bluuebunny/crossref_metadata_2025 huggingface dataset:
Homozygous splice site variant affecting the first von Willebrand factor A domain of COL12A1 in a patient with myopathic Ehlers‐Danlos syndrome
Authors: Furuhata‐Yoshimura Megumi , Yamaguchi Tomomi , Izu Yayoi , Kosho Tomoki
Published: June 2023

Myopathic Ehlers‐Danlos syndrome (mEDS) is a subtype of EDS that is caused by abnormalities in COL12A1. Up‐to‐date, 24 patients from 15 families with mEDS have been reported, with 14 families showing inheritance in an autosomal dominant manner and one family in an autosomal recessive manner. We encountered an additional patient with autosomal recessive mEDS. The patient is a 47‐year‐old Japanese man, born to consanguineous parents with no related features of mEDS. After birth, he presented with hypotonia, weak spontaneous movements, scoliosis, and torticollis. He had soft palms but no skin hyperextensibility or fragility. Progressive scoliosis, undescended testes, and muscular torticollis required surgery. During adulthood, he worked normally and had no physical concerns. Clinical exome analysis revealed a novel homozygous variant in COL12A1 (NM_004370.6:c.395‐1G > A) at the splice acceptor site of exon 6, leading to in‐frame skipping of exon 6. The patient was diagnosed with mEDS. The milder manifestations in the current patient compared with previously reported patients with mEDS might be related to the site of the variant. The variant is located in the genomic region encoding the first von Willebrand factor A domain, which affects only the long isoform of collagen XII, in contrast to the variants in previously reported mEDS patients that affected both the long and short isoforms. Further studies are needed to delineate comprehensive genotype–phenotype correlation of the disorder.
Association of body mass index and hypoglycemia with mortality rates among sepsis patients: A retrospective sub‐analysis of the FORECAST study
Authors: Tanikawa Atsushi , Kudo Daisuke , Ohbe Hiroyuki , Kushimoto Shigeki
Published: June 2023

Aim

Hypoglycemia at admission is associated with high mortality in sepsis patients. However, the influence of body mass index (BMI) on this association remains unknown. Therefore, this study assesses the association of hypoglycemia at admission with mortality in patients with sepsis according to BMI.

Methods

This was a secondary analysis of a multicenter, prospective cohort study of 59 intensive care units in Japan. We included 1184 patients (age ≥16 years) with severe sepsis and excluded those with missing data on glucose level, BMI, or survival at discharge. The initial blood glucose level of <70 mg/dL was defined as hypoglycemia. Patients were assigned to the hypoglycemia or non‐hypoglycemia group as per BMI category (<18.5 [low], 18.5–24.9 [normal], and ≥25 [high] kg/m2). The main outcome was in‐hospital mortality. Multivariate logistic regression models were used to evaluate BMI category‐by‐hypoglycemia interactions.

Results

Overall, 1103 patients, including 65 with hypoglycemia, were analyzed. In the normal BMI group, patients with hypoglycemia had a higher in‐hospital mortality rate (18/38, 47.4%) than those without (119/584, 20.4%). There was a significant interaction between normal BMI and hypoglycemia affecting in‐hospital mortality; however, this effect was not observed for other BMI categories (odds ratio, 2.32; 95% confidence interval, 1.05–5.07; p‐value for interaction = 0.0476).

Conclusion

The relationship between patients with sepsis and hypoglycemia on admission may differ according to BMI. Hypoglycemia on admission may be associated with high mortality in patients with normal BMI, but not in those with low or high BMI.
Potential of uniaxial electrospun composite nanofibers based on polycaprolactone and polyvinyl alcohol in guided bone regeneration
Authors: Jiang Kongzhao , Liu Guomin , Cheng Zhiqiang , Sun Maolei , Liu Yun , Jiao Kun , Jia Wenyuan , Wang Shaoru , Dai Zhihui , Yang Yuheng , Liu Liping , Yang Tao , Jiang Xuanzuo , Luo Yungang , Liu Zhihui
Published: June 2023

Polycaprolactone and polyvinyl alcohol are commonly used polymers with biocompatibility and biodegradability. However, the poor mechanical properties of polycaprolactone and the high swelling properties of polyvinyl alcohol hinder their application in guided tissue/bone regeneration. In this study, a new strategy for preparing absorbable guided bone regeneration (GBR) membrane was innovatively put forward, which was to simply blend them in formic acid in different proportions (0%/100%, 25%/75%, 50%/50%, 75%/25%, and 100%/0% wt/wt) and obtain nanofiber membrane by uniaxial electrospinning. The nano‐structure was confirmed by scanning electron microscope, and the change of chemical functional groups was confirmed by Fourier transform infrared spectroscopy. In addition, the proper polymer proportion (75%/25%) was selected through some tests. The results show that the nanofiber membrane has suitable wettability (104.083 ± 2.512°), sufficient Young's modulus (90.895 ± 7.431 MPa), the lowest swelling rate (33.705 ± 1.806%) and shrinkage rate (1.878 ± 3.252%), and no cytotoxicity. Its biodegradability and osteogenic effects in vitro were also investigated to show the potential applied in GBR.
‘Standing back’ or ‘stepping up’? Exploring climate change education policy influence in England
Authors: Greer Kate , King Heather , Glackin Melissa
Published: June 2023

This paper explores the nature of climate change education‐related policy influence in England at a time when public consciousness about the need to accelerate climate change action was heightened, and as the 2018 climate strikes gathered momentum around the world. Informed by Foucault's concept of ‘governmentalities’, and using data generated through 24 exploratory interviews and reflexive thematic analysis, we examine the extent to which influential individuals were advocating for policy change. We discuss the nature of policy influence with particular reference to the ‘stances’ that individuals adopted relative to climate change education policy influence and noting a common tendency exhibited amongst participants which was a tendency towards ‘deference’. Coupling our insights with theorisations of dissent, we consider how ‘infra‐political dissent’ could support key individuals to ‘step up’ and influence for more effective policy relative to climate change education, and to other areas of education or environment policy.
Adults with autism using self‐management to decrease problem behavior: A review of the literature
Authors: McHugh Ashley B. , Zane Thomas , Monroe‐Gulick Amalia Louise
Published: June 2023

The purpose of this literature review was to examine the state of research on the use of self‐management procedures in reducing problem behaviors in adults diagnosed with an intellectual disability. Studies were located by conducting a systematic search of literature across various journals. Seventeen studies were included in the review and were evaluated along the dimensions of adherence to quality research design and outcomes. Results showed that self‐management techniques were associated with decreased levels of challenging behaviors across adults with intellectual disability and autism spectrum disorder. However, the quality of research design was inconsistent, decreasing confidence in a causal relationship between self‐management and reduction in challenging behaviors. This review should encourage more research in using self‐management procedures with individuals having intellectual disability, especially with adults.
Corporate scope 3 carbon emission reporting as an enabler of supply chain decarbonization: A systematic review and comprehensive research agenda
Authors: Hettler Maximilian , Graf‐Vlachy Lorenz
Published: June 2023

Firms worldwide are currently investigating ways to decarbonize global supply chains. Corporate scope 3 carbon emission reporting is a critical first step but is not yet a common activity for most firms. The current literature on corporate scope 3 reporting is highly fragmented and does not offer a comprehensive overview, and findings from scopes 1 and 2 emission reporting are often not readily transferrable. Therefore, we conduct a systematic literature review, develop an encompassing research framework, and generate a comprehensive research agenda. Our results identify several patterns in the literature, such as the widespread use of the Carbon Disclosure Project as a data source, a broad agreement on poor comprehensiveness of scope 3 reports, and an overall low amount of empirical research. We contribute a holistic overview of the complex issue of scope 3 reporting and develop numerous promising research avenues.
Optimization of carotenoid production by Umbelopsis ramanniana
Authors: Kizilay Hatice Kübra , Küçükçetin Ahmet , Demir Muammer
Published: June 2023

Umbelopsis ramanniana was investigated to increase carotenoid production. Nine different carbon sources and six different nitrogen sources were evaluated for the maximum carotenoid production. The most effective nitrogen and carbon sources were KNO3 and lactose, respectively. Then, the optimization of medium components for enhancement of carotenoid production by Umbelopsis ramanniana was achieved using Plackett–Burman design. Box–Behnken response surface methodology was applied to further optimize carotenoid and biomass production. Carbon to nitrogen ratio, lactose concentration, and shaking speed were studied as variables in Box–Behnken design. The optimum conditions for carotenoid and biomass production were determined as 32.42 g/L of lactose concentration, 20:1 of carbon to nitrogen ratio, and shaking speed of 130 rpm. The maximum carotenoid and biomass production under optimized conditions were 1141 μg/L (β‐carotene‐Eq) and 13.14 g/L, respectively. When compared to the control fermentation, carotenoid, and biomass production were increased by about 2 and 1.3 folds, respectively.
NNeduca: A software environment to teach artificial neural networks
Authors: Jovanović Nenad , Stamenković Srećko , Jovanović Stefan
Published: June 2023

Artificial neural networks are an integral part of the curriculum in many undergraduate computer science programs. This paper introduces NNeduca, a simulation software system designed to teach undergraduate students the fundamental concepts of artificial neural networks. The system is written in Java and aims to provide an intuitive user interface, support for research and learning activities, and the ability to expand. This tool allows students to design and train a neural network with any architecture they desire and visualize some artificial neural network theoretical concepts such as definitions, topologies, training methods, and structure. An overview of educational software systems to aid in learning the fundamental concepts of neural networks was created based on a systematic literature review. A comparison of existing simulation systems and the developed NNeduca tool was performed in this paper. The evaluation was carried out using a newly developed model for assessing the quality of selected systems using established criteria formed as a result of a thorough examination of relevant methods of evaluating educational software. The usability evaluation results show that the NNeduca tool received the highest ratings, indicating that it can significantly improve the teaching process in artificial neural network courses.
A systematic review and meta‐analysis of predictive and prognostic models for outcome prediction using positron emission tomography radiomics in head and neck squamous cell carcinoma patients
Authors: Philip Mahima Merin , Welch Andy , McKiddie Fergus , Nath Mintu
Published: June 2023

Background

Positron emission tomography (PET) images of head and neck squamous cell carcinoma (HNSCC) patients can assess the functional and biochemical processes at cellular levels. Therefore, PET radiomics‐based prediction and prognostic models have the potentials to understand tumour heterogeneity and assist clinicians with diagnosis, prognosis and management of the disease. We conducted a systematic review of published modelling information to evaluate the usefulness of PET radiomics in the prediction and prognosis of HNSCC patients.

Methods

We searched bibliographic databases (MEDLINE, Embase, Web of Science) from 2010 to 2021 and considered 31 studies with pre‐defined inclusion criteria. We followed the CHARMS checklist for data extraction and performed quality assessment using the PROBAST tool. We conducted a meta‐analysis to estimate the accuracy of the prediction and prognostic models using the diagnostic odds ratio (DOR) and average C‐statistic, respectively.

Results

Manual segmentation method followed by 40% of the maximum standardised uptake value (SUVmax) thresholding is a commonly used approach. The area under the receiver operating curves of externally validated prediction models ranged between 0.60–0.87, 0.65–0.86 and 0.62–0.75 for overall survival, distant metastasis and recurrence, respectively. Most studies highlighted an overall high risk of bias (outcome definition, statistical methodologies and external validation of models) and high unclear concern in terms of applicability. The meta‐analysis showed the estimated pooled DOR of 6.75 (95% CI: 4.45, 10.23) for prediction models and the C‐statistic of 0.71 (95% CI: 0.67, 0.74) for prognostic models.

Conclusions

Both prediction and prognostic models using clinical variables and PET radiomics demonstrated reliable accuracy for detecting adverse outcomes in HNSCC, suggesting the prospect of PET radiomics in clinical settings for diagnosis, prognosis and management of HNSCC patients. Future studies of prediction and prognostic models should emphasise the quality of reporting, external model validation, generalisability to real clinical scenarios and enhanced reproducibility of results.
BRCA2 reversion mutation confers resistance to olaparib in breast cancer
Authors: Yamamoto Shinya , Kawashima Kei , Fujiwara Yoshie , Adachi Shoko , Narui Kazutaka , Hosaka Chiaki , Takahashi Rina , Tsuyuki Sho , Sugimori Makoto , Tanoshima Miki , Sasamoto Mahato , Oshi Masanori , Yamada Akimitsu , Kunisaki Chikara , Endo Itaru
Published: June 2023

Key Clinical Message

A rare missense mutation was identified as a reversion mutation using cancer genomic profiling and a suspected mechanism underlying resistance to olaparib in breast cancer.

A 34‐year‐old woman with breast cancer and BRCA2: p.Gln3047Ter was treated with olaparib. After tumor progression, cancer genomic profiling testing using liquid biopsy revealed BRCA2 p.Gln3047Ter and p.Gln3047Tyr, with 48.9% and 0.37% allele frequency, respectively. These findings shed light on reversion mutation as a mechanism of resistance to olaparib in breast cancer.
Molecular and Crystal Structure, Spectroscopy, and Photochemistry of a Dispiro Compound Bearing the Tetraoxane Pharmacophore
Authors: Amado Patrícia S. M. , Lopes Susy , Brás Elisa M. , Paixão José A. , Takano Ma‐aya , Abe Manabu , Fausto Rui , Cristiano Maria L. S.
Published: June 2023

The molecular structure and photochemistry of dispiro[cyclohexane‐1,3′‐[1,2,4,5]tetraoxane‐6′,2′′‐tricyclo[3.3.1.13,7]decan]‐4‐one (TX), an antiparasitic 1,2,4,5‐tetraoxane was investigated using matrix isolation IR and EPR spectroscopies, together with quantum chemical calculations undertaken at the DFT(B3LYP)/6‐311++G(3df,3pd) level of theory, with and without Grimme's dispersion correction. Photolysis of the matrix‐isolated TX, induced by in situ broadband (λ>235 nm) or narrowband (λ in the range 220–263 nm) irradiation, led to new bands in the infrared spectrum that could be ascribed to two distinct photoproducts, oxepane‐2,5‐dione, and 4‐oxohomoadamantan‐5‐one. Our studies show that these photoproducts result from initial photoinduced cleavage of an O−O bond, with the formation of an oxygen‐centered diradical that regioselectivity rearranges to a more stable (secondary carbon‐centered)/(oxygen‐centered) diradical, yielding the final products. Formation of the diradical species was confirmed by EPR measurements, upon photolysis of the compound at λ=266 nm, in acetonitrile ice (T=10–80 K). Single‐crystal X‐ray diffraction (XRD) studies demonstrated that the TX molecule adopts nearly the same conformation in the crystal and matrix‐isolation conditions, revealing that the intermolecular interactions in the TX crystal are weak. This result is in keeping with observed similarities between the infrared spectrum of the crystalline material and that of matrix‐isolated TX. The detailed structural, vibrational, and photochemical data reported here appear relevant to the practical uses of TX in medicinal chemistry, considering its efficient and broad parasiticidal properties.
Stabilizing Nitroxide Spin Labels for Structural and Conformational Studies of Biomolecules by Maleimide Treatment
Authors: Wang Xi‐Wei , Zhang Xing , Cui Chao‐Yu , Li Bin , Goldfarb Daniella , Yang Yin , Su Xun‐Cheng
Published: June 2023

Nitroxide (NO) spin radicals are effective in characterizing structures, interactions and dynamics of biomolecules. The EPR applications in cell lysates or intracellular milieu require stable spin labels, but NO radicals are unstable in such conditions. We showed that the destabilization of NO radicals in cell lysates or even in cells is caused by NADPH/NADH related enzymes, but not by the commonly believed reducing reagents such as GSH. Maleimide stabilizes the NO radicals in the cell lysates by consumption of the NADPH/NADH that are essential for the enzymes involved in destabilizing NO radicals, instead of serving as the solo thiol scavenger. The maleimide treatment retains the crowding properties of the intracellular components and allows to perform long‐time EPR measurements of NO labeled biomolecules close to the intracellular conditions. The strategy of maleimide treatment on cell lysates for the EPR applications has been demonstrated on double electron‐electron resonance (DEER) measurements on a number of NO labeled protein samples. The method opens a broad application range for the NO labeled biomolecules by EPR in conditions that resemble the intracellular milieu.
Bioorthogonal Drug Release from Nanometric Micelles in Living Cells
Authors: Madegard Léa , Girard Melissa , Yaw Benjamin Riss , Porte Karine , Audisio Davide , Papot Sébastien , Taran Frédéric
Published: June 2023

We explored a bioorthogonal approach to release drugs from stimuli‐responsive micelles inside tumor cells. The concept relies on sydnonimine‐based micelles that undergo quantitative cleavage in presence of cyclooctynes, hence releasing their content within living cells. Four cleavable micelles were developed to allow massive burst release of Entinostat, a potent histone deacetylase inhibitor, following their internalization inside cancer cells. A comparative study on the influence of the bioorthogonal‐mediated versus passive drug release from micelles was carried out. The results indicated that a fast release of the drug triggered a stronger antiproliferative activity on tumor cells compared to the passive diffusion of the drug from the micelles core. These finding may be of great interest for the development of new nanomedicines.
Titandioxid
Authors: Schubert Ulrich
Published: June 2023

Die wichtigsten Rohstoffe für TiO2 sind natürliche TiO2‐Vorkommen und das Mineral Ilmenit (FeTiO3). Beim „Chlorid‐Prozess“ werden diese durch Behandlung mit Kohlenstoff und Chlor bei hohen Temperaturen zu TiCl4 aufgeschlossen, das dann durch „Verbrennen“ mit Sauerstoff oder Wasserstoff‐Sauerstoff‐Gemischen zu TiO2 umgesetzt wird. Eine alternative Methode ist die Behandlung der Rohstoffe mit konzentrierter Schwefelsäure und Ausfällen von TiO2 aus den dabei erhaltenen Titanylsulfat‐Lösungen. Neben diesen beiden großtechnischen Prozessen zur Herstellung von TiO2‐Pulvern spielen Sol‐Gel‐Verfahren eine Rolle, beispielsweise zur Synthese von Nanostrukturen, Beschichtungen oder porösem TiO2, bei denen T(OR)4 hydrolysiert wird. TiO2 ist das wichtigste Weißpigment und als solches in unserem Leben allgegenwärtig. Bis vor kurzem wurde TiO2 auch Lebensmitteln als Farbstoff zugesetzt. Diese Verwendung wurde aber mittlerweile in der EU untersagt, da genotoxische Effekte nicht mit Sicherheit ausgeschlossen werden können. Ein zweites wichtiges Anwendungsgebiet ergibt sich aus den Halbleiter‐Eigenschaften von TiO2. Aufgrund der Größe der Bandlücke wird UV‐Strahlung absorbiert. Daraus ergeben sich Anwendungen von Sonnenschutzcremes bis zum photokatalytischen Abbau von organischen Schadstoffen.
Palladium‐Catalyzed [4 + 4] Cycloaddition of Homo‐TMM All‐Carbon 1,4‐Dipole Precursors for Construction of Benzofuro[3,2‐b]azocines and Furo[3,2‐b]azocines
Authors: Chen Ying , Zang Meng , Wang Weijie , Liu Yang‐Zi , Luo Xiaoyan , Deng Wei‐Ping
Published: June 2023

Comprehensive Summary

We developed a novel Pd‐catalyzed [4 + 4] cycloaddition of (benzo)furan‐derived azadienes with homo‐TMM all‐carbon 1,4‐dipoles in situ generated from α‐allyl malonate derivatives, affording an array of benzofuro[3,2‐b]azocines and furo[3,2‐b]azocines with good to excellent yields (up to 96%) and exclusive regioselectivities. This methodology featured mild reaction conditions and good functional group tolerance. The synthetic utility was demonstrated by a gram‐scale reaction. Furthermore, the catalytic asymmetric [4 + 4] cycloaddition version has also been explored.
Difluoroalkylation/Lactonization of Alkenes with BrCF2CO2K via Photoredox Catalysis: Access to α,α‐Difluoro‐γ‐lactones†
Authors: Zhang Min , Li Qiang , Lin Jin‐Hong , Xiao Ji‐Chang
Published: June 2023

Comprehensive Summary

Due to its unique electronic properties, the difluoromethylene group (CF2) has served as a valuable unity in the design of biologically active molecules. Since γ‐lactones display a broad range of biological properties, α,α‐difluoro‐γ‐lactones may exhibit unexpected biological activities, and thus their synthesis has received increasing attention. Traditional synthetic methods suffer from tedious multi‐ step processes, and very few effective methods have been reported recently. Herein, we describe the difunctionalization of alkenes with BrCF2CO2K under photoredox catalysis with the use of a boron‐Lewis acid for the access to α,α‐difluoro‐γ‐lactones. In this transformation, the alkene substrates and the used reagents, including BrCF2CO2K and the boron‐Lewis acid, PhB(OH)2 or BF3·THF, are cheap and widely available. High efficiency and atom economy may make this protocol attractive.
Rapid Access to Free Phenols by Photocatalytic Acceptorless Dehydrogenation of Cyclohexanones at Room Temperature
Authors: Min Lin , Lin Jiani , Shu Wei
Published: June 2023

Comprehensive Summary

Phenols are ubiquitous substructures in natural products and bioactive compounds. However, practical methods for the direct construction of phenols under mild conditions remain challenging. Herein, a photocatalytic acceptorless hydrogen‐evolution aromatization of cyclohexanones or cyclohexenones at room temperature has been developed. The reaction features the visible‐light and cobalt co‐catalyzed sequential dehydrogenation of in‐situ formed enol silyl ethers, which are regarded as a challenging process. This operationally simple method enables the synthesis of a series of phenols with diverse substitution patterns from cyclohexanones or cyclohexenones. Moreover, diverse substituted 1,2‐, 1,3‐, and 1,4‐benzenediols were obtained from cyclohexanediones, providing a general and straightforward method for the synthesis of phenols from simple starting materials under mild conditions.
Association between diabetes mellitus and reduced efficacy of pembrolizumab in non–small cell lung cancer
Authors: Leshem Yasmin , Dolev Yardenna , Siegelmann‐Danieli Nava , Sharman Moser Sarah , Apter Lior , Chodick Gabriel , Nikolaevski‐Berlin Alla , Shamai Sivan , Merimsky Ofer , Wolf Ido
Published: June 2023

Background

Diabetes mellitus (DM) is a highly prevalent chronic metabolic disorder. Although DM has been associated with immune dysfunction, the effect of DM on the efficacy of immunotherapy is unknown. This study aimed to evaluate the impact of DM on the efficacy of pembrolizumab in metastatic non–small cell lung cancer (NSCLC).

Methods

The authors reviewed the medical records of consecutive metastatic NSCLC patients treated with first‐line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center. For validation, a computerized data from Maccabi Healthcare Services, a 2.5–million‐member state health service was used.

Results

Of the 203 eligible patients, 51 (25%) had DM. Patients with DM had a significantly shorter median progression‐free survival (PFS) (5.9 vs. 7.1 months, p = .004) and overall survival (OS) (12 vs. 21 months, p = .006). The shorter OS in diabetic patients was more pronounced when pembrolizumab was given alone (12 vs. 27 months, p = .03) than when combined with chemotherapy (14.3 vs. 19.4 months, p = .06). Multivariate analysis confirmed DM as an independent risk factor for shorter PFS (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.11−2.50, p = .01) and OS (HR, 1.73; 95% CI, 1.09−2.76, p = .02). In a validation cohort of 452 metastatic NSCLC patients, the time on pembrolizumab treatment was shorter in diabetic patients (p = .025), with only 19.6% of patients remaining on treatment at 12 months compared to 31.7% of the nondiabetic patients.

Conclusions

This study suggests immunotherapy is less beneficial in diabetic NSCLC patients. More work is needed to verify our findings and explore similar effects in other cancer entities.
Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic‐phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML
Authors: Tiribelli Mario , Latagliata Roberto , Breccia Massimo , Capodanno Isabella , Miggiano Maria Cristina , Cavazzini Francesco , Bucelli Cristina , Attolico Immacolata , Crescenzi Sabrina Leonetti , Russo Sabina , Annunziata Mario , Sorà Federica , Bonifacio Massimiliano , Mulas Olga , Loglisci Giuseppina , Maggi Alessandro , Binotto Gianni , Crisà Elena , Scortechini Anna Rita , Leporace Anna Paola , Sancetta Rosaria , Murgano Pamela , Abruzzese Elisabetta , Stagno Fabio , Rapezzi Davide , Luzi Debora , Vincelli Iolanda , Bocchia Monica , Fava Carmen , Malato Alessandra , Crugnola Monica , Pizzuti Michele , Lunghi Francesca , Galimberti Sara , Dalmazzo Matteo , Fanin Renato , Scalzulli Emilia , Foà Robin , Iurlo Alessandra , Saglio Giuseppe , Specchia Giorgina
Published: June 2023

Background

Imatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic‐phase chronic myeloid leukemia (CP‐CML). The choice of TKI is based on a combined evaluation of the patient’s and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP‐CML to correlate the choice with the patient’s features.

Methods

A total of 1967 patients with CP‐CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second‐generation (2G) TKI.

Results

Second‐generation TKIs were chosen for most patients aged <45 years (69.2%), whereas imatinib was used in 76.7% of patients aged >65 years (p < .001). There was a predominant use of imatinib in intermediate/high European long–term survival risk patients (60.0%/66.0% vs. 49.7% in low‐risk patients) and a limited use of 2G‐TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with >3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018–2019 compared to 2012–2017 (53.2%; p = .002). In multivariable analysis, factors correlated with imatinib use were age > 65 years, spleen size, the presence of comorbidities, and ≥3 concomitant medications.

Conclusions

This observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP‐CML, with 2G‐TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use.
Regulating Efficient and Selective Single‐atom Catalysts for Electrocatalytic CO2 Reduction
Authors: Wang Shuo , Feng Shao‐Yang , Zhao Cong‐Cong , Zhao Ting‐Ting , Tian Yu , Yan Li‐Kai
Published: June 2023

Anchoring transition metal (TM) atoms on suitable substrates to form single‐atom catalysts (SACs) is a novel approach to constructing electrocatalysts. Graphdiyne with sp−sp2 hybridized carbon atoms and uniformly distributed pores have been considered as a potential carbon material for supporting metal atoms in a variety of catalytic processes. Herein, density functional theory (DFT) calculations were performed to study the single TM atom anchoring on graphdiyne (TM1−GDY, TM=Sc, Ti, V, Cr, Mn, Co and Cu) as the catalysts for CO2 reduction. After anchoring metal atoms on GDY, the catalytic activity of TM1−GDY (TM=Mn, Co and Cu) for CO2 reduction reaction (CO2RR) are significantly improved comparing with the pristine GDY. Among the studied TM1−GDY, Cu1−GDY shows excellent electrocatalytic activity for CO2 reduction for which the product is HCOOH and the limiting potential (UL) is −0.16 V. Mn1−GDY and Co1−GDY exhibit superior catalytic selectivity for CO2 reduction to CH4 with UL of −0.62 and −0.34 V, respectively. The hydrogen evolution reaction (HER) by TM1−GDY (TM=Mn, Co and Cu) occurs on carbon atoms, while the active sites of CO2RR are the transition metal atoms . The present work is expected to provide a solid theoretical basis for CO2 conversion into valuable hydrocarbons.
Chiral and Luminescent Organic Radicals
Authors: Wang Mengqi , Zhao Engui , He Zikai
Published: June 2023

Chiral luminescent materials are a class of materials capable of emitting circularly polarized light (CPL). Radicals are unique open‐shell compounds with exceptional photoelectromagnetic properties that can be exploited in constructing novel chiral luminescent materials. This Concept discussed three main catalogues for producing organic CPL radicals, intrinsic chiral luminescent radicals, luminescent radicals with chiral substitutions, and field‐regulation‐induced chiral luminescent radicals. The brief review of their properties aims at providing basic guidelines and supporting further development of novel chiral luminescent radical systems.
UAV‐IoT collaboration: Energy and time‐saving task scheduling scheme
Authors: Banerjee Anuradha , Gupta Sachin Kumar , Gupta Parul , Sufian Abu , Srivastava Ashutosh , Kumar Manoj
Published: June 2023

UAVs are capable of providing significant potential to IoT devices through sensors, cameras, GPS systems, and so forth. Therefore, the smart UAV‐IoT collaborative system has become a current hot research topic. However, other concerns require in‐depth investigation and study, such as resource allocation, security, privacy preservation, trajectory optimization, intelligent decision‐making, energy harvesting, and so forth. Here, we suggest a task‐scheduling method that splits IoT devices into distinct clusters based on physical proximity and saves time and energy. Cluster heads can apply an auto regressive moving average (ARMA) model to predict intelligently the timestamp of the arrival of the next task and associated estimated payments. Based on the overall expected payment, a cluster head can smartly advise the UAV about its time of next arrival. According to the findings of the simulation, the proposed ETTS algorithm significantly outperforms Task TSIE and TDMA‐WS in terms of energy use (67%) and delays (36%).
Energy‐optimized cluster head selection based on enhanced remora optimization algorithm in underwater wireless sensor network
Authors: Kumar Tiwari Keshav , Singh Samayveer
Published: June 2023

With the technological advancements, wireless sensor network (WSN) has played an impeccable role in monitoring the underwater applications. Underwater WSN (UWSN) is supported by WSN but subjected to data dissemination in an acoustic medium. Due to challenging conditions in underwater scenario, the limited battery resources of these sensor nodes stem to a crucial research problem that needs to address the energy‐efficient routing in UWSN. In this research work, we intend to propose an energy‐optimized cluster head (CH) selection based on enhanced remora optimization algorithm (ECERO) in UWSN. Since CH devours the maximum energy among the nodes, we perform selection of CH based on EROA while considering energy, Euclidean distance from sink, node density, network's average energy, acoustic path loss model and lastly, the adaptive quantity of CHs in the network. Further, to reduce the load on CH node, we introduce the concept of sleep scheduling among the closely located cluster nodes. The proposed work improves the performance of recently proposed EOCSR algorithm by great magnitude which claims to mitigate hot‐spot problem, but EOCSR still suffers from the same due to relaying a large magnitude of data.
Thoracic SMARCA4‐deficient undifferentiated tumor with associated granulomatous reaction and response to pembrolizumab
Authors: Marshall Mason , Khader Samer , Beasley Scott , Lajara Sigfred
Published: June 2023

Thoracic SMARCA4‐deficient undifferentiated tumor (SMARCA4‐UT) is a rare entity that was recently described in the current World Health Organization Classification of Tumors. These lesions are highly aggressive with dismal prognosis, and most patients present with metastasis at the time of diagnosis. While there are about 100 cases of SMARCA4‐UT described in the literature, there are only few existing reports that describe the cytomorphology of these lesions. We present a patient with masses involving the mediastinum, right lung, right supraclavicular lymph node and right adrenal gland. Subsequent core‐needle biopsy of the right supraclavicular lymph node showed epithelioid to pleomorphic tumor cells with prominent nucleoli and associated granulomatous inflammation. The tumor cells were positive for CD34 and synaptophysin, and were negative for cytokeratins. SMARCA4 and SMARCA2 both showed loss of expression, which led to the diagnosis of SMARCA4‐UT. The patient underwent treatment with pembrolizumab (PD‐1 blocker), carboplatin, etoposide, and radiotherapy, resulting in an almost 55% reduction in the size of the primary tumor. Our case illustrates that an associated granulomatous inflammation might be an uncommon presentation of an already rare malignancy, and awareness of this phenomenon would prevent from mistaking SMARCA4‐UT for other more well‐known entities that can present with granulomas.
Heart transplantation in patients bridged with mechanical circulatory support: outcome comparison with matched controls
Authors: Bartfay Sven‐Erik , Bobbio Emanuele , Esmaily Sorosh , Bergh Niklas , Holgersson Jan , Dellgren Göran , Bollano Entela , Karason Kristjan
Published: June 2023

Aims

Due to the shortage of heart donors, increasing numbers of heart transplantation (HTx) candidates are receiving long‐term mechanical circulatory support (MCS) as bridge‐to‐transplantation. Treatment with MCS is associated with increased formation of anti‐human leukocyte antigen antibodies (allosensitization), but whether this affects post‐HTx outcomes is unclear.

Methods and results

We included all adult patients who received long‐term MCS as bridge‐to‐transplantation and underwent subsequent HTx at our centre between 2008 and 2018. We also enrolled medically treated HTx recipients without prior MCS as controls. These controls were matched by age, sex, diagnosis, and transplantation era. Outcome parameters were compared between the two study groups. A total of 126 patients (48 ± 15 years, 84% male) were included of whom 64 were bridged with MCS and 62 were matched controls. Pre‐HTx allosensitization occurred more frequently in the MCS group than in the control group (27% vs. 11%, P = 0.03). At post‐HTx year 10, the overall survival probability was 84% among patients treated with MCS and 90% among those medically managed (P = 0.32). At post‐HTx year 1, freedom from treated rejections (≥ISHLT 2R) was 69% in the MCS group and 70% in the control group (P = 0.94); and freedom from any rejection was 8% and 5%, respectively (P = 0.98). There were no differences in renal function or cardiac allograft vasculopathy (grade ≥ 1) between groups at 1, 3, and 5 years post‐HTx.

Conclusions

Although patients treated with MCS had a higher frequency of pre‐HTx allosensitization, there were no significant differences in post‐HTx graft survival, biopsy‐proven rejections, or renal function as compared with patients not bridged with MCS.
Paediatric heart transplantation during the COVID‐19 pandemic in Iran: single‐centre experience
Authors: Mahdavi Mohammad , Hejri Golnar Mortaz , Shahzadi Hossein , Dehaki Maziar Gholampour , Houshmand Golnaz
Published: June 2023

Aims

Transplant services were imposed to the multiple challenges of insufficient facilities and resources during the COVID‐19 pandemic. Thus, each centre modified and altered its routine practice to maintain the service. We report our experience in Iran's single‐centre paediatric heart transplantation unit during the 2 year pandemic in transplant rate and early transplant outcomes.

Methods and results

We retrospectively reviewed all paediatric heart transplants performed at our centre between 19 February 2020 and February 2022. We studied the number and percentage of paediatric transplanted patients who developed COVID‐19, in‐hospital outcome, 30 day survival and left ventricular function during the first month of the follow‐up visit. From February 2020 to February 2022, 59 transplants were performed compared with 62 patients from February 2018 to 2020. Compared with the year before the pandemic, the heart transplant rate was reduced by 34% in the first year of the pandemic; however, it bounced back in the second year with a 19% increase. The in‐hospital mortality rate during the 2 year pandemic was (11.8%). One death occurred related to COVID‐19 acute respiratory distress syndrome. The in‐hospital COVID‐19 infection rate was 11 patients (18%). In the 30 day follow‐up, the overall 30 day survival rate was 88%, and the 30 day rejection rate was 10%. The mean left ventricular ejection fraction was (53.6 ± 4.9), the mean left ventricular global longitudinal strain was −16.9 ± 3.3, and the mean right ventricular global longitudinal strain was −17.0 ± 3.8 with no significant difference between patients with in‐hospital COVID and other recipients (P = 0.1, P = 0.2 and P = 0.2).

Conclusions

Throughout the pandemic, although we experienced a reduction in the transplant rate in the first year, with the increasing vaccination rate in health care and later in the general population, we continued to maintain our transplant rate by incorporating safety protocols and more resources.
Short‐chain polyphosphates: Extraction effects on migration and size estimation of Saccharomyces cerevisiae extracts with polyacrylamide gel electrophoresis
Authors: Manoukian Lori , Stein Robin S. , Correa José A. , Frigon Dominic , Omelon Sidney
Published: June 2023

Polyacrylamide gel electrophoresis is commonly used to characterize the chain length of polyphosphates (polyP), more generally called condensed phosphates. After separation, nonradioactive, optical polyP staining is limited to chain lengths greater than 15 monomers with toluidine blue or 4′,6‐diamidino‐2‐phenylindole. PolyP chain lengths longer than 62monomers were correlated to the shortest DNA ladders. In this study, synthetic linear polyPs (Sigma‐Aldrich “Type 45”, estimated mean length of 45 monomers), trimetaphosphate (trimetaP: 3 ring), tripolyphosphate (tripolyP), pyrophosphate (PPi), and inorganic orthophosphate (o‐Pi) were visualized after separation by an in situ hydrolytic degradation process to o‐Pi that was subsequently stained with methyl green. Statistically insignificant migration reduction of synthetic short‐chain polyP after perchloric acid or phenol–chloroform extraction was confirmed with the Friedman test. 31P diffusion–ordered NMR spectroscopy confirmed that extraction also reduced PPi diffusivity by <10%. Linear regression between the Rf peak migration value and the logarithm of synthetic polyP molecular weights enabled estimation of extracted polyP chain lengths from 2 to 45 monomers. Linear polyP extracts from Saccharomyces cerevisiae grown in aerobic conditions were generally shorter than extracts cultured in anaerobic conditions. Extractions from both aerobic and anaerobic S. cerevisiae included tripolyP and o‐Pi, but no PPi.
The effect of macroeconomic news announcements on the implied volatility of commodities: The role of survey releases
Authors: Fernandez‐Perez Adrian , López Raquel
Published: June 2023

We examine the response of the implied volatility in crude oil, gold, and silver commodity markets to macroeconomic news announcements. We find that macroeconomic releases reduce uncertainty in commodity markets consistent with the hypothesis of uncertainty resolution following scheduled news announcements, while macroeconomic releases from the category of survey news announcements increase it. This result can be explained by the qualitative nature of these surveys and their ability to provide information in advance of major official macroeconomic indicators. Nevertheless, we show that survey news announcements can also be useful in resolving commodity market uncertainty in periods of heightened global financial turmoil and when the manufacturing sector of the largest economies is in contraction.
Associations between neuropsychiatric symptoms of affective and vegetative domains and brain morphology in aging people with mild cognitive impairment and Alzheimer's disease
Authors: Cannizzaro Adriana , Ronat Lucas , El Haffaf Lyna Mariam , Hanganu Alexandru ,   for the ADNI
Published: June 2023

Objective

Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and even more in Alzheimer's disease (AD). The symptom‐based cluster including nighttime disturbances, depression, appetite changes, anxiety, and apathy (affective and vegetative symptoms) was associated with an increased risk of dementia in MCI and has common neuroanatomical associations. Our objective was to investigate the differences in brain morphology associations with affective and vegetative symptoms between three groups: cognitively normal older adults (CN), MCI and AD.

Material and Methods

Alzheimer's Disease Neuroimaging Initiative data of 223 CN, 367 MCI and 175 AD, including cortical volumes, surface areas and thicknesses and severity scores of the five NPS were analyzed. A whole‐brain vertex‐wise general linear model was performed to test for intergroup differences (CN‐MCI, CN‐AD, AD‐MCI) in brain morphology associations with five NPS. Multiple regressions were conducted to investigate cortical change as a function of NPS severity in the AD‐MCI contrast.

Results

We found (1) signature differences in nighttime disturbances associations with prefrontal regions in AD‐MCI, (2) signature differences in NPS associations with temporal regions in AD‐MCI for depression and in CN‐AD for anxiety, (3) decreased temporal metrics in MCI as nighttime disturbances and depression severity increased, (4) decreased pars triangularis metrics in AD as nighttime disturbances and apathy severity increased.

Conclusion

Each NPS seems to have a signature on brain morphology. Affective and vegetative NPS were primarily associated with prefrontal and temporal regions. These signatures open the possibility of potential future assessments of links between brain morphology and NPS on an individual level.
‘Scorched Earth: The portrait of health in Brazil after the Bolsonaro's administration and the first 100 days of the Lula Government in health’
Authors: Chioro Arthur , Gomes Temporão José , Massuda Adriano , Costa Humberto , Castro Márcia , Trindade Nísia
Published: June 2023

This article is a rejoinder to the rebuttal letter authored by Jair Bolsonaro's former Minister of Health and Secretary of Primary Care to our initial article, ‘From Bolsonaro to Lula: The opportunity to rebuild universal healthcare in Brazil during the government transition,’ published in the International Journal of Health Planning and Management. We aim to refute the claims that we consider unsubstantiated and disconnected from reality, while reiterating the risks posed by authoritarian and antidemocratic far‐right governments, such as Bolsonarism in Brazil, to the sustainability and resilience of universal health systems. This political threat is gaining momentum across several countries worldwide, thereby endangering the Democratic Rule of Law, institutions, and social policies. Furthermore, we emphasise the significant actions implemented during the first 100 days of President Lula's government, which align with the priorities established during the governmental transition process and strengthen the prospects of reconstructing and fortifying the Brazilian universal health system.
Prevalence and risk factors of obstetric violence in the Gaza strip: A retrospective study from a conflict setting
Authors: Ismail Alaa M. , Ismail Anas , Hirst Jane Elizabeth
Published: June 2023

Objectives

To assess the prevalence and risk factors of obstetric violence (OV) among laboring women in the past 5 years in the Gaza Strip (GS).

Methods

Women who delivered between January 2017 and December 2021 were invited to complete an anonymous online survey between November 2021 and February 2022 to explore their experiences of labor.

Results

Seven hundred twenty‐two women completed the online questionnaire. Two‐thirds (484; 67.2%) were in their 20s, and half (362; 50.1%) were from low socioeconomic households. A vast majority (508; 70.4%) delivered in a government hospital. Four out of ten (300; 41.6%) reported experiencing at least one form of OV. Among these women, the types of OV reported were physical (143; 47.8%), psychological (122; 40.8%), verbal (109; 36.4%), and sexual (13; 4.4%). Delivery in private facilities (adjusted odds ratio [AOR] 0.45, 95% confidence interval [CI] 0.32–0.74) and prior knowledge of the care provider (AOR 0.37, 95% CI 0.23–0.59) were both independently protective for OV. In contrast, women's awareness of OV increased their likelihood of reporting it (AOR 3.45, 95% CI 2.37–5.01).

Conclusion

GS has an alarming prevalence of reported OV. Increasing awareness of OV, identifying its causes, and developing locally led initiatives to eliminate it are urgently needed.
Endogenous endophthalmitis secondary to perirenal abscess
Authors: Lizana Nemecio , Parrao Diego , Larrañaga Matías , Figueroa‐Vercellino Juan P , Pozo Karen , Bravo Juan Cristóbal
Published: June 2023

Introduction

Endogenous Endophthalmitis is a rare ocular infection but with poor visual prognosis for most patients. Its most frequent etiology is Klebsiella spp., associated with hepatic abscesses and less frequently with perirenal abscesses.

Case presentation

We present a 61‐year‐old woman with a history of poorly controlled diabetes mellitus 2 that consulted several times for acute pyelonephritis with torpid evolution, associated with endogenous endophthalmitis in her right eye that required evisceration.

Conclusion

Adequate management of acute pyelonephritis can avoid local or distant complications, such as endogenous endophthalmitis, an infection with poor visual prognosis that requires high clinical suspicion for timely management with better visual outcomes and lower morbimortality.