bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the application of functional near-infrared spectroscopy in differentiating subjective cognitive decline and mild cognitive impairment
Authors: Wang Zheng , Niu Chaojie , Duan Yong , Yang Hao , Mi Jinpeng , Liu Chao , Chen Guodong , Guo Qihao
Published: December 2024

Introduction

Alzheimer’s disease (AD) is a common neurological disorder. Based on clinical characteristics, it can be categorized into normal cognition (NC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia (AD). Once the condition begins to progress, the process is usually irreversible. Therefore, early identification and intervention are crucial for patients. This study aims to explore the sensitivity of fNIRS in distinguishing between SCD and MCI.

Methods

An in-depth analysis of the Functional Connectivity (FC) and oxygenated hemoglobin (HbO) characteristics during resting state and different memory cognitive tasks is conducted on two patient groups to search for potential biomarkers. The 33 participants were divided into two groups: SCD and MCI.

Results

Functional connectivity strength during the resting state and hemodynamic changes during the execution of Verbal Fluency Tasks (VFT) and MemTrax tasks were measured using fNIRS. The results showed that compared to individuals with MCI, patients with SCD exhibited higher average FC levels between different channels in the frontal lobe during resting state, with two channels’ FC demonstrating significant ability to distinguish between SCD and MCI. During the VFT task, the overall average HbO concentration in the frontal lobe of SCD patients was higher than that of MCI patients from 5 experimental paradigm. Receiver operating characteristic analysis indicated that the accuracy of the above features in distinguishing SCD from MCI was 78.8%, 72.7%, 75.8%, and 66.7%, respectively.

Discussion

fNIRS could potentially serve as a non-invasive biomarker for the early detection of dementia.
Evaluating a 12-week aerobic exercise intervention in adults with persisting post-concussive symptoms
Authors: Mercier Leah J. , McIntosh Samantha J. , Boucher Chloe , Joyce Julie M. , Batycky Julia , Galarneau Jean-Michel , Burma Joel S. , Smirl Jonathan D. , Esser Michael J. , Schneider Kathryn J. , Dukelow Sean P. , Harris Ashley D. , Debert Chantel T.
Published: December 2024

Background

Although guidelines support aerobic exercise in sub-acute mild traumatic brain injury (mTBI), evidence for adults with persisting post-concussive symptoms (PPCS) after mTBI is lacking. The objective was to evaluate the impact of a sub-symptom threshold aerobic exercise intervention on overall symptom burden and quality of life in adults with PPCS.

Methods

This prospective cohort study was nested within the ACTBI Trial (Aerobic Exercise for treatment of Chronic symptoms following mild Traumatic Brain Injury). A total of 50 adults with a diagnosis of mTBI, PPCS and exercise intolerance completed a 12-week sub-symptom threshold aerobic exercise intervention either immediately after enrollment (i-AEP group; n = 27) or following 6-weeks of stretching (d-AEP group; n = 23). Data from all participants (n = 50) were included in the combined AEP (c-AEP) group. The primary outcome was symptom burden on the Rivermead Post Concussion Symptoms Questionnaire (RPQ). Secondary outcomes included measures of quality of life and specific post-concussive symptoms (depressive and anxiety symptoms, functional impact of headache, fatigue, sleep, dizziness and exercise tolerance). Heart rate, blood pressure and heart rate variability were also assessed to understand autonomic function response to intervention.

Results

Participants were a mean (SD) of 42.6 (10.9) years old (74% female) and 25.1 (14.1) months post-mTBI. Following 12-weeks of intervention participants had a significant improvement in symptom burden on the RPQ (i-AEP: mean change = −9.415, p < 0.001; d-AEP: mean change = −3.478, p = 0.034; c-AEP: mean change = −6.446, p < 0.001). Participants also had significant improvement in quality of life (i-AEP: mean change = 9.879, p < 0.001; d-AEP: mean change = 7.994, p < 0.001, c-AEP: mean change = 8.937, p < 0.001), dizziness (i-AEP: mean change = −11.159, p = 0.001; d-AEP: mean change = −6.516, p = 0.019; c-AEP: −8.837, p < 0.001) and exercise tolerance (i-AEP: mean change = 5.987, p < 0.001; d-AEP: mean change = 3.421, p < 0.001; c-AEP: mean change = 4.703, p < 0.001). Headache (mean change = −5.522, p < 0.001) and depressive symptoms (mean change = −3.032, p = 0.001) improved in the i-AEP group. There was no change in measures of autonomic function.

Conclusion

A 12-week aerobic exercise intervention improves overall symptom burden, quality of life and specific symptom domains in adults with PPCS. Clinicians should consider prescription of progressive, individualized, sub-symptom threshold aerobic exercise for adults with PPCS even if presenting with exercise intolerance and months-to-years of symptoms.
Selective otolithic dysfunction in patients presenting with acute spontaneous vertigo: consideration based on MRI
Authors: Kim Keun-Tae , Park Sangeun , Lee Sun-Uk , Park Euyhyun , Kim Byungjun , Kim Ji-Soo
Published: December 2024

Objective

Acute unilateral peripheral vestibulopathy or vestibular neuritis (AUPV/VN) manifests as acute onset vertigo, often accompanied by nausea, vomiting, and moderate gait instability. It is suspected when vestibular hypofunction is documented on video-head impulse (video-HITs) and caloric tests in the presence of contralesionally beating horizontal-torsional nystagmus. Herein, we report patients presenting with acute vestibular syndrome (AVS) showing selective otolithic dysfunction in the presence of normal caloric and video-HITs and abnormal enhancement of the peripheral vestibular structures on MRI.

Methods

We retrospectively reviewed the medical records of patients presenting with AVS between September 2019 and April 2024 at a tertiary referral hospital in South Korea. All patients underwent extensive neurotologic evaluation, including cervical and ocular vestibular-evoked myogenic potentials (cVEMP and oVEMP, respectively), subjective visual vertical, video-oculography, video-HITs, caloric tests, and audiometry. Patients also underwent MRI according to a standard protocol for the inner ear and internal acoustic canal with an additional 3D-fluid attenuated inversion recovery sequence acquired 4 h after intravenous gadolinium injection.

Results

We identified four patients with selective otolith dysfunction. Video-HITs and caloric test results were normal in all patients, except one with a canal paresis on the opposite side of otolithic dysfunction. Patients usually showed abnormal oVEMP (n = 3) and cVEMP (n = 2) or subjective visual vertical (n = 3). Gadolinium enhancements were found in the vestibule (n = 3), inferior (n = 2) or superior (n = 1) vestibular nerves on dedicated inner ear MRI.

Discussion

Selective otolithic dysfunction can present with AVS, which can be easily overlooked. A thorough neurotologic evaluation and MRI dedicated to the inner ear can help detect selective otolithic dysfunction, expanding the clinical spectrum of AVS.
The role of Aha1 in cancer and neurodegeneration
Authors: Blagg Brian S.J. , Catalfano Kevin C.
Published: December 2024

The 90 kDa Heat shock protein (Hsp90) is a family of ubiquitously expressed molecular chaperones responsible for the stabilization and maturation of >400 client proteins. Hsp90 exhibits dramatic conformational changes to accomplish this, which are regulated by partner proteins termed co-chaperones. One of these co-chaperones is called the activator or Hsp90 ATPase activity homolog 1 (Aha1) and is the most potent accelerator of Hsp90 ATPase activity. In conditions where Aha1 levels are dysregulated including cystic fibrosis, cancer and neurodegeneration, Hsp90 mediated client maturation is disrupted. Accumulating evidence has demonstrated that many disease states exhibit large hetero-protein complexes with Hsp90 as the center. Many of these include Aha1, where increased Aha1 levels drive disease states forward. One strategy to block these effects is to design small molecule disruptors of the Hsp90/Aha1 complex. Studies have demonstrated that current Hsp90/Aha1 small molecule disruptors are effective in both models for cancer and neurodegeration.
Structural equation modeling of dietary patterns and association with vitamin D levels in children aged 9–16 years in Guangzhou, China
Authors: Guo Jiaying , Huang Jie , Luo Shiyun , Zeng Chunzi , Su Zheng , Fu Jinhan , Zhang Weiwei , Bai Zhijun , Zhang Zhoubin , Zhu Huilian , Li Yan
Published: December 2024

Background

Vitamin D deficiency and insufficiency represent critical public health concerns on a global scale. Due to the increase in indoor activities, the role of dietary intake of vitamin D has become increasingly prominent. However, previous studies have focused solely on a single food item.

Objectives

This study aimed to identify dietary patterns among school-aged children in rural areas of Guangzhou, China, and to explore their association with vitamin D levels.

Methods

A total of 2,346 children aged 6–17 years were included in this cross-sectional study. Demographic, lifestyle, and dietary data were collected through structured questionnaires. Dietary patterns were identified using factor analysis, while linear regression and structural equation modeling were employed to analyze the relationship between these patterns and vitamin D levels.

Results

Three distinct dietary patterns emerged: a fruits and vegetables pattern, high-protein pattern, and snack pattern. Analysis revealed that a higher adherence to the fruits and vegetables dietary pattern was associated with lower vitamin D levels. Conversely, among girls, a stronger preference for the high-protein dietary pattern was positively correlated with higher vitamin D levels.

Conclusion

The fruits and vegetables pattern emerged as a risk factor for inadequate internal vitamin D levels. In girls, the high-protein pattern functioned as a protective factor. These findings offer valuable insights and policy recommendations for enhancing the health status of children in rural communities.
The role of preoperative serum thyroglobulin in the diagnosis and treatment of differentiated thyroid cancer: a systematic review and meta-analysis
Authors: Lu Ying , Zhao Hao , Liu ChunHao , Kuang ZiFeng , Li XiaoYi
Published: December 2024

Background

Serum thyroglobulin (Tg) is a critical marker for monitoring tumor recurrence and metastasis in patients who have undergone total thyroidectomy for differentiated thyroid cancer (DTC). While the definitive role of preoperative serum Tg in DTC is not yet established, studies suggest its importance in differentiating between benign and malignant thyroid nodules with indeterminate cytology, as well as in predicting distant metastasis (DM) in patients with DTC.

Methods

A thorough literature review was conducted on the use of preoperative serum Tg in differentiating between benign and malignant thyroid nodules, and in evaluating the extent of DTC lesions. Relevant studies were systematically searched in PubMed, Embase, Cochrane, Scopus, and ClinicalTrials databases. A meta-analysis was performed on studies where the ratios between serum Tg diagnostic thresholds and the upper limit of the reference range were similar.

Results

Recent studies showed significantly elevated preoperative serum Tg levels in patients with DTC compared with normal individuals. However, there are inconsistencies in the serum Tg levels between patients with preoperative DTC and benign thyroid nodules across different studies. In patients with thyroid nodules who had indeterminate cytology (negative Tg antibody), the preoperative serum Tg levels were significantly higher in malignant nodules than in benign ones (meta-analysis: odds ratio: 2.59, 95% confidence intervals: 1.59–4.21, P = 0.0001). Although the meta-analysis indicated that high preoperative serum Tg is a risk factor for central lymph node metastasis in patients with DTC (meta-analysis: odds ratio: 1.68, 95% confidence interval: 1.32–2.14, P < 0.0001), some studies suggest that high preoperative serum Tg in patients with DTC does not necessarily lead to central lymph node metastasis. Furthermore, preoperative serum Tg might possess a suggestive value regarding the likelihood of DTC patients developing DM.

Conclusion

Preoperative serum Tg shows promise in differentiating between benign and malignant nodules in thyroid nodule patients with indeterminate cytology. However, further research is necessary to determine its predictive significance for lymph node metastasis and DM in patients with DTC.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42024472074.
BTK inhibition in primary central nervous system lymphoma: mechanisms, clinical efficacy, and future perspectives
Authors: Xing Yurou , Zhao Kejia , Zhang Yi , Wang Yongsheng
Published: December 2024

The prognosis of primary central nervous system lymphoma (PCNSL) patients is relatively poor, and there is currently no standard treatment plan. Most patients choose high-dose chemotherapy based on methotrexate. While traditional chemotherapy combined with biological therapy has achieved limited results, some patients still do not respond to treatment or cannot tolerate its toxicity and side effects. Bruton’s tyrosine kinase (BTK) is a key enzyme in B-cell receptor signaling, and its activation is critical for B-cell survival and proliferation. In recent years, BTK inhibitors have shown great potential in treating lymphomas derived from various B cells because of their strong targeting ability and relatively few side effects. They may also be a reasonable treatment choice for PCNSL. This article reviews the mechanism of action, clinical research, adverse reactions, and other issues of BTK inhibitors in treating PCNSL to provide a reference for individualized treatment of patients with PCNSL.
Factors associated with knowledge and practice of breast self-examination among female governmental school teachers in Gondar Town, Northwest Ethiopia, 2019
Authors: Yazew Birhaneslasie Gebeyehu , Alemu Biresaw Wassihun , Walle Tarkie Abebe
Published: December 2024

Background

Breast cancer is the most common cancer among women globally, and early detection through breast self-examination can improve survival rates. However, this practice is limited in developing countries like Ethiopia.

Objective

This study aimed to assess the factors influencing knowledge and practices related to breast self-examination among female governmental school teachers in Gondar Town, Northwest Ethiopia.

Methods

A cross-sectional study was conducted from May 1 to 30, 2019, with 422 female teachers in Gondar metropolis governmental schools selected through simple random sampling. Data were collected using a self-administered questionnaire and analyzed using EPI INFO version 7 and SPSS version 20.

Result

A total of 415 female teachers participated in the study, with a response rate of 98.3%. The mean age of respondents was 38.64 years. Only 41.9% had good knowledge of breast self-examination, while 14.5% reported good practice. Factors associated with knowledge included secondary education, higher degrees, and exposure to information. Factors influencing practice included having a degree or higher education and prior experience with breast self-examination.

Conclusion and recommendation

The study revealed low levels of knowledge and practice of breast self-examination among female teachers. Educational level was significantly associated with both knowledge and practice. Recommendations include implementing health education campaigns, organizing events like breast cancer awareness days, and forming support groups in schools to promote awareness and encourage regular breast self-examination among female teachers in Ethiopia.
Total neoadjuvant therapy based on short-course radiotherapy versus standard long-course chemoradiotherapy for locally advanced rectal cancer: a systematic review and meta-analysis of randomized controlled trials
Authors: Pu Wenji , Chen Wenqi , Jing Haiman , Li Jishi , Jiang Yong , Li Shasha , Wen Weijie , Xu Zhiyuan , Jin Jing
Published: December 2024

Background

We conducted the meta-analysis to compare the therapeutic effects of total neoadjuvant therapy (TNT) based on short-course radiotherapy followed by consolidation chemotherapy (SCRT/CCT) and long-course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) according to certain significant randomized controlled trials (RCTs).

Methods

The researchers retrieved several databases, including PubMed, Embase, Web of Science, and the Cochrane Library, to collect all the relevant literature published since the establishment of the databases until July 30, 2024, and then screened to determine the qualified literature and extracted the relevant information. Finally, RevMan 5.4 software was utilized to conduct the meta-analysis for determining the 95% confidence interval (CI) and pooled risk ratio (RR). There were 9 study indicators, including the pathologic complete remission (pCR) rate, tumor downstaging rate, R0 resection rate, sphincter preservation rate, disease-free survival (DFS), overall survival (OS), acute ≥3 grade toxicity rate, surgery complication rate, and distant recurrence rate. When moderate, even severe, heterogeneity was found, a random-effect model was applied; otherwise, a fixed-effect model was used for the analysis.

Results

A total of 6 eligible RCTs and 2259 participants were included in this meta-analysis. Compared with the standard LCCRT, TNT treatment on the basis of SCRT/CCT increased the pCR rate significantly [RR = 1.67, 95% CI (1.36, 2.04), P < 0.00001], especially in ≥ 4 cycles of the CCT arm [RR = 1.77, 95% CI: (1.41–2.23), p < 0.00001], and led to a similar tumor downstaging rate [RR = 0.99, 95% CI (0.85, 1.15), P = 0.92]. Moreover, survival outcomes, distant recurrence rate, and surgical indicators were comparable between the two groups.

Conclusion

For LARC patients, the SCRT/CCT regimen not only has a higher pCR rate, equivalent OS, and comparable additional indicators versus standard LCCRT but also shortens the treatment time, costs less, and improves patients’ adherence to the innovative anti-tumor therapy; hence, with the concept of acute toxicity control, it could be further widely and safely utilized, especially in resource-limited settings.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024600180.
Exploring the role of Epstein-Barr virus infection on the clinical features and survival in locally advanced cervical cancer: a retrospective cohort study
Authors: Castro-Uriol Denisse , Vera Juana , Valcarcel Bryan , López-Ilasaca Marco , Yabar Alejandro , Cámara Anaís , Malpica Luis , Beltrán Brady
Published: December 2024

Introduction

Epstein-Barr virus (EBV) infection has been linked to cervical cancer (CC), but few have described the clinical and outcome features of patients with CC and EBV infection.

Methods

We conducted a single-center matched cohort study on 94 patients with CC. Real-time Polymerase chain reaction (RT-PCR) was used to detect EBNA-1 (Epstein-Barr nuclear antigen 1) and LMP-1 (Latent membrane protein 1). We used Kaplan-Meier and Cox regression analysis to evaluate the effect of EBV infection on overall survival (OS) and progression-free survival (PFS). Females with a positive EBV status were matched to those without infection using a propensity score.

Results

Of the 94 patients in our cohort, 21 (22%) had a positive EBV status. Before and after matching, there were no differences in baseline clinical and sociodemographic features between patients diagnosed with CC with and without EBV infection. Most patients received concurrent chemoradiotherapy (73%) as frontline treatment. With a median follow-up of 67 months, the 5-year OS was 42% (95% CI: 33–55%) and the 5-year PFS was 37% (95% CI: 37–49%) in the entire population. Patients with EBV-positive status had comparable 5-year OS (50% vs. 37%, p-value=0.490; Hazard Ratio [HR] 0.77, 95% CI 0.36-1.62) and 5-year PFS (44% vs. 37%, p-value=0.750; HR 0.89, 95% CI 0.43-1.83) to those with EBV-negative CC, respectively.

Conclusion

Females with CC and EBV infection have similar clinical features and outcomes compared to those without EBV infection.
Efficacy and safety of camrelizumab for the treatment of cervical cancer: a systematic review and meta-analysis
Authors: Mi Xiaodong , Tuo Fei , Lin Tong
Published: December 2024

Background

Cervical cancer (CC) is a prevalent malignancy in women and ranks fourth in global cancer-related mortality. The prognosis for women with metastatic or recurring cervical cancer is unfavorable. Camrelizumab is a humanized high-affinity IgG4-kappa monoclonal antibody targeting programmed cell death 1 (PD-1), which has been progressively documented as a therapy for advanced cervical cancer with good result metrics. Nonetheless, a comprehensive investigation of Camrelizumab’s efficacy in treating cervical cancer has yet to be conducted.

Methods

We conducted a search across PubMed, Ovid Medline, Embase, Web of Science, Cochrane Library, Scopus, ProQuest, CNKI, Wan Fang, VIP database, and CBMdisc, restricting the establishment date of the databases to October 2024. The ROBINS-I Scale was utilized to evaluate the methodological quality of the included studies. Furthermore, information about CR, PR, SD, PD, ORR, DCR, median OS, median PFS, adverse events (AEs), and other relevant data was obtained. A meta-analysis was performed utilizing a random-effects model and effect size for illness.

Results

This meta-analysis included six trials, including 238 people with CC. The aggregated outcomes for patients were as follows: CR (0.097, 95% CI: 0.032-0.186), PR (0.465, 95% CI: 0.291-0.638), SD (0.264, 95% CI: 0.124-0.403), PD (0.174, 95% CI: 0.051-0.296), ORR (0.577, 95% CI: 0.354-0.799), DCR (0.784, 95% CI: 0.652-0.916), AEs (all grades: 0.836, 95% CI: 0.629-1.000, ≥grade III: 0.472, 95% CI: 0.111-0.834). The predominant treatment-related adverse events included anemia (≤grade II: 0.295, 95% CI: 0.187-0.402; ≥grade III: 0.124, 95% CI: 0.018-0.230), elevated aspartate aminotransferase (≤grade II: 0.196, 95% CI: 0.013-0.380; ≥grade III: 0.030, 95% CI: 0.007-0.053), neutropenia (≤grade II: 0.206, 95% CI: 0.150-0.261; ≥grade III: 0.114, 95% CI: 0.066-0.162), thrombocytopenia (≤grade II: 0.295, 95% CI: 0.187-0.402), and fatigue (≤grade II: 0.174, 95% CI: 0.046-0.303).

Conclusions

This meta-analysis demonstrates that camrelizumab is efficacious and well-tolerated in patients with cervical cancer.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024527065.
Magnitude and factors associated with low birth weight among newborns in public health facilities of Mekelle City, northern Ethiopia: a multi-center study
Authors: Teklehaimanot Gebremichael Aregawi , Gebreslasie Kahsay Zenebe , Werid Woldu Mammo , Gebresilassie Berhanu , Kidanemariam Gebregziabher , Tsegay Etsay Weldekidan , Gufue Zenawi Hagos , Mengesha Meresa Berwo
Published: December 2024

Background

Low birth weight is a key determinant of child survival, significantly influencing rates of infant and childhood mortality, morbidity, and disability. While some studies have been conducted in our region, there is still a gap in evidence regarding the maternal characteristics associated with low birth weight. Hence, this study aimed to determine the proportion of newborns with low birth weight and determinant factors, particularly focusing on maternal characteristics.

Method

A facility-based cross-sectional study was conducted from 21 March to 20 April 2020 involving mothers and their newborns at selected public health facilities in Mekelle City. The sample included 447 participants, with two public hospitals and three health centers chosen by a lottery method. Systematic random sampling was applied to select mother–newborn pairs. Data were collected using a structured, interviewer-administered questionnaire and analyzed using the Statistical Package for Social Sciences version 21. Bivariate and multivariate logistic regression analyses, with a 95% confidence interval (CI), were used to identify factors associated with low birth weight.

Results

The study included 447 mothers of newborns, achieving a 100% response rate. The proportion of low birth weight was 14.3%. Significant factors associated with low birth weight included attending the first antenatal care (ANC) visit in the third trimester [adjusted odds ratio (AOR) = 3.66, 95% CI: 1.28–10.44], not receiving additional nutrition during pregnancy (AOR = 4.16, 95% CI: 1.38–12.58), experiencing obstetric complications during the current pregnancy (AOR = 7.72, 95% CI: 2.76–21.59), and a gestational age at birth of less than 37 weeks (AOR = 5.36, 95% CI: 1.96–14.67).

Conclusion and recommendation

This study revealed a substantial incidence of low birth weight. The initiation of the first antenatal care visit in the third trimester, failure to supplement nutrition during pregnancy, the occurrence of obstetric complications during pregnancy, and a gestational age at birth less than 37 weeks were all found to be significantly correlated with this condition. It is recommended that policymakers strengthen maternal and child health services, especially through the focused ANC program, to improve outcomes. Health facilities should promote awareness of the importance of initiating ANC visits early, with an emphasis on nutritional counseling throughout pregnancy.
Improving the quality of life of children and parents with nocturnal enuresis: the role of health education
Authors: Liao Jianrong , Zhu Lin , Xie Danfeng , Wang Xiaomeng , Zhou Ping
Published: December 2024

The sleep disorder nocturnal enuresis (NE) affects children's health and quality of life, as well as places a heavy burden on their families. Treatment improves the child's quality of life. Unfortunately, some parents do not seek treatment for their children because they are unaware or misinformed about NE. The goal of health education is to enhance or maintain the patient's health status, thereby enhancing the patient's quality of life through positive coping strategies. Educating children and parents about NE is an effective way for nurses to raise their awareness. Furthermore, they can improve the quality of life of children by promoting their active participation in treatment. The purpose of this paper is to review information about NE and explore the role of health education in improving children's and parents' quality of life.
Cutaneous adverse events associated with BRAF and MEK inhibitors: a systematic review and meta-analysis
Authors: Qian Junhui , Wan Jinlong , Yao Qin , Chen Yin , Ling Tao , Zhang Yuejuan , Tang Zhihua
Published: December 2024

Aim

Cutaneous adverse events (CAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized. To determine the association of BRAF and MEK inhibitor treatment with CAEs in patients with melanoma compared with BRAF inhibitor alone.

Method

PubMed, Cochrane, Embase and Web of Science were systematically searched for BRAF and MEK inhibitors from database inception through 10 May 2024. Randomized clinical trials reporting on CAEs in patients with melanoma being treated with BRAF and MEK inhibitors compared with patients with melanoma being treated with BRAF inhibitor monotherapy were selected. Pooled Risk ratios (RRs) and 95% CIs were determined using random-effects analyses. The selected end points were alopecia, cutaneous squamous-cell carcinoma, hyperkeratosis, keratoacanthoma, palmoplantar erythrodysaesthesia syndrome, palmoplantar keratoderma, rash, photosensitivity reaction, and skin papilloma. All-grade and high-grade (≥3) CAEs were recorded.

Results

Comparing with BRAF and MEK inhibitors, treatment with BRAF inhibitors alone was associated with an increased risk of rash (RR, 0.73; 95% CI, 0.54–0.99; p = 0.039; I2 = 88%), alopecia (RR, 0.28; 95% CI, 0.20–0.41; P < 0.001; I2 = 76%), hyperkeratosis (RR, 0.30; 95% CI, 0.22–0.41; P < 0.001; I2 = 56%), palmoplantar erythrodysaesthesia syndrome (RR, 0.21; 95% CI, 0.10–0.47; P < 0.001; I2 = 81%), palmoplantar keratoderma (RR, 0.39; 95% CI, 0.26–0.57; P < 0.001; I2 = 29%), Skin papilloma (RR, 0.25; 95% CI, 0.12–0.52; P < 0.001; I2 = 77%), cutaneous squamous-cell carcinoma (RR, 0.21; 95% CI, 0.11–0.42; P < 0.001; I2 = 50%), and keratoacanthoma (RR, 0.22; 95% CI, 0.12–0.40; P < 0.001; I2 = 0%).

Conclusion

Therapy with BRAF and MEK inhibitors was associated with a lower risk of CAEs, especially rash, alopecia, hyperkeratosis, palmoplantar erythrodysaesthesia syndrome, palmoplantar keratoderma, skin papilloma, cutaneous squamous-cell carcinoma, and keratoacanthoma, compared with BRAF inhibitor alone. The risks of photosensitivity reaction was similar between the assessed groups. The findings may help to balance between beneficial melanoma treatment and cutaneous morbidity and mortality.
Large language models facilitating modern molecular biology and novel drug development
Authors: Liu Xiao-huan , Lu Zhen-hua , Wang Tao , Liu Fei
Published: December 2024

The latest breakthroughs in information technology and biotechnology have catalyzed a revolutionary shift within the modern healthcare landscape, with notable impacts from artificial intelligence (AI) and deep learning (DL). Particularly noteworthy is the adept application of large language models (LLMs), which enable seamless and efficient communication between scientific researchers and AI systems. These models capitalize on neural network (NN) architectures that demonstrate proficiency in natural language processing, thereby enhancing interactions. This comprehensive review outlines the cutting-edge advancements in the application of LLMs within the pharmaceutical industry, particularly in drug development. It offers a detailed exploration of the core mechanisms that drive these models and zeroes in on the practical applications of several models that show great promise in this domain. Additionally, this review delves into the pivotal technical and ethical challenges that arise with the practical implementation of LLMs. There is an expectation that LLMs will assume a more pivotal role in the development of innovative drugs and will ultimately contribute to the accelerated development of revolutionary pharmaceuticals.
The protective effects of gastrodin on neurological disorders: an update and future perspectives
Authors: Shi Zhouying , Zhang Yali , Xiao Yuhua , Shi Zhoujing , Wei Xiaotong , Wang Bin , Yuan Yue , Li Ping
Published: December 2024

Neurological disorders are characterized by high mortality and disability rates. Furthermore, the burden associated with disability and mortality resulting from neurological disorders has been increasing at an alarming rate. Botanical drugs and their bioactive components have emerged as a prominent area of research, offering a promising avenue for developing novel alternatives for treating neurological diseases. Gastrodin is the principal active component derived from the traditional Chinese medicinal plant Gastrodia elata Blume (GEB). Existing literature reveals that gastrodin exerts various pharmacological protective actions against neurological disorders. This review aimed to collate novel literature on gastrodin for treating neurological disorders from Web of Science, PubMed, Embase and CNKI. The pharmacokinetics of gastrodin, its therapeutic role in neurological disorders, the main mechanisms of action and clinical application were addressed. Furthermore, a detailed overview of gastrodin drug delivery systems and physical enhancement methods was presented, offering invaluable insights into potential research and the extensive applications of gastrodin.
Mechanistic analysis of Tanshinone IIA’s regulation of the ATM/GADD45/ORC signaling pathway to reduce myocardial ischemia-reperfusion injury
Authors: Sang Yiwei , Du Jiangnan , Zulikala Dilimulati , Sang Zhongqiang
Published: December 2024

Background

By far, one of the best treatments for myocardial ischemia is reperfusion therapy. The primary liposoluble component of Danshen, a traditional Chinese herbal remedy, Tanshinone ⅡA, has been shown to have cardiac healing properties. The purpose of this work is to investigate the processes by which Tanshinone ⅡA influences myocardial ischemia-reperfusion injury (MIRI) in the H9C2 cardiac myoblast cell line, as well as the association between Tanshinone ⅡA and MIRI.

Methods and results

The cardiac cells were divided into a normal group, a model group and Tanshinone ⅡA treatment groups. After 4 h of culture with the deprivation of oxygen and glucose, the cells were incubated normally for 2 h. The success of the model and the capacity of Tanshinone ⅡA to heal cardiac damage were validated by the outcomes of cell viability, morphology, and proliferation. The efficacy of Tanshinone ⅡA in treating MIRI was further confirmed by the scratch assay and biomarker measurement. The differentially expressed genes were examined using transcriptome sequencing. The Ataxia-Telangiectasia Mutated (ATM)/Growth Arrest and DNA Damage (GADD45)/Origin Recognition Complex (ORC) signaling pathway was identified as being crucial to this process by KEGG pathway analysis and GO enrichment. Molecular docking and RT-qPCR were used to confirm our results. The crucial function of the ATM/GADD45/ORC pathway was further confirmed by the addition of an ATM inhibitor, which inhibited the expression of ATM.

Conclusion

Tanshinone ⅡA can relieve the myocardial ischemia-reperfusion injury in cardiac cells by activating the ATM/GADD45/ORC pathway.
A mini-review on ancient mathematics’ modern applications with an emphasis on the old Babylonian mathematics for MEMS systems
Authors: Niu Jing-Yan , Feng Guang-Qing
Published: December 2024

This paper offers a concise overview regarding ancient Chinese mathematics, centering on the Ying Buzu Shu, He Chengtian inequality, and the frequency formulation stemming from them. Moreover, it delves into the Max-min approach and Chunhui He’s iterative algorithm. What’s more, the spotlight is cast on ancient Chinese mathematics, which bears certain similarities to the ancient Babylonian mathematical tradition. Subsequently, the old Babylonian algorithm for computing square roots is adapted to tackle the hurdle of nonlinear differential equations. To showcase the potential of this approach, a set of Micro-Electro-Mechanical systems (MEMS) problems are utilized to exemplify the effectiveness of the modified old Babylonian algorithm in attaining high-precision analytical solutions, accompanied by an exploration of its prospective applications.
Leaf senescence characteristics and economic benefits of rice under alternate wetting and drying irrigation and blended use of polymer-coated and common urea
Authors: Qi Dongliang , Chen Si , Yue Wenjun , Duan Yonggang
Published: December 2024

Water-saving irrigation and the mixed application of controlled-release nitrogen fertilizer (CRNF) and common urea (CU; with a higher nitrogen release rate) have shown promise in improving rice yield with high resource use efficiency. However, the physiological mechanism underlying this effect remains largely unknown. This study involved a field experiment on rice in Jingzhou City, Central China, in 2020 and 2021. Two irrigation regimes were employed [alternate wetting and drying irrigation (AWD) and conventional flood irrigation (CI)], with three nitrogen (N) compounding modes [00% CU (N1), 60% CRNF + 40% CU (N2), and 100% CRNF (N3)] with an equal N rate of 240 kg ha−1. The results indicated a significant interactive effect of watering regimes and N compounding modes on net photosynthetic rate (Pn), leaf area index (LAI), and SPAD values; activities of superoxide dismutase (SOD), peroxidases (POD), catalase (CAT), glutamine synthetase (GS), glutamine 2-oxoglutarate amidotransferase (GOGAT), and nitrate reductase (NR); and the contents of malondialdehyde (MDA) and soluble protein in rice leaves. Compared with N1, N2 and N3 increased the Pn, LAI, and SPAD values; activities of SOD, POD, CAT, NR, GS, and GOGAT; and soluble protein content but decreased MDA content in the post-growth (heading and maturity) stages by 8.7%–31.2% under the two irrigation regimes. Compared to CI (traditional irrigation), AWD had higher Pn, LAI, and SPAD values; activities of SOD, POD, CAT, NR, GS, and GOGAT; and soluble protein content (increased by 12.1%–38.0%, and lower MDA content (reduced by 13.1%–27.6%) irrespective of N compounding modes. This suggested that AWD combined with N2 and N3 could delay the leaf senescence of rice, thus achieving a larger grain yield. Moreover, AWD significantly decreased water costs (irrigation amount) and labor costs (irrigation frequency), thus increasing total income. N2 decreased fertilizer costs with a higher or comparable total income compared with N3. Therefore, the AWDN2 treatment achieved the highest net income (13,907.1 CNY ha−1 in 2020 and 14,085.7 CNY ha−1 in 2021). AWD interacted with 60% CRNF + 40% (N2) to delay leaf senescence by improving photosynthesis, antioxidant defense system, osmoregulation, and N assimilation, contributing to high grain yield and net income in rice.
Extending beyond traditional forage: potential nutritional benefits of native plants in extreme arid insular regions
Authors: Pérez-Reverón Raquel , Perdomo-González Adolfo , de la Roza-Delgado Begoña , Rodríguez Covadonga , Pérez-Pérez José A. , Díaz-Peña Francisco J.
Published: December 2024

The scarcity, unstable nutritional quality and environmental cost of imported forages in arid insular regions like Fuerteventura in the Canary Islands (Spain) need exploring sustainable local alternatives. This study evaluated the nutritional quality of twelve native and endemic plant species categorized into legumes, grasses, and a mixed group, cultivated under controlled conditions. The bromatological profiles, focusing on fiber, protein, lipids, and minerals, showed significant differences among plants in key parameters of forage quality: neutral detergent fiber (NDF; 24.2–71.3%), acid detergent fiber (ADF; 9.0–40.5%), acid detergent lignin (ADL; 2.0–15.8%), crude protein (CP; 6.1–20.9%), total lipids (TL; 1.5–6.3%), ash content (25.4–88.6%), enzymatic organic matter digestibility (EOMD; 5.9–10.9 MJ/kg), metabolizable energy (ME; 5.9–10.9 MJ/kg), and relative feed value (RFV; 74.8–317.9). Among lipids, all species had a high proportion of polyunsaturated fatty acids (PUFA; 34.7–63.1% of total fatty acids), mainly α-linolenic acid (ALA; 18:3 n-3; 24.8–54.4%) and linoleic acid (LA; 18:2 n-6; 6.4–25.0%). Other beneficial lipid molecules for animal health such as γ-linolenic acid (GLA; 18:3 n-6), stearidonic acid (SDA; 18:4n-3) and phytosterols (PTS) were detected in specific species. Mineral composition analysis revealed that only Ca, Na, Fe and Cu levels were near or above the established maximum tolerable levels (MTLs) in some species. According to literature, most of the species had a similar or slightly lower nutritional value compared to conventional forages such as alfalfa. Thus, the evaluated native species pool could serve as alternative feed for ruminants during forage shortages, suggesting their combined use to improve livestock health and product quality. This research emphasizes the untapped potential of native plant biodiversity to enhance sustainable agro-livestock practices in arid regions, supporting livestock nutrition and conserving unique botanical heritage.
Genetic parameters of growth and leaf traits and genetic gains with MGIDI in three Populus simonii × P. nigra families at two spacings
Authors: Wang Tianxin , Ren Jingshan , Huang Qinjun , Li Jinhua
Published: December 2024

New genotypes of hybrid from the Aigeiros and Tacamahaca sections, which encompass economically important species of Populus L., have great potential to significantly enhance genetic gain from selection. Growth and its functional and structural determinants exhibiting a high level of variability are not only controlled by genetics, but also affected by environment, as well as genotype and environment interaction (G×E). The preceding research on the intersectional progenies derived from eight families (P. simonii × P. nigra) and their respective parents has indicated that leaf traits exhibiting robust genetic control were employed for selection of hybrid genotypes displaying multiple traits. The goals of this research with the progenies 3 families across two spacing trials were to (1) assess the GEI in progeny genotypes for multiple traits, (2) estimate the genetic parameters for important traits, (3) identify the genotypes with superior productive performance, adaptability, and genotypic stability using the MGIDI index, (4) select genotypes that exhibit high performance and genotypic stability across multiple traits using the MGIDI index. We found that the progeny genotypes showed considerable variation in growth and leaf morphology response to the spacings and genotype interaction effects were significant (P ≤ 0.001) for most of the traits studied in the progeny of each family and the joint family. The highest broad-sense heritability was observed for petiole length, while the lowest heritability values were recorded for stomatal length among the eight traits studied in both each family and the joint family. The MGIDI, assuming selection intensity of 15%, identified 26, 25, 35, and 86 genotypes in the three families and the joint family, respectively. The selected hybrids of each family and the joint family exhibited the desired genetic gains, including positive gains for leaf area (6.87%-11.2%), petiole length (3.81%-13.7%) and plant height (1.30%-10.4%). The interpretation of strengths and weaknesses as illustrated by the MGIDI provides guidance for the breeders to develop poplar hybrids performed well in desired traits, such as growth and other yield contributors i.e. leaf traits. The tested progeny genotypes of three families provided a valuable addition to the hybrid selection for rapid juvenile growth.
Leveraging RNA interference technology for selective and sustainable crop protection
Authors: Qi Hong-Yue , Zhang Dan-Dan , Liu Binhui , Chen Jie-Yin , Han Dongfei , Wang Dan
Published: December 2024

Double-stranded RNA (dsRNA) has emerged as key player in gene silencing for the past two decades. Tailor-made dsRNA is now recognized a versatile raw material, suitable for a wide range of applications in biopesticide formulations, including insect control to pesticide resistance management. The mechanism of RNA interference (RNAi) acts at the messenger RNA (mRNA) level, utilizing a sequence-dependent approach that makes it unique in term of effectiveness and specificity compared to conventional agrochemicals. Two primary categories of small RNAs, known as short interfering RNAs (siRNAs) and microRNAs (miRNAs), function in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Furthermore, the application of RNAi in crop protection can be achieved by employing plant-incorporated protectants through plant transformation, but also by non-transformative strategies such as the use of formulations of sprayable RNAs as direct control agents, resistance factor repressors or developmental disruptors. This review explores the agricultural applications of RNAi, delving into its successes in pest-insect control and considering its broader potential for managing plant pathogens, nematodes, and pests. Additionally, the use of RNAi as a tool for addressing pesticide-resistant weeds and insects is reviewed, along with an evaluation of production costs and environmental implications.
Perceived social support and psychological wellbeing: testing the moderated mediation model of self-compassion and culture
Authors: Tannous-Haddad Lubna , Barel Efrat , Tzischinsky Orna
Published: December 2024

Introduction

Self-compassion and self-coldness mediate the relationship between perceived social support and wellbeing, depression, anxiety and stress. However, this mediation has not been studied in intercultural contexts yet. The current crosssectional study explores the mediation effects of both constructs among Arabs and Jews in Israel.

Methods

Participants were 496 adults—309 Jews (62.3%) and 187 Arabs (37.7%) with an average age of 40.3. Respondents completed online standardized measures of self-compassion, self-coldness, perceived social support, wellbeing, depression, anxiety, and stress. The data were analyzed using PROCESS macro model 4 and 59.

Results

Testing the indirect effects of self-compassion and self-coldness on the relationship between perceived social support and wellbeing facets, we found a mediation effect for both constructs. We also found that culture moderated the mediation processes and found a stronger mediation effect for self-compassion among Arabs than Jews, but no moderation of culture on the mediation effect of self-coldness.

Discussion

These results emphasize the importance of considering cultural context when designing support interventions aimed at promoting wellbeing by enhancing self-compassion. The differential mediation effect by self-compassion and self-coldness contributes to growing research pointing to a need to further explore the influence of different components of self-compassion in different cultures.
The valuation of older adult homecare services under a joint medical-social budgetary perspective
Authors: Leung Eman , Guan Jingjing , Chu Amanda M. Y. , Ching Sam C. C. , Liu Yilin , Chen Frank Youhua
Published: December 2024

Background

Homecare, a cornerstone of public health, is essential for health systems to achieve the Sustainable Development Goal (SDG) of universal health coverage while maintaining its own sustainability. Notwithstanding homecare’s system-level significance, there is a lack of economic evaluations of homecare services in terms of their system-wide cost-savings. Specifically, decisions informed by a joint medical-social budgetary perspective can maximize the allocative efficiency of assigning a diverse service mix to address the complex needs of the older adult population. However, little is known regarding which homecare service mix is most system-wide cost-effective when paired with which clinical profiles.

Methods

Valuation of homecare’s complex interventions was performed under a generalized cost-effectiveness analysis (GCEA) framework with proportional hazard-adjusted metrics representing the common numeraire between medical and social care.

Results

Instrumental homecare, on its own or combined with either one or both of the other homecare services, yielded the greatest cost savings compared to other services or the lack thereof. When expressed under a joint medical-social budgetary perspective, instrumental homecare can reduce medical costs of HK$34.53 (US$4.40) and HK$85.03 (US$10.84) for every HK$1 (US$0.13) invested in instrumental and instrumental-restorative homecare, respectively.

Conclusion

Instrumental homecare can increase hospitalization-free days among community-dwelling older adult and yield significant net system-wide cost savings. Thus, the current study demonstrated the feasibility of data-informed decision-making in system-wide resource allocation under a joint medical-social budget perspective.