bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coupling dairy wastewaters for nutritional balancing and water recycling: sustainable heterologous 2-phenylethanol production by engineered cyanobacteria
Authors: Usai Giulia , Cordara Alessandro , Mazzocchi Elena , Re Angela , Fino Debora , Pirri Candido Fabrizio , Menin Barbara 
Published: March 2024

Microalgae biotechnology is hampered by the high production costs and the massive usage of water during large-volume cultivations. These drawbacks can be softened by the production of high-value compounds and by adopting metabolic engineering strategies to improve their performances and productivity. Today, the most sustainable approach is the exploitation of industrial wastewaters for microalgae cultivation, which couples valuable biomass production with water resource recovery. Among the food processing sectors, the dairy industry generates the largest volume of wastewaters through the manufacturing process. These effluents are typically rich in dissolved organic matter and nutrients, which make it a challenging and expensive waste stream for companies to manage. Nevertheless, these rich wastewaters represent an appealing resource for microalgal biotechnology. In this study, we propose a sustainable approach for high-value compound production from dairy wastewaters through cyanobacteria. This strategy is based on a metabolically engineered strain of the model cyanobacterium Synechococcus elongatus PCC 7942 (already published elsewhere) for 2-phenylethanol (2-PE). 2-PE is a high-value aromatic compound that is widely employed as a fragrance in the food and cosmetics industry thanks to its pleasant floral scent. First, we qualitatively assessed the impact of four dairy effluents on cyanobacterial growth to identify the most promising substrates. Both tank-washing water and the liquid effluent of exhausted sludge resulted as suitable nutrient sources. Thus, we created an ideal buffer system by combining the two wastewaters while simultaneously providing balanced nutrition and completely avoiding the need for fresh water. The combination of 75% liquid effluent of exhausted sludge and 25% tank-washing water with a fine-tuning ammonium supplementation yielded 180 mg L−1 of 2-PE and a biomass concentration of 0.6 gDW L-1 within 10 days. The mixture of 90% exhausted sludge and 10% washing water produced the highest yield of 2-PE (205 mg L−1) and biomass accumulation (0.7 gDW L−1), although in 16 days. Through these treatments, the phosphates were completely consumed, and nitrogen was removed in a range of 74%–77%. Overall, our approach significantly valorized water recycling and the exploitation of valuable wastewaters to circularly produce marketable compounds via microalgae biotechnology, laying a promising groundwork for subsequent implementation and scale-up.
Metabolic syndrome traits exhibit genotype-by-environment interaction in relation to socioeconomic status in the Mexican American family heart study
Authors: Diego Vincent P. , Manusov Eron G. , Mao Xi , Almeida Marcio , Peralta Juan M. , Curran Joanne E. , Mahaney Michael C. , Göring Harald , Blangero John , Williams-Blangero Sarah 
Published: March 2024

Background: Socioeconomic Status (SES) is a potent environmental determinant of health. To our knowledge, no assessment of genotype-environment interaction has been conducted to consider the joint effects of socioeconomic status and genetics on risk for metabolic disease. We analyzed data from the Mexican American Family Studies (MAFS) to evaluate the hypothesis that genotype-by-environment interaction (GxE) is an essential determinant of variation in risk factors for metabolic syndrome (MS).Methods: We employed a maximum likelihood estimation of the decomposition of variance components to detect GxE interaction. After excluding individuals with diabetes and individuals on medication for diabetes, hypertension, or dyslipidemia, we analyzed 12 MS risk factors: fasting glucose (FG), fasting insulin (FI), 2-h glucose (2G), 2-h insulin (2I), body mass index (BMI), waist circumference (WC), leptin (LP), high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG), total serum cholesterol (TSC), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Our SES variable used a combined score of Duncan’s socioeconomic index and education years. Heterogeneity in the additive genetic variance across the SES continuum and a departure from unity in the genetic correlation coefficient were taken as evidence of GxE interaction. Hypothesis tests were conducted using standard likelihood ratio tests.Results: We found evidence of GxE for fasting glucose, 2-h glucose, 2-h insulin, BMI, and triglycerides. The genetic effects underlying the insulin/glucose metabolism component of MS are upregulated at the lower end of the SES spectrum. We also determined that the household variance for systolic blood pressure decreased with increasing SES.Conclusion: These results show a significant change in the GxE interaction underlying the major components of MS in response to changes in socioeconomic status. Further mRNA sequencing studies will identify genes and canonical gene pathways to support our molecular-level hypotheses.
Compositional features analysis by machine learning in genome represents linear adaptation of monkeypox virus
Authors: Zhang Sen , Li Ya-Dan , Cai Yu-Rong , Kang Xiao-Ping , Feng Ye , Li Yu-Chang , Chen Yue-Hong , Li Jing , Bao Li-Li , Jiang Tao 
Published: March 2024

Introduction: The global headlines have been dominated by the sudden and widespread outbreak of monkeypox, a rare and endemic zoonotic disease caused by the monkeypox virus (MPXV). Genomic composition based machine learning (ML) methods have recently shown promise in identifying host adaptability and evolutionary patterns of virus. Our study aimed to analyze the genomic characteristics and evolutionary patterns of MPXV using ML methods.Methods: The open reading frame (ORF) regions of full-length MPXV genomes were filtered and 165 ORFs were selected as clusters with the highest homology. Unsupervised machine learning methods of t-distributed stochastic neighbor embedding (t-SNE), Principal Component Analysis (PCA), and hierarchical clustering were performed to observe the DCR characteristics of the selected ORF clusters.Results: The results showed that MPXV sequences post-2022 showed an obvious linear adaptive evolution, indicating that it has become more adapted to the human host after accumulating mutations. For further accurate analysis, the ORF regions with larger variations were filtered out based on the ranking of homology difference to narrow down the key ORF clusters, which drew the same conclusion of linear adaptability. Then key differential protein structures were predicted by AlphaFold 2, which meant that difference in main domains might be one of the internal reasons for linear adaptive evolution.Discussion: Understanding the process of linear adaptation is critical in the constant evolutionary struggle between viruses and their hosts, playing a significant role in crafting effective measures to tackle viral diseases. Therefore, the present study provides valuable insights into the evolutionary patterns of the MPXV in 2022 from the perspective of genomic composition characteristics analysis through ML methods.
Deep analysis of skin molecular heterogeneities and their significance on the precise treatment of patients with psoriasis
Authors: Zhang Shengxiao , Chang Minjing , Zheng Leilei , Wang Can , Zhao Rong , Song Shan , Hao Jiawei , Zhang Lecong , Wang Caihong , Li Xiaofeng 
Published: March 2024

BackgroundPsoriasis is a highly heterogeneous autoinflammatory disease. At present, heterogeneity in disease has not been adequately translated into concrete treatment options. Our aim was to develop and verify a new stratification scheme that identifies the heterogeneity of psoriasis by the integration of large-scale transcriptomic profiles, thereby identifying patient subtypes and providing personalized treatment options whenever possible.MethodsWe performed functional enrichment and network analysis of upregulated differentially expressed genes using microarray datasets of lesional and non-lesional skin samples from 250 psoriatic patients. Unsupervised clustering methods were used to identify the skin subtypes. Finally, an Xgboost classifier was utilized to predict the effects of methotrexate and commonly prescribed biologics on skin subtypes.ResultsBased on the 163 upregulated differentially expressed genes, psoriasis patients were categorized into three subtypes (subtypes A–C). Immune cells and proinflammatory-related pathways were markedly activated in subtype A, named immune activation. Contrastingly, subtype C, named stroma proliferation, was enriched in integrated stroma cells and tissue proliferation-related signaling pathways. Subtype B was modestly activated in all the signaling pathways. Notably, subtypes A and B presented good responses to methotrexate and interleukin-12/23 inhibitors (ustekinumab) but inadequate responses to tumor necrosis factor-α inhibitors and interleukin-17A receptor inhibitors. Contrastly, subtype C exhibited excellent responses to tumor necrosis factor-α inhibitors (etanercept) and interleukin-17A receptor inhibitors (brodalumab) but not methotrexate and interleukin-12/23 inhibitors.ConclusionsPsoriasis patients can be assorted into three subtypes with different molecular and cellular characteristics based on the heterogeneity of the skin's immune cells and the stroma, determining the clinical responses of conventional therapies.
Exercise intensity governs tumor control in mice with breast cancer
Authors: Gomes-Santos Igor L. , Kumar Ashwin S. , Hausmann Franziska , Meyer Max N. , Shiferaw Sarah Z. , Amoozgar Zohreh , Jain Rakesh K. , Fukumura Dai 
Published: March 2024

IntroductionExercise is recommended as an adjunct therapy in cancer, but its effectiveness varies. Our hypothesis is that the benefit depends on the exercise intensity.MethodsWe subjected mice to low intensity (Li), moderate intensity (Mi) or high intensity (Hi) exercise, or untrained control (Co) groups based on their individual maximal running capacity.ResultsWe found that exercise intensity played a critical role in tumor control. Only Mi exercise delayed tumor growth and reduced tumor burden, whereas Li or Hi exercise failed to exert similar antitumor effects. While both Li and Mi exercise normalized the tumor vasculature, only Mi exercise increased tumor infiltrated CD8+ T cells, that also displayed enhanced effector function (higher proliferation and expression of CD69, INFγ, GzmB). Moreover, exercise induced an intensity-dependent mobilization of CD8+ T cells into the bloodstream.ConclusionThese findings shed light on the intricate relationship between exercise intensity and cancer, with implications for personalized and optimal exercise prescriptions for tumor control.
Identification of immunological patterns characterizing immune-related psoriasis reactions in oncological patients in therapy with anti-PD-1 checkpoint inhibitors
Authors: Morelli Martina , Carbone Maria Luigia , Scaglione Giovanni Luca , Scarponi Claudia , Di Francesco Valentina , Pallotta Sabatino , De Galitiis Federica , Rahimi Siavash , Madonna Stefania , Failla Cristina Maria , Albanesi Cristina 
Published: March 2024

IntroductionImmunotherapy with biologics targeting programmed cell death protein-1 (PD-1) is highly effective in the treatment of various malignancies. Nevertheless, it is frequently responsible for unexpected cutaneous manifestations, including psoriasis-like dermatitis. The pathogenesis of anti-PD-1-induced psoriasis has yet to be clarified, even though it is plausible that some innate and adaptive immunity processes are in common with canonical psoriasis. The genetic predisposition to psoriasis of patients could also be a contributing factor. Here, we investigated the immunological and genetic profiles of two patients with metastatic melanoma and one patient affected by lung cancer, who developed severe psoriasis after receiving anti-PD-1 nivolumab therapy.MethodsThe immune patterns of the three patients were compared with those detectable in classical, chronic plaque-type psoriasis or paradoxical psoriasis induced by anti-TNF-α therapy, mostly sustained by adaptive and innate immunity processes, respectively. Therefore, immunohistochemistry and mRNA analyses of innate and adaptive immunity molecules were conducted on skin biopsy of patients. Genetic analysis of polymorphisms predisposing to psoriasis was carried out by NGS technology.ResultsWe found that anti-PD-1-induced psoriasis showed immunological features similar to chronic psoriasis, characterized by the presence of cellular players of adaptive immunity, with abundant CD3+, CD8+ T cells and CD11c+ dendritic cells infiltrating skin lesions, and producing IL-23, IL-6, TNF-α, IFN-γ and IL-17. On the contrary, a lower number of innate immunity cells (BDCA2+ plasmacytoid dendritic cells, CD15+ neutrophils, CD117+ mast cells) and reduced IFN-α/β, lymphotoxin (LT)-α/β, were observed in anti-PD-1-induced psoriasis lesions, as compared with anti-TNF-α-induced paradoxical psoriasis. Importantly, the disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5) psoriasis autoantigen was significantly upregulated in psoriasis lesions of anti-PD-1-treated patients, at levels comparable with chronic plaque-type psoriasis. Finally, NGS analysis revealed that all patients carried several allelic variants in psoriasis susceptibility genes, such as HLA-C, ERAP1 and other genes of the major psoriasis susceptibility PSORS1 locus.DiscussionOur study showed that adaptive immunity predominates over innate immunity in anti-PD-1-induced psoriasis lesions, consistently with the local ADAMTSL5 overexpression. The presence of numerous SNPs in psoriasis susceptibility genes of the three patients also suggested their strong predisposition to the disease.
Prognostic analysis of high-flow nasal cannula therapy and non-invasive ventilation in mild to moderate hypoxemia patients and construction of a machine learning model for 48-h intubation prediction—a retrospective analysis of the MIMIC database
Authors: Fu Wei , Liu Xiaoqing , Guan Lili , Lin Zhimin , He Zhenfeng , Niu Jianyi , Huang Qiaoyun , Liu Qi , Chen Rongchang 
Published: March 2024

BackgroundThis study aims to investigate the clinical outcome between high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) therapy in mild to moderate hypoxemic patients on the first ICU day and to develop a predictive model of 48-h intubation.MethodsThe study included adult patients from the MIMIC III and IV databases who first initiated HFNC or NIV therapy due to mild to moderate hypoxemia (100 &lt; PaO2/FiO2 ≤ 300). The 48-h and 30-day intubation rates were compared using cross-sectional and survival analysis. Nine machine learning and six ensemble algorithms were deployed to construct the 48-h intubation predictive models, of which the optimal model was determined by its prediction accuracy. The top 10 risk and protective factors were identified using the Shapley interpretation algorithm.ResultA total of 123,042 patients were screened, of which, 673 were from the MIMIC IV database for ventilation therapy comparison (HFNC n = 363, NIV n = 310) and 48-h intubation predictive model construction (training dataset n = 471, internal validation set n = 202) and 408 were from the MIMIC III database for external validation. The NIV group had a lower intubation rate (23.1% vs. 16.1%, p = 0.001), ICU 28-day mortality (18.5% vs. 11.6%, p = 0.014), and in-hospital mortality (19.6% vs. 11.9%, p = 0.007) compared to the HFNC group. Survival analysis showed that the total and 48-h intubation rates were not significantly different. The ensemble AdaBoost decision tree model (internal and external validation set AUROC 0.878, 0.726) had the best predictive accuracy performance. The model Shapley algorithm showed Sequential Organ Failure Assessment (SOFA), acute physiology scores (APSIII), the minimum and maximum lactate value as risk factors for early failure and age, the maximum PaCO2 and PH value, Glasgow Coma Scale (GCS), the minimum PaO2/FiO2 ratio, and PaO2 value as protective factors.ConclusionNIV was associated with lower intubation rate and ICU 28-day and in-hospital mortality. Further survival analysis reinforced that the effect of NIV on the intubation rate might partly be attributed to the other impact factors. The ensemble AdaBoost decision tree model may assist clinicians in making clinical decisions, and early organ function support to improve patients’ SOFA, APSIII, GCS, PaCO2, PaO2, PH, PaO2/FiO2 ratio, and lactate values can reduce the early failure rate and improve patient prognosis.
Elastic modulus of cadaveric acetabular labrum correlates with ultrashort echo time (UTE) apparent spin-spin (T2*) and spin-lattice (T1) relaxation times
Authors: Moazamian Dina , Hananouchi Takehito , Shaterian Mohammadi Hamidreza , Tayarani Alireza , Dorthé Erik W. , D'lima Darryl , Jerban Saeed 
Published: March 2024

IntroductionThe acetabulum labrum plays a critical role in hip function. Medical imaging techniques for measuring changes in labral properties due to its degeneration may help improve our knowledge of its role in hip osteoarthritis (OA). This study aimed to explore the correlation between the mechanical properties of the acetabulum labrum and ultrashort echo time (UTE) MRI properties.Material and methodAcetabular labrum specimens were dissected from 12 fresh-frozen human cadaveric hip joints (64.6 ± 11.6 years old at the time of death, 7 female). UTE Cones sequences were used to measure apparent spin-spin (T2*) and spin-lattice (T1) relaxation times using a knee coil at 3 T in a clinical MR scanner. The stiffness and the elastic modulus (E) of the specimens were measured before MRI scans using uniaxial tensile tests. Spearman's rank correlation coefficients of Tendons' UTE-T2* and -T1 with their mechanical properties were calculated.ResultsThe human labrum specimen elastic modulus showed a significant inverse correlation with UTE-T2* (R = −0.66, P &lt; 0.01) and with UTE-T1 (R = −0.56, P = 0.05). The stiffness of the specimens showed significant inverse correlations with UTE-T2* (R = −0.53, P = 0.01) and UTE-T1 (R = −0.63, P = 0.02).ConclusionThis study highlighted the potential of UTE-MRI techniques for the mechanical assessment of the acetabular labrum. UTE-MRI may improve labrum degeneration detection and monitoring, which requires further investigations.
Acute urinary retention due to corpus cavernosum penile metastasis from lung adenocarcinoma after targeted therapy: a case report and review of the literature
Authors: Yan Wei , Fu Hui , Liu Huiqun , Liu Zhentian , Qi Xueliang , Chen Tanxiu 
Published: March 2024

BackgroundMetastasis in penile corpus cavernosum from adenocarcinoma of lung is a rare but fatal disease, which was reported in cases without series studies. It causes various clinical symptoms seriously affecting the quality of life.Case presentationA 72-year-old male smoker patient, who had a history of adenocarcinoma of lung after targeted therapy 36 months before, was admitted to Jiangxi Cancer Hospital because of presenting with aggressive dysuria and penis pain for one hour. A Foley catheter was inserted into the patient’s bladder with difficulty. Immediately do a bladder puncture. Emergency pelvic computed tomography (CT): a soft tissue nodule of 1.1 cm×1.4 cm was found in the cavernous area of the middle part of the penis, and the proximal urethra was dilated with a wide diameter of about 1.5 cm. The diagnosis of metastatic lung adenocarcinoma from the primary was made by CT-guided biopsy.ConclusionThe penis may be a site of metastasis from primary lung cancer, especially for old patient. Metastasis to the penis usually indicates that the primary lung cancer is at an advanced stage and the prognosis is very poor. More research is necessary to understand the underlying mechanism of adenocarcinoma of lung metastasis.
Long-term outcomes of liver transplantation for biliary atresia and results of policy changes: over 20 years of follow-up experience
Authors: Kwon Yiyoung , Ahn Yoon Ji , Yang Jaehun , Kim Eun Sil , Choe Yon Ho , Lee Sanghoon , Kim Mi Jin 
Published: March 2024

ObjectiveBiliary atresia (BA) patients develop chronic liver disease after the Kasai operation and are eventually indicated for liver transplantation (LT). The purposes of this study were to analyze long-term outcomes after LT and risk factors that affect complications to reduce graft failure.Study designOverall, 145 pediatric patients who underwent LT between June 1996 and June 2020 after a diagnosis of BA were included. We performed a retrospective analysis of medical records and evaluated patient and graft survival, cumulative incidence of complications, risk factors, and the results of policy changes.ResultsPatient and graft survival rates in over 20 years were 95.8% and 91.0%, respectively. Post-transplantation lymphoproliferative disease was frequently observed in the early period of immunosuppression within the first 1–2 years after LT. The incidence of cholangitis and rejection steadily increased over time. Weight-to-portal vein size was evaluated as a risk factor for cholangitis and bile duct strictures (OR = 12.82, p = 0.006 and OR = 16.54, p = 0.015, respectively). When evaluated using 2013 as a reference point, the split graft indication was expanded and the group that received LT after 2013 had a significantly lower survival over time compared with that of the group that received LT before 2013 (p = 0.006).ConclusionThis study revealed time differences in prevalence of complications. The evaluation of weight-to-duct or vessel size is a more important factor in considering complications than the graft-to-recipient weight ratio. Survival outcomes may have been altered by a policy change that affects the donor type ratio in transplantation.
Referent data for investigations of upper limb accelerometry: harmonized data from three cohorts of typically-developing children
Authors: Lang Catherine E. , Hoyt Catherine R. , Konrad Jeffrey D. , Bell Kayla R. , Marrus Natasha , Bland Marghuretta D. , Lohse Keith R. , Miller Allison E. 
Published: March 2024

AimThe rise of wearable sensing technology shows promise for addressing the challenges of measuring motor behavior in pediatric populations. The current pediatric wearable sensing literature is highly variable with respect to the number of sensors used, sensor placement, wearing time, and how data extracted from the sensors are analyzed. Many studies derive conceptually similar variables via different calculation methods, making it hard to compare across studies and clinical populations. In hopes of moving the field forward, this report provides referent upper limb wearable sensor data from accelerometers on 25 variables in typically-developing children, ages 3–17 years.MethodsThis is a secondary analysis of data from three pediatric cohorts of children 3–17 years of age. Participants (n = 222) in the cohorts wore bilateral wrist accelerometers for 2–4 days for a total of 622 recording days. Accelerometer data were reprocessed to compute 25 variables that quantified upper limb movement duration, intensity, symmetry, and complexity. Analyses examined the influence of hand dominance, age, gender, reliability, day-to-day stability, and the relationships between variables.ResultsThe majority of variables were similar on the dominant and non-dominant sides, declined slightly with age, and were not different between boys and girls. ICC values were moderate to excellent. Variation within individuals across days generally ranged from 3% to 32%. A web-based R shiny object is available for data viewing.InterpretationWith the use of wearable movement sensors increasing rapidly, these data provide key, referent information for researchers as they design studies, and analyze and interpret data from neurodevelopmental and other pediatric clinical populations. These data may be of particularly high value for pediatric rare diseases.