bluuebunny/crossref_metadata_2025 huggingface dataset:
Studi Literatur: Konsep Kurikulum Merdeka pada Satuan Pendidikan Anak Usia Dini
Authors: Shalehah Nur Azziatun
Published: May 2023

Kurikulum merupakan ruh dalam penyelenggaraan proses pembelajaran di satuan pendidikan, sehingga adalah hal yang wajar jika terus terjadi perbaikan dan tranformasi pada sebuah kurikulum. Saat ini, kurikulum merdeka dicetuskan sebagai bagian solusi untuk memperbaiki pengajaran dan pembelajaran di Indonesia. Kurikulum merdeka ini erat kaitannya dengan konsep merdeka belajar yang memberikan keluwesan belajar pada peserta didik. Artikel ini bertujuan untuk membahas bagaimana konsep kurikulum merdeka, khususnya di jenjang PAUD. Penelitian ini menggunakan metode deskriptif kualitatif dengan studi kepustakaan digunakan untuk mengumpulkan data. Temuan penelitian menunjukkan bahwa konsep kurikulum merdeka memungkinkan peserta didik menjadi pusat pembelajaran yang berkesempatan untuk mengeksplor lingkungan di sekitarnya dengan tuntunan seorang pendidik. Pembelajaran berbasis proyek merupakan salah satu model pembelajaran yang dapat mendukung konsep “merdeka belajar” pada peserta didik. Pofil pelajar pancasila juga menjadi inovasi dalam kurikulum merdeka, mencakup 6 dimensi. Penilaian dan hasil belajar pada kurikulum merdeka mengacu pada standar acuan Standar Nasional Pendidikan yang kemudian disebut sebagai capaian pembelajaran, mencakup nilai-nilai agama dan karakter, identitas diri atau jati diri, serta dasar-dasar literasi dan STEAM (sains, teknologi, teknik, seni dan matematika).
ANALISIS KEMAMPUAN MOTORIK KASAR MELALUI PERMAINAN TRADISIONAL LOMPAT TALI PADA ANAK TUNAGRAHITA BERAT
Authors: Nur Cahyati Ngaisah  , Na’imah  , Khamim Zarkasih Putro
Published: May 2023

Anak tunagrahita kategori idiot cenderung mengalami keterlambatan dalam beberapa aspek kemampuan salah satunya kemampuan motorik kasar. Hal itu dipengaruhi oleh anak tunagrahita yang pasif dan jarang melakukan aktivitas gerak membuat otot-otot, otak dan saraf tidak berkoordinasi dengan optimal. Untuk mengoptimalkan kememampuan motorik anak dapat dilakukan melalui aktivitas yang digemari anak yang mengandung banyak gerakan dalam kegiatannya salah satunya melalui permainan tradisional lompat tali dalam melatih tiga kategori gerak dasar yaitu lokomotor, non lokomotor dan manipulatif. Tujuan penelitian ini untuk mendeskripsikan perkembangan kamampuan motorik anak tunagrahita kategori berat melalui permainan tradisional lompat tali yang dilakukan di sekolah SLB-C Darma Rena Ring Putra II.  Metode penelitian menggunakan pendekatan kualitatif dengan teknik pengambilan data melalui observasi dan wawancara. Teknik analisis data yaitu reduksi data, penyajian data, penarikan kesimpulan dengan pengujian keabsahan data menggunakan teknik triangulasi. Hasil penelitian menunjukan bahwa kemampuan motorik kasar anak tunagrahita berat dapat di stimulasi menggunkaan permainan tradisional lompat tali yang menciptakan berbagai macam gerak tubuh secara optimal. Sehingga dapat melatih anak dalammelakukan berbagai macam gerak dengan rasa percaya diri dan berani melakukannya seperti berjalan, berlari, mengangkat satu kaki, dan melompat.
PENGARUH MEDIA KOKORU TERHADAP KEMAMPUAN MOTORIK HALUS ANAK DI TAMAN KANAK-KANAK PEMBANGUNAN LABORATORIUM UNIVERSITAS NEGERI PADANG
Authors: Resa Resa Tifeni Az-Zahra , Suryana
Published: May 2023

Penelitian ini dilatarbelakangi oleh pentingnya mengembangkan kemampuan motorik halus anak di TK Pengembangan Laboratorium Universitas Negeri Padang. Penelitian ini menggunakan pendekatan kuantitatif dalam bentuk Quasi Eksperimen. Populasi penelitian ini adalah seluruh siswa TK Pengembangan Laboratorium Universitas Negeri Padang, dengan sampel kelas B2 dan B3 yang masing-masing berjumlah 15 anak. Teknik pengumpulan data yang peneliti gunakan adalah tes lisan, tes tindakan dan dokumentasi. Teknik analisis data menggunakan uji normalitas, uji homogenitas, dan uji hipotesis. Alat pengumpulan data menggunakan lembar pernyataan. Kemudian data diolah dengan uji beda (t-test) dengan menggunakan aplikasi SPSS 22.0 for windows. Berdasarkan hasil analisis data penelitian, rata-rata pretest kelas eksperimen 10,73 dan kelas kontrol 10,53, sedangkan rata-rata posttest kelas eksperimen 15,07 dan kelas kontrol 12,27. Berdasarkan data pre-test dan post-test, rata-rata gain score untuk kelas eksperimen adalah 4,33 sedangkan rata-rata gain score untuk kelas kontrol adalah 1,73. Berdasarkan nilai sig (2-tailed) adalah 0,00 < 0,05. Dengan demikian terdapat perbedaan yang signifikan antara kelas kontrol dan kelas eksperimen. Sehingga dapat disimpulkan bahwa Ha diterima dan H0 ditolak. Dengan hasil penelitian bahwa penggunaan media kokoru berpengaruh terhadap motorik halus anak usia dini.
Flooding resilience is determined by leaf age in Arabidopsis thaliana
Authors:   , Rankenberg Thomas Hendrik
Published: May 2023

Flooding events lead to major crop losses every year, this is expected to increase due to climate change. The resilience to flooding stress is not uniform throughout a plant: the older leaves are typically the first to die whereas the young leaves and the meristem survive for longer. In this thesis I describe some of the mechanisms that control this age-dependent flooding tolerance using the model organism Arabidopsis thaliana.

During a flooding event, old leaves went into a state of senescence faster than young leaves. This process was found to be in part controlled by the transcription factor ORESARA1 (ORE1), which induced the expression of senescence-related genes primarily in old leaves. Although ORE1 protein accumulated in both old and young leaves during flooding, it was activated by phosphorylation specifically in old leaves. Knocking out ORE1 reduced the senescence of old leaves during flooding and improved flooding tolerance. When floodwaters subside, this typically poses a second round of stress for plants as they are suddenly exposed to light and air. Leaves can rapidly dehydrate during the post-flooding phase, and this was found to be more severe in old leaves than young leaves. Although old leaves recovering from flooding stress showed a strong transcriptional response to dehydration and abscisic acid (ABA), their stomata had a reduced sensitivity to ABA which could contribute to their increased water loss.

The results presented in this thesis highlight how different processes lead to variation with leaf age in flooding resilience. Understanding these mechanisms can help in developing novel crop varieties that are more tolerant to flooding stress across all of their tissues.
Providing Expert Consultation in a World Living with COVID-19
Authors: Lloyd Jenny
Published: May 2023

After a welcome by Paolo Antonio Grossi, the appointed chair by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Department of Medicine & Surgery, University of Insubria, Varese, Italy; Ann-Brit Eg Hansen, Department of Infectious Diseases, Copenhagen University Hospital – Amager and Hvidovre, Denmark and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, summarised the objectives of the meeting and introduced the speakers. In their opening presentation, Tobias Welte, Department of Pulmonary and Infectious Diseases, Hannover University School of Medicine, Germany, described how the COVID-19 pandemic has evolved, in terms of variants, mortality rates, vaccinations, immunity, and antivirals. Welte then presented a hypothetical case study to illustrate how older patients with comorbidities can initially have mild symptoms, but may then deteriorate and require hospitalisation. Stephen Thomas, State University of New York Upstate Medical University, Syracuse, USA, then described the efficacy and potential side effects of the BNT162b2 (Pfizer–BioNTech, New York City, USA, and Mainz, Germany, respectively) vaccine, and the need for, and benefits of, booster doses. Thomas also described the added benefits of the newer bivalent vaccines in a world where COVID-19 is constantly mutating. Marta Boffito, HIV, Sexual and Gender Health, Dermatology, Chelsea and Westminster Hospital NHS Foundation Trust, Imperial College London, UK, then outlined various factors that increase the risk of progression to severe COVID-19 disease, including older age, immunocompromised status, and underlying health conditions (e.g., obesity, hypertension, heart disease, and chronic kidney disease [CKD]). Such patients can benefit from antiviral medications such as nirmatrelvir/ritonavir, although potential drug–drug interactions must be considered. Roger Paredes, Department of Infectious Diseases and IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain, and Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA, revisited the case study to highlight the importance of early COVID-19 diagnosis among high-risk patients to enable the use of nirmatrelvir/ritonavir, which is only approved within 5 days of symptom onset for non-hospitalised adults at increased risk of progression to severe COVID-19. Paredes went on to discuss antiviral treatments in more detail, describing a randomised controlled trial (EPIC-HR) and two large real-world studies that showed that nirmatrelvir/ritonavir could significantly reduce the risk of hospitalisation and death due to COVID-19 among high-risk patients. To conclude, Hansen highlighted the importance of regular updates to COVID-19 management guidelines, given the ongoing and evolving nature of COVID-19, as well as the importance of identifying high-risk patients early in their disease course to enable the use of nirmatrelvir/ritonavir.
Influence of Good Corporate Governance and Audit Quality on Discretionary Accrual with Performance as Mediation at Aneka Industry in Indonesia
Authors: Dr. Indrayati Dr. Indrayati , Ernawati Widi Dwi , Utami H Kuni , Bakhrudin Bakhrudin
Published: May 2023

Earnings management is engineering by managers to show better profits for bonus plans and company performance. This study aims to empirically examine the influence of good corporate governance and audit quality on earnings management with performance as a moderating variable in various industrial companies on the Indonesian stock exchange. The population of this study is various industrial companies with a sample of 180 companies during 2017-2022 with data processing using partial least squares (PLS) from secondary data from the Indonesian stock exchange's financial reports. The results of the study indicate that there is a significant effect of good corporate governance and audit quality on earnings management and performance is successful as a moderating variable in the effect of good corporate governance and audit quality on earnings management.
From Worriers to Warriors: Leading while Black in a Predominantly White Institution
Authors: Watson Dr. Dwight C. , Yarbrough Dr. Kenny E.
Published: May 2023

This manuscript captures the leadership development of two Black leaders at a Predominantly White Institution (PWI) as they navigated their way through the whirlwind of decisions that needed to be made during the 2020-2021 academic year of the pandemic and social and racial unrest. The leaders were the chancellor and the associate vice chancellor of equity, diversity, inclusion, and support programs. The leaders serve at a regional comprehensive university in a state system in the Midwest with a population of 11,900 students, including a 2-year campus. During the 2020-2021 academic year, the leaders embarked on an investigation of Whiteness through the lens of Blackness as they developed programs, practices, policies, and protocols to assist students, faculty, staff, and fellow administrators with decisions during a time of conflict, criticisms, and crisis.
Helping a Small Family Business Firm Become Socially Responsible
Authors: El-Rahbani George , Bonnet Marc , Cohanier Bruno
Published: May 2023

The purpose of this paper is to address a gap in the literature regarding the adoption of Social Responsibility (SR) in small businesses and its impact on overall performance. This issue comes from that most of the research has been undertaken in big firms and the subsequent results applied to small businesses. This is a major drawback since the dynamics in large companies and sometimes huge multinationals differ from the ones of small businesses which mostly focus on income. Family businesses find themselves at loggerheads with their stakeholders in an attempt to be socially responsible as they perceive the act as additional expenses. We argue small businesses have to rethink and invent new ways of being socially responsible for operating in a threatening environment. This paper relates an intervention research procedure based on the Socio-Economic Approach to Management (Savall, 1976) which applied management tools aiming to internally reduce dysfunctions and externally reach strategic objectives. The effect of the intervention research on socially responsible activities of small business firms and the results towards stakeholders are detailed emphasizing the increase in administrative personnel's efficiency and productivity towards stakeholders.
Role Perceived ValueAs the Mediating Variable of The Effect of Service Quality on User Satisfaction (Study on KRI Operations At the Military Seaborne Command)
Authors: Sasongko Widyo , Pahala Yosi , Suhalis Adenan
Published: May 2023

Quality of service in general greatly affects the satisfaction of its users. Synopsis In this thesis, we conduct research on service quality on user satisfaction in KRI operations at the Military Cross-Sea Command. This thesis uses a quantitative research method based on preliminary data, a structural equation model, used to examine data sourced from the Military Maritime Command. The conclusions from this study are that Perceived Value is influenced by the Quality of Service for KRI Kolinlamil users.
The Influence of Leadership and Discipline on Work Motivation and Its Impact on the Performance of Employees at the Office of Cooperatives, UKM, Industry and Trade, Bungo Regency
Authors: Aldino Wahyu , Prihatiningsih Astuti
Published: May 2023

The purpose of this study was to examine the influence of leadership, discipline, motivation and performance. The influence of leadership, discipline, motivation and performance of employees tested either directly or indirectly. To examine issues directly above the survey conducted by distributing questionnaires to employeesof the industry and trade SME cooperative service officeof Bungo. Data was analyzed by path analysis. The results of this study indicate that the leadership, discipline and work motivation influence simultaneously and partially on performance.Where is the leadership, discipline, motivation and performance of employees at the SME cooperative service office of the industry and trade, where are the good categories, Discipline are in both categories, motivation and performance of employees are in both categories.The analysis tool in this research uses descriptive method verification. Where is the use of a range of scales, while in the verification using path analysis or path analysis.
Longing for Belonging: Forwarding Andrew Walls’ Thoughts on Migration and Mission through an Ethnographic Study on Diasporic Chinese in Singapore's Christian Communities
Authors: Jia Chyi Hwang Jackie
Published: May 2023

This study on migration and Chinese Christianity uncovers both the potential and limitations in the late Professor Andrew Walls’ conception of how migration shapes global Christianity. Using an ethnographic approach, I examine how international students from China engaged in a quest for jia (home, family, belonging) by interacting with Singapore's Chinese Christian communities. For these students from China and the Singaporean Chinese Christians who encounter them, the personal narratives on both sides exhibit three traits: (1) a give-and-take relationship between different notions of ‘Chineseness’, (2) a transnational sense of family, and (3) an understanding of ecclesiology that is under negotiation. The ethnographic profile of Chinese hybridity that emerges shows how Walls’ ideas can be refined by a better understanding of co-ethnic Chinese Christianity which lies beyond China's geopolitical boundaries.
Unearthing Treasure in Clay Jars: T. C. Chao and the Formation of Chinese Dogmatic Theology
Authors: Sampson John
Published: May 2023

T. C. Chao (1888–1979) was a leading Chinese Protestant theologian renowned for his creative works of Chinese theology. Although scholars have traced significant changes and shifts in Chao’s theology in the 1940s, a particular formal aspect of his mature thinking has not received the attention it deserves. Chao began to emphasise and practise a particular form of Chinese theology in the 1940s and early 1950s, namely, doctrinal or dogmatic theology. This paper traces the development of Chao’s dogmatic theology and examines one representative dogmatic locus in his thinking, the doctrine of the Trinity. It argues that Chao’s turn to dogmatics not only richly illuminates a crucial aspect of his mature life and thought, but also sheds light on the legacy of Andrew Walls, whose work highlights Christianity’s cross-cultural diffusion and the gospel’s encounter with the cultural worlds it takes root within.
Perception of Immigration among University Students (A Comparative Analysis Istanbul-Şırnak Example)
Authors: BAYRAM Kayhan , ŞENGÜL Fatma Nur
Published: May 2023

The subject of our study is the attitude of university students towards immigrants, especially Syrian immigrants, who migrated to Türkiye for various reasons. A survey technique was used to explain these attitudes. Some demographic questions about attitudes towards immigrants and the “Immigrant (Syrian) Perception Scale” were included in the survey. The study population consists of university students, and the sample group consists of university students studying in Şırnak and Istanbul. A total of 302 university students, 151 from Istanbul and 151 from Şırnak, participated in the study, using snowball and purposive sampling methods. As a result of the study, it was seen that the attitude of university students towards immigrants was negative, they found immigrants disturbing in terms of economy and security, and it was determined that university students were disturbed by the presence of immigrants. It has been determined that university students residing in Istanbul have a more negative attitude towards Syrian immigrants than those residing in Şırnak. In addition, it has been determined that as the education level, age, and religiosity increase, the attitude towards immigrants becomes more positive; but it does not differ according to gender, or economic level.
Assessing the Efficacy of New Chemistry Insecticides against Subterranean Termite
Authors: Nisar Muhammad Shahid , Rashid Abdul , Mujtaba Muhammad Majid , Ramzan Hassan , Malik Saba
Published: May 2023

Termite attacks can significantly reduce crop and forest productivity by 10 to 25 percent, with traditional chemical insecticides commonly used in Pakistan. The present study, however, aimed to assess the effectiveness of ten different insecticides in controlling subterranean termites at various concentrations and time intervals. Fipronil and Chlorpyrifos were the most effective insecticides at a concentration of 125 ppm, resulting in 100% mortality rates after 24 hours of exposure, while Emamectin Benzoate had the lowest mortality rates, but gradually increased over time. All insecticides tested at a concentration of 250 ppm resulted in varying degrees of mortality rates, with Imidacloprid, Fipronil, and Bifenthrin being the most effective. At a concentration of 500 ppm, all insecticides were effective, with Imidacloprid showing the fastest onset of mortality. Similarly, all insecticides at a concentration of 1000 ppm were effective, with Fipronil being the most effective insecticide. The data suggested that some insecticides were more effective than others in controlling subterranean termites, and the duration of exposure also played a crucial role in the effectiveness of the insecticides. The study found that higher dosages of new chemistry-based termiticides result in maximum subterranean termite mortality after a minimum exposure time. Fipronil, Imidacloprid, and Bifenthrin were the most effective treatments achieving 100% termite mortality at specific dosages and exposure times, while Chlorfenapyr and Emamectin Benzoate showed lower effectiveness. The new chemistry insecticides are considered eco-friendly, safe for humans and non-target fauna, and might be a competent choice for integrated pest management programs
Chemotherapy of Tomato Mosaic Disease using Ribavirin and 8-Azaguanine
Authors: Khaskheli Muhammad Sharif , Hajano Jamal-U-Ddin , Nizamani Zubair Ahmed , Gilal Arfan Ahmed , Jatoi Ghulam Hussain , Khan Malik Abdullah , Khan Asad Ali
Published: May 2023

Tomato mosaic disease (ToMD) caused by Tomato mosaic virus (ToMV) is a major threat to tomato production globally. In Pakistan, tomato is one of the most popular vegetables, and ToMD causes significant losses in fruit production, quality, and size. Various management strategies are implemented to control the disease. In this study, the efficacy of chemotherapy using ribavirin and 8-azaguanine was investigated. Seedlings of tomato plants were inoculated with sap from symptomatic tomato plants using the sap transmission technique to test the pathogenicity of the virus. Disease incidence and severity were recorded at weekly intervals for one month after inoculation. Ribavirin and 8-azaguanine were applied to tomato plants at different concentrations, and disease incidence and severity were observed weekly for one month after treatment. The results showed that the mechanically inoculated plants exhibited characteristic symptoms of ToMD, such as a mosaic pattern of color on the leaves. The disease incidence did not reduce with the application of ribavirin and 8-azaguanine, but the severity of the disease was significantly reduced. The plants treated with 1000 µM of ribavirin and 8-azaguanine had significantly lower severity scores compared to the untreated plants. However, the treated plants did not recover from the disease. The study found that ribavirin and 8-azaguanine are effective chemotropic agents in reducing the severity of ToMD, although they cannot cure the disease completely. Further studies are required to investigate the underlying mechanism of how ribavirin and 8-azaguanine suppress the symptoms of ToMD
Surveillance of Bacterial Canker of Peach in Azad Jammu and Kashmir, and its Bio-Management
Authors: Mehmood Basharat , Saeed Muhammad , Rehman Asif Ur , Saleem Saqib , Khan Muhammad Riaz , Younas Muhammad Tahir , Shafqat Muhammad , Khan Zahid Hussain , Rehman Shafiq-ur- , Hussain Sajjad
Published: May 2023

Bacterial canker of peach caused by Pseudomonas syringae is an increasing problem in Azad Jammu Kashmir with more than 50 pathovars on the basis of host. A detailed survey was conducted in peach growing areas of Azad Jammu and Kashmir for the determination of disease prevalence and incidence. Pathogen was isolated and characterized from the collected samples using LOPAT and GaTTA scheme. Furthermore the results of biochemical identification was confirmed using PCR followed by sequencing of obtained expected bands. For the bio-management of virulent pathogenic strains indigenous rhizobacterial isolates were obtained, characterized and evaluated using dual culture as well as in a greenhouse pot experiment against P. syringae pathovars. During a positive sampling method used for the surveillance it was found that maximum disease prevalence was 75% in district Bagh while there was 25% disease prevalence found in Haveli and Sudhanoti. Similarly maximum disease incidence was found in district Bagh that was 16%. A total of 32 isolates were recovered from the collected samples that were further screened on the basis of their virulence. It was found that the total of 18 isolates screened were similar to the already reported strains of P. syringae pv. syringae (Pss) on the basis of biochemical and molecular tools. From total 17 rhizobacterial isolates recovered were subjected to dual culture technique and was found that 06 isolates showed promising zone of inhibition upto 11.5 mm. The results of greenhouse evaluation revealed that the minimum disease incidence was recorded 3% using R-9 and R-17 in consortium against Pss as compared to the control treatment (39%). It was concluded that the ecofriendly management practices against this destructive disease must be adopted and appreciated
ANALYSIS OF STUDENTS’ PERCEIVED EASE OF USE AND RISKS OF USING DIGITAL WALLETS (E-WALLET) IN BANTEN
Authors: Purba Arini A. , Atriani Dewi , Husain Sabrina Wardatul Jannah , Sampetoding Eliyah A M , Sunani Avi
Published: May 2023

In the Pandemic Covid 19 era, technological developments are required to innovate continuously. One of the rapidly growing technological developments is the use of one of the Fintech, namely E-wallet. E-wallet is a technology that makes it easy for users to make payment transactions. The emergence of this E-wallet has had a significant impact, especially on young people who like an instant lifestyle. The research model is looking at two perceptions, namely the perception ease of use and the perception of risk. This research uses quantitative methods with data collection techniques using primary data. Primary data was obtained from the distribution of online questionnaires to 100 active students who using e-wallet in Banten. The results of this study was more than half of the respondent perceived that e wallet was easy and safety to use.
SECTORAL AND HOME COUNTRY DISTRIBUTION OF FOREIGN DIRECT INVESTMENT IN INDONESIA
Authors: Ramdhan Dadang
Published: May 2023

This study investigates the distribution of Foreign Direct Investment (FDI) across Indonesian economic sectors and home countries. Using descriptive statistics analysis of secondary data, the result shows that on average, FDI dominated the share of total investment, while domestic investment (DI) led the number of projects in Indonesia. FDI and DI mostly inflow to the chemical and pharmaceutical industry which is a part of manufacturing industries. The largest contributions of total FDI share come from Singapore and Japan. Investors from Japan reached the largest share of investment while investors from Singapore dominated the number of projects across Indonesian regions. Singapore reached the highest FDI share in Banten, Jakarta, Jawa Timur, Kalimantan Barat, Kalimantan Selatan, Kalimantan Tengah, Kepulauan Riau,Riau, Maluku Utara, Papua Barat, Sulawesi Utara, Sulawesi Barat, Sulawesi Selatan, and Sumatera Utara. Japan experienced the highest FDI in Jawa Barat and Jawa Tengah. This study can map the preference of investors from each home country. Investors from Australia and Mauritius mostly preferred to invest in the coal mining sector. Investors from Japan mostly preferred transport-related industries especially the industry of spare parts and accessories for four or more wheel motor vehicles. Investors from Singapore mostly selected telecommunication industries. Investors from South Korea mostly preferred to invest in plastic-related industries and processing industries. Some Investors from China invested in the electricity industry. Many investors from France also invested in the water supply sector. And Investors from the Republic of China mostly preferred to invest in the pulp, paper, and paperboard industry. The Indonesian Government needs to concern about the general characteristics of investors in home countries in attracting foreign investors. For policy purposes, knowing such characteristics provides scientific reasons for a government to have distinct strategies between different targeted home countries in order to attract foreign investors.
THE INFLUENCE OF HUMAN RESOURCES COMPETENCE, E-COMMERCE, AND WORKING CAPITAL ON MSME PERFORMANCE POST COVID-19
Authors: Nurlaila  , Desmiyawati  , Nurulita Suci
Published: May 2023

This study aims to analyze the effect of human resource competence, e-commerce, and working capital on the performance of MSMEs post-covid-19 in Meranti Islands Regency. The data used in this study is primary data, with a questionnaire as an instrument. The method used for sample selection is non-probability sampling technique. In this study, the total MSMEs in Meranti Islands Regency affected by COVID-19 were 8696 MSMEs. The research sample is 120 SMEs. However, only 100 MSMEs answered the questionnaire and could be processed. The data analysis technique used in this study is multiple linear regression analysis using Statistical Product and Service Solution (SPSS) data processing software version 23. The results show that the competence of human resources, e-commerce, and working capital affect the performance of MSMEs.
Cardiac output estimated from an uncalibrated radial blood pressure waveform: validation in an in-silico-generated population
Authors: Bikia Vasiliki , Rovas Georgios , Stergiopulos Nikolaos
Published: May 2023

Background: Cardiac output is essential for patient management in critically ill patients. The state-of-the-art for cardiac output monitoring bears limitations that pertain to the invasive nature of the method, high costs, and associated complications. Hence, the determination of cardiac output in a non-invasive, accurate, and reliable way remains an unmet need. The advent of wearable technologies has directed research towards the exploitation of wearable-sensed data to improve hemodynamical monitoring.

Methods: We developed an artificial neural networks (ANN)-enabled modelling approach to estimate cardiac output from radial blood pressure waveform. In silico data including a variety of arterial pulse waves and cardiovascular parameters from 3,818 virtual subjects were used for the analysis. Of particular interest was to investigate whether the uncalibrated, namely, normalized between 0 and 1, radial blood pressure waveform contains sufficient information to derive cardiac output accurately in an in silico population. Specifically, a training/testing pipeline was adopted for the development of two artificial neural networks models using as input: the calibrated radial blood pressure waveform (ANNcalradBP), or the uncalibrated radial blood pressure waveform (ANNuncalradBP).

Results: Artificial neural networks models provided precise cardiac output estimations across the extensive range of cardiovascular profiles, with accuracy being higher for the ANNcalradBP. Pearson’s correlation coefficient and limits of agreement were found to be equal to [0.98 and (−0.44, 0.53) L/min] and [0.95 and (−0.84, 0.73) L/min] for ANNcalradBP and ANNuncalradBP, respectively. The method’s sensitivity to major cardiovascular parameters, such as heart rate, aortic blood pressure, and total arterial compliance was evaluated.

Discussion: The study findings indicate that the uncalibrated radial blood pressure waveform provides sample information for accurately deriving cardiac output in an in silico population of virtual subjects. Validation of our results using in vivo human data will verify the clinical utility of the proposed model, while it will enable research applications for the integration of the model in wearable sensing systems, such as smartwatches or other consumer devices.
Biosynthesis of phyto-functionalized silver nanoparticles using olive fruit extract and evaluation of their antibacterial and antioxidant properties
Authors: Ullah Sami , Khalid Rimsha , Rehman Muhammad F. , Irfan Muhammad I. , Abbas Azhar , Alhoshani Ali , Anwar Farooq , Amin Hatem M. A.
Published: May 2023

The green synthesis of nanomaterials is of utmost interest as it offers an eco-friendly approach over chemical synthetic routes. However, the reported biosynthesis methods are often time-consuming and require heating or mechanical stirring. The current study reports a facile one-pot biosynthesis of silver nanoparticles (AgNPs) mediated by olive fruit extract (OFE) and sunlight irradiation of only 20 s. OFE acts as both a reducing and a capping agent for the formation of OFE-capped AgNPs (AgNPs@OFE). The as-synthesized NPs were systematically characterized by UV-vis spectrometry, Fourier transform infrared (FTIR) spectroscopy, scanning electrochemical microscopy with energy-dispersive X-ray (SEM-EDX), X-ray diffraction (XRD), dynamic light scattering (DLS), and cyclic voltammetry. SEM images confirmed the successful formation of monodispersed spherical AgNPs@OFE of approximately 77 nm. FTIR spectroscopy suggested the involvement of functional groups of phytochemicals from the OFE in the capping and reduction of Ag+to Ag. The particles revealed excellent colloidal stability as evidenced from the high zeta potential (ZP) value (−40 mV). Interestingly, using the disk diffusion method, AgNPs@OFE revealed higher inhibition efficiency against Gram-negative bacteria (Escherichia coli,Klebsiella oxytoca, and extensively drug-resistant (XDR)Salmonella typhi) than Gram-positive bacteria (Staphylococcus aureus), withEscherichia colishowing the highest inhibition zone of 27 mm. In addition, AgNPs@OFE exhibited maximum potent antioxidant scavenging potential against H2O2, followed by DPPH, O2−, and OH−free radicals. Overall, OFE can be considered an effective source for the sustainable production of stable AgNPs with potential antioxidant and antibacterial activities for biomedical applications.
Modeling cell-mediated immunity in human type 1 diabetes by engineering autoreactive CD8+ T cells
Authors: Peters Leeana D. , Yeh Wen-I , Arnoletti Juan M. , Brown Matthew E. , Posgai Amanda L. , Mathews Clayton E. , Brusko Todd M.
Published: May 2023

The autoimmune pathogenesis of type 1 diabetes (T1D) involves cellular infiltration from innate and adaptive immune subsets into the islets of Langerhans within the pancreas; however, the direct cytotoxic killing of insulin-producing β-cells is thought to be mediated primarily by antigen-specific CD8+ T cells. Despite this direct pathogenic role, key aspects of their receptor specificity and function remain uncharacterized, in part, due to their low precursor frequency in peripheral blood. The concept of engineering human T cell specificity, using T cell receptor (TCR) and chimeric antigen receptor (CAR)-based approaches, has been demonstrated to improve adoptive cell therapies for cancer, but has yet to be extensively employed for modeling and treating autoimmunity. To address this limitation, we sought to combine targeted genome editing of the endogenous TCRα chain gene (TRAC) via CRISPR/Cas9 in combination with lentiviral vector (LV)-mediated TCR gene transfer into primary human CD8+ T cells. We observed that knockout (KO) of endogenous TRAC enhanced de novo TCR pairing, which permitted increased peptide:MHC-dextramer staining. Moreover, TRAC KO and TCR gene transfer increased markers of activation and effector function following activation, including granzyme B and interferon-γ production. Importantly, we observed increased cytotoxicity toward an HLA-A*0201+ human β-cell line by HLA-A*02:01 restricted CD8+ T cells engineered to recognize islet-specific glucose-6-phosphatase catalytic subunit (IGRP). These data support the notion of altering the specificity of primary human T cells for mechanistic analyses of autoreactive antigen-specific CD8+ T cells and are expected to facilitate downstream cellular therapeutics to achieve tolerance induction through the generation of antigen-specific regulatory T cells.
Successful treatment of severe immune checkpoint inhibitor associated autoimmune hepatitis with basiliximab: a case report
Authors: Zarrabi Maiah , Hamilton Camille , French Samuel W. , Federman Noah , Nowicki Theodore S.
Published: May 2023

Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) and its corresponding ligand PD-L1 are being increasingly used for a wide variety of cancers, including refractory sarcomas. Autoimmune hepatitis is a known side effect of ICIs, and is typically managed with broad, non-specific immunosuppression. Here, we report a case of severe autoimmune hepatitis occurring after anti-PD-1 therapy with nivolumab in a patient with osteosarcoma. Following prolonged unsuccessful treatment with intravenous immunoglobulin, steroids, everolimus, tacrolimus, mycophenolate, and anti-thymoglobulin, the patient was eventually treated with the anti-CD25 monoclonal antibody basiliximab. This resulted in prompt, sustained resolution of her hepatitis without significant side effects. Our case demonstrates that basiliximab may be an effective therapy for steroid-refractory severe ICI-associated hepatitis.
Antibodies against Porphyromonas gingivalis in serum and saliva and their association with rheumatoid arthritis and periodontitis. Data from two rheumatoid arthritis cohorts in Sweden
Authors: Svärd Anna , Kastbom Alf , Ljungberg Karin Roos , Potempa Barbara , Potempa Jan , Persson G. Rutger , Renvert Stefan , Berglund Johan Sanmartin , Söderlin Maria K.
Published: May 2023

Background

Periodontitis and oral pathogenic bacteria can contribute to the development of rheumatoid arthritis (RA). A connection between serum antibodies to Porphyromonas gingivalis (P. gingivalis) and RA has been established, but data on saliva antibodies to P. gingivalis in RA are lacking. We evaluated antibodies to P. gingivalis in serum and saliva in two Swedish RA studies as well as their association with RA, periodontitis, antibodies to citrullinated proteins (ACPA), and RA disease activity.

Methods

The SARA (secretory antibodies in RA) study includes 196 patients with RA and 101 healthy controls. The Karlskrona RA study includes 132 patients with RA ≥ 61 years of age, who underwent dental examination. Serum Immunoglobulin G (IgG) and Immunoglobulin A (IgA) antibodies and saliva IgA antibodies to the P. gingivalis–specific Arg-specific gingipain B (RgpB) were measured in patients with RA and controls.

Results

The level of saliva IgA anti-RgpB antibodies was significantly higher among patients with RA than among healthy controls in multivariate analysis adjusted for age, gender, smoking, and IgG ACPA (p = 0.022). Saliva IgA anti-RgpB antibodies were associated with RA disease activity in multivariate analysis (p = 0.036). Anti-RgpB antibodies were not associated with periodontitis or serum IgG ACPA.

Conclusion

Patients with RA had higher levels of saliva IgA anti-RgpB antibodies than healthy controls. Saliva IgA anti-RgpB antibodies may be associated with RA disease activity but were not associated with periodontitis or serum IgG ACPA. Our results indicate a local production of IgA anti-RgpB in the salivary glands that is not accompanied by systemic antibody production.
A multifactorial analysis of FAP to regulate gastrointestinal cancers progression
Authors: Cai Jialing , Yang Depeng , Sun Handi , Xiao Lixing , Han Fang , Zhang Mengmeng , Zhou Lu , Jiang Meiyi , Jiang Qinghua , Li Yu , Nie Huan
Published: May 2023

Background

Fibroblast activation protein (FAP) is a cell-surface serine protease that has both dipeptidyl peptidase as well as endopeptidase activities and could cleave substrates at post-proline bond. Previous findings showed that FAP was hard to be detected in normal tissues but significantly up-regulated in remodeling sites like fibrosis, atherosclerosis, arthritis and embryonic tissues. Though increasing evidence has demonstrated the importance of FAP in cancer progression, no multifactorial analysis has been developed to investigate its function in gastrointestinal cancers until now.

Methods

By comprehensive use of datasets from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), scTIME Portal and Human Protein Atlas (HPA), we evaluated the carcinogenesis potential of FAP in gastrointestinal cancers, analyzing the correlation between FAP and poor outcomes, immunology in liver, colon, pancreas as well as stomach cancers. Then liver cancer was selected as example to experimentally validate the pro-tumor and immune regulative role of FAP in gastrointestinal cancers.

Results

FAP was abundantly expressed in gastrointestinal cancers, such as LIHC, COAD, PAAD and STAD. Functional analysis indicated that the highly-expressed FAP in these cancers could affect extracellular matrix organization process and interacted with genes like COL1A1, COL1A2, COL3A1 and POSTN. In addition, it was also observed that FAP was positively correlated to M2 macrophages infiltration across these cancers. To verify these findings in vitro, we used LIHC as example and over-expressed FAP in human hepatic stellate LX2 cells, a main cell type that produce FAP in tumor tissues, and then investigate its role on LIHC cells as well as macrophages. Results showed that the medium from FAP-over-expressed LX2 cells could significantly promote the motility of MHCC97H and SK-Hep1 LIHC cells, increase the invasion of THP-1 macrophages and induce them into pro-tumor M2 phenotype.

Conclusion

In summary, we employed bioinformatic tools and experiments to perform a comprehensive analysis about FAP. Up-regulation of FAP in gastrointestinal cancers was primarily expressed in fibroblasts and contributes to tumor cells motility, macrophages infiltration and M2 polarization, revealing the multifactorial role of FAP in gastrointestinal cancers progression.
Comparative analysis of CAR T-cell therapy access for DLBCL patients: associated challenges and solutions in the four largest EU countries
Authors: Canales Albendea Miguel Á. , Canonico Pier Luigi , Cartron Guillaume , Deiters Barthold , Jommi Claudio , Marks Reinhard , Rioufol Catherine , Sancho Cia Juan M. , Santoro Armando , Wagner-Drouet Eva M.
Published: May 2023

Introduction

CAR T-cell therapy has emerged as a promising new immuno-oncology treatment that engages the patient’s immune system to fight certain hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). In the European Union (EU), CAR T-cell therapies have been approved for relapsed/refractory (R/R) DLBCL patients since 2018, but patient access is often still limited or delayed. This paper is aimed at discussing challenges to access and possible solutions in the largest four EU countries.

Methods

The analysis relied on literature review, market data collection, since homogeneous data coming from registries were not available, and discussion with experts coming from all four countries.

Results

We calculated that in 2020, between 58% and 83% of R/R DLBCL patients (EMA approved label population) or between 29% and 71% of the estimated medically eligible R/R DLBCL patients, were not treated with a licensed CAR T-cell therapy. Common challenges along the patient journey that may result in limited access or delays to CAR T-cell therapy were identified. These include timely identification and referral of eligible patients, pre-treatment funding approval by authorities and payers, and resource needs at CAR T-cell centers.

Discussion

These challenges, existing best practices and recommended focus areas for health systems are discussed here, with the aim to inform necessary actions for overcoming patient access challenges for current CAR T-cell therapies as well as for future cell and gene therapies.
Guidance on C-reactive protein point-of-care testing and complementary strategies to improve antibiotic prescribing for adults with lower respiratory tract infections in primary care
Authors: Van Hecke Oliver , Bjerrum Lars , Gentile Ivan , Hopstaken Rogier , Melbye Hasse , Plate Andreas , Verbakel Jan Y. , Llor Carl , Staiano Annamaria
Published: May 2023

The world faces the threat of increasing antimicrobial resistance, and there is growing consensus that swift action must be taken to improve the rational use of antibiotics and increase the stewardship of antibiotics to safeguard this key resource in modern healthcare. This paper provides the perspective of an international group of experts on the role of C-reactive protein point-of-care testing (CRP POCT) and other complementary strategies to improve antibiotic stewardship in primary care, with regards to the diagnosis and treatment of adult patients presenting symptoms of lower respiratory tract infections (LRTIs). It provides guidance regarding the clinical assessment of symptoms in combination with C-reactive protein (CRP) results, at the point of care, to support the management decision, and discusses enhanced patient communication and delayed prescribing as complementary strategies to decrease the inappropriate use of antibiotics. Recommendation: CRP POCT should be promoted to improve the identification of adults presenting with symptoms of LRTIs in primary care who might gain additional benefit from antibiotic treatment. Appropriateness of antibiotic use can be maximized when CRP POCT is used together with complementary strategies such as enhanced communication skills training and delayed prescribing in addition to routine safety netting.
Interferons in COVID-19: missed opportunities to prove efficacy in clinical phase III trials?
Authors: Brzoska Josef , von Eick Harald , Hündgen Manfred
Published: May 2023

Interferons were repeatedly used in the therapy of COVID-19 due to their antiviral effects. Three recently published randomized controlled clinical phase III trials (WHO SOLIDARITY, ACTT-3, and SPRINTER) missed their primary objectives, i.e., a significant therapeutic effect of interferons was not demonstrated in these studies. In only one randomized controlled phase III trial (TOGETHER), a significant reduction in the hospitalization rate was revealed. Our study analyzes these findings, gives possible explanations for the failure of interferons, provides a proposal on how these agents could be successfully used, and also highlights the limitations of their employment in COVID-19. Interferons are apparently beneficial only if the patients are in the early stage of this disease and when they are usually not hospitalized, i.e., if the patients do not require oxygen support and/or if corticosteroids are not yet indicated. Furthermore, a higher dosage than the one used in the long-term treatment of multiple sclerosis with interferon beta or of chronic viral hepatitis with interferon alpha or lambda should be employed to achieve a better therapeutic effect in COVID-19.
Unraveling the Metabolic Requirements of the Gut Commensal Bacteroides ovatus
Authors: Fultz Robert , Ticer Taylor , Ihekweazu Faith D. , Horvath Thomas D. , Haidacher Sigmund J. , Hoch Kathleen M. , Bajaj Meghna , Spinler Jennifer K. , Haag Anthony M. , Buffington Shelly A. , Engevik Melinda A.
Published: May 2023

Background: Bacteroidetes are the most common bacterial phylum in the mammalian intestine and the effects of several Bacteroides spp. on multiple facets of host physiology have been previously described. Of the Bacteroides spp., Bacteroides ovatus has recently garnered attention due to its beneficial effects in the context of intestinal inflammation. In this study, we aimed to examine model host intestinal physiological conditions and dietary modifications to characterize their effects on B. ovatus growth.

Methods and Results: Using Biolog phenotypic microarrays, we evaluated 62 primary carbon sources and determined that B. ovatus ATCC 8384 can use the following carbohydrates as primary carbon sources: 10 disaccharides, 4 trisaccharides, 4 polysaccharides, 4 polymers, 3 L-linked sugars, 6 D-linked sugars, 5 amino-sugars, 6 alcohol sugars, and 15 organic acids. Proteomic profiling of B. ovatus bacteria revealed that a significant portion of the B. ovatus proteome contains proteins important for metabolism. Among the proteins, we found glycosyl hydrolase (GH) familes GH2, GH5, GH20, GH 43, GH88, GH92, and GH95. We also identified multiple proteins with antioxidant properties and reasoned that these proteins may support B. ovatus growth in the GI tract. Upon further testing, we showed that B. ovatus grew robustly in various pH, osmolarity, bile, ethanol, and H2O2 concentrations; indicating that B. ovatus is a well-adapted gut microbe.

Conclusion: Taken together, we have demonstrated that key host and diet-derived changes in the intestinal environment influence B. ovatus growth. These data provide the framework for future work toward understanding how diet and lifestyle interventions may promote a beneficial environment for B. ovatus growth.