bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGARUH EDUKASI DAGUSIBU TERHADAP TINGKAT PENGETAHUAN SISWA BEBERAPA SEKOLAH MENENGAH ATAS DI KOTA PADANG
Authors: Verawaty  , Dewi Irene Puspa , Salim Reny , Taslim Tuty , Selonni Fita , Manurung Tumpal
Published: January 2024

The public must be educated from an early age about drugs so that they do not make mistakes in using these drugs. One of the programs launched by the Indonesian Pharmacists Association (IAI) on how to obtain, use, store and dispose of medicines is DAGUSIBU education. This education is intended for all levels of society. The aim of this education is to provide education and understanding to high school students about DAGUSIBU and to see the influence of education on the level of knowledge of high school students. This educational activity began with a pretest to measure high school students' understanding of DAGUSIBU, after which education was carried out using lecture and question and answer methods. At the end of the education, high school students were given a posttest to measure high school students' understanding of DAGUSIBU after being given the education. To see the level of knowledge of high school students, we use the one group pretest-posttest design type of education. The number of educational participants was 173 students. The average level of knowledge of high school students before being given education was 49.93% (Poor) and the average level of knowledge of high school students after education was 72% (Enough). Based on these results, it appears that there is a significant change in knowledge between before and after education.
EDUKASI PENCEGAHAN KEKERASAN SEKSUAL PADA MURID TAMAN KANAK-KANAK (TK)
Authors: Hafsah  , Meliyana  , Riyanti Rika , Sumargiyanti  , Lestari Siska Marlina
Published: January 2024

This article discusses the efforts that can be made to prevent sexual violence against children through community dedication activities in children's schools (TK) students practiced to be able to provide early education for children thus reducing the incidence of sexual abuse in children. Sexual violence against children is a form of sexual abuse that can cause prolonged physical and psychological stress. Sexual violence against children is a widespread problem in various Indonesian provinces and requires preventive measures that can help children avoid sexual violence through both physical and non-physical contact. One form of effort that can be made by providing education to prevent sexual violence at an early age. The goal of dedication to this community, to provide education to kindergarten students on the prevention of sexual violence in order to avoid sexual violence that may occur in the future.
GAMBARAN FUNGSI GINJAL PASIEN DIABETES MELITUS TIPE II DI PUSKESMAS TLOGOSARI KULON KOTA SEMARANG
Authors: Rukminingsih Fef , Julianti Carla
Published: January 2024

Type II Diabetes Mellitus (DMTII) patients who are not treated properly can experience decreased renal function. The use of oral hypoglycemic drugs (OHG) can cause a decrease in renal function. Glomerular Filtration Rate (GFR) can describe a decrease in renal function. The aim of this study was to determine the description of renal function in DMTII patients at the Tlogosari Kulon Health Center, Semarang City. This research is a descriptive observational study. The sampling technique used was purposive sampling. Data was obtained from medical records of DMTII patients for the period September–December 2022. The inclusion criteria were patients with DMTII who received OHG therapy for at least one year, aged ≥45 years, had the most recent serum creatinine examination, with or without comorbidities. If the patient's data is incomplete or the patient has a history of renal problems, they will be excluded. Based on the research results, it was discovered that there were 55 DMTII patients, consisting of 39 patients (70.90%) women and 16 patients (29.10%) men. A total of 29 patients were aged between 60-69 years (52.73%). A total of 39 patients had comorbidities such as hypertension and/or dyslipidemia. A total of 76.36% received OHG combination therapy. Forty percent of patients experienced a decrease in GFR from mild-moderate to severe. The decrease in GFR is caused by the amount of OHG consumed and comorbid hypertension
Predicting Success of Live Facial Recognition Operational Deployments
Authors: Tansell Amy , Dalirrooyfard Mahsa , Cheale Thomas , Li Kairui , Rotous Ioannis
Published: January 2024

Is the use of Live Facial Recognition a good use of police resources? Mathematically, this can be posed as a conditional probability: given a wanted watchlist subject is at the location of the deployment, what is the probability that they will pass through the ‘zone of recognition’ of the cameras? To address the problem, probability and statistics were combined with an agent-based model to simulate the crowd dynamics conditional on the placement of the police van, the zone of recognition of the cameras, and the sign publicising the deployment. The study group discovered that, with additional time-dependent data of the detections made, the ensemble of models constructed have the potential to reliably advise the optimisation of success of future Live Facial Recognition deployments.
Fostering civic dispositions in the digital era 4.0 through local wisdom-based civic education
Authors: Makmur Chesa Syaqira
Published: January 2024

This study endeavours to scrutinize civic education grounded in indigenous wisdom to amplify civic dispositions in the era of digital 4.0. Through the prism of political integration, civic dispositions emerge as a pivotal constituent in propelling integrative conduct conducive to racial amalgamation and the amalgamation of the elite with the broader populace. The research methodology employed herein melds a comprehensive literature review with a qualitative descriptive approach. The findings of this inquiry proffer evidence that implementing civic education informed by indigenous wisdom can augment the civic dispositions of the nation's rising generation in the digital 4.0 epoch. Formulating citizenship resources and didactic materials founded on local knowledge elevates citizenship attitudes in the digital 4.0 milieu. The cultivation of exemplary civic character exerts a profound influence on good citizens. The cultivation of integrative societal behaviours holds the potential to culminate in the establishment of a potent national culture.
DE TRAMA Y LINAJE. EL CUERPO TEXTIL COMO ARCHIVO VIVO PARA NARRAR MEMORIA FEMENINA
Authors: Rivas Monje Fabiana
Published: January 2024

A partir de un breve recorrido de las tramas entre artes y feminismos en América Latina, realizo un énfasis en el arte y oficio textil para enlazar con los aportes del giro afectivo. El centro de la propuesta es compartir la confección de un libro textil en el marco de trabajo final de la diplomatura en Feminismos Comunitarios, Campesinos y Populares (2022) de la UNJu (Argentina). Desde mi propio cuerpo de costurera y feminista, habitante del sur del Sur, mi lugar de enunciación me remite a la utilización política del quehacer textil para confeccionar materialidad. El libro-textil, lo propongo como un conjuro de memorias que honra mi linaje femenino, mediante una escritura afectiva que pretende hacer de la palabra escrita un textil político. Una “narrativa corpo-emotiva feminista” que vengo ensayando en diversos formatos, y que desde mi cuerpo-como-territorio situado, me habilita puntos de fuga crítica hacia la  colonialidad del saber y la academia patriarcal, buscando exceder su canon. De esta forma, la escritura poética se torna política, a través de apuntes textiles que aportan a recuperar la memoria femenina de mi propia genealogía. Las técnicas textiles utilizadas fueron el fotobordado sobre fotografías de mis ancestras de ambos linajes; el bordado libre a máquina de coser doméstica para plasmar el texto en la tela, y la costura para confeccionar el cuerpo del libro. El ejercicio constituye un ensayo de artivismo feminista en contextos académicos.
Amélia de Mesquita
Authors: Da Paz Aline
Published: January 2024

O levantamento de 628 nomes de mulheres musicistas, alunas e professoras do Instituto Nacional de Música - principal instituição de ensino de música no Rio de Janeiro, capital do recém-inaugurado período republicano (1889) – após extensa pesquisa, resultou em uma listagem de 34 mulheres, cujos materiais musicais produzidos são parte de grandes acervos, tais como os da Biblioteca Nacional. Esse panorama apresentou um contexto em que a atuação profissional feminina na música se mostra relevante, contudo, pouco documentada. É nesse ambiente que encontramos Amélia de Mesquita, uma mulher que conseguiu romper barreiras pessoais e sociais se estabelecendo como compositora, professora e intérprete com grande relevância no contexto do final do século XIX e início do século XX.
Systematic computational hunting for small RNAs derived from ncRNAs during dengue virus infection in endothelial HMEC-1 cells
Authors: Gutierrez-Diaz Aimer , Hoffmann Steve , Gallego-Gómez Juan Carlos , Bermudez-Santana Clara Isabel
Published: January 2024

In recent years, a population of small RNA fragments derived from non-coding RNAs (sfd-RNAs) has gained significant interest due to its functional and structural resemblance to miRNAs, adding another level of complexity to our comprehension of small-RNA-mediated gene regulation. Despite this, scientists need more tools to test the differential expression of sfd-RNAs since the current methods to detect miRNAs may not be directly applied to them. The primary reasons are the lack of accurate small RNA and ncRNA annotation, the multi-mapping read (MMR) placement, and the multicopy nature of ncRNAs in the human genome. To solve these issues, a methodology that allows the detection of differentially expressed sfd-RNAs, including canonical miRNAs, by using an integrated copy-number-corrected ncRNA annotation was implemented. This approach was coupled with sixteen different computational strategies composed of combinations of four aligners and four normalization methods to provide a rank-order of prediction for each differentially expressed sfd-RNA. By systematically addressing the three main problems, we could detect differentially expressed miRNAs and sfd-RNAs in dengue virus-infected human dermal microvascular endothelial cells. Although more biological evaluations are required, two molecular targets of the hsa-mir-103a and hsa-mir-494 (CDK5 and PI3/AKT) appear relevant for dengue virus (DENV) infections. Here, we performed a comprehensive annotation and differential expression analysis, which can be applied in other studies addressing the role of small fragment RNA populations derived from ncRNAs in virus infection.
Targeting the nucleic acid oxidative damage repair enzyme MTH1: a promising therapeutic option
Authors: Ding Yifeng , Liu Qingquan
Published: January 2024

The accumulation of reactive oxygen species (ROS) plays a pivotal role in the development of various diseases, including cancer. Elevated ROS levels cause oxidative stress, resulting in detrimental effects on organisms and enabling tumors to develop adaptive responses. Targeting these enhanced oxidative stress protection mechanisms could offer therapeutic benefits with high specificity, as normal cells exhibit lower dependency on these pathways. MTH1 (mutT homolog 1), a homolog of Escherichia coli’s MutT, is crucial in this context. It sanitizes the nucleotide pool, preventing incorporation of oxidized nucleotides, thus safeguarding DNA integrity. This study explores MTH1’s potential as a therapeutic target, particularly in cancer treatment, providing insights into its structure, function, and role in disease progression.
BacPROTACs targeting Clp protease: a promising strategy for anti-mycobacterial drug discovery
Authors: Bonjorno Andressa Francielli , Pavan Aline Renata , Fernandes Guilherme F. S. , Scarim Cauê Benito , Castagnolo Daniele , Dos Santos Jean Leandro
Published: January 2024

Tuberculosis (TB) has claimed more lives over the course of two millennia than any other infectious disease worldwide. In 2021, the World Health Organization (WHO) estimated that 10.6 million people were diagnosed with TB, resulting in the deaths of 1.4 million HIV-negative individuals. The emergence of multidrug-resistant TB (MDR-TB), defined as resistance to at least rifampicin (RIF) and isoniazid (INH), and extensively drug-resistant TB (XDR-TB), poses the primary challenge to overcome in the coming years. We have recently conducted an extensive analysis of investments and research endeavours in the field, with the overarching objective of achieving the established milestone of TB eradication by the year 2030. Over the past several years, there has been notable progress in advancing a multitude of promising compounds, each possessing distinct mechanisms of action, into clinical phases of development. However, it is worth noting that strains of mycobacteria resistant to current antitubercular drugs have already emerged for some of these compounds The exploration of the innovative Proteolytic Target Chimeras (PROTACs) protein degradation approach has emerged as a viable avenue for the discovery of novel antimicrobials. While the ubiquitin system is exclusive to eukaryotic cells, certain bacteria use a similar degradation system that relies on the recognition of phosphorylated arginine residues (pArg) by the ClpC:ClpP (ClpCP) protease, thereby leading to protein degradation. In this opinion article, we have described and analized the advances in the use of PROTACs that leverage bacterial proteolytic machinery (BacPROTACs) to design new antitubercular agents. Scope Statement. The development of novel pharmaceuticals for tuberculosis treatment is deemed urgently necessary due to the emergence of resistant strains. In this context, the introduction of new technologies capable of alleviating the disease and attaining the objectives outlined by the World Health Organization is imperative. Among the innovative strategies, the degradation of proteins that are crucial for the survival of the bacillus holds promise for generating new medications, particularly those that are effective at treating latent (non-replicating) Mycobacterium tuberculosis. Within this perspective, we present the advancements and obstacles encountered in the exploration of new BacPROTAC compounds, with the intention of encouraging research and illuminating challenges associated with the implementation of BacPROTACs to address to the global tuberculosis crisis.
Online peer support for people with Amyotrophic Lateral Sclerosis (ALS): a narrative synthesis systematic review
Authors: Gerritzen Esther Vera , Lee Abigail Rebecca , McDermott Orii , Coulson Neil , Orrell Martin
Published: January 2024

Background

Amyotrophic Lateral Sclerosis (ALS) significantly impacts the lives of people with the diagnosis and their families. A supportive social environment is important for people with ALS to adopt effective coping strategies and health behaviours, and reduce depressive symptoms. Peer support can provide a supportive social environment and can happen in-person and online. Advantages of online peer support are that people can engage from their own home, at their own time and pace, and that it offers a variety of different platforms and modes of communication.

Objectives

To (1) explore the benefits and challenges of online peer support for people with ALS, and (2) identify successful elements of online peer support for people with ALS.

Methods

The method selected for this systematic review was a narrative synthesis. Six databases were systematically searched in April 2020 for articles published between 1989 and 2020. The search was updated in June 2022. The quality of the included studies was assessed with the Critical Appraisal Skills Programme qualitative research checklist.

Results

10,987 unique articles were identified through the systematic database search. Of those, 9 were included in this review. One of the main benefits of online peer support was that people could communicate using text rather than needing verbal communication, which can be challenging for some with ALS. Successful elements included using profile pages and graphics to identify others with similar or relevant experiences. Challenges included ALS symptoms which could make it difficult to use technological devices.

Conclusions

Peer support can provide a non-judgmental and supportive environment for people with ALS, in which they can exchange experiences and emotional support, which can help people in developing adaptive coping strategies. However, ALS symptoms may make it more difficult for people to use technological devices and engage in online peer support. More research is needed to identify what kind of specific barriers people with ALS experience, and how these could be overcome.
Reading experience drives L2 reading speed development: a longitudinal study of EAL reading habits
Authors: Schmidtke Daniel , Rahmanian Sadaf , Moro Anna L.
Published: January 2024

Introduction

The present longitudinal study tested the hypotheses that (i) learners become faster readers after intensive English language instruction, and that (ii) learners who read more English texts tend to make larger gains in reading speed.

Methods

Study participants were 142 L1 Cantonese or Mandarin English learners enrolled in an eight-month university bridging program. Participants completed a reading habits log each week, reporting information about their reading activity, including the type of texts they read, the amount of time they spent reading each text, and the number of pages they read.

Results

It was found that English language learners spent less time reading per page of text by program end, as shown by a significant linear weekly increase in reading speed. Critically, there was also a significant effect of reading experience: learners who read more pages of text than their peers during the bridging program tended to make the largest net gains in reading speed.

Discussion

The results support the idea that reading experience is a factor that contributes to reading speed development in English language learners.
Poor serum uric acid control increases risk for developing hypertension: a retrospective cohort study in China
Authors: Lin Zeyin , Wu Shaoyan , Chen Zhe , Luo Weijian , Lin Zhihui , Su Honghui , Guo Dongming
Published: January 2024

Background

Serum uric acid (SUA) has been suggested as a contributor of hypertension. However, reports on the relationship between changes in SUA and hypertension are limited. Hence, we aimed to investigate the potential impact of SUA, especially its change over time, on hypertension incidence.

Methods

This dynamic cohort included 6052 participants without hypertension at baseline. Participants were categorized into six grades based on whether baseline SUA was high and whether changes in SUA progressed to hyperuricemia or decreased to normal levels. Grades 1 to 6 represented the participants’ SUA control from best to worst. Logistic regression and restricted cubic spline (RCS) models were used to explore the association of the grades of SUA control and hypertension incidence.

Results

During a median follow-up of 6 years, 2550 (42.1%) participants developed hypertension. After adjusting confounding factors, compared to grade 1 with the best control of SUA, the odds ratios for grades 2 to 6 with worse control were 1.347 (1.109-1.636), 1.138 (0.764-1.693), 1.552 (1.245-1.934), 1.765 (1.170-2.663), and 2.165 (1.566-2.993), respectively. RCS indicated a linear correlation between the risk of hypertension and changes in SUA, and an elevated risk in participants with baseline hyperuricemia. Subgroup analyses showed that grades of SUA control had an interaction with systolic (P = 0.003) and diastolic blood pressure (P < 0.001). Sensitivity analyses further determined the robustness of the result that participants with poor SUA control have a higher risk of developing hypertension.

Conclusion

Poor SUA control, an increase in SUA over time, rises the risk of developing hypertension regardless of whether the initial SUA is normal or not. Initial hyperuricemia will exacerbate this risk. Effective SUA control should be an important measure for primary prevention of hypertension.
Collocation-analyzed multi-source ensembled wind speed data in lake district: a case study in Dongting Lake of China
Authors: Tan Shi-Qi , Guo Hai-Feng , Liao Chun-Hua , Ma Jing-Hao , Tan Wen-Zhi , Peng Wei-Ying , Fan Jia-Zhi
Published: January 2024

The lack of reliable near-surface wind data products in lake district regions significantly limits the efficiency of meteorological models, forecasts, services, and wind resource development. This is primarily due to a shortage of observation data and related studies, as well as insufficient validation and promotion of existing data products, which further hinders the comprehension and monitoring of local wind fields. In this study, comprehensive verification research was conducted on mainstream wind field products, namely, ERA5-Land (EC), GLDAS (GL), and HRCLDAS (HR) in the Dongting Lake area of China. This was achieved by utilizing a large volume of measured data and a triple collocation analysis (TCA) method. Additionally, an exploration into the optimal wind field data fusion method was undertaken. HR products demonstrate superior performance in capturing wind speed at the in situ measured scale, while GL outperforms at the grid scale, and EC products show relatively stable performance with minimal outliers. The long short-term memory (LSTM) neural network model, combined with time-series features, emerges as the most optimal data fusion model. LSTM fusion product is superior to the original product (except for HR products at the in situ measured scale), TCA-based weighted fusion products, and multi-layer fully connected neural network (MFCNN) on various parameters. This study quantifies the performance of mainstream wind products in lake areas and provides a benchmark for further application of these products. Furthermore, the successful implementation of an optimal wind data fusion method can provide valuable insights for related research, and the resulting wind fusion products can offer superior basic data support for local terminal applications.
B cell receptor repertoire abnormalities in autoimmune disease
Authors: Yuuki Hayato , Itamiya Takahiro , Nagafuchi Yasuo , Ota Mineto , Fujio Keishi
Published: January 2024

B cells play a crucial role in the immune response and contribute to various autoimmune diseases. Recent studies have revealed abnormalities in the B cell receptor (BCR) repertoire of patients with autoimmune diseases, with distinct features observed among different diseases and B cell subsets. Classically, BCR repertoire was used as an identifier of distinct antigen-specific clonotypes, but the recent advancement of analyzing large-scale repertoire has enabled us to use it as a tool for characterizing cellular biology. In this review, we provide an overview of the BCR repertoire in autoimmune diseases incorporating insights from our latest research findings. In systemic lupus erythematosus (SLE), we observed a significant skew in the usage of VDJ genes, particularly in CD27+IgD+ unswitched memory B cells and plasmablasts. Notably, autoreactive clones within unswitched memory B cells were found to be increased and strongly associated with disease activity, underscoring the clinical significance of this subset. Similarly, various abnormalities in the BCR repertoire have been reported in other autoimmune diseases such as rheumatoid arthritis. Thus, BCR repertoire analysis holds potential for enhancing our understanding of the underlying mechanisms involved in autoimmune diseases. Moreover, it has the potential to predict treatment effects and identify therapeutic targets in autoimmune diseases.
Characterization of a novel algicidal bacteria Arenibacter sp. strain 6A1 and its application to eliminate harmful algal blooms
Authors: Wu Sha , Tong Jing , Chen Jiahuan , Chen Minchun , Wang Liyan , Li Shuangfei , Hu Zhangli , Chen Huirong
Published: January 2024

Hazardous impacts caused by harmful algal blooms (HABs) have facilitated the development of novel effective approaches for controlling the frequent HABs. Recently, bacteria with algicidal effects, as a promising alternative tool for eliminating the HABs-forming species have received wide concerns. In the present study, a marine bacterial strain 6A1 with potent algicidal activity was successfully isolated from a bloom of Akashiwo sanguinea, and the characteristics related to its algicidal action were systematically investigated. Sequencing results of 16S rDNA suggested that this bacterium belongs to the genus Arenibacter in the family Flavobacteriaceae, while the phylogenetic analysis revealed that Arenibacter sp. strain 6A1 was the only algicidal bacterium in Arenibacter to date, according to the best of our knowledge. Arenibacter sp. strain 6A1 had an extraordinarily high algicidal performance when it was added to A. sanguinea culture with a volume fraction of 1.5% for 2 h. The algicidal performance of strain 6A1 was concentration-dependent and time-dependent. The best algicidal efficacy of strain 6A1 was seen during the stationary phase, while the resistance of A. sanguinea to strain 6A1 declined as the growth cycle progressed. Subsequently, the indirect algicidal mode of Arenibacter sp. strain 6A1 was verified and the algicidal compounds produced by strain 6A1 were proved to be heat-resistant. Further research showed that strain 6A1 caused a severe damage in photosynthesis, oxidative stress, and also damage in three HABs-forming algae to varying degrees. The greatest algicidal performance was found on unarmored dinoflagellate A. sanguinea, followed by raphidophyte Chattonella antiqua and armored dinoflagellate Alexandrium tamarense. The Arenibacter sp. strain 6A1 exhibited selective algicidal activity on a wide range of algal species, primarily targeting Pyrrophyta and Ochrophyta. The proposed bacteria (strain 6A1) can be a powerful and eco-friendly tool for emergency treatment of HABs caused by certain algal species in coastal water bodies.
Digital health for remote home monitoring of patients with COVID-19 requiring oxygen: a cohort study and literature review
Authors: Chaytee Johann , Dinh Aurélien , D’Anglejan Emma , Bouchand Frédérique , Jaffal Karim , Duran Clara , Le Gall Catherine
Published: January 2024

Background

The clinical course and outcome of COVID-19 vary widely, from asymptomatic and mild to critical. Elderly patients and patients with comorbidities are at increased risk of respiratory failure and oxygen requirements. Due to the massive surge, the pandemic has created challenges for overwhelmed hospitals. Thus, the original home management of COVID-19 patients requiring oxygen and remote monitoring by a web app and a nurse at home were implemented in our center. We aimed to evaluate the outcome of patients with COVID-19 requiring oxygen who benefited from home remote monitoring management.

Methods

We performed a retrospective cohort study on all COVID-19 patients requiring oxygen (< 5 L/min) who consulted from October 2020 to April 2021 at our emergency department and were managed with home remote monitoring by a web app and an in-home nurse. We also carried out a literature review of studies on COVID-19 patients requiring oxygen with remote monitoring.

Results

We included 300 patients [184 (61.3%) male patients, median age 51 years]. The main comorbidities were cardiovascular disease (n = 117; 39.0%), diabetes mellitus (n = 72; 24.0%), and chronic respiratory disease (n = 32; 10.7%). Among the 28 (9.3%) patients readmitted to the hospital, 6 (1.9%) were hospitalized in the intensive care unit, and 3 (0.9%) died. In the multivariable analysis, risk factors for unplanned hospitalization were chronic respiratory failure (odds ratio (OR) =4.476, 95%CI 1.565–12.80), immunosuppression (OR = 3.736, 95%CI 1.208–11.552), and short delay between symptoms onset and start of telemonitoring (OR = 0.744, 95%CI 0.653–0.847). In the literature review, we identified seven other experiences of remote monitoring management. Mortality rate and unplanned hospitalization were low (maximum 1.9 and 12%, respectively).

Conclusion

Our study confirms the safety of home remote monitoring of patients with COVID-19 who require oxygen, as well as our literature review. However, patients with chronic respiratory failure and immunosuppression should be closely monitored.
Type 3 gastric neuroendocrine neoplasms: the rising promise of conservative endoscopic management
Authors: Dell’Unto Elisabetta , Esposito Gianluca , Rinzivillo Maria , Marasco Matteo , Annibale Bruno , Panzuto Francesco
Published: January 2024

Gastric neuroendocrine neoplasms (g-NENs) are rare tumors arising from the gastric enterochromaffin-like cells. Recent data suggests an increased detection rate, attributed to more frequent esophagogastroduodenoscopies. While type 3 g-NENs were historically deemed aggressive, emerging research indicates potential for conservative management, especially endoscopic resection, in well-differentiated, small tumors. European guidelines now advocate for endoscopic intervention in selected cases, but North American guidelines remain more conservative. Key factors influencing outcomes are tumor size, grading, and depth of gastric wall infiltration. Endoscopic resection has shown promise for tumors confined to submucosal layers without lymphovascular invasion. Given the complexities, a multidisciplinary team approach is essential for management decisions. Current insights are largely based on retrospective studies, underscoring the need for prospective research to optimize endoscopic approaches.
Bioactive cytochalasans from the desert soil-derived fungus Chaetomium madrasense 375 obtained via a chemical engineering strategy
Authors: Guo Qingfeng , Shen Shenyu , Wang Xinyang , Shi Lei , Ren Yuwei , Li Dandan , Yin Zhenhua , Zhang Juanjuan , Yang Baocheng , Wang Xuewei , Ding Gang , Chen Lin
Published: January 2024

The chemical engineering of natural extracts has emerged as an effective strategy for the production of diverse libraries of chemicals, making it integral to drug discovery. A chemical engineering strategy based on the epoxidation and ring-opening reactions was used to prepare diversity-enhanced extracts of Chaetomium madrasense 375. Eleven unnatural cytochalasan derivatives (1–11) with unique functional groups, such as amine and isoxazole, were isolated and characterized from these chemically engineered extracts of C. madrasense 375. The identification of these new structures was accomplished through comprehensive spectroscopic analysis, supplemented by synthetic considerations. Notably, compounds 5 and 13–16 displayed potent phytotoxic effects on Arabidopsis thaliana, while compounds 1, 2, 5, 10, and 12 demonstrated inhibitory activities on LPS-induced NO production in RAW264.7 cells. Among them, compound 1 was found to be able to inhibit the upregulated expression of the inducible nitric oxide synthase (iNOS) protein induced by LPS, while also decreasing the production of pro-inflammatory cytokines (IL-6) and influencing the phosphorylation of p38, ERK1/2, and JNK at 100 μM. Our findings demonstrate that the chemical engineering of natural product extracts can be an efficient technique for the generation of novel bioactive molecules.
Transcriptional regulation of cellobiose utilization by PRD-domain containing Sigma54-dependent transcriptional activator (CelR) and catabolite control protein A (CcpA) in Bacillus thuringiensis
Authors: Zhang Liangwei , Xu Hong , Cheng Haijian , Song Fuping , Zhang Jie , Peng Qi
Published: January 2024

Cellobiose, a β-1,4-linked glucose dimer, is a major cellodextrin resulting from the enzymatic hydrolysis of cellulose. It is a major source of carbon for soil bacteria. In bacteria, the phosphoenolpyruvate (PEP): carbohydrate phosphotransferase system (PTS), encoded by the cel operon, is responsible for the transport and utilization of cellobiose. In this study, we analyzed the transcription and regulation of the cel operon in Bacillus thuringiensis (Bt). The cel operon is composed of five genes forming one transcription unit. β-Galactosidase assays revealed that cel operon transcription is induced by cellobiose, controlled by Sigma54, and positively regulated by CelR. The HTH-AAA+ domain of CelR recognized and specifically bound to three possible binding sites in the celA promoter region. CelR contains two PTS regulation domains (PRD1 and PRD2), which are separated by two PTS-like domains-the mannose transporter enzyme IIA component domain (EIIAMan) and the galactitol transporter enzyme IIB component domain (EIIBGat). Mutations of His-546 on the EIIAMan domain and Cys-682 on the EIIBGat domain resulted in decreased transcription of the cel operon, and mutations of His-839 on PRD2 increased transcription of the cel operon. Glucose repressed the transcription of the cel operon and catabolite control protein A (CcpA) positively regulated this process by binding the cel promoter. In the celABCDE and celR mutants, PTS activities were decreased, and cellobiose utilization was abolished, suggesting that the cel operon is essential for cellobiose utilization. Bt has been widely used as a biological pesticide. The metabolic properties of Bt are critical for fermentation. Nutrient utilization is also essential for the environmental adaptation of Bt. Glucose is the preferred energy source for many bacteria, and the presence of the phosphotransferase system allows bacteria to utilize other sugars in addition to glucose. Cellobiose utilization pathways have been of particular interest owing to their potential for developing alternative energy sources for bacteria. The data presented in this study improve our understanding of the transcription patterns of cel gene clusters. This will further help us to better understand how cellobiose is utilized for bacterial growth.
Longitudinal analysis of external quality assessment of immunoassay-based steroid hormone measurement indicates potential for improvement in standardization
Authors: Vierbaum Laura , Weiss Nathalie , Kaiser Patricia , Kremser Marcel , Wenzel Folker , Thevis Mario , Schellenberg Ingo , Luppa Peter B.
Published: January 2024

As hormonal disorders are linked to several diseases, the accurate quantitation of steroid hormone levels in serum is crucial in order to provide patients with a reliable diagnosis. Mass spectrometry-based methods are regarded as having the highest level of specificity and sensitivity. However, immunoassays are more commonly used in routine diagnostics to measure steroid levels as they are more cost effective and straightforward to conduct. This study analyzes the external quality assessment results for the measurement of testosterone, progesterone and 17β-estradiol in serum using immunoassays between early 2020 and May 2022. As reference measurement procedures are available for the three steroid hormones, the manufacturer-specific biases were normalized to the reference measurement values. The manufacturer-specific coefficients of variation were predominantly inconspicuous, below 20% for the three hormones when outliers are disregarded, however there were large differences between the various manufacturer collectives. For some collectives, the median bias to the respective reference measurement value was repeatedly greater than ±35%, which is the acceptance limit defined by the German Medical Association. In the case of testosterone and progesterone determination, some collectives tended to consistently over- or underestimate analyte concentrations compared to the reference measurement value, however, for 17β-estradiol determination, both positive and negative biases were observed. This insufficient level of accuracy suggests that cross-reactivity continues to be a fundamental challenge when antibody detection is used to quantify steroids with a high structural similarity. Distinct improvements in standardization are required to provide accurate analysis and thus, reliable clinical interpretations. The increased accuracy of the AX immunoassay for testosterone measurement, as observed in the INSTAND EQAs between 2020 and 2022, could be the result of a recalibration of the assay and raises hope for further improvement of standardization of immunoassay-based steroid hormone analyses in the coming years.
Novel germline variants in KMT2C in Chinese patients with Kleefstra syndrome-2
Authors: Yang Qi , Zhang Qiang , Yi Sheng , Zhang Shujie , Yi Shang , Zhou Xunzhao , Qin Zailong , Chen Biyan , Luo Jingsi
Published: January 2024

Kleefstra syndrome (KLEFS) refers to a rare inherited neurodevelopmental disorder characterized by intellectual disability (ID), language and motor delays, behavioral abnormalities, abnormal facial appearance, and other variable clinical features. KLEFS is subdivided into two subtypes: Kleefstra syndrome-1 (KLEFS1, OMIM: 610253), caused by a heterozygous microdeletion encompassing the Euchromatic Histone Lysine Methyltransferase 1 (EHMT1) gene on chromosome 9q34.3 or pathogenic variants in the EHMT1 gene, and Kleefstra syndrome-2 (KLEFS2, OMIM: 617768), caused by pathogenic variants in the KMT2C gene. More than 100 cases of KLEFS1 have been reported with pathogenic variants in the EHMT1 gene. However, only 13 patients with KLEFS2 have been reported to date. In the present study, five unrelated Chinese patients were diagnosed with KLEFS2 caused by KMT2C variants through whole-exome sequencing (WES). We identified five different variants of the KMT2C gene in these patients: c.9166C>T (p.Gln3056*), c.9232_9247delCAGCGATCAGAACCGT (p.Gln3078fs*13), c.5068dupA (p.Arg1690fs*10), c.10815_10819delAAGAA (p.Lys3605fs*7), and c.6911_6912insA (p.Met2304fs*8). All five patients had a clinical profile similar to that of patients with KLEFS2. To analyze the correlation between the genotype and phenotype of KLEFS2, we examined 18 variants and their associated phenotypes in 18 patients with KLEFS2. Patients carrying KMT2C variants presented with a wide range of phenotypic defects and an extremely variable phenotype. We concluded that the core phenotypes associated with KMT2C variants were intellectual disability, facial dysmorphisms, language and motor delays, behavioral abnormalities, hypotonia, short stature, and weight loss. Additionally, sex may be one factor influencing the outcome. Our findings expand the phenotypic and genetic spectrum of KLEFS2 and help to clarify the genotype–phenotype correlation.
Nutritional assessment and dietary intervention among survivors of childhood cancer: current landscape and a look to the future
Authors: Feit Talia , Beals Elizabeth , Dandekar Smita , Kadan-Lottick Nina , Joffe Lenat
Published: January 2024

Over 85% of childhood cancer patients become long-term survivors. Still, cancer and its therapies are associated with a myriad of long-term complications such that childhood cancer survivors (CCS) endure excess disease burden, morbidity, and mortality throughout their lifetimes. Existing literature suggests that CCS maintain poor dietary intake and nutritional status. Thus, as childhood cancer cure rates continue to improve, the role of diet and nutrition in mitigating many of the most common adverse long-term health outcomes among CCS has gained significant interest. Herein we present an in-depth review of existing scientific literature evaluating dietary intake and nutrition status among CCS and its impact on treatment-related health complications; as well as contemporary intervention strategies aimed at overcoming distinctive barriers and improving deleterious lifestyle behaviors in this heterogeneous, at-risk population. Patient-specific, clinical, and systemic factors act as barriers to the timely conduct of comprehensive dietary/nutritional assessments and provision of tailored, risk-based recommendations. This Mini Review discusses the current state of the science, persisting research gaps, and opportunities for advancement of assessment and intervention strategies to address the unique needs of CCS.

Search Strategy: We searched PubMed for peer-reviewed articles with the search terms “pediatric cancer,” “pediatric malignancy,” “pediatric oncology,” “childhood cancer,” “survivorship,” “cancer late effects,” “long-term follow-up,” “body mass index,” “nutritional status,” “malnutrition,” “body weight,” “body weight changes,” “body composition,” “obesity,” “overweight “, “Mediterranean diet,” “DASH diet,” “processed foods,” “micronutrients,” “antioxidants,” “vitamin D,” “calcium,” “selenium,” “zinc,” “metabolic syndrome,” “heart disease,” “cardiovascular disease,” “cardiometabolic disease,” “hypertension,” “hyperlipidemia,” “HDL,” “LDL,” and “small dense LDL” from January 1, 1995, to July 21, 2023. We also selected relevant articles from our personal files and from reference lists of identified papers. We prioritized publications after 2013; however, commonly cited and highly regarded (defined by high citation count and journal impact factor) older publications were also included. Randomized controlled trials, observational studies, retrospective studies, meta-analysis, editorials, and review articles were included, whereas conference abstracts and case reports were excluded. We only searched for articles published in English, or those translated into English.
Enhancing cognitive function in older adults: dietary approaches and implications
Authors: Polis Baruh , Samson Abraham O.
Published: January 2024

Natural aging encompasses physiological and psychological changes that impact overall health and quality of life. Mitigating these effects requires physical and mental exercise, coupled with proper nutrition. Notably, protein malnutrition emerges as a potential risk factor for senile dementia, with insufficient intake correlating with premature cognitive decline. Adequate protein intake in the elderly positively associates with memory function and lowers cognitive impairment risk. Considering diet as a modifiable risk factor for cognitive decline, extensive research has explored diverse dietary strategies to prevent dementia onset in older adults. However, conclusive results remain limited. This review aims to synthesize recent evidence on effective dietary approaches to enhance cognitive function and prognosis in older individuals. Specifically, the study evaluates complex multicomponent programs, protein-rich diets, and branched-chain amino acid supplementation. By addressing the nexus of nutrition and cognitive health, this review contributes to understanding viable interventions for promoting cognitive well-being in aging populations.
Case report: Malignant transformation of ovarian endometrioma during long term use of dienogest in a young lady
Authors: Chang Yi-Ting , Lu Ting-Fang , Sun Lou , Shih Yu-Hsiang , Hsu Shih-Tien , Liu Chin-Ku , Hwang Sheau-Feng , Lu Chien-Hsing
Published: January 2024

Endometriosis is a benign disease, which is also regarded as a precursor to ovarian malignancy. Dienogest is a progestin treatment for endometriosis with efficacy and tolerability. A 35-year-old Taiwanese lady with ovarian endometrioma had taken dienogest for the last 5 years. During sonographic follow-up, surgery was suggested owing to suspicious of malignant transformation of ovarian endometrioma. While she hesitated and turned to receive two cycles of oocyte retrieval because of nulliparity. Meanwhile, more papillary growth in the ovarian endometrioma with intratumor flow was found during follow-up. Laparoscopic enucleation was performed later, and pathology revealed clear cell carcinoma with peritoneal involvement, at least FIGO stage IIB. She then underwent debulking surgery to grossly no residual tumor and received adjuvant chemotherapy with no tumor recurrence in post-operative 17-months follow-up. Considering fertility preservation, conservative treatment of ovarian endometrioma is typically indicated for those women who have not yet completed childbearing. However, malignant transformation may still occur despite long-term progestin treatment. Therefore, careful image follow-up is still indispensable.
Does perinatal management have the potential to reduce the risk of intraventricular hemorrhage in preterm infants?
Authors: Korček Peter , Širc Jan , Berka Ivan , Kučera Jáchym , Straňák Zbyněk
Published: January 2024

Background

Intraventricular hemorrhage (IVH) is an important cause of neurodevelopmental impairment in preterm infants. A number of risk factors for IVH have already been proposed; however, some controversies regarding optimal perinatal management persist. This study aimed to identify perinatal and neonatal attributes associated with IVH in a representative population of preterm infants.

Methods

Perinatal data on 1,279 very preterm infants (<32 weeks of gestation) admitted to a tertiary neonatal intensive care unit were analyzed. The records were assessed using univariate analysis and logistic regression model to evaluate the risk factors for any and high–grade IVH (grade III–IV according to the classification by Papile) within the first week after birth.

Results

The incidence of any IVH was 14.3% (183/1,279); the rate of low–grade (I–II) and high–grade (III–IV) IVH was 9.0% (115/1,279) and 5.3% (68/1,279), respectively. Univariate analysis revealed multiple factors significantly associated with intraventricular hemorrhage: lower gestational age and birth weight, absence of antenatal steroids, vaginal delivery, low Apgar score at 5 min, delivery room intubation, surfactant administration, high frequency oscillation, pulmonary hypertension, pulmonary hemorrhage, tension pneumothorax, persistent ductus arteriosus, hypotension and early onset sepsis. Logistic regression confirmed lower gestational age, vaginal delivery, ductus arteriosus and early onset sepsis to be independent predictors for any IVH. Pulmonary hemorrhage, tension pneumothorax and early onset sepsis were independent risk factors for high–grade IVH. Complete course of antenatal steroids was associated with a lower risk for any (odds ratio 0.58, 95% confidence interval 0.39–0.85; P = .006) and for high–grade intraventricular hemorrhage (odds ratio 0.36, 95% confidence interval 0.20–0.65; P < .001).

Conclusion

The use of antenatal steroids and mode of delivery are crucial in the prevention of IVH; however, our study did not confirm the protective effect of placental transfusion. Severe respiratory insufficiency and circulatory instability remain to be powerful contributors to the development of IVH. Early detection and management of perinatal infection may also help to reduce the rate of brain injury and improve neurodevelopment in high–risk newborns.
Racial disparities in metastatic colorectal cancer outcomes revealed by tumor microbiome and transcriptome analysis with bevacizumab treatment
Authors: Feng Lei , Wang Rui , Zhao Qian , Wang Jun , Luo Gang , Xu Chongwen
Published: January 2024

Background: Metastatic colorectal cancer (mCRC) is a heterogeneous disease, often associated with poor outcomes and resistance to therapies. The racial variations in the molecular and microbiological profiles of mCRC patients, however, remain under-explored.

Methods: Using RNA-SEQ data, we extracted and analyzed actively transcribing microbiota within the tumor milieu, ensuring that the identified bacteria were not merely transient inhabitants but engaged in the tumor ecosystem. Also, we independently acquired samples from 12 mCRC patients, specifically, 6 White individuals and 6 of Black or African American descent. These samples underwent 16S rRNA sequencing.

Results: Our study revealed notable racial disparities in the molecular signatures and microbiota profiles of mCRC patients. The intersection of these data showcased the potential modulating effects of specific bacteria on gene expression. Particularly, the bacteria Helicobacter cinaedi and Sphingobium herbicidovorans emerged as significant influencers, with strong correlations to the genes SELENBP1 and SNORA38, respectively.

Discussion: These findings underscore the intricate interplay between host genomics and actively transcribing tumor microbiota in mCRC’s pathogenesis. The identified correlations between specific bacteria and genes highlight potential avenues for targeted therapies and a more personalized therapeutic approach.