bluuebunny/crossref_metadata_2025_split huggingface dataset:
p70S6K/Akt dual inhibitor DIACC3010 is efficacious in preclinical models of gastric cancer alone and in combination with trastuzumab
Authors: Fukuoka Shota , Koga Yoshikatsu , Yamauchi Mayumi , Koganemaru Shigehiro , Yasunaga Masahiro , Shitara Kohei , Doi Toshihiko , Yoshino Takayuki , Kuronita Toshio , Elenbaas Brian , Wahra Pamela , Zhang Hong , Crowley Lindsey , Jenkins Molly H. , Clark Anderson , Kojima Takashi 
Published: September 2023

AbstractThe PI3K-Akt-mTOR (PAM) pathway is implicated in tumor progression in many tumor types, including metastatic gastric cancer (GC). The initial promise of PAM inhibitors has been unrealized in the clinic, presumably due, in part, to the up-regulation of Akt signaling that occurs when the pathway is inhibited. Here we present that DIACC3010 (formerly M2698), an inhibitor of two nodes in the PAM pathway, p70S6K and Akt 1/3, blocks the pathway in in vitro and in vivo preclinical models of GC while providing a mechanism that inhibits signaling from subsequent Akt up-regulation. Utilizing GC cell lines and xenograft models, we identified potential markers of DIACC3010-sensitivity in Her2-negative tumors, i.e., PIK3CA mutations, low basal pERK, and a group of differentially expressed genes (DEGs). The combination of DIACC3010 and trastuzumab was evaluated in Her2-positive cell lines and models. Potential biomarkers for the synergistic efficacy of the combination of DIACC3010 + trastuzumab also included DEGs as well as a lack of up-regulation of pERK. Of 27 GC patient-derived xenograft (PDX) models tested in BALB/c nu/nu mice, 59% were sensitive to DIACC3010 + trastuzumab. Of the 21 HER2-negative PDX models, DIACC3010 significantly inhibited the growth of 38%. Altogether, these results provide a path forward to validate the potential biomarkers of DIACC3010 sensitivity in GC and support clinical evaluation of DIACC3010 monotherapy and combination with trastuzumab in patients with HER2- negative and positive advanced GCs, respectively.
Thermal performance evaluation of bio-bricks and conventional bricks in residential buildings in Aswan city, Egypt
Authors: Abd El-Hady Rania Emad , Mohamed Abdelaziz Farouk A. 
Published: September 2023

AbstractFrom raw material extraction to final product disposal, the construction industry is integrally involved in every stage of the greenhouse gas emissions life cycle. One of the main causes of the climate catastrophe is the increasing use of polluting energy sources to power our homes and businesses. This massive problem of global warming has now forced countries to act. To further address sustainability, they seek to reduce energy consumption and CO2 emissions by adopting more sustainable materials. The current trend in scientific research is to use waste resources to improve the properties of various materials to exacerbate the problems of climate change because of the use of traditional building materials. Therefore, one of the most environmentally friendly alternatives to the standard procedure is the use of agricultural residues to improve the quality of building materials. This improvement will modify the thermal properties of building materials such as bricks, which will lead to an improvement in energy efficiency inside buildings, especially residential buildings. As a result, the research focused solely on simulating several bio-brick alternatives that had been discovered in earlier studies in order to test their viability in terms of increasing the energy efficiency of residential buildings in one of the hot cities. The study demonstrated that using bio-building materials can lower energy usage. In addition to saving energy in residential constructions, rice straw cement bricks and sugarcane bricks have operating efficiency rates of roughly 7% and 12%, respectively. All these advancements over conventional brick reduce greenhouse gas emissions and carbon dioxide.
New onset diabetes mellitus and cardiovascular outcomes according to statin intensity in patients after drug-eluting stent implantation in Asian patients
Authors: Chung Jaehoon , Kim Hack-Lyoung , Lim Woo-Hyun , Seo Jae-Bing , Zo Joo-Heeg , Kim Myung-A , Kim Sang-Hyun 
Published: September 2023

AbstractWe investigated the effect of statin intensity on the development of new onset diabetes mellitus (NODM) in Korean patients after percutaneous coronary intervention (PCI). A total of 1013 consecutive patients without diabetes mellitus were retrospectively analyzed. All study patients received high- or moderate-intensity statin (high-intensity statin; 321 [31.7%], moderate-intensity statin; 692 [68.3%]). The primary endpoint was development of NODM, and the secondary one was the composite of cardiac death, non-fatal myocardial infarction, and any revascularization. In 264 pairs (528 patients) of propensity score-matched patient, NODM developed in 34 patients (6.4%) and composite cardiac events occurred in 73 patients (13.8%) during a median follow-up of 36.7 months. The incidence rate of NODM was significantly higher in patients with high-intensity statin than with moderate-intensity statin (8.3% vs. 4.5%, log-rank P = 0.026). The incidence rate of composite events was not significantly different between the two groups (12.5% vs.15.2%, log-rank P = 0.495). The use of high-intensity statins was associated with NODM after adjustment for multiple risk factors (adjusted hazard ratio, 2.18, 95% confidence interval 1.10‒4.51, P = 0.025). High-intensity statin therapy is associated with a higher incidence of NODM, but not with better cardiovascular outcomes, in Korean patients undergoing PCI. A new cholesterol lowering intensity-based approach rather than stain intensity-based approach to the high-risk patients without diabetes mellitus may be helpful in maximal treatment effect without safety concern of NODM in Asian patients.
Strong and aversive cold processing and pain facilitation in fibromyalgia patients relates to augmented thermal grill illusion
Authors: Bäumler Petra , Brenske Anna , Winkelmann Andreas , Irnich Dominik , Averbeck Beate 
Published: September 2023

AbstractThe thermal grill illusion (TGI) is assumed to result from crosstalk between the thermoreceptive and nociceptive pathways. To elucidate this further, we compared 40 female fibromyalgia patients to 20 healthy women in an exploratory cross-sectional study. Sensations (cold, warm/heat, unpleasantness, pain and burning) evoked by 20 °C, 40 °C and alternating 20 °C/40 °C (TGI) and somatosensory profiles according to standardized quantitative sensory testing (QST) were assessed on the palm of the dominant hand. Compared to healthy controls, fibromyalgia patients reported stronger thermal grill-evoked cold, warm, unpleasantness and pain as well as stronger and more aversive 20 °C- and 40 °C-evoked sensations. They showed a loss in warm, mechanical and vibration detection, a gain in thermal pain thresholds and higher temporal summation (TS). Among QST parameters higher TS in fibromyalgia patients was most consistently associated with an augmented TGI. Independently, an increased TGI was linked to cold (20 °C) but less to warm (40 °C) perception. In fibromyalgia patients all thermal grill-evoked sensations were positively related to a higher 20 °C-evoked cold sensation and/or 20 °C-evoked unpleasantness. In conclusion, the TGI appears to be driven mainly by the cold-input. Aversive cold processing and central pain facilitation in fibromyalgia patients seem to independently augment the activation of the pain pathway.
The color communication game
Authors: Brown Angela M. , Lindsey Delwin T. 
Published: September 2023

AbstractThere is clear diversity among speakers of a typical language in how colors are named. What is the impact of this diversity on the people’s ability to communicate about color? Is there a gap between a person’s general understanding of the color terms in their native language and how they understand a particular term that denotes a particular color sample? Seventy English-speaking dyads and 63 Somali-speaking dyads played the Color Communication Game, where the “sender” in each dyad named 30 color samples as they would in any color-naming study, then the “receiver” chose the sample they thought the sender intended to communicate. English speakers played again, under instructions to intentionally communicate color sample identity. Direct comparison of senders’ samples and receivers’ choices revealed categorical understanding of colors without considering color naming data. Although Somali-speaking senders provided fewer color terms, interpersonal Mutual Information (MI) calculated from color naming data was similarly below optimal for both groups, and English-speaking dyads’ MI did not improve with experience. Both groups revealed superior understanding of color terms because receivers showed better exactly-correct selection performance than was predicted by simulation from their senders’ color-naming data. This study highlights limitations on information-theoretic analyses of color naming data.
Impact of on-site pharmacists in residential aged care facilities on the quality of medicines use: a cluster randomised controlled trial (PiRACF study)
Authors: Haider Ibrahim , Kosari Sam , Naunton Mark , Niyonsenga Theo , Koerner Jane , Peterson Gregory , Davey Rachel 
Published: September 2023

AbstractResidents of residential aged care facilities (RACFs) have a high prevalence of use of potentially inappropriate medications (PIMs) and resultant medicines-related harm. This study investigated the effect of an on-site pharmacist model on PIMs use and other medication outcomes for residents in RACFs. A multi-facility, non-blind, cluster randomised controlled trial, with randomisation at the facility level, was conducted. Fifteen facilities enrolled and participated in the study, 7 facilities (560 residents) were allocated to the intervention arm and 8 facilities (737 residents) were allocated to the control arm. Each facility in the intervention arm employed an on-site pharmacist for 12 months to perform medication management activities as part of an interdisciplinary care team. The primary outcome was the proportion of residents taking at least one PIM according to the 2019 Beers® Criteria. Using generalised linear mixed-effects models, accounting for confounders and clustering, there was a significant reduction in the proportion of residents prescribed at least one PIM (odds ratio 0.50, 95% confidence interval, 0.335–0.750; p = 0.001) in the intervention arm. There were also significant decreases in the Anticholinergic Cognitive Burden scale and chlorpromazine equivalent daily dose of antipsychotics. The on-site pharmacist intervention significantly improved the appropriateness of medicines use in RACFs.
Characterization of a GH10 extremely thermophilic xylanase from the metagenome of hot spring for prebiotic production
Authors: Yin Yi-Rui , Li Xin-Wei , Long Chao-Hua , Li Lei , Hang Yu-Ying , Rao Meng-Di , Yan Xin , Liu Quan-Lin , Sang Peng , Li Wen-Jun , Yang Li-Quan 
Published: September 2023

AbstractA xylanase gene (named xyngmqa) was identified from the metagenomic data of the Gumingquan hot spring (92.5 °C, pH 9.2) in Tengchong City, Yunnan Province, southwest China. It showed the highest amino acid sequence identity (82.70%) to endo-1,4-beta-xylanase from Thermotoga caldifontis. A constitutive expression plasmid (denominated pSHY211) and double-layer plate (DLP) method were constructed for cloning, expression, and identification of the XynGMQA gene. The XynGMQA gene was synthesized and successfully expressed in Escherichia coli DH5α. XynGMQA exhibited optimal activity at 90 °C and pH 4.6, being thermostable by maintaining 100% of its activity after 2 h incubated at 80 °C. Interestingly, its enzyme activity was enhanced by high temperatures (70 and 80 °C) and low pH (3.0–6.0). About 150% enzyme activity was detected after incubation at 70 °C for 20 to 60 min or 80 °C for 10 to 40 min, and more than 140% enzyme activity after incubation at pH 3.0 to 6.0 for 12 h. Hydrolytic products of beechwood xylan with XynGMQA were xylooligosaccharides, including xylobiose (X2), xylotriose (X3), and xylotetraose (X4). These properties suggest that XynGMQA as an extremely thermophilic xylanase, may be exploited for biofuel and prebiotic production from lignocellulosic biomass.
Deposition is a phosphorus source for Fallopia japonica during early-stage primary succession
Authors: Katayama Sae , Sawakami Koichiro , Tateno Masaki 
Published: September 2023

AbstractPhosphorus is a key plant nutrient linked to plant growth during the early stages of primary succession in volcanic soils. Available phosphorus is thought to include soil and atmospheric phosphorus, but it is not well understood. Here, we focused on deposition as a potential phosphorus source. We evaluated the contribution of deposition to phosphorus uptake and growth in Fallopia japonica, a key pioneer species of primary succession. When we experimented with growing F. japonica under field conditions, F. japonica not covered by a roof absorbed more phosphorus than that covered by the roof, suggesting the influence of total (dry + wet) deposition. Furthermore, we tested the effects of deposition by treating F. japonica seedlings with wet deposition or distilled water in six volcanic soils. Plants that received the wet deposition treatment exhibited higher phosphorus contents and growth rates than those treated with distilled water. The phosphorus from wet deposition and the phosphorus from soil contributed nearly equally to F. japonica development. Our findings suggest that F. japonica grows during primary succession and builds up the phosphorus cycle by absorbing a trace amount of phosphorus from deposition and volcanic soils.
Influence of electric potential-induced by atmospheric pressure plasma on cell response
Authors: Okumura Takamasa , Chang Chia-Hsing , Koga Kazunori , Shiratani Masaharu , Sato Takehiko 
Published: September 2023

AbstractPlasma irradiation leads not only active species, but also reactive chemical species, ultraviolet light, electric fields, magnetic fields, and shock waves. To date the effects of reactive chemical species have been mainly discussed. To understand the biological effect caused by an electric potential induced with an atmospheric-pressure plasma, the behavior of cell stimulated by electric potential was investigated using HeLa cell. The cell concentration assay revealed that less than 20% of cells inactivated by potential stimulation and the remained cells proliferate afterward. Fluorescent microscopic observation revealed that potential stimulation is appreciable to transport the molecules through membrane. These results show that potential stimulation induces intracellular and extracellular molecular transport, while the stimulation has a low lethal effect. A possible mechanism for this molecular transport by potential stimulation was also shown using numerical simulation based on an equivalent circuit of the experimental system including adhered HeLa cell. The potential formation caused by plasma generation is decisive in the contribution of plasma science to molecular biology and the elucidation of the mechanism underlying a biological response induction by plasma irradiation.
Man vs the machine in the struggle for effective text anonymisation in the age of large language models
Authors: Patsakis Constantinos , Lykousas Nikolaos 
Published: September 2023

AbstractThe collection and use of personal data are becoming more common in today’s data-driven culture. While there are many advantages to this, including better decision-making and service delivery, it also poses significant ethical issues around confidentiality and privacy. Text anonymisation tries to prune and/or mask identifiable information from a text while keeping the remaining content intact to alleviate privacy concerns. Text anonymisation is especially important in industries like healthcare, law, as well as research, where sensitive and personal information is collected, processed, and exchanged under high legal and ethical standards. Although text anonymisation is widely adopted in practice, it continues to face considerable challenges. The most significant challenge is striking a balance between removing information to protect individuals’ privacy while maintaining the text’s usability for future purposes. The question is whether these anonymisation methods sufficiently reduce the risk of re-identification, in which an individual can be identified based on the remaining information in the text. In this work, we challenge the effectiveness of these methods and how we perceive identifiers. We assess the efficacy of these methods against the elephant in the room, the use of AI over big data. While most of the research is focused on identifying and removing personal information, there is limited discussion on whether the remaining information is sufficient to deanonymise individuals and, more precisely, who can do it. To this end, we conduct an experiment using GPT over anonymised texts of famous people to determine whether such trained networks can deanonymise them. The latter allows us to revise these methods and introduce a novel methodology that employs Large Language Models to improve the anonymity of texts.
Generation of potent antibacterial compounds through enzymatic and chemical modifications of the trans-δ-viniferin scaffold
Authors: Huber Robin , Marcourt Laurence , Héritier Margaux , Luscher Alexandre , Guebey Laurie , Schnee Sylvain , Michellod Emilie , Guerrier Stéphane , Wolfender Jean-Luc , Scapozza Leonardo , Köhler Thilo , Gindro Katia , Queiroz Emerson Ferreira 
Published: September 2023

AbstractStilbene dimers are well-known for their diverse biological activities. In particular, previous studies have demonstrated the high antibacterial potential of a series of trans-δ-viniferin-related compounds against gram-positive bacteria such as Staphylococcus aureus. The trans-δ-viniferin scaffold has multiple chemical functions and can therefore be modified in various ways to generate derivatives. Here we report the synthesis of 40 derivatives obtained by light isomerization, O-methylation, halogenation and dimerization of other stilbene monomers. The antibacterial activities of all generated trans-δ-viniferin derivatives were evaluated against S. aureus and information on their structure–activity relationships (SAR) was obtained using a linear regression model. Our results show how several parameters, such as the O-methylation pattern and the presence of halogen atoms at specific positions, can determine the antibacterial activity. Taken together, these results can serve as a starting point for further SAR investigations.
Xrn1-resistant RNA motifs are disseminated throughout the RNA virome and are able to block scanning ribosomes
Authors: Dilweg Ivar W. , Peer Jasper , Olsthoorn René C. L. 
Published: September 2023

AbstractRNAs that are able to prevent degradation by the 5’–3’ exoribonuclease Xrn1 have emerged as crucial structures during infection by an increasing number of RNA viruses. Several plant viruses employ the so-called coremin motif, an Xrn1-resistant RNA that is usually located in 3’ untranslated regions. Investigation of its structural and sequence requirements has led to its identification in plant virus families beyond those in which the coremin motif was initially discovered. In this study, we identified coremin-like motifs that deviate from the original in the number of nucleotides present in the loop region of the 5’ proximal hairpin. They are present in a number of viral families that previously did not have an Xrn1-resistant RNA identified yet, including the double-stranded RNA virus families Hypoviridae and Chrysoviridae. Through systematic mutational analysis, we demonstrated that a coremin motif carrying a 6-nucleotide loop in the 5’ proximal hairpin generally requires a YGNNAD consensus for stalling Xrn1, similar to the previously determined YGAD consensus required for Xrn1 resistance of the original coremin motif. Furthermore, we determined the minimal requirements for the 3’ proximal hairpin. Since some putative coremin motifs were found in intergenic regions or coding sequences, we demonstrated their capacity for inhibiting translation through an in vitro ribosomal scanning inhibition assay. Consequently, this study provides a further expansion on the number of viral families with known Xrn1-resistant elements, while adding a novel, potentially regulatory function for this structure.
Psychological states affecting initial pupil size changes after olfactory stimulation in healthy participants
Authors: Hatsukawa Hiroatsu , Ishikawa Masaaki 
Published: September 2023

AbstractOdor perception affects physiological and psychological states. Pupillary light reflex (PLR) parameters can be affected by olfactory stimulation and psychological states, although it remains unclear whether the olfactory stimulation-induced psychological changes can associate with PLR parameter changes. This study aimed to investigate effects of olfactory stimulation-induced psychological changes on PLR parameter changes with repeated measurements. We collected data on six mood subscales of the profile of mood states, and on five PLR parameter measurements from 28 healthy participants. Participants underwent a 10-min olfactory stimulation on different days with six odorants available with the T&T olfactometer. As obtained data were clustered, we used linear mixed-effects models for statistical analyses. The olfactory stimulation using the no-odor liquid did not affect mood states and the initial pupil size (INIT). The sweat odorant worsened all mood subscales including fatigue–inertia (Fatigue)/Vigor–Activity (Vigor), and decreased INIT compared to the no-odor liquid. When comparing INIT responses related to changes in mood subscales between the no-odor liquid and the sweat odorant, worsened states of Fatigue/Vigor were associated with decreased INIT in the sweat odorant. Fatigue/Vigor can be used as mental fatigue indicators. Thus, mental fatigue can be associated with decreased INIT in the olfactory stimulation.
The Warburg effect alters amino acid homeostasis in human retinal endothelial cells: implication for proliferative diabetic retinopathy
Authors: Gregory Andrew , Yumnamcha Thangal , Shawky Mohamed , Eltanani Shaimaa , Naghdi Armaan , Ross Bing X. , Lin Xihui , Ibrahim Ahmed S. 
Published: September 2023

AbstractProliferative diabetic retinopathy (PDR) remains a leading cause of blindness despite progress in screening and treatment. Recently, the Warburg effect, a metabolic alteration affecting amino acid (AA) metabolism in proliferating cells, has drawn attention regarding its role in PDR. This study aimed to investigate the impact of the Warburg effect on AA metabolism in human retinal endothelial cells (HRECs) subjected to PDR-associated risk factors and validate the findings in patients with PDR. In vitro experiments exposed HRECs to high glucose (HG) and/or hypoxia (Hyp), known inducers of the Warburg effect. The HG + Hyp group of HRECs exhibited significant differences in non-essential AAs with aliphatic non-polar side chains, mainly driven by elevated glycine concentrations. Pathway enrichment analysis revealed several glycine metabolism-related pathways significantly altered due to the Warburg effect induced by HG + Hyp. Crucially, vitreous humor samples from PDR patients displayed higher glycine levels compared to non-diabetic and diabetic patients without PDR. The odds ratio for PDR patients with glycine levels above the cut-off of 0.0836 µM was 28 (p = 0.03) compared to non-PDR controls. In conclusion, this study provides mechanistic insights into how a specific Warburg effect subtype contributes to glycine accumulation in PDR and supports glycine's potential as a biomarker for PDR pathogenesis.