bluuebunny/crossref_metadata_2025 huggingface dataset:
ABUSE OF PATENTABILITY CRITERIA WHEN PATENTING INVENTIONS RELATED TO MEDICINES
Authors: Kondratyuk Sergiy
Published: June 2023

It is well known that intellectual property monopolies for medicines reduce physical and economic availability. Main purpose of the study is to conduct brief review of foreign scholarly views on evergreening patenting practice in the field of pharmaceuticals, to demonstrate implications of such abusive practice and to exemplify good practices used in several countries to address the problem. Evergreening practice poses a serious challenge for healthcare system of Ukraine, but there are promising examples in several countries (e.g. Argentina, Brazil, India) of limiting evergreening.
A Brief Review of the Nutritive Value and Chemical Components of Bat Guano and Its Potential Use as a Natural Fertiliser in Agriculture
Authors: SITI-SYAMIM NURFATIHAH ABD RAHMAN  , ROBERTA CHAYA TAWIE TINGGA  , MOHAMAD FHAIZAL MOHAMAD BUKHORI  , SHARIFAH MONA ABD AZIZ ABDULLAH
Published: June 2023

New and improved fertilisers are constantly being introduced to the market to help increase crop yields. However, the common usage of chemical fertilisers had brought upon negative impacts to the environment and the study for sustainable fertiliser is still ongoing. This review will highlight the usage of bat guano as a valuable fertiliser which has a potential to diminish the effects of chemical fertiliser usage, increase yield and is cost effective. Its role as a fertiliser can support the agricultural growth and in turn provides additional care for plants. The chemical compositions of guano which was found to be subpar with other fertilisers support its usage of guano as an alternative for crop yield enhancement. Plant growth performance that shows a significant positive impact of guano on crops, further demonstrates its usage as organic fertilisers. In-depth study of the chemical composition of guano should be pursued as the fertiliser has high beneficial value to the ecology and economy.
Morphometric Studies of Accessions of Duranta erecta L. (Vebernaceae) Complex in Nigeria
Authors: ABDULQUADRI SAGAYA  , ABDULLAHI ALANAMU ABDULRAHAMAN
Published: June 2023

Studies were conducted to broaden the systematic knowledge of the genus Duranta erecta L., to contribute a better understanding of their taxonomic and evolutionary relationships. Previous studies have pointed out complexity in the taxonomy and nomenclature of the species. A total of 224 samples were collected from six geo-political zones of Nigeria, and were grouped into 38 accessions. The plants were compared using 21 morphological characters involving qualitative and quantitative characteristics. Multivariate analyses such as Principal Component Analysis (PCA) and Cluster Analysis (CA) were employed to evaluate the intraspecific variabilities. The results showed that all the plants exhibited significant differences in all the quantitative attributes with the variegated type having the longest and widest leaves ranging from 12.20 cm and 5.08 cm, respectively. The qualitative characters delimited the plants accessions into distinctive groups of eight morphological forms namely; green bush, yellow bush, variegated yellow, variegated white, variegated yellow double, plain yellow, broad green, thorny green type. The PCA showed that leaf length, leaf width, internode length and length of inflorescence were some of the quantitative characters while leaf shape, leaf colour, leaf margin, flower colour and leaf apex are some of the qualitative traits that accounted for the delimitation. Unpaired Weighted Group Multivariate Analysis (UPGMA) using the Euclidian separated the 38 accessions into two major clusters; cluster I (flower producing) and cluster II (non-flower producing) Duranta erecta. Morphological variations and field observations suggested that there could be gene flow among the accessions of Duranta erecta studied and gene flow is an important factor in population genetics, shaping the diversity of species.
THE MUSIC EVENTS IN KUCHING, SARAWAK POST-PANDEMIC TIMES: CHANGES AND PERCEPTION
Authors: Paul Nicole Ivanna , Ali Amaran Mazdan
Published: June 2023

This article discussed the changes experience by event organizers, how the public are adapting to the changes and their perception of music events in Kuching, Sarawak post-pandemic times. This study used mixed method, both quantitative and qualitative method approach. A total of 101 respondents participated in this study through survey. According to the findings, with a total mean of 4.41, hybrid music events should be conducted in post-pandemic to accommodate both onsite and offline audiences. From the event organizers perspective, 2 informants involved stated that there will be an improvement in music events such as increasing number of audiences, bigger venue, and better service & activities.
Does Empowering Victim to Earn a Living Reduces the Risk of Domestic Violence Severity? A Narrative Review and A Pilot Study
Authors: Chew Keng Sheng , Wong Shirly Siew-Ling , Siew Ke Lin , Kandasamy Vanitha
Published: June 2023

Defined as the act of causing or attempting to cause physical, psychological or sexual harm to a person by another person who is either a spouse, former spouse, adult child, parent or any other family members, domestic violence is a global public health issue including in Malaysia. One way to mitigate the risk of domestic violence is through the ability of a domestic violence victim to earn her own income. Unfortunately, although some studies have shown that the higher the income level of victim, the lesser the risk of domestic violence severity, other studies did not demonstrate this relationship. Additionally, different past studies have used different indicators in analyzing the impact of income level on domestic violence severity. Some studies used household income levels, whilst other studies used the victims’ individual income levels. This paper will discuss on the impact of economic empowerment to mitigate the severity of domestic violence including some conflicting findings in recent literature.  Using the Transtheoretical Model of Change and Walker’s cycle of abuse, this paper will also highlight the importance of creating awareness that domestic violence is not acceptable, adopting a non-judgmental attitude to minimize stigmatization and secondary traumatization as well as rendering social support in helping victims toward a journey of sustained change.
Exploring Asset-Based Community-led Development (ABCD) Elements for Determining Farm Technologies in Rural Rice Farming Community – Kelabit Highlands, Sarawak
Authors: Sam Mei Jean , Fung Hon-Ngen
Published: June 2023

Malaysia is a net importer of rice, and Sarawak itself contributes approximately 8.2% of total national rice production. Although Malaysia national policy targeting to achieve 80% self-sufficient level of rice for national food security agenda, another alternative is to explore some premium quality traditional rice varieties that potentially entering into premium market for the socioeconomic advancement especially for the rural areas. Traditionally, the choice of farm technologies are implemented through government direction in a top-down approach, through decisions, strategies, and diffusion processes driven by the agencies. This study aims to explore the elements of Asset-Based Community-led Development (ABCD) as an alternative to conventional needs-based development within a community of rice farmers based in the Kelabit Highlands – a rural community in the highlands of the East Malaysia state of Sarawak. The study collected interview data from rice farmers in the Kelabit Highlands community and also discussed the role of agencies and their efforts to form partnerships, and peer collaborations based on those assets identified and community strength. The study also evaluated the ABCD framework as a means to visualize community-based assets. Clarifying these factors would identify suitable farming technologies that are socially desirable in the Kelabit Highlands and determine a bottom up method for other rural communities to evaluate and pave a path forward in selecting farming technologies that fit into their landscape.

 

Keywords: ABCD, bottom-up, farm technologies, rice farming, top-down
Tropical Rainforests, Traditional Societies, and Dynamic Continuums. Toward a Regional History of Ethnicity in Borneo
Authors: Sellato Bernard
Published: June 2023

Environmental and human features, and the interactions between them, in a key research region of the island of Borneo, are here all consistently regarded as continuums. Integrated studies, combining the biological and social sciences, of these continuums should provide an alternative view of the interactions between environment and society and, through a reconstruction of the eco-cultural history of this region, allow new insights into the history of Southeast Asia.
IoT-based Eyes Closure Alert System for Drowsy Driver
Authors: Nursyuhada Amir Shariffuddin  , Ling Yeong Tyng
Published: June 2023

Internet of Things (IoTs) is a technology that links objects and mechanisms to the Internet. IoT devices are deployed in a number of areas within the transportation sector, notably in security and surveillance. The ability to track driving behaviour on the road using IoT can improve driver safety and reduce traffic accidents. In this paper, a prototype system to detect a driver’s drowsiness is proposed. In particular, a facial landmark is used to extract the eye region, the eye aspect ratio, and closure patterns. This system will audibly alert the driver and invoke third party notification if drowsiness of the driver is detected. Through this system, traffic accidents caused by drowsy drivers can be avoided and driving behaviour can be evaluated by relevant personnel or employers.
“Bitch”, “Ho” and “Pussy”: Messages of Popular Rap Music
Authors: Ahmad Daniel Faiz Ramlee  , John Dexter Sigan
Published: June 2023

This study aims to examine the messages of the popular rap songs. The specific objectives are: (1) to analyse the messages of rap songs in the Billboard Hot 100 Year-End Chart from 2017 to 2021, and (2) to analyse the level of misogyny in the rap songs listed in the Billboard Hot 100 Year-End Chart from 2017 to 2021. The descriptive study involved the analysis of messages in 25 popular rap songs. The content analysis of the songs showed that the most frequently used type of misogyny is sexual conquest messages found in 23 songs, followed by derogatory manner and physical aggression but rape and sexual assault messages were less frequently used. Most of the songs fall under the high level of misogyny. The most popular words used in these five songs are “bitch”, “hoes”, “ho”, “pussy glitter”, and “whores”. As the rap music is dominated by male singers, the misogyny messages promote a culture of toxic masculinity and reinforce the belief that men should be dominant in all aspects. The rap music normalises the idea of sexual violence, by making it acceptable or even desirable. The findings indicate that there is a need to promote positive messages in the music especially on woman empowerment.
Mizumi: Digital Sports Centre
Authors: Busang Trevor Roma
Published: June 2023

Digital sport is the product of merging electronic technology into sport activities.  It is a new generation of social activitise that can be integrated online and globally regardless of where you are.  Based on the popular animated series Pokemon, the concept is to have multiple areas with different activities engaging with the target users around the area.  The phrase "catch-em-all" usde to refer to the intention to capture the surrounding people and creating a new interactive area for the anime fans.  The buildings are divided by three to resemble the three legendary Pokemon Lake Guardians.  The spaces are also planned according to the gym leader theme from the game adapted from the anime.
TreeTop
Authors: Chiam Xin Ru
Published: June 2023

Where healing begins. Every day waking up preparing for work. At 5pm, tiredness, stress and depression are what's left to bring back home.  Breezy greenery, ambience of the habitats and interaction between residents and non-residents are experienced along the way back to the respective units at TreeTop.  Gusts of wind blow away the tiredness and stress.  Chirping of the insets minimise the sound of depression.
Isotropic and anisotropic mesh adaptation for RANS simulations of a nacelle under crosswind conditions
Authors: Laure Billon , Dimitrios Papadogiannis , Frédéric Alauzet
Published: June 2023

Mesh adaptation of unstructured meshes for aerodynamic simulations, that typically resolve the Reynolds Averaged Navier-Stokes (RANS) equations, is a promising approach to enable high numerical precision on complex geometries. Its objective is to minimize the discretization error without using empirical meshing guidelines. The most common approach of mesh adaptation is the “feature-based” isotropic mesh adaptation: from an initial flow prediction on an isotropic unstructured mesh, a local error estimator is computed using a flow variable. It is then used to adapt the mesh using isotropic tetrahedra. Additional near-wall resolution can be achieved by extruding prism layers from the walls. A more efficient approach is to use anisotropic mesh adaptation purely with tetrahedra that are stretched to follow the flow's preferential directions. In this work, we demonstrate the abilities of feature-based isotropic and anisotropic mesh adaptation on a complex flow phenomenon of importance for jet engines: flow separation in a nacelle under crosswind conditions. Two different solvers, adapted for either isotropic or anisotropic meshes, are employed. Results are compared with standard unstructured simulations with user-imposed mesh refinements and highlight the ability of mesh adaptation to automatically capture all the relevant flow phenomena without any user input and at reduced mesh size.
DAUR ULANG AIR LIMBAH MENGGUNAKAN REVERSE OSMOSIS UNTUK MAKE UP WATER COOLING TOWER DI PT NUTRICIA INDONESIA SEJAHTERA
Authors: Taufik Hidayat Ramadhon  , Zakijah Irfin  , Agung Nugroho
Published: June 2023

Penggunaan air bersih di PT Nutricia Indonesia Sejahtera berkisar antara 35-40 m3 sepanjang tahun 2022.  Penggunaan air bersih yang berasal dari PDAM dan sumur harus ditekan penggunaannya untuk mengurangi biaya produksi di perusahan tersebut. Unit cooling tower adalah unit yang paling besar menyerap penggunaan air bersih hingga mencapai 21 m3/hari. Salah satu inovasi yang memberikan dampak secara langsung terhadap upaya pengurangan penggunaan air bersih adalah mendaur ulang air limbah yang akan digunakan sebagai make up water cooling tower menggunakan reverse osmosis. Spesifikasi air sebelum masuk proses reverse osmosis memiliki parameter yang harus dipenuhi terutama kandungan TDS dari air limbah tersebut. Air limbah PT Nutricia Indonesia Sejahtera memiliki kandungan TDS sebesar 1225 mg/L. JIka spesifikasi air tersebut langsung diaplikasikan maka akan menyebabkan proses reverse osmosis mengalami permasalahan seperti fouling yang menyebabkan membran menjadi mampat, banyak aliran reject, periode proses cleaning yang cepat, sehingga proses menjadi tidak efisien dan air yang didaur ulang tidak maksimal. Tujuan dari penelitian ini adalah mencegah fouling dengan pretreatment tambahan sebelum memasuki reverse osmosis dengan menggunakan membran  Ultra Filtration (UF) jenis hollow fiber. Inovasi ini mampu menurunkan penggunaan air bersih di PT Nutricia Indonesia Sejahtera hingga 5.46 m3/hari.
Food allergy: cause or consequence of pediatric eosinophilic esophagitis? Potential implications of ultraprocessed foods in prevention and management
Authors: Carucci Laura , Votto Martina , Licari Amelia , Marseglia Gian Luigi , Berni Canani Roberto
Published: June 2023

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by eosinophilic infiltration, leading to esophageal dysfunction, inflammation, and fibrotic remodeling. In the last few decades, there has been an increased prevalence of EoE at an alarming rate in the pediatric age. The pathogenesis of EoE is still largely undefined, and this limits the definition of effective strategies for the prevention and management of this condition. EoE is considered a multifactorial disease arising from a negative interaction between environmental factors and genetic background, causing an impaired esophageal epithelial barrier with subsequent abnormal allergen exposure activating type 2 (Th2) inflammation. Food antigens have been suggested as key players in Th2 inflammation in pediatric patients with EoE, but emerging evidence suggests a potential role of other dietary factors, including ultraprocessed foods, as possible triggers for the occurrence of EoE. In this paper, we discuss the potential role of these dietary factors in the development of the disease, and we propose a new approach for the management of pediatric patients with EoE.
A novel hybrid bioprocess strategy addressing key challenges of advanced biomanufacturing
Authors: Reger Lucas Nik , Saballus Martin , Kappes Annika , Kampmann Markus , Wijffels Rene H. , Martens Dirk E. , Niemann Julia
Published: June 2023

Monoclonal antibodies (mAb) are commonly manufactured by either discontinuous operations like fed-batch (FB) or continuous processes such as steady-state perfusion. Both process types comprise opposing advantages and disadvantages in areas such as plant utilization, feasible cell densities, media consumption and process monitoring effort. In this study, we show feasibility of a promising novel hybrid process strategy that combines beneficial attributes of both process formats. In detail, our strategy comprises a short duration FB, followed by a fast media exchange and cell density readjustment, marking the start of the next FB cycle. Utilizing a small-scale screening tool, we were able to identify beneficial process parameters, including FB interval duration and reinoculation cell density, that allow for multiple cycles of the outlined process in a reproducible manner. In addition, we could demonstrate scalability of the process to a 5L benchtop system, using a fluidized-bed centrifuge as scalable media exchange system. The novel process showed increased productivity (+217%) as well as longer cultivation duration, in comparison to a standard FB with a significantly lower media consumption per produced product (−50%) and a decreased need for process monitoring, in comparison to a perfusion cultivation. Further, the process revealed constant glycosylation pattern in comparison to the perfusion cultivation and has strong potential for further scale-up, due to the use of fully scalable cultivation and media exchange platforms. In summary, we have developed a novel hybrid process strategy that tackles the key challenges of current biomanufacturing of either low productivity or high media consumption, representing a new and innovative approach for future process intensification efforts.
Anxiety in students with intellectual disabilities: the influence of staff-perceived social acceptance and rejection in the classroom
Authors: Hofmann Verena
Published: June 2023

Introduction

Students with intellectual disabilities often exhibit increased anxiety levels, which can be associated with additional limitations and severe emotional distress. This study investigated the role of social acceptance, social rejection, and general functioning in predicting anxiety.

Methods

Using data on 1,125 students in 179 special needs classrooms that was collected at the beginning and end of one school year, multilevel models were used to predict whether future anxiety was associated with prior staff-perceived social acceptance or rejection by classmates, and with general functioning.

Results

We found that greater staff-perceived social acceptance was related to a decrease in anxiety over the school year, however, no effect was found for rejection. Further, there was no moderating effect of students’ general functioning.

Discussion

Positive peer relationships in the classroom appear to contribute to lower anxiety, while negative relationships do not further worsen anxiety. Implications for special needs schools are discussed.
Epigenetic modification in diabetic kidney disease
Authors: Liu Zhe , Liu Jiahui , Wang Wanning , An Xingna , Luo Ling , Yu Dehai , Sun Weixia
Published: June 2023

Diabetic kidney disease (DKD) is a common microangiopathy in diabetic patients and the main cause of death in diabetic patients. The main manifestations of DKD are proteinuria and decreased renal filtration capacity. The glomerular filtration rate and urinary albumin level are two of the most important hallmarks of the progression of DKD. The classical treatment of DKD is controlling blood glucose and blood pressure. However, the commonly used clinical therapeutic strategies and the existing biomarkers only partially slow the progression of DKD and roughly predict disease progression. Therefore, novel therapeutic methods, targets and biomarkers are urgently needed to meet clinical requirements. In recent years, increasing attention has been given to the role of epigenetic modification in the pathogenesis of DKD. Epigenetic variation mainly includes DNA methylation, histone modification and changes in the noncoding RNA expression profile, which are deeply involved in DKD-related inflammation, oxidative stress, hemodynamics, and the activation of abnormal signaling pathways. Since DKD is reversible at certain disease stages, it is valuable to identify abnormal epigenetic modifications as early diagnosis and treatment targets to prevent the progression of end-stage renal disease (ESRD). Because the current understanding of the epigenetic mechanism of DKD is not comprehensive, the purpose of this review is to summarize the role of epigenetic modification in the occurrence and development of DKD and evaluate the value of epigenetic therapies in DKD.
Gut microbiota short-chain fatty acids and their impact on the host thyroid function and diseases
Authors: Mendoza-León María José , Mangalam Ashutosh K. , Regaldiz Alejandro , González-Madrid Enrique , Rangel-Ramírez Ma. Andreina , Álvarez-Mardonez Oscar , Vallejos Omar P. , Méndez Constanza , Bueno Susan M. , Melo-González Felipe , Duarte Yorley , Opazo Ma. Cecilia , Kalergis Alexis M. , Riedel Claudia A.
Published: June 2023

Thyroid disorders are clinically characterized by alterations of L-3,5,3’,5’-tetraiodothyronine (T4), L-3,5,3’-triiodothyronine (T3), and/or thyroid-stimulating hormone (TSH) levels in the blood. The most frequent thyroid disorders are hypothyroidism, hyperthyroidism, and hypothyroxinemia. These conditions affect cell differentiation, function, and metabolism. It has been reported that 40% of the world’s population suffers from some type of thyroid disorder and that several factors increase susceptibility to these diseases. Among them are iodine intake, environmental contamination, smoking, certain drugs, and genetic factors. Recently, the intestinal microbiota, composed of more than trillions of microbes, has emerged as a critical player in human health, and dysbiosis has been linked to thyroid diseases. The intestinal microbiota can affect host physiology by producing metabolites derived from dietary fiber, such as short-chain fatty acids (SCFAs). SCFAs have local actions in the intestine and can affect the central nervous system and immune system. Modulation of SCFAs-producing bacteria has also been connected to metabolic diseases, such as obesity and diabetes. In this review, we discuss how alterations in the production of SCFAs due to dysbiosis in patients could be related to thyroid disorders. The studies reviewed here may be of significant interest to endocrinology researchers and medical practitioners.
Using the behaviour change wheel and person-based approach to develop a digital self-management intervention for patients with adrenal insufficiency: the Support AI study protocol
Authors: Llahana Sofia , Mulligan Kathleen , Hirani Shashivadan P. , Wilson Stephanie , Baldeweg Stephanie E. , Grossman Ashley , Norton Christine , Sharman Philippa , McBride Pat , Newman Stanton
Published: June 2023

Introduction

Most patients with Adrenal insufficiency (AI) require lifelong glucocorticoid replacement. They need to increase glucocorticoids during physical illness or major stressful situations and require parenteral hydrocortisone in the event of an adrenal crisis. Patients with AI have impaired quality of life and high mortality; approximately 1 in 6-12 patients are hospitalised at least once/year from a potentially preventable adrenal crisis. Adoption of self-management behaviours are crucial; these include adherence to medication, following “sick day rules” and associated behaviours that aid prevention and treatment of adrenal crisis such as symptom monitoring, having extra tablets, carrying a medical-alert ID and injection kit, and self-injecting when necessary. Current patient education is ineffective at supporting self-management behaviour change or reducing adrenal crisis-related hospitalisations. This research study aims to gain an in-depth understanding of the barriers and enablers to self-management for patients with AI and to develop an evidence-based digital self-management behaviour change intervention.

Methods

The study is conducted in accordance with the MRC Framework for developing complex interventions. Underpinned by the Behaviour Change Wheel (BCW), the Theoretical Domains Framework (TDF), and the Person-Based Approach, this research will be conducted in two phases: Phase 1 will involve a sequential qualitative/quantitative mixed-methods study involving focus group interviews followed by a cross-sectional survey with patients with AI recruited from patient advocacy groups and endocrine clinics in the UK. Phase 2 will develop the Support AI, a website-based digital behaviour change intervention (DBCI) informed by Phase 1 findings to support self-management for patients with AI. The most appropriate behaviour change techniques (BCTs) will be selected utilising a nominal group technique with an Expert Panel of 10-15 key stakeholders. The design of the Support AI website will be guided by the Person-Based Approach using an Agile iterative “think-aloud” technique with 12-15 participants over 3 usability testing iterations.

Conclusion

A theory- and evidence-based digital behaviour change intervention will be developed which will be tested in a feasibility randomised trial following completion of this study. The projected benefit includes cost-effective health care service (reduced hospitalisations and demand for specialist services) and improved health outcomes and quality of life for patients with AI.
Arsenic pollution and arsenic-resistant bacteria of drying Urmia Salt Lake
Authors: Haghi Morteza , Diznabi Salar H. , Karaboz Ismail , Ersoy Omeroglu Esra
Published: June 2023

Extensive arsenic contamination of groundwater, rivers, and agricultural farms has led to widespread arsenic poisoning and consequent problems associated with health and economy. In recent years, many studies have been performed to understand bacterial arsenic detoxification and metabolism which has paved the way for bioremediation applications. This study attempted to isolate and characterize arsenic-resistant bacteria from the drying Urmia lake. As a result of the 16S rDNA analysis, six arsenic-resistant strains were identified as the members of Shouchella, Salipaludibacillus, and Evansella genera. For some of the strains, the maximum tolerance concentration for either arsenate or arsenite was considerably high, 320 and 16 mM, respectively. All the strains harbored the arsenate reductase gene (arsC). The arsenate permease (arsB) gene was identified in all strains except in strains S1, S12, and E15. The metabolic genes of respiratory arsenate reductase (arrB) and arsenite oxidase (arxA) were identified in none of these strains. This feature of the strains with the arsC gene region can be exploited to bioremediate arsenic from contaminated areas by using a two-step process. The second step can be carried out by the adsorption of arsenite to iron oxide or by precipitation with sulfide. Today, more and more ecosystems are being destroyed due to anthropogenic pollution, and it is important to reveal the negative effects and solutions of this situation on the ecosystems. So, the current study provides a potential source of bacteria for such studies that implement bioremediation practices to prevent arsenic catastrophe in vicinal territories, and reveals arsenic pollution in Urmia lake.
Hyperspectral imaging-based prediction of soluble sugar content in Chinese chestnuts
Authors: Yang Jinhui , Gong Bangchu , Jiang Xibing
Published: June 2023

Soluble sugars are critical determinants of fruit quality and play a significant role in human nutrition. Chestnuts, rich in soluble sugars, derive their sweetness from them. However, their content varies with cultivar, location, and environmental conditions. Traditional methods for determining soluble sugar content in chestnuts are time-consuming, laborious, and destructive. Therefore, there is a pressing need for rapid, non-destructive, and straightforward methods for determining soluble sugars in chestnuts to expedite genetic selection. This study aimed to develop a hyperspectral imaging-based prediction model for soluble sugar content in Chinese chestnuts. Firstly, abnormal samples were eliminated using ensemble partial least squares for outlier detection. We then compared the average original and block scale (BS) spectra, with the latter demonstrating significant differences. The BS pretreatment exhibited two small absorption peaks in the 403.7 ∼ 429.1 nm band and 454.7 ∼ 500 nm band, less fluctuation in the spectral curves from 503.2 to 687.2 nm, and a substantial increase in spectral absorption between 690.6 and 927.8 nm. Subsequently, we developed a partial least squares (PLS) model using BS pretreatment and regularized elimination (rep) variable selection, which showed better accuracy in predicting chestnut soluble sugar content than other variable selection methods. The model fitting accuracy after the spectra treatment was marginally better than that of the original spectra, with a calibration set correlation coefficient (R2) of 0.59 and root mean square error (RMSE) of 1.02, and a validation set R2 of 0.66 and RMSE of 0.94. The wavelengths at 464.3, 503.2, 539.3, 579, and 711.3 nm were identified as critical for developing the soluble sugar content prediction model. The study demonstrated the potential of Near-Infrared Spectroscopy (NIS) as a rapid and non-destructive method for predicting chestnut soluble sugar content, which could be beneficial for quality control and sorting in the food industry.
Nanopore long-read next-generation sequencing for detection of mitochondrial DNA large-scale deletions
Authors: Frascarelli Chiara , Zanetti Nadia , Nasca Alessia , Izzo Rossella , Lamperti Costanza , Lamantea Eleonora , Legati Andrea , Ghezzi Daniele
Published: June 2023

Primary mitochondrial diseases are progressive genetic disorders affecting multiple organs and characterized by mitochondrial dysfunction. These disorders can be caused by mutations in nuclear genes coding proteins with mitochondrial localization or by genetic defects in the mitochondrial genome (mtDNA). The latter include point pathogenic variants and large-scale deletions/rearrangements. MtDNA molecules with the wild type or a variant sequence can exist together in a single cell, a condition known as mtDNA heteroplasmy. MtDNA single point mutations are typically detected by means of Next-Generation Sequencing (NGS) based on short reads which, however, are limited for the identification of structural mtDNA alterations. Recently, new NGS technologies based on long reads have been released, allowing to obtain sequences of several kilobases in length; this approach is suitable for detection of structural alterations affecting the mitochondrial genome. In the present work we illustrate the optimization of two sequencing protocols based on long-read Oxford Nanopore Technology to detect mtDNA structural alterations. This approach presents strong advantages in the analysis of mtDNA compared to both short-read NGS and traditional techniques, potentially becoming the method of choice for genetic studies on mtDNA.
Regulating human genomic research in Africa: why a human rights approach is a more promising conceptual framework than genomic sovereignty
Authors: Kabata Faith , Thaldar Donrich
Published: June 2023

This article revisits the debate on the regulation of human genomic research, with a focus on Africa. The article comprehensively examines the concept of genomic sovereignty, which was invoked mainly in the global South as a conceptual framework for state regulation of human genomic research. It demonstrates that genomic sovereignty has no utility value in human genomic research as it violates the rights of individuals and researchers. By analysing Mexico’s regulatory approach based on genomic sovereignty and a divergent regulatory approach, viz Finland’s human genomic research framework, we show that a human rights approach is more promising as it aligns with the state obligations under the right of everyone to participate in and benefit from scientific progress and its applications in international human rights law. We conclude by recommending that African states should anchor regulation of human genomic research on a human rights framework based on the right to science.
Chromatin structure and context-dependent sequence features control prime editing efficiency
Authors: Kim Somang , Yuan Jimmy B. , Woods Wendy S. , Newton Destry A. , Perez-Pinera Pablo , Song Jun S.
Published: June 2023

Prime editing (PE) is a highly versatile CRISPR–Cas9 genome editing technique. The current constructs, however, have variable efficiency and may require laborious experimental optimization. This study presents statistical models for learning the salient epigenomic and sequence features of target sites modulating the editing efficiency and provides guidelines for designing optimal PEs. We found that both regional constitutive heterochromatin and local nucleosome occlusion of target sites impede editing, while position-specific G/C nucleotides in the primer-binding site (PBS) and reverse transcription (RT) template regions of PE guide RNA (pegRNA) yield high editing efficiency, especially for short PBS designs. The presence of G/C nucleotides was most critical immediately 5’ to the protospacer adjacent motif (PAM) site for all designs. The effects of different last templated nucleotides were quantified and observed to depend on the length of both PBS and RT templates. Our models found AGG to be the preferred PAM and detected a guanine nucleotide four bases downstream of the PAM to facilitate editing, suggesting a hitherto-unrecognized interaction with Cas9. A neural network interpretation method based on nonextensive statistical mechanics further revealed multi-nucleotide preferences, indicating dependency among several bases across pegRNA. Our work clarifies previous conflicting observations and uncovers context-dependent features important for optimizing PE designs.
Poetry and the expectation of the border
Authors: Smith Lytton
Published: June 2023

This essay explores a set of poetic texts—the Transborder Immigrant Tool (TBT); Amy Sara Carroll's “The Desert Survival Series/La serie de sobrevivencia del desierto”; and Claudia Rankine and John Lucas's video poem “Zidane” and the version of that poem included in Rankine's book Citizen—against the backdrop of recent United States Customs and Border Protection investment in autonomous surveillance towers, the development of the “100 mile” expanded border region, and 2022 practices by Republican governors to relocate migrants to the U.S. to Democrat states. I argue for the existence in the poetry of what I term “the expectation of the border”: the moment when we name the border not as a graspable and unchangeable line in physical space and legal jurisdiction, but as a conceptual reckoning with definitions of community, including but not limited to citizenship status. Drawing on citizenship theorist Engin Isin's argument that “poetic articulation” especially “captures the essence of the political,” this study suggests poetry as a specialized intervention in border politics and definitions of citizenship, including the conditions of the “hostile environment”.
In vaccinated individuals serum bactericidal activity against B meningococci is abrogated by C5 inhibition but not by inhibition of the alternative complement pathway
Authors: Ispasanie Emma , Muri Lukas , Schmid Marc , Schubart Anna , Thorburn Christine , Zamurovic Natasa , Holbro Thomas , Kammüller Michael , Pluschke Gerd
Published: June 2023

Introduction

Several diseases caused by the dysregulation of complement activation can be treated with inhibitors of the complement components C5 and/or C3. However, complement is required for serum bactericidal activity (SBA) against encapsulated Gram-negative bacteria. Therefore, C3 and C5 inhibition increases the risk of invasive disease, in particular by Neisseria meningitidis. As inhibitors against complement components other than C3 and C5 may carry a reduced risk of infection, we compared the effect of inhibitors targeting the terminal pathway (C5), the central complement component C3, the alternative pathway (FB and FD), and the lectin pathway (MASP-2) on SBA against serogroup B meningococci.

Methods

Serum from adults was collected before and after vaccination with the meningococcal serogroup B vaccine 4CMenB and tested for meningococcal killing. Since the B capsular polysaccharide is structurally similar to certain human polysaccharides, 4CMenB was designed to elicit antibodies against meningococcal outer membrane proteins.

Results

While only a few pre-vaccination sera showed SBA against the tested B meningococcal isolates, 4CMenB vaccination induced potent complement-activating IgG titers against isolates expressing a matching allele of the bacterial cell surface-exposed factor H-binding protein (fHbp). SBA triggered by these cell surface protein-specific antibodies was blocked by C5 and reduced by C3 inhibition, whereas alternative (factor B and D) and lectin (MASP-2) pathway inhibitors had no effect on the SBA of post-4CMenB vaccination sera.

Discussion

Compared to the SBA triggered by A,C,W,Y capsule polysaccharide conjugate vaccination, SBA against B meningococci expressing a matching fHbp allele was remarkably resilient against the alternative pathway inhibition.
T cells, NK cells, and tumor-associated macrophages in cancer immunotherapy and the current state of the art of drug delivery systems
Authors: Yang Ya-long , Yang Fei , Huang Zhuan-qing , Li Yuan-yuan , Shi Hao-yuan , Sun Qi , Ma Yue , Wang Yao , Zhang Ying , Yang Sen , Zhao Guan-ren , Xu Feng-hua
Published: June 2023

The immune system provides full protection for the body by specifically identifying ‘self’ and removing ‘others’; thus protecting the body from diseases. The immune system includes innate immunity and adaptive immunity, which jointly coordinate the antitumor immune response. T cells, natural killer (NK) cells and tumor-associated macrophages (TAMs) are the main tumor-killing immune cells active in three antitumor immune cycle. Cancer immunotherapy focusses on activating and strengthening immune response or eliminating suppression from tumor cells in each step of the cancer-immunity cycle; thus, it strengthens the body’s immunity against tumors. In this review, the antitumor immune cycles of T cells, natural killer (NK) cells and tumor-associated macrophages (TAMs) are discussed. Co-stimulatory and co-inhibitory molecules in the three activity cycles and the development of drugs and delivery systems targeting these molecules are emphasized, and the current state of the art of drug delivery systems for cancer immunotherapy are summarized.
Effectiveness and safety of anti-IL-5/Rα biologics in eosinophilic granulomatosis with polyangiitis: a two-year multicenter observational study
Authors: Nolasco Santi , Portacci Andrea , Campisi Raffaele , Buonamico Enrico , Pelaia Corrado , Benfante Alida , Triggiani Massimo , Spadaro Giuseppe , Caiaffa Maria Filomena , Scioscia Giulia , Detoraki Aikaterini , Valenti Giuseppe , Papia Francesco , Tomasello Alessandra , Crimi Nunzio , Scichilone Nicola , Pelaia Girolamo , Carpagnano Giovanna Elisiana , Crimi Claudia
Published: June 2023

Background

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis characterized by asthma, systemic manifestations, and blood and tissue eosinophilia.

Objective

To assess the effectiveness and safety of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in EGPA for 24 months.

Methods

We conducted a multicenter observational study, including patients with EGPA treated with anti-IL-5/Rα biologics in 9 Italian specialized facilities. Systemic disease activity, remission and relapse rate were evaluated from 3 to 24 months after treatment initiation. Respiratory outcomes, hematological parameters, corticosteroid (OCS) and immunosuppressants consumption were also assessed.

Results

49 patients with relapsing-refractory EGPA were included [26 (53.1%) benralizumab 30mg, 20 (40.8%) mepolizumab 100mg, 3 (6.1%) mepolizumab 300mg]. Overall, 38.8% and 57.1% achieved remission after 12 and 24 months, respectively (69.2% benralizumab and 43.5% mepolizumab). Lower OCS intake and higher blood eosinophil count at baseline were associated with remission at 24 months. Both biologics exerted beneficial effects on severe asthma outcomes. Indeed, 61.2% (61.5% benralizumab and 60.8% mepolizumab) remained exacerbation-free during treatment. Lung function parameters showed improvements in the overall cohort (all p<0.05), but began to decline from month 12, especially with mepolizumab. Marked reduction in blood eosinophils was registered with mepolizumab (p<0.0001), while benralizumab depleted both eosinophils (p<0.0001) and basophils (p<0.0001). In general, 69.6% (76% benralizumab and 61.9% mepolizumab) of OCS-dependent patients lowered their daily dose by 75%, while 28.3% discontinued these drugs. Immunosuppressants were suspended in 88.2% of cases. Adverse events were reported in 8.2% of patients.

Conclusions

These real-world data suggest that anti-IL-5/Rα biologics are effective and safe in the long-term as add-on treatments for patients with EGPA.
Resistance of hypervirulent Klebsiella pneumoniae to cathepsin B-mediated pyroptosis in murine macrophages
Authors: Kim Jin Kyung , Jung Hui-Jung , Hyun Miri , Lee Ji Yeon , Park Jong-Hwan , Suh Seong-Il , Baek Won-Ki , Kim Hyun ah
Published: June 2023

Introduction

Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a clinically significant global pathogen in the last decade. However, the host immune responses of the macrophages during hvKp infection are largely unknown. In the present study, we aimed to compare the cytotoxic effects of hvKp and classical K. pneumoniae (cKp) in murine macrophages.

Results

We found that the activation of caspase-1 -dependent pyroptosis was higher in cKp-infected macrophages compared with that in hvKp-infected macrophages. In Caspase-1 deficiency macrophages, pyroptosis diminished during infection. Both hvKp and cKp strains led to nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome formation and lysosomal cathepsin B activation, thus resulting in pyroptosis. Compared with the cKp strain, the hvKp strain inhibited these phenomena in murine macrophages.

Conclusion

HvKp infection resulted in different levels of pyroptosis via the activation of cathepsin B-NLRP3-caspase-1 in murine macrophages. Therefore, the manipulation of pyroptotic cell death is a potential target for host response during hvKp infection in macrophages.
PGE2-EP2/EP4 signaling elicits mesoCAR T cell immunosuppression in pancreatic cancer
Authors: Akbari Behnia , Soltantoyeh Tahereh , Shahosseini Zahra , Jadidi-Niaragh Farhad , Hadjati Jamshid , Brown Christine E. , Mirzaei Hamid Reza
Published: June 2023

Introduction

For many years, surgery, adjuvant and combination chemotherapy have been the cornerstone of pancreatic cancer treatment. Although these approaches have improved patient survival, relapse remains a common occurrence, necessitating the exploration of novel therapeutic strategies. CAR T cell therapies are now showing tremendous success in hematological cancers. However, the clinical efficacy of CAR T cells in solid tumors remained low, notably due to presence of an immunosuppressive tumor microenvironment (TME). Prostaglandin E2, a bioactive lipid metabolite found within the TME, plays a significant role in promoting cancer progression by increasing tumor proliferation, improving angiogenesis, and impairing immune cell’s function. Despite the well-established impact of PGE2 signaling on cancer, its specific effects on CAR T cell therapy remain under investigation.

Methods

To address this gap in knowledge the role of PGE2-related genes in cancer tissue and T cells of pancreatic cancer patients were evaluated in-silico. Through our in vitro study, we manufactured fully human functional mesoCAR T cells specific for pancreatic cancer and investigated the influence of PGE2-EP2/EP4 signaling on proliferation, cytotoxicity, and cytokine production of mesoCAR T cells against pancreatic cancer cells.

Results

In-silico investigations uncovered a significant negative correlation between PGE2 expression and gene signature of memory T cells. Furthermore, in vitro experiments demonstrated that the activation of PGE2 signaling through EP2 and EP4 receptors suppressed the proliferation and major antitumor functions of mesoCAR T cells. Interestingly, the dual blockade of EP2 and EP4 receptors effectively reversed PGE2-mediated suppression of mesoCAR T cells, while individual receptor antagonists failed to mitigate the PGE2-induced suppression.

Discussion

In summary, our findings suggest that mitigating PGE2-EP2/EP4 signaling may be a viable strategy for enhancing CAR T cell activity within the challenging TME, thereby improving the efficacy of CAR T cell therapy in clinical settings.
Changes in patient-reported outcomes in patients with non-idiopathic pulmonary fibrosis fibrotic interstitial lung disease and progressive pulmonary fibrosis
Authors: Takei Reoto , Matsuda Toshiaki , Fukihara Jun , Sasano Hajime , Yamano Yasuhiko , Yokoyama Toshiki , Kataoka Kensuke , Kimura Tomoki , Suzuki Atsushi , Furukawa Taiki , Fukuoka Junya , Johkoh Takeshi , Kondoh Yasuhiro
Published: June 2023

Background

Health-related quality of life (HRQoL) captures different aspects of the fibrotic interstitial lung disease (FILD) evaluation from the patient’s perspective. However, little is known about how HRQoL changes in patients with non-idiopathic pulmonary fibrosis (IPF) FILD, especially in those with progressive pulmonary fibrosis (PPF). The aim of this study is to clarify whether HRQoL deteriorates in patients with non-IPF FILD and to evaluate the differences in the changes in HRQoL between those with and without PPF.

Methods

We collected data from consecutive patients with non-IPF FILD and compared annual changes in HRQoL over 2 years between patients with PPF and those without. The St George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were used to assess HRQoL. Changes in the SGRQ and CAT scores for 24 months from baseline were evaluated with a mixed-effect model for repeated measures.

Results

A total of 396 patients with non-IPF FILD were reviewed. The median age was 65 years and 202 were male (51.0%). The median SGRQ and CAT scores were 29.6 and 11, respectively. Eighty-six (21.7%) showed PPF. Both SGRQ and CAT scores were significantly deteriorated in patients with PPF compared to those without PPF (p < 0.01 for both). Clinically important deterioration in the SGRQ and CAT scores were observed in 40.0 and 35.7% of patients with PPF and 11.7 and 16.7% of those without, respectively. PPF was significantly associated with clinically important deterioration in the SGRQ score (odds ratio 5.04; 95%CI, 2.61–9.76, p < 0.01) and CAT score (odds ratio 2.78; 95%CI, 1.27–6.06, p = 0.02).

Conclusion

The SGRQ and CAT scores were significantly deteriorated in patients with non-IPF FILD and PPF. Considering an evaluation of HRQoL would be needed when assessing PPF.