bluuebunny/crossref_metadata_2025 huggingface dataset:
In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer
Authors: Zafar Imran , Safder Arfa , Imran Afridi Hassan , Riaz Sania , -ur-Rehman Rizwan , Unar Ahsanullah , Un Nisa Fakhar , Gaafar Abdel-Rhman Z. , Bourhia Mohammed , Wondmie Gezahign Fentahun , Sharma Rohit , Kumar Dileep
Published: October 2023

Introduction: Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments.

Material and Methods: For in vitro study we used thin layer chromatography (TAC) for phytochemical screening, total antioxidant capacity (TLC) assay for antioxidant capacity, and hemolytic activity test for toxicity of Neuropilins (NRPs). We performed bioinformatic analyses to predict protein structures, molecular docking, pharmacophore modeling, and virtual screening to reveal interactions with oncogenes. We conducted 200 ns Molecular Dynamics (MD) simulations and MMGBSA calculations to assess the complex dynamics and stability.

Results: We identified phytochemical constituents in Nigella sativa leaves, including tannins, saponins, steroids, and cardiac glycosides, while phlobatannins and terpenoids were absent. The leaves contained 9.4% ± 0.04% alkaloids and 1.9% ± 0.05% saponins. Methanol extract exhibited the highest yield and antioxidant capacity, with Total Flavonoid Content at 127.51 ± 0.76 mg/100 g and Total Phenolic Content at 134.39 ± 0.589 mg GAE/100 g. Hemolysis testing showed varying degrees of hemolysis for different extracts. In-silico analysis indicated stable Neuropilin complexes with key signaling pathways relevant for anti-cancer therapy. Molecular docking scores at different possesses (0, C-50, C −80, C-120,C −150, C −200 ns) revealed strong hydrogen bonding in the complexes and showed −12.9, −11.6, and −11.2 binding Affinities (kcal/mol) to support their stability. Our MD simulations analysis at 200ns confirmed the stability of Neuropilin complexes with the signaling pathways protein PI3K. The calculated binding free energies using MMGBSA provided valuable quantitative information on ligand potency on different time steps. These findings highlight the potential health benefits of N. sativa leaves and their possible role in anti-cancer treatments targeting angiogenesis.

Conclusion:Nigella sativa leaves have shown significant medical potential due to their bioactive compounds, which exhibit strong properties in supporting organogenic processes related to cancer. Furthermore, studies have highlighted the promising role of neuropilins in anticancer treatment, demonstrating stable interactions and potential as targeted therapy specifically for breast cancer.
Artificial intelligence-enhanced 12-lead electrocardiography for identifying atrial fibrillation during sinus rhythm (AIAFib) trial: protocol for a multicenter retrospective study
Authors: Baek Yong-Soo , Kwon Soonil , You Seng Chan , Lee Kwang-No , Yu Hee Tae , Lee So-Ryung , Roh Seung-Young , Kim Dong-Hyeok , Shin Seung Yong , Lee Dae In , Park Junbeom , Park Yae Min , Suh Young Ju , Choi Eue-Keun , Lee Sang-Chul , Joung Boyoung , Choi Wonik , Kim Dae-Hyeok
Published: October 2023

Introduction

Atrial fibrillation (AF) is the most common arrhythmia, contributing significantly to morbidity and mortality. In a previous study, we developed a deep neural network for predicting paroxysmal atrial fibrillation (PAF) during sinus rhythm (SR) using digital data from standard 12-lead electrocardiography (ECG). The primary aim of this study is to validate an existing artificial intelligence (AI)-enhanced ECG algorithm for predicting PAF in a multicenter tertiary hospital. The secondary objective is to investigate whether the AI-enhanced ECG is associated with AF-related clinical outcomes.

Methods and analysis

We will conduct a retrospective cohort study of more than 50,000 12-lead ECGs from November 1, 2012, to December 31, 2021, at 10 Korean University Hospitals. Data will be collected from patient records, including baseline demographics, comorbidities, laboratory findings, echocardiographic findings, hospitalizations, and related procedural outcomes, such as AF ablation and mortality. De-identification of ECG data through data encryption and anonymization will be conducted and the data will be analyzed using the AI algorithm previously developed for AF prediction. An area under the receiver operating characteristic curve will be created to test and validate the datasets and assess the AI-enabled ECGs acquired during the sinus rhythm to determine whether AF is present. Kaplan–Meier survival functions will be used to estimate the time to hospitalization, AF-related procedure outcomes, and mortality, with log-rank tests to compare patients with low and high risk of AF by AI. Multivariate Cox proportional hazards regression will estimate the effect of AI-enhanced ECG multimorbidity on clinical outcomes after stratifying patients by AF probability by AI.

Discussion

This study will advance PAF prediction based on AI-enhanced ECGs. This approach is a novel method for risk stratification and emphasizes shared decision-making for early detection and management of patients with newly diagnosed AF. The results may revolutionize PAF management and unveil the wider potential of AI in predicting and managing cardiovascular diseases.

Ethics and dissemination

The study findings will be published in peer-reviewed publications and disseminated at national and international conferences and through social media. This study was approved by the institutional review boards of all participating university hospitals. Data extraction, storage, and management were approved by the data review committees of all institutions.

Clinical Trial Registration

[cris.nih.go.kr], identifier (KCT0007881).
SGMS2 in primary osteoporosis with facial nerve palsy
Authors: Pihlström Sandra , Richardt Sampo , Määttä Kirsi , Pekkinen Minna , Olkkonen Vesa M. , Mäkitie Outi , Mäkitie Riikka E.
Published: October 2023

Pathogenic heterozygous variants in SGMS2 cause a rare monogenic form of osteoporosis known as calvarial doughnut lesions with bone fragility (CDL). The clinical presentations of SGMS2-related bone pathology range from childhood-onset osteoporosis with low bone mineral density and sclerotic doughnut-shaped lesions in the skull to a severe spondylometaphyseal dysplasia with neonatal fractures, long-bone deformities, and short stature. In addition, neurological manifestations occur in some patients. SGMS2 encodes sphingomyelin synthase 2 (SMS2), an enzyme involved in the production of sphingomyelin (SM). This review describes the biochemical structure of SM, SM metabolism, and their molecular actions in skeletal and neural tissue. We postulate how disrupted SM gradient can influence bone formation and how animal models may facilitate a better understanding of SGMS2-related osteoporosis.
Tocilizumab for the fifth progression of cystic childhood craniopharyngioma—a case report
Authors: de Vos-Kerkhof Evelien , Buis Dennis R. , Lequin Maarten H. , Bennebroek Carlien A. , Aronica Eleonora , Hulleman Esther , Zwaveling-Soonawala Nitash , van Santen Hanneke M. , Schouten-van Meeteren Antoinette Y. N.
Published: October 2023

We present the case of a 15-year-old girl, with a fifth cystic progression of an adamantinomatous craniopharyngioma after multiple surgeries and previous local radiotherapy. She had severe visual impairment, panhypopituitarism including diabetes insipidus, and several components of hypothalamic damage, including morbid obesity and severe fatigue. To prevent further late effects hampering her quality of survival, she was treated biweekly with intravenous tocilizumab, an anti-interleukin-6 agent, which stabilized the cyst for a prolonged time. Based on the biology of adamantinomatous craniopharyngioma, this immune-modulating treatment seems promising for the treatment of this cystic tumor in order to reduce surgery and delay or omit radiotherapy.
Serum uric acid is related to liver and kidney disease and 12-year mortality risk after myocardial infarction
Authors: Heerkens Luc , van Westing Anniek C. , Voortman Trudy , Kardys Isabella , Boersma Eric , Geleijnse Johanna M.
Published: October 2023

Objective

To study the associations of non-alcoholic fatty liver disease (NAFLD), chronic kidney disease (CKD), and serum uric acid (SUA) in patients with post–myocardial infarction (MI) patients, and the relationship of SUA with 12-year mortality risk.

Methods

We included 3,396 patients (60–80 years old, 78% men) of the Alpha Omega Cohort. Multivariable prevalence ratios (PRs) were obtained for the association of NAFLD [fatty liver index (FLI), ≥77 (women) and ≥79 (men)] with CKD [estimated glomerular filtration rate (eGFR), <60 mL/min per 1.73 m2]. We calculated sensitivity and specificity of SUA to detect the (combined) presence and absence of NAFLD and CKD. Cause-specific mortality was monitored from enrolment (2002–2006) through December 2018. Hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality in SUA categories were obtained from multivariable Cox models.

Results

Median baseline FLI was 67 (men, 68; women, 64), and mean ± SD eGFR was 81 ± 20 mL/min per 1.73 m2 (17% with CKD). Sex-specific FLI was associated with higher CKD prevalence (PRtertile3 vs. tertile1, 1.94; 95% confidence interval: 1.57, 2.39). Baseline SUA was 0.36 ± 0.09 mmol/L. With increasing SUA concentrations, specificity for the presence of NAFLD, CKD, or both increased, and sensitivity decreased. During 12 (interquartile range, 9–14) years of follow-up, 1,592 patients died (713 from CVD). HRs ranged from 1.08 (0.88, 1.32) for SUA ≤0.25 mmol/L to 2.13 (1.75, 2.60) for SUA >0.50 mmol/L vs. SUA >0.30–0.35 mmol/L for all-cause mortality. For CVD mortality, HRs ranged from 1.05 (0.77, 1.44) to 2.43 (1.83, 3.25).

Conclusions

NAFLD and CKD were strongly associated, which was reflected by higher SUA concentrations. SUA was a strong predictor of 12-year mortality risk after MI.
Preoperative and postoperative blood testosterone levels in patients with acromegaly: a prospective study
Authors: Zhang Duoxing , Guo Xiaopeng , Feng Ming , Bao Xinjie , Deng Kan , Yao Yong , Lian Wei , Xing Bing , Wang Hanbi
Published: October 2023

Purpose

To investigate the prevalence of low blood testosterone level (LTL) and its determinant factors among active male acromegaly patients, as well as the effect of surgery on LTL in male acromegaly patients.

Methods

A retrospective, single-center study focused on 252 male acromegaly patients aged 18 years–60 years diagnosed in the Peking Union Medical College Hospital from January 2015 to December 2018 was carried out. The measurements of preoperative and postoperative testosterone levels, serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and other clinical data were analyzed.

Results

Forty per cent of subjects included were diagnosed with LTL pre surgery. Patients were divided into normal testosterone level (NTL) and LTL groups based on their testosterone level. There were significant differences (p < 0.01) between groups in the presence of macroadenomas, invasion of the cavernous sinus, compression of the optic chiasm, and serum GH and prolactin levels pre surgery. Invasion of the cavernous sinus [odds ratio (OR) = 4.299; p = 0.000] and serum prolactin level (OR = 1.023, p = 0.001) were independent predictors of LTLs in male patients before surgical intervention. A total of 67.9% of LTL patients recovered during the follow-up, with a new-onset rate of 3.4%. Body mass index, invasion of the cavernous sinus, GH, IGF-1, and prolactin levels, the presence of a prolactin-secreting tumor, and recovery from acromegaly were significantly different (p < 0.05) in the NTL group and in the LTL group during the follow-up. The presence of a prolactin-secreting tumor (OR = 0.224; p = 0.001) and recovery from acromegaly (OR = 0.168; p = 0.006) were independent predictors of LTLs in male acromegaly patients during the follow-up.

Conclusion

The invasiveness of tumor and levels of blood prolactin are independent factors for LTLs before surgery, whereas GH and IGF-1 levels are not. Most male patients can recover from LTL after tumor restriction surgery: those who recover from acromegaly have a better chance of recovering from LTL.
The characteristic and potential of green trade between China and regional comprehensive economic partnership countries
Authors: Xu Yujie , Liao Xianchun , Li Meicun
Published: October 2023

This paper analyze the characteristics of green trade between China and Regional Comprehensive Economic Partnership (RCEP) countries from 2001 to 2020, and then adopts a stochastic frontier gravity (SFG) model and trade inefficiency (TIE) model to analyze the trade potential and the influencing factors of green trade between China and RCEP countries. The main conclusions are as follows: the green trade value continues to grow, with Japan and South Korea as the main green trade partners. The competitive advantage of Chinese green products and the complementarity of RCEP countries towards Chinese green products are both increasing. Per capita GDP, population of RCEP countries promote the green trade, while the geographical distance hinders green trade. In the item of TIE, governance ability and economic freedom promote the efficiency of green trade, while differences in environmental regulation and tariff rate hinders trade efficiency. At present, China has significant green trade potential with RCEP countries. The efficiency of green trade between China and Japan, South Korea, Singapore, Vietnam, and Australia is relatively low. China should actively tap into the demand for green trade and further develop the potential of green trade.
Shining a spotlight on m6A and the vital role of RNA modification in endometrial cancer: a review
Authors: Jin Zujian , Sheng Jingjing , Hu Yingying , Zhang Yu , Wang Xiaoxia , Huang Yiping
Published: October 2023

RNA modifications are mostly dynamically reversible post-transcriptional modifications, of which m6A is the most prevalent in eukaryotic mRNAs. A growing number of studies indicate that RNA modification can finely tune gene expression and modulate RNA metabolic homeostasis, which in turn affects the self-renewal, proliferation, apoptosis, migration, and invasion of tumor cells. Endometrial carcinoma (EC) is the most common gynecologic tumor in developed countries. Although it can be diagnosed early in the onset and have a preferable prognosis, some cases might develop and become metastatic or recurrent, with a worse prognosis. Fortunately, immunotherapy and targeted therapy are promising methods of treating endometrial cancer patients. Gene modifications may also contribute to these treatments, as is especially the case with recent developments of new targeted therapeutic genes and diagnostic biomarkers for EC, even though current findings on the relationship between RNA modification and EC are still very limited, especially m6A. For example, what is the elaborate mechanism by which RNA modification affects EC progression? Taking m6A modification as an example, what is the conversion mode of methylation and demethylation for RNAs, and how to achieve selective recognition of specific RNA? Understanding how they cope with various stimuli as part of in vivo and in vitro biological development, disease or tumor occurrence and development, and other processes is valuable and RNA modifications provide a distinctive insight into genetic information. The roles of these processes in coping with various stimuli, biological development, disease, or tumor development in vivo and in vitro are self-evident and may become a new direction for cancer in the future. In this review, we summarize the category, characteristics, and therapeutic precis of RNA modification, m6A in particular, with the purpose of seeking the systematic regulation axis related to RNA modification to provide a better solution for the treatment of EC.
Combining CSPG4-CAR and CD20-CCR for treatment of metastatic melanoma
Authors: Teppert Karin , Winter Nora , Herbel Vera , Brandes Caroline , Lennartz Simon , Engert Fabian , Kaiser Andrew , Schaser Thomas , Lock Dominik
Published: October 2023

The prognosis for patients with metastatic melanoma is poor and treatment options are limited. Genetically-engineered T cell therapy targeting chondroitin sulfate proteoglycan 4 (CSPG4), however, represents a promising treatment option, especially as both primary melanoma cells as well as metastases uniformly express CSPG4. Aiming to prevent off-tumor toxicity while maintaining a high cytolytic potential, we combined a chimeric co-stimulatory receptor (CCR) and a CSPG4-directed second-generation chimeric antigen receptor (CAR) with moderate potency. CCRs are artificial receptors similar to CARs, but lacking the CD3ζ activation element. Thus, T cells expressing solely a CCR, do not induce any cytolytic activity upon target cell binding, but are capable of boosting the CAR T cell response when both CAR and CCR engage their target antigens simultaneously. Here we demonstrate that co-expression of a CCR can significantly enhance the anti-tumor response of CSPG4-CAR T cells in vitro as well as in vivo. Importantly, this boosting effect was not dependent on co-expression of both CCR- and CAR-target on the very same tumor cell, but was also achieved upon trans activation. Finally, our data support the idea of using a CCR as a powerful tool to enhance the cytolytic potential of CAR T cells, which might open a novel therapeutic window for the treatment of metastatic melanoma.
Circulating donor-derived cell-free DNA as a marker for rejection after lung transplantation
Authors: Li Yunhui , Liang Bin
Published: October 2023

Objective

Recently, circulating donor-derive cell free DNA (dd-cfDNA) has gained growing attention in the field of solid organ transplantation. The aim of the study was to analyze circulating dd-cfDNA levels in graft rejection, ACR and AMR separately for each rejection type compared with non-rejection, and assessed the diagnostic potential of dd-cfDNA levels in predicting graft rejection after lung transplantation.

Methods

A systematic search for relevant articles was conducted on Medline, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases without restriction of languages. The search date ended on June 1, 2023. STATA software was used to analyze the difference between graft rejection, ACR, AMR and stable controls, and evaluate the diagnostic performance of circulating dd-cfDNA in detecting graft rejection.

Results

The results indicated that circulating dd-cfDNA levels in graft rejection, ACR, and AMR were significantly higher than non-rejection (graft rejection: SMD=1.78, 95% CI: 1.31-2.25, I2 = 88.6%, P< 0.001; ACR: SMD=1.03, 95% CI: 0.47-1.59, I2 = 89.0%, P < 0.001; AMR: SMD= 1.78, 95% CI: 1.20-2.35, I2 = 89.8%, P < 0.001). Circulating dd-cfDNA levels distinguished graft rejection from non-rejection with a pooled sensitivity of 0.87 (95% CI: 0.80-0.92) and a pooled specificity of 0.82 (95% CI: 0.76-0.86). The corresponding SROC yield an AUROC of 0.90 (95% CI: 0.87-0.93).

Conclusion

Circulating dd-cfDNA could be used as a non-invasive biomarker to distinguish the patients with graft rejection from normal stable controls.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023440467.
Evaluating the impact of testing strategies for the detection of nosocomial COVID-19 in English hospitals through data-driven modeling
Authors: Evans Stephanie , Stimson James , Pople Diane , Wilcox Mark H. , Hope Russell , Robotham Julie V.
Published: October 2023

Introduction

During the first wave of the COVID-19 pandemic 293,204 inpatients in England tested positive for SARS-CoV-2. It is estimated that 1% of these cases were hospital-associated using European centre for disease prevention and control (ECDC) and Public Health England (PHE) definitions. Guidelines for preventing the spread of SARS-CoV-2 in hospitals have developed over time but the effectiveness and efficiency of testing strategies for preventing nosocomial transmission has not been explored.

Methods

Using an individual-based model, parameterised using multiple datasets, we simulated the transmission of SARS-CoV-2 to patients and healthcare workers between March and August 2020 and evaluated the efficacy of different testing strategies. These strategies were: 0) Testing only symptomatic patients on admission; 1) Testing all patients on admission; 2) Testing all patients on admission and again between days 5 and 7, and 3) Testing all patients on admission, and again at days 3, and 5-7. In addition to admissions testing, patients that develop a symptomatic infection while in hospital were tested under all strategies. We evaluated the impact of testing strategy, test characteristics and hospital-related factors on the number of nosocomial patient infections.

Results

Modelling suggests that 84.6% (95% CI: 84.3, 84.7) of community-acquired and 40.8% (40.3, 41.3) of hospital-associated SARS-CoV-2 infections are detectable before a patient is discharged from hospital. Testing all patients on admission and retesting after 3 or 5 days increases the proportion of nosocomial cases detected by 9.2%. Adding discharge testing increases detection by a further 1.5% (relative increase). Increasing occupancy rates, number of beds per bay, or the proportion of admissions wrongly suspected of having COVID-19 on admission and therefore incorrectly cohorted with COVID-19 patients, increases the rate of nosocomial transmission. Over 30,000 patients in England could have been discharged while incubating a non-detected SARS-CoV-2 infection during the first wave of the COVID-19 pandemic, of which 3.3% could have been identified by discharge screening. There was no significant difference in the rates of nosocomial transmission between testing strategies or when the turnaround time of the test was increased.

Discussion

This study provides insight into the efficacy of testing strategies in a period unbiased by vaccines and variants. The findings are relevant as testing programs for SARS-CoV-2 are scaled back, and possibly if a new vaccine escaping variant emerges.
Comparative analyses of the bacterial communities present in the spontaneously fermented milk products of Northeast India and West Africa
Authors: Sessou Philippe , Keisam Santosh , Gagara Mariama , Komagbe Gwladys , Farougou Souaïbou , Mahillon Jacques , Jeyaram Kumaraswamy
Published: October 2023

Introduction

Spontaneous fermentation of raw cow milk without backslopping is in practice worldwide as part of the traditional food culture, including “Doi” preparation in earthen pots in Northeast India, “Kindouri” of Niger and “Fanire” of Benin prepared in calabash vessels in West Africa. Very few reports are available about the differences in bacterial communities that evolved during the spontaneous mesophilic fermentation of cow milk in diverse geographical regions.

Methods

In this study, we used high throughput amplicon sequencing of bacterial 16S rRNA gene to investigate 44 samples of naturally fermented homemade milk products and compared the bacterial community structure of these foods, which are widely consumed in Northeast India and Western Africa.

Results and discussion

The spontaneous milk fermentation shared the lactic acid bacteria, mainly belonging to Lactobacillaceae (Lactobacillus) and Streptococcaceae (Lactococcus) in these two geographically isolated regions. Indian samples showed a high bacterial diversity with the predominance of Acetobacteraceae (Gluconobacter and Acetobacter) and Leuconostoc, whereas Staphylococcaceae (Macrococcus) was abundant in the West African samples. However, the Wagashi cheese of Benin, prepared by curdling the milk with proteolytic leaf extract of Calotrophis procera followed by natural fermentation, contained Streptococcaceae (Streptococcus spp.) as the dominant bacteria. Our analysis also detected several potential pathogens, like Streptococcus infantarius an emerging infectious foodborne pathogen in Wagashi samples, an uncultured bacterium of Enterobacteriaceae in Kindouri and Fanire samples, and Clostridium spp. in the Doi samples of Northeast India. These findings will allow us to develop strategies to address the safety issues related to spontaneous milk fermentation and implement technological interventions for controlled milk fermentation by designing starter culture consortiums for the sustainable production of uniform quality products with desirable functional and organoleptic properties.
Niclosamide as a chemical probe for analyzing SARS-CoV-2 modulation of host cell lipid metabolism
Authors: Garrett Timothy J. , Coatsworth Heather , Mahmud Iqbal , Hamerly Timothy , Stephenson Caroline J. , Ayers Jasmine B. , Yazd Hoda S. , Miller Megan R. , Lednicky John A. , Dinglasan Rhoel R.
Published: October 2023

Introduction

SARS-CoV-2 subverts host cell processes to facilitate rapid replication and dissemination, and this leads to pathological inflammation.

Methods

We used niclosamide (NIC), a poorly soluble anti-helminth drug identified initially for repurposed treatment of COVID-19, which activates the cells’ autophagic and lipophagic processes as a chemical probe to determine if it can modulate the host cell’s total lipid profile that would otherwise be either amplified or reduced during SARS-CoV-2 infection.

Results

Through parallel lipidomic and transcriptomic analyses we observed massive reorganization of lipid profiles of SARS-CoV-2 infected Vero E6 cells, especially with triglycerides, which were elevated early during virus replication, but decreased thereafter, as well as plasmalogens, which were elevated at later timepoints during virus replication, but were also elevated under normal cell growth. These findings suggested a complex interplay of lipid profile reorganization involving plasmalogen metabolism. We also observed that NIC treatment of both low and high viral loads does not affect virus entry. Instead, NIC treatment reduced the abundance of plasmalogens, diacylglycerides, and ceramides, which we found elevated during virus infection in the absence of NIC, resulting in a significant reduction in the production of infectious virions. Unexpectedly, at higher viral loads, NIC treatment also resulted in elevated triglyceride levels, and induced significant changes in phospholipid metabolism.

Discussion

We posit that future screens of approved or new partner drugs should prioritize compounds that effectively counter SARS-CoV-2 subversion of lipid metabolism, thereby reducing virus replication, egress, and the subsequent regulation of key lipid mediators of pathological inflammation.
Developmental landscape of computational techniques to explore the potential phytochemicals from Punica granatum peels for their antioxidant activity in Alzheimer’s disease
Authors: Parveen Shagufta , Batool Aneeqa , Shafiq Nusrat , Rashid Maryam , Sultan Ayesha , Wondmie Gezahign Fentahun , Bin Jardan Yousef A. , Brogi Simone , Bourhia Mohammed
Published: October 2023

Alzheimer’s disease (AD) is more commonly found in women than in men as the risk increases with age. Phytochemicals are screenedin silicofromPunica granatumpeels for their antioxidant activity to be utilized for Alzheimer’s disease. Alzheimer’s disease is inhibited by the hormone estrogen, which protects the brain from the bad effects of amyloid beta and acetylcholine (ACh), and is important for memory processing. For the purpose, a library of about 1,000 compounds fromP. granatumwere prepared and studied by applying integrated computational calculations like 3D-QSAR, molecular docking, MD simulation, ADMET, and density functional theory (DFT). The 3D-QSAR model screened the active compounds B25, B29, B35, B40, B45, B46, B48, B61, and B66 by the field points and activity atlas model from the prepared library. At the molecular level, docking was performed on active compounds for leading hit compounds such as B25 and B35 that displayed a high MolDock score, efficacy, and compatibility with drug delivery against the antioxidant activity. Optimization of the structure and chemical reactivity parameter of the hit compound was calculated by DFT. Moreover, ADMET prediction was evaluated to check the bioavailability and toxicity of the hit compound. Hesperidin(B25)is found to be a hit compound after the whole study and can be synthesized for potent drug discovery in the future.
Aging increases proprioceptive error for a broad range of movement speed and distance estimates in the upper limb
Authors: Tulimieri Duncan Thibodeau , Semrau Jennifer A.
Published: October 2023

Previous work has identified age-related declines in proprioception within a narrow range of limb movements. It is unclear whether these declines are consistent across a broad range of movement characteristics that more closely represent daily living. Here we aim to characterize upper limb error in younger and older adults across a range of movement speeds and distances. The objective of this study was to determine how proprioceptive matching accuracy changes as a function of movement speed and distance, as well as understand the effects of aging on these accuracies. We used an upper limb robotic test of proprioception to vary the speed and distance of movement in two groups: younger (n = 20, 24.25 ± 3.34 years) and older adults (n = 21, 63 ± 10.74 years). The robot moved one arm and the participant was instructed to mirror-match the movement with their opposite arm. Participants matched seven different movement speeds (0.1–0.4 m/s) and five distances (7.5–17.5 cm) over 350 trials. Spatial (e.g., End Point Error) and temporal (e.g., Peak Speed Ratio) outcomes were used to quantify proprioceptive accuracy. Regardless of the speed or distance of movement, we found that older controls had significantly reduced proprioceptive matching accuracy compared to younger control participants (p ≤ 0.05). When movement speed was varied, we observed that errors in proprioceptive matching estimates of spatial and temporal measures were significantly higher for older adults for all but the slowest tested speed (0.1 m/s) for the majority of parameters. When movement distance was varied, we observed that errors in proprioceptive matching estimates were significantly higher for all distances, except for the longest distance (17.5 cm) for older adults compared to younger adults. We found that the magnitude of proprioceptive matching errors was dependent on the characteristics of the reference movement, and that these errors scaled increasingly with age. Our results suggest that aging significantly negatively impacts proprioceptive matching accuracy and that proprioceptive matching errors made by both groups lies along a continuum that depends on movement characteristics and that these errors are amplified due to the typical aging process.
A transducer positioning method for transcranial focused ultrasound treatment of brain tumors
Authors: Gao Penghao , Sun Yue , Zhang Gongsen , Li Chunsheng , Wang Linlin
Published: October 2023

Purpose

As a non-invasive method for brain diseases, transcranial focused ultrasound (tFUS) offers higher spatial precision and regulation depth. Due to the altered path and intensity of sonication penetrating the skull, the focus and intensity in the skull are difficult to determine, making the use of ultrasound therapy for cancer treatment experimental and not widely available. The deficiency can be effectively addressed by numerical simulation methods, which enable the optimization of sonication modulation parameters and the determination of precise transducer positioning.

Methods

A 3D skull model was established using binarized brain CT images. The selection of the transducer matrix was performed using the radius positioning (RP) method after identifying the intracranial target region. Simulations were performed, encompassing acoustic pressure (AP), acoustic field, and temperature field, in order to provide compelling evidence of the safety of tFUS in sonication-induced thermal effects.

Results

It was found that the angle of sonication path to the coronal plane obtained at all precision and frequency models did not exceed 10° and 15° to the transverse plane. The results of thermal effects illustrated that the peak temperatures of tFUS were 43.73°C, which did not reach the point of tissue degeneration. Once positioned, tFUS effectively delivers a Full Width at Half Maximum (FWHM) stimulation that targets tumors with diameters of up to 3.72 mm in a one-off. The original precision model showed an attenuation of 24.47 ± 6.13 mm in length and 2.40 ± 1.42 mm in width for the FWHM of sonication after penetrating the skull.

Conclusion

The vector angles of the sonication path in each direction were determined based on the transducer positioning results. It has been suggested that when time is limited for precise transducer positioning, fixing the transducer on the horizontal surface of the target region can also yield positive results for stimulation. This framework used a new transducer localization method to offer a reliable basis for further research and offered new methods for the use of tFUS in brain tumor-related research.
A pooled long-term follow-up after radiotherapy for prostate cancer with and without a rectal hydrogel spacer: impact of hydrogel on decline in sexual quality of life
Authors: Seymour Zachary A. , Pinkawa Michael , Daignault-Newton Stephanie , Bosch Walter , Michalski Jeff M. , Gay Hiram , Hamstra Daniel A.
Published: October 2023

Purpose

The purpose of this study was to analyze the impact of prostate rectal spacers on sexual quality of life (QOL) following external beam radiation therapy (RT).

Methods and materials

Patient- reported QOL was evaluated using the Expanded Prostate Cancer Index Composite (EPIC). Patients were pooled from two sources: a randomized controlled trial and a non-randomized cohort of patients from a single institution. Both cohorts used the same spacing product and QOL instrument. Analysis was limited to those with good baseline pre-treatment sexual QOL (EPIC >/= 60). Differences in QOL summary score and individual items were assessed compared with baseline and between treatment arms.

Results

A total of 128 men had good baseline sexual function and were evaluated (64% with spacer and 36% without) with QOL data available for median 33 months (range: 2.5–69.4 months). Men without spacer were more likely to have declines in sexual function (p < 0.0001), bother (p = 0.0002), and sexual summary score (p < 0.0001). A minimally important difference of 10 points (1xMID) and 20 point (2xMID) was more likely without rectal spacer [10 points: odds ratio 3.53, (95% confidence interval 1.11–11.2), p = 0.032; 20 points: odds ratio 3.29, (95% confidence interval 1.16–9.33), p = 0.025]. Seven of 13 QOL items were statistically superior with hydrogel (six of nine functional and one of four bother), while no items were statistically superior for control. At baseline, more men treated with hydrogel had erections sufficient for intercourse; however, when analyzed only by the men with best baseline erectile potential and excluding those with worse function, the benefit of rectal spacing was maintained with a higher likelihood of preservation of erections sufficient for intercourse in those treated with hydrogel.

Conclusion

In this pooled analysis of QOL after prostate RT, the utilization of a hydrogel spacer was associated with better sexual QOL, less men with measurable declines in sexual QOL, and higher rates of adequate erectile function.
Risk factors for acute exacerbation of interstitial lung disease during chemotherapy for lung cancer: a systematic review and meta-analysis
Authors: Wang Zhen , Bai Jiayu , Liu Yujia , Li Peng , Jiao Guangyu
Published: October 2023

Purpose

The aim of this study was to investigate the risk factors for acute exacerbation (AE) of interstitial lung disease caused by chemotherapy for lung cancer.

Methods

We searched PubMed, Embase, and The Cochrane Library databases from the establishment of each database to April 2023. Eligible studies were included, and the data on risk factors related to AE caused by chemotherapy in interstitial lung disease were extracted.

Results

A total of 878 articles were retrieved and 21 met the inclusion criteria. The studies included 1,275 patients with lung cancer combined with interstitial lung disease. The results of the meta-analysis showed four significant risk factors for AE of interstitial lung disease, namely age < 70 years (odds ratio [OR]: 1.98, 95% confidence interval [CI]: 1.05–3.72), forced vital capacity (FVC) (MD=-9.33, 95% CI: -13.7–4.97), usually interstitial pneumonia (UIP) pattern on computed tomography (CT) (OR: 2.11, 95% CI: 1.43–3.11), and serum surfactant protein D (SP-D) (SMD: 0.35, 95% CI: 0.03–0.67).

Conclusion

When patients with lung cancer complicated with interstitial lung disease are aged < 70 years, have a UIP pattern on CT, have lower FVC values, and have higher serum levels of SP-D, chemotherapy should be carried out with care.
Reduced glucose concentration enhances ultradian rhythms in Pdcd5 promoter activity in vitro
Authors: Ting Isaiah J. , Psomas Andreas , Skene Debra J. , Van der Veen Daan R.
Published: October 2023

Intrinsically driven ultradian rhythms in the hourly range are often co-expressed with circadian rhythms in various physiological processes including metabolic processes such as feeding behaviour, gene expression and cellular metabolism. Several behavioural observations show that reduced energy intake or increased energy expenditure leads to a re-balancing of ultradian and circadian timing, favouring ultradian feeding and activity patterns when energy availability is limited. This suggests a close link between ultradian rhythmicity and metabolic homeostasis, but we currently lack models to test this hypothesis at a cellular level. We therefore transduced 3T3-L1 pre-adipocyte cells with a reporter construct that drives a destabilised luciferase via the Pdcd5 promotor, a gene we previously showed to exhibit robust ultradian rhythms in vitro. Ultradian rhythmicity in Pdcd5 promotor driven bioluminescence was observed in >80% of all cultures that were synchronised with dexamethasone, whereas significantly lower numbers exhibited ultradian rhythmicity in non-synchronised cultures (∼11%). Cosine fits to ultradian bioluminescence rhythms in cells cultured and measured in low glucose concentrations (2 mM and 5 mM), exhibited significantly higher amplitudes than all other cultures, and a shorter period (6.9 h vs. 8.2 h, N = 12). Our findings show substantial ultradian rhythmicity in Pdcd5 promotor activity in cells in which the circadian clocks have been synchronised in vitro, which is in line with observations of circadian synchronisation of behavioural ultradian rhythms. Critically, we show that the amplitude of ultradian rhythms is enhanced in low glucose conditions, suggesting that low energy availability enhances ultradian rhythmicity at the cellular level in vitro.
Effects of combined treatment with transcranial and peripheral electromagnetic stimulation on performance and pain recovery from delayed onset muscle soreness induced by eccentric exercise in young athletes. A randomized clinical trial
Authors: Keriven Hugo , Sánchez Sierra Alberto , González de-la-Flor Ángel , García-Arrabé María , Bravo-Aguilar María , de la Plaza San Frutos Marta , Garcia-Perez-de-Sevilla Guillermo , Tornero-Aguilera Jose Francisco , Clemente-Suarez Vicente Javier , Domínguez-Balmaseda Diego
Published: October 2023

Background: There is a common interest in finding a common consensus in the approach of athletes suffering from DOMS with the aim of accelerating recovery and thereby enhancing performance. The objective of this study was to observe the effects of a paired-associative transcranial and peripheral electromagnetic stimulation on young athletes suffering from DOMS, induced by 1 h of eccentric and plyometric exercises.

Methods: Forty-eight young athletes participated in this randomized control trial: 13 were assigned to the peripheral group (P); 12 were in the control group (Cont); 11 were assigned to the transcranial group (T) and 12 were included in the paired-associative group (Comb). The Visual Analogue Scale (VAS) of pain perception and the mechanical Pressure Pain Threshold (PPT) were the tools used to analyze the symptoms of DOMS. On the other hand, the Half Squat (HS) test evaluated with an accelerometer, and the 30 m sprint velocity (30-mSP) test were used to observe the evolution of the sports performance of the lower limbs. All evaluations were performed before and after the eccentric exercise session that caused DOMS, as well as at 24–48, and 72 h afterward.

Results: The AS group improved the symptoms of the induced DOMS, since significant positive differences were observed in the VAS and PPT compared to the other groups (p < 0.001). In addition, the AS group showed a significant improvement in the HS and the 30-mSP tests (p < 0.001). Based on the results a treatment with both peripheral and transcranial electromagnetic stimulation improves recovery and performance in athletes at 72 h, although these data would need to be verified in future research with a larger sample size.

Conclusion: Paired-associative electromagnetic stimulation improved DOMS symptomatology, velocity, and sports performance in the lower limbs.
Changes in stress pathways as a possible mechanism of aerobic exercise training on brain health: a scoping review of existing studies
Authors: Molina-Hidalgo Cristina , Stillman Chelsea M. , Collins Audrey M. , Velazquez-Diaz Daniel , Ripperger Hayley S. , Drake Jermon A. , Gianaros Peter J. , Marsland Anna L. , Erickson Kirk I.
Published: October 2023

Physical activity (PA) in the form of aerobic exercise (AE) preserves and improves neurocognitive function across the lifespan. However, a mechanistic understanding of the pathways by which aerobic exercise impacts brain health is still lacking, particularly with respect to stress-related pathways. One mechanistic hypothesis is that AE improves neurocognitive health in part by modifying circulating levels of stress-related hormones and signaling factors associated with the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS), as commonly measured by the biomarkers cortisol (CORT) and salivary α-amylase (sAA). Thus, this hypothesis predicts that changes in stress biomarkers, such as CORT and sAA, are possible explanatory pathways mediating the positive effects of AE on neurocognitive health. In the present review article, we provide a summary of available studies examining the possibility that exercise-induced changes to stress biomarkers could partly account for exercise-related improvements in neurocognitive health. Our review indicates that despite the intuitive appeal of this hypothesis, there is insufficient evidence available to conclude that chronic and habitual AE affects neurocognitive health by altering stress biomarker pathways. The cross-sectional nature of the majority of reviewed studies highlights the need for well-controlled studies to adequately test this hypothesis.
Comprehensive insights into herbicide resistance mechanisms in weeds: a synergistic integration of transcriptomic and metabolomic analyses
Authors: Sen Madhab Kumar , Bhattacharya Soham , Bharati Rohit , Hamouzová Katerina , Soukup Josef
Published: October 2023

Omics techniques, including genomics, transcriptomics, proteomics, and metabolomics have smoothed the researcher’s ability to generate hypotheses and discover various agronomically relevant functions and mechanisms, as well as their implications and associations. With a significant increase in the number of cases with resistance to multiple herbicide modes of action, studies on herbicide resistance are currently one of the predominant areas of research within the field of weed science. High-throughput technologies have already started revolutionizing the current molecular weed biology studies. The evolution of herbicide resistance in weeds (particularly via non-target site resistance mechanism) is a perfect example of a complex, multi-pathway integration-induced response. To date, functional genomics, including transcriptomic and metabolomic studies have been used separately in herbicide resistance research, however there is a substantial lack of integrated approach. Hence, despite the ability of omics technologies to provide significant insights into the molecular functioning of weeds, using a single omics can sometimes be misleading. This mini-review will aim to discuss the current progress of transcriptome-based and metabolome-based approaches in herbicide resistance research, along with their systematic integration.
Exploring burnout among preschool teachers in rural China: a job demands-resources model perspective
Authors: Zhao Na , Huo Ming , Van Den Noortgate Wim
Published: October 2023

Rural preschool teachers are increasingly experiencing job burnout, which could lead to their intention to leave and negatively impact education quality. This research explored the prevalence of job burnout among preschool teachers in rural China. It further investigated the potential influence of job-related characteristics on their levels of burnout. This study surveyed 10,581 preschool teachers across 34 counties in 18 provinces in China, utilizing multilevel structural equation models to analyze the situation and factors influencing job burnout. The findings indicate that the situation regarding job burnout among preschool teachers is not encouraging, particularly in the western areas and independent public kindergartens. Job resources were found to be associated with a reduction in burnout, while job demands had the opposite effect. The findings also revealed that job demands served as a mediating variable between job resources and job burnout. Moreover, the results also showed that reduced job burnout among preschool teachers was related to teacher cooperation, decision making, kindergarten resources and salary. On the other hand, role commitments, business issues, and classroom management were associated with increased burnout among preschool teachers. Furthermore, the impact of demands and resources on burnout was found to be intensified by kindergarten variables. To address the issue of burnout, it is essential to recognize the diversity and heterogeneity of kindergartens and take specific measures to reduce work demands while providing adequate and specific resources. Attention should be given to diversity and integration to ensure a positive work environment that can effectively prevent job burnout among preschool teachers.