bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theoretical Investigations of Palladium‐Catalyzed [3+2] Annulation via Benzylic and meta C−H Bond Activation
Authors: Yoshimoto Rie , Taborosi Attila , He Qiyuan , Ano Yusuke , Chatani Naoto , Mori Seiji 
Published: August 2023

AbstractThe palladium‐catalyzed reaction of aromatic amides with maleimides results in the formation of a double C−H bond activation product, which occurs at both the benzylic and meta positions. Computational chemistry studies suggest that the first C−H bond activation unfolds via a six‐membered palladacycle, maleimide insertion, protonation of the Pd−N bond, and then activation of the meta C−H bond. The process concludes with reductive elimination, producing an annulation product. The energy decomposition analysis (EDA) showed that the deformation energy favors the ortho C−H bond activation process. However, this route is non‐productive. The interaction energy controls the site where the maleimide is inserted into the Pd−C(sp3) bond, which determines its site selectivity. The energetic span model indicates that the meta C−H bond activation step is the one that determines the turnover frequency. Regarding the directing group, it has been concluded that the strong Pd−S bonding and the destabilizing effect of the deformation energy allow the 2‐thiomethylphenyl to function effectively as a directing group.
Evaluation of a single‐use disk stack centrifuge for improved efficiency and sustainability at 1000 L GMP manufacturing scale
Authors: Walker Joshua , Lam Yik , Loman Abdullah , Smelko John P. , Rohr Michael 
Published: August 2023

AbstractDirect depth filtration is an established technology for single‐use harvest operation. Advantages of direct depth filtration include familiarity with depth filtration in downstream processes and simplicity of the operation. Drawbacks include low capacity, large footprint, labor‐intensive set‐up, high water use, and high waste in the form of discarded filters. Single‐use centrifugation is emerging as an alternative to depth filtration for the single‐use harvest step. Within the single‐use centrifugation space, disc stack centrifugation represents the newest entrant. In this study, we evaluated the performance of the GEA kytero single‐use disc stack centrifuge to clarify two monoclonal antibody‐producing cell culture fluids. The separation performance of the GEA kytero centrifuge varied between the two cell culture fluids, with differences in centrate turbidity and centrate filterability measured. A comparison was then performed to determine resource savings, compared to direct two‐stage depth filtration, when using a GEA kytero centrifuge to harvest a 1000 L bioreactor. The analysis concluded that replacement of the first stage of depth filters with a GEA kytero centrifuge has the potential to decrease the required second stage depth filtration area by up to 80%. The decrease in depth filter area resulting from the use of the GEA kytero would result in a decrease in the harvest step footprint, a decrease in buffer volume required to prime and rinse depth filters, and a decrease in the volume of plastic waste. An economic comparison of the GEA kytero single‐use centrifuge against a direct depth filtration step found that for a 1000 L harvest step, the GEA kytero centrifuge may reduce costs by up to 20% compared with two‐stage direct depth filtration.
A multicenter, phase II trial of GC1118, a novel anti‐EGFR antibody, for recurrent glioblastoma patients with EGFR amplification
Authors: Choi Seung Won , Jung Hyun Ae , Cho Hee‐Jin , Kim Tae Min , Park Chul‐Kee , Nam Do‐Hyun , Lee Se‐Hoon 
Published: August 2023

AbstractBackgroundWe evaluated the therapeutic efficacy of GC1118, a novel anti‐epidermal growth factor receptor (EGFR) monoclonal antibody, in recurrent glioblastoma (GBM) patients with EGFR amplification.MethodsThis study was a multicenter, open‐label, single‐arm phase II trial. Recurrent GBM patients with EGFR amplification were eligible: EGFR amplification was determined using fluorescence in situ hybridization analysis when a sample had both the EGFR/CEP7 ratio of ≥2 and a tight cluster EGFR signal in ≥10% of recorded cells. GC1118 was administered intravenously at a dose of 4 mg/kg once weekly. The primary endpoint was the 6‐month progression‐free survival rate (PFS6). Next‐generation sequencing was performed to investigate the molecular biomarkers related to the response to GC1118.ResultsBetween April 2018 and December 2020, 21 patients were enrolled in the study and received GC1118 treatment. Eighteen patients were eligible for efficacy analysis. The PFS6 was 5.6% (95% confidence interval, 0.3%–25.8%, Wilson method). The median progression‐free survival was 1.7 months (range: 28 days–7.2 months) and median overall survival was 5.7 months (range: 2–22.0 months). GC1118 was well tolerated except skin toxicities. Skin rash was the most frequent adverse event and four patients experienced Grade 3 skin‐related toxicity. Genomic analysis revealed that the immune‐related signatures were upregulated in patients with tumor regression.ConclusionThis study did not meet the primary endpoint (PFS6); however, we found that immune signatures were significantly upregulated in the tumors with regression upon GC1118 therapy, which signifies the potential of immune‐mediated antitumor efficacy of GC1118.
The prediction of early progressive disease in patients with hepatocellular carcinoma receiving atezolizumab plus bevacizumab
Authors: Takeuchi Yasuto , Nouso Kazuhiro , Fujioka Shin‐ichi , Kariyama Kazuya , Kobashi Haruhiko , Uematsu Shuji , Moriya Akio , Hagihara Hiroaki , Takabatake Hiroyuki , Nakamura Shinichiro , Yabushita Kazuhisa , Kikuchi Tatsuya , Oyama Atsushi , Adachi Takuya , Wada Nozomu , Onishi Hideki , Shiraha Hidenori , Takaki Akinobu 
Published: August 2023

AbstractBackground and AimsThe IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first‐line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real‐world clinical practice.MethodsA total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied. We investigated the frequency of early progressive disease (e‐PD; PD within 9 weeks) and analyzed the risk factors for e‐PD.ResultsThere were 47 patients (25.5%) diagnosed as e‐PD. Patients with e‐PD had a worse performance status (PS) and albumin–bilirubin (ALBI) and Child‐Pugh (C‐P) scores and a significantly higher rate of a systemic therapy than those with non‐e‐PD. A multivariate analysis showed that PS ≥1 (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.9–10, p < 0.001), ALBI score ≥−2.30 (OR = 2.1, 95% CI = 1.0–4.5, p = 0.044) and the history of a systemic therapy (OR = 3.0, 95% CI = 1.4–6.4, p = 0.0038) were significant and independent determinants of e‐PD. When examining the liver function trends in e‐PD patients, the ALBI scores at 3 and 6 weeks after starting therapy were significantly higher than before the treatment (p < 0.001).ConclusionsThe liver function and systemic therapy are useful predictors of e‐PD in HCC patients treated with atezolizumab plus bevacizumab in real‐world clinical practice.
Heterogeneous tumor microenvironment in pancreatic ductal adenocarcinoma: An emerging role of single‐cell analysis
Authors: Byeon Sooin , du Toit‐Thompson Taymin , Gillson Josef , Gill Anthony J. , Samra Jaswinder S. , Mittal Anubhav , Sahni Sumit 
Published: August 2023

AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies in the world, for which the mortality is almost as high as the disease incidence and is predicted to be the second‐highest cause of cancer‐related deaths by 2030. These cancerous tumors consist of diversified gene expressions within the different cellular subpopulations that include neoplastic ductal cells, cancer‐associated fibroblasts, and immune cells, all of which collectively facilitate cellular heterogeneity in the PDAC tumor microenvironment (TME). Active intratumoral interaction within the cell populations in TME induces the proliferation of cancerous cells, accounting for tumorigenesis and rapid metastasis.MethodsThis review will focus on novel findings uncovering PDAC heterogeneity in different cellular subpopulations using single‐cell RNA‐sequencing (scRNA‐seq) and other single‐cell analysis technologies. It will further explore the emerging role of single‐cell technologies in assessing the role of different subpopulations of neoplastic ductal cells, cancer‐associated fibroblasts, and immune cells in PDAC progression.Results and ConclusionThe application of scRNA‐seq in PDAC has started to unveil associations between disease progression and heterogeneity in pancreatic TME and could influence future PDAC treatment. Recent advances in scRNA‐seq have uncovered comprehensive analyses of heterogeneous ecosystems present within the TME. These emerging findings underpins further need for a more in‐depth understanding of intratumoral heterogeneity in the PDAC microenvironment.
Phytochemical Profiling and Pharmacological Evaluation of Leaf Extracts of Ruellia tuberosa L.: An In Vitro and In Silico Approach
Authors: Sharma Akanksha , Kumar Adarsh , Singh Ankit Kumar , Singh Harshwardhan , Kumar K. Jayaram , Kumar Pradeep 
Published: August 2023

AbstractThe present study was designed to appraise the photoprotective, antioxidant, and antibacterial bioactivities of Ruellia tuberosa leaves extracts (RtPE, RtChl, RtEA, RtAc, RtMe, and RtHMe). The results showed that, RtHMe extracts of R. tuberosa was rich in total phenolic content, i. e., 1.60 mgGAE/g dry extract, while highest total flavonoid content was found in RtAc extract, i. e., 0.40 mgQE/g. RtMe showed effective antioxidant activity (%RSA: 58.16) at the concentration of 120 μL. RtMe, RtEA and RtHMe exhibited effective in vitro antibacterial activity against Gram‐negative bacteria (E. coli). In silico docking studies revealed that paucifloside (−11.743 kcal/mol), indole‐3‐carboxaldehyde (−7.519 kcal/mol), nuomioside (−7.275 kcal/mol), isocassifolioside (−6.992 kcal/mol) showed best docking score against PDB ID 2EX8 [penicillin binding protein 4 (dacB) from Escherichia coli, complexed with penicillin‐G], PDB ID 6CQA (E. coli dihydrofolate reductase protein complexed with inhibitor AMPQD), PDB ID 2Y2I [Penicillin‐binding protein 1B in complex with an alkyl boronate (ZA3)] and PDB ID 2OLV (from S. aureus), respectively. Docked phytochemicals also showed good drug likeness properties.
Anti‐Inflammatory Activity of Lauraceae Plant Species and Prediction Models Based on Their Metabolomics Profiling Data
Authors: Gonçalves Vasconcelos de Alcântara Bianca , Neto Albert Katchborian , Garcia Daniela Aparecida , Casoti Rosana , Branquinho Oliveira Tiago , Chagas de Paula Ladvocat Ana Claudia , Edrada‐Ebel RuAngelie , Gomes Soares Marisi , Ferreira Dias Danielle , Chagas de Paula Daniela Aparecida 
Published: August 2023

AbstractThe Lauraceae is a botanical family known for its anti‐inflammatory potential. However, several species have not yet been studied. Thus, this work aimed to screen the anti‐inflammatory activity of this plant family and to build statistical prediction models. The methodology was based on the statistical analysis of high‐resolution liquid chromatography coupled with mass spectrometry data and the ex vivo anti‐inflammatory activity of plant extracts. The ex vivo results demonstrated significant anti‐inflammatory activity for several of these plants for the first time. The sample data were applied to build anti‐inflammatory activity prediction models, including the partial least square acquired, artificial neural network, and stochastic gradient descent, which showed adequate fitting and predictive performance. Key anti‐inflammatory markers, such as aporphine and benzylisoquinoline alkaloids were annotated with confidence level 2. Additionally, the validated prediction models proved to be useful for predicting active extracts using metabolomics data and studying their most bioactive metabolites.
State‐of‐the‐Art Review on the Applications of Nonlinear and Artificial Intelligence‐Based Controllers in Petrochemical Processes
Authors: Ansari Tuba Siraj , Taqvi Syed Ali Ammar 
Published: August 2023

AbstractPetrochemical industries are facing severe challenges in controlling nonlinear processes which are to be analyzed and monitored to develop efficient control models for improved efficiency and productivity. This review focuses on the control theory of petrochemical processes along with linear and nonlinear controllers with their limitations as well as on the application of artificial intelligence (AI)‐based controllers in multiple sectors of petrochemical industries. The findings and results from the review prove that the AI control technique is a promising one in the future for uncertain dynamic systems. The paper also covers a review of the vinyl chloride monomer (VCM) process and a recent control study on the plant. Being a nonlinear system, VCM requires advanced control techniques to control the uncertain dynamics of the process. The study shows a gap in the development of control strategies applied to VCM in terms of sustainability, efficiency, and environment‐concerned issues. Valuable insights for researchers, practitioners, and engineers engaged in process control and automation in the petrochemical industry are provided.
Fasciotomy on a female patient with acquired factor VIII: A case report and literature review of management
Authors: Lovell Katie , Peters Bethlehem , Pasli Melisa , Kennedy Katie , Liles Darla , Pories Walter 
Published: August 2023

Key Clinical MessageAcquired factor VIII inhibitors can be a rare cause of extensive intramuscular bleeding requiring fasciotomy. The subsequent postoperative period requires close monitoring due to high risk of fatal blood loss.AbstractAcquired factor VIII inhibitors are a rare cause of often extensive bleeding and subsequently large hematomas. This disorder's overall mortality can reach 38%, largely due to immunosuppression and subsequent infections or an underlying cause such as malignancy. The patient in this case study presented with a hematoma and extensive ecchymosis of the hand and forearm, which continued to progress, precipitating compartment syndrome of the hand and forearm and ultimately requiring fasciotomy. The combination of factors led to significant blood loss in the postoperative period requiring major fluid resuscitation and intensive care unit (ICU) level care. Due to this disorder's rarity and overall mortality, we present this case report with a literature review for management of acquired hemophilia in the setting of urgent fasciotomy.
Functional Molecular Crystals from the Arylation of a Halogenoplatinum Complex: Stimuli Responsiveness, Comproportionation, and π‐Bridged Dimerization
Authors: Seki Tomohiro , Korenaga Daiki 
Published: August 2023

AbstractA chloroplatinum complex was arylated to obtain stimuli‐responsive molecular crystals. The resulting arylplatinum complex showed polymorph‐dependent emission, mechano‐ and thermochromic luminescence as well as comproportionation and π‐bridged dimerization. Simple mixing of structurally similar arylplatinum complexes at room temperature resulted in the transfer of their aryl groups (comproportionation), which allowed their mechanochromic profiles to be tuned. We also found that recrystallization of the complex afforded a dimerized product in which two platinum ions are bridged by aryl groups resulting in a very short (3.0466(10) Å) Pt−Pt distance.
Guest Uptake and Exchange in One‐Dimensional Channels of Metal‐Organic‐Framework Films
Authors: Kanj Anemar Bruno , Heinke Lars 
Published: August 2023

AbstractThe mass transfer in a film of metal‐organic framework with one‐dimensional pores, oriented perpendicular to the substrate surface, was gravimetrically explored. The diffusion coefficients of the probe molecules cyclohexane and p‐xylene were determined from the transient uptake curves. When exchanging cyclohexane by p‐xylene in the MOF pores, the mass transfer was significantly slower than the plain, single‐component uptakes. However, a single‐file‐diffusion situation, where mutual passage is hindered, tremendously slowing down the mass transfer, was not found.
Red blood cell count and risk of adverse outcomes in patients with mildly reduced left ventricular ejection fraction
Authors: Liu Zhican , Zhu Yunlong , Zhang Lingling , Wu Mingxin , Huang Haobo , Peng Ke , Zhao Wenjiao , Chen Sihao , Peng Xin , Li Na , Zhang Hui , Zhou Yuying , Peng Yiqun , Fan Jie , Zeng Jianping 
Published: August 2023

AbstractBackgroundAnemia is associated with increased rates of heart failure (HF)‐related mortality and hospitalization. No studies have focused on the association between the red blood cell (RBC) count and the prognosis of patients with HF with mildly reduced left ventricular ejection fraction (HFmrEF). We retrospectively analyzed the effect of the RBC count on outcome events in patients with HFmrEF.MethodsWe investigated the association of the RBC count with outcome events in 1691 patients with HFmrEF (mean age: 68 years; 35% female) in Xiangtan Central Hospital. Using Cox proportional hazards models, the RBC count was assessed as both a continuous and categorical variable.ResultsDuring follow‐up (median: 33 months), cardiovascular death occurred in 168 patients (114 men and 54 women). After adjusting for established risk factors, each 1.0 × 1012 cell/L increase in the RBC count was associated with a 28% lower risk of cardiovascular death in men and a 43% lower risk in women. Patients with low RBC counts had a 0.5‐fold higher risk of cardiovascular death than those with normal RBC counts. The hazard ratio for men was 1.42 (95% confidence interval [CI]: 1.07–1.89), and the hazard ratio for women was 1.79 (95% CI: 1.20–2.67). The RBC count was not significantly associated with the composite endpoint of cardiovascular death and HF readmission (cardiovascular events) (p > .05).ConclusionsA decreased RBC count is associated with increased cardiovascular mortality in patients with HFmrEF. Correcting a low RBC count might potentially reduce the risk of cardiovascular death in patients with HFmrEF.
Pharmacokinetics and Pharmacodynamics of Burixafor Hydrobromide (GPC‐100), a Novel C‐X‐C Chemokine Receptor 4 Antagonist and Mobilizer of Hematopoietic Stem/Progenitor Cells, in Mice and Healthy Subjects
Authors: Sukhtankar Devki D. , Chang Li‐wen , Tsai Cheng‐yuan , Cardarelli Pina M. , Caculitan Niña G. 
Published: August 2023

AbstractAdequate mobilization of hematopoietic stem cells (HSCs), especially CD34+ cells, is necessary for stem cell transplantation in patients with hematological malignancies or autoimmune diseases. Burixafor is an inhibitor of the C‐X‐C Chemokine Receptor 4 that disrupts the C‐X‐C motif chemokine 12 (CXCL12)/CXCR4 axis in the bone marrow, releasing HSCs into circulation. In mice, a single intravenous dose of burixafor was rapidly absorbed (time to maximum concentration, 5 minutes) and increased peripheral white blood cell counts within 30 minutes. Additionally, burixafor was administered to 64 healthy subjects in a randomized, double‐blind, placebo‐controlled, single‐ascending‐dose study to evaluate safety, pharmacokinetics, and pharmacodynamics. Subjects received burixafor intravenous doses ranging from 0.10 to 4.40 mg/kg in 8 cohorts. Single doses were generally safe and well tolerated. Gastrointestinal events were reported at doses of 2.24 mg/kg or greater. Exposure (maximum concentration and area under the concentration–time curve) increased in an approximately dose‐proportional manner. Time to maximum concentration occurred with a median of 0.26–0.30 hours that was not dose proportional. As expected, white blood cell, CD133+ cell, and CD34+ cell concentrations generally increased with the increases in burixafor dose from 0.10 to 3.14 mg/kg. At maximal levels, the CD34+ cell counts increased 3‐ to 14‐fold from baseline levels. These results provide support for continued clinical development of burixafor.
A Novel Colorimetric and Fluorometric Dual‐Channel Chemosensor based on A Conjugated Perylene‐Benzothiazole System for Highly Selective Detection of Cyanide in Aqueous Media
Authors: Nguyen Thao Phuong Le , Nguyen Cam Hong Thi , Nguyen Thiet‐Quoc , Tran Chau Duc , Nguyen Tam Huu , Nguyen Le‐Thu T. , Nguyen Ha Tran 
Published: August 2023

AbstractA novel cyanine compound based on the conjugated perylene‐benzothiazole system (PBI) as a colorimetric and fluorometric dual‐channel sensor for cyanide (CN−) detection was synthesized and characterized via UV‐vis and fluorescence spectroscopy. PBI exhibited a high sensitivity and rapid optical response for CN− due to the intramolecular charge transfer (ICT) mechanism. The detection limit of PBI for CN− was 1.15×10−7 M in the mixture of DMSO/H2O (1 : 1, v/v). Moreover, probe PBI demonstrated high selectivity and sensitivity for CN− over other common anions, including Cl−, Br−, F−, I−, AcO−, ClO4−, HSO4−, SO42−, NO2−, NO3− and SCN−. This work provided a simple and effective approach to trace the toxic CN− ion with rapid response, high selectivity, and sensitivity that is possibly applied in environmental control and agricultural management.
Young people's experience of the therapeutic alliance: A systematic review
Authors: Dimic Tamara , Farrell Aoife , Ahern Elayne , Houghton Sharon 
Published: August 2023

AbstractObjectiveThe aim of this systematic review was to synthesise qualitative evidence on young people's conceptualisation, utilisation and experiences of the therapeutic alliance in individual psychotherapy or counselling and its role in bringing about change.MethodThe thematic synthesis method was used to synthesise data. The methodological quality of included studies was assessed using the CASP checklist for qualitative research.ResultsFour superordinate analytical themes were generated: (1) valuable therapist qualities, (2) conditions for the development and maintenance of the therapeutic alliance, (3) therapeutic processes and (4) barriers to the development of the therapeutic alliance. Findings indicate that young people appreciated the uniqueness of the therapeutic relationship that provided a sense of safety, choice and autonomy. Flexibility and accessibility were noted as important elements of therapeutic alliance building as they elicited a sense of agency. Young people emphasised the non‐linear nature of therapy and prioritised process variables such as improvement in self‐understanding, self‐efficacy and self‐worth.ConclusionThe current systematic review is a comprehensive overview of qualitative studies of experiences of therapy from young people's perspectives. Important practical implications derived from this review as the role of autonomy in the change process and the formation and maintenance of the therapeutic relationship were outlined as important elements in youth therapy.