bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Carbohydrate Associated Antigen Analogs as Potential Binders for Siglec‐7
Authors: Di Carluccio Cristina , Milanesi Francesco , Civera Monica , Abreu Celeste , Sattin Sara , Francesconi Oscar , Molinaro Antonio , Vaněk Ondřej , Marchetti Roberta , Silipo Alba 
Published: August 2023

AbstractWe investigated two recently synthesized and characterized sialyl derivatives, bearing the Neu5Ac‐α‐(2‐6)‐Gal epitope, as promising binders for Siglec‐7, an inhibitory Siglec mainly found on natural killer cells. A variety of sialoglycan structures can be recognized by Siglec‐7 with implications in the modulation of immune responses. Notably, overexpression of sialylated glycans recognized by Siglec‐7 can be associated with the progression of several tumors, including melanoma and renal cell carcinoma. NOE‐based NMR techniques, including Saturation Transfer Difference and transferred‐NOESY NMR, together with molecular docking and dynamic simulations were combined to shed light on the molecular basis of Siglec‐7 recognition of two conformationally constrained Sialyl‐Tn antigen analogs. We, therefore, identify the ligands epitope mapping and their conformational features and propose 3D models accurately describing the protein‐ligand complexes. We found that the binding site of Siglec‐7 can accommodate both synthetic analogs, with the sialic acid mainly involved in the interaction. Moreover, the flexibility of Siglec‐7 loops allows a preferred accommodation of the more rigid compound bearing a biphenyl moiety at position 9 of the sialic acid that contributed to the interaction to a large extent. Our findings provided insights for developing potential novel high affinity ligands for Siglec‐7 to hinder tumor evasion.
Azodicarboxylate‐Mediated Peptide Cyclisation: Application to Disulfide Bond Formation in Solution and Solid Phase
Authors: Serre Alexandra R. E. , Nwokolo Gabriel C. , Spencer Hannah L. M. , Bell Timothy J. , Barnieh Francis M. , Hughes Laurie , Falconer Robert A. , Morais Goreti Ribeiro 
Published: August 2023

AbstractCyclic peptides are important molecules, playing key roles in protein architecture, as chemical probes, and increasingly as crucial structural elements of clinically‐useful therapeutics. Herein we report methodology using azodicarboxylates as efficient reagents for the facile synthesis of cyclic peptides through a disulfide bridge. The utility of this approach in both solution and solid‐phase, and compatibility with common amino acid side chain functionalities is demonstrated, resulting in cyclic peptides in good yield and purity. This approach has significant potential application for synthesis of molecules of biological or therapeutic significance.
Use of Formic Acid as a CO Surrogate for the Reduction of Nitroarenes in the Presence of Dienes: A Two‐Step Synthesis of N‐Arylpyrroles via 1,2‐Oxazines
Authors: Fouad Manar Ahmed , Ferretti Francesco , Galiè Simone , Ragaini Fabio 
Published: August 2023

AbstractFormic acid, activated by acetic anhydride and a base, was employed as a CO surrogate to deoxygenate nitroarenes to nitrosoarenes, a reaction catalyzed by a palladium/phenanthroline complex in the homogeneous phase. Nitrosoarenes were trapped by conjugated dienes to give 3,6‐dihydro‐2H‐[1,2]‐oxazines. The latter were then transformed into N‐arylpyrroles employing CuCl as the catalyst. The reaction was designed to give the best results for pyrroles lacking any substituent in the 2 and 5 positions, which are difficult to produce employing most pyrrole syntheses.
Asymmetric electrode design with built‐in nitrogen transfer channel achieving maximized three‐phase reaction region for electrochemical ammonia synthesis
Authors: Wang Chao , Cheng Qiyang , Wang Mengfan , Liu Sisi , He Yanzheng , Deng Chengwei , Sun Yi , Qian Tao , Xu Na , Rosei Federico , Yan Chenglin 
Published: August 2023

AbstractCarbon‐free electrochemical nitrogen reduction reaction (NRR) is an appealing strategy for green ammonia synthesis, but there is still a significant performance bottleneck. Conventional working electrode is usually flooded by the electrolyte during the NRR test, and only the surface material could get access to the nitrogen, which inevitably gives rise to sluggish reaction rate. Herein, an asymmetric electrode design is proposed to tackle this challenge. An aerophilic layer is constructed on one face of the electrocatalyst‐loaded electrode, while the other side maintains its original structure, aiming to achieve facilitated nitrogen transfer and electrolyte permeation within the conductive skeleton simultaneously. This asymmetric architecture affords extensive three‐phase reaction region within the electrode as demonstrated by the combination of theoretical simulations and experimental measurements, which gives full play to the loaded electrocatalyst. As expected, the proof‐of‐concept asymmetric electrode delivers an NH3 yield rate of 40.81 μg h−1 mg−1 and a Faradaic efficiency of 71.71% at −0.3 V versus the reversible hydrogen electrode, which are more than 4 and 7 times that of conventional electrode, respectively. This work presents a versatile strategy for enhancing the interfacial reaction kinetics and is instructive to electrode design for gas‐involved electrochemical reactions.
Valproate associated brain volume‐loss in pediatric epilepsy—A case series
Authors: Umlauf Johanna , Rau Alexander , Demerath Theo , Bast Thomas , Schönberger Jan , Urbach Horst , Jacobs Julia , Klotz Kerstin A. 
Published: August 2023

AbstractBrain atrophy associated with valproate therapy is known from single case reports and is frequently accompanied by cognitive deterioration. We present a case series of incidental findings of brain volume loss in children treated with valproate and employed automatic brain volumetry to assess the effect size of volume loss. 3D T1w datasets were automatically segmented into white matter, gray matter, and cerebrospinal fluid using the SPM‐12 algorithm. Respective volumes of cerebrum and cerebellum were read out and normalized to the total intracranial volume. We identified six patients (median age 148.5 [85–178] months) who had received valproate for a median time of 5 (2–23) months prior to MRI in which a loss of brain volume was noted. None had reported the occurrence of new clinical symptoms. Volumetry showed a volume loss of up to 28% for cerebral GM, 25% for cerebellar GM, 10% for cerebral WM, and 20% for cerebellar WM. A volume loss of >5% in at least one of the subvolumes was found in all patients, with the more prominent volume loss in the cerebrum and in gray matter. In one patient, post‐valproate MRI was available and showed normalization of brain volume. Our case series indicates that valproate therapy might be associated with an asymptomatic volume loss of brain parenchyma in children with epilepsy and that this volume loss is assessable with automatic volumetry.
Psychological impact of COVID‐19 among undergraduate students in Jordan: A cross‐sectional study
Authors: Alfarajat Loai , Alnjadat Rafi , Salem Aziza , Alnawafleh Ahmad , Hadid Lourance Al 
Published: August 2023

AbstractBackgroundPsychopathology could be brought on by an immune system disruption triggered by an infection. Psychiatric residual effects have been noted following prior coronavirus outbreaks.MethodThis study is a cross‐sectional study that examined the psychopathological influence of the COVID‐19 pandemic among survivor students compared to students who have never been diagnosed as positive COVID‐19 patients (i.e., healthy students). Further, the study identified the relationship between sociodemographic profiles and mental health. To examine the significance of psychological health differences we used the DASS‐21, to measure depression, anxiety, and stress scales. There were seven questions to assess each dimension within the psychological scales. The respondents were selected randomly via online sources and completed the online self‐reporting questionnaire between August 23 and October 2, 2021.ResultsA total of 750 students completed the online questionnaire, with 677 participants (90.27% of those originally surveyed) included in the final analysis of this study. The mean score of the stress scale for healthy students (M = 16.88, SD = 12.3, N = 537) demonstrated a significantly lower mean compared to COVID‐19 survival students (M = 21.7, SD = 11.01, N = 140), t(675) = −4.22, p < 0.001. The mean of the depression scale for healthy students (M = 16.18, SD = 11.94) demonstrated significantly lower mean compared to COVID‐19 survival students (M = 20.91, SD = 11. 90), t(675) = −4.18, p < 0.001. The mean of the anxiety scale for healthy students (M = 12.50, SD = 10.72) demonstrated significantly lower mean compared to COVID‐19 survival students (M = 19.43, SD = 11. 25), t(675) = −6.74, p < 0.001.ConclusionUniversity students who were infected with COVID‐19 had a traumatic experience, and thus developed psychological symptoms greater than students with no history of this infection.
Breaking down barriers: The potential of smarter CAR‐engineered NK cells against solid tumors
Authors: Khawar Muhammad B. , Gao Guangzhong , Rafiq Mussarat , Shehzadi Anila , Afzal Ali , Abbasi Muddasir H. , Sheikh Nadeem , Afzal Nimra , Ashraf Muhammad A. , Hamid Syeda E. , Shahzaman Sara , Kawish Naseer , Sun Haibo 
Published: August 2023

AbstractNatural killer (NK) cells are considered to be the foremost fighters of our innate immune system against foreign invaders and thus tend to promptly latch onto the virus‐infected and tumor/cancerous cells, killing them through phagocytosis. At present, the application of genetically engineered Chimeric antigen receptor (CAR) receptors ensures a guaranteed optimistic response with NK cells and would not allow the affected cells to dodge or escape unchecked. Hence the specificity and uniqueness of CAR‐NK cells over CAR‐T therapy make them a better immunotherapeutic choice to reduce the load of trafficking of numerous tumor cells near the healthy cell populations in a more intact way than offered by CAR‐T immunotherapy. Our review mainly focuses on the preclinical, clinical, and recent advances in clinical research trials and further strategies to achieve an augmented and efficient cure against solid tumors.
Investigation of the Effect of Lasmiditan on the Pharmacokinetics of P‐Glycoprotein and Breast Cancer Resistance Protein Substrates
Authors: Luffer‐Atlas Debra , Wilbraham Darren , Posada Maria M. , Landry John , Tsai Max , Pearlman Eric M. 
Published: August 2023

AbstractLasmiditan is an in vitro inhibitor of P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP) efflux transporters. We aimed to confirm predictions from physiologically based pharmacokinetic models of lasmiditan, and assess the safety and tolerability of rosuvastatin and dabigatran co‐administered with lasmiditan. In this open‐label, post‐marketing drug–drug interaction, phase 1 clinical trial, eligible participants were adults aged 21‐70 years with a body mass index of 18.5‐35.0 kg/m2. Part 1 (P‐gp, 150 mg dabigatran etexilate with 200 mg lasmiditan) and part 2 (BCRP, 10 mg rosuvastatin with 200 mg lasmiditan) employed similar designs: a single dose of probe substrate administered on day −2 with pharmacokinetic evaluation; 1‐week washout; lasmiditan administered on days 8 and 9 alone; lasmiditan co‐administered with a single dose of probe substrate on day 10, with pharmacokinetic evaluation of probe substrate and lasmiditan. Sixty‐six participants were included in part 1 and 30 participants were included in part 2. Following dabigatran co‐administration with lasmiditan, versus dabigatran alone, 90% confidence intervals for geometric least‐squares (LS) mean ratios of area under the plasma concentration–time curve from time 0 extrapolated to infinity (AUC0–∞) and maximum observed drug concentration (Cmax) were not contained within the non‐effect boundaries (0.80 to 1.25). Dabigatran AUC0–∞ increased by 25% and Cmax increased by 22%. The median time of maximum observed drug concentration (tmax) for dabigatran was 2.0 to 3.0 hours. Following rosuvastatin co‐administration with lasmiditan, versus rosuvastatin alone, 90%CIs for geometric LS mean ratios of AUC0–∞ and Cmax were contained within non‐effect boundaries (0.80‐1.25). Rosuvastatin AUC0–∞ increased by 15% and Cmax increased by 7%. The median tmax for rosuvastatin was 4.0 hours. Results suggest that lasmiditan has a weak effect on P‐gp substrates and no clinically relevant effect on BCRP substrates.
Therapeutic Drug Monitoring of Imatinib and N‐Desmethyl Imatinib in Chronic Myeloid Leukemia Patients Using LC‐MS/MS in a Cohort Study
Authors: Huang Xiaoxing , Liu Yiwei , Chen Jie , Zheng Heng , Ding Yufeng , He Zheng 
Published: August 2023

AbstractImatinib is an oral tyrosine kinase inhibitor (TKI) and first‐line therapy for patients with chronic myeloid leukemia (CML). There is a positive correlation between serum imatinib concentrations and treatment response. However, the specific relationship between the blood concentration of imatinib and its influencing factors remains unclear. This study collected basic information from 102 patients using imatinib as first‐line treatment for CML. Further, we analyzed the individual differences in imatinib concentration and explored its influencing factors. Through intra‐day and inter‐day precision studies, we found that the precision for the imatinib assay methodology was within ±13% and that the recovery rate was above 85%. There is notable individual variation in the blood concentration of imatinib; the recommended treatment concentration is 860‐1500 ng/mL, with only 41.40% of patients achieving this concentration. Also, there was a negative correlation between age and imatinib trough concentration (Ctrough), as is observed between age and N‐desmethyl imatinib. Moreover, compared with the adolescent group, the serum imatinib Ctrough for groups aged 17‐47 and 48‐68 years was significantly reduced. Further analysis shows that imatinib Ctrough values reaching therapeutic concentrations (59%) increased dramatically for patients with CML aged 17‐47 years. Moreover, groups dosed with 400 mg/day resulted in therapeutic imatinib concentrations for 68% of patients with CML, which was the best performance. The established method was validated, with acceptable accuracy, precision, linearity, and stability, as required, and then successfully applied to the therapeutic drug monitoring of imatinib. Age, dose, and metabolites can influence the imatinib concentration and its therapeutic effect in patients with CML.
The Influence of Dexmedetomidine as an Adjuvant in Intrathecal Labor Analgesia: A Multicenter Study on Efficacy and Maternal Satisfaction
Authors: Lao Chengyi , Zhu Maoling , Yang Yu , Lin Xuejiang , Huang Ruiping , Wei Xiaofen , Wei Xiaoyu 
Published: August 2023

AbstractIn this study, we examined the impact of dexmedetomidine (DEX) on the effectiveness of epidural analgesia and labor outcomes. We administered different doses of DEX combined with 0.1% ropivacaine for epidural analgesia to evaluate the clinical effects and safety. To assess the effects of different concentrations of DEX in parturient women receiving epidural analgesia, we conducted a randomized double‐blind trial. We selected 400 parturient women and randomly assigned them to 4 groups, with 100 parturient women in each group: S0.1 (0.1 µg/mL DEX), S0.2 (0.2 µg/mL DEX), S0.3 (0.3 µg/mL DEX), and a control group (0.3 µg/mL sufentanil). Post‐analgesia, we recorded the Bromage score, duration of labor, method of delivery, bleeding, neonatal Apgar score, adverse reactions, and maternal satisfaction. The number of patients with a Bromage score of ≥2 and the incidence of bradycardia were higher in the S0.3 group compared with the other 3 groups (P < .05), whereas the high satisfaction rate was lower in the S0.3 group (P < .05). Moreover, we found that the number of times that additional patient‐controlled analgesia was administered was higher in the S0.1 group compared with the remaining 3 groups (P < .05). The control group exhibited a higher incidence of pruritus than the other 3 groups (P < .05). In conclusion, when administering spinal anesthesia for the relief of labor pain, epidural analgesia with 0.1% ropivacaine combined with 0.2 µg/mL DEX provides relatively ideal analgesic effects, higher maternal satisfaction, and reduces the incidence of pruritus, compared with the combination of 0.1% ropivacaine and 0.3 µg/mL sufentanil.
Mass‐produced gram‐negative bacterial outer membrane vesicles activate cancer antigen‐specific stem‐like CD8+ T cells which enables an effective combination immunotherapy with anti‐PD‐1
Authors: Won Solchan , Lee Changjin , Bae Seoyoon , Lee Jaemin , Choi Dongsic , Kim Min‐Gang , Song Sunghyun , Lee Jaewook , Kim Eunhye , Shin HaYoung , Basukala Anita , Lee Tae Ryong , Lee Dong‐Sup , Gho Yong Song 
Published: August 2023

AbstractDespite the capability of extracellular vesicles (EVs) derived from Gram‐negative and Gram‐positive bacteria to induce potent anti‐tumour responses, large‐scale production of bacterial EVs remains as a hurdle for their development as novel cancer immunotherapeutic agents. Here, we developed manufacturing processes for mass production of Escherichia coli EVs, namely, outer membrane vesicles (OMVs). By combining metal precipitation and size‐exclusion chromatography, we isolated 357 mg in total protein amount of E. coli OMVs, which was equivalent to 3.93 × 1015 particles (1.10 × 1010 particles/μg in total protein amounts of OMVs) from 160 L of the conditioned medium. We show that these mass‐produced E. coli OMVs led to complete remission of two mouse syngeneic tumour models. Further analysis of tumour microenvironment in neoantigen‐expressing tumour models revealed that E. coli OMV treatment causes increased infiltration and activation of CD8+ T cells, especially those of cancer antigen‐specific CD8+ T cells with high expression of TCF‐1 and PD‐1. Furthermore, E. coli OMVs showed synergistic anti‐tumour activity with anti‐PD‐1 antibody immunotherapy, inducing substantial tumour growth inhibition and infiltration of activated cancer antigen‐specific stem‐like CD8+ T cells into the tumour microenvironment. These data highlight the potent anti‐tumour activities of mass‐produced E. coli OMVs as a novel candidate for developing next‐generation cancer immunotherapeutic agents.
The DERMACLEAR study: Verification results of a natural language processing system in dermatology
Authors: Ortiz de Frutos Francisco J. , Giménez‐Arnau Ana M. , Puig Lluís , Silvestre Juan F. , Serra Esther , Salgado‐Boquete Laura , García‐Patos Vicente , Estebaranz Jose L. L. , Notario Jaime , Martin‐Santiago Ana , Pontevia Gabriel M. , Martín Víctor , Guinea Guillermo , Terradas Pau , Daudén Esteban 
Published: August 2023

AbstractBackgroundAccurately determining the epidemiology of dermatological diseases such as hidradenitis suppurativa (HS), psoriasis (PsO), chronic urticaria (CU) and/or atopic dermatitis (AD) is challenging due to variations in prevalence and disease severity in the reported literature.ObjectivesThe DERMACLEAR study aims to use natural language processing (NLP) to assess the proportions of patients with HS, PsO, CU and/or AD, and obtain information on patient profiles, patient journeys, and disease and healthcare burden in Spain. Here, the study design and objectives of the DERMACLEAR study are described and the precision of the NLP system used is assessed.MethodsThis study will retrospectively collect patient information from electronic health records (EHRs) at dermatology departments from seven tertiary hospitals in Spain. The NLP system was developed by IOMED Medical Solutions and was verified internally (IOMED scientific team) and externally (principal investigators of each hospital) to determine its precision in identifying patients with HS, PsO, CU and/or AD. Furthermore, internal verification was performed on other medical variables relevant to the study.ResultsTo date, the DERMACLEAR study has retrospectively collected data from 54,458 patients with HS, PsO, CU and/or AD (HS: 5045; PsO: 32,559; CU: 8397; AD: 12,492). The average precision of the NLP system to identify patients diagnosed with HS, PsO, CU, and/or AD across all hospitals exceeded 95% via external and internal verification.ConclusionsResults from the DERMACLEAR study will increase the real‐world evidence of clinical practice, obtaining a large amount of information on patients with the studied diseases. The NLP system used is precise in identifying patients diagnosed with HS, PsO, CU and/or AD, and other medical variables from EHRs, highlighting that it is a valid system to use in the DERMACLEAR study.
Developing a relational playbook for cardiology teams to cultivate supportive learning environments, enhance clinician well‐being, and veteran care
Authors: Gilmartin Heather M. , Connelly Brigid , Hess Edward , Mueller Candice , Plomondon Mary E. , Waldo Stephen W. , Battaglia Catherine 
Published: August 2023

AbstractIntroductionDespite the Veterans Health Administration (VA) efforts to become a learning health system (LHS) and high‐reliability organization (HRO), interventions to build supportive learning environments within teams are not reliably implemented, contributing to high levels of burnout, turnover, and variation in care. Supportive learning environments build capabilities for teaching and learning, empower teams to safely trial and adapt new things, and adopt highly reliable work practices (eg, debriefs). Innovative approaches to create supportive learning environments are needed to advance LHS and HRO theory and research into practice.MethodsTo guide the identification of evidence‐based interventions that cultivate supportive learning environments, the authors used a longitudinal, mixed‐methods design and LHS and HRO frameworks. We partnered with the 81 VA cardiac catheterization laboratories and conducted surveys, interviews, and literature reviews that informed a Relational Playbook for Cardiology Teams.ResultsThe Relational Playbook resources and 50 evidence‐based interventions are organized into five LHS and HRO‐guided chapters: Create a positive culture, teamwork, leading teams, joy in work, communication, and high reliability. The interventions are designed for managers to integrate into existing meetings or trainings to cultivate supportive learning environments.ConclusionsLHS and HRO frameworks describe how organizations can continually learn and deliver nearly error‐free services. The Playbook resources and interventions translate LHS and HRO frameworks for real‐world implementation by healthcare managers. This work will cultivate supportive learning environments, employee well‐being, and Veteran safety while providing insights into LHS and HRO theory, research, and practice.
FRANCES HESSELBEIN—UNCOMMON LEADER—UNCOMMON LEADERSHIP
Authors: Ward William E. (Kip) 
Published: August 2023

AbstractThe author, a retired U.S. Army General, describes his long friendship and collaboration with Frances Hesselbein. The friendship and collaboration also extended to the author’s wife, Joyce, including one of the latter’s volunteer organizations, the Martin Luther King, Jr. Scholarship Foundation. The author addresses Frances’s work and leadership in the greater context of leadership studies, He notes that “every so often, you can be blessed and privileged to get a PhD level education on leadership by witnessing the personal, first hand example of a great leader. This was the leadership class Frances Hesselbein conducted every time the opportunity presented itself to be in her presence.” In further amplifying these leadership lessons, he writes: “When being in the presence of a great leader, all you must do is observe, watch how they operate, what they do in signaling the importance of the action and how they value and utilize all the people in the organization.”