bluuebunny/crossref_metadata_2025 huggingface dataset:
Framing of space and place: an insight into George Town World Heritage Site, Penang, Malaysia
Authors: Bakri A F , Kamarudin H , Qamaruz Zaman N , Samadi Z , Abdul Ghani M Z
Published: August 2023

In architecture and urban design, the meaning, interpretations, identities, and uses of space and place are contentious topics. By framing space, which becomes a mechanism for the authorised group to manage power, it is possible to programme users’ activities regarding how to occupy space and location. This paper examines the construction of space and place in an urban, multicultural, and postcolonial World Heritage City. The qualitative research takes place at the George Town World Heritage Site (WHS) in Malaysia, specifically the ‘Street of Harmony’. The study contributes to a better understanding of the relationship between the World Heritage city and its local communities through field observations and semi-structured interviews with the communities. Policy (heritage and conservation and education), community-based, tourism, heritage, and politics are the identified frames. The street is portrayed in a number of ways, including the way in which a person’s daily activities are framed by the confines of their home. Understanding this contributes to the future practicable and nondisruptive practice of urban regeneration, resulting in a resilient and sustainable community.
Thai temple area: facilities assessment for emergency shelter use
Authors: Limsaksri Doungjai , Rugwongwan Yanin
Published: August 2023

An emergency shelter is a place where people live temporarily in case of an emergency. In Thailand, the emergency shelter usually is constructed by amending the temple area or using the temple area itself. Since the purpose of the temple is to be a place for religious activities, the amount of the area may not fit for being an emergency shelter. The purpose of this research are to evaluate the adequacy of the residential area and the supporting rate for the number of people in the community. For the research method, this research uses the temple area surveying in the case study temple. The result found that using the temple area as the emergency shelter is not sufficient when compared to the population in the surrounding communities. In conclusion, using the temple area as an emergency shelter is a policy based on the fact that the temple is a convenient and accessible public space located very close to the community. Normally, these temples are used for religious rituals and monks’ activities, so the physique of the building is mainly to support those types of activities. But when the temple needs to be modified into an emergency shelter, the amount of space are not sufficient to support the people from the communities around the temple and making it more difficult for the victims to live.
Assessing the Effect of High-Density Housing on Mental Health of Urban Population. Case Study: Federal Territory of Kuala Lumpur
Authors: Marzukhi Marlyana Azyyati , Ghazali Nur Masyitah , Yaman Rostam , Leh Oliver Ling Hoon , Nasrudin Na’asah
Published: August 2023

The increasing trends of urbanisation and the increasing prevalence of people having depression, anxiety, and stress worldwide are alarming. Urbanisation has exerted pressure on housing provision for urban dwellers, and more high-density housing is built to accommodate the migration of people to urban areas. This study aims to assess the effect of living in urban high-density residential on mental disorders of urban population. To understand the relationship between urban high-density living and mental disorders, a questionnaire survey was distributed to the dwellers of urban high-density residents in Federal Territory of Kuala Lumpur based on the characteristics of density, open spaces, and facilities provision. Responses are analysed using Spearman’s Correlation for the questionnaire. The questionnaire surveys show relatively high symptomatology of depression, anxiety and stress and a strong correlation value with high-density living. These results suggest that most people living in an urban high-density living may risk developing mental disorders. On this basis, mental health’s requisites should be considered when designing high-density housing and can support government policies such as in Sustainable Development Goals (SDG), in Ministry of Health policies, in PLANMalaysia development policies, State Structure Plans, District Local Plans, and others related organisation and research.
Toward Healthy Urban Streets: Richness of Roadside Tree Species in Industrial Area of Shah Alam, Selangor
Authors: Ruziman Hasya Hannani , Ismail Asmida , Mohti Azian , Abdullah Muhammad Fuad , Pardi Faezah
Published: August 2023

Roadside trees are distinct component of urban forests, providing benefits to reduce radiation heat and air pollution. However, urban settlements due to overpopulation might affect the abundance of roadside trees. Hence, this study was conducted to assess the species richness and diversity of roadside trees in Shah Alam. All trees with 1-metre height and above in Section 15 and 16 were measured and identified as referred to the Landscape Department of Shah Alam City Council (MBSA) computerised database. The data was analysed for their taxonomic composition and species diversity. A total of 5,523 trees were recorded where 4,087 trees in Section 15 and 1,426 trees in Section 16. Fabaceae was the most dominant family in both sections where their three leading species such as Peltophorum pterocarpum, Pterocarpus indicus, Roystonea regia accounted for 14.7% of the planted trees. Section 15 was relatively higher in taxonomic composition with 11 families and 25 species than Section 16, with 8 families and 18 species. The values for Species Diversity Index are considered high in both sections with 8.37 despite the environmental impact from the industrial activities. Thus, it is suggested that future research should include the potential risks of biodiversity loss for proper management practices in urban settings.
Managing the impact of COVID-19 crisis on tourism sector in protected area: A case study in Pahang National Park
Authors: Abdullah M F , Noor M I M , Ahmad B E , Yusoh M P , Pardi F
Published: August 2023

The COVID-19 pandemic has caused major disruptions to the world economy and the tourism industry, particularly in rural areas like the Pahang National Park in Malaysia. This study utilized qualitative research through the phenomenology approach to understand the impact of the pandemic on local tourism businesses in Pahang National Park. Through in-depth interviews with 12 informants from various backgrounds, the study found that there were four main impacts of COVID-19 on the rural tourism sector in Pahang National Park, including a lack of tourist arrivals, closure of small tourism-related businesses, loss of income, and job insecurity. The study aims to provide insight into creating safety measures and action plans for the tourist industry, and suggests that diversifying and having a secondary source of income can help protect livelihoods. The success of rural tourism in times of crisis depends on the development of new economic models and practical community tourism strategies.
A Survey on Homebuyers Behaviour towards the Housing Market in Klang Valley
Authors: Nordin Muhamad Saiful Alizan , Rahim Norbaya Ab
Published: August 2023

Study on home buyers’ behaviour is significant as current improvements can be made by evaluating the trend of past behaviour while the future improvement is based on current behaviour. Although extensive research has been carried out, most of the research are focused on preference-related behaviour while too little attention has been paid on behaviour towards market condition. Therefore, this paper aims to assess the behaviour of home buyers towards the housing market in Klang Valley. Conceptual framework has been developed by incorporating three (3) behavioural attributes of home buyers namely housing market perceptions, informational influence as well as housing market expectations. Questionnaire survey has been distributed to 224 respondents who bought the house in Klang Valley. The data were analysed using a descriptive statistic and thematic analysis. The empirical results revealed that majority of home buyers aware that the price is rising and optimistically forecast the trend to be continued for both short and long terms while the future purchase possibilities are expected at difficult level. Finally, the main sources of information frequently used by home buyers are human sources followed by networked sources, printed media, organisational sources as well as other sources. The study also signifies the existence of herd behaviour in most of home buyers’ decision. This paper proposed a new conceptual model for studying the home buyers’ behaviour.
Assessing the soundscape of heritage streets in Melaka: the ISO/TS 12913-2:2018 method of data collection
Authors: Jalil Nurul Amira Abd , Samadi Zalina , Din Nazli Che , Hanapi Nurul Liyana
Published: August 2023

The value of heritage sites is often distinguished through their architectural and physical features. However, the characteristic of a place is forged through the combination of multiple sensory elements. Acoustic is an essential element in the study of heritage spaces related to music, performance, congregations, etc. However, in the study of heritage sites, the acoustic elements are often overlooked even though they are an important element that adds spirit to the place. How people perceive their environment aurally is just as important as how they perceive it visually. This paper discusses the application of soundscape assessment methods recommended in ISO/TS 12913-2:2018. The technical specification presented comprehensive guidelines and alternatives on how a soundscape assessment should be conducted. The field study method and all its data collection protocols are reviewed and explored for implementation in the study of heritage streets in Melaka World Heritage Site. Characterising the soundscape profile of Melaka heritage streets will assist in understanding another facet of user experience and the acoustic ecology of the site.
Outdoor Thermal Comfort of Urban’s Pedestrian in Tropical City of Kuala Lumpur
Authors: Ishak N M , Abdullah J. , Rahman N A A
Published: August 2023

In recent years, urbanization in the city have given impact to the climate change of the environment. The increase in urban air temperature have decrease the thermal comfort or ruin the experience of the pedestrian in outdoor spaces. This research explores the impact of air temperature on pedestrian outdoor thermal comfort in shaded spaces of tropical city of Kuala Lumpur. Findings are presented from field measurement based on the environmental parameters on case study area. Surveys are conducted which includes 199 randomly selected pedestrians to subjectively observe their feeling and preferences of the outdoor thermal comfort towards the climatic outdoor temperature. Hence, the result concluded that the urban pedestrian walkway has a significantly high temperature. However, the results show that presence of shading structure improve their comfort being in outdoor spaces. This conclude that thermal sensation of pedestrian can be improved with shading structure and it can increase the walkability of pedestrians. The space can also increase the pedestrian’s comfort with help of mechanical ventilation. Thus, it is recommended for outdoor pedestrian spaces to provide shading and have proper ventilation to reduce heat and make pedestrian feels comfortable outdoor.
Assessing criteria on sustainable campus development of public universities in Malaysia through content analysis
Authors: Nadzmy Nur Fardeana Enche , Adnan Hamimah , Yaman Rostam
Published: August 2023

Sustainability is no longer just a fiercely disputed topic with broad consequences in academia and society, it is also vital for organisations in a number of industries including higher education institutions (HEIs). However, the lack of implementation of Sustainable Campus Development (SCD) in universities jeopardised the continuation of the sustainable agenda towards achieving the sustainable goal. Therefore, this paper aim is to assess the criteria contributing to SCD among public universities in Malaysia through content analysis. A list of participating public universities in UI-GreenMetric Ranking (UI-GMR) was assessed. The web content of sixteen (16) websites was examined and any relevant PDF documents that were related to the university sustainability reports were also analysed. Five (5) numbers of universities were selected to present sustainable initiatives to fulfil sustainable development criteria hence achieving UI-GMR. The initiatives were compiled based on six (6) criteria listed in UI-GMR and a relation between the Sustainable Development Goals (SDGs) and the UI-GMR were also determined. Although the initiatives provided by universities vary from one another, there are similarities in contributing to sustainability by providing campus practices towards the sustainability. From the findings, Universiti Utara Malaysia (UUM) has taken the sustainable development initiatives the most while Universiti Sains Malaysia (USM) has taken the least sustainable initiatives. Some limitations apply to the findings due to the established criteria obtained content from the websites without human validation and resulted to inadequate assessment and may be influenced by other causes such as technological difficulties and the degree of information transparency. Hence, additional analysis may be useful to obtain more robust data by incorporating other method which is through an in-depth face-to-face interview with sustainable campus leaders.
Site Suitability Analysis for Sea Turtle Nesting Area by using AHP and GIS
Authors: Azizan Nor Hidayah , Naharudin Nabilah , Hashim Nurhanisah , Rusli Mohd Uzair
Published: August 2023

Sea turtles are among the endangered marine life not only in Malaysia but also in the world. There are various criteria required in finding a suitable turtle nest site, it may be necessary to suit the needs of the environment in the study area, and it was found that there are four (4) most important criteria in studying turtle nesting suitability site namely (1) sand temperature, (2) vegetation, (3) beach slope, and (4) sand particle size. The use of GIS with the help of AHP can get a better result in finding the site suitability for sea turtle nesting by using weighted overlay analysis. The highest weight value is sand particle size with 0.616, followed by beach slope with 0.220, sand temperature with 0.114, and vegetation with 0.049 was derived from the use of AHP techniques. As a result, the suitability index in the study area was measured and analyzed with the sea turtles’ activities. As a result, the suitability index in the study area was measured and analyzed with the sea turtles’ activities. It was found that there is a low correlation between the site suitability index and the sea turtles’ activities which matches the expert’s opinion that though the site is deemed suitable for sea turtles nesting, they may not be crawled up and nest due to other external factors. The sites with the highest index were verified to be the most suitable by the experts as it is true that sea turtles were ascending to the sites for nesting. In conclusion, integrating GIS with the help of AHP can be an important technique to find a suitable site for the sea turtle nesting area.
Analyzing the Effectiveness of Support Vector Machine and Random Forest Classifiers in Delineating the Green Area
Authors: Nadzri Iklil Faqihah Mohamad , Khalid Nafisah , Wahab Warishah Abdul , Hashim Nurhanisah
Published: August 2023

Due to human limitations in exploring the world, the existence of remote sensing technology has made it possible and affordable for humans to study the green cover in the modern world, especially over a large region. This is so that details of the objects can be captured and monitored by satellites or other aircraft by measuring the wavelengths of radiation that are both emitted and reflected from the area. For the past decades, various approaches have been utilized by researchers to detect green areas such as deep learning, machine learning, object based and pixel-based classification. Thus, this study aims to evaluate the effectiveness of machine learning classifiers such as Support Vector Machine (SVM) and Random Forest (RF) in detecting and delineating the green area in Universiti Teknologi Mara (UiTM) Shah Alam. Based on the study, the overall accuracy obtained by the SVM classifier is 80% with a 0.75 kappa coefficient, whereas the RF classifier managed to get 79% with a 0.74 kappa. Even though the result of both classifiers is almost the same, the accuracy of detecting green area by the SVM classifier is 93% which outperforms the RF classifier with an accuracy of 88%. This shows that the SVM classifier is more effective than the RF classifier. The detection and delineation of the green area using both machine learning approaches also showed using a map so that it is easier to be analyzed and observed.
Ecological risk assessment of Kaeng Krachan National Park emphasis on Land Use/Land Cover (LULC)
Authors: Rathnayake R M P J , Rattanapun P , Chaisri B , Dubsok A , Wachirasirodom R , Kittipongvises S
Published: August 2023

Land use/land cover (LULC) changes with time, signify disturbances and conservation patterns of landscape types in an environment. Kaeng Krachan National Park (KKNP) is a UNESCO world heritage site with rich biodiversity and provides habitat for indigenous communities who are relying on farming. The study was conducted by calculating landscape ecological risk indices of classified Landsat images based on five landscape classes (Water, Grassland, Built-up-land, Forest, and Cultivated land). Landscape loss indices were calculated based on classified Landsat images. Assigning landscape loss indices in grid cells calculated the ecological risk indices of the area. Ecological risk indices were lowest (ERI ≤ 0.0005), lower (ERI ≤ 0.001), medium (ERI ≤ 0.005), higher (ERI ≤ 0.01), and highest (ERI ≤ 0.015). Ecological risk indices were higher on the east border of KKNP proximate to the semi-urban settlements. The highest risk area demarcates waterbodies and extensively cultivated land. The LULC areas which show the higher variation of changes from 2013 to 2022 are grasslands and forest cover. The changes in the LULC pattern have increased the risk in cultivated land areas and grasslands due to farming obligations. The provision of land permits and land use limitations are addressed issues to conserve KKNP for conservation.
Biofilm Fabrication from Cellulose Acetate of Oil Palm Empty Fruit Bunch and Corn Starch as Bio-polybag Material for Eco-friendly Plantation
Authors: Purba Ibnu Tryansar , Sani Kalimaya Qolbi , Sayekti Nur , Ramadhani Sabela Sanata , Waluyo Joko , Pranolo Sunu Herwi , Kaavessina Mujtahid
Published: August 2023

The utilization of polybags is prevalent among agriculturalists as a nursery container in one of the processes in agricultural and plantation activities. The polybag currently used is derived from petroleum and tough to decompose, causing various environmental problems such as soil contamination which interferes with plant growth. On the other hand, Indonesia has a superior palm oil commodity that increases annually. This accumulation provokes an increasing quantity of palm oil waste. Oil palm empty fruit bunch (OPEFB) is the highest considerable solid waste in the CPO production (0.23 kg/kg fresh fruit bunch) containing cellulose (40.37%). It is potentially used as bio-polybags decomposable easily. This study aims to determine the preparation method and the composition’s consequence on the characterization of OPEFB cellulose-based-bio-polybags. The technique used in producing bio-polybags is solution casting. This study’s concentration variants were adjusted to the ANOVA (23 factorial design) statistical results by conversion regression equation concerning corn starch, cellulose acetate, and CaCO3. Mechanical assessments include tensile strength (1.461 – 8.442 MPa) and elongation (2.611% – 8.808%). The structural test might consider the quality of the biofilm. This innovation is desired to decrease conventional polybag usage and promote sustainable bio-polybag as eco-friendly nursery containers in the vegetable plantation.
Preparation of nanoporous SiO2/C derived from rice husk as anode material in SiO2/C||LiFePO4 full-cell through alkaline activation treatment
Authors: Pham Thanh Liem , Le Huu Phuoc , Le My Loan Phung , Vu Tan Phat , Tran Van Man
Published: August 2023

Silicon-based materials such as pure silicon (Si), silicon monoxide (SiO), silica (SiO2), are considered promising anode for future high power energy Li-ion batteries. Among them, SiO2 has garnered attention owing to its outstanding features such as high theoretical capacity (1961 mAh g−1), abundant reserve, and low-cost processing. However, the large expansion and shrinkage of the Si and SiO2 volume during lithiation/delithiation reaction are still the main barriers for practical application. In this study, SiO2 derived from rice husks and activated by KOH displayed a nanoporous structure with a porous matrix carbon that can absorb the volume expansion during lithiation process and facilitate the diffusion of Li+ ion along the pores to minimise the dendrite growth at the local area. Through activation treatment, the surface area of SiO2 increases up to 278.875 m2 g−1 with a pore volume of 0.191 cm3 g−1 and the average pore diameter is about 0.771 nm. The cycling results showed that rice husk ash mixed with KOH at a ratio of 1:0.5 offered the best capacity retention of SiO2/C anode material in half-cell. In full-cell configuration of SiO2/C||LiFePO4, the the negative electrode/positive electrode capacity ratio (N/P) ratio of 1.2 exhibited the most stable performance with the highest capacity retention.
Integrating multiple regulations on enzyme activity: the case of phosphoenolpyruvate carboxykinases
Authors: Rojas Bruno E , Iglesias Alberto A
Published: August 2023

Abstract. Data on protein post-translational modifications (PTMs) increased exponentially in the last years due to the refinement of mass spectrometry techniques and the development of databases to store and share datasets. Nevertheless, these data per se do not create comprehensive biochemical knowledge. Complementary studies on protein biochemistry are necessary to fully understand the function of these PTMs at the molecular level and beyond, for example, designing rational metabolic engineering strategies to improve crops. Phosphoenolpyruvate carboxykinases (PEPCKs) are critical enzymes for plant metabolism with diverse roles in plant development and growth. Multiple lines of evidence showed the complex regulation of PEPCKs, including PTMs. Herein, we present PEPCKs as an example of the integration of combined mechanisms modulating enzyme activity and metabolic pathways. PEPCK studies strongly advanced after the production of the recombinant enzyme and the establishment of standardized biochemical assays. Finally, we discuss emerging open questions for future research and the challenges in integrating all available data into functional biochemical models.
An Exploratory Pilot Study of Neuropsychological Performance in Two Huntington Disease Centers of Excellence Clinics
Authors: Rossetti M Agustina , Anderson Kendra M , Hay Kaitlyn R , Del Bene Victor A , Celka Andrea S , Piccolino Adam , Nelson Sheese Amelia L , Huynh Melissa , Zhu Liang , Claassen Daniel O , Furr Stimming Erin , Considine Ciaran M
Published: August 2023

Objectives

To describe the characteristics of patients receiving a clinical referral for neuropsychological evaluation in two Huntington’s Disease Society of America Centers of Excellence (HDSA COE). In this exploratory pilot study, we used an empirically supported clinical neuropsychological battery to assess differences in cognitive performance between premanifest and manifest HD patient groups (compared with each other and normative expectations).

Method

Clinical data from 76 adult genetically confirmed patients referred for neuropsychological evaluations was retrospectively collected from two HDSA COEs. ANOVA and Chi-square tests were used to compare variables between pre-manifest (n = 14) and manifest (n = 62) groups for demographic, cognitive, neuropsychiatric, and disease severity variables.

Results

Our clinics serviced a disproportionate number of motor manifest patients. Six measures were excluded from analyses due to infrequent administration. The full WAIS-IV Digit Span was disproportionately administered to the manifest group. The premanifest group showed stronger cognitive performance with effect sizes in the large range on subtests of the WAIS-IV Digit Span, HVLT-R, SDMT, and verbal fluency.

Conclusions

This is the first study to assess an empirically supported neuropsychological research battery in a clinical setting with a relatively large sample size given the rarity of HD. The battery adequately captured areas of impairment across the disease spectrum. Application of the current battery with larger premanifest samples is warranted.
Approximate estimation of cell-type resolution transcriptome in bulk tissue through matrix completion
Authors: Wang Weixu , Zhou Xiaolan , Wang Jing , Yao Jun , Wen Haimei , Wang Yi , Sun Mingwan , Zhang Chao , Tao Wei , Zou Jiahua , Ni Ting
Published: August 2023

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for uncovering cellular heterogeneity. However, the high costs associated with this technique have rendered it impractical for studying large patient cohorts. We introduce ENIGMA (Deconvolution based on Regularized Matrix Completion), a method that addresses this limitation through accurately deconvoluting bulk tissue RNA-seq data into a readout with cell-type resolution by leveraging information from scRNA-seq data. By employing a matrix completion strategy, ENIGMA minimizes the distance between the mixture transcriptome obtained with bulk sequencing and a weighted combination of cell-type-specific expression. This allows the quantification of cell-type proportions and reconstruction of cell-type-specific transcriptomes. To validate its performance, ENIGMA was tested on both simulated and real datasets, including disease-related tissues, demonstrating its ability in uncovering novel biological insights.
Multi-task prediction-based graph contrastive learning for inferring the relationship among lncRNAs, miRNAs and diseases
Authors: Sheng Nan , Wang Yan , Huang Lan , Gao Ling , Cao Yangkun , Xie Xuping , Fu Yuan
Published: August 2023

Motivation

Identifying the relationships among long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and diseases is highly valuable for diagnosing, preventing, treating and prognosing diseases. The development of effective computational prediction methods can reduce experimental costs. While numerous methods have been proposed, they often to treat the prediction of lncRNA-disease associations (LDAs), miRNA-disease associations (MDAs) and lncRNA-miRNA interactions (LMIs) as separate task. Models capable of predicting all three relationships simultaneously remain relatively scarce. Our aim is to perform multi-task predictions, which not only construct a unified framework, but also facilitate mutual complementarity of information among lncRNAs, miRNAs and diseases.

Results

In this work, we propose a novel unsupervised embedding method called graph contrastive learning for multi-task prediction (GCLMTP). Our approach aims to predict LDAs, MDAs and LMIs by simultaneously extracting embedding representations of lncRNAs, miRNAs and diseases. To achieve this, we first construct a triple-layer lncRNA–miRNA-disease heterogeneous graph (LMDHG) that integrates the complex relationships between these entities based on their similarities and correlations. Next, we employ an unsupervised embedding model based on graph contrastive learning to extract potential topological feature of lncRNAs, miRNAs and diseases from the LMDHG. The graph contrastive learning leverages graph convolutional network architectures to maximize the mutual information between patch representations and corresponding high-level summaries of the LMDHG. Subsequently, for the three prediction tasks, multiple classifiers are explored to predict LDA, MDA and LMI scores. Comprehensive experiments are conducted on two datasets (from older and newer versions of the database, respectively). The results show that GCLMTP outperforms other state-of-the-art methods for the disease-related lncRNA and miRNA prediction tasks. Additionally, case studies on two datasets further demonstrate the ability of GCLMTP to accurately discover new associations. To ensure reproducibility of this work, we have made the datasets and source code publicly available at https://github.com/sheng-n/GCLMTP.
Effects of lactate, super-GDF9, and low oxygen tension during bi-phasic in vitro maturation on the bioenergetic profiles of mouse cumulus–oocyte complex
Authors: Akin Nazli , Ates Gamze , von Mengden Lucia , Herta Anamaria-Cristina , Meriggioli Cecilia , Billooye Katy , Stocker William A , Ghesquiere Brecht , Harrison Craig A , Cools Wilfried , Klamt Fabio , Massie Ann , Smitz Johan , Anckaert Ellen
Published: August 2023

In vitro maturation (IVM) is an alternative assisted reproductive technology with reduced hormone-related side effects and treatment burden compared to conventional IVF. Capacitation (CAPA)-IVM is a bi-phasic IVM system with improved clinical outcomes compared to standard monophasic IVM. Yet, CAPA-IVM efficiency compared to conventional IVF is still suboptimal in terms of producing utilizable blastocysts. Previously, we have shown that CAPA-IVM leads to a precocious increase in cumulus cell (CC) glycolytic activity during cytoplasmic maturation. In the current study, considering the fundamental importance of CCs for oocyte maturation and cumulus–oocyte complex (COC) microenvironment, we further analyzed the bioenergetic profiles of maturing CAPA-IVM COCs. Through a multi-step approach, we (i) explored mitochondrial function of the in vivo and CAPA-IVM matured COCs through real-time metabolic analysis with Seahorse analyzer, and to improve COC metabolism (ii) supplemented the culture media with lactate and/or super-GDF9 (an engineered form of growth differentiation factor 9) and (iii) reduced culture oxygen tension. Our results indicated that the pre-IVM step is delicate and prone to culture-related disruptions. Lactate and/or super-GDF9 supplementations failed to eliminate pre-IVM-induced stress on COC glucose metabolism and mitochondrial respiration. However, when performing pre-IVM culture under 5% oxygen tension, CAPA-IVM COCs showed similar bioenergetic profiles compared to in vivo matured counterparts. This is the first study providing real-time metabolic analysis of the COCs from a bi-phasic IVM system. The currently used analytical approach provides the quantitative measures and the rational basis to further improve IVM culture requirements.
τ-censored weighted Benjamini–Hochberg procedures under independence
Authors: Zhao Haibing , Zhou Huijuan
Published: August 2023

In the field of multiple hypothesis testing, auxiliary information can be leveraged to enhance the efficiency of test procedures. A common way to make use of auxiliary information is by weighting p-values. However, when the weights are learned from data, controlling the finite-sample false discovery rate becomes challenging, and most existing weighted procedures only guarantee false discovery rate control in an asymptotic limit. In a recent study conducted by Ignatiadis & Huber (2021), a novel τ-censored weighted Benjamini–Hochberg procedure was proposed to control the finite-sample false discovery rate. The authors employed the cross-weighting approach to learn weights for the p-values. This approach randomly splits the data into several folds and constructs a weight for each p-value Pi using the p-values outside the fold containing Pi. Cross-weighting does not exploit the p-value information inside the fold and only balances the weights within each fold, which may result in a loss of power. In this article, we introduce two methods for constructing data-driven weights for τ-censored weighted Benjamini–Hochberg procedures under independence. They provide new insight into masking p-values to prevent overfitting in multiple testing. The first method utilizes a leave-one-out technique, where all but one of the p-values are used to learn a weight for each p-value. This technique masks the information of a p-value in its weight by calculating the infimum of the weight with respect to the p-value. The second method uses partial information from each p-value to construct weights and utilizes the conditional distributions of the null p-values to establish false discovery rate control. Additionally, we propose two methods for estimating the null proportion and demonstrate how to integrate null-proportion adaptivity into the proposed weights to improve power.
Blurring cluster randomized trials and observational studies: Two-Stage TMLE for subsampling, missingness, and few independent units
Authors: Nugent Joshua R , Marquez Carina , Charlebois Edwin D , Abbott Rachel , Balzer Laura B
Published: August 2023

Cluster randomized trials (CRTs) often enroll large numbers of participants; yet due to resource constraints, only a subset of participants may be selected for outcome assessment, and those sampled may not be representative of all cluster members. Missing data also present a challenge: if sampled individuals with measured outcomes are dissimilar from those with missing outcomes, unadjusted estimates of arm-specific endpoints and the intervention effect may be biased. Further, CRTs often enroll and randomize few clusters, limiting statistical power and raising concerns about finite sample performance. Motivated by SEARCH-TB, a CRT aimed at reducing incident tuberculosis infection, we demonstrate interlocking methods to handle these challenges. First, we extend Two-Stage targeted minimum loss-based estimation to account for three sources of missingness: (i) subsampling; (ii) measurement of baseline status among those sampled; and (iii) measurement of final status among those in the incidence cohort (persons known to be at risk at baseline). Second, we critically evaluate the assumptions under which subunits of the cluster can be considered the conditionally independent unit, improving precision and statistical power but also causing the CRT to behave like an observational study. Our application to SEARCH-TB highlights the real-world impact of different assumptions on measurement and dependence; estimates relying on unrealistic assumptions suggested the intervention increased the incidence of TB infection by 18% (risk ratio [RR]=1.18, 95% confidence interval [CI]: 0.85–1.63), while estimates accounting for the sampling scheme, missingness, and within community dependence found the intervention decreased the incident TB by 27% (RR=0.73, 95% CI: 0.57–0.92).
Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn’s Disease
Authors: Hurych Jakub , Mascellani Bergo Anna , Lerchova Tereza , Hlinakova Lucie , Kubat Michal , Malcova Hana , Cebecauerova Dita , Schwarz Jan , Karaskova Eva , Hecht Tomas , Vyhnanek Radim , Toukalkova Lenka , Dotlacil Vojtech , Greinerova Katerina , Cizkova Anabela , Horvath Rudolf , Bronsky Jiri , Havlik Jaroslav , Hradsky Ondrej , Cinek Ondrej
Published: August 2023

Background and Aims

Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn’s disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA].

Methods

Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab.

Results

We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test.

Conclusions

Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.
Derivation and external validation of machine-learning models for risk stratification in chest pain with normal troponin
Authors: Fernández-Cisnal Agustín , Lopez-Ayala Pedro , Valero Ernesto , Koechlin Luca , Catarralá Arturo , Boeddinghaus Jasper , Noceda José , Nestelberger Thomas , Miró Òscar , Julio Núñez , Mueller Christian , Sanchis Juan
Published: August 2023

Aims

Risk stratification of patients with chest pain and a high-sensitivity cardiac troponin T (hs-cTnT) concentration <upper reference limit (URL) is challenging. The aim of this study was to develop and externally validate clinical models for risk prediction of 90-day death or myocardial infarction in patients presenting to the emergency department with chest pain and an initial hs-cTnT concentration <URL.

Methods and results

Four machine-learning-based models and one logistic regression (LR) model were trained on 4075 patients (single-centre Spanish cohort) and externally validated on 3609 patients (international prospective Advantageous Predictors of Acute Coronary syndromes Evaluation cohort). Models were compared with GRACE and HEART scores and a single undetectable hs-cTnT-based strategy (u-cTn; hs-cTnT < 5 ng/L and time from symptoms onset >180 min). Probability thresholds for safe discharge were derived in the derivation cohort. The endpoint occurred in 105 (2.6%) patients in the training set and 98 (2.7%) in the external validation set. Gradient boosting full (GBf) showed the best discrimination (area under the curve = 0.808). Calibration was good for the reduced neural network and LR models. Gradient boosting full identified the highest proportion of patients for safe discharge (36.7 vs. 23.4 vs. 27.2%; GBf vs. LR vs. u-cTn, respectively) with similar safety (missed endpoint per 1000 patients: 2.2 vs. 3.5 vs. 3.1, respectively). All derived models were superior to the HEART and GRACE scores (P < 0.001).

Conclusion

Machine-learning and LR prediction models were superior to the HEART, GRACE, and u-cTn for risk stratification of patients with chest pain and a baseline hs-cTnT <URL. Gradient boosting full models best balanced discrimination, calibration, and efficacy, reducing the need for serial hs-cTnT determination by more than one-third.

Clinical trial registration

ClinicalTrials.gov number, NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587.
Ultrasound features and risk stratification system in NIFT-P and other follicular-patterned thyroid tumors
Authors: Matrone Antonio , Gambale Carla , Pieroni Erica , De Napoli Luigi , Torregrossa Liborio , Materazzi Gabriele , Elisei Rossella
Published: August 2023

Objective

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFT-P) is an encapsulated follicular variant of papillary thyroid carcinoma (PTC) with nonaggressive clinical behavior. However, since its diagnosis is exclusively possible after surgery, it represents a clinical challenge. Neck ultrasound (US) shows good sensitivity and specificity in suggesting malignancy in thyroid nodules. However, little information is available about its ability in identifying NIFT-P.

Design

The aim of this study was to evaluate the US features of NIFT-P, comparing them with other follicular-patterned thyroid tumors, and to test the ability of the main US risk stratification system (RSS) in identifying NIFT-P.

Methods

We retrospectively evaluated 403 consecutive patients submitted to thyroid surgery, with positive histology for at least 1 nodule being NIFT-P, follicular variant of PTC (FV-PTC), follicular thyroid carcinoma (FTC), or follicular adenoma (FA).

Results

The US features of NIFT-P (n = 116), FV-PTC (n = 170), FTC (n = 76), and FA (n = 90) were reported. Follicular variant of PTC and FTC more frequently showed irregular margins, presence of calcifications, “taller than wide” shape, and the absence of halo compared with NIFT-P. Furthermore, FTC and also FA were larger and more frequently hypoechoic than NIFT-P. Most cases (77%) showed an indeterminate cytology. Regardless of the US RSS considered, NIFT-P and FA were less frequently classified in the high-suspicious category compared with FV-PTC and FTC.

Conclusions

Ultrasound features of NIFT-P are frequently superimposable to those of nodules with low suspicion of malignancy. The NIFT-P is almost never classified in the high-suspicious category according to the main US RSS. Therefore, although the preoperative identification of NIFT-P remains a challenge, neck US can be integrated in the algorithm of management of nodules with indeterminate cytology, suggesting a possible conservative approach in those with low-suspicious features.
Modern subcutaneous implantable defibrillator therapy in patients with cardiomyopathies and channelopathies: data from a large multicentre registry
Authors: Migliore Federico , Biffi Mauro , Viani Stefano , Pittorru Raimondo , Francia Pietro , Pieragnoli Paolo , De Filippo Paolo , Bisignani Giovanni , Nigro Gerardo , Dello Russo Antonio , Pisanò Ennio , Palmisano Pietro , Rapacciuolo Antonio , Silvetti Massimo Stefano , Lavalle Carlo , Curcio Antonio , Rordorf Roberto , Lovecchio Mariolina , Valsecchi Sergio , D’Onofrio Antonio , Botto Giovanni Luca
Published: August 2023

Aims

Patients with cardiomyopathies and channelopathies are usually younger and have a predominantly arrhythmia-related prognosis; they have nearly normal life expectancy thanks to the protection against sudden cardiac death provided by the implantable cardioverter defibrillator (ICD). The subcutaneous ICD (S-ICD) is an effective alternative to the transvenous ICD and has evolved over the years. This study aimed to evaluate the rate of inappropriate shocks (IS), appropriate therapies, and device-related complications in patients with cardiomyopathies and channelopathies who underwent modern S-ICD implantation.

Methods and results

We enrolled consecutive patients with cardiomyopathies and channelopathies who had undergone implantation of a modern S-ICD from January 2016 to December 2020 and who were followed up until December 2022. A total of 1338 S-ICD implantations were performed within the observation period. Of these patients, 628 had cardiomyopathies or channelopathies. The rate of IS at 12 months was 4.6% [95% confidence interval (CI): 2.8–6.9] in patients with cardiomyopathies and 1.1% (95% CI: 0.1–3.8) in patients with channelopathies (P = 0.032). No significant differences were noted over a median follow-up of 43 months [hazard ratio (HR): 0.76; 95% CI: 0.45–1.31; P = 0.351]. The rate of appropriate shocks at 12 months was 2.3% (95% CI: 1.1–4.1) in patients with cardiomyopathies and 2.1% (95% CI: 0.6–5.3) in patients with channelopathies (P = 1.0). The rate of device-related complications was 0.9% (95% CI: 0.3–2.3) and 3.2% (95% CI: 1.2–6.8), respectively (P = 0.074). No significant differences were noted over the entire follow-up. The need for pacing was low, occurring in 0.8% of patients.

Conclusion

Modern S-ICDs may be a valuable alternative to transvenous ICDs in patients with cardiomyopathies and channelopathies. Our findings suggest that modern S-ICD therapy carries a low rate of IS.

Clinical Trial Registration

URL: http://clinicaltrials.gov/Identifier: NCT02275637.
Genome-wide association analysis identifies natural allelic variants associated with panicle architecture variation in African rice, Oryza glaberrima Steud
Authors: Ntakirutimana Fabrice , Tranchant-Dubreuil Christine , Cubry Philippe , Chougule Kapeel , Zhang Jianwei , Wing Rod A , Adam Hélène , Lorieux Mathias , Jouannic Stefan
Published: August 2023

African rice (Oryza glaberrima Steud), a short-day cereal crop closely related to Asian rice (Oryza sativa L.), has been cultivated in Sub-Saharan Africa for ∼ 3,000 years. Although less cultivated globally, it is a valuable genetic resource in creating high-yielding cultivars that are better adapted to diverse biotic and abiotic stresses. While inflorescence architecture, a key trait for rice grain yield improvement, has been extensively studied in Asian rice, the morphological and genetic determinants of this complex trait are less understood in African rice. In this study, using a previously developed association panel of 162 O. glaberrima accessions and new SNP variants characterized through mapping to a new version of the O. glaberrima reference genome, we conducted a genome-wide association study of four major morphological panicle traits. We have found a total of 41 stable genomic regions that are significantly associated with these traits, of which 13 co-localized with previously identified QTLs in O. sativa populations and 28 were unique for this association panel. Additionally, we found a genomic region of interest on chromosome 3 that was associated with the number of spikelets and primary and secondary branches. Within this region was localized the O. sativa ortholog of the PHYTOCHROME B gene (Oglab_006903/OgPHYB). Haplotype analysis revealed the occurrence of natural sequence variants at the OgPHYB locus associated with panicle architecture variation through modulation of the flowering time phenotype, whereas no equivalent alleles were found in O. sativa. The identification in this study of genomic regions specific to O. glaberrima indicates panicle-related intra-specific genetic variation in this species, increasing our understanding of the underlying molecular processes governing panicle architecture. Identified candidate genes and major haplotypes may facilitate the breeding of new African rice cultivars with preferred panicle traits.