The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models.

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × âˆ¼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding motifs particularly sensitive to variants. Furthermore, combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci. It also enables models for transferring known eQTLs to difficult-to-profile tissues (e.g., from skin to heart). Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

Decoding the Genomics of Abdominal Aortic Aneurysm.

A key aspect of genomic medicine is to make individualized clinical decisions from personal genomes. We developed a machine-learning framework to integrate personal genomes and electronic health record (EHR) data and used this framework to study abdominal aortic aneurysm (AAA), a prevalent irreversible cardiovascular disease with unclear etiology. Performing whole-genome sequencing on AAA patients and controls, we demonstrated its predictive precision solely from personal genomes. By modeling personal genomes with EHRs, this framework quantitatively assessed the effectiveness of adjusting personal lifestyles given personal genome baselines, demonstrating its utility as a personal health management tool. We showed that this new framework agnostically identified genetic components involved in AAA, which were subsequently validated in human aortic tissues and in murine models. Our study presents a new framework for disease genome analysis, which can be used for both health management and understanding the biological architecture of complex diseases. VIDEO ABSTRACT.

Genetic Screens to Analyze Pattern Formation of Egg and Embryo in Drosophila: A Personal History.

In Drosophila development, the axes of the egg and future embryo are established during oogenesis. To learn about the underlying genetic and molecular pathways that lead to axis formation, I conducted a large-scale genetic screen at the beginning of my independent career. This led to the eventual understanding that both anterior-posterior and dorsal-ventral pattern information is transmitted from the oocyte to the surrounding follicle cells and in turn from the follicle cells back to the oocyte. How I came to conduct this screen and what further insights were gained by studying the mutants isolated in the screen are the topics of this autobiographical article.

Threats to personal control fuel similarity attraction.

We propose that experiencing a lack of personal control will increase people's preferences for self-similar others and that this effect would be explained by a greater need for structure. Our hypotheses received support across 11 longitudinal, experimental, and archival studies composed of data from 60 countries (5 preregistered studies, N = 90,216). In an analysis of cross-country archival data, we found that respondents who indicated a lower sense of personal control were less likely to prefer to live with neighbors who had a different religion, race, or spoke a different language (Study 1). Study 2 found that participants who perceived lower (vs. higher) personal control indicated greater liking for coworkers who they perceived to be more self-similar across a wide range of characteristics (e.g., gender, personality). Studies 3a and 3b, two live-interaction experiments conducted in the United States and China, provided additional causal evidence for control-motivated similarity attraction. A causal experimental chain (Studies 4a to 4c) and a manipulation-of-mediation-as-a-moderator study (Study 5) provided evidence for the mediating effects of the need for structure. Study 6, a longitudinal study with Chinese employees, found that workers who reported perceiving a lower (vs. higher) sense of personal control preferred more self-similar coworkers, and this effect was mediated by a greater desire for structure. Finally, exploring downstream consequences, Studies 7a and 7b found that control-motivated similarity attraction was associated with a greater preference for homogenous (vs. diverse) groups. These findings highlight how the fundamental motive for personal control shapes the structure of social life.

US state vaccine mandates did not influence COVID-19 vaccination rates but reduced uptake of COVID-19 boosters and flu vaccines compared to bans on vaccine restrictions.

During the COVID-19 pandemic, some US states mandated vaccination for certain citizens. We used state-level data from the CDC to test whether vaccine mandates predicted changes in COVID-19 vaccine uptake, as well as related voluntary behaviors involving COVID-19 boosters and seasonal influenza vaccines. Results showed that COVID-19 vaccine adoption did not significantly change in the weeks before and after states implemented vaccine mandates, suggesting that mandates did not directly impact COVID-19 vaccination. Compared to states that banned vaccine restrictions, however, states with mandates had lower levels of COVID-19 booster adoption as well as adult and child flu vaccination, especially when residents initially were less likely to vaccinate for COVID-19. This research supports the notion that governmental restrictions in the form of vaccination mandates can have unintended negative consequences, not necessarily by reducing uptake of the mandated vaccine, but by reducing adoption of other voluntary vaccines.

Brain decoding of spontaneous thought: Predictive modeling of self-relevance and valence using personal narratives.

The contents and dynamics of spontaneous thought are important factors for personality traits and mental health. However, assessing spontaneous thoughts is challenging due to their unconstrained nature, and directing participants' attention to report their thoughts may fundamentally alter them. Here, we aimed to decode two key content dimensions of spontaneous thought-self-relevance and valence-directly from brain activity. To train functional MRI-based predictive models, we used individually generated personal stories as stimuli in a story-reading task to mimic narrative-like spontaneous thoughts (n = 49). We then tested these models on multiple test datasets (total n = 199). The default mode, ventral attention, and frontoparietal networks played key roles in the predictions, with the anterior insula and midcingulate cortex contributing to self-relevance prediction and the left temporoparietal junction and dorsomedial prefrontal cortex contributing to valence prediction. Overall, this study presents brain models of internal thoughts and emotions, highlighting the potential for the brain decoding of spontaneous thought.

The Importance, Challenges, and Possible Solutions for Sharing Proteomics Data While Safeguarding Individuals' Privacy.

Proteomics data sharing has profound benefits at the individual level as well as at the community level. While data sharing has increased over the years, mostly due to journal and funding agency requirements, the reluctance of researchers with regard to data sharing is evident as many shares only the bare minimum dataset required to publish an article. In many cases, proper metadata is missing, essentially making the dataset useless. This behavior can be explained by a lack of incentives, insufficient awareness, or a lack of clarity surrounding ethical issues. Through adequate training at research institutes, researchers can realize the benefits associated with data sharing and can accelerate the norm of data sharing for the field of proteomics, as has been the standard in genomics for decades. In this article, we have put together various repository options available for proteomics data. We have also added pros and cons of those repositories to facilitate researchers in selecting the repository most suitable for their data submission. It is also important to note that a few types of proteomics data have the potential to re-identify an individual in certain scenarios. In such cases, extra caution should be taken to remove any personal identifiers before sharing on public repositories. Data sets that will be useless without personal identifiers need to be shared in a controlled access repository so that only authorized researchers can access the data and personal identifiers are kept safe.

Personal hardship narrows the partisan gap in COVID-19 and climate change responses.

The COVID-19 pandemic in the United States was characterized by a partisan gap. Democrats were more concerned about this novel health threat, more willing to socially distance, and more likely to support policies aimed at mitigating the spread of the virus than Republicans. In cross-sectional analyses of three nationally representative survey waves in 2020, we find that adverse experience with COVID-19 is associated with a narrowing of the partisan gap. The mean difference between Republicans and Democrats in concern, policy support, and behavioral intentions narrows or even disappears at high levels of self-reported adverse experience. Reported experience does not depend on party affiliation and is predicted by local COVID-19 incidence rates. In contrast, analyses of longitudinal data and county-level incidence rates do not show a consistent relationship among experience, partisanship, and behavior or policy support. Our findings suggest that self-reported personal experience interacts with partisanship in complex ways and may be an important channel for concern about novel threats such as the COVID-19 pandemic. We find consistent results for self-reported experience of extreme weather events and climate change attitudes and policy preferences, although the association between extreme weather and experience and climate change is more tenuous.

From flesh to bones: Multi-omics approaches in forensic science.

Recent advancements in omics techniques have revolutionised the study of biological systems, enabling the generation of high-throughput biomolecular data. These innovations have found diverse applications, ranging from personalised medicine to forensic sciences. While the investigation of multiple aspects of cells, tissues or entire organisms through the integration of various omics approaches (such as genomics, epigenomics, metagenomics, transcriptomics, proteomics and metabolomics) has already been established in fields like biomedicine and cancer biology, its full potential in forensic sciences remains only partially explored. In this review, we have presented a comprehensive overview of state-of-the-art analytical platforms employed in omics research, with specific emphasis on their application in the forensic field for the identification of the cadaver and the cause of death. Moreover, we have conducted a critical analysis of the computational integration of omics approaches, and highlighted the latest advancements in employing multi-omics techniques for forensic investigations.

Development of a coding SNP panel for tracking the origin of whole-exome sequencing samples.

Whole-exome sequencing (WES) is widely used to diagnose complex genetic diseases and rare conditions. The implementation of a robust and effective quality control system for sample identification and tracking throughout the WES process is essential. We established a multiplex panel that included 22 coding single-nucleotide polymorphism (cSNP) loci. The personal identification and paternity identification abilities of the panel were evaluated, and a preliminary validation of the practical feasibility of the panel was conducted in a clinical WES case. These results indicate that the cSNP panel could be a useful tool for sample tracking in WES.

Modulation of multisensory nociceptive neurons in monkey cortical area 7b and behavioral correlates.

Wide-range thermoreceptive neurons (WRT-EN) in monkey cortical area 7b that encoded innocuous and nocuous cutaneous thermal and threatening visuosensory stimulation with high fidelity were studied to identify their multisensory integrative response properties. Emphasis was given to characterizing the spatial and temporal effects of threatening visuosensory input on the thermal stimulus-response properties of these multisensory nociceptive neurons. Threatening visuosensory stimulation was most efficacious in modulating thermal evoked responses when presented as a downward ("looming"), spatially congruent, approaching and closely proximal target in relation to the somatosensory receptive field. Both temporal alignment and misalignment of spatially aligned threatening visual and thermal stimulation significantly increased mean discharge frequencies above those evoked by thermal stimulation alone, particularly at near noxious (43°C) and mildly noxious (45°C) temperatures. The enhanced multisensory discharge frequencies were equivalent to the discharge frequency evoked by overtly noxious thermal stimulation alone at 47°C (monkey pain tolerance threshold). A significant increase in behavioral mean escape frequency with shorter escape latency was evoked by multisensory stimulation at near noxious temperature (43°C), which was equivalent to that evoked by noxious stimulation alone (47°C). The remarkable concordance of elevating both neural discharge and escape frequency from a nonnociceptive and prepain level by near noxious thermal stimulation to a nociceptive and pain level by multisensory visual and near noxious thermal stimulation and integration is an elegantly designed defensive neural mechanism that in effect lowers both nociceptive response and pain thresholds to preemptively engage nocifensive behavior and, consequently, avert impending and actual injurious noxious thermal stimulation.NEW & NOTEWORTHY Multisensory nociceptive neurons in cortical area 7b are engaged in integration of threatening visuosensory and a wide range of innocuous and nocuous somatosensory (thermoreceptive) inputs. The enhancement of neuronal activity and escape behavior in monkey by multisensory integration is consistent and supportive of human psychophysical studies. The spatial features of visuosensory stimulation in peripersonal space in relation to somatic stimulation in personal space are critical to multisensory integration, nociception, nocifensive behavior, and pain.

Sustainability of personal social networks of people with Down syndrome.

Research continues to demonstrate that the characteristics of one's social network could have an impact on the development of Alzheimer's disease. Given the predisposition of people with Down syndrome to develop Alzheimer's disease, analysis of their social networks has become an emerging focus. Previous pilot research demonstrated that the personal networks of people with DS could be quantitatively analyzed, with no difference between self-report and parent-proxy report. This manuscript focuses on a 12-month follow-up period with the same original participants (24 adults with Down syndrome). Their social networks demonstrated sustainability, but not improvement, as reported by people with DS (mean network size: 8.88; mean density: 0.73; mean constraint: 0.44; mean effective size: 3.58; mean max degree: 6.04; mean degree: 4.78) and their proxies (mean network size: 7.90; mean density: 0.82; mean constraint: 53.13; mean effective size: 2.87; mean max degree: 5.19; mean degree: 4.30). Intentional and continued efforts are likely needed in order to improve the social network measures of people with Down syndrome.

Zap the clap with DNA: a novel microbicide for preventing Neisseria gonorrhoeae infection.

Each year, Neisseria gonorrhoeae (Ngo) causes over 1.5 million new infections in the United States, and >87 million worldwide. The absence of a vaccine for preventing gonorrhea, the rapid emergence of multidrug-resistant and extremely drug-resistant Ngo strains, and the limited number of antibiotics available for treating gonorrhea underscore the importance of developing new modalities for addressing Ngo infection. Here, we describe DNA-based microbicides that kill Ngo but not commensals. Previously, we showed that Ngo is killed when it takes up differentially methylated DNA with homology to its genome. We exploited this Achilles heel to develop a new class of microbicides for preventing Ngo infection. These microbicides consist of DNA molecules with specific sequences and a methylation pattern different from Ngo DNA. These DNAs kill low-passage and antibiotic-resistant clinical isolates with high efficiency but leave commensals unharmed. Equally important, the DNAs are equally effective against Ngo whether they are in buffered media or personal lubricants. These findings illustrate the potential of this new class of practical, low-cost, self-administered DNA-based microbicides for preventing Ngo transmission during sexual intercourse.

Biomineralization-Inspired Copper Sulfide Decorated Aramid Textiles via In Situ Anchoring toward Versatile Wearable Thermal Management.

Designing smart textiles for personal thermal management (PTM) is an effective strategy for thermoregulation and energy saving. However, the manufacture of versatile high-performance thermal management textiles for complex real-world environments remains a challenge due to the limitations of functional integration, material properties, and preparation procedures. In this study, an aramid fabric based on in situ anchored copper sulfide nanostructure is developed. The textile with excellent solar and Joule heating properties can effectively keep the body warm even at low energy inputs. Meanwhile, the reduced infrared emissivity of the textile decreases the thermal radiation losses and helps to maintain a constant body temperature. Impressively, the textile integrates superb electromagnetic shielding, near-complete UV protection properties, and ideal resistance to fire and bacteria. This work provides a simple strategy for fabricating multi-functional integrated wearable devices with flexibility and breathability, which is highly promising in versatile PTM applications.

A Janus Textile with Tunable Heating Modes toward Precise Personal Thermal Management in Cold Conditions.

Passive heating textiles (PHTs) have drawn increasing attention due to the advantages of energy-conservation heating. However, the heating capabilities of current PHTs are typically static and non-tunable, presenting poor adaptation to dynamic winter. Herein, a novel Janus textile with tunable heating modes is developed by constructing a customized structure with asymmetric optical properties. This Janus textile is created by coating one side of a cotton fabric with silver nanowires (AgNWs) and then applying transition metal carbides/nitrides (MXene) to the other side. The MXene side exhibits high solar absorptivity and low mid-infrared emissivity, while the AgNWs side has moderate solar absorptivity and mid-infrared emissivity. This structure ensures that the solar and radiative heating temperatures of the MXene side are 16 °C and 1.7 °C higher than those of the AgNWs side. This distinction allows for on-demand, accurate adjustments in solar and radiative heating capabilities by flipping the textile according to ambient temperature. Furthermore, this innovative design also features desired electric heating, thermal camouflage, self-cleaning and antibacterial properties, electromagnetic interference shielding, durability, and wearability. The Janus textile enables precise thermoregulation of the human body to adapt to variable cold weather, making it essential for optimal personal thermal management and climate change mitigation.

A Durable Textile With Advanced Thermal Functions and Electromagnetic Shielding.

In the face of increasingly variable cold climates and diverse individual temperature regulation demands, personal thermal management (PTM) textiles with electromagnetic shielding have obtained significant attention. However, the PTM textiles face several challenges, including single heating mode, insufficient durability, and complex preparation processes. Herein, an all-day PTM textile Cotton@PDA/AgNPs (CPANS) with energy-free PRH, energy-saving solar heating, compensatory electrical heating, electromagnetic interference (EMI) shielding, and outstanding durability is fabricated by sequentially growing polydopamine (PDA) and silver nanoparticles (AgNPs) on the cotton fabric (CF). The CPANS exhibits low mid-infrared emissivity (36.6%) and high absorptivity (70.8%), which guarantees the energy-saving heating capability. Moreover, the conductivity of the CPANS is ≈11109 S m-1, enabling an electrical heating temperature of ≈177 °C under a low voltage of 1.1 V and superb EMI shielding effectiveness (≈60 dB). The remarkable adhesive properties of the PDA ensure that the desired durability of the CPANS remains high even after rigorous physical treatments. This innovation shows enormous potential for wearable integrated garments in the future and offers a new ideal for PTM fabrics in the cold.

A High-Performance Passive Radiative Cooling Metafabric with Janus Wettability and Thermal Conduction.

With the development of industry and global warming, passive radiative cooling textiles have recently drawn great interest owing to saving energy consumption and preventing heat-related illnesses. Nevertheless, existing cooling textiles often lack efficient sweat management capacity and wearable comfort under many practical conditions. Herein, a hierarchical cooling metafabric that integrates passive radiation, thermal conduction, sweat evaporation, and excellent wearable comfort is reported through an electrospinning strategy. The metafabric presents excellent solar reflectivity (99.7%, 0.3-2.5 µm) and selective infrared radiation (92.4%, 8-13 µm), given that the unique optical nature of materials and wettability gradient/micro-nano hierarchical structure design. The strong moisture-wicking effect (water vapor transmission (WVT) of 2985 g m-2 d-1 and directional water transport index (R) of 1029.8%) and high heat-conduction capacity can synergistically enhance the radiative cooling efficiency of the metafabric. The outdoor experiment reveals that the metafabric can obtain cooling temperatures of 13.8 °C and 19.3 °C in the dry and sweating state, respectively. Meanwhile, the metafabric saves ≈19.3% of annual energy consumption compared with the buildings with HAVC systems in Shanghai. The metafabric also demonstrates desirable breathability, mechanical strength, and washability. The cost-effective and high-performance metafabric may offer a novel avenue for developing next-generation personal cooling textiles.

Multifunctional Sandwich-Structured Super-Hygroscopic Zinc-Based MOF-Overlayed Cooling Wearables for Special Personal Thermal Management.

Personal protective equipment pays attention exclusively to external safety protection and ignores the internal thermoregulation of physiological state in association with sweating. Herein, a super-hygroscopic calcium-doped poly(sodium 4-styrenesulfonate) and superhydrophobic metal-organic-framework-overlayed wearables (Ca-PSS/MOF) integrated cooling wearable is proposed for special personal thermal management (PTM). Compared to the pristine fabric, the superhydrophobic MOF wearables exhibit anti-fouling and antibacterial capabilities, and the antibacterial efficiency is up to 99.99% and 98.99% against E. coli and S. aureus, respectively. More importantly, Ca-PSS/MOF demonstrate significant heat index changes up to 25.5 °C by reducing relative humidity dramatically from 91.0% to 60.0% and temperature from 36.5 to 31.6 °C during the running test. The practical feasibility of the Ca-PSS/MOF cooling wearables is well proved with the protective suit of the fireman. Owing to these multifunctional merits, the sandwich-structured cooling Ca-PSS/MOF are expected to provide new insights for designing the next-generation multifunctional apparel for PTM.

An Innovative Azobenzene-Based Photothermal Fabric with Excellent Heat Release Performance for Wearable Thermal Management Device.

Azobenzene (azo)-based photothermal energy storage systems have garnered great interest for their potential in solar energy conversion and storage but suffer from limitations including rely on solvents and specific wavelengths for charging process, short storage lifetime, low heat release temperature during discharging, strong rigidity and poor wearability. To address these issues, an azo-based fabric composed of tetra-ortho-fluorinated photo-liquefiable azobenzene monomer and polyacrylonitrile fabric template is fabricated using electrospinning. This fabric excels in efficient photo-charging (green light) and discharging (blue light) under visible light range, solvent-free operation, long-term energy storage (706 days), and good capacity of releasing high-temperature heat (80-95 °C) at room temperature and cold environments. In addition, the fabric maintains high flexibility without evident loss of energy-storage performance upon 1500 bending cycles, 18-h washing or 6-h soaking. The generated heat from charged fabric is facilitated by the Z-to-E isomerization energy, phase transition latent heat, and the photothermal effect of 420 nm light irradiation. Meanwhile, the temperature of heat release can be personalized for thermal management by adjusting the light intensity. It is applicable for room-temperature thermal therapy and can provide heat to the body in cold environments, that presenting a promising candidate for wearable personal thermal management.

Attitudes, knowledge, and risk perceptions of patients who received elective genomic testing as a clinical service.

PURPOSE: Elective genomic testing (EGT) is increasingly available clinically. Limited real-world evidence exists about attitudes and knowledge of EGT recipients. METHODS: After web-based education, patients who enrolled in an EGT program at a rural nonprofit health care system completed a survey that assessed attitudes, knowledge, and risk perceptions. RESULTS: From August 2020 to April 2022, 5920 patients completed the survey and received testing. Patients most frequently cited interest in learning their personal disease risks as their primary motivation. Patients most often expected results to guide medication management (74.0%), prevent future disease (70.4%), and provide information about risks to offspring (65.4%). Patients were "very concerned" most frequently about the privacy of genetic information (19.8%) and how well testing predicted disease risks (18.0%). On average, patients answered 6.7 of 11 knowledge items correctly (61.3%). They more often rated their risks for colon and breast cancers as lower rather than higher than the average person but more often rated their risk for a heart attack as higher rather than lower than the average person (all P < .001). CONCLUSION: Patients pursued EGT because of the utility expectations but often misunderstood the test's capabilities.