bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-traumatic stress disorder among LGBTQ people: a systematic review and meta-analysis
Authors: Marchi Mattia , Travascio Antonio , Uberti Daniele , De Micheli Edoardo , Grenzi Pietro , Arcolin Elisa , Pingani Luca , Ferrari Silvia , Galeazzi Gian M.
Published: July 2023

Aims

Lesbian, gay, bisexual, transgender and queer people (LGBTQ) are at increased risk of traumatization. This systematic review aimed to summarize data regarding the risk of post-traumatic stress disorder (PTSD) for LGBTQ people and their subgroups.

Methods

Medline, Scopus, PsycINFO and EMBASE were searched until September 2022. Studies reporting a comparative estimation of PTSD among LGBTQ population and the general population (i.e., heterosexual/cisgender), without restrictions on participants’ age and setting for the enrolment, were identified. Meta-analyses were based on odds ratio (OR and 95% confidence intervals [CI]), estimated through inverse variance models with random effects.

Results

The review process led to the selection of 27 studies, involving a total of 31,903 LGBTQ people and 273,842 controls, which were included in the quantitative synthesis. Overall, LGBTQ people showed an increased risk of PTSD (OR: 2.20 [95% CI: 1.85; 2.60]), although there was evidence of marked heterogeneity in the estimate (I2 = 91%). Among LGBTQ subgroups, transgender people showed the highest risk of PTSD (OR: 2.52 [95% CI: 2.22; 2.87]) followed by bisexual people (OR: 2.44 [95% CI: 1.05; 5.66]), although these comparisons are limited by the lack of data for other sexual and gender minorities, such as intersex people. Interestingly, the risk of PTSD for bisexual people was confirmed also considering lesbian and gay as control group (OR: 1.44 [95% CI: 1.07; 1.93]). The quality of the evidence was low.

Conclusions

LGBTQ people are at higher risk of PTSD compared with their cisgender/heterosexual peers. This evidence may contribute to the public awareness on LGBTQ mental health needs and suggest supportive strategies as well as preventive interventions (e.g., supportive programs, counselling, and destigmatizing efforts) as parts of a tailored health-care planning aimed to reduce psychiatric morbidity in this at-risk population.
A Path to Research in Space Physics
Authors: McPherron R. L.
Published: July 2023

Success in research depends on multiple factors, many outside the control of an individual. I was born during the Great Depression, began school during World War II, and was 12 years old before I lived in a house with running water, electricity, or a telephone. In the second or third grade, I decided to be a scientist, and all my activities after that contributed to this goal. In this paper, I summarize a few early events and focus on my activities in the Ph.D. Physics program at Berkeley, and my first few years after graduation. Being well‐prepared, hardworking, self‐sufficient, and blessed by fortunate circumstances is important. However, good fortune is insufficient if you are not proactive. Once success seems to be within grasp, it is important to consistently promote your ideas and communicate them in lectures and publications. Space Physics research exploded the year I started my research providing abundant opportunities for discoveries. There were few competitors, and significant resources were available. I was fortunate to be educated at one of the first space research centers and find a permanent position at another. Circumstances have changed in the 60 years since I began research. The opportunities for quick discoveries and rapid recognition have moved away from my field of magnetospheric physics. New instruments, new methods of analysis, large amounts of data, and advanced modeling tools are needed to make incremental advances.
Simulation of a Dust‐And‐Rain Event Across the Red Sea Using WRF‐Chem
Authors: Parajuli Sagar P. , Stenchikov Georgiy L. , Ukhov Alexander , Morrison Hugh , Shevchenko Illia , Mostamandi Suleiman
Published: July 2023

We present simulations of a series of dust‐and‐rain events in July/August 2020 that caused significant loss of life and property over northeast Africa and the Red Sea coast using convection‐permitting Weather Research and Forecasting‐Chem simulations at 1.5 km horizontal grid spacing coupled with prognostic dust and aerosol scheme together with a double‐moment cloud microphysical scheme. The model generally captures the optical properties and vertical profiles of dust but has difficulty reproducing the seasonal dust plumes that originate over northeast Africa and reach the western Arabian Peninsula through the Tokar gap. Overlapping of synoptic events with local, diurnal‐scale, convective features caused continuous rainfall over the study domain in July/August 2020. The model well simulates the synoptically‐driven clouds over the ocean (∼4–8 km) and daytime deep convective clouds over the land but cannot reproduce cumulus clouds over the ocean advected from land, which leads to some biases in simulating peak rainfall rates. Although our simulations do not explicitly consider aerosol particles as ice nuclei, the model reproduces the cirrus clouds found at ∼10–15 km height during the study period. Simulations with a planetary boundary layer (PBL) scheme better represented the diurnal profile of surface temperature and winds, as well as the rainfall distribution, than without using a PBL scheme. Dust generally enhanced rainfall during the synoptic rain event through indirect effects but suppressed rainfall during sea‐breeze‐induced convective events through dust direct effects by weakening the sea‐breeze circulation.
Impact of Forbush Decreases and Geomagnetic Storms on the Atmospheric Ozone Profiles
Authors: Kilifarska Natalya , Peqini Klaudio
Published: July 2023

The sensitivity of atmospheric ozone to geomagnetic storms and reduced cosmic rays' (CRs) intensity (called Forbush decrease [FD]) has been noticed for many years. However, it is still unclear what the factors affecting ozone density are—whether these are the complex changes induced by geomagnetic storms in the upper atmosphere and ionosphere, or it is the severe reduction of CRs accessing Earth's lower atmosphere. Analyzing two strong geomagnetic storms, accompanied by FDs, and another FD occurred in geomagnetically quiet conditions, we conclude that observed ozone changes support the idea about the existence of an additional source of ozone in the lower stratosphere. The ion‐molecular reactions of catalytic ozone production are initiated by secondary ionization, produced by cosmic radiation at these levels. This conclusion is supported by the fact that the strongest ozone depletion beneath its maximum is found in regions with the severest reduction of CR flux. Moreover, the time delay of ozone response (∼2 days), is short enough to be attributed to changes in circulation. In addition, we have examined the changes in the sea level pressure during the analyzed events and found out that the surface pressure follows dynamically the spatial pattern of the ozone changes, forced by the reduced amount of precipitating energetic particles in the atmosphere.
Deep learning identifies a T-cell exhaustion-dependent transcriptional signature for predicting clinical outcomes and response to immune checkpoint blockade
Authors: Zhang Zicheng , Chen Hongyan , Yan Dongxue , Chen Lu , Sun Jie , Zhou Meng
Published: July 2023

Immune checkpoint blockade (ICB) therapies have brought unprecedented advances in cancer treatment, but responses are limited to a fraction of patients. Therefore, sustained and substantial efforts are required to advance clinical and translational investigation on managing patients receiving ICB. In this study, we investigated the dynamic changes in molecular profiles of T-cell exhaustion (TEX) during ICB treatment using single-cell and bulk transcriptome analysis, and demonstrated distinct exhaustion molecular profiles associated with ICB response. By applying an ensemble deep-learning computational framework, we identified an ICB-associated transcriptional signature consisting of 16 TEX-related genes, termed ITGs. Incorporating 16 ITGs into a machine-learning model called MLTIP achieved reliable predictive power for clinical ICB response with an average AUC of 0.778, and overall survival (pooled HR = 0.093, 95% CI, 0.031–0.28, P < 0.001) across multiple ICB-treated cohorts. Furthermore, the MLTIP consistently demonstrated superior predictive performance compared to other well-established markers and signatures, with an average increase in AUC of 21.5%. In summary, our results highlight the potential of this TEX-dependent transcriptional signature as a tool for precise patient stratification and personalized immunotherapy, with clinical translation in precision medicine.
BMI and well-being in people of East Asian and European ancestry: a Mendelian randomisation study
Authors: O’Loughlin Jessica , Casanova Francesco , Hughes Amanda , Fairhurst-Hunter Zammy , Li Liming , Chen Zhengming ,   China Kadoorie Biobank Collaborative Group, Bowden Jack , Watkins Ed , Freathy Rachel M. , Howe Laura D. , Walters Robin G. , Tyrrell Jessica
Published: July 2023

Previous studies have linked higher body mass index (BMI) to lower subjective well-being in adult European ancestry populations. However, our understanding of these relationships across different populations is limited. Here, we investigated the association between BMI and well-being in people of (a) East Asian and (b) European ancestry in the China Kadoorie Biobank (CKB) and UK Biobank (UKB), respectively. Mendelian randomisation (MR) methods were used to test the relationship between BMI with (a) health satisfaction and (b) life satisfaction. One-sample MR enabled us to test effects in men and women separately and to test the role of cultural contexts by stratifying our analyses by urban and rural home location in both China and the UK. Further, we implemented a control function method to test the linearity of the BMI-well-being relationship. We found evidence of different associations between BMI and well-being in individuals of East Asian versus European ancestry. For example, a genetically instrumented higher BMI tentatively associated with higher health satisfaction in people of East Asian ancestry, especially in females (ß: 0.041, 95% CI: 0.002, 0.081). In contrast, there was a robust inverse association between higher genetically instrumented BMI and health satisfaction in all European ancestry UKB participants (ß: −0.183, 95% CI: −0.200, −0.165, Pdifference < 1.00E−15). We also showed the importance of considering non-linear relationships in the MR framework by providing evidence of non-linear relationships between BMI and health and life satisfaction. Overall, our study suggests potential setting-specific causality in the relationship between BMI and subjective well-being, with robust differences observed between East Asians and Europeans when considering very similar outcomes. We highlight the importance of (a) considering potential non-linear relationships in causal analyses and (b) testing causal relationships in different populations, as the casual nature of relationships, especially relationships influenced by social processes, may be setting-specific.
Anticoagulant therapy and home blood pressure-associated risk for stroke/bleeding events in elderly patients with non-valvular atrial fibrillation: the sub-cohort study of ANAFIE registry
Authors: Kario Kazuomi , Hasebe Naoyuki , Okumura Ken , Yamashita Takeshi , Akao Masaharu , Atarashi Hirotsugu , Ikeda Takanori , Koretsune Yukihiro , Shimizu Wataru , Suzuki Shinya , Tsutsui Hiroyuki , Toyoda Kazunori , Hirayama Atsushi , Yasaka Masahiro , Yamaguchi Takenori , Teramukai Satoshi , Kimura Tetsuya , Morishima Yoshiyuki , Takita Atsushi , Inoue Hiroshi
Published: July 2023

The benefits of direct oral anticoagulants (DOACs) and warfarin in elderly Japanese patients with non-valvular atrial fibrillation (NVAF) and high home systolic blood pressure (H-SBP) are unclear. This sub-cohort study of the ANAFIE Registry estimated the incidence of clinical outcomes in patients receiving anticoagulant therapy (warfarin and DOACs) stratified by H-SBP levels (<125 mmHg, ≥125–<135 mmHg, ≥135–<145 mmHg and ≥145 mmHg). Of the overall ANAFIE population, 4933 patients who underwent home blood pressure (H-BP) measurements were analyzed; 93% received OACs (DOACs: 3494, 70.8%; warfarin: 1092, 22.1%). In the warfarin group, at <125 mmHg and ≥145 mmHg, the respective incidence rates (per 100 person-years) were 1.91 and 5.89 for net cardiovascular outcome (a composite of stroke/systemic embolic events (SEE) and major bleeding), 1.31 and 3.39 for stroke/SEE, 0.59 and 3.91 for major bleeding, 0.59 and 3.43 for intracranial hemorrhage (ICH), and 4.01 and 6.24 for all-cause death. Corresponding incidence rates in the DOACs group were 1.64 and 2.65, 1.00 and 1.88, 0.78 and 1.69, 0.55 and 1.31, and 3.43 and 3.51. In warfarin-treated patients, the incidence rates of net cardiovascular outcome, stroke/SEE, major bleeding, and ICH were significantly increased at H-SBP ≥ 145 mmHg versus <125 mmHg. In the DOAC group, although there was no significant difference between H-SBP < 125 mmHg and ≥145 mmHg, the incidence rates of these events tended to increase at ≥145 mmHg. These results suggest that strict BP control guided by H-BP is required in elderly NVAF patients receiving anticoagulant therapy.
The role of vaccination and public awareness in forecasts of Mpox incidence in the United Kingdom
Authors: Brand Samuel P. C. , Cavallaro Massimo , Cumming Fergus , Turner Charlie , Florence Isaac , Blomquist Paula , Hilton Joe , Guzman-Rincon Laura M. , House Thomas , Nokes D. James , Keeling Matt J.
Published: July 2023

Beginning in May 2022, Mpox virus spread rapidly in high-income countries through close human-to-human contact primarily amongst communities of gay, bisexual and men who have sex with men (GBMSM). Behavioural change arising from increased knowledge and health warnings may have reduced the rate of transmission and modified Vaccinia-based vaccination is likely to be an effective longer-term intervention. We investigate the UK epidemic presenting 26-week projections using a stochastic discrete-population transmission model which includes GBMSM status, rate of formation of new sexual partnerships, and clique partitioning of the population. The Mpox cases peaked in mid-July; our analysis is that the decline was due to decreased transmission rate per infected individual and infection-induced immunity among GBMSM, especially those with the highest rate of new partners. Vaccination did not cause Mpox incidence to turn over, however, we predict that a rebound in cases due to behaviour reversion was prevented by high-risk group-targeted vaccination.
Immunoproteasome-specific subunit PSMB9 induction is required to regulate cellular proteostasis upon mitochondrial dysfunction
Authors: Kim Minji , Serwa Remigiusz A. , Samluk Lukasz , Suppanz Ida , Kodroń Agata , Stępkowski Tomasz M. , Elancheliyan Praveenraj , Tsegaye Biniyam , Oeljeklaus Silke , Wasilewski Michal , Warscheid Bettina , Chacinska Agnieszka
Published: July 2023

Perturbed cellular protein homeostasis (proteostasis) and mitochondrial dysfunction play an important role in neurodegenerative diseases, however, the interplay between these two phenomena remains unclear. Mitochondrial dysfunction leads to a delay in mitochondrial protein import, causing accumulation of non-imported mitochondrial proteins in the cytosol and challenging proteostasis. Cells respond by increasing proteasome activity and molecular chaperones in yeast andC. elegans. Here, we demonstrate that in human cells mitochondrial dysfunction leads to the upregulation of a chaperone HSPB1 and, interestingly, an immunoproteasome-specific subunit PSMB9. Moreover, PSMB9 expression is dependent on the translation elongation factor EEF1A2. These mechanisms constitute a defense response to preserve cellular proteostasis under mitochondrial stress. Our findings define a mode of proteasomal activation through the change in proteasome composition driven by EEF1A2 and its spatial regulation, and are useful to formulate therapies to prevent neurodegenerative diseases.
Active self-assembly of piezoelectric biomolecular films via synergistic nanoconfinement and in-situ poling
Authors: Zhang Zhuomin , Li Xuemu , Peng Zehua , Yan Xiaodong , Liu Shiyuan , Hong Ying , Shan Yao , Xu Xiaote , Jin Lihan , Liu Bingren , Zhang Xinyu , Chai Yu , Zhang Shujun , Jen Alex K.-Y. , Yang Zhengbao
Published: July 2023

Piezoelectric biomaterials have attracted great attention owing to the recent recognition of the impact of piezoelectricity on biological systems and their potential applications in implantable sensors, actuators, and energy harvesters. However, their practical use is hindered by the weak piezoelectric effect caused by the random polarization of biomaterials and the challenges of large-scale alignment of domains. Here, we present an active self-assembly strategy to tailor piezoelectric biomaterial thin films. The nanoconfinement-induced homogeneous nucleation overcomes the interfacial dependency and allows the electric field applied in-situ to align crystal grains across the entire film. The β-glycine films exhibit an enhanced piezoelectric strain coefficient of 11.2 pm V−1 and an exceptional piezoelectric voltage coefficient of 252 × 10−3 Vm N−1. Of particular significance is that the nanoconfinement effect greatly improves the thermostability before melting (192 °C). This finding offers a generally applicable strategy for constructing high-performance large-sized piezoelectric bio-organic materials for biological and medical microdevices.
Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy
Authors: Liu Xiaoyu , Zhuang Yaping , Huang Wei , Wu Zhuozhuo , Chen Yingjie , Shan Qungang , Zhang Yuefang , Wu Zhiyuan , Ding Xiaoyi , Qiu Zilong , Cui Wenguo , Wang Zhongmin
Published: July 2023

The response rate of pancreatic cancer to chemotherapy or immunotherapy pancreatic cancer is low. Although minimally invasive irreversible electroporation (IRE) ablation is a promising option for irresectable pancreatic cancers, the immunosuppressive tumour microenvironment that characterizes this tumour type enables tumour recurrence. Thus, strengthening endogenous adaptive antitumour immunity is critical for improving the outcome of ablation therapy and post-ablation immune therapy. Here we present a hydrogel microsphere vaccine that amplifies post-ablation anti-cancer immune response via releasing its cargo of FLT3L and CD40L at the relatively lower pH of the tumour bed. The vaccine facilitates migration of the tumour-resident type 1 conventional dendritic cells (cDC1) to the tumour-draining lymph nodes (TdLN), thus initiating the cDC1-mediated antigen cross-presentation cascade, resulting in enhanced endogenous CD8+ T cell response. We show in an orthotopic pancreatic cancer model in male mice that the hydrogel microsphere vaccine transforms the immunologically cold tumour microenvironment into hot in a safe and efficient manner, thus significantly increasing survival and inhibiting the growth of distant metastases.
An RNA modification enzyme directly senses reactive oxygen species for translational regulation in Enterococcus faecalis
Authors: Lee Wei Lin , Sinha Ameya , Lam Ling Ning , Loo Hooi Linn , Liang Jiaqi , Ho Peiying , Cui Liang , Chan Cheryl Siew Choo , Begley Thomas , Kline Kimberly Ann , Dedon Peter
Published: July 2023

Bacteria possess elaborate systems to manage reactive oxygen and nitrogen species (ROS) arising from exposure to the mammalian immune system and environmental stresses. Here we report the discovery of an ROS-sensing RNA-modifying enzyme that regulates translation of stress-response proteins in the gut commensal and opportunistic pathogen Enterococcus faecalis. We analyze the tRNA epitranscriptome of E. faecalis in response to reactive oxygen species (ROS) or sublethal doses of ROS-inducing antibiotics and identify large decreases in N2-methyladenosine (m2A) in both 23 S ribosomal RNA and transfer RNA. This we determine to be due to ROS-mediated inactivation of the Fe-S cluster-containing methyltransferase, RlmN. Genetic knockout of RlmN gives rise to a proteome that mimics the oxidative stress response, with an increase in levels of superoxide dismutase and decrease in virulence proteins. While tRNA modifications were established to be dynamic for fine-tuning translation, here we report the discovery of a dynamically regulated, environmentally responsive rRNA modification. These studies lead to a model in which RlmN serves as a redox-sensitive molecular switch, directly relaying oxidative stress to modulating translation through the rRNA and the tRNA epitranscriptome, adding a different paradigm in which RNA modifications can directly regulate the proteome.
Structural basis of CXC chemokine receptor 1 ligand binding and activation
Authors: Ishimoto Naito , Park Jae-Hyun , Kawakami Kouki , Tajiri Michiko , Mizutani Kenji , Akashi Satoko , Tame Jeremy R. H. , Inoue Asuka , Park Sam-Yong
Published: July 2023

Neutrophil granulocytes play key roles in innate immunity and shaping adaptive immune responses. They are attracted by chemokines to sites of infection and tissue damage, where they kill and phagocytose bacteria. The chemokine CXCL8 (also known as interleukin-8, abbreviated IL-8) and its G-protein-coupled receptors CXCR1 and CXCR2 are crucial elements in this process, and also the development of many cancers. These GPCRs have therefore been the target of many drug development campaigns and structural studies. Here, we solve the structure of CXCR1 complexed with CXCL8 and cognate G-proteins using cryo-EM, showing the detailed interactions between the receptor, the chemokine and Gαi protein. Unlike the closely related CXCR2, CXCR1 strongly prefers to bind CXCL8 in its monomeric form. The model shows that steric clashes would form between dimeric CXCL8 and extracellular loop 2 (ECL2) of CXCR1. Consistently, transplanting ECL2 of CXCR2 onto CXCR1 abolishes the selectivity for the monomeric chemokine. Our model and functional analysis of various CXCR1 mutants will assist efforts in structure-based drug design targeting specific CXC chemokine receptor subtypes.
Carbene-stabilized enantiopure heterometallic clusters featuring EQE of 20.8% in circularly-polarized OLED
Authors: Ma Xiao-Hong , Li Jing , Luo Peng , Hu Jia-Hua , Han Zhen , Dong Xi-Yan , Xie Guohua , Zang Shuang-Quan
Published: July 2023

Bright and efficient chiral coinage metal clusters show promise for use in emerging circularly polarized light-emitting materials and diodes. To date, highly efficient circularly polarized organic light-emitting diodes (CP-OLEDs) with enantiopure metal clusters have not been reported. Herein, through rational design of a multidentate chiral N-heterocyclic carbene (NHC) ligand and a modular building strategy, we synthesize a series of enantiopure Au(I)-Cu(I) clusters with exceptional stability. Modulation of the ligands stabilize the chiral excited states of clusters to allow thermally activated delayed fluorescence, resulting in the highest orange-red photoluminescence quantum yields over 93.0% in the solid state, which is accompanied by circularly polarized luminescence. Based on the solution process, a prototypical orange-red CP-OLED with a considerably high external quantum efficiency of 20.8% is prepared. These results demonstrate the extensive designability of chiral NHC ligands to stabilize polymetallic clusters for high performance in chiroptical applications.
Increased precipitation over land due to climate feedback of large-scale bioenergy cultivation
Authors: Li Zhao , Ciais Philippe , Wright Jonathon S. , Wang Yong , Liu Shu , Wang Jingmeng , Li Laurent Z. X. , Lu Hui , Huang Xiaomeng , Zhu Lei , Goll Daniel S. , Li Wei
Published: July 2023

Bioenergy with carbon capture and storage (BECCS) is considered to be a key technology for removing carbon dioxide from the atmosphere. However, large-scale bioenergy crop cultivation results in land cover changes and activates biophysical effects on climate, with earth’s water recycling altered and energy budget re-adjusted. Here, we use a coupled atmosphere-land model with explicit representations of high-transpiration woody (i.e., eucalypt) and low-transpiration herbaceous (i.e., switchgrass) bioenergy crops to investigate the range of impact of large-scale rainfed bioenergy crop cultivation on the global water cycle and atmospheric water recycling. We find that global land precipitation increases under BECCS scenarios, due to enhanced evapotranspiration and inland moisture advection. Despite enhanced evapotranspiration, soil moisture decreases only slightly, due to increased precipitation and reduced runoff. Our results indicate that, at the global scale, the water consumption by bioenergy crop growth would be partially compensated by atmospheric feedbacks. Thus, to support more effective climate mitigation policies, a more comprehensive assessment, including the biophysical effects of bioenergy cultivation, is highly recommended.
High throughput single cell long-read sequencing analyses of same-cell genotypes and phenotypes in human tumors
Authors: Shiau Cheng-Kai , Lu Lina , Kieser Rachel , Fukumura Kazutaka , Pan Timothy , Lin Hsiao-Yun , Yang Jie , Tong Eric L. , Lee GaHyun , Yan Yuanqing , Huse Jason T. , Gao Ruli
Published: July 2023

Single-cell nanopore sequencing of full-length mRNAs transforms single-cell multi-omics studies. However, challenges include high sequencing errors and dependence on short-reads and/or barcode whitelists. To address these, we develop scNanoGPS to calculate same-cell genotypes (mutations) and phenotypes (gene/isoform expressions) without short-read nor whitelist guidance. We apply scNanoGPS onto 23,587 long-read transcriptomes from 4 tumors and 2 cell-lines. Standalone, scNanoGPS deconvolutes error-prone long-reads into single-cells and single-molecules, and simultaneously accesses both phenotypes and genotypes of individual cells. Our analyses reveal that tumor and stroma/immune cells express distinct combination of isoforms (DCIs). In a kidney tumor, we identify 924 DCI genes involved in cell-type-specific functions such as PDE10A in tumor cells and CCL3 in lymphocytes. Transcriptome-wide mutation analyses identify many cell-type-specific mutations including VEGFA mutations in tumor cells and HLA-A mutations in immune cells, highlighting the critical roles of different mutant populations in tumors. Together, scNanoGPS facilitates applications of single-cell long-read sequencing technologies.
Temperature-pressure phase diagram of confined monolayer water/ice at first-principles accuracy with a machine-learning force field
Authors: Lin Bo , Jiang Jian , Zeng Xiao Cheng , Li Lei
Published: July 2023

Understanding the phase behaviour of nanoconfined water films is of fundamental importance in broad fields of science and engineering. However, the phase behaviour of the thinnest water film – monolayer water – is still incompletely known. Here, we developed a machine-learning force field (MLFF) at first-principles accuracy to determine the phase diagram of monolayer water/ice in nanoconfinement with hydrophobic walls. We observed the spontaneous formation of two previously unreported high-density ices, namely, zigzag quasi-bilayer ice (ZZ-qBI) and branched-zigzag quasi-bilayer ice (bZZ-qBI). Unlike conventional bilayer ices, few inter-layer hydrogen bonds were observed in both quasi-bilayer ices. Notably, the bZZ-qBI entails a unique hydrogen-bonding network that consists of two distinctive types of hydrogen bonds. Moreover, we identified, for the first time, the stable region for the lowest-density $$4\cdot {8}^{2}$$
4
⋅

8

2

monolayer ice (LD-48MI) at negative pressures (<−0.3 GPa). Overall, the MLFF enables large-scale first-principle-level molecular dynamics (MD) simulations of the spontaneous transition from the liquid water to a plethora of monolayer ices, including hexagonal, pentagonal, square, zigzag (ZZMI), and hexatic monolayer ices. These findings will enrich our understanding of the phase behaviour of the nanoconfined water/ices and provide a guide for future experimental realization of the 2D ices.
polyBERT: a chemical language model to enable fully machine-driven ultrafast polymer informatics
Authors: Kuenneth Christopher , Ramprasad Rampi
Published: July 2023

Polymers are a vital part of everyday life. Their chemical universe is so large that it presents unprecedented opportunities as well as significant challenges to identify suitable application-specific candidates. We present a complete end-to-end machine-driven polymer informatics pipeline that can search this space for suitable candidates at unprecedented speed and accuracy. This pipeline includes a polymer chemical fingerprinting capability called polyBERT (inspired by Natural Language Processing concepts), and a multitask learning approach that maps the polyBERT fingerprints to a host of properties. polyBERT is a chemical linguist that treats the chemical structure of polymers as a chemical language. The present approach outstrips the best presently available concepts for polymer property prediction based on handcrafted fingerprint schemes in speed by two orders of magnitude while preserving accuracy, thus making it a strong candidate for deployment in scalable architectures including cloud infrastructures.
Predicting scale-dependent chromatin polymer properties from systematic coarse-graining
Authors: Kadam Sangram , Kumari Kiran , Manivannan Vinoth , Dutta Shuvadip , Mitra Mithun K. , Padinhateeri Ranjith
Published: July 2023

Simulating chromatin is crucial for predicting genome organization and dynamics. Although coarse-grained bead-spring polymer models are commonly used to describe chromatin, the relevant bead dimensions, elastic properties, and the nature of inter-bead potentials are unknown. Using nucleosome-resolution contact probability (Micro-C) data, we systematically coarse-grain chromatin and predict quantities essential for polymer representation of chromatin. We compute size distributions of chromatin beads for different coarse-graining scales, quantify fluctuations and distributions of bond lengths between neighboring regions, and derive effective spring constant values. Unlike the prevalent notion, our findings argue that coarse-grained chromatin beads must be considered as soft particles that can overlap, and we derive an effective inter-bead soft potential and quantify an overlap parameter. We also compute angle distributions giving insights into intrinsic folding and local bendability of chromatin. While the nucleosome-linker DNA bond angle naturally emerges from our work, we show two populations of local structural states. The bead sizes, bond lengths, and bond angles show different mean behavior at Topologically Associating Domain (TAD) boundaries and TAD interiors. We integrate our findings into a coarse-grained polymer model and provide quantitative estimates of all model parameters, which can serve as a foundational basis for all future coarse-grained chromatin simulations.
The Sherpa hypothesis: Phenotype-Preserving Disordered Proteins stabilize the phenotypes of neurons and oligodendrocytes
Authors: Norris Vic , Oláh Judit , Krylov Sergey N. , Uversky Vladimir N. , Ovádi Judit
Published: July 2023

Intrinsically disordered proteins (IDPs), which can interact with many partner proteins, are central to many physiological functions and to various pathologies that include neurodegeneration. Here, we introduce the Sherpa hypothesis, according to which a subset of stable IDPs that we term Phenotype-Preserving Disordered Proteins (PPDP) play a central role in protecting cell phenotypes from perturbations. To illustrate and test this hypothesis, we computer-simulate some salient features of how cells evolve and differentiate in the presence of either a single PPDP or two incompatible PPDPs. We relate this virtual experiment to the pathological interactions between two PPDPs, α-synuclein and Tubulin Polymerization Promoting Protein/p25, in neurodegenerative disorders. Finally, we discuss the implications of the Sherpa hypothesis for aptamer-based therapies of such disorders.
MetaFlux: Meta-learning global carbon fluxes from sparse spatiotemporal observations
Authors: Nathaniel Juan , Liu Jiangong , Gentine Pierre
Published: July 2023

We provide a global, long-term carbon flux dataset of gross primary production and ecosystem respiration generated using meta-learning, calledMetaFlux. The idea behind meta-learning stems from the need to learn efficiently given sparse data by learning how to learn broad features across tasks to better infer other poorly sampled ones. Using meta-trained ensemble of deep models, we generate global carbon products on daily and monthly timescales at a 0.25-degree spatial resolution from 2001 to 2021, through a combination of reanalysis and remote-sensing products. Site-level validation finds that MetaFlux ensembles have lower validation error by 5–7% compared to their non-meta-trained counterparts. In addition, they are more robust to extreme observations, with 4–24% lower errors. We also checked for seasonality, interannual variability, and correlation to solar-induced fluorescence of the upscaled product and found that MetaFlux outperformed other machine-learning based carbon product, especially in the tropics and semi-arids by 10–40%. Overall, MetaFlux can be used to study a wide range of biogeochemical processes.
Transgenerational and intergenerational effects of early childhood famine exposure in the cohort of offspring of Leningrad Siege survivors
Authors: Tolkunova Kristina , Usoltsev Dmitrii , Moguchaia Ekaterina , Boyarinova Maria , Kolesova Ekaterina , Erina Anastasia , Voortman Trudy , Vasilyeva Elena , Kostareva Anna , Shlyakhto Evgeny , Konradi Alexandra , Rotar Oxana , Artomov Mykyta
Published: July 2023

Famine exposure during early life development can affect disease risk in late-life period, yet, transmission of phenotypic features from famine-exposed individuals to the next generations has not been well characterized. The purpose of our case–control study was to investigate the association of parental starvation in the perinatal period and the period of early childhood with the phenotypic features observed in two generations of descendants of Leningrad siege survivors. We examined 54 children and 30 grandchildren of 58 besieged Leningrad residents who suffered from starvation in early childhood and prenatal age during the Second World War. Controls from the population-based national epidemiological ESSE-RF study (n = 175) were matched on sex, age and body mass index (BMI). Phenotypes of controls and descendants (both generations, children and grandchildren separately) were compared, taking into account multiple testing. Comparison of two generations descendants with corresponding control groups revealed significantly higher creatinine and lower glomerular filtration rate (GFR), both in meta-analysis and in independent analyses. The mean values of GFR for all groups were within the normal range (GFR less than 60 mL/min/1.73 m2 was recorded in 2 controls and no one in DLSS). Additionally, independent of the creatinine level, differences in the eating pattern were detected: insufficient fish and excessive red meat consumption were significantly more frequent in the children of the Leningrad siege survivors compared with controls. Blood pressure, blood lipids and glucose did not differ between the groups. Parental famine exposure in early childhood may contribute to a decrease in kidney filtration capacity and altered eating pattern in the offspring of famine-exposed individuals.
Multimodal multitask learning for predicting MCI to AD conversion using stacked polynomial attention network and adaptive exponential decay
Authors: Ho Ngoc-Huynh , Jeong Yang-Hyung , Kim Jahae
Published: July 2023

Early identification and treatment of moderate cognitive impairment (MCI) can halt or postpone Alzheimer’s disease (AD) and preserve brain function. For prompt diagnosis and AD reversal, precise prediction in the early and late phases of MCI is essential. This research investigates multimodal framework-based multitask learning in the following situations: (1) Differentiating early mild cognitive impairment (eMCI) from late MCI and (2) predicting when an MCI patient would acquire AD. Clinical data and two radiomics features on three brain areas deduced from magnetic resonance imaging were investigated (MRI). We proposed an attention-based module, Stack Polynomial Attention Network (SPAN), to firmly encode clinical and radiomics data input characteristics for successful representation from a small dataset. To improve multimodal data learning, we computed a potent factor using adaptive exponential decay (AED). We used experiments from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort study, which included 249 eMCI and 427 lMCI participants at baseline visits. The proposed multimodal strategy yielded the best c-index score in time prediction of MCI to AD conversion (0.85) and the best accuracy in MCI-stage categorization ($$83.19\%$$83.19%). Moreover, our performance was equivalent to that of contemporary research.
Direct numerical simulation of an unsteady wall-bounded turbulent flow configuration for the assessment of large-eddy simulation models
Authors: Engelmann Linus , Hasslberger Josef , Baik Seung-Jin , Klein Markus , Kempf Andreas
Published: July 2023

A new benchmark case for the evaluation of direct numerical simulation (DNS) and large-eddy simulation (LES) models and methods is presented in this study. The known Taylor–Green vortex is modified by replacing the periodic boundary conditions in one direction with a no-slip boundary. A passive scalar is added and transported from the wall into the fluid. The addition of walls allows for the study of transient-instationary flows in a simple geometry with clean boundary and initial conditions, which is a key requirement for the assessment of LES modeling strategies. The added scalar mimics heat transfer through the wall. The case features reasonable computational cost for highly-resolved LES and DNS calculations. Simulations of the wall-bounded Taylor–Green vortex are easy to setup and do not require additional modeling. The proposed modification of the case is compared to the default Taylor–Green vortex and the difference in flow-physics is discussed. A detailed convergence study with four meshes, each of them refined by a factor of 2, has been conducted. The results reveal that converged second-order statistics can be obtained up to a dimensionless time of $$t/t_0 = 20$$

t
/

t
0

=
20

. Beyond that, due to the unsteady chaotic nature of the flow, some uncertainties remain. The results show that the case features challenging (near-wall) flow dynamics, which cannot be covered using the default Taylor–Green vortex and hence, justify the proposed case as a useful benchmark.
Persistent Dirac for molecular representation
Authors: Wee Junjie , Bianconi Ginestra , Xia Kelin
Published: July 2023

Molecular representations are of fundamental importance for the modeling and analysing molecular systems. The successes in drug design and materials discovery have been greatly contributed by molecular representation models. In this paper, we present a computational framework for molecular representation that is mathematically rigorous and based on the persistent Dirac operator. The properties of the discrete weighted and unweighted Dirac matrix are systematically discussed, and the biological meanings of both homological and non-homological eigenvectors are studied. We also evaluate the impact of various weighting schemes on the weighted Dirac matrix. Additionally, a set of physical persistent attributes that characterize the persistence and variation of spectrum properties of Dirac matrices during a filtration process is proposed to be molecular fingerprints. Our persistent attributes are used to classify molecular configurations of nine different types of organic-inorganic halide perovskites. The combination of persistent attributes with gradient boosting tree model has achieved great success in molecular solvation free energy prediction. The results show that our model is effective in characterizing the molecular structures, demonstrating the power of our molecular representation and featurization approach.
Description of the menstrual cycle status, energy availability, eating behavior and physical performance in a youth female soccer team
Authors: Paludo Ana Carolina , Gimunová Marta , Michaelides Marcos , Kobus Magdalena , Parpa Koulla
Published: July 2023

The aim of the study was to describe the menstrual status and perception, risk of low energy availability (LEA) and the presence of orthorexia nervosa (ON) in youth female from a soccer team. Also, verify the possible effect of LEA and ON on physical performance. Data from 19 female players (14.6 ± 1.42 yr) belonging to a soccer team from Cyprus was taken during pre-season. The menstrual cycle status was evaluated by specific questions, LEA by the Low Energy Availability in Females Questionnaire (LEAF-Q), ON by the ORTO-R questionnaire and physical performance by jump, handgrip and cardiorespiratory exercise tests. Players were separated into the risk of LEA and ON. Comparison and correlation tests were performed with a significance set at p < 0.05. As the main results, 66.7% of players perceived that the menstrual period affects their performance in the game, 83.3% did not communicate with coaches about their menstrual cycle; the prevalence of risk of LEA was 26.3%; players with risk of LEA also presented higher scores ON; neither LEA nor ON presented a significant association with players performance. The findings highlighted that youth players perceived an impact of the menstrual period on performance, but did not communicate with the coach about it. Players with the risk of LEA and high values of ON seem not to be associated with a decrease in physical performance during the pre-season evaluation. Attention is required as the players were assessed once. Monitoring these parameters throughout the sports season is recommended to obtain better clarification about the topic.
Impact of mixing coriander oil with goat feed on the chemical, microbiological and sensory characterizations of bio rayeb milk
Authors: Abd-Rabou Hagar S. , Mansour Hanem M. M. , Matloup O. H. , Sallam S. M. A. , Elazab M. A.
Published: July 2023

This research aimed to investigate the properties of bio rayeb milk that results from goats fed on feed supplemented with different concentrations of coriander oil. The study design included a control treatment (C) and two coriander oil concentrations, a low level of (0.95%) T1 and a high level of (1.9%) T2. A probiotic starter culture, Direct Vat Set (DVS) of lactobacillus delbrueckii ssp. bulgaricus and streptococcus salivarius ssp. thermophilus in the ratio (1:1) was used to prepare bio rayeb. All treatments were stored at 4 °C for 2 weeks and analyzed on day one and at the end of storage. Results showed that the coagulation time during bio rayeb manufacturing remained consistent at almost 6 h for all batches. However, using a high coriander oil level (1.90%) significantly decreased the apparent viscosity and the content of monounsaturated fatty acids. The DPPH inhibition and the content of monounsaturated fatty acids increased. The electrophoresis chromatogram exhibited a high degree of proteolysis in T2 compared to the control and T1. Microbiologically, yeast, molds, and coliforms were absent in all treatments. Feeding goats on provender supplemented with a low concentration of coriander oil may positively impact the resultant milk's technological and sensorial properties.
Levels and health risk assessments of Phthalate acid esters in indoor dust of some microenvironments within Ikeja and Ota, Nigeria
Authors: Anake Winifred U. , Nnamani Esther A.
Published: July 2023

The levels, profiles of Phthalate acid esters (PAEs) and their associated health risk in children and adults using indoor dust samples were assessed from nine (9) microenvironments in Nigeria. Six PAEs congeners were determined using Gas Chromatography–Mass Spectrometry and the human health risk assessments of PAEs exposure to children and adults were computed using the United States Environmental Protection Agency (USEPA) exposure model. The mean concentrations of the total PAEs (Σ6PAEs) in indoor dust across the study locations ranged from 1.61 ± 0.12 to 53.3 ± 5.27 μg/g with 72.0% of di-n-octyl phthalate (DnOP) as the most predominant contributor of PAEs in sample locations B, C, D, E, F and G. PAEs estimated daily intake results exceeded the USEPA value of 20 and 50 kg/bw/day for children and adults respectively in some locations. Non-carcinogenic risk exposure indicated no risk (HI < 1), while the carcinogenic risk was within the recommended threshold of 1.00 × 10–4 to 1.00 × 10–6 for benzyl butyl phthalate and bis-2-ethylhexyl phthalate. From our findings, lower levels of PAEs were observed in locations with good ventilation system. Also, the human health risk evaluation indicated indoor dust ingestion as the dominant exposure route of PAEs for both children and adults, while the children were at a higher risk of PAEs exposure. To protect children susceptible to these endocrine-disrupting pollutants, soft vinyl children’s toys and teething rings should be avoided. Appropriate policies and procedures on the reduction of PAEs exposure to humans should be enacted by all stakeholders, including government regulatory agencies, industries, school administrators and the entire community.
Transfer-learning is a key ingredient to fast deep learning-based 4D liver MRI reconstruction
Authors: Gulamhussene Gino , Rak Marko , Bashkanov Oleksii , Joeres Fabian , Omari Jazan , Pech Maciej , Hansen Christian
Published: July 2023

Time-resolved volumetric magnetic resonance imaging (4D MRI) could be used to address organ motion in image-guided interventions like tumor ablation. Current 4D reconstruction techniques are unsuitable for most interventional settings because they are limited to specific breathing phases, lack temporal/spatial resolution, and have long prior acquisitions or reconstruction times. Deep learning-based (DL) 4D MRI approaches promise to overcome these shortcomings but are sensitive to domain shift. This work shows that transfer learning (TL) combined with an ensembling strategy can help alleviate this key challenge. We evaluate four approaches: pre-trained models from the source domain, models directly trained from scratch on target domain data, models fine-tuned from a pre-trained model and an ensemble of fine-tuned models. For that the data base was split into 16 source and 4 target domain subjects. Comparing ensemble of fine-tuned models (N = 10) with directly learned models, we report significant improvements (P < 0.001) of the root mean squared error (RMSE) of up to 12% and the mean displacement (MDISP) of up to 17.5%. The smaller the target domain data amount, the larger the effect. This shows that TL + Ens significantly reduces beforehand acquisition time and improves reconstruction quality, rendering it a key component in making 4D MRI clinically feasible for the first time in the context of 4D organ motion models of the liver and beyond.