bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses
Authors: Kelly Ronan J. , Landon Blair V. , Zaidi Ali H. , Singh Dipika , Canzoniero Jenna V. , Balan Archana , Hales Russell K. , Voong K. Ranh , Battafarano Richard J. , Jobe Blair A. , Yang Stephen C. , Broderick Stephen , Ha Jinny , Marrone Kristen A. , Pereira Gavin , Rao Nisha , Borole Aryan , Karaindrou Katerina , Belcaid Zineb , White James R. , Ke Suqi , Amjad Ali I. , Weksler Benny , Shin Eun Ji , Thompson Elizabeth , Smith Kellie N. , Pardoll Drew M. , Hu Chen , Feliciano Josephine L. , Anagnostou Valsamo , Lam Vincent K. 
Published: March 2024

AbstractGastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab–relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses. Primary endpoint was safety; the secondary endpoint was feasibility; exploratory endpoints included pathological complete (pCR) and major pathological response (MPR), recurrence-free survival (RFS) and overall survival (OS). The study met its primary safety endpoint in Arm A, although Arm B required modification to mitigate toxicity. pCR and MPR rates were 40% and 53.5% for Arm A and 21.4% and 57.1% for Arm B. Most common adverse events were fatigue, nausea, thrombocytopenia and dermatitis. Overall, 2-year RFS and OS rates were 72.5% and 82.6%, respectively. Higher baseline programmed cell death ligand 1 (PD-L1) and LAG-3 expression were associated with deeper pathological responses. Exploratory analyses of circulating tumor DNA (ctDNA) showed that patients with undetectable ctDNA post-ICI induction, preoperatively and postoperatively had a significantly longer RFS and OS; ctDNA clearance was reflective of neoantigen-specific T cell responses. Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613.
A synthetic digital city dataset for robustness and generalisation of depth estimation models
Authors: Li Jihao , Hu Jincheng , Huang Yanjun , Chen Zheng , Gao Bingzhao , Jiang Jingjing , Zhang Yuanjian 
Published: March 2024

AbstractExisting monocular depth estimation driving datasets are limited in the number of images and the diversity of driving conditions. The images of datasets are commonly in a low resolution and the depth maps are sparse. To overcome these limitations, we produce a Synthetic Digital City Dataset (SDCD) which was collected under 6 different weather driving conditions, and 6 common adverse perturbations caused by the data transmission. SDCD provides a total of 930 K high-resolution RGB images and corresponding perfect observed depth maps. The evaluation shows that depth estimation models which are trained on SDCD provide a clearer, smoother, and more precise long-range depth estimation compared to those trained on one of the best-known driving datasets KITTI. Moreover, we provide a benchmark to investigate the performance of depth estimation models in different adverse driving conditions. Instead of collecting data from the real world, we generate the SDCD under severe driving conditions with perfect observed data in the digital world, enhancing depth estimation for autonomous driving.
B-cell receptor signaling activity identifies patients with mantle cell lymphoma at higher risk of progression
Authors: Gambino Simona , Quaglia Francesca Maria , Galasso Marilisa , Cavallini Chiara , Chignola Roberto , Lovato Ornella , Giacobazzi Luca , Caligola Simone , Adamo Annalisa , Putta Santosh , Aparo Antonino , Ferrarini Isacco , Ugel Stefano , Giugno Rosalba , Donadelli Massimo , Dando Ilaria , Krampera Mauro , Visco Carlo , Scupoli Maria Teresa 
Published: March 2024

AbstractMantle cell lymphoma (MCL) is an incurable B-cell malignancy characterized by a high clinical variability. Therefore, there is a critical need to define parameters that identify high-risk patients for aggressive disease and therapy resistance. B-cell receptor (BCR) signaling is crucial for MCL initiation and progression and is a target for therapeutic intervention. We interrogated BCR signaling proteins (SYK, LCK, BTK, PLCγ2, p38, AKT, NF-κB p65, and STAT5) in 30 primary MCL samples using phospho-specific flow cytometry. Anti-IgM modulation induced heterogeneous BCR signaling responses among samples allowing the identification of two clusters with differential responses. The cluster with higher response was associated with shorter progression free survival (PFS) and overall survival (OS). Moreover, higher constitutive AKT activity was predictive of inferior response to the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. Time-to-event analyses showed that MCL international prognostic index (MIPI) high-risk category and higher STAT5 response were predictors of shorter PFS and OS whilst MIPI high-risk category and high SYK response predicted shorter OS. In conclusion, we identified BCR signaling properties associated with poor clinical outcome and resistance to ibrutinib, thus highlighting the prognostic and predictive significance of BCR activity and advancing our understanding of signaling heterogeneity underlying clinical behavior of MCL.
Chitosan combined with humic applications during sensitive growth stages to drought improves nutritional status and water relations of sweet potato
Authors: Elshamly Ayman M. S. , Iqbal Rashid , Elshikh Mohamed S. , Alwasel Yasmeen A. , Chaudhary Talha 
Published: March 2024

AbstractThe current decline in freshwater resources presents a significant global challenge to crop production, a situation expected to intensify with ongoing climate change. This underscores the need for extensive research to enhance crop yields under drought conditions, a priority for scientists given its vital role in global food security. Our study explores the effects of using humic and chitosan treatments to alleviate drought stress during critical growth phases and their impact on crop yield and water efficiency. We employed four different irrigation strategies: full irrigation, 70% irrigation at the early vine development stage, 70% irrigation during the storage root bulking stage, and 85% irrigation across both stages, complemented by full irrigation in other periods. The plants received either humic treatments through foliar spray or soil application, or chitosan foliar applications, with tap water serving as a control. Our findings highlight that the early vine development stage is particularly vulnerable to drought, with a 42.0% decrease in yield observed under such conditions. In normal growth scenarios, foliar application of humic substances significantly improved growth parameters, resulting in a substantial increase in yield and water efficiency by 66.9% and 68.4%, respectively, compared to the control treatment under full irrigation. For sweet potatoes irrigated with 70% water at the storage root bulking stage, ground application of humic substances outperformed both foliar applications of chitosan and humic in terms of yield results. The highest tuber yield and water efficiency were attained by combining chitosan and humic ground applications, regardless of whether 70% irrigation was used at the storage root bulking stage or 85% irrigation during both the early vine development and storage root bulking stages.
A remarkable assemblage of petroglyphs and dinosaur footprints in Northeast Brazil
Authors: Troiano Leonardo P. , dos Santos Heloísa B. , Aureliano Tito , Ghilardi Aline M. 
Published: March 2024

AbstractThe Serrote do Letreiro Site, found on the northwest periphery of the Sousa Basin, Brazil, presents a remarkable convergence of paleontological and archaeological elements. It is constituted of sub-horizontal "lajeiros", or rock outcrops, intermingled with endemic Caatinga vegetation. The three prominent outcrops feature fossilized footprints of theropod, sauropod, and iguanodontian dinosaurs from the Early Cretaceous Period. Adjacent to these dinosaur tracks, indigenous petroglyphs adorn the surface. The petroglyphs, mainly characterized by circular motifs, maintain a striking resemblance to other petroglyphs found in the states of Paraíba and Rio Grande do Norte. This study primarily endeavors to delineate the site's major characteristics while concentrating on the relationship between the dinosaur footprints and the petroglyphs. It concurrently assesses the preservation status of this invaluable record, shedding light on its implications for the realms of paleontology, archaeology, and cultural heritage studies.
Study on the characteristics of increased mechanical stiffness according to changes in LCP shape to reinforce clavicle fractures
Authors: Kim Soo Min , Kim Seong-tak , Han Dong-woon , Kim Dae-Geun 
Published: March 2024

AbstractThe clavicle has various anatomic shapes unique to each individual. Additionally, with the increase in high-energy traumas such as sports injuries and traffic accidents, the patterns of fractures become complex and complicated. Thus, there is a need for a variety of shapes of locking compression plates (LCP) to accommodate different types of fractures and facilitate quicker rehabilitation. The aim of this study is to present different types of LCP that secure fracture fragments and distribute stress evenly, in comparison to typical anatomical LCPs, for reinforcing clavicle fractures. Three models were compared in this study: the typical shape, the center hole removed shape, and the double-curved wing shape. The DICOM (Digital Imaging and Communications in Medicine) file obtained from the computed tomography scan of the patient’s clavicle was used to extract the three-dimensional (3D) clavicle structure. Finite element analysis (FEA) simulation was employed to analyze the structural changes of the LCP under external forces. A reinforced jig was used to apply the same type of external force to each LCP, and an experiment was conducted to analyze the mechanical impact of the LCP’s structural characteristics. When comparing the stress values at the fracture zone point, resulting from the FEA simulation with applied bending forces, it was calculated that the stress dispersion effect was approximately ten times greater when transitioning from a typical LCP shape to a double-curved partial wing structure. Moreover, the ultimate stress increased 3.33 times, from 241.322 to 804.057 N, as the LCP design changed under cantilever bending conditions. This double-curved wing LCP design reduces stress concentration at the fracture site and minimizes stress in the fracture area when subjected to cantilever bending forces. Consequently, this newly designed LCP has the potential to decrease complications related to the plate and accelerate rehabilitation protocols.
Hydraulic characterization and start-up of a novel circulating flow bio-carriers
Authors: Li Xingyu , Li Guang , Yu Yunyong , Jia Hongsheng , Ma Xiaoning , Yang Hong , Opoku Prince Atta 
Published: March 2024

AbstractHigh-quality biofilm carriers are crucial for the formation of biofilm, but problems such as slow biofilm growth on the carrier surface have been troubling a large number of researchers. The addition of a carrier changes the flow state in the reactor, which in turn affects the microbial attachment and the quantity of microorganisms. Also, aerobic microorganisms need to use dissolved oxygen in the water to remove water pollutants. In this paper, a novel recirculating flow carrier with a hollow cylinder structure is proposed, with a certain number of hollow inverted circular plates placed at equal distances inside. In this paper, the hydraulic residence time, aeration volume, and the spacing of the inflow plates of the recirculating flow biofilm carrier, which are three important factors affecting the hydraulic characteristics of the reactor, are first investigated. At the same time, it was compared with the common combined carrier to find the optimal operating conditions for the hydraulic characteristics. Secondly, a reactor start-up study was carried out to confirm that the new recirculating flow biofilm carrier could accelerate the biofilm growth by changing the hydraulic characteristics. The results showed that under the same conditions, the hydraulic properties of the reactor were better with the addition of the recirculating flow carrier, with an effective volume ratio of 98% and a significant reduction in short flows and dead zones. The stabilized removal of COD, NH3-N, and TN in the reactor with the addition of the recirculating flow carrier reached about 94%, 99%, and 91% respectively, at the beginning of the 15th day, which effectively proved the feasibility of the recirculating flow carrier.
CPMI-ChatGLM: parameter-efficient fine-tuning ChatGLM with Chinese patent medicine instructions
Authors: Liu Can , Sun Kaijie , Zhou Qingqing , Duan Yuchen , Shu Jianhua , Kan Hongxing , Gu Zongyun , Hu Jili 
Published: March 2024

AbstractChinese patent medicine (CPM) is a typical type of traditional Chinese medicine (TCM) preparation that uses Chinese herbs as raw materials and is an important means of treating diseases in TCM. Chinese patent medicine instructions (CPMI) serve as a guide for patients to use drugs safely and effectively. In this study, we apply a pre-trained language model to the domain of CPM. We have meticulously assembled, processed, and released the first CPMI dataset and fine-tuned the ChatGLM-6B base model, resulting in the development of CPMI-ChatGLM. We employed consumer-grade graphics cards for parameter-efficient fine-tuning and investigated the impact of LoRA and P-Tuning v2, as well as different data scales and instruction data settings on model performance. We evaluated CPMI-ChatGLM using BLEU, ROUGE, and BARTScore metrics. Our model achieved scores of 0.7641, 0.8188, 0.7738, 0.8107, and − 2.4786 on the BLEU-4, ROUGE-1, ROUGE-2, ROUGE-L and BARTScore metrics, respectively. In comparison experiments and human evaluation with four large language models of similar parameter scales, CPMI-ChatGLM demonstrated state-of-the-art performance. CPMI-ChatGLM demonstrates commendable proficiency in CPM recommendations, making it a promising tool for auxiliary diagnosis and treatment. Furthermore, the various attributes in the CPMI dataset can be used for data mining and analysis, providing practical application value and research significance.
The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer
Authors: Hagi Takaomi , Vangveravong Suwanna , Takchi Rony , Gong Qingqing , Goedegebuure S. Peter , Tiriac Herve , Van Tine Brian A. , Powell Matthew A. , Hawkins William G. , Spitzer Dirk 
Published: March 2024

AbstractCancer selective apoptosis remains a therapeutic challenge and off-target toxicity has limited enthusiasm for this target clinically. Sigma-2 ligands (S2) have been shown to enhance the cancer selectivity of small molecule drug candidates by improving internalization. Here, we report the synthesis of a novel drug conjugate, which was created by linking a clinically underperforming SMAC mimetic (second mitochondria-derived activator of caspases; LCL161), an inhibitor (antagonist) of inhibitor of apoptosis proteins (IAPinh) with the sigma-2 ligand SW43, resulting in the new chemical entity S2/IAPinh. Drug potency was assessed via cell viability assays across several pancreatic and ovarian cancer cell lines in comparison with the individual components (S2 and IAPinh) as well as their equimolar mixtures (S2 + IAPinh) both in vitro and in preclinical models of pancreatic and ovarian cancer. Mechanistic studies of S2/IAPinh-mediated cell death were investigated in vitro and in vivo using syngeneic and xenograft mouse models of murine pancreatic and human ovarian cancer, respectively. S2/IAPinh demonstrated markedly improved pharmacological activity in cancer cell lines and primary organoid cultures when compared to the controls. In vivo testing demonstrated a marked reduction in tumor growth rates and increased survival rates when compared to the respective control groups. The predicted mechanism of action of S2/IAPinh was confirmed through assessment of apoptosis pathways and demonstrated strong target degradation (cellular inhibitor of apoptosis proteins-1 [cIAP-1]) and activation of caspases 3 and 8. Taken together, S2/IAPinh demonstrated efficacy in models of pancreatic and ovarian cancer, two challenging malignancies in need of novel treatment concepts. Our data support an in-depth investigation into utilizing S2/IAPinh for the treatment of cancer.
Fabrication of pore-filling cation-exchange membrane from waste polystyrene and Spunbond Meltblown Spunbond (SMS) non-woven polypropylene fabric as the substrate
Authors: Asgari Hadi , Ghavipanjeh Farideh , Sabour Mohammad Reza , Emadzadeh Daryoush 
Published: March 2024

AbstractCommercial ion-exchange membranes are typically thick, possessing limited mechanical strength, and have relatively high fabrication costs. In this study, we utilize a three-layer polypropylene fabric known as Spunbond Meltblown Spunbond (SMS) as the substrate. This choice ensures that the resulting membrane exhibits high strength and low thickness. SMS substrates with various area densities, including 14.5, 15, 17, 20, 25, and 30 g/m2, were coated with different concentrations of waste polystyrene solution (ranging from 5 × 104 to 9 × 104 mg/l) before undergoing sulfonation using concentrated sulfuric acid. The physicochemical and mechanical properties of the membrane were characterized and compared with those of commercial Neosepta CMX and Nafion-117 cation-exchange membranes. Remarkably, the fabricated membrane exhibited good performance compared to commercial ones. The cation-exchange capacity (2.76 meq/g) and tensile strength (37.15 MPa) were higher, and the electrical resistance (3.603Ω) and the thickness (130 μm) were lower than the commercial membranes.
Reforming CO2 bio-mitigation utilizing Bacillus cereus from hypersaline realms in pilot-scale bubble column bioreactor
Authors: Barla Rachael J. , Raghuvanshi Smita , Gupta Suresh 
Published: March 2024

AbstractThe bubble column reactor of 10 and 20 L capacity was designed to bio-mitigate 10% CO2 (g) with 90% air utilizing thermophilic bacteria (Bacillus cereus SSLMC2). The maximum biomass yield during the growth phase was obtained as 9.14 and 10.78 g L−1 for 10 and 20 L capacity, respectively. The maximum removal efficiency for CO2 (g) was obtained as 56% and 85% for the 10 and 20 L reactors, respectively. The FT-IR and GC–MS examination of the extracellular and intracellular samples identified value-added products such as carboxylic acid, fatty alcohols, and hydrocarbons produced during the process. The total carbon balance for CO2 utilization in different forms confirmed that B. cereus SSLMC2 utilized 1646.54 g C in 10 L and 1587 g of C in 20 L reactor out of 1696.13 g of total carbon feed. The techno-economic assessment established that the capital investment required was $286.21 and $289.08 per reactor run of 11 days and $0.167 and $0.187 per gram of carbon treated for 10 and 20 L reactors, respectively. The possible mechanism pathways for bio-mitigating CO2 (g) by B. cereus SSLMC2 were also presented utilizing the energy reactions. Hence, the work presents the novelty of utilizing thermophilic bacteria and a bubble column bioreactor for CO2 (g) bio-mitigation.
Application of droplet digital PCR in minimal residual disease monitoring of rare fusion transcripts and mutations in haematological malignancies
Authors: Ip Beca B. K. , Wong Anthony T. C. , Law Janet Hei Yin , Au Chun Hang , Ma Shing Yan , Chim James C. S. , Liang Raymond H. S. , Leung Anskar Y. H. , Wan Thomas S. K. , Ma Edmond S. K. 
Published: March 2024

AbstractLeukaemia of various subtypes are driven by distinct chromosomal rearrangement or genetic abnormalities. The leukaemogenic fusion transcripts or genetic mutations serve as molecular markers for minimal residual disease (MRD) monitoring. The current study evaluated the applicability of several droplet digital PCR assays for the detection of these targets at RNA and DNA levels (atypical BCR::ABL1 e19a2, e23a2ins52, e13a2ins74, rare types of CBFB::MYH11 (G and I), PCM1::JAK2, KMT2A::ELL2, PICALM::MLLT10 fusion transcripts and CEBPA frame-shift and insertion/duplication mutations) with high sensitivity. The analytical performances were assessed by the limit of blanks, limit of detection, limit of quantification and linear regression. Our data demonstrated serial MRD monitoring for patients at molecular level could become “digitalized”, which was deemed important to guide clinicians in treatment decision for better patient care.
Understanding the role of head size and neck length in micromotion generation at the taper junction in total hip arthroplasty
Authors: Bologna Federico A. , Putame Giovanni , Audenino Alberto L. , Terzini Mara 
Published: March 2024

AbstractModular hip implants allow intra-operative adjustments for patient-specific customization and targeted replacement of damaged elements without full implant extraction. However, challenges arise from relative micromotions between components, potentially leading to implant failure due to cytotoxic metal debris. In this study magnitude and directions of micromotions at the taper junction were estimated, aiming to understand the effect of variations in head size and neck length. Starting from a reference configuration adhering to the 12/14 taper standard, six additional implant configurations were generated by varying the head size and/or neck length. A musculoskeletal multibody model of a prothesized lower limb was developed to estimate hip contact force and location during a normal walking task. Following the implant assembly, the multibody-derived loads were imposed as boundary conditions in a finite element analysis to compute the taper junction micromotions as the relative slip between the contacting surfaces. Results highlighted the L-size head as the most critical configuration, indicating a 2.81 μm relative slip at the mid-stance phase. The proposed approach enables the investigation of geometric variations in implants under accurate load conditions, providing valuable insights for designing less risky prostheses and informing clinical decision-making processes.