bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep eutectic solvents for next-generation cyclodextrin science
Authors: Komiyama Makoto
Published: November 2024

In cyclodextrin science, water is employed as a solvent almost exclusively, and this imposes non-negligible limitations to the scope of applications. Accordingly, deep eutectic solvents, constructed from hydrogen-bonding donors and acceptors, have been attracting much interest as important substitutes for water. This review comprehensively covers chemical and physicochemical features of cyclodextrins in these eco-friendly solvents. In one category, cyclodextrins or their derivatives are dissolved as solutes in conventional deep eutectic solvents. All of α-, β-, and γ-cyclodextrins efficiently form inclusion complexes with various guest molecules, exactly as observed in water. Notably, chemically modified cyclodextrins (e.g. 2-hydroxypropyl-cyclodextrins) form even more stable inclusion complexes than native cyclodextrins. Alternatively, deep eutectic solvents are prepared by combining cyclodextrins with other hydrogen-bonding components. The cyclodextrin units in these mixtures also form inclusion complexes with guest molecules. It has been proposed that enhanced flexibility of cylindrical structures of cyclodextrins allows effective induced-fit to stabilize inclusion complexes. The applications of these systems range widely, from catalysis for organic synthesis to extraction, analysis, pharmaceutics, and many other fields. High solubilities of cyclodextrins and various chemicals in these solvents guarantee high productivity in target transformations. These unique systems promise further innovation.
Dexmedetomidine regulates exosomal miR-29b-3p from macrophages and alleviates septic myocardial injury by promoting autophagy in cardiomyocytes via targeting glycogen synthase kinase 3β
Authors: Yu Tianyi , Liu Hsinying , Gao Min , Liu Dan , Wang JiaQiang , Zhang Jie , Wang Jizhuang , Yang Peilang , Zhang Xiong , Liu Yan
Published: November 2024

Background

Our previous research suggested that dexmedetomidine (Dex) promotes autophagy in cardiomyocytes, thus safeguarding them against apoptosis during sepsis. However, the underlying mechanisms of Dex-regulated autophagy have remained elusive. This study aimed to explore the role of exosomes and how they participate in Dex-induced cardioprotection in sepsis. The underlying microRNA (miRNA) mechanisms and possible therapeutic targets for septic myocardial injury were identified.

Methods

We first collected plasma exosomes from rats with sepsis induced by caecal ligation and puncture (CLP) with or without Dex treatment, and then incubated them with H9c2 cells to observe the effect on cardiomyocytes. Subsequently, the differential expression of miRNAs in plasma exosomes from each group of rats was identified through miRNA sequencing. miR-29b-3p expression in circulating exosomes of septic or non-septic patients, as well as in lipopolysaccharide-induced macrophages after Dex treatment, was analysed by quantitative real-time polymerase chain reaction (qRT–PCR). The autophagy level of cardiomyocytes after macrophage-derived exosome treatment was assessed by an exosome tracing assay, western blotting, and an autophagic flux assay. Specific miRNA mimics and inhibitors or small interfering RNAs were used to predict and evaluate the function of candidate miRNA and its target genes by qRT-PCR, annexin V/propyl iodide staining, autophagy flux analysis, and western blotting.

Results

We found that plasma-derived exosomes from Dex-treated rats promoted cardiomyocyte autophagy and exerted antiapoptotic effects. Additionally, they exhibited a high expression of miRNA, including miR-29b-3p. Conversely, a significant decrease in miR-29b-3p was observed in circulating exosomes from CLP rats, as well as in plasma exosomes from sepsis patients. Furthermore, Dex upregulated the lipopolysaccharide-induced decrease in miR-29b-3p expression in macrophage-derived exosomes. Exosomal miR-29b-3p from macrophages is thought to be transferred to cardiomyocytes, thus leading to the promotion of autophagy in cardiomyocytes. Database predictions, luciferase reporter assays, and small interfering RNA intervention confirmed that glycogen synthase kinase 3β (GSK-3β) is a target of miR-29b-3p. miR-29b-3p promotes cardiomyocyte autophagy by inhibiting GSK-3β expression and activation.

Conclusions

These findings demonstrate that Dex attenuates sepsis-associated myocardial injury by modulating exosome-mediated macrophage–cardiomyocyte crosstalk and that the miR-29b-3p/GSK-3β signaling pathway represents a hopeful target for the treatment of septic myocardial injury.
From communities to interpretable network and word embedding: an unified approach
Authors: Prouteau Thibault , Dugué Nicolas , Guillot Simon
Published: November 2024

Modelling information from complex systems such as humans social interaction or words co-occurrences in our languages can help to understand how these systems are organized and function. Such systems can be modelled by networks, and network theory provides a useful set of methods to analyze them. Among these methods, graph embedding is a powerful tool to summarize the interactions and topology of a network in a vectorized feature space. When used in input of machine learning algorithms, embedding vectors help with common graph problems such as link prediction, graph matching, etc In Natural Language Processing (NLP), such a vectorization process is also employed. Word embedding has the goal of representing the sense of words, extracting it from large text corpora. Despite differences in the structure of information in input of embedding algorithms, many graph embedding approaches are adapted and inspired from methods in NLP. Limits of these methods are observed in both domains. Most of these methods require long and resource greedy training. Another downside to most methods is that they are black-box, from which understanding how the information is structured is rather complex. Interpretability of a model allows understanding how the vector space is structured without the need for external information, and thus can be audited more easily. With both these limitations in mind, we propose a novel framework to efficiently embed network vertices in an interpretable vector space. Our Lower Dimension Bipartite Framework (LDBGF) leverages the bipartite projection of a network using cliques to reduce dimensionality. Along with LDBGF, we introduce two implementations of this framework that rely on communities instead of cliques: SINr-NR and SINr-MF. We show that SINr-MF can perform well on classical graphs and SINr-NR can produce high-quality graph and word embeddings that are interpretable and stable across runs.
Device–device interference triggered by an abandoned pacemaker: a case report
Authors: Wang Dong , Mueller-Leisse Johanna , Hillmann Henrike A K , Eiringhaus Jörg , Duncker David
Published: November 2024

Background

Cardiac implantable electronic devices (CIEDs) are prone to electromagnetic interference. Common sources include household electronics and industrial machinery. However, medical equipment can also trigger interferences and cause CIED malfunction.

Case summary

We report on a 79-year-old male with sudden onset of presyncope. He has a long history of device therapy, including an active VVI leadless pacemaker and an abandoned abdominal pacemaker with epicardial leads. Automatic reactivation of the abandoned pacemaker due to reaching end-of-life mode led to interaction with the active pacemaker, inhibiting it in its function. Due to elevated capture threshold and insufficient output, pacing by the reactivated pacemaker was accompanied by intermittent loss of myocardial capture and patient symptoms. By changing the mode to VOO and increasing the pacing rate of the active pacemaker, the interaction was prevented as an intermittent solution. The final therapy consisted of explanting the pulse generator of the abdominal pacemaker.

Discussion

We present a patient with a deactivated abandoned cardiac pacemaker, which self-activated after reaching end-of-life mode and triggered an interaction with his active pacemaker. This case emphasizes the importance of explanting old devices to avoid potential interaction.
Shared genetic associations and aetiology between obstructive sleep apnoea and cardiovascular diseases: a genome-wide cross-trait analysis and bidirectional Mendelian randomization analysis
Authors: Feng Kun , Yang Jinyue , Liu Kai
Published: November 2024

Aims

Study aimed to investigate the genetic correlations and potential causal relationships between obstructive sleep apnoea (OSA) and various cardiovascular diseases (CVDs), aiming to enhance understanding of shared genetic mechanisms and improve recognition and treatment of OSA in patients with CVDs.

Methods and results

Utilizing genome-wide association study (GWAS) data, we analysed shared genetics between OSA and CVDs using linkage disequilibrium score regression, multi-trait analysis of GWAS (MTAG), and genotype–tissue expression analysis. We further investigated causal relationships using Bayesian co-localization tests, bidirectional Mendelian randomization, and latent causal variable analysis. We found strong associations between OSA and multiple CVDs: coronary artery disease (CAD), heart failure (HF), myocardial infarction (MI), stroke, and atrial fibrillation (AF). Novel single-nucleotide polymorphisms related to CVDs were identified during single-trait MTAG analysis. By applying cross-trait MTAG, we identified 15 shared loci between OSA and CAD, 25 shared loci between OSA and MI, and 7 shared loci between OSA and HF. Shared genes are primarily expressed in the blood, heart, kidney, liver, muscle, and pancreas. Mendelian randomization analysis indicated a significant causal effect of OSA on HF and AF as a causal factor for OSA. Latent causal variable analysis suggested that AF was causally associated with OSA, while HF showed partial causality.

Conclusion

Our study suggests strong genetic correlations between OSA and several CVDs. Further research is needed on the associations between OSA and CVDs, as well as the mechanisms of the identified loci.
Ventricular arrhythmias in association with athletic cardiac remodelling
Authors: D’Ambrosio Paolo , Claessen Guido , Kistler Peter M , Heidbuchel Hein , Kalman Jonathan M , La Gerche André
Published: November 2024

Athletes are predisposed to atrial arrhythmias but the association between intense endurance exercise training, ventricular arrhythmias (VAs), and sudden cardiac death is less well established. Thus, it is unclear whether the ‘athlete’s heart’ promotes specific arrhythmias or whether it represents a more general pro-arrhythmogenic phenotype. Whilst direct causality has not been established, it appears possible that repeated exposure to high-intensity endurance exercise in some athletes contributes to formation of pro-arrhythmic cardiac phenotypes that underlie VAs. Theories regarding potential mechanisms for exercise-induced VAs include repeated bouts of myocardial inflammation and stretch-induced cellular remodelling. Small animal models provide some insights, but larger animal and human data are sparse.

The current clinical approach to VAs in athletes is to differentiate those with and without structural or electrical heart disease. However, if the athlete’s heart involves a degree of pro-arrhythmogenic remodelling, then this may not be such a simple dichotomy. Questions are posed by athletes with VAs in combination with extreme remodelling. Some markers, such as scar on magnetic resonance imaging, may point towards a less benign phenotype but are also quite common in ostensibly healthy athletes. Other clinical and invasive electrophysiology features may be helpful in identifying the at-risk athlete.

This review seeks to discuss the association between athletic training and VAs. We will discuss the potential mechanisms, clinical significance, and approach to the management of athletes with VAs.
A review of multimodal deep learning methods for genomic-enabled prediction in plant breeding
Authors: Montesinos-López Osval A , Chavira-Flores Moises , Kiasmiantini  , Crespo-Herrera Leo , Saint Piere Carolina , Li HuiHui , Fritsche-Neto Roberto , Al-Nowibet Khalid , Montesinos-López Abelardo , Crossa José
Published: November 2024

Deep learning methods have been applied when working to enhance the prediction accuracy of traditional statistical methods in the field of plant breeding. Although deep learning seems to be a promising approach for genomic prediction, it has proven to have some limitations, since its conventional methods fail to leverage all available information. Multimodal deep learning methods aim to improve the predictive power of their unimodal counterparts by introducing several modalities (sources) of input information. In this review, we introduce some theoretical basic concepts of multimodal deep learning and provide a list of the most widely used neural network architectures in deep learning, as well as the available strategies to fuse data from different modalities. We mention some of the available computational resources for the practical implementation of multimodal deep learning problems. We finally performed a review of applications of multimodal deep learning to genomic selection in plant breeding and other related fields. We present a meta-picture of the practical performance of multimodal deep learning methods to highlight how these tools can help address complex problems in the field of plant breeding. We discussed some relevant considerations that researchers should keep in mind when applying multimodal deep learning methods. Multimodal deep learning holds significant potential for various fields, including genomic selection. While multimodal deep learning displays enhanced prediction capabilities over unimodal deep learning and other machine learning methods, it demands more computational resources. Multimodal deep learning effectively captures intermodal interactions, especially when integrating data from different sources. To apply multimodal deep learning in genomic selection, suitable architectures and fusion strategies must be chosen. It is relevant to keep in mind that multimodal deep learning, like unimodal deep learning, is a powerful tool but should be carefully applied. Given its predictive edge over traditional methods, multimodal deep learning is valuable in addressing challenges in plant breeding and food security amid a growing global population.
FOXO3 Longevity Genotype Mitigates Risk Posed by Hypertension on Incident Coronary Artery Disease in Middle-Aged Men: Kuakini Honolulu Heart Program
Authors: Chen Randi , Morris Brian J , Donlon Timothy A , Nakagawa Kazuma , Allsopp Richard C , Willcox Bradley J , Masaki Kamal H
Published: November 2024

Background

This study tested whether the carriage of the longevity-associated G-allele of FOXO3 SNP rs2802292 (TG/GG) protects against incident coronary artery disease (CAD) in men with hypertension.

Methods

Subjects were American men residing on Oahu having Japanese (n = 5415) or Okinawan (n = 897) ancestry and free of CAD at baseline (1965–1968) when aged 45–68 years.

Results

During the follow-up, there were 1 629 incident CAD cases. Adjusting for age and cardiovascular disease risk factors, the main effect Cox model showed that in men of Japanese ancestry, hypertension was a strong predictor of CAD (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.44–1.80), p < .0001), but TG/GG genotype was not associated with CAD (HR 0.92; 95% CI = 0.82–1.02; p = .11). A full Cox model showed the interaction of TG/GG with hypertension was significant (β = –0.23, p = .038). Stratified by hypertension status, TG/GG genotype TG/GG had a protective effect against CAD in each group (HR 0.83; 95% CI 0.71–0.96; p = .021 in men of Japanese heritage, and HR 0.66; 95% CI 0.43–1.01; p = .054 in men of Okinawan heritage). No association with CAD was seen in normotensive men having either Japanese (HR 1.04; 95% CI 0.89–1.22; p = .61) or Okinawan (HR 0.95; 95% CI 0.66–1.38; p = .79) heritage.

Conclusions

The present prospective study found that longevity-associated FOXO3 genotype did not independently affect the risk of CAD in all men. Rather, it was associated with protection against incident CAD in men with hypertension. Hypertensive middle-aged men with FOXO3TT genotype may merit particular attention in CAD prevention programs.
In-plane dynamic analysis of supershear rupture transition due to poroelastic pressurization
Authors: Mu Changqing , Song Yongjia , Hu Hengshan
Published: November 2024

Although pore fluid has received increased attention in the problems of earthquake rupture, its effects on coseismic rupture are not fully understood. In this paper, we numerically simulate dynamic rupture in saturated poroelastic media to study the interplay between poroelastic pressurization and rupture evolution. Particular attention is paid to the physical process of the supershear transition. The spontaneous rupture is assumed to be governed by slip weakening law and the fault is treated as a leaky interface where pore pressure equilibrium is delayed. Results show that the pore pressure induced by coseismic mechanical deformation can strengthen the fault on the extensional side but weaken the fault on the compressional side. As a result, the poroelastic pressurization on the compressional side can promote the occurrence of the transition to supershear rupture while its strengthening effect on the extensional side can suppress this transition even in the state of high-initial shear stress. Meanwhile, it is found that the permeability distribution along the fault plane also affects rupture evolution. Faults with nucleation zones located in low-permeability regions are more likely to undergo a supershear rupture.
Evolution of Plant Genome Size and Composition
Authors: He Bing , Liu Wanfei , Li Jianyang , Xiong Siwei , Jia Jing , Lin Qiang , Liu Hailin , Cui Peng
Published: November 2024

The rapid development of sequencing technology has led to an explosion of plant genome data, opening up more opportunities for research in the field of comparative evolutionary analysis of plant genomes. In this review, we focus on changes in plant genome size and composition, examining the effects of polyploidy, whole-genome duplication, and alternations in transposable elements on plant genome architecture and evolution, respectively. In addition, to address gaps in the available information, we also collected and analyzed 234 representative plant genome data as a supplement. We aim to provide a comprehensive, up-to-date summary of information on plant genome architecture and evolution in this review.
Right ventricular outlet tract reconstruction for tetralogy of Fallot: systematic review and network meta-analysis
Authors: Yamaguchi Akira , Shimoda Tomonari , Kinami Hiroo , Yasuhara Jun , Takagi Hisato , Fukuhara Shinichi , Kuno Toshiki
Published: November 2024

OBJECTIVES

Concerns persist regarding pulmonary regurgitation after transannular patch repair (TAP) for tetralogy of Fallot. Despite the introduction of various architectural preservation techniques, the optimal strategy remains controversial. Our goal was to compare different right ventricular outlet tract reconstruction techniques.

METHODS

PubMed, EMBASE and Cochrane Central were searched through March 2024 to identify comparative studies on right ventricular outlet tract reconstruction techniques (PROSPERO ID: CRD42024519404). The primary outcome was mid-term pulmonary regurgitation, with secondary outcomes including postoperative mortality, postoperative pulmonary regurgitation, length of intensive care unit stays, postoperative right ventricular outlet tract pressure gradient and mid-term mortality. We performed a network meta-analysis to compare outcomes among TAP, valve-repairing (VR), TAP with neo-valve creation (TAPN) and valve-sparing (VS).

RESULTS

Two randomized controlled studies and 32 observational studies were identified with 8890 patients. TAP carried a higher risk of mid-term pulmonary regurgitation compared to TAPN [hazard ratio, 0.53; 95% confidence interval (CI) (0.33; 0.85)] and VS [hazard ratio, 0.27; 95% CI (0.19; 0.39)], with no significant difference compared to VR. VS was also associated with reduced postoperative mortality compared to TAP [risk ratio, 0.31; 95% CI (0.18; 0.56)], in addition to reduced ventilation time. TAP also carried an increased risk of postoperative pulmonary regurgitation compared to the other groups. The groups were comparable in terms of length of intensive care unit stay, right ventricular outlet tract pressure gradient and mid-term mortality.

CONCLUSIONS

VR was associated with a reduced risk of postoperative pulmonary regurgitation, whereas TAPN was associated with reduced risks of both postoperative and mid-term pulmonary regurgitation.
Global Well-Posedness for the Derivative Nonlinear Schrödinger Equation with Periodic Boundary Condition
Authors: Bahouri Hajer , Perelman Galina
Published: November 2024

We prove global well-posedness for the derivative nonlinear Schrödinger equation on the torus in the Sobolev space $H^{1}(\mathbb{T})$ provided that the mass of initial data is strictly less than $8\pi $.
Sheaths are diverse and abundant cell surface layers in archaea
Authors: Medvedeva Sofia , Borrel Guillaume , Gribaldo Simonetta
Published: November 2024

Prokaryotic cells employ multiple protective layers crucial for defense, structural integrity, and cellular interactions in the environment. Archaea often feature an S-layer, with some species possessing additional and remarkably resistant sheaths. The archaeal sheath has been studied in Methanothrix and Methanospirillum, revealing a complex structure consisting of amyloid proteins organized into rings. Here, we conducted a comprehensive survey of sheath-forming proteins (SH proteins) across archaeal genomes. Structural modeling reveals a rich diversity of SH proteins, indicating the presence of a sheath in members of the TACK superphylum (Thermoprotei), as well as in the methanotrophic ANME-1. SH proteins are present in up to 40 copies per genome and display diverse domain arrangements suggesting multifunctional roles within the sheath, and potential involvement in cell–cell interaction with syntrophic partners. We uncover a complex evolutionary dynamic, indicating active exchange of SH proteins in archaeal communities. We find that viruses infecting sheathed archaea encode a diversity of SH-like proteins and we use them as markers to identify 580 vOTUs potentially associated with sheathed archaea. Structural modeling suggests that viral SH proteins can form complexes with the host SH proteins. We propose a previously unreported egress strategy where the expression of viral SH-like proteins may disrupt the integrity of the host sheath and facilitate viral exit during lysis. Together, our results significantly expand knowledge of the diversity and evolution of the archaeal sheath, which has been largely understudied but might have an important role in shaping microbial communities.
Biotics and bacterial function: impact on gut and host health
Authors: Kandari Anwar , Odat Ma’en Al , Alzaid Fawaz , Scott Karen P
Published: November 2024

The human gut microbiota, the vast community of microbes inhabiting the gastrointestinal tract, plays a pivotal role in maintaining health. Bacteria are the most abundant organism, and the composition of bacterial communities is strongly influenced by diet. Gut bacteria can degrade complex dietary carbohydrates to produce bioactive compounds such as short-chain fatty acids. Such products influence health, by acting on systemic metabolism, or by virtue of anti-inflammatory or anti-carcinogenic properties. The composition of gut bacteria can be altered through overgrowth of enteropathogens (e.g. Campylobacter, Salmonella spp.), leading to dysbiosis of the gut ecosystem, with some species thriving under the altered conditions whereas others decline. Various “biotics” strategies, including prebiotics, probiotics, synbiotics, and postbiotics, contribute to re-establishing balance within the gut microbial ecosystem conferring health benefits. Prebiotics enhance growth of beneficial members of the resident microbial community and can thus prevent pathogen growth by competitive exclusion. Specific probiotics can actively inhibit the growth of pathogens, either through the production of bacteriocins or simply by reducing the gastrointestinal pH making conditions less favorable for pathogen growth. This review discusses the importance of a balanced gut ecosystem, and strategies to maintain it that contribute to human health.
Impact of a hub-and-spoke approach to hospital antimicrobial stewardship programmes on antibiotic use in Zambia
Authors: Kalungia Aubrey Chichonyi , Kampamba Martin , Banda David , Bambala Andrew Munkuli , Marshall Sarah , Newport Melanie , Clair-Jones Anja St , Alutuli Luke , Chambula Elias , Munsaka Lucky , Hamachila Audrey , Mwila Chiluba , Chanda Duncan , Chizimu Joseph , Chilengi Roma , Okorie Michael
Published: November 2024

Background

Antimicrobial stewardship programmes (ASPs) aim to optimize antibiotic use and prevent antimicrobial resistance.

Objective

This study assessed the impact of ASPs, initiated using a hub-and-spoke approach, on antibiotic use in Zambian public hospitals.

Methods

A pre–post study was conducted in 10 ASP-naive hospitals across Zambia using the Centers for Disease Control and Prevention (CDC)’s hospital-based ASP core elements (i.e. leadership, accountability, pharmacy expertise, stewardship actions, tracking progress, reporting and education) checklist and the global point prevalence survey methodology. The intervention involved technical staff from a national ‘hub’ hospital with an established ASP providing on-site orientation and mentorship to multidisciplinary teams of healthcare workers at 10 ‘spoke’ hospitals to build capacity in antimicrobial stewardship. ASP core elements and inpatient antibiotic use prevalence (AUP) were assessed before and 12 months after ASP implementation. Data were statistically analysed.

Results

The adoption of ASP core elements improved significantly (P = 0.001, 95% CI: −17.8 to −5.42). AUP decreased from 50.1% (±5.8, n = 1477) to 44.3% (±4.6, n = 1400) after 12 months, though the reduction was not statistically significant (P = 0.442; 95% CI: −9.8 to 21.6), with ‘Watch’ list antibiotics remaining the most commonly prescribed across the hospitals.

Conclusions

The hub-and-spoke approach successfully catalysed ASPs in public hospitals in Zambia, demonstrating the potential for improving antibiotic use practices over time, provided structural challenges are addressed. This approach and insights can guide stakeholders in Zambia and similar settings in enhancing hospital ASPs.
Unraveling Uncertainty: The Impact of Biological and Analytical Variation on the Prediction Uncertainty of Categorical Prediction Models
Authors: Martens Remy J H , van Doorn William P T M , Leers Mathie P G , Meex Steven J R , Helmich Floris
Published: November 2024

Background

Interest in prediction models, including machine learning (ML) models, based on laboratory data has increased tremendously. Uncertainty in laboratory measurements and predictions based on such data are inherently intertwined. This study developed a framework for assessing the impact of biological and analytical variation on the prediction uncertainty of categorical prediction models.

Methods

Practical application was demonstrated for the prediction of renal function loss (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) and 31-day mortality (advanced ML model) in 6360 emergency department patients. Model outcome was calculated in 100 000 simulations of variation in laboratory parameters. Subsequently, the percentage of discordant predictions was calculated with the original prediction as reference. Simulations were repeated assuming increasing levels of analytical variation.

Results

For the ML model, area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity were 0.90, 0.44, and 0.96, respectively. At base analytical variation, the median [2.5th–97.5th percentiles] percentage of discordant predictions was 0% [0%–28.8%]. In addition, 7.2% of patients had >5% discordant predictions. At 6× base analytical variation, the median [2.5th–97.5th percentiles] percentage of discordant predictions was 0% [0%–38.8%]. In addition, 11.7% of patients had >5% discordant predictions. However, the impact of analytical variation was limited compared with biological variation. AUROC, sensitivity, and specificity were not affected by variation in laboratory parameters.

Conclusions

The impact of biological and analytical variation on the prediction uncertainty of categorical prediction models, including ML models, can be estimated by the occurrence of discordant predictions in a simulation model. Nevertheless, discordant predictions at the individual level do not necessarily affect model performance at the population level.
Cecal metabolomics of 2 divergently selected rabbit lines revealed microbial mechanisms correlated to intramuscular fat deposition
Authors: Zubiri-Gaitán Agostina , Martínez-Álvaro Marina , Blasco Agustín , Hernández Pilar
Published: November 2024

The gastrointestinal microbiota plays a key role in the host physiology and health through a complex host–microbiota co-metabolism. Metabolites produced by microbial metabolism can travel through the bloodstream to reach distal organs and affect their function, ultimately influencing the development of relevant production traits such as meat quality. Meat quality is a complex trait made up of a number of characteristics and intramuscular fat content (IMF) is considered to be one of the most important parameters. In this study, 52 rabbits from 2 lines divergently selected for IMF (high-IMF (H) and low-IMF (L) lines) were used to perform an untargeted metabolomic analysis of their cecal content, with the aim to obtain information on genetically determined microbial metabolism related to IMF. A large, correlated response to selection was found in their cecal metabolome composition. Partial least squares discriminant analysis was used to identify the pathways differentiating the lines, which showed a classification accuracy of 99%. On the other hand, 2 linear partial least squares analyses were performed, one for each line, to extract evidence on the specific pathways associated with IMF deposition within each line, which showed predictive abilities (estimated using the Q2) of approximately 60%. The most relevant pathways differentiating the lines were those related to amino acids (aromatic, branched-chain, and gamma-glutamyl), secondary bile acids, and purines. The higher content of secondary bile acids in the L-line was related to greater lipid absorption, while the differences found in purines suggested different fermentation activities, which could be related to greater nitrogen utilization and energy efficiency in the L-line. The linear analyses showed that lipid metabolism had a greater relative importance for IMF deposition in the L-line, whereas a more complex microbial metabolism was associated with the H-line. The lysophospholipids and gamma-glutamyl amino acids were associated with IMF in both lines; the nucleotide and secondary bile acid metabolisms were mostly associated in the H-line; and the long-chain and branched-chain fatty acids were mostly associated in the L-line. A metabolic signature consisting of 2 secondary bile acids and 2 protein metabolites was found with 88% classification accuracy, pointing to the interaction between lipid absorption and protein metabolism as a relevant driver of the microbiome activity influencing IMF.
Modeling of skeletal development and diseases using human pluripotent stem cells
Authors: Hojo Hironori , Tani Shoichiro , Ohba Shinsuke
Published: November 2024

Human skeletal elements are formed from distinct origins at distinct positions of the embryo. For example, the neural crest produces the facial bones, the paraxial mesoderm produces the axial skeleton, and the lateral plate mesoderm produces the appendicular skeleton. During skeletal development, different combinations of signaling pathways are coordinated from distinct origins during the sequential developmental stages. Models for human skeletal development have been established using human pluripotent stem cells (hPSCs) and by exploiting our understanding of skeletal development. Stepwise protocols for generating skeletal cells from different origins have been designed to mimic developmental trails. Recently, organoid methods have allowed the multicellular organization of skeletal cell types to recapitulate complicated skeletal development and metabolism. Similarly, several genetic diseases of the skeleton have been modeled using patient-derived induced pluripotent stem cells and genome-editing technologies. Model-based drug screening is a powerful tool for identifying drug candidates. This review briefly summarizes our current understanding of the embryonic development of skeletal tissues and introduces the current state-of-the-art hPSC methods for recapitulating skeletal development, metabolism, and diseases. We also discuss the current limitations and future perspectives for applications of the hPSC-based modeling system in precision medicine in this research field.
Heat transfer and entropy generation analysis of ternary nanofluid
Authors: Liang Ruishi , Hanif Hanifa , Song Jie , Alzahrani S S
Published: November 2024

In light of the rising demand for improved heat transfer in thermal systems, this work offers a unique technique for boosting heat transfer capacity and reducing entropy generation using a ternary nanofluid. Moreover, constant pressure gradient, magnetic field, Joule heating, and thermal radiation also contribute to the flow dynamics. The 2D mathematical model is solved numerically using a finite difference method and the simulations are done in MATLAB. The obtained results show that ternary nanoparticles not only increase the thermal rates but are also helpful in maintaining the irreversibility of a system. It is also observed that the heat transfer of the base fluid increased by 7.5%, 8.3%, and 8.5% on adding TiO$_2$, CuO$-$TiO$_2$, and MgO$-$CuO$-$TiO$_2$ nanoparticles, respectively.
Left Atheist Activism and Crime of Genocide in Francoist Spain
Authors: Kazyrytski Leanid
Published: November 2024

This article examines whether the mass killings of people with leftist ideology by the Franco regime can be interpreted as genocide in accordance with the provisions of international law. The present study underscores the influence of religion on the configuration of Francoist criminal policy and provides evidence that allows Francoist repression to be considered as genocide. Individuals with leftist ideologies were presented not only as a political group but also as a religious group with atheist and non-Catholic beliefs. In this sense, the mass political repression conducted by the Franco regime fulfils the objective elements (actus reus) of genocide due to the fact the religious element played a significant role in justifying the annihilation of Republicans. The victims of Francoist repression were in fact selected not only because they belonged to a certain political movement or party but also because they belonged to a certain religious group.
Low-dose add-on methadone for cancer pain management: a retrospective analysis of 102 Japanese patients
Authors: Sato Tetsumi , Fukutomi Akira , Kawamura Taiichi , Kawakami Kyohei , Sato Tetsu , Kamo Yoshiko , Suzuki Tomomi , Hagiya Shota , Tanaka Rei
Published: November 2024

Background

Methadone was introduced in 2013 for the treatment of intractable cancer pain in Japan and is indicated for patients receiving opioid doses ≧60 mg/day as an oral morphine equivalent. Low-dose (≦10 mg/day) add-on methadone to prior opioids has been reported from European countries to successfully relieve various types of intractable cancer pain; however, there are few reports of such use in Japan. The aim of this study was to analyze more than a hundred cases with low-dose add-on methadone to treat intractable pain in Japanese cancer patients.

Methods

All cases in which 5 or 10 mg/day of methadone was added to prior opioids by the Palliative Care Team or Division of Palliative Medicine in our hospital during the period between April 2016 and September 2023 were extracted and analyzed retrospectively on electrical medical charts.

Results and conclusions

A total of 102 cases were extracted with a male-to-female ratio of 60:42, and the age (mean ± SD) was 62.8 ± 14.7 years old. Methadone was introduced in an inpatient setting to 86 patients. The major pathologies that caused intractable pain were spinal metastases in 48, pelvis or pelvic floor lesions in 29 and pleural and/or chest wall lesions in 16. The most common mechanism of pain was the mixture of somatic and neuropathic components. The major opioids administered prior to methadone included tapentadol in 46 patients, hydromorphone in 36 and oxycodone in 19. The dose of the prior opioids [median, (interquartile range: IQR)] was 97, (62.8–167.3) (range: 15–1313) mg/day of oral morphine equivalent. Radiotherapy, chemotherapy and nerve blocks were performed as concomitant therapies in 48, 22 and 11 patients, respectively (with some overlap). The number of rescue doses [median (IQR)] was significantly decreased from three (two to five) on the day before methadone to one (zero to four) after seven days from methadone initiation. The side effects leading to discontinuation of methadone were drowsiness in three cases, nausea in three cases and dizziness in one case (with some overlap). Compared with complete switching from other opioids, low-dose add-on methadone can reduce the possibility of major dose discrepancies and can be quickly adjusted by combined opioid reduction/increase. Low-dose add-on methadone can be an effective and safe method for intractable cancer pain.
Awareness and implementation of comprehensive genomic profiling and cancer support for adolescents and young adults among healthcare professionals in Osaka, Japan
Authors: Nishida Tsutomu , Miyamoto Miwa , Yasuda Junko , Ninomiya Yukie , Kosugi Satoru , Mizuki Masao , Eguchi Hidetoshi , Imamura Hiroshi
Published: November 2024

Background

Comprehensive genomic profiling (CGP) and specialized support for adolescent and young adult (AYA) cancer patients are crucial yet underexplored areas of healthcare in Japan. This study investigated awareness of CGP testing and support for AYA cancer patients among healthcare professionals in Osaka.

Methods

An anonymous online survey was conducted from 31 January to 31 March 2024. The survey targeted all staff, including doctors, nurses, technicians, pharmacists and others, from eight Toyono Medical Area Cancer Medical Network Council hospitals. The survey included questions on basic demographics, awareness of CGP testing and support provided to patients with AYA cancer.

Results

Among the 720 respondents, 41.9% were aware of CGP testing, while 20.3% were unaware. Regarding AYA cancer, 60.7% were aware and 14.3% were unaware. Only 7.5% had frequent contact with AYA patients and 96.8% recognized the need for education and information. Awareness of CGP was greater among doctors (72.5%) than among other professionals (34.4%); similarly, AYA cancer awareness was higher among doctors (73.9%) than among other professionals (57.7%). CGP awareness among doctors varied by years of experience and institutional type, being highest in core and cooperative hospitals (80 and 78.6%, respectively) and among doctors with more than 21 years of experience (90%).

Conclusions

This study reveals significant gaps in CGP and AYA cancer awareness among healthcare professionals in Osaka, Japan, with doctors demonstrating higher awareness levels than other professionals. There is a pressing need for targeted educational programs to enhance the understanding and implementation of CGP and support AYA cancer patients.
Some or Other: Partitive Disanaphors Across Languages
Authors: Kapitonov Ivan , Bowler Margit
Published: November 2024

We present a cross-linguistically robust pattern of polyfunctionality between indefinite, partitive, and disanaphoric (‘another’) use of a single lexical item. In examining the connection between these different uses, we argue that a uniform semantics underlies all of them. We employ the salience theory of definiteness, with the specific implementation in a dynamic semantics with choice functions, to model the full spectrum of the attested uses without invoking implicit variables. The core meaning is the partitive implication, whereas the indefinite and the discourse-familiar disanaphoric readings are underspecified in the semantics and are argued to be additional construals conditioned by discourse factors. The partitive meaning, however, is shown itself to be subject to variable pragmatic packaging across languages, from being a part of the truth conditions to a postsupposition.
Redo phalloplasty and/or urethraplasty after previous flap failure in phalloplasty in transgender men: surgical considerations and outcomes
Authors: van der Sluis Wouter B , Al-Tamimi Muhammed , Pigot Garry L S , Buncamper Marlon , Smit Jan Maerten , van de Grift Tim C , Mullender Margriet G , Bouman Mark-Bram
Published: November 2024

Background

Primary phalloplasty in transgender men can be performed using a single or double free or pedicled flap to reconstruct the shaft and, if desired, the urethra. Vascular complications may result in total or partial loss of the used flap(s). Surgical management after flap loss in primary phalloplasty presents a challenge to the reconstructive surgeon.

Aim

To describe our experience with surgical reconstructive management after primary phalloplasty flap loss in transgender men and report on the clinical and participant-reported outcomes.

Methods

All transgender men who underwent a secondary reconstructive procedure after failure of the primary procedure between January 1989 and December 2023, at our institution, were identified. A retrospective chart review was conducted, recording relevant demographic and clinical data. In addition, participants were invited to complete a non-validated questionnaire consisting of questions regarding surgical outcomes, (sexual) functionality, and sexuality.

Outcomes

Surgical outcomes, flap failure, and self-reported outcomes.

Results

Eighteen individuals were included in this study, who underwent flap reconstruction of the phalloplasty shaft (n = 7), the urethra (n = 4), or both (n = 7). Primary phalloplasty was performed with urethral lengthening (UL) in 16 (89%) and without in 2 (11%). There were no redo phalloplasty flap failures. In those with UL 13/16 (81%) were able to void while standing. Eleven individuals completed the follow-up questionnaire. Most participants were “satisfied” (45%) or “very satisfied” (27%) with the appearance of their penis. All participants (strongly) agreed that when looking back, they would undergo the surgery all over again.

Clinical implications

Practical surgical tips, deducted from our experiences, are provided for gender surgeons performing (revision) phalloplasty and urethroplasty.

Strengths and Limitations

Strengths are the unique set of surgical reconstruction cases that has taught us valuable lessons. Data from this study can be used to optimize pre-operative counseling regarding flap loss complications and the outcomes of the subsequent management. Weaknesses comprise the retrospective nature, the low number of included individuals, and use of non-validated questionnaires for self-reported outcomes.

Conclusion

Flap loss after primary phalloplasty in transgender men is a serious complication. Successful secondary reconstruction of the phalloplasty can be performed using a new pedicled or free flap.
Modified calculation of the IIEF6—a more accurate assessment of erectile function in middle-aged men
Authors: Kirchhoff Florian P , Hübner Rebekka D , Kron Martina , Schiele Stefan , Schulwitz Helga , Peter Cornelia , Meissner Valentin H , Jahnen Matthias , Gschwend Jürgen E , Herkommer Kathleen
Published: November 2024

Background

The Erectile Function Domain of the International Index of Erectile Function (IIEF6) is inaccurate in assessing erectile function in men who are not practicing sexual intercourse. Improvement through a modification was recently tested on patients after radical prostatectomy. This study examines the application of this modification in a population-based cohort of middle-aged men.

Aim

To assess the feasibility of a modified IIEF6 in a population-based random sample of 50-year old men in Germany.

Methods

4924 men were included. IIEF6, Erection Hardness Score (EHS), and causes for the absence of sexual intercourse within the previous 4 weeks were assessed. Modified calculation (double weighting of non-intercourse IIEF6 questions) was applied in case of absence due to external circumstances.

Outcomes

Impact of the modification on erectile dysfunction (ED) prevalence and agreement between IIEF6 and EHS in ED classification.

Results

As a result of the modified calculation, ED prevalence in the overall study sample decreased by 6.2% to a rate of 27.2%. Agreement between IIEF6 and EHS was increased from 2.7% to 73.4% in men with no sexual intercourse due to external circumstances.

Clinical Implications

An additional inquiry into the reason for the absence of sexual intercourse and modified calculation enhances the accuracy of IIEF6 in evaluating erectile function of the individual man.

Strengths and Limitations

This study comprises a large population-based sample. As the study population was exclusively 50-year-old men, results may not be representative of the population average.

Conclusion

A more accurate evaluation of an individual man’s erectile function may be achieved by using a modified version of the IIEF6.
Evolution of light-dependent functions of GIGANTEA
Authors: Patnaik Alena , Mishra Priyanka , Dash Anish , Panigrahy Madhusmita , Panigrahi Kishore C S
Published: November 2024

GIGANTEA (GI) is a multifaceted plant-specific protein that originated in a streptophyte ancestor. The current known functions of GI include circadian clock control, light signalling, flowering time regulation, stomata response, chloroplast biogenesis, accumulation of anthocyanin, chlorophyll, and starch, phytohormone signalling, senescence, and response to drought, salt, and oxidative stress. Six decades since its discovery, no functional domains have been defined, and its mechanism of action is still not well characterized. In this review, we explore the functional evolution of GI to distinguish between ancestral and more recently acquired roles. GI integrated itself into various existing signalling pathways of the circadian clock, blue light, photoperiod, and osmotic and oxidative stress response. It also evolved parallelly to acquire new functions for chloroplast accumulation, red light signalling, and anthocyanin production. In this review, we have encapsulated the known mechanisms of various biological functions of GI, and cast light on the evolution of GI in the plant lineage.