bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential impact of the European Green Agreement on EU and Hungarian crop production
Authors: Szabó Levente , Madai Hajnalka , Nábrádi András
Published: February 2023

European arable farming, including Hungarian arable farming, faces a huge dilemma: how to contribute to and maintain the global food supply while reducing greenhouse gas emissions while main taining biodiversity, but reducing inputs that are potentially damaging to society and the environment while ensuring that no more land is taken out of production? Not to mention that the increasingly urgent need to tackle climate change is also placing additional demands on EU agricultural decision-makers. Under the European Green Deal (GD), the 'From Farm to Fork' (F2F) strategy will help achieve climate neutrality by 2050, with a target of a 55% reduction in greenhouse gas emissions by 2030. Achieving this will require significant changes in food production, a shift in crop health strategies and accelerated innovation in the agricultural sector. The study addresses these issues. Our first hypothesis (A1) is that the GD and F2F strategies can be implemented without problems and without losses. Our second assumption (A2) is that the know-how solutions and the technological conditions for precision agriculture that are already available exist, and that all of these already justify the feasibility of A1. In order to prove this, we have reviewed recent and up-to-date literature on DG and F2F. For A1, we found that there are pro and con findings in the literature. However, the summary finding is not positive. The conclusion of the studies, based on data calculations, is that EU agriculture faces huge additional costs if it is to maintain production and reduce environmental pressures. Their calculations suggest that more people will be disadvantaged by the decisions, and that millions of euros could be lost to the public. However, the article also shows that there are many cases where positive results can be achieved even with reduced chemical use. Facts and figures from international and Hungarian technological and know-how solutions and their trials at plant level show that the DG's objectives are already partially achievable. It has been established that the systematic use of precision technologies allows to increase the natural and at the same time the economic efficiency. In our work we have used the results of primary and recent secondary research. We have shown the downsides of GD, but also that with targeted support, the objectives of sustainability and GD can be approached. Changes in 2022, drastic price increases for inputs including fertilizers and pesticides, inflation at a 20-year high, energy prices spiraling out of control, and an almost unprecedented drought affecting crop production and horticulture, point to the need for a radical change in technology, thinking and regulation. And all this to ensure that there is enough affordable food in Hungary, that there are export products within and outside the Community, and that those working in agriculture have a decent living.
Huzursuz Bacak Sendromu Olan Hastalarda Enflamasyonun Nötrofil Lenfosit Ve Platelet Lenfosit Oranlarının Diğer Parametreler İle Beraber Değerlendirlmesi
Authors: DURU Hüseyin , DURU Gül , ASKER İhsan
Published: February 2023

Huzursuz Bacaklar sendromu (HBS) bacaklarda hareket ettirme isteği ihtiyacı olan uyku bozukluğudur. HBS etyolojisi tam olarak aydınlatılamamış olmakla enflamasyonun da rol oynadığını düşünülmektedir. Nötrofil-lenfosit oranı (NLO), platelet-lenfosit oranı (PLO) sistemik enflamasyonun göstergesi açısından kullanılabilmektedir. Biz bu çalışmada HBS tanılı hastalarda enflamatuvar göstergeler olarak kabul edilen parametreleri ölçerek ve diğer bazı parametreler ile kıyaslayarak enflamasyonun HBS’deki rolünü belirlemeyi amaçladık. HBS tanılı 190 hasta çalışmaya dahil edildi. Tam kan sayımı, C-reaktif protein, ürik asit ölçümleri ve Nötrofil-lenfosit oranı (NLO), platelet-lenfosit oranı (PLO), ferritin, eritrosit sedimantasyon hızı, kalsiyum düzeyleri değerlendirildi ve karşılaştırıldı. White Blood Cell-lenfosit oranı ve Nötrofil-lenfosit oranı (NLO) arasında istatistiksel anlamlı ve orta düzeyli korelasyon bulunmaktadır. Nötrofil-lenfosit oranı (NLO), platelet-lenfosit oranı (PLO) arasında istatistiksel anlamlı ve orta düzeyli korelasyon bulunmaktadır. Demiri düsük olan grupta Nötrofil-lenfosit oranı (NLO), platelet-lenfosit oranı (PLO) arasında istatistiksel anlamlı ve orta düzeyli korelasyon bulunmaktadır. Ca+2 düsük olan grupta Nötrofil-lenfosit oranı (NLO) arasında istatistiksel anlamlı ve orta düzeyli korelasyon bulunmaktadır (r=0,548). Ferritin düsük olan grupta Nötrofil-lenfosit oranı (NLO), platelet-lenfosit oranı (PLO) arasında istatistiksel anlamlı ve orta düzeyli korelasyon bulunmaktadır. Bizim çalışmamızda HBS tanılı hastalarda nötrofil sayısında artma, lenfosit sayısında azalma ve Nötrofil-lenfosit oranında (NLO) artma olduğunu gösterdik. Çalışmamız HBS patofizyolojisinde enflamasyonun rolü olduğunu desteklemektedir.
Rejuvenasi Peraturan Pengelolaan Prekursor: Ratio Legis dan Efektivitas
Authors: Alfath Tahegga Primananda , Anita Kristy
Published: February 2023

This legal research aims to examine the legal aspect ratio of legal instruments relating to pharmaceutical precursors as they relate to rejuvenation efforts; while at the same time reviewing based on the perspective of legal effectiveness on the regulation of pharmaceutical precursors. The results of this study state that the ratio of precursors to legislative regulation can be seen from three approaches, namely philosophical, juridical, and sociological. On the philosophical aspect, the 1945 Constitution provides an obligation to the government to provide welfare for matters related to health, the use of pharmaceutical precursors by the public. Then, from a juridical aspect, there are various legal products related to the management and utilization of pharmaceutical precursors; as the legal instruments are interrelated with each other. Sociologically, the illegal production and use of psychotropic substances through precursors will disrupt the economy, security and public health. However, the regulation on precursors has not been implemented in terms of structure, substance, effectiveness or culture; Thus, there are still many deviations in the management of precursors in the community.

KEYWORDS: Rejuvenation, Pharmaceutical Precursors, Law Effectiveness
Perancangan Rainwater Harvesting dengan Communal Rainwater Tank di Desa Baturinggit Kabupaten Karangasem
Authors: Yekti Mawiti Infantri , Bethania Corry Fanny , Pariartha I Putu Gustave Suryantara
Published: February 2023

Desa Baturinggit mengalami kekeringan terutama di musim kemarau sehingga mengalami kekurangan air untuk kehidupan sehari-hari. Umumnya masyarakat di Desa Baturinggit dalam memperoleh air, mereka membeli sumber air baku di perkotaan. Selain itu, keterbatasan sumber air baku diakibatkan oleh kurangnya pemasokan air yang diterima warga dari PDAM. Penelitian ini menggunakan metode neraca air dengan simulasi antara kebutuhan air dengan jumlah air hujan pada lokasi. Penentuan curah hujan kawasan rerata menggunakan metode rerata aljabar. Uji konsistensi data yang digunakan yaitu dengan menggunakan metode RAPS. Analisis frekuensi hujan dikerjakan menggunakan metode Log Pearson Type III dengan menentukan besaran hujan jam-jaman pada kala ulang 5 tahun. Perhitungan kebutuhan air menggunakan Standar Nasional Indonesia dengan jumlah penduduk di kawasan tersebut. Kala ulang 5 tahun dengan distribusi hujan jam ke 1, 2, 3, dan 4 mempunyai debit sebesar 0.005 m3/dt, 0.002 m3/dt, 0.002 m3/dt, 0.001 m3/dt. Communal rainwater tank direncanakan dengan dimensi panjang 12 meter, lebar 9 meter, dan kedalaman 1.2 meter. Jenis pipa yang digunakan untuk talang air menggunakan pipa PVC dengan ukuran 3 dim disetiap rumah dengan kecepatan aliran terbesar di pipa sebesar 1.5 m/dt. Waktu maksimal pengisian communal rainwater tank didapat selama sebesar 184 jam.
Upaya Pemenuhan Kebutuhan Lahan Parkir di Stasiun Kereta Api Bojonegoro
Authors: Rodhi Nova Nevila , Putra M Bagas Dwi Permana
Published: February 2023

Stasiun kereta api Bojonegoro merupakan stasiun terbesar di wilayah Bojonegoro yang melayani banyak keberangkatan dan kedatangan kereta api. Saat ini stasiun kereta api Bojonegoro telah dilengkapi fasilitas yang lumayan lengkap untuk memberikan pelayanan yang baik. Salah satunya adalah ruang parkir pengunjung. Dengan adanya calon penumpang yang semakin meningkat menyebabkan kendaraan di lokasi area parkir semakin padat, bahkan terdapat kendaraan yang parkir di luar ruang parkir yang telah disediakan. Berdasarkan hal tersebut, maka makalah ini membahas terkait evaluasi lahan parkir yang telah tersedia di stasuin kereta api Bojonegoro dengan menggunakan metode deskriptif kuantitatif. Hasil evaluasi menunjukkan bahwa nilai indeks parkir kendaraan roda dua dan roda empat di hari  akhir pekan memliki nilai >100% yang artinya ruang parkir untuk sepeda motor dan mobil di hari akhir pekan tidak memenuhi standar. Selain itu evaluasi juga dilihat dari analisis satuan ruang parkir (SRP), dalam hal ini hasilnya menujukkan bahwa pada saat hari akhir pekan kebutuhan SRP lebih banyak, yaitu sebesar 79 kebutuhan SRP sepeda motor, sedangkan SRP sepeda motor yang tersedia berjumlah 50, untuk mobil kebutuhan SRP sebesar  26, sedangkan yang telah tersedia adalah sebesar 16 SRP, sehingga dalam hal ini perlu diadakan penambahan ruang parkir di stasiun kereta api Bojonegoro.

ABSTRACTBojonegoro Railway Station is the largest station among all sub-station in Bojonegoro where every day busy traffic both departure and arriving turn over. Nowadays, Bojonegoro Railway Station is completely equipped with some facilities to support better services. One of the facilities provided is the parking lot for the visitor. The improvement of the users caused the vehicles to load the parking lot. Moreover, some visitors also park their vehicles outside the parking lot. Using descriptive quantitative, this article focused to evaluate the use of the parking lot provided by Bojonegoro Railway Station services. The result of the evaluation showed that the parking index value of vehicles reach more than 100% on weekends. It indicated that the parking area provided for vehicles, especially during the weekend is not able to equip the visitors’ needs or is below the standard. Besides, the evaluation also viewed from SRP analysis (parking space unit) which indicated that during the weekend, the need of SRP (parking space unit) increased to 79 (seventy-nine) spaces for motorcycles while the available space for motorcycles is only 50 (fifty) spaces/units. On the other hand, the space needed for the car reached 26 (twenty-six) units while the availability of the space is only able to cover 16 (sixteen) units. The results indicated the need for the stakeholders to accommodate the improvement of the parking area at Bojonegoro railway station.
Operationalizing ulul albab on a spiritual leader: A case of TV AlHijrah Malaysia
Authors: Abdul Wahid Nur Kamariah , Sabian Nur Arfifah Abdul , Sarif Suhaimi Md.
Published: February 2023

Purpose – The purpose of the paper is to explore on how the leadership of TV AlHijrah Malaysia, counter the economic crisis brought by Covid19 pandemic that they have succeeded in creating tv program like My QuranTime which led them to be awarded for ASEAN Inspiring Award Winner 2021 Innovation, Inspire, Creativity, the top ASEAN Award 2021. The interest of the paper is to understand how the transposition of spiritual leadership into Islamic leadership model could be explained practically. Methodology – The paper adopts qualitative research approach by employing interviews as the research instruments for the interest of the paper to go into in-depth understanding as well as to get the explanation on the leadership style of the leader of the organization Findings – The paper discovered that a new emerging element define as ulul albab has become the main contributor in explaining the transposition od spiritual leadership into Islamic leadership model element by explaining the elements of human capital aspects. Simultaneously, the findings have also able to explain the performance of the subject during such crisis in terms of the ability to transform the followers as well as organizational performances Implications – Potentially all Muslim leaders could improve their understanding of Islamic leadership from the lenses of spiritual leadership on taking the organization towards the desirable outcomes, covering the elements of organizational as well followers’ performance.Originality – The paper is believed to be with the original value as it only focuses on explaining the transposition of spiritual leadership into Islamic leadership model, by focusing on one specific organization, namely TV AlHijrah, that the emergence of ulul albab in explaining the human capital is seen as among the contribution.
Strengthening social media capabilities to improve private Islamic higher education marketing performance
Authors: Riofita Hendra , Dimasadra Waldana
Published: February 2023

Purpose – This research is conducted to strengthen social media capabilities to improve Private Islamic Higher Education marketing performance as well as the number of prospective students.Methodology – The design of this study is a survey. The data processed with SPSS and Amos program are collected from the elements of leaders of Indonesian private Islamic higher education. Multi-stage sampling and simple random methods are applied.Findings – Digital public relations and digital network empowerment, respectively has a very significant role to strengthen social media capabilities to improve Private Islamic Higher Education marketing performance and as well as the number of prospective students. Implications – The findings of this research encourage Private Islamic Higher Education to apply both digital public relations and digital network empowerment on social media. Originality – This research develops digital public relations and digital network empowerment as intervening variables, considering that both digital constructs have the capabilities to realize the marketing-related activities through a collaborative relationship approach required by social media to attract prospective students to join Private Islamic Higher Education.
Aspek-Aspek Pengembangan Pendidikan Sosio-Kultural Dalam Keluarga Muslim
Authors:   UIN Walisongo, Semarang, Amalia Asri Andika , Rahma Raisya Miftakhul ,   UIN Walisongo, Semarang
Published: February 2023

Education is essential for humans in facing the complex life. In Islam, the first education starts from the family. The family is the initial environment that forms and grows individual personality through habitual instillation by parents. The purpose of this research is to discuss Islamic religious education in the family through a socio-cultural perspective. The method used by researchers is library research method by collecting literature sources from books, journals, and other related articles. This study found that the development of sociocultural education in Muslim families can be carried out through three aspects, helping each other, community unity and brotherhood of community. In constructing these socio-cultural values, parents play an important role in providing exemplary education, habits, advice, attention, rewards and punishments for children in accordance with Islamic law.
Physico-Chemical Study of Pomegranates of Different Degrees of Maturity
Authors: Hafizov Gharib , Hafizov Samir
Published: February 2023

The results of physico-chemical studies of individual fruit parts, including crusts, partitions, juice and seeds themselves, extracted from immature (green), unripe and mature fruits of three harvest periods are presented: 20.VII, 01.IX and 15.X. The analyses were carried out in 2019-20 during the period of active growth and ripening of fruits in the varieties Spring, Iridanaly, Guleisha pink and wild pomegranate from the Geokchay region (Azerbaijan) using standard and generally accepted physico-chemical methods. The ripe fruit (130-288 g) consisted of 60-113% of the peel (peel together with partitions), 53-140% of the juice and 17-85% of the seeds themselves. The edible part of the ripened fruits (53.85-73.2 of the total weight of the fruit) consisted of 58.54-78.65% juice and 21.35 -41.46% seeds, fresh juice contained 15.7-17.7% solids, including 12.04-13.84% sugar, 0.17-0.30% protein, 0.15—0.23% pectin, 0.30-0.40% ash and 0.26-0.57% total polyphenols. The concentrations of solids, protein, ash and total polyphenols in the seeds themselves, remaining after the extraction of juice from the grains of ripe fruits, were 50.0-58.2, 4.13-5.75, 0.60-1.0 and 0.08-0.32%, respectively. There were fewer total polyphenols, flavonoids, chlorogenic acids, catechins and leucoanthocyanins in ripe fruits, and more ascorbic acid, anthocyanins and proanthocyanidins than in unripe ones. The period from the second half of July to the beginning of September is the time of a real “boom” of common polyphenols.
Screw Apophysiodesis for Chronic Ischial Apophysitis Refractory to Apophyseal Drilling in a Teenage Athlete
Authors: Zebrack Joshua P. , Kalisvaart Michael , O'Mara Timothy J.
Published: February 2023

Case:

A 17-year-old elite male soccer player, initially treated for chronic ischial apophysitis with transapophyseal drilling 18 months before, presented with persistent apophysitis symptoms and unfused apophysis on imaging. An open screw apophysiodesis was performed. The patient was able to gradually return to play and, within 8 months, was competing symptom-free at a high-level soccer academy. At 1 year postoperatively, the patient was still playing soccer and continued to be asymptomatic.

Conclusion:

In refractory cases not responding to conservative management or transapophyseal drilling, screw apophysiodesis may be used to obtain apophyseal closure with symptom resolution.
Production Scheduling Analysis To Minimize Inject–Blow Production Makespan on PT.XYZ Using Differential Evolution Algorithm Method
Authors: Fauziyah Dzati , Sukmono Tedjo
Published: February 2023

This study discusses the problem of job-shop scheduling at one of the well-known mineral water companies in Indonesia. This company produces a number of products in several types with different routes from each other. However, in reality, the effectiveness of production lies in the range of 54.8%–69.2%, so it is still far from running time production where the expected target is 80% for inject and 90% for blow. Where production scheduling is a complex problem so it takes the right method to get the optimal solution for these problems. The research method used is the differential evolution algorithm method, where this method aims to minimize the makespan value (total completion time of all jobs) on the job-shop production route so as to obtain optimal scheduling results and improve the existing system. Scheduling obtained through the differential evolution algorithm method produces a makespan value of x minutes, while the company's schedule has a makespan value of y minutes. So that the proposed scheduling results in a decrease of x% compared to company scheduling.
Finished Paint Warehouse Re-Layout Using Slp and Shared Storage Methods to Minimize Material Handling Costs
Authors: Hidayatulloh Riqi , Cahyana Atikha Sidhi
Published: February 2023

Re-Layout finished paint warehouse use method Systematic Layout Planning (SLP) and Shared Storage could reduce wastage caused by layout lack of facilities max, for example distance long distance cause fare material handling Becomes big and heaps or paint arrangement that is not efficient.From result study Re - layout done use method Systematic Layout Planning (SLP) and Shared Storage obtained results efficiency as much as 59.74% of distance initial 25,967 m to 10,452 m after use layout proposal and that take effect to results fare material handling every company month can spend Rp. 5,959.99.12 for layout beginning be Rp. 2,817,056.32 per month after use proposal layout so that can save as much as 52.27%
The Relationship Between Sleep Quality and Body Mass Index with Work Fatigue in Male Production Workers at PT. Moya Kasri Wira East Java
Authors: Hadi Fajar Alifka , Putra Boy Isma
Published: February 2023

From the results of initial observations at PT Moya Kasri Wira Jatim in the process of setting the quality target of ice blocks, so that the workforce working in the company must meet the targets. Of the 26 male workers we interviewed experienced fatigue. This is due to the demands of targets that must be met and workers work in a less conducive physical environment, namely a lot of dust that can harm breathing, and working at temperatures high enough so that workers sweat a lot. This study used observational analytics that aimed to see the relationship between Fatigue with Body Mass Index (BMI) and Sleep Quality. The result indicates that there is significant corelation between BMI and fatigue with significance value p=0,030 < α (0,05), and also there is significant relationship between sleeping quality and work fatigue with significance value p = 0,008 < α (0,05). So, it is concluded that there is corelation between sleeping quality and BMI with work fatigue.
Web-Based Household Cash Finance Application
Authors: Ardyansyah Ach Nur , Hindarto Hindarto
Published: February 2023

Regulating financial management has become a problem that will be faced by every adult human being. To be able to manage finances well, every individual needs to learn to understand the design of cash inflows and outflows as a design of needs and wants. To make it easier to make this financial plan, various tools have been created. In this modern era, an application has become familiar among everyone. To make this application, there needs to be a research first. And after getting the results of the analysis, it was identified that with use that includes a small scale, the application should be simple and easy to use. With various basic features such as recording cash in, recording cash out and the most important is monthly reports that can be monitored. Applications for programming are sublime text 3, Xampp and databases from MySQL. This application runs on a web base so that it can be run universally by every individual.
Design And Build Electric Trolly To Accelerate The Distribution Of Goods In The Warehouse
Authors: Imron Ali , Anshory Izza
Published: February 2023

Using manual trolly because it takes a long time and is quite draining. The purpose of this study is to make a breakthrough tool that can help in the process of distributing goods in the warehouse so as to make time more efficient and not drain so much energy that the employee expends. In the manufacture of this electric trolly there are 2 methods, namely the first in making this trolly design can be climbed by the trolly driver The second method of this trolly moves with a 24V dc motor and there is a load cell sensor so that the trolly user can know the weight of the goods transported by this trolly then there is an infrared sensor to read the rotation of the trolly wheel and the reading results of the loadcell and infrared sensor are managed by the arduino microcontroller. From the results of the research, this tool runs according to its function, which is to be able to assist the work of employees in distributing goods in the warehouse so that it can make work time more efficient.
Classification of patients with lithium-treated bipolar disorder based on gene expression: Dirichlet Bayesian network model
Authors: Salari Nader , Shahsavari Soodeh , Almasi Afshin , Pilangorgi Sahar Souri
Published: February 2023

Backgrounds: Dirichlet Bayesian network (DBN) model is a method with score-based structural learning, leading to a more accurate knowledge of the structure of the Bayesian network. Therefore, the DBN was used in this study to classify gene expression data in bipolar disorder (BD) with lithium treatment.
Methods: In this study, gene expression data of patients with BD, including 47323 genes, were used, of which 30 received standard treatment and 30 received lithium treatment. The first essential variables were selected using partial least squares (PLS) regression to analyze and classify the data. The plaid algorithm was used to discover identical patterns and biclusters of gene expression data. We implemented principal component analysis (PCA) to represent a component for each bicluster. Then we created the DBN model toclassify the correlation network. Finally, the accuracy of the prediction model was evaluated using Receiver operating characteristic (ROC) curve analysis. R3.6.2 software was used to analyze the data.
Results: In this analysis, the number of essential and significant genes discovered using PLS regression was 10788. We used the plaid algorithm and nine homogeneous biclusters were discovered. The representative component of the biclusters was selected with at least 75% of the variance in the data using PCA. Then the classification was performed using DBN which the model's accuracy was 0.86 and the model's precision was 0.91.
Conclusions: This study demonstrates the potential of an ensemble approach, which can be developed for network analysis for thousands of genes. Combining models produces more robust and accurate models than single models. Also, network analysis is a desirable approach to detect subtle but coordinated changes in the mutual and related expression of a set of genes. This method can help study other diseases using existing datasets.
Naturally occurring Dinactin targets cpsA of LytR-Cps2A-Psr family protein as well as kills Mycobacterium tuberculosis by disrupting proton motive force
Authors: Tan Chen , wang yan , dong qi , Bai Yajuan , Li Yuxin , feng jia , Ren Xuanxiu , Lu Hao , Lu Weijia , Wang Chenchen , Tang Jia , li pei , wang rui , Chen Huanchun , Wang Xiangru
Published: February 2023

Tuberculosis is still a global threat, and new drugs are desperately needed to combat the spread of multidrug-resistant Mycobacterium tuberculosis. Historically, natural products have been an important source of drugs against infectious diseases, like tuberculosis. Here, we identified a natural macrotetrolide dinactin with antituberculosis activity against susceptible and non-replicating Mycobacterium tuberculosis. Dinactin can synergistically enhance the antituberculosis effect of rifampicin and isoniazide against wild-type and drug-resistant strains. Dinactin also demonstrates antituberculosis activity in macrophage and Galleria mellonella models. Interestingly, dinactin possesses the properties of the ionophore. It not only enhances cations transport across the cell membrane and can alter membrane permeability but also causes the dissipation of proton motive force and metabolic perturbations. By selecting spontaneous resistant mutants and whole genome sequencing, we successfully identified non-synonymous single nucleotide polymorphisms in the cpsA gene of the LytR-Cps2A-Psr family. The dinactin-resistant mutants decrease the in vitro drug sensitivity to dinactin without cross-resistant with first-line antituberculosis drugs. Subsequently, genetic studies and molecular biology assays confirm the cpsA as the principal target. These findings suggest that dinactin could be a promising antibiotic for treating drug-resistant tuberculosis.
Feasibility of an Evolutionary Tumor Board for Generating Novel Personalized Therapeutic Strategies
Authors: Robertson-Tessi Mark , Brown Joel , Poole Maria , Johnson Matthew , Marusyk Andriy , Gallaher Jill , Luddy Kimberly , Whelan Christopher , West Jeffrey , Strobl Maximillian , Turati Virginia , Enderling Heiko , Schell Michael , Tan AikChoon , Boyle Theresa , Makanji Rikesh , Farinhas Joaquim , Soliman Hatem , Lemanne Dawn , Gatenby Robert , Reed Damon , Anderson Alexander , Chung Christine
Published: February 2023

The current paradigm of clinical trials treating patients until disease progression using maximum tolerated dose does not account for the dynamic tumor-host-drug interactions that result in acquired resistance. Here, we present the concept of an Evolutionary Tumor Board (ETB) and report interim results from a prospective, non-interventional pilot study in which novel therapeutic strategies based on evolutionary principles were developed under the ETB framework. The ETB approach relies on an interdisciplinary team that integrates clinical, preclinical, and theoretical knowledge and the application of mathematical modeling to predict patient responses to different therapies, including novel approaches derived from eco-evolutionary first principles. We have previously proposed several evolutionary therapies that aim to enhance the efficacy of an overall treatment regimen, using existing agents for a given disease. Key among these evolutionary therapies is the idea of “first-strike second-strike”, where different agents are administered in sequence, and new strikes are applied as soon as the efficacy of the previous strike is nearing a minimum, as opposed to waiting until progression is identified on periodic imaging. This approach requires careful analysis of longitudinal patient data coupled with predictive dynamics generated by mathematical models. Here we describe the ETB process and the interim results from 15 patients enrolled in the feasibility trial. In addition, we describe the challenges faced as well as the solutions that can be implemented via improved modeling approaches, better patient data collection, and a reassessment of how we understand tumor dynamics in the light of evolutionary principles.
A casein kinase TaCK2α contributes to wheat resistance to Puccinia triticina
Authors: Zhang Yanjun , Ma Qiuying , Geng Huaimin , Wang Shen , Cui Zhongchi , Wang Haiyan , Liu Daqun
Published: February 2023

Background The casein kinase 2 (CK2), one of the major multifunctional protein kinases in plant cells, is expressed ubiquitously and is essential for survival in response to different stresses. However, the role of CK2 in the interaction between wheat and Puccinia triticina (Pt) is still unknown.
Results Our earlier studies have found that one casein kinase CK2 named TaCK2α was screened from RNA-seq data in wheat line TcLr19 inoculated by Pt. In this study, quantitative real-time PCR (qPCR) analysis showed that TaCK2αexpression was induced by Pt race PHNT and signaling molecules, suggesting that it might play a role in the interaction of wheat-Pt associated with abscisic acid (ABA) and ethylene (ETH) signaling molecules. To further determine the function of the TaCK2αgene in wheat resistance to Pt, protein-mediated phenotyping assays in vivo and antifungal activity assays in vitrodemonstrated that wheat leaves infiltrated with pure TaCK2α protein developed significantly less disease compared to control leaves. Then virus-induced gene silencing (VIGS) system confirmed that TaCK2α was involved in regulating wheat resistance to Pt. In addition, 24 candidates with potential interacting with TaCK2α (2 disease resistance related protein, 11 stress resistance related protein, 1 photosynthesis related proteins, and 10 functional indeterminate protein) were selected in wheat by pull-down assay combination with mass spectrometry (MS). Conclusions Overall, our results indicate that TaCK2α gene mediated wheat resistance to Pt, laying a good foundation to analyze the molecular mechanisms of CK2 in plant resistance to biotic stress.
Complete genome analysis and biological characterization of a novel Clostridium perfringens phage vB_CP_qdyz_P5
Authors: Wang Yue , Zhao Gang , Wang Jingxue , Lin Hong
Published: February 2023

A novel lytic Clostridium perfringens phage, named vB_CP_qdyz_P5, was isolated and characterized in this study. Genome analysis revealed that vB_CP_qdyz_P5 has a linear double-stand DNA of 18888 bp with a G+C content of 28.8%. There were 27 opening reading frames in its genome. Moreover, vB_CP_qdyz_P5 showed good temperature (below 70℃) and pH (4 to 12) stabilities as well as a very strong lysis ability with a high burst size(207pfu/cell). Phylogenetic analysis indicated that vB_CP_qdyz_P5 might be a novel phage of the family Guelinviridae.
Chatbots and Robots: A framework for the self-management of occupational stress
Authors: Yorita Akihiro , Egerton Simon , Chan Carina , Flower Rebecca , Kubota Naoyuki
Published: February 2023

We have developed a stress management framework aimed at helping healthcare professionals manage occupational stress. A chatbot is used to gather pertinent information from a user through regular conversation which is processed via a fuzzy inference model to derive their level of occupational Comprehensibility, Manageability, Meaningful and overall occupational Sense of Coherence (SOC). This analysis feeds into a Peer Support model which selects the best intervention aimed at enhancing a user’s stress-coping abilities and reducing their levels of occupational stress. A trial has been conducted with working adults, and the results demonstrate that the approach is able to measure user stress and provide accurate analysis and relevant peer support.
The association between sex and neonatal respiratory distress syndrome
Authors: Fang Keren , Yue Shaojie , Wang Shuo , Wang Mingjie , Yu Xiaohe , Ding Ying , Lv Mei , Liu Yang , Cao Chuanding , Liao Zhengchang
Published: February 2023

Background: To investigate the association between sex and neonatal respiratory distress syndrome (NRDS).
Methods: Infants born at our hospital and transferred to the neonatal department within 1 hour were retrospectively analyzed. Depending on whether they developed NRDS during their hospital stay, the infants was divided into NRDS and non-NRDS groups. There were 142 infants in the NRDS group (95 males and 47 females) and 310 infants in the non-NRDS group (180 males and 140 females). The infants’ data on gestational age, sex, birth weight, white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), immunoglobulin M (IgM), gestational diabetes mellitus(GD), antenatal steroids use, meconium-stained amniotic fluid, and preterm premature rupture of membranes(PPROM）were gathered.
Results: 452 infant (265 males and 187 females) were involved for the purpose of collecting basic characteristic. Multivariate analysis, males had a 1.87 times higher risk of NRDS than females (P<0.05) after controlling for the confounding effects of gestational age, birth weight, WBC, PLT, CRP, IgM, GD, antenatal steroids use, meconium-stained amniotic fluid, and PPROM.
Conclusions: Sex was associated with NRDS; males had a considerably higher risk of NRDS than females.
Therapeutic effect of V8 affecting mitophagy and endoplasmic reticulum stress in acute myeloid leukemia mediated by ROS and CHOP signaling
Authors: Hui Hui , Guo Yongjian , Zhu Mengyuan , Wang Zhanyu , Chen Hongyu , Qing Yingjie , Wang Hongzheng , Xu Jingyan , Li Hui
Published: February 2023

Acute myeloid leukemia (AML) is a disease of malignant proliferation of abnormally or poorly differentiated myeloid cells of the hematopoietic system. The clinical treatments of non-M3 AML are experiencing a lack of effective drugs. V8 is a newly synthesized derivative of the natural flavonoid wogonin, which belongs to the potential anticancer drug, and has shown significant antitumor activityin vitroandin vivo. In this study, we investigated the effects of V8 on AML cell lines and primary AML cells and the underlying mechanisms. The results showed that V8 inhibited the growth and induced the apoptosis of AML cell lines (ME-1, Kasumi-1, and U937) and primary AML cells in a concentration-dependent manner. Meanwhile, we revealed that V8-induced apoptosis was accompanied by mitochondrial injury, such as the reduction of mitochondrial membrane potential and ATP production, activation of endoplasmic reticulum stress (ERS) characterized by GRP78 and caspase-12 expression upregulation. Mechanism studies have shown that V8 induced mitochondrial injury and inhibited mitophagy via elevating the intracellular ROS level. In addition, V8 activated PERK-p-eIF2α-ATF4 and Ire1α-XBP1 pathways and induced apoptosis of AML cells via selectively activating CHOP. Correspondingly, the degree of apoptosis and expression of apoptosis-related proteins were alleviated after the elimination of cytoplasmic ROS with N-Acetyl-L-cysteine (NAC) and knocking out CHOP in the cells by transfection with CHOP shRNA, implicating that mitochondrial injury-triggered upregulation of ROS and CHOP played an important role in V8-induced apoptosis of AML cells. In primary AML cells-bearingNOD/SCIDmice model and U937 cells-inoculatingBALB/cnude mice xenografts transplantation tumor model, administration of V8 markedly prolonged survival time and inhibited the xenografts growth via CHOP-mediated ERSin vivo. In conclusion, our study provides a new insight into the mechanism of V8-induced apoptosis, suggesting the potential of V8 as a promising agent against AML.
Vascularized patient-derived tumoroids supplemented with immune cells to predict response towards treatment for lung cancer patients
Authors: Lê Hélène , Ponté Charlotte , Desforges Jules , Hua Guoqiang , Idoux-Gillet Ysia , Lindner Véronique , Olland Anne , Falcoz Pierre-Emanuel , Zaupa Cécile , Quéméneur Eric , Balloul Jean-Marc , Jessel Nadia
Published: February 2023

We here describe a prototype of a patient-derived tumoroid that prefigures the precision medicine approach by helping experimental assessment of response to current treatments. The introduction of microvessels to help forming a tumor-connected vasculature, and of peripheral blood immune cells was shown to be essential for the representativeness of the model. The study is based on a cohort of 11 patients at various stages of the disease. Noteworthy, this predictive vascularized, and immunocompetent micromodel can be obtained within 2 weeks, matching the constraints of the patient journey. Histological analyses confirmed that major features of the original tumor were conserved. Transcriptomic analysis confirmed the functionality of the tumoroid. The responses to either anti-angiogenic treatment or platinum-based chemotherapy regimen highlighted the role of immune mechanisms. We also discussed the possibility to apply this original experimental model to the analysis of response to immune checkpoint blockers, or oncolytic vector-based therapies.
The contribution of multiplexing single cell RNA sequencing in acute myeloid leukemia
Authors: Madaci Lamia , Gard Charlyne , Nin Sébastien , Venton Geoffroy , Rihet Pascal , Puthier Denis , Loriod Béatrice , Costello Régis
Published: February 2023

After decades during which the treatment of acute myeloid leukemia consisted in cytarabine + anthracycline, targeted therapies have appeared, first based on monoclonal antibodies (anti-CD52, anti-CD123) and then on specific inhibitors of molecular mutations (anti-IDH, IDH2 or FLT3). What should be the place of these therapeutic options considering the tumor heterogeneity inherent to leukemia diagnosis and the clonal drift of which this type of tumor is capable? Targeted drugs would require an analysis of the various therapeutic targets not in the total population but at the individual cell level. Indeed, the prognostic value and therapeutic interest of a given molecular target are certainly not the same if it is a cell in terminal differentiation with low proliferative potential or, on the contrary, a stem cell with strong capacities of both proliferation and self-renewal. However, this cell-by-cell analysis is fraught with several pitfalls. The first one is scientific because the comparison of two different single cell analysis experiments is delicate, in spite of the different techniques aiming at standardizing the results. The second pitfall is practical, as each single cell experiment is very costly from a financial point of view but also very time consuming. The solution is therefore to be able to process several samples at the same time, which is the specificity of the cell hashing technique. In this study we demonstrate that the cell hashing technique can be used for the analysis of acute myeloid leukemia cells. We compared the cell hashing technique with the classic single cell analysis and demonstrated a good concordance of different parameters: quality control, gene expression correlation, expression analysis of leukemic blast markers in both patients. The technique could thus in the future be part of the biological assessment of acute myeloid leukemia and contribute to the individualization and optimization of their management, particularly in the context of the use of targeted therapies.
New statistical selection method for pleiotropic variants associated with both quantitative and qualitative traits
Authors: Kim Kipoong , Jun Tae-Hwan , Ha Bo-Keun , Wang Shuag , Sun Hokeun
Published: February 2023

Background Identification of pleiotropic variants associated with multiple phenotypic traits has received increasing attention in genetic association studies. Overlapping genetic associations from multiple traits help to detect weak genetic associations missed by single-trait analyses. Many statistical methods were developed to identify pleiotropic variants with most of them being limited to quantitative traits when pleiotropic effects on both quantitative and qualitative traits have been observed. This is a statistically challenging problem because there does not exist an appropriate multivariate distribution to model both quantitative and qualitative data together. Alternatively, meta-analysis methods can be applied, which basically integrate summary statistics of individual variants associated with either a quantitative or a qualitative trait without accounting for correlations among genetic variants.
Results We propose a new statistical selection method based on a unified selection score quantifying how a genetic variant, i.e., a pleiotropic variant associates with both quantitative and qualitative traits. In our extensive simulation studies where various types of pleiotropic effects on both quantitative and qualitative traits were considered, we demonstrated that the proposed method outperforms the existing meta-analysis methods in terms of true positive selection. We also applied the proposed method to a peanut dataset with 6 quantitative and 2 qualitative traits, and a cowpea dataset with 2 quantitative and 6 qualitative traits. We were able to detect some potentially pleiotropic variants missed by the existing methods in both analyses.
Conclusions The proposed method is able to locate pleiotropic variants associated with both quantitative and qualitative traits. It has been implemented into an R package `UNISS', which can be downloaded from http://github.com/statpng/uniss
Aerosol-induced effects on pre- and developed Indian summer monsoon and the corresponding onset and withdrawal
Authors: Huang Kuan-Tzu , Sui Chung-Hsiung , Lo Min-Hui , Kuo Yu-Yang , Chang Chiung-Wen June
Published: February 2023

The NCAR Community Earth System Model is used to study aerosol direct effect on Indian summer monsoon (ISM). We perform two sets of 30-year simulations subject to prescribed perpetual SST annual cycle: CTL and AERO. The two differ by anthropogenic emissions over Indian Peninsula that is included in AERO. We examine the differences in the onset and withdrawal between CTL and AERO. The results show that, relative to the ISM evolution in CTL, the transition of ISM from spring to fall in AERO exhibits a similar ensemble-mean onset date with larger spread and more abrupt change, and an earlier but more gradual withdrawal. The difference is related to aerosols-induced circulation changes in the pre-monsoon environment, including upward motion from the Ganges basin to Indian Peninsula, and strengthened anticyclonic circulation over the Arabia Sea and eastern Bay of Bengal. The changes in AERO-CTL for the developed monsoon period feature a northward shift of monsoon flow such that westerly within 10°-20°N is weaker but the tropical ITCZ (0°-10°N) and the local meridional circulation over northern India are stronger. The earlier monsoon withdrawal in AERO relative to CTL is attributed to the aerosol induced anticyclonic flow within 10°-25°N and cyclonic flow within 0°-10°N over eastern India and Bay of Bengal that resemble the transitional changes in the monsoon withdrawal. The anthropogenic aerosols also cause a 16% (32%) increase in concentration (AOD) by natural dust over India that is transported from the Middle East by aerosols-induced westerly wind in the pre-monsoon season.
Evaluation of TGF-β isoforms based on selected clinical parameters in asthmatic patients.
Authors: Koćwin Marcelina , Jonakowski Mateusz , Majos Alicja , Szemraj Janusz , Kuna Piotr , Panek Michał
Published: February 2023

Introduction: The Transforming Growth Factor β (TGF-β) has attracted particular attention from researchers in the context of the pathogenesis and development of asthma and allergic diseases. Undoubtedly, TGF-β is one of the main cytokines involved in mediating inflammation and bronchial remodeling. It stimulates fibroblasts and myofibroblasts, and regulates processes of extracellular matrix remodeling, thus contributing to fibrosis and bronchial remodeling. In long-term inflammation, the airways become stiffened and airflow is impaired, which is sometimes reflected by lower values of spirometric parameters. What may also be observed in aging organs are intensified fibrotic processes.
Methods: The aim of the study was to evaluate the correlation between concentrations of all the TGF-β1-3 isoforms and selected clinical parameters, including pulmonary function indices assessed by spirometry.The study included 41 asthmatic patients and 28 healthy volunteers recruited from the Department of Allergology and the Allergy and Pulmonology Outpatient Clinic of the N. Barlicki University Teaching Hospital No. 1 in Lodz. The participants underwent a full medical examination and spirometry, and blood samples were collected from them for serum TGF-β levels. Individual isoforms of TGF-β1, TGF-β2 and TGF-β3 were determined by ELISA. The data obtained were then subjected to statistical analysis using Student's t-test, the Mann-Whitney U-test, Fisher's t-test, Pearson's correlation.
Results: The obtained results show significantly increased TGF-β1 and TGF-β2 levels among the elderly, both diseased and healthy individuals. Additionally, higher TGF-β1 and TGF-β2 concentrations correlate significantly with a decreased FEV1%/FVC ratio, while TGF-β2 alone also correlates negatively with FEV1 and FVC values.
Conclusion: The TGF-β1 and TGF-β2 isoforms have been shown to be associated with the pathogenesis of asthma. Expression of TGF-β1 and TGF-β2 increases with age. Higher concentrations of TGF-β1 and TGF-β2 significantly translate into worsening spirometric values. It is worth continuing research on TGF-β as a potential marker of remodeling in asthma.