bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineered immunologic niche monitors checkpoint blockade response and probes mechanisms of resistance
Authors: Raghani Ravi M. , Urie Russell R. , Ma Jeffrey A. , Escalona Guillermo , Schrack Ian A. , DiLillo Katarina M. , Kandagatla Pridvi , Decker Joseph T. , Morris Aaron H. , Arnold Kelly B. , Jeruss Jacqueline S. , Shea Lonnie D. 
Published: June 2024

AbstractAntibodies to programmed cell death protein 1 (anti‐PD‐1) have become a promising immunotherapy for triple negative breast cancer (TNBC), blocking PD‐L1 signaling from pro‐tumor cells through T cell PD‐1 receptor binding. Nevertheless, only 10%–20% of PD‐L1+ metastatic TNBC patients who meet criteria benefit from immune checkpoint blockade (ICB), and biomarkers to predict patient response have been elusive. We have previously developed an immunological niche, consisting of a microporous implant in the subcutaneous space, that supports tissue formation whose immune composition is consistent with that within vital organs. Herein, we investigated dynamic gene expression within this immunological niche to provide biomarkers of response to anti‐PD‐1. In a 4T1 model of metastatic TNBC, we observed sensitivity and resistance to anti‐PD‐1 based on primary tumor growth and survival. The niche was biopsied before, during, and after anti‐PD‐1 therapy, and analyzed for cell types and gene expression indicative of treatment refractivity. Myeloid cell‐to‐lymphocyte ratios were altered between ICB‐sensitivity and resistance. Longitudinal analysis of gene expression implicated dynamic myeloid cell function that stratified sensitivity from resistance. A niche‐derived gene signature predicted sensitivity or resistance prior to therapy. Analysis of the niche to monitor immunotherapy response presents a new opportunity to personalize care and investigate mechanisms underlying treatment resistance.Summary: A remote implant identified biomarkers that predict anti‐PD‐1 response before therapy, providing a unique tool to understand heterologous immunotherapy resistance in triple negative breast cancer.
Integration of the key potentially inappropriate drugs in pediatrics list within the electronic health record in a tertiary care children's hospital
Authors: Kapoor Seerat , Mabry William A. , Naik Dhyana , Bobo Kelly S. 
Published: June 2024

AbstractIntroductionThe key potentially inappropriate drugs in pediatrics (KIDs) List raises awareness of medications and excipients that should be used cautiously in specific age groups, appropriately monitored, or avoided. This project used the KIDs List to identify opportunities to improve our clinical decision support program and adjust the medication formulary.MethodsOur team used the Plan, Do, Study, Act (PDSA) cycle to assess items and take actions that included no change, creation of an alert or task for pharmacists or providers, referral for additional study, inventory modification, and modification of dose range alerts.ResultsOur initial assessment of 34 formulary items identified 10 items (29%) with the recommendations from the KIDs list in place; 72% (24/34) were referred for further study. In the preliminary phase, 15% (5/34) were submitted to pharmacy information technology (IT) to develop an alert, 24% (8/34) needed inventory modifications, 24% (8/34) required dose range alert adjustments, and 9% (3/34) were referred for additional study. Final actions included the development of six new alerts, inventory modification for nine medications, dose range checking for eight medications, and no change for 11 medications.DiscussionThe PDSA cycle was an effective process that allowed the team to assess each medication using a systematic approach and encouraged additional analysis when needed. We were able to compare the KIDs List recommendations to current clinical decision support parameters and make adjustments or develop new alerts within the electronic health record to match the current standard. This initiative had a team‐based approach, included key stakeholders, and is replicable in other institutions.
Plasma C‐terminal agrin fragment concentrations across adulthood: Reference values and associations with skeletal muscle health
Authors: Pratt Jedd , Motanova Evgeniia , Pessanha Ludmilla , Narici Marco , Boreham Colin , De Vito Giuseppe 
Published: June 2024

AbstractBackgroundIncreasing interest surrounds the utility of blood‐based biomarkers for diagnosing sarcopenia. C‐terminal agrin fragment (CAF), a marker of neuromuscular junction stability, is amongst the most promising candidates; however, a dearth of reference data impedes the incorporation of its use in public health settings. This study aimed to establish reference values for plasma CAF concentrations across adulthood in a large, well‐characterized cohort of healthy adults; and comprehensively examine the association between plasma CAF levels and skeletal muscle health.MethodsOne thousand people aged between 18 and 87 years took part in this study (mean age = 50.4 years; 51% females). Body composition and muscle strength were examined using DXA and hand dynamometry. Plasma CAF concentrations were measured, in duplicate, using commercially available ELISA kits. Sarcopenia and individual sarcopenia signatures [low skeletal muscle index (SMI) only/low grip strength only] were classified using the EWGSOP2 algorithm.ResultsDetailed reference CAF values, according to sex and age, are presented. A significant but modest age‐related increase in plasma CAF concentration was observed (P = 0.018). Across adulthood, CAF concentrations were negatively associated with grip strength and SMI (both P < 0.001). In people ≥50 years old, CAF concentrations were 22.6% higher in those with sarcopenia (P < 0.001), 11.3% higher in those with low SMI (P = 0.006) and 9.6% higher in those with low grip strength (P = 0.0034), compared with controls. People in the highest CAF concentration quartile, had 3.25 greater odds for sarcopenia (95% CI = 1.41–7.49, P = 0.005), 2.76 greater odds for low SMI (95% CI = 1.24–5.22, P = 0.012), and 2.56 greater odds for low grip strength (95% CI = 1.07–5.57, P = 0.037), compared with those in the lowest quartile. People with a CAF Z‐score ≥2 had 9.52 greater odds for sarcopenia (95% CI = 3.01–30.05, P < 0.001) compared with a Z‐score <1. Plasma CAF concentration had an acceptable level of diagnostic accuracy for sarcopenia (AUC = 0.772, 95% CI = 0.733–0.807, P < 0.001).ConclusionsThe reference values presented herein may guide the clinical interpretation of circulating CAF and help identify people at risk of poor skeletal muscle outcomes for inclusion in therapeutic interventions. Our findings add clarity to existing data, demonstrating a robust relationship between circulating CAF and skeletal muscle integrity in the largest adult cohort to date, and support the use of CAF as an accessible, cost‐effective screening tool for sarcopenia. However, further research into the prognostic utility of plasma CAF, and the establishment of normative data from other populations, are urgently needed if routine CAF screening is to be embedded into public healthcare settings.
Insights into the heterogeneity of the tumor microenvironment in lung adenocarcinoma and squamous carcinoma through single‐cell transcriptomic analysis: Implications for distinct immunotherapy outcomes
Authors: Fang Xinyun , Li Dianke , Wan Shiyue , Hu Junjie , Zhang Peng , Jie Dai , Chen Linsong , Jiang Gening , Song Nan 
Published: June 2024

AbstractBackgroundImmune checkpoint blockade has emerged as a key strategy to the therapy landscape of non‐small cell lung cancer (NSCLC). However, notable differences in immunotherapeutic outcomes exist between the two primary NSCLC subtypes: lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). This disparity may stem from the tumor immune microenvironment's heterogeneity at the transcriptome level.MethodsBy integrative analysis of transcriptomic characterization of 38 NSCLC patients by single‐cell RNA sequencing, the present study revealed a distinct tumor microenvironment (TME) between LUAD and LUSC, with relevant results further confirmed in bulk transcriptomic and multiplex immunofluorescence (mIF) validation cohort of neoadjuvant immunotherapy patients.ResultsLUAD exhibited a more active immune microenvironment compared to LUSC. This included highly expression of HLA I/II in cancer cells, reinforced antigen presentation potential of dendritic cells and enhanced cytotoxic activity observed in T/NK cells. In LUSC, cancer cells highly expressed genes belonging to the aldo‐keto reductases, glutathione S‐transferases and aldehyde dehydrogenase family, negatively correlating with immunotherapy outcomes in the validation cohort of our center. Further analysis revealed elevated infiltrated cancer‐associated fibroblasts (CAFs) in LUSC, which was corroborated in The Cancer Genome Atlas cohort. Corresponding increased infiltration of ADH1B+ CAFs in major pathologic response (MPR) patients and the higher presence of FAP+ CAFs in non‐MPR patients were demonstrated by multiplex mIF. Moreover, upregulating immunosuppressive extracellular matrix remodeling was identified in LUSC.ConclusionsThese comprehensive analyses advance the understanding of the differences in TME between LUAD and LUSC, offering insights for patient selection and developing subtype‐specific treatment strategies.
Ramsey‐type problems on induced covers and induced partitions toward the Gyárfás–Sumner conjecture
Authors: Chiba Shuya , Furuya Michitaka 
Published: June 2024

AbstractGyárfás and Sumner independently conjectured that for every tree , there exists a function such that every ‐free graph satisfies , where and are the chromatic number and the clique number of , respectively. This conjecture gives a solution of a Ramsey‐type problem on the chromatic number. For a graph , the induced SP‐cover number (resp. the induced SP‐partition number ) of is the minimum cardinality of a family of induced subgraphs of such that each element of is a star or a path and (resp. ). Such two invariants are directly related concepts to the chromatic number. From the viewpoint of this fact, we focus on Ramsey‐type problems for two invariants and , which are analogies of the Gyárfás‐Sumner conjecture, and settle them. As a corollary of our results, we also settle other Ramsey‐type problems for widely studied invariants.
Multi‐centre digital radiography reject analysis for different clinical room use types: The establishment of local reject reference levels for public hospital departments
Authors: Serra Daniel , Neep Michael J , Ryan Elaine 
Published: June 2024

AbstractIntroductionReject analysis in digital radiography helps guide the training of staff to reduce patient radiation dose and improve department efficiency. The purpose of this study was to perform a multi‐centre, vendor agnostic reject analysis across different room usage types, and to provide benchmarks for comparison.MethodsRetrospective reject and exposure log data were collected via USB from fixed general X‐ray systems across multiple Australian sites, for collation and analysis. The overall reject rate, local reject reference level, absolute and relative reject rates for body part categories, reject rates by room usage types and the reject rate for each reason of rejection were calculated.ResultsData were collected from 44 X‐ray systems, across 11 hospitals. A total of 2,031,713 acquired images and 172,495 rejected images were included. The median reject rate was 9.1%. The local reject reference level (LRRL), set as the 75th percentile of all reject rates, was 10.6%. Median reject rates by room type were emergency (7.4%), inpatients + outpatients (9.6%), outpatients (9.2%), and hybrid (10.1%). The highest absolute reject rates by body part were chest (2.1%) and knee (1.4%). The highest relative rates by body part were knee (18.1%) and pelvis (17.2%). The most frequent reasons for image rejection were patient positioning (76%) and patient motion (7.5%).ConclusionsThe results compare well with previously published data. The range of reject rates highlights the need to analyse typical reject rates in different ways. With analysis feedback to participating sites and the implementation of standardised reject reasons, future analysis should monitor whether reject rates reduce.
Treatment of hydrocarbon marine pollution with cloud point extraction
Authors: Ghouas H. , Haddou B. , Canselier J. P. , Kameche M. 
Published: June 2024

AbstractThe release of hydrocarbons (HC) into the marine environment has serious consequences, both economically and ecologically. This work presents an efficient process to remove HC pollution from seawater: cloud point extraction (CPE), considered to be a reliable, inexpensive, and environmentally friendly method, using the readily biodegradable nonionic surfactants Lutensol ON30 and Tergitol 15‐S‐7. A real salt water sample with a high chemical oxygen demand (COD = 1700 mg O2/L) was thus treated. First, the phase diagrams of the binary systems (water–surfactant), and the pseudo‐binary systems (water–surfactant–HC), were determined. Second, after a 24 h settling time, considered as optimal, the extraction results, that is, residual soluble COD, residual percentage of surfactant in the dilute phase and volume fraction of coacervate at equilibrium, were expressed in terms of temperature and initial surfactant concentration. For each parameter, the results obtained were modeled using the response surface methodology and represented on three‐dimensional diagrams. They show that the COD can be reduced to 10 and 15 mg O2/L, using Lutensol ON30 and Tergitol 15‐S‐7, respectively, under seawater temperature conditions. Finally, it was shown that the surfactant can be recycled. The present work demonstrates that CPE can reduce the HC content of seawater on a laboratory scale.
Design of double‐core‐shell structural materials for the extraction of non‐steroidal anti‐inflammatory drugs
Authors: Liu Hongmei , Dang Shihao , Ye Baogui , Fan Hua , Tao Caihong 
Published: June 2024

In this work, core‐shell material with a special structure was designed and applied in solid‐phase extraction (SPE) for non‐steroidal anti‐inflammatory drugs (NSAIDs) combined with high‐performance liquid chromatography. Based on the advantages of core‐shell ZIF‐8@ZIF‐67 (Zeolite imidazole ester framework materials [ZIFs]), effective derivatization treatment was carried out to partially vulcanize the original ZIFs, resulting in a special and new double‐core‐shell structural material CoS/ZIF‐67/ZnS/ZIF‐8 (ZIFs@ZnS@CoS) with porous surface and center hollow. The multiple forces caused by the rich chemical structure, the large specific surface area caused by the special pore structure, and the effective protection of the ZIFs core by sulfide shell make the designed material have higher extraction efficiency and longer service life, compared with ZIF‐8@ZIF‐67 and ZIF‐8. At the same time, the established analytical method for non‐steroidal drugs had a high recovery rate (98.93%–102.10%), low detection limit (0.11–0.27 µg/L), and wide linear range (1–200 µg/L) within a good correlation coefficient R2 (0.9978–0.9993). Satisfactory results were also obtained from the extraction of NSAIDs from the Yellow River water samples. These results indicate that the designed double‐core‐shell structure material can effectively exert its structural advantages and become a promising extraction material.
Association between metabolically healthy obesity and risk of dementia: A systematic review and meta‐analysis
Authors: Su Yanyi , Li Yuecai , Ding Rongqi , Zheng Ziyi , Wang Jiaqi , Fu Qixiang , Deng Jialin , Zhou Hong 
Published: June 2024

AbstractBackgroundSome studies suggest that the metabolic alterations linked to obesity in humans may increase the likelihood of developing dementia. However, there are currently no existing meta‐analyses exploring the possible occurrence of dementia in patients with metabolically healthy obesity (MHO). In the present study, we aimed to investigate a potential correlation between individuals with MHO and the likelihood of developing dementia.MethodOur research focused on searching three databases to locate pertinent studies starting from January 10, 2023. We used sensitivity analysis, the Egger's test, and a visual funnel plot to separately assess the reliability of the research results and publication bias. We conducted this study according to a pre‐established protocol in the PROSPERO registry (CRD42023449459).ResultsWe incorporated three potential cohort investigations. Individuals with good metabolic health and obesity showed a decreased likelihood of developing dementia compared with those who were metabolically healthy but not obese (hazard ratio (HR) = 0.79; 95% confidence interval (CI) 0.68–0.92). In contrast, individuals who were metabolically unhealthy and nonobese had an increased likelihood of developing dementia (HR = 1.33; 95% CI 1.25–1.42), whereas the population with metabolically unhealthy obesity did not exhibit a notable association with dementia onset (HR = 1.06; 95% CI 0.83–1.37).ConclusionAccording to our meta‐analysis, patients with MHO had a reduced likelihood of developing general dementia and Alzheimer disease. Maintaining a well‐functioning metabolism can provide advantages in reducing the occurrence of dementia.
Linear analytical model for the seismic response of a straight‐jointed shield tunnel
Authors: Lu Jian‐Fei , Shi Meng‐Qin , Miao Yong‐Hong 
Published: June 2024

AbstractIn this study, the segment joint and ring joint of the lining of the straight‐jointed tunnel are simplified as an equivalent open cylindrical shell with a small central angle and an equivalent closed cylindrical shell with a small width, and the lining of the straight‐jointed tunnel is thus simplified as an equivalent continuous periodic shell (ECPS) described by the cylindrical shell theory. Since the ECPS lining is periodic along the longitudinal direction, the tunnel‐soil system can thus be treated as a periodic system, which is referred to as the periodic tunnel‐soil system (PTSS) in this study. Based on the proposed ECPS lining model, an analytical method for the tunnel with the ECPS lining (ECPS tunnel) under seismic waves is established in this study. By employing the periodicity condition for the PTSS as well as the wave function expansion method, the representation for the wave field in the soil is established. With the aforementioned cylindrical shell theory and Fourier series expansion method, the convolution type constitutive relation for the ECPS lining and the Fourier space equations of motion are derived. By using the soil‐lining continuity condition and aforementioned formulations for the ECPS lining and soil, the coupled Fourier space equations of motion for the PTSS are established, with which the response of the ECPS lining and scattered waves in the soil can be determined.
Effect of curing agents n‐octylamine and m‐xylene diamine on the mechanical and memory properties of E51 epoxy resin
Authors: Wan Tao , Wang Bo , Wang Yujiang , Han Qing , Liu Kuiren , Chen Jianshe , Li Binchuan , Fu Daxue , Wei Shicheng 
Published: June 2024

AbstractThe effects of curing agents n‐octylamine (OA) and m‐xylene diamine (MXDA) on the mechanical and memory properties of E51 epoxy resin (EP) are investigated in this work. The curing mechanism and thermal stability of OA and MXDA with EP are also investigated via Fourier‐transform infrared spectroscopy and thermogravimetric analysis, the influence of curing agent ratios on the thermo‐dynamic mechanical properties of EP are investigated through dynamic thermo‐mechanical analysis, and the relationship between the storage modulus, the hysteresis phase angle and the temperature are constructed. Moreover, the cross‐linking densities of the EP with different curing agent ratios are calculated using Archimedes's method. Besides, the effects of different proportions of curing agents on the mechanical properties of EP are studied. The results show that with the increases of MXDA ratio, the phase transition temperature, crosslink density, recovery temperature, recovery rate, the tensile strength, tensile modulus, strain strength, and strain modulus are enhanced, however, the hysteresis phase angle MXDA ratio and the tenacity decrease. Finally, the shape memory mechanism of E51 is discussed.
Multi‐regional sequencing reveals the genetic and immune heterogeneity of non‐cancerous tissues in gastric cancer
Authors: Zhou Yong , Li Shen , Hu Yingqi , Xu Xiao , Cui Jiantao , Li Shuaicheng , Li Ziyu , Ji Jiafu , Xing Rui 
Published: June 2024

AbstractGastric cancer (GC) is one of the most heterogeneous tumors. However, research on normal tissue adjacent to the tumor (NAT) is very limited. We performed multi‐regional omics sequencing on 150 samples to assess the genetic basis and immune microenvironment in NAT and matched primary tumor or lymph node metastases. NATs demonstrated different mutated genes compared with GC, and NAT genomes underwent independent evolution with low variant allele frequency. Mutation profiles were predominated by aging and smoking‐associated signatures in NAT instead of signatures associated with genetic instability. Although the immune microenvironment within NATs shows substantial intra‐patient heterogeneity, the proportion of shared TCR clones among NATs is five times higher than that of tumor regions. These findings support the notion that subclonal expansion is not pronounced in NATs. We also demonstrated remarkable intra‐patient heterogeneity of GCs and revealed heterogeneity of focal amplification of CD274 (encoding PD‐L1) that leads to differential expression. Finally, we identified that monoclonal seeding is predominant in GC, which is followed by metastasis‐to‐metastasis dissemination in individual lymph nodes. These results provide novel insights into GC carcinogenesis. © 2024 The Pathological Society of Great Britain and Ireland.
Low‐dose immune tolerance induction for severe hemophilia A inhibitor patients: Immunosuppressants are generally not necessary for inhibitor‐titer below 200 BU/mL
Authors: Li Zhengping , Sun Jie , Li Zekun , Chen Zhenping , Liu Guoqing , Yao Wanru , Cheng Xiaoling , Li Gang , Zhen Yingzi , Ai Di , Zhou Yaohan , Mao Qianqian , Poon Man‐Chiu , Wu Runhui 
Published: June 2024

ABSTRACTImportanceIt remained unclear that the efficacy comparison between low‐dose immune tolerance induction (LD‐ITI) incorporating immunosuppressants (IS) when severe hemophilia A (SHA) patients had inhibitor‐titer ≥200 Bethesda Units (BU)/mL (LD‐ITI‐IS200 regimen) and LD‐ITI combining with IS when SHA patients had inhibitor‐titer ≥40 BU/mL (LD‐ITI‐IS40 regimen).ObjectiveTo compare the efficacy of the LD‐ITI‐IS200 regimen with that of the LD‐ITI‐IS40 regimen for SHA patients with high‐titer inhibitors.MethodsA prospective cohort study on patients receiving LD‐ITI‐IS200 compared to those receiving LD‐ITI‐IS40 from January 2021 to December 2023. Both received LD‐ITI [FVIII 50 IU/kg every other day]. IS (rituximab + prednisone) was added when peak inhibitor tier ≥200 BU/mL in the LD‐ITI‐IS200 regimen and ≥40 BU/mL in the LD‐ITI‐IS40 regimen. Success is defined as a negative inhibitor plus FVIII recovery ≥66% of the expected.ResultsWe enrolled 30 patients on LD‐ITI‐IS200 and 64 patients on LD‐ITI‐IS40, with similar baseline clinical characteristics. A lower IS‐use rate was discovered in the LD‐ITI‐IS200 regimen compared to the LD‐ITI‐IS40 regimen (30.0% vs. 62.5%). The two regimens (LD‐ITI‐IS200 vs. LD‐ITI‐IS40) had similar success rate (70.0% vs. 79.7%), median time to success (9.4 vs. 10.6 months), and annualized bleeding rate during ITI (3.7 vs. 2.8). The cost to success was lower for LD‐ITI‐IS200 than for LD‐ITI‐IS40 (2107 vs. 3256 US Dollar/kg). Among patients with peak inhibitor‐titer 40–199 BU/mL, 10 non‐IS‐using (on LD‐ITI‐IS200 regimen) and 28 IS‐using (on LD‐ITI‐IS40 regimen) had similar success rates (70.0% vs. 78.6%) and time to success (9.0 vs. 8.8 months).InterpretationIn LD‐ITI, IS are not necessary for inhibitor titer <200 BU/mL.