor type, CNS tumor with BRD4::LEUTX fusion, has been described. As only a few CNS tumors with BRD4::LEUTX fusions have been described, we herein characterize a cohort of 9 such cases (4 new, 5 previously published) to further describe their clinicopathologic and molecular features. We demonstrate that CNS embryonal tumor with BRD4::LEUTX fusion comprises a well-defined methylation class/cluster. We find that patients are young (4 years or younger), with large tumors at variable locations, and frequently with evidence of leptomeningeal/cerebrospinal fluid (CSF) dissemination. Histologically, tumors were highly cellular with high-grade embryonal features. Immunohistochemically, 5/5 cases showed synaptophysin and 4/5 showed OLIG2 expression, thus overlapping with CNS neuroblastoma, FOXR2-activated. DNA copy number profiles were generally flat; however, two tumors had chromosome 1q gains. No recurring genomic changes, besides the presence of the fusion, were found. The LEUTX portion of the fusion transcript was constant in all cases assessed, while the BRD4 portion varied but included a domain with proto-oncogenic activity in all cases. Two patients with clinical follow up available had tumors with excellent response to chemotherapy. Two of our patients were alive without evidence of recurrence or progression after gross total resection and chemotherapy at 16 and 33 months. One patient relapsed, and the last of our four patients died of disease one month after diagnosis. Overall, this case series provides additional evidence for this as a distinct tumor type defined by the presence of a specific fusion as well as a distinct DNA methylation signature. Studies on larger series are required to further characterize these tumors.
Selective damage induced by pigment-medium interactions in a Neoplasticist oil canvas painting: Composition dans le cône avec couleur orange by G. Vantongerloo (1929)
Authors: Izzo Francesca Caterina , Gnemmi Margherita , Herrero-Cortell Miguel Ángel , García-Castillo Ana María , Martínez-López María Teresa , Fuster-López Laura
Published: March 2024

This research focuses on the study of pigment-medium interactions in the film forming, ageing and degradation mechanisms of modern white oil paints observed in the Neoplasticist painting Composition dans le cône avec couleur orange by G. Vantongerloo (1929), conserved in the Institut Valencià d’Art Modern (IVAM). The observation of selective vertical cracks and the significant presence of protrusions in the painting suggested that the observed degradation phenomena were specific to the coloured area. To understand the composition of pigments governing the film formation processes and later degradation phenomena in the oil paint films, a hybrid experimental approach was taken, aimed at understanding the physical, chemical and mechanical mechanisms involved. For this purpose, digital portable microscopy and multiband imaging analyses were carried out. Furthermore, the technical study involved the use of micro-invasive analysis such as μ-Raman, ATR-FTIR spectroscopy and GC–MS analysis for a more comprehensive understanding of the nature of the binding media and products resulting from the auto-oxidation, film-forming, hydrolysis, and degradation processes of the lipidic binding media. The results obtained suggest that on-going degradation phenomena are closely linked to the chemical interaction between pigment and binding medium.