bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of a unique Ni2+-dependent heterohexameric metformin hydrolase
Authors: Zhou Ning-Yi , Li Tao , Xu Zhi-Jing , Zhang Shu-Ting , Xu Jia , Pan Piao-Piao 
Published: January 2024

Abstract

The biguanide drug metformin is prescribed worldwide as a first-line blood glucose-lowering medication for type 2 diabetes, leading to its presence in the environment around the world. Despite mounting evidence indicating that metabolic interactions of metformin with environmental or intestinal microbes affect ecological and human health, little is known about the fate of metformin by microbial catabolism. Here, we characterized a Ni2+-dependent bacterial enzyme that catalyzes the hydrolysis of metformin to form guanylurea and dimethylamine. The metformin hydrolase MetCaCb is a heterohexamer with an uneven α2β4 stoichiometry. Both subunits are from the arginase protein family, members of which are typically homomultimers. Either subunit alone is catalytically inactive, but together they work as an active enzyme highly specific for metformin. The crystal structure of the MetCaCb complex clearly shows the coordination of the binuclear metal cluster only in MetCa, following a geometry typical for arginase family enzymes. A unique pseudoenzyme MetCb, which evolved without a binuclear metal cluster, contributes to hydrolase activity as a protein binder of its active cognate. An in-silico search and functional assay led to the discovery of a group of MetCaCb-like protein pairs exhibiting metformin hydrolase activity in the environment. Our findings not only establish the genetic and biochemical foundation for metformin catabolism but also provide new insights into the adaption of the ancient arginase family proteins toward newly occurred substrate.
Capecitabine and Oxaliplatin（CAPEOX） combined with Sintilimab plus bevacizumab biosimilar（IBI305）for first-line treatment of advanced gastric or esophagogastric junction adenocarcinoma: study protocol of a single-arm, phase Ib/II trial
Authors: Dai Ruihong , Zhang Pengfei , Cheng Mo , Bi Feng , Zhou Jitao , Liu Ming 
Published: January 2024

Abstract
Gastric cancer is the fifth most diagnosed cancer in the world and the third leading cause of cancer-related death. For patients with advanced gastric cancer, systemic treatment combined with immune immune check point Inhibitors is the first choice. However, the median survival time after first-line chemotherapy for advanced gastric cancer is about 15 months, and treatment still faces bottlenecks. Bevacizumab is a humanized monoclonal antibody that inhibits the binding of human VEGF to its receptor. Although AVAGAST did not reach its primary objective, chemotherapy combined with bevacizumab in the AVAGAST study significantly improved the median progression-free survival (mPFS) and objective response rate (ORR) in the first-line treatment of advanced gastric cancer. The combination of chemotherapy with immunotherapy has become the standard treatment for gastric cancer. Furthermore, immunotherapy and bevacizumab have a synergistic effect; hence, whether the addition of bevacizumab to chemotherapy combined with immunotherapy can bring clinical benefits to gastric cancer patients needs to be explored.
Methods and analysis
This was a single-arm, open-label, prospective Phase 1b/II clinical study involving a total of 57 cases. In Phase 1b, patients with advanced or metastatic stomach adenocarcinoma or esophagogastric junction received CAPEOX (Oxaliplatin and capecitabine) along with sintilimab (200 mg intravenously every 3 weeks) and bevacizumab (7.5, 10, or 15 mg/kg intravenously every 3 weeks) in a 3+3 dose escalation Phase to determine the maximum tolerated dose and dose-limiting toxicities. In Phase 2, patients with advanced gastric or esophagogastric junction adenocarcinoma received CAPEOX plus sintilizumab and bevacizumab. The primary objectives were dose-limiting toxicities (Phase 1b) and ORR (Phase 2). Secondary objectives include PFS, overall survival, disease control rate, duration of response, adverse effects, quality of life, and safety.
Ethics and Communication
This trial was approved by the Ethics Committee of West China Hospital. The final results of this trial will be published in a peer-reviewed journal upon completion.
Trial registration: ClinicalTrials.gov Identifier: NCT05640609. Registration date: December 23, 2022
A multi-objective optimization method for community detection using a novel heuristic search
Authors: Moradi Mehdi , Mohammadi Kamyar , Moradi Parham 
Published: January 2024

Abstract
Identifying structural patterns of complex networks is crucial to the study of community detection. The study of complex networks has recently been facilitated by several evolutionary methods. The main challenges of using evolutionary-based methods are their lower accuracies and their limitations in handling large networks. The evolutionary-based approaches treat most of these methods as single-objective tasks. Investigating a problem with multiple objectives can lead to a more precise identification of the community structure in a network. This is because each objective can capture distinct properties or aspects of the network, resulting in a more comprehensive understanding of its structure. In our paper, we introduce MOGGA+, which is a combination of a multi-objective genetic algorithm and local search strategies, aimed at tackling these issues. The local search strategy is primarily employed to accelerate convergence and enhance the precision of method. The solutions in MOCGA+ are represented using a vector-based method. The number of communities does not need to be known before the search begins because the utilization of this representation type diminishes the exploration range. Through experiments conducted on both LFR and real-world networks, the suggested method has demonstrated the ability to identify communities with higher accuracy while requiring fewer generations.
Geographic Restrictions for COVID-19 Stimulus Spending and Public Health Outcomes: Evidence from Big Data in Seoul, South Korea
Authors: Lee Kwan Ok , Lee Hyojung , Lee Jieun 
Published: January 2024

Abstract
During the COVID-19 pandemic, the stimulus payments program has proven to be an effective means of boosting economic activity. Despite the plausible link between these programs and public health outcomes, however, there has been little research on this subject. Our study examines whether the unique policy design restricting geographic locations for COVID-19 stimulus spending could mitigate the spread of the virus. We utilize weekly mobile phone-based mobility data, credit card transaction data, and official COVID-19 cases at a detailed geographic level in Seoul, South Korea. Event-study and difference-in-differences models examined the effects of stimulus payment programs on human mobility and consumer spending patterns. Using the coefficients derived from the model estimating the relationship between COVID-19 infections and commuting inflows, we conduct counterfactual simulations to investigate the role of a geographic restriction in mitigating the potential side effects on public health. The event-study results confirmed a significant increase in people’s mobility in Seoul after the disbursement of stimulus payments as stimulus benefits started to translate into increased economic activities. Yet, an additional difference-in-differences analysis based on the card transaction data indicates that a significant share of stimulus transactions was made in the recipients’ own neighbourhood. Our simulation testing the differences between policy scenarios with and without geographic restrictions in possible COVID-19 cases indicates that geographic restrictions reduce possible COVID-19 cases by 6.5% compared to the counterfactual scenario (without geographic restrictions). Our findings highlight the importance of geographic restrictions as a policy component in addressing the potential side effects of the stimulus program.
Thermal properties of ASR products
Authors: Honorio Tulio , Razki Syrine , Bourdot Alexandra , Benboudjema Farid 
Published: January 2024

Abstract

Thermal and themo-mechanical properties of alkali-silica reaction (ASR) products are poorly studied.
The existent property data refers to theoretical considerations and do not account for the fact that ASR products can be crystalline, nanocrystalline and potentially amorphous.
Here, the thermal conductivity, heat capacity, and coefficient of thermal expansion of crystalline structures (based on Na- and K-shlykovite), nanocrystalline structure (based on defective K-shlykovite structures), and amorphous ASR product are calculated using molecular simulations.
Semi-classical estimates of the thermal conductivity, heat capacity, and standard molar entropy are provided.
The anisotropy of thermal conductivity and thermal expansion is quantified.
Nanoacoustics parameters (sound velocities, phonon free path and relaxation time) are calculated.
These results contribute to completing property data for ASR products.
Factors for a clinical prediction score to determine complication development after cellulitis diagnosis in adult patients
Authors: Tienpratarn Welawat , Yuksen Chaiyaporn , Pauly Joseph Daniel , Vu Diana , Benbourenane Anisa Noiwong , Sangskul Nuttamon 
Published: January 2024

Abstract
Background Cellulitis is defined as a bacterial infection of the skin and subcutaneous tissue that can cause multiple complications, such as sepsis and necrotizing fasciitis. In extreme cases, it may lead to multiorgan failure and death. We sought to analyze the clinical factors that contribute to the development of complicated disease, including demographics, clinical presentation, initial vital signs, and laboratory studies.
Methods Our study is a retrospective cohort study carried out in a university-based tertiary care hospital in Bangkok, Thailand. All adult patients who presented with cellulitis from January 1, 2018, to December 31, 2022, were evaluated for eligibility and inclusion in this study. All related variables for both outcomes, septicemia and necrotizing fasciitis, were gathered from electronic medical records and analyzed.
Results Of the 1,560 visits to this hospital, 47 cases reported at least one complication, with septicemia noted in 27 visits (6.68%) and necrotizing fasciitis in 20 visits (1.27%). From the multivariable logistic regression analysis, six variables emerge as predictors of cellulitis complications. These are: Age≥ 65 years, Body Mass Index ≥ 30 kg/m2, diabetes mellitus, body temperature ≥ 37.3°C, systolic blood pressure < 100 mmHg, and involvement of lower extremities. The predictive score was developed from these factors and was named the Ramathibodi Necrotizing Fasciitis/Septicemia (RAMA-NFS) Prediction Score. Our predictive score has an accuracy of 82.3% (95% CI 0.77-0.88). Patients in the high-risk group (RAMA NFS score > 6) have a likelihood ratio of 3.7 times to develop complications of cellulitis.
Conclusion In our study, the RAMA-NFS Prediction Score predicts complications in adult patients who present with cellulitis. External validation of this predictive score is still needed for further practical application.
Cholesterol homeostasis and oxidative stress-related novel plasma biomarkers for MSA patients
Authors: Lin Shau-Ping , Wang Hsiang-Hsuan Lin , Huang Jing-Wen , Kuo Mingche , Tsai Yi-Tzang , Lu Chia-Chen , Chen Yan-Hong , Phoa Frederick Kin Hing , Kung Pin-Jui , Lin Yan-Han , Chu Yung-Tsai , Ju Yan-Ru , Shen Tang-Long , Hong Chien-Tai , Ochiya Takahiro , Ueda Koji , Wu Ruey-Meei 
Published: January 2024

Abstract

Multiple system atrophy (MSA) is an atypical parkinsonism that mimics the clinical manifestation of Parkinson’s disease (PD) but is characterized by distinct pathological hallmarks and poor medication response. Identifying reliable biomarkers for MSA facilitates differential diagnosis and promotes targeted treatments. Here, we profiled plasma-derived extracellular vesicle (EV) proteomics in patients with MSA or PD and healthy controls (HC), based on liquid chromatography‒mass spectrometry (LC‒MS/MS). A modified linear programming system termed Biomedical Oriented Logistic Dantzig (BOLD) Selector was implemented for the identification of the EV proteins that were significantly associated with MSA through an oversaturated proteomic dataset comprising 1272 entries. As a result, the top-ranked EV protein candidates incorporated into our constructed logistic regression formula for differentiating MSA patients with HC were LCAT, CRKL, Kallistatin and CSE1L, and APOE, ALDH4A1, ABCC4, and kallistatin for separating MSA from typical PD patients. These EV proteins are most strongly attributed to “cholesterol transport” by gene ontology analysis. The other major biological processes highlighted for these candidates include modulators for oxidative stress, inflammation, and demyelination processes. Innovative therapeutic approaches targeting these candidates aiming at regulating cholesterol balance, reducing oxidative stress, and alleviating glial inflammation hold promise for neuroprotection against the lethal neurodegenerative disorders.
Association between antidepressant use and delirium in older adults: an analysis of the World Health Organization’s global pharmacovigilance database
Authors: Minoc Elise-Marie , Villain Cédric , Benbrika Soumia , Chrétien Basile , Descatoire Pablo , Heraudeau Marie , Sassier Marion , Pierre Mélissa , Martinaud Olivier , Dolladille Charles , Lelong-Boulouard Véronique 
Published: January 2024

Abstract
Background
Psychoactive drugs frequently cause delirium adverse events in older adults. However, few data on the relationship between antidepressants and delirium are available. Here, we investigated the association between antidepressant prescription and pharmacovigilance reports of delirium in older adults.
Methods
Using the World Health Organization’s VigiBase® global pharmacovigilance database from 1967 to 2022, we performed a disproportionality analysis in order to probe the putative associations between each antidepressant class (non-selective monoamine reuptake inhibitors (NSMRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), alpha-2-adrenergic receptor antagonists, and other antidepressants) and reports of delirium in people aged 65 or over. We calculated the reporting odds ratios (r-OR) and their 95% confidence interval ([95%CI]) with logistic regression models before and after adjustment for confounding factors. Secondary analyses were performed for each drug and within each class by age group (65–74, and 75 and over). We also studied the reports of concomitant delirium and hyponatremia.
Results
Our main analysis included 87,524 cases of delirium. After adjustment for confounders, a significant association was found between delirium and all antidepressant classes other than SNRIs. Intraclass disparities were found for the association between the most frequently prescribed antidepressants and reports of delirium. An elevated risk of reports of concomitant delirium and hyponatremia was found for SSRIs (4.46 [4.01–4.96]), SNRIs (1.25 [1.07–1.46]), MAOIs (1.72 [1.41–2.09]), and the “other antidepressants” class (1.47 [1.30–1.65]).
Conclusions
There was a significant association between reports of delirium and antidepressant classes (other than SNRIs). However, this association varied from one drug to another within a given antidepressant class. Moreover, this association could not always be explained by antidepressant-induced hyponatremia.
Durability Characteristics of Geopolymer Concrete Produced Using Gold Ore Tailings Along with Recycled Coarse Aggregates
Authors: Lokesha Eshwarayya Bolluru , Aruna Mangalpady , Reddy Sandi Kumar 
Published: January 2024

Abstract
The gold ore tailings (GOTs) are one of the major waste in the mining sector. The disposal of these tailings could be the problem to human health and major environmental concern from several years. Hence, the attempt should be made for effective utilization of industrial waste in the construction industry in different forms. In this research work, the GOTs were used as an alternative material to the river sand (RS) in the production of geopolymer concrete (GPC). The developed GPC samples were tested to know the durability characteristics, such as resistance to sulphates and chlorides. The sulphate attack test was conducted by immersing the conventional concrete (CC) and GPC samples in 5% magnesium sulphate (MgSO4) solution for a period of 28 days, 56 days, 90 days, 180 days, 270 days, and 365 days. In this test, the GPC samples showed the reduction in compressive strength and weight, which is slightly more when compared to CC samples, for 270 and 365 days of exposure condition. The rapid chloride penetration test (RCPT) was also conducted to know the chloride ion penetration in which GPC samples exhibited less chloride penetration when compared to CC samples. Further, the toxic characteristic leaching procedure (TCLP) analysis showed that the GOTs has very high concentration of hazardous metals, such as arsenic (As), zinc (Zn), iron (Fe), and mercury (Hg). But the concentration of cyanide (CN−) was minimum in GOTs. In this regard, geopolymerization would be a better method for immobilizing the hazardous metals present in GOTs.
Pharmacological management of acute agitation in psychiatric patients: an umbrella review
Authors: Uribe Erasmo Saucedo , Bravo-Rodríguez Cynthia Alejandra , Navarrete-Juárez Miguel Emanuel , Medrano-Juarez Samantha Berenice , Lucio Rodrigo Huereca , Rojas-Guzman Kevin Eduardo , Lozano-Carrillo Luis Carlos 
Published: January 2024

Abstract
Background
the main characteristics present in patients with psychomotor agitation include restlessness, excessive motor activity, irritability, heightened responsiveness to internal and external stimuli, and unstable clinical condition. This umbrella review evaluates the efficacy and safety of pharmacological interventions for patients with psychiatric disorders presenting psychomotor agitation, aged 18 years or older. A comprehensive literature search was conducted to identify umbrella reviews that met the inclusion criteria of our study, and none were found that specifically investigated the efficacy and safety of pharmacological interventions for agitated psychiatric patients with both psychological and behavioral symptoms. The primary objective is to determine the efficacy and safety of pharmacological interventions for managing agitated psychiatric patients in both inpatient and emergency department settings. Secondary objectives include assessing the safety and efficacy of pharmacological interventions by specific diagnosis, including psychotic disorders, mood disorders, personality disorders, and substance use disorders.
Method
a comprehensive literature search for published and unpublished meta-analyses and systematic reviews assessing the efficacy and safety of pharmacological treatment for agitation in psychiatric inpatients and emergency department patients was conducted across various databases (PubMed, Ovid MEDLINE, EMBASE, PSYCINFO). Included reviews comprised those that incorporated randomized controlled trials (RCTs) or non-randomized controlled trials (NRCTs) comparing the efficacy and safety of pharmacological interventions for agitated psychiatric patients (with both psychological and behavioral symptoms).
Results
a total of 20 meta-analyses and systematic reviews met the inclusion criteria for this umbrella review. The results are presented by grouping medications into drug classes, providing information on the most used dosage, median dose, average dose, and dose range for each medication. Furthermore, medications most frequently used for specific psychiatric diagnoses, such as psychotic disorders, bipolar disorder, personality disorders, and substance use disorders, are also highlighted.
Conclusion
this umbrella review offers a comprehensive overview of the pharmacological management of agitation in patients with psychiatric disorders. Among the most frequently used medications in the reviewed studies were haloperidol, olanzapine, and lorazepam. The findings underscore the importance of tailored treatment approaches and the need for further research to refine the management of agitation in psychiatric settings.
Identification of a circRNA-miRNA-mRNA interactome associated with Parkinson’s Disease progression
Authors: Leier André , Shrestha Lisa 
Published: January 2024

Abstract
Circular RNAs (circRNAs) constitute a distinctive subclass of RNAs characterized by their covalently closed loop structure, playing regulatory roles in fundamental cellular processes. Due to their increased stability and ubiquitous expression in major tissues and organs, circular RNAs have been widely studied as potential molecular targets in various diseases, including in Parkinson’s Disease (PD) and other neurodegenerative diseases. However, a comprehensive understanding of the precise involvement of circRNAs in the progression of PD has been lacking. In this study, we have utilized large-scale, longitudinal, and deep RNA-seq data from two independent cohorts, namely the Parkinson’s Progression Marker Initiative (PPMI) and the Parkinson’s Disease Biomarker Program (PDBP), to characterize circRNA expression in patients of early PD stage. We identified 12 circRNAs that were found differentially expressed in PD patients over time. Additionally, we were able to map a competing endogenous RNA (ceRNA) network with potential downstream miRNA-mRNA targets and, with the help of co-expression analysis, to identify genes associated with PD progression. Our findings provide compelling evidence for a dysregulated circRNA interactome as an indicator of disease progression. Changes in the expression of some of this interactome’s key molecules, including circRNAs, miRNAs, and gene targets, are significantly associated with PD hallmarks, pathways, and/or changes in UPDRS III scores in PD patients.