bluuebunny/crossref_metadata_2025 huggingface dataset:
Analisa Penerapan Pengendalian Risiko Pada Pembiayaan di BMT Rahmat Kediri
Authors: Oktapian Meldi Candra , Fauzi Ahmad
Published: April 2024

Manajemen risiko diperlukan untuk meningkatkan mutu lembaga keuangan mikro syariah semisal BMT. Penerapan manajemen risiko yang tepat mampu menciptakan sistem pengendalian internal yang baik dalam lembaga keuangan mikro syariah, sehingga dapat segera dilakukan tindakan korektif yang selaras dengan strategi dan cita-cita lembaga keuangan mikro syariah. Penelitian ini menggunakan pendekatan kualitatif dengan jenis penelitian deskriptif. Teknik pengumpulan data menggunakan metode observasi, metode wawancara dan metode dokumentasi. Hasil penelitian menyatakan bahwa Penerapan manajemen risiko pembiayaan pada BMT Rahmat menggunakan panduan survey prinsip 5C yang mana terdiri dari: Character, Capacity, Capital, Collateral, Condition of economic. Penerapan manajemen risiko pembiayaan pada BMT Rahmat dengan tiga tahapan mulai dari awal pembiayaan sampai penyelesian pembiayaan sesuai dengan teori menejemen risiko yang terdiri dari identifikasi risiko, pengukuran risiko, pemanytauan risiko, pengendalian risiko. Identifikasi, pengukuran dan pemantauan risiko serta pengendaliannya sudah dilakukan sejak tahap awal dan tahap kedua sedangkan tahap ketiga yang merupakan tahap penyelesaian pembiayaan bermasalah sudah masuk kategori pengendalian risiko.
Strategi Packaging Produk UMKM Oleh Rumah Kurasi Kediri dalam Meningkatkan Minat Beli Konsumen
Authors: Sutantri  , Syawahidul Haq Muhammad
Published: April 2024

Indonesia memiliki banyak sektor industri yang dapat dikembangkan, khususnya pada bidang makanan dan minuman. Beraneka jenis produk yang dihasilkan oleh para pelaku bisnis UMKM juga tidak kalah dari pengusaha besar. Kondisi persaingan pasar di Indonesia yang cukup kompetitif menjadi aspek yang tidak lepas dari perhatian, mereka harus saling bersaing untuk mampu menjadi yang diminati di pasar. Perlu adanya kurasi produk untuk melakukan pengecekan kualitas produk UMKM agar dapat memiliki nilai jual tinggi dalam sektor pasar tradisional, modern, dan juga internasional. Penelitian ini bertujuan guna mengetahui pengaruh kurasi packaging umkm yang dilakukan oleh rumah kurasi kediri dalam meningkatkan minat beli konsumen. Metode penelitian menggunakan pendekatan kualitatif deskriptif dengan penelitian lapangan (field research). Sumber data merupakan sumber primer yang didapat dari hasil wawancara dan observasi partisipatif dan sumber sekunder berupa website, dan beberapa dokumen tertulis. Teknik analisis data melalui tahap reduksi data, penyajian data dan penarikan kesimpulan. Hasil dari penelitian ini adalah bahwa dalam kemasan packaging harus tercantum detail produk secara lengkap yang akan membuat konsumen percaya dengan produk UMKM, Desain kemasan harus menarik sebagaimna prinsip desain, diskusi dan edukasi sebelum membuat desain kemasan merupakan suatu hal yang harus dilakukan untuk mencegah terjadinya salah persepsi antara desainer dan pelanggan, konsisten, tekun, serta jam terbang tinggi merupakan prasayrat untuk menjadi desainer yang mahir dan yang terpenting adalah pelayanan yang ramah.
The Impact of Different Basic Trust Types During Critical Situations: The Case of Saudi Arabia and Kuwait
Authors: Kaşıkcı Tamer , Yetim Mustafa
Published: April 2024

The primary objective of this study is to elucidate the impact of ontological security on states’ foreign policy preferences. The study posits that foreign policy preferences are closely related with their basic trust, a product of the intricate interplay between actor’s agentic capacity and its internal and external environment. This theoretical proposition is subsequently subjected to comparative examination within the contexts of Saudi Arabia and Kuwait. The study contends that despite sharing similar concerns regarding physical and ontological security, these two actors have pursued distinct foreign policy trajectories regarding the Arab uprisings and normalization with Israel that owe to differing types of basic trust. In doing so, the study aims to contribute to the ontological security literature from two perspectives: 1) to refine and elucidate the scope of the basic trust concept by reinterpreting it and highlighting its central role in ontological security analysis, and 2) to contribute to the practical applications of the field by applying the concepts developed in the ontological security literature to case studies of Saudi Arabia and Kuwait.
LEGISLATIVE CONFLICTS OF POSTPONEMENT OF SERVING A SENTENCE
Authors: Smirnov Aleksandr Mihajlovich
Published: April 2024

This article discusses the possibility of postponement of execution and serving of punishment fixed in the law. The social necessity of the existence of this institution of law is determined by normative legal acts defining the strategy of development of a healthy, law-abiding, value-oriented society. It is noted that the legal totality under study provides the possibility of implementing socially useful institutions, such as full-fledged upbringing and education of children in the family; voluntary and conscientious treatment for drug addiction; assistance to vulnerable categories of citizens in connection with the occurrence of various emergency situations. The text of the work analyzes the norms of the Criminal and Criminal Procedure Codes of the Russian Federation, regulating the grounds and procedure for granting a convicted person a reprieve from serving his sentence. The author points out a certain legislative inconsistency in the issues of legal regulation of the object of research. In conclusion, the general idea of further reforming the institution of postponement of serving a sentence is proposed.
Educational work with convicts as a subinstitute of penal enforcement law
Authors: Teplyashin Pavel Vladimirovich
Published: April 2024

The article substantiates that the means of correction of convicts are subinstitutions of penal enforcement law. Arguments of special importance of such means of correction as educational work are given. The legal nature of the subinstitute of educational work with convicts is established. The conclusion is formulated that this subinstitute is a public-law procedural permanently operating complex subinstitute of federal action dispersed in several legal acts. It consists of several normative regulations of an imperative nature, regulating first of all the features of the legal content of the criminal-executive legal relations arising and existing regarding the correction of persons serving a criminal sentence.
Section 7 of the Criminal Code of the People’s Republic of China «Parole»: author’s translation and a brief comparative analysis with article 79 Criminal Code of the Russian Federation
Authors: Bal’chindorzhieva Ojuna , Mjahanova Aleksandra , Skiba Andrey
Published: April 2024

The article contains the text of the author’s translation of articles 81-86 sec. 7 «Parole» of the Criminal Code of the People’s Republic of China. Within the framework of a brief comparative analysis with Article 79 of the Criminal Code of the Russian Federation, a number of features of the institution of parole under Chinese law are highlighted: it is focused on preventing the commission of new crimes; it is not applied to certain categories of persons; correctional influence by state bodies and public organizations continues after the release of a person, etc.
The procedural participation of non-governmental organisations and national human rights institutions within the European Convention system and beyond
Authors:   , Erken Elif
Published: April 2024

Every year, thousands of individuals turn to the European Court of Human Rights in Strasbourg alleging that a state party to the European Convention on Human Rights has violated one or more of their rights enshrined in the Convention. In the event that the Court agrees with the applicant, and finds that the state in question has failed to protect the individual against a violation of a Convention right, the judgment is transmitted to the Council of Europe’s Committee of Ministers, which keeps track of the implementation process of the Court’s judgments. However, Strasbourg is not the sole domain of states, individual applicants, the Court, and the Committee of Ministers. Non-governmental organisations are present at virtually every stage, from the beginning of a case to its very end. Although to a lesser extent, National Human Rights Institutions are involved as well. This dissertation explores the role of these two actors within the European Convention system and beyond and, in doing so, provides a further, deeper understanding of their participation. More particularly, by employing qualitative empirical methods, it considers firstly, the current involvement of these actors in the execution process of the Court’s judgments. Secondly, it examines whether a greater role for these actors is desirable, thereby drawing inspiration from the role given to non-governmental organisations under the European Social Charter and from the participation of national human rights institutions in the Inter-American System of Human Rights.
PELATIHAN JURU BUKU KSP/USP KOPERASI BERBASIS KOMPETENSI SKKNI KABUPATEN/KOTA DI PROVINSI SUMATERA SELATAN
Authors: Setyanto Eddy , Hidayat R Taufik , Andini Lembah Dewi
Published: April 2024

Cooperatives as economic entities based on the principles of togetherness and shared prosperity require the existence of bookkeepers who are skilled and knowledgeable in managing finances and administration. Training for KSP/USP Cooperative Bookkeepers Based on Competency in Districts/Cities in South Sumatra Province has had a positive impact on the competency, skills and knowledge of Savings and Loans Cooperative/Usp bookkeepers. The training methods used include a practical approach with a focus on direct application in the cooperative context. The training participants consisted of cooperative bookkeepers from various cooperatives in different regions in South Sumatra province. Training focuses on basic understanding of organizational management, cooperative accounting, cash flow management, accurate financial reporting, and the application of technology in administration. The training results showed a significant increase in the bookkeeper's technical skills and conceptual knowledge after attending the training. Participants also reported increased confidence in managing their day-to-day administrative tasks. Apart from that, this training also encourages collaboration between cooperatives and the exchange of best practices in financial management. The final result is that participants are provided with a certificate from BNSP. In conclusion, competency-based training has proven effective in improving the skills and knowledge of cooperative bookkeepers. This has important implications in increasing the operational efficiency of cooperatives as well as increasing members' and stakeholders' trust in cooperative financial management
SISTEM MANAJEMEN PEMANTAUAN KEBUTUHAN GIZI ANAK DALAM MASA PERTUMBUHAN DI DESA KARANGJAYA
Authors: Budiman Indra Adi , Chaniago Herman , Abidin Dindin , Azhari Adli , Ridha Kusuma Rizki
Published: April 2024

Karangjaya Village is a rural village where people work in agriculture or small businesses. The majority of the population lives below the poverty line, and access to health services and nutritious food is limited. As a result, child health is a major concern in Karangjaya Village with high rates of malnutrition and stunting in children under five years old. The aim of the community service is to help support an effective and efficient nutrition monitoring programme, so as to help reduce malnutrition and better manage children's health. The method of implementing the service applies counselling in the form of organising seminars for 20 mothers in Karangjaya Village. The results showed an increase in community knowledge about healthy eating patterns, which is expected to reduce the number of malnutrition in Karangjaya Village. Monitoring and evaluation showed positive results, with some children showing improved nutritional status after receiving appropriate treatment. Thus, the nutrition management system in Karangjaya Village contributes significantly to improving children's health and nutrition.
BayesAge: A maximum likelihood algorithm to predict epigenetic age
Authors: Mboning Lajoyce , Rubbi Liudmilla , Thompson Michael , Bouchard Louis-S. , Pellegrini Matteo
Published: April 2024

Introduction: DNA methylation, specifically the formation of 5-methylcytosine at the C5 position of cytosine, undergoes reproducible changes as organisms age, establishing it as a significant biomarker in aging studies. Epigenetic clocks, which integrate methylation patterns to predict age, often employ linear models based on penalized regression, yet they encounter challenges in handling missing data, count-based bisulfite sequence data, and interpretation.

Methods: To address these limitations, we introduce BayesAge, an extension of the scAge methodology originally designed for single-cell DNA methylation analysis. BayesAge employs maximum likelihood estimation (MLE) for age inference, models count data using binomial distributions, and incorporates LOWESS smoothing to capture non-linear methylation-age dynamics. This approach is tailored for bulk bisulfite sequencing datasets.

Results: BayesAge demonstrates superior performance compared to scAge. Notably, its age residuals exhibit no age association, offering a less biased representation of epigenetic age variation across populations. Furthermore, BayesAge facilitates the estimation of error bounds on age inference. When applied to down-sampled data, BayesAge achieves a higher coefficient of determination between predicted and actual ages compared to both scAge and penalized regression.

Discussion: BayesAge presents a promising advancement in epigenetic age prediction, addressing key challenges encountered by existing models. By integrating robust statistical techniques and tailored methodologies for count-based data, BayesAge offers improved accuracy and interpretability in predicting age from bulk bisulfite sequencing datasets. Its ability to estimate error bounds enhances the reliability of age inference, thereby contributing to a more comprehensive understanding of epigenetic aging processes.
Probing the active site of Class 3 L-asparaginase by mutagenesis. I. Tinkering with the zinc coordination site of ReAV
Authors: Pokrywka Kinga , Grzechowiak Marta , Sliwiak Joanna , Worsztynowicz Paulina , Loch Joanna I. , Ruszkowski Milosz , Gilski Miroslaw , Jaskolski Mariusz
Published: April 2024

ReAV, the inducible Class-3 L-asparaginase from the nitrogen-fixing symbiotic bacterium Rhizobium etli, is an interesting candidate for optimizing its enzymatic potential for antileukemic applications. Since it has no structural similarity to known enzymes with this activity, it may offer completely new ways of approach. Also, as an unrelated protein, it would evade the immunological response elicited by other asparaginases. The crystal structure of ReAV revealed a uniquely assembled protein homodimer with a highly specific C135/K138/C189 zinc binding site in each subunit. It was also shown before that the Zn2+ cation at low and optimal concentration boosts the ReAV activity and improves substrate specificity, which indicates its role in substrate recognition. However, the detailed catalytic mechanism of ReAV is still unknown. In this work, we have applied site-directed mutagenesis coupled with enzymatic assays and X-ray structural analysis to elucidate the role of the residues in the zinc coordination sphere in catalysis. Almost all of the seven ReAV muteins created in this campaign lost the ability to hydrolyze L-asparagine, confirming our predictions about the significance of the selected residues in substrate hydrolysis. We were able to crystallize five of the ReAV mutants and solve their crystal structures, revealing some intriguing changes in the active site area as a result of the mutations. With alanine substitutions of Cys135 or Cys189, the zinc coordination site fell apart and the mutants were unable to bind the Zn2+ cation. Moreover, the absence of Lys138 induced atomic shifts and conformational changes of the neighboring residues from two active-site Ser-Lys tandems. Ser48 from one of the tandems, which is hypothesized to be the catalytic nucleophile, usually changes its hydration pattern in response to the mutations. Taken together, the results provide many useful clues about the catalytic mechanism of the enzyme, allowing one to cautiously postulate a possible enzymatic scenario.
Discussion paper: implications for the further development of the successfully in emergency medicine implemented AUD2IT-algorithm
Authors: Przestrzelski Christopher , Jakob Antonina , Jakob Clemens , Hoffmann Felix R.
Published: April 2024

The AUD2IT-algorithm is a tool to structure the data, which is collected during an emergency treatment. The goal is on the one hand to structure the documentation of the data and on the other hand to give a standardised data structure for the report during handover of an emergency patient. AUD2IT-algorithm was developed to provide residents a documentation aid, which helps to structure the medical reports without getting lost in unimportant details or forgetting important information. The sequence of anamnesis, clinical examination, considering a differential diagnosis, technical diagnostics, interpretation and therapy is rather an academic classification than a description of the real workflow. In a real setting, most of these steps take place simultaneously. Therefore, the application of the AUD2IT-algorithm should also be carried out according to the real processes. A big advantage of the AUD2IT-algorithm is that it can be used as a structure for the entire treatment process and also is entirely usable as a handover protocol within this process to make sure, that the existing state of knowledge is ensured at each point of a team-timeout. PR-E-(AUD2IT)-algorithm makes it possible to document a treatment process that, in principle, does not have to be limited to the field of emergency medicine. Also, in the outpatient treatment the PR-E-(AUD2IT)-algorithm could be used and further developed. One example could be the preparation and allocation of needed resources at the general practitioner. The algorithm is a standardised tool that can be used by healthcare professionals of any level of training. It gives the user a sense of security in their daily work.
Shear wave velocity prediction based on 1DCNN-BiLSTM network with attention mechanism
Authors: Feng Gang , Liu Wen-Qing , Yang Zhe , Yang Wei
Published: April 2024

The Shear wave (S-wave) velocity is an essential parameter in reservoir characterization and evaluation, fluid identification, and prestack inversion. However, the cost of obtaining S-wave velocities directly from dipole acoustic logging is relatively high. At the same time, conventional data-driven S-wave velocity prediction methods exhibit several limitations, such as poor accuracy and generalization of empirical formulas, inadequate exploration of logging curve patterns of traditional fully connected neural networks, and gradient explosion and gradient vanishing problems of recurrent neural networks (RNNs). In this study, we present a reliable and low-cost deep learning (DL) approach for S-wave velocity prediction from real logging data to facilitate the solution of these problems. We designed a new network sensitive to depth sequence logging data using conventional neural networks. The new network is composed of one-dimensional (1D) convolutional, bidirectional long short-term memory (BiLSTM), attention, and fully connected layers. First, the network extracts the local features of the logging curves using a 1D convolutional layer, and then extracts the long-term sequence features of the logging curves using the BiLSTM layer, while adding an attention layer behind the BiLSTM network to further highlight the features that are more significant for S-wave velocity prediction and minimize the influence of other features to improve the accuracy of S-wave velocity prediction. Afterward, the nonlinear mapping relationship between logging data and S-wave velocity is established using several fully connected layers. We applied the new network to real field data and compared its performance with three traditional methods, including a long short-term memory (LSTM) network, a back-propagation neural network (BPNN), and an empirical formula. The performance of the four methods was quantified in terms of their coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE). The new network exhibited better performance and generalization ability, with R2 greater than 0.95 (0.9546, 0.9752, and 0.9680, respectively), RMSE less than 57 m/s (56.29, 23.18, and 30.17 m/s, respectively), and MAE less than 35 m/s (34.68, 16.49, and 21.47 m/s, respectively) for the three wells. The test results demonstrate the efficacy of the proposed approach, which has the potential to be widely applied in real areas where S-wave velocity logging data are not available. Furthermore, the findings of this study can help for a better understanding of the superiority of deep learning schemes and attention mechanisms for logging parameter prediction.
Writing performance in primary grade: exploring the links between cognitive and motivational variables
Authors: Rocha Renata S. , Magalhães Sofia , Castro São Luís , Limpo Teresa
Published: April 2024

Current theoretical models of writing suggest that cognitive and motivational processes interact with each other during written production. However, despite the growing interest in motivational variables in writing, there are still few efforts to study them together with cognitive variables. Therefore, this study aimed to test the possibility that the cognitive processes of transcription and executive functions may be related to writing performance, through their link with the writing-motivational variables of self-efficacy and attitudes. For that, 157 Portuguese third and fourth graders planned and completed one opinion essay, performed transcription tasks, and completed motivation-related questionnaires. Furthermore, schoolteachers completed an executive function questionnaire about each student and provided their school grades. Results showed that motivation, specifically self-efficacy, did not predict Grade 3 and 4 writing performance. However, attitudes were predictors of written planning and text length. More specifically, attitudes and handwriting fluency contributed to text length just as attitudes and spelling accuracy contributed to written planning. There was no evidence of indirect effects from cognitive variables on writing performance via motivation variables. These findings provide original information on the links between cognition and motivation in writing, which may be useful to guide the teaching of writing. In line with effective instructional approaches to writing, current findings further support the importance of jointly targeting the cognitive and affective dimensions of writing.
Use of specifications-based grading in an online, asynchronous graduate organic chemistry course
Authors: Moster Caleb A. , Zingales Sarah Kathryn
Published: April 2024

Specifications-based grading is an alternative grading scheme that emphasizes student proficiency of learning objectives. Course grades are determined by the number of objectives completed rather than the number of points accumulated. At the University of Saint Joseph, CHEM 510 Intermediate Organic Chemistry is the foundation course that all incoming graduate students take in their first semester of the fully online, asynchronous MS programs in Chemistry and Biochemistry. Students in CHEM 510 complete the entire course online and at their own pace within the structured due dates, which presents unique challenges compared with synchronous learning modalities. With these considerations in mind, CHEM 510 was revised to use a specifications-based grading scheme with an a la carte assessment menu and token system. Generally, students found the alternative grading scheme helpful, but they needed additional instructions and time to adjust to the new grading system. By the end of the semester, students expressed their appreciation for the ability to choose their assessment method, work at their own pace, and use the token system for extensions/retakes. The instructor found that implementation of specifications grading took greater time for the initial course setup, but did not require more time than points-based grading once the course began. One large positive outcome was that student-instructor interactions were more frequently about the content of the course rather than grades. Overall, there was a slight increase in the course’s pass rate compared to the pass rate prior to the change in grading modality. We believe that the implementation of the a la carte assessment menu accommodates a more diverse population of learners without sacrificing the integrity of student learning. Additionally, we believe that the diverse assessment opportunities were critical for the successful implementation of specifications-based learning in the online classroom environment, though further extension of the menu in synchronous, in-person classroom settings may be challenging.
Impact of industrial policy on urban green innovation: empirical evidence of China’s national high-tech zones based on double machine learning
Authors: Cao Wei , Jia Yu , Tan Benwei
Published: April 2024

Effective industrial policies need to be implemented, particularly aligning with environmental protection goals to drive the high-quality growth of China’s economy in the new era. Setting up national high-tech zones falls under the purview of both regional and industrial policies. Using panel data from 163 prefecture-level cities in China from 2007 to 2019, this paper empirically analyzes the impact of national high-tech zones on the level of urban green innovation and its underlying mechanisms. It utilizes the national high-tech zones as a quasi-natural experiment and employs a double machine learning model. The study findings reveal that the policy for national high-tech zones greatly enhances urban green innovation. This conclusion remains consistent even after adjusting the measurement method, empirical samples, and controlling for other policy interferences. The findings from the heterogeneity analysis reveal that the impact of the national high-tech zone policy on green innovation exhibits significant regional heterogeneity, with a particularly significant effect in the central and western regions. Among cities, there is a notable push for green innovation levels in second-tier, third-tier, and fourth-tier cities. The moderating effect results indicate that, at the current stage of development, transportation infrastructure primarily exerts a negative moderating effect on how the national high-tech zone policy impacts the level of urban green innovation. This research provides robust empirical evidence for informing the optimization of the industrial policy of China and the establishment of a future ecological civilization system.
Navigating equity in global access to genome therapy expanding access to potentially transformative therapies and benefiting those in need requires global policy changes
Authors: Lee Tsung-Ling , Sawai Tsutomu
Published: April 2024

In December 2023, the US Food and Drug Administration and the UK Medicines and Healthcare Products Regulatory Agency granted the first regulatory approval for genome therapy for sickle cell disease. This approval brings hope to those suffering from this debilitating genetic disease. However, several barriers may hinder global patient access, including high treatment costs, obtaining informed consent for minors, inadequate public health infrastructure, and insufficient regulatory oversight. These barriers reflect the structural inequalities inherent in global health governance, where patient access often depends on social and institutional arrangements. This article addresses concerns around informed consent, treatment costs, and patient access, and proposes corresponding policy reforms. We argue that these discussions should be framed within a broader global context that considers social and institutional structures, global research priorities, and a commitment to health equity.
Clinical relevance of HLA-DQ eplet mismatch and maintenance immunosuppression with risk of allosensitization after kidney transplant failure
Authors: Tran Jenny , Alrajhi Ibrahim , Chang Doris , Sherwood Karen R. , Keown Paul , Gill Jagbir , Kadatz Matthew , Gill John , Lan James H.
Published: April 2024

The optimal immunosuppression management in patients with a failed kidney transplant remains uncertain. This study analyzed the association of class II HLA eplet mismatches and maintenance immunosuppression with allosensitization after graft failure in a well characterized cohort of 21 patients who failed a first kidney transplant. A clinically meaningful increase in cPRA in this study was defined as the cPRA that resulted in 50% reduction in the compatible donor pool measured from the time of transplant failure until the time of repeat transplantation, death, or end of study. The median cPRA at the time of failure was 12.13% (interquartile ranges = 0.00%, 83.72%) which increased to 62.76% (IQR = 4.34%, 99.18%) during the median follow-up of 27 (IQR = 18, 39) months. High HLA-DQ eplet mismatches were significantly associated with an increased risk of developing a clinically meaningful increase in cPRA (p = 0.02) and de novo DQ donor-specific antibody against the failed allograft (p = 0.02). We did not observe these associations in patients with high HLA-DR eplet mismatches. Most of the patients (88%) with a clinically meaningful increase in cPRA had both a high DQ eplet mismatch and a reduction in their immunosuppression, suggesting the association is modified by immunosuppression. The findings suggest HLA-DQ eplet mismatch analysis may serve as a useful tool to guide future clinical studies and trials which assess the management of immunosuppression in transplant failure patients who are repeat transplant candidates.
Immune checkpoint inhibitors in the treatment of hepatocellular carcinoma
Authors: Akbulut Zeynep , Aru Başak , Aydın Furkan , Yanıkkaya Demirel Gülderen
Published: April 2024

Despite advances in cancer treatment, hepatocellular carcinoma (HCC), the most common form of liver cancer, remains a major public health problem worldwide. The immune microenvironment plays a critical role in regulating tumor progression and resistance to therapy, and in HCC, the tumor microenvironment (TME) is characterized by an abundance of immunosuppressive cells and signals that facilitate immune evasion and metastasis. Recently, anti-cancer immunotherapies, therapeutic interventions designed to modulate the immune system to recognize and eliminate cancer, have become an important cornerstone of cancer therapy. Immunotherapy has demonstrated the ability to improve survival and provide durable cancer control in certain groups of HCC patients, while reducing adverse side effects. These findings represent a significant step toward improving cancer treatment outcomes. As demonstrated in clinical trials, the administration of immune checkpoint inhibitors (ICIs), particularly in combination with anti-angiogenic agents and tyrosine kinase inhibitors, has prolonged survival in a subset of patients with HCC, providing an alternative for patients who progress on first-line therapy. In this review, we aimed to provide an overview of HCC and the role of the immune system in its development, and to summarize the findings of clinical trials involving ICIs, either as monotherapies or in combination with other agents in the treatment of the disease. Challenges and considerations regarding the administration of ICIs in the treatment of HCC are also outlined.
PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy
Authors: Ren Xiaohui , Wang Lijuan , Liu Likun , Liu Juan
Published: April 2024

Immunotherapy has been developed, which harnesses and enhances the innate powers of the immune system to fight disease, particularly cancer. PD-1 (programmed death-1) and PD-L1 (programmed death ligand-1) are key components in the regulation of the immune system, particularly in the context of cancer immunotherapy. PD-1 and PD-L1 are regulated by PTMs, including phosphorylation, ubiquitination, deubiquitination, acetylation, palmitoylation and glycosylation. PROTACs (Proteolysis Targeting Chimeras) are a type of new drug design technology. They are specifically engineered molecules that target specific proteins within a cell for degradation. PROTACs have been designed and demonstrated their inhibitory activity against the PD-1/PD-L1 pathway, and showed their ability to degrade PD-1/PD-L1 proteins. In this review, we describe how PROTACs target PD-1 and PD-L1 proteins to improve the efficacy of immunotherapy. PROTACs could be a novel strategy to combine with radiotherapy, chemotherapy and immunotherapy for cancer patients.
Aging brain: exploring the interplay between bone marrow aging, immunosenescence, and neuroinflammation
Authors: Müller Ludmila , Di Benedetto Svetlana
Published: April 2024

Aging is a complex process characterized by a myriad of physiological changes, including alterations in the immune system termed immunosenescence. It exerts profound effects on both the bone marrow and the central nervous system, with significant implications for immunosenescence in neurological contexts. Our mini-review explores the complex relationship between bone marrow aging and its impact on immunosenescence, specifically within the context of neurological diseases. The bone marrow serves as a crucial hub for hematopoiesis and immune cell production, yet with age, it undergoes significant alterations, including alterations in hematopoietic stem cell function, niche composition, and inflammatory signaling. These age-related shifts in the bone marrow microenvironment contribute to dysregulation of immune cell homeostasis and function, impacting neuroinflammatory processes and neuronal health. In our review, we aim to explore the complex cellular and molecular mechanisms that link bone marrow aging to immunosenescence, inflammaging, and neuroinflammation, with a specific focus on their relevance to the pathophysiology of age-related neurological disorders. By exploring this interplay, we strive to provide a comprehensive understanding of how bone marrow aging impacts immune function and contributes to the progression of neurological diseases in aging individuals. Ultimately, this knowledge can hold substantial promise for the development of innovative therapeutic interventions aimed at preserving immune function and mitigating the progression of neurological disorders in the elderly population.
The association between perceived cause of glaucoma and illness perceptions
Authors: Choe Eunice , Poleon Shervonne , Thomas Tracy , Racette Lyne
Published: April 2024

Purpose

The perceived cause of disease is an important factor that has been linked with treatment outcomes but has not been fully assessed in primary open-angle glaucoma (POAG). This study assessed the accuracy of patients’ perceived cause of POAG and identified associations between accuracy, illness perceptions, medication adherence, and quality of life (QoL).

Methods

The Brief Illness Perception Questionnaire (BIPQ) was used to assess illness perceptions and asked patients to rank the three most important causes of their disease in order of importance. POAG risk factors recognized by the American Academy of Ophthalmology were used to code responses as accurate or inaccurate based on the following three methods: (1) coding any reported cause, regardless of rank, (2) coding only the first-ranked cause, and (3) coding and weighting all reported causes. Medication adherence was measured electronically. QoL was measured using the Glaucoma Quality of Life questionnaire. Mann–Whitney U test was used to detect differences in illness perceptions, medication adherence, and QoL between accuracy groups.

Results

A total of 97 patients identified a cause of their POAG and were included in this analysis. A higher proportion of patients reported an accurate cause (86.6% using method 1, 78.4% using method 2, and 79.4% using method 3; all p < 0.001). Mean medication adherence was 86.0% ± 17.8 and was similar across accuracy groups (all p > 0.05). Using method 2 (p = 0.045) and method 3 (p = 0.028), patients who reported an accurate cause of their POAG believed that their illness would last for a longer time compared to patients who reported an inaccurate cause. Method 3 also revealed that patients who reported an accurate cause of their POAG had lower perceived understanding of their illness (p = 0.048) compared to patients who reported an inaccurate cause. There were no differences in QoL between accuracy groups (all p > 0.05).

Conclusion

This study highlights the association between perceived cause of POAG and illness perceptions related to knowledge level and POAG duration. Future studies should assess associations between perceived cause of disease and other critical dimensions of illness perception.
Whole-genome analysis suggesting probiotic potential and safety properties of Pediococcus pentosaceus DSPZPP1, a promising LAB strain isolated from traditional fermented sausages of the Basilicata region (Southern Italy)
Authors: Tathode Madhura S. , Bonomo Maria Grazia , Zappavigna Silvia , Mang Stefania Mirela , Bocchetti Marco , Camele Ippolito , Caraglia Michele , Salzano Giovanni
Published: April 2024

Introduction

Many lactic acid bacteria (LAB) strains are currently gaining attention in the food industry and various biological applications because of their harmless and functional properties. Given the growing consumer demand for safe food, further research into potential probiotic bacteria is beneficial. Therefore, we aimed to characterize Pediococcus pentosaceus DSPZPP1, a LAB strain isolated from traditional fermented sausages from the Basilicata region of Southern Italy.

Methods

In this study, we analyzed the whole genome of the P. pentosaceus DSPZPP1 strain and performed in silico characterization to evaluate its applicability for probiotics and use in the food industry.

Results and Discussion

The whole-genome assembly and functional annotations revealed many interesting characteristics of the DSPZPP1 strain. Sequencing raw reads were assembled into a draft genome of size 1,891,398 bp, with a G + C content of 37.3%. Functional annotation identified 1930 protein-encoding genes and 58 RNAs including tRNA, tmRNA, and 16S, 23S, and 5S rRNAs. The analysis shows the presence of genes that encode water-soluble B-group vitamins such as biotin, folate, coenzyme A, and riboflavin. Furthermore, the analysis revealed that the DSPZPP1 strain can synthesize class II bacteriocin, penocin A, adding importance to the food industry for bio-enriched food. The DSPZPP1 genome does not show the presence of plasmids, and no genes associated with antimicrobial resistance and virulence were found. In addition, two intact bacteriophages were identified. Importantly, the lowest probability value in pathogenicity analysis indicates that this strain is non-pathogenic to humans. 16 s rRNA-based phylogenetic analysis and comparative analysis based on ANI and Tetra reveal that the DSPZPP1 strain shares the closest evolutionary relationship with P. pentosaceus DSM 20336 and other Pediococcus strains. Analysis of carbohydrate active enzymes (CAZymes) identified glycosyl transferases (GT) as a main class of enzymes followed by glycoside hydrolases (GH). Our study shows several interesting characteristics of the isolated DSPZPP1 strain from fermented Italian sausages, suggesting its potential use as a promising probiotic candidate and making it more appropriate for selection as a future additive in biopreservation.
Epidemiological and clinical characteristics of death from hemorrhagic fever with renal syndrome: a meta-analysis
Authors: Lu Wei , Kuang Lin , Hu Yuxing , Shi Jialing , Li Qi , Tian Wen
Published: April 2024

Introduction

Hemorrhagic fever with renal syndrome (HFRS) is an acute infectious disease comprising five stages: fever, hypotension, oliguria, diuresis (polyuria), and convalescence. Increased vascular permeability, coagulopathy, and renal injury are typical clinical features of HFRS, which has a case fatality rate of 1–15%. Despite this, a comprehensive meta-analyses of the clinical characteristics of patients who died from HFRS is lacking.

Methods

Eleven Chinese- and English-language research databases were searched, including the China National Knowledge Infrastructure Database, Wanfang Database, SinoMed, VIP Database, PubMed, Embase, Scopus, Cochrane Library, Web of Science, Proquest, and Ovid, up to October 5, 2023. The search focused on clinical features of patients who died from HFRS. The extracted data were analyzed using STATA 14.0.

Results

A total of 37 articles on 140,295 patients with laboratory–confirmed HFRS were included. Categorizing patients into those who died and those who survived, it was found that patients who died were older and more likely to smoke, have hypertension, and have diabetes. Significant differences were also observed in the clinical manifestations of multiple organ dysfunction syndrome, shock, occurrence of overlapping disease courses, cerebral edema, cerebral hemorrhage, toxic encephalopathy, convulsions, arrhythmias, heart failure, dyspnea, acute respiratory distress syndrome, pulmonary infection, liver damage, gastrointestinal bleeding, acute kidney injury, and urine protein levels. Compared to patients who survived, those who died were more likely to demonstrate elevated leukocyte count; decreased platelet count; increased lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase levels; prolonged activated partial thromboplastin time and prothrombin time; and low albumin and chloride levels and were more likely to use continuous renal therapy. Interestingly, patients who died received less dialysis and had shorter average length of hospital stay than those who survived.

Conclusion

Older patients and those with histories of smoking, hypertension, diabetes, central nervous system damage, heart damage, liver damage, kidney damage, or multiorgan dysfunction were at a high risk of death. The results can be used to assess patients’ clinical presentations and assist with prognostication.

Systematic review registration:https://www.crd.york.ac.uk/prospero/, (CRD42023454553).
Integrating biological knowledge for mechanistic inference in the host-associated microbiome
Authors: Santangelo Brook E. , Apgar Madison , Colorado Angela Sofia Burkhart , Martin Casey G. , Sterrett John , Wall Elena , Joachimiak Marcin P. , Hunter Lawrence E. , Lozupone Catherine A.
Published: April 2024

Advances in high-throughput technologies have enhanced our ability to describe microbial communities as they relate to human health and disease. Alongside the growth in sequencing data has come an influx of resources that synthesize knowledge surrounding microbial traits, functions, and metabolic potential with knowledge of how they may impact host pathways to influence disease phenotypes. These knowledge bases can enable the development of mechanistic explanations that may underlie correlations detected between microbial communities and disease. In this review, we survey existing resources and methodologies for the computational integration of broad classes of microbial and host knowledge. We evaluate these knowledge bases in their access methods, content, and source characteristics. We discuss challenges of the creation and utilization of knowledge bases including inconsistency of nomenclature assignment of taxa and metabolites across sources, whether the biological entities represented are rooted in ontologies or taxonomies, and how the structure and accessibility limit the diversity of applications and user types. We make this information available in a code and data repository at: https://github.com/lozuponelab/knowledge-source-mappings. Addressing these challenges will allow for the development of more effective tools for drawing from abundant knowledge to find new insights into microbial mechanisms in disease by fostering a systematic and unbiased exploration of existing information.
Genome sequencing and comparative genome analysis of Rhizoctonia solani AG-3
Authors: Xu Shanshan , Shen Chengmeng , Li Chengyun , Dong Wenhan , Yang Genhua
Published: April 2024

Rhizoctonia solani AG-3 is a plant pathogenic fungus that belongs to the group of multinucleate Rhizoctonia. According to its internal transcribed spacer (ITS) cluster analysis and host range, it is divided into TB, PT, and TM subgroups. AG-3 TB mainly causes tobacco target spots, AG-3 PT mainly causes potato black scurf, and AG-3 TM mainly causes tomato leaf blight. In our previous study, we found that all 36 tobacco target spot strains isolated from Yunnan (Southwest China) were classified into AG-3 TB subgroup, while only two of the six tobacco target spot strains isolated from Liaoning (Northeast China) were classified into AG-3 TB subgroup, and the remaining four strains were classified into AG-3 TM subgroup, which had a unique taxonomic status, and there was no previous report on the whole genome information of AG-3 TM subgroup. In this study, the whole genomes of R. solani AG-3 strains 3T-1 (AG-3 TM isolated from Liaoning) and MJ-102 (AG-3 TB isolated from Yunnan) isolated from tobacco target spot in Liaoning and Yunnan were sequenced by IIumina and PacBio sequencing platforms. Comparative genomic analysis was performed with the previously reported AG-3 PT strain Rhs1AP, revealing their differences in genomes and virulence factors. The results indicated that the genome size of 3T-1 was 42,103,597 bp with 11,290 coding genes and 49.74% GC content, and the genome size of MJ-102 was 41,908,281 bp with 10,592 coding genes and 48.91% GC content. Through comparative genomic analysis with the previously reported strain Rhs1AP (AG-3 PT), it was found that the GC content between the genomes was similar, but the strains 3T-1 and MJ-102 contained more repetitive sequences. Similarly, there are similarities between their virulence factors, but there are also some differences. In addition, the results of collinearity analysis showed that 3T-1 and MJ-102 had lower similarity and longer evolutionary distance with Rhs1AP, but the genetic relationship between 3T-1 and MJ-102 was closer. This study can lay a foundation for studying the molecular pathogenesis and virulence factors of R. solani AG-3, and revealing its genomic composition will also help to develop more effective disease control strategies.