bluuebunny/crossref_metadata_2025_split huggingface dataset:
Land-use competition in 1.5°C climate stabilization: is there enough land for all potential needs?
Authors: Gurgel Angelo , Morris Jennifer , Haigh Martin , Robertson Andy D. , van der Ploeg Robin , Paltsev Sergey 
Published: November 2024

Achieving a low-carbon future requires a comprehensive approach that combines emission mitigation options from economic activities with the sustainable use of land for numerous needs: food production, energy production, carbon sequestration, nature preservation and broad ecosystem services. Using the MIT Integrated Global System (IGSM) framework we analyze land-use competition in a 1.5°C climate stabilization scenario, in which demand for bioenergy and natural sinks increase along with the need for sustainable farming and food production. We find that to address the numerous trade-offs, effective approaches to nature-based solutions (NBS) and agriculture practices are essential. With proper regulatory policies and radical changes in current practices, global land is sufficient to provide increased consumption of food per capita (without large diet changes) over the century while also utilizing 2.5–3.5 billion hectares (Gha) of land for NBS practices that provide a carbon sink of 3–6 gigatonnes (Gt) of CO2 per year as well as 0.4–0.6 Gha of land for energy production—0.2–0.3 Gha for 50–65 exajoules (EJ) per year of bioenergy and 0.2–0.35 Gha for 300–600 EJ/year of wind and solar power generation. We list the competing uses of land to reflect the trade-offs involved in land use decisions, and note that while there is sufficient land in our scenario, attaining this outcome, capable of delivering a 1.5°C future, requires effective policies and measures at national and global levels that promote efficient land use for food, energy and nature (including carbon sequestration) and ensure long-term commitments by decision makers from governments and industry in order to realize the benefits of climate change mitigation.
Multi-omics insights implicate the remodeling of the intestinal structure and microbiome in aging
Authors: Chen Shaohua , Wang Chengbang , Zou Xiong , Li Hanwen , Yang Guanglin , Su Xiaotao , Mo Zengnan 
Published: November 2024

BackgroundAging can impair the ability of elderly individuals to fight infections and trigger persistent systemic inflammation, a condition known as inflammaging. However, the mechanisms underlying the development of inflammaging remain unknown.MethodsWe conducted 16S rRNA sequencing of intestinal contents from young and old C57BL/6J mice to elucidate changes in gut microbiota diversity and microbial community composition after aging. Aging-related differential bacterial taxa were then identified, and their abundance trends were validated in human samples. The variances in intestinal barrier function and circulating endotoxin between groups were also assessed. Furthermore, widely targeted metabolomics was conducted to characterize metabolic profiles after aging and to investigate the key metabolic pathways enriched by the differential metabolites.ResultsOur findings demonstrated an increase in relative proportion of pathogenic bacteria with age, a trend also revealed in healthy populations of different age groups. Additionally, aging individuals exhibited reduced intestinal barrier function and increased circulating endotoxin levels. Widely targeted metabolomics revealed a significant increase in various secondary bile acid metabolites after aging, positively correlated with the relative abundance of several aging-related bacterial taxa. Furthermore, old group had lower levels of various anti-inflammatory or beneficial metabolites. Enrichment analysis identified the starch and sucrose metabolism pathway as potentially the most significantly impacted signaling pathway during aging.ConclusionThis study aimed to provide insights into the complex interactions involved in organismal inflammaging through microbial multi-omics. These findings lay a solid foundation for future research aimed at identifying novel biomarkers for the clinical diagnosis of aging-related diseases or potential therapeutic targets.
Predicting thyroid involvement in primary Sjögren’s syndrome: development and validation of a predictive nomogram
Authors: Yang Yixuan , Du Yanyuan , Ren Zhaoyang , Mei Qingqing , Jiang Mengyao , Liu Wenjing , Zhang Huadong , Cui Bingnan 
Published: November 2024

IntroductionPatients with Primary Sjögren’s syndrome (pSS) are at a higher risk of thyroid disorders than the general population. This retrospective analysis of 202 patients with pSS was conducted to uncover risk factors associated with thyroid involvement and to create a predictive model for this condition.MethodsWe analyzed 202 patients with pSS from Guang’anmen Hospital, China Academy of Chinese Medical Sciences, with 105 cases of thyroid involvement and 97 without. The Least Absolute Shrinkage and Selection Operator method was used to identify key variables for our risk model. These variables were then subjected to multivariate logistic regression to develop the model. The accuracy of the model was assessed through the C-index, receiver operating characteristic curves, calibration plots, and decision curve analysis, with internal validation via bootstrapping.ResultsHigh-sensitivity C-reactive protein (HCRP), pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and aspartate aminotransferase (AST) were incorporated into the nomogram. The model showed robust discrimination and calibration abilities. Decision curve analysis indicated the clinical utility of our nomogram in intervening on the probability thresholds of thyroid disease.ConclusionBy integrating HCRP, pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and AST, our thyroid risk nomogram can predict the risk of thyroid involvement in patients with pSS, aiding in more informed treatment strategies.
Factors affecting treatment delays among malaria patients presenting at health facilities in Guinea, 2022–2023
Authors: Diallo Elhadj Marouf , Kourouma Karifa , Diakite Nouman , Diallo Abdourahamane , Blanquet Marie , Toure Abdoulaye , Gerbaud Laurent , Camara Alioune 
Published: November 2024

BackgroundEarly identification and management of cases are key for controlling and eliminating malaria. This study aimed to assess the factors associated with the delay malaria treatment in Guinea.MethodsCross-sectional study was conducted at 60 health facilities in eight administrative regions from December 2022 to March 2023. Patients with a diagnosis of malaria through either microscopy or a rapid diagnostic test (RDT), were interviewed using a standardized questionnaire. Treatment delays were defined as seeking care 48 hours after the onset of symptoms. Logistic regression was performed to assess factors associated with treatment delay. Adjusted odds ratio (OR) and confidence interval (CI) were used to explain the associated factors.Results3,300 malaria patients were included and the findings showed a median time of symptoms onset and access of malaria treatment was 3.04 days. Alarmingly, only 800 (24.24%) of all cases sought and received treatment within 48 hours of symptom onset. The multivariate logistic regression indicated that children under 5 years of age who attempted self-medication for fever were 4.32 times more likely to experience a delay in treatment than those who sought immediate medical care in health facilities (OR:4.32, 95% CI: 2.96–6.36). Children whose parents had no formal education were 3.05 times more likely to experience a delay in treatment (OR:3.05, 95% CI: 1.66–5.60). Moreover, when the disease was considered non-severe the first time by caregivers, OR = 1.71 (95% CI: 1.26–2.33). For those 5 years old and above, using university hospital OR = 4.01, (95% CI: 2.01–8.44), living in Forest Guinea OR = 3.14, (95% CI 1.93–5.10) and Middle Guinea OR = 1.46 (95% CI: 1.09–1.95) were more likely to experience delay treatment.ConclusionsThe proportion of malaria patients with treatment within 48 is low, significantly falling short of the national targets. This substantial delay in treatment was attributed to factors such the lack of formal education, self-medication practices, and failure to recognize the illness severity. These findings underscore the urgent need for NMCP to enhance awareness regarding the importance of early presentation at health facilities, with targeted interventions.
A three-classification model for identifying migraine with right-to-left shunt using lateralization of functional connectivity and brain network topology: a resting-state fMRI study
Authors: Nie Weifang , Zeng Weiming , Yang Jiajun , Wang Lei , Shi Yuhu 
Published: November 2024

IntroductionRight-to-left shunting has been significantly associated with migraine, although the neural mechanisms remain complex and not fully elucidated. The aim of this study was to investigate the variability of brain asymmetry in individuals with migraine with right-to-left shunting, migraine without right-to-left shunting and normal controls using resting-state fMRI technology and to construct a three-classification model.MethodsFirstly, asymmetries in functional connectivity and brain network topology were quantified to laterality indices. Secondly, the laterality indices were employed to construct a three-classification model using decision tree and random forest algorithms. Ultimately, through a feature score analysis, the key brain regions that contributed significantly to the classification were extracted, and the associations between these brain regions and clinical features were investigated.ResultsOur experimental results showed that the initial classification accuracy reached 0.8961. Subsequently, validation using an independent sample set resulted in a classification accuracy of 0.8874. Further, after expanding the samples by the segmentation strategy, the classification accuracies were improved to 0.9103 and 0.9099. Additionally, the third sample set yielded a classification accuracy of 0.8745. Finally, 9 pivotal brain regions were identified and distributed in the default network, the control network, the visual network, the limbic network, the somatomotor network and the salience/ventral attention network.DiscussionThe results revealed distinct lateralization features in the brains of the three groups, which were closely linked to migraine and right-to-left shunting symptoms and could serve as potential imaging biomarkers for clinical diagnosis. Our findings enhanced our understanding of migraine and right-to-left shunting mechanisms and offered insights into assisting clinical diagnosis.
Efficacy and safety of Latilactobacillus curvatus LB-P9 on hair health: a randomized, double-blind, placebo-controlled clinical trial
Authors: Choi Sun Young , Ko Eun Jung , Seok Joon , Han Hye Sung , Yoo Kwang Ho , Song MiKyung , Song Kyoungsub , Kim Beom Joon 
Published: November 2024

IntroductionNumerous factors influence hair health, including genetic predisposition, hormonal changes, stress, nutritional deficiencies, medical conditions, or medications. With the rising interest in maintaining hair health, alternative approaches such as functional cosmetics and food products are gaining attention. Probiotics, health-beneficial live microorganisms, are emerging as potential candidates for improving hair health. Therefore, this study aimed to evaluate the effects and safety of oral intake of Latilactobacillus curvatus LB-P9 on hair health.MethodsThe study was a randomized, double-blind, placebo-controlled clinical trial involving participants (aged 18–60 years old) with mild to moderate hair damage. Participants were randomly assigned to the test (receiving LB-P9 supplements) or control (receiving a placebo) groups, respectively. Efficacy was assessed using measures such as hair luster, elasticity, and participant satisfaction. Safety evaluations comprised physical examinations, vital sign measurements, laboratory tests, and observation of adverse reactions.ResultsOverall, 80 participants were enrolled in the trial. Significant improvements were observed in hair luster, elasticity, and participant satisfaction in the test group compared to the control group. In the test group, the hair luster parameter increased by 1.65 ± 2.30 (LBNT) at 24 weeks (p &lt; 0.001), indicating a 19% improvement over the control group. Subgroup analysis revealed significant improvement in hair luster among females with short hair. Additionally, hair tensile strength, reflecting hair elasticity and participant satisfaction are increased by 10.27 ± 16.40 (gf/mm2) at 24 weeks (p = 0.001) in the test group. The subjective indicator of participant satisfaction, which improves as survey scores decrease, significantly decreased in the test group by −17.81 ± 14.35 points (p &lt; 0.001) after 24 weeks of consuming the test food than before consuming it. No significant adverse reactions were reported, and safety evaluations indicated no adverse effects linked to LB-P9 consumption.ConclusionProbiotics, including LB-P9, may serve as an alternative in the management of hair health. The findings of this study support the possible benefits of LB-P9 supplementation in enhancing hair luster and elasticity.
Association of phenylalanine and tyrosine metabolism with mortality and response to nutritional support among patients at nutritional risk: a secondary analysis of the randomized clinical trial EFFORT
Authors: Buchmueller Lena C. , Wunderle Carla , Laager Rahel , Bernasconi Luca , Neyer Peter J. , Tribolet Pascal , Stanga Zeno , Mueller Beat , Schuetz Philipp 
Published: November 2024

BackgroundElevated phenylalanine serum level is a surrogate marker of whole-body proteolysis and has been associated with increased mortality in critically ill patients. Tyrosine is a metabolite of phenylalanine and serves as a precursor of thyroid hormones and catecholamines with important functions in the oxidative stress response among others. Herein, we examined the prognostic significance of phenylalanine, tyrosine, as well as its metabolites nitrotyrosine, L-3,4-dihydroxyphenylalanine (DOPA), and dopamine regarding clinical outcomes and response to nutritional therapy in patients at nutritional risk.MethodsThis is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled trial investigating individualized nutritional support compared to standard care in patients at risk of malnutrition. The primary outcome was 30-day all-cause mortality.ResultsWe analyzed data of 238 patients and found a significant association between low plasma levels of phenylalanine [adjusted HR 2.27 (95% CI 1.29 to 3.00)] and tyrosine [adjusted HR 1.91 (95% CI 1.11 to 3.28)] with increased 30-day mortality. This association persisted over a longer period, extending to 5 years. Additionally, trends indicated elevated mortality rates among patients with low nitrotyrosine and high DOPA and dopamine levels. Patients with high tyrosine levels showed a more pronounced response to nutritional support compared to patients with low tyrosine levels (HR 0.45 versus 1.46, p for interaction = 0.02).ConclusionIn medical inpatients at nutritional risk, low phenylalanine and tyrosine levels were associated with increased short-and long-term mortality and patients with high tyrosine levels showed a more pronounced response to nutritional support. Further research is warranted to gain a deeper understanding of phenylalanine and tyrosine pathways, their association with clinical outcomes in patients at nutritional risk, as well as their response to nutritional therapy.Clinical trial registrationwww.clinicaltrials.gov, identifier NCT02517476.
Efficacy and safety of first-line immune checkpoint inhibitor combination therapies in patients with advanced esophageal squamous cell carcinoma: a network meta-analysis
Authors: Wang Chenglong , Cai Tongze , Wei Jiangcun , Huang Ying , Xiao Lin , Li Tong , Qin Zujie 
Published: November 2024

BackgroundWe performed a network meta-analysis of phase III trials to compare the efficacy and safety of first-line regimens for patients with advanced esophageal squamous cell carcinoma (ESCC).MethodsA systematic review and Bayesian network meta-analysis were conducted by retrieving relevant literature from PubMed, Embase, the Cochrane Library, and the Web of Science. We included published sources of randomized clinical trials comparing immunotherapy combinations for treating advanced ESCC.ResultsWe analyzed seven studies involving eight immunotherapy combinations and 4688 patients. For patients without programmed death-ligand 1 (PD-L1) selection, it was found that the combination of toripalimab and chemotherapy provided better overall survival than chemotherapy alone (hazard ratio = 0.58, 95% confidence interval (CI) 0.43-0.78). Compared with chemotherapy alone, Sintilimab or camrelizumab plus chemotherapy seemed to achieve the best progression-free survival (hazard ratio = 0.56, 95% CI 0.46-0.68). Nivolumab plus chemotherapy appeared to provide the best objective response rate, with significant differences versus chemotherapy alone (odds ratio = 0.49, 95% CI 0.38-0.64). Nivolumab plus ipilimumab resulted in a relatively lower incidence of adverse events of grade ≥3 than other regimens.ConclusionsThe combination of immune checkpoint inhibitors (ICIs) with chemotherapy provided a high probability of more effective treatment in comparison with chemotherapy alone for patients with advanced ESCC. Toripalimab and sintilimab plus chemotherapy were ranked as providing the highest OS and PFS benefit in the first-line setting, respectively.
Efficacy and safety of regorafenib for the treatment of metastatic colorectal cancer in routine clinical practice: results from a Spanish hospital
Authors: Sotoca Rubio Pilar , Barrill Corpa Ana María , Alia Navarro Víctor , Pérez de Aguado Rodríguez Patricia , Moreno Doval Jaime , Calvo Pérez Juan Carlos , Guerrero Serrano Patricia , García Merino Carlos , García de Quevedo Suero Coral , Fernández-Fradejas Jorge , Serrano Domingo Juan José , Martínez Delfrade Íñigo , Morón García Blanca Isabel , Ferreiro Monteagudo María Reyes , de Frutos González Belén 
Published: November 2024

IntroductionRegorafenib is indicated as treatment in third-line and beyond in patients with metastatic colorectal cancer.Methods This is a retrospective study of a cohort of patients with mCRC treated with regorafenib in Hospital Universitario Ramón y Cajal, in Madrid, Spain.ResultsWith the aim to assess the efficacy and safety of regorafenib, 91 patients treated between 2013 and 2023 were included. Only 1.1% of patients achieved disease control. Median progression free survival was 2.40 months and median overall survival was 4.76 months. The most frequent adverse events were fatigue and hand-foot skin reaction (59.34% and 28.57%, respectively).DiscussionOur results confirm the safety of regorafenib as treatment of mCRC in real clinical practice. Although our population is less pretreated than in the CORRECT trial, our disease control rate was inferior. This difference may be due to a worse baseline status and a high percentage of hepatic disease showed in our patients.
A real−world pharmacovigilance study of FDA Adverse Event Reporting System events for pralsetinib
Authors: Yin Yi , Sun Fengli , Jin Youpeng 
Published: November 2024

BackgroundPralsetinib, a selective oral inhibitor of rearranged during transfection (RET) fusion proteins and oncogenic RET mutants, has shown significant efficacy in treating RET fusion-positive non-small cell lung cancer and thyroid cancer. However, since pralsetinib was approved in the United States in September 2020, there have been limited reports of post-marketing adverse events (AEs). In this study, we aimed to analyze the AE signals with pralsetinib on the basis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to provide instructions in clinical practice.MethodsAll AE reports were obtained from the FAERS database from the first quarter (Q3) of 2020 to the second quarter (Q2) of 2024. Various signal quantification techniques were used for analysis, including reporting odds ratios, proportional reporting ratios, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker (MGPS)-based empirical Bayesian geometric mean.ResultsOut of 8,341,673 case reports in the FAERS database, 1,064 reports of pralsetinib as the “primary suspected (PS)” AEs were recorded, covering 26 system organ classes and 256 preferred terms. Of the reports, 62.5% were from consumers rather than healthcare professionals. The most common systems were general disorders and administration site conditions (n = 704), investigations (n = 516), and gastrointestinal disorders (n = 405). A total of 95 significant disproportionality preferred terms (PTs) conformed to the four algorithms simultaneously. AEs that ranked the top three at the PT level were hypertension (n = 80), asthenia (n = 79), and anemia (n = 65). Of the 95 PTs with significant disproportionation, unexpected significant AEs such as increased blood calcitonin, increased myocardial necrosis marker, and bacterial cystitis were observed, which were not mentioned in the drug’s instructions. The median onset time of pralsetinib-associated AEs was 41 days [interquartile range (IQR) 14–86 days]. The majority of the AEs occurred in 30 days (42.86%).ConclusionOur pharmacovigilance analysis of real-world data from the FEARS database revealed the safety signals and potential risks of pralsetinib usage. These results can provide valuable evidence for further clinical application of pralsetinib and are important in enhancing clinical medication safety.
Effect of NLRP3 inflammasome induced astrocyte phenotype alteration in morphine tolerance
Authors: Yuan Zhenyu , Lu Boxuan , Zhang Meiling , Lu Yinxiao , Wang Zhihui , Zhang Wenhao , Cheng Hao , Wu Zhifang , Ji Qing 
Published: November 2024

IntroductionMorphine is a widely used analgesic, but its prolonged use often leads to tolerance, limiting its therapeutic efficacy. Research implicates the NLRP3 inflammasome and reactive astrocytes in the development of morphine tolerance, with reactive astrocytes classified into A1 neurotoxic and A2 neuroprotective phenotypes. This study explores the role of the NLRP3 inflammasome and the transformation of astrocyte phenotypes in the progression of morphine tolerance.MethodsA model of morphine tolerance was established by administering morphine intrathecally for seven consecutive days. To inhibit NLRP3 inflammasome activation, we coadministered MCC950, a selective NLRP3 inhibitor. Thermal withdrawal latency was used to assess tolerance development. Protein and mRNA levels of GFAP, IL-18, NLRP3, C3 (A1 marker), and S100A10 (A2 marker) in the spinal cord were measured using Western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). Immunofluorescence was employed to assess the colocalization of C3 and GFAP.ResultsSeven days of morphine administration induced tolerance, which was associated with increased levels of GFAP, IL-18, NLRP3, and C3, and a decreased level of S100A10. Coadministration of morphine and MCC950 significantly slowed the development of morphine tolerance and reversed changes in NLRP3, IL-18, GFAP, C3, and S100A10 protein levels.DiscussionOur findings indicate a significant link between NLRP3 inflammasome activation and morphine tolerance, suggesting that NLRP3 contributes to the transformation of astrocytes to the A1 phenotype. Inhibiting NLRP3 inflammasome activation holds promise in reversing astrocyte phenotype changes, potentially mitigating morphine tolerance.