bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Wrist Flexion And Leg Muscle Explosive Power Against Volleyball Smash Ability
Authors: Sistiasih Vera Septi , Nurrohman Dwi , Rumpoko Satrio Sakti , Sholeh Muchammad
Published: October 2024

This study aims to determine the relationship between wrist flexion and leg muscle explosive power on the volleyball smash ability of athletes at the Kusuma Bhirawa Ponorogo club. Smash ability is the most important technique in scoring points in volleyball, and in the Kusuma Bhirawa club there are still some athletes who can be said to be still lacking in smash ability, especially in the accuracy of the smash, in that case it can be influenced by factors that can support the athlete's smash ability. Therefore, the authors conducted this study which aimed to find out whether there is a relationship between wrist flexion and leg muscle explosive power on athletes' smash ability. The sample in this study used 15 athletes taken using the Purposive Sampling method. This study uses a type of correlation research, and data collection techniques in this study are carried out using test measurement instruments, including: 1. Vertical jump test, 2. Geniometer test, and 3. Smash Accuracy Test.
Influence of Programmed Physical Training on the Performance of Table Tennis Athletes
Authors: Ahady Muhammad Yan , Simatupang Ayman Faiz , Naibaho Sahdiaman , Rafael Kevin , Pasaribu Kevin Hans
Published: October 2024

This study aims to explore the influence of a programmed physical training program on enhancing the performance of table tennis athletes at the local table tennis club level. The study utilizes a quantitative research approach with a case study design. Research participants consist of 30 table tennis athletes from one local table tennis club. Data were collected through physical tests covering measurements of muscle strength, agility, and cardiovascular endurance, as well as direct observation of athlete performance during table tennis training sessions. The results of the study indicate a significant improvement in muscle strength, agility, and cardiovascular endurance of athletes after participating in the programmed physical training program. Regression analysis also confirms a positive relationship between the level of participation in the programmed physical training program and athlete performance improvement. The practical implications of this research are that local table tennis clubs can utilize programmed physical training programs as a strategy to enhance their athletes' performance. However, this study has limitations that need to be considered, including the limited generalizability of the results due to being conducted in only one local table tennis club. Therefore, further research with larger samples and diversification of table tennis clubs is needed to confirm these findings more broadly.
Survey on the Effectiveness of the Online Learning Process Due to the Coronavirus (Covid-19) Pandemic in Floor Gymnastics Course
Authors: Kurniawan Ari Wibowo , Hasan Ahmad Nur Hamzah
Published: October 2024

The purpose of this study was to determine the level of effectiveness of the online learning process in floor gymnastics for students of 2019 Physical Education, Health and Recreation, State University of Malang. This study used a quantitative descriptive research design with a survey method. The sample taken in this study is 60% of the total population, namely 139 students of PJKR 2019. Data collection uses a questionnaire instrument based on google form, with five indicators in it (student interest, attractiveness, benefits, technology, interactive quality). The results of this study can be concluded that online learning in floor gymnastics courses can be declared quite effective for PJKR 2019 students. This is evidenced by the results of research that have been carried out with five indicators, as follows: 99 students out of 139 PJKR 2019 students stated that they were quite interested follow online learning in floor gymnastics with a percentage of 71.22%; 59% or 82 students stated that online learning is quite interesting to do; online learning was also stated to be quite beneficial for PJKR 2019 students with a percentage of 58% or 81 students answered quite useful; on the technology indicator, the results were 79% in the medium category; online learning is stated to be quite interactive in floor gymnastics subjects with a percentage of 63.31%.
Basic Movement Skills for Middle Distance Running in Students Junior High School
Authors: Laksana Anak Agung Ngurah Putra , Adnyana I Wayan , Jenaru Kandidus Jimyanto
Published: October 2024

This study aims to determine the basic movement ability of middle-distance running in junior high school students. The method of this research is descriptive qualitative which is carried out on students of class VIII A SMP Widya Sakti Denpasar. The sample in this study was 32 students from class VIII A. Data collection techniques used triangulation, namely observation, interviews, and questionnaires. Analysis of the data used is the analysis of Miles and Huberman, namely the analysis of interactive model data through the steps of data collection, data reduction, data presentation, and drawing conclusions. The results of the observations showed that there were students in the good category with the percentage of results as much as 50% (16 students) and the sufficient category with the percentage of the results of the observation scores as much as 50% (16 students). The results of the interview data show that the learning process has not been maximized due to inhibiting factors. The results of the questionnaire data showed as many as 12 students (37.5%) were in the good category and as many as 20 students (62.5%) were in the sufficient category. Based on the three sources of data, the results of the study indicate that the students' ability to perform the basic movements of middle-distance running is not yet maximal. This research can be used as a reference for teachers, coaches and sports activists in improving the ability to run basic movements, namely by coordinating physical conditions and infrastructure.
Propozycja nowelizacji art. 10 § 1 Kodeksu karnego skarbowego (o właściwe ujęcie funkcji błędu co do okoliczności stanowiącej znamię czynu zabronionego w prawie karnym skarbowym)
Authors: Pohl Łukasz
Published: October 2024

This article formulates a proposal to amend the Fiscal Penal Code to include the function of an error as to a circumstance constituting the substantiation of a prohibited act. This proposal refers directly to including this function in the Criminal Code. Thus, the article proposes that the statutory definition of the function of the contemplated error should be limited in the Fiscal Penal Code to the exclusion of guilt, emphasizing at the same time, within the framework of this proposal, that such a consequence is produced not by every error of the indicated type, but only by an error which has been recognized as excusable.
Neutralita – spása České republiky?
Authors: Jiří Štěpanovský
Published: October 2024

Neutrality – Salvation of Czech Republic?
Digenean parasites in saddled seabream Oblada melanurus (Teleostei, Sparidae)
Authors: Boukadoum Affaf , Gharbi Kamilia , Tazerouti Fadila
Published: October 2024

In an attempt to contribute to the understanding of the biodiversity of Digenea in Algeria, we analysed for the first time the community structure of the digenean fauna of Oblada melanurus (Linnaeus, 1758). From June 2022 to July 2023, 172 specimens of O. melanurus were sampled from various locations off the Algerian waters and their digestive tracts were examined to collect the digenean parasites. We analysed the community structure by calculating the parasitological parameters. Also, a species accumulation curve (SAC) was generated to evaluate the sampling effort, and the Chi-square test was performed to evaluate the effects of seasonal variation on the prevalence of parasites. We collected 434 Digenea, which belonged to three species: Lepocreadium album (Stossich, 1890) Stossich, 1904 (Lepocreadiidae Odhner, 1905); Mag-nibursatus bartolii Kostadinova, Power, Fernandez, Balbuena, Raga & Gibson, 2003 (Derogenidae Nicoll, 1910) and Macvi-caria dubia (Stossich, 1905) Bartoli, Bray & Gibson, 1989 (Opecoelidae Ozaki, 1925). Our findings include a new geographical record for M. dubia and the first report of L. album and M. bartolii from this particular host in Algeria. L. album had the high-est prevalence and mean abundance values, while M. dubia had the highest mean intensity. According to the Chi-square test, significant differences in prevalence between seasons were observed only for L. album and M. bartolii. We offered the first insights into the Digenea fauna parasitizing O. melanurus in Algeria, enriching the knowledge of digenean biodiversity in Algerian marine fish. Additionally, we shed light on the seasonal variations in the prevalence of these digeneans. This study may serve as a valuable reference for future research on Digenea in other marine species and regions.
Navigating IT Careers in the Age of AI : Human Skills in an Automated Future
Authors: Rajesh Kamisetty
Published: October 2024

This article investigates the current state of AI (Artificial Intelligence), its market, and the potential impacts of AI on future jobs. The AI revolution is not only transforming the labour market across the world but also augmenting business processes and procedures in various areas. We explore the evolving relationship between human workers and AI systems in IT by analysing current trends, industry reports, and expert predictions. Nature and Extent of jobs that are likely to be affected by Automation are also a part of the study. The article offers insights into the ever-changing nature of IT roles, identifies critical skills for future success, and presents recommendations for professionals seeking to thrive in an AI-augmented work environment.
Artificial Intelligence in Cybersecurity : Advancing Threat Modeling and Vulnerability Assessment
Authors: Chirag Gajiwala
Published: October 2024

This article examines the transformative role of Artificial Intelligence (AI) in revolutionizing cybersecurity practices, with a particular focus on threat modeling and vulnerability assessment. As cyber threats grow increasingly sophisticated, traditional security measures often fall short in providing comprehensive protection. We explore how AI and machine learning algorithms enhance the accuracy and efficiency of threat modeling by analyzing vast datasets to identify patterns and anomalies indicative of potential security risks. The article also investigates AI's contribution to vulnerability assessment, highlighting its capacity for continuous monitoring and real-time analysis of diverse data sources, including network traffic, system logs, and threat intelligence feeds. By simulating various attack scenarios and prioritizing security vulnerabilities, AI-driven tools enable organizations to adopt a more proactive and dynamic approach to cybersecurity. While acknowledging the challenges and ethical considerations associated with AI implementation in this domain, this article underscores the significant potential of AI in fortifying cyber defenses and safeguarding digital assets in an ever-evolving threat landscape.
“We’ve lost you Ian”: Multi-modal corpus innovations in capturing, processing and analysing professional online spoken interactions
Authors: O'Keeffe Anne , Knight Dawn , Mark Geraldine , Fitzgerald Christopher , McNamara Justin , Adolphs Svenja , Cowan Benjamin , Fahey Palma Tania , Farr Fiona , Peraldi Sandrine
Published: October 2024

Online communication via video platforms has become a standard component of workplace interaction for many businesses and employees. The rapid uptake in the use of virtual meeting platforms due to COVID-19 restrictions meant that many people had to quickly adjust to communication via this medium without much (if any) training as to how workplace communication is successfully facilitat- ed on these platforms. The Interactional Variation Online project aims to analyse a corpus of virtual meetings to gain a multi-modal understanding of this context of language use. This paper describes one component of the project, namely guidelines that can be replicated when constructing a corpus of multi-modal data derived from recordings of online meetings. A further aim is to determine typical fea- tures of virtual meetings in comparison to face-to-face meetings so as to inform good practice in virtual workplace interactions. By looking at how non-verbal behaviour, such as head movements, gaze, pos- ture, and spoken discourse interact in this medium, we both undertake a holistic analysis of interaction in virtual meetings and produce a template for the development of multi-modal corpora for future analysis.
Building LANA-CASE, a spoken corpus of American English conversation: Challenges and innovations in corpus compilation
Authors: Hanks Elizabeth , McEnery Tony , Egbert Jesse , Larsson Tove , Biber Douglas , Reppen Randi , Baker Paul , Brezina Vaclav , Brookes Gavin , Clarke Isobelle , Bottini Raffaella
Published: October 2024

The Lancaster-Northern Arizona Corpus of Spoken American English (LANA-CASE) is a collaborative project between Lancaster University and Northern Arizona University to create a publicly available, large-scale corpus of American English conversation. In this article, we describe the design of LANA-CASE in terms of the challenges that have arisen and how these have been addressed – including decisions related to operationalizing the domain, sampling the data, recruiting participants, and selecting instruments for data collection. In addressing these challenges, we were able to draw on and further develop strategies established in the creation of other spoken corpora (including the British English counterpart to LANA-CASE, the Spoken British National Corpus 2014) as well as to implement recent theoretical and technical innovations related to each step. We hope that this discussion can inform future projects focused on the design and construction of spoken corpora.
Compiling a corpus of African American Language from oral histories
Authors: Moeller Sarah , Davis Alexis , Previlon Wilermine , Bottini Michael , Tang Kevin
Published: October 2024

African American Language (AAL) is a marginalized variety of American English that has been understudied due to a lack of accessible data. This lack of data has made it difficult to research language in African American communities and has been shown to cause emerging technologies such as Automatic Speech Recognition (ASR) to perform worse for African American speakers. To address this gap, the Joel Buchanan Archive of African American Oral History (JBA) at the University of Florida is being compiled into a time-aligned and linguistically annotated corpus. Through Natural Language Processing (NLP) techniques, this project will automatically time-align spoken data with transcripts and automatically tag AAL features. Transcription and time-alignment challenges have arisen as we ensure accuracy in depicting AAL morphosyntactic and phonetic structure. Two linguistic studies illustrate how the African American Corpus from Oral Histories betters our understanding of this lesser-studied variety.
Pemisahan Metil Ester Minyak Goreng Bekas Menjadi Biokerosin
Authors: Suryanto A. , S. Katili Chintiya , Erni Erni , Alif Rahmatullah , Resky Muhammad
Published: October 2024

Peningkatan kebutuhan energi yang dinamis menjadi perhatian dan ancaman akan menipisnya ketersediaan minyak mentah dan pentingnya menjaga kesehatan lingkungan masyarakat demi kesinambungan ekosistem mahluk hidup dalam menjaga perlunya energi yang sehat. Proses penggantian bahan bakar minyak fosil dengan minyak nabati perlu dikembangkan untuk menghasilkan biokerosin. Biokerosin adalah suatu bahan bakar minyak nabati yang diproduksi dengan bahan baku biomassa yang diyakini lebih unggul dari minyak bakar fosil atau minyak tanah. Minyak goreng bekas adalah minyak goreng yang telah digunakan berkali-kali oleh konsumen. Minyak goreng bekas dapat digunakan sebagai bahan baku untuk memproduksi biokerosin atau minyak tanah. Tujuan dari penelitian ini untuk mengetahui pengaruh suhu pada proses distilasi vakum, untuk menghasilkan biokerosin. Sifat fisik pada biokerosin hasil destilasi metil ester dengan GC (Gas Choromatography). Hasil analisa umum menunjukkan bahwa volume destilat yang diperoleh pada suhu 250℃ adalah 26 ml. Dari hasil analisa uji sampel dan olah data menunjukkan bahwa biokerosin dapat diproduksi dengan metode destilasi vakum dengan kontrol suhu 250 ℃ menggunakan metil ester dari minyak goreng bekas.
Pengaruh Variasi Konsentrasi Asam Organik Terhadap Nilai Recovery Nikel Pada Proses Leaching Nikel Laterit
Authors: Arifin Mubdiana , Bakhri Syamsul , Juradi Muhammad Idris , Bakri Suriyanto , Nurhawaisyah Sitti Ratmi , Angga Mulia Muhammad Ilham
Published: October 2024

Nikel merupakan salah satu hasil pertambangan yang banyak dimanfaatkan dalam berbagai bidang kehidupan. Nikel digunakan sebagai bahan paduan logam dan pelapis logam. Proses pengolahan nikel dari bijih nikel laterit jenis limonit dengan metode Atmospheric Pressure Acid Leaching (APAL) dinilai lebih murah dibandingkan metode hidrometalurgi lainnya, karena konsumsi energi dan biaya operasionalnya cukup rendah, sehingga dapat dijadikan salah satu metode pengolahan nikel alternatif. Tujuan dari penelitian ini untuk mengetahui pengaruh peningkatan konsentrasi pelarut asam organik terhadap persen perolehan nikel. Media pelarut yang digunakan adalah larutan asam asetat (CH3COOH). Sebelum proses pelindian, dilakukan uji karakterisasi awal menggunakan analisis XRD, XRF dan AAS untuk mengetahui komposisi mineralogi dan kimia sampel bijih nikel yang akan digunakan. Penelitian ini dilakukan dengan menggunakan konsentrasi asam asetat yaitu 2,5, 5, 7,5, dan 10 M, ukuran partikel -200 mesh, suhu operasi 90°C, kecepatan pengadukan 200 rpm, dan waktu pelindian selama 120 menit. Analisa kandungan nikel setelah proses pelindian menggunakan analisis AAS, kemudian dihitung persen pereolehan nikelnya. Hasil penelitian menunjukkan konsentrasi asam asetat berpengaruh terhadap perolehan nikel. Peningkatan konsentrasi asam asetat juga meningkatkan persentase perolehan nikel. Hasil terbaik pada proses pelindian yaitu pada konsentrasi asam asetat 10 M dengan perolehan nikel sebesar 96,159%.
The Effects of Adding CaCOᴣ and Glycerol as Filler in The Synthesis of Bioplastic Made from Corn Starch
Authors: Safira Ajeng Listiani , Suffah Nurullia , Hendrawati Tri Yuni , Astuti Erna
Published: October 2024

Plastic is one of the items widely used by the world's population, including in industry. Apart from being cheaper, plastic also has the advantage of being waterproof and having good strength to withstand the load carried. However, plastic has weaknesses in the decomposition process and can cause environmental pollution. Corn has a high percentage of starch content and is easy to cultivate in Indonesia, so corn has the potential to become one of the raw materials used in making bioplastics to reduce the plastic waste produced. This research aims to determine the effect of adding CaCOᴣ and glycerol fillers in synthesizing bioplastics from corn starch. The method applied in this research is pouring the solution. Based on research, the reaction to make bioplastic from corn starch with CaCO3 filler and glycerol is an esterification reaction. The higher the CaCO₃ content in bioplastics, the smaller the percent elongation value produced, the tensile strength properties will decrease, and this will result in the %w loss value decreasing. The low tensile strength is due to the presence of empty holes in the bioplastic product. Meanwhile, more glycerol will cause an increase in the percent elongation value, a decrease in tensile strength, and easy degradation. The bioplastic that has specification close to SNI standards was obtained using 5 ml of glycerol and 2 grams of CaCO₃ for 100 g of corn starch.
Implementasi Tri Hita Karana Dalam Mengembangkan Sikap Sosial Religius Siswa Hindu Di SMPN 1 Balai Riam
Authors: Pawang Pawang , Sumarni Nyoman
Published: October 2024

Setiap manusia membutuhkan kehidupan yang aman, tentram dan damai. Hal tersebut akan dapat terwujud apabila setiap orang mampu untuk saling menjaga antar satu dengan yang laiinya. Menjaga hubungan yang harmonis dengan Tuhan, menjaga hubungan yang harmonis dengan sesama manusia dan hubungan yang harmonis dengan alam lingkungan. Ketiga hubungan tersebut dalam agama hindu di sebut dengan Tri Hita Karana yaitu tiga penyebab kebahagiaan. Pemahaman dan implementasi dari ketiga konsep tersebut perlu dilakukan sedini mungkin, mengingat dampak negatif dari perkembangan teknologi yang tidak dapat di hindari. Siswa SMPN 1 Balai Riam telah memiliki pemahaman yang cukup memadai tahadap konsep Tri Hita Karana. Pemahaman mulai dari konsep parhyangan, pawongan dan palemahan sudah dimiliki dengan baik. Implementasi dari pemahaman konsep Tri Hita Karana untuk lebih berkembangnya sikap sosial siswa dilakukan dengan beberapa strategi yaitu a) Pelaksanaan sembahyang bersama-sama maupun secara individu; b) melaksanakan kegiatan social kemanusiaan melalui Menjaga Hubungan Baik dengan Guru, Menjaga Hubungan Baik Sesama Siswa, Menjaga Hubungan Baik antara Siswa dengan Masyarakat; c) Kegiatan Membersihkan Lingkungan yang dilaksanakan sesuai dengan program yang telah ditetapkan oleh sekolah.
The NILAI NILAI PENDIDIKAN KARAKTER ANAK USIA DINI DALAM KITAB SLOKANTARA
Authors: Harianti Dwi -
Published: October 2024

Penelitian ini bertujuan untuk mengetahui nilai-nilai Pendidikan karakter yang terdapat dalam kitab Slokantara. Metode yang digunakan adalah metode kualitatif. Sumber data diperoleh melalui studi kepustakaan Kitab Slokantara dijadikan sebagai pustaka primer yang didukung oleh sumber-sumber sastra Hindu lainnya. Hasil penelitian menunjukkan bahwa terdapat nilai religius, jujur, kerja keras, komunikatif/bersahabat, cinta damai, tanggung jawab, dan peduli sosial dalam kitab Slokantara. Nilai-nilai pendidikan karakter dalam kitab Slokantara dapat dijadikan sebagai salah satu referensi dalam proses pendidikan anak usia dini demi terbentuknya anak yang suputra. Proses internalisasi nilai-nilai Pendidikan karakter dapat dilakukan dengan berbagai metode diantaranya yaitu metode bercerita, karyawisata, bermain peran, dan eksperimen. Setiap anak diharapkan mendapatkan proses Pendidikan terbaik dari keluarga, sekolah, dan masyarakat demi terwujudkan manusia berkarakter.
Hat Optimization of Redox Flow Battery Flow Fields Through Physics-Informed Reinforcement Learning
Authors: Shah Vivaan , Venu Ganeshan , Lopes Colin
Published: October 2024

The realization of a low-carbon economy and the large-scale transition to renewable energy encompasses some of the most pressing challenges of the era. A developing technology in the energy sector is the vanadium redox flow battery (VRFB). This is a promising long-term energy storage solution that can alleviate the intermittency of renewable sources while boasting benefits over the traditional lithium-ion centered grid structure. However, VRFBs require further enhancement before becoming dominant market players; one target area of improvement is the design of the flow fields (FF) that facilitate pressure consistency, distributed diffusion, and uniform electron transfer between the electrodes and active species ions in an electrolyte solution. Guided by their increasingly pervasive nature, I plan to analyze the effectiveness of physics-informed machine learning techniques to design and maximize these favorable characteristics in a FF, with the end goal being a method to improve VRFB performance without being cost-intensive. Specifically, I will implement a SARSA network that will iteratively improve FF design through reinforcement learning. I will train the network using a FF path generation algorithm and physical simulation of each iteration with components derived from relevant fluid dynamics. Then, I will evaluate it against the three standard FF designs. With guidance, I would love to be able to construct the optimized FF and VRFB in real life. I ask for mentorship and funding from the THINK team to help me in this endeavor as I take my first steps in the field of energy research.
Organic input incorporation for enhancing sustainability and economic viability of cowpea in North-Western Himalayan region
Authors: Sharma Tarun , Singh Janardan , Madaik Sparsh , Kumar Pardeep , Singh Akashdeep , Rana Bharat Bhushan , Chauhan Garima
Published: October 2024

Cowpea (Vigna unguiculata L. [Walp.]) cultivation encounters a plethora of challenges such as suboptimal productivity levels, declined income levels, and poor soil health under conventional fertilization systems. Therefore, the present field investigation was undertaken at the Research Farm, Department of Agronomy, CSKHPKV, Palampur in the rainy season of 2019 to evaluate eight combinations of organic farming and Zero Budget Natural Farming (NF) based inputs, i.e., Beejamrita (100 ml kg−1 of seed) + Jeewamrita (187.5 L ha−1); Beejamrita (100 ml kg−1 of seed) + GhanaJeewamrita (250 kg ha−1); Beejamrita (100 ml kg−1 of seed) + Jeewamrita (187.5 L ha−1) + GhanaJeewamrita (250 kg ha−1); farm yard manure (FYM) 10 Mg ha−1; FYM (10 Mg ha−1) + GhanaJeewamrita (250 kg ha−1); biofertilizers (PSBs and Rhizobium at 10 g kg−1 of seed) + FYM (10 Mg ha−1) + vermiwash (1:10); biofertilizers (PSBs and Rhizobium at 10 g kg−1 of seed) + vermicompost (7.5 Mg ha−1) + vermiwash (1:10); absolute (untreated) control; in a randomized complete block design with three replications for their influence over cowpea productivity, profitability, and energetics. The results of the investigation revealed that applying FYM (10 Mg ha−1) and GhanaJeewamrita (250 kg ha−1) in combination resulted in significantly higher grain yield(1,070.5 kg ha−1), economic net returns (766.61 USD ha−1), net energy gains (78,230 MJ ha−1), and considerably improved soil microbial biomass carbon (133.92 mg g−1 of soil), nitrogen (27.40 mg g−1 of soil), urease (52.20 (mg g−1 urea of soil h−1), and dehydrogenase activity (5.21mg g−1 TPF of soil h−1). Improved soil biological properties in the present study might have been responsible for considerable increment in cowpea yield and profitability. Therefore, in-combination application-based module of FYM (10 Mg ha−1) and GhanaJeewamrita (250 kg ha−1) can be recommended for enhancing productivity and profitability of cowpea cultivation under North-Western Himalayan agro-ecological conditions. This study contributes valuable insights for organic input strategies in regions facing similar challenges.
Treatment with novel topoisomerase inhibitors in Ewing sarcoma models reveals heterogeneity of tumor response
Authors: Lee Unsun , Szabova Ludmila , Collins Victor J. , Gordon Melanie , Johnson Kristine , Householder Deborah , Jorgensen Stephanie , Lu Lucy , Bassel Laura , Elloumi Fathi , Peer Cody J. , Nelson Ariana E. , Varriano Sophia , Varma Sudhir , Roberts Ryan D. , Ohler Zoe Weaver , Figg William D. , Sharan Shyam K. , Pommier Yves , Heske Christine M.
Published: October 2024

Introduction

The topoisomerase 1 (TOP1) inhibitor irinotecan is a standard-of-care agent for relapsed Ewing sarcoma (EWS), but its efficacy is limited by chemical instability, rapid clearance and reversibility, and dose-limiting toxicities, such as diarrhea. Indenoisoquinolines (IIQs) represent a new class of clinical TOP1 inhibitors designed to address these limitations.

Methods

In this study, we evaluated the preclinical efficacy of three IIQs (LMP400, LMP744, and LMP776) in relevant models of EWS. We characterized the pharmacokinetics of IIQs in orthotopic xenograft models of EWS, optimized the dosing regimen through tolerability studies, and tested the efficacy of IIQs in a panel of six molecularly heterogeneous EWS patient-derived xenograft (PDX) models. For each PDX, we conducted whole genome and RNA sequencing, and methylation analysis.

Results

We show that IIQs potently inhibit the proliferation of EWS cells in vitro, inducing complete cell growth inhibition at nanomolar concentrations via induction of DNA damage and apoptotic cell death. LMP400 treatment induced ≥30% tumor regression in two of six PDX models, with more durable regression compared to irinotecan treatment in one of these models. RNA sequencing of PDX models identified a candidate predictive biomarker gene signature for LMP400 response. These data, along with pharmacogenomic data on IIQs in sarcoma cell lines, are available at a new interactive public website: https://discover.nci.nih.gov/rsconnect/EwingSarcomaMinerCDB/.

Discussion

Our findings suggest that IIQs may be promising new agents for a subset of EWS patients.
Tle6 deficiency in male mice led to abnormal sperm morphology and reduced sperm motility
Authors: Kazama Kousuke , Miyagoshi Yuki , Nishizono Hirofumi
Published: October 2024

Infertility affects over 15% of the global population, and genetic mutations are a substantial cause of infertility. Recent studies have focused on the subcortical maternal complex and its role in early embryonic development. TLE6, a core protein in the subcortical maternal complex, is crucial for female fertility; however, its role in male germ cells remains poorly understood. In this study, we generated a novel Tle6 knockout mouse model using CRISPR-Cas9 to examine the impact of Tle6 mutations on male fertility. Tle6 knockout males exhibited a reduced total sperm count compared to wild-type mice, with a marked decrease in highly motile sperm. Histological observation of Tle6+/− mouse testes showed no apparent structural changes, though impaired sperm maturation was observed. Immunofluorescence staining showed that TLE6 localizes to the midpiece of sperm. It was also confirmed that the expression of Tle6 is reduced in Tle6+/− male mice. In addition, Tle6+/− mice exhibited a significant increase in serum testosterone levels compared to wild-type mice. Changes in the expression of genes related to sperm function were also observed in the testes of Tle6 knockout mice. These findings suggest that TLE6 is involved in sperm production and function, and that mutations in TLE6 may impair the production of functional sperm in humans, potentially leading to infertility.
Degradation of malachite green by UV/H2O2 and UV/H2O2/Fe2+ processes: kinetics and mechanism
Authors: Wilayat Sumaira , Fazil Perveen , Khan Javed Ali , Zada Amir , Ali Shah Muhammad Ishaq , Al-Anazi Abdulaziz , Shah Noor S. , Han Changseok , Ateeq Muhammad
Published: October 2024

This work investigated the photochemical degradation of malachite green (MG), a cationic triphenylmethane dye used as a coloring agent, fungicide, and antiseptic. UV photolysis was ineffective in the removal of MG as only 12.35% degradation of MG (10 mg/L) was achieved after 60 min of irradiation. In contrast, 100.00% degradation of MG (10 mg/L) was observed after 60 min of irradiation in the presence of 10 mM H2O2 by UV/H2O2 at pH 6.0. Similarly, complete removal (100.00%) of MG was observed at 30 min of the reaction time by UV/H2O2/Fe2+ employing [MG]0 = 10 mg/L, [H2O2]0 = 10 mM, [Fe2+]0 = 2.5 mg/L, and [pH]0 = 3.0. For the UV/H2O2 process, the degradation efficiency was higher at pH 6.0 than at pH 3.0 as the kobs values were 0.0873 and 0.0690 min−1, respectively. However, UV/H2O2/Fe2+ showed higher reactivity at pH 3.0 than at pH 6.0. Chloride and nitrate ions slightly inhibited the removal efficiency of MG by both UV/H2O2 and UV/H2O2/Fe2+ processes. Moreover, three degradation products (DPs) of MG, (i) 4-dimethylamino-benzophenone (DABP), (ii) 4-amino-benzophenone (ABP), and (iii) 4-dimethylamino-phenol (DAP), were identified by GC-MS during the UV/H2O2 treatment. These DPs were found to demonstrate higher aquatic toxicity than the parent MG, suggesting that researchers should focus on the removal of target pollutants as well as their DPs. Nevertheless, the results of this study indicate that both UV/H2O2 and UV/H2O2/Fe2+ processes could be implemented to alleviate the harmful environmental impacts of dye and textile industries.
Phenotypic and genetic characterization of daptomycin non-susceptible Staphylococcus aureus strains selected by adaptive laboratory evolution
Authors: Xu Yanlei , Xiao Yanghua , Zhao Huilin , Wang Bingjie , Yu Jingyi , Shang Yongpeng , Zhou Ying , Wu Xiaocui , Guo Yinjuan , Yu Fangyou
Published: October 2024

Background

Daptomycin non-susceptible Staphylococcus aureus (DNS) strains pose a serious clinical threat, yet their characteristics remain poorly understood.

Methods

DNS derivatives were generated by exposing S. aureus strains to subinhibitory concentrations of daptomycin. Competition experiment and growth kinetics experiment were used to observe the growth of bacteria. Galleria mellonella larvae and mouse skin abscess models were used to observe the virulence of bacteria. Transmission electron microscopy (TEM), cytochrome C experiment and biofilm formation experiment were used to observe the drug resistance phenotype. And homologous recombination was used to study the role of mutations.

Results

Phenotypic profiling of DNS strains revealed impaired growth, increased cell wall thickness, enhanced biofilm formation, reduced negative surface charge, and attenuated virulence compared to their wild-type strains. Whole genome sequencing identified mutations in mprF, cls2, and saeR in DNS strains. Allelic replacement experiments validated the roles of MprF L341F and Cls2 F60S substitutions in augmenting daptomycin non-susceptibility in Newman. Deletion of saeR in the NewmanMprFL341F strain and complementation of saeR in the Newman-DNS strain did not directly alter daptomycin susceptibility. However, the deletion of saeR was found to enhance competitive fitness under daptomycin pressure.

Conclusion

This work validates adaptive laboratory evolution (ALE) for modeling clinical DNS strains and uncovers contributions of mprF, cls2, and saeR mutations to the adaptation and resistance mechanisms of S. aureus against daptomycin. These findings enrich our understanding of how S. aureus acquired resistance to daptomycin, thus paving the way for the development of more effective treatment strategies and offering potential molecular markers for resistance surveillance.
Association between gout and kidney stone: results from mendelian randomization and the NHANES study
Authors: Jin Shengkai , Geng Haochen , Lu Yichen , Zhou Yuhua , Lv Jing , Fu Chaowei , Zhang Yuwei , Li Menglu , Feng Ninghan
Published: October 2024

Background

Kidney stones are a common urologic disease with an increasing incidence year by year, and there are similar influences between gout status and kidney stone incidence. Therefore the contribution of gout status to the incidence of kidney stones is unclear. The aim of this study was to investigate the relationship between gout status and kidney stones and to further explore the causal relationship by Mendelian randomization (MR) analysis.

Method

An epidemiologic study of 49,693 participants in the 2009–2018 National Health and Nutrition Examination Survey (NHANES) was conducted to examine the association between the two. The causal relationship between gout status and kidney stones was assessed by Mendelian randomization analysis of data from the GWAS database.

Result

A total of 28,742 participants were included in the NHANES analysis. We found that gout status was associated with an increased risk of kidney stones [odds ratio (OR) = 1.45 (95%CI, 1.243–1.692); p < 0.001]. In the MR analysis, we found a causal relationship between gout status and the risk of developing kidney stones (OR = 1.047, 95%CI, 1.011–1.085, p = 0.009).

Conclusion

There may be an association between gout status and kidney stone risk. This finding requires further large-sample studies and adequate follow-up.
Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry
Authors: Cuesta-Martín de la Cámara Ricardo , Torices-Pajares Andrea , Miguel-Berenguel Laura , Reche-Yebra Keren , Frauca-Remacha Esteban , Hierro-Llanillo Loreto , Muñoz-Bartolo Gema , Lledín-Barbacho María Dolores , Gutiérrez-Arroyo Almudena , Martínez-Feito Ana , López-Granados Eduardo , Sánchez-Zapardiel Elena
Published: October 2024

Background

Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients.

Methods

Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study. Based on their EBV serological (S) and viral load (VL) status, patients were categorized into IP-SNEG, IP-SPOSVLNEG and IP-SPOSVLPOS groups. T-cell response was assessed at two timepoints by stimulating cells with EBV peptides (PepTivator®) and performing intracellular-cytokine and activation-induced marker staining. Background subtraction was used to determine EBV-specific T-lymphocyte frequency.

Results

Polyfunctional CD8+ T cells indicated previous EBV contact (IP-SNEG 0.00% vs IP-SPOS 0.04% and HC 0.02%; p=0.001 and p=0.01, respectively). Polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was increased in serology-positive (IP-SNEG 0.01% vs IP-SPOS 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-SPOSVLPOS 0.43% vs IP-SPOSVLNEG 0.07% and HC 0.03%; p=0.03 and p=0.001, respectively) patients. Central-memory cells were increased among serology-positive adults (IP-SNEG 0.00% vs IP-SPOS 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-SNEG patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-SPOSVLPOS patients had cleared viral loads and, subsequently, decreased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- cells (first visit 0.43% vs second visit 0.10%, p=0.81).

Conclusion

Polyfunctional CD8+ EBV-specific T-cell response allows detecting EBV previous contact in liver-transplant children. %CD8+CD107a+IFNɣ+IL2-TNFα- is increased in patients with positive viral loads. Central memory CD4+ T-cell population more effectively determines prior EBV-exposure in adults.
High-resolution mapping of significant wave heights in the Northeast Pacific and Northwest Atlantic using improved multi-source satellite altimetry fusion method
Authors: Yang Hongbin , Liang Bingchen , Gao Huijun , Shao Zhuxiao
Published: October 2024

Significant wave height (SWH) is an important parameter to reflect wave state, which is of great significance in ocean engineering. However, the current wave observation methods have limitations in capturing wave field data with high spatial resolution. In this study, to generate the SWHs field over the Northeast Pacific and Northwest Atlantic, multi-source satellite altimeter data (CRYOSAT-2, SARAL, JASON-3, SENTINEL-3A, SENTINEL-3B, HY-2B and CFOSAT) are fused with a spatial resolution of 0.125° x 0.125° and a temporal resolution of 1 day. We employ the Inverse Distance Weighting (IDW) method and the IDW-based spatiotemporal (IDW-ST) method for data fusion. The fusion results exhibit a consistent spatial distribution characteristic, but the results of the IDW method display the visible trajectory. Moreover, the IDW-ST method, which incorporates time factors, shows great agreement between the fused SWH and buoy data. However, when the water depth change near the grid point has a great influence on the fusion, the complexity of bathymetric topography makes the traditional two-dimensional spatial fusion methods inadequate. Therefore, an improved method is proposed based on the IDW-ST fusion method, which introduces the water depth factor and significantly enhances fusion accuracy in regions where bathymetric variations greatly affect fusion results. The proposed method can be used to generate reliable SWH fields, especially in complex bathymetric topography conditions, and provide significant support for marine infrastructure design, ocean energy utilization and marine disaster protection.
Metal regeneration during an ex-situ disturbance experiment on deep-sea sediments from the polymetallic nodule area of western Pacific
Authors: Yang Juan , Xing Zhaohui , Liu Baolin , Sun Dong , Wang Chunsheng , Han Luwei , Xia Jianxin , Zhang Wenquan , Song Chengbing
Published: October 2024

The ecological implications of deep-sea mining, particularly the considerable discharge of suspended sediments during operational processes, have attracted substantial concerns. In order to reveal the metal regeneration dynamics in the polymetallic nodule area of the western Pacific Ocean, ex-situ sediment disturbance experiments were conducted on a research vessel. After two levels of regulated stirring disturbance were exerted for half an hour, the concentrations of 12 dissolved metals and physicochemical parameters, including Eh and pH, were monitored continuously in the overlying water for three days. Porewater samples were also collected at the starting and ending time of each experiment to detect the change of dissolved metal profiles within the sediments. The findings revealed that the sediment disturbance led to fluctuations in the concentrations of metals in the overlying water, with manganese exhibiting the most pronounced change at a coefficient of 208%. The temporal patterns of dissolved metal concentrations demonstrated a coherent behavior among certain metals, such as Li, V, Co, Ni, Rb, Mo, and Cs, which displayed an overall increase, ultimately surpassing the initial concentrations in the overlying water. In line with this, the metal concentration profiles in the porewater were also elevated. Spearman correlation analysis confirmed the synchronized behavior of these metals. The results suggested that the metals mobility might be governed by physicochemical factors in the overlying water. Moreover, the sedimentary features, such as grain size composition, and the morphological state of metals in sediments played pivotal roles in the differential responses of metal groups to sediment disturbance across stations. Conversely, the disturbance intensity was found to have a relatively minor impact on the dissolved metal behavior. The findings from the ex-situ experiments provided critical insights for predicting metal regeneration related to deep-sea mining, which are expected to be validated through rigorous monitoring protocols during future in-situ mining trials.
Perihilar cholangiocarcinoma masquerading as intrahepatic cholestasis of pregnancy: a case report and review of the literature
Authors: Xiao Chao , Cao Cheng-Jian , Xiao Xue , Cheng Qi-Jun
Published: October 2024

Cholangiocarcinoma (CCA) is a tumor that arises from the epithelium of the intrahepatic bile ducts. It is rarely diagnosed in individuals under 40 years of age and has a very aggressive nature: 95% of patients die within 5 years. We present the first detailed report of a case of perihilar CCA (pCCA) presenting during pregnancy masquerading as intrahepatic cholestasis of pregnancy (ICP). First, the patient exhibited typical pruritus, particularly in her limbs; second, a raised biomarker of total bile acid (TBA) was noted; third, the onset occurred in the second trimester, aligning with the epidemiological profile; and finally, importantly, there was no mass detected in her liver. First-line drugs were given to treat ICP, but they failed, and ultimately, the condition was identified as pCCA. Following an inadequate excision, traditional Chinese medicine was administered. After 26 months, she succumbed to cachexia. As gestational symptoms are sometimes associated with pregnancy-related disorders, pCCA in pregnant women is frequently misdiagnosed. Symptoms such as jaundice, pruritus, and dilated bile ducts in pregnant women may indicate pCCA. In addition, the appropriate treatment for pCCA in pregnant women may be surgery or chemotherapy; if surgery is not an option, chemotherapy may also help extend the gestational week. Our work is important and can educate on the diagnosis and treatment of pregnancy-related diseases, such as ICP and pCCA.
68-channel neural signal processing system-on-chip with integrated feature extraction, compression, and hardware accelerators for neuroprosthetics in 22 nm FDSOI
Authors: Guo Liyuan , Weiße Annika , Zeinolabedin Seyed Mohammad Ali , Schüffny Franz Marcus , Stolba Marco , Ma Qier , Wang Zhuo , Scholze Stefan , Dixius Andreas , Berthel Marc , Partzsch Johannes , Walter Dennis , Ellguth Georg , Höppner Sebastian , George Richard , Mayr Christian
Published: October 2024

Introduction

Multi-channel electrophysiology systems for recording of neuronal activity face significant data throughput limitations, hampering real-time, data-informed experiments. These limitations impact both experimental neurobiology research and next-generation neuroprosthetics.

Methods

We present a novel solution that leverages the high integration density of 22nm fully-depleted silicon-on-insulator technology to address these challenges. The proposed highly integrated programmable System-on-Chip (SoC) comprises 68-channel 0.41 μW/Ch recording frontends, spike detectors, 16-channel 0.87–4.39 μW/Ch action potentials and 8-channel 0.32 μW/Ch local field potential codecs, as well as a multiply-accumulate-assisted power-efficient processor operating at 25 MHz (5.19 μW/MHz). The system supports on-chip training processes for compression, training, and inference for neural spike sorting. The spike sorting achieves an average accuracy of 91.48 or 94.12% depending on the utilized features. The proposed programmable SoC is optimized for reduced area (9 mm2) and power. On-chip processing and compression capabilities free up the data bottlenecks in data transmission (up to 91% space saving ratio), and moreover enable a fully autonomous yet flexible processor-driven operation.

Discussion

Combined, these design considerations overcome data-bottlenecks by allowing on-chip feature extraction and subsequent compression.
Association of non-high-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol ratio (NHHR) with gout prevalence: a cross-sectional study
Authors: Guo Xia , Chu Haoxuan , Xu Hanchi , Wang Shipeng , He Jiahuan , Wang Yushi
Published: October 2024

Background

The non-high-density lipoprotein cholesterol (non-HDL-C)-to-high-density lipoprotein cholesterol (HDL-C) ratio (NHHR) is a strong lipid marker that has been associated with atherogenic features. This study aimed to investigate the potential association between the NHHR and gout prevalence.

Methods

This study investigated the relationship between the NHHR and gout by analyzing data gathered from the National Health and Nutrition Examination Survey (NHANES), a research study conducted in the United States from 2007 to 2018. All participants in NHANES provided written informed consent prior to participation. The NHHR was calculated as the ratio of non-HDL-C to HDL-C. Total cholesterol (TC) and HDL-C levels were sourced from NHANES laboratory data. Gout was assessed using a questionnaire. Weighted logistic regression analysis, subgroup analysis, and smoothed curve fitting were performed.

Results

This study included 30,482 participants. The fully adjusted models showed that for each unit increase in NHHR in continuous variables, there was a 10% higher likelihood of gout prevalence (OR: 1.10, 95% CI: 1.05, 1.16). Analysis of the NHHR quartiles revealed that patients in the highest quartile had a notably greater probability of developing gout than those in the lowest quartile. (Q4 vs. Q1, OR: 1.34, 95% CI: 1.05, 1.71). Subgroup analyses yielded consistent results across categories, indicating a significant positive association between the NHHR and gout. E-value analysis suggested robustness to unmeasured confounding. Interaction tests showed that the race, education level, marital relationship, poverty-income ratio (PIR), hypertension, smoking habits, estimated glomerular filtration rate (eGFR), lipid-lowering therapy, and diabetes had no discernible effects on this association. The p-values for all the interactions were > 0.05. Nevertheless, the relationship between the NHHR and gout was significantly affected by the age and sex of the participants (interaction p < 0.05).

Conclusion

Among adults in the United States, elevated NHHR levels are correlated with increased odds of gout prevalence.