bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Lethal Inhibitors and Inhibitor Combinations for Mono-Driver versus Multi-Driver Triple-Negative Breast Cancer Cells
Authors: Ku Geng Chia , Chapdelaine Abygail G. , Ayrapetov Marina K. , Sun Gongqin
Published: August 2022

There are no signaling-based targeted therapies for triple-negative breast cancer. The development of targeted cancer therapy relies on identifying oncogenic signaling drivers, understanding their contributions to oncogenesis and developing inhibitors to block such drivers. In this study, we determine that DU-4475 is a mono-driver cancer cell line relying on BRAF and the mitogen-activated protein kinase pathway for viability and proliferation. It is fully and lethally inhibited by BRAF or Mek inhibitors at low nM concentrations, but it is resistant to inhibitors targeting other signaling pathways. The inhibitory lethality caused by blocking Mek or BRAF is through apoptosis. In contrast, MDA-MB-231 is a multi-driver triple-negative breast cancer cell line dependent on both Src and the KRAS-activated mitogen-activated kinase pathway for proliferation and viability. Blocking each pathway alone only partially inhibits cell proliferation without killing them, but the combination of dasatinib, an Src inhibitor, and trametinib, a Mek inhibitor, achieves synthetic lethality. The combination is highly potent, with an IC50 of 8.2 nM each, and strikingly synergistic, with a combination index of less than 0.003 for 70% inhibition. The synthetic lethality of the drug combination is achieved by apoptosis. These results reveal a crucial difference between mono-driver and multi-driver cancer cells and suggest that pharmacological synthetic lethality may provide a basis for effectively inhibiting multi-driver cancers.
Targeted Therapy for Hepatocellular Carcinoma: Old and New Opportunities
Authors: Laface Carmelo , Fedele Palma , Maselli Felicia Maria , Ambrogio Francesca , Foti Caterina , Molinari Pasquale , Ammendola Michele , Lioce Marco , Ranieri Girolamo
Published: August 2022

Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver, accounting for 90% of all recorded cases. HCC is the third most common cause of cancer-related death, with a 5-year survival rate of just 3%. In the advanced stages, systemic treatments allow doctors to obtain clinical benefits, although the prognosis remains very poor. In the past few decades, new molecular targeted therapies against receptor tyrosine kinases have been developed and clinically evaluated. Sorafenib was the first oral tyrosine kinase inhibitor (TKI) approved for the treatment of advanced HCC in 2007. Subsequently, other TKIs, including Cabozantinib, Regorafenib, Lenvatinib, and vascular endothelial growth factor receptor (VEGFR) inhibitors such as Ramucirumab and VEGF inhibitors such as Bevacizumab have been approved as first- or second-line treatments. More recently, the combination of immune checkpoint inhibitors and VEGF inhibitors (Atezolizumab plus Bevacizumab) have been analyzed and approved for the treatment of advanced HCC. On the basis of the poor prognoses and the meager benefits deriving from the available systemic therapies, research into new treatments is extremely necessary. In this review, we focus on the available systemic therapies for advanced HCC, with a look toward the future.
High Accuracy Indicators of Androgen Suppression Therapy Failure for Prostate Cancer—A Modeling Study
Authors: Meade William , Weber Allison , Phan Tin , Hampston Emily , Resa Laura Figueroa , Nagy John , Kuang Yang
Published: August 2022

Prostate cancer is a serious public health concern in the United States. The primary obstacle to effective long-term management for prostate cancer patients is the eventual development of treatment resistance. Due to the uniquely chaotic nature of the neoplastic genome, it is difficult to determine the evolution of tumor composition over the course of treatment. Hence, a drug is often applied continuously past the point of effectiveness, thereby losing any potential treatment combination with that drug permanently to resistance. If a clinician is aware of the timing of resistance to a particular drug, then they may have a crucial opportunity to adjust the treatment to retain the drug’s usefulness in a potential treatment combination or strategy. In this study, we investigate new methods of predicting treatment failure due to treatment resistance using a novel mechanistic model built on an evolutionary interpretation of Droop cell quota theory. We analyze our proposed methods using patient PSA and androgen data from a clinical trial of intermittent treatment with androgen deprivation therapy. Our results produce two indicators of treatment failure. The first indicator, proposed from the evolutionary nature of the cancer population, is calculated using our mathematical model with a predictive accuracy of 87.3% (sensitivity: 96.1%, specificity: 65%). The second indicator, conjectured from the implication of the first indicator, is calculated directly from serum androgen and PSA data with a predictive accuracy of 88.7% (sensitivity: 90.2%, specificity: 85%). Our results demonstrate the potential and feasibility of using an evolutionary tumor dynamics model in combination with the appropriate data to aid in the adaptive management of prostate cancer.
Current Trends in Inpatient Care and In-Hospital Mortality of Cholangiocarcinoma in Germany: A Systematic Analysis between 2010 and 2019
Authors: Roderburg Christoph , Essing Tobias , Kehmann Linde , Krieg Sarah , Labuhn Simon , Kandler Jennis , Luedde Tom , Loosen Sven H.
Published: August 2022

Background: Cholangiocarcinoma (CCA) is a rare malignant disease of the biliary tract with an increasing incidence and a high mortality worldwide. Systematic data on epidemiological trends, treatment strategies, and in-hospital mortality of CCA in Germany are largely missing. However, the evaluation and careful interpretation of these data could help to further improve the treatment strategies and outcome of CCA patients in the future. Methods: Standardized hospital discharge data from the German Federal Statistical Office were used to evaluate epidemiological and clinical trends as well as the in-hospital mortality of CCA in Germany between 2010 and 2019. Results: A total of 154,515 hospitalized CCA cases were included into the analyses. The number of cases significantly increased over time (p < 0.001), with intrahepatic CCA (62.5%) being the most prevalent tumor localization. Overall, in-hospital mortality was 11.4% and remained unchanged over time. In-hospital mortality was significantly associated with patients’ age and tumor localization. The presence of clinical complications such as (sub)acute liver failure, acute respiratory distress syndrome (ARDS), or acute renal failure significantly increased in-hospital mortality up to 77.6%. In-hospital mortality was significantly lower among patients treated at high annual case volume centers. Finally, treatment strategies for CCA significantly changed over time and showed decisive differences with respect to the hospitals’ annual case volume. Conclusions: Our data provide a systematic overview on hospitalized CCA patients in Germany. We identified relevant clinical and epidemiological risk factors associated with an increased in-hospital mortality that could help to further improve framework conditions for the management of CCA patients in the future.
Encephalitis in Patients with COVID-19: A Systematic Evidence-Based Analysis
Authors: Islam Md Asiful , Cavestro Cinzia , Alam Sayeda Sadia , Kundu Shoumik , Kamal Mohammad Amjad , Reza Faruque
Published: August 2022

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) predominantly infects the respiratory system, several investigations have shown the involvement of the central nervous system (CNS) along the course of the illness, with encephalitis being one of the symptoms. The objective of this systematic review was to evaluate the characteristics (clinical, neuro-radiological aspects, and laboratory features) and outcomes of encephalitis in COVID-19 patients. PubMed, Scopus, and Google Scholar databases were searched from 1 December 2019 until 21 July 2022 to identify case reports and case series published on COVID-19 associated with encephalitis. The quality of the included studies was assessed by the Joanna Briggs Institute critical appraisal checklists. This systematic review included 79 studies, including 91 COVID-19 patients (52.7% male) experiencing encephalitis, where 85.6% were adults (49.3 ± 20.2 years), and 14.4% were children (11.2 ± 7.6 years). RT-PCR was used to confirm 92.2% of the COVID-19 patients. Encephalitis-related symptoms were present in 78.0% of COVID-19 patients at the time of diagnosis. In these encephalitis patients, seizure (29.5%), confusion (23.2%), headache (20.5%), disorientation (15.2%), and altered mental status (11.6%) were the most frequently reported neurologic manifestations. Looking at the MRI, EEG, and CSF findings, 77.6%, 75.5%, and 64.1% of the patients represented abnormal results. SARS-CoV-2-associated or -mediated encephalitis were the most common type observed (59.3%), followed by autoimmune encephalitis (18.7%). Among the included patients, 66.7% were discharged (37.8% improved and 28.9% fully recovered), whereas 20.0% of the reported COVID-19-positive encephalitis patients died. Based on the quality assessment, 87.4% of the studies were of high quality. Although in COVID-19, encephalitis is not a typical phenomenon, SARS-CoV-2 seems like a neuropathogen affecting the brain even when there are no signs of respiratory illness, causing a high rate of disability and fatality.
Preclinical Enzyme Replacement Therapy with a Recombinant β-Galactosidase-Lectin Fusion for CNS Delivery and Treatment of GM1-Gangliosidosis
Authors: Weesner Jason Andrew , Annunziata Ida , Yang Tianhong , Acosta Walter , Gomero Elida , Hu Huimin , van de Vlekkert Diantha , Ayala Jorge , Qiu Xiaohui , Fremuth Leigh Ellen , Radin David N. , Cramer Carole L. , d’Azzo Alessandra
Published: August 2022

GM1-gangliosidosis is a catastrophic, neurodegenerative lysosomal storage disease caused by a deficiency of lysosomal β-galactosidase (β-Gal). The primary substrate of the enzyme is GM1-ganglioside (GM1), a sialylated glycosphingolipid abundant in nervous tissue. Patients with GM1-gangliosidosis present with massive and progressive accumulation of GM1 in the central nervous system (CNS), which leads to mental and motor decline, progressive neurodegeneration, and early death. No therapy is currently available for this lysosomal storage disease. Here, we describe a proof-of-concept preclinical study toward the development of enzyme replacement therapy (ERT) for GM1-gangliosidosis using a recombinant murine β-Gal fused to the plant lectin subunit B of ricin (mβ-Gal:RTB). We show that long-term, bi-weekly systemic injection of mβ-Gal:RTB in the β-Gal−/− mouse model resulted in widespread internalization of the enzyme by cells of visceral organs, with consequent restoration of enzyme activity. Most importantly, β-Gal activity was detected in several brain regions. This was accompanied by a reduction of accumulated GM1, reversal of neuroinflammation, and decrease in the apoptotic marker caspase 3. These results indicate that the RTB lectin delivery module enhances both the CNS-biodistribution pattern and the therapeutic efficacy of the β-Gal ERT, with the potential to translate to a clinical setting for the treatment of GM1-gangliosidosis.
How Azanucleosides Affect Myeloid Cell Fate
Authors: Stein Anna , Platzbecker Uwe , Cross Michael
Published: August 2022

The azanucleosides decitabine and azacytidine are used widely in the treatment of myeloid neoplasia and increasingly in the context of combination therapies. Although they were long regarded as being largely interchangeable in their function as hypomethylating agents, the azanucleosides actually have different mechanisms of action; decitabine interferes primarily with the methylation of DNA and azacytidine with that of RNA. Here, we examine the role of DNA methylation in the lineage commitment of stem cells during normal hematopoiesis and consider how mutations in epigenetic regulators such as DNMT3A and TET2 can lead to clonal expansion and subsequent neoplastic progression. We also consider why the efficacy of azanucleoside treatment is not limited to neoplasias carrying mutations in epigenetic regulators. Finally, we summarise recent data describing a role for azacytidine-sensitive RNA methylation in lineage commitment and in the cellular response to stress. By summarising and interpreting evidence for azanucleoside involvement in a range of cellular processes, our review is intended to illustrate the need to consider multiple modes of action in the design and stratification of future combination therapies.
GPT2 Is Induced by Hypoxia-Inducible Factor (HIF)-2 and Promotes Glioblastoma Growth
Authors: Zhang Bo , Chen Yan , Bao Lei , Luo Weibo
Published: August 2022

Hypoxia-inducible factor (HIF) directly activates the transcription of metabolic enzymes in response to hypoxia to reprogram cellular metabolism required for tumor cell proliferation. Through analyzing glutamate-linked aminotransferases, we here identified glutamate pyruvate transaminase 2 (GPT2) as a direct HIF-2 target gene in human glioblastoma (GBM). Hypoxia upregulated GPT2 mRNA and protein levels in GBM cells, which required HIF-2 but not HIF-1. HIF-2 directly bound to the hypoxia response element of the human GPT2 gene, leading to its transcription in hypoxic GBM cells. GPT2 located at the nucleus and mitochondria and reduced α-ketoglutarate levels in GBM cells. Genetic or pharmacological inhibition of GPT2 decreased GBM cell growth and migration under normoxia and hypoxia. Knockout of GPT2 inhibited GBM tumor growth in mice. Collectively, these findings uncover a hypoxia-inducible aminotransferase GPT2 required for GBM progression.
MIP-Based Screen-Printed Potentiometric Cell for Atrazine Sensing
Authors: Alberti Giancarla , Zanoni Camilla , Spina Stefano , Magnaghi Lisa Rita , Biesuz Raffaela
Published: August 2022

This work presents the development of a MIP-based screen-printed potentiometric cell for sensing the pesticide atrazine. The cell comprises three screen-printed electrodes; the working and the counter are obtained by graphite-ink and the pseudo-reference by silver/silver chloride-ink. All electrodes are printed on the support of polyester. Obviously, only the working and the pseudo-reference electrodes are connected for potentiometric measurements. The prepolymeric mixture was composed of the reagents at the following molar ratio: 1 atrazine (ATZ):5 methacrylic acids (MAA):4 ethylene glycol dimethacrylate (EGDMA). An amount of 7 µL of the prepolymeric solution was drop coated on the graphite working electrode of the cell, and the polymerization was carried out in an oven at 70 °C overnight. The specific sites obtained after polymerization and template elution can be viewed as the ionophore of a usual ISE membrane. The active ion is the atrazine in its protonated form, positively charged, so the determination was carried out in aqueous solutions at pHs1.5. At these conditions, the potential increases linearly with atrazine concentration ranging from 5 × 10−7 to 5 × 10−6 M; the limit of detection obtained is 4 × 10−7 M. The slope of the calibration curve E vs. log c (obtained as an average value of the slope of different standardization performed with several electrodes) is 40(6) mV/dec; the sub-Nernstian behavior can be ascribed to the interference of the anions present in the solution media.
Liquid Chromatography on the Different Methods for the Determination of Lipophilicity: An Essential Analytical Tool in Medicinal Chemistry
Authors: Soares José X. , Santos Álvaro , Fernandes Carla , Pinto Madalena M. M.
Published: August 2022

Lipophilicity is one of many parameters involved in the biological activity of drugs, as it affects their pharmacokinetic and pharmacodynamic behavior. Generally, lipophilicity is assessed by the partition coefficient of a compound between a nonpolar phase (n-octanol) and an aqueous phase (water), expressed as P (partition coefficient) or as its decimal logarithm (Log P). The gold standard method for the experimental determination of Log P is the shake-flask method. In this context, chromatographic methods enable the direct and simple quantification of the partitioned compound between the two phases. This review discusses the use of liquid chromatography (LC) for direct and indirect determination of lipophilicity. Beyond the classical isotropic log P determination, methods for assessing anisotropic lipophilicity are also reviewed. Several examples are discussed that highlight the versatility of LC technique and current trends. The last section of this review focuses on a case study describing an experience of our group and emphasizing the dual role of LC in determining Log P.
Highly Sensitive Ethanol Sensing Using NiO Hollow Spheres Synthesized via Hydrothermal Method
Authors: Li Qingting , Zeng Wen , Zhou Qu , Wang Zhongchang
Published: August 2022

Excessive ethanol gas is a huge safety hazard, and people will experience extreme discomfort after inhalation, so efficient ethanol sensors are of great importance. This article reports on ethanol gas sensors that use NiO hollow spheres assembled from nanoparticles, nanoneedles, and nanosheets prepared by the hydrothermal method. All of the samples were characterized for performance evaluation. The sensors based on the NiO hollow spheres showed a good response to ethanol, and the hollow spheres assembled from nanosheets (NiO-S) obtained the best ethanol gas-sensing performance. NiO-S provided a larger response value (38.4) at 350 °C to 200 ppm ethanol, and it had good stability and reproducibility. The nanosheet structure and the fluffy surface of NiO-S obtained the largest specific surface area (55.20 m2/g), and this structure was beneficial for the sensor to adsorb more gas molecules in an ethanol atmosphere. In addition, the excellent sensing performance could ascribe to the larger Ni3+/Ni2+ of NiO-S, which achieved better electronic properties. Furthermore, in terms of commercial production, the template-free preparation of NiO-S eliminated one step, saving time and cost. Therefore, the sensors based on NiO-S will serve as candidates for ethanol sensing.
Aminoquinoxaline-Based Dual Colorimetric and Fluorescent Sensors for pH Measurement in Aqueous Media
Authors: Ermakova Elizaveta V. , Cheprakov Andrey V. , Bessmertnykh-Lemeune Alla
Published: August 2022

This research is focused on the development of pH indicators based on the quinoxaline signaling group for acidic aqueous solutions (pH 1–5). A push–pull quinoxaline QC1 in which two electron-donating (3-aminopropyl)amino substituents are attached to positions 6 and 7 of the electron-deficient quinoxaline moiety was prepared using the palladium-catalyzed C–N cross-coupling reaction. The 3-aminopropyl residues are mostly protonated in aqueous solutions below pH 8, thus serving as hydrophilizing substituents that render quinoxaline derivative QC1 water-soluble in this range of acidities and useful for measurements in the pH range of 1–5. This chromophore is a dual optical chemosensor that exhibits shifts of both absorption and emission bands in response to external stimuli. The presence of naturally relevant metal cations (13 ions) does not interfere with spectrophotometric and fluorescence measurements of the optical response of aminoquinoxaline in the visible region. Moreover, these spectral changes are easily observed by the naked eye, allowing for rapid semi-quantitative analyses under “in-field” conditions.
Positive Parenting Behaviors and Child Development in Ceará, Brazil: A Population-Based Study
Authors: Rocha Hermano A. L. , Correia Luciano L. , Leite Álvaro J. M. , Rocha Sabrina G. M. O. , Albuquerque Lucas de S. , Machado Márcia M. T. , Campos Jocileide S. , e Silva Anamaria C. , Sudfeld Christopher R.
Published: August 2022

Parenting practices have been identified as a key determinant of children’s developmental outcomes. The aim of this study was to evaluate the association of parenting practices with child development in a cross-sectional population-based study in a low-income state in northeastern Brazil. The study included data on 3566 caregiver–child pairs, and the children were aged 0–66 months. Positive parenting behaviors (PPBs) were conceptualized in areas of interactive play, social development, and speech and language interactions. Child development was evaluated using the Brazilian Ages and Stages Questionnaire. Linear regression analysis was used to assess the relationships. We found that a greater number of PPBs was associated with better child development domain scores. Among infants < 1 year, each additional PPB was associated with a 0.32 standardized mean difference (SMD) greater communication (95% CI: 0.24–0.41) and 0.38 SMD greater problem-solving scores (95% CI: 0.24–0.52). Among children aged 4–6 years old, each additional PPB was associated with improved communication (SMD: 0.22; 95% CI: 0.13–0.32), problem solving (SMD: 0.21; 95% CI: 0.10–0.32) and personal–social domain scores (SMD: 0.26; 95% CI: 0.17–0.36). Our findings indicate that PPB were robustly associated with better outcomes across developmental domains among Brazilian children. Programs and interventions that support PPB can contribute to improvements in development outcomes.
Role of Ultrasound Evaluation of Temporomandibular Joint in Juvenile Idiopathic Arthritis: A Systematic Review
Authors: Marino Achille , De Lucia Orazio , Caporali Roberto
Published: August 2022

Background: Juvenile idiopathic arthritis (JIA) is childhood’s most frequent chronic rheumatic disease. JIA is a broad term that includes all arthritides starting before 16 years, lasting at least six weeks, and of unknown cause. The temporomandibular joint (TMJ) could be involved in JIA both at onset and during the disease course. The presence of TMJ synovitis might severely impair dentofacial maturation in pediatric patients. The ultrasound (US) application to detect early signs of TMJ synovitis in children with JIA has provided contradictory results. We sought to assess the current role of TMJ US in JIA through a systematic literature review. Methods: The systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Results: The literature search found 345 records. After duplicates removal, 253 records were screened, 20 full-text articles were reviewed to assess their eligibility, and 7 of them were included in the qualitative analysis. Joint effusion was the most recorded parameter, followed by bony condylar abnormalities. Compared to contrast enhancement MRI, the capability to detect signs of active synovitis of TMJ by US is low, especially at the early stages. Conclusion: Understanding how US may help diagnose and manage children with JIA is advisable for several reasons. MRI cannot be frequently repeated, may need sedation, and is expensive. The constant technical improvement of US will undoubtedly allow for better evaluation of what, in the past, was not clear or not even captured by sonography. So far, the role of US in the assessment of TMJ involvement in JIA is indubitably secondary to the MRI. Even so, we think that a baseline MRI of TMJ and the repetition of the sonography over time might both help the interpretation of US images and intercept significative changes.
Antibiotherapy in Children with Cystic Fibrosis—An Extensive Review
Authors: Ciuca Ioana Mihaiela , Dediu Mihaela , Popin Diana , Pop Liviu Laurentiu , Tamas Liviu Athos , Pilut Ciprian Nicolae , Almajan Guta Bogdan , Popa Zoran Laurentiu
Published: August 2022

In cystic fibrosis (CF), the respiratory disease is the main factor that influences the outcome and the prognosis of patients, bacterial infections being responsible for severe exacerbations. The etiology is often multi-microbial and with resistant strains. The aim of this paper is to present current existing antibiotherapy solutions for CF-associated infections in order to offer a reliable support for individual, targeted, and specific treatment. The inclusion criteria were studies about antibiotherapy in CF pediatric patients. Studies involving adult patients or those with only in vitro results were excluded. The information sources were all articles published until December 2021, in PubMed and ScienceDirect. A total of 74 studies were included, with a total number of 26,979 patients aged between 0–18 years. We approached each pathogen individual, with their specific treatment, comparing treatment solutions proposed by different studies. Preservation of lung function is the main goal of therapy in CF, because once parenchyma is lost, it cannot be recovered. Early personalized intervention and prevention of infection with reputable germs is of paramount importance, even if is an asymmetrical challenge. This research received no external funding.
Pediatric Minimally Invasive Surgery—A Bibliometric Study on 30 Years of Research Activity
Authors: Shu Boshen , Feng Xiaoyan , Martynov Illya , Lacher Martin , Mayer Steffi
Published: August 2022

Background: Pediatric minimally invasive surgery (MIS) is a standard technique worldwide. We aimed to analyze the research activity in this field. Methods: Articles on pediatric MIS (1991–2020) were analyzed from the Web of Science™ for the total number of publications, citations, journals, and impact factors (IF). Of these, the 50 most cited publications were evaluated in detail and classified according to the level of evidence (i.e., study design) and topic (i.e., surgical procedure). Results: In total, 4464 publications and 53,111 citations from 684 journals on pediatric MIS were identified. The 50 most cited papers were published from 32 institutions in the USA/Canada (n = 28), Europe (n = 19), and Asia (n = 3) in 12 journals. Four authors (USA/Europe) contributed to 26% of the 50 most cited papers as first/senior author. Hot topics were laparoscopic pyeloplasty (n = 9), inguinal hernia repair (n = 7), appendectomy, and pyloromyotomy (n = 4 each). The majority of publications were retrospective studies (n = 33) and case reports (n = 6) (IF 5.2 ± 3.2; impact index 16.5 ± 6.4; citations 125 ± 39.4). They were cited as often as articles with high evidence levels (meta-analyses, n = 2; randomized controlled trials, n = 7; prospective studies, n = 2) (IF 12.9 ± 22.5; impact index 14.0 ± 6.5; citations 125 ± 34.7; p > 0.05). Conclusions: Publications on laparoscopic pyeloplasty, inguinal hernia repair, appendectomy, and pyloromyotomy are cited most often in pediatric MIS. However, the relevant number of studies with strong evidence for the advantages of MIS in pediatric surgery is missing.
Single Nucleotide Polymorphisms May Increase the Risk of Aspiration Pneumonia in Post-Stroke Patients with Dysphagia
Authors: Park Hae-Yeon , Oh Hyun-Mi , Kim Tae-Woo , Kim Youngkook , Park Geun-Young , Hwang Hyemi , Im Sun
Published: August 2022

This study aimed to evaluate whether genetic polymorphism is associated with an increased risk of infection, specifically post-stroke aspiration pneumonia. Blood samples were obtained from a total of 206 post-stroke participants (males, n = 136; mean age, 63.8 years). Genotyping was performed for catechol-O-methyltransferase (rs4680, rs165599), dopamine receptors (DRD1; rs4532, DRD2; rs1800497, DRD3; rs6280), brain-derived neurotrophic factor (rs6265), apolipoprotein E (rs429358, rs7412), and the interleukin-1 receptor antagonist gene (rs4251961). The subjects were stratified into two groups, aged < 65 (young) and ≥ 65 (elderly). Functional parameters and swallowing outcomes were measured at enrollment and at 3 months post-onset. The primary outcome was the incidence of aspiration pneumonia. Analysis of the association between genetic polymorphisms and aspiration pneumonia history showed that a minor C rs429358 allele was associated with the occurrence of aspiration pneumonia in the young group, both in the additive and the dominant models (odds ratio: 4.53; 95% CI: 1.60–12.84, p = 0.004). In the multivariable analysis, the minor C rs429358 allele increased the risk of post-stroke aspiration pneumonia in young stroke patients by 5.35 (95% CI: 1.64–20.88). In contrast, no such association was observed in the elderly group. Apolipoprotein E polymorphism may affect the risk of post-stroke aspiration pneumonia.
Cloning and Molecular Characterization of HSL and Its Expression Pattern in HPG Axis and Testis during Different Stages in Bactrian Camel
Authors: Nan Jinghong , Wang Qi , Yan Qiu , Wang Jie , Zhang Yong , Zhao Xingxu
Published: August 2022

Hormone-sensitive lipase (HSL) is a key enzyme in animal fat metabolism and is involved in the rate-limiting step of catalyzing the decomposition of fat and cholesterol. It also plays an important regulatory role in maintaining seminiferous epithelial structure, androgen synthesis and primordial germ cell differentiation. We previously reported that HSL is involved the synthesis of steroids in Bactrian camels, although it is unclear what role it plays in testicular development. The present study was conducted to characterize the biological function and expression pattern of the HSL gene in the hypothalamic pituitary gonadal (HPG) axis and the development of testis in Bactrian camels. We analyzed cloning of the cDNA sequence of the HSL gene of Bactrian camels by RT-PCR, as well as the structural features of HSL proteins, using bioinformatics software, such as ProtParam, TMHMM, Signal P 4.1, SOPMA and MEGA 7.0. We used qRT-PCR, Western blotting and immunofluorescence staining to clarify the expression pattern of HSL in the HPG axis and testis of two-week-old (2W), two-year-old (2Y), four-year-old (4Y) and six-year-old (6Y) Bactrian camels. According to sequence analysis, the coding sequence (CDS) region of the HSL gene is 648 bp in length and encodes 204 amino acids. According to bioinformatics analysis, the nucleotide and amino acid sequence of Bactrian camel HSL are most similar to those of Camelus pacos and Camelusdromedarius, with the lowest sequence similarity with Mus musculus. In adult Bactrian camel HPG axis tissues, both HSL mRNA and protein expression were significantly higher in the testis than in other tissues (hypothalamus, pituitary and pineal tissues) (p < 0.05). The expression of mRNA in the testis increased with age and was the highest in six-year-old testis (p < 0.01). The protein expression levels of HSL in 2Y and 6Y testis were clearly higher than in 2W and 4Y testis tissues (p < 0.01). Immunofluorescence results indicate that the HSL protein was mainly localized in the germ cells, Sertoli cells and Leydig cells from Bactrian camel testis, and strong positive signals were detected in epididymal epithelial cells, basal cells, spermatocytes and smooth muscle cells, with partially expression in hypothalamic glial cells, pituitary suspensory cells and pineal cells. According to the results of gene ontology (GO) analysis enrichment, HSL indirectly regulates the anabolism of steroid hormones through interactions with various targets. Therefore, we conclude that the HSL gene may be associated with the development and reproduction of Bactrian camels in different stages of maturity, and these results will contribute to further understanding of the regulatory mechanisms of HSL in Bactrian camel reproduction.
An Urban Governance Framework for Including Environmental Migrants in Sustainable Cities
Authors: Kelman Ilan , Clark-Ginsberg Aaron
Published: August 2022

This article proposes an urban governance framework for including environmental migrants in sustainable cities. It outlines the links among environmental migration, vulnerability, and sustainability, showing how vulnerability and sustainability are not about the environment or the human condition as snapshots in space and time, but rather are long-term, multi-scalar, ever-evolving processes. This theoretical baseline is followed by a description of some practical approaches already applied for including environmental migrants in sustainable cities. The wide variety and lack of cohesion justifies the need for a framework, leading to three principal characteristics of a governance framework suitable for addressing vulnerability and environmental migration for urban sustainability: horizontally and vertically networked, inclusive, and evidence-based. As the framework’s three dimensions represent principles or overarching structural solutions rather than presenting operational guidance, the concluding discussion covers the framework’s limitations and a research agenda.
The In Vitro Impact of Two Scaffold-Type Structure Dental Ceramics on the Viability, Morphology, and Cellular Migration of Pharyngeal Cancer Cells
Authors: Fabricky Mihai M. C. , Racea Robert Cosmin , Macasoi Ioana , Pinzaru Iulia , Sinescu Cosmin , Manea Horatiu Cristian , Rusu Laura-Cristina , Stoian Dana , Buzatu Roxana , Dinu Stefania
Published: August 2022

There is a growing trend with respect to the use of ceramic materials in dental practice. With an increase in the number of cases of head and neck cancer, the use of dental implants in these patients is subject to controversy. Consequently, the purpose of the present study was to evaluate the impact of two ceramic materials on the viability, proliferation, migration, and structure of the cytoskeleton and nuclei of pharyngeal cancer cells. Therefore, samples of the two ceramic were immersed in artificial saliva with three different pH values in order to better simulate the natural biological environment. A 21-day immersion period was followed by testing of the saliva on pharyngeal cancer cell line Detroit-562 for its viability, morphology, and migration, as well as its effects on the nucleus and cytoskeleton. The results of the study after stimulation of Detroit-562 cells for 72 h with the three types of artificial saliva in which the ceramic materials were immersed indicated the following: (i) viability of cells did not change significantly, with the percentage of viable cells not falling below 90%; (ii) no morphological changes were recorded, with the shape and number of cells being similar to that of the control cells; (iii) the scratch assay method indicated that the two types of ceramics do not stimulate cell migration; and (iv) fluorescence immunocytochemistry revealed that both the nucleus and the cytoskeleton distributions were unaltered, as they were observed in unstimulated cells. The preliminary results of the study indicate that the investigated ceramic materials did not interact unfavorably with tumor cells when immersed in artificial saliva, thereby supporting the possibility of their safe use in cancer patients.
Biobased Materials for the Development of Biodegradable Slow-Release Fertilizers
Authors: Boberski Przemysław , Torchała Kamila , Studnik Hanna , Wójcik Jan , Główka Marek , Kuźnik Nikodem
Published: August 2022

According to the regulations of the European Parliament on fertilizer products, by July 2024, all substances used for coating fertilizers should be biodegradable. A series of coated fertilizers was prepared, which differed in the amount of applied coating layer. The core of the composition was granular ammonium nitrate, which contains 27% nitrogen. The effects of the amount of oil layers were examined. The article shows the results of IR testing and Iodine Value of the materials used. The coated fertilizer was evaluated for the release of nutrients under water conditions according to the standard ISO 21263, and the water samples were taken after every day for a 7-day period. The nitrogen content was analysed by elemental analysis. Microscopic pictures of the fertilizer composition were taken before release. The obtained product had potential controlled-release properties and was environmentally friendly. The tested material shows high potential as a component of a two-layer coated fertilizer. This type of fertilizer could be particularly useful in agricultural and horticultural applications.
Statistical Analysis Methods Applied to Early Outpatient COVID-19 Treatment Case Series Data
Authors: Gkioulekas Eleftherios , McCullough Peter A. , Zelenko Vladimir
Published: August 2022

When confronted with a public health emergency, significant innovative treatment protocols can sometimes be discovered by medical doctors at the front lines based on repurposed medications. We propose a statistical framework for analyzing the case series of patients treated with such new protocols, that enables a comparison with our prior knowledge of expected outcomes, in the absence of treatment. The goal of the proposed methodology is not to provide a precise measurement of treatment efficacy, but to establish the existence of treatment efficacy, in order to facilitate the binary decision of whether the treatment protocol should be adopted on an emergency basis. The methodology consists of a frequentist component that compares a treatment group against the probability of an adverse outcome in the absence of treatment, and calculates an efficacy threshold that has to be exceeded by this probability, in order to control the corresponding p-value and reject the null hypothesis. The efficacy threshold is further adjusted with a Bayesian technique, in order to also control the false positive rate. A random selection bias threshold is then calculated from the efficacy threshold to control for random selection bias. Exceeding the efficacy threshold establishes the existence of treatment efficacy by the preponderance of evidence, and exceeding the more demanding random selection bias threshold establishes the existence of treatment efficacy by the clear and convincing evidentiary standard. The combined techniques are applied to case series of high-risk COVID-19 outpatients that were treated using the early Zelenko protocol and the more enhanced McCullough protocol.
How Hard Is It to Detect Surveillance? A Formal Study of Panopticons and Their Detectability Problem
Authors: Liagkou Vasiliki , Nastou Panayotis E. , Spirakis Paul , Stamatiou Yannis C.
Published: August 2022

The Panopticon (which means “watcher of everything”) is a well-known prison structure of continuous surveillance and discipline studied by Bentham in 1785. Today, where persistent, massive scale, surveillance is immensely facilitated by new technologies, the term Panopticon vaguely characterizes institutions with a power to acquire and process, undetectably, personal information. In this paper we propose a theoretical framework for studying Panopticons and their detectability status. We show, based on the Theory of Computation, that detecting Panopticons, modelled either as a simple Turing Machine or as an Oracle Turing Machine, is an undecidable problem. Furthermore, we show that for each sufficiently expressive formal system, we can effectively construct a Turing Machine for which it is impossible to prove, within the formal system, its Panopticon status. Finally, we discuss how Panopticons can be physically detected by the heat they dissipate each time they acquire, effortlessly, information in the form of an oracle and we investigate their detectability status with respect to a more powerful computational model than classical Turing Machines, the Infinite Time Turing Machines (ITTMs).
Effect of Ultrasonic Degassing on Mg-Ca Binary Alloy by Ultrasonic Treatment
Authors: Jia Zheng , Yu Bing , Fu Li
Published: August 2022

The effect of ultrasonic treatment parameters, including ultrasonic treatment duration, frequency resonance, and treatment temperature, on the degassing of Mg-3.03Ca alloys was investigated. The results indicated that the optimum degassing efficiency could be obtained under the ultrasonic resonant condition. When applying ultrasonic treatment for 90 s with 150 W at 700 °C, the minimum hydrogen content and the highest degassing efficiency are obtained, respectively (42.8 cm3/100 g and 27.5%). The ultrasonic treatment can remove the gas from the melt and refine the microstructures. Finally, the mechanism of ultrasonic degassing and refinement was analyzed.
Microstructural and Mechanical Properties of a Heat-Treated EV31A Magnesium Alloy Fabricated Using the Stir-Casting Process
Authors: Somasundaram M. , NarendraKumar U.
Published: August 2022

This study aims to prepare a stir-cast EV31A magnesium alloy and investigate the effects of the T4 condition (solid solution strengthening) and T6 condition (solid solution strengthening cum age hardening) on the phases, microstructure, mechanical properties, and fractography. The solid solution at 520 °C for 8 h allows the Rare-Earth Elements (REE) to dissolve in the Mg matrix, but the solubility is limited by the presence of Zn. This phenomenon is responsible for the T4 heat-treated alloy’s strengthening, which raises the UTS to 212 MPa. The formation of new grains within the grains causes an increase in grain boundaries and dislocations during the T6 heat treatment process, increasing the strength (UTS) of the EV31A alloy to 230 MPa. In all three test conditions, the fractography of tensile samples revealed a cleavage-ductile/mixed mode fracture. As expected, the fine-grained T6 sample exhibited superior strengthening at the expense of ductility.
Pyrolyzed Bacterial Cellulose as the Backbone of the Cathode Catalyst-CoFe2O4 for the Li-O2 Battery
Authors: Wang Xiangjun , Chi Yongqing , Wu Peng , Liu Wen
Published: August 2022

In this paper, CoFe2O4@pyrolyzed bacterial cellulose (CFO@PBC) nanocomposites were synthesized by a hydrothermal process and an in situ composite technique as the cathode for rechargeable Li-O2 batteries (LOB). CoFe2O4@Ketjenblack (CFO@KB) were prepared in the same way as the comparison. The as-prepared materials were characterized by SEM, XRD, and BET. The LOB with CFO@PBC-3 showed a maximum initial discharge capacity of 2660 mAh g−1 (electrode) at the current density of 100 mAg−1, while the mass ratio of CoFe2O4 and pyrolyzed bacterial cellulose was 3. The cyclic voltammetry of the CFO@PBC nanocomposite electrodes was investigated at 0.1 mVs−1 in the voltage window of 2.0–4.5 V. With the limited capacity of 640 mAh g−1 (electrode), the CFO@PBC-3 electrode showed the best cycle stability and higher cutoff voltage of discharging. The pyrolyzed bacterial cellulose, as the fibrous 3D backbone in CFO@PBC nanocomposite electrodes, produced better results than the CFO@KB.
Functional and Survival Outcomes of Patients following the Harrington Procedure for Complex Acetabular Metastatic Lesions
Authors: Plaud Andrea , Gaillard Jean , Gouin François , Le Thuaut Aurélie , Ageneau Peggy , Berchoud Juliane , Fouasson-Chailloux Alban , Crenn Vincent
Published: August 2022

Background: The Harrington surgical technique makes it possible to manage complex, extensive bone lesions using pins and cement to consolidate bone for acetabular cup positioning. However, it may be associated with a high reoperation rate, and the functional results of this surgery are not precisely described in the literature. Methods: In a monocentric retrospective study including all patients operated on using the Harrington procedure associated with THA between 2005 and 2020, we aimed to assess preoperative and postoperative function, reoperation-free survival, and overall survival. Results: Functional improvement was significant for Parker scores (preoperative: 3.6 ± 2.0; 6-month follow-up: 6.6 ± 3.2; 12-month follow-up: 7.6 ± 2.1) and Musculoskeletal Tumor Society (MSTS) scores (preoperative: 31.1 ± 16.2%; 6-month follow-up: 67.7 ± 30.6%; 12-month follow-up: 82.4 ± 24.0%). Of the 21 patients included, the reoperation-free survival rate was 76.1% [CI 95%: 58.1–99.7] at six and twelve months, with the main complications being pin migration (50.0%) and infection (25%). The patient overall survival rate was 76.2% [95% CI: 59.9–96.7] at six months and 61.9% [95% CI: 59.9–96.7] at 12 months. Discussion: These results underlined significant functional improvements following a conventional Harrington procedure, with acceptable reoperation rates.
Time to Surgery for Patients with Esophageal Cancer Undergoing Trimodal Therapy in Ontario: A Population-Based Cross-Sectional Study
Authors: Hanna Nader M. , Nguyen Paul , Chung Wiley , Groome Patti A.
Published: August 2022

Patients with resectable esophageal cancer are recommended to undergo chemoradiotherapy before esophagectomy. A longer time to surgery (TTS) and/or time to consultation (TTC) may be associated with inferior cancer-related outcomes and heightened anxiety. Thoracic cancer surgery centers (TCSCs) oversee esophageal cancer management, but differences in TTC/TTS between centers have not yet been examined. This Ontario population-level study used linked administrative healthcare databases to investigate patients with esophageal cancer between 2013–2018, who underwent neoadjuvant chemoradiotherapy and then surgery. TTC and TTS were time from diagnosis to the first surgical consultation and then to surgery, respectively. Patients were assigned a TCSC based on the location of the surgery. Patient, disease, and diagnosing physician characteristics were investigated. Quantile regression was used to model TTS/TTC at the 50th and 90th percentiles and identify associated factors. The median TTS and TTC were 130 and 29 days, respectively. The adjusted differences between the TCSCs with the longest and shortest median TTS and TTC were 32 and 18 days, respectively. Increasing age was associated with a 16-day longer median TTS. Increasing material deprivation was associated with a 6-day longer median TTC. Significant geographic variability exists in TTS and TTC. Therefore, the investigation of TCSC characteristics is warranted. Shortening wait times may reduce patient anxiety and improve the control of esophageal cancer.
Land Uses for Pasture and Cacao Cultivation Modify the Odonata Assemblages in Atlantic Forest Areas
Authors: Santos Laís R. , Rodrigues Marciel E.
Published: August 2022

Tropical forests such as the Atlantic Forest are under constant threats from the impact of human activities, mostly being caused by the loss of native forest areas for other land uses. This study aimed to evaluate the effect of changes in land use for pasture and cacao cultivation on the richness and composition of Odonata assemblages in comparison to native forest areas. We also evaluated the species as possible indicators of these different land uses. In total, 64 streams were sampled in southern Bahia, Brazil. A total of 84 species were recorded. The results indicated that changes in land use modify the richness and composition of Odonata assemblages. Regarding composition, our results indicated a difference among the assemblages in the three land use areas and that the native areas maintain more stable assemblages. According to the indicator species analysis, 13 species were recorded as possible bioindicators for different land uses. Changes in aquatic ecosystems and their surroundings caused by different land uses a select group of different species groups, modifying Odonata diversity among these areas. Notably, land uses that maintain a certain integrity of the environment, as in the case of cacao cultivation, are the best alternatives for conserving Odonata biodiversity in comparison with pasture.