bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic remodeling to improve the efficacy of immunotherapy in human glioblastoma: pre-clinical evidence for development of new immunotherapy approaches
Authors: Lofiego Maria Fortunata , Piazzini Francesca , Caruso Francesca Pia , Marzani Francesco , Solmonese Laura , Bello Emma , Celesti Fabrizio , Costa Maria Claudia , Noviello Teresa , Mortarini Roberta , Anichini Andrea , Ceccarelli Michele , Coral Sandra , Di Giacomo Anna Maria , Maio Michele , Covre Alessia ,   The EPigenetic Immune-oncology Consortium Airc (EPICA) investigators
Published: March 2024

Background

Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor, that is refractory to standard treatment and to immunotherapy with immune-checkpoint inhibitors (ICI). Noteworthy, melanoma brain metastases (MM-BM), that share the same niche as GBM, frequently respond to current ICI therapies. Epigenetic modifications regulate GBM cellular proliferation, invasion, and prognosis and may negatively regulate the cross-talk between malignant cells and immune cells in the tumor milieu, likely contributing to limit the efficacy of ICI therapy of GBM. Thus, manipulating the tumor epigenome can be considered a therapeutic opportunity in GBM.

Methods

Microarray transcriptional and methylation profiles, followed by gene set enrichment and IPA analyses, were performed to study the differences in the constitutive expression profiles of GBM vs MM-BM cells, compared to the extracranial MM cells and to investigate the modulatory effects of the DNA hypomethylating agent (DHA) guadecitabine among the different tumor cells. The prognostic relevance of DHA-modulated genes was tested by Cox analysis in a TCGA GBM patients’ cohort.

Results

The most striking differences between GBM and MM-BM cells were found to be the enrichment of biological processes associated with tumor growth, invasion, and extravasation with the inhibition of MHC class II antigen processing/presentation in GBM cells. Treatment with guadecitabine reduced these biological differences, shaping GBM cells towards a more immunogenic phenotype. Indeed, in GBM cells, promoter hypomethylation by guadecitabine led to the up-regulation of genes mainly associated with activation, proliferation, and migration of T and B cells and with MHC class II antigen processing/presentation. Among DHA-modulated genes in GBM, 7.6% showed a significant prognostic relevance. Moreover, a large set of immune-related upstream-regulators (URs) were commonly modulated by DHA in GBM, MM-BM, and MM cells: DHA-activated URs enriched for biological processes mainly involved in the regulation of cytokines and chemokines production, inflammatory response, and in Type I/II/III IFN-mediated signaling; conversely, DHA-inhibited URs were involved in metabolic and proliferative pathways.

Conclusions

Epigenetic remodeling by guadecitabine represents a promising strategy to increase the efficacy of cancer immunotherapy of GBM, supporting the rationale to develop new epigenetic-based immunotherapeutic approaches for the treatment of this still highly deadly disease.
Prevalence and genotype distribution of HPV infections among women in Chengdu,China
Authors: Zhang Junying , Zha Tianzhi , Wang Xuemei , He Weijun
Published: March 2024

Background

Human papilloma virus (HPV) infection among female is the cause of cervical cancer and genital warts. In China, the HPV vaccination rate and the target population screening rate among females are low, and the aims of this study on the genotype distribution and prevalence of HPV infection were to provide more targeted strategies for the prevention and treatment of cervical cancer and HPV-related diseases.

Methods

Polymerase chain reaction-reverse dot blot (PCR-RDB) was adopted for HPV genotyping test, the prevalence and 23 genotypes distribution of HPV infections among 181,705 women in Chengdu from 2013 to 2020 were analysed.

Results

The overall prevalence rate of HPV infection among 181,705 cases was 23.28%, the prevalence of HR-HPV at the age group < 20 years, 60–69 years and ≥ 70 years were higher than the overall prevalence.The prevalence of HPV showed a bimodal U-shaped curve with age; the first and second peak common occurred among females < 20 years old (42.97%) and 60–69 years old (37.56%), respectively.The top five genotypes of HPV infection among females in Chengdu were HPV52/16/58/81/53. Single infection (73.26%) was the main HPV infection pattern, followed by double infection (19.17%) and multiple infection (7.57%), the infection rate of HPV showed a gradual declined as the patterns of HPV coinfections increased, low-risk and high-risk coinfection was higher in low-risk HPV infection (43.68%) and lower in high-risk HPV infection (13.59%). The prevalence of genotypes − 6 and − 81 infection was the second highest at the age group of 20 and 40–59, respectively, while the prevalence of HPV16 was the highest at the age group of ≥ 70 among 23 genotypes among the 181,705 women.

Conclusions

The prevalence of HPV infections among women in Chengdu is higher than domestic certain developed citys, among the five vaccines available, nonavalent vaccine is more suitable for Chengdu females. For young females prioritizing vaccination is essential in the current context.Double screening for HPV DNA is important in middle-aged women (30–49 years), and screening should not be lacking in older women (> 65 years). Additionally,for patients with genital warts, it is necessary to screen for high-risk HPV infection and provide appropriate management and treatment. Given the limitations of this study, future HPV research should aim to achieve full coverage of the target population, and our studies should also include cellular or pathological data of HPV-positive cases, vaccination rates, and various lifestyle details.
Traditional knowledge of animal-derived medicines used by Gelao community in Northern Guizhou, China
Authors: Liu Xiaoqi , Li Shuo , Feng Yi , Chen Xingxing , Ma Yuhan , Xiao Hai , Zhao Yongxia , Liu Sha , Zheng Guishen , Yang Xiujuan , Wu Faming , Xie Jian
Published: March 2024

Introduction

This study aims to document and preserve the traditional medicinal knowledge of the Gelao community in Northern Guizhou, China, providing valuable insights for modern pharmacological research and the development of these traditional remedies.

Methods

Our methodology encompassed a blend of literature review, community interviews, and participatory observation to delve into the traditional knowledge of animal-derived medicines among the Gelao community. We employed quantitative ethnological and ecological assessment techniques to evaluate the significance of these practices. Informed consent was secured before conducting interviews, with a focus on ascertaining the types of medicines familiar to the informants, including their local names, sources, methods of preparation, application techniques, diseases treated, frequency of use, and safety considerations.

Results

Our research cataloged 55 varieties of animal-derived medicines utilized by the Gelao people. Out of these, 34 originate from wild animals, mainly encompassing small insects, reptiles, and aquatic species; the remaining 21 are derived from domesticated animals, largely involving their tissues, organs, and various physiological or pathological by-products. These medicines are primarily applied in treating pediatric ailments (13 types), internal disorders (11 types), gynecological issues (3 types), dermatological problems (7 types), ENT conditions (3 types), trauma-related injuries (5 types), joint and bone ailments (5 types), infections (2 types), dental issues (2 types), and urolithiasis (1 type), with three types being used for other miscellaneous conditions. Commonly utilized medicines, such as honey, Blaps beetle, chicken gallstones, and snake-based products, are preferred for their availability, edibility, and safety within the Gelao communities.

Conclusion

The Gelao community’s traditional medicines represent a rich diversity of animal sources, showcasing extensive expertise and knowledge in their processing and clinical applications. This wealth of traditional knowledge offers novel perspectives for the contemporary pharmacological study and development of these remedies. Additionally, our research plays a crucial role in aiding the preservation and continuation of this invaluable cultural heritage.
Trachelogenin alleviates osteoarthritis by inhibiting osteoclastogenesis and enhancing chondrocyte survival
Authors: Jiang Tao , Zhang Jiahui , Ruan Beite , Xi Xiaobing , Yang Zhuo , Liu Jianmin , Zhao Hongyan , Xu Xing , Jiang Min
Published: March 2024

Background

Osteoarthritis (OA) is a prevalent global health concern associated with the loss of articular cartilage and subchondral bone. The lack of disease-modifying drugs for OA necessitates the exploration of novel therapeutic options. Our previous study has demonstrated that traditional Chinese medical herb Trachelospermum jasminoides (Lindl.) Lem. extract suppressed osteoclastogenesis and identified trachelogenin (TCG) as a representative compound. Here, we delved into TCG’s potential to alleviate OA.

Methods

We initially validated the in vivo efficacy of TCG in alleviating OA using a rat OA model. Subsequently, we isolated primary bone marrow-derived macrophages in vitro to investigate TCG's impact on osteoclastogenesis. We further employed a small molecule pull-down assay to verify TCG's binding target within osteoclasts. Finally, we isolated primary mouse chondrocytes in vitro to study TCG's regulatory effects and mechanisms on chondrocyte survival.

Results

TCG preserved subchondral bone integrity and protected articular cartilage in a rat OA model. Subsequently, in vitro experiments unveiled TCG's capability to inhibit osteoclastogenesis and function through binding to Ras association proximate 1 (Rap1) and inhibiting its activation. Further study demonstrated that TCG inhibited Rap1/integrin αvβ3/c-Src/Pyk2 signaling cascade, and consequently led to failed F-actin ring formation. Besides, TCG promoted the proliferation of mouse primary chondrocytes while suppressing apoptosis in vitro. This is attributed to TCG's ability to upregulate HIF1α, thereby promoting glycolysis.

Conclusion

TCG exerted inhibitory effects on osteoclastogenesis through binding to Rap1 and inhibiting Rap1 activation, consequently preventing subchondral bone loss. Moreover, TCG enhanced chondrocyte survival by upregulating HIF1α and promoting glycolysis. These dual mechanisms collectively provide a novel approach to prevented against cartilage degradation.
Single-cell deconvolution algorithms analysis unveils autocrine IL11-mediated resistance to docetaxel in prostate cancer via activation of the JAK1/STAT4 pathway
Authors: Cheng Bisheng , Li Lingfeng , Luo Tianlong , Wang Qiong , Luo Yong , Bai Shoumin , Li Kaiwen , Lai Yiming , Huang Hai
Published: March 2024

Background

Docetaxel resistance represents a significant obstacle in the treatment of prostate cancer. The intricate interplay between cytokine signalling pathways and transcriptional control mechanisms in cancer cells contributes to chemotherapeutic resistance, yet the underlying molecular determinants remain only partially understood. This study elucidated a novel resistance mechanism mediated by the autocrine interaction of interleukin-11 (IL-11) and its receptor interleukin-11 receptor subunit alpha(IL-11RA), culminating in activation of the JAK1/STAT4 signalling axis and subsequent transcriptional upregulation of the oncogene c-MYC.

Methods

Single-cell secretion profiling of prostate cancer organoid was analyzed to determine cytokine production profiles associated with docetaxel resistance.Analysis of the expression pattern of downstream receptor IL-11RA and enrichment of signal pathway to clarify the potential autocrine mechanism of IL-11.Next, chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) was performed to detect the nuclear localization and DNA-binding patterns of phosphorylated STAT4 (pSTAT4). Coimmunoprecipitation and reporter assays were utilized to assess interaction between pSTAT4 and the cotranscription factor CREB-binding protein (CBP) as well as their role in c-MYC transcriptional activity.

Results

Autocrine secretion of IL-11 was markedly increased in docetaxel-resistant prostate cancer cells. IL-11 stimulation resulted in robust activation of JAK1/STAT4 signalling. Upon activation, pSTAT4 translocated to the nucleus and associated with CBP at the c-MYC promoter region, amplifying its transcriptional activity. Inhibition of the IL-11/IL-11RA interaction or disruption of the JAK1/STAT4 pathway significantly reduced pSTAT4 nuclear entry and its binding to CBP, leading to downregulation of c-MYC expression and restoration of docetaxel sensitivity.

Conclusion

Our findings identify an autocrine loop of IL-11/IL-11RA that confers docetaxel resistance through the JAK1/STAT4 pathway. The pSTAT4-CBP interaction serves as a critical enhancer of c-MYC transcriptional activity in prostate cancer cells. Targeting this signalling axis presents a potential therapeutic strategy to overcome docetaxel resistance in advanced prostate cancer.

Graphical Abstract
Improving chemical reaction yield prediction using pre-trained graph neural networks
Authors: Han Jongmin , Kwon Youngchun , Choi Youn-Suk , Kang Seokho
Published: March 2024

Graph neural networks (GNNs) have proven to be effective in the prediction of chemical reaction yields. However, their performance tends to deteriorate when they are trained using an insufficient training dataset in terms of quantity or diversity. A promising solution to alleviate this issue is to pre-train a GNN on a large-scale molecular database. In this study, we investigate the effectiveness of GNN pre-training in chemical reaction yield prediction. We present a novel GNN pre-training method for performance improvement.Given a molecular database consisting of a large number of molecules, we calculate molecular descriptors for each molecule and reduce the dimensionality of these descriptors by applying principal component analysis. We define a pre-text task by assigning a vector of principal component scores as the pseudo-label to each molecule in the database. A GNN is then pre-trained to perform the pre-text task of predicting the pseudo-label for the input molecule. For chemical reaction yield prediction, a prediction model is initialized using the pre-trained GNN and then fine-tuned with the training dataset containing chemical reactions and their yields. We demonstrate the effectiveness of the proposed method through experimental evaluation on benchmark datasets.
Accuracy of heart failure ascertainment using routinely collected healthcare data: a systematic review and meta-analysis
Authors: Goonasekera Michelle. A. , Offer Alison , Karsan Waseem , El-Nayir Muram , Mallorie Amy E. , Parish Sarah , Haynes Richard J. , Mafham Marion M.
Published: March 2024

Background

Ascertainment of heart failure (HF) hospitalizations in cardiovascular trials is costly and complex, involving processes that could be streamlined by using routinely collected healthcare data (RCD). The utility of coded RCD for HF outcome ascertainment in randomized trials requires assessment. We systematically reviewed studies assessing RCD-based HF outcome ascertainment against “gold standard” (GS) methods to study the feasibility of using such methods in clinical trials.

Methods

Studies assessing International Classification of Disease (ICD) coded RCD-based HF outcome ascertainment against GS methods and reporting at least one agreement statistic were identified by searching MEDLINE and Embase from inception to May 2021. Data on study characteristics, details of RCD and GS data sources and definitions, and test statistics were reviewed. Summary sensitivities and specificities for studies ascertaining acute and prevalent HF were estimated using a bivariate random effects meta-analysis. Heterogeneity was evaluated using I2 statistics and hierarchical summary receiver operating characteristic (HSROC) curves.

Results

A total of 58 studies of 48,643 GS-adjudicated HF events were included in this review. Strategies used to improve case identification included the use of broader coding definitions, combining multiple data sources, and using machine learning algorithms to search free text data, but these methods were not always successful and at times reduced specificity in individual studies. Meta-analysis of 17 acute HF studies showed that RCD algorithms have high specificity (96.2%, 95% confidence interval [CI] 91.5–98.3), but lacked sensitivity (63.5%, 95% CI 51.3–74.1) with similar results for 21 prevalent HF studies. There was considerable heterogeneity between studies.

Conclusions

RCD can correctly identify HF outcomes but may miss approximately one-third of events. Methods used to improve case identification should also focus on minimizing false positives.
Serum proteome analysis identifies a potential biomarker for axial psoriatic arthritis
Authors: Lu Chaofan , Yang Fan , He Shihao , Yu Hongxia , Wang Qian , Li Mengtao , Zeng Xiaofeng , Leng Xiaomei
Published: March 2024

Background

To identify potential serum biomarkers for differentiating between axial psoriatic arthritis (axPsA) and peripheral psoriatic arthritis (pPsA).

Methods

Serum samples were collected from patients with PsA to create a biomarker discovery cohort and a verification cohort. Patients with PsA were classified into axial or peripheral subtypes based on imaging criteria. Untargeted proteomics technology was used in the discovery phase to screen for biomarkers, and candidate biomarkers were evaluated using enzyme-linked immunosorbent assay (ELISA) in the verification phase.

Results

We identified 45 significantly differentially expressed proteins (DEPs) between axPsA (n = 20) and pPsA (n = 20) with liquid chromatography-mass spectrometry. Among these DEPs, serum pigment epithelium-derived factor (PEDF) was identified as a candidate biomarker using the Boruta algorithm and lasso regression. Results of ELISA further confirmed that the level of serum PEDF expression was significantly higher in axPsA (n = 37) than in pPsA (n = 51) at the verification cohort (37.9 ± 10.1 vs. 30.5 ± 8.9 μg/mL, p < 0.001). Receiver operating characteristics analysis showed that PEDF had an area under the curve (AUC) of 0.72. Serum PEDF was positively correlated with body mass index and C-reactive protein. Additionally, there was a tendency towards a positive correlation between PEDF and the Bath Ankylosing Spondylitis Disease Activity Index.

Conclusions

This study provided a comprehensive characterization of the proteome in axPsA and pPsA and identified a candidate biomarker, PEDF, that may contribute to early diagnosis for axPsA.
Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice
Authors: Zhou Ling , Lu Yunlong , Liu Wei , Wang Shanglong , Wang Lingling , Zheng Pengdou , Zi Guisha , Liu Huiguo , Liu Wukun , Wei Shuang
Published: March 2024

A drug conjugate consists of a cytotoxic drug bound via a linker to a targeted ligand, allowing the targeted delivery of the drug to one or more tumor sites. This approach simultaneously reduces drug toxicity and increases efficacy, with a powerful combination of efficient killing and precise targeting. Antibody‒drug conjugates (ADCs) are the best-known type of drug conjugate, combining the specificity of antibodies with the cytotoxicity of chemotherapeutic drugs to reduce adverse reactions by preferentially targeting the payload to the tumor. The structure of ADCs has also provided inspiration for the development of additional drug conjugates. In recent years, drug conjugates such as ADCs, peptide‒drug conjugates (PDCs) and radionuclide drug conjugates (RDCs) have been approved by the Food and Drug Administration (FDA). The scope and application of drug conjugates have been expanding, including combination therapy and precise drug delivery, and a variety of new conjugation technology concepts have emerged. Additionally, new conjugation technology-based drugs have been developed in industry. In addition to chemotherapy, targeted therapy and immunotherapy, drug conjugate therapy has undergone continuous development and made significant progress in treating lung cancer in recent years, offering a promising strategy for the treatment of this disease. In this review, we discuss recent advances in the use of drug conjugates for lung cancer treatment, including structure-based drug design, mechanisms of action, clinical trials, and side effects. Furthermore, challenges, potential approaches and future prospects are presented.
Simultaneous determination of ethyl glucuronide, cocaine, cocaethylene, and benzoylecgonine in hair by using LC–MS/MS
Authors: Shin Dong Won , Kim Seon Yeong , Suh Sung Ill , Kim Jin Young
Published: March 2024

Alcohol and cocaine (COC) are commonly co-used drugs that cause addiction and have harmful effects. Their abuse may threaten the health of the abuser and public safety by causing serious accidents or crimes. The recidivism rate of drug-related crimes closely correlates with alcoholism. Several incidences of alcohol consumption in combination with drug abuse have been reported. Here, liquid chromatography tandem mass spectrometric method was developed to simultaneously analyze ethyl glucuronide (EtG), a metabolite of ethanol; COC; cocaethylene (CE), an alcohol-derived metabolite of COC; and benzoylecgonine (BZE), a major metabolite of COC, to determine the concurrent use of alcohol with COC. For pre-treatment, ultracentrifugation (5 min, 50,000 g) and mixed-mode anion exchange solid-phase extraction were used to increase the recovery of target compounds and minimize the matrix effect of hair. The lower limits of quantification were: 7 pg/mg (EtG), 2 pg/mg (COC), 10 pg/mg (CE), and 1 pg/mg (BZE). The correlation coefficient (r) of the calibration curve within the quantified range of target compounds was ≥ 0.9978. The intra- and inter-day accuracies were − 6.1–9.7% and − 9.3–8.3%, and intra- and inter-day precisions were 0.5–10.3% and 0.6–14.4%, respectively. The recovery, matrix effect, process efficiency, and autosampler stability were 89.2–104.8%, 81.6–105.4%, 81.5–107.1%, and 96.6–109.7%, respectively. The novel analytical method was validated with hair samples from individuals suspected of alcohol and COC use, and the method could distinguish between independent and concurrent use. Based on the findings, the analytical approach developed in this study is anticipated to be valuable in drug and alcohol dependence tests that require the simultaneous detection of alcohol and COC abuse.
Impedance of electric field sensors in magnetized plasmas: particle-in-cell simulations
Authors: Fukasawa Ibuki , Miyake Yohei , Usui Hideyuki , Kusachi Koshiro , Kurita Satoshi , Kojima Hirotsugu
Published: March 2024

To obtain both the intensities and phases of electric fields, it is necessary to calibrate the data observed by the sensor by consulting the sensor characteristics. The frequency profile of the sensor impedance obtained from the simulation is roughly consistent with that obtained from the theory. However, some differences are identified in the frequency profile of the sensor impedance obtained from the simulation compared to the theory. We conducted simulations using the particle-in-cell (PIC) simulation tool to analyze the impedance of electric field sensors immersed in magnetized space plasmas. The simulation model comprised a dipole sensor placed in a three-dimensional simulation box filled with electrons and ions. The dipole sensor was represented by perfect conductor rods. We carefully selected simulation parameters and employed an appropriate feeding technique to accurately evaluate the sensor impedance. We observed significant changes in the frequency dependence of the sensor impedance as cyclotron frequency varied. To understand the simulation results, we introduced the linear dispersion relation. By comparing the real part of the sensor impedance with the $$\omega-k$$

ω
-
k

diagram, we found that the impedance peaks corresponded to frequencies at which branches of plasma waves were present, with $$k=k_{\text{half}}$$

k
=

k
half

, representing half the wavelength equal to the tip-to-tip sensor length, i.e., the sensor can be assumed as the half-wavelength dipole antenna.

Graphical Abstract
Evaluating mean platelet volume and platelet distribution width as predictors of early-onset pre-eclampsia: a prospective cohort study
Authors: Udeh Patience Ijeoma , Olumodeji Ayokunle Moses , Kuye-Kuku Taiwo Olufunmilayo , Orekoya Oluwaseun Olubowale , Ayanbode Olufemi , Fabamwo Adetokunbo Olusegun
Published: March 2024

Background

Platelets are pivotal players in the pathophysiology of pre-eclampsia, with observed lower counts in affected individuals compared to normotensive counterparts. Despite advancements, the elusive cause of pre-eclampsia persists, motivating intense global efforts to identify reliable predictors. The currently recommended predictors of pre-eclampsia are not readily available in many resource-limited regions like Nigeria. This cohort study explores the potential of mean platelet volume (MPV) and platelet distribution width (PDW) as predictive markers of early-onset pre-eclampsia. Both platelet indices are components of the full blood count, a widely available routine test in pregnancy.

Methods

In this prospective cohort study, 648 healthy pregnant women attending antenatal care at Lagos State University Teaching Hospital and General Hospital Ifako-Ijaiye, Lagos, were recruited between 14-18weeks gestational age. Platelet count (PC), MPV and PDW were measured from their venous blood at recruitment. Participants were monitored until 34weeks of gestation, focusing on the occurrence of early-onset preeclampsia as the outcome of interest. Individuals with chronic medical conditions were excluded from the study. Data analysis involved t-test, Chi-Square and Mann–Whitney U tests, with statistical significance set at a confidence level of 95% and p < 0.05. Sensitivity, specificity, and predictive values were determined using receiver operating characteristics (ROC) curves.

Results

The incidence of early-onset pre-eclampsia in the study was 5.9%. Women who later developed pre-eclampsia had higher median MPV and PDW at 14-18weeks (10.8 fl. and 24.8 fl.) compared to normotensive women (8.1 fl. and 13.3 fl.)(p < 0.001). The median PC was lower in pre-eclamptics (190 × 103/µl) compared to normotensives(264 × 103/µl)(p < 0.001). Using Youden’s test, cut-off values identified: PC < 211.5 × 103/µl, MPV > 9.4 fl., and PDW > 21.3 fl., predicted early-onset pre-eclampsia with 96.6% sensitivity and 65.6% specificity for PC; 79.3% sensitivity and 97.7% specificity for PDW; and 82.8% sensitivity and 96.1% specificity for MPV. Cut-offs of PC < 185 × 103/µl, MPV > 10.7 fl., and PDW > 28.3 fl., predicted severe early-onset pre-eclampsia with 100.0% sensitivity and 90.9% specificity for PC, 100.0% sensitivity and 99.4% specificity for MPV, and 100.0% sensitivity and 99.8% specificity for PDW, with corresponding area under the ROC curves of 0.983, 0.996, and 0.998, respectively.

Conclusion

The evaluation of MPV and PDW between 14 and 18 weeks of gestation appears to be a reliable predictor of severe early-onset pre-eclampsia.
Prevalence and determinants of minimum dietary diversity for women of reproductive age in Uganda
Authors: Kimuli Derrick , Nakaggwa Florence , Namuwenge Norah , Nsubuga Rebecca N. , Kasule Kenneth , Nyakwezi Sheila , Odong Jimmy , Isabirye Paul , Sevume Solome , Mubiru Norbert , Mwehire Daniel , Matovu Fatuma , Wandera Bonnie , Amuron Barbara , Bukenya Daraus
Published: March 2024

Background

Globally, over a billion women of reproductive age (WRA) suffer from some kind of undernutrition micronutrient deficiencies, and/or anemia as a result of inadequate dietary diversity. This leads to poor maternal and child health outcomes, however, there is limited research on population level research on minimum dietary diversity for women (MDD-W). This study assessed the prevalence and predictors of MDD-W among WRA in Uganda.

Methods

This study was a secondary analysis of data from the lot quality assurance sampling (LQAS) survey conducted across 55 Ugandan districts between May and September 2022. Women of various ages were interviewed across 5 study subgroups that this study used to construct its study population (WRA). Descriptive analyses, tests for outcome differences, and multilevel mixed-effects logistic regression were conducted at a 5% statistical significance level using STATA version 17. The results were reported using Adjusted Odds Ratios (aOR) as the measure of the outcome.

Results

The study analyzed responses from 29,802 WRA with a mean age of 27.8 (± 6.8) years. Only 8.8% (95% CI 8.5–9.3) achieved the MDD-W, the least proportion was observed in the South-Central region (3.13%). In the adjusted analysis, WRA who were older than 25 years (aOR 1.1, 95% CI 1.1–1.3, p < 0.001), had secondary education (aOR = 1.4, 95% CI 1.1–1.7, p = 0.003) or above (aOR = 1.7, 95% CI 1.3–2.2, p < 0.001), and used modern contraceptives (aOR = 1.1, 95% CI 1.0-1.3, p = 0.01) were more likely to achieve the MDD-W. Conversely, WRA who travelled longer distances to the nearest household water source (aOR = 0.8, 95% CI 0.7–0.9, p = 0.002) and those residing in larger households (aOR = 0.9, 95% CI 0.8-1.0, p = 0.019) were less likely to achieve the MDD-W.

Conclusion

A low proportion of WRA met the MDD-W. Age, education level, household sizes and use of modern contraception were predictors of MDD-W among WRA in Uganda. MDD-W-related program efforts in Uganda should strengthen multisectoral collaboration with prioritization of younger women, education, household sizes and access to safe water sources.
Effect of COVID-19 Pandemic Lockdowns on Body Mass Index of Primary School Children from Different Socioeconomic Backgrounds
Authors: Piesch Ludwig , Stojan Robert , Zinner Jochen , Büsch Dirk , Utesch Katharina , Utesch Till
Published: March 2024

Background

Childhood obesity is associated with various health outcomes. Restrictive measures to contain the spread of the Coronavirus Disease 2019 (COVID-19) pandemic, like lockdowns and school closures, affected children’s daily structure, physical activity, dietary habits, and sleep quality, possibly exacerbating risk factors for childhood obesity and higher body mass index (BMI) in children. Poor socioeconomic conditions may have led to relatively higher risk for elevated BMI levels following pandemic measures. In this study, the impact of measures related to the COVID-19 pandemic on the BMI of third graders was investigated regarding children’s socioeconomic background (SEB).

Methods

Data from 41,728 children (8.84 ± 0.56 years, 20,431 female) were collected in the context of a cohort study. Children were tested either before the pandemic (preCOVID: Sept2017–March2020,n = 26,314), or following the first (postLDI: Aug2020–Dec2020,n = 6657) or second lockdown in Germany (postLDII: Aug2021–Jan2022,n = 8757). SEB was based on the official school type classification of the state of Berlin. Outcome was BMI standard deviation scores (SDS).

Results

Significant effects of Time and SEB revealed elevated BMIs in postLDI(M = 0.23,p = 0.011) and postLDII(M = 0.22,p = 0.011) compared to preCOVID(M = 0.17) cohorts and higher BMIs for children with lower SEB (b = − 0.13, p < 0.001). A significant Time × SEB interaction indicated that the effect of SEB on children’s BMI increased in response to lockdowns, especially in postLDII(b = − 0.05, p = 0.006). Results suggest that the COVID-19-related measures lead to increased BMI in children, and that children of lower SEB were at particular risk for higher BMIs following lockdowns.

Conclusions

These findings highlight the dependency of children’s BMI on societal circumstances. Over the course of two lockdowns in Germany, children have experienced BMI increments, particularly in low socioeconomic areas. Authorities are called into action to counteract increasing rates of childhood weight by promoting physical activity of children and establishing related post-pandemic offers.
Construction of individualised care programmes for patients with pancreatic cancer with postoperative weight-loss control based on the Delphi method: a cross-sectional study in China
Authors: Chen Leying , Huang Zhongyan , Tian Qiuju , Zha Qinghua , Zhang Shiyu , Chen Zhe , Dong Ziyun , Zhou Yuqing , Zhang Ming , Wei Xiaoyan
Published: March 2024

Background

At present, clinical nutritional care for patients with pancreatic cancer focuses more on the observation of the effect of enteral parenteral nutrition, and there is a lack of personalised care plans for weight-loss control. We used the Delphi method to construct a set of personalised nursing programmes to effectively control the rate of postoperative weight loss in patients with pancreatic cancer.

Methods

This study was a cross-sectional investigation. Through literature analysis, literature review and data review, a personalised nursing plan for the postoperative weight-loss control in patients with pancreatic cancer was preliminarily developed. From October to December 2022, the Delphi method was adopted to conduct two questionnaires for 32 experts working in fields related to pancreatic diseases in Grade-A tertiary hospitals from four different departments. After statistical processing, the personalised nursing plan was determined according to the perceived level of importance, coefficient of variation, full score rate and recognition rate of the indicators.

Results

The recovery rates of the two rounds of consultation were 93.75% and 100%, respectively, and the overall authority coefficient of the experts was 0.918, which represented ‘authoritative’. In terms of importance, the coefficient of variation was 0–0.137; in terms of feasibility, the coefficient of variation ranged from 0.09 to 0.194. Finally, a scheme consisting of 36 entries in 8 dimensions was built. This programme is comprehensive in content, meets the nutritional diagnosis and treatment needs of patients in the stage of postoperative rehabilitation, provides relatively comprehensive nutritional assessment and support and has a robust system and feasibility.

Conclusions

The individualised nursing plan for patients with pancreatic cancer with postoperative weight-loss control based on the Delphi method is highly scientific and reliable and has positive significance.
Association between dietary phytochemical index and risk of benign prostatic hyperplasia: a case-control study
Authors: Mousavi Seyedeh Neda , Nouri Maryam , Yousefi Rad Esmaeil , Kazemi Reza , Birjandi Mehdi , Coe Shelly , Saboori Somayeh
Published: March 2024

Background

Dietary intake of phytochemicals has been associated with a reduced risk of chronic diseases, but research on their relationship with benign prostatic hyperplasia (BPH) is limited. This case-control study aimed to investigate the association between a Dietary Phytochemical Index (DPI) and BPH risk in a Middle-Eastern population.

Methods

The study recruited 112 BPH patients and 112 age-matched healthy controls (40–75 years) from Al-Zahra Hospital Clinic in Isfahan, Iran between 2021 and 2022. Dietary intake was assessed using a validated food-frequency questionnaire, and DPI was calculated as the ratio of energy intake from phytochemical-rich foods to total daily energy intake. Logistic regression analysis was performed, adjusting for potential confounders.

Results

In the crude model, participants in the highest DPI tertile had a 70% lower odds of BPH compared to those in the lowest tertile (OR:0.3, 95% CI 0.15–0.61, P-trend = 0.001). After adjusting for confounders, this inverse association remained significant (OR:0.23, 95% CI 0.15–0.63, P-trend = 0.001). Participants with higher DPI consumed more whole grains (p = 0.02), nuts (p < 0.001), legumes (p = 0.02), fruits (p < 0.001), vegetables (p < 0.001), olives and oilve products (p = 0.02), and tomato and its products (p < 0.001) in their diet compared to the lowest tertile. However, red meat (p = 0.03) and refined grains (p < 0.001) were consumed in higher amounts in the lowest tertile compared to the highest DPI tertile.

Conclusions

This study demonstrates a protective association between DPI and BPH risk in the Middle-Eastern population. Encouraging higher intake of phytochemical-rich foods may help reduce the risk of BPH, highlighting the relevance of nutritional science in promoting prostate health.
Phenotypic characterization of ESBL-producing urinary isolates of E. coli and Klebsiella spp. in a tertiary care children's hospital in Nepal
Authors: Pantha Santosh , Parajuli Hiramani , Arjyal Charu , Karki Shovana Thapa , Shrestha Dhiraj
Published: March 2024

Background

The production of extended-spectrum beta-lactamases (ESBLs) among uropathogens, particularly E. coli and Klebsiella spp., poses a severe public health concern. This study explored the epidemiology of ESBL-producing E. coli and Klebsiella spp. isolated from urine samples obtained at a tertiary care children's hospital in Nepal.

Methods

A cross-sectional study was conducted from August 2016 to February 2017. A total of 745 clean catch urine samples were obtained from pediatric patients under the age of 13 and subjected to semiquantitative culture. E. coli and Klebsiella spp. were identified using standard laboratory protocols. Antibiotic susceptibility testing was performed using the Kirby-Bauer disc diffusion method, and ESBL producers were phenotypically identified using the combined disk method.

Results

Among the bacterial isolates, E. coli predominated, accounting for 139 (81.8%) positive cases. Notably, E. coli showed high susceptibility to nitrofurantoin, with 117 (84.2%) isolates being susceptible. Meanwhile, K. pneumoniae showed high susceptibility to gentamicin, with 21 (91.3%) isolates being susceptible. Of the 163 isolates of E. coli and Klebsiella spp., 62 (38.0%) were identified as multidrug-resistant (MDR), with 42 (25.8%) confirmed as phenotypic ESBL producers. Remarkably, all 41 (100%) ESBL-producing E. coli isolates were susceptible to imipenem.

Conclusions

The prevalence of ESBL producers among E. coli and K. pneumoniae isolates from pediatric patients underscores the importance of antimicrobial stewardship. Nitrofurantoin and gentamicin emerge as effective empirical treatment choices against these pathogens in children. However, the high rates of multidrug resistance and ESBL production highlight the necessity for routine surveillance, and early detection strategies to manage such infections effectively.
Designing Ti-6Al-4V microstructure for strain delocalization using neural networks
Authors: Ahmadikia Behnam , Beyerlein Adolph L. , Hestroffer Jonathan M. , Kumar M. Arul , Beyerlein Irene J.
Published: March 2024

The deformation behavior of Ti-6Al-4V titanium alloy is significantly influenced by slip localized within crystallographic slip bands. Experimental observations reveal that intense slip bands in Ti-6Al-4V form at strains well below the macroscopic yield strain and may serially propagate across grain boundaries, resulting in long-range localization that percolates through the microstructure. These connected, localized slip bands serve as potential sites for crack initiation. Although slip localization in Ti-6Al-4V is known to be influenced by various factors, an investigation of optimal microstructures that limit localization remains lacking. In this work, we develop a novel strategy that integrates an explicit slip band crystal plasticity technique, graph networks, and neural network models to identify Ti-6Al-4V microstructures that reduce the propensity for strain localization. Simulations are conducted on a dataset of 3D polycrystals, each represented as a graph to account for grain neighborhood and connectivity. The results are then used to train neural network surrogate models that accurately predict localization-based properties of a polycrystal, given its microstructure. These properties include the ratio of slip accumulated in the band to that in the matrix, fraction of total applied strain accommodated by slip bands, and spatial connectivity of slip bands throughout the microstructure. The initial dataset is enriched by synthetic data generated by the surrogate models, and a grid search optimization is subsequently performed to find optimal microstructures. Describing a 3D polycrystal with only a few features and a combination of graph and neural network models offer robustness compared to the alternative approaches without compromising accuracy. We show that while each material property is optimized through a unique microstructure solution, elongated grain shape emerges as a recurring feature among all optimal microstructures. This finding suggests that designing microstructures with elongated grains could potentially mitigate strain localization without compromising strength.
Baseline and early response 2-[18F]FDG-PET/MRI for prediction of radiotherapy outcome in uterine cervical squamous cell carcinoma: a prospective single-center observational cohort study
Authors: Strandberg Sara , Jonsson Joakim , Zarei Maryam , Aglund Kristina , Blomqvist Lennart , Söderkvist Karin
Published: March 2024

Background

Should early response imaging predict tumor response to therapy, personalized treatment adaptations could be feasible to improve outcome or reduce the risk of adverse events. This prospective single-center observational study on 2-fluorine-18-fluoro-deoxy-glucose (2-[18F]FDG) positron-emission tomography/magnetic resonance imaging (PET/MRI) features aims to investigate the association between semantic 2-[18F]FDG-PET/MRI imaging parameters and outcome prediction in uterine cervical squamous cell carcinoma (CSCC) treated with radiotherapy.

Results

Eleven study participants with previously untreated CSCC were examined with 2-[18F]FDG-PET/MRI at baseline and approximately one week after start of curative radiotherapy. All study participants had at least 24 months clinical follow-up. Two patients relapsed during the follow-up period. Reduced tumor size according to visual assessment was present in 9/11 participants (median change in sum of largest diameters (SLD) − 10.4%; range − 2.5 to − 24.6%). The size reduction was less pronounced in the relapse group compared to the no relapse group, with median change in SLD − 4.9%, versus − 10.4%. None of the reductions qualified as significantly reduced or increased in size according to RECIST 1.1., hence all participants were at this stage classified as non-responders/stable disease. Median baseline functional tumor volume (FTV) for the relapse group was 126 cm3, while for the no relapse group 9.3 cm3. Median delta FTV in the relapse group was 50.7 cm3, representing an actual increase in metabolically active volume, while median delta FTV in the no relapse group was − 2.0 cm3. Median delta apparent diffusion coefficient (ADC) was lower in the relapse group versus the no relapse group (− 3.5 mm2/s vs. 71 mm2/s).

Conclusions

Early response assessment with 2-[18F]FDG-PET/MRI identified potentially predictive functional imaging biomarkers for prediction of radiotherapy outcome in CSCC, that could not be recognized with tumor measurements according to RECIST 1.1. These biomarkers (delta FTV and delta ADC) should be further evaluated.

Trial registration Clinical Trials, NCT02379039. Registered 4 March 2015—Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/study/NCT02379039.
Research progress on the electrophysiological indicators to predict the efficacy of vagus nerve stimulation for drug-refractory epilepsy
Authors: Li Guangli , Li Zhenguang , Liu Yingting
Published: March 2024

Vagus nerve stimulation (VNS) is an important treatment option for drug-refractory epilepsy (DRE), with well-established efficacy and safety in clinical practice for more than 20 years. However, it is very difficult to find the optimal electrophysiological indicators for the effectiveness of VNS on DRE because the mechanism of action is unknown. In this review, we provide an update of the potential applications of VNS outcomes in patients with drug-resistant epilepsy. Electroencephalographic (EEG) activity, event-related potentials, EEG synchronization levels, magnetoencephalographic, laryngeal muscle evoked potentials, and heart rate variability are potential biomarkers for VNS outcomes in people with DRE.
Sustainable and one-pot fabrication of peptide chelated calcium from fish scale hydrolysates
Authors: Dai Hongjie , Cao Yingnan , Fu Yu , Tang Mi , Feng Xin , Ma Liang , Zhang Yuhao
Published: March 2024

Fish scales, considered as low-value by-products, contain peptides and hydroxyapatite that can be applied to produce peptide chelated calcium directly. This study developed a sustainable and one-pot fabrication method for the peptide-chelated calcium from fish scale hydrolysates (FSP-Ca). During pepsin hydrolysis, the releases of peptides (FSP), calcium, and phosphate from fish scales occurred simultaneously, and the chelation was also effectively performed. After a 6-h hydrolysis, the yield of FSP was 46.18%, and the dissolution rate of calcium was 49.53%. Under the optimal conditions (pH 7, chelation time of 25 min, and chelation temperature of 48 °C), a high chelation rate of 86.16% was obtained, with a calcium content of 81.8 mg/g. The results of UV absorption, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) confirmed the successful chelation between FSP and calcium derived from fish scales. The –NH2, –COO–, N–H, C=O, C–H, and –OH groups in FSP participated in the formation of FSP-Ca.

Graphical Abstract
Chlorogenic acid regulates the expression of protein phosphatase 2A subunit B in the cerebral cortex of a rat stroke model and glutamate-exposed neurons
Authors: Kang Ju-Bin , Son Hyun-Kyoung , Park Dong-Ju , Jin Yeung-Bae , Koh Phil-Ok
Published: March 2024

Background

Ischemic stroke is a serious neurological disorder caused by blockages in cerebral artery. Protein phosphatase 2A (PP2A) is a phosphatase that performs a critical role in cell signaling and growth. PP2A subunit B acts as a neuroprotective agent in the nerve system. Chlorogenic acid, which is mainly found in roasted coffee, has antioxidant, anti-inflammatory, and anti-apoptotic effects. We hypothesized that chlorogenic acid modulates PP2A subunit B expression in ischemic stroke models and glutamate-mediated neurons. Middle artery occlusion (MCAO) surgery was operated and chlorogenic acid (30 mg/kg) or phosphate buffer saline was treated 2 h after MCAO. The cerebral cortex was collected 24 h after surgery and the change of PP2A subunit B expression was analyzed. Glutamate and/or chlorogenic acid were treated in cultured neurons, further study was performed.

Results

A decrease in PP2A subunit B expression in MCAO animals was identified. Chlorogenic acid alleviated this decrease due to ischemic injury. Moreover, the number of PP2A subunit B-positive cells in the ischemic cerebral cortex was significantly decreased, chlorogenic acid alleviated this decrease. We also found protective effects of chlorogenic acid in neurons exposed to glutamate. Glutamate decreased the expression of PP2A subunit B and chlorogenic acid mitigated this decrease. Our results elucidated that chlorogenic acid performs neuroprotective functions and attenuates the reduction of PP2A subunit B by brain damage and glutamate-mediated excitotoxicity.

Conclusions

We showed that chlorogenic acid attenuated the decrease of PP2A subunit B in ischemic injury and neurons exposed to glutamate. Since PP2A subunit B contributes to the protection of brain tissue, we can suggest that chlorogenic acid preserves neurons by modulating PP2A subunit B during ischemic damage.