bluuebunny/crossref_metadata_2025 huggingface dataset:
Cutaneous B‐cell lymphomas: 2023 update on diagnosis, risk‐stratification, and management
Authors: Hristov Alexandra C. , Tejasvi Trilokraj , Wilcox Ryan A.
Published: May 2023

Disease Overview

Approximately one‐fourth of primary cutaneous lymphomas are B‐cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL, LT).

Diagnosis

Diagnosis and disease classification is based on histopathologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B‐cell lymphomas from systemic B‐cell lymphomas with secondary skin involvement.

Risk‐Stratification

Disease histopathology remains the most important prognostic determinant in primary cutaneous B‐cell lymphomas. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with 5‐year survival rates that exceed 95%. In contrast, PCDLBCL, LT is an aggressive lymphoma with an inferior prognosis.

Risk‐Adapted Therapy

PCFCL and PCMZL patients with solitary or relatively few skin lesions may be effectively managed with local radiation therapy. While single‐agent rituximab may be employed for patients with more widespread skin involvement, multiagent chemotherapy is rarely appropriate. In contrast, management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL.
Distribution of cardiorespiratory fitness in children and adolescents at different latitudes
Authors: Yang Xiaofang , Yin Xiaojian , Huang Wenying , Duan Zhongyang , Wu Huipan , Li Yuqiang , Li Ming , Zhang Ting , Zhou Caiyou , Xu Haihong
Published: May 2023

Objective

To explore the differences and characteristics of cardiorespiratory fitness (CRF) among children and adolescents in regions with different latitudes in China.

Methods

A total of 9892 children and adolescents aged 7–22 years were selected from seven administrative regions in China by the stratified cluster random sampling method. CRF was measured by performance on the 20 m shuttle run test (20mSRT) and estimated maximal oxygen consumption (VO2max). One‐way ANOVA, one‐way ANCOVA, and the Lambda Mu and Sigma methods were used to analyze the data.

Results

Overall, the VO2max of children and adolescents at high latitudes was significantly lower than that of children at low and middle latitudes. The P10, P50, and P90 20mSRT values for children and adolescents of most age groups in high latitudes were less than those in low and middle latitudes. The 20mSRT‐Z and VO2max‐Z scores among children and adolescents aged 7–22 in high latitudes were lower than those in middle and low latitudes after adjusting for age, per capita gross domestic product (GDP), and per capita disposable income.

Conclusion

In general, the CRF of children and adolescents at high latitudes was less than that at low and middle latitudes. Effective measures should be taken to improve CRF in children and adolescents at high latitudes.
The news about rollover protective structures: Findings from an analysis of news from Iowa, Nebraska, Kansas, and Missouri
Authors: Perez‐Sanz Sarah B. , Garcia Kim , Mejia Pamela , Dorfman Lori , Echard Jessica , Sorensen Julie A. , Milkovich Pamela J.
Published: May 2023

Introduction

Rollover protective structures (ROPS) can prevent fatal tractor overturns, a leading cause of death among farmers. This content analysis aims to understand how this life‐saving strategy appears in news about farm safety.

Methods

As part of a larger study of farm safety news coverage from four agricultural states, we conducted a content analysis of articles that mentioned ROPS.

Results

Few (10%) articles about farm safety explicitly mentioned ROPS. When ROPS were mentioned, they were described in terms of their potential to save lives or prevent injury.

Conclusion

Despite proven success, ROPS—and programs to make ROPS more widely available to farmers—are all but absent from news coverage in key agricultural states. This represents a missed opportunity not only to motivate farmers to install ROPS, but also to demonstrate to policymakers the importance of establishing and maintaining funding to prevent the most frequent cause of death on farms. Farmers face barriers to installing life‐saving equipment. Without an increase in ROPS utilization and improved access to prevention programs, farmers, especially low‐income farmers, will remain at disproportionate risk for death and injury.
Rod‐cone dystrophy in an adult with GNB1‐related disorder: An expansion of the phenotype and natural history
Authors: Yang Xiao‐Ru , Kassam Faazil , Innes A. Micheil
Published: May 2023

GNB1‐related disorder is characterized by intellectual disability, abnormal tone, and other variable neurologic and systemic features. GNB1 encodes the β1 subunit of the heterotrimeric G‐protein, a complex with a key role in signal transduction. Consistent with its particularly high expression in rod photoreceptors, Gβ1 forms a subunit of retinal transducin (Gαtβ1γ1), which mediates phototransduction. In mice, GNB1 haploinsufficiency has been associated with retinal dystrophy. In humans, however, although vision and eye movement abnormalities are common in individuals with GNB1‐related disorder, rod‐cone dystrophy is not yet an established feature of this condition. We expand the phenotype of GNB1‐related disorder with the first confirmed report of rod‐cone dystrophy in an affected individual, and contribute to a further understanding of the natural history of this condition in a mildly affected 45‐year‐old adult.
Maternal adverse childhood experiences, child mental health, and the mediating effect of maternal depression: A cross‐sectional, population‐based study in rural, southwestern Uganda
Authors: Kim Andrew Wooyoung , Rieder Amber D. , Cooper‐Vince Christine E. , Kakuhikire Bernard , Baguma Charles , Satinsky Emily N. , Perkins Jessica M. , Kiconco Allen , Namara Elizabeth B. , Rasmussen Justin D. , Ashaba Scholastic , Bangsberg David R. , Tsai Alexander C. , Puffer Eve S.
Published: May 2023

Objectives

This study aimed to examine the intergenerational effects of maternal adverse childhood experiences (ACEs) and child mental health outcomes in rural Uganda, as well as the potentially mediating role of maternal depression in this pathway. Additionally, we sought to test the extent to which maternal social group membership attenuated the mediating effect of maternal depression on child mental health.

Methods

Data come from a population‐based cohort of families living in the Nyakabare Parish, a rural district in southwestern Uganda. Between 2016 and 2018, mothers completed surveys about childhood adversity, depressive symptoms, social group membership, and their children's mental health. Survey data were analyzed using causal mediation and moderated‐mediation analysis.

Results

Among 218 mother–child pairs, 61 mothers (28%) and 47 children (22%) showed symptoms meeting cutoffs for clinically significant psychological distress. In multivariable linear regression models, maternal ACEs had a statistically significant association with severity of child conduct problems, peer problems, and total child difficulty scores. Maternal depression mediated the relationship between maternal ACEs and conduct problems, peer problems, and total difficulty, but this mediating effect was not moderated by maternal group membership.

Conclusions

Maternal depression may act as a potential mechanism linking maternal childhood adversity with poor child mental health in the next generation. Within a context of elevated rates of psychiatric morbidity, high prevalence of childhood adversity, and limited healthcare and economic infrastructures across Uganda, these results emphasize the prioritization of social services and mental health resources for rural Ugandan families.
Leveraging African American family connectors for Alzheimer's disease genomic studies
Authors: Byfield Grace , Starks Takiyah D. , Luther Ronqeiya , Edwards Christopher L. , Lloyd Shawnta L. , Caban‐Holt Allison , Adams Larry Deon , Vance Jeffery M. , Cuccaro Michael , Haines Jonathan L. , Reitz Christiane , Pericak‐Vance Margaret A. , Byrd Goldie S.
Published: May 2023

INTRODUCTION

The underrepresentation of African Americans (AAs) in Alzheimer's disease (AD) research may limit potential benefits from translational applications. This article describes an approach to recruit AA families into an AD genomic study and characteristics of seeds (family connectors) used to overcome recruitment barriers of AA families into AD research.

METHODS

A four‐step outreach and snowball sampling approach relying on family connectors was used to recruit AA families. Descriptive statistics of a profile survey were gathered to understand the demographic and health characteristics of family connectors.

RESULTS

Twenty‐five AA families (117 participants) were enrolled in the study via family connectors. Most family connectors self‐identified as female (88%), were 60 years of age or older (76%), and attained post‐secondary education (77%).

DISCUSSION

Community‐engaged strategies were essential to recruit AA families. Relationships between study coordinators and family connectors build trust early in the research process among AA families.

Highlights

Community events were most effective for recruiting African American families.

Family connectors were primarily female, in good health, and highly educated.

Systematic efforts by researchers are necessary to “sell” a study to participants.
Asymmetric Total Synthesis of Cytotrienin A: Late‐Stage Installation of C11 Side Chain onto the Macrolactam Scaffold
Authors: Tateishi Yuki , Sato Ryo , Komatsu Shingo , Noguchi Masatsugu , Nagasawa Shota , Sasano Yusuke , Kanoh Naoki , Iwabuchi Yoshiharu
Published: May 2023

Cytotrienin A, an ansamycin‐class antibiotic, exhibits potent apoptosis‐inducing activity and has attracted much attention as a lead compound for anticancer drugs. Herein, we report a new asymmetric synthetic route to cytotrienin A, employing an unexplored approach involving the late‐stage installation of a C11 side chain onto the macrolactam core. In this strategy, we utilized the redox properties of hydroquinone and installed a side chain on the sterically hindered C11 hydroxy group by the traceless Staudinger reaction. This study also demonstrated that the boron‐Wittig/iterative Suzuki–Miyaura cross‐coupling sequence was effective for the concise and selective construction of the (E,E,E)‐conjugated triene moiety. The developed route opens new opportunities for the structure–activity relationship studies of the side chains of these ansamycin antibiotics and the preparation of other synthetic analogs and chemical probes for further biological studies.
Disc‐Like Silver Nanocluster Ag93 Built with Bicapped Hexagonal Prismatic Ag15 and Ino Decahedral Ag13 Units
Authors: Hu Feng , He Rui‐Lin , Guan Zong‐Jie , Liu Chun‐Yu , Wang Quan‐Ming
Published: May 2023

The reduction of alkynyl‐silver and phosphine‐silver precursors with a weak reducing reagent Ph2SiH2 led to the formation of a novel silver nanocluster [Ag93(PPh3)6(C≡CR)50]3+ (R=4‐CH3OC6H4), which is the largest structurally characterized cluster of clusters. This disc‐shaped cluster has a Ag69 kernel consisting of a bicapped hexagonal prismatic Ag15 unit wrapped by six Ino decahedra through edge‐sharing. This is the first time that Ino decahedra are used as a building block to assemble a cluster of clusters. Moreover, the central silver atom has a coordination number of 14, which is the highest in metal nanoclusters. This work provides a diverse metal packing pattern in metal nanoclusters, which is helpful for understanding metal cluster assembling mechanisms.
Photochemical Deracemization of 3‐Substituted Oxindoles
Authors: Großkopf Johannes , Heidecker Alexandra A. , Bach Thorsten
Published: May 2023

Racemic 3‐substituted oxindoles were successfully converted into enantiomerically pure or enriched material (up to 99 % ee) upon irradiation at λ=366 nm in the presence of a chiral benzophenone catalyst (10 mol %). The photochemical deracemization process allows predictable editing of the stereogenic center at carbon atom C3. Light energy compensates for the associated loss of entropy and enables the decoupling of potentially reversible reactions, i.e. a hydrogen atom transfer to (photochemical) and from (thermal) the carbonyl group of the catalyst. The major enantiomer is continuously enriched in several catalytic cycles. The obtained oxindoles were shown to be valuable intermediates for further transformations, which proceeded with complete retention at the stereogenic center.
Modular Oxime Formation by a trans‐AT Polyketide Synthase
Authors: Minas Hannah A. , François Romain M. M. , Hemmerling Franziska , Fraley Amy E. , Dieterich Cora L. , Rüdisser Simon H. , Meoded Roy A. , Collin Sabrina , Weissman Kira J. , Gruez Arnaud , Piel Jörn
Published: May 2023

Modular trans‐acyltransferase polyketide synthases (trans‐AT PKSs) are enzymatic assembly lines that biosynthesize complex polyketide natural products. Relative to their better studied cis‐AT counterparts, the trans‐AT PKSs introduce remarkable chemical diversity into their polyketide products. A notable example is the lobatamide A PKS, which incorporates a methylated oxime. Here we demonstrate biochemically that this functionality is installed on‐line by an unusual oxygenase‐containing bimodule. Furthermore, analysis of the oxygenase crystal structure coupled with site‐directed mutagenesis allows us to propose a model for catalysis, as well as identifying key protein‐protein interactions that support this chemistry. Overall, our work adds oxime‐forming machinery to the biomolecular toolbox available for trans‐AT PKS engineering, opening the way to introducing such masked aldehyde functionalities into diverse polyketides.
Alkali Chloride Adducts of Acyclic Acylaluminum: Synthesis, Structure, and Reactivity Studies
Authors: Feng Genfeng , Yamashita Makoto
Published: May 2023

Two acyclic acylaluminums and one cyclic acylaluminum dimer were synthesized by reaction of the recently reported Al‐anion with acyl chloride. The reaction of the acylaluminums with TMSOTf and DMAP gave a ring‐expanded iminium‐substituted aluminate and a 2‐C−H cleaved product. In the reaction of acylaluminums toward C=O and C=N bonds, acyclic acylaluminums reacted as an acyl nucleophile, while the cycilc dimer showed no reactivity. Amide‐bond forming ligation using acyclic acylaluminums and hydroxylamines was further demonstrated. Throughout the study, acyclic acylaluminums exhibited higher reactivity than that of the cyclic dimer.
Phase‐Engineered Robust Cocatalyst of NiFe Bicarbonate with Pt Dopant for Enhanced Photocatalytic Water Splitting
Authors: Shao Mengmeng , Fu Shushu , Cao Yongyong , Hao Shiji , Dang Haifeng , Chen Min , Jin Jutao , Wang Wenlong , Wang Jiaxing , Zuo Lina , Zhang Dexing , Wang Xiaoji
Published: May 2023

Exploring efficient cocatalysts capable of accelerating surface catalytic reaction is of great significance for the development of solar‐driven hydrogen production. Herein, on the basis of NiFe hydroxide, we developed a series of Pt doped NiFe‐based cocatalysts to promote the photocatalytic hydrogen production of graphitic carbon nitride (g‐C3N4). We find that the Pt doping can trigger phase reconstruction of NiFe hydroxide and lead to the formation of NiFe bicarbonate, which displays higher catalytic activity toward hydrogen evolution reaction (HER). The Pt doped NiFe bicarbonate modified g‐C3N4 shows excellent photocatalytic activity with H2 evolution rate up to 100 μmol/h, which is more than 300 times that of pristine g‐C3N4. The experimental and calculation results demonstrate that the greatly improved photocatalytic HER activity of g‐C3N4 is not only due to the efficient carrier separation, but also attributed to the accelerated HER kinetics. Our work may provide guidance for designing novel and superior photocatalysts.
Autism severity level affects working memory and planning but not inhibition, shifting and emotional control
Authors: Memisevic Haris , Pasalic Arnela , Saletovic Amra
Published: May 2023

Autistic children often have difficulties in executive functions (EF). These difficulties can, in turn, affect their everyday functioning. It is less clear in what way EF are affected by the severity of autism symptoms in children. We hypothesize that autism severity level does not have the same effect across the different components of EF. In this study, we examined how EF are affected by the autism severity level in a sample of 52 autistic children aged 4–7 years (mean age‐ 5.4 years, SD‐ 0.9 years). EF were measured through teachers' reports on the Behavior Rating Inventory of Executive Functions‐ Preschool Version. Autism severity level was measured with the Social Communication Questionnaire‐ Current Form. The results of this study showed that autism severity level impacted two EF, namely Planning and Working memory, and did not affect three EF components: Inhibition, Shifting, and Emotional Control. These results indicate that the cool or cognitive EF are more affected by autism severity level than hot EF. We conclude the article with suggestions for improving EF in autistic children.
Characteristics and clinical outcomes in young‐onset cholangiocarcinoma
Authors: Reddy Sarah , Goksu Suleyman Yasin , Sanford Nina N. , Kainthla Radhika , Hsiehchen David , Sanjeevaiah Aravind , Jones Amy L. , Karagkounis Georgios , Al Mutar Salwan , Ahn Chul , Beg Muhammad S. , Kazmi Syed M.
Published: May 2023

Background

While the incidence of cholangiocarcinoma is rising, little is known about young‐onset disease. We compared clinical characteristics and outcomes between patients with young‐onset cholangiocarcinoma, diagnosed between the ages of 18 and <50 years, and patients with typical‐onset cholangiocarcinoma, diagnosed at age 50 years or greater.

Methods

We used the National Cancer Database to identify patients with young‐onset cholangiocarcinoma (n = 2520) and typical‐onset cholangiocarcinoma (n = 23,826). We compared the frequency of demographic and clinical characteristics between the two groups. We compared overall survival between the two groups using multivariable Cox regression analysis after adjusting for age, gender, race/ethnicity, comorbidity, facility type, tumor location, tumor stage, surgical status, and receipt of radiotherapy, chemotherapy and surgery.

Results

When compared to patients with typical‐onset disease (median age 68 years), patients with young‐onset cholangiocarcinoma (median age 44 years) were more likely to be non‐White (35.0% vs. 27.4%, p < 0.01), and had lower overall comorbidity burden. Patients with young‐onset disease had a greater proportion of intrahepatic cholangiocarcinoma (56.0% vs. 45.5%, p < 0.001) and stage IV disease (50.5% vs. 43.5%, p < 0.001). Younger patients were more likely than typical‐onset patients to receive definitive surgery (30.9% vs. 25.0%, p < 0.001), radiation (27.7% vs. 19.6%, p < 0.001) and chemotherapy (73.1% vs. 50.1%, p < 0.001). In adjusted analyses, patients with young‐onset disease had a 15% decreased risk of death, compared with patients with typical‐onset disease (HR 0.85 [95% CI 0.80–0.89], p < 0.001).

Conclusions

Patients with young‐onset cholangiocarcinoma may represent a demographically and clinically distinct group from those with more typical‐onset disease.
Plasma cell myeloma with RAS/BRAF mutations is frequently associated with a complex karyotype, advanced stage disease, and poorer prognosis
Authors: Li Nianyi , Lin Pei , Zuo Zhuang , You M. James , Shuai Wen , Orlowski Robert , Manasanch Elisabet E. , Li Shaoying , Xu Jie , Garces Sofia , Jelloul Fatima Zahra , Tang Zhenya , Wang Wei , Medeiros L. Jeffrey , Yin C. Cameron
Published: May 2023

BACKGROUND

Mutations in the RAS‐MAPK pathway, such as KRAS, NRAS, and BRAF, are known as high‐risk factors associated with poor prognosis in patients with various cancers, but studies in myeloma have yielded mixed results.

METHODS

We describe the clinicopathologic, cytogenetic, molecular features, and outcomes of 68 patients with RAS/BRAF‐mutated myeloma, and compare with 79 patients without any mutations.

RESULTS

We show that KRAS, NRAS, and BRAF were mutated in 16%, 11%, and 5% of cases, respectively. RAS/BRAF‐mutated patients had lower hemoglobin and platelet counts, higher levels of serum lactate dehydrogenase and calcium, higher percentage of bone marrow plasma cells, and more advanced R‐ISS stage. RAS/BRAF mutations were associated with complex karyotype and gain/amplification of CKS1B. The median overall survival and progression‐free survival were significantly shorter for RAS/BRAF‐mutated patients (69.0 vs. 220.7 months, p = 0.0023 and 46.0 vs. 60.6 months, p = 0.0311, respectively). Univariate analysis revealed that KRAS mutation, NRAS mutation, lower hemoglobin, elevated lactate dehydrogenase, higher R‐ISS stage, complex karyotype, gain/amplification of CKS1B, monosomy 13/RB1 deletion and lack of autologous stem cell transplantation were associated with poorer prognosis. Multivariate analysis showed that KRAS mutation, lower hemoglobin level, higher level of serum calcium, higher ISS stage, and lack of autologous stem cell transplantation predict inferior outcome.

CONCLUSIONS

RAS/BRAF mutations occur in 30%–40% of myeloma cases and are associated with higher tumor burden, higher R‐ISS stage, complex karyotype, and shorter overall survival and progression‐free survival. These findings support testing for RAS/BRAF mutations in myeloma patients and underscore the potential therapeutic benefits of RAS/BRAF inhibitors.
Who, where, when: Colorectal cancer disparities by race and ethnicity, subsite, and stage
Authors: Primm Kristin M. , Malabay Andrea Joyce , Curry Taylor , Chang Shine
Published: May 2023

Background

There are well‐established disparities in colorectal cancer (CRC) outcomes between White and Black patients; however, assessments of CRC disparities for other racial/ethnic groups are limited.

Methods

The Surveillance, Epidemiology, and End Results database identified patients aged 50–74 years with CRC adenocarcinoma from 2000 to 2019. Trends in age‐adjusted incidence rates were computed by stage at diagnosis and subsite across five broad race/ethnic groups (White, Black, Asian/Pacific Islander [API], American Indian/Alaskan Native [AIAN], and Hispanic) and four API subgroups (East Asian, Southeast Asian, South Asian, and Pacific Islander) Multivariable logistic regression evaluated associations between race/ethnicity and diagnosis stage. Multivariable Cox proportional hazards models assessed differences in cause‐specific survival (CSS).

Results

Hispanic, AIAN, Southeast Asian, Pacific Islander, and Black patients were 3% to 28% more likely than Whites to be diagnosed with distant stage CRC, whereas East Asian and South Asians had similar or lower risk of distant stage CRC. From Cox regression analysis, Black, AIAN, and Pacific Islanders also experienced worse CSS, while East Asian and South Asian patient groups experienced better CSS. No significant differences in CSS were observed among Hispanic, Southeast Asian, and White patients. When stratified by stage, Black patients had worse CSS across all stages (early, hazard ratio (HR) = 1.38; regional, HR = 1.22; distant, HR: 1.07, p < 0.05 for all).

Conclusion

Despite advances in CRC screening, treatment and early detection efforts, marked racial/ethnic disparities in incidence, stage at diagnosis, and survival persist. Findings demonstrate the extent to which aggregating heterogenous populations masks significant variability in CRC outcomes within race/ethnic subgroups.
MiR‐503 pleiotropically regulates epithelial‐mesenchymal transition and targets PTK7 to control lung cancer metastasis
Authors: Tsai Tzu‐Hsiu , Gow Chien‐Hung , Liu Yi‐Nan , Tsai Meng‐Feng , Chang Tzu‐Hua , Wu Shang‐Gin , Hsieh Min‐Shu , Su Kang‐Yi , Shih Jin‐Yuan
Published: May 2023

Objective

In lung cancer patients, most deaths are caused by the distant dissemination of cancer cells. Epithelial–mesenchymal transition (EMT) and collective cell migration are distinct and important mechanisms involved in cancer invasion and metastasis. Additionally, microRNA dysregulation contributes significantly to cancer progression. In this study, we aimed to explore the function of miR‐503 in cancer metastasis.

Methods

Molecular manipulations (silencing or overexpression) were performed to investigate the biological functions of miR‐503 including migration and invasion. Reorganization of cytoskeleton was assessed using immunofluorescence and the relationship between miR‐503 and downstream protein tyrosine kinase 7 (PTK7) was assessed using quantitative real‐time PCR, immunoblotting, and reporter assays. The tail vein metastatic animal experiments were performed.

Results

Herein, we demonstrated that the downregulation of miR‐503 confers an invasive phenotype in lung cancer cells and provided in vivo evidence that miR‐503 significantly inhibits metastasis. We found that miR‐503 inversely regulates EMT, identified PTK7 as a novel miR‐503 target, and showed the functional effects of miR‐503 on cell migration and invasion were restored upon reconstitution of PTK7 expression. As PTK7 is a Wnt/planar cell polarity protein crucial for collective cell movement, these results implicated miR‐503 in both EMT and collective migration. However, the expression of PTK7 did not influence EMT induction, suggesting that miR‐503 regulates EMT through mechanisms other than PTK7 inhibition. Furthermore, we discovered that PTK7 mechanistically activates focal adhesion kinase (FAK) and paxillin, thereby controlling the reorganization of the cortical actin cytoskeleton.

Conclusion

Collectively, miR‐503 is capable of governing EMT and PTK7/FAK signaling independently to control the invasion and dissemination of lung cancer cells, indicating that miR‐503 represents a pleiotropic regulator of cancer metastasis and hence a potential therapeutic target for lung cancer.
Clinical outcomes after CPX‐351 in patients with high‐risk acute myeloid leukemia: A comparison with a matched cohort from the Spanish PETHEMA registry
Authors: Bernal Teresa , Moreno Ainhoa Fernández , de LaIglesia Almudena , Benavente Celina , García‐Noblejas Ana , Belmonte Daniel García , Riaza Rosalía , Salamero Olga , Foncillas Maria Angeles , Roldán Alicia , Concepción Víctor Noriega , González Laura Llorente , Bergua Burgués Juan Miguel , Lorente de Uña Soraya , Rodríguez‐Macías Gabriela , de la Fuente Burguera Adolfo , García Pérez Maria José , López‐Lorenzo Jose Luis , Martínez Pilar , Aláez Concepción , Callejas Marta , Martínez‐Chamorro Carmen , Roca José Rifón , Barciela Lourdes Amador , Mena Durán Armando V. , Gómez Correcha Karoll , Lavilla Rubira Esperanza , Amigo María Luz , Vall‐llovera Ferran , Garrido Ana , García‐Fortes María , de Miguel Llorente Dunia , Leonardo Anastasia Aules , Cervero Carlos , Jordá Rosa Coll , Pérez‐Encinas Manuel M. , Zarzuela Marta Polo , Figuera Angela , Rad Guillermo , Martínez‐Cuadrón David , Montesinos Pau
Published: May 2023

Background

CPX‐351 is approved for the treatment of therapy related acute myeloid leukemia (t‐AML) and AML with myelodysplastic related changes (MRC‐AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched cohorts of real‐life patients.

Methods

Retrospective analysis of AML patients treated with CPX‐351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry.

Results

Median age of 79 patients treated with CPX‐351 was 67 years old (interquartile range 62–71), 53 were MRC‐AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX‐351 was 52%, 60‐days mortality 18%, measurable residual disease <0.1% in 54% (12 out of 22) of them. Stem cell transplant (SCT) was performed in 27 patients (34%), median OS was 10.3 months, and 3‐year relapse incidence was 50%. Using PSM, we obtained two comparable cohorts treated with CPX‐351 (n = 52) or IC (n = 99), without significant differences in CR/CRi (60% vs. 54%) and median OS (10.3 months vs. 9.1 months), although more patients were bridged to SCT in the CPX‐351 group (35% vs. 12%). The results were confirmed when only 3 + 7 patients were included in the historical cohort. In multivariable analyses, SCT was associated with better OS (HR 0.33 95% CI: 0.18–0.59), p < 0.001.

Conclusion

Larger post‐authorization studies may provide evidence of the clinical benefits of CPX‐351 for AML in the real‐life setting.
Orbitals‐Driven Insights on the Reactivity of Boron Oxide with Dioxygen for Methane Oxidation on Singlet and Triplet Spin States
Authors: Rawal Parveen , Gupta Puneet
Published: May 2023

Boron‐based compounds such as frustrated Lewis pairs and borylenes that mimic transition‐metal(TM)‐like reactivity have attracted significant interest in recent years. This work examines the reactivity of boron oxide (B2O3) towards dioxygen for methane activation. Density functional theory in combination with orbital analysis were utilized to derive mechanistic pathways for methane‐to‐formaldehyde conversion over B2O3 in presence of closed‐shell singlet and triplet O2. Multiple pathways were screened on the triplet spin state. Best route via the triplet spin state depicts the interaction of B2O3 with dioxygen (O1=O2) and CH4 at a barrier of 49.8 kcal mol−1, to produce an intermediate having a B−O1−O2H unit and a free CH3 radical, which later react together at a barrier of 57.6 kcal mol−1, to finally yield HCHO. In the singlet spin state, a free CH3 radical does not form instead an intermediate with a B−O1−O2−CH3 unit is found after crossing a barrier of 41.1 kcal mol−1, which further undergoes via a relatively lower barrier of 23.4 kcal mol−1 to yield HCHO. Thus, the singlet pathway is energetically preferred over the triplet one. Orbitals further capture that at singlet and triplet states, methane activation follows a hydride and a hydrogen‐atom‐transfer mechanism, respectively.
Considerations for the Scale‐up of in vitro Transaminase‐Catalyzed Asymmetric Synthesis of Chiral Amines
Authors: Madsen Julie Østerby , Woodley John M.
Published: May 2023

In vitro transaminase catalyzed asymmetric synthesis is not a new phenomenon in the biocatalytic toolbox. Our group published a review on process consideration for these reactions in 2011, in which process metrics and the unfavorable reaction equilibrium was deduced to be the main bottlenecks at the time. Now, a decade later, this has been solved by different process methods presented in this review, with the development of enzymatic cascades one of the main solutions. Today, the new bottleneck is the downstream processing, due to the complexity of transaminase reactions, in which a ketone and an amine as substrates and a new ketone and a new amine as products. How to recover the produced amine from the resulting product mixture is considered and will be the key challenge for scale‐up of such systems in the near future.
Effect of Polymeric Ligand Grafting Region on Confined Assembly of Gold Nanorods in cylindrical nanopores
Authors: Li Fan , Gong Xianxian , Ren Rui , Xiong Bijin , Zhu Jintao
Published: May 2023

The grafting region of polymeric ligands exhibit a significant influence on the assembly behavior of polymer tethered gold nanorods (AuNRs) in confined space. In this work, the effect of core size, molecular weight and grafting region of ligands on the assembly structure in cylindrical nanopores was investigated. It is found that polystyrene end‐tethered AuNR (AuNR@End−PS) exhibits a dumbbell‐like shape, while the AuNR with PS tethered on the entire surface (AuNR@Full−PS) shows a rod‐like morphology that gradually transforms into a spherical shape as the molecular weight increases. AuNR@End−PS is affected by the special steric hindrance at both ends, and prefers to form special structures such as inclination arrangement, whereas AuNR@Full−PS prefers to be arranged shoulder‐to‐shoulder in a chain‐like assembly. The confinement effect was studied as well by varying the diameter of pores. The results show that the nanoparticles prefer to arrange into a regular and ordered assembly structure in the strong confinement spaces. Under the synergy of confined spaces and ligands at both ends, the AuNRs@End−PS are more likely to form a tilted order‐assembly structure. The results of this work could provide new ideas and guidance for the preparation of ordered assembly of AuNRs with novel structures.
The Best of Both Worlds: Combining the Power of MICs and WCAs To Generate Stable and Crystalline CrI‐Tetracarbonyl Complexes with π‐Accepting Ligands
Authors: Bens Tobias , Walter Robert R. M. , Beerhues Julia , Schmitt Manuel , Krossing Ingo , Sarkar Biprajit
Published: May 2023

Here we present stable and crystalline chromium(I) tetracarbonyl complexes with pyridyl‐MIC (MIC=mesoionic carbene) ligands and weakly coordinating anions (WCA=[Al(ORF)4]−, RF=C(CF3)3 and BArF=[B(ArF)4]−, ArF=3,5‐(CF3)2C6H3). The complexes were fully characterized via crystallographic, spectroscopic and theoretical methods. The influence of counter anions on the IR and EPR spectroscopic properties of the CrI complexes was investigated, and the electronic innocence versus non‐innocence of WCAs was probed. These are the first examples of stable and crystalline [Cr(CO)4]+ complexes with a chelating
accepting ligand, and the data presented here are of relevance for both the photochemical and the electrochemical properties of these classes of compounds.
Sulfur Dioxide Oxidation by Zinc and Zinc Oxide Nitrate/Nitrite Complexes in the Gas Phase: An Interplay between Redox‐Active Ligands and Metal
Authors: Salvitti Chiara , Bandeira Nuno A. G. , Pepi Federico , de Petris Giulia , Troiani Anna
Published: May 2023

Different oxidative pathways of sulfur dioxide promoted by ZnO(NO3)2−, Zn(NO3)2−and Zn(NO2)(NO3)−are revealed by a joint investigation by mass spectrometry and theoretical calculations. The reactions are triggered by [Zn2+‐O−⋅]+or by the low‐valence Zn+through oxygen ion transfer or electron transfer to SO2, respectively. The NOx−ligands intervene in the oxidation only when sulfur dioxide is converted to SO3−or SO2−, leading to the formation of zinc sulfate and zinc sulfite coordinated to nitrate or nitrite anions. Kinetic analyses show that the reactions are fast and efficient, and theory discloses the elementary steps, namely oxygen ion transfer, oxygen atom transfer and electron transfer, occurring through similar energy landscapes for the three reactive anions.
Advances to Stabilize Photoactive Phase of FAPbI3 Perovskite†
Authors: Li Kailin , Zhou Huanping
Published: May 2023

Comprehensive Summary

Recently, hybrid organic–inorganic perovskite materials have drawn widespread attention because of their outstanding optoelectrical properties (i.e., high absorption coefficient, long carrier diffusion distance), hence they are suitable light‐absorbing materials for photovoltaic application. Among all perovskite materials, formamidinium lead iodide (FAPbI3) based solar cells exhibit impressive power conversion efficiency (PCE) at laboratory stage, showing great potential to compete with silicon‐based solar cell. However, FAPbI3 still suffers from poor phase stability which is the prior problem that needs to be addressed before its further commercialization. To be precise, the photoactive phase (α phase) is thermodynamically metastable at room temperature, which not only makes α phase tend to transform into photoinactive phase (δ phase), but also causes competitive crystallization between two phases during the film preparation process, making it hard to fabricate pure α‐FAPbI3 films. In our review, we summarized key factors that are vital for obtaining high‐quality FAPbI3 perovskite thin films and enhancing the stability of FAPbI3 photoactive phase. First of all, precursor solution stability is of great importance since the conditions of precursor solution determine the nucleation and crystal growth process of perovskite. By introducing coordinating additives, using FAPbI3 single crystal as raw material or applying co‐solution strategy, the impurities formed by side reaction during precursor solution aging can be effectively suppressed, thus the stability of FAPbI3 solution can be greatly prolonged. Second, the crystallization kinetics of FAPbI3 have been systematically manipulated to obtain dense and large grain size perovskite films. Through introducing intermediate phase, regulating the surface energy, and retarding the crystal growth of FAPbI3 in crystallization process, not only films without pinholes and fewer grain boundaries can be obtained, the pre‐formed δ phase at room temperature can also be well‐suppressed, thus high‐quality α‐FAPbI3 films can be obtained. Third, how to thermodynamically enhance the phase stability of acquired FAPbI3 film has been extensively studied. The Gibbs free energy of FAPbI3 photoactive phase can be reduced through composition engineering, dimension engineering and external additives engineering, hence the phase transition barrier from α phase to δ phase has been significantly improved, which further enhance the phase stability of α‐FAPbI3. Lastly, we pointed out challenges of each method and proposed potential applications of mentioned strategies on improving the stability of all kinds of perovskite materials, thus further boost the commercialization of perovskite solar cell devices.
Tobacco use and cancer‐related symptom burden: Analysis of the US Population Assessment of Tobacco and Health Study
Authors: Price Sarah N. , Palmer Amanda M. , Fucito Lisa M. , Graboyes Evan M. , Baker Nathaniel L. , Rojewski Alana M. , Toll Benjamin A.
Published: May 2023

Background

Understanding the relationship between tobacco use and symptom burden may inform tobacco treatment interventions tailored to the needs of individuals with cancer.

Methods

The study included 1409 adult cancer survivors from Wave 5 of the US Food and Drug Administration Population Assessment of Tobacco and Health (PATH) Study. A multivariate analysis of variance controlling for age, sex, and race/ethnicity assessed the association of cigarette smoking and vaping on cancer‐related symptom burden (fatigue, pain, emotional problems) and quality of life (QoL). Generalized linear mixed models controlling for the same factors were used to assess associations among symptom burden, QoL, and quit‐smoking intentions, quit‐smoking likelihood, and past 12‐month smoking quit attempts.

Results

Weighted rates of current cigarette smoking and vaping were 14.21% and 2.88%, respectively. Current smoking was associated with greater fatigue (p < .0001; partial η

2
 = .02), pain (p < .0001; partial η

2
 = .08), emotional problems (p < .0001; partial η

2
 = .02), and worse QoL (p < .0001; partial η

2
 = .08). Current vaping was associated with greater fatigue (p = .001; partial η

2
 = .008), pain (p = .009; partial η

2
 = .005), and emotional problems (p = .04; partial η

2
 = .003), but not worse QoL (p = .17). Higher cancer symptom burden was not associated with reduced interest in quitting, likelihood of quitting, or odds of past year quit attempts (p > .05 for each).

Conclusions

Among adults with cancer, current smoking and vaping were associated with greater symptom burden. Survivors' interest in and intentions to quit smoking were not related to symptom burden. Future research should examine the role of tobacco cessation in improving symptom burden and QoL.
Localization of relaxin‐like gonad‐stimulating peptide expression in starfish reveals the gonoducts as a source for its role as a regulator of spawning
Authors: Feng Yuling , Piñon Gonzalez Victor M. , Lin Ming , Egertová Michaela , Mita Masatoshi , Elphick Maurice R.
Published: May 2023

Oocyte maturation and gamete release (spawning) in starfish are triggered by relaxin‐like gonad‐stimulating peptide (RGP), a neuropeptide that was first isolated from the radial nerve cords of these animals. Hitherto, it has generally been assumed that the radial nerve cords are the source of RGP that triggers spawning physiologically. To investigate other sources of RGP, here we report the first comprehensive anatomical analysis of its expression, using both in situ hybridization and immunohistochemistry to map RGP precursor transcripts and RGP, respectively, in the starfish Asterias rubens. Cells expressing RGP precursor transcripts were revealed in the ectoneural epithelium of the radial nerve cords and circumoral nerve ring, arm tips, tube feet, cardiac stomach, pyloric stomach, and, most notably, gonoducts. Using specific antibodies to A. rubens RGP, immunostaining was revealed in cells and/or fibers in the ectoneural region of the radial nerve cords and circumoral nerve ring, tube feet, terminal tentacle and other arm tip‐associated structures, body wall, peristomial membrane, esophagus, cardiac stomach, pyloric stomach, pyloric caeca, and gonoducts. Our discovery that RGP is expressed in the gonoducts of A. rubens proximal to its gonadotropic site of action in the gonads is important because it provides a new perspective on how RGP may act as a gonadotropin in starfish. Thus, we hypothesize that it is the release of RGP from the gonoducts that triggers gamete maturation and spawning in starfish, while RGP produced in other parts of the body may regulate other physiological/behavioral processes.
Glucose‐hexamethylenetetramine‐derived Co, N Co‐doped Carbon Nanoflowers with Encapsulated Co@Co3O4 as Efficient Bifunctional Oxygen Electrocatalyst for Zinc‐air Batteries
Authors: Zhang Xiangtai , Hu Shuozhen , Zhang Mingyuan , Zhang Xinsheng
Published: May 2023

Developing low‐cost, eco‐friendly, and efficient bifunctional electrocatalysts for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is an important issue for zinc‐air batteries. In this study, HMT‐Co/G‐700 catalyst with nanoflower structure and Co, N co‐doped carbon encapsulated Co@Co3O4 nanoparticles are synthesized from D‐glucose, hexamethylenetetramine (HMT), and Co(NO3)2. HMT is presented as the complex to uniformly disperse Co@Co3O4 nanoparticles, dope nitrogen, and create the nanoflower structure. The nanoflower structure enhances high surface area to expose the active sites. The formation of Co3O4 via mild oxidation of Co surface provides oxygen vacancies to adsorb O2. HMT‐Co/G‐700 catalyst exhibits excellent ORR electrocatalytic property, i. e. high onset potential (1.03 V), high half‐wave potential (0.83 V), low Tafel slope (85.9 mV dec−1), and superior OER activity. Especially, the HMT‐Co/G‐700 catalyst assembled rechargeable zinc‐air battery present high‐power density (111.0 mW cm−2) and long cycle life at 10 mA cm−2 (576 cycles).
Pharmacokinetics, Safety, and Tolerability of Brivaracetam in Healthy Elderly Participants
Authors: Stockis Armel , Nicolas Jean‐Marie , Sargentini‐Maier Maria Laura , Krauwinkel Walter
Published: May 2023

The pharmacokinetics, metabolism, safety, and tolerability of the antiseizure medication brivaracetam (BRV) were characterized in 16 healthy elderly participants (8 men/8 women) aged 65–78 years who received a single 200‐mg oral dose of BRV on day 1, followed by 200 mg twice daily from day 3 until day 12. BRV and three metabolites were determined in plasma and urine. Adverse events, vital signs, electrocardiograms, laboratory tests, general and neurological examinations, and psychometric rating scales were recorded at regular intervals. No clinically relevant changes or abnormalities were detected. The adverse events were similar to those observed in pivotal trials. Rating scales indicated transiently increased sedation and decreased alertness. BRV pharmacokinetics and metabolism were unchanged relative to younger populations. Based on our observations in this healthy elderly population receiving oral BRV 200 mg twice daily (twice the maximum recommended dose), dose reductions are not warranted relative to other, younger populations. Further investigations may be necessary in frail elderly populations aged >80 years.
Early Decision Making in a Randomized Phase II Trial of Atezolizumab in Biliary Tract Cancer Using a Tumor Growth Inhibition‐Survival Modeling Framework
Authors: Shemesh Colby S. , Chan Phyllis , Marchand Mathilde , Gonçalves Antonio , Vadhavkar Shweta , Wu Benjamin , Li Chunze , Jin Jin Y. , Hack Stephen P. , Bruno Rene
Published: May 2023

We assess the longitudinal tumor growth inhibition (TGI) metrics and overall survival (OS) predictions applied to patients with advanced biliary tract cancer (BTC) enrolled in IMbrave151 a multicenter randomized phase II, double‐blind, placebo‐controlled trial evaluating the efficacy and safety of atezolizumab with or without bevacizumab in combination with cisplatin plus gemcitabine. Tumor growth rate (KG) was estimated for patients in IMbrave151. A pre‐existing TGI‐OS model for patients with hepatocellular carcinoma in IMbrave150 was modified to include available IMbrave151 study covariates and KG estimates and used to simulate IMbrave151 study outcomes. At the interim progression‐free survival (PFS) analysis (98 patients, 27 weeks follow‐up), clear separation in tumor dynamic profiles with a faster shrinkage rate and slower KG (0.0103 vs. 0.0117 week−1; tumor doubling time 67 vs. 59 weeks; KG geometric mean ratio of 0.84) favoring the bevacizumab containing arm was observed. At the first interim analysis for PFS, the simulated OS hazard ratio (HR) 95% prediction interval (PI) of 0.74 (95% PI: 0.58–0.94) offered an early prediction of treatment benefit later confirmed at the final analysis, observed HR of 0.76 based on 159 treated patients and 34 weeks of follow‐up. This is the first prospective application of a TGI‐OS modeling framework supporting gating of a phase III trial. The findings demonstrate the utility for longitudinal TGI and KG geometric mean ratio as relevant end points in oncology studies to support go/no‐go decision making and facilitate interpretation of the IMbrave151 results to support future development efforts for novel therapeutics for patients with advanced BTC.
Crystal Growth and Photoelectric Properties of Dimethylammonium Doped CsPbBr3
Authors: Guo Xiaoling , Xie Huidong , Zhang Ruiqing , Tang Zuobin , Wang Kangkang , Yang Chang
Published: May 2023

Metal halide perovskites are widely studied in photoluminescence and photodetection applications owing to their outstanding optical and electrical properties. The optoelectronic properties and stability of the material can be improved by the modification of the A‐site ions doping. Herein, a series of dimethylammonium (DMA) doped CsPbBr3 single crystals, Cs1−xDMAxPbBr3 (x = 0.1–0.4), is prepared by a solvent evaporation method. The phase, density, infrared spectra, UV–vis diffuse reflectance spectra, fluorescence spectra, and photoelectric response of the Cs1−xDMAxPbBr3 series are tested. The results show that as the DMA content increases, the lattice parameters increase, while the bandgap energy and the density decrease when x ≤ 0.3. The A‐site doping of DMA improves the optoelectronic properties of the crystals and shows the greatest photocurrent response at x = 0.1.