Fostering relational autonomy in end-of-life care: a procedural approach and three-dimensional decision-making model.

Respect for patient autonomy is paramount in resolving ethical tensions in end-of-life care. The concept of relational autonomy has contributed to this debate; however, scholars often use this concept in a fragmented manner. This leads to partial answers on ascertaining patients' true wishes, meaningfully engaging patients' significant others, balancing interests among patients and significant others, and determining clinicians' obligations to change patients' unconventional convictions to enhance patient autonomy. A satisfactory solution based on relational autonomy must incorporate patients' competence (apart from decisional capacity), authenticity (their true desires or beliefs) and the involvement level of their significant others. To that end, we argue that John Christman's procedural approach to relational autonomy provides critical insights, such as the diachronic or socio-historical personhood, sustained critical reflection and his recent explication of the nature of asymmetrical relationships and helpful interlocutors. This study reviews Christman's account, proposes minor modifications and advocates for an integrated three-dimensional model for medical decision-making. Clarifying the relationship among the three elements promotes an ethical framework with a coherent understanding of relational autonomy. This model not only provides a descriptive and normative framework for end-of-life care practice but also reconsiders the nature of the clinician-patient relationship and its normative implications. We further present a case study to illustrate the merits of our proposed model. Altogether, our proposal will help navigate complex medical decision-making, foster trust and negotiate shared values between patients and their significant others, particularly in end-of-life care.

Evaluating shared decision making for dialysis initiation: A qualitative study on patient refusal of long-term dialysis in Taiwan.

RATIONALE: Previous studies have explored shared decision making (SDM) implementation to determine the renal replacement therapy modality; however, the SDM approach for dialysis initiation, especially when patients refuse physician suggestions for long-term dialysis, remains unclear. AIMS AND OBJECTIVES: This study aimed to explore physicians' responses towards patients' refusal of long-term dialysis during the SDM process and the thinking processes of both physicians and patients regarding dialysis refusal. METHOD: We conducted in-depth semi-structured interviews with 10 patients diagnosed with end-stage renal disease, each of whom refused long-term dialysis after physicians employed the SDM framework, and nine nephrologists at the Chang Gung Memorial Hospital, Taiwan, from March to May 2020. Interviews were audio-recorded, transcribed, and translated from Mandarin to English. They were then thematically analysed. RESULTS: Three main themes on dialysis initiation SDM implementation and the differences between physician and patient perceptions on patient treatment refusal were yielded. While the SDM approach for dialysis initiation developed by nephrologists in Taiwan respects patient decisions, physicians often actively persuade patients to undergo dialysis in case of treatment refusal. The motivation behind this approach is to promote the patient's best medical interests, particularly post-dialysis life quality, and to ensure a 'rational' medical decision is made. However, patients' perceptions of treatment refusal differ significantly from those of physicians, and their decision-making process is often iterative and based on comprehensive evaluation of immediate concerns beyond biomedical factors. CONCLUSIONS: Findings suggest that the current physician-led SDM approach for dialysis initiation characterises active persuasion with physicians' perspectives predominating the clinical encounter. To improve SDM implementation, we propose that physicians should acknowledge and understand patients' reasoning for dialysis refusal and the distinction between objective health and subjective well-being during the decision-making process.

Scenario- and discussion-based approach for teaching preclinical medical students the socio-philosophical aspects of psychiatry.

BACKGROUND: This study used a scenario- and discussion-based approach to teach preclinical medical students the socio-philosophical aspects of psychiatry and qualitatively evaluated the learning outcomes in a medical humanities course in Taiwan. METHODS: The seminar session focused on three hypothetical psychiatry cases. Students discussed the cases in groups and were guided by facilitators from multiple disciplines and professions. At the end of the semester, students submitted a narrative report comprising their reflections on the cases and discussions. The authors utilized content analysis to categorize students' narratives into three facets, namely, the philosophical, social and individual. RESULTS: In total 163 preclinical medical students participated in the class; 150 of them mentioned the scenario-based lesson in their reports; 33.3% of these reports discussed the case at the philosophical dimension (n = 50), 45.3% at the social dimension (n = 68), and 26.6% at the individual dimension (n = 40). Four major themes emerged: (1) a psychiatric diagnosis has far-reaching consequences for an individual's life, (2) the social structure affects how patients experience psychiatric disorders, (3) students related personal experience or those of friends and family to understand psychiatric disorders, and (4) medical humanities are of particular importance in psychiatric education. CONCLUSIONS: This study demonstrated that the scenario-based discussions led by a multidisciplinary team of facilitators can benefit medical students with limited clinical experience to contemplate the socio-philosophical aspects of psychiatry. The authors suggest that this pedagogical model during preclinical education should be encouraged.

The Past Contribution and Future Fate of Genetic Variants under Climate Change in an Island Population of Musa itinerans.

AbstractGenetic variation within species is crucial for sessile species to adapt to novel environments when facing dramatic climate changes. However, the debate continues whether standing ancestral variation adaptive to current environmental variability is sufficient to guarantee future suitability. Using wild banana Musa itinerans, we investigated the relative contribution of standing ancestral variation versus new mutations to environmental adaptation and inferred their future fate. On the continental island of Taiwan, local populations immigrated from the Southeast Asian continent during the ice age and have been isolated since then. This allows the classification of genetic variants into standing ancestral variation (polymorphic in Taiwan and the continent) and new mutations (polymorphic only in Taiwan). For temperature-related variables where Taiwan is mainly within the ancestral climatic range, standing ancestral variation had a slightly stronger association than new mutations. New mutations were more important for precipitation-related variables, where northeastern Taiwan had much more winter rainfall than most of continental Southeast Asia. Upon future climate change, new mutations showed higher genetic offset in regions of abrupt transition between allele frequency and local environments, suggesting their greater spatial heterogeneity of future vulnerability.

Sources of Calcium at Connexin 36 Gap Junctions in the Retina.

Synaptic plasticity is a fundamental feature of the CNS that controls the magnitude of signal transmission between communicating cells. Many electrical synapses exhibit substantial plasticity that modulates the degree of coupling within groups of neurons, alters the fidelity of signal transmission, or even reconfigures functional circuits. In several known examples, such plasticity depends on calcium and is associated with neuronal activity. Calcium-driven signaling is known to promote potentiation of electrical synapses in fish Mauthner cells, mammalian retinal AII amacrine cells, and inferior olive neurons, and to promote depression in thalamic reticular neurons. To measure local calcium dynamics in situ, we developed a transgenic mouse expressing a GCaMP calcium biosensor fused to Connexin 36 (Cx36) at electrical synapses. We examined the sources of calcium for activity-dependent plasticity in retina slices using confocal or Super-Resolution Radial Fluctuations imaging. More than half of Cx36-GCaMP gap junctions responded to puffs of glutamate with transient increases in fluorescence. The responses were strongly dependent on NMDA receptors, in keeping with known activity-dependent signaling in some amacrine cells. We also found that some responses depended on the activity of voltage-gated calcium channels, representing a previously unrecognized source of calcium to control retinal electrical synaptic plasticity. The high prevalence of calcium signals at electrical synapses in response to glutamate application indicates that a large fraction of electrical synapses has the potential to be regulated by neuronal activity. This provides a means to tune circuit connectivity dynamically based on local activity.

Demographic history and distinct selection signatures of two domestication genes in mungbean.

Domestication is the long and complex process underlying the evolution of crops, in which artificial directional selection transformed wild progenitors into the desired form, affecting genomic variation and leaving traces of selection at targeted loci. However, whether genes controlling important domestication traits follow the same evolutionary pattern expected under the standard selective sweep model remains unclear. With whole-genome resequencing of mungbean (Vigna radiata), we investigated this issue by resolving its global demographic history and targeted dissection of the molecular footprints of genes underlying 2 key traits representing different stages of domestication. Mungbean originated in Asia, and the Southeast Asian wild population migrated to Australia about 50 thousand generations ago. Later in Asia, the cultivated form diverged from the wild progenitor. We identified the gene associated with the pod shattering resistance trait, VrMYB26a, with lower expression across cultivars and reduced polymorphism in the promoter region, reflecting a hard selective sweep. On the other hand, the stem determinacy trait was associated with VrDet1. We found that 2 ancient haplotypes of this gene have lower gene expression and exhibited intermediate frequencies in cultivars, consistent with selection favoring independent haplotypes in a soft selective sweep. In mungbean, contrasting signatures of selection were identified from the detailed dissection of 2 important domestication traits. The results suggest complex genetic architecture underlying the seemingly simple process of directional artificial selection and highlight the limitations of genome-scan methods relying on hard selective sweeps.

Neurobeachin controls the asymmetric subcellular distribution of electrical synapse proteins.

The subcellular positioning of synapses and their specialized molecular compositions form the fundamental basis of neural circuits. Like chemical synapses, electrical synapses are constructed from an assortment of adhesion, scaffolding, and regulatory molecules, yet little is known about how these molecules localize to specific neuronal compartments. Here, we investigate the relationship between the autism- and epilepsy-associated gene Neurobeachin, the neuronal gap junction channel-forming Connexins, and the electrical synapse scaffold ZO1. Using the zebrafish Mauthner circuit, we find Neurobeachin localizes to the electrical synapse independently of ZO1 and Connexins. By contrast, we show Neurobeachin is required postsynaptically for the robust localization of ZO1 and Connexins. We demonstrate that Neurobeachin binds ZO1 but not Connexins. Finally, we find Neurobeachin is required to restrict electrical postsynaptic proteins to dendrites, but not electrical presynaptic proteins to axons. Together, the results reveal an expanded understanding of electrical synapse molecular complexity and the hierarchical interactions required to build neuronal gap junctions. Further, these findings provide novel insight into the mechanisms by which neurons compartmentalize the localization of electrical synapse proteins and provide a cell biological mechanism for the subcellular specificity of electrical synapse formation and function.

Environment as a limiting factor of the historical global spread of mungbean.

While the domestication process has been investigated in many crops, the detailed route of cultivation range expansion and factors governing this process received relatively little attention. Here, using mungbean (Vigna radiata var. radiata) as a test case, we investigated the genomes of more than 1000 accessions to illustrate climatic adaptation's role in dictating the unique routes of cultivation range expansion. Despite the geographical proximity between South and Central Asia, genetic evidence suggests mungbean cultivation first spread from South Asia to Southeast, East and finally reached Central Asia. Combining evidence from demographic inference, climatic niche modeling, plant morphology, and records from ancient Chinese sources, we showed that the specific route was shaped by the unique combinations of climatic constraints and farmer practices across Asia, which imposed divergent selection favoring higher yield in the south but short-season and more drought-tolerant accessions in the north. Our results suggest that mungbean did not radiate from the domestication center as expected purely under human activity, but instead, the spread of mungbean cultivation is highly constrained by climatic adaptation, echoing the idea that human commensals are more difficult to spread through the south-north axis of continents.

Mungbean, also known as green gram, is an important crop plant in China, India, the Philippines and many other countries across Asia. Archaeological evidence suggests that humans first cultivated mungbeans from wild relatives in India over 4,000 years ago. However, it remains unclear how cultivation has spread to other countries and whether human activity alone dictated the route of the cultivated mungbean's expansion across Asia, or whether environmental factors, such as climate, also had an impact. To understand how a species of plant has evolved, researchers may collect specimens from the wild or from cultivated areas. Each group of plants of the same species they collect in a given location at a single point in time is known collectively as an accession. Ong et al. used a combination of genome sequencing, computational modelling and plant biology approaches to study more than 1,000 accessions of cultivated mungbean and trace the route of the crop's expansion across Asia. The data support the archaeological evidence that mungbean cultivation first spread from South Asia to Southeast Asia, then spread northwards to East Asia and afterwards to Central Asia. Computational modelling of local climates and the physical characteristics of different mungbean accessions suggest that the availability of water in the local area likely influenced the route. Specifically, accessions from arid Central Asia were better adapted to drought conditions than accessions from wetter South Asia. However, these drought adaptations decreased the yield of the plants, which may explain why the more drought tolerant accessions have not been widely grown in wetter parts of Asia. This study shows that human activity has not solely dictated where mungbean has been cultivated. Instead, both human activity and the various adaptations accessions evolved in response to their local environments shaped the route the crop took across Asia. In the future these findings may help plant breeders to identify varieties of mungbean and other crops with drought tolerance and other potentially useful traits for agriculture.

Association between Self-Stigma and Suicide Risk in Individuals with Schizophrenia: Moderating Effects of Self-Esteem and Perceived Support from Friends.

This cross-sectional study assessed the moderating effects of self-esteem and perceived support from friends on the association between self-stigma and suicide risk in individuals with schizophrenia. We included 300 participants (267 with schizophrenia and 33 with schizoaffective disorder). Suicide risk was assessed using items adopted from the suicide module of the Mini-International Neuropsychiatric Interview; self-stigma was assessed using the Self-Stigma Scale-Short; perceived support from friends was assessed using the Friend Adaptation, Partnership, Growth, Affection, and Resolve Index; and self-esteem was assessed using the Rosenberg Self-Esteem Scale. A moderation analysis was performed to examine the moderating effects of self-esteem and perceived support from friends on the association between self-stigma and suicide risk. The results indicated that self-stigma was positively associated with suicide risk after the effects of other factors were controlled for. Both perceived support from friends and self-esteem significantly reduced the magnitude of suicide risk in participants with self-stigma. Our findings highlight the value of interventions geared toward ameliorating self-stigma and enhancing self-esteem in order to reduce suicide risk in individuals with schizophrenia.

Comparing the Psychometric Properties among Three Versions of the UCLA Loneliness Scale in Individuals with Schizophrenia or Schizoaffective Disorder.

The UCLA Loneliness Scale (Version 3; UCLA-LSV3) is widely used for assessing loneliness. Nevertheless, the validity of this scale for assessing loneliness in individuals with schizophrenia or schizoaffective disorder has not been determined. Additionally, studies validating the eight-item and three-item versions of UCLA-LSV3 have not included individuals with severe mental illness; therefore, whether the short versions are comparable to the full 20-item version of UCLA-LSV3 for this population is unclear. The present study examined the unidimensional structure, internal consistency, concurrent validity, and test-retest reliability of the Chinese versions of UCLA-LSV3 (i.e., 20-item, 8-item, and 3-item versions) to determine which version is most appropriate for assessing loneliness in individuals with schizophrenia or schizoaffective disorder in Taiwan. A total of 300 participants (267 with schizophrenia and 33 with schizoaffective disorder) completed the scales, comprising UCLA-LSV3, the Center for Epidemiological Studies Depression Scale (CES-D), the suicidality module of the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiological Version (K-SADS-E), and the family and peer Adaptation, Partnership, Growth, Affection, and Resolve (APGAR) index. Construct validity was evaluated through confirmatory factor analysis. The three versions of UCLA-LSV3 were compared with the CES-D, the suicidality module of the K-SADS-E, and the family and peer APGAR index to establish concurrent validity. The results indicated that all three versions of UCLA-LSV3 exhibited acceptable to satisfactory psychometric properties in terms of unidimensional constructs, concurrent validity, and test-retest reliability. The full version of UCLA-LSV3 had the best performance, followed by the eight-item version and the three-item version. Moreover, the three versions had relatively strong associations with each other. Therefore, when deliberating which version of UCLA-LSV3 is the best choice for assessing loneliness in individuals with schizophrenia or schizoaffective disorder, healthcare providers and therapists should consider time availability and practicality.

Whole genome resequencing and complementation tests reveal candidate loci contributing to bacterial wilt (Ralstonia sp.) resistance in tomato.

Tomato (Solanum lycopersicum) is one of the most economically important vegetable crops worldwide. Bacterial wilt (BW), caused by the Ralstonia solanacearum species complex, has been reported as the second most important plant pathogenic bacteria worldwide, and likely the most destructive. Extensive research has identified two major loci, Bwr-6 and Bwr-12, that contribute to resistance to BW in tomato; however, these loci do not completely explain resistance. Segregation of resistance in two populations that were homozygous dominant or heterozygous for all Bwr-6 and Bwr-12 associated molecular markers suggested the action of one or two resistance loci in addition to these two major QTLs. We utilized whole genome sequence data analysis and pairwise comparison of six BW resistant and nine BW susceptible tomato lines to identify candidate genes that, in addition to Bwr-6 and Bwr-12, contributed to resistance. Through this approach we found 27,046 SNPs and 5975 indels specific to the six resistant lines, affecting 385 genes. One sequence variant on chromosome 3 captured by marker Bwr3.2dCAPS located in the Asc (Solyc03g114600.4.1) gene had significant association with resistance, but it did not completely explain the resistance phenotype. The SNP associated with Bwr3.2dCAPS was located within the resistance gene Asc which was inside the previously identified Bwr-3 locus. This study provides a foundation for further investigations into new loci distributed throughout the tomato genome that could contribute to BW resistance and into the role of resistance genes that may act against multiple pathogens.

De novo SNP calling reveals the genetic differentiation and morphological divergence in genus Amaranthus.

Amaranth species (Amaranthus spp.) serve as pseudo cereals and also as traditional leafy vegetables worldwide. In addition to high vigor and richness in nutrients, drought and salinity tolerance makes amaranth a promising vegetable to acclimatize to the effects of global climate change. The World Vegetable Center gene bank conserves ∼1,000 amaranth accessions, and various agronomic properties of these accessions were recorded during seed regeneration over decades. In this study, we verified the taxonomic annotation of the germplasm based on a 15K single-nucleotide polymorphism (SNP) set. Given that the yield components of grain amaranth are different from those of leaf amaranth, we observed that grain amaranth species presented larger inflorescences and earlier flowering than leaf amaranth species. Dual-purpose amaranth showed larger leaves than leaf amaranth and later flowering than grain amaranth, which seemed reasonable because farmers can harvest more leaves during the prolonged vegetable stage, which also provides recovery time to enrich grain production. Considering frequent interspecific hybridization among species of the grain amaranth complex, we performed an interspecific genome-wide association study (GWAS) for days to flowering, identifying a AGL20/SOC1 homolog. Another GWAS using only A. tricolor L. accessions revealed six candidate genes homologous to lba1, bri1, sgs1, and fca. These homologous genes were involved in the regulation of flowering time in Arabidopsis thaliana (L.) Heynh. This study revealed the usefulness of genotypic data for species demarcation in the genus Amaranthus and the potential of interspecific GWAS to detect quantitative trait loci (QTL) across different species, opening up the possibility of targeted introduction of specific genetic variants into different Amaranthus species.

Prospects and potentials of underutilized leafy Amaranths as vegetable use for health-promotion.

Climate change causes environmental variation worldwide, which is one of the most serious threats to global food security. In addition, more than 2 billion people in the world are reported to suffer from serious malnutrition, referred to as 'hidden hunger.' Dependence on only a few crops could lead to the loss of genetic diversity and high fragility of crop breeding in systems adapting to global scale climate change. The exploitation of underutilized species and genetic resources, referred to as orphan crops, could be a useful approach for resolving the issue of adaptability to environmental alteration, biodiversity preservation, and improvement of nutrient quality and quantity to ensure food security. Moreover, the use of these alternative crops will help to increase the human health benefits and the income of farmers in developing countries. In this review, we highlight the potential of orphan crops, especially amaranths, for use as vegetables and health-promoting nutritional components. This review highlights promising diversified sources of amaranth germplasms, their tolerance to abiotic stresses, and their nutritional, phytochemical, and antioxidant values for vegetable purposes. Betalains (betacyanins and betaxanthins), unique antioxidant components in amaranth vegetables, are also highlighted regarding their chemodiversity across amaranth germplasms and their stability and degradation. In addition, we discuss the physiological functions, antioxidant, antilipidemic, anticancer, and antimicrobial activities, as well as the biosynthesis pathway, molecular, biochemical, genetics, and genomic mechanisms of betalains in detail.

Ecological factors influence balancing selection on leaf chemical profiles of a wildflower.

Balancing selection is frequently invoked as a mechanism that maintains variation within and across populations. However, there are few examples of balancing selection operating on loci underpinning complex traits, which frequently display high levels of variation. We investigated mechanisms that may maintain variation in a focal polymorphism-leaf chemical profiles of a perennial wildflower (Boechera stricta, Brassicaceae)-explicitly interrogating multiple ecological and genetic processes including spatial variation in selection, antagonistic pleiotropy and frequency-dependent selection. A suite of common garden and greenhouse experiments showed that the alleles underlying variation in chemical profile have contrasting fitness effects across environments, implicating two ecological drivers of selection on chemical profile: herbivory and drought. Phenotype-environment associations and molecular genetic analyses revealed additional evidence of past selection by these drivers. Together, these data are consistent with balancing selection on chemical profile, probably caused by pleiotropic effects of secondary chemical biosynthesis genes on herbivore defence and drought response.

SIGLEC-3 (CD33) serves as an immune checkpoint receptor for HBV infection.

Chronic hepatitis B (CHB) infection is rarely eradicated by current antiviral nucleos(t)ide analogues. We found that α2,6-biantennary sialoglycans of HBV surface antigen (HBsAg) bound human SIGLEC-3 (CD33) by IP and ELISA, and the binding affinity between SIGLEC-3 and α2,6-biantennary sialoglycans was determined by biolayer interferometry (equilibrium dissociation constant [KD]: 1.95 × 10-10 ± 0.21 × 10-10 M). Moreover, HBV activated SIGLEC-3 on myeloid cells and induced immunosuppression by stimulating immunoreceptor tyrosine-based inhibitory motif phosphorylation and SHP-1/-2 recruitment via α2,6-biantennary sialoglycans on HBsAg. An antagonistic anti-SIGLEC-3 mAb reversed this effect and enhanced cytokine production in response to TLR-7 agonist GS-9620 in PBMCs from CHB patients. Moreover, anti-SIGLEC-3 mAb alone was able to upregulate the expression of molecules involved in antigen presentation, such as CD80, CD86, CD40, MHC-I, MHC-II, and PD-L1 in CD14+ cells. Furthermore, SIGLEC-3 SNP rs12459419 C, which expressed a higher amount of SIGLEC-3, was associated with increased risk of hepatocellular carcinoma (HCC) in CHB patients (HR: 1.256, 95% CI: 1.027-1.535, P = 0.0266). Thus, blockade of SIGLEC-3 is a promising strategy to reactivate host immunity to HBV and lower the incidence of HCC in the CHB patient population.

The ecological, genetic and genomic architecture of local adaptation and population differentiation in Boechera stricta.

Differential local adaptation restricts gene flow between populations inhabiting distinct environments, resulting in isolation by adaptation. In addition to the statistical inferences of genotype-environment associations, an integrative approach is needed to investigate the effect of local adaptation on population divergence at the ecological, genetic and genomic scale. Here, we combine reciprocal transplant, genome-environment association and QTL mapping to investigate local adaptation in Boechera stricta (Drummond's rockcress). With reciprocal transplant experiment, we found local genetic groups exhibit phenotypic characteristics corresponding to the distinct selection forces from different water availability. At the genetic level, the local allele of a major fitness QTL confers higher and sturdier flowering stalks, maximizing the fecundity fitness component under sufficient water supply, and its genetic variation is associated with precipitation across the landscape. At the genomewide scale, we further showed that multiple loci associated with precipitation are highly differentiated between genetic groups, suggesting that local adaptation has a widespread effect on reducing gene flow. This study provides one of the few comprehensive examples demonstrating how local adaptation facilitates population divergence at the trait, gene and genome level.

Variation in Parasitoid Virulence of Tetrastichus brontispae during the Targeting of Two Host Beetles.

In host-parasitoid interactions, antagonistic relationship drives parasitoids to vary in virulence in facing different hosts, which makes these systems excellent models for stress-induced evolutionary studies. Venom compositions varied between two strains of Tetrastichus brontispae, Tb-Bl and Tb-On. Tb-Bl targets Brontispa longissima pupae as hosts, and Tb-On is a sub-population of Tb-Bl, which has been experimentally adapted to a new host, Octodonta nipae. Aiming to examine variation in parasitoid virulence of the two strains toward two hosts, we used reciprocal injection experiments to compare effect of venom/ovarian fluids from the two strains on cytotoxicity, inhibition of immunity and fat body lysis of the two hosts. We found that Tb-Onvenom was more virulent towards plasmatocyte spreading, granulocyte function and phenoloxidase activity than Tb-Blvenom. Tb-Blovary was able to suppress encapsulation and phagocytosis in both hosts; however, Tb-Onovary inhibition targeted only B. longissima. Our data suggest that the venom undergoes rapid evolution when facing different hosts, and that the wasp has good evolutionary plasticity.

Understanding family dynamics in adult-to-adult living donor liver transplantation decision-making in Taiwan: Motivation, communication, and ambivalence.

This study investigated how multiple family members co-construct the ethical significance of living donor liver transplantation (LDLT) and how the family structure and dynamics of donor-recipient-caregiver relationships shape the communication and decision-making process within the sociocultural context of Taiwan. We conducted in-depth interviews with 36 participants from 13 families at the Chang Gung Memorial Hospital from February to December 2019. Interviews were audio recorded, transcribed, and translated from Mandarin to English and analyzed utilizing grounded theory and thematic analysis. Our findings revealed that LDLT in Taiwan is not merely a personal choice of either donor or recipient but essentially a collaborative process of family-centered medical decision-making, intertwined with socioeconomic conditions, cultural and social norms, gender roles, and the division of labor in the household. The notion of reciprocity and indebtedness for family members is a central theme underlying the entire process of motivation, deliberation, and decision-making, thereby reinforcing the naturalness of LDLT. However, our study highlighted that donors from families with traditional gender hierarchy and power imbalance may experience psychological and social vulnerabilities. Conclusively, we suggest that healthcare professionals should be sensitive to the contextual and relational factors involved in family dynamics and provide appropriate support to the ambivalent donors.

Somatic mutation distributions in cancer genomes vary with three-dimensional chromatin structure.

Somatic mutations in driver genes may ultimately lead to the development of cancer. Understanding how somatic mutations accumulate in cancer genomes and the underlying factors that generate somatic mutations is therefore crucial for developing novel therapeutic strategies. To understand the interplay between spatial genome organization and specific mutational processes, we studied 3,000 tumor-normal-pair whole-genome datasets from 42 different human cancer types. Our analyses reveal that the change in somatic mutational load in cancer genomes is co-localized with topologically-associating-domain boundaries. Domain boundaries constitute a better proxy to track mutational load change than replication timing measurements. We show that different mutational processes lead to distinct somatic mutation distributions where certain processes generate mutations in active domains, and others generate mutations in inactive domains. Overall, the interplay between three-dimensional genome organization and active mutational processes has a substantial influence on the large-scale mutation-rate variations observed in human cancers.

Enhancement of fucosylated N-glycan isomer separation with an ultrahigh column temperature in porous graphitic carbon liquid chromatography-mass spectrometry.

Due to the heterogeneous and isomeric nature of glycans, the development of an advanced separation of distinct glycan isomers is essential for glycan research and application. In this study, we utilized porous graphite carbon (PGC) chromatography for the separation of isomeric oligosaccharides without reduction or chemical derivatization at 190 °C in a custom-built heating oven. Furthermore, the fine structures of glycan isomers could be identified by using ultrahigh temperature PGC liquid chromatography mass spectrometry (UHT-PGC-LCMS). A nonreduced hydrolyzed dextran was applied to verify the performance of UHT-PGC. When the temperature of the PGC column was increased from 25 to 190 °C, the liquid chromatography separation power of the nonreduced dextran ladder significantly increased. The advantage of the UHT-PGC column was its high peak capacity with gradient elution in 10 min at 190 °C, 6700 psi, and a 250 µL/min flow rate for native glycan analysis. Four synthetic Lewis antigen isomers were used to elucidate the separation effectiveness in UHT-PGC. Moreover, mass spectrometry-based sequencing to generate specific diagnostic ions from the four synthetic Lewis antigens was used to predict isomeric glycans based on the relative intensity ratio (RIR) of diagnostic ions. The intensities of the diagnostic ions of synthetic isomers were used to identify each isomer of the fucosylated glycan. The results clearly showed that terminal Lewis A and X residues were in the 3- and 6-arms of N-glycan, respectively.