bluuebunny/crossref_metadata_2025 huggingface dataset:
PREHISTORIC BRONZE AGE RADIOCARBON CHRONOLOGY AT POLITIKO-TROULLIA, CYPRUS
Authors: Falconer Steven E , Ridder Elizabeth , Pilaar Birch Suzanne E , Fall Patricia L
Published: January 2023

Politiko-Troullia has generated the largest radiocarbon (14C) dataset from a Prehistoric Bronze Age settlement on Cyprus. We present Bayesian modeling of 25 calibrated AMS ages, which contributes to an emerging multi-site 14C chronology for Cyprus covering most of the Prehistoric Bronze Age. Our analysis places the six stratified phases of occupation at Troullia between about 2050 and 1850 cal BCE, in contrast to a longer estimated occupation inferred from pottery analysis. We provide a rare 14C determination for the transition from Prehistoric Bronze Age 1 to 2 just after 2000 cal BCE, associated with a major architectural dislocation at Politiko-Troullia in response to local landscape erosion, possibly due to increased regional precipitation. We present a regional 14C model for Prehistoric Bronze Age Cyprus combining the chronology for Politiko-Troullia with modeled 14C ages from Sotira Kaminoudhia and Marki Alonia, which is bolstered by individual ages from five other settlements on Cyprus. Through the Prehistoric Bronze Age, agrarian villages on Cyprus developed the foundations for the emergence of urbanized settlement and society during the ensuing Protohistoric Bronze Age. Politiko-Troullia, in conjunction with other key settlements on Cyprus, provides a significant independent contribution to increasingly robust Bronze Age 14C chronologies in the Eastern Mediterranean.
Out of the frying pan and into the fire: effects of volcanic heat and other stressors on the conservation of a critically endangered plant in Hawai‘i
Authors: Gill Nathan S , Stallman Jeffery K , Pratt Linda , Lewicki Jennifer , Elias Tamar , Nadeau Patricia A , Yelenik Stephanie
Published: January 2023

Loss of local biodiversity resulting from abrupt environmental change is a significant environmental problem throughout the world. Extinctions of plants are particularly important yet are often overlooked. Drawing from a case in Hawai‘i, a global hotspot for plant and other extinctions, we demonstrate an effort to better understand and determine priorities for the management of an endangered plant (‘Ihi makole or Portulaca sclerocarpa) in the face of rapid and extreme environmental change. Volcanic heat emissions and biological invasions have anecdotally been suggested as possible threats to the species. We integrated P. sclerocarpa outplanting with efforts to collect geological and ecological data to gauge the role of elevated soil temperatures and invasive grasses in driving P. sclerocarpa mortality and population decline. We measured soil temperature, soil depth, surrounding cover and P. sclerocarpa survivorship over three decades. The abundance of wild P. sclerocarpa decreased by 99.7% from the 1990s to 2021. Only 51% of outplantings persisted through 3–4 years. Binomial regression and structural equation modelling revealed that, among the variables we analysed, high soil temperatures were most strongly associated with population decline. Finding the niche where soil temperatures are low enough to allow P. sclerocarpa survival but high enough to limit other agents of P. sclerocarpa mortality may be necessary to increase population growth of this species.
Neural networks with dimensionality reduction for predicting temperature change due to plastic deformation in a cold rolling simulation
Authors: Hou Chun Kit Jeffery , Behdinan Kamran
Published: January 2023

Cold rolling involves large deformation of the workpiece leading to temperature increase due to plastic deformation. This process is highly nonlinear and leads to large computation times to fully model the process. This paper describes the use of dimension-reduced neural networks (DR-NNs) for predicting temperature changes due to plastic deformation in a two-stage cold rolling process. The main objective of these models is to reduce computational demand, error, and uncertainty in predictions. Material properties, feed velocity, sheet dimensions, and friction models are introduced as inputs for the dimensionality reduction. Different linear and nonlinear dimensionality reduction methods reduce the input space to a smaller set of principal components. The principal components are fed as inputs to the neural networks for predicting the output temperature change. The DR-NNs are compared against a standalone neural network and show improvements in terms of lower computational time and prediction uncertainty.
Risk of parental psychiatric disorders among adolescents with major depressive disorder according to response to antidepressant treatment: does the type of antidepressant matter?
Authors: Tsai Shih-Jen , Hsu Ju-Wei , Huang Kai-Lin , Bai Ya-Mei , Su Tung-Ping , Chen Tzeng-Ji , Chen Mu-Hong
Published: January 2023

Background

The genetic load for major depressive disorder (MDD) may be higher in people who develop MDD earlier in life. This study aimed to investigate whether the parents of adolescents with MDD were more likely to have MDD, bipolar disorder (BD), schizophrenic disorder (SZ), alcohol use disorder, or substance use disorder than the parents of adolescents without MDD. We also examined whether the response to antidepressant treatment predicted the likelihood of parental psychiatric disorders.

Methods

In all, 1,758 adolescents aged 12–19 years with antidepressant-resistant depression, 7,032 (1:4) age-/sex-matched adolescents with antidepressant-responsive depression and 7,032 (1:4) age-/sex-matched controls were included. Parental psychiatric disorders of individuals enrolled were assessed.

Results

The parents of the adolescents with MDD were more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than the parents of the control group. The parents of adolescents who were antidepressant resistant and the mothers of adolescents who were either treatment resistant or treatment responsive were more likely to be diagnosed with a psychiatric disorder.

Discussion

Our study demonstrated that parents of adolescents with MDD may be more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than parents of adolescents without MDD, suggesting the within-disorder transmission and cross-disorder transmission of these psychiatric disorders. Furthermore, the parent’s sex and the response to antidepressant treatment may affect the within-disorder transmission of MDD.
Kant on Despondent Moral Failure
Authors: Moran Kate
Published: January 2023

Typically, Kant describes maxims that violate the moral law as engaging in a kind of comparative judgement: the person who makes a false promise judges it best – at least subjectively – to deceive her friend. I argue that this is not the only possible account of moral failure for Kant. In particular, when we examine maxims of so-called despondency (Verzagtheit) we find that some maxims are resistant to comparative judgement. I argue that this is true for at least two reasons: first, the despondent agent has a maxim to avoid suffering at all costs; second, this anxious preoccupation with suffering makes the despondent agent prone to failures associated with the imagination and its role in creating an ideal of happiness.
Do Male and Female Legislators Have Different Twitter Communication Styles?
Authors: Butler Daniel M. , Kousser Thad , Oklobdzija Stan
Published: January 2023

Communication is a fundamental step in the process of political representation, and an influential stream of research hypothesizes that male and female politicians talk to their constituents in very different ways. To build the broad dataset necessary for this analysis, we harness the massive trove of communication by American politicians through Twitter. We adopt a supervised learning approach that begins with the hand coding of over 10,000 tweets and then use these to train machine learning algorithms to categorize the full corpus of over three million tweets sent by the lower house state legislators who were serving in the summer of 2017. Our results provide insights into politicians’ behavior and the consequence of women’s underrepresentation on what voters learn about legislative activity.
Calling time on the imperial lawn and the imperative for greenhouse gas mitigation
Authors: Gillman Len N. , Bollard Barbara , Leuzinger Sebastian
Published: January 2023

Non-technical summary

As green spaces, lawns are often thought to capture carbon from the atmosphere. However, once mowing, fertlising and irrigation are taken into account, we show that they become carbon sources, at least in the long run. Converting unused urban and rural lawn and grassland to treescapes can make a substantial contribution to reducing greenhouse gas emissions and increasing carbon absorption from the atmosphere. However, it is imperative for governing bodies to put in place appropriate policies and incentives in order to achieve this.

Technical summary

Mown grass or lawn is a ubiquitous form of vegetation in human-dominated landscapes and it is often claimed to perform an ecosystem service by sequestering soil carbon. If lawn maintenance is included, however, we show that lawns become net carbon emitters. We estimate that globally, if one-third of mown grass in cities was returned to treescapes, 310–1630 million tonnes of carbon could be absorbed from the atmosphere, and up to 43 tonnes of carbon equivalent per hectare of emissions could be avoided over a two-decade time span. We therefore propose that local and central governments introduce policies to incentivise and/or regulate the conversion of underutilised grass into treescapes.

Social media summary

If unused lawns were planted with trees, a gigaton of carbon could be removed from the atmosphere over two decades.
Investigations into differential glyphosate sensitivity between two horseweed (Conyza canadensis) growth types
Authors: Fisher Justine L. , Sprague Christy L. , Patterson Eric L. , Schramski John A.
Published: January 2023

Horseweed [Conyza canadensis (L.) Cronquist] grows in one of two distinct growth phenotypes, “rosette” and “upright” growth types, and they have recently been observed co-occurring in Michigan fields. Previous research found that upright plants from two glyphosate-resistant populations were 3- and 4-fold less sensitive to glyphosate than their rosette siblings. Further experiments were conducted to investigate whether differential glyphosate sensitivity of the growth types was due to glyphosate retention, absorption, or translocation. The total amount of glyphosate retained on the C. canadensis leaf surface was similar for both growth types; however, on a per-weight and per-area bases, the upright growth type retained 21% and 18% less glyphosate, respectively. Glyphosate absorption was up to 85% at 168 h after treatment (HAT), and was not different between the rosette and upright growth types or between the susceptible (S) and resistant (R) biotypes. Additionally, there was no difference in translocation between the two growth types within each biotype at any time point. Interestingly, at 168 HAT, [14C]glyphosate translocation was higher in the S rosette compared with the two growth types from the R biotype; however, the S upright type was similar to both R growth types. Thus, glyphosate resistance in the R biotype may be due to an alternative mechanism rather than impaired translocation, which has been cited as the primary mechanism of glyphosate resistance in C. canadensis. These results suggest that reduced glyphosate retention on a per-weight and per-area bases of the upright growth type may contribute to increased glyphosate tolerance due to a diluted concentration of glyphosate in the plant. However, another factor is likely related to the mechanism of resistance within the R biotype, which is contributing to a 3-fold difference in glyphosate sensitivity between the two growth types, such as alterations in EPSPS gene expression or changes in undescribed metabolism genes.
Prediction of the Diurnal Variation of Summertime Precipitation Over the Sichuan Basin by a Regional Model
Authors: Li Juan , Jiang Xingwen , Schiemann Reinhard , Chen Haoming , Li Yueqing , Heng Zhiwei
Published: January 2023

The nocturnal precipitation over the Sichuan Basin (SCB) exhibits obvious spatial variation, most of the existing numerical research of precipitation event over the SCB is based on case studies. In this study, the long‐term climatological evaluation of the prediction of diurnal spatio‐temporal evolution of precipitation and relevant physical mechanism over the SCB by 9 and 3 km operational numerical weather prediction model is carried out. It is found that the SWC‐WARMS model with 9 km grid spacing overestimates the summer precipitation, especially over the western slopes of the SCB. The northeastward timing delay of the precipitation peak over the SCB is well reproduced in the model, with predicted precipitation peaking at midnight over the southwestern SCB and in the early morning over the northeastern SCB. However, the predicted diurnal peak of precipitation appears 2–3 hr earlier than the observed peak. Increasing horizontal resolution to 3 km reduces the wet bias and improves the diurnal phase of precipitation. Compared to reanalysis, the predicted easterly anomalous wind appears earlier and the anomalous wind speed is stronger. Moreover, the predicted atmosphere is too unstable, which is associated with “warm below and cold above” vertical biases in temperature and wet biases in specific humidity. Thus, model precipitation peaks too early in the day over the SCB, and is overestimated. The weakening of the predicted southwesterly flow in the middle troposphere weakens the northeastward propagation of precipitation after midnight over the SCB. The most significant improvements are found for the diurnal variation of low‐level anomalous wind speed in the 3 km resolution model, contributing to a more realistic representation of precipitation over the SCB.
A Compact Passive Quad‐Band Negative Group Delay Circuit With Stepped Impedance Resonator and Defected Microstrip Structure
Authors: Zhang Li , Yang Shuhui , Guo Qingxin , Xiao Huaibao , Wang Ling , Li Bin , Zhang Hui
Published: January 2023

Based on two‐stage stepped impedance resonator (SIR) and defected microstrip structure (DMS) with an E‐shaped slot, a novel compact passive quad‐band negative group delay circuit (NGDC) is proposed whose resonation frequencies and group delay performance are mainly determined by the SIR and the DMS. In order to help reveal the working mechanism of the quad‐band NGDC, an equivalent circuit of the NGDC is developed. It is composed of the transmission lines and serial‐parallel LC networks, and its S‐parameters are derived by using the theory of transmission matrix. The theoretical and simulated results for the transmission characteristics of the NGDC agree well with each other. To validate the design concept, a prototype of the proposed quad‐band NGDC was fabricated and measured. The measured results show that at the frequencies of 2.64, 7.88, 13.08, and 18.18 GHz, the negative group delay values achieve −5.4, −3.1, −1.18, and −1.14 ns, with |S21| values of −17.2, −20.5, −12.8, and −18.1 dB, respectively. Compared with the recently reported works, the proposed NGDC exhibits the largest number of operation frequency bands. Furthermore, it does not use lumped resistors and has miniaturized dimension.
Systems Biology Graphical Notation: Process Description language Level 1
Authors: Moodie Stuart , Le Novere Nicolas , Demir Emek , Mi Huaiyu , Schreiber Falk
Published: January 2023

Standard graphical representations have played a crucial role in science and engineering throughout the last century. Without electrical symbolism, it is very likely that our industrial society would not have evolved at the same pace. Similarly, specialized notations such as the Feynmann notation or the process flow diagrams did a lot for the adoption of concepts in their own fields. With the advent of Systems Biology, and more recently of Synthetic Biology, the need for precise and unambiguous descriptions of biochemical interactions has become more pressing. While some ideas have been advanced over the last decade, with a few detailed proposals, no actual community standard has emerged. The Systems Biology Graphical Notation (SBGN) is a graphical representation crafted over several years by a community of biochemists, modellers and computer scientists. Three orthogonal and complementary languages have been created, the Process Diagrams, the Entity Relationship Diagrams and the Activity Flow Diagrams. Using these three idioms a scientist can represent any network of biochemical interactions, which can then be interpreted in an unambiguous way. The set of symbols used is limited, and the grammar quite simple, to allow its usage in textbooks and its teaching directly in high schools. The first level of the SBGN Process Diagram has been publicly released. Software support for SBGN Process Diagram was developed concurrently with its specification in order to speed-up public adoption. Shared by the communities of biochemists, genomicians, theoreticians and computational biologists, SBGN languages will foster efficient storage, exchange and reuse of information on signalling pathways, metabolic networks and gene regulatory maps.
PathExpand: Extending biological pathways using molecular interaction networks
Authors: Glaab Enrico , Baudot Anais , Krasnogor Natalio , Valencia Alfonso
Published: January 2023

We present a methodology for extending pre-defined protein sets representing cellular pathways and processes by mapping them onto a protein-protein interaction network, and extending them to include densely interconnected interaction partners. The added proteins display distinctive network topological features and molecular function annotations, and can be proposed as putative new components, and/or as regulators of the communication between the different cellular processes. Finally, these extended pathways and processes are used to analyze their enrichment in cancer mutated genes. Significant associations between mutated genes and certain processes are identified, enabling an analysis of the influence of previously non-annotated cancer mutated genes.
Maximizing decision rate in multisensory integration
Authors: Drugowitsch Jan , Pouget Alexandre , DeAngelis Gregory , Angelaki Dora
Published: January 2023

Effective decision-making in an uncertain world requires making use of all available information, even if distributed across different sensory modalities, as well as trading off the speed of a decision with its accuracy. In tasks with a fixed stimulus presentation time, animal and human subjects have previously been shown to combine information from several modalities in a statistically optimal manner. Furthermore, for easily discriminable stimuli and under the assumption that reaction times result from a race-to-threshold mechanism, multimodal reaction times are typically faster than predicted from unimodal conditions when assuming independent (parallel) races for each modality. However, due to a lack of adequate ideal observer models, it has remained unclear whether subjects perform optimal cue combination when they are allowed to choose their response times freely.Based on data collected from human subjects performing a visual/vestibular heading discrimination task, we show that the subjects exhibit worse discrimination performance in the multimodal condition than predicted by standard cue combination criteria, which relate multimodal discrimination performance to sensitivity in the unimodal conditions. Furthermore, multimodal reaction times are slower than those predicted by a parallel race model, opposite to what is commonly observed for easily discriminable stimuli.Despite violating the standard criteria for optimal cue combination, we show that subjects still accumulate evidence optimally across time and cues, even when the strength of the evidence varies with time. Additionally, subjects adjust their decision bounds, controlling the trade-off between speed and accuracy of a decision, such that they feature correct decision rates close to the maximum achievable value.
Histone deacetylase inhibitors promote breast cancer metastasis by elevating NEDD9 expression
Authors: Hu Zonglong , Wei Fan , Su Yi , Wang Yafang , Shen Yanyan , Fang Yanfen , Ding Jian , Chen Yi
Published: January 2023

Histone deacetylase (HDAC) is a kind of protease that modifies histone to regulate gene expression, and is usually abnormally activated in tumors. The approved pan-HDAC inhibitors have demonstrated clinical benefits for patients in some hematologic malignancies. Only limited therapeutic success in breast cancer has been observed in clinical trials. In this study, we declare that pan-HDAC inhibitors targeting NEDD9-FAK pathway exacerbate breast cancer metastasis in preclinical models, which may severely impede their clinical success. NEDD9 is not an oncogene, however, it has been demonstrated recently that there are high level or activity changes of NEDD9 in a variety of cancer, including leukemia, colon cancer, and breast cancer. Mechanistically, pan-HDAC inhibitors enhance H3K9 acetylation at the nedd9 gene promoter via inhibition of HDAC4 activity, thus increase NEDD9 expression, and then activate FAK phosphorylation. The realization that pan-HDAC inhibitors can alter the natural history of breast cancer by increasing invasion warrants clinical attention. In addition, although NEDD9 has been reported to have a hand in breast cancer metastasis, it has not received much attention, and no therapeutic strategies have been developed. Notably, we demonstrate that FAK inhibitors can reverse breast cancer metastasis induced by upregulation of NEDD9 via pan-HDAC inhibitors, which may offer a potential combination therapy for breast cancer.
COVID-19-associated monocytic encephalitis (CAME): histological and proteomic evidence from autopsy
Authors: Zhang Pei-Pei , He Zhi-Cheng , Yao Xiao-Hong , Tang Rui , Ma Jie , Luo Tao , Zhu Chuhong , Li Tian-Ran , Liu Xindong , Zhang Dingyu , Zhang Shuyang , Ping Yi-Fang , Leng Ling , Bian Xiu-Wu
Published: January 2023

Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages and infiltrating inflammatory cells were quantitatively evaluated by immunohistochemical staining, ultrastructural examination under electron microscopy, and an image threshold method, in postmortem brains from nine critically ill COVID-19 patients and nine age-matched cadavers of healthy individuals. Differentially expressed proteins were identified by quantitative proteomic assays. Histopathological findings included neurophagocytosis, microglia nodules, satellite phenomena, extensive edema, focal hemorrhage, and infarction, as well as infiltrating mononuclear cells. Immunostaining of COVID-19 brains revealed extensive activation of both microglia and astrocytes, severe damage of the blood–brain barrier (BBB) and various degrees of perivascular infiltration by predominantly CD14+/CD16+/CD141+/CCR7+/CD11c+ monocytes and occasionally CD4+/CD8+ T lymphocytes. Quantitative proteomic assays combined with bioinformatics analysis identified upregulated proteins predominantly involved in immune responses, autophagy and cellular metabolism in COVID-19 patient brains compared with control brains. Proteins involved in brain development, neuroprotection, and extracellular matrix proteins of the basement membrane were downregulated, potentially caused by the activation of transforming growth factor β receptor and vascular endothelial growth factor signaling pathways. Thus, our results define histopathological and molecular profiles of COVID-19-associated monocytic encephalitis (CAME) and suggest potential therapeutic targets.
Impaired belief updating and devaluation in adult women with bulimia nervosa
Authors: Berner Laura A. , Fiore Vincenzo G. , Chen Joanna Y. , Krueger Angeline , Kaye Walter H. , Viranda Thalia , de Wit Sanne
Published: January 2023

Recent models of bulimia nervosa (BN) propose that binge-purge episodes ultimately become automatic in response to cues and insensitive to negative outcomes. Here, we examined whether women with BN show alterations in instrumental learning and devaluation sensitivity using traditional and computational modeling analyses of behavioral data. Adult women with BN (n = 30) and group-matched healthy controls (n = 31) completed a task in which they first learned stimulus-response-outcome associations. Then, participants were required to repeatedly adjust their responses in a “baseline test”, when different sets of stimuli were explicitly devalued, and in a “slips-of-action test”, when outcomes instead of stimuli were devalued. The BN group showed intact behavioral sensitivity to outcome devaluation during the slips-of-action test, but showed difficulty overriding previously learned stimulus-response associations on the baseline test. Results from a Bayesian learner model indicated that this impaired performance could be accounted for by a slower pace of belief updating when a new set of previously learned responses had to be inhibited (p = 0.036). Worse performance and a slower belief update in the baseline test were each associated with more frequent binge eating (p = 0.012) and purging (p = 0.002). Our findings suggest that BN diagnosis and severity are associated with deficits in flexibly updating beliefs to withhold previously learned responses to cues. Additional research is needed to determine whether this impaired ability to adjust behavior is responsible for maintaining automatic and persistent binge eating and purging in response to internal and environmental cues.
Interactions between perceived stress and microbial-host immune components: two demographically and geographically distinct pregnancy cohorts
Authors: Peñalver Bernabé Beatriz , Maki Pauline M. , Cunningham Janet L. , Eisenlohr-Moul Tory , Tussing-Humphreys Lisa , Carroll Ian M. , Meltzer-Brody Samantha , Gilbert Jack A. , Kimmel Mary
Published: January 2023

Higher stress during pregnancy associates with negative outcomes and elevated inflammation. The gut microbiota, reflecting environment and social interactions, alongside host immune responses have the potential to better understand perceived stress and identify when stress is excessive in pregnancy. Two U.S. cohorts of 84 pregnant individuals, composed of urban women of color and suburban white women, completed the Perceived Stress Scale-10 (PSS-10) and provided fecal and blood samples at two time points. Confirmatory Factor Analysis assessed the robustness of a two-factor PSS-10 model (Emotional Distress/ED and Self-Efficacy/SE). Gut microbiota composition was measured by 16 S rRNA amplicon sequencing and the immune system activity was assessed with a panel of 21 T-cell related cytokines and chemokines. ED levels were higher in the suburban compared to the urban cohort, but levels of SE were similar. ED and SE levels were associated with distinct taxonomical signatures and the gut microbiota data improved the prediction of SE levels compared with models based on socio-demographic characteristics alone. Integration of self-reported symptoms, microbial and immune information revealed a possible mediation effect ofBacteroides uniformisbetween the immune system (through CXCL11) and SE. The study identified links between distinct taxonomical and immunological signatures with perceived stress. The data are congruent with a model where gut microbiome and immune factors, both impacting and reflecting factors such as close social relationships and dietary fiber, may modulate neural plasticity resulting in increased SE during pregnancy. The predictive value of these peripheral markers merit further study.
A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1
Authors: Yuan Shuai , He Shao-Hua , Li Lu-Yao , Xi Shu , Weng Hong , Zhang Jin-Hui , Wang Dan-Qi , Guo Meng-Meng , Zhang Haozhe , Wang Shuang-Ying , Ming Dao-Jing , Liu Meng-Yang , Hu Hailiang , Zeng Xian-Tao
Published: January 2023

SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer through the N6-methyladenosine (m6A) reader YTHDC1 and the transcription factor HOXB13. We have shown that the level of SLC12A5 was increased in prostate cancer, in comparison to its normal counterparts, and further elevated in castration-resistant prostate cancer (CRPC). The enhanced expression of SLC12A5 mRNA was associated with neuroendocrine prostate cancer (NEPC) progression and poor survival in prostate cancer. Furthermore, we demonstrated that SLC12A5 promoted the castration resistance development of prostate cancer in addition to the cell proliferation and migration. Interestingly, SLC12A5 was detected in the cell nucleus and formed a complex with nuclear m6A reader YTHDC1, which in turn upregulated HOXB13 to promote the prostate cancer progression. Therefore, our findings reveal a mechanism that how the potassium-chloride cotransporter SLC12A5 promotes the tumor progression and provide a therapeutic opportunity for prostate cancer to apply the neurological disorder drug SLC12A5 inhibitors.
Illustrating new understanding of adsorbed water on silica for inducing tetrahedral cobalt(II) for propane dehydrogenation
Authors: Huang Zijun , He Dedong , Deng Weihua , Jin Guowu , Li Ke , Luo Yongming
Published: January 2023

Highly dispersed metal sites on the surface of silica, achieved from immobilization of metal precursor within hydroxyl groups, has gained increasing attention in the field of heterogeneous catalyst. However, the special role of adsorbed water derived by hydroxyl groups on the silica is generally ignored. Herein, a new understanding of adsorbed water on the formation of highly dispersed tetrahedral Co(II) (Td-cobalt(II)) sites is illustrated. It is indicated that sufficient adsorbed water induces the transformation of precursor of Co(NO3)2 into intermediate of [Co(H2O)6]2+. Subsequently, [Co(H2O)6]2+ makes the highly dispersed Td-cobalt(II) sites to be available during direct H2-reduction process. A systematic characterization and DFT calculation prove the existence of the adsorbed water and the importance of the intermediate of [Co(H2O)6]2+, respectively. The as-synthesized catalyst is attempted to the propane dehydrogenation, which shows better reactivity when compared with other reported Co based catalysts.
A phase II study of palbociclib plus letrozole plus trastuzumab as neoadjuvant treatment for clinical stages II and III ER+ HER2+ breast cancer (PALTAN)
Authors: Ademuyiwa Foluso O. , Northfelt Donald W. , O’Connor Tracey , Levine Ellis , Luo Jingqin , Tao Yu , Hoog Jeremy , Laury Marie L. , Summa Tracy , Hammerschmidt Trish , Guo Zhanfang , Frith Ashley , Weilbaecher Katherine , Opyrchal Mateusz , Aft Rebecca , Clifton Katherine , Suresh Rama , Bagegni Nusayba , Hagemann Ian S. , Iglesia Michael D. , Ma Cynthia X.
Published: January 2023

Patients with ER+/HER2+ breast cancer (BC) are less likely to achieve pathological complete response (pCR) after chemotherapy with dual HER2 blockade than ER−/HER2+ BC. Endocrine therapy plus trastuzumab is effective in advanced ER+/HER2+ BC. Inhibition of CDK4/6 and HER2 results in synergistic cell proliferation reduction. We combined palbociclib, letrozole, and trastuzumab (PLT) as a chemotherapy-sparing regimen. We evaluated neoadjuvant PLT in early ER+/HER2+ BC. Primary endpoint was pCR after 16 weeks. Research biopsies were performed for whole exome and RNA sequencing, PAM50 subtyping, and Ki67 assessment for complete cell cycle arrest (CCCA: Ki67 ≤ 2.7%). After 26 patients, accrual stopped due to futility. pCR (residual cancer burden—RCB 0) was 7.7%, RCB 0/I was 38.5%. Grade (G) 3/4 treatment-emergent adverse events occurred in 19. Among these, G3/4 neutropenia was 50%, hypertension 26.9%, and leucopenia 7.7%. Analysis indicated CCCA in 85% at C1 day 15 (C1D15), compared to 27% at surgery after palbociclib was discontinued. Baseline PAM50 subtyping identified 31.2% HER2-E, 43.8% Luminal B, and 25% Luminal A. 161 genes were differentially expressed comparing C1D15 to baseline. MKI67, TK1, CCNB1, AURKB, and PLK1 were among the genes downregulated, consistent with CCCA at C1D15. Molecular Signatures Database gene-sets analyses demonstrated downregulated processes involved in proliferation, ER and mTORC1 signaling, and DNA damage repair at C1D15, consistent with the study drug’s mechanisms of action. Neoadjuvant PLT showed a pCR of 7.7% and an RCB 0/I rate of 38.5%. RNA sequencing and Ki67 data indicated potent anti-proliferative effects of study treatments. ClinicalTrials.gov- NCT02907918.
Anagen hair follicles transplanted into mature human scars remodel fibrotic tissue
Authors: Plotczyk Magdalena , Jiménez Francisco , Limbu Summik , Boyle Colin J. , Ovia Jesse , Almquist Benjamin D. , Higgins Claire A.
Published: January 2023

Despite the substantial impact of skin scarring on patients and the healthcare system, there is a lack of strategies to prevent scar formation, let alone methods to remodel mature scars. Here, we took a unique approach inspired by how healthy hairbearing skin undergoes physiological remodelling during the regular cycling of hair follicles. In this pilot clinical study, we tested if hair follicles transplanted into human scars can facilitate tissue regeneration and actively remodel fibrotic tissue, similar to how they remodel the healthy skin. We collected full-thickness skin biopsies and compared the morphology and transcriptional signature of fibrotic tissue before and after transplantation. We found that hair follicle tranplantation induced an increase in the epidermal thickness, interdigitation of the epidermal-dermal junction, dermal cell density, and blood vessel density. Remodelling of collagen type I fibres reduced the total collagen fraction, the proportion of thick fibres, and their alignment. Consistent with these morphological changes, we found a shift in the cytokine milieu of scars with a long-lasting inhibition of pro-fibrotic factors TGFβ1, IL13, and IL-6. Our results show that anagen hair follicles can attenuate the fibrotic phenotype, providing new insights for developing regenerative approaches to remodel mature scars.
Entering into a self-regulated learning mode prevents detrimental effects of feedback removal on memory
Authors: Vavra Peter , Sokolovič Leo , Porcu Emanuele , Ripollés Pablo , Rodriguez-Fornells Antoni , Noesselt Toemme
Published: January 2023

Incentives can decrease performance by undermining intrinsic motivation. How such an interplay of external reinforcers and internal self-regulation influences memory processes, however, is less known. Here, we investigated their interaction on memory performance while learning the meaning of new-words from their context. Specifically, participants inferred congruent meanings of new-words from semantic context (congruent trials) or lack of congruence (incongruent trials), while receiving external feedback in the first or second half of trials only. Removing feedback during learning of congruent word meanings lowered subsequent recognition rates a day later, whereas recognition remained high in the group, which received feedback only in the second half. In contrast, feedback did not substantially alter recognition rates for learning that new-words had no congruent meanings. Our findings suggest that external reinforcers can selectively impair memories if internal self-regulated processes are not already established, but whether they do so depends on what is being learned (specific word-meanings vs. unspecific incongruence). This highlights the relevance of self-regulated learning in education to support stable memory formation.
RePP Africa – a georeferenced and curated database on existing and proposed wind, solar, and hydropower plants
Authors: Peters Rebecca , Berlekamp Jürgen , Tockner Klement , Zarfl Christiane
Published: January 2023

Promoting a transition to low-carbon energy systems to mitigate climate change requires an optimization of renewable energy (RE) planning. However, curated data for the most promising RE technologies, hydro-, wind and solar power, are missing, which limits data-based decision-making support. Here, a spatially explicit database for existing and proposed renewable power plants is provided: The Renewable Power Plant database for Africa (RePP Africa) encompasses 1074 hydro-, 1128 solar, and 276 wind power plant records. For each power plant, geographic coordinates, country, construction status, and capacity (in megawatt) are reported. The number of RePP Africa records exceeds the respective values in other existing open-access databases and matches available cumulative capacity data reported by international energy organizations best with deviations <13% for hydro-, <23% for wind, and <32% for solar power plants. This contemporary database is the most harmonized open-accessible reference source on RE power plants across Africa for stakeholders from science, (non-)governmental organizations, consulting, and industry; providing a fundamental data basis for the development of an integrated sustainable RE mix.
Impact of albuminuria on the various causes of death in diabetic patients: a nationwide population-based study
Authors: Cho Semin , Huh Hyuk , Park Sehoon , Lee Soojin , Jung Sehyun , Kim Minsang , Lee Kyu-na , Paek Jin Hyuk , Park Woo Yeong , Jin Kyubok , Han Seungyeup , Joo Kwon Wook , Lim Chun Soo , Kim Yon Su , Han Kyungdo , Kim Yaerim , Kim Dong Ki
Published: January 2023

Diabetes mellitus (DM) is a well-known risk factor for mortality, and the risk is exacerbated by coexisting diabetic kidney disease (DKD). We aimed to explore the impact of DM on each cause of mortality according to kidney function and the presence of albuminuria. Data on subjects with DM were extracted from the Nationwide Health Insurance Database of South Korea between 2009 and 2012. Subjects were divided by eGFR and albuminuria into five groups. To evaluate the risk of diabetes, we used the Cox proportional hazards model. A total of 2,614,662 patients were enrolled in this study. Most causes of death showed a higher incidence in an advanced stage of DKD. In addition to all-cause mortality and cardiovascular death, the risk of death from neoplasms and diseases of the endocrine, respiratory, and digestive systems is increased by albuminuria. The synergistic effect of a reduced eGFR and the presence of albuminuria was prominent in death from circulatory diseases, and endocrine and metabolic diseases. The risk for mortality was different according to the stage of DKD. Even in patients with a favorable eGFR, the presence of albuminuria significantly increased the risk for mortality, especially that due to cardiovascular causes.
Healthcare workers’ mental health and perception towards vaccination during COVID-19 pandemic in a Pediatric Cancer Hospital
Authors: Alalawi Mai , Makhlouf Mohamad , Hassanain Omnya , Abdelgawad Ahmed A. , Nagy Mohamed
Published: January 2023

The consistent increase of Coronavirus disease 2019 (COVID-19) cases parallel with the rate of deaths and the controversial response regarding the vaccines caused an increase in the burden of psychological diseases. This study aimed to evaluate the psychological condition of healthcare workers (HCWs) in a pediatric cancer hospital and to identify the knowledge, attitude, and perception (KAP) of HCWs toward COVID-19 vaccination. A cross-sectional observational study was conducted between April to May 2021. A validated, confidential survey was employed to measure the mental health of HCWs and the KAP toward COVID-19 vaccines. The total responses were 395, of which 11.4% physicians, 18.5% pharmacists, and 70.1% were nurses. Sixty-six percent of HCWs had different degrees of anxiety and depression. Nurses significantly accounted for the highest anxiety levels (P = 0.003), while the cumulative anxiety score was significantly higher in HCWs who had a positive history of COVID-19 infection (P = 0.026). Although 67.6% of HCWs believe that “vaccines are essential for us,”, the vaccination rate was 21.3%. The Factors associated with not receiving the vaccine were younger ages (P = 0.014), nurses (P = 3.6987 × 10–7), negative history of COVID-19 infection (P = 0.043) and believing that infections can happen after taking the vaccine (P = 1.5833 × 10–7). Healthcare organizations must take serious intervention to decrease the mental load on HCWs and facilitate the vaccination process.
Genetically-predicted placental gene expression is associated with birthweight and adult body mass index
Authors: Jasper Elizabeth A. , Hellwege Jacklyn N. , Piekos Jacqueline A. , Jones Sarah H. , Hartmann Katherine E. , Mautz Brian , Aronoff David M. , Edwards Todd L. , Edwards Digna R. Velez
Published: January 2023

The placenta is critical to human growth and development and has been implicated in health outcomes. Understanding the mechanisms through which the placenta influences perinatal and later-life outcomes requires further investigation. We evaluated the relationships between birthweight and adult body mass index (BMI) and genetically-predicted gene expression in human placenta. Birthweight genome-wide association summary statistics were obtained from the Early Growth Genetics Consortium (N = 298,142). Adult BMI summary statistics were obtained from the GIANT consortium (N = 681,275). We used S-PrediXcan to evaluate associations between the outcomes and predicted gene expression in placental tissue and, to identify genes where placental expression was exclusively associated with the outcomes, compared to 48 other tissues (GTEx v7). We identified 24 genes where predicted placental expression was significantly associated with birthweight, 15 of which were not associated with birthweight in any other tissue. One of these genes has been previously linked to birthweight. Analyses identified 182 genes where placental expression was associated with adult BMI, 110 were not associated with BMI in any other tissue. Eleven genes that had placental gene expression levels exclusively associated with BMI have been previously associated with BMI. Expression of a single gene, PAX4, was associated with both outcomes exclusively in the placenta. Inter-individual variation of gene expression in placental tissue may contribute to observed variation in birthweight and adult BMI, supporting developmental origins hypothesis.
Immunogenicity of a secreted, C-terminally truncated, form of bovine viral diarrhea virus E2 glycoprotein as a potential candidate in subunit vaccine development
Authors: Lo Yi Ting , Ryan Martin D. , Luke Garry A. , Chang Wan Chen , Wu Hsing Chieh
Published: January 2023

Both current live, attenuated, and killed virus vaccines for bovine viral diarrhea virus (BVDV) have their limitations. Here, we report the development of a BVDV subunit vaccine by (i) the expression of a secreted form of a recombinant E2 glycoprotein using BHK21 cells and (ii) determination of the immune responses in mice. The E2 glycoprotein was modified by deletion of the C-terminal transmembrane anchor domain and fusion to a V5 epitope tag. This allowed detection using anti-V5 monoclonal antibodies together with simple purification of the expressed, secreted, form of E2 from the cell media. Furthermore, we genetically fused green fluorescent protein (GFP) linked to E2 via a Thosea asigna virus 2A (T2A) ribosome skipping sequence thereby creating a self-processing polyprotein [GFP-T2A-BVDV-E2trunk-V5], producing discrete [GFP-T2A] and [E2trunk-V5] translation products: GFP fluorescence acts, therefore, as a surrogate marker of E2 expression, BALB/c mice were inoculated with [E2trunk-V5] purified from cell media and both humoral and cellular immune responses were observed. Our antigen expression system provides, therefore, both (i) a simple antigen purification protocol together with (ii) a feasible strategy for further, large-scale, production of vaccines.
Carbohydrate digestive enzyme inhibition, hepatoprotective, antioxidant and antidiabetic benefits of Persea americana
Authors: Ehikioya Christian Omonzokpea , Osagie Aishat Mary , Omage Sylvia Oghogho , Omage Kingsley , Azeke Marshall Arebojie
Published: January 2023

The medicinal use of Persea americana in the treatment of some diseases like hypertension, diabetes, is often with dearth of supporting scientific proof. Thus, we evaluated its ethnomedicinal benefits for possible scientific justification. Thirty healthy Wistar rats were randomly grouped in fives. Alloxan was used to induce diabetes in the rats in groups II to VI. The diabetic rats in group II were treated with glibenclamide, while those in group III were not treated. Also, the diabetic rats in groups IV to VI were treated with the ethanol extracts of the stem bark, leaf, and root of P. americana respectively. The parts of P. americana comparatively possess highest amounts of phenols (250.50 ± 0.68—bark), saponin (436.80 ± 3.76—leaf), flavonoid (382.80 ± 0.67—leaf) and tannins (58.34 ± 0.09—root). The extracts exhibited high reducing property (FRAP and total reducing), as well as high ABTS and DPPH free radical scavenging ability. The enzyme (alpha-glycosidase and alpha-amylase) inhibitory activity of P. americana increases with increasing concentration of the extracts. Administration of methanol extracts of P. americana bark, leaf and root to alloxan-induced diabetic rats resulted in significant (P < 0.05) decreases in AST, ALP, ALT, Total bilirubin, LPO, plasma glucose and significant (P < 0.05) increases in GSH, CAT and SOD. These effects were like that of glibenclamide. The enzyme inhibitory, hepatoprotective, antioxidant and antidiabetic properties of P. americana are some of the benefits derived from its consumption and ethnomedicinal use.
Multimodal imaging of cubic Cu2O@Au nanocage formation via galvanic replacement using X-ray ptychography and nano diffraction
Authors: Grote Lukas , Hussak Sarah-Alexandra , Albers Leif , Stachnik Karolina , Mancini Federica , Seyrich Martin , Vasylieva Olga , Brückner Dennis , Lyubomirskiy Mikhail , Schroer Christian G. , Koziej Dorota
Published: January 2023

Being able to observe the formation of multi-material nanostructures in situ, simultaneously from a morphological and crystallographic perspective, is a challenging task. Yet, this is essential for the fabrication of nanomaterials with well-controlled composition exposing the most active crystallographic surfaces, as required for highly active catalysts in energy applications. To demonstrate how X-ray ptychography can be combined with scanning nanoprobe diffraction to realize multimodal imaging, we study growing Cu2O nanocubes and their transformation into Au nanocages. During the growth of nanocubes at a temperature of 138 °C, we measure the crystal structure of an individual nanoparticle and determine the presence of (100) crystallographic facets at its surface. We subsequently visualize the transformation of Cu2O into Au nanocages by galvanic replacement. The nanocubes interior homogeneously dissolves while smaller Au particles grow on their surface and later coalesce to form porous nanocages. We finally determine the amount of radiation damage making use of the quantitative phase images. We find that both the total surface dose as well as the dose rate imparted by the X-ray beam trigger additional deposition of Au onto the nanocages. Our multimodal approach can benefit in-solution imaging of multi-material nanostructures in many related fields.