bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of metabolites associated with preserved muscle volume after aneurysmal subarachnoid hemorrhage due to high protein supplementation and neuromuscular electrical stimulation
Authors: Gusdon Aaron M. , Savarraj Jude P. J. , Feng Diana , Starkman Adam , Li Guoyan , Bodanapally Uttam , Zimmerman William , Ryan Alice S. , Choi Huimahn A. , Badjatia Neeraj
Published: July 2024

The INSPIRE randomized clinical trial demonstrated that a high protein diet (HPRO) combined with neuromuscular electrical stimulation (NMES) attenuates muscle atrophy and may improve outcomes after aneurysmal subarachnoid hemorrhage We sought to identify specific metabolites mediating these effects. Blood samples were collected from subjects on admission prior to randomization to either standard of care (SOC; N = 12) or HPRO + NMES (N = 12) and at 7 days. Untargeted metabolomics were performed for each plasma sample. Sparse partial least squared discriminant analysis identified metabolites differentiating each group. Correlation coefficients were calculated between each metabolite and total protein per day and muscle volume. Multivariable models determined associations between metabolites and muscle volume. Unique metabolites (18) were identified differentiating SOC from HPRO + NMES. Of these, 9 had significant positive correlations with protein intake. In multivariable models, N-acetylleucine was significantly associated with preserved temporalis [OR 1.08 (95% CI 1.01, 1.16)] and quadricep [OR 1.08 (95% CI 1.02, 1.15)] muscle volume. Quinolinate was also significantly associated with preserved temporalis [OR 1.05 (95% CI 1.01, 1.09)] and quadricep [OR 1.04 (95% CI 1.00, 1.07)] muscle volume. N-acetylserine and β-hydroxyisovaleroylcarnitine were associated with preserved temporalis or quadricep volume. Metabolites defining HPRO + NMES had strong correlations with protein intake and were associated with preserved muscle volume.
Healthcare resource utilization and economic burden of multiple sclerosis in Chinese patients: results from a real-world survey
Authors: Sun Chenhan , Jia Yusheng , Li Hainan , Qiao Xuanqi , Tang Mi , Geng Meiyan , Jones Eddie , Pike James , Unsworth Mia , Hu Min
Published: July 2024

Multiple sclerosis (MS) is uncommon in China and the standard of care is underdeveloped, with limited utilization of disease-modifying treatment (DMT). An understanding of real-world disease burden (including direct medical, non-medical, and indirect costs, such as loss of productivity), is currently lacking in this population. To investigate the overall burden of managing patients with MS in China, a cross-sectional survey of physicians and their consulting patients with MS was conducted in 2021. Physicians provided information on healthcare resource utilization (HCRU; consultations, hospitalizations, tests, medication) and associated costs. Patients provided data on changes in their life, productivity, and impairment of daily activities due to MS. Results were stratified by disease severity using generalized linear models, with a p value < 0.05 considered statistically significant. Patients with more severe disease had greater HCRU, including hospitalizations, consultations and tests/scans, and incurred higher direct and indirect costs and productivity loss, compared with those with milder disease. However, the use of DMT was higher in patients with mild disease severity. With the low uptake and limited efficacy of non-DMT drugs, Chinese patients with MS experience a high disease burden and significant unmet needs. Therapeutic interventions could help save downstream costs and lessen societal burden.
Disulfiram downregulates ferredoxin 1 to maintain copper homeostasis and inhibit inflammation in cerebral ischemia/reperfusion injury
Authors: Yang Shuai , Li Xudong , Yan Jinhong , Jiang Fangchao , Fan Xuehui , Jin Jing , Zhang Weihua , Zhong Di , Li Guozhong
Published: July 2024

In the current study, we aimed to investigate whether disulfiram (DSF) exerts a neuroprotective role in cerebral ischemiareperfusion
(CI-RI) injury by modulating ferredoxin 1 (FDX1) to regulate copper ion (Cu) levels and inhibiting inflammatory
responses. To simulate CI-RI, a transient middle cerebral artery occlusion (tMCAO) model in C57/BL6 mice was employed. Mice were administered with or without DSF before and after tMCAO. Changes in infarct volume after tMCAO were observed using TTC staining. Nissl staining and hematoxylin–eosin (he) staining were used to observe the morphological changes of nerve cells at the microscopic level. The inhibitory effect of DSF on initial inflammation was verified by TUNEL assay, apoptosis-related protein detection and iron concentration detection. FDX1 is the main regulatory protein of copper death, and the occurrence of copper death will lead to the increase of HSP70 stress and inflammatory response. Cuproptosis-related proteins and downstream inflammatory factors were detected by western blotting, immunofluorescence staining, and immunohistochemistry. The content of copper ions was detected using a specific kit, while electron microscopy was employed to examine mitochondrial changes. We found that DSF reduced the cerebral infarction volume, regulated the expression of cuproptosis-related proteins, and modulated copper content through down regulation of FDX1 expression. Moreover, DSF inhibited the HSP70/TLR-4/NLRP3 signaling pathway. Collectively, DSF could regulate Cu homeostasis by inhibiting FDX1, acting on the HSP70/TLR4/NLRP3 pathway to alleviate CI/RI. Accordingly, DSF could mitigate inflammatory responses and safeguard mitochondrial integrity, yielding novel therapeutic targets and mechanisms for the clinical management of ischemia–reperfusion injury.
Synthesis, fungal biotransformation, and evaluation of the antimicrobial potential of chalcones with a chlorine atom
Authors: Krawczyk-Łebek Agnieszka , Żarowska Barbara , Dymarska Monika , Janeczko Tomasz , Kostrzewa-Susłow Edyta
Published: July 2024

Chalcones are intermediate products in the biosynthesis of flavonoids, which possess a wide range of biological properties, including antimicrobial and anticancer activities. The introduction of a chlorine atom and the glucosyl moiety into their structure may increase their bioavailability, bioactivity, and pharmacological use. The combined chemical and biotechnological methods can be applied to obtain such compounds. Therefore, 2-chloro-2′-hydroxychalcone and 3-chloro-2′-hydroxychalcone were synthesized and biotransformed in cultures of two strains of filamentous fungi, i.e. Isaria fumosorosea KCH J2 and Beauveria bassiana KCH J1.5 to obtain their novel glycosylated derivatives. Pharmacokinetics, drug-likeness, and biological activity of them were predicted using cheminformatics tools. 2-Chloro-2′-hydroxychalcone, 3-chloro-2′-hydroxychalcone, their main glycosylation products, and 2′-hydrochychalcone were screened for antimicrobial activity against several microbial strains. The growth of Escherichia coli 10,536 was completely inhibited by chalcones with a chlorine atom and 3-chlorodihydrochalcone 2′-O-β-d-(4″-O-methyl)-glucopyranoside. The strain Pseudomonas aeruginosa DSM 939 was the most resistant to the action of the tested compounds. However, chalcone aglycones and glycosides with a chlorine atom almost completely inhibited the growth of bacteria Staphylococcus aureus DSM 799 and yeast Candida albicans DSM 1386. The tested compounds had different effects on lactic acid bacteria depending on the tested species. In general, chlorinated chalcones were more effective in the inhibition of the tested microbial strains than their unchlorinated counterparts and aglycones were a little more effective than their glycosides.
A novel deforestation risk and baseline allocation model for the next generation of nested REDD+ projects
Authors: Freund Jeremy , Pauly Maren , Gochberg Will , Dangremond Emily M. , Korchinsky Mike
Published: July 2024

Nature-based solutions that use a counterfactual scenario depend heavily on the methodology used to determine the business as usual (BAU) case, i.e., the “baseline.” Reducing emissions from deforestation and forest degradation (REDD+) projects traditionally set baselines using a “reference area” as a control for estimating BAU deforestation and emissions in the treatment (project) area. While the REDD+ market is shifting from project-based to nested approaches as countries increase their efforts to meet nationally determined contributions (NDCs) to the Paris agreement’s global climate target, methodologies for allocating national baselines are not yet formalized and tested, despite an urgent need to scale the market. We present a novel method for mapping deforestation risk and allocating national forest reference emission levels (FREL) to projects: baseline allocation for assessed risk (BAAR). This approach provides a spatial predictor of future deforestation using a dynamic vector, and a method for allocating a FREL to differentiated risk areas at the project level. Here, we present BAAR using 34 REDD+ projects in the Democratic Republic of the Congo (DRC). We demonstrate the importance of risk-based FREL allocations to balance fitness for purpose and scientific rigor. We show how BAAR can be used by governments to focus voluntary carbon market finance in areas at highest risk of imminent deforestation, while maintaining alignment with nationally determined contribution (NDC) goals.
Optimizing immunofluorescence with high-dynamic-range imaging to enhance PD-L1 expression evaluation for 3D pathology assessment from NSCLC tumor tissue
Authors: Huang Hsien-Neng , Kuo Chun-Wei , Hung Yu-Ling , Yang Chia-Hung , Hsieh Yu-Han , Lin Yu-Chieh , Chang Margaret Dah-Tsyr , Lin Yen-Yin , Ko Jen-Chung
Published: July 2024

Assessing programmed death ligand 1 (PD-L1) expression through immunohistochemistry (IHC) is the golden standard in predicting immunotherapy response of non-small cell lung cancer (NSCLC). However, observation of heterogeneous PD-L1 distribution in tumor space is a challenge using IHC only. Meanwhile, immunofluorescence (IF) could support both planar and three-dimensional (3D) histological analyses by combining tissue optical clearing with confocal microscopy. We optimized clinical tissue preparation for the IF assay focusing on staining, imaging, and post-processing to achieve quality identical to traditional IHC assay. To overcome limited dynamic range of the fluorescence microscope’s detection system, we incorporated a high dynamic range (HDR) algorithm to restore the post imaging IF expression pattern and further 3D IF images. Following HDR processing, a noticeable improvement in the accuracy of diagnosis (85.7%) was achieved using IF images by pathologists. Moreover, 3D IF images revealed a 25% change in tumor proportion score for PD-L1 expression at various depths within tumors. We have established an optimal and reproducible process for PD-L1 IF images in NSCLC, yielding high quality data comparable to traditional IHC assays. The ability to discern accurate spatial PD-L1 distribution through 3D pathology analysis could provide more precise evaluation and prediction for immunotherapy targeting advanced NSCLC.
An arctic breeding songbird overheats during intense activity even at low air temperatures
Authors: O’Connor Ryan S. , Love Oliver P. , Régimbald Lyette , Le Pogam Audrey , Gerson Alexander R. , Elliott Kyle H. , Hargreaves Anna L. , Vézina François
Published: July 2024

Birds maintain some of the highest body temperatures among endothermic animals. Often deemed a selective advantage for heat tolerance, high body temperatures also limits birds’ thermal safety margin before reaching lethal levels. Recent modelling suggests that sustained effort in Arctic birds might be restricted at mild air temperatures, which may require reductions in activity to avoid overheating, with expected negative impacts on reproductive performance. We measured within-individual changes in body temperature in calm birds and then in response to an experimental increase in activity in an outdoor captive population of Arctic, cold-specialised snow buntings (Plectrophenax nivalis), exposed to naturally varying air temperatures (− 15 to 36 °C). Calm buntings exhibited a modal body temperature range from 39.9 to 42.6 °C. However, we detected a significant increase in body temperature within minutes of shifting calm birds to active flight, with strong evidence for a positive effect of air temperature on body temperature (slope = 0.04 °C/ °C). Importantly, by an ambient temperature of 9 °C, flying buntings were already generating body temperatures ≥ 45 °C, approaching the upper thermal limits of organismal performance (45–47 °C). With known limited evaporative heat dissipation capacities in these birds, our results support the recent prediction that free-living buntings operating at maximal sustainable rates will increasingly need to rely on behavioural thermoregulatory strategies to regulate body temperature, to the detriment of nestling growth and survival.
Durian fruit pulp extract enhances intracellular glutathione levels, mitigating oxidative stress and inflammation for neuroprotection
Authors: Khaksar Gholamreza , Myint Su Lwin Lwin , Hasriadi  , Towiwat Pasarapa , Sirikantaramas Supaart , Rodsiri Ratchanee
Published: July 2024

Durian (Durio zibethinus L.) fruit pulp is a rich source of γ-glutamylcysteine (γ-EC), a direct precursor to the antioxidant glutathione (GSH). This study elucidated the in vitro neuroprotective potential of unripe durian fruit pulp extract (UDE) against H2O2-induced neurotoxicity in SH-SY5Y cells and neuroinflammation in lipopolysaccharide (LPS)-stimulated BV-2 cells. Treatments with γ-EC, GSH standards, or UDE exhibited no cytotoxicity in SH-SY5Y and BV-2 cells, except at high concentrations. A 4-h pretreatment with 100 µM γ-EC or UDE containing 100 µM γ-EC significantly increased SH-SY5Y cell viability post H2O2 induction. Moreover, a similar pretreatment reduced LPS-stimulated production of proinflammatory cytokines in BV-2 cells. The neuroprotective effect of UDE is primarily attributed to γ-EC provision and the promotion of GSH synthesis, which in turn elevates intracellular GSH levels and reduces proinflammatory cytokines. This study identifies γ-EC in UDE as a potential neuroprotective biomarker boosting intracellular GSH levels, providing insights into UDE's therapeutic potential.
Study on the differences between Hoek–Brown parameters and equivalent Mohr–Coulomb parameters in the calculation slope critical acceleration and permanent displacement
Authors: Li Cheng , Zhao Xi , Xu Xingqian , Qu Xin
Published: July 2024

Mohr–Coulomb (MC) strength criterion has been widely used in many classical analytical expressions and numerical modeling due to its simple physical calculation, but the MC criterion is not suitable for describing the failure envelope of rock masses. In order to directly apply MC parameters to analytical expressions or numerical modeling in rock slope stability analysis, scholars established a criterion for converting Hoek–Brown (HB) parameters to equivalent MC parameters. However, the consistency of HB parameters and equivalent MC parameters in calculating critical acceleration of slope needs to be further explored and confirmed. Therefore, HB parameters are converted into equivalent MC parameters by considering the influence of slope angle (1# case and 2# case when slope angle is not considered and slope angle is considered respectively). Then, the lower-bound of finite element limit analysis is used for numerical modeling, and the results of calculating critical acceleration using HB parameters and equivalent MC parameters are compared, and the influence of related parameters on the calculation of critical acceleration is studied. Finally, the influence of different critical accelerations on the calculation of slope permanent displacement is further analyzed through numerical cases and engineering examples. The results show that: (1) In the 1# case, the critical acceleration obtained by the equivalent MC parameters are significantly larger than that obtained by the 2 #case and the HB parameters, and this difference becomes more obvious with the increase of slope angle. The critical acceleration obtained by the 2# case is very close to the HB parameters; (2) In the 1# case, slope height is inversely proportional to ΔAc (HB(Ac) − 1#(Ac)), and with the increase of slope height, ΔAc decreases, while in the 2# case, the difference of ΔAc (HB(Ac)  − 2#(Ac)) is not significant; (3) In the 1# case, the sensitivity of the HB parameters to ΔAc is D > GSI > mi > σci, but in the 2# case, there is no sensitivity-related regularity; (4) The application of HB parameters and equivalent MC parameters in slope permanent displacement is studied through numerical cases and engineering examples, and the limitations of equivalent MC parameters in rock slope stability evaluation are revealed.
Design and radiosynthesis of class-IIa HDAC inhibitor with high molar activity via repositioning the 18F-radiolabel
Authors: Xu Sulan , Huang Chun-Han , Eyermann Christopher , Georgakis Georgios V. , Turkman Nashaat
Published: July 2024

The design and radiosynthesis of [18F]NT376, a high potency inhibitor of class-IIa histone deacetylases (HDAC) is reported. We utilized a three-step radiochemical approach that led to the radiosynthesis of [18F]NT376 in a good radiochemical yield, (17.0 ± 3%, decay corrected), high radiochemical purity (> 97%) and relatively high molar activity of 185.0 GBq/µmol (> 5.0 Ci/µmol). The repositioning of the 18F-radiolabel into a phenyl ring (18F-Fluoro-aryl) of the class-IIa HDAC inhibitor avoided the shortcomings of the direct radiolabeling of the 5-trifluoromethyl-1,2,4-oxadiazole moiety that was reported by us previously and was associated with low molar activity (0.74–1.51 GBq/µmol, 20–41 mCi/µmol). This radiochemical approach could find a wider application for radiolabeling similar molecules with good radiochemical yield and high molar activity.
Direct design of ground-state probabilistic logic using many-body interactions for probabilistic computing
Authors: He Yihan , Luo Sheng , Fang Chao , Liang Gengchiau
Published: July 2024

In this work, an innovative design model aimed at enhancing the efficacy of ground-state probabilistic logic with a binary energy landscape (GSPL-BEL) is presented. This model enables the direct conversion of conventional CMOS-based logic circuits into corresponding probabilistic graphical representations based on a given truth table. Compared to the conventional approach of solving the configuration of Ising model-basic probabilistic gates through linear programming, our model directly provides configuration parameters with embedded many-body interactions. For larger-scale probabilistic logic circuits, the GSPL-BEL model can fully utilize the dimensions of many-body interactions, achieving minimal node overhead while ensuring the simplest binary energy landscape and circumventing additional logic synthesis steps. To validate its effectiveness, hardware implementations of probabilistic logic gates were conducted. Probabilistic bits were introduced as Ising cells, and cascaded conventional XNOR gates along with passive resistor networks were precisely designed to realize many-body interactions. HSPICE circuit simulation results demonstrate that the probabilistic logic circuits designed based on this model can successfully operate in free, forward, and reverse modes, exhibiting the simplest binary probability distributions. For a 2-bit × 2-bit integer factorizer involving many-body interactions, compared to the logic synthesis approach, the GSPL-BEL model significantly reduces the number of consumed nodes, the solution space (in the free-run mode), and the number of energy levels from 12, 4096, and 9–8, 256, and 2, respectively. Our findings demonstrate the significant potential of the GSPL-BEL model in optimizing the structure and performance of probabilistic logic circuits, offering a new robust tool for the design and implementation of future probabilistic computing systems.
Analysis of eligibility criteria in Alzheimer’s and related dementias clinical trials
Authors: Mitchell Alexandra K. , Ehrenkranz Rebecca , Franzen Sanne , Han Sae H. , Shakur Mujaahida , McGowan Melissa , Massett Holly A.
Published: July 2024

Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer’s Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity.
Estimating Hardening Soil-Brick model parameters for sands based on CPTU tests and laboratory experimental evidence
Authors: Truty Andrzej
Published: July 2024

The Hardening Soil-Brick model for soils is designed to carry out complex numerical analyses of soil-structure interaction problems taking into account strong stiffness variation in the range of small strains. However, to calibrate its parameters advanced triaxial and oedometric tests are required. In case of uncemented sands laboratory testing is usually difficult. Therefore, to facilitate calibration procedures, a CPTU based method, enhanced by an experimental evidence derived from advanced triaxial drained and oedometric tests, has been proposed and verified. It is shown in the paper that using exclusively the CPTU test results one can calibrate most important model parameters for sands with accuracy that is sufficient for solving real life problems. The major goal of this paper is to identify correlations between all reference stiffness moduli, then verify them, and finally link with the CPTU based identification procedures. It is shown in the paper that such correlations exist and they exhibit very high coefficients of determination. Moreover, as the seismic version of the CPTU test is not often available in the practice, an enhanced procedure for identification of very small strain shear stiffness modulus has been proposed and then verified, using set of the SCPTU tests conducted in Gdańsk sands (Poland).
Analysis of hemodynamics and impedance using bioelectrical impedance analysis in hypovolemic shock-induced swine model
Authors: Park Hoonsung , Lee Hanyoung , Baik Seungmin , Lee Jae-Myeong
Published: July 2024

To treat hypovolemic shock, fluid infusion or blood transfusion is essential to address insufficient volume. Much controversy surrounds resuscitation in hypovolemic shock. We aimed to identify the ideal fluid combination for treating hypovolemic shock-induced swine model, analyzing bioelectrical impedance and hemodynamics. Fifteen female three-way crossbred pigs were divided into three different groups. The three resuscitation fluids were (1) balanced crystalloid, (2) balanced crystalloid + 5% dextrose water, and (3) balanced crystalloid + 20% albumin. The experiment was divided into three phases and conducted sequentially: (1) controlled hemorrhage (1 L bleeding, 60 min), (2) resuscitation phase 1 (1 L fluid infusion, 60 min), and (3) resuscitation phase 2 (1 L fluid infusion, 60 min). Bioelectrical impedance analysis was implemented with a segmental multifrequency bioelectrical impedance analyzer. A total of 61 impedance measurements were assessed for each pig at six different frequencies in five segments of the pig. Pulse rate (PR), mean arterial pressure (MAP), stroke volume (SV), and stroke volume variation (SVV) were measured using a minimally invasive hemodynamic monitoring device. The three-dimensional graph showed a curved pattern when infused with 1 L of balanced crystalloid + 1 L of 5% dextrose water and 1.6 L of balanced crystalloid + 400 ml of 20% albumin. The 1M impedance increased in all groups during the controlled hemorrhage, and continuously decreased from fluid infusion to the end of the experiment. Only balanced crystalloid + 20% albumin significantly restored MAP and SV to the same level as the start of the experiment after the end of fluid infusion. There were no significant differences in MAP and SV from the time of recovery to the initial value of 1M impedance to the end of fluid infusion in all groups. The change and the recovery of hemodynamic indices such as MAP and SV coincide with the change and the recovery of 1M impedance. Using balanced crystalloid mixed with 20% albumin in hypovolemic shock-induced swine model may be helpful in securing hemodynamic stability, compared with balanced crystalloid single administration.
Identification of a novel lactylation-related gene signature predicts the prognosis of multiple myeloma and experiment verification
Authors: Sun Cheng , Zhang Wanqiu , Liu Hao , Ding Yangyang , Guo Jingjing , Xiong Shudao , Zhai Zhimin , Hu Wei
Published: July 2024

Multiple myeloma (MM) is an incurable hematological malignancy with poor survival. Accumulating evidence reveals that lactylation modification plays a vital role in tumorigenesis. However, research on lactylation-related genes (LRGs) in predicting the prognosis of MM remains limited. Differentially expressed LRGs (DELRGs) between MM and normal samples were investigated from the Gene Expression Omnibus database. Univariate Cox regression and LASSO Cox regression analysis were applied to construct gene signature associated with overall survival. The signature was validated in two external datasets. A nomogram was further constructed and evaluated. Additionally, Enrichment analysis, immune analysis, and drug chemosensitivity analysis between the two groups were investigated. qPCR and immunofluorescence staining were performed to validate the expression and localization of PFN1. CCK-8 and flow cytometry were performed to validate biological function. A total of 9 LRGs (TRIM28, PPIA, SOD1, RRP1B, IARS2, RB1, PFN1, PRCC, and FABP5) were selected to establish the prognostic signature. Kaplan–Meier survival curves showed that high-risk group patients had a remarkably worse prognosis in the training and validation cohorts. A nomogram was constructed based on LRGs signature and clinical characteristics, and showed excellent predictive power by calibration curve and C-index. Moreover, biological pathways, immunologic status, as well as sensitivity to chemotherapy drugs were different between high- and low-risk groups. Additionally, the hub gene PFN1 is highly expressed in MM, knocking down PFN1 induces cell cycle arrest, suppresses cell proliferation and promotes cell apoptosis. In conclusion, our study revealed that LRGs signature is a promising biomarker for MM that can effectively early distinguish high-risk patients and predict prognosis.
Enhanced chondrogenic potential in GelMA-based 3D cartilage model via Wnt3a surface immobilization
Authors: Imere Angela , Foster Nicola C. , Hajiali Hadi , Okur Kerime Ebrar , Wright Abigail L. , Barroso Ines A. , Haj Alicia J. El
Published: July 2024

Cartilage tissue engineering aims to develop functional substitutes for treating cartilage defects and osteoarthritis. Traditional two-dimensional (2D) cell culture systems lack the complexity of native cartilage, leading to the development of 3D regenerative cartilage models. In this study, we developed a 3D model using Gelatin Methacryloyl (GelMA)-based hydrogels seeded with Y201 cells, a bone marrow mesenchymal stem cell line. The model investigated chondrogenic differentiation potential in response to Wnt3a stimulation within the GelMA scaffold and validated using known chondrogenic agonists. Y201 cells demonstrated suitability for the model, with increased proteoglycan content and upregulated chondrogenic marker expression under chondrogenic conditions. Wnt3a enhanced cell proliferation, indicating activation of the Wnt/β-catenin pathway, which plays a role in cartilage development. GelMA hydrogels provided an optimal scaffold, supporting cell viability and proliferation. The 3D model exhibited consistent responses to chondrogenic agonists, with TGF-β3 enhancing cartilage-specific extracellular matrix (ECM) production and chondrogenic differentiation. The combination of Wnt3a and TGF-β3 showed synergistic effects, promoting chondrogenic differentiation and ECM production. This study presents a 3D regenerative cartilage model with potential for investigating cartilage biology, disease mechanisms, and drug screening. The model provides insights into complex cartilage regeneration mechanisms and offers a platform for developing therapeutic approaches for cartilage repair and osteoarthritis treatment.
System-agnostic prediction of pharmaceutical excipient miscibility via computing-as-a-service and experimental validation
Authors: Antipas Georgios S. E. , Reul Regina , Voges Kristin , Kyeremateng Samuel O. , Ntallis Nikolaos A. , Karalis Konstantinos T. , Miroslaw Lukasz
Published: July 2024

We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with Copovidone VA64 polymer at temperature relevant for the pharmaceutical hot melt extrusion process. The computations were performed in lieu of running exhaustive hot melt extrusion experiments to identify surfactant-polymer miscibility limits. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal, and mechanical mixture critical points were detected on molar Gibbs free energy profiles at 180 °C. We established tight agreement between the computed stability (miscibility) limits of 9.0 and 10.0 wt% vs. the experimental 7 and 9 wt% for the Vitamin E TPGS and Tween 80 systems, respectively, and identified different destabilizing mechanisms applicable to each system. This paradigm supports that computational stability prediction may serve as a physically meaningful, resource-efficient, and operationally sensible digital twin to experimental screening tests of pharmaceutical systems. This approach is also relevant to amorphous solid dispersion drug delivery systems, as it can identify critical stability points of active pharmaceutical ingredient/excipient mixtures.
A prognostic model for anoikis-related genes in pancreatic cancer
Authors: Song Wenbin , Hu Haiyang , Yuan Zhengbo , Yao Hao
Published: July 2024

Anoikis, a distinct form of programmed cell death, is crucial for both organismal development and maintaining tissue equilibrium. Its role extends to the proliferation and progression of cancer cells. This study aimed to establish an anoikis-related prognostic model to predict the prognosis of pancreatic cancer (PC) patients. Gene expression data and patient clinical profiles were sourced from The Cancer Genome Atlas (TCGA-PAAD: Pancreatic Adenocarcinoma) and the International Cancer Genome Consortium (ICGC-PACA: Pancreatic Ductal Adenocarcinoma). Non-cancerous pancreatic tissue gene expression data were obtained from the Genotype-Tissue Expression (GTEx) project. The R package was used to construct anoikis-related PC prognostic models, which were later validated with the ICGC-PACA database. Survival analyses demonstrated a poorer prognosis for patients in the high-risk group, consistent across both TCGA-PAAD and ICGC-PACA datasets. A nomogram was designed as a predictive tool to estimate patient mortality. The study also analyzed tumor mutations and immune infiltration across various risk groups, uncovering notable differences in tumor mutation patterns and immune landscapes between high- and low-risk groups. In conclusion, this research successfully developed a prognostic model centered on anoikis-related genes, offering a novel tool for predicting the clinical trajectory of PC patients.
Dispersal of Late Triassic clam shrimps across Pangea linking northwestern Gondwana and central Pangea rift basins
Authors: Alarcón Carlos M. , Colombi Carina E. , Gallego Oscar F. , Drovandi Juan M. , Monferran Mateo D.
Published: July 2024

Clam shrimps are a group of freshwater crustaceans who prospered during the Late Triassic. They were abundant in lacustrine sedimentary records of continental basins distributed throughout Pangea during this time. However, they show significant taxonomic differences between the clamp shrimp faunas from the rift basins of central Pangea and the southern Gondwanan basins. In this contribution, we show new fossil clam shrimp assemblages from the lacustrine sedimentary successions of the Eastern Cordillera of Colombia (the Bocas and Montebel formations), providing information on the Late Triassic species that inhabited the northwestern Gondwana basins. This study demonstrates that the basins of northwestern Gondwana shared Norian clamp shrimp species with rift basins of central Pangea and differed in their faunas with the basins of the southern portion of Gondwana. In addition, the Late Triassic clam shrimps paleobiogeographic distribution reflects the dispersal of this fauna throughout fluvial-lacustrine environments established in the rift valleys along the central Pangea. Therefore, the rift valleys produced during the early fragmentation of central Pangea could have acted as corridors for dispersion. Simultaneously, rift valleys also provided paleobiogeographic barriers that isolated the central Pangea clam shrimp faunas from southern Gondwana.
The role of water bridge on gas adsorption and transportation mechanisms in organic shale
Authors: Li Binhui , Liu Yong , Lan Yubo , Li Jiawei , Lang Yue , Rahman Sheikh S.
Published: July 2024

This work introduces and discusses the impacts of the water bridge on gas adsorption and diffusion behaviors in a shale gas-bearing formation. The density distribution of the water bridge has been analyzed in micropores and meso-slit by molecular dynamics. Na+ and Cl− have been introduced into the system to mimic a practical encroachment environment and compared with pure water to probe the deviation in water bridge distribution. Additionally, practical subsurface scenarios, including pressure and temperature, are examined to reveal the effects on gas adsorption and diffusion properties, determining the shale gas transportation in realistic shale formation. The outcomes suggest carbon dioxide (CO2) usually has higher adsorption than methane (CH4) with a water bridge. Increasing temperature hinders gas adsorption, density distribution decreases in all directions. Increasing pressure facilitates gas adsorption, particularly as a bulk phase in the meso-slit, whereas it restricts gas diffusion by enhancing the interaction strength between gas and shale. Furthermore, ions make the water bridge distributes more unity and shifts to the slit center, impeding gas adsorption onto shale while encouraging gas diffusion. This study provides updated guidelines for gas adsorption and transportation characteristics and supports the fundamental understanding of industrial shale gas exploration and transportation.
Optimization of thorium solvent extraction process from feed solution with Cyanex 272 by response surface methodology (RSM)
Authors: Khanramaki F. , Keshtkar A. R.
Published: July 2024

Due to the limited reserves of uranium, the abundance of thorium compared to it and other advantages, the development of the thorium fuel cycle is of interest in different countries. The optimization of thorium extraction from a feed solution produced by Saghand ore with bis(2,4,4-trimethylpentyl) phosphinic acid (Cyanex 272) on a laboratory scale was evaluated by response surface method. The operating variables include Cyanex 272 concentration of 0.001 to 0.2 mol/L, pH of 0 to 2, equilibrium time of 5 to 60 min and aqueous to organic phase ratio of 0.5 to 2.5 were conducted. The value of R2 = 0.9695 and an error of less than 4% indicate the validity of the model. Therefore, the model is in good agreement with the experimental results. It can be said that there are significant interactions between operational parameters, which vindicate different feedbacks of the system in different operational conditions. The results showed that the 4 mol/L sulfuric acid was a suitable agent for recovering thorium ions from the loaded organic phase. In optimum conditions, the thorium purity percentage and thorium stripping efficiency were obtained 98.99 and 94.12%, respectively.
The association between TSH and thyroid hormones in the normal or subclinical dysfunction range with left ventricular diastolic dysfunction
Authors: Jun Ji Eun , Kim Tae Hyuk , Kim Sun Wook , Chung Jae Hoon , Kim Jae Hyeon , Lee You-Bin , Kang Mira
Published: July 2024

Thyroid hormones modulate the cardiovascular system. However, the effects of subclinical thyroid dysfunction and euthyroidism on cardiac function remain unclear. We investigated the association between left ventricular (LV) diastolic dysfunction and subclinical thyroid dysfunction or thyroid hormones within the reference range. This cross-sectional study included 26,289 participants (22,197 euthyroid, 3,671 with subclinical hypothyroidism, and 421 with subclinical thyrotoxicosis) who underwent regular health check-ups in the Republic of Korea. Individuals with thyroid stimulating hormone (TSH) levels > 4.2 µIU/mL and normal free thyroxine (FT4, 0.78–1.85 ng/dL) and triiodothyronine (T3, 76–190 ng/dL) levels were defined as having subclinical hypothyroidism. Individuals with serum TSH levels < 0.4 µIU/mL and normal FT4 and T3 levels were defined as having subclinical thyrotoxicosis. The cardiac structure and function were evaluated using echocardiography. LV diastolic dysfunction with normal ejection fraction (EF) was defined as follows: EF of > 50% and (a) E/e’ ratio > 15, or (b) E/e’ ratio of 8–15 and left atrial volume index ≥ 34 mL/m2. Subclinical hypothyroidism was significantly associated with cardiac indices regarding LV diastolic dysfunction. The odds of having LV diastolic dysfunction was also increased in participants with subclinical hypothyroidism (adjusted odds ratio [AOR] 1.36, 95% confidence interval [CI], 1.01–1.89) compared to euthyroid participants. Subclinical thyrotoxicosis was not associated with LV diastolic dysfunction. Among the thyroid hormones, only serum T3 was significantly and inversely associated with LV diastolic dysfunction even within the normal range. Subclinical hypothyroidism was significantly associated with LV diastolic dysfunction, whereas subclinical thyrotoxicosis was not. Serum T3 is a relatively important contributor to LV diastolic dysfunction compared to TSH or FT4.
Genome-wide identification of the sorghum OVATE gene family and revelation of its expression characteristics in sorghum seeds and leaves
Authors: An Yanlin , Xia Xiaobo , Zhang Xiaoqin , Liu Li , Jiang Sixia , Jing Tingting , Zhang Feng
Published: July 2024

The OVATE gene family plays an important role in regulating the development of plant organs and resisting stress, but its expression characteristics and functions in sorghum have not been revealed. In this study, we identified 26 OVATE genes in the sorghum BTx623 genome, which were divided into four groups and distributed unevenly across 9 chromosomes. Evolutionary analysis showed that after differentiation between sorghum and Arabidopsis, the OVATE gene family may have experienced unique expansion events, and all OVATE family members were negatively selected. Transcriptome sequencing and RT-qPCR results showed that OVATE genes in sorghum showed diverse expression characteristics, such as gene SORBl_3001G468900 and SORBl_3009G173400 were significantly expressed in seeds, while SORBI_3005G042700 and SORBI_3002G417700 were only highly expressed in L1. Meantime, in the promoter region, a large number of hormone-associated cis-acting elements were identified, and these results suggest that members of the OVATE gene family may be involved in regulating specific development of sorghum leaves and seeds. This study improves the understanding of the OVATE gene family of sorghum and provides important clues for further exploration of the function of the OVATE gene family.
Effect of storage conditions on lignocellulose biofuels properties
Authors: Wzorek Małgorzata , Król Anna , Junga Robert , Małecka Joanna , Yilmaz Ersel , Kolasa-Więcek Alicja
Published: July 2024

This article examines the effects of different storage conditions on selected physicochemical properties of three types of agro-biomass pellets: sunflower husks, wheat straw and hemp hurds, and wood pellets. The tests were carried out in a climatic chamber, which allows simulation of real storage conditions, i.e. conditions with high air humidity and variable (±) ambient air temperatures. The results showed higher degradability of agro-biomass pellets compared to woody biomass. The pellets degraded to a less extent at varying  ± temperatures than at high humidity (90% RH). After complete moisture saturation, durability decreases for agro-pellets by an average of 9%, while after freezing and defreezing for sunflower husk pellets and woody pellets durability decreases by 2%, and for hemp hurd pellets by 11%. In contrast, strength-by-dropping index for agro-pellets decreased by 20% after being in the environment (30 °C and 90%RH) and 15% under varying temperature conditions. No change in the energy parameters of all pellets in the dry matter was noted. On the other hand, an increase in the moisture content of pellets when they are stored under different environmental conditions results in a decrease in calorific value.
Optimization of hydrothermal autoclaving parameters for the synthesis of porous ceramics from porcelain tile polishing residue
Authors: Zhao Liang , Yao Shuang , Zhao Jiayu
Published: July 2024

Porous ceramics were synthesized using porcelain tile polishing residue (PTPR) and slaked lime (Ca(OH)2) as a reinforcing agent through a hydrothermal autoclaving method. The process parameters, including the quantity of slaked lime added, the hydrothermal autoclaving temperature, and the reaction duration, were optimized meticulously. The composition, structure, thermal and physical properties of the samples were thoroughly analyzed via Brunauer–Emmett–Teller (BET) measurements, powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The results indicated that the incorporation of slaked lime and hydrothermal autoclaving led to the formation of calcium silicate hydrate, which corresponded with an enhancement in the strength of the sample. Notably, when the quantity of slaked lime added was optimized at 30 wt%, the formation of tobermorite (5CaO·6SiO2·5H2O) was detected. At a hydrothermal autoclaving temperature of 150 °C, the formation of only sheet-like calcium silicate hydrate was observed. In contrast, at an elevated temperature of 180 °C and 210 °C, needle-like tobermorite was successfully synthesized. The porous ceramic with the most favorable structure was obtained through autoclaving at 180 °C for 10 h with 30 wt% slaked lime, exhibiting a total pore volume of 0.11 mL/g, a specific surface area of 26.35 m2/g, and a mesoporous volume fraction of 90.40%.
Sleep–wake changes and incident depressive symptoms in midlife women
Authors: Luo Jing , Lin Song
Published: July 2024

Our study aimed to investigate the relationship between sleep–wake changes and depressive symptoms events among midlife women. We enrolled 1579 women aged 44–56 years who had no clinically relevant depressive symptoms at baseline. Depressive symptoms were assessed at each visit using the Center for Epidemiologic Studies Depression scale. At the third and fourth follow-up visits, women reported their sleep habits. The sleep midpoint was defined as the time to fall asleep plus one-half of the sleep duration. Sleep–wake changes were determined by the difference in the midpoint of sleep between the third and fourth visits, which were 1 year apart. The median follow-up time was 7 years (range 1–7 years). Cox proportional hazard models were fitted to calculate hazard ratios and 95% confidence intervals for the incidence of depressive symptoms associated with sleep–wake changes. After adjusting for potential confounding factors, the hazard ratio (95% confidence interval) of depressive symptoms for severe sleep midpoint changes was 1.51 (1.12, 2.05) compared with mild sleep midpoint changes. This relationship remained statistically significant and changed little when additionally controlling for sleep duration, sleep quality, insomnia symptoms, use of sleep medications, use of nervous medications, glucose, insulin, lipids, dietary energy intake, and C-reactive protein. Our findings indicate that exposure to long-term severe sleep–wake changes increases the risk of depressive symptoms in midlife women.
Development and validation of an intraoperative hypothermia nomograph model for patients undergoing video-assisted thoracoscopic lobectomy: a retrospective study
Authors: Xia Fuhai , Li Qiang , Xu Liqin , Chen Xi , Li Gen , Li Li , Cheng Zhineng , Zhang Jie , Deng Chaoliang , Li Jing , Chen Rui
Published: July 2024

This study aimed to develop and internally validate a nomogram model for assessing the risk of intraoperative hypothermia in patients undergoing video-assisted thoracoscopic (VATS) lobectomy. This study is a retrospective study. A total of 530 patients who undergoing VATS lobectomy from January 2022 to December 2023 in a tertiary hospital in Wuhan were selected. Patients were divided into hypothermia group (n = 346) and non-hypothermia group (n = 184) according to whether hypothermia occurred during the operation. Lasso regression was used to screen the independent variables. Logistic regression was used to analyze the risk factors of hypothermia during operation, and a nomogram model was established. Bootstrap method was used to internally verify the nomogram model. Receiver operating characteristic (ROC) curve was used to evaluate the discrimination of the model. Calibration curve and Hosmer Lemeshow test were used to evaluate the accuracy of the model. Decision curve analysis (DCA) was used to evaluate the clinical utility of the model. Intraoperative hypothermia occurred in 346 of 530 patients undergoing VATS lobectomy (65.28%). Logistic regression analysis showed that age, serum total bilirubin, inhaled desflurane, anesthesia duration, intraoperative infusion volume, intraoperative blood loss and body mass index were risk factors for intraoperative hypothermia in patients undergoing VATS lobectomy (P < 0.05). The area under ROC curve was 0.757, 95% CI (0.714–0.799). The optimal cutoff value was 0.635, the sensitivity was 0.717, and the specificity was 0.658. These results suggested that the model was well discriminated. Calibration curve has shown that the actual values are generally in agreement with the predicted values. Hosmer–Lemeshow test showed that χ2 = 5.588, P = 0.693, indicating that the model has a good accuracy. The DCA results confirmed that the model had high clinical utility. The nomogram model constructed in this study showed good discrimination, accuracy and clinical utility in predicting patients with intraoperative hypothermia, which can provide reference for medical staff to screen high-risk of intraoperative hypothermia in patients undergoing VATS lobectomy.