bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbiome affects the response to immunotherapy in non‐small cell lung cancer
Authors: Ren Shengnan , Feng Lingxin , Liu Haoran , Mao Yuke , Yu Zhuang 
Published: April 2024

AbstractBackgroundImmunotherapy has revolutionized cancer treatment. Recent studies have suggested that the efficacy of immunotherapy can be further enhanced by the influence of gut microbiota. In this study, we aimed to investigate the impact of bacteria on the effectiveness of cancer immunotherapy by combining analysis of clinical samples with validation in animal models.MethodsIn order to characterize the diversity and composition of microbiota and its relationship with response to immune checkpoint inhibitors (ICIs), 16S ribosomal RNA (rRNA) and GC–MS sequencing was performed on 71 stool samples from patients with advanced non‐small cell lung cancer (NSCLC) prior to treatment with immune checkpoint blockade (ICB). Furthermore, fecal microbiota transplantation (FMT) was performed from different patients into mice and a subcutaneous tumor model established using the Lewis lung cancer cell line to evaluate the therapeutic effect of PD‐1 on mice with varying gut microbiota.ResultsThe results demonstrated a significant association between elevated gut microbiota diversity and response to treatment with ICIs, p < 0.05. Faecalibacterium was markedly increased in the gut microbiota of responders (R), accompanied by increased short‐chain fatty acid (SCFA) levels, especially butanoic acid, acetic acid and hexanoic acid, p < 0.05. Additionally, FMT from R and nonresponders (NR) could promote an anticancer effect and reduce the expression of Ki‐67 cells in tumors in mice, p < 0.05. Moreover, R and NR FMT did not alter PD‐L1 expression in the tumor tissues of mice, p > 0.05. The diversity of gut microbiota consistently correlated with an optimistic prognosis in NSCLC patients with immunotherapy, which could be functionally mediated by SCFAs.ConclusionThe findings of the present study indicated that the diversity of gut microbiota and SCFAs is related to the efficacy of immunotherapy. FMT can effectively delay tumor progression, and enhance the effect of immunotherapy, thus providing evidence for improving the efficacy of immunotherapy in NSCLC patients.
Severe cutaneous adverse reactions associated with the immune checkpoint inhibitors: A case/non‐case analysis using the Food and Drug Administration Adverse Event Reporting System
Authors: Godfrey Hannah , Jedlowski Patrick , Thiede Rebecca 
Published: April 2024

AbstractBackground/ObjectivesThe immune checkpoint inhibitors (ICIs) have been increasingly associated with severe cutaneous adverse reactions (SCARs). These reactions, including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are uncommon but potentially lethal. Despite the severity of these reactions and growing association with the ICIs, their specific risk and mortality rates have been largely unexplored.MethodsA case/non‐case analysis was performed using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine the reporting odds ratios (RORs) for ICI‐associated SCARs cases under two conditions: (1) ICIs compared with all drugs in FAERS and (2) ICIs compared with a reference group of pooled anticancer drugs to control for underlying malignancy.ResultsA statistically significant ROR for SJS (ROR: 5.44), TEN (ROR: 5.81) and DRESS (ROR: 1.38) were identified under Condition 1. Under Condition 2, this significance was maintained for SJS (ROR: 7.31), TEN (ROR: 7.40) and DRESS (ROR: 3.90), and mild significance was identified for AGEP (ROR: 1.89). Mortality rates for the ICIs were increased compared with the anticancer medications (28.5% vs. 24.5% for SJS, 55.3% vs. 46% for TEN, 3.0% vs. 2.1% for AGEP and 7.1% vs. 6.1% for DRESS).ConclusionsOur results suggest an association between SCARs and the ICIs independent of cancer status.
Natural history of clinical outcomes and hepatic decompensation in metabolic dysfunction‐associated steatotic liver disease
Authors: Noureddin Nabil , Huang Daniel Q. , Bettencourt Ricki , Siddiqi Harris , Majzoub Abdul M. , Nayfeh Tarek , Tamaki Nobuharu , Izumi Namiki , Nakajima Atsushi , Idilman Ramazan , Gumussoy Mesut , Oz Digdem Kuru , Erden Ayse , Gidener Tolga , Allen Alina M. , Ajmera Veeral , Loomba Rohit 
Published: April 2024

SummaryBackground & AimsThe natural progression of hepatic decompensation in metabolic dysfunction‐associated steatotic liver disease (MASLD) is not well‐characterised. We aimed to describe it by conducting a retrospective analysis.MethodsThis longitudinal, retrospective analysis of well‐characterised MASLD cohorts followed for hepatic decompensation and death. The sequence of liver‐related events was evaluated, and the median time between hepatic decompensation episodes and death versus. transplantation was measured.ResultsOf the 2016 patients identified, 220 (11%) developed at least one episode of hepatic decompensation during a median follow‐up of 3.2 years. Ascites was the most common first liver‐related event [153 (69.5%)], followed by hepatic encephalopathy (HE) [55 (25%)] and variceal haemorrhage (VH) [30 (13.6%)]. Eighteen out of the 220 (8.1%) patients had more than one liver‐related event as their first hepatic decompensation. Among the patients who had the first episode, 87 (39.5%) had a second episode [44 (50.5%) HE, 31 (35.6%) ascites, and 12 (13.7%) VH]. Eighteen out of 220 (8.1%) had a third episode [10 (55.5%) HE, 6 (33.3%) VH, and 2 (11.1%) ascites]. Seventy‐three out of 220 (33.1%) died, and 31 (14%) received liver transplantation. The median time from the first episode to the second was 0.7 years and 1.3 years from the second episode to the third. The median survival time from the first episode to death or transplantation was 2.0 years.ConclusionThe most common first liver‐related event in MASLD patients is ascites. The median survival from the first hepatic decompensation to either death or transplantation is 2 years.
Quercetin alleviates hyperoxia‐induced bronchopulmonary dysplasia by inhibiting ferroptosis through the MAPK/PTGS2 pathway: Insights from network pharmacology, molecular docking, and experimental evaluations
Authors: Deng Xianhui , Chen Dan , Xie Anni , Li Shengpeng , Chen Ailing , Zhou Qin , Yu Renqiang 
Published: April 2024

AbstractQuercetin, a bioactive natural compound renowned for its potent anti‐inflammatory, antioxidant, and antiviral properties, has exhibited therapeutic potential in various diseases. Given that bronchopulmonary dysplasia (BPD) development is closely linked to inflammation and oxidative stress, and quercetin, a robust antioxidant known to activate NRF2 and influence the ferroptosis pathway, offers promise for a wide range of age groups. Nonetheless, the specific role of quercetin in BPD remains largely unexplored. This study aims to uncover the target role of quercetin in BPD through a combination of network pharmacology, molecular docking, computer analyses, and experimental evaluations.
A systematic review of the association between food insecurity and behaviours related to caries development in adults and children in high‐income countries
Authors: Cope A. L. , Chestnutt I. G. 
Published: April 2024

AbstractObjectivesTo synthesize and appraise the evidence regarding the relationship between food insecurity and behaviours associated with dental caries development in adults and children in high‐income countries.MethodsA systematic review including observational studies assessing the association between food insecurity and selected dietary (free sugar consumption) and non‐dietary factors (tooth brushing frequency; use of fluoridated toothpaste; dental visiting; oral hygiene aids; type of toothbrush used; interdental cleaning frequency and mouthwash use) related to dental caries development in adults and children in high‐income countries. Studies specifically looking at food insecurity during the COVID‐19 pandemic were excluded. Searches were performed in MEDLINE, Embase, Global Health and Scopus from inception to 25 May 2023. Two authors screened the search results, extracted data and appraised the studies independently and in duplicate. Study quality was assessed using the Newcastle–Ottawa Scale (with modifications for cross‐sectional studies). Vote counting and harvest plots provided the basis for evidence synthesis.ResultsSearches identified 880 references, which led to the inclusion of 71 studies with a total of 526 860 participants. The majority were cross‐sectional studies, conducted in the USA and reported free sugar consumption. Evidence for the association between food insecurity and free sugar intake from 4 cohort studies and 61 cross‐sectional studies including 336 585 participants was equivocal, particularly in the sugar‐sweetened beverage (SSB) consumption post‐hoc subgroup, where 20 out of 46 studies reported higher SSB consumption in food insecure individuals. There was consistent, but limited, evidence for reduced dental visiting in adults experiencing food insecurity compared to food secure adults from 3 cross‐sectional studies including 52 173 participants. The relationship between food insecurity and dental visiting in children was less clear (3 cross‐sectional studies, 138 102 participants). A single cross‐sectional study of 3275 children reported an association between food insecurity and reported failure to toothbrush the previous day.ConclusionsThis review did not identify clear associations between food insecurity and behaviours commonly implicated in the development of dental caries that would explain why individuals experiencing food insecurity are more likely to have dental caries than those who have food security. There was some evidence of decreased dental visiting in adults experiencing food insecurity. Common methodological weaknesses across the evidence base related to the selection of participants or control of potentially confounding variables. Consequently, the quality of evidence for all outcomes was downgraded to very low. More research is needed to explore access to oral hygiene products and household environments conducive to habitual oral self‐care in food insecure populations.
The potential of phosphorylated α‐synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy
Authors: Abdul‐Rahman Toufik , Herrera‐Calderón Ranferi Eduardo , Ahluwalia Arjun , Wireko Andrew Awuah , Ferreira Tomas , Tan Joecelyn Kirani , Wolfson Maximillian , Ghosh Shankhaneel , Horbas Viktoriia , Garg Vandana , Perveen Asma , Papadakis Marios , Ashraf Ghulam Md , Alexiou Athanasios 
Published: April 2024

AbstractIntroductionMultiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by the presence of glial cytoplasmic inclusions (GCIs) containing aggregated α‐synuclein (α‐Syn). Accurate diagnosis and monitoring of MSA present significant challenges, which can lead to potential misdiagnosis and inappropriate treatment. Biomarkers play a crucial role in improving the accuracy of MSA diagnosis, and phosphorylated α‐synuclein (p‐syn) has emerged as a promising biomarker for aiding in diagnosis and disease monitoring.MethodsA literature search was conducted on PubMed, Scopus, and Google Scholar using specific keywords and MeSH terms without imposing a time limit. Inclusion criteria comprised various study designs including experimental studies, case‐control studies, and cohort studies published only in English, while conference abstracts and unpublished sources were excluded.ResultsIncreased levels of p‐syn have been observed in various samples from MSA patients, such as red blood cells, cerebrospinal fluid, oral mucosal cells, skin, and colon biopsies, highlighting their diagnostic potential. The α‐Syn RT‐QuIC assay has shown sensitivity in diagnosing MSA and tracking its progression. Meta‐analyses and multicenter investigations have confirmed the diagnostic value of p‐syn in cerebrospinal fluid, demonstrating high specificity and sensitivity in distinguishing MSA from other neurodegenerative diseases. Moreover, combining p‐syn with other biomarkers has further improved the diagnostic accuracy of MSA.ConclusionThe p‐syn stands out as a promising biomarker for MSA. It is found in oligodendrocytes and shows a correlation with disease severity and progression. However, further research and validation studies are necessary to establish p‐syn as a reliable biomarker for MSA. If proven, p‐syn could significantly contribute to early diagnosis, disease monitoring, and assessing treatment response.
SIRT3 alleviates painful diabetic neuropathy by mediating the FoxO3a‐PINK1‐Parkin signaling pathway to activate mitophagy
Authors: Yang Jing , Yu Zhuoying , Jiang Ye , Zhang Zixian , Tian Yue , Cai Jie , Wei Min , Lyu Yanhan , Yang Dongsheng , Shen Shixiong , Xing Guo‐Gang , Li Min 
Published: April 2024

AbstractIntroductionPainful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development of PDN, but its pathogenesis and mechanism have not been fully investigated.MethodsIn this study, we used high‐fat diet/low‐dose streptozotocin‐induced rats as a model of type 2 diabetes mellitus. Behavioral testing, whole‐cell patch‐clamp recordings of dorsal root ganglion (DRG) neurons, and complex sensory nerve conduction velocity studies were used to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, and transmission electron microscopy were used to evaluate the function and morphology of mitochondria in DRG. Real‐time PCR, western blot, and immunofluorescence were performed to investigate the mechanism.ResultsWe found that damaged mitochondria were accumulated and mitophagy was inhibited in PDN rats. The expression of sirtuin 3 (SIRT3), which is an NAD+‐dependent deacetylase in mitochondria, was inhibited. Overexpression of SIRT3 in DRG neurons by intrathecally administered LV‐SIRT3 lentivirus ameliorated neurological and mitochondrial dysfunctions. This was evidenced by the reversal of allodynia and nociceptor hyperexcitability, as well as the restoration of MMP and ATP levels. Overexpression of SIRT3 restored the inhibited mitophagy by activating the FoxO3a‐PINK1‐Parkin signaling pathway. The effects of SIRT3 overexpression, including the reversal of allodynia and nociceptor hyperexcitability, the improvement of impaired mitochondria and mitophagy, and the restoration of PINK1 and Parkin expression, were counteracted when FoxO3a siRNA was intrathecally injected.ConclusionThese results showed that SIRT3 overexpression ameliorates PDN via activation of FoxO3a‐PINK1‐Parkin‐mediated mitophagy, suggesting that SIRT3 may become an encouraging therapeutic strategy for PDN.
Privacy preserving support vector machine based on federated learning for distributed IoT‐enabled data analysis
Authors: Chen Yu‐Chi , Hsu Song‐Yi , Xie Xin , Kumari Saru , Kumar Sachin , Rodrigues Joel , Alzahrani Bander A. 
Published: April 2024

AbstractIn a smart city, IoT devices are required to support monitoring of normal operations such as traffic, infrastructure, and the crowd of people. IoT‐enabled systems offered by many IoT devices are expected to achieve sustainable developments from the information collected by the smart city. Indeed, artificial intelligence (AI) and machine learning (ML) are well‐known methods for achieving this goal as long as the system framework and problem statement are well prepared. However, to better use AI/ML, the training data should be as global as possible, which can prevent the model from working only on local data. Such data can be obtained from different sources, but this induces the privacy issue where at least one party collects all data in the plain. The main focus of this article is on support vector machines (SVM). We aim to present a solution to the privacy issue and provide confidentiality to protect the data. We build a privacy‐preserving scheme for SVM (SecretSVM) based on the framework of federated learning and distributed consensus. In this scheme, data providers self‐organize and obtain training parameters of SVM without revealing their own models. Finally, experiments with real data analysis show the feasibility of potential applications in smart cities. This article is the extended version of that of Hsu et al. (Proceedings of the 15th ACM Asia Conference on Computer and Communications Security. ACM; 2020:904‐906).
Novel algorithm machine translation for language translation tool
Authors: Jayasakthi Velmurugan K. , Sumathy G. , Pradeep K. V. 
Published: April 2024

AbstractFuzzy matching techniques are the presently used methods in translating the words. Neural machine translation and statistical machine translation are the methods used in MT. In machine translator tool, the strategy employed for translation needs to handle large amount of datasets and therefore the performance in retrieving correct matching output can be affected. In order to improve the matching score of MT, the advanced techniques can be presented by modifying the existing fuzzy based translator and neural machine translator. The conventional process of modifying architectures and encoding schemes are tedious process. Similarly, the preprocessing of datasets also involves more time consumption and memory utilization. In this article, a new spider web based searching enhanced translation is presented to be employed with the neural machine translator. The proposed scheme enables deep searching of available dataset to detect the accurate matching result. In addition, the quality of translation is improved by presenting an optimal selection scheme for using the sentence matches in source augmentation. The matches retrieved using various matching scores are applied to an optimization algorithm. The source augmentation using optimal retrieved matches increases the translation quality. Further, the selection of optimal match combination helps to reduce time requirement, since it is not necessary to test all retrieved matches in finding target sentence. The performance of translation is validated by measuring the quality of translation using BLEU and METEOR scores. These two scores can be achieved for the TA‐EN language pairs in different configurations of about 92% and 86%, correspondingly. The results are evaluated and compared with other available NMT methods to validate the work.
Anglo–Dutch financial connections and contrasts in the late eighteenth century: The Amsterdam phase of the 1772–3 credit crisis
Authors: Berre Stein , Kosmetatos Paul 
Published: April 2024

AbstractWe examine the Amsterdam phase of the 1772–3 financial crisis using the British experience in the same episode as comparative context. We conclude that, notwithstanding some direct exposures by Amsterdam institutions to the principals of the London crisis, the main linkage between the two outbreaks was the requirement for cash margin on loans backed by British East India Company shares. No significant contagion via the bills of exchange network spread from London to Amsterdam in the period separating the two outbreaks, but some feeding back of distress to London is noticeable after the Dutch outbreak. The crisis was rooted in credit expansion, a deterioration in asset risk profiles, and speculation in West Indian mortgage securities and British equity markets. Speculators were enabled by information inefficiencies in the specialized and layered Amsterdam markets, and by the absence of a gatekeeper who could have regulated the provision of credit to them. To contain the outbreak, the Dutch drew on the cohesion of an informal club of insiders who led business and civic affairs. Though the credit markets resumed normal operations relatively quickly, the incurred losses were transformative for their long term prospects by devastating some of their most important firms.
Improvement in insulin sensitivity after switching from an integrase inhibitor‐based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain
Authors: Calza Leonardo , Giglia Maddalena , Colangeli Vincenzo , Bon Isabella , Vitale Salvatore , Viale Pierluigi 
Published: April 2024

AbstractObjectivesWe performed an observational, retrospective, cohort study to assess changes in insulin sensitivity after a switch from dolutegravir/lamivudine (DOL/3TC) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) to doravirine/tenofovir disoproxil fumarate/3TC (DOR/TDF/3TC) in virologically suppressed people living with HIV with recent significant weight gain.MethodsAll non‐diabetic patients with HIV treated with DOL/3TC or BIC/F/TAF for ≥12 months, with HIV RNA <20 copies/mL, and with a weight increase ≥3 kg in the last year, who underwent a switch to DOR/TDF/3TC were enrolled into the study. Serum levels of glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA‐IR) index were evaluated every 6 months during a 12‐month follow‐up.ResultsOverall, 81 patients were enrolled: 41 were treated with DOL/3TC and 40 with BIC/F/TAF. At baseline, median HOMA‐IR index was 3.18 and insulin resistance (HOMA‐IR index >2.5) was present in 49 subjects (60%). At 12 months after the switch to DOR/TDF/3TC, change in mean serum glucose concentration was not significant, but the reduction in median concentration of insulin was significant (−3.54 mcrUI/L [interquartile range −4.22 to −2.87]; p = 0.012), associated with a significant reduction in mean HOMA‐IR index (−0.54 [interquartile range −0.91 to −0.18]; p = 0.021). A significant reduction in total and low‐density lipoprotein cholesterol was also reported, whereas decreases in mean body weight and mean body mass index were not significant.ConclusionsIn our retrospective study in virologically suppressed people living with HIV treated with DOL/3TC or BIC/F/TAF and with recent weight gain, the switch to DOR/TDF/3TC led to a significant improvement in insulin sensitivity and plasma lipids, with a trend to decreased body weight.
A large exophytic plaque on the shoulder of a skin of color patient
Authors: Williams Kirk , Yaldo Marissa , Olds Hailey , Moossavi Meena 
Published: April 2024

AbstractA 75‐year‐old Black man presented for evaluation of a skin lesion on his right shoulder. The lesion had been present for 3 months and was bleeding. A physical exam demonstrated a 2.7 cm exophytic, crusted, blue‐to‐purple plaque. A shave biopsy was performed, and histopathological examination revealed anastomosing strands of basaloid cells in the dermis, leading to a diagnosis of fibroepithelioma of pinkus (FeP). FeP is a rare variant of basal cell carcinoma. It typically presents as a solitary, pink, pedunculated papule on the lower back, but the presentation can vary. This case contributes to the scarce literature on the occurrence of FeP in skin of color populations. Here, we raise the possibility that FeP may present differently in skin of color patients compared to white patients. Greater clinician awareness can foster improved identification, management, and understanding of FeP in diverse populations.
The paradox of platypnoea–orthodeoxia syndrome
Authors: Leaver Benjamin A. , Cliff Edward R. S. , Jefford Michael , Fogarty Samuel , Zentner Dominica 
Published: April 2024

AbstractPlatypnoea–orthodeoxia is a rare clinical syndrome characterised by dyspnoea and oxygen desaturation in the upright position which improves when supine. It requires two components: a sufficiently sized anatomical vascular defect (typically intra‐cardiac or intra‐pulmonary) combined with a functional component that promotes positional right‐to‐left shunting. We describe the rare occurrence of a patient with platypnoea–orthodeoxia syndrome (POS) because of a paradoxical shunt through a patent foramen ovale caused by a large right atrial line‐associated thrombus in a male with metastatic oesophageal cancer undergoing chemotherapy. This case is a timely reminder to consider POS amongst differentials for hypoxia as it is often treatable if recognised.