bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular and computational analysis of a novel pathogenic variant in emopamil-binding protein (EBP) involved in cholesterol biosynthetic pathway causing a rare male EBP disorder with neurologic defects (MEND syndrome)
Authors: Bibi Hadiba , Ahmad Riaz , Rahman Fatima , Maqbool Shazia , Naeem Muhammad , Efthymiou Stephanie , Houlden Henry 
Published: January 2025

Abstract
Background
Male EBP disorder with neurologic defects (MEND syndrome) is an extremely rare disorder with a prevalence of less than 1/1,000,000 individuals worldwide. It is inherited as an X-linked recessive disorder caused by impaired sterol biosynthesis due to nonmosaic hypomorphic EBP variants. MEND syndrome is characterized by variable clinical manifestations including intellectual disability, short stature, scoliosis, digital abnormalities, cataracts, and dermatologic abnormalities. The goal of this study was to investigate the disease-causing variants in a family of two patients affected with MEND syndrome.

Methods
The genomic DNA of the two patients with MEND syndrome was subjected to whole exome sequencing to identify disease-causing variants. Segregation of the identified variant was tested through Sanger sequencing. Several in-silico tools were used to evaluate the pathogenicity of the variant. Protein’s 3D structure analysis systems were used to predict the impact of the identified variant on the binding and function of the mutated EBP protein including AlphaFold, PyMOL, AutoDock, ChimeraX and Discovery Studio.

Results
A novel pathogenic missense EBP variant NM_006579.3:c.556T > C (Trp186Arg) was found segregating in the affected family. In-silico analysis and molecular docking results supported the pathogenicity of the identified variant.

Conclusion
Our study expands the mutation spectrum of EBP and adds to the restricted reports of MEND patients. It strengthens the body of evidence that supports the role of EBP in the MEND syndrome phenotype. To our knowledge, this is the first report of this disorder from Pakistan.
Challenges of Investigating Compartmentalized Brain Energy Metabolism Using Nuclear Magnetic Resonance Spectroscopy in vivo
Authors: Duarte João M. N. 
Published: January 2025

Abstract
Brain function requires continuous energy supply. Thus, unraveling brain metabolic regulation is critical not only for our basic understanding of overall brain function, but also for the cellular basis of functional neuroimaging techniques. While it is known that brain energy metabolism is exquisitely compartmentalized between astrocytes and neurons, the metabolic and neuro-energetic basis of brain activity is far from fully understood. 1H nuclear magnetic resonance (NMR) spectroscopy has been widely used to detect variations in metabolite levels, including glutamate and GABA, while 13C NMR spectroscopy has been employed to study metabolic compartmentation and to determine metabolic rates coupled brain activity, focusing mainly on the component corresponding to excitatory glutamatergic neurotransmission. The rates of oxidative metabolism in neurons and astrocytes are both associated with the rate of the glutamate-glutamine cycle between neurons and astrocytes. However, any possible correlation between energy metabolism pathways and the inhibitory GABAergic neurotransmission rate in the living brain remains to be experimentally demonstrated. That is due to low GABA levels, and the consequent challenge of determining GABAergic rates in a non-invasive manner. This brief review surveys the state-of-the-art analyses of energy metabolism in neurons and astrocytes contributing to glutamate and GABA synthesis using 13C NMR spectroscopy in vivo, and identifies limitations that need to be overcome in future studies.
Shifting units, shifting views: how product mass and protein content influence environmental impact of Icelandic lamb
Authors: Shrivastava Sankalp , Gudjónsdóttir María , Thorkelsson Gudjon , Ögmundarson Ólafur 
Published: January 2025

Abstract

Purpose
Lamb meat is a crucial protein source in Icelanders’ diets. Extensive grazing lands, locally grown hay feed, and traditional farming methods are often used as arguments for Icelandic lamb meat’s environmental friendliness. However, no life cycle assessment (LCA) study exists to corroborate these arguments. This study conducts a national-level LCA to evaluate the environmental performance of lamb meat based on two functional units to identify key hotspot processes in its production.

Method
This study conducts a cradle-to-farm gate LCA at the national level for two functional units: 1 kg of edible lamb meat (ELM) and 100 g of ELM protein produced in Iceland in 2019. The multifunctionality between wool and meat is handled using mass allocation.
The environmental impacts were estimated using the ReCiPe 2016 v1.1 mid-point (H) impact assessment method, emphasizing selected environmental categories: global warming, fossil resource scarcity, land use, and terrestrial ecotoxicity. In addition, the study conducts a scenario-based variability analysis by taking minimum and maximum values of inventory data to estimate the possible range of environmental impacts. Lastly, an overall uncertainty analysis and a global sensitivity analysis of the key hotspot process shed light on the variability and sensitivity of the LCA results.

Result and discussion
For the 18 ReCiPe impact categories, animal and feed (hay) production are the hotspot processes, followed by feed (grazing) as a hotspot for land use. The global warming impact for 1 kg of ELM ranges 41–53 kg CO2 equivalent, and for 100 g of protein, 19–29 kg CO2 equivalent. Fossil resource scarcity impact for 1 kg of ELM impact ranges 2.5–3.6 kg oil equivalent, and for 100 g protein, 1–2 kg oil equivalent. Terrestrial ecotoxicity impacts for 1 kg of ELM range 46–69 kg 1,4-DCB, and for 100 g protein, 21–37 kg 1,4-DCB. Lastly, land use impacts for 1 kg of ELM range 562–2448 m2a crop equivalent, and for 100 g protein, 261–1324 m2a crop equivalent.

Conclusion
With its traditional farming practices, Icelandic lamb meat production is close to an extensive farming system, which is in line with its higher global warming impact per kg ELM. Additionally, due to low hay yield and high fertilization rate, the impact on other impact categories is still higher compared to an extensive system. This perspective shifts when analyzed per 100 g of protein, where it performs close to the global average.
Frailty and neurocognitive impairments in Chinese survivors of childhood cancer
Authors: Wei Yihui , Deng Weishang , To Kenneth Kin-Wah , Lam Teddy Tai-Ning , Tso Winnie Wan-Yee , Chan Agnes Sui-Yin , Ness Kirsten K. , Li Chi Kong , Cheung Yin Ting 
Published: January 2025

Abstract
Purpose
This study aimed to evaluate the prevalence and predictors of frailty and the association between frailty and neurocognitive impairments among Chinese survivors of childhood cancer.

Methods
A total of 185 survivors of childhood cancer were recruited from a long-term follow-up clinic in Hong Kong (response rate: 94.4%; 48.1% female; mean age 28.9 years, standard deviation = 6.7 years). Frailty was assessed using the Fried frailty criteria. Neurocognitive outcomes were evaluated using a performance-based test. Multivariable logistic regression was used to identify the predictors of frailty. Multivariable generalized linear models were used to explore the associations between frailty and cognitive outcomes.

Results
The proportions of survivors with frailty and pre-frailty were 22.7% and 27.0%, respectively. “Frail” survivors were more likely to be diagnosed with cancer at a younger age (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.87–0.99, P = 0.041) and to have coexisting chronic health conditions (OR = 4.63, 95% CI: 1.68–12.80, P = 0.003) than “non-frail” and “pre-frail” survivors. Survivors with frailty exhibited worse attention detectability (unstandardized point estimate [Est] = 4.57, standard error [SE] = 1.69, P = 0.007), omissions (Est = 3.68, SE = 1.15, P = 0.001), and cognitive flexibility (Est = 8.08, SE = 3.08, P = 0.009) than “non-frail” and “pre-frail” survivors.

Conclusions
More than one fifth of the participating Chinese survivors of childhood cancer were identified as phenotypically frail. Frailty was associated with worse performance in attention and executive function.

Implications for Cancer Survivors
The findings highlight the needs for regular monitoring and early interventions that can modify the aging pathway in the cancer continuum, to mitigate frailty and improve psychosocial outcomes during long-term cancer survivorship.
Navigating the Economic Burden of Multiple Myeloma: Insights into Cost-effectiveness of CAR-T and Bispecific Antibody Therapies
Authors: Keesari Praneeth Reddy , Samuels Diana , Vegivinti Charan Thej Reddy , Pulakurthi Yashwitha Sai , Kudithi Revathi , Dhar Meekoo , Janakiram Murali 
Published: January 2025

Abstract
Purpose of Review
Multiple myeloma is a chronic malignancy and with evolving treatment options, understanding the economic burden and cost-effectiveness of therapies is crucial for clinicians and researchers.

Recent Findings
In this, we review the recent approval of Bispecific antibodies and CAR-T for myeloma and their cost implications, including direct and indirect costs. We compare this to current regimens and provide cost comparisons in this review.

Summary
We conclude that the use of more effective therapies such as CAR-T in earlier lines of therapies may be more cost-effective depending on the country and model used. Further studies are essential to better understand the cost-effectiveness of bispecific antibodies including head-to-head comparisons to CAR-T therapy.
Neurotheology: Practical Applications with Regard to Integrative Psychiatry
Authors: Newberg Andrew B. 
Published: January 2025

Abstract

Purpose of Review
Neurotheology is a nascent field of research and scholarship that seeks to understand the relationship between the brain and religious and spiritual phenomena. In the context of integrative psychiatry, neurotheology offers an intriguing intermediary between understanding how spirituality and religion affect brain function, and how this might be related to changes in mental health.

Recent Findings
A number of research studies over the years have observed that religious and spiritual beliefs, practices, and experiences can have a profound impact on a person’s psyche. Many times, the effects are positive leading to lower depression, anxiety and distress. However, there are times that religion and spirituality can lead to negative beliefs and behaviors. Neurotheology seeks to understand both the positive and negative effects of religion and spirituality on mental health from a brain perspective. In addition, neurotheology offers important philosophical insights into the nature of the human mind and how we perceive the reality around us.

Summary
This review evaluates these many topics as it considers how neurotheology can have practical applications with regard to integrative psychiatry.
Examining viewers’ impulsive buying behaviour in sports livestreaming commerce
Authors: Liu Haoyu , Tan Kim Hua , Chung Leanne , Yoshie Osamu , Ieiri Yuya 
Published: January 2025

AbstractLivestreaming commerce is increasingly influencing the sports industry’s supply chain. This study seeks to understand how the quality of the service characteristics enhance customer flow experiences and encourage buying behaviour. It also delves into the relationship between flow experience and impulsive buying behaviour, particularly examining how fan identification moderates this dynamic. Data from 274 participants, who recounted their recent shopping experiences while watching sports on SLSPs, were analysed. Structural equation modelling analysis largely confirmed the hypothesis that content quality, para-social interactivity, and ease of use significantly contribute to viewers’ flow experiences, which, in turn, affect impulsive buying behaviour. Moreover, fan identification was found to amplify the positive effect of flow experience on impulsive buying behaviour. This research adds depth to the fields of platform service operations by exploring the links between service characteristics, impulsive buying behaviours, and the role of fan identification within SLSP contexts. The findings offer valuable insights for SLSP operations managers looking to influence viewers’ purchasing decisions and increase sales and enhance business performance.
Assignment of the N-terminal domain of mouse cGAS
Authors: Aucharova Hanna , Linser Rasmus 
Published: January 2025

AbstractCyclic GMP-AMP synthase (cGAS) is a DNA-sensing enzyme that is a member of the nucleotidyltransferase (NTase) family and functions as a DNA sensor. The protein is comprised of a catalytic NTase core domain and an unstructured hypervariable N-terminal domain (NTD) that was reported to increase protein activity by providing an additional DNA-binding surface. We report nearly complete 1H, 15N, and 13C backbone chemical-shift assignments of mouse cGAS NTD (residues 5-146), obtained with a set of 3D and 4D solution NMR experiments. Analysis of the chemical-shift values confirms that the NTD is intrinsically disordered. These resonance assignments can provide the basis for further studies such as activation by DNA and protein-protein interactions.
Boys’ Love as Conditional Resilience: How Gay and Bisexual Men from Hong Kong Consume Boys’ Love
Authors: Chui Don Lok Tung , Chan Lik Sam 
Published: January 2025

AbstractBoys’ Love (BL) is a fictional genre that depicts homoerotic relationships between two men. As it is often regarded as created by women and for women, most BL-related studies have focused on its female participants. In recent decades, the BL subculture has transformed into a transnational cultural phenomenon. Although such popularity may suggest that more homoerotic media products are available to gay/bisexual men, the heteronormative nature of BL may drive away gay/bisexual audiences. This study investigates the experiences of consuming BL among gay/bisexual men in Hong Kong. The findings show that gay/bisexual audiences enjoy the aspects of BL that resonate with their personal experiences and fantasies. Through the process of queer reading, BL helps gay/bisexual audiences develop resilience to cope with the stresses that they encounter as sexual minorities in Hong Kong. However, due to the gap between what is depicted in BL and reality, such resilience is circumscribed, which means that BL only provides conditional resilience to its gay/bisexual audience in Hong Kong.
On the Isoperimetric and Isodiametric Inequalities and the Minimisation of Eigenvalues of the Laplacian
Authors: Farrington Sam 
Published: January 2025

Abstract
We consider the problem of minimising the k-th eigenvalue of the Laplacian with some prescribed boundary condition over collections of convex domains of prescribed perimeter or diameter. It is known that these minimisation problems are well-posed for Dirichlet eigenvalues in any dimension

$$d\ge 2$$

d
≥
2

and any sequence of minimisers converges to the ball of unit perimeter or diameter respectively as

$$k\rightarrow +\infty $$

k
→
+
∞

. In this paper, we show that the same is true in the case of Neumann eigenvalues under diameter constraint in any dimension and under perimeter constraint in dimension

$$d=2$$

d
=
2

. We also consider these problems for Robin eigenvalues and mixed Dirichlet–Neumann eigenvalues, under an additional geometric constraint.
Enhanced drug delivery in cancer therapy: role of TMPRSS4 protease in liposomal engineering
Authors: Kim Ji Hoon , Kwak Jeong Hun , Choi Ho Joong , Lee Dosang , Park Jung Hyun , Kim Ok-Hee , Kim Say-June 
Published: January 2025

AbstractThis research centers on leveraging the proteolytic activity of TMPRSS4 (transmembrane protease, serine 4), a transmembrane protease frequently found on tumor cell membranes, for the development of anticancer therapeutics. A novel liposome design was developed, incorporating transmembrane peptides (TMPRSS4-cleavable peptides; TCPs) on the surface that are selectively degradable by TMPRSS4, aimed at improving intracellular delivery efficiency. The efficacy of TCP-liposomes (TCP-L) in targeting tumor cells and delivering cargo was evaluated in comparison to control liposomes (CL). The liposomes were manufactured using a microfluidic technique, where TCPs were attached via sonication, and doxorubicin (DOX) was encapsulated as necessary. To compare the efficiency of intracellular cargo delivery, the fabricated liposomes were tested across various cancer cell lines and in an in vivo xenograft model of gastric cancer. In vitro studies showed DOX TCP-L significantly enhanced doxorubicin release in lung, colon, gastric, and pancreatic cancer cell lines compared to DOX CL (P < 0.05). In vivo experiments using the gastric cancer xenograft model demonstrated the highest Total Radiant Efficiency (TRE) in the 100 μg DOX TCP-L group (P < 0.05), followed by 50 μg DOX TCP-L, 100 μg DOX CL, and 50 μg DOX CL. Immunohistochemical staining of excised xenograft tumor tissues revealed an increase in the pro-apoptotic marker Bax and a decrease in the anti-apoptotic marker Mcl-1 in the DOX TCP-L group compared to the DOX CL group. The findings suggest that TCP-L enhance intracellular cargo delivery, likely due to TMPRSS4-induced liposomal destabilization in cancer cells, showcasing the potential of TCP-L for improved drug delivery in cancer treatment.
TICK: A Knowledge Processing Infrastructure for Cognitive Trust in Human–Robot Interaction
Authors: Diab Mohammed , Demiris Yiannis 
Published: January 2025

AbstractIn order to assess trust within domains necessitating Human–Robot Interaction (HRI), such as social and assistive robotics, a multifaceted cognitive infrastructure is essential to facilitate shared knowledge among the participants. This knowledge encompasses information pertaining to the behaviour, beliefs, intentions, and situational awareness of the participants, including assessments of vulnerability, reliability, and risk. The developed knowledge takes the form of a domain-agnostic ontology with multiple layers, allowing for reusability across diverse HRI tasks, and resulting in actions that can be undertaken by a participant to establish trust with the other party. This research introduces the concept of Trust-Inferring Infrastructure for Cognitive Knowledge (TICK) for domains requiring HRI, comprising three key constructs: performance, process, and purpose. Subsequently, the proposed infrastructure is evaluated through real-world scenarios involving humans as trustors and robots as trustees. To validate TICK in these real scenarios, a multimodal sensory module has been integrated into the reasoning mechanism, enhancing the robots’ capabilities in understanding human intentions, perceiving the current situation, offering advice to humans, personalising their behaviour to build human trust, and evolving the robot’s trustworthiness based on its performance during interactions. Trust is automatically assessed based on proximity and adherence to the robots’ recommendations. Furthermore, to quantitatively assess the scalability and flexibility of the proposed approach, a series of experiments were conducted involving a kitchen domain handover task between humans and a table-top robotic arm in a lab setting, encompassing various types of objects and different scene contexts.
Branch canker battles: understanding and managing the Botryosphaeriaceae in avocado
Authors: Möller Heike , Slippers Bernard , van den Berg Noëlani 
Published: January 2025

Abstract
Avocado holds an important position in global agriculture and economic development. However, this thriving industry faces significant challenges from fungal pathogens, particularly those in the Botryosphaeriaceae. These fungi have emerged as major pathogens across various hosts, causing branch cankers, dieback, and fruit rots in avocados. These diseases reduce fruit quality and lead to substantial yield losses, threatening the profitability and sustainability of avocado production. This review consolidates current knowledge on Botryosphaeriaceae species affecting avocados, with a focus on their diversity, disease dynamics, detection methods, management strategies, and recent omics advances related to species reported in avocados. Given the escalating global production and economic importance of avocados, understanding, and effectively managing Botryosphaeriaceae infections is crucial. The review aims to identify research gaps and propose future research avenues to enhance disease management practices in avocado cultivation.
New semisynthetic α-glucosidase inhibitor from a doubly-chemically engineered extract
Authors: Osella María I. , Salazar Mario O. , Solís Carlos M. , Furlan Ricardo L. E. 
Published: January 2025

AbstractChemically engineered extracts represent a promising source of new bioactive semi-synthetic molecules. Prepared through direct derivatization of natural extracts, they can include constituents enriched with elements and sub-structures that are less common in natural products compared to drugs. Fourteen such extracts were prepared through sequential reactions with hydrazine and a fluorinating reagent, and their α-glucosidase inhibition properties were compared. For the most bioactive mixture, a chemically modified propolis extract, enzyme inhibition increased 22 times due to the reaction sequence. Bio-guided fractionation led to the isolation of a new fluorinated pyrazole produced within the extract by chemical transformation of the flavonoid chrysin. The inhibitor results from the action of the two reagents used on four common functional groups present in natural products (carbonyl, phenol, aromatic carbon, and a double bond). The reactions led to the opening of a 6-member oxygenated heterocycle to produce a 5-member nitrogenated one, as well as the dehydroxylation and fluorination in two different positions of one of the aromatic rings of the natural starting material, all within a complex mixture of natural products. Overall, these transformations led to an approximately 20-fold increase in the α-glucosidase inhibition by the isolated inhibitor compared to its natural precursor.
Graphical Abstract