bluuebunny/crossref_metadata_2025 huggingface dataset:
Elucidating the Excited State Behavior of Pyridyl Pyridinium Systems via Computational and Transient Absorption Studies of Tetrahedral Multichromophoric Arrays and their Model Compounds
Authors: Ventura Barbara , Veclani Daniele , Venturini Alessandro , Armaroli Nicola , Baroncini Massimo , Ceroni Paola , Marchini Marianna
Published: August 2023

The tetrahedral shape‐persistent molecule 14+, containing four identical pyridyl pyridinium units connected via a sp3 hybridized carbon atom, has been investigated in detail by means of steady‐state and time resolved spectroscopy. Remarkable photophysical properties are observed, particularly in comparison with protonated and methylated analogues (1H48+, 1Me48+), which exhibit substantially shorter excited state lifetimes and lower emission quantum yields. Theoretical studies have rationalized the behavior of the tetrameric molecules relative to the monomers, with DFT and TD‐DFT calculations corroborating steady‐state (absorption and emission) and transient absorption spectra. The behavior of the monomeric compounds (each consisting in one of the four identical subunits of the tetramers, i. e., 2+, 2H2+ and 2Me2+) considerably differs from that of the tetramers, indicating a strong electronic interaction between the subunits in the tetrameric species, likely promoted by the homoconjugation through the connecting sp3 C atom. 2+ is characterized by a peculiar S1‐S2 excited state inversion, whereas the short‐lived emitting S1 state of 2H2+ and 2Me2+ exhibits a partial charge‐transfer character, as substantiated by spectro‐electrochemical studies. Among the six investigated systems, only 14+ is a sizeable luminophore (Φem=0.15), which is related to the peculiar features of its singlet state.
Multi‐responsive Electropolymer Surface Coatings Based on Azo Molecular Switches and Carbazoles: Light, pH, and Electrochemical Control of Z→E Isomerization in Thin Films
Authors: Gibalova Anna , Kortekaas Luuk , Simke Julian , Ravoo Bart Jan
Published: August 2023

Light‐responsive surfaces are attracting increasing interest, not least because their physicochemical properties can be selectively and temporally controlled by a non‐invasive stimulus. Most existing immobilization strategies involve the chemical attachment of light‐responsive moieties to the surface, although this approach often suffers from a low surface concentration of active species or a high inhomogeneity of applied coatings. Herein, electropolymerization of carbazoles as a facile and rapid approach for preparing light‐responsive azo‐based surface coatings is presented. The electrochemical oxidative polymerization of bis‐carbazole containing azo‐monomers yields stable films, in which the photochemical properties and specific pH sensitivity of azo molecular switches are retained. Moreover, the molecular design enables electrocatalytic control over Z→E azo double bond isomerization facilitated by the conductive polycarbazole backbone. Ultimately, the high degree of control over macromolecular properties yields conductive surface coatings responsive to a range of stimuli, showing great promise as a strategy for versatile application in organic electronics.
Relationship between survivorship care plans and unmet information needs, quality of life, satisfaction with care, and propensity to engage with, and attend, follow‐up care
Authors: Hill Rebecca E. , Mercieca‐Bebber Rebecca , Fardell Joanna E. , Wakefield Claire E. , Signorelli Christina , Webber Kate , Cohn Richard J. ,   ANZCHOG Study Group
Published: August 2023

Background

The impact of survivorship care plans (SCPs) on the proximal and distal outcomes of adult and childhood cancer survivors, and parent proxies, is unclear. This study aimed to determine the relationship between SCP receipt and these outcomes.

Methods

A cross‐sectional survey of adult and childhood cancer survivors (and parent proxies for survivors aged younger than 16 years) across Australia and New Zealand was conducted. Multivariate regression models were fitted to measure the impact of SCP receipt on proximal (unmet information needs and propensity to engage with, and attend, cancer‐related follow‐up care) and distal outcomes (quality of life and satisfaction with cancer‐related follow‐up care) with control for cancer history and sociodemographic factors.

Results

Of 1123 respondents, 499 were adult cancer survivors and 624 were childhood cancer survivors (including 222 parent proxies). We found that SCP receipt was predictive of greater attendance at, and awareness of, cancer‐related follow‐up care (adult: odds ratio [OR], 2.46; 95% CI, 1.18–5.12; OR, 2.38; 95% CI, 1.07–5.29; child/parent: OR, 2.61; 95% CI, 1.63–4.17; OR, 1.63; 95% CI, 1.06–2.50; respectively). SCP receipt also predicted fewer unmet information needs related to “follow‐up care required” and “possible late effects” (adult: OR, 0.44; 95% CI, 0.20–0.96; OR, 0.29; 95% CI, 0.13–0.64; child/parent: OR, 0.46; 95% CI, 0.30–0.72; OR, 0.57; 95% CI, 0.38–0.85; respectively). In terms of distal outcomes, SCP receipt predicted a better global quality of life for adult cancer survivors (β, 0.08; 95% CI, −0.01–7.93), proxy‐reported health‐related quality of life (β, 0.15; 95% CI, 0.44–7.12), and satisfaction with follow‐up care for childhood cancer survivors (OR, 2.93; 95% CI, 1.64–5.23).

Conclusions

Previous studies have shown little impact of SCPs on distal end points. Results suggest that SCPs may be beneficial to cancer survivors’ proximal and distal outcomes.
Pneumocystis jirovecii pneumonia after CD4+ T‐cell recovery subsequent to CD19‐targeted chimeric antigen receptor T‐cell therapy: A case report and brief review of literature
Authors: Kawata Kento , Shima Haruko , Shinjoh Masayoshi , Yamazaki Fumito , Kurosawa Takumi , Yaginuma Mizuki , Takada Hiroshi , Shimada Hiroyuki
Published: August 2023

Background

CD19‐targeted chimeric antigen receptor (CAR)‐T cell therapy involves administration of patient‐derived T cells that target B cells, resulting in B‐cell depletion and aplasia. In immunity against Pneumocystis jirovecii (Pj), CD4+ T cells and, more recently, B cells, are generally considered important. Antigen presentation by B cells to CD4+ T cells is particularly important. Trimethoprim‐sulfamethoxazole (TMP/SMX) for Pj pneumonia (PJP) prophylaxis is generally discontinued when the CD4+ T‐cell count is >200/μL. Here we report the first case, to our knowledge, of PJP in a patient with a CD4+ T cell count of >200/μL after CAR‐T cell therapy.

Case

A 14‐year‐old girl developed hemophagocytic lymphohistiocytosis (HLH) after cord blood transplantation (CBT) for relapsed precursor B‐cell acute lymphoblastic leukemia (B‐ALL). Twenty‐one months after CBT, she was diagnosed with combined second relapse in the bone marrow and central nervous system. The patient was treated with CD19‐targeted CAR‐T cell therapy for the relapse. After CAR‐T cell therapy, the patient remained in remission and continued to receive TMP/SMX for PJP prophylaxis. Seven months after CAR‐T cell therapy, CD4+ T cells recovered and TMP/SMX was discontinued. The B‐cell aplasia persisted. Ten months after CAR‐T cell therapy, the patient developed PJP. The patient was also considered to have macrophage hyperactivation at the onset of PJP. Treatment with immunoglobulin, TMP/SMX, and prednisolone was initiated, and the patient's symptoms rapidly ameliorated.

Conclusion

The patient in the present case developed PJP despite a CD4+ T‐cell count of >200/μL after CAR‐T cell therapy, probably because of inadequate CD4+ T‐cell activation caused by B‐cell depletion after CAR‐T cell therapy and repeated abnormal macrophage immune responses after CBT. It is important to determine the duration of TMP/SMX for prophylaxis after CAR‐T cell therapy according to each case, as well as the CD4+ T‐cell count.
Altered emotional response pattern related to complex trauma in patients with borderline personality disorder
Authors: Lopez‐Villatoro Jose M. , Diaz‐Marsa Marina , Garcia‐Ramos Adriana , Galvez‐Merlin Alejandra , Carrasco Jose L.
Published: August 2023

Introduction

This work aims to demonstrate, through the International Affective Picture System (IAPS) responses, an altered emotional pattern in borderline personality disorder (BPD) patients and to find a specific emotional response pattern by understanding their relationship with traumatic experiences and attachment bonds towards their primary caregivers.

Method

A total of 50 BPD patients and 39 control patients were evaluated using the IAPS, and its assessment was carried out through the Self‐Assessment Manikin (SAM). Paternal and maternal attachment bonds as well as traumatic experiences in BPD patients were evaluated. Statistical associations were analysed in the different variables.

Results

Significant differences between BPD and control patients were found in all emotional response components for pleasant, unpleasant and neutral images (p < .01), with one exception, the arousal in pleasant images. Patients' experience of traumatic experiences was positively related to scores on the happiness component of pleasant imagery (p = .057) and on the arousal component of unpleasant imagery (p = .058). Poorer maternal bonding in BPD patients was significantly related to lower scores on happiness (p < .01) and dominance (p < .05) components of pleasant imagery and all emotional response components for unpleasant imagery (p < .01).

Conclusions

The results of the study confirm an impaired emotional response pattern in patients with borderline personality disorder (BPD), showing an emotional response to pleasant images similar to that of depression, while the pattern found to unpleasant images could be related to the complex trauma observed in these patients, which includes PTSD experiences such as sexual abuse and attachment trauma experiences.
DNA isolation and genome sequence of the 134‐year‐old holotype specimen of Boletus subvelutipes Peck
Authors: Shumskaya Maria , Mironov Kirill S. , Ballesteros Jesús A. , Safonov Igor , Halling Roy E.
Published: August 2023

Molecular characterization of type specimens is a powerful tool used in clarifying species identity/circumscription, as well as establishing the taxonomic and phylogenetic status of organisms in question. However, DNA sequencing of aged herbarium collections can be a challenge due to the quantity and quality of DNA still present in the specimens. Herein, we report a custom DNA isolation protocol suitable for processing minute quantities of old specimen tissue and its utilization via high‐throughput sequencing technologies to obtain, for the first time, the genome assembly of the 134‐year‐old holotype of Boletus subvelutipes Peck, a North American fleshy pored mushroom of taxonomic and historical significance. A side‐by‐side evaluation of our DNA isolation method with that of a commercial “kit” by Qiagen is also presented. By relying on the type material, we have established the genetic identity of B. subvelutipes, as well as providing preliminary phylogenetic evidence for its generic affinities in Neoboletus within Boletaceae. The reference genome of the B. subvelutipes holotype provides a resource for future comparative genomic studies, taxonomic revisions in Boletaceae, and other evolutionary studies of fungi.
High‐resolution diving data collected from foraging area reveal that leatherback turtles dive faster to forage longer
Authors: Migneault Amy , Bennison Ashley , Doyle Thomas K. , James Michael C.
Published: August 2023

Despite multiple studies examining the diving behavior of leatherback sea turtles (Dermochelys coriacea) at coarse resolution over broad distances, there is still a paucity of high‐resolution diving data collected in areas where foraging has been confirmed. Short‐term (~1–3 h) deployments of suction cup tags with time–depth recorders (TDRs) on 10 free‐swimming leatherback turtles in a foraging area off Nova Scotia, Canada during August and September (2007–2014), captured a total of 161 dives. High‐resolution (1–5 s sampling rate) dive profile data indicated variability in diving behavior between and within individuals. On average, turtles spent 55.7% of their time diving and 44.3% at the surface. Turtles generally performed short (mean duration = 250.4 s [SD = 47.9 s]) and shallow dives (mean depth = 24.3 m [SD = 5.8 m]). We recorded a mean dive descent rate of 0.32 m/s, which is faster than values recorded for leatherbacks in tropical waters. This may reflect differences in environment, behavioral mode (e.g., foraging vs. inter‐nesting), and body condition. Linear mixed‐effects models suggest a significant positive correlation between descent rate and mean depth, maximum depth, and integrated vertical bottom movement (IVBM). Turtles with faster descent rates dove deeper and increased their predicted foraging behavior (IVBM, or the sum of absolute differences in depth changes while at the bottom portion of their dives). Models additionally showed that dive time, bottom time, and IVBM were all positively correlated to the post‐dive surfacing. This suggests that turtles required more time at the surface to recover and/or handle prey following longer dives characterized by increased vertical movement at the bottom portion of the dive. Dives were complex; the application of standard dive type/shape analysis may be over‐simplified and inappropriate for leatherbacks foraging in these habitats. These results portray a novel and detailed look at the foraging dynamics of a diving marine reptile.
Suppression of weed communities by granivores over time in an agroecosystem
Authors: Lundgren Jonathan G. , Anderson Randy L.
Published: August 2023

Invertebrate granivore communities can consume numerous weed seeds in cropland, but how this granivory influences weed recruitment over time in continuous no‐till systems is unknown. Weed and surface‐active granivore communities were determined in soybeans (Glycine max) over 3 years in eastern South Dakota. We examined seed removal rates of sentinel redroot pigweed, green foxtail, and lambsquarters (Chenopodium album) seeds and applied gut content analysis of granivores to determine which species consume immuno‐marked seeds of green foxtail (Setaria viridis). Weed stands with low diversity and high biomass production were associated with granivore community complexity. In turn, granivore community complexity was associated with weed communities with low diversity and high biomass in the subsequent growing season. Fall seed consumption, as measured by seed removal rates and gut content analysis of foxtail seed markers, was positively correlated with weed recruitment in the subsequent growing season. Seed specialists behaved differently toward focal weed species than the granivore community at large. Gryllus pennsylvanicus abundance was correlated with higher green foxtail consumption and removal rates. None of the other dominant green foxtail consumers revealed a similar set of responses. We propose a feedback mechanism whereby granivore community complexity in cropland leads to larger but fewer weeds over multiple years. Weed communities with these characteristics then lead to more complex granivore communities. If these relationships persist over time with minimal disturbance in continuous no‐till cropping systems without pesticides, this feedback loop could reduce weed cover.
Synthesis and Characterization of Phosphate‐Catecholate Chelated Nd(III), Zr(IV), and Al(III) Complexes
Authors: Chen Ting , Ju Shaoying , Tong Mengnan , Zhao Yufen , Wu Yile , Stephan Douglas W.
Published: August 2023

Metal phosphates are important catalysts and materials in synthesis chemistry. Herein, we describe the synthesis and characterization of phosphate‐catecholate chelated Nd(III), Zr(IV) and Al(III) chlorides (2–5). These species are achieved via ethyl chloride elimination reaction of oxophosphoranes with corresponding metal chlorides. The product 2–5 represent a new serial of monometallic and bimetallic phosphate‐catecholate chelated metal complexes stabilized by both P−O and catecholate‐O donors. These findings pave the way for future explorations of such species in catalysis.
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

We 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

Cyclic 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

Formic 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

Carbon‐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

Brain 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

Background

Psychopathology could be brought on by an immune system disruption triggered by an infection. Psychiatric residual effects have been noted following prior coronavirus outbreaks.

Method

This 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.

Results

A 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.

Conclusion

University 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

Natural 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

Lasmiditan 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

Imatinib 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

In 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

Despite 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

Background

Accurately 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.

Objectives

The 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.

Methods

This 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.

Results

To 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.

Conclusions

Results 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

Introduction

Despite 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.

Methods

To 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.

Results

The 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.

Conclusions

LHS 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

The 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.”
LEADERS: MAKE PEOPLE FEEL SPECIAL
Authors: Deierlein Tom
Published: August 2023

The author, a technology and nonprofit executive with a military background, knew Frances Hesselbein for a decade. When he first met her, in similarity to the circumstances of many other people, she had an immediate and profound effect: “I left feeling special and with an odd sense of empowerment that I could achieve whatever goals I had set.” He later became a professional mentor for “her mentoring and development program for teens, the Hesselbein Global Academy For Student Leadership and Civic Engagement Fifth Annual Leadership Summit at the University of Pittsburgh in July of 2013.” In drawing lessons from these experiences and encounters, the author writes: “We all meet dozens of people every day. We really have no idea what struggles and challenges they might be facing. If given the chance to talk or listen to them – take a few extra moments to help them feel special.”
THE WORLD ACCORDING TO FRANCES HESSELBEIN
Authors: Patouillet Leland D.
Published: August 2023

The author relates stories about his friendship with Frances Hesselbein, and how he was mentored by her. The major segment of the article is about the creation of the Frances Hesselbein Global Academy for Student Leadership and Civic Engagement at the University of Pittsburgh, where the author had a long career. He writes: “Frances continues to have a profound impact on my thinking today. One of her big ideas called for carrying a big basket. Frances explained it was important to adopt and adapt a given idea. This concept has become part of my DNA.” Frances’s leadership ideas are further explored, including the following, as related by the author: “Another big idea I learned from Frances was the need to establish a common language leading to a common vision resulting in common ground.”
Healthy Shrimps on the Platter: Encouraging Eco‐Friendly Means to Promote Shrimp Aquaculture Industry
Authors: Yadav Kanika , Verma Arunima Kumar , Pathak Ajey Kumar , Awasthi Abhishek
Published: August 2023

Shrimps contribute a considerable share to global food demands and are presumed to be one of the most popular delicacies worldwide. The nutrition value of shrimps is also very high. Shrimp aquaculture industry faces a lot of challenges due to anthropogenic or non‐anthropogenic reasons. Occurrence of disease is one of the chief reasons involved in management of shrimp aquaculture. The shrimps are highly fragile species and are markedly prone to various viral, bacterial, and fungal diseases. Past few decades of shrimp aquaculture have experienced deadly devastations due to viral and bacterial outbreaks. In order to prevent the recurrent disease, usage of the antibiotics has become customary practice as a therapeutic measure. The repercussion of using antibiotics in aquaculture is biomagnifications of toxic residues that further get accumulated in the food chains and food webs, eventually causing pollution in the environment. Hence, proper sanitation practices when synergistically used with immunostimulants, immunomodulators, pathogen free stocks, etc. can help the shrimp industry flourish in the current times. In the present paper, the importance of shrimps is described as food and eco‐friendly measures to preserve the global shrimp industry so that it can meet the escalating food demands globally.
Sustainable Urban Sanitation and Septage Management: A Study of Small Towns in Uttar Pradesh
Authors: Gupta A. K. , Joshi Mahendra
Published: August 2023

When sanitation is first conceived, its scope is restricted to the removal of human waste using methods such as cesspools, open ditches, pit latrines, bucket systems, and the like. Today, it refers to a more comprehensive concept that encompasses the elimination of solid and liquid waste, the hygiene of food, as well as personal, domestic, and environmental cleanliness. Sanitation is one of the fundamental factors that determines both quality of life and the indicator of human growth. Infections can be avoided altogether by adhering to proper sanitation practices, which stop the contamination of water and soil. As a result, the concept of sanitation is broadened to encompass not only personal hygiene but also the cleanliness of the home, the provision of clean water, the removal of waste products (including feces and urine), and the disposal of waste water. The government of India has implemented the Swachchatam Sarvekshan programme and begun developing protocols like as ODF, ODF+, and ODF++ in order to guarantee the long‐term viability of inclusive sanitation infrastructure and the efficient application of these facilities. In light of this, the purpose of the current article is to investigate the state of urban sanitation and the management of septage in a few select small towns in the Indian state of Uttar Pradesh. The information used in the paper has been collected through filed survey.
Insight into Molecular Interaction between Viral Envelop Protein VP26 and Eco‐Friendly Phytochemical Quercetin
Authors: Kumar Santosh , Verma Arunima Kumar , Thakur Gaurav , Dwivedi Arti , Awasthi Abhishek
Published: August 2023

White spot disease (WSD) is one of the most devastating diseases that has deteriorated shrimp production since past several decades. It is caused by white spot syndrome virus (WSSV) in almost all the species of shrimps across the globe. Understanding the complete disease mechanism and postulating a consolidated drug/antiviral is still under way. The major envelop proteins that assist the virus to penetrate into the shrimp are VP28, VP26, VP24, and VP19. VP26 a major constituent of the envelope plays a significant role in maintaining the structure of the envelope as well as helps the virus instigate the infection. The drugs and antiviral used to treat any viral infection conventionally efflux several toxic by‐products that degrade the structural properties of the environment. Since quercetin is a natural product obtained from plant sources, hence its degradation does not leave any toxic residues in the environment. This study has tried to understand the structural aspects of the viral envelop protein VP26. Additionally, the study has also tried to understand the interaction of a flavonoid quercetin with VP26. Computational approaches are used to explore the binding cavity of VP26 as well as trace the amino acid interactions shown by quercetin inside the binding cavity of VP26. The study reveals that quercetin shows good compatibility with VP26. Thus, using quercetin as an antiviral and mapping more detailed interaction of VP26‐quercetin can open pathway for development of antiviral against white spot disease.
Nursing students' perception of nursing knowledge: A qualitative study
Authors: Jensen Kari Toverud , Jerpseth Heidi
Published: August 2023

Aim

To explore nursing students' perception of nursing knowledge.

Design

Qualitative interview study.

Methods

Semistructured individual interviews with nine nursing students in their third year were conducted via a cloud‐based video communication app. Transcriptions were analysed based on Braun and Clarke's thematic analysis. The Consolidated Criteria for Reporting Qualitative Research checklist for qualitative research was used.

Results

The findings show that the participants emphasised that values are the prerequisites of and basis for performing professional nursing. The students found it difficult to define nursing knowledge and to distinguish nursing knowledge from other subjects. The thematic analysis resulted in two themes: values—a prerequisite of nursing knowledge, and nursing knowledge—an umbrella of knowledge.

Conclusion

Nursing knowledge seems to be difficult both to clarify and to demarcate for the students. However, the participants considered values to be important and vital to becoming a professional nurse.

Implications for the profession

This study addresses students' perceptions of values, nursing knowledge and what it consists of, and how this is experienced. An understanding of the nursing students' perceptions of what they consider to be important values and how they understand nursing knowledge is important in making the profession clearer and more distinguishable.

Impact

The impact of this study means that nurse education needs to emphasise a more argumentative and visible education where nursing knowledge and values are more prominent than today.

Reporting Method

COREQ.

Public Contribution

No patient or public contribution.