bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Insight into Intraspecies Distinctions in Pseudoalteromonas distincta: Carotenoid-like Synthesis Traits and Genomic Heterogeneity
Authors: Balabanova Larissa , Nedashkovskaya Olga , Otstavnykh Nadezhda , Isaeva Marina , Kolpakova Oksana , Pentehina Iuliia , Seitkalieva Aleksandra , Noskova Yulia , Stepochkina Varvara , Son Oksana , Tekutyeva Liudmila
Published: February 2023

Advances in the computational annotation of genomes and the predictive potential of current metabolic models, based on more than thousands of experimental phenotypes, allow them to be applied to identify the diversity of metabolic pathways at the level of ecophysiology differentiation within taxa and to predict phenotypes, secondary metabolites, host-associated interactions, survivability, and biochemical productivity under proposed environmental conditions. The significantly distinctive phenotypes of members of the marine bacterial species Pseudoalteromonas distincta and an inability to use common molecular markers make their identification within the genus Pseudoalteromonas and prediction of their biotechnology potential impossible without genome-scale analysis and metabolic reconstruction. A new strain, KMM 6257, of a carotenoid-like phenotype, isolated from a deep-habituating starfish, emended the description of P. distincta, particularly in the temperature growth range from 4 to 37 °C. The taxonomic status of all available closely related species was elucidated by phylogenomics. P. distincta possesses putative methylerythritol phosphate pathway II and 4,4′-diapolycopenedioate biosynthesis, related to C30 carotenoids, and their functional analogues, aryl polyene biosynthetic gene clusters (BGC). However, the yellow-orange pigmentation phenotypes in some strains coincide with the presence of a hybrid BGC encoding for aryl polyene esterified with resorcinol. The alginate degradation and glycosylated immunosuppressant production, similar to brasilicardin, streptorubin, and nucleocidines, are the common predicted features. Starch, agar, carrageenan, xylose, lignin-derived compound degradation, polysaccharide, folate, and cobalamin biosynthesis are all strain-specific.
Multidimensional Profiling of Human Body Hairs Using Qualitative and Semi-Quantitative Approaches with SR-XRF, ATR-FTIR, DSC, and SEM-EDX
Authors: Cloete Karen J. , Šmit Žiga , Gianoncelli Alessandra
Published: February 2023

This study aimed to assess the potential of a multidimensional approach to differentiate body hairs based on their physico-chemical properties and whether body hairs can replace the use of scalp hair in studies linked to forensic and systemic intoxication. This is the first case report controlling for confounding variables to explore the utility of multidimensional profiling of body hair using synchrotron synchrotron microbeam X-ray fluorescence (SR-XRF) for longitudinal and hair morphological region mapping) and benchtop methods, including attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) (complemented with chemometrics analysis), energy dispersive X-ray analysis (EDX) (complemented with heatmap analysis), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) analysis (complemented by descriptive statistics) to profile different body hairs in terms of their elemental, biochemical, thermal, and cuticle properties. This multidimensional approach provided supportive information to emphasize the intricate and rather complex interplay between the organization and levels of elements and biomolecules within the crystalline and amorphous matrix of different body hairs responsible for the differences in physico-chemical properties between body hairs that are predominantly affected by the growth rate, follicle or apocrine gland activity, and external factors such as cosmetic use and exposure to environmental xenobiotics. The data from this study may have important implications for forensic science, toxicology and systemic intoxication, or other studies involving hair as a research matrix.
Application Progress of the Single Domain Antibody in Medicine
Authors: Tang Huaping , Gao Yuan , Han Jiangyuan
Published: February 2023

The camelid-derived single chain antibody (sdAb), also termed VHH or nanobody, is a unique, functional heavy (H)-chain antibody (HCAb). In contrast to conventional antibodies, sdAb is a unique antibody fragment consisting of a heavy-chain variable domain. It lacks light chains and a first constant domain (CH1). With a small molecular weight of only 12~15 kDa, sdAb has a similar antigen-binding affinity to conventional Abs but a higher solubility, which exerts unique advantages for the recognition and binding of functional, versatile, target-specific antigen fragments. In recent decades, with their unique structural and functional features, nanobodies have been considered promising agents and alternatives to traditional monoclonal antibodies. As a new generation of nano-biological tools, natural and synthetic nanobodies have been used in many fields of biomedicine, including biomolecular materials, biological research, medical diagnosis and immune therapies. This article briefly overviews the biomolecular structure, biochemical properties, immune acquisition and phage library construction of nanobodies and comprehensively reviews their applications in medical research. It is expected that this review will provide a reference for the further exploration and unveiling of nanobody properties and function, as well as a bright future for the development of drugs and therapeutic methods based on nanobodies.
Stable Expression of dmiR-283 in the Brain Promises Positive Effects in Endurance Exercise on Sleep–Wake Behavior in Aging Drosophila
Authors: Li Qiufang , Wang Lingxiao , Cao Yurou , Wang Xiaoya , Tang Chao , Zheng Lan
Published: February 2023

Sleep–wake stability is imbalanced with natural aging, and microRNAs (miRNAs) play important roles in cell proliferation, apoptosis, and aging; however, the biological functions of miRNAs in regulating aging-related sleep–wake behavior remain unexplored. This study varied the expression pattern of dmiR-283 in Drosophila and the result showed that the aging decline in sleep–wake behavior was caused by the accumulation of brain dmiR-283 expression, whereas the core clock genes cwo and Notch signaling pathway might be suppressed, which regulate the aging process. In addition, to identify exercise intervention programs of Drosophila that promote healthy aging, mir-283SP/+ and Pdf > mir-283SP flies were driven to perform endurance exercise for a duration of 3 weeks starting at 10 and 30 days, respectively. The results showed that exercise starting in youth leads to an enhanced amplitude of sleep–wake rhythms, stable periods, increased activity frequency upon awakening, and the suppression of aging brain dmiR-283 expression in mir-283SP/+ middle-aged flies. Conversely, exercise performed when the brain dmiR-283 reached a certain accumulation level showed ineffective or negative effects. In conclusion, the accumulation of dmiR-283 expression in the brain induced an age-dependent decline in sleep–wake behavior. Endurance exercise commencing in youth counteracts the increase in dmiR-283 in the aging brain, which ameliorates the deterioration of sleep–wake behavior during aging.
TGF-β-3 Induces Different Effects from TGF-β-1 and -2 on Cellular Metabolism and the Spatial Properties of the Human Trabecular Meshwork Cells
Authors: Watanabe Megumi , Sato Tatsuya , Tsugeno Yuri , Higashide Megumi , Furuhashi Masato , Ohguro Hiroshi
Published: February 2023

To compare the effects among three TGF-β isoforms (TGF-β-1, TGF-β-2, and TGF-β-3) on the human trabecular meshwork (HTM), two-dimensional (2D) and three-dimensional (3D) cultures of commercially available certified immortalized HTM cells were used, and the following analyses were conducted: (1) trans-endothelial electrical resistance (TEER) and FITC dextran permeability measurements (2D); (2) a real-time cellular metabolic analysis (2D); (3) analysis of the physical property of the 3D HTM spheroids; and (4) an assessment of the gene expression levels of extracellular matrix (ECM) components (2D and 3D). All three TGF-β isoforms induced a significant increase in TEER values and a relative decrease in FITC dextran permeability in the 2D-cultured HTM cells, but these effects were the most potent in the case of TGF-β-3. The findings indicated that solutions containing 10 ng/mL of TGF-β-1, 5 ng/mL of TGF-β-2, and 1 ng/mL of TGF-β-3 had nearly comparable effects on TEER measurements. However, a real-time cellular metabolic analysis of the 2D-cultured HTM cells under these concentrations revealed that TGF-3-β induced quite different effects on the metabolic phenotype, with a decreased ATP-linked respiration, increased proton leakage, and decreased glycolytic capacity compared with TGF-β-1 and TGF-β-2. In addition, the concentrations of the three TGF-β isoforms also caused diverse effects on the physical properties of 3D HTM spheroids and the mRNA expression of ECMs and their modulators, in many of which, the effects of TGF-β-3 were markedly different from TGF-β-1 and TGF-β-2. The findings presented herein suggest that these diverse efficacies among the TGF-β isoforms, especially the unique action of TGF-β-3 toward HTM, may induce different effects within the pathogenesis of glaucoma.
Genomic Survey of Flavin Monooxygenases in Wild and Cultivated Rice Provides Insight into Evolution and Functional Diversities
Authors: Gaba Yashika , Bhowal Bidisha , Pareek Ashwani , Singla-Pareek Sneh Lata
Published: February 2023

The flavin monooxygenase (FMO) enzyme was discovered in mammalian liver cells that convert a carcinogenic compound, N-N′-dimethylaniline, into a non-carcinogenic compound, N-oxide. Since then, many FMOs have been reported in animal systems for their primary role in the detoxification of xenobiotic compounds. In plants, this family has diverged to perform varied functions like pathogen defense, auxin biosynthesis, and S-oxygenation of compounds. Only a few members of this family, primarily those involved in auxin biosynthesis, have been functionally characterized in plant species. Thus, the present study aims to identify all the members of the FMO family in 10 different wild and cultivated Oryza species. Genome-wide analysis of the FMO family in different Oryza species reveals that each species has multiple FMO members in its genome and that this family is conserved throughout evolution. Taking clues from its role in pathogen defense and its possible function in ROS scavenging, we have also assessed the involvement of this family in abiotic stresses. A detailed in silico expression analysis of the FMO family in Oryza sativa subsp. japonica revealed that only a subset of genes responds to different abiotic stresses. This is supported by the experimental validation of a few selected genes using qRT-PCR in stress-sensitive Oryza sativa subsp. indica and stress-sensitive wild rice Oryza nivara. The identification and comprehensive in silico analysis of FMO genes from different Oryza species carried out in this study will serve as the foundation for further structural and functional studies of FMO genes in rice as well as other crop types.
The Link between Prostanoids and Cardiovascular Diseases
Authors: Beccacece Livia , Abondio Paolo , Bini Carla , Pelotti Susi , Luiselli Donata
Published: February 2023

Cardiovascular diseases are the leading cause of global deaths, and many risk factors contribute to their pathogenesis. In this context, prostanoids, which derive from arachidonic acid, have attracted attention for their involvement in cardiovascular homeostasis and inflammatory processes. Prostanoids are the target of several drugs, but it has been shown that some of them increase the risk of thrombosis. Overall, many studies have shown that prostanoids are tightly associated with cardiovascular diseases and that several polymorphisms in genes involved in their synthesis and function increase the risk of developing these pathologies. In this review, we focus on molecular mechanisms linking prostanoids to cardiovascular diseases and we provide an overview of genetic polymorphisms that increase the risk for cardiovascular disease.
Approaches for sRNA Analysis of Human RNA-Seq Data: Comparison, Benchmarking
Authors: Bezuglov Vitalik , Stupnikov Alexey , Skakov Ivan , Shtratnikova Victoria , Pilsner J. Richard , Suvorov Alexander , Sergeyev Oleg
Published: February 2023

Expression analysis of small noncoding RNA (sRNA), including microRNA, piwi-interacting RNA, small rRNA-derived RNA, and tRNA-derived small RNA, is a novel and quickly developing field. Despite a range of proposed approaches, selecting and adapting a particular pipeline for transcriptomic analysis of sRNA remains a challenge. This paper focuses on the identification of the optimal pipeline configurations for each step of human sRNA analysis, including reads trimming, filtering, mapping, transcript abundance quantification and differential expression analysis. Based on our study, we suggest the following parameters for the analysis of human sRNA in relation to categorical analyses with two groups of biosamples: (1) trimming with the lower length bound = 15 and the upper length bound = Read length − 40% Adapter length; (2) mapping on a reference genome with bowtie aligner with one mismatch allowed (-v 1 parameter); (3) filtering by mean threshold > 5; (4) analyzing differential expression with DESeq2 with adjusted p-value < 0.05 or limma with p-value < 0.05 if there is very little signal and few transcripts.
Response to Abemaciclib and Immunotherapy Rechallenge with Nivolumab and Ipilimumab in a Heavily Pretreated TMB-H Metastatic Squamous Cell Lung Cancer with CDKN2A Mutation, PIK3CA Amplification and TPS 80%: A Case Report
Authors: Dias e Silva Douglas , Borba Guilherme Bes , Beal Juliana Rodrigues , Botrus Gehan , Osawa Akemi , Araújo Sérgio Eduardo Alonso , Moura Fernando , Guendelmann Rafael Aliosha Kaliks , Uson Junior Pedro Luiz Serrano
Published: February 2023

Inactivation of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene is considerably more frequent in squamous cell lung cancer (SqCLC) than in other subtypes of lung cancer and may be a promising target for this histology. Here, we present the course of diagnosis and treatment of a patient with advanced SqCLC, harboring not only CDKN2A mutation but also PIK3CA amplification, Tumor Mutational Burden-High (>10 mutations/megabase), and a Tumor Proportion Score of 80%. After disease progression on multiple lines of chemotherapy and immunotherapy, he responded favorably to treatment with the CDK4/6i Abemaciclib and later achieved a durable partial response to immunotherapy rechallenge with a combination of anti-PD-1 and anti-CTLA-4, nivolumab, and ipilimumab.
Addressing Critical Issues Related to Storage and Stability of the Vault Nanoparticle Expressed and Purified from Komagataella phaffi
Authors: Tomaino Giulia , Pantaleoni Camilla , Ami Diletta , Pellecchia Filomena , Dutriaux Annie , Barbieri Linda , Garbujo Stefania , Natalello Antonino , Tortora Paolo , Frascotti Gianni
Published: February 2023

The vault nanoparticle is a eukaryotic assembly consisting of 78 copies of the 99-kDa major vault protein. They generate two cup-shaped symmetrical halves, which in vivo enclose protein and RNA molecules. Overall, this assembly is mainly involved in pro-survival and cytoprotective functions. It also holds a remarkable biotechnological potential for drug/gene delivery, thanks to its huge internal cavity and the absence of toxicity/immunogenicity. The available purification protocols are complex, partly because they use higher eukaryotes as expression systems. Here, we report a simplified procedure that combines human vault expression in the yeast Komagataella phaffii, as described in a recent report, and a purification process we have developed. This consists of RNase pretreatment followed by size-exclusion chromatography, which is far simpler than any other reported to date. Protein identity and purity was confirmed by SDS-PAGE, Western blot and transmission electron microscopy. We also found that the protein displayed a significant propensity to aggregate. We thus investigated this phenomenon and the related structural changes by Fourier-transform spectroscopy and dynamic light scattering, which led us to determine the most suitable storage conditions. In particular, the addition of either trehalose or Tween-20 ensured the best preservation of the protein in native, soluble form.
NUF2 Promotes Breast Cancer Development as a New Tumor Stem Cell Indicator
Authors: Deng Yang , Li Jiapeng , Zhang Yingjie , Hu Hao , Wan Fujian , Min Hang , Zhou Hao , Gu Lixing , Liao Xinghua , Zhou Jingjiao , Zhou Jun
Published: February 2023

Multiple new subtypes of breast cancer (BRCA) are identified in women each year, rendering BRCA the most common and rapidly expanding form of cancer in females globally. NUF2 has been identified as a prognostic factor in various human cancers, regulating cell apoptosis and proliferation. However, its role in BRCA prognosis has not been clarified. This study explored the role of NUF2 in breast cancer development and prognosis using informatic analysis combined with in vivo intracellular studies. Through the online website TIMER, we evaluated the transcription profile of NUF2 across a variety of different cancer types and found that NUF2 mRNA was highly expressed in BRCA patients. Its transcription level was found to be related to the subtype, pathological stage, and prognosis of BRCA. The R program analysis showed a correlation of NUF2 with cell proliferation and tumor stemness in the BRCA patient samples. Subsequently, the association between the NUF2 expression level and immune cell infiltration was analyzed using the XIANTAO and TIMER tools. The results revealed that NUF2 expression was correlated with the responses of multiple immune cells. Furthermore, we observed the effect of NUF2 expression on tumor stemness in BRCA cell lines in vivo. The experimental results illuminated that the overexpression of NUF2 statistically upregulated the proliferation and tumor stemness ability of the BRCA cell lines MCF-7 and Hs-578T. Meanwhile, the knockdown of NUF2 inhibited the abilities of both cell lines, a finding which was verified by analyzing the subcutaneous tumorigenic ability in nude mice. In summary, this study suggests that NUF2 may play a key role in the development and progression of BRCA by affecting tumor stemness. As a stemness indicator, it has the potential to be one of the markers for the diagnosis of BRCA.
Litter Deposition and Nutrient Cycling of Invaded Environments by Cryptostegia madagascariensis at Tropical Cambisols from Northeastern Brazil
Authors: Souza Tancredo , Lucena Edjane Oliveira de , de Andrade Leonaldo Alves , da Silva Lucas Jónatan Rodrigues , Nascimento Gislaine dos Santos , Freitas Helena
Published: February 2023

Cryptostegia madagascariensis is an invasive plant species that covers 11% of the Brazilian northeastern territory, but its role on the litter trait in tropical ecosystems remains unclear. Here, we analyzed and compared the litter deposition, litter nutrient content, soil organic matter, and the litter decay rate from invaded and non-invaded environments by C. madagascariensis at a tropical Cambisol. The PCA analysis revealed that litter deposition, litter quality, and soil organic matter were correlated with the invaded environment. We grew plant species in greenhouse conditions to obtain a standard litter material to use in our litter bags in field conditions. We found that litter decay rate was higher in the invaded environment than in the non-invaded one. Our results suggest that C. madagascariensis changes litter traits in tropical ecosystems that in turn create negative plant–soil feedback to the native species by creating a physical barrier on soil surface and to promote its own rhizosphere.
Reconsidering Read and Spontaneous Speech: Causal Perspectives on the Generation of Training Data for Automatic Speech Recognition
Authors: Gabler Philipp , Geiger Bernhard C. , Schuppler Barbara , Kern Roman
Published: February 2023

Superficially, read and spontaneous speech—the two main kinds of training data for automatic speech recognition—appear as complementary, but are equal: pairs of texts and acoustic signals. Yet, spontaneous speech is typically harder for recognition. This is usually explained by different kinds of variation and noise, but there is a more fundamental deviation at play: for read speech, the audio signal is produced by recitation of the given text, whereas in spontaneous speech, the text is transcribed from a given signal. In this review, we embrace this difference by presenting a first introduction of causal reasoning into automatic speech recognition, and describing causality as a tool to study speaking styles and training data. After breaking down the data generation processes of read and spontaneous speech and analysing the domain from a causal perspective, we highlight how data generation by annotation must affect the interpretation of inference and performance. Our work discusses how various results from the causality literature regarding the impact of the direction of data generation mechanisms on learning and prediction apply to speech data. Finally, we argue how a causal perspective can support the understanding of models in speech processing regarding their behaviour, capabilities, and limitations.
Co-Channel Interference Management for Heterogeneous Networks Using Deep Learning Approach
Authors: Ahmad Ishtiaq , Hussain Sajjad , Mahmood Sarmad Nozad , Mostafa Hala , Alkhayyat Ahmed , Marey Mohamed , Abbas Ali Hashim , Abdulateef Rashed Zainab
Published: February 2023

The co-channel interference for mobile users (MUs) of a public safety network (PSN) in the co-existence of heterogeneous networks such as unmanned aerial vehicles (UAVs) and LTE-based railway networks (LRNs) needs a thorough investigation, where UAVs are deployed as mobile base stations (BSs) for cell-edge coverage enhancement. Moreover, the LRN is employed for the train, and its control signal demands high reliability and low latency. It is necessary to provide higher priority to LRN users when allocating resources from shared radio access channels (RACs). By considering both sharing and non-sharing of RACs, co-channel interference was analyzed in the downlink network of the PSN, UAV, and LRN. By offloading more PSN MUs to the LRN or UAVs, the resource utilization of the LRN and UAV BSs was enhanced. In this paper, we aimed to adopt deep-learning (DL)-based enhanced inter-cell interference coordination (eICIC) and further enhanced ICIC (FeICIC) strategies to deal with the interference from the PSN to the LRN and UAVs. Moreover, a DL-based coordinated multipoint (CoMP) for coordinated scheduling technique was utilized along with FeICIC and eICIC to enhance the performance of PSN MUs. In the simulation results, the performance of DL-based interference management was compared with simple eICI, FeICIC, and coordinated scheduling CoMP. The DL-based FeICIC and CoMP for coordinated scheduling performed best with shared RACs.
Bioconversion of Different Waste Streams of Animal and Vegetal Origin and Manure by Black Soldier Fly Larvae Hermetia illucens L. (Diptera: Stratiomyidae)
Authors: Naser El Deen Somaya , van Rozen Klaas , Elissen Hellen , van Wikselaar Piet , Fodor Istvan , van der Weide Rommie , Hoek-van den Hil Elise Federica , Rezaei Far Arya , Veldkamp Teun
Published: February 2023

Black soldier fly larvae (BSFL) are considered a commercially viable solution for global organic waste problems. The objective of this study was to assess the feasibility of rearing BSFL on a wide range of low-value waste streams and its potential to transform them into high-quality animal feed and fertilizer. Six waste streams of different origins were selected and each tested in triplicate. Several parameters were analysed: growth performance, waste reduction index (WRI), conversion efficiency (ECI) and larval composition. Frass composition was also analysed. Larvae reared on fast food waste (FFW) had the highest ECI and WRI and the lowest values when reared on pig manure slurry mixed with silage grass (PMLSG) and slaughter waste (SW). The highest protein content was found for larvae reared on mushroom stems (MS) although this substrate had the lowest protein content. Moreover, the frass nutritional profile was proportionally related to the substrate’s nutritional profile: the protein-rich substrate (SW) resulted in protein-rich frass and the low-protein substrate (MS) resulted in protein-poor frass. The same was true for the lipid content. In conclusion, this study showed that BSFL can be successfully reared on a wide range of waste streams that can affect the larval and frass chemical compositions.
Mating-Induced Common and Sex-Specific Behavioral, Transcriptional Changes in the Moth Fall Armyworm (Spodoptera frugiperda, Noctuidae, Lepidoptera) in Laboratory
Authors: Wu Ting , Cao Da-Hu , Liu Yu , Yu Hong , Fu Da-Ying , Ye Hui , Xu Jin
Published: February 2023

The intermediate process between mating and postmating behavioral changes in insects is still poorly known. Here, we studied mating-induced common and sex-specific behavioral and transcriptional changes in both sexes of Spodoptera frugiperda and tested whether the transcriptional changes are linked to postmating behavioral changes in each sex. A behavioral study showed that mating caused a temporary suppression of female calling and male courting behavior, and females did not lay eggs until the next day after the first mating. The significant differences on daily fecundity under the presence of males or not, and the same or novel males, suggest that females may intentionally retain eggs to be fertilized by novel males or to be fertilized competitively by different males. RNA sequencing in females revealed that there are more reproduction related GO (gene ontology) terms and KEGG (Kyoto encyclopedia of genes and genomes) pathways (mainly related to egg and zygote development) enriched to upregulated DEGs (differentially expressed genes) than to downregulated DEGs at 0 and 24 h postmating. In males, however, mating induced DEGs did not enrich any reproduction related terms/pathways, which may be because male reproductive bioinformatics is relatively limited in moths. Mating also induced upregulation on soma maintenance (such as immune activity and stress reaction) related processes in females at 0, 6 and 24 h postmating. In males, mating also induced upregulation on soma maintenance related processes at 0 h postmating, but induced downregulation on these processes at 6 and 24 h postmating. In conclusion, this study demonstrated that mating induced sex-specific postmating behavioral and transcriptional changes in both sexes of S. frugiperda and suggested that the transcriptional changes are correlated with postmating physiological and behavioral changes in each sex.
Preliminary Evidence That Fiji Water Has Protective Effects against Aluminum Toxicity in Honey Bees (Apis mellifera)
Authors: Stauch Kiri Li N. , Chicas-Mosier Ana M. , Abramson Charles I.
Published: February 2023

Researchers have determined that bioavailable aluminum chloride (AlCl3) may affect honey bee behavior (e.g., foraging patterns and locomotion) and physiology (e.g., abdominal spasms). The purpose of these experiments was to determine if Fiji water reduces the impacts of AlCl3 toxicity in bees by measuring circadian rhythmicity (number of times bees crossed the centerline during the day and night), average daily activity (average number of times bees crossed the centerline per day), and mortality rates (average number of days survived) using an automated monitor apparatus. Overall, the AlCl3 before and after Fiji groups had significantly higher average daily activity and rhythmicity rates compared to their respective AlCl3 before and after deionized water (DI) groups. One of the AlCl3 before DI groups exhibited no difference in rhythmicity rates compared to its respective AlCl3 after Fiji group. Overall, these results suggest that Fiji water might exert protective effects against AlCl3. The AlCl3 groups paired with Fiji water had higher activity and rhythmicity levels compared to the AlCl3 groups paired with DI. It is important for researchers to continue to study aluminum and possible preventatives for aluminum uptake.
Impact of COVID-19 Pandemic on Frontline Pembrolizumab-Based Treatment for Advanced Lung Cancer
Authors: Tanvetyanon Tawee , Chen Dung-Tsa , Gray Jhanelle E.
Published: February 2023

Background: Pembrolizumab monotherapy or pembrolizumab plus chemotherapy has become an important frontline treatment for advanced non-small cell lung cancer (NSCLC). To date, it remains unclear how the coronavirus disease 2019 (COVID-19) pandemic impacted the treatment outcome. Methods: A quasi-experimental study was conducted based on a real-world database, comparing pandemic with pre-pandemic patient cohorts. The pandemic cohort consisted of patients who initiated treatment from March to July 2020, with follow-up through March 2021. The pre-pandemic cohort consisted of those initiating treatment between March and July 2019.The outcome was overall real-world survival. Multivariable Cox-proportional hazard models were constructed. Results: Analyses included data from 2090 patients: 998 in the pandemic cohort and 1092 in the pre-pandemic cohort. Baseline characteristics were comparable, with 33% of patients having PD-L1 expression level ≥50% and 29% of patients receiving pembrolizumab monotherapy. Among those treated with pembrolizumab monotherapy (N = 613), there was a differential impact of the pandemic on survival by PD-L1 expression levels (p-interaction = 0.02). For those with PD-L1 level < 50%, survival was better in the pandemic cohort than the pre-pandemic cohort: hazard ratio (HR) 0.64 (95% CI: 0.43–0.97, p = 0.03). However, for those with PD-L1 level ≥ 50%, survival was not better in the pandemic cohort: HR 1.17 (95% CI: 0.85–1.61, p = 0.34). We found no statistically significant impact of the pandemic on survival among patients treated with pembrolizumab plus chemotherapy. Conclusions: The COVID-19 pandemic was associated with an increase in survival among patients with lower PD-L1 expression who were treated with pembrolizumab monotherapy. This finding suggests an increased efficacy of immunotherapy due to viral exposure in this population.
Exploring the Cardiotoxicity Spectrum of Anti-Cancer Treatments: Definition, Classification, and Diagnostic Pathways
Authors: Mauro Ciro , Capone Valentina , Cocchia Rosangela , Cademartiri Filippo , Riccardi Ferdinando , Arcopinto Michele , Alshahid Maie , Anwar Kashif , Carafa Mariano , Carbone Andreina , Castaldo Rossana , Chianese Salvatore , Crisci Giulia , D’Assante Roberta , De Luca Mariarosaria , Franzese Monica , Galzerano Domenico , Maffei Vincenzo , Marra Alberto Maria , Mazza Alfredo , Ranieri Brigida , D’Agostino Anna , Rega Salvatore , Romano Luigia , Scagliarini Sarah , Sepe Chiara , Vriz Olga , Izzo Raffaele , Cittadini Antonio , Bossone Eduardo , Salzano Andrea
Published: February 2023

Early detection and treatment of cancer have led to a noticeable reduction in both mortality and morbidity. However, chemotherapy and radiotherapy could exert cardiovascular (CV) side effects, impacting survival and quality of life, independent of the oncologic prognosis. In this regard, a high clinical index of suspicion is required by the multidisciplinary care team in order to trigger specific laboratory tests (namely natriuretic peptides and high-sensitivity cardiac troponin) and appropriate imaging techniques (transthoracic echocardiography along with cardiac magnetic resonance, cardiac computed tomography, and nuclear testing (if clinically indicated)), leading to timely diagnosis. In the near future, we do expect a more tailored approach to patient care within the respective community along with the widespread implementation of digital health tools.
Early Strokes Are Associated with More Global Cognitive Deficits in Adults with Sickle Cell Disease
Authors: Couette Maryline , Forté Stéphanie , Oudin Doglioni Damien , Mekontso-Dessap Armand , Calvet David , Kuo Kevin H. M. , Bartolucci Pablo
Published: February 2023

This study sought to link neurocognitive profiles in sickle cell disease (SCD) patients with clinical characteristics. We conducted a prospective cohort study of adults with SCD who underwent comprehensive neuropsychological assessment at the UMGGR clinic at Henri Mondor Hospital, Créteil (France). A cluster analysis was performed based on neuropsychological testing scores. The association between clusters and clinical profiles was assessed. Between 2017 and 2021, 79 patients with a mean age of 36 [range 19–65] years were included. On principal component analysis, a 5-factor model presented the best fit (Bartlett’s sphericity test [χ2 (171) = 1345; p < 0.001]), explaining 72% of the variance. The factors represent distinct cognitive domains and anatomical regions. On hierarchical classification, three clusters emerged. Cluster 1 (n = 24) presented deficits in all five factors compared to Cluster 3 (n = 33). Cluster 2 (n = 22) had deficits in all factors, but to a lesser extent than Cluster 1. MoCA scores mirrored the severity of these cognitive deficits. Age, genotype and stroke prevalence did not differ significantly between clusters. However, the time of first stroke occurrence differed significantly between Cluster 1 and 2–3: 78% of strokes occurred during childhood, whereas 80% and 83% occurred during adulthood in Clusters 2 and 3, respectively. Educational attainment was also reduced in Cluster 1. SCD patients with childhood stroke seem to be at increased risk of a global cognitive deficit profile. In addition to existing methods of primary and secondary stroke prevention, early neurorehabilitation should be prioritized in order to reduce the long-term cognitive morbidity of SCD.
Challenges for Optimization of Reverse Shoulder Arthroplasty Part II: Subacromial Space, Scapular Posture, Moment Arms and Muscle Tensioning
Authors: Bauer Stefan , Blakeney William G. , Wang Allan W. , Ernstbrunner Lukas , Corbaz Jocelyn , Werthel Jean-David
Published: February 2023

In part II of this comprehensive review on the optimization of reverse shoulder arthroplasty (RSA), we focus on three other challenges: 1. “Conservation of sufficient subacromial and coracohumeral space”; 2. “Scapular posture”; and 3. “Moment arms and muscle tensioning”. This paper follows a detailed review of the basic science and clinical literature of the challenges in part I: 1. “External rotation and extension” and 2. “Internal rotation”. “Conservation of sufficient subacromial and coracohumeral space” and “Scapular posture” may have a significant impact on the passive and active function of RSA. Understanding the implications of “Moment arms and muscle tensioning” is essential to optimize active force generation and RSA performance. An awareness and understanding of the challenges of the optimization of RSA help surgeons prevent complications and improve RSA function and raise further research questions for ongoing study.
Blastocyst Transplantation Strategies in Women of Different Ages
Authors: Yang Dandan , Chai Menghan , Yang Ni , Yang Han , Wen Xingxing , Wang Jing , Fan Yongqi , Cao Yunxia , Zhang Zhiguo , Chen Beili
Published: February 2023

(1) Background: Single blastocyst transfers (SBT) and double blastocyst transfers (DBT) are widely used in clinical practice. The objective of this study was to investigate the application of these two strategies in women of different ages. (2) Methods: Analysis was carried out on 5477 frozen embryo transfer cycles of women in different ages. All the cycles were divided into three groups according to the age of the included women: <35, 35–39, and >39. The live birth rate (LBR) and multiple birth rate (MBR) between the SBT and DBT among these groups, respectively, were compared. (3) Results: In the women < 35 group, the LBR was similar in SBT and DBT, but the MBR was higher in DBT than SBT. In women 35–39, with >10 oocytes retrieved, the MBR in DBT was significantly higher than SBT, but there was no significant difference in LBR between the two groups; with ≤10 oocytes retrieved, the LBR in DBT were significantly higher than SBT, but the MBT was not significantly different between the two groups. In women > 39, the LBR and MBR were lower in the SBT than DBT, but the differences were not statistically significant. (4) Conclusions: Selective SET is appropriate for most young women, whereas older women are advised to make individualized choices based on the number of oocytes retrieved and blastocyst quality.
Dietary Fiber Intake Influences Changes in Ankylosing Spondylitis Disease Status
Authors: Song Chuan , Wang Lei , Ji Xiaojian , Wang Yiwen , Hu Lidong , Liu Xingkang , Zhang Jiaxin , Liao Simin , Yan Yishu , Zhu Jian , Huang Feng
Published: February 2023

The objectives of this study were to characterize dietary fiber (DF) intake in patients with ankylosing spondylitis (AS), to assess whether DF intake affects disease activity in AS, and to investigate the effect of DF intake on disease activity in AS in the context of functional bowel disease (FBD) symptoms. We recruited 165 patients with AS and divided them into two groups according to whether they had a high DF intake > 25 g/d to investigate the characteristics of people with high DF intake. Some 72 of the 165 AS patients (43%) met the criteria for high DF intake, which was more common in patients with negative FBD symptoms (68%). Data analysis revealed that DF intake was negatively associated with AS disease activity and did not differ statistically significantly from FBD symptoms. Multivariate adjusted models were used to explore the effect of DF intake on AS disease activity. ASDAS-CRP and BASDAI were stable and negatively correlated across models in both groups with and without FBD symptoms. Thus, DF intake positively affected disease activity in patients with AS. ASDAS-CRP and BASDAI were negatively correlated with DF intake.
Temporary Mechanical Circulatory Support in Patients with Cardiogenic Shock: Clinical Characteristics and Outcomes
Authors: Abiragi Michael , Singer-Englar Tahli , Cole Robert M. , Emerson Dominic , Esmailian Fardad , Megna Dominick , Moriguchi Jaime , Kobashigawa Jon A. , Kittleson Michelle M.
Published: February 2023

Patients with cardiogenic shock may require stabilization with temporary mechanical circulatory support (tMCS) to assess candidacy for definitive therapy, including heart transplantation (HTx) or durable MCS, and/or maintain stability while on the HTx waiting list. We describe the clinical characteristics and outcomes of patients with cardiogenic shock who underwent intra-aortic balloon pump (IABP) vs. Impella [Abiomed, Danvers, MA, USA] placement at a high-volume advanced heart failure center. We assessed patients ≥ 18 years who received IABP or Impella support for cardiogenic shock from 1 January 2020 to 31 December 2021. Ninety patients were included, 59 (65.6%) with IABP and 31 (34.4%) with Impella. Impella was used more frequently in less stable patients, as evidenced by higher inotrope scores, greater ventilator support, and worse renal function. While patients on Impella support had higher in-hospital mortality, despite the worse cardiogenic shock in patients for whom clinicians chose Impella support, over 75% were successfully stabilized to recovery or transplantation. Clinicians elect Impella support over IABP for less stable patients, though a high proportion are successfully stabilized. These findings demonstrate the heterogeneity of the cardiogenic shock patient population and may inform future trials to assess the role of different tMCS devices.
The Rate of Avoidable Pancreatic Resections at a High-Volume Center: An Internal Quality Control and Critical Review
Authors: Surci Niccolò , Rösch Christiane , Kirchweger Patrick , Havranek Lukas , von Boetticher Paul , Fischer Ines , Wundsam Helwig , Biebl Matthias , Függer Reinhold
Published: February 2023

Background: The incidence of benign diseases among pancreatic resections for suspected malignancy still represents a relevant issue in the surgical practice. This study aims to identify the preoperative pitfalls that led to unnecessary surgeries at a single Austrian center over a twenty-year period. Methods: Patients undergoing surgery for suspected pancreatic/periampullary malignancy between 2000 and 2019 at the Linz Elisabethinen Hospital were included. The rate of “mismatches” between clinical suspicion and histology was considered as primary outcome. All cases that, despite that, fulfilled the indication criteria for surgery were defined as minor mismatches (MIN-M). Conversely, the true avoidable surgeries were identified as major mismatches (MAJ-M). Results: Among the 320 included patients, 13 (4%) presented with benign lesions at definitive pathology. The rate of MAJ-M was 2.8% (n = 9), and the most frequent causes of misdiagnoses were autoimmune pancreatitis (n = 4) and intrapancreatic accessory spleen (n = 2). In all MAJ-M cases, various mistakes within the preoperative workup were detected: lack of multidisciplinary discussion (n = 7, 77.8%); inappropriate imaging (n = 4, 44.4%); lack of specific blood markers (n = 7, 77.8%). The morbidity and mortality rates for mismatches were 46.7% and 0. Conclusion: All avoidable surgeries were the result of an incomplete pre-operative workup. The adequate identification of the underlying pitfalls could lead to minimize and, potentially, overcome this phenomenon with a concrete optimization of the surgical-care process.
Clinical Impacts of Interventions for Physical Activity and Sedentary Behavior on Patients with Chronic Obstructive Pulmonary Disease
Authors: Tashiro Hiroki , Takahashi Koichiro
Published: February 2023

Recently, physical activity has increasingly become the focus in patients with chronic obstructive airway disease (COPD) because it is a strong predictor of COPD-related mortality. In addition, sedentary behavior, which is included as a category of physical inactivity including such behaviors as sitting or lying down, has an independent clinical impact on COPD patients. The present review examines clinical data related to physical activity, focusing on the definition, associated factors, beneficial effects, and biological mechanisms in patients with COPD and with respect to human health regardless of COPD. The data related to how sedentary behavior is associated with human health and COPD outcomes are also examined. Lastly, possible interventions to improve physical activity or sedentary behavior, such as bronchodilators and pulmonary rehabilitation with behavior modification, to ameliorate the pathophysiology of COPD patients are described. A better understanding of the clinical impact of physical activity or sedentary behavior may lead to the planning of a future intervention study to establish high-level evidence.
Weight-Based Bisphosphonate Administration for Multiple Myeloma Patients and the Risks of Skeletal Complications
Authors: Bahk Ji Hoon , Jo Woo-Lam , Kwon Soon-Yong , Park Hyung Chul , Lim Young Wook
Published: February 2023

High-dose bisphosphonate for multiple myeloma patients might elevate risks of skeletal complications earlier than general expectations. This study aims to find incidences of atypical femoral fracture (AFF) and medication-related osteonecrosis of the jaw (MRONJ), elucidate their risk factors, and suggest cut-off values for the safer dosing of high-dose bisphosphonate treatment. By using the clinical data warehouse of a single institute, retrospective cohort data of multiple myeloma-diagnosed patients with high-dose bisphosphonate (pamidronate or zoledronate) treatment from 2009 to 2019 was extracted. Among 644 patients, the incidence of prominent AFF requiring surgery was 0.93% (6/644) and MRONJ was diagnosed in 11.8% (76/644) of the study population. For both AFF and MRONJ, the total potency-weighted sum of total dose per body weight (OR = 1.010, p = 0.005) were significant on logistic regression. Cutoffs of the potency-weighted total dose (mg) per body weight (kg) for AFF and MRONJ were 77.00 and 57.70 mg/kg, respectively. After roughly one year of treatment with high-dose zoledronate (about four years for pamidronate), an earlier thorough re-evaluation of skeletal complications should be taken. Body weight adjustments for accumulative dose calculation in terms of permissible dosing should be taken into consideration.
Can Methotrexate Be Employed as Monotherapy for Bullous Pemphigoid? Analysis of Efficiency and Tolerance of Methotrexate Treatment in Patients with Bullous Pemphigoid
Authors: Wojtczak Magdalena , Nolbrzak Amanda , Woźniacka Anna , Żebrowska Agnieszka
Published: February 2023

The European Academy of Dermatology and Venerology (EADV) consensus states that the treatment of choice for bullous pemphigoid is systemic glucocorticosteroid therapy. Bearing in mind that long-term steroid therapy is associated with numerous side effects, an effective and safer treatment regimen for these patients is still being sought. A retrospective analysis was performed of the medical reports of patients with diagnosed bullous pemphigoid. The study included 40 patients with moderate or severe disease, and who had continued ambulatory treatment for at least six months. The patients were divided into two groups: one treated with methotrexate in monotherapy, or with combined methotrexate and systemic steroid therapy. A slightly better survival rate was noted in the methotrexate group. No significant differences were observed between the groups in time to achieve clinical remission. The combination therapy group demonstrated more frequent disease recurrence and exacerbations during treatment, and a higher mortality rate. None of the patients in either group presented with severe side effects related to methotrexate treatment. The treatment of bullous pemphigoid with methotrexate in monotherapy is an effective and safe therapeutic method for elderly patients.
Chitotriosidase and Neopterin as Potential Biomarkers for the Evaluation of Complicated Cholecystitis—A Pilot Study
Authors: Nechita Vlad-Ionuţ , Hajjar Nadim Al , Drugan Cristina , Cătană Cristina-Sorina , Moiş Emil , Nechita Mihaela-Ancuţa , Graur Florin
Published: February 2023

Gallstones are a common surgical pathology. Laparoscopic cholecystectomy represents the elective treatment. Complicated cases can increase the rate of conversion, the duration, and the difficulty of the intervention, along with the hospitalization period. A prospective cohort study was conducted on 51 patients with gallstones. Only subjects with normal renal, pancreatic, and hepatic functions were included. The severity of cholecystitis was evaluated by considering the ultrasound examination, intraoperative findings, and pathology report. We evaluated two potential biomarkers, namely neopterin and chitotriosidase, by comparing their levels before and after the intervention for chronic (n = 36) and complicated (n = 15) cases, as well as their eventual association with the hospitalization period. Subjects with complicated cholecystitis had significantly higher (p = 0.01) neopterin levels at presentation (16.82 nmol/L vs. 11.92 nmol/L, median values), but the differences in chitotriosidase activity between complicated (170.00 nmol/mL/h) and chronic (160.00 nmol/mL/h) cases were not significant (p = 0.66). Patients with neopterin levels above the cut-off value 14.69 nmol/L had a 3.34 times higher risk of complicated cholecystitis. Twenty-four hours after the laparoscopic cholecystectomy, the differences in neopterin level and chitotriosidase activity between chronic and complicated cases were not significant. A significant decrease in chitotriosidase activity was observed after the intervention, only for complicated cases (190 nmol/mL/h vs. 145 nmol/mL/h, p = 0.007); for neopterin, the postoperative decrease was not statistically significant (19.42 nmol/L vs. 10.92 nmol/L, p = 0.06). No significant association with the hospitalization period was observed. Neopterin may be a useful biomarker for complicated cholecystitis, and chitotriosidase may have prognostic utility in early patient follow-up.