bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of starch‐based flocculant by multi‐component grafting copolymerization and its application in oily wastewater treatment
Authors: Liu Xiwen , Guo Qiaoxia , Ren Shenyong , Guo Junkang , Wei Chongbin , Chang Jiaxin , Shen Baojian
Published: November 2022

The grafting copolymerization of methacryloxyethyl trimethyl ammonium chloride (DMC), acrylamide (AM) and polyaluminum chloride (PAC) on starch was initiated by KMnO4, HIO4and H2SO4composite system. The modification of starch was combined its best attributes with those of inorganic and organic polymers and therefore enhanced the flocculation effect when it was used as flocculants by increasing the charge neutralization, adsorption bridging and aggregation ability. The main influence factors on oil removal ratio were investigated through orthogonal experimental design, and the optimal preparation conditions were obtained. The grafted copolymer was characterized through a series of physicochemical techniques (i.e., SEC‐MALS,13C MAS NMR,27Al NMR, FTIR, SEM, and TGA and XRD), which indicated the PAC, PAM and PDMC were successfully grafted on the starch.
Novel benzenesulfonamide‐thiouracil conjugates with a flexible N‐ethyl acetamide linker as selective CA IX and CA XII inhibitors
Authors: Abdel‐Mohsen Heba T. , El Kerdawy Ahmed M. , Petreni Andrea , Supuran Claudiu T.
Published: November 2022

Novel benzenesulfonamide derivatives linked to diverse functionalized thiouracils through a flexible N‐ethyl acetamide linker were designed and synthesized as carbonic anhydrase (CA) inhibitors. The synthesized candidates demonstrated a potent inhibitory activity against four different CA isoforms in the nanomolar range. Compound 10d showed more than twofold higher potency than the reference AAZ against CA II with Ki of 5.65 and 12 nM, respectively. Moreover, compounds 10d and 20 revealed potent activity against CA IX with Ki of 18.1 and 14.2 nM, respectively. In addition, 10c, 10d, 11b, 11c, and 20 demonstrated high potency against the CA XII isozyme with a Ki range of 4.18–4.8 nM. Most of the synthesized derivatives displayed preferential selectivity toward the CA IX and CA XII isoforms over CA I and CA II. Compounds 11a and 20 exhibited favorable selectivity toward CA IX over CA II with a selectivity index (SI) of 14.36 and 16.62, respectively, and toward CA XII over CA II with SI of 71.01 and 51.19, respectively. Molecular docking simulations showed that the synthesized conjugates adopted comparable binding modes in the CA I, CA II, CA IX, and CA XII isoforms, involving the deep fitting of the sulfonamide moiety in the base of the CA active site via chelation of the Zn2+ ion and H‐bond interaction with the key amino acids Thr199 and/or Thr200. Moreover, the N‐ethyl acetamide flexible linker enables the substituted thiouracils and fused thiouracil tail to achieve multiple interactions with the surrounding hydrophobic and hydrophilic regions.
Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Morand Eric , Pike Marilyn , Merrill Joan T. , van Vollenhoven Ronald , Werth Victoria P. , Hobar Coburn , Delev Nikolay , Shah Vaishali , Sharkey Brian , Wegman Thomas , Catlett Ian , Banerjee Subhashis , Singhal Shalabh
Published: November 2022

Objective

To assess the efficacy and safety of deucravacitinib, an oral, selective, allosteric inhibitor of TYK2, in a phase II trial in adult patients with active systemic lupus erythematosus (SLE).

Methods

Adults with active SLE were enrolled from 162 sites in 17 countries. Patients (n = 363) were randomized 1:1:1:1 to receive deucravacitinib 3 mg twice daily, 6 mg twice daily, 12 mg once daily, or placebo. The primary end point was SLE Responder Index 4 (SRI‐4) response at week 32. Secondary outcomes assessed at week 48 included SRI‐4, British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) response, Cutaneous Lupus Erythematosus Disease Area and Severity Index 50 (CLASI‐50), Lupus Low Disease Activity State (LLDAS), and improvements in active (swollen plus tender), swollen, and tender joint counts.

Results

At week 32, the percentage of patients achieving SRI‐4 response was 34% with placebo compared to 58% with deucravacitinib 3 mg twice daily (odds ratio [OR] 2.8 [95% confidence interval (95% CI) 1.5, 5.1]; P < 0.001 versus placebo), 50% with 6 mg twice daily (OR 1.9 [95% CI 1.0, 3.4]; P = 0.02 versus placebo), and 45% with 12 mg once daily (OR 1.6 [95% CI 0.8, 2.9]; nominal P = 0.08 versus placebo). Response rates were higher with deucravacitinib treatment for BICLA, CLASI‐50, LLDAS, and joint counts compared to placebo. Rates of adverse events were similar across groups, except higher rates of infections and cutaneous events, including rash and acne, with deucravacitinib treatment. Rates of serious adverse events were comparable, with no deaths, opportunistic infections, tuberculosis infections, major adverse cardiovascular events, or thrombotic events reported.

Conclusion

Deucravacitinib treatment elicited higher response rates for SRI‐4 and other end points compared with placebo, with an acceptable safety profile, in adult patients with active SLE.

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Functionalized electrodes embedded in nanopores: read‐out enhancement?
Authors: Fyta Maria
Published: November 2022

In this review, functionalized nanogaps embedded in nanopores are discussed in view of their high biosensitivity in detecting biomolecules, their length, type, and sequence. Specific focus is given on nanoelectrodes functionalized with tiny nanometer‐sized diamond‐like particles offering vast functionalization possibilities for gold junction electrodes. This choice of the functionalization, in turn, offers nucleotide‐specific binding possibilities improving the detection signals arising from such functionalized electrodes potentially embedded in a nanopore. The review sheds light onto the use and enhancement of the tunnelling recognition in functionalized nanogaps towards sensing DNA nucleotides and mutation detection, providing important input for a practical realization.
Making and Breaking of C−N Bonds: Applications in the Synthesis of Unsymmetric Tertiary Amines and α‐Amino Carbonyl Derivatives
Authors: Jyoti Roy Vishal , Pathania Vishali , Raha Roy Sudipta
Published: November 2022

An operationally simple process has been developed for the synthesis of unsymmetrical amines and α‐amino carbonyl derivatives in the absence of a catalyst, ligand, oxidant, or any additives. Contrary to known reductive amination methods, this protocol is amenable to substrates containing other reducible groups. This process effectively results in consecutive cleavage and formation of C−N bonds. DFT studies and Hammett analysis provide useful insight into the mechanism. The role of noncovalent interactions as a stabilizing factor have been examined in the protocol. A wide range of alkyl‐bromides have been coupled efficiently with a variety of dimethyl anilines to get unsymmetric tertiary amines with yields up to 90%. This methodology was further extended to the synthesis of α‐amino carbonyl derivatives with yields up to 93%.
Nickel‐Catalyzed Aminocarbonylation of Aryl Iodides with 1 atm CO
Authors: Liu Ning , Wu Xianqing , Qu Jingping , Chen Yifeng
Published: November 2022

Reported here is a nickel‐catalyzed aminocarbonylation of aromatic iodides with (hetero)aryl anilines and alkyl amines under atmospheric CO pressure. The reaction features with broad substrate scope with excellent functional group tolerance, providing an expedient method for the construction of amide analogues. Notably, amino alcohols can be selectively transformed into the corresponding amides successfully without interfering the hydroxyl group under the current standard conditions.
Predictors of individual differences in minimally verbal peer communication exchanges following peer‐oriented social intervention
Authors: Kedar Maayan , Bauminger‐Zviely Nirit
Published: November 2022

School‐age children on the autism spectrum who are minimally verbal (MVAS) use a limited repertoire of spontaneous communicative spoken words and reveal large heterogeneity in cognitive functioning. Despite the challenges to form peer social engagement posed by their unique social‐communicative profile, few interventions have targeted peer interactions in the MVAS population. This study explored predictors of individual differences in treatment response among 54 school‐age minimally verbal autistic children (8–16 years) following an RCT “school‐based peer social intervention” (S‐PSI) that compared two peer‐oriented intervention modalities (conversation versus collaboration) versus a waitlisted control group. We examined autistic‐symptom severity, age, verbal and nonverbal IQ, executive functions, and sensory‐processing profile for their contribution to children's ability to form relevant spontaneous communication exchanges with a peer partner. Main findings revealed that larger deficits in sensory‐processing (sensory‐avoidance and sensory low‐registration) and in executive functions contributed to greater growth in “relevant” (i.e., adequately attuned, participatory, reciprocal) communication following both interventions, but not for the waitlisted controls. Additionally, older participants with lower verbal and nonverbal IQ improved communication's relevancy more after the conversation intervention, whereas the collaboration intervention was more beneficial for younger participants. Lower autistic‐symptom severity contributed to larger growth in relevancy for all groups. By identifying individual‐level predictors of spontaneous, attuned, participatory, and reciprocal (i.e., “relevant”) communication exchanges with peers, we optimized S‐PSI personalization for this uniquely nonverbal, heterogeneous MVAS population. These new channels for tailoring peer interventions to better meet individuals' needs may result in reduced social isolation and loneliness and enhanced well‐being.
Validation of case definition algorithms for the ascertainment of congenital anomalies
Authors: Nava de Escalante Yonabeth , Abayomi Aanu , Langlois Sylvie , Ye Xibiao , Erickson Anders , Ngo Henry , Armour Rosemary , Okamoto Reiko , Arbour Laura , Bedard Tanya , Der Kenny , Van Allen Margot , Skarsgard Erik , Lavoie Martin , Henry Bonnie
Published: November 2022

Background

Congenital anomalies (CA) are one of the leading causes of infant mortality and long‐term disability. Many jurisdictions rely on health administrative data to monitor these conditions. Case definition algorithms can be used to monitor CA; however, validation of these algorithms is needed to understand the strengths and limitations of the data. This study aimed to validate case definition algorithms used in a CA surveillance system in British Columbia (BC), Canada.

Methods

A cohort of births between March 2000 and April 2002 in BC was linked to the Health Status Registry (HSR) and the BC Congenital Anomalies Surveillance System (BCCASS) to identify cases and non‐cases of specific anomalies within each surveillance system. Measures of algorithm performance were calculated for each CA using the HSR as the reference standard. Agreement between both databases was calculated using kappa coefficient. The modified Standards for Reporting Diagnostic Accuracy guidelines were used to enhance the quality of the study.

Results

Measures of algorithm performance varied by condition. Positive predictive value (PPV) ranged between approximately 73%–100%. Sensitivity was lower than PPV for most conditions. Internal congenital anomalies or conditions not easily identifiable at birth had the lowest sensitivity. Specificity and negative predictive value exceeded 99% for all algorithms.

Conclusion

Case definition algorithms may be used to monitor CA at the population level. Accuracy of algorithms is higher for conditions that are easily identified at birth. Jurisdictions with similar administrative data may benefit from using validated case definitions for CA surveillance as this facilitates cross‐jurisdictional comparison.
Novel strategy to improve hepatocyte differentiation stability through synchronized behavior‐driven mechanical memory of iPSCs
Authors: Kim Mee‐Hae , Thanuthanakhun Naruchit , Kino‐oka Masahiro
Published: November 2022

Cellular homeostasis is assumed to be regulated by the coordination of dynamic behaviors. Lack of efficient methods for synchronizing large quantities of cells makes studying cell culture strategies for bioprocess development challenging. Here, we demonstrate a novel application of botulinum hemagglutinin (HA), an E‐cadherin function‐blocking agent, to synchronize behavior‐driven mechanical memory in human induced pluripotent stem cell (hiPSC) cultures. Application of HA to hiPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration‐and time‐dependent manner. Interestingly, cytoskeleton rearrangement in cells with prolonged exposure to HA resulted in mechanical memory synchronization with Yes‐associated protein, which increased pluripotent cell homogeneity. Synchronized hiPSCs have higher capability to differentiate into functional hepatocytes than unsynchronized hiPSCs, resulting in improved efficiency and robustness of hepatocyte differentiation. Thus, our strategy for cell behavior synchronization before differentiation induction provides an approach against the instability of differentiation of pluripotent cells.
Electron microscopy analysis of soft materials with freeze‐fracture techniques
Authors: Kim Wantae , Yoon Dong Ki
Published: November 2022

Electron microscopy (EM) is a technique that observes the complex microstructure of a sample with a resolution of several Å using high‐energy electrons with a short wavelength. It is very effective for visualizing nanostructures that would not be observed with an optical microscope. However, there are limitations in that the observation must be carried out with a very thin film in a vacuum, and the electron beam may damage the samples. The sample may be out of the desired state or damaged, and the image may be distorted. As a solution to these problems, a freeze‐fracture technique can be proposed. Freeze‐fracture method is a process of rapidly freezing a sample and then fracturing it to produce a metal replica of the morphology of the bulk of the surface. This article includes an overview and principles of freeze‐fracture techniques and examples of analysis of various soft structures.
How green value co‐creation mediates the relationship between institutional pressure and firm performance: A moderated mediation model
Authors: Tian Hong‐Hong , Huang Shi‐Zheng , Cheablam Onanong
Published: November 2022

It is a crucial issue for enterprises to resolve environmental protection‐related institutional pressure along with the implementation of strict environmental policies and the enhancement of public environmental awareness. Thus, in this study, we surveyed 312 firms in the Yangtze River Delta of China to investigate the relationship among institutional pressure, green value co‐creation, and firm performance by applying a moderated mediation model. Results indicate that institutional pressure positively affects both green value co‐creation and firm performance, whereas green value co‐creation also has a positive effect on firm performance. Furthermore, green value co‐creation mediates the relationship between institutional pressure and firm performance. However, organizational inertia moderates the mediating effect of green value co‐creation on the correlation between institutional pressure and firm performance. These findings enhance our understanding of the relationship among institutional pressure, green value co‐creation, and firm performance, as well as providing implications for further research and practice.
A challenging case of rheumatoid arthritis‐associated aortitis presenting with erythema nodosum after ST‐segment elevation myocardial infarction: A case report
Authors: Kaewnamchai Siripat , Temnithikul Bhakinai , Ruchakorn Nopparat , Angkananard Teeranan
Published: November 2022

Rheumatoid arthritis is a systemic inflammatory disease that has many extra‐articular manifestations. Cardiovascular involvement, including coronary vasculitis and aortitis and skin lesion of erythema nodosum are uncommon findings of patients with rheumatoid arthritis, and thus, it is challenging for diagnosis of this case from those unusual extra‐articular presentation.
Idiopathic common carotid artery laceration: A case report
Authors: Suzuki Natsumi , Katoh Mitsuhiko , Koda Kento , Kuriyama Masakazu , Nagano Gentaro , Yasuhara Kazuo
Published: November 2022

Carotid artery injury is a rare disease often caused by neck trauma or irradiation of head and neck cancer. It is not easy to diagnose quickly without these backgrounds. Herein, we report a case of a 52‐year‐old man with no history of trauma or irradiation whose carotid artery was found to be injured. It was suggested that patients without any other disease but hypertension could have carotid artery injury. Additionally, it was challenging to detect extravasation from the carotid artery by computed tomography scan and ultrasonography in the emergency department. We should consider the possibility of carotid artery injury when examining patients with sudden neck swelling, even without any history of trauma or irradiation.
Limbus vertebrae of the cervical spine: A case report
Authors: Pappa Eleni , Chatzikomninos Ioannis
Published: November 2022

Limbus vertebra is a common radiological finding in an adult, especially in the mid‐lumbar region. However it is less commonly seen in the mid cervical region. A case of an anterior limbus vertebra seen on the cervical spine on an adult suffering from a T5 fracture is reported.
Optimised Protocol for Drying Aqueous Enzyme Solutions in Organic Solvents – Comparison of Free and Immobilised Candida antarctica Lipase B
Authors: Tjørnelund Helena D. , Brask Jesper , Woodley John M. , Peters Günther H. J.
Published: November 2022

Here, we propose an optimised protocol for controlling the initial water activity (aw) in organic reaction mixtures with soluble lipase to ensure reproducible and consistent enzyme activity measurements. Pre‐equilibration above saturated salt solutions was used to set aw of the reaction media, where aw was tracked with a hygrometer. Consistent stirring of the suspension and volume correction to compensate for solvent evaporation were found to be critical. The protocol was tested on Candida antarctica lipase B (CALB) in soluble and immobilised forms in three organic solvents (acetonitrile, methyl tert‐butyl ether, and hexane) at four different water activities ranging from 0.12 to 0.97. Soluble and immobilised CALB had similar aw‐profiles and showed the highest enzyme activity in hexane. The optimised protocol expands the possibility to study enzyme kinetics from immobilised enzymes to soluble enzymes.
Mathematical modeling and simulation of porosity on thermomechanical properties of UHTCs under hypersonic conditions
Authors: Zuccarini Carmine , Ramachandran Karthikeyan , Russo Stefano , Jayakody Yasith C. , Jayaseelan Doni Daniel
Published: November 2022

Ultrahigh temperature ceramics (UHTCs) were analyzed for their suitability in hypersonic flight conditions using balanced heat equations, transport equation, and finite element modeling technique. Mathematical model was derived on the assumption that the induced porosity follows linear and parabolic solutions of Laplace equation and applied external load mimicking hypersonic conditions with critical heat flux ranging between 7 and 44 MW/m2. Simulations were carried out with four different UHTCs combinations and the results outlined a temperature rise exceeding 4700°C with deformation observed on the fixed area and where the heat flux was generated. The influence of porosity had a greater impact on the performance of the material as it led to a reduction in deformation compared to dense samples. Porous UHTCs exhibited a good thermal shock resistance owing to the release of thermal stresses through pores, which also enhanced the thermal insulation of the structure.
Placing CF2 in the Center: Major Physicochemical Changes Upon a Minor Structural Alteration in Gem‐Difunctional Compounds
Authors: Saphier Sigal , Katalan Shahaf , Yacov Guy , Berliner Anat , Redy‐Keisar Orit , Fridkin Gil , Ghindes‐Azaria Lee , Columbus Ishay , Pevzner Alexander , Drug Eyal , Prihed Hagit , Gershonov Eytan , Eichen Yoav , Elias Shlomi , Parvari Galit , Zafrani Yossi
Published: November 2022

Fluorine atoms play an important role in all branches of chemistry and accordingly, it is very important to study their unique and varied effects systematically, in particular, the structure‐physicochemical properties relationship. The present study describes exceptional physicochemical effects resulting from a H/F exchange at the methylene bridge of gem‐difunctional compounds. The Δlog P(CF2‐CH2) values, that is, the change in lipophilicity, observed for the CH2/CF2 replacement in various α,α‐phenoxy‐ and thiophenoxy‐esters/amides, diketones, benzodioxoles and more, fall in the range of 0.6–1.4 units, which for most cases, is far above the values expected for such a replacement. Moreover, for compounds holding more than one such gem‐difunctional moiety, the effect is nearly additive, so one can switch from a hydrophilic compound to a lipophilic one in a limited number of H/F exchanges. DFT studies of some of these systems revealed that polarity, conformational preference as well as charge distributions are strongly affected by such hydrogen to fluorine atom substitution. The pronounced effects described, are a result of the interplay between changes in polarity, H‐bond basicity and molecular volume, which were obtained with a very low ‘cost’ in terms of molecular weight or steric effects and may have a great potential for implementation in various fields of chemical sciences.
Synthesis and Characterization of Hypervalent Pentacoordinate Carbon Compounds Bearing a 7‐6‐7‐Ring Skeleton
Authors: Yamamoto Yohsuke , Shi Yuan , Masui Takashi , Saito Daigo , Inoue Tatsuya , Sato Hitomi , Dohi Chisato , Muneta Emiko , Shang Rong , Nakamoto Masaaki
Published: November 2022

To stabilize SN2 transition state‐like penta‐coordinate carbon species, triaryl‐substituted cationic carbon compounds bearing a moderately flexible 7‐6‐7‐ring skeleton with sulfur donors were synthesized and characterized. Electronic effects of para substituents (R=Cl, F, H, CH3, SMe, OMe) of the two equatorial aryl groups bound to the cationic central carbon were investigated systematically along with a planar bidentate thioxanthene derivative. X‐ray analysis on their solid‐state structures showed that the parent (R=H), chloro‐, fluoro‐ and methyl‐derivatives were tetracoordinate carbon (sulfonium) structures, while the p‐MeO and thioxanthenyl system were pentacoordinate carbocation structures. The Hammett substituent constants for the para substituents (σp+) correlates well with the bonding in these compounds. The methylthio‐derivative with intermediate Hammett substituent constants (p‐MeS; σp+=−0.60) showed a tetracooridnate solid‐state structure, though solution UV‐Vis properties suggested the presence of a penta‐coordinate structure. These findings amount to the first unambiguous solution evidence of the hypervalent apical 3c–4e interactions in pentacoordinate carbon compounds.
Body mass index during maintenance therapy and relapse risk in children with acute lymphoblastic leukemia: A Children's Oncology Group report
Authors: Wadhwa Aman , Chen Yanjun , Hageman Lindsey , Hoppmann Anna L. , Angiolillo Anne , Dickens David S. , Lew Glen , Neglia Joseph P. , Ravindranath Yaddanapudi , Ritchey A. Kim , Termuhlen Amanda , Wong F. Lennie , Landier Wendy , Bhatia Smita
Published: November 2022

Background

Obesity at diagnosis of childhood acute lymphoblastic leukemia (ALL) is associated with greater risk of relapse; whether this association extends to obesity during maintenance is unstudied.

Methods

This study used data from AALL03N1 to calculate median body mass index (BMI) for 676 children over 6 consecutive months during maintenance therapy; BMI percentile (BMI%ile) were operationalized as normal/underweight (<85%ile), overweight/obese (85%–98%ile), and extreme obesity (≥99%ile). Hazard of relapse was estimated using multivariable proportional subdistributional hazards regression after adjusting for all relevant demographic and clinical predictors.

Results

Median age at study enrollment was 6 years and median length of follow‐up was 7.9 years. Overall, 43.3% of the cohort was underweight/normal weight, 44.8% was overweight/obese, and 11.8% had extreme obesity. Cumulative incidence of relapse at 4 years from study enrollment was higher among those with extreme obesity (13.6% ± 4.5%) compared to those with underweight/normal weight (9.0% ± 2.1%). Multivariable analysis revealed that children with extreme obesity had a 2.4‐fold (95% confidence interval [CI], 1.1–5.0; p = .01) greater hazard of relapse compared to those who were underweight/normal weight. Overweight/obese patients were at comparable risk to those who were underweight/normal weight (hazard ratio, 0.8; 95% CI, 0.4–1.6). Erythrocyte thioguanine nucleotide (TGN) levels were significantly lower among children with extreme obesity compared to those with underweight/normal weight (141.6 vs. 168.8 pmol/8 × 108 erythrocytes; p = .0002), however, the difference in TGN levels did not explain the greater hazard of relapse among those with extreme obesity.

Conclusions

Extreme obesity during maintenance therapy is associated with greater hazard of relapse in children with ALL. Underlying mechanisms of this association needs further investigation.

Lay summary

Findings from this study demonstrate that extreme obesity during maintenance therapy is associated with a greater hazard of relapse among children with acute lymphoblastic leukemia.

We show that children with obesity have lower levels of erythrocyte thioguanine nucleotides even after adjusting for adherence to oral chemotherapy.

However, these lower levels do not explain the greater hazard of relapse, paving the way for future studies to explore this association.
Clinical characteristics, prognostic factors, and long‐term outcomes associated with epithelial malignancies of the thymus: A 20‐year single‐institution experience
Authors: Altshuler Ellery , Mathavan Akash , Mathavan Akshay , Krekora Urszula , Mathavan Mohit , Hones Keegan , Daily Karen
Published: November 2022

Background

Thymic epithelial tumors are rare and include thymomas and thymic carcinomas. There is scarce literature characterizing prognostic factors and long‐term outcomes in these tumors.

Aims

This review aims to describe disease features of thymomas and thymic carcinomas and to report clinical differences among thymoma histological subtypes.

Methods and Results

A retrospective chart review was performed at the University of Florida Shands Hospital, a tertiary care academic medical center in Gainesville, Florida, USA. The review included clinical data of adults with thymic epithelial tumors diagnosed between 2001 and 2021. Significant associations among demographics, histology, stage, and outcomes were investigated. Thymoma subgroup analysis was performed using histological subtype and sex. Forty patients with thymoma and seven patients with thymic carcinoma were included in the final analysis. Among those with thymomas, patients with subtype B1, B2, or B3 tumors were younger, had larger tumors, and presented with higher stage disease when compared to those with subtypes A or AB. Tumor recurrence was most common in subtype B2 and B3 tumors (50.0% and 16.7% vs. 0%; p < .01). However, there was no significant difference in overall survival between histologic subtypes. Compared to females, males with thymomas had superior overall survival (103.0 vs. 62.9 months; p = .021) despite presenting with larger tumors (9.8 vs. 5.8 cm; p = .041). Concomitant myasthenia gravis was associated with increased recurrence but not worsened mortality. Compared to thymomas, patients with thymic carcinoma presented with higher‐stage disease and had poorer 5‐year survival (50.0% vs. 93.1%; p < .01).

Conclusion

This study affirmed pathologic stage and resectability as prognostic factors for thymic epithelial tumors. New findings include inferior overall survival in female patients and higher recurrence rates in those with thymomas and concomitant myasthenia gravis.
Pharmacokinetics of the Multi‐kinase Inhibitor Pexidartinib: Mass Balance and Dose Proportionality
Authors: Zahir Hamim , Greenberg Jonathan , Hsu Ching , Watanabe Kengo , Makino Chie , He Ling , LaCreta Frank
Published: November 2022

Pexidartinib is an oral small‐molecule tyrosine kinase inhibitor that selectively targets colony‐stimulating factor 1 receptor. Two phase 1 single‐center trials were conducted in healthy subjects to determine the absorption, distribution, metabolism, and excretion of pexidartinib using radiolabeled drug and to assess the dose proportionality of pexidartinib following single oral doses. In the mass balance study, eight male subjects received a single oral dose of [14C]‐pexidartinib 400 mg with radioactivity assessed in plasma, urine, and feces samples taken at various timepoints postdose. In the dose‐proportionality study, 18 subjects received single doses of pexidartinib 200, 400, and 600 mg using randomization sequences. Peak pexidartinib and total radioactivity were observed at 1.75–2.0 hours after the oral dose and then declined in a multiphasic manner. The overall mean recovery of administered radioactivity was 92.2% over 240 hours with 64.8% in the feces and 27.4% in the urine. Major components detected in plasma were pexidartinib and glucuronide (M5, ZAAD‐1006a), with M5 and pexidartinib detected in urine and feces, respectively. A glucuronide of dealkylated form (M1) in the urine and multiple oxidized forms (M2, M3, and M4) in feces were detected. The dose‐proportionality study found dose‐proportional drug exposure between the 200‐ and 400‐mg doses and slightly less than proportional exposure between the 400‐ and 600‐mg doses. These results from these studies provide insight into pexidartinib disposition after oral administration and support the development of dosing guidance in subjects with renal or hepatic impairment or subjects taking cytochrome P450 3A and uridine disphosphate‐glucuronosyl transferase inhibitors and inducers.
ML‐IDSDN: Machine learning based intrusion detection system for software‐defined network
Authors: Alzahrani Abdulsalam O. , Alenazi Mohammed J. F.
Published: November 2022

Software‐defined networking (SDN) has been developed to separate network control plane from forwarding plane which can decrease operational costs and the time it takes to deploy new services compared to traditional networks. Despite these advantages, this technology brings threats and vulnerabilities. Consequently, developing high‐performance real‐time intrusion detection systems (IDSs) to classify malicious activities is a vital part of SDN architecture. This article introduces two created datasets generated from SDN using Mininet and Ryu controller with different feature extraction tools that contain normal traffic and different types of attacks (Fin flood, UDP flood, ICMP flood, OS probe scan, port probe scan, TCP bandwidth flood, and TCP syn flood) that is used for training a number of supervised binary classification machine learning algorithms such as k‐nearest neighbor, AdaBoost, decision tree (DT), random forest, naive Bayes, multilayer perceptron, support vector machine, and XGBoost. The DT algorithm has achieved high scores to fit a real‐time application achieving F1 score on attack class of 0.9995, F1 score on normal class of 0.9983, and throughput score of 6,737,147.275 samples per second with a total number of three features. In addition, using data preprocessing to reduce the model complexity, thereby increasing the overall throughput to fit a real‐time system.
Defective Metal‐Organic Frameworks with Tunable Porosity and Metal Active Sites for Significantly Improved Performance in Styrene Oxidation
Authors: Guo Penghu , Cheng Huicheng , Zeng Xingye , Tao Leiming , Peng Baoxiang , Zhang Shuhua , Fischer Roland A. , Muhler Martin
Published: November 2022

Metal active sites and sufficient porosity in metal‐organic frameworks (MOFs) are crucial parameters determining the performances of catalysis, guest molecule adsorption, etc. Herein, through in situ introduction of Ru sites with different levels to Cu‐BTC structure together with post‐synthetic activation at 180 °C, a series of hierarchically porous CuRu‐BTC (HP‐CuRu‐BTC) MOFs were obtained. Besides, selective thermal decomposition (STD) treatment was carried out at 240 °C to further tune the hierarchical pores and metal sites, yielding rare case of metal nanoparticles (NPs)@HP‐CuRu‐BTC composites. After full characterization by XRD, N2 physisorption, SEM, ICP and XPS, these HP‐CuRu‐BTC and NPs@HP‐CuRu‐BTC samples possess high surface area (682–1199 m2 g−1), hierarchical pores and highly distributed metal sites with reduced oxidation states (Cu+ and Ru2+), indicating regulation of both metal sites and hierarchical pores. The HP‐CuRu‐BTC and NPs@HP‐CuRu‐BTC were further employed as catalysts for the heterogeneous styrene oxidation reaction under mild condition. Compared to microporous Cu‐BTC with unary metal component, HP‐CuRu‐BTC‐3 and NPs@HP‐CuRu‐BTC‐3 exhibited more than 2 times higher styrene conversion after 7 hours reaction under same condition.
Prediction of Busulfan Clearance by Predose Plasma Metabolomic Profiling
Authors: McCune Jeannine S. , Navarro Sandi L. , Baker K. Scott , Risler Linda J. , Phillips Brian R. , Randolph Timothy W. , Shireman Laura , Schoch H. Gary , Deeg H. Joachim , Zhang Yuzheng , Men Alex , Maton Loes , Huitema Alwin D. R.
Published: November 2022

Intravenous busulfan doses are often personalized to a target plasma exposure (targeted busulfan) using an individual’s busulfan clearance (BuCL). We evaluated whether BuCL could be predicted by a predose plasma panel of 841 endogenous metabolomic compounds (EMCs). In this prospective cohort of 132 hematopoietic cell transplantation (HCT) patients, all had samples collected immediately before busulfan administration (preBU) and 96 had samples collected 2 weeks before busulfan (2‐week‐preBU). BuCL was significantly associated with 37 EMCs after univariate linear regression analysis and controlling for false discovery (< 0.05) in the 132 preBU samples. In parallel, with preBU samples, we included all 841 EMCs in a least absolute shrinkage and selection operator–penalized regression which selected 13 EMCs as predominantly associated with BuCL. Then, we constructed a prediction model by estimating coefficients for these 13 EMCs, along with sex, using ordinary least‐squares. When the resulting linear prediction model was applied to the 2‐week‐preBU samples, it explained 40% of the variation in BuCL (adjusted R2 = 0.40). Pathway enrichment analysis revealed 18 pathways associated with BuCL. Lysine degradation followed by steroid biosynthesis, which aligned with the univariate analysis, were the top two pathways. BuCL can be predicted before busulfan administration with a linear regression model of 13 EMCs. This pharmacometabolomics method should be prioritized over use of a busulfan test dose or pharmacogenomics to guide busulfan dosing. These results highlight the potential of pharmacometabolomics as a precision medicine tool to improve or replace pharmacokinetics to personalize busulfan doses.
Study finds gaps in follow‐up care, especially for transition‐age youth
Authors: Knopf Alison
Published: November 2022

A study of more than 100,000 emergency room visits and 95,000 mental health hospitalizations of youth and young adults with private insurance found that fewer than half who visited the emergency room, and less than two‐thirds of those who were hospitalized received follow‐up care within 30 days.
Effect of tobacco and nicotine in causing staining of dental hard tissues and dental materials: A systematic review and meta‐analysis
Authors: Karanjkar Rijula R. , Preshaw Philip M. , Ellis Janice S. , Holliday Richard
Published: November 2022

Introduction

Dental staining is a common concern for tobacco users. However, little is known about which components of tobacco are responsible for the staining and whether nicotine may be implicated. This is of increasing relevance with the popularity of novel products such as heated‐tobacco products and electronic cigarettes (E‐cigarettes).

Objectives

This systematic review aimed to establish the evidence base for the effect if any, of the various tobacco and nicotine products in causing staining of dental hard tissues and materials.

Material and Methods

This systematic review was performed in accordance with the preferred reporting items for systematic reviews and meta‐analyses guidelines. There were four structured population intervention comparison outcomesquestions. A search was conducted up to December 2021 in three databases: MEDLINE, EMBASE, and Web of Science, and manual searching of relevant sources was also completed. Two researchers individually reviewed the titles then abstracts and finally full articles. A reporting quality appraisal was conducted appropriately to the study methodology.

Results

Of the 815 records titles identified, 56 full‐text articles were assessed for eligibility, of which 27 were included for analysis. The included studies were mainly laboratory studies of varying reporting quality. There was evidence from 18 studies that tobacco exposure caused staining of dental hard tissues (pooled results from three studies‐ enamel/dentine; mean difference [MD]: 16.22; 95% confidence interval[12.11, 20.32; I2: 96%)and materials (pooled result from four studies—resin composite; MD: 11.90; 95% CI: 11.47, 12.34; I2: 100%). There was limited evidence that E‐cigarettes 99%) and heated tobacco products (HTPs; pooled results from three studies–−1.07, 6.54; I2: 99%) cause staining, but this was lower than with traditional tobacco/found 11 compounds, of which 8 were terpenoids, from tobacco products implicated in causing staining. Finally, there was some evidence that resin composites stained more than other materials.

Conclusions

Tobacco smoking causes dental staining. There was limited evidence that E‐cigarettes and HTPs did cause dental staining that was less intense than that caused by traditional tobacco products.
Adaptation of a multiple myeloma minimal residual disease multicolor flow cytometry assay for real‐world practice
Authors: McMillan Annabel , Tran Thien‐An , Galas‐Filipowicz Daria , Camilleri Marquita , Lecat Catherine , Ainley Louise , Guo Yanping , Yong Kwee , Sive Jonathan
Published: November 2022

Background

Achieving minimal residual disease (MRD) negativity following treatment for multiple myeloma (MM) is associated with improved progression free and overall survival. In the UK, MRD assessments in MM are not incorporated into routine clinical use outside trials. Widely used in other haematological malignancies, there is a role for widening the availability of myeloma MRD assays to laboratories outside larger treating centers.

Methods

We set up and assessed concordance of a multicolor flow cytometry (MCF) assay for MM MRD in collaboration with a reference center including validity following delayed processing of samples using an optimized fixation step. We then conducted a real‐world snapshot of MRD results in a cohort of newly diagnosed transplant‐eligible patients treated with UK standard induction therapies at the time of analysis.

Results

43 MCF MRD samples run in parallel with a reference center showed high correlation and minimal bias. 24 samples were split and processed in duplicate both fixed and fresh, with strong correlation, minimal bias, and no change in plasma cell phenotype by flow markers confirming a 6‐day delay in processing did not affect assay performance. A real‐world snapshot found 17% (10/58) of patients were MRD‐negative post‐bortezomib‐based triplet induction therapy.

Conclusions

We successfully adopted a reference MCF MM MRD method which was stable for up to 6 days following sample collection potentially allowing broader access of this assay to smaller laboratories which would facilitate further investigation of the prognostic value and clinical utility of MRD assessments outside the trial setting in real‐world practice.
Time course, factors related to, and prognostic impact of venoarterial extracorporeal membrane flow in cardiogenic shock
Authors: Montero Santiago , Rivas‐Lasarte Mercedes , Huang Florent , Chommeloux Juliette , Demondion Pierre , Bréchot Nicolas , Hékimian Guillaume , Franchineau Guillaume , Persichini Romain , Luyt Charles‐Édouard , Garcia‐Garcia Cosme , Bayes‐Genis Antoni , Lebreton Guillaume , Cinca Juan , Leprince Pascal , Combes Alain , Alvarez‐Garcia Jesus , Schmidt Matthieu
Published: November 2022

Aims

Venoarterial extracorporeal membrane oxygenation (VA‐ECMO) is currently one of the most used devices in refractory cardiogenic shock. However, there is a lack of evidence on how to set the ‘optimal’ flow. We aimed to describe the evolution of VA‐ECMO flows in a cardiogenic shock population and determine the risk factors of ‘high‐ECMO flow’.

Methods and results

A 7 year database of patients supported with VA‐ECMO was used. Based on the median flow during the first 48 h of the VA‐ECMO run, patients were classified as ‘high‐flow’ or ‘low‐flow’, respectively, when median ECMO flow was ≥3.6 or <3.6 L/min. Outcomes included rates of ventilator‐associated pneumonia, ECMO‐related complications, days on ECMO, days on mechanical ventilation, intensive care unit and hospitalization lengths of stay, and in‐hospital and 60 day mortality. Risk factors of high‐ECMO flow were assessed using univariate and multivariate cox regression. The study population included 209 patients on VA‐ECMO, median age was 51 (40–59) years, and 78% were males. The most frequent aetiology leading to cardiogenic shock was end‐stage dilated cardiomyopathy (57%), followed by acute myocardial infarction (23%) and fulminant myocarditis (17%). Among the 209 patients, 105 (50%) were classified as ‘high‐flow’. This group had a higher rate of ischaemic aetiology (16% vs. 30%, P = 0.023) and was sicker at admission, in terms of worse Simplified Acute Physiology Score II score [40 (26–58) vs. 56 (42–74), P < 0.001], higher lactate [3.6 (2.2–5.8) mmol/L vs. 5.2 (3–9.7) mmol/L, P < 0.001], and higher aspartate aminotransferase [97 (41–375) U/L vs. 309 (85–939) U/L, P < 0.001], among others. The ‘low‐flow’ group had less ventilator‐associated pneumonia (40% vs. 59%, P = 0.007) and less days on mechanical ventilation [4 (1.5–7.5) vs. 6 (3–12) days, P = 0.009]. No differences were found in lengths of stay or survival according to the ECMO flow. The multivariate analysis showed that risk factors independently associated with ‘high‐flow’ were mechanical ventilation at cannulation [odds ratio (OR) 3.9, 95% confidence interval (CI) 2.1–7.1] and pre‐ECMO lactate (OR 1.1, 95% CI 1.0–1.2).

Conclusions

In patients with refractory cardiogenic shock supported with VA‐ECMO, sicker patients had higher support since early phases, presenting thereafter higher rates of ventilator‐associated pneumonia but similar survival compared with patients with lower flows.
Ultrasound‐ and Microwave‐Assisted Extractions Facilitate Oil Recovery from Gilthead Seabream (Sparus aurata) By‐Products and Enhance Fish Oil Quality Parameters
Authors: Keskin Çavdar Hasene , Bilgin Hakkı , Fadıloğlu Sibel , Yılmaz Fatih Mehmet
Published: November 2022

This research aimed to analyze ultrasound (UAE) and microwave‐assisted extraction (MAE) as novel technologies for utilizing gilthead seabream (Sparus aurata) by‐products to produce high‐quality fish oil for human consumption. The impacts of extraction parameters, namely, temperature, time, solvent‐to‐solid ratio, and their interactions on the extraction yield, are investigated using response surface methodology (RSM), and a central composite rotatable design. The optimized conditions are 15.47 mL g−1 of solvent‐to‐solid ratio, 38 min, and 42 °C for UAE and 15.84 mL g−1 of solvent‐to‐solid ratio, 18 min, and 40 °C for MAE. Under optimal conditions, the maximum extraction yields are 38.40 and 36.70% (g/g) for UAE and MAE, respectively. Both UAE and MAE have significantly higher mass transfer rates (61.70 and 121.58 g h−1, respectively) than Soxhlet extraction (10.78 g h−1). The fatty acid composition, physicochemical, and oxidation analyses of fish oils confirm the suitability of both UAE and MAE for the recovery of high‐quality oils from fish processing by‐products. The valorized oils mainly include unsaturated fatty acids (≈75%) and are rich in oleic acid. Furthermore, scanning electron microscopy analysis reveals that the key driving force for fast oil extraction is the structural degradation of fish by‐products caused by ultrasound and microwave.

Practical Applications: Due to environmental and economic viewpoints, the validation of fish oil from fish industry by‐products has become a popular research topic recently. Alternative recovery techniques such as ultrasound‐ (UAE) and microwave‐assisted extraction (MAE) protocols may have additional benefits in producing functional oils. Interactive effects of process parameters determine the success of the extraction technique; therefore optimization is a critical approach when applying the extraction protocols. This study shows that UAE and MAE techniques significantly enhanced oil extraction rate from gilthead seabream (Sparus aurota) by‐products at lower temperatures and by using lower amounts of solvent. UVA and MAE increase oxidative stability and do not change the fatty acid composition. Hence, the by‐product of the gilthead seabream can be a sustainable and food‐grade fish oil source and UAE and MAE can be a good alternative to the conventional (Soxhlet) extraction by providing high yield and quality oil.
Lung cancer patients with positive programmed death‐ligand 1 expression endure graver postoperative pain
Authors: Wang Lu , Zhou Jian , Liu Huixin , Xu Hao , Li Huifang , Feng Yi , Tian Xue
Published: November 2022

Background

Postoperative pain after video‐assisted thoracoscopic surgery (VATS) is common in lung cancer patients, and it is unclear whether cancer itself participates in pain regulation. Programmed cell death ligand‐1 (PD‐L1) expressed by tumours may be analgesic. Our study aimed to detect the association between PD‐L1 and acute postoperative pain.

Methods

We reviewed patients who underwent VATS for lung cancer with tumour PD‐L1 expression analysed in our centre from Jan 2017 to Jul 2020. They were divided into PD‐L1 (−) group and PD‐L1 (+) group and were further divided into four subgroups according to opioids for postoperative analgesia: sufentanil PD‐L1 (−), sufentanil PD‐L1 (+), oxycodone PD‐L1 (−), and oxycodone PD‐L1 (+). We compared the numeric rating scale (NRS) for the first three postoperative days at rest or cough between groups.

Results

A total of 369 patients (167 in PD‐L1 (−) vs. 202 in PD‐L1 (+)) were included. On the first postoperative day, NRS at cough in the PD‐L1 (+) patients were higher than those in the PD‐L1 (−) patients (2.91 ± 1.07 vs. 2.66 ± 1.01, p = 0.018). On the third day, NRS at cough in PD‐L1 (+) patients was higher (2.50 ± 1.02 vs. 2.26 ± 1.09, p = 0.043). For patients with oxycodone, NRS was higher in PD‐L1 (+) than in PD‐L1 (−) (p = 0.041) at cough after surgery. In contrast, those with sufentanil did not significantly differ in NRS between groups.

Conclusions

Patients with PD‐L1 (+) suffered graver pain in the early postoperative period after VATS for lung cancer compared with PD‐L1 (−) on tumours. Analgesia with sufentanil seemed to overcome this effect better than oxycodone.

Significance

We demonstrated that patients with positive programmed cell death ligand‐1 (PD‐L1) on tumours suffered graver pain in the early postoperative period after video‐assisted thoracoscopic surgery for lung cancer and reacted differently with opioids. It might be beneficial to adjust analgesic protocols according to tumour PD‐L1 expression for individualized postoperative pain management.