bluuebunny/crossref_metadata_2025 huggingface dataset:
A multinational survey of potential participant perspectives on ocular gene therapy
Authors: Britten-Jones Alexis Ceecee , McGuinness Myra B. , Chen Fred K. , Grigg John R. , Mack Heather G. , Ayton Lauren N.
Published: April 2024

Amidst rapid advancements in ocular gene therapy, understanding patient perspectives is crucial for shaping future treatment choices and research directions. This international cross-sectional survey evaluated knowledge, attitudes, and perceptions of ocular genetic therapies among potential recipients with inherited retinal diseases (IRDs). Survey instruments included the Attitudes to Gene Therapy-Eye (AGT-Eye), EQ-5D-5L, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and Patient Attitudes to Clinical Trials (PACT-22) instruments. This study included 496 participant responses (89% adults with IRDs; 11% parents/guardians/carers) from 35 countries, with most from the United States of America (USA; 69%) and the United Kingdom (11%). Most participants (90%) indicated they would likely accept gene therapy if it was available, despite only 45% agreeing that they had good knowledge of gene therapy. The main sources of information were research registries (60% of participants) and the internet (61%). Compared to data from our recently published Australian national survey of people with IRDs (n = 694), USA respondents had higher knowledge of gene therapy outcomes, and Australian respondents indicated a higher perceived value of gene therapy treatments. Addressing knowledge gaps regarding outcomes and financial implications will be central to ensuring informed consent, promoting shared decision-making, and the eventual clinical adoption of genetic therapies.
Multifunctional carbon nanotubes coated stainless steel mesh for electrowetting, hydrophobic, and dye absorption behavior
Authors: Park Hyeong Kwang Benno , Kebaili Imen , Boukhris Imed , Joo Yun Hwan , Sung Tae Hyun , Kumar Anuruddh
Published: April 2024

Electrowetting behaviour for carbon nanotubes (CNT) grown on stainless steel mesh was investigated. The effect of temperature, time, and applied bias voltage on the contact angle of water droplets was studied. The impact of temperature variation on contact angle was also performed for the temperature ranging from 25 to 70 °C. A decrement of contact angle by 68% was observed for the mentioned range indicating a transition from a hydrophobic to hydrophilic nature. A similar trend was observed on the application of electric potential to the CNT-modified stainless-steel mesh ranging from 0 to 8 V with a transition of contact angle from 146 to 30 deg respectively. A comparative analysis for the contact angle variation with time for CNT-coated mesh and uncoated mesh was performed for 180 min. It is observed that uncoated mesh shows a reduction in contact angle to 0 deg with time while the CNT coated mesh shows surplus hydrophobicity with a 2 deg decrement in the extent of time. CNT-modified mesh successfully absorbs 95% of rhodamine B (RB) dye and detergent from water in 10 cycles.
Characterization of a putative orexin receptor in Ciona intestinalis sheds light on the evolution of the orexin/hypocretin system in chordates
Authors: Rinne Maiju K. , Urvas Lauri , Mandrika Ilona , Fridmanis Dāvids , Riddy Darren M. , Langmead Christopher J. , Kukkonen Jyrki P. , Xhaard Henri
Published: April 2024

Tunicates are evolutionary model organisms bridging the gap between vertebrates and invertebrates. A genomic sequence in Ciona intestinalis (CiOX) shows high similarity to vertebrate orexin receptors and protostome allatotropin receptors (ATR). Here, molecular phylogeny suggested that CiOX is divergent from ATRs and human orexin receptors (hOX1/2). However, CiOX appears closer to hOX1/2 than to ATR both in terms of sequence percent identity and in its modelled binding cavity, as suggested by molecular modelling. CiOX was heterologously expressed in a recombinant HEK293 cell system. Human orexins weakly but concentration-dependently activated its Gq signalling (Ca2+ elevation), and the responses were inhibited by the non-selective orexin receptor antagonists TCS 1102 and almorexant, but only weakly by the OX1-selective antagonist SB-334867. Furthermore, the 5-/6-carboxytetramethylrhodamine (TAMRA)-labelled human orexin-A was able to bind to CiOX. Database mining was used to predict a potential endogenous C. intestinalis orexin peptide (Ci-orexin-A). Ci-orexin-A was able to displace TAMRA-orexin-A, but not to induce any calcium response at the CiOX. Consequently, we suggested that the orexin signalling system is conserved in Ciona intestinalis, although the relevant peptide-receptor interaction was not fully elucidated.
Nano round polycrystalline adsorbent of chicken bones origin for Congo red dye adsorption
Authors: Ofudje Edwin Andrew , Al-Ahmary Khairia Mohammed , Alshdoukhi Ibtehaj F. , Alrahili Mazen Rzeeg , Kavil Yasar N. , Alelyani Saeed Saad , Bakheet Ammar M. , Al-Sehemi Abdullah G.
Published: April 2024

Nano round polycrystalline adsorbent (NRPA) of chicken bones origin was utilize as effective adsorbent in Congo red dye removal via aqueous media. The NRPA adsorbent was prepared via thermal decomposition and its structure was investigated with the aids of Transmission Electron Microscopy, Fourier Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy, Energy Dispersive X-ray Analysis (EDX), and X-ray Diffractometer (XRD). A monophasic apatite phase was confirmed from XRD investigation, while functional groups analysis showed that NRPA possessed CO32−, PO43− and OH− absorption bands. The maximum adsorption capacities derived from Langmuir isotherm is 98.216 mg g−1. From the combined values of n from Freundlich and separation factor (RL) of Langmuir models, the adsorption of CR by NRPA is favourable. Thermodynamic values of 5.280 kJ mol−1 and 16.403 kJ mol−1 K−1 were found for ΔH° and ΔS° respectively. The entire values of ΔG° which ranges from − 35.248 to − 459.68 kJ mol−1 were all negative at different temperatures. Thus, nano polycrystalline adsorbent of chicken bone origin can serve as excellent adsorbent in Congo red dye removal from waste water.
Short-term outcome after treatment of talocrural instability in cats using modified type II transarticular external skeletal fixation
Authors: Gadallah Shaaban , El-Sunsafty Mohamed , Sharshar Ahmed , Misk Tarik , Fischer Carolin , Jaehrig Rodja , Feichtenschlager Christian , Kramer Martin , Hammad Amal
Published: April 2024

Transarticular external skeletal fixation (TESF) is repeatedly used for temporary stabilisation of tarsal joint in cats. Hence, this study aimed to evaluate the use of temporary modified type II TESF for management of talocrural instability (TCI) in cats without joint arthrodesis and to rate short-term outcomes and complications. Medical records of all cats treated for TCI between January 2012 and December 2021 were reviewed. Information was collected including signalment, degree of lameness, type of TCI, accompanying soft tissue and bone injuries, and post-operative follow-up assessment including time of frame removal, complications, degree of lameness, range of joint motion and ankylosis. Surgical management didn’t involve debridement of the articular cartilage. Eighty-five percent of cats had satisfactory joint stability at the time of frame removal. Eighteen cats exhibited minor complications, six cats had major complications, and 8 cats showed persistent lameness. All cats showed reduction of joint motion range by 20°–30° directly after frame removal while returned to normal in 79% of cats 4 weeks later. Variable degrees of joint ankylosis were reported. In conclusion, this study supports the use of temporary modified type II TESF for management of TCI in cats without joint involvement as an excellent alternative to tarsal arthrodesis.
Rosemary and neem: an insight into their combined anti-dandruff and anti-hair loss efficacy
Authors: Hashem Mona M. , Attia Dalia , Hashem Yomna A. , Hendy Moataz S. , AbdelBasset Safa , Adel Farah , Salama Maha M.
Published: April 2024

Dandruff, a common scalp disorder characterized by flaking dead skin, is often treated with conventional topical products. However, limitations exist due to potential side effects and high costs. Therefore, searching for natural, cost-effective solutions for dandruff and hair loss is crucial. Rosemary herb and neem tree, both cultivated in Egypt, possess well-documented anti-inflammatory properties derived from their rich phenolic phytoconstituents. This study formulated a standardized combined extract of rosemary and neem (RN-E 2:1) into hair gel and leave-in tonic formats. This extract demonstrated superior efficacy against Malassezia furfur (a causative agent of dandruff) and Trichophyton rubrum (associated with scalp disorders) compared to the conventional antifungal agent, ketoconazole. The combined extract (RN-E 2:1) also exhibited potent anti-inflammatory activity. Additionally, the suppression of iNOS expression is considered concentration-dependent. Quality control verified formulation stability, and ex-vivo studies confirmed effective ingredient penetration into the epidermis, the primary site of fungal presence. Remarkably, both formulations outperformed the standard treatment, minoxidil in hair growth trials. These findings highlight the potential of natural extracts for scalp and hair health.
Stable diesel microemulsion using diammonium ionic liquids and their effects on fuel properties, particle size characteristics and combustion calculations
Authors: El Nagy H. A. , Mohamed Mahmoud Abd El-Aziz
Published: April 2024

Ecofriendly and stable Fuel Microemulsions based on renewable components were prepared through solubilizing ethanol in diesel and waste cooking oil blend (4:1). New diquaternary ammonium ionic liquids (3a & 3b) were synthesized through a quaternization reaction of the synthesized dihaloester with diethyl ethanolamine tridecantrioate and triethyl amine tridecantrioate, respectively. The chemical structures were elucidated by NMR spectroscopy. It was observed from DLS analyses that the ethanol particles in all samples have sizes between 4.77 to 11.22 nm. The distribution becomes narrower with the decrease in the ionic liquid concentrations. The fuel properties fall within the ASTM D975 acceptable specifications and are close to the neat diesel properties. The Cetane index were 53 and 53.5, heating values were 38.5 and 38.5 MJ/kg, viscosities were 2.91 and 2.98 mm2/s, densities were 8.26 and 8.29 g/mL and flash points were 49 °C and 48 °C for 3a1 and 3b1 microemulsions, respectively. The particle sizes of samples were examined by DLS for 160 days and they were significantly stable. The amount of ethanol solubilized increases with the increase in the amount of the synthesized ionic liquids and cosurfactant. The combustion calculations pointed out that the microemulsions 3a1 and 3b1 need 13.07 kg air/kg fuel and 12.79 kg air/kg fuel, respectively, which are less than the air required to combust the pure diesel. According to theoretical combustion, using ionic liquids saves the air consumption required for combustion and reduces the quantities of combustion products. The prepared microemulsions were successfully used as a diesel substitute due to their improved combustion properties than pure diesel and low pollution levels.
Differential gene expression in decidualized human endometrial stromal cells induced by different stimuli
Authors: Doi-Tanaka Yumiko , Tamura Isao , Shiroshita Amon , Fujimura Taishi , Shirafuta Yuichiro , Maekawa Ryo , Taketani Toshiaki , Sato Shun , Sugino Norihiro
Published: April 2024

Decidualization can be induced by culturing human endometrial stromal cells (ESCs) with several decidualization stimuli, such as cAMP, medroxyprogesterone acetate (MPA) or Estradiol (E2). However, it has been unclear how decidualized cells induced by different stimuli are different. We compared transcriptomes and cellular functions of decidualized ESCs induced by different stimuli (MPA, E2 + MPA, cAMP, and cAMP + MPA). We also investigated which decidualization stimulus induces a closer in vivo decidualization. Differentially expressed genes (DEGs) and altered cellular functions by each decidualization stimuli were identified by RNA-sequence and gene-ontology analysis. DEGs was about two times higher for stimuli that use cAMP (cAMP and cAMP + MPA) than for stimuli that did not use cAMP (MPA and E2 + MPA). cAMP-using stimuli altered the cellular functions including angiogenesis, inflammation, immune system, and embryo implantation whereas MPA-using stimuli (MPA, E2 + MPA, and cAMP + MPA) altered the cellular functions associated with insulin signaling. A public single-cell RNA-sequence data of the human endometrium was utilized to analyze in vivo decidualization. The altered cellular functions by in vivo decidualization were close to those observed by cAMP + MPA-induced decidualization. In conclusion, decidualized cells induced by different stimuli have different transcriptome and cellular functions. cAMP + MPA may induce a decidualization most closely to in vivo decidualization.
A large non-parasitic population of Savalia savaglia (Bertoloni, 1819) in the Boka Kotorska Bay (Montenegro)
Authors: Canessa Martina , Trainito Egidio , Bavestrello Giorgio , Petović Slavica , Đorđević Nikola , Mačić Vesna
Published: April 2024

The golden coral Savalia savaglia is a long-living ecosystem engineer of Mediterranean circalittoral assemblages, able to induce necrosis of gorgonians’ and black corals’ coenenchyme and grow on their cleaned organic skeleton. Despite its rarity, in Boka Kotorska Bay (Montenegro) a shallow population of more than 1000 colonies was recorded close to underwater freshwater springs, which create very peculiar environmental conditions. In this context, the species was extremely abundant at two sites, while gorgonians were rare. The abundance and size of S. savaglia colonies and the diversity of the entire benthic assemblage were investigated by photographic sampling in a depth range of 0–35 m. Several living fragments of S. savaglia spread on the sea floor and small settled colonies (< 5 cm high) suggested a high incidence of asexual reproduction and a non-parasitic behaviour of this population. This was confirmed by studying thin sections of the basal portion of the trunk where the central core, generally represented by the remains of the gorgonian host skeleton, was lacking. The S. savaglia population of Boka Kotorska Bay forms the unique Mediterranean assemblage of the species deserving the definition of animal forest. Recently, temporary mitigation measures for anthropogenic impact were issued by the Government of Montenegro. Nevertheless, due to the importance of the sites the establishment of a permanent Marine Protected Area is strongly recommended.
Sequential mediation analysis of physical activity, healthy diet, BMI, and academic burnout in the Pakistani educational landscape
Authors: Rehman Shazia , Addas Abdullah , Rahman Md Anisur , Shahiman Muhammad Ali , Li Zexuan
Published: April 2024

Research has indicated a negative impact of physical activity on academic burnout among students, however, there is a paucity of evidence about the underlying mechanism of this association in Pakistani students. The present research seeks to investigate the relationship between physical activity and academic burnout by investigating the potential mediating effects of adherence to the Mediterranean diet (MD) and body mass index (BMI). A sample of 596 students using a cross-sectional survey design was gathered from two public universities (Riphah International University and Mohammed Ali Jinnah University) in Rawalpindi, Pakistan from June to July 2022. The study participants were asked to fill out the Physical Activity Rating Scale-3, the Learning Burnout Scale, and the Test of Adherence to MD questionnaires. The study employed descriptive, bivariate, and path analysis through regression utilizing the SPSS software version 27. The findings demonstrated a negative correlation between academic burnout and BMI, physical activity, and adherence to the MD. The relationship between physical activity and academic burnout was mediated by BMI. Physical activity and academic burnout were inversely correlated, with adherence to the MD and BMI interacting as sequential mediators. The outcomes of this research have expanded our knowledge of the association between physical activity and academic burnout and have suggested crucial and appropriate strategies for addressing student academic burnout.
A household survey of the prevalence of subjective cognitive decline and mild cognitive impairment among urban community-dwelling adults aged 30 to 65
Authors: Pinyopornpanish Kanokporn , Buawangpong Nida , Soontornpun Atiwat , Thaikla Kanittha , Pateekhum Chanapat , Nantsupawat Nopakoon , Wiwatkunupakarn Nutchar , Jiraporncharoen Wichuda , Angkurawaranon Chaisiri
Published: April 2024

While it is possible to detect cognitive decline before the age of 60, and there is a report indicating that certain cognitive abilities peak in one's 30s, the evidence regarding cognitive problems in populations younger than 65 years is scarce. This study aims to (1) determine the proportion of community-dwelling adults with different cognitive status, and (2) determine the prevalence of neuropsychiatric behaviors. A population-based survey was conducted in Chiang Mai, Thailand. Individuals aged 30 to 65 were recruited and assessed for demographic data, memory complaints, cognitive performance, and neuropsychiatric symptoms using self-reported questionnaires. In a total of 539 participants, 33.95% had mild cognitive impairment (MCI), 7.05% had subjective cognitive decline (SCD), and 52.50% had neuropsychiatric symptoms. The risk of MCI increased with age, and neuropsychiatric symptoms were significantly higher in those with MCI or SCD than in those without (p < 0.001). The most common complaints were sleep problems, anxiety, and irritability. Screening for MCI in adults aged < 65 years might be useful. However, further investigation on the appropriate age to screen and the program’s cost-effectiveness is suggested.
Expression of the Arabidopsis redox-related LEA protein, SAG21 is regulated by ERF, NAC and WRKY transcription factors
Authors: Evans Kelly V. , Ransom Elspeth , Nayakoti Swapna , Wilding Ben , Mohd Salleh Faezah , Gržina Irena , Erber Lieselotte , Tse Carmen , Hill Claire , Polanski Krzysztof , Holland Alistair , Bukhat Sherien , Herbert Robert J. , de Graaf Barend H. J. , Denby Katherine , Buchanan-Wollaston Vicky , Rogers Hilary J.
Published: April 2024

SAG21/LEA5 is an unusual late embryogenesis abundant protein in Arabidopsis thaliana, that is primarily mitochondrially located and may be important in regulating translation in both chloroplasts and mitochondria. SAG21 expression is regulated by a plethora of abiotic and biotic stresses and plant growth regulators indicating a complex regulatory network. To identify key transcription factors regulating SAG21 expression, yeast-1-hybrid screens were used to identify transcription factors that bind the 1685 bp upstream of the SAG21 translational start site. Thirty-three transcription factors from nine different families bound to the SAG21 promoter, including members of the ERF, WRKY and NAC families. Key binding sites for both NAC and WRKY transcription factors were tested through site directed mutagenesis indicating the presence of cryptic binding sites for both these transcription factor families. Co-expression in protoplasts confirmed the activation of SAG21 by WRKY63/ABO3, and SAG21 upregulation elicited by oligogalacturonide elicitors was partially dependent on WRKY63, indicating its role in SAG21 pathogen responses. SAG21 upregulation by ethylene was abolished in the erf1 mutant, while wound-induced SAG21 expression was abolished in anac71 mutants, indicating SAG21 expression can be regulated by several distinct transcription factors depending on the stress condition.
Seasonal diet partition among top predators of a small island, Iriomote Island in the Ryukyu Archipelago, Japan
Authors: Tobe Alisa , Sato Yukuto , Wachi Nakatada , Nakanishi Nozomi , Izawa Masako
Published: April 2024

Small islands tend to lack predators because species at higher trophic levels often cannot survive. However, two exceptional top predators—the Iriomote cat Prionailurus bengalensis iriomotensis, and the Crested Serpent Eagle Spilornis cheela perplexus—live on the small Iriomote Island in the Ryukyu Archipelago. To understand how these predators coexist with limited resources, we focused on their seasonal diets between which conflicts are considered to occur. To compare the diets, we used DNA metabarcoding analysis of faecal samples. In the summer, we identified 16 unique prey items from Iriomote cat faecal samples and 15 unique prey items from Crested Serpent Eagle faecal samples. In the winter, we identified 37 and 14, respectively. Using a non-metric multidimensional scaling and a permutational multivariate analysis of variance, our study reveals significant differences in the diet composition at the order level between the predators during both seasons. Furthermore, although some prey items at the species-to-order level overlapped between them, the frequency of occurrence of most prey items differed in both seasons. These results suggest that this difference in diets is one of the reasons why the Iriomote cat and the Crested Serpent Eagle are able to coexist on such a small island.
Network analysis of anxiety and depressive symptoms during the COVID-19 pandemic in older adults in the United Kingdom
Authors: Ramos-Vera Cristian , García O’Diana Angel , Basauri-Delgado Miguel , Calizaya-Milla Yaquelin E. , Saintila Jacksaint
Published: April 2024

The health crisis caused by COVID-19 in the United Kingdom and the confinement measures that were subsequently implemented had unprecedented effects on the mental health of older adults, leading to the emergence and exacerbation of different comorbid symptoms including depression and anxiety. This study examined and compared depression and anxiety symptom networks in two specific quarantine periods (June–July and November–December) in the older adult population in the United Kingdom. We used the database of the English Longitudinal Study of Aging COVID-19 Substudy, consisting of 5797 participants in the first stage (54% women) and 6512 participants in the second stage (56% women), all over 50 years of age. The symptoms with the highest centrality in both times were: “Nervousness (A1)” and “Inability to relax (A4)” in expected influence and predictability, and “depressed mood (D1”; bridging expected influence). The latter measure along with "Irritability (A6)" overlapped in both depression and anxiety clusters in both networks. In addition, a the cross-lagged panel network model was examined in which a more significant influence on the direction of the symptom "Nervousness (A1)" by the depressive symptoms of "Anhedonia (D6)", "Hopelessness (D7)", and "Sleep problems (D3)" was observed; the latter measure has the highest predictive capability of the network. The results report which symptoms had a higher degree of centrality and transdiagnostic overlap in the cross-sectional networks (invariants) and the cross-lagged panel network model of anxious and depressive symptomatology.
Conspecific interactions predict social transmission of fear in female rats
Authors: Seese Sydney , Tinsley Carolyn E. , Wulffraat Grace , Hixon J. Gregory , Monfils Marie-H.
Published: April 2024

Social transmission of fear occurs in a subset of individuals, where an Observer displays a fear response to a previously neutral stimulus after witnessing or interacting with a conspecific Demonstrator during memory retrieval. The conditions under which fear can be acquired socially in rats have received attention in recent years, and suggest that social factors modulate social transmission of information. We previously found that one such factor, social rank, impacts fear conditioning by proxy in male rats. Here, we aimed to investigate whether social roles as determined by nape contacts in females, might also have an influence on social transmission of fear. In-line with previous findings in males, we found that social interactions in the home cage can provide insight into the social relationship between female rats and that these relationships predict the degree of fear acquired by-proxy. These results suggest that play behavior affects the social transfer/transmission of information in female rats.
BioBBC: a multi-feature model that enhances the detection of biomedical entities
Authors: Alamro Hind , Gojobori Takashi , Essack Magbubah , Gao Xin
Published: April 2024

The rapid increase in biomedical publications necessitates efficient systems to automatically handle Biomedical Named Entity Recognition (BioNER) tasks in unstructured text. However, accurately detecting biomedical entities is quite challenging due to the complexity of their names and the frequent use of abbreviations. In this paper, we propose BioBBC, a deep learning (DL) model that utilizes multi-feature embeddings and is constructed based on the BERT-BiLSTM-CRF to address the BioNER task. BioBBC consists of three main layers; an embedding layer, a Long Short-Term Memory (Bi-LSTM) layer, and a Conditional Random Fields (CRF) layer. BioBBC takes sentences from the biomedical domain as input and identifies the biomedical entities mentioned within the text. The embedding layer generates enriched contextual representation vectors of the input by learning the text through four types of embeddings: part-of-speech tags (POS tags) embedding, char-level embedding, BERT embedding, and data-specific embedding. The BiLSTM layer produces additional syntactic and semantic feature representations. Finally, the CRF layer identifies the best possible tag sequence for the input sentence. Our model is well-constructed and well-optimized for detecting different types of biomedical entities. Based on experimental results, our model outperformed state-of-the-art (SOTA) models with significant improvements based on six benchmark BioNER datasets.
Stability of soil slope in Almaty covered with steel slag under the effect of rainfall
Authors: Abishev Rezat , Satyanaga Alfrendo , Pernebekova Gulnur , Rahardjo Harianto , Zhai Qian , Shon Chang-Seon , Moon Sung-Woo , Kim Jong
Published: April 2024

The issue of rainfall-induced slope failure has attracted more attention from geotechnical engineers as a consequence of global warming. Current cumulative waste disposal has generated scientific interest in the utilization of waste materials in geotechnical design for climate change adaptation measures. Taking into consideration the effect of slope height and angle, steel slag—a waste product derived from the production of steel—was investigated as a slope cover against rainfall. To assess the stability of the slope and the infiltration of water into the soil, numerical analyses were conducted using both SEEP/W and SLOPE/W software in conjunction with rainfall conditions. Based on the findings, it can be concluded that increasing the slope's elevation and inclination will have an adverse effect on its safety factor. Steel slag can nevertheless be utilized for minimizing rainwater infiltration into the slope, as indicated by the pore-water pressure variations and graphs of the safety factor versus time. For a 20-m slope height, steel slag slopes have demonstrated a lower factor of safety difference in comparison to the initial slope without remediation. Regardless of slope angle and slope height, the safety factor reduces marginally during rainfall.
A combination of virtual screening, molecular dynamics simulation, MM/PBSA, ADMET, and DFT calculations to identify a potential DPP4 inhibitor
Authors: Zare Fateme , Ataollahi Elaheh , Mardaneh Pegah , Sakhteman Amirhossein , Keshavarz Valiollah , Solhjoo Aida , Emami Leila
Published: April 2024

DPP4 inhibitors can control glucose homeostasis by increasing the level of GLP-1 incretins hormone due to dipeptidase mimicking. Despite the potent effects of DPP4 inhibitors, these compounds cause unwanted toxicity attributable to their effect on other enzymes. As a result, it seems essential to find novel and DPP4 selective compounds. In this study, we introduce a potent and selective DPP4 inhibitor via structure-based virtual screening, molecular docking, molecular dynamics simulation, MM/PBSA calculations, DFT analysis, and ADMET profile. The screened compounds based on similarity with FDA-approved DPP4 inhibitors were docked towards the DPP4 enzyme. The compound with the highest docking score, ZINC000003015356, was selected. For further considerations, molecular docking studies were performed on selected ligands and FDA-approved drugs for DPP8 and DPP9 enzymes. Molecular dynamics simulation was run during 200 ns and the analysis of RMSD, RMSF, Rg, PCA, and hydrogen bonding were performed. The MD outputs showed stability of the ligand–protein complex compared to available drugs in the market. The total free binding energy obtained for the proposed DPP4 inhibitor was more negative than its co-crystal ligand (N7F). ZINC000003015356 confirmed the role of the five Lipinski rule and also, have low toxicity parameter according to properties. Finally, DFT calculations indicated that this compound is sufficiently soft.
An AGO10:miR165/6 module regulates meristem activity and xylem development in the Arabidopsis root
Authors: Mirlohi Shirin , Schott Gregory , Imboden André , Voinnet Olivier
Published: April 2024

The RNA-silencing effector ARGONAUTE10 influences cell fate in plant shoot and floral meristems. ARGONAUTE10 also accumulates in the root apical meristem (RAM), yet its function(s) therein remain elusive. Here, we show that ARGONAUTE10 is expressed in the root cell initials where it controls overall RAM activity and length. ARGONAUTE10 is also expressed in the stele, where post-transcriptional regulation confines it to the root tip’s pro-vascular region. There, variations in ARGONAUTE10 levels modulate metaxylem-vs-protoxylem specification. Both ARGONAUTE10 functions entail its selective, high-affinity binding to mobile miR165/166 transcribed in the neighboring endodermis. ARGONAUTE10-bound miR165/166 is degraded, likely via SMALL-RNA-DEGRADING-NUCLEASES1/2, thus reducing miR165/166 ability to silence, via ARGONAUTE1, the transcripts of cell fate-influencing transcription factors. These include PHABULOSA (PHB), which controls meristem activity in the initials and xylem differentiation in the pro-vasculature. During early germination, PHB transcription increases while dynamic, spatially-restricted transcriptional and post-transcriptional mechanisms reduce and confine ARGONAUTE10 accumulation to the provascular cells surrounding the newly-forming xylem axis. Adequate miR165/166 concentrations are thereby channeled along the ARGONAUTE10-deficient yet ARGONAUTE1-proficient axis. Consequently, inversely-correlated miR165/166 and PHB gradients form preferentially along the axis despite ubiquitous PHB transcription and widespread miR165/166 delivery inside the whole vascular cylinder.
LATS1 controls CTCF chromatin occupancy and hormonal response of 3D-grown breast cancer cells
Authors: Ramírez-Cuéllar Julieta , Ferrari Roberto , Sanz Rosario T , Valverde-Santiago Marta , García-García Judith , Nacht A Silvina , Castillo David , Le Dily Francois , Neguembor Maria Victoria , Malatesta Marco , Bonnin Sarah , Marti-Renom Marc A , Beato Miguel , Vicent Guillermo P
Published: April 2024

The cancer epigenome has been studied in cells cultured in two-dimensional (2D) monolayers, but recent studies highlight the impact of the extracellular matrix and the three-dimensional (3D) environment on multiple cellular functions. Here, we report the physical, biochemical, and genomic differences between T47D breast cancer cells cultured in 2D and as 3D spheroids. Cells within 3D spheroids exhibit a rounder nucleus with less accessible, more compacted chromatin, as well as altered expression of ~2000 genes, the majority of which become repressed. Hi-C analysis reveals that cells in 3D are enriched for regions belonging to the B compartment, have decreased chromatin-bound CTCF and increased fusion of topologically associating domains (TADs). Upregulation of the Hippo pathway in 3D spheroids results in the activation of the LATS1 kinase, which promotes phosphorylation and displacement of CTCF from DNA, thereby likely causing the observed TAD fusions. 3D cells show higher chromatin binding of progesterone receptor (PR), leading to an increase in the number of hormone-regulated genes. This effect is in part mediated by LATS1 activation, which favors cytoplasmic retention of YAP and CTCF removal.
MolPhase, an advanced prediction algorithm for protein phase separation
Authors: Liang Qiyu , Peng Nana , Xie Yi , Kumar Nivedita , Gao Weibo , Miao Yansong
Published: April 2024

We introduce MolPhase, an advanced algorithm for predicting protein phase separation (PS) behavior that improves accuracy and reliability by utilizing diverse physicochemical features and extensive experimental datasets. MolPhase applies a user-friendly interface to compare distinct biophysical features side-by-side along protein sequences. By additional comparison with structural predictions, MolPhase enables efficient predictions of new phase-separating proteins and guides hypothesis generation and experimental design. Key contributing factors underlying MolPhase include electrostatic pi-interactions, disorder, and prion-like domains. As an example, MolPhase finds that phytobacterial type III effectors (T3Es) are highly prone to homotypic PS, which was experimentally validated in vitro biochemically and in vivo in plants, mimicking their injection and accumulation in the host during microbial infection. The physicochemical characteristics of T3Es dictate their patterns of association for multivalent interactions, influencing the material properties of phase-separating droplets based on the surrounding microenvironment in vivo or in vitro. Robust integration of MolPhase’s effective prediction and experimental validation exhibit the potential to evaluate and explore how biomolecule PS functions in biological systems.
Sesquiterpenoids and hexanorcucurbitacin from Aquilaria malaccensis agarwood with anti-inflammatory effects by inhibiting the STAT1/AKT/MAPK/NLRP3 pathway
Authors: Ma Chi Thanh , Huang Tianqi , Yu Jae Sik , Ly Tu Loan , Vu Huynh Kim Long , Kwon Sung Won , Park Jeong Hill , Yang Hyun Ok
Published: April 2024

A rare hexanortriterpenoid significantly attenuated the proinflammatory mediators, STAT1/AKT/MAPK, and MAPK/NLRP3 signaling pathways for preventing neuroinflammatory disorders in BV2 microglial cells.
Controllable synthesis of an atomic Sn-anchoring carbon host for excellent long-cycle-life zinc metal batteries
Authors: Liu Lantao , Li Yiming , Zhang Hu , Dong Fang , Wang Shuaize , Sun Ziyu , Zhang Gaixia , Chen Xiaohong , Omanovic Sasha , Sun Shuhui , Song Huaihe
Published: April 2024

An atomic Sn-anchoring carbon host was developed for guiding/controlling zinc metal deposition, inhibiting the HER and dendrite formation, and constructing anodes with high energy density and long service life.
Small CdS nanorods via sacrificial synthesis on perovskite nanocrystals – synthesis and hierarchical assembly
Authors: Lawera Zuzanna , Parzyszek Sylwia , Pociecha Damian , Lewandowski Wiktor
Published: April 2024

Precise control of the size and assembly of semiconductor nanorods (NRs) will enhance emerging photonic technologies.
Escape sites from the endo-lysosomal trafficking route manipulate exocytosis of nanoparticles in polar epithelium
Authors: Wang Lingling , Li Yuting , Liu Xi , Xing Liyun , Wu Ruinan , Huang Yuan
Published: April 2024

MNPs escaping from early endosomes and late endosomes are prone to entering the ER/GA for efficient basolateral exocytosis. However, MNPs escaping from lysosomes are detained within cells by autophagosomes.
Photochemical cyclopropanation in aqueous micellar media – experimental and theoretical studies
Authors: Milton Joseph P. , Milanowski Adam , Andersson Martin , Gryko Dorota
Published: April 2024

Photochemical cyclopropanation of styrenes with diazo compounds or their precursors can be performed in micellar systems. COSMO-RS studies revealed that the reactivity correlates with the predicted critical micelle concentration, with higher CMC values delivering higher yields.
Regioselective synthesis of isoquinolinonediones through remote unactivated C(sp3)–H bonds
Authors: Huang Lei , Sun Jun , Sun Boxuan , Song Shengjie , Li Jianjun
Published: April 2024

A novel remote-site-selective cascade addition/cyclization protocol for free alcohols and sulfonamides to build in one step isoquinolinonedione skeletons without pre-activation was developed.
High conductivity characteristics of phosphorus-doped nanocrystalline silicon thin films by KrF pulsed excimer laser irradiation method
Authors: Wang Xiang , Song Chao , Xu Boxu , Yang Huan
Published: April 2024

P-doped silicon nanocrystals with an average diameter of 2–3 nm are formed by using KrF pulsed excimer laser irradiation method. The dark conductivity as high as 25.7 S cm−1 can be obtained in P-doped nc-Si films after laser irradiation.
Finely tuned water structure and transport in functionalized carbon nanotube membranes during desalination
Authors: Qin Lanlan , Zhou Jian
Published: April 2024

Molecular dynamics simulations were performed to tune the transport of water molecules in nanostructured membrane in a desalination process.
Understanding the decomposition process of the Pt1Ag24(SPhCl2)18 nanocluster at the atomic level
Authors: Jiang Kefan , Ma Along , Li Yuansheng , Wang Jiawei , Yin Zhengmao , Wang Shuxin
Published: April 2024

By investigating the decomposition of Pt1Ag24(SR)18, we synthesized two Pt1Ag24(SR)20 nanoclusters (NC-I and NC-II) and a Pt1Ag4 complex. Analysis showed that Pt1Ag4's ligands directly stem from type I and II ligands in NC-I.
Unveiling the potential of nonconjugate linkers (sp3-cores) in through-space charge transfer emitters and host materials for thermally activated delayed fluorescence organic light emitting diodes
Authors: Bommireddy Purusottam Reddy , Musalikunta Chandra Sekhar , Lee Young-Woong , Suh Youngsuk , Godumala Mallesham , Park Si-Hyun
Published: April 2024

Nonconjugate linkers (sp3 cores) are a versatile platform for molecular design for TADF OLEDs. The introduction of an sp3 core disrupts direct conjugation between donor and acceptor units, preventing immediate charge transfer between them.
Pyrazino[2,3-f][1,10]phenanthroline-based color-tunable thermally activated delayed fluorescence emitters with AIE characteristics for high-efficiency organic light-emitting diodes
Authors: Yadav Pratima , Madagyal Sunil , Chaudhari Aniket , Ganesan Gokul , Su Guan-Yu , Chen Yi-Ting , Chetti Prabhakar , Chang Chih-Hao , Kothavale Shantaram , Chaskar Atul
Published: April 2024

Colour tunable TADF emitters with strong AIE characteristics exhibited EQEs above 20%.
Aktualisierte Leitlinien für Herzpatienten mit Diabetes
Authors: Gollmer Johannes , Zirlik Andreas , Bugger Heiko
Published: April 2024

Individuals with type 2 diabetes are subjected to a disproportionately increased risk for development and progression of cardiovascular disease. Positive outcomes of recent clinical trials have led to the introduction of seminal novel therapeutic options for patients with type 2 diabetes and accompanying cardiovascular risk factors and disease. Consequently, the European Society of Cardiology published an update of the existing guideline for the management of these patients. The aim of this article is to provide a simplified and pragmatic algorithm for diagnostics and treatment for the vast majority of patients with type 2 diabetes, based on current guideline recommendations.
„Ich möchte nur da sein dürfen“
Authors: Stifft-Beyer Ulrike
Published: April 2024

Anscheinend wie aus heiterem Himmel, erleidet eine Klientin mittleren Alters eine heftige Panikattacke mit Einlieferung in die Notaufnahme, worauf sie wiederholt Rezidive erleidet und sich aus ihrem Umfeld zunehmend zurückzieht. Wie sich im Therapieverlauf zeigt, liegt dem Angstgeschehen der verinnerlichte Glaubenssatz „Ich bin es nicht wert, hier zu sein“ zugrunde, der auf traumatischen Erfahrungen durch die Mutter beruht. Im Rahmen einer Gesprächstherapie nach Rogers – fußend auf den Säulen Akzeptanz, Einfühlung und Echtheit –, der Arbeit mit Glaubenssätzen und einer EMDR-Traumatherapie kann die Klientin den Zusammenhang erkennen, Selbstakzeptanz aufbauen und die Panik vollständig überwinden.
Injury Risk Analysis among Judo Athletes with Intellectual
Disabilities
Authors: Morales Jose , Iteya Misaki , Mulroy James , Kons Rafael , Simenko Jozef , Fukuda David H. , Escobar-Molina Raquel , Guerra-Balic Myriam , Pierantozzi Emanuela , Moragas Marta
Published: April 2024

The main aim of this study was to evaluate injury prevalence, incidence rate, and
burden in judo athletes with intellectual disabilities (ID) who participate in
international competitions. This retrospective cross-sectional study analyzed
data from the past year for 182 judo athletes with ID. Data was collected using
a self-reported questionnaire, adapted from previous research, that included
questions about injuries impacting training or competition, injury type,
mechanism, severity, diagnosis, and location on the body. The injury prevalence
among judo athletes with ID occurred most often during training (68.2%) and
primarily affected the lower extremities (35%). Age group and injury prevalence
were significantly related (χ2=7.91; P=0.04), while gender,
weight, and ability level were not. Results were closer to those previously
reported for conventional judo, which is likely due to the lower practice
intensity among judo athletes with ID. Injury prevalence was lower than in prior
studies, but the incidence rates aligned when considering training time in judo
athletes with ID. Injury burden analysis revealed that females had a lower
burden than males, while older athletes experienced a higher burden than younger
athletes. Most injuries occur during training, which is likely attributable to
safety-focused competition rules.
Risk of Postpartum Hemorrhage in Hypertensive Disorders of Pregnancy: Stratified by Severity
Authors: Cagino Kristen A. , Wiley Rachel L. , Ghose Ipsita , Ciomperlik Hailie N. , Sibai Baha M. , Mendez-Figueroa Hector , Chauhan Suneet P.
Published: April 2024

Objective We aimed to determine the composite maternal hemorrhagic outcome (CMHO) among individuals with and without hypertensive disorders of pregnancy (HDP), stratified by disease severity. Additionally, we investigated the composite neonatal adverse outcome (CNAO) among individuals with HDP who had postpartum hemorrhage (PPH) versus did not have PPH.

Study Design Our retrospective cohort study included all singletons who delivered at a Level IV center over two consecutive years. The primary outcome was the rate of CMHO, defined as blood loss ≥1,000 mL, use of uterotonics, mechanical tamponade, surgical techniques for atony, transfusion, venous thromboembolism, intensive care unit admission, hysterectomy, or maternal death. A subgroup analysis was performed to investigate the primary outcome stratified by (1) chronic hypertension, (2) gestational hypertension and preeclampsia without severe features, and (3) preeclampsia with severe features. A multivariable regression analysis was performed to investigate the association of HDP with and without PPH on a CNAO which included APGAR <7 at 5 minutes, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, seizures, neonatal sepsis, meconium aspiration syndrome, ventilation >6 hours, hypoxic–ischemic encephalopathy, or neonatal death.

Results Of 8,357 singletons, 2,827 (34%) had HDP. Preterm delivery <37 weeks, induction of labor, prolonged oxytocin use, and magnesium sulfate usage were more common in those with versus without HDP (p < 0.001). CMHO was higher among individuals with HDP than those without HDP (26 vs. 19%; adjusted relative risk [aRR] = 1.11, 95% CI: 1.01–1.22). In the subgroup analysis, only individuals with preeclampsia with severe features were associated with higher CMHO (n = 802; aRR = 1.52, 95% CI: 1.32–1.75). There was a higher likelihood of CNAO in individuals with both HDP and PPH compared to those with HDP without PPH (aRR = 1.49, 95% CI: 1.06–2.09).

Conclusion CMHO was higher among those with HDP. After stratification, only those with preeclampsia with severe features had an increased risk of CMHO. Among individuals with HDP, those who also had a PPH had worse neonatal outcomes than those without hemorrhage.

Key Points
European Pediatric Surgeons' Association Survey on Timing of Inguinal Hernia Repair in Premature Infants
Authors: Soyer Tutku , Pio Luca , Gorter Ramon , Martinez Leopoldo , Dingemann Jens , Pederiva Federica , Dariel Anne , Zani-Ruttenstock Elke , Kakar Mohit , Hall Nigel J.
Published: April 2024

Aim This article evaluates the practice patterns of European Pediatric Surgeons' Association (EUPSA) members regarding the timing of inguinal hernia (IH) repair in premature infants.

Methods Online survey containing 29 questions distributed to EUPSA members during January 2023.

Results A total of 180 responds were received. Overall, IH repair prior to discharge was favored by 60% of respondents when there was a history of incarceration and 56% when there was not. In the case of very/extremely premature infants (< 32 weeks) with no history of incarceration, fewer (43%) respondents postpone the surgery until after discharge. The majority of respondents cited the risk of incarceration as the reason for advocating surgery prior to discharge, whereas a reduced risk of apnea was the most cited reason for respondents who prefer delayed surgery. Open approach under general anesthesia was favored by 54% of respondents, with 27% of them preferring open approach with spinal anesthesia. Laparoscopic surgery for premature infants is used in 11% while 7% of them preferred in all premature infants including extremely/very premature ones. Contralateral side evaluation was never done by 40% of respondents and 29% only performed it only during laparoscopic repair. The majority of respondents (77%) indicated that they have an overnight stay policy for premature infants < 45 weeks of gestation.

Conclusion There is variation in the practice patterns of pediatric surgeons in the treatment of IH in premature infants. Due to the concern for the high risk of incarceration, IH repair before discharge was the most prevalent practice. Lower risk of postoperative apnea was cited as the most common reason for delaying surgery. Randomized studies are required to establish the optimal timing for IH repair in premature infants.