bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Intersection of Religion and Culture: A Phenomenological Inquiry into the Cokaiba Tradition among the Fagogoru Community in Central Halmahera Regency
Authors: Alhadar Muhdi , Rahmat Rahmat , Assagaf Fahima , Khitab Wassam Muhammad
Published: April 2024

In sociological contexts, the interaction between culture and religious content naturally reflects the dynamic nature of social phenomena, arising from the harmonization of societal norms and religious principles. The Cokaiba tradition exemplifies this intersection, blending cultural heritage with Islamic commemoration. This study utilizes a phenomenological approach to explore the significance of the Cokaiba tradition within Halmahera society in North Maluku, aiming to elucidate broader perspectives on the interplay between culture and religion. Through qualitative research rooted in phenomenology, this study investigates the dynamics of the Cokaiba tradition within the Fagogoru Community in Central Halmahera, North Maluku. Data collection involves immersive engagement with key informants, including religious figures, community leaders, practitioners of the tradition, and local residents, through interviews, observations, and documentation. Findings reveal the emergence of Cokaiba as a fusion of cultural heritage and Islamic celebration, embodying principles of monotheism and serving as a means to propagate Islam within the region. Despite diverse interpretations, the convergence of religion and culture within Cokaiba fosters harmonious coexistence, facilitating the integration of religious values with cherished cultural practices. However, limitations include the challenge of fully capturing individual experiences and perceptions with a phenomenological approach and the potential lack of generalizability due to the study's focus on the Fagogoru Community. Future research incorporating a broader range of perspectives and cultural contexts would enhance understanding of the intricate dynamics between religion and culture manifested in traditions like Cokaiba.
STRATEGI BUMDES DALAM MENINGKATKAN PENDAPATAN ASLI DESA (STUDI PADA BUMDES SARI TANI, DESA RIMBO RECAP, KECAMATAN CURUP SELATAN, KABUPATEN REJANG LEBONG)
Authors: Yopisah  , Fadli  , Lisa M.N Puspita
Published: April 2024

The purpose of this study was to analyze the Sari Tani BUMDes strategy in increasing village original income in Rimbo Recap Village, south Curup District, Rejang Lebong Regency. The sample used in this study was Sari Tani BUMDes in Rimbo Recap Village, Curup Selatan District, Rejang Lebong Regency. This study uses Porter's five forces analysis test method. The results of this study indicate that the challenges faced by BUMDes Sari Tani are also the presence of newcomers. Where there will always be newcomers because similar business actors are doing the same business, people's purchasing power is currently still standard 50/50. This is caused by a lack of marketing in the business, the threat is the emergence of new business actors who become competitors. As for the solution taken by BUMDes Sari Tani through innovation in presenting interesting programs, the power of BUMDes Sari Tani's suppliers is not too influential. Because BUMDes Sari Tani is one of the central government programs so that the central government provides assistance through the regional government in supporting its business activities, BUMDes Sari Tani gets competitors from similar business actors, of course, because in the area around where BUMDes Sari Tani is located the business actor has a different regional topography. so that the business carried out is also the same and what can differentiate these businesses is the superiority of the commodities produced by the business actors themselves as well as innovations in the field of other services.
PENGARUH METODE RGEC TERHADAP NILAI PERUSAHAAN PADA BANK KONVENSIONAL YANG TERDAFTAR DI BEI
Authors: Rahandhika Ivan Adyaksana  , Vidya Vitta Adhivinna  , M.Sulkhanul Umam  , Fitria Nuri Agustin
Published: April 2024

The purpose of this study is to determine how the influence of RGEC indirectly or not on company value. This research was conducted on conventional banking companies listed on the Indonesia Stock Exchange (IDX) in the period 2017 – 2021. This research uses quantitative methods by obtaining 38 conventional banking companies using this data analysis technique using smartPLS. From the results of the study shows that risk profile has a significant negative influence on company value, GCG (Good Corporate Governance) has a significant positive influence on company value, Earning has a significant positive influence on company value, and Capital has a significant positive influence on company value. The company’s own value uses PBV (Price Book Value).
ANTROPOMETRIC ANALYSIS OF ATATÜRK UNIVERSITY CAMPUS
Authors: Demir Metin , Rüzgar Aykut , Aksoy Özlem Burcu , Caner Ahmet Mesut , Duran Gülşen
Published: April 2024

Anthropometry is an important parameter that should always be considered in the architecture and landscape architecture professions, helping designers determine the bare minimum space required to accommodate the human body when performing outdoor/indoor related activities. Anthropometric analogies focus on the human body and its relationship to the design goal. Within the scope of the study, the concept of anthropometry was explained in the literature, and the relationship between Landscape Architecture and Anthropometry and anthropometric standards were examined. Atatürk University campus was chosen as the research area, and current applications were investigated in line with anthropometric data. The evaluation of landscape construction elements regarding anthropometric standards has been examined under two headings. These; consist of 1. Floor elements (Stairs, Ramps, Roads, Sidewalks, Flooring elements), 2. Equipment Elements (Lighting elements, Trash cans, Seating elements, Sign boards, limiters, and Vegetative elements). In this study, the ergonomic and anthropometric correct and incorrect applications of landscape reinforcement elements in the example of Atatürk University Campus were revealed, and suggestions were made on correcting the inaccurate and incomplete applications.
About the activities of the Perm Krai Pardon Commission
Authors: Borovyh Ljubov’ , Solov’eva Elena
Published: April 2024

The article highlights a relatively small practice concerning the activities of the Perm Krai Pardon commission. Goal – to summarize the results of the activities of the Perm Krai Pardon Commission. The work of the Perm Krai pardon Commission from 2018 to 2021 was reviewed. A tendency has been established to reduce the number of persons applying for clemency on the territory of Russia, which is due to the general orientation of criminal legislation towards humanization. In addition, it is proved that the President of the Russian Federation is not connected with the regional position determined by the commission on pardoning and the head of the subject of the Russian Federation regarding the expediency of applying a pardon to a convicted person.
THE LEGAL BASIS FOR THE ACTIVITIES OF PENAL ENFORCEMENT INSPECTIONS FOR THE EXECUTION OF PUNISHMENT IN THE FORM OF CORRECTIONAL LABOR IN RELATION TO JUVENILE CONVICTS
Authors: Babkina Elena Viktorovna , Nikitin Dmitriy Alekseevich
Published: April 2024

The article analyzes the legal basis of the activities of penal enforcement inspections for the execution of punishment in the form of correctional labor in relation to juvenile convicts. The problems of an organizational and legal nature in the implementation of this type of punishment are revealed. Attention is drawn to the peculiarities of the execution of correctional labor in relation to certain categories of minors. The features of the interaction of penal enforcement inspections with other bodies and institutions of state power in the execution of this type of criminal punishment are considered.
DISCIPLINARY RESPONSIBILITY OF CONVICTS: DIRECTIONS FOR IMPROVING RUSSIAN PENAL ENFORCEMENT LEGISLATION BASED ON FOREIGN EXPERIENCE
Authors: Davydova Irina
Published: April 2024

The article examines the shortcomings of the penal enforcement legislation regulating the grounds, types and procedure for the application of disciplinary penalties to convicts, reveals the specifics of the legal regulation of disciplinary liability of convicts in the Penitentiary Code of France. Based on the analysis, the prospects for the introduction in Russia of various categories of disciplinary offenses and penalties that can be applied for them are determined; the legislative consolidation of the procedure for imposing penalties aimed at ensuring guarantees of the rights of convicts, the implementation of such institutions as the postponement of the application of disciplinary measures, early release from their execution.
RECIDIVISM AS A CRIMINAL CONSEQUENCE OF CRIMINAL RECORD: CONTRADICTIONS OF RUSSIAN CRIMINAL LAW
Authors: SHURANOVA OLGA ALEXANDROVNA
Published: April 2024

Criminal liability continues to have an impact on the convicted person even after serving a criminal sentence until the repayment of the criminal record or its early withdrawal. As a criminal consequence, a criminal record is one of the main factors contributing to the formation of recidivism, recidivism. The question arises about the correctness of the content of the specified criminal law consequence, its contradiction to some principles of criminal law. The article analyzes the problems associated with the existence of criminal law norms that dictate the further application of criminal law to citizens who are in the status of convicts. The question is raised that these norms do not fully correspond to the principles of justice and equality of citizens before the law. The author has studied the recurrence of crimes, penitentiary relapse as one of the criminal consequences of a criminal record, and analyzed the growth of recidivism. The data of judicial statistics and statistics of the Ministry of Internal Affairs of Russia are analyzed. The analysis concluded that Article 86 of the Criminal Code of the Russian Federation has many contradictions that affect the number of repeat offenses. The author’s solution to the problem of setting the repayment dates of a criminal record is proposed.
Historical imprints on genetic population structure in direct-developing beach whelks (Bullia digitalis)
Authors: Bezuidenhout K , Nel R , Schoeman D , Grant WS , Hauser L
Published: April 2024

Marine organisms often show deep genetic divergence between lineages that are characterized by shallow population structure. The distinction of historical and contemporary demographic forces in creating and maintaining these genetic patterns is crucial for management and conservation. In this study, we examined the genetic population structure of Bullia digitalis, a lecithotrophic sandy beach whelk that lacks a pelagic larval phase and is thus expected to show limited connectivity between populations. Mitochondrial (mt)DNA cytochrome c oxidase subunit I (COI; 540 bp, n = 214) and a reanalysis of allozyme data (14 loci, n = 735) among populations along the cool southeast Atlantic (west) and warm-temperate southwest Indian Ocean (south) coasts of southern Africa showed a strong phylogeographic break across Cape Point with mtDNA (ΦRT = 0.6, p < 0.001), but a weak break with allozymes (FRT = 0.002, p = 0.004). MtDNA gene flow occurred asymmetrically from the west to the south coast. Although there was no mtDNA differentiation between populations on either side of that break (ΦSR = 0.0), there was weak but significant isolation by distance (IBD) among south coast samples (r2 = 0.20, p = 0.039). In contrast, significant allozyme differentiation was detected on small spatial scales but without overall IBD. MtDNA mismatch analysis indicated a recent range expansion, suggesting historic population expansions, most likely during periods of lower sea levels and greater habitat continuity along southern African shores. Thus, the apparent mtDNA connectivity among populations of beach whelks likely reflects historic, rather than contemporary, gene flow.
Defining the role of Sabellaria alveolata reefs as nursery areas for juvenile fish: first evidence from drone-based imagery and underwater visual census data
Authors: Ventura D , Dubois SF , Cardella E , Colloca F , Tiralongo F , Rakaj A , Bonifazi A , Jona Lasinio G , Mancini E , Bertocci I , Casoli E , Mancini G , Valente T , Belluscio A , Ardizzone G , Gravina MF
Published: April 2024

The biogenic reefs built by the honeycomb worm Sabellaria alveolata constitute priority habitats along Atlanto-Mediterranean coastal areas. Despite their wide extent and important ecological role, the nursery value of S. alveolata reefs remains unclear, and more information is needed to define how such structured habitats affect juvenile fish assemblages. In this study, habitat use by juveniles of 7 fish species was investigated by underwater visual census (UVC) at 3 study sites representing a gradient of complexity of Sabellaria reef habitats, spanning from a large and uniform reef to patchy and isolated small reef formations. Sabellaria reef metrics derived by drone-based cartography and GIS analysis were used to quantitatively monitor the seasonal structural changes occurring due to the natural dynamics of the reefs. We also tested the potential effect of Sabellaria habitats on the growth and relative condition factor (Kn) of white seabream Diplodus sargus juveniles. Five of the 7 surveyed species, especially sparid fishes, showed a clear preferential association with Sabellaria formations. Generalized additive modelling revealed a significant effect of the compactness ratio on estimated fish densities at high and low index values. The juvenile fish sampled on Sabellaria reefs exhibited higher values of Kn than those sampled on rocky habitats, supporting the hypothesis that structural complexity positively affected their condition. We provide evidence on habitat use by juveniles, suggesting that the presence of the Sabellaria reef may act as a nursery and affect local fish density in Mediterranean coastal waters.
Orthogonal linker chemistries applied in core-crosslinked polymeric micelles
Authors:   , Hebels Erik Reinhard
Published: April 2024

CCPMs have shown great potential in preclinical models and even clinical evaluation,
with there being a continued need for the development of orthogonal linker chemistries
for the crosslinking and triggered release of API cargos, also with increasing API
complexity. The aim of this thesis was to expand the toolbox available to this regard:
• Implement NCL as a crosslinking tool to obtain CCPMs using two different, well
described thermosensitive diblock copolymer systems, namely mPEG-PNIPAM and
mPEG-pHPMAmLacn.
• Study the crosslinking efficiency and stability of CCPMs formed by two different
crosslinking approaches, either by using a small molecule crosslinker or with crossreactive
complementary polymers.
• Demonstrate improved compatibility of fragile compounds (therapeutic and
diagnostic) with CCPMs using NCL as a crosslinking reaction.
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• Assess the state of the art for the use of AuNCs in biomedical applications in
diagnostic, therapeutic and theranostic capacity.
• Develop linking technologies, using light induced (AuNC based) and reduction
sensitive (disulfide based) release triggers for the release of APIs.
• Apply reduction sensitive release linker technology to promising but challenging
API classes, namely therapeutic peptides and siRNA, with entrapment in CCPMs.
• Keeping an eye on industrial applicability
Biphasic Ventilatory Response to Hypoxia in Unanesthetized Rats
Authors: Maxová H , Vízek M
Published: April 2024

To determine the role of postinspiratory inspiratory activity of the diaphragm in the biphasic ventilatory response to hypoxia in unanesthetized rats, we examined diaphragmatic activity at its peak (DI), at the end of expiration (DE), and ventilation in adult unanesthetized rats during poikilocapnic hypoxia (10 % O2) sustained for 20 min. Hypoxia induced an initial increase in ventilation followed by a consistent decline. Tidal volume (VT), frequency of breathing (fR), DI and DE at first increased, then VT and DE decreased, while fR and DI remained enhanced. Phasic activation of the diaphragm (DI - DE) increased significantly at 10, 15 and 20 min of hypoxia. These results indicate that 1) the ventilatory response of unanesthetized rats to sustained hypoxia has a typical biphasic character and 2) the increased end-expiratory activity of the diaphragm limits its phasic inspiratory activation, but this increase cannot explain the secondary decline in tidal volume and ventilation.
Cardiovascular and Hormonal Changes with Different Angles of Head-up Tilt in Men
Authors: László Z , Rössler A , Hinghofer-Szalky HG
Published: April 2024

The purpose of this study was to assess the endocrine status, thoracic impedance, blood concentration, and hemodynamic dose-responses using different angles of passive head-up tilt (HUT) ranging from 12° to 70° in the same subjects. Measurements were performed during 20 min supine position (pre-HUT), 30 min upright (HUT12, HUT30, HUT53, or HUT70), and 20 min supine (post-HUT); subjects 70 min in the supine position only (HUT0) served as resting controls. Norepinephrine increased above resting control values by 19, 44, 80, and 102 %; epinephrine by 30, 41, 64, and 68 %; aldosterone by 29, 62, 139, and 165 %; plasma renin activity n. s., 41, 91, and 89 %; vasopressin n.s., 27, 47, and 59 %; thoracic bioimpedance n. s., 8, 13, and 16 %; heart rate n. s., 5, 26, and 45 %, and mean arterial pressure n. s., 5, 7, and 10 %; at min 27 of HUT12, HUT30, HUT53, and HUT70, respectively. Pulse pressure decreased with HUT53 and HUT70 by 4 and 10 %. Hematocrit increased by 0.2, 1.7, 6.3, and 7.2 %, respectively. Blood density increased by 2.3 and 3.0 g/l, plasma density by 1.7 and 1.8 g/l with HUT53 and HUT70. After finishing HUT, heart rate fell to values which stayed below pre-HUT, and also below resting control levels for ł 5 min ("post-orthostatic bradycardia") even after the lowest orthostatic load (HUT12). Thoracic impedance and arterial pressure remained increased after terminating HUT30, HUT53, and HUT70. In conclusion, passive orthostatic loading of different extent produces specific dose-responses of different magnitude in the endocrine system, blood composition, thoracic impedance, and hemodynamic variables. The heart rate is depressed even after HUT12, while arterial blood pressure and thoracic impedance exceed pre-stimulus levels after greater head-up tilt, indicating altered cardiovascular response after passive orthostasis.
OCT-4 and DAZL expression in benign and malignant breast lesions: a prospective case control study
Authors: Plakas Georgios , Navrozoglou Iordanis , Paschopoulos Minas , Stefos Theodoros , Stefanidis Konstantinos
Published: April 2024

Purpose: The impact of cancer stem cells on breast cancer tumor biology has been poorly investigated during the last years. In the present study we sought to identify the expression of OCT-4 and DAZL, two prominent stem cell biomarkers, on malignant breast lesions. Methods: A retrospective analysis of patients that underwent simple or radical mastectomy was performed. Immunohistochemical expression of OCT-4 and DAZL was sought, and real time PCR was also applied in deparaffinized tissue samples retrieved from the pathology bank of our hospital. Results: Eighteen women aged 43-84 years old (median 57 years) were included in the present study. Of those, 10 women had invasive ductal carcinoma, 4 women had in situ ductal carcinoma and 4 women had invasive lobular carcinoma. Immunohistochemistry of tissue samples did not reveal expression of OCT-4, whereas DAZL was expressed in only 3 samples. Real time PCR was available in 13 samples as the control gene (G6PD) was not expressed in 5 samples. The 13 studied breast cell samples showed positive expression for the Oct-4 gene. In the same population the expression of DAZL varied significantly with 9 samples showing complete absence of expression and 4 providing a small signal in the last cycles, indicating barely detectable expression. The expression was significant in lobular carcinoma cases compared to cases with invasive or in situ ductal carcinoma. Conclusion: The findings of our study indicate the difficulty of retrieving reliable tissue samples following the process of deparaffinization and points towards the need for prospective case control studies that will be based on fresh tissue samples for the analysis of stem cell markers. Nevertheless, it also indicates a potentially increased expression of stemness markers in lobular carcinoma samples compared to ductal cancer cases, an observation that requires further research in the future.
Late Scholastic Arguments for the Existence of Prime Matter
Authors: Polloni Nicola
Published: April 2024

Scholastic hylomorphism conceives prime matter and substantial form as metaphysical parts of every physical substance. During the early modern period, both hylomorphic constituents faced significant criticism as scientists and philosophers sought to replace Aristotelianism with physical explanations for the workings of the universe. This paper focuses specifically on prime matter and delves into the arguments put forth by four 16th-century scholastic philosophers – Toledo, Fonseca, Góis, and Suárez – in their attempts to establish the existence of prime matter. Firstly, I analyse a set of arguments rooted in substantial change, which emphasize the crucial role of a persistent, common substrate in the processes of generation and corruption. Secondly, I explore a set of ex-nihilo arguments and, thirdly, I examine a series of demonstrations based on the interplay between accidental and substantial change. Although these three sets of arguments converge on the necessity of a common substrate for substantial change to occur, they fall short of demonstrating that this substrate is both prime and shared by all natural entities. Fourthly, I turn to a set of arguments centred on the impossibility of infinite regress, designed to complement those related to natural change, and I assess additional arguments that do not primarily focus on substantial change. Lastly, I draw my conclusions on these argumentative strategies to demonstrate the existence of prime matter.
Peran Kader Perempuan Partai Keadilan Sejahtera (PKS) dalam Optimalisasi Partisipasi Politik Perempuan Melalui Program Pemberdayaan di Kota Depok Pasca Pemilu 2019
Authors: Haq Vivih Asviah
Published: April 2024

Rumah Keluarga Indonesia menjadi strategi bagi PKS dalam menjaring kader-kader perempuan baru. PKS menjadikan perempuan sebagai bagian dari aktivitas politik partainya. Kesuksesan program ini membawa pengaruh bagi PKS yaitu dengan terdapatnya peningkatan jumlah kader perempuan baru periode 2021 hingga 2023. Penelitian ini mengkaji mengenai peranan politik kader perempuan Partai Keadilan Sejahtera dalam melakukan program RKI guna menjaring kader-kader baru. Penelitian ini menggunakan metode kualitatif deskriptif. Data yang dikumpulkan melalui wawancara dan observasi. Subjek dalam penelitian ini adalah para kader PKS Depok dan masyarakat khususnya kalangan perempuan yang terlibat di dalam program Rumah Keluarga Indonesia. Teori yang digunakan dalam penelitian ini adalah teori peran representatif perempuan di dalam politik yang dikemukakan oleh Anne Phillips dan Hana Pitkin. Hasil penelitian menunjukkan bahwa program RKI menunjukkan keberhasilan bagi PKS dengan adanya kenaikan jumlah kader baru, PKS menggunakan strategi peran representatif deskriptif dan juga simbolik untuk melakukan pendekatan dengan masyarakat, sehingga masyarakat mampu mempercayai bahwa PKS adalah partai yang cocok dan sejalan dengan visi-misinya.
SDGs 4.1.1(a): TINGKAT KETIMPANGAN GENDER KEMAMPUAN NUMERASI SISWA KELAS VIII SMP DI KABUPATEN TANGERANG
Authors: Pamungkas Aan Subhan , Manurung Felisia Oktovia
Published: April 2024

Kesetaraan gender merupakan salah satu tujuan dari Sustainable Development Goals (SDGs) yang dirumuskan untuk menciptakan kesetaraan peran gender pada perempuan dan laki-laki, salah satunya dalam bidang pendidikan. Tujuan ini memiliki kesinambungan terhadap tujuan SDGs yang lainnya, salah satunya dalam mewujudkan pendidikan berkualitas yang dapat dinilai melalui kemampuan literasi dan numerasi. Selama pelaksanaannya, terjadi kesenjangan antar kelompok dalam dimensi pemberdayaan menurut Human Development Report sebesar 17,4 dari 24,6, serta berada pada peringkat ke-6 di negara ASEAN, dan siswa perempuan cenderung lebih unggul dari laki-laki. Penelitian ini bertujuan untuk mengungkapkan tingkat kesenjangan gender dan hal-hal yang mempengaruhinya pada siswa tiap antar kelompok gender untuk memperdalam penelitian sebelumnya yang mengkaji terkait kemampuan numerasi siswa antar kelompok gender, terutama pada siswa kelas VIII SMP yang berwilayah di Kabupaten Tangerang. Penelitian dilakukan dengan pendekatan kualitatif dan kuantitatif serta metode studi kasus. Pada penelitian ini didapatkan hasil bahwa tingkat kesenjangan gender antar kelompok terhadap kemampuan numerasi umumnya berada di kategori ‘tidak ada kesenjangan gender’, namun siswa perempuan cenderung lebh unggul dibandingkan dengan siswa laki-laki.
bootGSEA: a bootstrap and rank aggregation pipeline for multi-study and multi-omics enrichment analyses
Authors: Hemandhar Kumar Shamini , Tapken Ines , Kuhn Daniela , Claus Peter , Jung Klaus
Published: April 2024

Introduction: Gene set enrichment analysis (GSEA) subsequent to differential expression analysis is a standard step in transcriptomics and proteomics data analysis. Although many tools for this step are available, the results are often difficult to reproduce because set annotations can change in the databases, that is, new features can be added or existing features can be removed. Finally, such changes in set compositions can have an impact on biological interpretation.

Methods: We present bootGSEA, a novel computational pipeline, to study the robustness of GSEA. By repeating GSEA based on bootstrap samples, the variability and robustness of results can be studied. In our pipeline, not all genes or proteins are involved in the different bootstrap replicates of the analyses. Finally, we aggregate the ranks from the bootstrap replicates to obtain a score per gene set that shows whether it gains or loses evidence compared to the ranking of the standard GSEA. Rank aggregation is also used to combine GSEA results from different omics levels or from multiple independent studies at the same omics level.

Results: By applying our approach to six independent cancer transcriptomics datasets, we showed that bootstrap GSEA can aid in the selection of more robust enriched gene sets. Additionally, we applied our approach to paired transcriptomics and proteomics data obtained from a mouse model of spinal muscular atrophy (SMA), a neurodegenerative and neurodevelopmental disease associated with multi-system involvement. After obtaining a robust ranking at both omics levels, both ranking lists were combined to aggregate the findings from the transcriptomics and proteomics results. Furthermore, we constructed the new R-package “bootGSEA,” which implements the proposed methods and provides graphical views of the findings. Bootstrap-based GSEA was able in the example datasets to identify gene or protein sets that were less robust when the set composition changed during bootstrap analysis.

Discussion: The rank aggregation step was useful for combining bootstrap results and making them comparable to the original findings on the single-omics level or for combining findings from multiple different omics levels.
A review on machine learning approaches in cardiac tissue engineering
Authors: Kalkunte Nikhith , Cisneros Jorge , Castillo Edward , Zoldan Janet
Published: April 2024

Cardiac tissue engineering (CTE) holds promise in addressing the clinical challenges posed by cardiovascular disease, the leading global cause of mortality. Human induced pluripotent stem cells (hiPSCs) are pivotal for cardiac regeneration therapy, offering an immunocompatible, high density cell source. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) exhibit vital functional deficiencies that are not yet well understood, hindering their clinical deployment. We argue that machine learning (ML) can overcome these challenges, by improving the phenotyping and functionality of these cells via robust mathematical models and predictions. This review paper explores the transformative role of ML in advancing CTE, presenting a primer on relevant ML algorithms. We focus on how ML has recently addressed six key address six key challenges in CTE: cell differentiation, morphology, calcium handling and cell-cell coupling, contraction, and tissue assembly. The paper surveys common ML models, from tree-based and probabilistic to neural networks and deep learning, illustrating their applications to better understand hiPSC-CM behavior. While acknowledging the challenges associated with integrating ML, such as limited biomedical datasets, computational costs of learning data, and model interpretability and reliability, we examine suggestions for improvement, emphasizing the necessity for more extensive and diverse datasets that incorporate temporal and imaging data, augmented by synthetic generative models. By integrating ML with mathematical models and existing expert knowledge, we foresee a fruitful collaboration that unites innovative data-driven models with biophysics-informed models, effectively closing the gaps within CTE.
Improved diagnostic markers for invasive pulmonary aspergillosis in COPD patients
Authors: Long Zhiwei , Li Xiaotong , Li Zhengtu , Hu Jieying , Qiu Ye , Li Shaoqiang , Zhan Yangqing , Ye Feng , Wang Yan
Published: April 2024

Background

The prevalence of invasive pulmonary aspergillosis (IPA) among patients with chronic obstructive pulmonary disease (COPD) is steadily increasing, leading to high mortality. Although early diagnosis can significantly reduce mortality, the efficacy of current diagnostic methods is limited. Consequently, there is a need for novel approaches for early IPA detection.

Methods

This retrospective study involved 383 hospitalized COPD patients with GOLD stages III and IV. The IPA group (67 patients) and non-IPA group (316 patients) were identified at the First Affiliated Hospital of Guangzhou Medical University between January 2016 and February 2022. We analyzed common serological indicators in our hospital to identify predictive indicators for the early diagnosis of IPA in COPD patients.

Results

The sensitivity and specificity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), lactate dehydrogenase (LDH), and ceruloplasmin (CER) for diagnosing IPA in COPD patients were as follows: CRP (91.2%, 57.7%), ESR (77.5%, 73.0%), PCT (60.5%, 71.4%), LDH (50.0%, 88.8%), and CER (60.7%, 74.3%). Combinations of biomarkers, such as CRP-ESR, CRP-LDH, ESR-LDH, ESR-CER, and LDH-CER, showed promising diagnostic potential, with larger area under the curve (AUC) values for IPA diagnosis in COPD patients. However, no statistically significant difference was observed between the diagnostic efficacy of single biomarkers and combined biomarkers. Notably, compared to those in the unassisted ventilation group, the patients in the assisted ventilation group (including noninvasive ventilation and tracheal intubation/incision-assisted ventilation group) exhibited significantly greater PCT and LDH levels, while the CER significantly decreased (p=0.021). There were no significant differences in biomarker levels between the ICU group and the non-ICU group. CRP (p<0.01), ESR (p=0.028), PCT (p<0.01), and CER (p<0.01) were positively correlated with hospitalization duration, whereas LDH was not correlated with hospitalization duration.

Conclusion

Our study highlights the diagnostic potential of CRP, ESR, PCT, LDH, and CER for IPA in COPD patients. CRP and LDH can also initially predict the need for assisted ventilation, while CRP can initially estimate the length of hospitalization. This study represents the first report of the potential of CER for diagnosing IPA, suggesting its significance for further research.
Where have all the flowers gone? A call for federal leadership in deer management in the United States
Authors: Blossey Bernd , Hare Darragh , Waller Donald M.
Published: April 2024

Forests in the United States continue to lose biodiversity and many fail to regenerate due to high deer (family Cervidae) abundance. Declines in biodiversity and overall ecosystem health due to high deer populations increases prevalence of wildlife and human diseases associated with increasing tick abundances and decreases forest resilience and the ability to deliver benefits provided by healthy ecosystems. In the eastern and midwestern United States, white-tailed deer (Odocoileus virginianus) are the main stressor, while in the western U.S. elk (Cervus elaphus) and black-tailed and mule deer (Odocoileus hemionus) can become equally problematic. Federal and State Wildlife Agencies are responsible for environmental stewardship and management of deer, migratory and endangered species, yet they lack authority to address human health concerns or commercial interests (we acknowledge tribal authority to manage wildlife as an important contributor to conservation). Furthermore, State Wildlife Agencies have retained their traditional focus to manage wildlife for recreational hunters while neglecting their obligations to manage wildlife in the interest of all citizens rather than special interest groups. Fragmented institutional arrangements and widely scattered responsibilities for human health, environmental conservation and management, agriculture, and commerce among tribal, federal, and state agencies have allowed deer impacts to grow into nationwide conservation and human health crises. Given that local, regional, and state-level initiatives have failed to provide appropriate remedies, federal leadership is now essential to integrate concerns among disciplines, policy domains, regions, habitats, and biota. We recommend developing a National Strategy to build strong collaborative efforts and diverse and inclusive relationships across environmental, human health and economic interests. These should reach beyond state boundaries to comprehensively address interrelated deer, human health, forest, and conservation crises. A well-coordinated and collaborative approach has the potential to overcome traditional turf battles between tribal, state, and federal interests by recognizing joint responsibilities and obligations to manage wildlife as a public trust resource. This collective approach can protect species before they become endangered, avoiding further declines in environmental and human health.
Redefining governance: a critical analysis of sustainability transformation in e-governance
Authors: Abbas Qaiser , Alyas Tahir , Alghamdi Turki , Alkhodre Ahmad B. , Albouq Sami , Niazi Mushtaq , Tabassum Nadia
Published: April 2024

With the rapid growth of information and communication technologies, governments worldwide are embracing digital transformation to enhance service delivery and governance practices. In the rapidly evolving landscape of information technology (IT), secure data management stands as a cornerstone for organizations aiming to safeguard sensitive information. Robust data modeling techniques are pivotal in structuring and organizing data, ensuring its integrity, and facilitating efficient retrieval and analysis. As the world increasingly emphasizes sustainability, integrating eco-friendly practices into data management processes becomes imperative. This study focuses on the specific context of Pakistan and investigates the potential of cloud computing in advancing e-governance capabilities. Cloud computing offers scalability, cost efficiency, and enhanced data security, making it an ideal technology for digital transformation. Through an extensive literature review, analysis of case studies, and interviews with stakeholders, this research explores the current state of e-governance in Pakistan, identifies the challenges faced, and proposes a framework for leveraging cloud computing to overcome these challenges. The findings reveal that cloud computing can significantly enhance the accessibility, scalability, and cost-effectiveness of e-governance services, thereby improving citizen engagement and satisfaction. This study provides valuable insights for policymakers, government agencies, and researchers interested in the digital transformation of e-governance in Pakistan and offers a roadmap for leveraging cloud computing technologies in similar contexts. The findings contribute to the growing body of knowledge on e-governance and cloud computing, supporting the advancement of digital governance practices globally. This research identifies monitoring parameters necessary to establish a sustainable e-governance system incorporating big data and cloud computing. The proposed framework, Monitoring and Assessment System using Cloud (MASC), is validated through secondary data analysis and successfully fulfills the research objectives. By leveraging big data and cloud computing, governments can revolutionize their digital governance practices, driving transformative changes and enhancing efficiency and effectiveness in public administration.
FAT-GEMs: (field assisted) transparent gaseous-electroluminescence multipliers
Authors: Leardini S. , Saá-Hernández A. , Kuźniak M. , González-Díaz D. , Azevedo C. D. R. , Lucas F. , Amedo P. , Cortez A. F. V. , Fernández-Posada D. , Mehl B. , Nieradka G. , de Oliveira R. , Peskov V. , Sworobowicz T. , Williams S.
Published: April 2024

The idea of implementing electroluminescence-based amplification through transparent multi-hole structures (FAT-GEMs) has been entertained for some time. Arguably, for such a technology to be attractive it should perform at least at a level comparable to conventional alternatives based on wires or meshes. We present now a detailed calorimetric study carried out for 5.9 keV X-rays in xenon, for pressures ranging from 2 to 10 bar, resorting to different geometries, production and post-processing techniques. At a reference voltage 5 times above the electroluminescence threshold (EEL,th ∼ 0.7 kV/cm/bar), the number of photoelectrons measured for the best structure was found to be just 18% below that obtained for a double-mesh with the same thickness and at the same distance. The energy resolution stayed within 10% (relative) of the double-mesh value. An innovative characteristic of the structure is that vacuum ultraviolet (VUV) transparency of the polymethyl methacrylate (PMMA) substrate was achieved, effectively, through tetraphenylbutadiene (TPB) coating of the electroluminescence channels combined with indium tin oxide (ITO) coating of the electrodes. This resulted in a × 2.25-increased optical yield (compared to the bare structure), that was found to be in good agreement with simulations if assuming a TPB wavelength-shifting-efficiency at the level of WLSE=0.74–1.28, compatible with expected values. This result, combined with the stability demonstrated for the TPB coating under electric field (over 20 h of continuous operation), shows great potential to revolutionize electroluminescence-based instrumentation.
Constructing and storytelling: accommodating different play orientations in learning spatial thinking
Authors: Sonneveld Leonie , Klapwijk Remke M. , Stappers Pieter Jan
Published: April 2024

Spatial ability is malleable and belongs in the preschool. For preschoolers, many analytical activities with one correct answer such as tangram have been developed. Less is known about employing open-ended design assignments to creatively practice spatial thinking. Little attention has been paid to the mutual qualitative differences between children when engaged in spatial thinking and insight in children’s motivation is lacking. As design and play have much in common, our first study investigated play orientations during free play of 49 Dutch preschoolers during free play in a low and a high SES school. Participative interviews and observations in the construction and home corners of two schools uncovered different play orientations– construction and pretend play - and either a focus on open-ended objects or on defined objects. In a subsequent study, the influence of these play and object orientations on how children design was investigated. This study with 13 children also used generative design research methods grounded in ethnographic research and therapeutic practices. Using an empathic, story-based, open-ended design challenge, results showed that play-orientations of children influence the length and nature of the design activities as well as the design outcomes. Children with a pretend-play orientation are longer engaged and talk more about the character involved. They usually built organic structures with a variety of objects, while construction-oriented children mainly built sturdy and geometrical structures and mainly used open-ended objects. In all play orientations, spatial thinking was practiced and children were spatially challenged. For example, in all orientations difficulties arose around getting the character in out the structure, however, as different structures were build, the nature of these difficulties were also different. Open-ended design activities that contain characters and problems children can empathize with are a valuable addition to the palette of activities to develop spatial thinking in early classrooms. Our study shows that design activities stimulate children to practice spatial thinking in a creative context and have the ability to engage children with a pretend-play orientation who are otherwise less engaged in construction. The play-orientations and object-orientations are informative for research and the development of spatial educational interventions aiming at a diversity of learners.
Whole genome sequencing of recombinant viruses obtained from co-infection and superinfection of Vero cells with modified vaccinia virus ankara vectored influenza vaccine and a naturally occurring cowpox virus
Authors: Diaz-Cánova Diana , Moens Ugo , Brinkmann Annika , Nitsche Andreas , Okeke Malachy Ifeanyi
Published: April 2024

Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and animals. However, one biosafety concern about the use of MVA vectored vaccine is the potential for MVA to recombine with naturally occurring orthopoxviruses in cells and hosts in which it multiplies poorly and, therefore, producing viruses with mosaic genomes with altered genetic and phenotypic properties. We previously conducted co-infection and superinfection experiments with MVA vectored influenza vaccine (MVA-HANP) and a feline Cowpox virus (CPXV-No-F1) in Vero cells (that were semi-permissive to MVA infection) and showed that recombination occurred in both co-infected and superinfected cells. In this study, we selected the putative recombinant viruses and performed genomic characterization of these viruses. Some putative recombinant viruses displayed plaque morphology distinct of that of the parental viruses. Our analysis demonstrated that they had mosaic genomes of different lengths. The recombinant viruses, with a genome more similar to MVA-HANP (>50%), rescued deleted and/or fragmented genes in MVA and gained new host ranges genes. Our analysis also revealed that some MVA-HANP contained a partially deleted transgene expression cassette and one recombinant virus contained part of the transgene expression cassette similar to that incomplete MVA-HANP. The recombination in co-infected and superinfected Vero cells resulted in recombinant viruses with unpredictable biological and genetic properties as well as recovery of delete/fragmented genes in MVA and transfer of the transgene into replication competent CPXV. These results are relevant to hazard characterization and risk assessment of MVA vectored biologicals.
Immune response profiles from humans experimentally exposed to Phlebotomus duboscqi bites
Authors: de Araujo Fernanda Fortes , Abdeladhim Maha , Teixeira Clarissa , Hummer Kelly , Wilkerson Matthew D. , Ressner Roseanne , Lakhal-Naouar Ines , Ellis Michael W. , Meneses Claudio , Nurmukhambetova Saule , Gomes Regis , Tolbert W. David , Turiansky George W. , Pazgier Marzena , Oliveira Fabiano , Valenzuela Jesus G. , Kamhawi Shaden , Aronson Naomi
Published: April 2024

Introduction

Cutaneous leishmaniasis is a neglected vector-borne parasitic disease prevalent in 92 countries with approximately one million new infections annually. Interactions between vector saliva and the human host alter the response to infection and outcome of disease.

Methods

To characterize the human immunological responses developed against saliva of Phlebotomus duboscqi, a Leishmania major (L. major) vector, we repeatedly exposed the arms of 14 healthy U.S volunteers to uninfected P. duboscqi bites. Blood was collected a week after each exposure and used to assess total IgG antibodies against the proteins of P. duboscqi salivary gland homogenate (SGH) and the levels of IFN-gamma and IL-10 from peripheral blood mononuclear cells (PBMCs) stimulated with SGH or recombinant sand fly proteins. We analyzed skin punch biopsies of the human volunteer arms from the insect bite site and control skin site after multiple P. duboscqi exposures (four volunteers) using immunohistochemical staining.

Results

A variety of immediate insect bite skin reactions were observed. Late skin reactions to insect bites were characterized by macular hyperpigmentation and/or erythematous papules. Hematoxylin and eosin staining showed moderate mononuclear skin infiltrate with eosinophils in those challenged recently (within 2 months), eosinophils were not seen in biopsies with recall challenge (6 month post bites). An increase in plasma antigen-specific IgG responses to SGH was observed over time. Western Blot results showed strong plasma reactivity to five P. duboscqi salivary proteins. Importantly, volunteers developed a cellular immunity characterized by the secretion of IFN-gamma upon PBMC stimulation with P. duboscqi SGH and recombinant antigens.

Discussion

Our results demonstrate that humans mounted a local and systemic immune response against P. duboscqi salivary proteins. Specifically, PduM02/SP15-like and PduM73/adenosine deaminase recombinant salivary proteins triggered a Th1 type immune response that might be considered in future development of a potential Leishmania vaccine.
IMPROVE: a feature model to predict neoepitope immunogenicity through broad-scale validation of T-cell recognition
Authors: Borch Annie , Carri Ibel , Reynisson Birkir , Alvarez Heli M. Garcia , Munk Kamilla K. , Montemurro Alessandro , Kristensen Nikolaj Pagh , Tvingsholm Siri A. , Holm Jeppe Sejerø , Heeke Christina , Moss Keith Henry , Hansen Ulla Kring , Schaap-Johansen Anna-Lisa , Bagger Frederik Otzen , de Lima Vinicius Araujo Barbosa , Rohrberg Kristoffer S. , Funt Samuel A. , Donia Marco , Svane Inge Marie , Lassen Ulrik , Barra Carolina , Nielsen Morten , Hadrup Sine Reker
Published: April 2024

Background

Mutation-derived neoantigens are critical targets for tumor rejection in cancer immunotherapy, and better tools for neoepitope identification and prediction are needed to improve neoepitope targeting strategies. Computational tools have enabled the identification of patient-specific neoantigen candidates from sequencing data, but limited data availability has hindered their capacity to predict which of the many neoepitopes will most likely give rise to T cell recognition.

Method

To address this, we make use of experimentally validated T cell recognition towards 17,500 neoepitope candidates, with 467 being T cell recognized, across 70 cancer patients undergoing immunotherapy.

Results

We evaluated 27 neoepitope characteristics, and created a random forest model, IMPROVE, to predict neoepitope immunogenicity. The presence of hydrophobic and aromatic residues in the peptide binding core were the most important features for predicting neoepitope immunogenicity.

Conclusion

Overall, IMPROVE was found to significantly advance the identification of neoepitopes compared to other current methods.