bluuebunny/crossref_metadata_2025 huggingface dataset:
Active Corrosion Protection by Epoxy Coating on Li2CO3-Pretreated Anodized Aluminum Alloy 2024-T3
Authors: Minhas Badar , Dino Sahib , Huang Luyao , Wu Dequan
Published: January 2022

The fast leaching and robust barrier property of inhibitors are the basic fundamentals for the formation of active protective coatings to protect aluminum alloys. Herein, an active protective surface was developed based on an epoxy coating and an underlying lithium carbonate (Li2CO3)-treated anodized aluminum alloy 2024-T3. The morphology of the Li-LDH layer was studied to know its formation mechanism. The electrochemical studies revealed that the fast and adequate leaching of lithium led to a substantial increment of corrosion resistance of the scratched coating in 3.5 wt% NaCl from 1 to 8 days. Time of flight secondary ion mass spectroscopy (ToF-SIMS) results indicated that Li was distributed in the lateral direction and covered the scratched area. The 3D images indicated that different lithium compounds were formed and 90% of the scratched area was covered with the lithium protective layer over immersion time. A combined approach of morphology observations, electrochemical measurements, and ToF-SIMS showed the lithium protective layer offered good corrosion resistance. On the contrary, lithium provided fast and adequate leaching from the coating, demonstrating good active protection for aluminum and its alloys.
Multi-Scale Imaging of Vascular Pathologies in Cardiovascular Disease
Authors: Tiwari Ashish , Elgrably Betsalel , Saar Galit , Vandoorne Katrien
Published: January 2022

Cardiovascular disease entails systemic changes in the vasculature. The endothelial cells lining the blood vessels are crucial in the pathogenesis of cardiovascular disease. Healthy endothelial cells direct the blood flow to tissues as vasodilators and act as the systemic interface between the blood and tissues, supplying nutrients for vital organs, and regulating the smooth traffic of leukocytes into tissues. In cardiovascular diseases, when inflammation is sensed, endothelial cells adjust to the local or systemic inflammatory state. As the inflamed vasculature adjusts, changes in the endothelial cells lead to endothelial dysfunction, altered blood flow and permeability, expression of adhesion molecules, vessel wall inflammation, thrombosis, angiogenic processes, and extracellular matrix production at the endothelial cell level. Preclinical multi-scale imaging of these endothelial changes using optical, acoustic, nuclear, MRI, and multimodal techniques has progressed, due to technical advances and enhanced biological understanding on the interaction between immune and endothelial cells. While this review highlights biological processes that are related to changes in the cardiac vasculature during cardiovascular diseases, it also summarizes state-of-the-art vascular imaging techniques. The advantages and disadvantages of the different imaging techniques are highlighted, as well as their principles, methodologies, and preclinical and clinical applications with potential future directions. These multi-scale approaches of vascular imaging carry great potential to further expand our understanding of basic vascular biology, to enable early diagnosis of vascular changes and to provide sensitive diagnostic imaging techniques in the management of cardiovascular disease.
The Prognostic Capacity of the Radiographic Assessment for Lung Edema Score in Patients With COVID-19 Acute Respiratory Distress Syndrome—An International Multicenter Observational Study
Authors: Valk Christel M. A. , Zimatore Claudio , Mazzinari Guido , Pierrakos Charalampos , Sivakorn Chaisith , Dechsanga Jutamas , Grasso Salvatore , Beenen Ludo , Bos Lieuwe D. J. , Paulus Frederique , Schultz Marcus J. , Pisani Luigi
Published: January 2022

Background: The radiographic assessment for lung edema (RALE) score has an association with mortality in patients with acute respiratory distress syndrome (ARDS). It is uncertain whether the RALE scores at the start of invasive ventilation or changes thereof in the next days have prognostic capacities in patients with COVID-19 ARDS.

Aims and Objectives: To determine the prognostic capacity of the RALE score for mortality and duration of invasive ventilation in patients with COVID-19 ARDS.

Methods: An international multicenter observational study included consecutive patients from 6 ICUs. Trained observers scored the first available chest X-ray (CXR) obtained within 48 h after the start of invasive ventilation (“baseline CXR”) and each CXRs thereafter up to day 14 (“follow-up CXR”). The primary endpoint was mortality at day 90. The secondary endpoint was the number of days free from the ventilator and alive at day 28 (VFD-28).

Results: A total of 350 CXRs were scored in 139 patients with COVID-19 ARDS. The RALE score of the baseline CXR was high and was not different between survivors and non-survivors (33 [24–38] vs. 30 [25–38], P = 0.602). The RALE score of the baseline CXR had no association with mortality (hazard ratio [HR], 1.24 [95% CI 0.88–1.76]; P = 0.222; area under the receiver operating characteristic curve (AUROC) 0.50 [0.40–0.60]). A change in the RALE score over the first 14 days of invasive ventilation, however, had an independent association with mortality (HR, 1.03 [95% CI 1.01–1.05]; P < 0.001). When the event of death was considered, there was no significant association between the RALE score of the baseline CXR and the probability of being liberated from the ventilator (HR 1.02 [95% CI 0.99–1.04]; P = 0.08).

Conclusion: In this cohort of patients with COVID-19 ARDS, with high RALE scores of the baseline CXR, the RALE score of the baseline CXR had no prognostic capacity, but an increase in the RALE score in the next days had an association with higher mortality.
A Genomic Perspective Across Earth’s Microbiomes Reveals That Genome Size in Archaea and Bacteria Is Linked to Ecosystem Type and Trophic Strategy
Authors: Rodríguez-Gijón Alejandro , Nuy Julia K. , Mehrshad Maliheh , Buck Moritz , Schulz Frederik , Woyke Tanja , Garcia Sarahi L.
Published: January 2022

Our view of genome size in Archaea and Bacteria has remained skewed as the data has been dominated by genomes of microorganisms that have been cultivated under laboratory settings. However, the continuous effort to catalog Earth’s microbiomes, specifically propelled by recent extensive work on uncultivated microorganisms, provides an opportunity to revise our perspective on genome size distribution. We present a meta-analysis that includes 26,101 representative genomes from 3 published genomic databases; metagenomic assembled genomes (MAGs) from GEMs and stratfreshDB, and isolates from GTDB. Aquatic and host-associated microbial genomes present on average the smallest estimated genome sizes (3.1 and 3.0 Mbp, respectively). These are followed by terrestrial microbial genomes (average 3.7 Mbp), and genomes from isolated microorganisms (average 4.3 Mbp). On the one hand, aquatic and host-associated ecosystems present smaller genomes sizes in genera of phyla with genome sizes above 3 Mbp. On the other hand, estimated genome size in phyla with genomes under 3 Mbp showed no difference between ecosystems. Moreover, we observed that when using 95% average nucleotide identity (ANI) as an estimator for genetic units, only 3% of MAGs cluster together with genomes from isolated microorganisms. Although there are potential methodological limitations when assembling and binning MAGs, we found that in genome clusters containing both environmental MAGs and isolate genomes, MAGs were estimated only an average 3.7% smaller than isolate genomes. Even when assembly and binning methods introduce biases, estimated genome size of MAGs and isolates are very similar. Finally, to better understand the ecological drivers of genome size, we discuss on the known and the overlooked factors that influence genome size in different ecosystems, phylogenetic groups, and trophic strategies.
Insight Into the Anti-staphylococcal Activity of JBC 1847 at Sub-Inhibitory Concentration
Authors: Ronco Troels , Kappel Line H. , Aragao Maria F. , Biagi Niccolo , Svenningsen Søren , Christensen Jørn B. , Permin Anders , Saaby Lasse , Holmstrøm Kim , Klitgaard Janne K. , Sabat Artur J. , Akkerboom Viktoria , Monaco Monica , Tinelli Marco , Friedrich Alexander W. , Jana Bimal , Olsen Rikke H.
Published: January 2022

Multidrug-resistant pathogens constitute a serious global issue and, therefore, novel antimicrobials with new modes of action are urgently needed. Here, we investigated the effect of a phenothiazine derivative (JBC 1847) with high antimicrobial activity on Staphylococcus aureus, using a wide range of in vitro assays, flow cytometry, and RNA transcriptomics. The flow cytometry results showed that JBC 1847 rapidly caused depolarization of the cell membrane, while the macromolecule synthesis inhibition assay showed that the synthesis rates of DNA, RNA, cell wall, and proteins, respectively, were strongly decreased. Transcriptome analysis of S. aureus exposed to sub-inhibitory concentrations of JBC 1847 identified a total of 78 downregulated genes, whereas not a single gene was found to be significantly upregulated. Most importantly, there was downregulation of genes involved in adenosintrifosfat (ATP)-dependent pathways, including histidine biosynthesis, which is likely to correlate with the observed lower level of intracellular ATP in JBC 1847–treated cells. Furthermore, we showed that JBC 1847 is bactericidal against both exponentially growing cells and cells in a stationary growth phase. In conclusion, our results showed that the antimicrobial properties of JBC 1847 were primarily caused by depolarization of the cell membrane resulting in dissipation of the proton motive force (PMF), whereby many essential bacterial processes are affected. JBC 1847 resulted in lowered intracellular levels of ATP followed by decreased macromolecule synthesis rate and downregulation of genes essential for the amino acid metabolism in S. aureus. Bacterial compensatory mechanisms for this proposed multi-target activity of JBC 1847 seem to be limited based on the observed very low frequency of resistance toward the compound.
Human Milk Oligosaccharides Exhibit Biofilm Eradication Activity Against Matured Biofilms Formed by Different Pathogen Species
Authors: Jarzynka Sylwia , Spott Riccardo , Tchatchiashvili Tinatini , Ueberschaar Nico , Martinet Mark Grevsen , Strom Kamila , Kryczka Tomasz , Wesołowska Aleksandra , Pletz Mathias W. , Olędzka Gabriela , Makarewicz Oliwia
Published: January 2022

Human milk oligosaccharides (HMOs) have been shown to exhibit plenty of benefits for infants, such as prebiotic activity shaping the gut microbiota and immunomodulatory and anti-inflammatory activity. For some pathogenic bacteria, antimicrobial activity has been proved, but most studies focus on group B streptococci. In the present study, we investigated the antimicrobial and antibiofilm activities of the total and fractionated HMOs from pooled human milk against four common human pathogenic Gram-negative species (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Burkholderia cenocepacia) and three Gram-positive species (Staphylococcus aureus, Enterococcus faecium, and Enterococcus faecalis). The activity of HMOs against enterococci and B. cenocepacia are addressed here for the first time. We showed that HMOs exhibit a predominant activity against the Gram-positive species, with E. faecalis being the most sensitive to the HMOs, both in planktonic bacteria and in biofilms. In further tests, we could exclude fucosyllactose as the antibacterial component. The biological significance of these findings may lie in the prevention of skin infections of the mother’s breast as a consequence of breastfeeding-induced skin laceration and/or protection of the infants’ nasopharynx and lung from respiratory pathogens such as staphylococci.
Multiple Precursor Proteins of Thanatin Isoforms, an Antimicrobial Peptide Associated With the Gut Symbiont of Riptortus pedestris
Authors: Lee Junbeom , Cha Wook Hyun , Lee Dae-Weon
Published: January 2022

Thanatin is an antimicrobial peptide (AMP) generated by insects for defense against bacterial infections. In the present study, we performed cDNA cloning of thanatin and found the presence of multiple precursor proteins from the bean bug, Riptortus pedestris. The cDNA sequences encoded 38 precursor proteins, generating 13 thanatin isoforms. In the phylogenetic analysis, thanatin isoforms were categorized into two groups based on the presence of the membrane attack complex/perforin (MACPF) domain. In insect-bacterial symbiosis, specific substances are produced by the immune system of the host insect and are known to modulate the symbiont’s population. Therefore, to determine the biological function of thanatin isoforms in symbiosis, the expression levels of three AMP genes were compared between aposymbiotic insects and symbiotic R. pedestris. The expression levels of the thanatin genes were significantly increased in the M4 crypt, a symbiotic organ, of symbiotic insects upon systemic bacterial injection. Further, synthetic thanatin isoforms exhibited antibacterial activity against gut-colonized Burkholderia symbionts rather than in vitro-cultured Burkholderia cells. Interestingly, the suppression of thanatin genes significantly increased the population of Burkholderia gut symbionts in the M4 crypt under systemic Escherichia coli K12 injection. Overgrown Burkholderia gut symbionts were observed in the hemolymph of host insects and exhibited insecticidal activity. Taken together, these results suggest that thanatin of R. pedestris is a host-derived symbiotic factor and an AMP that controls the population of gut-colonized Burkholderia symbionts.
Controlling Synthetic Cell-Cell Communication
Authors: Smith Jefferson M. , Chowdhry Razia , Booth Michael J.
Published: January 2022

Synthetic cells, which mimic cellular function within a minimal compartment, are finding wide application, for instance in studying cellular communication and as delivery devices to living cells. However, to fully realise the potential of synthetic cells, control of their function is vital. An array of tools has already been developed to control the communication of synthetic cells to neighbouring synthetic cells or living cells. These tools use either chemical inputs, such as small molecules, or physical inputs, such as light. Here, we examine these current methods of controlling synthetic cell communication and consider alternative mechanisms for future use.
Beyond the Lesion: Back to High Fidelity DNA Synthesis
Authors: Kaszubowski Joseph D. , Trakselis Michael A.
Published: January 2022

High fidelity (HiFi) DNA polymerases (Pols) perform the bulk of DNA synthesis required to duplicate genomes in all forms of life. Their structural features, enzymatic mechanisms, and inherent properties are well-described over several decades of research. HiFi Pols are so accurate that they become stalled at sites of DNA damage or lesions that are not one of the four canonical DNA bases. Once stalled, the replisome becomes compromised and vulnerable to further DNA damage. One mechanism to relieve stalling is to recruit a translesion synthesis (TLS) Pol to rapidly synthesize over and past the damage. These TLS Pols have good specificities for the lesion but are less accurate when synthesizing opposite undamaged DNA, and so, mechanisms are needed to limit TLS Pol synthesis and recruit back a HiFi Pol to reestablish the replisome. The overall TLS process can be complicated with several cellular Pols, multifaceted protein contacts, and variable nucleotide incorporation kinetics all contributing to several discrete substitution (or template hand-off) steps. In this review, we highlight the mechanistic differences between distributive equilibrium exchange events and concerted contact-dependent switching by DNA Pols for insertion, extension, and resumption of high-fidelity synthesis beyond the lesion.
Aged Microglia in Neurodegenerative Diseases: Microglia Lifespan and Culture Methods
Authors: Yoo Hyun-Jung , Kwon Min-Soo
Published: January 2022

Microglia have been recognized as macrophages of the central nervous system (CNS) that are regarded as a culprit of neuroinflammation in neurodegenerative diseases. Thus, microglia have been considered as a cell that should be suppressed for maintaining a homeostatic CNS environment. However, microglia ontogeny, fate, heterogeneity, and their function in health and disease have been defined better with advances in single-cell and imaging technologies, and how to maintain homeostatic microglial function has become an emerging issue for targeting neurodegenerative diseases. Microglia are long-lived cells of yolk sac origin and have limited repopulating capacity. So, microglial perturbation in their lifespan is associated with not only neurodevelopmental disorders but also neurodegenerative diseases with aging. Considering that microglia are long-lived cells and may lose their functional capacity as they age, we can expect that aged microglia contribute to various neurodegenerative diseases. Thus, understanding microglial development and aging may represent an opportunity for clarifying CNS disease mechanisms and developing novel therapies.
The Impact of Hyponatremia on the Severity of Childhood Tuberculous Meningitis
Authors: Salih Rashid , Toorn Ronald van , Seddon James A. , Solomons Regan S.
Published: January 2022

Introduction: Hyponatremia and/or hypoglycorrhachia are commonly encountered biochemical derangements during the acute stage of childhood tuberculous meningitis (TBM). Few studies have explored the correlation between these derangements and the staging of TBM disease (severity), or explored their role as biomarkers for vascular ischemic events, hydrocephalus, or seizures.

Methods: We aimed to identify the prevalence and the correlation between serum hyponatremia (mild, moderate and severe) and/or hypoglycorrhachia in relation to clinical TBM features such as stage of disease, seizures and stroke in children diagnosed with definite and probable TBM, between 1985 and 2015, at Tygerberg Hospital, Cape town, South Africa.

Results: The prevalence of hyponatremia was 344 out of 481 (71.5%) patients; 169 (49.1%) had mild hyponatremia, 146 (42.4%) moderate hyponatremia and 29 (8.4%) severe hyponatremia. Children with severe hyponatremia had higher frequency of stroke [odds ratio (OR) 4.36, 95% confidence interval (CI) 1.24–15.35; p = 0.01], brainstem dysfunction (OR 7.37, 95% CI 2.92–18.61; p < 0.01), cranial nerve palsies (OR 2.48, 95% CI 1.04–5.91; p = 0.04) and non-communicating hydrocephalus (OR 2.66, 95% CI 1.09–6.44; p = 0.03). Children with moderate hyponatremia and mild hyponatremia compared to those without hyponatremia similarly were more likely to exhibit signs of brainstem dysfunction (OR 1.91, 95% CI 1.11–3.28; p = 0.02) and hydrocephalus (OR 3.18, 95% CI 1.25–8.09; p = 0.01), respectively. On multivariable analysis only brainstem dysfunction was significantly associated with severe hyponatremia [adjusted odds ratio (aOR) 4.46, 95% CI 1.62–12.30; p < 0.01]. Children with hypoglycorrhachia compared to normoglycorrhachia were more likely to have had longer symptom duration prior to admission (OR 1.87, 95% CI 1.09–3.20; p = 0.02), non-communicating hydrocephalus (OR 1.64, 95% CI 0.99–2.71; p = 0.05), higher cerebrospinal white cell counts (OR 3.00, 95% CI 1.47–6.12; p < 0.01) and higher CSF protein concentrations (OR 2.51, 95% CI 1.49–4.20; p < 0.01). On multivariable analysis raised CSF protein concentration >1 g/L was significantly associated with hypoglycorrhachia (aOR 2.52, 95% CI 1.44–4.40; p < 0.01). Death rates did not differ by sodium level category or presence of hypoglycorrachia, however an increasing trend of children that had demised was noted the more severe the sodium category.

Conclusion: Hyponatremia and/or hypoglycorrhachia occur in more than two-thirds of children with TBM. Severe TBM disease complications such as brainstem dysfunction was associated with moderate hyponatremia, while severe hyponatremia was associated with brainstem dysfunction, stroke, cranial nerve palsies and non-communicating hydrocephalus. Cerebrospinal fluid (CSF) glucose depletion correlated with non-communicating hydrocephalus and increased CSF inflammation.
Neural Advantages of Older Musicians Involve the Cerebellum: Implications for Healthy Aging Through Lifelong Musical Instrument Training
Authors: Yamashita Masatoshi , Ohsawa Chie , Suzuki Maki , Guo Xia , Sadakata Makiko , Otsuka Yuki , Asano Kohei , Abe Nobuhito , Sekiyama Kaoru
Published: January 2022

This study compared 30 older musicians and 30 age-matched non-musicians to investigate the association between lifelong musical instrument training and age-related cognitive decline and brain atrophy (musicians: mean age 70.8 years, musical experience 52.7 years; non-musicians: mean age 71.4 years, no or less than 3 years of musical experience). Although previous research has demonstrated that young musicians have larger gray matter volume (GMV) in the auditory-motor cortices and cerebellum than non-musicians, little is known about older musicians. Music imagery in young musicians is also known to share a neural underpinning [the supramarginal gyrus (SMG) and cerebellum] with music performance. Thus, we hypothesized that older musicians would show superiority to non-musicians in some of the abovementioned brain regions. Behavioral performance, GMV, and brain activity, including functional connectivity (FC) during melodic working memory (MWM) tasks, were evaluated in both groups. Behaviorally, musicians exhibited a much higher tapping speed than non-musicians, and tapping speed was correlated with executive function in musicians. Structural analyses revealed larger GMVs in both sides of the cerebellum of musicians, and importantly, this was maintained until very old age. Task-related FC analyses revealed that musicians possessed greater cerebellar-hippocampal FC, which was correlated with tapping speed. Furthermore, musicians showed higher activation in the SMG during MWM tasks; this was correlated with earlier commencement of instrumental training. These results indicate advantages or heightened coupling in brain regions associated with music performance and imagery in musicians. We suggest that lifelong instrumental training highly predicts the structural maintenance of the cerebellum and related cognitive maintenance in old age.
Cysteine String Protein Controls Two Routes of Export for Misfolded Huntingtin
Authors: Pink Desmond , Donnelier Julien , Lewis John D. , Braun Janice E. A.
Published: January 2022

Extracellular vesicles (EVs) are secreted vesicles of diverse size and cargo that are implicated in the cell-to-cell transmission of disease-causing-proteins in several neurodegenerative diseases. Mutant huntingtin, the disease-causing entity in Huntington’s disease, has an expanded polyglutamine track at the N terminus that causes the protein to misfold and form toxic intracellular aggregates. In Huntington’s disease, mutant huntingtin aggregates are transferred between cells by several routes. We have previously identified a cellular pathway that is responsible for the export of mutant huntingtin via extracellular vesicles. Identifying the EV sub-populations that carry misfolded huntingtin cargo is critical to understanding disease progression. In this work we expressed a form of polyglutamine expanded huntingtin (GFP-tagged 72Qhuntingtinexon1) in cells to assess the EVs involved in cellular export. We demonstrate that the molecular chaperone, cysteine string protein (CSPα; DnaJC5), facilitates export of disease-causing-polyglutamine-expanded huntingtin cargo in 180–240 nm vesicles as well as larger 10–30 μm vesicles.
Nutrition by Design: Boosting Selenium Content and Fresh Matter Yields of Salad Greens With Preharvest Light Intensity and Selenium Applications
Authors: Zhu Xudong , Yang Tianbao , Sanchez Charles A. , Hamilton Jeffrey M. , Fonseca Jorge M.
Published: January 2022

Selenium (Se) is an essential mineral in multiple human metabolic pathways with immune modulatory effects on viral diseases including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HIV. Plant-based foods contain Se metabolites with unique functionalities for the human metabolism. In order to assess the value of common salad greens as Se source, we conducted a survey of lettuce commercially grown in 15 locations across the USA and Canada and found a tendency for Se to accumulate higher (up to 10 times) in lettuce grown along the Colorado river basin region, where the highest amount of annual solar radiation of the country is recorded. In the same area, we evaluated the effect of sunlight reduction on the Se content of two species of arugula [Eruca sativa (E. sativa) cv. “Astro” and Diplotaxis tenuifolia (D. tenuifolia) cv. “Sylvetta”]. A 90% light reduction during the 7 days before harvest resulted in over one-third Se decline in D. tenuifolia. The effect of light intensity on yield and Se uptake of arugula microgreens was also examined under indoor controlled conditions. This included high intensity (HI) (160 μ mol−2 s−1 for 12 h/12 h light/dark); low intensity (LI) (70 μ mol m−2 s−1 for 12 h/12 h light/dark); and HI-UVA (12 h light of 160 μ mol m−2 s−1, 2 h UVA of 40 μ mol m−2 s−1, and 10 h dark) treatments in a factorial design with 0, 1, 5, and 10 ppm Se in the growing medium. HI and HI-UVA produced D. tenuifolia plants with 25–100% higher Se content than LI, particularly with the two higher Se doses. The addition of Se produced a marked increase in fresh matter (>35% in E. sativa and >45% in D. tenuifolia). This study (i) identifies evidence to suggest the revision of food composition databases to account for large Se variability, (ii) demonstrates the potential of introducing preharvest Se to optimize microgreen yields, and (iii) provides the controlled environment industry with key information to deliver salad greens with targeted Se contents.
A Systematic Review and Meta-Analysis of the Effectiveness of Neuroprotectants for Paclitaxel-Induced Peripheral Neuropathy
Authors: Leen Alisha Joan , Yap Dominic Wei Ting , Teo Chong Boon , Tan Benjamin Kye Jyn , Molassiotis Alex , Ishiguro Hiroshi , Fan Sarah Wei Xian , Sundar Raghav , Soon Yu Yang , Bandla Aishwarya
Published: January 2022

Background

Paclitaxel-induced peripheral neuropathy (PIPN) is a disabling side effect of paclitaxel with few effective preventive strategies. We aim to determine the efficacy of pharmacological and non-pharmacological neuroprotective interventions in preventing PIPN incidence.

Methods

Biomedical literature databases were searched from years 2000 to 2021 for trials comparing neuroprotective interventions and control. Meta-analysis was performed using the random-effects model. The primary outcome was the incidence of PIPN.

Results

Of 24 relevant controlled trials, 14 were eligible for meta-analysis. Pooled results from seven non-pharmacological trials were associated with a statistically significant 48% relative reduction of PIPN risk with low heterogeneity. Conversely, pooled results from six pharmacological trials were associated with a significant 20% relative reduction of PIPN risk with moderate heterogeneity. Both pharmacological and non-pharmacological approaches appear effective in reducing PIPN incidence in the treatment arm compared to control (pooled RR < 1).

Conclusion

Current evidence suggests that both interventions may reduce PIPN risk. Non-pharmacological interventions appear more effective than pharmacological interventions.
Case Report: A Novel Non-Reciprocal ALK Fusion: ALK-GCA and EML4-ALK Were Identified in Lung Adenocarcinoma, Which May Respond to Alectinib Adjuvant-Targeted Therapy
Authors: Zhai Xiaoqian , Wu Qiang , Pu Dan , Yin Liyuan , Wang Weiya , Zhu Daxing , Xu Feng
Published: January 2022

Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancers (NSCLCs) have favorable and impressive response to ALK tyrosine kinase inhibitors (TKIs). However, ALK rearrangement had approximately 90 distinct fusion partners. Patients with different ALK fusions might have distinct responses to different-generation ALK-TKIs. In this case report, we identified a novel non-reciprocal ALK fusion: ALK-grancalcin (GCA) (A19: intragenic) and EML4-ALK (E20: A20) by next-generation sequencing (NGS) in a male lung adenocarcinoma patient who was staged as IIIB-N2 after surgery. After a multidisciplinary discussion, the patient received alectinib adjuvant targeted therapy and postoperative radiotherapy (PORT). He is currently in good condition, and disease-free survival (DFS) has been 20 months so far, which has been longer than the median survival time of IIIB NSCLC patients. Our study extended the spectrum of ALK fusion partners in ALK + NSCLC, and we reported a new ALK fusion: ALK-GCA and EML4-ALK and its sensitivity to alectinib firstly in lung cancer. It is vital for clinicians to detect fusion mutations of patients and report timely the newfound fusions and their response to guide treatment.
Effects of Perioperative Epidural Analgesia on Cancer Recurrence and Survival
Authors: Zhang Donghang , Jiang Jingyao , Liu Jin , Zhu Tao , Huang Han , Zhou Cheng
Published: January 2022

Surgical resection is the main curative avenue for various cancers. Unfortunately, cancer recurrence following surgery is commonly seen, and typically results in refractory disease and death. Currently, there is no consensus whether perioperative epidural analgesia (EA), including intraoperative and postoperative epidural analgesia, is beneficial or harmful on cancer recurrence and survival. Although controversial, mounting evidence from both clinical and animal studies have reported perioperative EA can improve cancer recurrence and survival via many aspects, including modulating the immune/inflammation response and reducing the use of anesthetic agents like inhalation anesthetics and opioids, which are independent risk factors for cancer recurrence. However, these results depend on the cancer types, cancer staging, patients age, opioids use, and the duration of follow-up. This review will summarize the effects of perioperative EA on the oncological outcomes of patients after cancer surgery.
Identification of SRXN1 and KRT6A as Key Genes in Smoking-Related Non-Small-Cell Lung Cancer Through Bioinformatics and Functional Analyses
Authors: Zhou Jiazhen , Jiang Guanqing , Xu Enwu , Zhou Jiaxin , Liu Lili , Yang Qiaoyuan
Published: January 2022

Background

Lung cancer is the leading cause of cancer-related mortality worldwide. Although cigarette smoking is an established risk factor for lung cancer, few reliable smoking-related biomarkers for non-small-cell lung cancer (NSCLC) are available. An improved understanding of these biomarkers would further the development of new biomarker-targeted therapies and lead to improvements in overall patient survival.

Methods

We performed bioinformatic analysis to screened potential target genes, then quantitative PCR, western, siRNA, CCK-8, flow cytometry, tumorigenicity assays in nude mice were performed to validated the function.

Results

In this study, we identified 83 smoking-related genes (SRGs) based on an integration analysis of two Gene Expression Omnibus (GEO) datasets, and 27 hub SRGs with potential carcinogenic effects by analyzing a dataset of smokers with NSCLC in The Cancer Genome Atlas (TCGA) database. A survival analysis revealed three genes with potential prognostic value, namely SRXN1, KRT6A and JAKMIP3. A univariate Cox analysis revealed significant associations of elevated SRXN1 and KRT6A expression with prognosis. A receiver operating characteristic (ROC) curve analysis indicated the high diagnostic value of SRXN1 and KRT6A for smoking and cancer. Quantitative PCR and western blotting validated the increased expression of SRXN1 and KRT6A mRNA and protein, respectively, in lung cancer cell lines and NSCLC tissues. In patients with NSCLC, SRXN1 and KRT6A expression was associated with the tumor–node–metastasis (TNM) stage, presence of metastasis, history of smoking and daily smoking consumption. Furthermore, inhibition of SRXN1 or KRT6A suppressed viability and enhanced apoptosis in the A549 human lung carcinoma cell line. Tumorigenicity assays in nude mice confirmed that the siRNA-mediated downregulation of SRXN1 and KRT6A expression inhibited tumor growth in vivo.

Conclusions

In summary, SRXN1 and KRT6A act as oncogenes in NSCLC and might be potential biomarkers of smoking exposure and the early diagnosis and prognosis of NSCLC in smokers, which is vital for lung cancer therapy.
Foot-to-Foot Contact Among Initial Goal-Directed Movements Supports the Prognostic Value of Fidgety Movements in HIE-Cooled Infants
Authors: Ferrari Fabrizio , Bedetti Luca , Bertoncelli Natascia , Roversi Maria Federica , Della Casa Elisa , Guidotti Isotta , Ori Luca , D'Amico Roberto , Valeri Lara , Lugli Licia , Lucaccioni Laura , Berardi Alberto
Published: January 2022

Background: Few studies conducted to date have observed general movements in infants affected by hypoxic–ischemic encephalopathy (HIE) who underwent therapeutic hypothermia. We investigated whether foot-to-foot contact (FF) could support the predictive value of fidgety movements (FMs) in infants affected by HIE and treated with brain cooling.

Methods: Spontaneous motility was video recorded for 3–5 min at 12 weeks post-term age in 58 full-term newborn infants affected by perinatal asphyxia who were cooled due to moderate to severe HIE. FF and FMs were blindly scored by three independent observers. At 24 months, each patient underwent a neurological examination by Amiel-Tison and Grenier.

Results: At 24 months, 47 infants had developed typically at neurological examination, eight had developed mild motor impairment, and three developed cerebral palsy (CP). At 12 weeks, 34 (58.6%) infants had shown normal FMs, four of whom developed mild motor impairment. Twenty-four infants (41.4%) exhibited abnormal or no FMs, four of whom developed mild motor impairment and three developed CP. FF was present in 20 infants (34.5%), two of whom developed mild motor impairment. FF was absent in 38 infants (65.5%), six of whom developed mild motor impairment and three developed CP. Both FMs and FF, considered separately, were 100% sensitive for predicting CP at 24 months, but only 61 and 36%, respectively, were specific. Summing the two patterns together, the specificity increases to 73%, considering only CP as an abnormal outcome, and increases to 74% when considering CP plus mild motor impairment. Unexpectedly, fidgety movements were absent in 24 infants with typical motor outcomes, 17 of whom showed a typical motor outcome.

Conclusions: FF is already part of motor repertoire at 12 weeks and allows a comparison of spontaneous non-voluntary movements (FMs) to pre-voluntary movements (FF). FF supports FMs for both sensitivity and specificity. A second video recording at 16–18 weeks, when pedipulation is present in healthy infants, is suggested: it may better define the presence or absence of goal-directed motility.
Reappraisal of the Subtropical Guidelines on Palivizumab Prophylaxis in Congenital Heart Disease
Authors: Chiu Shuenn-Nan , Wang Ching-Chia , Lin Ming-Tai , Chen Chun-An , Lu Chun-Wei , Hua Yu-Chuan , Wu Jing-Ming , Wu Mei-Hwan , Wang Jou-Kou
Published: January 2022

Objective: To define the impact of associated abnormalities on the efficacy of the novel subtropical guidelines for palivizumab prophylaxis on respiratory syncytial virus (RSV)-related hospitalizations in patients with hemodynamically significant congenital heart disease (hsCHD).

Method: This prospective study enrolled every patient seen at a tertiary care center for hsCHD, who was born between 2014 and 2018 and received at least 1 dose of palivizumab, according to the subtropical guidelines. The patients were followed until the age of 2 years.

Results: A total of 772 patients (49% male) were enrolled. Cyanotic CHD was seen in 46% of patients, of whom 23% had associated abnormalities. Lung/airway abnormalities (14%) were the most common followed by the genetic syndromes associated with CHD (7.3%). Among the 772 patients, RSV-related hospitalizations occurred in 3.2 and 2.2% children aged ≤ 12 and 13–24 months, respectively. Most of the RSV infections occurred in patients no longer satisfying the criteria for palivizumab prophylaxis. The patients with associated abnormalities but not the type of CHD, patient age, and patient sex were risk factors for RSV-related hospitalizations. The rates of RSV-related hospitalizations, admission to the intensive care unit, and endotracheal intubation were higher for patients with associated anomalies than for other patients before 24 months of age (10.2 vs. 4.0%, 67 vs. 33%, and 39 vs. 4.2%, p = 0.004, 0.06, 0.013, respectively).

Conclusion: Children with abnormalities, especially genetic syndromes and lung/airway problems associated with CHD, are at high risk for RSV-related hospitalization. Our current subtropical guidelines for palivizumab prophylaxis in patients with hsCHD, should be revised to include the results of this study.
A Narrative Review on the Update in the Prevalence of Infantile Colic, Regurgitation, and Constipation in Young Children: Implications of the ROME IV Criteria
Authors: Muhardi Leilani , Aw Marion M. , Hasosah Mohammed , Ng Ruey Terng , Chong Sze Yee , Hegar Badriul , Toro-Monjaraz Erick , Darma Andy , Cetinkaya Merih , Chow Chung Mo , Kudla Urszula , Vandenplas Yvan
Published: January 2022

Regurgitation, colic, and constipation are frequently reported Functional Gastrointestinal Disorders (FGIDs) in the first few years of life. In 2016, the diagnostic criteria for FGIDs were changed from ROME III to ROME IV. This review assesses the prevalence of the most frequent FGIDs (colic, regurgitation and constipation) among children aged 0–5 years after the introduction of the later criteria. Articles published from January 1, 2016 to May 1, 2021 were retrieved from PubMed and Google Scholar using relevant keywords. A total of 12 articles were further analyzed based on the inclusion and exclusion criteria. This review consists of two studies (17%) from the Middle East, three (25%) from Asia, two (17%) from the USA, three (25%) from Europe, and one (8%) from Africa. Three studies (25%) were based on data obtained from healthcare professionals, while the rest were parent or caregiver reports. About half of the retrieved studies used the ROME IV criteria. Among infants aged 0–6 months, the reported prevalence of colic ranged between 10–15%, whilst that of regurgitation was 33.9%, and constipation was 1.5%. Among infants aged 0–12 months, the reported prevalence of regurgitation and constipation were 3.4–25.9% and 1.3–17.7%, respectively. The reported prevalence of constipation was 1.3–26% among children aged 13–48 months and 13% among children aged 4–18 years. Despite the large variations due to differences in diagnostic criteria, study respondents and age group, the prevalence of infantile colic was higher, while that for infantile regurgitation and constipation were similar using the ROME IV or III criteria.
Berberine Reduces Lipid Accumulation by Promoting Fatty Acid Oxidation in Renal Tubular Epithelial Cells of the Diabetic Kidney
Authors: Rong Qingfeng , Han Baosheng , Li Yafeng , Yin Haizhen , Li Jing , Hou Yanjuan
Published: January 2022

Abnormal lipid metabolism in renal tubular epithelial cells contributes to renal lipid accumulation and disturbed mitochondrial bioenergetics which are important in diabetic kidney disease. Berberine, the major active constituent of Rhizoma coptidis and Cortex phellodendri, is involved in regulating glucose and lipid metabolism. The present study aimed to investigate the protective effects of berberine on lipid accumulation in tubular epithelial cells of diabetic kidney disease. We treated type 2 diabetic db/db mice with berberine (300 mg/kg) for 12 weeks. Berberine treatment improved the physical and biochemical parameters of the db/db mice compared with db/m mice. In addition, berberine decreased intracellular lipid accumulation and increased the expression of fatty acid oxidation enzymes CPT1, ACOX1 and PPAR-α in tubular epithelial cells of db/db mice. The mitochondrial morphology, mitochondrial membrane potential, cytochrome c oxidase activity, mitochondrial reactive oxygen species, and mitochondrial ATP production in db/db mice kidneys were significantly improved by berberine. Berberine intervention activated the AMPK pathway and increased the level of PGC-1α. In vitro berberine suppressed high glucose-induced lipid accumulation and reversed high glucose-induced reduction of fatty acid oxidation enzymes in HK-2 cells. Importantly, in HK-2 cells, berberine treatment blocked the change in metabolism from fatty acid oxidation to glycolysis under high glucose condition. Moreover, berberine restored high glucose-induced dysfunctional mitochondria. These data suggested that berberine alleviates diabetic renal tubulointerstitial injury through improving high glucose-induced reduction of fatty acid oxidation, alleviates lipid deposition, and protect mitochondria in tubular epithelial cells.
Perceptions About Biosimilar Medicines Among Belgian Patients in the Ambulatory Care
Authors: Vandenplas Yannick , Barbier Liese , Simoens Steven , Van Wilder Philippe , Vulto Arnold G. , Huys Isabelle
Published: January 2022

Background and objectives: Biosimilar medicines have been on the European market for 15 years. Despite the extensive and positive experience with biosimilars across Europe, their uptake remains limited in Belgium. One of the possible factors limiting uptake in clinical practice is the inadequate understanding and lack of trust in biosimilars among patients. This study aimed to assess the level of knowledge and perceptions about biosimilar medicines among Belgian patients in the ambulatory care.

Methods: This study consisted of online questionnaires among Belgian patients in the ambulatory care (i.e., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn’s disease, ulcerative colitis, diabetes mellitus type I and II). The results were collected between December 2020 and February 2021. The data were analyzed with descriptive and inferential statistics.

Results: In total, 657 patients across all disease areas of interest participated in this study. Only 38% of patients had heard of biosimilars before. Of those patients, most (58%) were aware that biosimilars are as safe and effective as their reference product. The vast majority of respondents (68%) would agree with transitioning to a biosimilar if their physician prescribed it, only 3% would never agree with a transition to a biosimilar. If a physician would propose to change their current originator biological therapy with its biosimilar, nearly all patients (95%) want their physician to explain the decision and inform them. For additional information about biosimilars, Belgian patients prefer brochures or folders (41%), or available resources on the internet (35%). Physicians were indicated as the preferred source of information (95%), followed by pharmacists (51%), academia (39%), and patient associations (35%). Most patients require information regarding the safety and efficacy (78%), price and reimbursement (64%), and the clinical development process (56%) of the biosimilar.

Conclusion: Belgian patients require information about biosimilar medicines. However, most patients are open and positive towards transitioning their current biological therapy with its biosimilar if sufficiently supported by their healthcare providers.
Biphasic Effect of Pirfenidone on Angiogenesis
Authors: Gan Donghao , Cheng Wenxiang , Ke Liqing , Sun Antonia RuJia , Jia Qingyun , Chen Jianhai , Xu Zhanwang , Xu Juan , Zhang Peng
Published: January 2022

Pirfenidone (PFD), a synthetic arsenic compound, has been found to inhibit angiogenesis at high concentrations. However, the biphasic effects of different PFD concentrations on angiogenesis have not yet been elucidated, and the present study used an in vitro model to explore the mechanisms underlying this biphasic response. The effect of PFD on the initial angiogenesis of vascular endothelial cells was investigated through a Matrigel tube formation assay, and the impact of PFD on endothelial cell migration was evaluated through scratch and transwell migration experiments. Moreover, the expression of key migration cytokines, matrix metalloproteinase (MMP)-2 and MMP-9, was examined. Finally, the biphasic mechanism of PFD on angiogenesis was explored through cell signaling and apoptosis analyses. The results showed that 10–100 μM PFD has a significant and dose-dependent inhibitory effect on tube formation and migration, while 10 nM–1 μM PFD significantly promoted tube formation and migration, with 100 nM PFD having the strongest effect. Additionally, we found that a high concentration of PFD could significantly inhibit MMP-2 and MMP-9 expression, while low concentrations of PFD significantly promoted their expression. Finally, we found that high concentrations of PFD inhibited EA.hy926 cell tube formation by promoting apoptosis, while low concentrations of PFD promoted tube formation by increasing MMP-2 and MMP-9 protein expression predominantly via the EGFR/p-p38 pathway. Overall, PFD elicits a biphasic effect on angiogenesis through different mechanisms, could be used as a new potential drug for the treatment of vascular diseases.
QNet: A Scalable and Noise-Resilient Quantum Neural Network Architecture for Noisy Intermediate-Scale Quantum Computers
Authors: Alam Mahabubul , Ghosh Swaroop
Published: January 2022

Quantum machine learning (QML) is promising for potential speedups and improvements in conventional machine learning (ML) tasks. Existing QML models that use deep parametric quantum circuits (PQC) suffer from a large accumulation of gate errors and decoherence. To circumvent this issue, we propose a new QML architecture called QNet. QNet consists of several small quantum neural networks (QNN). Each of these smaller QNN’s can be executed on small quantum computers that dominate the NISQ-era machines. By carefully choosing the size of these QNN’s, QNet can exploit arbitrary size quantum computers to solve supervised ML tasks of any scale. It also enables heterogeneous technology integration in a single QML application. Through empirical studies, we show the trainability and generalization of QNet and the impact of various configurable variables on its performance. We compare QNet performance against existing models and discuss potential issues and design considerations. In our study, we show 43% better accuracy on average over the existing models on noisy quantum hardware emulators. More importantly, QNet provides a blueprint to build noise-resilient QML models with a collection of small quantum neural networks with near-term noisy quantum devices.
Efficient Criteria of Quantumness for a Large System of Qubits
Authors: Watabe Shohei , Serikow Michael Zach , Kawabata Shiro , Zagoskin Alexandre
Published: January 2022

In order to model and evaluate large-scale quantum systems, e.g., quantum computer and quantum annealer, it is necessary to quantify the “quantumness” of such systems. In this paper, we discuss the dimensionless combinations of basic parameters of large, partially quantum coherent systems, which could be used to characterize their degree of quantumness. Based on analytical and numerical calculations, we suggest one such number for a system of qubits undergoing adiabatic evolution, i.e., the accessibility index. Applying it to the case of D-Wave One superconducting quantum annealing device, we find that its operation as described falls well within the quantum domain.