bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Eye Strain in Medical Undergraduate Students during COVID-19 Pandemic
Authors: Shrestha Priyanka , Singh Pradhan Pranil Man
Published: November 2024

Background: Digital devices have been an integral part of our daily lives. With the emergence of COVID-19 pandemic we have gone through strict lockdowns. Most educational institutions conducted classes virtually. This increased the symptoms of digital eye strain. This study aims to assess the prevalence, symptoms, and level of awareness regarding digital eye strain in medical undergraduate students following the COVID-19 pandemic.Methods: Our study was a questionnaire-based cross-sectional study with a duration of 3 months. All the undergraduate medical students studying at Kathmandu Medical College Teaching Hospital were included in the study. A self-administered questionnaire was sent to each student electronically via google forms. Descriptive statistics, frequency tables, and percentages were calculated.Results: A total of 208 students were included in the study. The mean age of participants was 22.7±1.6 years (Mean ± SD) with a mean duration of online classes being11.39 ± 5.2 months (Mean ± SD) . The average screen time of students before the start of online classes was 4.14 (SD=2.13) hours. The average screen time after the start of online classes was 7.93 (SD=2.44) hours, an increase of 91.54%. The overall prevalence of digital eye strain among the respondents was 90.8% (n=189).Conclusions: The prevalence of digital eye strain in our study was high. The average screen time increased significantly following COVID-19. Therefore, it is important to create awareness regarding digital eye strain and practices that decrease the symptoms of digital eye strain. Keywords: COVID- 19; eye strain; medical students.
Evaluation of Errors on Death Certificates
Authors: Atreya Alok , Acharya Bina , Yadav Purushottam Prasad , Menezes Ritesh G , Nepal Samata
Published: November 2024

Background: Death certificates provide vital data for disease surveillance and health policy. However, errors are common globally, undermining data reliability. This study analyzed prevalence and types of errors in death certificates at a tertiary hospital in Nepal.Methods: A cross-sectional study reviewed all death certificates issued at Lumbini Medical College, Nepal from April 2020 to April 2022. Certificates were assessed for errors including improper sequencing, absent time intervals, abbreviations, illegible writing, and inaccurate immediate, antecedent, and underlying causes of death as per international guidelines. Errors were classified as major or minor.Results: Of 139 certificates, none were error-free. The most common error was incorrectly or incompletely filling the immediate cause of death (77.7%). Other errors included absent time of death (17.3%), abbreviations (57.6%), illegible writing (22.3%), and omitting the hospital stamp/medical council registration number (8.6%). Based on international criteria, 76.3% had minor errors, 23% had both major and minor errors. Conclusions: This study found a high rate of errors in death certification at a tertiary hospital in Nepal, undermining data accuracy. Regular training and monitoring with feedback are recommended to improve certification practices. Accurate cause-of-death data is vital for healthcare policy and decision-making in Nepal.Keywords: Cause of death; certification; international classification of diseases; major errors and minor errors.
Pengaruh Metode Variasi Latihan Terhadap Kemampuan Servis Atas Bola Voli Putri Pada Ekstrakurikuler SMPN 8 Kota Lubuklinggau
Authors: Kurniawan Edi , Syafrial  , Raibowo Septian , Rizky Oddie Barnanda , Prabowo Andika
Published: November 2024

Penelitian ini bertujuan untuk mengetahui dampak variasi latihan terhadap kemampuan servis atas bola voli siswi pada ekstrakurikuler di SMPN 8 Kota Lubuklinggau. Metode penelitian yang digunakan adalah pendekatan kuantitatif dengan jenis eksperimen semu. Popolasi dari penelitian ini berjumlah 40 siswi. Sampel terdiri dari 30 siswi yang dipilih menggunakan teknik purposive sampling berdasarkan kriteria siswi yang sudah pernah mengikuti perlombaan. Instrumen yang digunakan adalah tes servis atas. Teknik pengumpulan data menggunakan tes servis atas diawal atau pretest dan tes servis atas posttest setelah melaksanakan latihan. Hasil penelitian menunjukkan adanya pengaruh signifikan variasi latihan terhadap kemampuan servis atas bola voli siswi pada ekstrakurikuler di SMPN 8 Kota Lubuklinggau, dengan nilai thitung sebesar 9.135 yang lebih besar dari ttabel sebesar 2.048 pada taraf signifikansi α = 0.05. Terjadi peningkatan persentase sebesar 36.56%, sehingga hipotesis alternatif (Ha) diterima.
ABSTRACT
This study aims to determine the impact of variations in training on female students' extracurricular volleyball service abilities at SMPN 8 Lubuklinggau City. The research method used is a quantitative approach with a quasiexperimental type. The population of this research was 40 female students. The sample consisted of 30 female students who were selected using a purposive sampling technique based on the criteria of students who had previously participated in competitions. The instrument used is the top service test. The data collection technique uses a top service test at the beginning or pretest and a posttest top service test after carrying out the exercise. The results of the research show that there is a significant influence of training variations on female students' volleyball serving ability in extracurricular activities at SMPN 8 Lubuklinggau City, with a t value of 9.135 which is greater than the t table of 2.048 at a significance level of α = 0.05. There was an increase in the percentage of 36.56%, so the alternative hypothesis (Ha) was accepted.
Analisis Minat Generasi Milenial Di Kelurahan Padang Rambun Untuk Melakukan Aktivitas Olahraga Di Ruang Terbuka Kelurahan Padang Rambun Kabupaten Seluma
Authors: Karlina Ria , Pujianto Dian , Raibowo Septian , Prabowo Andika , Permadi Andes
Published: November 2024

Penelitian ini bertujuan untuk mengetahui hasil analisa minat generasi milenial untuk melakukan aktivitas olahraga. Penelitian ini menggunakan jenis penelitian deskriptif menggunakan pendekatan kualitatif. Penelitian ini menggunakan desain penelitian deskriptif analitis. Subjek penelitian ini adalah generasi milenial di Kelurahan Padang Rambun, objek penelitian ini adalah minat generasi milenial untuk melakukan aktivitas olahraga di Kelurahan Padang Rambun. Instrument penelitian yang digunakan berupa observasi, wawancara, angket dan dokumentasi. Berdasarkan hasil validasi ahli materi diperoleh hasil 87.2% dan 98.4% dikategorikan sangat layak untuk dibagikan ke responden. Berdasarkan hasil perhitungan deskriptif persentase diperoleh hasil dari faktor intrinsik minat generasi milenial diperoleh hasil rata-rata 70.9% kategori tinggi. Dari faktor ekstrinsik minat generasi milenial diperoleh rata-rata 74.5% kategori tinggi. Dari aktivitas olahraga minat generasi milenial diperoleh rata-rata 75.1% kategori tinggi. Dari hasil keseluruhan keseluruhan minat generasi milenial rata-rata 72.2% kategori tinggi.                       
Abstract
This study aims to determine the results of analyzing the millennial generation's interest in doing sports activities. This research uses descriptive research using a qualitative approach. This study used an analytical descriptive research design. The subject of this research is the millennial generation in Padang Rambun Village, the object of this research is the interest of the millennial generation in doing sports activities in Padang Rambun Ward. The research instruments used are observation, interviews, questionnaires and documentation. Based on the results of validation expert a result of 87.2% and a result of 98.4% categorized as very feasible to be distributed to respondents. Based on the results of the descriptive percentage calculation, the results of the intrinsic factors of millennial generation interest obtained an average result of 70.9% in the high category. From extrinsic factors, the interest of the millennial generation obtained an average of 74.5% in the high category. From sports activities, the interest of the millennial generation obtained an average of 75.1% in the high category. From the overall results, the overall interest of the millennial generation averaged 72.2% in the high category. It can be concluded that the overall interest of the millennial generation is categorized as high.
Aeroelastic assessment of the second flexure mode excitation in a low pressure ratio fan
Authors: Tateishi Atsushi , Aotsuka Mizuho , Kusuda Shinya , Tanaka Nozomi , Enoki Tomonori , Murooka Takeshi
Published: November 2024

During the development of high by-pass aircraft engine fans, stall flutter often becomes a major issue because it restricts their part-speed operability at near-stall conditions. Stall flutter is usually experienced on the first flexure mode, where a few nodal diameters are dominant. However, our recent tests showed strong non-synchronous excitation for the second flexure (2F) mode containing multiple nodal diameters, which is a distinguishing characteristic from well-known stall flutter. This paper aims to understand the mechanism of the observed 2F excitation. Aerodynamic damping is evaluated by nonlinear transient CFD simulations across a range of fan massflow near stall. The aerodynamic damping turns negative when vortex shedding near the blade tip spills upstream and interacts with the leading edge of the neighbouring blade. Also, the vortex shedding behaviour and resulting aerodynamic damping clearly depend on the blade amplitude. The vortex shedding has broadband spectra for both frequency and circumferential modes under low amplitude, and they lock on the blades’ motion under large amplitude. From these observations, it is concluded that the observed 2F excitation can be categorized into non-synchronous vibrations found in recent literature. The coincidence of blade vibration and vortex shedding is also discussed from unsteady signal processing.
Regulation of α-Ketoglutarate levels by Myc affects metabolism and demethylation in porcine early embryos
Authors: Ding Ran , Zhou Yongfeng , Zhang Qi , Kong Xiangjie , Li Qi , Zhang Sheng , Chen Yibing , An Xinglan , Li Ziyi
Published: November 2024

The Myc family is essential for cell proliferation, differentiation, and metabolism, particularly in embryonic development and stem cell functions. However, the specific role of Myc in porcine early embryonic development is not fully understood. This study observed high Myc expression during the four-cell stage of porcine embryos. Inhibition of Myc using 10058-F4 impaired embryonic development, disrupted energy metabolism, and increased DNA methylation. Mechanistically, these effects were dependent on α-KG, a TCA cycle intermediate and cofactor for TET demethylation enzymes. Sequencing analysis of four-cell embryos post-Myc inhibition revealed downregulation of key metabolic enzymes related to α-KG, such as CS, IDH2, leading to reduced α-KG levels. Supplementation with α-Ketoglutarate (α-KG) mitigated the negative effects of Myc inhibition, including lower blastocyst rates, decreased ATP levels, and increased 5 mC levels. In conclusion, Myc regulates the expression of key metabolic enzymes during the four-cell stage, influencing early embryonic metabolism and epigenetic reprogramming.
Interference of metal ions on the bioluminescent signal of firefly, Renilla, and NanoLuc luciferases in high-throughput screening assays
Authors: Canyelles i Font Francesca , Żukowski Krzysztof , Khan Masroor A. , Kwiatek Dorota , Kolanowski Jacek L.
Published: November 2024

Bioluminescent high-throughput screening (HTS) assays, based largely on the activity of firefly (FLuc), Renilla (RLuc), and/or NanoLuc (NLuc) luciferases, are widely utilised in research and drug discovery. In this study, we quantify the luciferase-based real-life HTS assay interference from biologically and environmentally relevant metal ions ubiquitously present in buffers, environmental and biological matrices, and as contaminants in plastics and compound libraries. We also provide insights into the cross-effects of metal ions and other key experimental and biological reagents (e.g., buffer types, EDTA, and glutathione) to inform HTS assay design, validation, and data interpretation. A total of 21 ions were screened in three robust HTS assays (“SC” assays) based on the luminescence of FLuc, RLuc, and NLuc luciferases. Three newly optimised HEPES buffer variants (“H” assays) were developed for direct luciferase comparison. Interference in bioluminescent signal generation was quantified by calculating the IC50 values from concentration-dependent experiments for selected highly active and relevant metal ions. Metal ion inhibition mechanisms were probed by variations in specific reagents, EDTA, GSH, and the sequence of addition and buffer composition. In this study, we revealed a significant impact of metal ions’ salts on luciferase-mediated bioluminescence, even at biologically and environmentally relevant concentrations. The extent of signal interference largely aligned with the Irving–Williams series of metal ion–ligand affinities (Cu > Zn > Fe > Mn > Ca > Mg), supporting previous reports on metal ion-dependent FLuc inhibition. However, the absolute magnitude and relative extent of signal reduction by metal ions’ salts differed between SC and H assays and between luciferases, suggesting a complex network of metal ions’ interactions with enzymes, substrates, reactants, and buffer elements. The diversity of the tested conditions and variability of responses provided insights into potential interference mechanisms and synergies that may exacerbate or alleviate interference. The beneficial influence of EDTA and the impact of glutathione, present natively in cells, on bioluminescence readout were pinpointed. Given the ubiquity of metal ions in analysed samples, the causative role in false-positive generation in drug discovery, and the wide breadth of luciferase-based assays used in screening, awareness and quantification of metal influence are crucial for developing assay validation protocols and ensuring reliable screening data, ultimately increasing the critical robustness of bioluminescence-based HTS assays.
Recent progress and perspectives of advanced Ni-based cathodes for aqueous alkaline Zn batteries
Authors: Ma Yanfen , Song Xin , Hu Wenjing , Xiong Jiawei , Chu Pan , Fan Yanchen , Zhang Biao , Zhou Hongyu , Liu Chenguang , Zhao Yi
Published: November 2024

Rechargeable aqueous alkaline Zn-Ni batteries (AZNBs) are considered a potential contender for energy storage fields and portable devices due to their inherent safety, high output voltage, high theoretical capacity and environmental friendliness. Despite the facilitated development of AZNBs by many investigations, its practical application is still restricted by inadequate energy density, sluggish kinetics, and poor stability. Therefore, Ni-based cathodes with boosted redox chemistry and enhanced structural integrity is essential for the high-performance AZNBs. Herein, this review focus on critical bottlenecks and effective design strategies of the representative Ni-based cathode materials. Specifically, nanostructured optimization, defect engineering, ion doping, heterostructure regulation and ligand engineering have been employed from the fundamental aspects for high-energy and long-lifespan Ni-based cathodes. Finally, further exploration in failure mechanism, binder-free battery configurations, practical application scenarios, as well as battery recycling are considered as valuable directions for the future development of advanced AZNBs.
Green credit policy and firm’s labor productivity: evidence from Chinese heavily-polluting enterprises
Authors: Lan Yong , Zhang Shuangshuang , Zhou Ping , Li Hailing , Dong Xuesong
Published: November 2024

Taking the “Green Credit Guidelines” (also known as “Green Credit Policy”, GCP) in 2012 as a quasi-natural experiment, this study adopts the panel datasets between 2010 and 2019 for Chinese manufacturing firms listed publicly to examine the effects of GCP on the labor productivity of Chinese heavily-polluting companies. The findings indicate that: (1) Upon introducing GCP, it can improve labor productivity of Chinese heavily-polluting companies, a result of the promotion effect of GCP on commercial credit and technological innovation. (2) The implementation of GCP can enhance the commercial credit of Chinese heavily-polluting enterprises and relieve its financing constraints to some degree. (3) The implementation of GCP can further the innovation activities of Chinese heavily-polluting companies and realize the re-test of the “Porter effect”. (4) The heterogeneity test indicates that GCP exerts a pronounced promoting influence on state-owned and large heavily-polluting enterprises in eastern China. Those conclusions are still valid after robustness tests. This research offers empirical evidence and policy wisdom for promoting the green conversion of manufacturing enterprises.
Spatial-temporal evolution characteristics and driving factors of carbon emission prediction in China-research on ARIMA-BP neural network algorithm
Authors: Zhao Sanglin , Li Zhetong , Deng Hao , You Xing , Tong Jiaang , Yuan Bingkun , Zeng Zihao
Published: November 2024

China’s total carbon emissions account for one-third of the world’s total. How to reach the peak of carbon emissions by 2030 and achieve carbon neutrality by 2060 is an important policy orientation at present. Therefore, it is of great significance to analyze the characteristics and driving factors of temporal and spatial evolution on the basis of effective calculation and prediction of carbon emissions in various provinces for promoting high-quality economic development and realizing carbon emission reduction. Based on the energy consumption data of 30 provinces in China from 2000 to 2021, this paper calculates and predicts the total carbon emissions of 30 provinces in China from 2000 to 2035 based on ARIMA model and BP neural network model, and uses ArcGIS and standard elliptic difference to visually analyze the spatial and temporal evolution characteristics, and further uses LMDI model to decompose the driving factors affecting carbon emissions. The results show that: (1) From 2000 to 2035, China’s total carbon emissions increased year by year, but the growth rate of carbon emissions gradually decreased; The carbon emission structure is “secondary industry > residents’ life > tertiary industry > primary industry”, and the growth rate of carbon in secondary industry and residents’ life is faster, while the change trend of primary industry and tertiary industry is smaller; (2) The spatial distribution of carbon emissions in China’s provinces presents a typical pattern of “eastern > central > western” and “northern > southern”, and the carbon emission centers tend to move to the northwest; (3) The regions with high level of digital economy, advanced industrial structure and new quality productivity have relatively less carbon emissions, which has significant group difference effect; (4) The intensity effect of energy consumption is the main factor driving the continuous growth of carbon emissions, while the per capita GDP and the structure effect of energy consumption are the main factors restraining carbon emissions, while the effects of industrial structure and population size are relatively small. Based on the research conclusion, this paper puts forward some policy suggestions from energy structure, industrial structure, new quality productivity and digital economy.
Case report: The outcomes of neoadjuvant immunotherapy combined with chemotherapy in pulmonary sarcomatoid carcinoma: case series and literature review
Authors: Guo Xiaokang , Wang Jingjing , Li Daosheng , Wang Bin , Zhu Hui , Guo Hongbo
Published: November 2024

Background

Pulmonary sarcomatoid carcinoma (PSC) is a highly aggressive malignancy with a significant risk of recurrence even after surgical intervention, leading to a dismal prognosis. In recent years, perioperative immunotherapy has demonstrated promising results in resectable non-small cell lung cancer (NSCLC). However, there is a lack of studies reporting the efficacy of perioperative immunotherapy in PSC.

Case presentation

We report the clinical outcomes of four patients diagnosed with locally advanced PSC who underwent neoadjuvant immunotherapy in combination with chemotherapy from 2021 to 2023 in our hospital. Prior to surgery, these patients received 2 to 4 cycles of neoadjuvant treatment. Post-treatment imaging assessments indicated a partial response (PR) in all cases, and each patient successfully achieved R0 resection. Pathological evaluations demonstrated significant pathological responses: one patient attained Pathological Complete Response (PCR), two patients exhibited Major Pathological Response (MPR), and one patient showed PR. Currently, all four patients remain alive without evidence of tumor progression. Notably, the patient who achieved PCR has maintained a disease-free survival (DFS) exceeding 32 months post-surgery, while their event-free survival (EFS) has surpassed 36 months.

Conclusions

Neoadjuvant immunotherapy in combination with chemotherapy has provided new promise for the treatment of locally advanced PSC with surgical potential. But these findings still need to be verified by further prospective researches.
Effects of COVID-19 virus-like particles on the behavioral and cognitive performance of human apolipoprotein E targeted replacement mice
Authors: O’Niel Abigail , Pederson Alexandra , Saltontall Elizabeth , Nguyen Kayla , Pantoja Monzerrat , Chaudhari Mitali , Sandholm Phoebe , Yoon Eric , Harrison Henry F. , Boutros Sydney , Hirsch Alec J. , Raber Jacob
Published: November 2024

Introduction

The effects of viral infections might be apolipoprotein E (apoE) isoform-dependent. In humans, there are three major apoE isoforms, E2, E3, and E4. E4 is associated with the enhanced entry of several viruses into the brain and their disease progression. A concern of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the development of post-acute COVID-19 syndrome, also known as long COVID. Genetic risk factors for developing long COVID were reported.

Methods

In this study, we used virus-like particles (VLPs) that include expression of the SARS-CoV-2 nucleocapsid (N), membrane (M), and envelope (E) structural proteins together with S. In the current study, we used human E2, E3, and E4 targeted replacement mice to assess whether these VLPs affect body weight, behavioral and cognitive performance, and circadian body temperatures. Using VLPs allow working outside an ABSL-3 facility.

Results

The effects of VLPs on some behavioral measures were apoE isoform-dependent, with the E2 mice being more affected than E3 or E4 mice. The overall decreased activity in the open field containing objects in week 2 indicate that VLPs can also reduce activity levels in an apoE isoform-independent fashion.

Discussion

The results of the current study indicate that even in the absence of viral replication, detrimental effects of VLPs on behavioral measures and circadian body temperatures are seen.
Species identification of modern and archaeological shark and ray skeletal tissues using collagen peptide mass fingerprinting
Authors: Buckley Michael , Oldfield Ellie-May , Oliveira Cristina , Boulanger Clara , Kitchener Andrew C. , Fuller Nicole R. , Ardren Traci , Thompson Victor D. , Fitzpatrick Scott M. , LeFebvre Michelle J.
Published: November 2024

Introduction

Elasmobranchs, such as sharks and rays, are among the world’s most endangered vertebrates, with over 70% loss in abundance over the past 50 years due to human impacts. Zooarchaeological baselines of elasmobranch diversity, distribution, and exploitation hold great promise for contributing essential historical contexts in the assessment of contemporary patterns in their taxonomic diversity and vulnerability to human-caused extinction. Yet, the historical ecology of elasmobranchs receives relatively less archaeological attention compared to that of ray-finned fishes or marine mammals, largely due to issues of taxonomic resolution across zooarchaeological identifications.

Methods

We explore the use of Zooarchaeology by Mass Spectrometry (ZooMS) for species identification in this unstudied group, using an archaeological case study from the marine environments of the Florida Keys, a marine biodiversity hotspot that is home to an array of elasmobranch species and conservation efforts. By comparison with 39 modern reference species, we could distinguish 12 taxa within the zooarchaeological assemblage from the Clupper archaeological site (Upper Matecumbe Key) that included nine sharks, two rays and a sawfish.

Results and discussion

The results indicate that, through additional complexity of the collagen peptide mass fingerprint, obtained due to the presence of the cartilaginous type II collagen, ZooMS collagen peptide mass fingerprinting provides exceptionally high taxonomic resolution in this group, yielding species-level identifications in all cases where sufficient reference material was used. This case study also highlights the added value of ZooMS for taxa that are more difficult to distinguish in zooarchaeological analyses, such as vertebrae of the Atlantic sharpnose shark (Rhizoprionodon terraenovae) and the hammerhead sharks (Sphyrna spp.) in the Florida Keys. Therefore, the application of collagen peptide mass fingerprinting to elasmobranchs offers great potential to improve our understanding of their archaeological past and historical ecology.
Effectiveness of sofosbuvir-based treatments for patients with hepatitis C virus genotype 6 infection: a real-world study from East China
Authors: Jiang Fan-Rong , Ye Xiao-Ting , Huang He-Qing , Hu Yu-Tao , Wang Dong-Hui , Jiang Su-Wen , Wang Jia-Lan , Hu Ai-Rong
Published: November 2024

Background

Over the past decade, the proportion of hepatitis C virus (HCV) genotypes (GT) 1 and 2 has decreased in almost all regions of China, while GT 3 and 6 have emerged as new challenges. GT 6 is unique in many respects, like high genetic variability and emerging resistant variants. This study aims to assess the efficacy of sofosbuvir (SOF)-based treatments in patients with GT 6 chronic hepatitis C (CHC).

Methods

A retrospective analysis was conducted on patients with GT 6 HCV infection, who were diagnosed between July 2018 and May 2023. All patients received a 12-week course of SOF-based treatments. The primary efficacy endpoint was sustained virologic response (SVR), which is defined as having undetectable HCV RNA at 12 weeks after treatment completion (SVR12). The efficacy data for SVR12 were analyzed using both the evaluated population (EP) and per-protocol population (PP). For the PP populations, efficacy data were stratified using Forrester plots.

Results

A total of 201 patients were included in the study. In PP population, the end of treatment virological response rate was 99.48% (190/191), the SVR12 rate was 99.31% (143/144), and the SVR24 rate was 100.00% (75/75). Only one patient with genotype 6a experienced a relapse 12 weeks after the completion of treatment, but her HCV RNA was undetectable both at the end of treatment and 24 weeks after the end of treatment. Additionally, the normalization rates of alanine transaminase (ALT) and aspartate aminotransferase (AST) were significantly higher at the end of treatment (EOT) compared to baseline (27.36% vs. 93.03%, 36.32% vs. 95.02%, p < 0.001). Significant improvements were observed in the levels of total bilirubin, ALT, AST, albumin, globulin, albumin/globulin ratio, gamma-glutamyl transferase, alkaline phosphatase, platelet, fibrosis-4 (FIB-4), and aspartate transaminase to platelet ratio index (APRI) between baseline and EOT (p < 0.05).

Conclusion

SOF-based treatments achieved high virological and biochemical response rates in patients with HCV GT 6 infection.
Gut microbiota profiling in injection drug users with and without HIV-1 infection in Puerto Rico
Authors: Aluthge Nirosh , Adams Seidu , Davila Carmen A. , Gocchi Carrasco Nova R. , Chiou Kathy S. , Abadie Roberto , Bennett Sydney J. , Dombrowski Kirk , Major Angel M. , Valentín-Acevedo Aníbal , West John T. , Wood Charles , Fernando Samodha C.
Published: November 2024

Introduction

The full extent of interactions between human immunodeficiency virus (HIV) infection, injection drug use, and the human microbiome is unclear. In this study, we examined the microbiomes of HIV-positive and HIV-negative individuals, both drug-injecting and non-injecting, to identify bacterial community changes in response to HIV and drug use. We utilized a well-established cohort of people who inject drugs in Puerto Rico, a region with historically high levels of injection drug use and an HIV incidence rate disproportionately associated with drug use.

Methods

Using amplicon-based 16S rDNA sequencing, we identified amplicon sequence variants (ASVs) that demonstrated significant variations in the composition of microbial communities based on HIV status and drug use.

Results and discussion

Our findings indicate that the HIV-positive group exhibited a higher abundance of ASVs belonging to the genera Prevotella, Alloprevotella, Sutterella, Megasphaera, Fusobacterium, and Mitsuokella. However, Bifidobacteria and Lactobacillus ASVs were more abundant in injectors than in non-injectors. We examined the effect of drug use on the gut microbiome in both HIV-infected and non-infected patients, and found that multiple drug use significantly affected the microbial community composition. Analysis of differential of bacterial taxa revealed an enrichment of Bifidobacterium spp., Faecalibacterium spp., and Lactobacillus spp. in the multiple drug-injecting group. However, in the non-injecting group, Parabacteroides spp., Prevotella spp., Paraprevotella spp., Sutterella spp., and Lachnoclostridium spp. The presence of multiple drug-injecting groups was observed to be more prevalent. Our findings provide detailed insight into ASV-level changes in the microbiome in response to HIV and drug use, suggesting that the effect of HIV status and drug injection may have different effects on microbiome composition and in modulating gut bacterial populations.
Comprehensive prognostic gene identification and functional characterization of GRAMD1A in Wilms tumor: development of risk prediction models and therapeutic implications
Authors: Zeng Qiang , Tao Junfeng , Qin Lilu , Zeng Yong , Liu Zhong , Xu Mingxian , Zeng Linshan
Published: November 2024

Background

Wilms tumor (WT) is the most common pediatric kidney cancer, with survival rates exceeding 90% in localized cases. However, advanced or recurrent WT remains difficult to treat due to poor prognosis and limited knowledge of its molecular mechanisms. Gene expression profiling has shown promise in identifying prognostic markers and therapeutic targets. This study aimed to identify key prognostic genes and pathways in WT, construct risk prediction models, and validate their role in tumor progression.

Methods

RNA sequencing and clinical data from 136 WT patients were obtained from the TARGET database. Differential gene expression analysis was conducted using GEO datasets GSE11024 and GSE66405 to compare WT and normal kidney tissues. Identified differentially expressed genes (DEGs) underwent Gene Ontology (GO) and KEGG pathway enrichment analysis to explore biological functions and pathways associated with WT progression. Univariate Cox regression was used to assess the association between DEGs and overall survival (OS) and progression-free survival (PFS). LASSO regression models were developed for risk stratification, and model accuracy was evaluated using time-dependent ROC curves. External validation confirmed key hub genes, while functional assays in WT cell lines (WiT-49) assessed the role of GRAMD1A in tumor behavior.

Results

A total of 3,395 DEGs were identified, with 1,564 upregulated and 1,831 downregulated genes. Enrichment analyses revealed significant pathways involved in cell cycle regulation and metabolic reprogramming. Six key genes (GRAMD1A, PLXNA3, SPR, EBAG9, RBM47, and RIDA) were associated with both OS and PFS. LASSO models demonstrated strong predictive performance, with GRAMD1A identified as a major risk factor. External validation confirmed differential expression, and functional assays showed that GRAMD1A silencing significantly inhibited WT cell viability, proliferation, migration, and invasion.

Conclusions

This study identifies novel prognostic genes and potential therapeutic targets in WT. GRAMD1A, SPR, EBAG9, RBM47, and RIDA play critical roles in WT progression, with GRAMD1A as a key oncogenic factor, offering potential for risk stratification and future therapeutic intervention.
Case Report: Sudden death caused by methylene chloride poisoning
Authors: Shang Ruikai , Tian Qiaoxin , Liu Yuru , Liu Hongyu , Zhang Xiangxing , Shi Mengdi , Jian Xiangdong , Li Qilu
Published: November 2024

Dichloromethane is widely used as an organic solvent in aerospace, electronics, and medicine. Cases of poisoning caused by this substance are rare. Recently, we successfully treated a patient with an acute dichloromethane poisoning. During the production process, owing to pipeline leakage and lack of personal protection, the patient was poisoned by dichloromethane inhalation, fell from a height, and experienced a sudden cardiac arrest. After successful cardiopulmonary resuscitation, the patient was transferred to a local hospital for diagnosis and treatment and then to our hospital. After two visits to our hospital for systematic diagnosis and active treatment with fluid infusion, anti-infection therapy, glucocorticoids, ventilator-assisted respiration, chest strap fixation, and nutritional support, the patient achieved clinical recovery.
A sulfonimide derivative of bezafibrate as a dual inhibitor of cyclooxygenase-2 and PPARα
Authors: Ammazzalorso Alessandra , Tacconelli Stefania , Contursi Annalisa , Hofling Ulrika , Cerchia Carmen , Di Berardino Sara , De Michele Alessandra , Amoroso Rosa , Lavecchia Antonio , Patrignani Paola
Published: November 2024

Background

PPARα and cyclooxygenase (COX)-2 are overexpressed in certain types of cancer. Thus, developing a dual inhibitor that targets both could be more effective as an anticancer agent than single inhibitors. We have previously shown that an analog of the bezafibrate named AA520 is a PPARα antagonist. Herein, we report the identification of AA520 as a potent COX-2 inhibitor using in silico approaches. In addition, we performed a thorough pharmacological characterization of AA520 towards COX-1 and COX-2 in different in vitro models.

Methods

AA520 was characterized for inhibiting platelet COX-1 and monocyte COX-2 activity in human whole blood (HWB) and for effects on lipidomics of eicosanoids using LC-MS/MS. The kinetics of the interaction of AA520 with COX-2 was assessed in the human colon cancer cell line, HCA-7, expressing only COX-2, by testing the COX-2 activity after extensive washing of the cells. The impact of AA520 on cancer cell viability, metabolic activity, and cytotoxicity was tested using the MTT reagent.

Results

In HWB, AA520 inhibited in a concentration-dependent fashion LPS-stimulated leukocyte prostaglandin (PG) E2 generation with an IC50 of 0.10 (95% CI: 0.05–0.263) μM while platelet COX-1 was not affected up to 300 μM. AA520 did not affect LPS-induced monocyte COX-2 expression, and other eicosanoids generated by enzymatic and nonenzymatic pathways. AA520 inhibited COX-2-dependent PGE2 generation in the colon cancer cell line HCA7. Comparison of the inhibition of COX-2 and its reversibility by AA520, indomethacin (a time-dependent inhibitor), acetylsalicylic acid (ASA) (an irreversible inhibitor), and ibuprofen (a reversible inhibitor) showed that the compound is acting by forming a tightly bound COX-2 interaction. This was confirmed by docking and molecular dynamics studies. Moreover, AA520 (1 μM) significantly reduced MTT in HCA7 cells.

Conclusion

We have identified a highly selective COX-2 inhibitor with a unique scaffold. This inhibitor retains PPARα antagonism at the same concentration range. It has the potential to be effective in treating certain types of cancer, such as hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC), where COX-2 and PPARα are overexpressed.
Assessment of the potential for carbon sink enhancement in the overlapping ecological project areas of China
Authors: Xu Xiaojuan , Jiao Fusheng , Lin Dayi , Qiu Jie , Zou Changxin , Zhang Kun
Published: November 2024

Ecological engineering can significantly improve ecosystem carbon sequestration. However, few studies have projected the carbon sink trends in regions where ecological engineering projects overlap and have not considered the different climate change conditions and land use scenarios. Using the ensemble empirical mode decomposition method and machine learning algorithms (enhanced boosted regression trees), the aims of this study to elucidate the stability of carbon sinks and their driving mechanisms in areas where ecological projects overlap and to predict the potential enhancement in carbon sinks under varying climate and human activity scenarios. The findings revealed that: (1) The carbon sinks clearly and steadily increased in regions where five ecological projects were implemented from 1982 to 2019. In contrast, the carbon sinks did not significantly increase in regions with two or three ecological projects. (2) As the number of ecological projects increased, the impact of human activities on the carbon sinks gradually decreased. In eastern China, rapid economic development and significant interference from human activities hindered the growth of carbon sinks. In contrast, in western China, the warming and humidification trend of the climate, large-scale afforestation, and other ecological projects have significantly improved carbon sinks. (3) The regions with five overlapping ecological projects exhibited the greatest enhancement and stability of carbon sinks under different scenarios. Compared with the SSP585 scenario, under the SSP126 scenario, the carbon sinks increased, and their stability was greater. Achieving carbon neutrality requires major ecological projects to account for the limitations imposed by climatic conditions. Instead of isolated projects or the implementation of single restoration measures, a comprehensive approach that uses the synergistic effects of combined ecological strategies is recommended.
Plant growth-promoting effects of a novel Lelliottia sp. JS-SCA-14 and comparative genome analysis
Authors: Jeon Byeong Jun , Park Jin-Soo , Hong Sung-Chul , Lee Eun Ha , Choi Jaeyoung , Kim Jeong Do
Published: November 2024

Bacteria associated with plants play crucial roles in promoting plant growth and health by aiding in nutrient acquisition, including phosphorus. This study presents the isolation and genomic characterization of a potentially new bacterial strain, Lelliottia sp. JS-SCA-14, which exhibits significant plant growth-promoting effects through phosphorus solubilization. A comparative phylogenomic analysis of the complete genome of strain JS-SCA-14 and its closely related strains revealed a unique genomic profile, suggesting it could be a novel species. Genomic identity calculations indicated that JS-SCA-14 significantly deviates from strains belonging to closely related genera, such as Buttiauxella, Citrobacter, Enterobacter, Leclercia, and Lelliottia. A biochemical assay comparing JS-SCA-14 and a closely related strain, Lelliottia jeotgali PFL01T, showed differing patterns in carbon source utilization and enzyme activities. To assess the plant growth-promoting capabilities of strain JS-SCA-14, tests were conducted to evaluate its siderophore-producing and phosphate-solubilizing abilities. Seed germination assays demonstrated an improvement in germination, seedling length, and vigor compared to untreated controls. Notably, the phosphate-dissolving strain JS-SCA-14 led to a significant increase of 34.4% in fresh weight and 35.4% in dry weight of tomato plants compared to the negative control. These findings underscore the significant potential of strain JS-SCA-14 in solubilizing phosphate, thereby enhancing phosphorus availability in the rhizosphere and promoting plant growth and development. This study contributes to our understanding of plant-microbe interactions and suggests the potential application of strain JS-SCA-14 as a bioinoculant for sustainable agriculture and plant nutrient management strategies.
The impact of challenge and hindrance stressors on knowledge hiding: the mediating role of job crafting and work withdrawal
Authors: Wang Le , Jia Yongtang , Xie Kun
Published: November 2024

The purpose of this study is to explore the impact of challenge and hindrance stressors on employees’ knowledge-hiding behavior, based on self-reported data from 493 Chinese preschool teachers. The findings indicate that both challenge and hindrance stressors significantly increase knowledge hiding, with hindrance stressors exerting a more pronounced effect. Furthermore, the study reveals the mediating roles of job crafting and work withdrawal, highlighting the distinct mechanisms involved with these stressors. Specifically, challenge stressors increase the likelihood of knowledge hiding through work withdrawal while simultaneously decreasing it through job crafting; notably, the former pathway has a greater effect. In contrast, hindrance stressors consistently exert detrimental effects, amplifying the probability of knowledge hiding through both mediators, which explains their stronger impact compared to challenge stressors. Additionally, empowering leadership plays a crucial moderating role in this relationship. The adverse influence of hindrance stressors on knowledge hiding, as mediated by job crafting, intensifies under high levels of empowering leadership. These findings not only validate the newly constructed parallel mediation model within an educational context but also provide practical strategies for kindergarten administrators regarding knowledge management. Such strategies include effectively distinguishing and managing different types of job stressors, enhancing skills to empower employees, and organizing regular knowledge-sharing activities.
The function(s) of consciousness: an evolutionary perspective
Authors: Lacalli Thurston
Published: November 2024

The functions of consciousness, viewed from an evolutionary standpoint, can be categorized as being either general or particular. There are two general functions, meaning those that do not depend on the particulars of how consciousness influences behavior or how and why it first evolved: of (1) expanding the behavioral repertoire of the individual through the gradual accumulation of neurocircuitry innovations incorporating consciousness that would not exist without it, and (2) reducing the time scale over which preprogrammed behaviors can be altered, from evolutionary time, across generations, to real-time. But neither answers Velmans’ question, of why consciousness is adaptive in a proximate sense, and hence why it would have evolved, which depends on identifying the particular function it first performed. Memory arguably plays a role here, as a strong case can be made that consciousness first evolved to make motivational control more responsive, though memory, to the past life experiences of the individual. A control mechanism of this kind could, for example, have evolved to consciously inhibit appetitive behaviors, whether consciously instigated or not, that would otherwise expose the individual to harm. There is then the question of whether, for amniote vertebrates, a role in memory formation and access would have led directly to a wider role for consciousness in the way the brain operates, or if some other explanation is required. Velmans’ question might then have two answers, the second having more to do with the advantages of global oversight for the control of behavior, as in a global workspace, or for conferring meaning on sensory experience in a way that non-conscious neural processes cannot. Meaning in this context refers specifically to the way valence is embodied in the genomic instructions for assembling the neurocircuitry responsible for phenomenal contents, so it constitutes an embodied form of species memory, and a way of thinking about the adaptive utility of consciousness that is less concerned with real-time mechanistic events than with information storage on an evolutionary time scale.
Longitudinal predictors for internalizing and externalizing symptomatology at age 4: KUNO-Kids cohort study
Authors: Jarvers Irina , Kandsperger Stephanie , Ecker Angelika , Brandstetter Susanne , Kabesch Michael , Köninger Angela , Melter Michael , Kerzel Sebastian , Kittel Jochen , Apfelbacher Christian , Brunner Romuald
Published: November 2024

Introduction

Numerous early-life risk factors are thought to significantly contribute to the development of psychological problems in toddlerhood. However, these factors have seldom been investigated concomitantly and longitudinally, and few studies include both mothers and fathers. This study examines the longitudinal impact of early environmental, parental, and child-specific risk factors on children’s internalizing and externalizing symptomatology at age 4.

Methods

Families were recruited from a perinatal center at birth and completed self-report questionnaires at birth, 4 weeks postpartum, 6 months postpartum, and annually thereafter. The final population-based sample consisted of n = 560 mothers (and fathers) who gave birth after June 2015, with children who turned 4 years old before March 31, 2021. The primary outcomes, children’s internalizing and externalizing symptomatology at age 4, were measured using the Strengthsand Difficulties Questionnaire. Linear mixed effect models were used to estimate growth curves for predictors between 4 weeks and 4 years postpartum, which were subsequently entered into multivariable linear regressions to predict internalizing and externalizing symptomatology at age 4.

Results

The study identified several key risk factors: environmental (lack of social support, lower parental education, male sex), parental (poor parental mental health, increased parenting stress, parental sleep difficulties) and child-specific (children’s low physical health, children’s reduced sleep quality, temperament).

Discussion

The findings underscore that most identified risk factors are related to children’s temperament, mental and physical health of parents, their experienced stress, and families’ social support networks. These insights highlight the importance of targeted interventions focusing on improving parental mental health, reducing stress, and enhancing social support to mitigate early-life psychological problems in children.