bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shannon index analysis in TCR sequencing for patients with lung adenocarcinoma: The clinical implications.
Authors: Jiang Bo , Lin Yangui , Hui Hongliang , Li Huaming , Zhang Yiqian , Zhou Shuxiong , Zhang Xiaoni , Li Hui , Huang Zhijuan , Liu Yuanyuan , Dong Linfeng 
Published: June 2024

e20053 Background: Immune repertoire (IR) is the collection of functionally diverse T and B cells in an individual's circulatory repertoire at a particular time. The CDR3 is the main variation region of the CDR of T cell receptors (TCRs), which directly determines the antigen specificity of the receptor. The purpose of this study was to investigate the differences in TCRs between tumor patients and healthy people by using NGS sequencing of the CDR3 region of the human TRB. Shannon indices and Simpson indices were used to evaluate the TCR richness and evenness. Methods: From 2018 to 2022, a total of 537 cases of lung adenocarcinoma and 85 cases of healthy individual PBMC in China were collected. We identified 59 V and 14 J genes in the TRB CDR3 region by amplicon sequencing, and analyzed the differences between Shannon_index and simpson index. Results: TCR diversity were significantly higher in healthy people compared to lung adenocarcinoma patients as determined by Shannon index analysis ( P = 0.006), and the uniformity of TCRs in the latter group was lower (Simpson index 0.997 and 0.992 for controls and cases, respectively). For different age groups of lung cancer patients (age 20-44, n = 66; age 45-59, n = 205; age 60-74, n = 221; age 75-90, n = 45), the overall abundance and uniformity of T cells in lung cancer patients decreased with the increase of age (Shannon index: 7.91, 7.63, 7.38, 6.99, respectively. Simpson Index: 0.996, 0.994, 0.991, 0.986 respectively). The downward trend in the Shannon index between healthy individuals and lung adenocarcinoma patients exhibit a high correlation (spearman r = 1, P < 0.01), indicating that age rather than cancer may be the main factor in immune decline in patients with lung adenocarcinoma. In terms of gender, the abundance and uniformity of T cell types in male patients were lower than that in female patients (male: Shannon index = 7.36, Simpson index = 0.991; Female: Shannon index = 7.61, Simpson index = 0.994), suggesting higher levels of immunity in the female patients. Conclusions: The Shannon index (immune diversity) in TCR sequencing was significantly different between lung adenocarcinoma patients and healthy individuals. In patients with lung adenocarcinoma, immunity declines more due to aging than the cancer itself. TCR diversity was lower in male lung adenocarcinoma patients than in female patients. In conclusion, Shannon index (immune diversity) in TCR sequencing can be used as a predictor of lung adenocarcinoma.
Predicting pathological response to neoadjuvant immunotherapy plus chemotherapy in resectable non-small cell lung cancer through liquid biopsy.
Authors: Lei Siyu , Xu Haiyan , Yang Yaning , Tian Linyan , Wang Yan 
Published: June 2024

e20073 Background: Neoadjuvant immunotherapy (ICI) plus chemotherapy (CT) provides a significant benefit compared to CT alone in resectable non-small cell lung cancer (NSCLC). However, further research is needed to identify the populations benefitting from this combined strategy. Methods: Patients (pts) diagnosed with stage II-III resectable NSCLC who opted for neoadjuvant ICI plus CT were enrolled. Plasma samples were collected before treatment initiation (T1) and before surgery (T2). A next-generation sequencing (NGS) platform spanning 769 cancer-related genes was utilized to detect circulating tumor DNA (ctDNA). The ctDNA concentration was presented as haploid genome equivalents (hGE) per mL of plasma. Additionally, low-pass whole-methylome sequencing was employed to explore three features of cell-free DNA, including methylated fragment ratio (MFR), fragment size index (FSI), and chromosomal aneuploidy of featured fragments (CAFF). Clinical and pathological data was obtained from medical records. Results: Out of 24 pts enrolled, 18 pts were evaluable on both platforms. The major pathological response (MPR) rate was 70.8% (17/24), and the pathological complete response (pCR) rate was 37.5% (9/24). Squamous cell carcinoma (SCC) showed a higher MPR rate than adenocarcinoma (P = 0.014). Pts with clinical T stage 2 showed a trend toward a higher MPR rate than those with T stage 3/4 (P = 0.069). No single molecular biomarker was found to be independently associated with MPR or pCR at T1. A linear discriminant model was constructed based on clinical T stage, MFR, and hGE at T1, which predicted both MPR and pCR with an accuracy of 83.3% (n = 18). In pts with SCC (n = 15), the accuracy of this model in predicting MPR and pCR was 80.0% and 86.7%, respectively. Moreover, the CAFF score at T2 was significantly higher in non-MPR pts than in MPR pts (P = 0.003). The dynamic change of CAFF score [calculation: (T2-T1) / T1] was also significantly related to MPR (P = 0.006). Conclusions: Baseline cfDNA features and clinical parameters effectively predicted pathological response of neoadjuvant ICI plus CT in resectable NSCLC, which could potentially serve as a tool for identifying patients that would benefit most from the combined approach.
Prognostic impact of clinical stage on non-surgical patients with pleural mesothelioma.
Authors: Knapp Brendan , Cittolin Santos Giordano Fabricio , Wu Ningying , Flanagan Mary Ellen , Baral Maun , Gao Feng , Rohatgi Anjali , Ward Jeffrey , Govindan Ramaswamy , Morgensztern Daniel 
Published: June 2024

e20096 Background: Most patients with pleural mesothelioma (PM) are not surgical candidates and receive systemic therapy. Clinical stage is usually not reported in mesothelioma clinical trials. We evaluated the prognostic impact of clinical stage in mesothelioma using a large database with the hypothesis that M1 patients will have worse OS compared to M0 patients. Methods: The Surveillance, Epidemiology and End Results (SEER) Program was used to identify adult patients with PM diagnosed between 2004 and 2020, who received chemotherapy and did not undergo surgery. Patients with unknown stage were excluded. Staging was subdivided into I, II-III and IV for better accuracy. Age, sex, and stage were included in multivariable analyses (MVAs) using a Cox proportional hazard regression model. Unadjusted OS was estimated by the Kaplan-Meier method and compared using log-rank tests. Results: Among the 10,422 patients, 2,644 (25.4%) met the inclusion criteria. Histology classification was not available for 1,120 patients (42.4%), which were reported as malignant mesothelioma. Most patients were male (78.3%) and older than 70 years (54.5%). There were 970 patients (36.7%) with stage I, 893 (33.8%) with stage II-III and 781 (29.5%) with stage IV. The median OS for all patients was 11 months, with 1-year, 3-year and 5-year OS of 43.9%, 10.3% and 4.3% respectively. The median OS for stages I, II-III, and IV was 13 months, 11 months, and 9 months respectively, with 1-year OS of 50.5%, 42.8% and 36.9% respectively and 5-year OS for stages I, II-III, and IV of 5.3%, 3.0% and 4.9% respectively. The median and 1-year OS were 12 months and 46.8% respectively for M0 and 9 months and 36.9% respectively for M1 (p < 0.001). For patient with M0, the median OS for N0, N1 and N2 was 12 months, 11 months, and 11 months, respectively. In MVA, worse OS was observed in patients with age 71 or older compared to < 60 (HR 1.24, 1.09-1.4), and in male patients compared to females (HR 1.27, 1.15.-1.4). Stage IV was associated with worse OS when compared to stage II-III (HR 1.11, 1.001-1.23, p = 0.04) and stage I (HR 1.34, 1.21-1.49, p < 0.001) while stage II-III was associated with worse OS compared to stage I (HR 1.21, 1.1-1.33, p = 0.0001). Conclusions: Clinical stage is a significant predictor for outcomes in patients with unresected pleural mesothelioma treated with chemotherapy, has been underreported, and should be included in clinical trials for a better evaluation of novel treatment strategies.
3-CMC, 4-CMC, and 4-BMC Human Metabolic Profiling: New Major Pathways to Document Consumption of Methcathinone Analogues?
Authors: Berardinelli Diletta , Taoussi Omayema , Daziani Gloria , Tavoletta Francesco , Ricci Giovanna , Tronconi Livio P. , Adamowicz Piotr , Busardò Francesco P. , Carlier Jeremy 
Published: June 2024

Abstract
Synthetic cathinones represent one of the largest and most abused new psychoactive substance classes, and have been involved in numerous intoxications and fatalities worldwide. Methcathinone analogues like 3-methylmethcathinone (3-MMC), 3-chloromethcathinone (3-CMC), and 4-CMC currently constitute most of synthetic cathinone seizures in Europe. Documenting their consumption in clinical/forensic casework is therefore essential to tackle this trend. Targeting metabolite markers is a go-to to document consumption in analytical toxicology, and metabolite profiling is crucial to support investigations. We sought to identify 3-CMC, 4-CMC, and 4-bromomethcathinone (4-BMC) human metabolites. The substances were incubated with human hepatocytes; incubates were screened by liquid chromatography-high-resolution tandem mass spectrometry and data were mined with Compound Discoverer (Themo Scientific). 3-CMC-positive blood, urine, and oral fluid and 4-CMC-positive urine and saliva from clinical/forensic casework were analyzed. Analyses were supported by metabolite predictions with GLORYx freeware. Twelve, ten, and ten metabolites were identified for 3-CMC, 4-CMC, and 4-BMC, respectively, with similar transformations occurring for the three cathinones. Major reactions included ketoreduction and N-demethylation. Surprisingly, predominant metabolites were produced by combination of N-demethylation and ω-carboxylation (main metabolite in 3-CMC-positive urine), and combination of β-ketoreduction, oxidative deamination, and O-glucuronidation (main metabolite in 4-CMC-positive urine). These latter metabolites were detected in negative-ionization mode only and their non-conjugated form was not detected after glucuronide hydrolysis; this metabolic pathway was never reported for any methcathinone analogue susceptible to undergo the same transformations. These results support the need for comprehensive screening strategies in metabolite identification studies, to avoid overlooking significant metabolites and major markers of consumption.

Graphical Abstract
Cenicriviroc Suppresses and Reverses Steatohepatitis by Regulating Macrophage Infiltration and M2 Polarization in Mice
Authors: Chen Guanliang , Yu Yanwen , Zhu Yuqin , Nagashimada Mayumi , Wang Yajiao , Nagata Naoto , Xu Liang 
Published: June 2024

Abstract
The inhibition of hepatic macrophage and Kupfer cell recruitment and activation is a potential strategy for treating insulin resistance and nonalcoholic steatohepatitis (NASH). Cenicriviroc (CVC), a dual C-C chemokine receptor 2 (CCR2) and CCR5 antagonist, has shown antifibrotic activity in murine models of NASH and has been evaluated in clinical trials on patients with NASH. This study investigated the effects of CVC on macrophage infiltration and polarization in a lipotoxic model of NASH. C57BL/6 mice were fed a high-cholesterol, high-fat (CL) diet or a CL diet containing 0.015% CVC (CL + CVC) for 12 weeks. Macrophage recruitment and activation were assayed by immunohistochemistry and flow cytometry. CVC supplementation attenuated excessive hepatic lipid accumulation and peroxidation and alleviated glucose intolerance and hyperinsulinemia in the mice that were fed the CL diet. Flow cytometry analysis revealed that compared with the CL group, mice fed the CL + CVC diet had fewer M1-like macrophages, more M2-like macrophages, and fewer T cell counts, indicating that CVC caused an M2-dominant shift of macrophages in the liver. Similarly, CVC decreased lipopolysaccharide-stimulated M1-like macrophage activation, whereas it increased interleukin-4-induced M2-type macrophage polarization in vitro. In addition, CVC attenuated hepatic fibrosis by repressing hepatic stellate cell activation. Lastly, CVC reversed insulin resistance as well as steatosis, inflammation, and fibrosis of the liver in mice with pre-existing NASH. In conclusion, CVC prevented and reversed hepatic steatosis, insulin resistance, inflammation, and fibrogenesis in the liver of NASH mice via M2 macrophage polarization.
Ethnic Disparities in the Risk Factors, Morbidity, and Mortality of Cardiovascular Disease in People With Diabetes
Authors: Nair Lekshmi , Asuzu Peace , Dagogo-Jack Sam 
Published: June 2024

Abstract
Cardiovascular disease (CVD) is the leading cause of death in people with diabetes. Compared with European Americans, African Americans have more favorable lipid profiles, as indicated by higher high-density lipoprotein cholesterol, lower triglycerides, and less dense low-density lipoprotein particles. The less atherogenic lipid profile translates to lower incidence and prevalence of CVD in African Americans with diabetes, despite higher rates of hypertension and obesity. However, African Americans with CVD experience worse clinical outcomes, including higher mortality, compared with European Americans. This mini-review summarizes the epidemiology, pathophysiology, mechanisms, and management of CVD in people with diabetes, focusing on possible factors underlying the “African American CVD paradox” (lower CVD incidence/prevalence but worse outcomes). Although the reasons for the disparities in CVD outcomes remain to be fully elucidated, we present a critical appraisal of the roles of suboptimal control of risk factors, inequities in care delivery, several biological factors, and psychosocial stress. We identify gaps in current knowledge and propose areas for future investigation.
In Vitro Investigation of Insulin Dynamics During 4 Hours of Simulated Cardiopulmonary Bypass
Authors: Schweizer Thilo , Nossen Caroline M. , Galova Barbara , Schild Christof , Huber Markus , Bally Lia , Vogt Andreas , Siepe Matthias , Nagler Michael , Fischer Kady , Guensch Dominik P. 
Published: June 2024

BACKGROUND:
Hyperglycemia is common in patients undergoing cardiovascular surgery with cardiopulmonary bypass. We hypothesize that intraoperative hyperglycemia may be, at least partially, attributable to insulin loss due to adhesion on artificial surfaces and/or degradation by hemolysis. Thus, our primary aim was to investigate the loss of insulin in 2 different isolated extracorporeal circulation circuits (ECCs), that is, a conventional ECC (cECC) with a roller pump, and a mini-ECC (MiECC) system with a centrifugal pump. The secondary aim was to assess and compare the relationship between changes in insulin concentration and the degree of hemolysis in our 2 ECC models.

METHODS:
Six cECC and 6 MiECC systems were primed with red packed blood cells and thawed fresh-frozen plasma (1:1). Four additional experiments were performed in cECC using only thawed fresh-frozen plasma. Human insulin (Actrapid) was added, targeting a plasma insulin concentration of 400 mU/L. Insulin concentration and hemolysis index were measured at baseline and hourly thereafter. The end points were the change in insulin level after 4 hours compared to baseline and hemolysis index after 4 hours. The insulin concentration and hemolysis index were analyzed by means of a saturated linear mixed-effect regression model with a random offset for each experiment to account for the repeated measure design of the study, resulting in mean estimates and 95% confidence intervals (CIs) of the primary end points as well as of pairwise contrasts with respect to ECC type.

RESULTS:
Insulin concentration decreased by 63% (95% CI, 48%–77%) in the MiECC and 92% (95% CI, 77%–106%) in the cECC system that contained red blood cells. Insulin loss was significantly higher in the cECC system compared to the MiECC (P = .022). In the cECC with only plasma, insulin did not significantly decrease (−4%; 95% CI, −21% to 14%). Hemolysis index in MiECC increased from 68 (95% CI, 46–91) to 76 (95% CI, 54–98) after 4 hours, in cECC from 81 (95% CI, 59–103) to 121 (95% CI, 99–143). Hemolysis index and percent change of insulin showed an excellent relationship (r = −0.99, P < .01).

CONCLUSIONS:
Our data showed that insulin levels substantially decreased during 4 hours of simulated cardiopulmonary bypass only in the ECC that contained hemoglobin. The decrease was more pronounced in the cECC, which also exhibited a greater degree of hemolysis. Our results suggest that insulin degradation by hemolysis products may be a stronger contributor to insulin loss than adhesion of insulin molecules to circuit surfaces.
The Pressure Reactivity Index as a Measure for Cerebrovascular Autoregulation: Validation in a Porcine Cranial Window Model
Authors: Klein Samuel P. , Decraene Brecht , De Sloovere Veerle , Kempen Bavo , Meyfroidt Geert , Depreitere Bart 
Published: June 2024

BACKGROUND AND OBJECTIVES:
Pressure reactivity index (PRx) has been proposed as a metric associated with cerebrovascular autoregulatory (CA) function and has been thoroughly investigated in clinical research. In this study, PRx is validated in a porcine cranial window model, developed to visualize pial arteriolar autoregulation and its limits.

METHODS:
We measured arterial blood pressure, intracranial pressure, pial arteriolar diameter, and red blood cell (RBC) velocity in a closed cranial window piglet model during gradual balloon catheter–induced arterial hypotension (n = 10) or hypertension (n = 10). CA limits were derived through piecewise linear regression of calculated RBC flux vs cerebral perfusion pressure (CPP), leading for each arteriole to 1 lower limit of autoregulation (LLA) and 2 upper limits of autoregulation (ULA1 and ULA2). Autoregulation limits were compared with PRx thresholds, and receiver operating curve analysis was performed with and without CPP binning. A linear mixed effects model of PRx was performed.

RESULTS:
Receiver operating curve analysis indicated an area under the curve (AUC) for LLA prediction by a PRx of 0.65 (95% CI: 0.64-0.67) and 0.77 (95% CI: 0.69-0.86) without and with CPP binning, respectively. The AUC for ULA1 prediction by PRx was 0.69 (95% CI: 0.68-0.69) without and 0.75 (95% CI: 0.68-0.82) with binning. The AUC for ULA2 prediction was 0.55 (95% CI: 0.55-0.58) without and 0.63 (95% CI 0.53-0.72) with binning. The sensitivity and specificity of binned PRx were 65%/90% for LLA, 69%/71% for ULA1, and 59%/74% for ULA2, showing wide interindividual variability. In the linear mixed effects model, pial arteriolar diameter changes were significantly associated with PRx changes (P = .002), whereas RBC velocity (P = .28) and RBC flux (P = .24) were not.

CONCLUSION:
We conclude that PRx is predominantly determined by pial arteriolar diameter changes and moderately predicts CA limits. Performance to detect the CA limits varied highly on an individual level. Active therapeutic strategies based on PRx and the associated correlation metrics should incorporate these limitations.
Boosting external quantum efficiency of a WSe2 photodetector across visible and NIR spectra through harnessing plasmonic hot electrons
Authors: Shi Linlin , Zhao Ziyang , Jiao Jinyang , Ji Ting , Wang Wenyan , Cui Yanxia , Li Guohui 
Published: June 2024

The layered two-dimensional material tungsten diselenide ( WSe2 ) has triggered tremendous interests in the field of optoelectronic devices due to its exceptional carrier transport property. Nevertheless, the limited absorption of WSe2 in the near infrared (NIR) band poses a challenge for the application of WSe2 photodetectors in night vision, telecommunication, etc. Herein, the enhanced performance of the WSe2 photodetector is demonstrated through the incorporation of titanium nitride nanoparticles (TiN NPs), complemented by an atomically-thick Al2O3 layer that aids in suppressing the dark current. It is demonstrated that TiN NPs can dramatically enhance the absorption of light in the proposed WSe2 photodetector in the NIR regime. This enhancement boosts photocurrent responses through the generation of plasmonic hot electrons, leading to external quantum efficiency (EQE) enhancement factors of 379.66% at 850 nm and 178.47% at 1550 nm. This work presents, for the first time, to our knowledge, that the WSe2 photodetector is capable of detecting broadband light spanning from ultraviolet to the telecommunication range, all achieved without the reliance on additional semiconductor materials. This achievement opens avenues for the advancement of cost-effective NIR photodetectors.
Mortality risk associated with occupational exposures in people with small airways obstruction
Authors: Quintero-Santofimio Valentina , Minelli Cosetta , Potts James , Vermeulen Roel , Kromhout Hans J. , Knox-Brown Ben , Feary Johanna , Amaral Andre F. S. 
Published: June 2024

Background
Small airways obstruction (SAO) has been associated with occupational exposures. Whether exposure to harmful occupational agents impacts the survival of people with SAO is unknown. Our aim was to estimate the mortality risk associated with occupational exposures among people with SAO.

Methods
We used data from UK Biobank participants with SAO, defined as a ratio of forced expiratory volume in three seconds to forced expiratory volume in six seconds (FEV3/FEV6) below the lower limit of normal. We assigned lifetime occupational exposures to participants with available occupational histories using the ALOHA+ Job Exposure Matrix. Mortality data were provided by the National Death Registries. We used Cox regression to assess the association of all-cause mortality with lifetime occupational exposures (vapours, gases, dusts, fumes—VGDF; solvents; pesticides; metals), adjusting for potential confounders.

Results
The 13,942 participants with SAO had a mean age of 56±7 years, 59% were females and 94.2% were of White ancestry. Overall, there were 457 deaths over a median follow-up of 12.8 years. A greater mortality risk was associated with exposure to VGDF, with hazard ratios of 1.32 (95%CI: 1.04–1.78) for low levels and 1.41 (95%CI: 1.11–1.78) for moderate levels of cumulative exposure. There was no evidence of association for the other occupational exposures.

Conclusion
Lifetime occupational exposure to VGDF in people with SAO may have a detrimental effect on their survival. Future respiratory health surveillance programmes of people exposed to VGDF should consider assessment for SAO and focus on primary prevention through adequate exposure control.
New records in the flora of Siberia and Kazakhstan
Authors: Bolbotov Gleb A. , German Dmitry A. , Gudkova Polina D. , Shmakov Alexander I. , Anisimov Andrey V. , Golyakov Pavel V. , Smirnov Sergey V. , Kechaykin Aleksey A. 
Published: June 2024

New data on the occurrence of 14 vascular plant species of Cruciferae, Liliaceae, Poaceae and Rosaceae in Kazakhstan and Siberia are reported. Fritillaria leucanthta, Potentilla exuta, P. kryloviana and P. × habievii are recorded for the first time from Kazakhstan; Cardamine occulta and Sisymbrium irio – from Siberia. Erysimum amurense is a novelty for the flora of Yakutia; Cardamine hirsuta, Сynodon dactylon and Rorippa austriaca are newly found in Altai Krai; Potentilla agrimonioides is for the first time recorded from the Kalbinskiy Ridge. For Potentilla crantzii, the first reliable finding in Kazakhstan is presented, and the second locality of P. × jakovlevii, a narrow neoendemic of Altai-within-Kazakhstan, is registered. Сynodon is recorded as a new genus for the flora of the Altai Krai while occurrence of Lepidium affine in Kemerovo Province is not confirmed. For each species, a list of recorded localities and brief data on general distribution are provided supplied with morphological comments where needed. Additionally, photos of Fritillaria leucanthta and Potentilla crantzii in their natural habitat are presented along with an image of the herbarium specimen of Potentilla × jakovlevii and morphological comparison of inflorescence and spikelet of Cynodon vs. Digitaria.