bluuebunny/crossref_metadata_2025 huggingface dataset:
Decision framework for public-private partnership in agricultural commodities
Authors: Sumantri Y , Gapsari F , Lau S K , Prinyapol N
Published: May 2024

Public-private partnerships are critical to advancing sustainability in the agricultural sector and increasing global food security. Partnerships are a means of increasing productivity and encouraging growth in the agricultural sector. The Partnership encourages private sector participation to reduce risks that occur in the agricultural sector. The aim of this research is to understand how supply chains are configured, to identify drivers of supply chain partnerships and to synthesize partnership strategies. Currently, agricultural areas in East Java are trying to build sustainable partnerships to improve farmers’ abilities in managing the agricultural sector. By using data from surveys and observations of 50 private companies and 50 farmers spread across the research object locations, it was found that there was quite a significant interaction between intensive coordination, partnership quality, quantity and quality of partners. The mechanisms used in partnerships can encourage sustainable agricultural management. It is hoped that the implementation of these findings can encourage partnerships between the private sector and the public sector to achieve significant development. It is hoped that this partnership can play an important role in addressing agricultural problems. Partnerships are formed to create shared values in the form of an institutional framework to address the root of problems.
The role of garlic attributes in shaping Indonesian consumers’ purchase intention: results from an online survey
Authors: Kiloes AM , Puspitasari  , Khaririyatun N
Published: May 2024

Garlic is a commodity that is highly needed by consumers, both for culinary, health and medicinal purposes. Because of the importance of this commodity, Indonesia has become the largest importer of garlic because its production is unable to meet demand. It is important to identify garlic attributes shapes Indonesian consumers purchase intention so that strategies can be developed to improve the quality of local garlic. This study was conducted specifically to determine the level of importance of several garlic attributes from the perspective of consumers. We conducted an online survey in the Greater Jakarta Area and Bandung, involving 493 respondents, to investigate what attributes they consider when buying garlic, in addition to asking several other descriptive questions. Majority of respondents give a high importance to bulb size, clove size, aroma, colour and price. Meanwhile, for the production location and packaging attributes, the majority of respondents gave a low importance. Our survey results surprisingly showed that more than 70% of respondents did not know where the garlic they consumed was produced. The conclusion from this survey show that physical attributes are still important for Indonesian consumers, so the development of local garlic really needs to pay attention to these physical attributes, for example through breeding programs and cultivation practices that can produce garlic characteristics in accordance with consumer wants.
Enhancing local garlic industry performance through marketing chain analysis
Authors: Puspitasari  , Kiloes A M , Saleh Y , Hayati N Q , Nurmalinda  , Sugandi D , Swastika D K S , Sulistyaningrum A , Waryat  , Rinaldi J
Published: May 2024

Ensuring the viability of local garlic businesses in Indonesia is contingent on the strategic development of effective marketing approaches. The study aimed to conduct a comprehensive mapping and problem identification analysis within the marketing chain of domestically produced garlic sourced from various production centers across Indonesia. The selection of the respondents adhered to the snowball sampling method. Our investigation uncovered a pattern in Java, where a significant portion of high-quality garlic was predominantly allocated to seed requirements, serving government development programs, and mandatory planting programs for garlic importers. Conversely, lower-quality garlic was channeled into local markets, which in turn shaped consumers’ perceptions of their overall quality. In contrast, East Lombok successfully established a clear delimitation between seed production and garlic cultivation. This demarcation allows for a wide spectrum of garlic qualities in the market, ranging from the best to the lowest. The pattern in East Lombok serves as a potential model for other production centers seeking to ensure the long-term sustainability of the garlic business. By leveraging insights gained from the East Lombok pattern, production centers can improve the accessibility of high-quality local garlic for consumers, thereby reshaping perceptions and fostering the sustained growth of the garlic industry.
The Analysis of feldspar characteristic as ceramic material at Mount Ragas, Jepara, Central Java
Authors: Winarno T , Marin J , Ayuningtyas P , Herdatama S R , Pudyanarendra S
Published: May 2024

The ceramic industry in Indonesia is growing rapidly so it needs a lot of raw and mixture materials for ceramics. One of the materials needed in the manufacture of ceramics is feldspar. At Mount Ragas, located in Clering Village, Donorojo, Jepara, Central Java, there are feldspar deposits which have the potential to supply the demand of the ceramic industry. The purpose of the study was to determine the geological conditions, mineralogical composition, chemical composition and characteristic of feldspar in ceramic industry. The research methods used were geological mapping, petrographic analysis and XRF geochemical analysis. The lithology of research area consists of andesite and alluvium deposits. Andesite is composed of plagioclase (andesine), alkali feldspar, quartz, hornblende, pyroxene and opaque mineral. The chemical composition of feldspar consists of SiO2 (61.03-65.01%), Al2O3 (20.23-22.5%), K2O (5.27-5.52%), Na2O (4.65-5.1%), CaO (0.43-0.65%), Fe2O3 (0.61-2.13%), MgO (<0.01%), MnO2 (<0.01%), TiO2 (0.09-0.11%), Cr2O3 (<0.01%), LOI (1.65-1.73%). Based on SNI No. 1145-1984, no samples meet the requirements for porcelain materials, only sample SMP-05 meets the requirements for sanitary materials and samples SMP-04, SMP-05 and SMP-06 meet the requirements for pottery material. Based on the standard from PT Semarang Mineral Pembangunan, feldspar samples that meet the requirements for glass materials are SMP-04 and SMP-05 and samples that meet the requirements for ceramic materials are SMP-01, SMP-02, SMP-03 and SMP-06.
Utilization of fly ash and bottom ash from TanjungJati B Coal-Fired Power Plant in Jepara, Central Java, on the quality of cellular lightweight concrete
Authors: Nurkhamim  , Wardani I R , Adjie D P W , Purwanta J , Inmarlinianto
Published: May 2024

The research aims to address waste-related issues by producing Cellular Lightweight Concrete (CLC) bricks using fly ash and bottom ash as fine aggregates. The variations used encompass cement, fly ash, bottom ash, and sand compositions. The ratio between cement and fine aggregates utilized is 1:3. The variations in the composition of fine aggregates include P (100% sand), F (100% fly ash), B (100% bottom ash), F1B1 (50% fly ash and 50% bottom ash), F1B2 (33.3% fly ash and 66.7% bottom ash), F1B3 (25% fly ash and 75% bottom ash), F2B1 (6.7% fly ash and 33.3% bottom ash), and F3B1 (25% fly ash and 75% bottom ash). The parameters employed comprise compressive strength testing, density, and water absorption evaluation of the CLC bricks at ages 14, 28, and 35 days, also thermal conductivity at the 35-days sample. The sample age exhibits a proportional relationship with compressive strength and water absorption, while displaying an inverse relationship with density. At the 35-day sample age, the F composition demonstrates the highest compressive strength (14.74MPa) and the lowest water absorption (11%). Meanwhile, the B composition exhibits a compressive strength value of 5.9MPa and the lowest density (1.12g/cm2). Conversely, the P composition showcases the highest density (1.59g/cm2). Density affects thermal conductivity, the lower the density, the lower the thermal conductivity, which means that the heat conductivity will be smaller.
Geothermal potential area analysis using Landsat 8 OLI/TIRS and digital elevation model images (case study: Lawu Mount, Central Java)
Authors: Utama P P , Yoni D R , Amalia D , Ulhaq I D , Arya M S F
Published: May 2024

Mount Lawu is one of the volcanoes in Central Java Province with hidden geothermal potential. This research aims to identify geothermal potential areas, especially hydrothermal alteration areas, using Landsat 8 imagery in Mount Lawu, Central Java. Hydrothermal alteration serves as a crucial indicator in the exploration of geothermal potential in an area. Multispectral image processing methods of Landsat 8 are employed to map the distribution patterns of hydrothermal alterations in the study area, together with the anomaly of temperature and heatflux in the surface. This approach involves principal component analysis and spectral alteration indications that combine information from various image channels. Lithology and lineament density analysis strengthen the delineation and analysis of the geothermal potential area. The western-northwestern part of Mount Lawu is the most potential region for geothermal resources based on the distribution of hydrothermal alteration areas and the high density of faulted regions, which are also supported by geothermal manifestations such as hotspring sites in the area.
Source rock characterization based on geochemical observations using Well BO-1, Central Sumatra Basin
Authors: Herlienda Elizabeth K.G. , Sutadiwiria Yarra , Setiaji Ronoatmojo Imam , Cahyaningratri P.R. , Ali Jambak Moehammad , Livsey Andy
Published: May 2024

The Central Sumatra Basin, characterized as a tertiary back-arc basin, stands as one of Indonesia’s foremost hydrocarbon-producing basins. Consequently, in the pursuit of hydrocarbon exploration endeavors, a comprehensive analysis of the potential source rocks within this region becomes imperative. The focal point of this study is the BO-1 well, situated within the Pematang Formation. Geochemical analysis methods, specifically leveraging Total Organic Carbon (TOC) and Rock-Eval Pyrolysis data, were employed to assess the quality, quantity, and maturity of the source rock. The research findings reveal a noteworthy organic material content at a fair-to-good level, registering an average TOC value of 0.69% and a Potential Yield of 1,994 mg/g, both falling within the fair-to-good classification. The Hydrogen Index value designates the source rock as type III kerogen, indicating a propensity for gaseous product generation. Maturity evaluation places the source rock within an immature to mature range, with a maximum temperature range of 383-452°C. In summary, the analysis discerns the source rock within the research area as an effective type, characterized by a substantial organic material abundance at a fair-to-good level and a mature maturity level. This conclusion is reinforced by the lithology of the research area, predominantly comprising mudstone, recognized for its richness in organic material.
Depositional system of Halang Formation from Ci Mande and Panaruban River outcrop: an interpretive based on lithofacies and trace fossil
Authors: Herdiansyah Firman , Helman Hamdani Ahmad , Muljana Budi , Burhannudinnur Muhammad , Jambak Ali , Syavitri Dewi , Deva Ananta Adistayana Putu
Published: May 2024

This paper focuses on confusing various theories of Middle to Late Miocene sedimentary rocks, especially the Halang Formation in the CiMande and Panaruban River Banyumas Central Java. Previous studies revealed miscellaneous conclusions regarding the depositional system of this formation. This research was conducted with field observations, consisting of 2 measured stratigraphy section. Lithofacies and trace fossils are identified by making detailed vertical records of outcrops. The lithofacies association are: B1 is Massive Sandstone, B2a is Parallel Laminated Sandstone, B2b is cross-laminated sandstone, C2 is interbedded sandstone and shale, D1 is Siltstone, E1 is Mudstone, and F2 is Coherent deposits. Four variations of trace fossils include Thallasinoides, Skolithos, Chondrites and Rhizocorallium. It is classified into Skolithos Ichnofacies and Cruziana Ichnofacies in the lower shoreface. Skolithos and Cruziana ichnofacies association in the submarine fan due to local sediments preserved trace fossils are not ultimately consolidating. Based on the facies association, it has characteristics resulting from the turbidite mechanism, which was deposited in the deep marine fan environment precisely in parts of suprafan lobes on midfan. Conversely, the presence and diversity of trace fossils indicate that these sediments were deposited in shallow marine. The conclusion is that the sediment in which the trace fossils are preserved has been partially lithified, and the deposition reworked by gravity in the suprafan lobes on the midfan.
Study on the Influence of Salinity, TDS, GWL and Land Use in the Coastal Region of Kebumen Regency with a Statistical Approach
Authors: Radityo D , Pratomo S U
Published: May 2024

This study investigates the impact of salinity levels, total dissolved solids (TDS), groundwater levels (GWL), and land use patterns in the coastal region of Kebumen Regency, employing a statistical approach. Coastal areas are often vulnerable to salinity variations, which can significantly affect the surrounding ecosystems and land utilization. The research aims to discern the correlation between TDS, salinity levels, GWL and land use practices in this specific region, employing statistical analysis as a means of quantifying and understanding these relationships. Total dissolved solids (TDS) represent the concentration of inorganic salts, minerals, and ions in water bodies and play a crucial role in the overall water quality of coastal areas. Salinity levels, on the other hand, directly affect TDS and are influenced by factors such as tidal patterns and freshwater input. Groundwater levels affect salinity and TDS. Land use practices, including agricultural, residential, and industrial activities, profoundly impact coastal ecosystems and are often influenced by salinity levels. This study utilizes statistical methods to analyze the complex interplay between TDS, salinity, GWL, and land use in the Kebumen Regency coastal region. By examining data related to TDS, salinity, GWL, and land utilization, this research seeks to contribute valuable insights into the sustainable management of coastal environments. The findings of this study are expected to inform decision-making processes for the benefit of local communities and ecosystems, guiding future policies and practices for the preservation and balanced development of coastal areas in Kebumen Regency
Formulating flood mitigation through public participation, remote sensing analysis, and flood genetic understanding: study case Samarinda City flood January 2020
Authors: Rachman M G , Kurniawan O , Nugraha A
Published: May 2024

Samarinda, a city characterized by its unique topography and proximity to major rivers, has been grappling with recurring and escalating flood events. The frequency and severity of these floods have been well-documented in numerous past academic studies, underscoring the pressing need for innovative flood mitigation strategies. In response to this challenge, this study employs a multi-faceted approach by incorporating public participation, remote sensing analysis, and flood genetic understanding. To facilitate a comprehensive flood mitigation strategy, we initiated the collection of real-time reports from the public during flood events. The participation of the local community in this data collection process has provided critical insights into the dynamics of flood occurrence and its impacts. The integration of crowdsourced data has been instrumental in augmenting our understanding of the local flood patterns. In parallel, we harnessed the capabilities of the Sentinel-1 satellite to conduct remote sensing analysis, enabling us to identify and map inundated areas during specific flood events. This approach, utilizing Sentinel-1, has been validated in prior flood studies. Our research further combines these datasets, merging live reports with remote sensing flood mapping to detect and assess affected areas. We introduce a novel categorization system based on flood genetics, dividing the floodprone region into three distinct zones according to hydrogeological condition of each water catchment area. We divided the area into three zones based on its genetic. This model guides us to the innovative approach enriching our flood mitigation strategy based on those valuable insights. The culmination of our study is the formulation of tailored mitigation plans for each of the three identified flood genetic zones. Incorporating public participation, remote sensing, and flood genetic understanding, our study provides a holistic framework for flood mitigation in the flood-prone city of Samarinda. By harnessing the collective intelligence of the community, leveraging cutting-edge technology, and integrating advanced scientific concepts, we present a comprehensive approach to address and mitigate the ongoing flood challenges in the region.
The Prospect of Typhoon Landfall Observation Utilizing L-band InSAR
Authors: Setiawan Naufal , Arief Syachrul , Furuya Masato , Heki Kosuke
Published: May 2024

The cyclonic phenomenon, particularly typhoons within the 100° E to 180° E longitude region, bring significant devastation through intense rainfall and strong winds, causing secondary effects like landslides and floods upon landfall. This results in infrastructural damage and loss of life, ranking storm-related disasters, including typhoons, second only to earthquakes in casualties, emphasizing the need for a robust observation system. While higher income countries benefit from established radar and meteorological stations for continuous monitoring, this study highlights the critical necessity for an additional monitoring system in lower income countries. We investigate the applicability of Interferometric Synthetic Aperture Radar (InSAR) during typhoon landfall, particularly in densely vegetated areas where longer wavelengths like L-band (for instance, the Advanced Land Observing Satellite (ALOS/PALSAR) and ALOS-2/PALSAR-2) are suitable. By analyzing typhoon occurrences and confirming landfall using weather radar from 2007 to 2011 (ALOS/PALSAR observation period) and 2014 to 2023 (ALOS-2/PALSAR-2 observation period), our study successfully identifies the landfall of the Jebi typhoon on September 4, 2018. InSAR processing reveals significant phase gradients linked to dense water vapor during landfall, corroborated by comparisons with sea-level Zenith Wet Delay (ZWD) from Global Navigation Satellite System (GNSS) data and hourly precipitation rates from the Automated Meteorological Data Acquisition System (AMeDAS). The concurrence of InSAR results with ZWD values and rainfall data from meteorological stations validates the potential of L-band InSAR in observing typhoon landfalls.
Analysis of scale problem using acidizing stimulation in field Z Kalrez Petroleum (Seram) LTD.
Authors: Subekti Henk , Idrus Sumina
Published: May 2024

The annual decrease in production at well Z occurs due to scale deposits that impede fluid flow. Scale is a production problem due to the mixing of two types of water with different properties so that the solubility limit of the compound in the formation water is exceeded. To overcome the scale, stimulation is carried out with an acidizing method using a type of acid (HCL 10%). Evaluation was conducted to determine the effect of acidizing stimulation on scale based on productivity index (PI), inflow performance relationship (IPR) curve and comparison of stimulation methods. Evaluation of test results after acidizing stimulation of well Z experienced an increase in production. Productivity Index increased from 4.748 bpd/psi to 9.036 bpd/psi. Based on the IPR curve before acidizing, the maximum flow rate (Q max) = 324.107 bpd, increased to Qmax = 769.021 bpd. Based on the Cost Benefit Analysis (CBA), the Acidizing Stimulation method (10% formic Acid) was chosen to overcome the scale problem because the B/C ratio >1 or 1.9 means that for every 1 US$ invested in the Acidizing Stimulation method (10% formic Acid), a savings ratio of 1.9 will be obtained. So it is very reasonable to decide that the Acidizing Stimulation method (10% formic Acid), is feasible and more useful and efficient.
Evaluation of the application of the Havlena-Odeh method for determining reservoir OOIP with dual pressure maintenance
Authors: Kumala Sari Alvita , Taufiq Fathaddin Muhammad , Prakoso Suryo
Published: May 2024

Reservoir “X” produced since 2009, it has a very high level of complexity that is not found in other reservoirs in Indonesia at this time. This level of complexity can be seen in the dynamics/behavior aspect of the reservoir and the integrated dual pressure maintenance system. The update of subsurface data completes the level of confidence in calculating the estimated reserves of the reservoir. Havlena-Odeh’s Classic Material Balance approach has not been able to accommodate the uncertain aquifer (We) behavior (changing with time, complex unsteady state). This study intends to evaluate the applicability of the Havlena-Odeh material balance model in predicting original oil in place (OOIP) of reservoir with dual pressure maintenance. Based on the calculation results, Havlena-Odeh method was modified for this reservoir types to determine OOIP. This modified We formula is successful to represent in place counting of Havlenah Odeh Rules. A convergent original oil in-place estimate of 1,299,002,483.24 barrels of Oil is obtained
Laboratory study on the performance of AOS surfactant in increasing oil recovery
Authors: Pauhesti P , Satiawati L , Yasmaniar G , Saputra A K , Kalasnikova A
Published: May 2024

The decline in oil recovery in the oil and gas field is a problem that must be faced along with increasing energy needs. Efforts are made to increase oil recovery reserves with advanced methods, namely Enhanced Oil Recovery. In this study, an AOS (alpha olefin sulfonate) surfactant solution was used. Tests were conducted with varying concentrations at a salinity of 7,000 ppm. Phase behavior tests were also conducted for 7 days at 80 °C. The oil recovery value of the surfactant solution was also investigated. The testing stages carried out were density, interfacial tension, and core flooding tests. After making the surfactant solution sample, a density test was conducted at 30 and 80 °C. Finally, the core flooding test. The IFT results of the surfactant solution reached the critical micelle concentration (CMC) point so that it could reduce the interfacial tension well between oil and formation water in the reservoir with an interfacial tension value of 0.8212087 dyne/cm. Core flooding results are based on surfactants that reach the CMC point. There is a surfactant with a concentration of 1% Salinity 7,000 ppm at the CMC point with a recovery factor of 7.2727%.
Study of CO Gas Dilution in Forcing Ventilation System at Ramp Down KKRB 4 Utama, Pongkor, West Java
Authors: Yulianti R , Hartami P N , Aryanto R , Herdyanti M K , Suliestyah  , Pattiruhu D L
Published: May 2024

CO is a hazardous gas formed from the reaction of explosives that lack oxygen balance. These explosives have the potential to generate toxic gases, including CO. It is crucial to minimize CO concentration at the work site by ensuring proper air circulation. This study aims to examine the impact of varying ducting distances on CO gas dilution, using the gas diffusion coefficient value as a basis. The research method employed is observational, involving the assessment of CO gas dilution in the tested tunnel at varying distances from the working front to the sensor. The research was conducted on the Ramp Down KKRB 4 Utama. Result of the research is the most ideal carbon monoxide reduction time at RD KKRB 4 Utama is shown at sensor placement distance 1 using the blow system, where A Sensor takes 2.21 hours and B Sensor takes 1.06 hours to reach a concentration level below the TLV (Threshold Limit Value) 50 ppm.
The advances in the recovery process for precious metals from nickel slag, a review
Authors: Fadliah  , Raya I , Taba P , Burhanuddinnur M , Gaffar M , Dahani W , Palit C , Putri T W , Nur A
Published: May 2024

The creation of nickel-smelting products including important metals like nickel, cobalt, and copper is a persistent issue in the nickel mining business. Another secondary source of precious metals is nickel slag. In addition, the massive amounts of nickel slag generated by the nickel smelter sector will pollute the environment, particularly the soil, since the smelting slag contains hazardous materials. This study examines techniques for recovering precious metals from nickel slag by reviewing publications from Springer Link, Google Scholar, MDPI, ScienceDirect, Membrane Journal, and other authors. The two types of metal recovery techniques from nickel slag that were examined were hydrometallurgical and pyrometallurgical techniques. This review article describes a pyrometallurgical method that involves roasting and selective reduction. In the meantime, the hydrometallurgical techniques were examined in the high-pressure oxidative acid leaching process, the atmospheric acid leaching method, and the bioleaching process. A roadmap for research designs that can be used to recover valuable metals from nickel slag sustainably has been created due to the completed literature evaluation.
Geotourism of Telomoyo Volcano complex: an in-depth analysis for future development
Authors: Yudiantoro D F , Afrilita  , Pambudi S , Subandrio A , Choiriyah S U , Aryanto N C D , Apriniyadi M , Al Farizzi M I , Lukita A D , Santosa W B , Riyadurrizqy M S
Published: May 2024

Indonesia is located between the three world tectonic plates, the Eurasian Plate, the Indo-Australian Plate and the Pacific Plate. The collision of these three plates creates a series of volcanoes and tectonics activity in various regions, especially the subduction of the Indo-Australian Plate in southern Java. This subduction forming a row of tertiary-aged volcanoes in the south of the island of Java and quaternary in the central part of the island of Java. One of the Quaternary Volcanoes on the island of Java that is extends in a northwest-southeast, the volcanoes are Ungaran - Telomoyo - Merbabu - Merapi. The use of the geotourism analysis method is used to develop the existing geotourism potential in the Telomoyo Volcano Complex by carrying out a geodiversity inventory carried out through field activities to collect geological component data in the research area. The data collected is minerals, rocks, geological and morphological structures or landscapes that include several stages of work include categorization, assessment, evaluation, clustering and determination of geodiversity. This work is accomplished by identifying geoheritage to increase geological diversity into geological heritage through the stages of determining geodiversity and then classified to determine the status, value, meaning and function of geoheritage. The score ranking carried out to determine the geoheritage ranking by comparing the geotourism of the research location with the geotourism of other locations. The Telomoyo Volcano Complex holds a variety of unique and interesting geological phenomena so it had a promising geological conservation-based tourism potential. However, the lack of public knowledge about the potential for geology-based tourism or geotourism has caused the development of this tourism potential to be less than optimal and less desirable. Education, development and good management of the tourism sector are needed so that the potential of geotourism can be recognized by the wider community and can have a good impact, especially for the surrounding community, especially in the economic field.
Biofabrication of 3D adipose tissue via assembly of composite stem cell spheroids containing adipo-inductive dual-signal delivery nanofibers
Authors: Lee Sangmin , Lee Jeongbok , Choi Soomi , Kim Eunhyung , Kwon Hyunseok , Lee Jinkyu , Kim Sung Min , Shin Heungsoo
Published: May 2024

Reconstruction of large 3D tissues based on assembly of micro-sized multi-cellular spheroids has gained attention in tissue engineering. However, formation of 3D adipose tissue from spheroids has been challenging due to the limited adhesion capability and restricted cell mobility of adipocytes in culture media. In this study, we addressed this problem by developing adipo-inductive nanofibers enabling dual delivery of indomethacin and insulin. These nanofibers were introduced into composite spheroids comprising human adipose-derived stem cells (hADSCs). This approach led to a significant enhancement in the formation of uniform lipid droplets, as evidenced by the significantly increased Oil red O-stained area in spheroids incorporating indomethacin and insulin dual delivery nanofibers (56.9 ± 4.6%) compared to the control (15.6 ± 3.5%) with significantly greater gene expression associated with adipogenesis (C/EBPA, PPARG, FABP4, and adiponectin) of hADSCs. Furthermore, we investigated the influence of culture media on the migration and merging of spheroids and observed significant decrease in migration and merging of spheroids in adipogenic differentiation media. Conversely, the presence of adipo-inductive nanofibers promoted spheroid fusion, allowing the formation of macroscopic 3D adipose tissue in the absence of adipogenic supplements while facilitating homogeneous adipogenesis of hADSCs. The approach described here holds promise for the generation of 3D adipose tissue constructs by scaffold-free assembly of stem cell spheroids with potential applications in clinical and organ models.
A comprehensive review of protein-centric predictors for biomolecular interactions: from proteins to nucleic acids and beyond
Authors: Jia Pengzhen , Zhang Fuhao , Wu Chaojin , Li Min
Published: May 2024

Proteins interact with diverse ligands to perform a large number of biological functions, such as gene expression and signal transduction. Accurate identification of these protein–ligand interactions is crucial to the understanding of molecular mechanisms and the development of new drugs. However, traditional biological experiments are time-consuming and expensive. With the development of high-throughput technologies, an increasing amount of protein data is available. In the past decades, many computational methods have been developed to predict protein–ligand interactions. Here, we review a comprehensive set of over 160 protein–ligand interaction predictors, which cover protein–protein, protein−nucleic acid, protein−peptide and protein−other ligands (nucleotide, heme, ion) interactions. We have carried out a comprehensive analysis of the above four types of predictors from several significant perspectives, including their inputs, feature profiles, models, availability, etc. The current methods primarily rely on protein sequences, especially utilizing evolutionary information. The significant improvement in predictions is attributed to deep learning methods. Additionally, sequence-based pretrained models and structure-based approaches are emerging as new trends.
Single-cell RNA-seq data analysis reveals functionally relevant biomarkers of early brain development and their regulatory footprints in human embryonic stem cells (hESCs)
Authors: Alamin Md , Humaira Sultana Most , Babarinde Isaac Adeyemi , Azad A K M , Moni Mohammad Ali , Xu Haiming
Published: May 2024

The complicated process of neuronal development is initiated early in life, with the genetic mechanisms governing this process yet to be fully elucidated. Single-cell RNA sequencing (scRNA-seq) is a potent instrument for pinpointing biomarkers that exhibit differential expression across various cell types and developmental stages. By employing scRNA-seq on human embryonic stem cells, we aim to identify differentially expressed genes (DEGs) crucial for early-stage neuronal development. Our focus extends beyond simply identifying DEGs. We strive to investigate the functional roles of these genes through enrichment analysis and construct gene regulatory networks to understand their interactions. Ultimately, this comprehensive approach aspires to illuminate the molecular mechanisms and transcriptional dynamics governing early human brain development. By uncovering potential links between these DEGs and intelligence, mental disorders, and neurodevelopmental disorders, we hope to shed light on human neurological health and disease. In this study, we have used scRNA-seq to identify DEGs involved in early-stage neuronal development in hESCs. The scRNA-seq data, collected on days 26 (D26) and 54 (D54), of the in vitro differentiation of hESCs to neurons were analyzed. Our analysis identified 539 DEGs between D26 and D54. Functional enrichment of those DEG biomarkers indicated that the up-regulated DEGs participated in neurogenesis, while the down-regulated DEGs were linked to synapse regulation. The Reactome pathway analysis revealed that down-regulated DEGs were involved in the interactions between proteins located in synapse pathways. We also discovered interactions between DEGs and miRNA, transcriptional factors (TFs) and DEGs, and between TF and miRNA. Our study identified 20 significant transcription factors, shedding light on early brain development genetics. The identified DEGs and gene regulatory networks are valuable resources for future research into human brain development and neurodevelopmental disorders.
Secukinumab in adult patients with lichen planus: efficacy and safety results from the randomized placebo-controlled proof-of-concept PRELUDE study
Authors: Passeron Thierry , Reinhardt Maximilian , Ehst Benjamin , Weiss Jonathan , Sluzevich Jason , Sticherling Michael , Reygagne Pascal , Wohlrab Johannes , Hertl Michael , Fazel Nasim , Muscianisi Elisa , Fan Heng , Hampele Isabelle , Compagno Nicolò
Published: May 2024

Background

Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden, representing a population with a clear unmet need for new treatments.

Objectives

To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP) that is inadequately controlled by topical corticosteroids.

Methods

PRELUDE was a randomized double-blind placebo-controlled phase II proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomized to either secukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W) or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator’s Global Assessment (IGA) score ≤ 2 at week 16.

Results

Overall, 111 patients were randomized (n = 37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the three cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤ 2 response at week 16 with SECQ4W vs. placebo in the MLP {37.5% [95% credibility interval (Crl) 20.3–57.2] vs. 23.1% (95% Crl 6.5–49.2)} and LPP cohorts [37.5% (95% Crl 20.2–57.3) vs. 30.8% (95% Crl 10.8–57.6)]. In the LPP cohort, a sustained response for IGA ≤ 2 from week 16 to week 32 was achieved with SECQ4W (week 16, 37.5%; week 32, 45.8%), and a substantial improvement was observed in IGA ≤ 2 response in patients from this cohort who switched from placebo (week 16, 30.8%) to SECQ2W after week 16 (week 32, 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals.

Conclusions

PRELUDE is the first randomized controlled basket trial evaluating interleukin (IL)-17A inhibition with secukinumab across three subtypes of LP. Secukinumab was well tolerated and safe, showing different response rates across the three subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of IL-17A across LP subtypes. The novel IGA score showed significant correlation with both patient- and physician-reported outcome measurements.
Neuropathy target esterase activity defines phenotypes among PNPLA6 disorders
Authors: Liu James , He Yi , Lwin Cara , Han Marina , Guan Bin , Naik Amelia , Bender Chelsea , Moore Nia , Huryn Laryssa A , Sergeev Yuri V , Qian Haohua , Zeng Yong , Dong Lijin , Liu Pinghu , Lei Jingqi , Haugen Carl J , Prasov Lev , Shi Ruifang , Dollfus Hélène , Aristodemou Petros , Laich Yannik , Németh Andrea H , Taylor John , Downes Susan , Krawczynski Maciej R , Meunier Isabelle , Strassberg Melissa , Tenney Jessica , Gao Josephine , Shear Matthew A , Moore Anthony T , Duncan Jacque L , Menendez Beatriz , Hull Sarah , Vincent Andrea L , Siskind Carly E , Traboulsi Elias I , Blackstone Craig , Sisk Robert A , Miraldi Utz Virginia , Webster Andrew R , Michaelides Michel , Arno Gavin , Synofzik Matthis , Hufnagel Robert B
Published: May 2024

Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear.

We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6-associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists.

Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker.
In Pursuit of Equanimity: Managing Change and Adversity in Early Modern English Households, c.1570–c.1670
Authors: Greenall Abigail
Published: May 2024

This article establishes equanimity as an important emotional ideal in the late sixteenth and seventeenth centuries. In showing how equanimity served to strengthen positive emotions and temper disruptive states, it promotes a more positive view of the era’s emotional landscape. The article employs the pursuit of equanimity as an intimate analytical device for uncovering the agency of ordinary people, and thus offers historians a new perspective on momentous change and adversity in the early modern period. It charts personal experiences of adversity—from physical and spiritual threats to familial disputes, uncertain patriarchal power and economic precarity—alongside individual management of religious, social and political change following the English Reformations and during the Civil War. Where other scholars have examined how different social groups reactively negotiated new realities, this microhistorical study of one gentry family in the North West of England urges historians to refocus their attention on the proactive courses that people took. Through a detailed examination of 541 manuscript letters, domestic decorative schemes, and archaeological evidence of ritual practices of protection, the article uncovers how the Moretons of Little Moreton Hall in Cheshire managed change and mitigated disaster. It discusses instances where equanimity played a persistent role in motivating the family’s actions and behaviours in daily life, and argues that practices designed to promote emotional harmony were crucial for preserving kinship networks and managing personal well-being, as well as gender relations within households, in early modern England.
Early survival in Atlantic salmon is associated with parental genotypes at loci linked to timing of maturation
Authors: Aykanat Tutku , McLennan Darryl , Metcalfe Neil B , Prokkola Jenni M
Published: May 2024

Large effect loci often contain genes with critical developmental functions and potentially broad effects across life stages. However, their life stage-specific fitness consequences are rarely explored. In Atlantic salmon, variation in two large-effect loci, six6 and vgll3, is linked to age at maturity and several physiological and behavioral traits in early life. By genotyping the progeny of wild Atlantic salmon that were planted into natural streams with nutrient manipulations, we tested if genetic variation in these loci is associated with survival in early life. We found that higher early-life survival was linked to the genotype associated with late maturation in the vgll3, but with early maturation in the six6 locus. These effects were significant in high nutrients but not in low-nutrient streams. The differences in early survival were not explained by additive genetic effects in the offspring generation but by maternal genotypes in the six6 locus and by both parents’ genotypes in the vgll3 locus. Our results suggest that indirect genetic effects of large-effect loci can be significant determinants of offspring fitness. This study demonstrates an intriguing case of how large-effect loci can exhibit complex fitness associations across life stages in the wild and indicates that predicting evolutionary dynamics is difficult.
Effect of abdominal tissue thickness on trabecular bone score and fracture risk in adults with diabetes: the Manitoba BMD registry
Authors: Leslie William D , Binkley Neil , Schousboe John T , Silva Barbara C , Hans Didier
Published: May 2024

Individuals with type 2 diabetes have lower trabecular bone score (TBS) and increased fracture risk despite higher bone mineral density. However, measures of trabecular microarchitecture from high-resolution peripheral computed tomography are not lower in type 2 diabetes. We hypothesized that confounding effects of abdominal tissue thickness may explain this discrepancy, since central obesity is a risk factor for diabetes and also artifactually lowers TBS. This hypothesis was tested in individuals aged 40 years and older from a large DXA registry, stratified by sex and diabetes status. When DXA-measured abdominal tissue thickness was not included as a covariate, men without diabetes had lower TBS than women without diabetes (mean difference −0.074, P < .001). TBS was lower in women with versus without diabetes (mean difference −0.037, P < .001), and men with versus without diabetes (mean difference −0.007, P = .042). When adjusted for tissue thickness these findings reversed, TBS became greater in men versus women without diabetes (mean difference +0.053, P < .001), in women with versus without diabetes (mean difference +0.008, P < .001), and in men with versus without diabetes (mean difference +0.014, P < .001). During mean 8.7 years observation, incident major osteoporotic fractures were seen in 7048 (9.6%). Adjusted for multiple covariates except tissue thickness, TBS predicted fracture in all subgroups with no significant diabetes interaction. When further adjusted for tissue thickness, HR per SD lower TBS remained significant and even increased slightly. In conclusion, TBS predicts fractures independent of other clinical risk factors in both women and men, with and without diabetes. Excess abdominal tissue thickness in men and individuals with type 2 diabetes may artifactually lower TBS using the current algorithm, which reverses after accounting for tissue thickness. This supports ongoing efforts to update the TBS algorithm to directly account for the effects of abdominal tissue thickness for improved fracture risk prediction.
Effective timing of hyaluronate gel injection in image-guided adaptive brachytherapy for uterine cervical cancer: a proposal of the ‘adjusted dose score’
Authors: Miyata Yusaku , Ogo Etsuyo , Murotani Kenta , Tsuda Naotake , Suzuki Gen , Tsuji Chiyoko , Akeda Ryosuke , Muraki Koichiro , Hattori Chikayuki , Abe Toshi
Published: May 2024

Hyaluronate gel injection (HGI) in the rectovaginal septum and vesicovaginal septum is effective in the setting of high-dose-rate image-guided adaptive brachytherapy (IGABT) for cervical cancer. We aimed to retrospectively investigate optimal conditions for HGI to achieve optimal dose distribution with a minimum number of HGI. We classified 50 IGABT plans of 13 patients with cervical cancer who received IGABT both with and without HGI in the rectovaginal septum and vesicovaginal septum into the following two groups: plan with (number of plans = 32) and plan without (number of plans = 18) HGI. The irradiation dose parameters of high-risk clinical target volume (CTVHR) and organs at risk per fraction were compared between these groups. We also developed the adjusted dose score (ADS), reflecting the overall irradiation dose status for four organs at risk and CTVHR in one IGABT plan and investigated its utility in determining the application of HGI. HGI reduced the maximum dose to the most exposed 2.0 cm3 (D2.0 cm3) of the bladder while increasing the minimum dose covering 90% of CTVHR and the percentage of CTVHR receiving 100% of the prescription dose in one IGABT plan without causing any associated complications. An ADS of ≥2.60 was the optimum cut-off value to decide whether to perform HGI. In conclusion, HGI is a useful procedure for improving target dose distribution while reducing D2.0 cm3 in the bladder in a single IGABT plan. The ADS can serve as a useful indicator for the implementation of HGI.
Impact of DNA ligase inhibition on the nick sealing of polβ nucleotide insertion products at the downstream steps of base excision repair pathway
Authors: Almohdar Danah , Kamble Pradnya , Basavannacharya Chandrakala , Gulkis Mitchell , Calbay Ozlem , Huang Shuang , Narayan Satya , Çağlayan Melike
Published: May 2024

DNA ligase (LIG) I and IIIα finalize base excision repair (BER) by sealing a nick product after nucleotide insertion by DNA polymerase (pol) β at the downstream steps. We previously demonstrated that a functional interplay between polβ and BER ligases is critical for efficient repair, and polβ mismatch or oxidized nucleotide insertions confound the final ligation step. Yet, how targeting downstream enzymes with small molecule inhibitors could affect this coordination remains unknown. Here, we report that DNA ligase inhibitors, L67 and L82-G17, slightly enhance hypersensitivity to oxidative stress-inducing agent, KBrO3, in polβ+/+ cells more than polβ-/- null cells. We showed less efficient ligation after polβ nucleotide insertions in the presence of the DNA ligase inhibitors. Furthermore, the mutations at the ligase inhibitor binding sites (G448, R451, A455) of LIG1 significantly affect nick DNA binding affinity and nick sealing efficiency. Finally, our results demonstrated that the BER ligases seal a gap repair intermediate by the effect of polβ inhibitor that diminishes gap filling activity. Overall, our results contribute to understand how the BER inhibitors against downstream enzymes, polβ, LIG1, and LIGIIIα, could impact the efficiency of gap filling and subsequent nick sealing at the final steps leading to the formation of deleterious repair intermediates.