bluuebunny/crossref_metadata_2025 huggingface dataset:
3D-printed wearable BaTiO3/PDMS piezoelectric nanogenerator for self-powered body movement sensing
Authors: Shi Xiaoquan , Sun Yazhou , Tian Haiying , Liu Haitao , Li Dekai
Published: October 2023

Flexible piezoelectric nanogenerators (PENGs) used in body movement real-time monitoring are of great interest for their wide application potential such as in the field of smart healthcare. In this work, a self-powered BaTiO3/Polydimethylsiloxane (PDMS) PENG for body movement sensing was successfully fabricated by extrusion 3D printing. Matrix system composed of different ratios of PDMS was selected based on the rheological property of materials. Experimental investigations were conducted to examine the impact of printing pressure and speed on the linewidth. Subsequently, the extrusion parameters for nanogenerators were determined based on the printed linewidth. The composite showed good ferroelectric property. After polarization, the nanogenerators exhibited an improvement in output performance of up to 55.2%. Additionally, the device demonstrated a good linear relationship between voltage and tapped force test by an electromechanical vibrator. Successful detection of body or muscle movement signals was achieved when the nanogenerator was mounted on the human finger, throat, or foot using a wearable sock, highlighting its potential for applications in self-powered wearable devices for smart healthcare.
Interpretable surrogate models to approximate the predictions of convolutional neural networks in glaucoma diagnosis
Authors: Sigut Jose , Fumero Francisco , Arnay Rafael , Estévez José , Díaz-Alemán Tinguaro
Published: October 2023

Deep learning systems, especially in critical fields like medicine, suffer from a significant drawback, their black box nature, which lacks mechanisms for explaining or interpreting their decisions. In this regard, our research aims to evaluate the use of surrogate models for interpreting convolutional neural network (CNN) decisions in glaucoma diagnosis. Our approach is novel in that we approximate the original model with an interpretable one and also change the input features, replacing pixels with tabular geometric features of the optic disc, cup, and neuroretinal rim. We trained CNNs with two types of images: original images of the optic nerve head and simplified images showing only the disc and cup contours on a uniform background. Decision trees were used as surrogate models due to their simplicity and visualization properties, while saliency maps were calculated for some images for comparison. The experiments carried out with 1271 images of healthy subjects and 721 images of glaucomatous eyes demonstrate that decision trees can closely approximate the predictions of neural networks trained on simplified contour images, with R-squared values near 0.9 for VGG19, Resnet50, InceptionV3 and Xception architectures. Saliency maps proved difficult to interpret and showed inconsistent results across architectures, in contrast to the decision trees. Additionally, some decision trees trained as surrogate models outperformed a decision tree trained on the actual outcomes without surrogation. Decision trees may be a more interpretable alternative to saliency methods. Moreover, the fact that we matched the performance of a decision tree without surrogation to that obtained by decision trees using knowledge distillation from neural networks is a great advantage since decision trees are inherently interpretable. Therefore, based on our findings, we think this approach would be the most recommendable choice for specialists as a diagnostic tool.
Investigating community-based care service factors delaying residential care home admission of community dwelling older adults and cost consequence
Authors: Jeon Yun-Hee , Simpson Judy M , Comans Tracy , Shin Mirim , Fethney Judith , McKenzie Heather , Crawford Tonia , Lang Catherine , Inacio Maria
Published: October 2023

Objectives

To examine factors contributing to delaying care home admission; and compare the rates of care home admission and cost consequence between two government subsidised programmes, Veterans’ Affairs Community Nursing (VCN) and Home Care Package (HCP).

Methods

Our national, population-based retrospective cohort study and cost analysis used existing, de-identified veterans’ claims databases (2010–19) and the Registry of Senior Australians Historical Cohort (2010–17), plus aggregate programme expenditure data. This involved 21,636 VCN clients (20,980 aged 65–100 years), and an age- and sex-matched HCP cohort (N = 20,980).

Results

Service factors associated with lower risk of care home admission in the VCN cohort were periodic (versus continuous) service delivery (HR 0.27 [95%CI, 0.24–0.31] for ≤18 months; HR 0.89 [95%CI, 0.84–0.95] for >18 months), and majority care delivered by registered nurses (versus personal care workers) (HR 0.86 [95%CI, 0.75–0.99] for ≤18 months; HR 0.91 [95%CI, 0.85–0.98] for >18 months). In the matched cohorts, the time to care home admission for VCN clients (median 28 months, IQR 14–42) was higher than for HCP clients (14, IQR 6–27). Within 5 years of service access, 57.6% (95%CI, 56.9–58.4) of HCP clients and 26.6% (95%CI, 26.0–27.2) of VCN clients had care home admission. The estimated cost saving for VCN recipients compared to HCP recipients over 5 years for relevant government providers was over A$1 billion.

Conclusions

Compared to an HCP model, individuals receiving VCN services remained at home longer, with potentially significant cost savings. This new understanding suggests timely opportunity for many countries’ efforts to enhance community-based care services.
The simulation argument reconsidered
Authors: Harris Keith Raymond
Published: October 2023

Some philosophers regard it as a serious possibility that we now exist within a simulation. That this hypothesis is somewhat probable has been defended extensively by Nick Bostrom. Notably, Bostrom does not defend the conclusion that we inhabit a simulation, but rather the disjunctive conclusion that the human species is very likely to die out before reaching a ‘posthuman stage’, that posthuman civilizations are extremely unlikely to run significant numbers of simulations, or that we almost certainly inhabit a simulation. Bostrom argues that there is no basis for strongly favouring one of these alternatives over its counterparts. The upshot is that it is fairly probable that we inhabit a simulation. I argue that posthuman civilizations are likely to be unwilling to run significant numbers of simulations, thereby undermining the case for assigning a somewhat high probability to the hypothesis that we live in a simulation.
ADAM22 ethnic-specific variant reducing binding of membrane-associated guanylate kinases causes focal epilepsy and behavioural disorder
Authors: Nosková Lenka , Fukata Yuko , Stránecký Viktor , Šaligová Jana , Bodnárová Oxana , Giertlová Mária , Fukata Masaki , Kmoch Stanislav
Published: October 2023

Pathogenic variants of ADAM22 affecting either its biosynthesis and/or its interactions with either LGI1 and/or PSD-95 have been recently identified in individuals with developmental and epileptic encephalopathy. Here, we describe a girl with seizures, delayed psychomotor development, and behavioural disorder, carrying a homozygous variant in ADAM22 (NM_021723.5:c.2714C > T). The variant has a surprisingly high frequency in the Roma population of the Czech and Slovak Republic, with 11 of 213 (∼5.2%) healthy Roma individuals identified as heterozygous carriers. Structural in silico characterization revealed that the genetic variant encodes the missense variant p.S905F, which localizes to the PDZ-binding motif of ADAM22. Studies in transiently transfected mammalian cells revealed that the variant has no effect on biosynthesis and stability of ADAM22. Rather, protein–protein interaction studies showed that the p.S905F variant specifically impairs ADAM22 binding to PSD-95 and other proteins from a family of membrane-associated guanylate kinases, while it has only minor effect on ADAM22–LGI1 interaction. Our study indicates that a significant proportion of epilepsy in patients of Roma ancestry may be caused by homozygous c.2714C > T variants in ADAM22. The study of this ADAM22 variant highlights a novel pathogenic mechanism of ADAM22 dysfunction and reconfirms an essential role of interaction of ADAM22 with membrane-associated guanylate kinases in seizure protection in humans.
Normative Overlaps between China and the Liberal International Society: China’s Developmentalist Human Rights
Authors: Karmazin Aleš
Published: October 2023

When different entities (actors) accept a certain norm or a particular agreement about normative principles, they are likely to have an overlapping but not necessarily fully shared understanding of the given norm. This article theorises and assesses the strength of such normative overlaps in international politics. It conceptualises normative overlaps as normative congruences across and within political orders. It follows a norm’s connection to constitutional layers of political orders (congruences within orders) and the way these constitutional layers of political orders, among which the norm is shared, overlap (congruences across orders). To do so, it builds upon and interconnects the literature on norms, especially norm diffusion, and the English School and constructivist literature on the composition of international order. The theoretical framework is utilised to analyse how China fits into the liberal international society, especially when it comes to human rights (HR) and humanitarian protection. The effect of the normative overlaps in this realm is China’s active engagement with the liberal HR regime, however, without deeper convergence or socialisation. The limits of convergence are underpinned by significant differences between the Chinese developmentalist and liberal conceptions of the moral purpose of politics.
Longitudinal Associations of Social Support and Gait Speed Decline in Aging
Authors: Pollak Chava , Verghese Joe , Blumen Helena M
Published: October 2023

Background

Social support predicts functional and cognitive decline in aging. Yet, the associations between social support and gait speed decline—a functional vital sign—are not well understood. This study examined associations between social support and gait speed decline in aging.

Methods

Social support and gait data from 542 older adults without dementia were examined (mean age 76.1 ± 6.5 years). Baseline emotional support, tangible support, affectionate support, positive social interactions, and overall support from the Medical Outcomes Study Social Support Survey were the predictors of interest. Annual change in simple (normal pace walking) and complex (walking while reciting alternate letters of the alphabet) gait speed (cm/s) were the outcomes of interest. Linear mixed effects models examined associations between social support and gait speed decline, after adjusting for gender, race, depressive symptoms, overall cognition, and comorbidities.

Results

The mean annual change in gait speed was 1.8 cm/s during simple walking and 1.13 cm/s during complex walking. Tangible support was the only category of social support that predicted decline in simple and complex gait speed over a median follow-up of 3 years. The annual decline in gait speed was 0.51 cm/s (p = .008, 95% confidence intervals [CI] 0.13, 0.89) and 0.58 cm/s (p = .007, CI 0.16, 1.0) greater among those with low tangible support than in those with high tangible support during simple and complex walking, respectively.

Conclusions

Tangible support is a potentially modifiable risk factor for gait speed decline. Further study is needed to examine mechanisms behind the observed associations and the potential for intervention.
Temporal Dynamics of Epigenetic Aging and Frailty From Midlife to Old Age
Authors: Mak Jonathan K L , Karlsson Ida K , Tang Bowen , Wang Yunzhang , Pedersen Nancy L , Hägg Sara , Jylhävä Juulia , Reynolds Chandra A
Published: October 2023

Background

DNA methylation-derived epigenetic clocks and frailty are well-established biological age measures capturing different aging processes. However, whether they are dynamically linked to each other across chronological age remains poorly understood.

Methods

This analysis included 1 309 repeated measurements in 524 individuals aged 50–90 years from the Swedish Adoption/Twin Study of Aging. Frailty was measured using a validated 42-item frailty index (FI). Five epigenetic clocks were calculated, including 4 principal component (PC)-based clocks trained on chronological age (PCHorvathAge and PCHannumAge) and aging-related physiological conditions (PCPhenoAge and PCGrimAge), and a pace of aging clock (DunedinPACE). Using dual change score models, we examined the dynamic, bidirectional associations between each of the epigenetic clocks and the FI over age to test for potential causal associations.

Results

The FI exhibited a nonlinear, accelerated increase across the older adulthood, whereas the epigenetic clocks mostly increased linearly with age. For PCHorvathAge, PCHannumAge, PCPhenoAge, and PCGrimAge, their associations with the FI were primarily due to correlated levels at age 50 but with no evidence of a dynamic longitudinal association. In contrast, we observed a unidirectional association between DunedinPACE and the FI, where a higher DunedinPACE predicted a subsequent increase in the FI, but not vice versa.

Conclusions

Our results highlight a temporal order between epigenetic aging and frailty such that changes in DunedinPACE precede changes in the FI. This potentially suggests that the pace of aging clock can be used as an early marker of the overall physiological decline at system level.
The Media Use Model: A metatheoretical framework for media processes and effects
Authors: Hoewe Jennifer , Ewoldsen David R
Published: October 2023

The Media Use Model (MUM) presents a metatheoretical framework that aims to unify several existing theories of media processes and effects. It uses a constraint satisfaction approach to coherence to explain the dynamic relationship between a media consumer’s motivations, expectations, individual differences, and, primarily, their cognitive processing during media use. The MUM includes six propositions, which represent stages during which a media consumer’s existing processing constraints are taken into consideration during their selection, interpretation, and comprehension of media content. It allows for both spontaneous and deliberate processing that can result in coherence or incommensurability, which then predicts continued media use or a change in media selection, respectively. Within this metatheoretical framework, (in)coherence is presented as a continuum where media consumers may have different interpretations of the same media content, which can then be used to understand their responses to it.
The Earliest Danish Testimonies About the Theresienstadt Ghetto: Gathered in Sweden by the World Jewish Congress, April 1945
Authors: Tarabini Silvia Goldbaum
Published: October 2023

In April 1945, even before the Theresienstadt ghetto’s liberation, the World Jewish Congress (WJC) began to document the experiences of the Danish Jewish survivors who had been brought to safety in Sweden. Collecting lists of fellow prisoners still in the ghetto and telegrams to relatives, the organization also gathered some of the earliest known written testimonies from Danish survivors. Though the author has to date only uncovered a small sample set of twenty-two testimonies within the organization’s archival holdings, these testimonies shed light on Danish survivors’ fresh memories and impressions of Theresienstadt. When compared to later testimonies, they provide insight into the changing focuses and concerns of survivors. Additionally, the name lists that the survivors compiled add information about their networks in the ghetto, and the telegrams that survivors sent through the WJC reveal their urgent efforts to both convey and obtain further information from relatives and friends abroad. These sources, written before the war had ended, thus provide a compelling and raw glimpse into Danish survivors’ early memories of ghetto life in Theresienstadt.
Exploring Predictive Biomarkers of Relapse in Ulcerative Colitis: A Proteomics Approach
Authors: Assadsangabi Arash , Evans Caroline A , Corfe Bernard M , Lobo Alan J
Published: October 2023

Introduction and aims

Risk stratification of subjects with a history of inflammatory bowel disease (IBD) into those likely to relapse and those who will remain quiescent continues to be a significant challenge. The aim of this study was to investigate whether certain proteomic signature profiles or biomarkers during remission are associated with future disease relapse in patients with ulcerative colitis (UC).

Methods

Endoscopic rectal samples from patients with UC in clinical, endoscopic, and histological remission at index endoscopy were collected, as well as samplers from normal control individuals. The patients were stratified to early relapsers (ERs) if they developed clinical signs of UC flare within 6 months of index endoscopy or nonrelapsers (NRs) if there was no relapse after 36 months of follow-up. The pooled rectal samples from ERs, NRs, and control individuals were subjected to nano-liquid chromatography and tandem mass spectrometry as per standard iTRAQ (isobaric tags for relative and absolute quantitation) workflow methodology. Selected proteomics-yielded candidates were subjected to orthogonal validation via immunoblotting, in a biomarker discovery exercise.

Results

Sixty-one patients were included, of whom 8 had clinical relapse within 6 months from the index endoscopy, and 43 patients had no clinical symptoms of relapse within the 36-month follow-up period. Ten patients who had clinical signs of relapse between 6 and 36 months were excluded. Seventeen control individuals were also included. Soluble proteomics analyses between ERs, NRs, and control individuals revealed a series of upregulated and downregulated proteins. Following orthogonal validation, upregulated TRX (P = .001) and IGHA1 (P = .001) were observed in ERs relative to NRs.

Conclusions

Several novel candidate tissue biomarkers have been identified in this study, which could discriminate patients with UC at risk of early relapse from those in long-term sustained remission. Our findings may pave the way for pre-emptive UC disease monitoring and therapeutic decision making.
Associations of Fish and Fish Oil Consumption With Incident Inflammatory Bowel Disease: A Population-Based Prospective Cohort Study
Authors: Fu Jiaying , Chai Chengwei , Chen Lan , Cai Miao , Ai Baozhuo , Li Haitao , Yuan Jinqiu , Lin Hualiang , Zhang Zilong
Published: October 2023

Background

We examined the associations of fish and fish oil consumption with inflammatory bowel disease (IBD) incidence.

Patients and Methods

We conducted a longitudinal analysis based on the UK Biobank, a population-based prospective cohort. Dietary consumption of fish and fish oil was collected by questionnaire. IBD incident cases were identified through links to National Health Services datasets. Cox proportional hazards regression models were used to assess the associations between oily fish, nonoily fish, and fish oil intake and IBD incidence with adjustment for various confounding factors.

Results

A total of 265 839 participants free of IBD at baseline were included, and 1554 incident IBD cases were identified during an average follow-up of 11.8 years. In fully adjusted models, we found that compared with participants who never ate oily fish, those having <1 serving/wk, 1 serving/wk, and >1 serving/wk had 9% (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.77-1.08), 19% (HR, 0.81; 95% CI, 0.69-0.96), and 12% (HR, 0.88; 95% CI, 0.73-1.06) lower risks of IBD, respectively, albeit not all statistically significant. A significant association was found between fish oil intake and a reduced risk of IBD (HR, 0.84; 95% CI, 0.75-0.93). We found no significant associations for nonoily fish. In a subsample (n = 105 714) of participants with multiple subsequent dietary reviews, we also found a negative association between the frequency of fish oil intake over time and incident IBD (P trend < .05).

Conclusions

Our findings indicate that oily fish and fish oil supplements might be protective factors against IBD.
On the Cohomology of GL(N) and Adjoint Selmer Groups
Authors: Tilouine Jacques , Urban Eric
Published: October 2023

We prove under certain conditions (local-global compatibility and vanishing of modulo $p$ cohomology), a generalization of a theorem of Galatius and Venkatesh. We consider the case of $\operatorname{\textsf{GL}}(N)$ over a CM field; we construct a Hecke-equivariant injection from the divisible group associated to the first fundamental group of a derived deformation ring to the Selmer group of the twisted dual adjoint motive with divisible coefficients and we identify its cokernel as the first Tate-Shafarevich group of this motive. Actually, we also construct similar maps for higher homotopy groups with values in exterior powers of Selmer groups, although with less precise control on their kernel and cokernel. By a result of Y. Cai generalizing previous results by Galatius-Venkatesh on the graded cohomology group of a locally symmetric space, our maps relate the (non-Eisenstein) localization of the graded cohomology group for a locally symmetric space to the exterior algebra of the Selmer group of the Tate dual of the adjoint representation. We generalize this to Hida families as well.
Comparison of the incidence of vancomycin-associated nephrotoxicity following the change from trough-guided dosing to AUC-guided doing using trough-only data
Authors: Yamada Yuto , Niwa Takashi , Ono Yurie , Yamada Shoya , Niwa Kyoko , Yasue Moeka , Yamamoto Taishi , Sumi Kazuyuki , Otsubo Manami , Kobayashi Ryo , Suzuki Akio
Published: October 2023

Objectives

Although use of AUC-guided vancomycin dosing was recommended in the revised 2020 consensus guideline, collection of multiple vancomycin serum samples to calculate AUC may cause clinical complications. AUC calculated from trough-only data (one-point AUC-guided dosing) has not been sufficiently validated. The aim of the present study was to compare the incidence of nephrotoxicity following the change from trough-guided to one-point AUC-guided dosing.

Methods

We conducted a single-centre, prospective cohort study to compare the incidence of nephrotoxicity between a trough-guided dosing group and one-point AUC-guided dosing group.

Results

One-point AUC-guided dosing significantly decreased the incidence of acute kidney injury (AKI) compared with trough-guided dosing (2.8% versus 17.4%, P = 0.002). Further, Kaplan–Meier plots for cumulative incidence of the AKI-free rate indicated that the onset of AKI was significantly longer in the one-point AUC-guided dosing group than in trough-guided dosing (HR, 6.5; 95% CI, 1.5–27.4; P = 0.011). Moreover, multivariate Cox proportional hazard analysis indicated that implementation of one-point AUC-guided dosing was a significant protective factor against the incidence of AKI (age-adjusted HR, 0.164; 95% CI, 0.04–0.69; P = 0.014).

Conclusions

Compared with trough concentration-guided dosing, AUC-guided dosing using one-point sampling markedly reduced the incidence of AKI, without additional serum sampling.
Systematic replication of smoking disease associations using survey responses and EHR data in the All of Us Research Program
Authors: Schlueter David J , Sulieman Lina , Mo Huan , Keaton Jacob M , Ferrara Tracey M , Williams Ariel , Qian Jun , Stubblefield Onajia , Zeng Chenjie , Tran Tam C , Bastarache Lisa , Dai Jian , Babbar Anav , Ramirez Andrea , Goleva Slavina B , Denny Joshua C
Published: October 2023

Objective

The All of Us Research Program (All of Us) aims to recruit over a million participants to further precision medicine. Essential to the verification of biobanks is a replication of known associations to establish validity. Here, we evaluated how well All of Us data replicated known cigarette smoking associations.

Materials and Methods

We defined smoking exposure as follows: (1) an EHR Smoking exposure that used International Classification of Disease codes; (2) participant provided information (PPI) Ever Smoking; and, (3) PPI Current Smoking, both from the lifestyle survey. We performed a phenome-wide association study (PheWAS) for each smoking exposure measurement type. For each, we compared the effect sizes derived from the PheWAS to published meta-analyses that studied cigarette smoking from PubMed. We defined two levels of replication of meta-analyses: (1) nominally replicated: which required agreement of direction of effect size, and (2) fully replicated: which required overlap of confidence intervals.

Results

PheWASes with EHR Smoking, PPI Ever Smoking, and PPI Current Smoking revealed 736, 492, and 639 phenome-wide significant associations, respectively. We identified 165 meta-analyses representing 99 distinct phenotypes that could be matched to EHR phenotypes. At P < .05, 74 were nominally replicated and 55 were fully replicated. At P < 2.68 × 10−5 (Bonferroni threshold), 58 were nominally replicated and 40 were fully replicated.

Discussion

Most phenotypes found in published meta-analyses associated with smoking were nominally replicated in All of Us. Both survey and EHR definitions for smoking produced similar results.

Conclusion

This study demonstrated the feasibility of studying common exposures using All of Us data.
Petrophysical properties identification and estimation of the Wufeng-Longmaxi shale gas reservoirs: a case study from South-West China
Authors: Kablan Or Aimon Brou Koffi , Chen Tongjun
Published: October 2023

Petrophysical properties are critical for shale gas reservoir characterization and simulation. The Wufeng-Longmaxi shale, in the south-eastern margin of the Sichuan Basin, is identified as a complex reservoir due to its variability in lithification and geological mechanisms. Thus, determining its characteristics is challenging. Based on wireline logs and pressure data analysis, a shale reservoir was identified, and petrophysical properties were described to obtain parameters to build a reservoir simulation model. The properties include shale volume, sand porosity, net reservoir thickness, total and effective porosities, and water saturation. Total and effective porosities were calculated using density method. Shale volume was estimated by applying the Clavier equation to gamma-ray responses. Sand porosity and net reservoir thickness were evaluated using the Thomas–Stieber model, and the Simandoux equation was used to compute water saturation. The results indicate that the reservoir is characterized by a relatively low porosity and high shale content, with shale unequally distributed in its laminated form (approximately 75%), dispersed (about 20%), and structural form (5%). This research workflow can efficiently evaluate shale reservoir parameters and provide a reliable approach for future reservoir development and fracture identification.
Imaging plant metabolism in situ
Authors: Horn Patrick J , Chapman Kent D
Published: October 2023

Mass spectrometry imaging (MSI) has emerged as an invaluable analytical technique for investigating the spatial distribution of molecules within biological systems. In the realm of plant science, MSI is increasingly employed to explore metabolic processes across a wide array of plant tissues, including those in leaves, fruits, stems, roots, and seeds, spanning various plant systems such as model species, staple and energy crops, and medicinal plants. By generating spatial maps of metabolites, MSI has elucidated the distribution patterns of diverse metabolites and phytochemicals, encompassing lipids, carbohydrates, amino acids, organic acids, phenolics, terpenes, alkaloids, vitamins, pigments, and others, thereby providing insights into their metabolic pathways and functional roles. In this review, we present recent MSI studies that demonstrate the advances made in visualizing the plant spatial metabolome. Moreover, we emphasize the technical progress that enhances the identification and interpretation of spatial metabolite maps. Within a mere decade since the inception of plant MSI studies, this robust technology is poised to continue as a vital tool for tackling complex challenges in plant metabolism.
Histone deacetylase 9 interacts with SiHAT3.1 and SiHDA19 to repress dehydration responses through H3K9 deacetylation in foxtail millet
Authors: Kumar Verandra , Singh Babita , Kumar Singh Roshan , Sharma Namisha , Muthamilarasan Mehanathan , Sawant Samir V , Prasad Manoj
Published: October 2023

Climate change inflicts several stresses on plants, of which dehydration stress severely affects growth and productivity. C4 plants possess better adaptability to dehydration stress; however, the role of epigenetic modifications underlying this trait is unclear. In particular, the molecular links between histone modifiers and their regulation remain elusive. In this study, genome-wide H3K9 acetylation (H3K9ac) enrichment using ChIP-sequencing was performed in two foxtail millet cultivars with contrasting dehydration tolerances (IC403579, cv. IC4—tolerant, and IC480117, cv. IC41—sensitive). It revealed that a histone deacetylase, SiHDA9, was significantly up-regulated in the sensitive cultivar. Further characterization indicated that SiHDA9 interacts with SiHAT3.1 and SiHDA19 to form a repressor complex. SiHDA9 might be recruited through the SiHAT3.1 recognition sequence onto the upstream of dehydration-responsive genes to decrease H3K9 acetylation levels. The silencing of SiHDA9 resulted in the up-regulation of crucial genes, namely, SiRAB18, SiRAP2.4, SiP5CS2, SiRD22, SiPIP1;4, and SiLHCB2.3, which imparted dehydration tolerance in the sensitive cultivar (IC41). Overall, the study provides mechanistic insights into SiHDA9-mediated regulation of dehydration stress response in foxtail millet.
Selenomethionine supplementation and expression of selenosugars, selenocysteine, and other selenometabolites in rat liver
Authors: Bierla Katarzyna , Szpunar Joanna , Lobinski Ryszard , Sunde Roger A
Published: October 2023

Selenomethionine (SeMet) as a methionine analog can be incorporated into protein. In turkeys, we recently found that selenium (Se) as selenite is not metabolized to SeMet but rather to selenosugars (seleno-N-acetyl galactosamine) bound to protein as well as to selenocysteine (Sec) in selenoproteins. To characterize the metabolism of SeMet, we fed rats graded levels of SeMet from 0 to 5 µg Se/g in a Se-deficient diet for 4 wk, and investigated the fate and accumulation of liver Se using high pressure liquid chromatography (HPLC) coupled with Se-specific inductively coupled plasma mass spectrometry (ICP–MS) and molecule specific (Orbitrap MS/MS) detection. Up to 0.24 µg Se/g (Se requirement for maximal glutathione peroxidase activity), Sec accounted for ∼40% of total liver Se whereas SeMet only accounted for 3–11%. Analysis of water-soluble extracts found negligible low molecular weight (LMW) Se species in rats fed 0 and 0.08 µg Se/g, including no SeMet. At 0.24 µg Se/g and above, SeMet accounted for only 10% of LMW Se species, whereas methyl- and glutathionyl-selenosugars accounted for 70% of LMW Se species. Above the Se requirement, SeMet was ∼30% of the proteinaceous amino acids, whereas Sec levels fell to 5% in rats fed 5 µg Se/g as SeMet. Last, considerably less inorganic Se was bound to liver protein with high SeMet as compared to selenite in a parallel study. SeMet is efficiently metabolized and mixes with the common Se metabolite pool, where Se is preferentially incorporated into Sec and Sec-selenoproteins until selenoproteins plateau; with high SeMet intake, Se is increasingly accumulated as LMW selenosugars and as selenosugar-decorated proteins.
The Limited and The Limitless: Harmonic Voltas and Puns in the Third Movement of Ben Johnston’s Seventh String Quartet
Authors: Willis Laurence Sinclair
Published: October 2023

Extended just intonation confronts us with musical problems arising from the sheer array and variety of pitch relationships that can be written, played, and heard. Through an analysis of Ben Johnston’s Seventh String Quartet as a case study, this essay addresses the diversity of these pitch relationships by suggesting a three-way categorization of just intonation ratios: primary intervals (simple integer ratios), ectopic intervals (ratios with no primary interval analogue), and intermediary intervals (ratios with a close primary interval analogue). I suggest a listening strategy based on the categorization resulting in two analytical models. A voltaic analysis recognizes changes in the pitch domain indicated by the differences between primary and intermediary intervals. A pitch pun analysis emphasizes the small magnitude of the differences between primary and intermediary intervals and the slow drift away from a secure sense of pitch place. Finally, I combine these views to compare the two analytical strategies as applied to the last measures of Johnston’s Seventh String Quartet and speculate on the implications of these strategies for hearing and conceiving of pitch intervals.
Functionally comparable but evolutionarily distinct nucleotide-targeting effectors help identify conserved paradigms across diverse immune systems
Authors: Nicastro Gianlucca G , Burroughs A Maxwell , Iyer Lakshminarayan M , Aravind L
Published: October 2023

While nucleic acid-targeting effectors are known to be central to biological conflicts and anti-selfish element immunity, recent findings have revealed immune effectors that target their building blocks and the cellular energy currency—free nucleotides. Through comparative genomics and sequence-structure analysis, we identified several distinct effector domains, which we named Calcineurin-CE, HD-CE, and PRTase-CE. These domains, along with specific versions of the ParB and MazG domains, are widely present in diverse prokaryotic immune systems and are predicted to degrade nucleotides by targeting phosphate or glycosidic linkages. Our findings unveil multiple potential immune systems associated with at least 17 different functional themes featuring these effectors. Some of these systems sense modified DNA/nucleotides from phages or operate downstream of novel enzymes generating signaling nucleotides. We also uncovered a class of systems utilizing HSP90- and HSP70-related modules as analogs of STAND and GTPase domains that are coupled to these nucleotide-targeting- or proteolysis-induced complex-forming effectors. While widespread in bacteria, only a limited subset of nucleotide-targeting effectors was integrated into eukaryotic immune systems, suggesting barriers to interoperability across subcellular contexts. This work establishes nucleotide-degrading effectors as an emerging immune paradigm and traces their origins back to homologous domains in housekeeping systems.
MethMarkerDB: a comprehensive cancer DNA methylation biomarker database
Authors: Zhu Zhixian , Zhou Qiangwei , Sun Yuanhui , Lai Fuming , Wang Zhenji , Hao Zhigang , Li Guoliang
Published: October 2023

DNA methylation plays a crucial role in tumorigenesis and tumor progression, sparking substantial interest in the clinical applications of cancer DNA methylation biomarkers. Cancer-related whole-genome bisulfite sequencing (WGBS) data offers a promising approach to precisely identify these biomarkers with differentially methylated regions (DMRs). However, currently there is no dedicated resource for cancer DNA methylation biomarkers with WGBS data. Here, we developed a comprehensive cancer DNA methylation biomarker database (MethMarkerDB, https://methmarkerdb.hzau.edu.cn/), which integrated 658 WGBS datasets, incorporating 724 curated DNA methylation biomarker genes from 1425 PubMed published articles. Based on WGBS data, we documented 5.4 million DMRs from 13 common types of cancer as candidate DNA methylation biomarkers. We provided search and annotation functions for these DMRs with different resources, such as enhancers and SNPs, and developed diagnostic and prognostic models for further biomarker evaluation. With the database, we not only identified known DNA methylation biomarkers, but also identified 781 hypermethylated and 5245 hypomethylated pan-cancer DMRs, corresponding to 693 and 2172 genes, respectively. These novel potential pan-cancer DNA methylation biomarkers hold significant clinical translational value. We hope that MethMarkerDB will help identify novel cancer DNA methylation biomarkers and propel the clinical application of these biomarkers.
Does MDMA have treatment potential in sexual dysfunction? A systematic review of outcomes across the female and male sexual response cycles
Authors: Wexler Ava , Dubinskaya Alexandra , Suyama Julie , Komisaruk Barry R , Anger Jennifer , Eilber Karyn
Published: October 2023

Introduction

Sexual health, an integral component of overall well-being, is frequently compromised by common yet underdiagnosed sexual dysfunctions. Traditional interventions encompass pharmaceutical and psychological treatments. Unconventional therapies, like MDMA, offer hope for sexual dysfunction. This review delves into MDMA’s effects on sexual responsiveness and its potential role in treating sexual dysfunction.

Objectives

The purpose of this review is to elucidate effects of MDMA on different domains of the female and male sexual response cycles.

Methods

We conducted a systematic review on the effects of MDMA on each domain of the female and male sexual response cycles. PubMed, MEDLINE, and EMBASE were queried, and results were screened using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms utilized were “MDMA” or “ecstasy” in combination with “desire,” “arousal,” “lubrication,” “orgasm,” “pleasure,” “libido,” “erection,” and “ejaculation.” Inclusion criteria for this review were MDMA use by study subjects and sexual outcomes in at least 1 domain of the female and/or male sexual response cycles were described and measured. Randomized controlled trials, cohort studies (both prospective and retrospective), surveys, and literature reviews published between January 2000 and June 2022 were included. Case reports and studies that did not address conditions of interest were excluded from analysis. Duplicated search results were screened out. The remaining studies were then read in full text to ensure they met inclusion and exclusion criteria for analysis.

Results

We identified 181 studies, of which 6 met criteria for assessment of the female sexual response cycle and 8 met criteria for assessment of the male sexual response cycle. Four of 6 studies reported increased sexual desire with MDMA use among women. Arousal and lubrication were improved with MDMA use in 3 of 4 studies, but they were not affected in 1 randomized control study. In men, 7 studies evaluated the effects of MDMA on desire and/or arousal, 5 studies measured impact on erection, 3 on orgasm, and 2 on ejaculation. Sixty percent of interview-based studies reported increased sexual desire in men, while 40% reported mixed or no effect. Two studies reported impairment of erection, 2 reported mixed effects, and 1 reported fear of erection impairment. In both men and women, all studies evaluating orgasm reported delay in achieving orgasm but increased intensity and pleasure if achieved. Primary outcome measures were variable and largely qualitative.

Conclusion

Our findings suggest that MDMA generally increases sexual desire and intensifies orgasm when achieved. While producing conflicting evidence on sexual arousal in both sexes, MDMA may impair erectile and ejaculatory function in men.
Characterization of Soybean Events with Enhanced Expression of the Microtubule-Associated Protein 65-1 (MAP65-1)
Authors: Kim Panya , Mahboob Samira , Nguyen Hanh T. , Eastman Samuel , Fiala Olivia , Sousek Matthew , Gaussoin Roch E. , Brungardt Jae L. , Jackson-Ziems Tamra A. , Roston Rebecca , Alfano James R. , Clemente Tom Elmo , Guo Ming
Published: October 2023

Microtubule-associated protein 65-1 (MAP65-1) protein plays an essential role in plant cellular dynamics through impacting stabilization of the cytoskeleton by serving as a crosslinker of microtubules. The role of MAP65-1 in plants has been associated with phenotypic outcomes in response to various environmental stresses. The Arabidopsis MAP65-1 ( AtMAP65-1) is a known virulence target of plant bacterial pathogens and is thus a component of plant immunity. Soybean events were generated that carry transgenic alleles for both AtMAP65-1 and GmMAP65-1, the soybean AtMAP65-1 homolog, under control of cauliflower mosaic virus 35S promoter. Both AtMAP65-1 and GmMAP65-1 transgenic soybeans are more resistant to challenges by the soybean bacterial pathogen Pseudomonas syringae pv. glycinea and the oomycete pathogen Phytophthora sojae, but not the soybean cyst nematode, Heterodera glycines. Soybean plants expressing AtMAP65-1 and GmMAP65-1 also display a tolerance to the herbicide oryzalin, which has a mode of action to destabilize microtubules. In addition, GmMAP65-1-expressing soybean plants show reduced cytosol ion leakage under freezing conditions, hinting that ectopic expression of GmMAP65-1 may enhance cold tolerance in soybean. Taken together, overexpression of AtMAP65-1 and GmMAP65-1 confers tolerance of soybean plants to various biotic and abiotic stresses.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Mitogen-Activated Protein Kinase Hog1 Regulates Fungal Development, Pathogenicity, and Stress Response in Botryosphaeria dothidea
Authors: Zhang Yihan , Zhu Meiqi , Wang Hongna , Yu Guolei , Guo Anqi , Ren Weichao , Li Baohua , Liu Na
Published: October 2023

The high-osmolarity glycerol mitogen-activated protein kinase (HOG-MAPK) pathway plays a central role in environmental stress adaptation in eukaryotes. However, the biological function of the HOG-MAPK pathway varies in different fungi. In this study, we investigated the HOG-MAPK pathway by inactivation of the core element Hog1 in Botryosphaeria dothidea, the causal agent of Botryosphaeria canker and apple ring rot. Targeted deletion of BdHOG1 resulted in the loss of conidiation ability and significant reduction of virulence. In addition, the Δ BdHog1 mutant exhibited hypersensitivity to osmotic stress but resistance to phenylpyrrole and dicarboximide fungicides. Comparative transcriptome analysis revealed that inactivation of BdHog1 influenced multiple metabolic pathways in B. dothidea. Taken together, our results suggest that BdHog1 plays a crucial role in development, virulence, and stress tolerance in B. dothidea, which provides a theoretical basis for the development of target-based fungicides.
Retracted: Methionine‐CBS axis promotes intracellular ROS levels by reprogramming serine metabolism
Authors: Chen Jingyun , Cui Xiangyan , Fang Ning , Wu Yu , Yu Shujian , Xiao Dong
Published: October 2023

As a non‐essential amino acid, cysteine could be obtained through both exogenous uptake and endogenous de novo synthesis pathways. Research has demonstrated that restricting the uptake of cystine could result in a depletion of intracellular cysteine and glutathione, ultimately leading to an increase in intracellular reactive oxygen species (ROS) levels. However, the role of methionine in regulating intracellular ROS levels is currently unclear. Here, we want to explore the role of methionine in regulating intracellular ROS levels. We found that methionine restriction could lead to a decrease in intracellular ROS levels, while supplementation with SAM can restore these levels through flow cytometry. Mechanically, we found that the methionine‐SAM axis relies on CBS when regulating intracellular ROS levels. Furthermore, we speculate and prove that the methionine‐SAM‐CBS axis alters the metabolism of serine, thereby reducing intracellular reductive power, therefore promoting intracellular ROS levels through changing metabolite levels and genetic methods. Finally, our study revealed that high expression of CBS in tumor cells could lead to increased intracellular ROS levels, ultimately resulting in faster proliferation rates. Together, our study confirmed that methionine plays a promoting role in the regulation of intracellular ROS levels.
Fragility of Statistically Significant Outcomes in Colonic Diverticular Disease Randomized Trials: A Systematic Review
Authors: McKechnie Tyler , Yang Shuling , Wu Kathy , Sharma Sahil , Lee Yung , Park Lily , Passos Edward , Doumouras Aristithes , Hong Dennis , Parpia Sameer , Bhandari Mohit , Eskicioglu Cagla
Published: October 2023

BACKGROUND:

The p value has been criticized for an oversimplified determination of whether a treatment effect exists. One alternative is the fragility index. It is a representation of the minimum number of non-events that would need to be converted to events to increase the p value above 0.05.

OBJECTIVE:

To determine the fragility index of randomized controlled trials assessing the efficacy of interventions for patients with diverticular disease since 2010 to assess the robustness of current evidence.

DATA SOURCES:

MEDLINE, Embase, and CENTRAL were searched from inception to August 2022.

STUDY SELECTION:

Articles were eligible for inclusion if they were randomized trials conducted between 2010 and 2022 with parallel, superiority designs evaluating interventions in patients with diverticular disease. Only randomized trials with dichotomous primary outcomes with an associated p-value of less than 0.05 were considered for inclusion.

INTERVENTION(S):

Any surgical or medical intervention for patients with diverticular disease.

MAIN OUTCOME MEASURES:

The fragility index was determined by adding events and subtracting non-events from the groups with the smaller number of events. Events were added until the p-value exceeded 0.05. The smallest number of events required was considered the fragility index.

RESULTS:

After screening 1,271 citations, 15 randomized trials met inclusion criteria. Nine of the studies evaluated surgical interventions and six evaluated medical interventions. The mean number of patients randomized and lost to follow-up per RCT was 92 (SD 35.3) and 9 (SD 11.4), respectively. The median fragility index was 1 (range: 0-5). The fragility indices for the included studies did not correlate significantly with any study characteristics.

LIMITATIONS:

Small sample, heterogeneity, and lack of inclusion of studies with continuous outcomes.

CONCLUSIONS:

The randomized trials evaluating surgical and medical interventions for diverticular disease are not robust. Changing a single outcome event in most studies was sufficient to make a statistically significant study finding non-significant.
Ferroptosis Involved in Cardiovascular Diseases: Mechanism Exploration of Ferroptosis' Role in Common Pathological Changes
Authors: Gao Dongjie , Hu Leilei , Lv Hao , Lian Lu , Wang Mingyang , Fan Xinbiao , Xie Yingyu , Zhang Junping
Published: October 2023

Regulated cell death is a controlled form of cell death that protects cells by adaptive responses in pathophysiological states. Ferroptosis has been identified as a novel method of controlling cell death in recent years. Several cardiovascular diseases (CVDs) are shown to be profoundly influenced by ferroptosis, and ferroptosis is directly linked to the majority of cardiovascular pathological alterations. Despite this, it is still unclear how ferroptosis affects the pathogenic alterations that take place in CVDs. Based on a review of the mechanisms that regulate ferroptosis, this review explores the most recent research on the role of ferroptosis in the major pathological changes associated with CVDs, to provide new perspectives and strategies for cardiovascular research and clinical treatment.