bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactones in the Synthesis of Prostaglandins and Prostaglandin Analogs
Authors: Tănase Constantin , Pintilie Lucia , Tănase Raluca Elena
Published: February 2021

In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF2α and 1,15-PGF2α lactones, many 1,15-lactones of E2, E3, F2, F3, A2, and A3 were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed.
Design and Evaluation of a Polypeptide that Mimics the Integrin Binding Site for EDA Fibronectin to Block Profibrotic Cell Activity
Authors: Zhang Lin , Yan Hongyu , Tai Yifan , Xue Yueming , Wei Yongzhen , Wang Kai , Zhao Qiang , Wang Shufang , Kong Deling , Midgley Adam C.
Published: February 2021

Fibrosis is characterized by excessive production of disorganized collagen- and fibronectin-rich extracellular matrices (ECMs) and is driven by the persistence of myofibroblasts within tissues. A key protein contributing to myofibroblast differentiation is extra domain A fibronectin (EDA-FN). We sought to target and interfere with interactions between EDA-FN and its integrin receptors to effectively inhibit profibrotic activity and myofibroblast formation. Molecular docking was used to assist in the design of a blocking polypeptide (antifibrotic 38-amino-acid polypeptide, AF38Pep) for specific inhibition of EDA-FN associations with the fibroblast-expressed integrins α4β1 and α4β7. Blocking peptides were designed and evaluated in silico before synthesis, confirmation of binding specificity, and evaluation in vitro. We identified the high-affinity EDA-FN C-C′ loop binding cleft within integrins α4β1 and α4β7. The polypeptide with the highest predicted binding affinity, AF38Pep, was synthesized and could achieve specific binding to myofibroblast fibronectin-rich ECM and EDA-FN C-C′ loop peptides. AF38Pep demonstrated potent myofibroblast inhibitory activity at 10 µg/mL and was not cytotoxic. Treatment with AF38Pep prevented integrin α4β1-mediated focal adhesion kinase (FAK) activation and early signaling through extracellular-signal-regulated kinases 1 and 2 (ERK1/2), attenuated the expression of pro-matrix metalloproteinase 9 (MMP9) and pro-MMP2, and inhibited collagen synthesis and deposition. Immunocytochemistry staining revealed an inhibition of α-smooth muscle actin (α-SMA) incorporation into actin stress fibers and attenuated cell contraction. Increases in the expression of mRNA associated with fibrosis and downstream from integrin signaling were inhibited by treatment with AF38Pep. Our study suggested that AF38Pep could successfully interfere with EDA-FN C-C′ loop-specific integrin interactions and could act as an effective inhibitor of fibroblast of myofibroblast differentiation.
Split Enzyme-Based Biosensors for Structural Characterization of Soluble and Insoluble β-Glucans
Authors: Yamanaka Daisuke , Kurita Suzuka , Hanayama Yuka , Adachi Yoshiyuki
Published: February 2021

β-Glucan is widely distributed in various plants and microorganisms and is composed of β-1,3-linked d-glucose units. It may have a branched short or long side chain of glucose units with β-1,6- or β-1,4-linkage. Numerous studies have investigated different β-glucans and revealed their bioactivities. To understand the structure-function relationship of β-glucan, we constructed a split-luciferase complementation assay for the structural analysis of long-chain β-1,6-branched β-1,3-glucan. The N- and C-terminal fragments of luciferase from deep-sea shrimp were fused to insect-derived β-1,3-glucan recognition protein and fungal endo-β-1,6-glucanase (Neg1)-derived β-1,6-glucan recognition protein, respectively. In this approach, two β-glucan recognition proteins bound to β-glucan molecules come into close proximity, resulting in the assembly of the full-length reporter enzyme and induction of transient luciferase activity, indicative of the structure of β-glucan. To test the applicability of this assay, β-glucan and two β-glucan recognition proteins were mixed, resulting in an increase in the luminescence intensity in a β-1,3-glucan with a long polymer of β-1,6-glucan in a dose-dependent manner. This simple test also allows the monitoring of real-time changes in the side chain structure and serves as a convenient method to distinguish between β-1,3-glucan and long-chain β-1,6-branched β-1,3-glucan in various soluble and insoluble β-glucans.
Genetic Therapy for Intervertebral Disc Degeneration
Authors: Roh Eun , Darai Anjani , Kyung Jae , Choi Hyemin , Kwon Su , Bhujel Basanta , Kim Kyoung , Han Inbo
Published: February 2021

Intervertebral disc (IVD) degeneration can cause chronic lower back pain (LBP), leading to disability. Despite significant advances in the treatment of discogenic LBP, the limitations of current treatments have sparked interest in biological approaches, including growth factor and stem cell injection, as new treatment options for patients with chronic LBP due to IVD degeneration (IVDD). Gene therapy represents exciting new possibilities for IVDD treatment, but treatment is still in its infancy. Literature searches were conducted using PubMed and Google Scholar to provide an overview of the principles and current state of gene therapy for IVDD. Gene transfer to degenerated disc cells in vitro and in animal models is reviewed. In addition, this review describes the use of gene silencing by RNA interference (RNAi) and gene editing by the clustered regularly interspaced short palindromic repeats (CRISPR) system, as well as the mammalian target of rapamycin (mTOR) signaling in vitro and in animal models. Significant technological advances in recent years have opened the door to a new generation of intradiscal gene therapy for the treatment of chronic discogenic LBP.
Ileum Gene Expression in Response to Acute Systemic Inflammation in Mice Chronically Fed Ethanol: Beneficial Effects of Elevated Tissue n-3 PUFAs
Authors: Hardesty Josiah E. , Warner Jeffrey B. , Song Ying L. , Rouchka Eric C. , McClain Craig J. , Warner Dennis R. , Kirpich Irina A.
Published: February 2021

Chronic alcohol consumption leads to disturbances in intestinal function which can be exacerbated by inflammation and modulated by different factors, e.g., polyunsaturated fatty acids (PUFAs). The mechanisms underlying these alterations are not well understood. In this study, RNA-seq analysis was performed on ileum tissue from WT and fat-1 transgenic mice (which have elevated endogenous n-3 PUFAs). Mice were chronically fed ethanol (EtOH) and challenged with a single lipopolysaccharide (LPS) dose to induce acute systemic inflammation. Both WT and fat-1 mice exhibited significant ileum transcriptome changes following EtOH + LPS treatment. Compared to WT, fat-1 mice had upregulated expression of genes associated with cell cycle and xenobiotic metabolism, while the expression of pro-inflammatory cytokines and pro-fibrotic genes was decreased. In response to EtOH + LPS, fat-1 mice had an increased expression of genes related to antibacterial B cells (APRIL and IgA), as well as an elevation in markers of pro-restorative macrophages and γδ T cells that was not observed in WT mice. Our study significantly expands the knowledge of regulatory mechanisms underlying intestinal alterations due to EtOH consumption and inflammation and identifies the beneficial transcriptional effects of n-3 PUFAs, which may serve as a viable nutritional intervention for intestinal damage resulting from excessive alcohol consumption.
Neurotrophins Time Point Intervention after Traumatic Brain Injury: From Zebrafish to Human
Authors: Cacialli Pietro
Published: February 2021

Traumatic brain injury (TBI) remains the leading cause of long-term disability, which annually involves millions of individuals. Several studies on mammals reported that neurotrophins could play a significant role in both protection and recovery of function following neurodegenerative diseases such as stroke and TBI. This protective role of neurotrophins after an event of TBI has also been reported in the zebrafish model. Nevertheless, reparative mechanisms in mammalian brain are limited, and newly formed neurons do not survive for a long time. In contrast, the brain of adult fish has high regenerative properties after brain injury. The evident differences in regenerative properties between mammalian and fish brain have been ascribed to remarkable different adult neurogenesis processes. However, it is not clear if the specific role and time point contribution of each neurotrophin and receptor after TBI is conserved during vertebrate evolution. Therefore, in this review, I reported the specific role and time point of intervention for each neurotrophic factor and receptor after an event of TBI in zebrafish and mammals.
Improving Amharic Speech Recognition System Using Connectionist Temporal Classification with Attention Model and Phoneme-Based Byte-Pair-Encodings
Authors: Emiru Eshete Derb , Xiong Shengwu , Li Yaxing , Fesseha Awet , Diallo Moussa
Published: February 2021

Out-of-vocabulary (OOV) words are the most challenging problem in automatic speech recognition (ASR), especially for morphologically rich languages. Most end-to-end speech recognition systems are performed at word and character levels of a language. Amharic is a poorly resourced but morphologically rich language. This paper proposes hybrid connectionist temporal classification with attention end-to-end architecture and a syllabification algorithm for Amharic automatic speech recognition system (AASR) using its phoneme-based subword units. This algorithm helps to insert the epithetic vowel እ[ɨ], which is not included in our Grapheme-to-Phoneme (G2P) conversion algorithm developed using consonant–vowel (CV) representations of Amharic graphemes. The proposed end-to-end model was trained in various Amharic subwords, namely characters, phonemes, character-based subwords, and phoneme-based subwords generated by the byte-pair-encoding (BPE) segmentation algorithm. Experimental results showed that context-dependent phoneme-based subwords tend to result in more accurate speech recognition systems than the character-based, phoneme-based, and character-based subword counterparts. Further improvement was also obtained in proposed phoneme-based subwords with the syllabification algorithm and SpecAugment data augmentation technique. The word error rate (WER) reduction was 18.38% compared to character-based acoustic modeling with the word-based recurrent neural network language modeling (RNNLM) baseline. These phoneme-based subword models are also useful to improve machine and speech translation tasks.
Adaptive Enterprise Architecture for the Digital Healthcare Industry: A Digital Platform for Drug Development
Authors: Masuda Yoshimasa , Zimmermann Alfred , Viswanathan Murlikrishna , Bass Matt , Nakamura Osamu , Yamamoto Shuichiro
Published: February 2021

Enterprise architecture (EA) is useful for effectively structuring digital platforms with digital transformation in information societies. Moreover, digital platforms in the healthcare industry accelerate and increase the efficiency of drug discovery and development processes. However, there is the lack of knowledge concerning relationships between EA and digital platforms, in spite of the needs of it. In this paper, we investigated and analyzed the process of drug design and development within the healthcare industry, together with related work in using an enterprise architecture framework for the digital era named the Adaptive Integrated Digital Architecture Framework (AIDAF), specifically supporting the design of digital platforms there. Based on this analysis, we evaluate a method and propose a new reference architecture for promoting digital platforms in the healthcare industry, with future specific aspects of them making effective use of Artificial Intelligence (AI). The practical and theoretical contributions include: (1) Streamlined processes through digital platforms in organizations. (2) Informal knowledge supply and sharing among organizational members through digital platforms. (3) Efficiency and effectiveness in planning production and business for drug development. The findings indicate that EA with digital platforms using the AIDAF contribute to digital transformation with effectiveness for new drugs in the healthcare industry.
Hyperintense Brain Lesions in Asymptomatic Low Risk Patients with Paroxysmal Atrial Fibrillation Undergoing Radiofrequency Pulmonary Vein Isolation
Authors: Wieczorek Joanna , Mizia-Stec Katarzyna , Lasek-Bal Anetta , Wieczorek Piotr , Woźniak-Skowerska Iwona , Wnuk-Wojnar Anna M. , Szydło Krzysztof
Published: February 2021

Background: The aim was to determine the occurrence, consequences and risk factors for brain white matter hyperintensities (WMH) assessed in magnetic resonance imaging (MRI) in low-risk patients with paroxysmal atrial fibrillation (AF) undergoing radiofrequency pulmonary vein isolation (PVI-RF). Methods: 74 patients with AF (median 58.5 years (IQR 50–63), 45 male) were included. Before and after a minimum of 6 months after PVI-RF, a brain MRI and a mini-mental state examination (MMSE) were performed. Results: Baseline WMH lesions were found in 55 (74.3%) patients and in 48 from 62 (77.4%) patients after PVI-RF. The WMH lesions were more frequent among older patients, with a higher CHA2DS2-Vasc (C—Congestive heart failure/LV dysfunction, H—Hypertension, A—Age, D—Diabetes mellitus, S—Stroke, V—Vascular Disease, Sc—Sex category). Factors affecting the severity of the WMH were: older age, the co-existence of the PFO and coronary artery disease (CAD). After a follow-up period, the factors predisposing to brain WMH lesions occurrence (age, higher BMI and CHA2DS2-Vasc score) and to the more advanced changes (age, higher CHA2DS2-Vasc score, CAD, PFO) were obtained. Conclusions: The presence and severity of cerebral microembolism are associated with age, higher CHA2DS2-Vasc score and the coexistence of PFO and CAD. PVI-RF procedure and its efficacy does not influence on MRI lesions. In this population, cerebral microembolism is not related to cognitive impairment.
Impact of Mastectomy on Body Image and Sexuality from a LGBTQ Perspective: A Narrative Review
Authors: Skórzewska Magdalena , Kurylcio Andrzej , Rawicz-Pruszyński Karol , Chumpia Wachirabhorn , Punnanan Buabongkoj , Jirapongvanich Sasiwan , Jiang Tianxiao , Mielko Jerzy
Published: February 2021

Although mastectomy could lead to a decrease in sexual performance among patients, only a handful of studies focused on the psychological and sexual behavioral aspects after the surgery. Research on post-mastectomy sexuality has focused mainly on female subjects but barely on lesbian, gay, bisexual, transgender, queer (LGBTQ), and male patients. This narrative review aimed to explore the importance of sexuality after mastectomy from a LGBTQ perspective. Each sexual minority group has been addressed individually. In general, sexual and gender minority breast cancer (BC) patients undergoing bilateral mastectomy expect a complex treatment plan in terms of physical and emotional outcomes. Bilateral mastectomy or top surgery for masculinization reasons was reported to be the most popular procedure among transmen, which resulted in a significant improvement in the quality of life. Heterosexual and lesbian female patients are willing to undergo mastectomy after repeated lumpectomies or to avoid radiation, despite potential post-operative somatic and quality-of-life complications. Transwomen would seek gender-affirming surgery to improve physical satisfaction and psychological well-being. There is not enough evidence for non-oncological reasons and consequences of mastectomy in gay men and cisgender heterosexual men. Establishing the awareness of the sexuality impact of mastectomy will allow the implementation of tailored perioperative psychological care.
Safety and Effectiveness of Edoxaban in Atrial Fibrillation Patients in Routine Clinical Practice: One-Year Follow-Up from the Global Noninterventional ETNA-AF Program
Authors: De Caterina Raffaele , Kim Young-Hoon , Koretsune Yukihiro , Wang Chun-Chieh , Yamashita Takeshi , Chen Cathy , Reimitz Paul-Egbert , Unverdorben Martin , Kirchhof Paulus
Published: February 2021

Non-vitamin K antagonist oral anticoagulants such as edoxaban are the standard of care for stroke prevention in patients with atrial fibrillation (AF). The Global Edoxaban Treatment in routiNe clinical prActice (ETNA)-AF program integrates prospective, observational, noninterventional regional studies from Europe, Japan, and other Asian countries, collecting data on patient characteristics and clinical outcomes in unselected patients treated with edoxaban for stroke prevention in AF. Overall, 26,823 patients completed a 1-year follow-up and were treated with edoxaban; either 60 or 30 mg once daily. The majority (82.6%) of patients received the recommended doses according to the local label. At baseline, the median (interquartile range) age was 75 (68, 80) years, the CHA2DS2-VASc score was 3.0 (2.0, 4.0), and the hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs, or alcohol (HAS-BLED) score was 2.0 (2.0, 3.0). At one year, there were 273 (1.12%/year) major bleeding events, including 75 (0.31%/year) intracranial hemorrhages and 140 (0.57%/year) major gastrointestinal (GI) bleeds. There were 214 ischemic strokes (0.87%/year). Mortality was 3.03%/year (745 deaths), and cardiovascular mortality accounted for 40% of all deaths (1.22%/year, 299 cardiovascular deaths). In conclusion, stroke, intracranial hemorrhage, and other major bleeding events were low in patients with AF treated with edoxaban in routine care. Even on anticoagulation, cardiovascular death remained common.
Small Vessel Disease: Another Component of the Hypertrophic Cardiomyopathy Phenotype Not Necessarily Associated with Fibrosis
Authors: De Gaspari Monica , Basso Cristina , Perazzolo Marra Martina , Elia Stefania , Bueno Marinas Maria , Angelini Annalisa , Thiene Gaetano , Rizzo Stefania
Published: February 2021

Background: Hypertrophic cardiomyopathy (HCM) is characterized by myocardial disarray, small vessel disease (SVD), and fibrosis. The relationship between SVD and replacement-type fibrosis is still unclear. Methods: Histopathologic assessment of replacement-type fibrosis and SVD in HCM patients with either end-stage heart failure (HF) or sudden cardiac death (SCD). Chronic ischemic heart disease (IHD) patients served as controls. Results: Forty HCM hearts, 10 HF and 30 SCD, were studied. Replacement-type fibrosis was detected in all HF and in 57% of SCD cases. In SCD, replacement-type fibrosis was associated with older age, greater septal thickness, SVD prevalence, and score (all p < 0.05). Prevalence of SVD did not show significant differences among SCD, HF, and IHD (73%, 100% and 95%, respectively), while SVD score was higher in HF than IHD and SCD (2.4, 1.95, and 1.18, respectively) and in areas with replacement-type fibrosis vs. those without in HF (3.4 vs. 1.4) and SCD (1.4 vs. 0.8) (all p < 0.05). Conclusions: SVD is a frequent feature in HCM independent of the clinical presentation. A higher SVD score is observed in HCM-HF and in areas with replacement-type fibrosis. Although SVD is part of the HCM phenotype, further remodeling of the microcirculation might occur secondarily to fibrosis.
Oral Complications of ICU Patients with COVID-19: Case-Series and Review of Two Hundred Ten Cases
Authors: Hocková Barbora , Riad Abanoub , Valky Jozef , Šulajová Zuzana , Stebel Adam , Slávik Rastislav , Bečková Zuzana , Pokorná Andrea , Klugarová Jitka , Klugar Miloslav
Published: February 2021

Background: The critically ill patients suffering from coronavirus disease (COVID-19) and admitted to the intensive care units (ICUs) are susceptible to a wide array of complications that can be life-threatening or impose them to long-term complications. The COVID-19 oral mucocutaneous complications require multidisciplinary management and research for their pathophysiological course and epidemiological significance; therefore, the objective of this study was to evaluate the prevalence and characteristics of the critically ill COVID-19 patients with oral complications. Methods: We described the clinical and microbiological characteristics of the critically ill COVID-19 patients in our ICU department (Banska Bystrica, Slovakia). In addition, we reviewed the current body of evidence in Ovid MEDLINE®, Embase, Cochrane Library, and Google Scholar for the oral mucocutaneous complications of ICU patients with COVID-19. Results: Three out of nine critically ill patients (33.3%) in our ICU department presented with oral complications including haemorrhagic ulcers and necrotic ulcers affecting the lips and tongue. The microbiological assessment revealed the presence of opportunistic pathogens, confirming the possibility of co-infection. On reviewing the current literature, two hundred ten critically ill patients were reported to have oral complications due to their stay in the ICU setting. Perioral pressure ulcers were the most common complication, followed by oral candidiasis, herpetic and haemorrhagic ulcers, and acute onset macroglossia. The prolonged prone positioning and mechanical ventilation devices were the primary risk factors for those oral complications, in addition to the immunosuppressive drugs. Conclusions: The multidisciplinary approach is strongly advocated for monitoring and management of COVID-19 patients, thus implying that dermatology and oral healthcare specialists and nurses should be integrated within the ICU teams.
Predicted Versus Non-Predicted Opioid Administration Using Preoperative Pain Sensitivity in Patients Undergoing Gynecological Surgery: A Randomized-Controlled Trial
Authors: Park Sun-Kyung , Kim Hansol , Yoo Seokha , Kim Won Ho , Lim Young-Jin , Kim Jin-Tae
Published: February 2021

Individualized administration of opioids based on preoperative pain sensitivity may improve postoperative pain profiles. This study aimed to examine whether a predicted administration of opioids could reduce opioid-related adverse effects after gynecological surgery. Patients were randomized to the predicted group or control group. Participants received a preoperative sensory test to measure pressure pain thresholds. Patients were treated with a higher or lower (15 or 10 μg/mL) dose of fentanyl via intravenous patient-controlled analgesia. The opioid dose was determined according to pain sensitivity in the predicted group, while it was determined regardless of pain sensitivity in the control group. The primary outcome was the incidence of nausea over the first 48 h postoperative period. Secondary outcomes included postoperative pain scores and opioid requirements. There was no difference in the incidence of nausea (40.0% vs. 52.5% in predicted and control groups, respectively; p = 0.191) and postoperative pain scores (3.3 vs. 3.5 in predicted and control groups, respectively; p = 0.691). However, opioid consumptions were lower in the predicted group compared to the control group (median 406.0 vs. 526.5 μg; p = 0.042). This study showed that offering a predicted dose of opioids according to pain sensitivity did not affect the incidence of nausea and pain scores.
Human Uterus Transplantation from Living and Deceased Donors: The Interim Results of the First 10 Cases of the Czech Trial
Authors: Fronek Jiri , Kristek Jakub , Chlupac Jaroslav , Janousek Libor , Olausson Michael
Published: February 2021

Introduction: Uterus transplantation (UTx) is a rapidly evolving treatment of uterine-factor infertility. We report the results of the first 10 UTx procedures performed at our institution. Methods: The program started in April 2016 as a two-arm study comparing the efficacy of UTx from live donors (LD) and deceased donors (DD). Results: Between April 2016 and April 2018, we performed five DD UTx and five LD UTx. Two grafts had to be removed early due to thrombosis. One graft was removed due to chronic rejection and previous herpes simplex infection at month 7. Graft survival is 70% at one year. Recipient survival is 100% at two years. Live donor survival is 100% at three years. Three live-births have been achieved, two from a LD and one from a graft from a nulliparous DD. Vaginal anastomotic stenosis occurred in 63% (5/8) of grafts. Self-expanding stents have shown preliminary suitability for the treatment of vaginal stenosis. Three recipients developed severe acute rejection. Conclusion: The interim results of our study demonstrate mid-term viability in 70% of grafts. The LD UTx produced two live births and the DD UTx produced one live birth. Nulliparous donors should be considered for donation.
New Challenges of Treatment for Locally Advanced Head and Neck Cancers in the Covid-19 Pandemic Era
Authors: Mireștean Camil Ciprian , Crișan Anda , Mitrea Adina , Buzea Călin , Iancu Roxana Irina , Iancu Dragoș Petru Teodor
Published: February 2021

Locally advanced head and neck cancer is a unique challenge for cancer management in the Covid-19 situation. The negative consequences of delaying radio-chemotherapy treatment make it necessary to prioritize these patients, the continuation of radiotherapy being indicated even if SARS-CoV-2 infection is confirmed in the case of patients with moderate and mild symptoms. For an early scenario, the standard chemo-radiotherapy using simultaneous integrated boost (SIB) technique is the preferred option, because it reduces the overall treatment time. For a late scenario with limited resources, hypo-fractionated treatment, with possible omission of chemotherapy for elderly patients and for those who have comorbidities, is recommended. Concurrent chemotherapy is controversial for dose values >2.4 Gy per fraction. The implementation of hypo-fractionated regimens should be based on a careful assessment of dose-volume constraints for organs at risks (OARs), using recommendations from clinical trials or dose conversion based on the linear-quadratic (LQ) model. Induction chemotherapy is not considered the optimal solution in this situation because of the risk of immunosuppression even though in selected groups of patients TPF regimen may bring benefits. Although the MACH-NC meta-analysis of chemotherapy in head and neck cancers did not demonstrate the superiority of induction chemotherapy over concurrent chemoradiotherapy, an induction regimen could be considered for cases with an increased risk of metastasis even in the case of a possible Covid-19 pandemic scenario.
Trough Concentrations of Specific Antibodies in Primary Immunodeficiency Patients Receiving Intravenous Immunoglobulin Replacement Therapy
Authors: Hassin Ori , Abu Freih Yahya , Hazan Ran , Lev Atar , Zrihen Keren S. , Somech Raz , Broides Arnon , Nahum Amit
Published: February 2021

Immunoglobulin replacement therapy is a mainstay therapy for patients with primary immunodeficiency (PID). The content of these preparations was studied extensively. Nevertheless, data regarding the effective specific antibodies content (especially in the nadir period), and, in different groups of PID patients is limited. We studied trough IgG concentrations as well as anti-Pneumococcus, anti-Haemophilus influenzae b, anti-Tetanus, and anti-Measles antibody concentrations in 17 PID patients receiving intravenous immunoglobulin (IVIg) compared with healthy controls matched for age and ethnicity. We also analyzed these results according to the specific PID diagnosis: X-linked agammaglobulinemia (XLA), combined immunodeficiency (CID), and ataxia telangiectasia (AT). We recorded a higher concentration of anti-pneumococcal polysaccharide antibodies in healthy controls compared to the entire group of PID patients. We also found significantly higher anti-tetanus toxoid antibody concentrations in the XLA patients, compared to CID patients. Anti-Haemophilus Influenzae b antibody titers were overall similar between all the groups. Interestingly, there were overall low titers of anti-Measles antibodies below protective cutoff antibody concentrations in most patients as well as in healthy controls. We conclude that relying on total IgG trough levels is not necessarily a reflection of effective specific antibodies in the patient’s serum. This is especially relevant to CID patients who may have production of nonspecific antibodies. In such patients, a higher target trough IgG concentration should be considered. Another aspect worth considering is that the use of plasma from adult donors with a waning immunity for certain pathogens probably affects the concentrations of specific antibodies in IVIg preparations.
Role of microRNAs in Lung Carcinogenesis Induced by Asbestos
Authors: Bersimbaev Rakhmetkazhy , Bulgakova Olga , Aripova Akmaral , Kussainova Assiya , Ilderbayev Oralbek
Published: February 2021

MicroRNAs are a class of small noncoding endogenous RNAs 19–25 nucleotides long, which play an important role in the post-transcriptional regulation of gene expression by targeting mRNA targets with subsequent repression of translation. MicroRNAs are involved in the pathogenesis of numerous diseases, including cancer. Lung cancer is the leading cause of cancer death in the world. Lung cancer is usually associated with tobacco smoking. However, about 25% of lung cancer cases occur in people who have never smoked. According to the International Agency for Research on Cancer, asbestos has been classified as one of the cancerogenic factors for lung cancer. The mechanism of malignant transformation under the influence of asbestos is associated with the genotoxic effect of reactive oxygen species, which initiate the processes of DNA damage in the cell. However, epigenetic mechanisms such as changes in the microRNA expression profile may also be implicated in the pathogenesis of asbestos-induced lung cancer. Numerous studies have shown that microRNAs can serve as a biomarker of the effects of various adverse environmental factors on the human body. This review examines the role of microRNAs, the expression profile of which changes upon exposure to asbestos, in key processes of carcinogenesis, such as proliferation, cell survival, metastasis, neo-angiogenesis, and immune response avoidance.
Optimization of Inventory Holding Cost Due to Price, Weight, and Volume of Items
Authors: Gurtu Amulya
Published: February 2021

The inventory carrying cost has been assumed uniform for all products in an organization or a warehouse. This assumption is not valid for a diversified range of items in an organization or warehouse. This paper tested this hypothesis of variations in inventory holding costs in a warehouse in two industries based on the physical nature and the price of products. It is found that organizations with a wide variety of products need to calculate the inventory holding cost for each item (SKU) rather than using an average percentage cost of inventory. Inventory holding costs of items in two different organizations were calculated based on the various factors, including the actual cost of space due to the voluminous nature of the items with their existing inventory policies. A variation in inventory holding costs for each item was observed. The variation was small for an organization with homogeneous input costs, and it was large for a multi-product organization. The overall savings in the inventory holding cost due to adjusting the inventory policies through this methodology was found to be about 3%, which is significant for a big organization. This analysis will affect the decision the determining inventory carrying cost, inventory policies (e.g., stocking levels), and pricing policies (e.g., quantity discounts) for retail organizations.
Land–Lake Linkage and Remote Sensing Application in Water Quality Monitoring in Lake Okeechobee, Florida, USA
Authors: Hajigholizadeh Mohammad , Moncada Angelica , Kent Samuel , Melesse Assefa M.
Published: February 2021

The state of water quality of lakes is highly related to watershed processes which will be responsible for the delivery of sediment, nutrients, and other pollutants to receiving water bodies. The spatiotemporal variability of water quality parameters along with the seasonal changes were studied for Lake Okeechobee, South Florida. The dynamics of selected four water quality parameters: total phosphate (TP), total Kjeldahl nitrogen (TKN), total suspended solid (TSS), and chlorophyll-a (chl-a) were analyzed using data from satellites and water quality monitoring stations. Statistical approaches were used to establish correlation between reflectance and observed water quality records. Landsat Thematic Mapper (TM) data (2000 and 2007) and Landsat Operational Land Imager (OLI) in 2015 in dry and wet seasons were used in the analysis of water quality variability in Lake Okeechobee. Water quality parameters were collected from twenty-six (26) monitoring stations for model development and validation. In the regression model developed, individual bands, band ratios and various combination of bands were used to establish correlation, and hence generate the models. A stepwise multiple linear regression (MLR) approach was employed and the results showed that for the dry season, higher coefficient of determination (R2) were found (R2 = 0.84 for chl-a and R2 = 0.67 for TSS) between observed water quality data and the reflectance data from the remotely-sensed data. For the wet season, the R2 values were moderate (R2 = 0.48 for chl-a and R2 = 0.60 for TSS). It was also found that strong correlation was found for TP and TKN with chl-a, TSS, and selected band ratios. Total phosphate and TKN were estimated using best-fit multiple linear regression models as a function of reflectance data from Landsat TM and OLI, and ground data. This analysis showed a high coefficient of determination in dry season (R2 = 0.92 for TP and R2 = 0.94 for TKN) and in wet season (R2 = 0.89 for TP and R2 = 0.93 for TKN). Based on the findings, the Multiple linear regression (MLR) model can be a useful tool for monitoring large lakes like Lake Okeechobee and also predict the spatiotemporal variability of both optically active (Chl-a and TSS) and inactive water (nutrients) quality parameters.
Landscape Sensitizing through Expansive Learning in Architectural Education
Authors: Kurjenoja Anne Kristiina , Schumacher Melissa , Carrera-Kurjenoja Janina
Published: February 2021

Expansive learning is a teaching–learning method adopted by the Department of Architecture of Universidad de las Américas Puebla, Mexico, to introduce architectural students to the field of landscape sensitizing. This approach has been especially valuable considering the particular cultural and natural values of the Mexican landscapes. In it, architectural students are introduced to co-configuration strategies along with co-working methods with the participation of specialists and local stakeholders and community on the “barefoot” bottom-up basis. The community of Tochimilco, Puebla, was selected as a case study through which students can learn how vulnerable rural landscapes and their natural environments can be protected, constructed, and developed. Therefore, studying natural landscape and environmental conditions of Tochimilco through data collection, fieldwork and student workshops was carried out to reinforce the understanding of landscape features, values, semiotics, and meanings in a Socio-Ecological System of landscape (SES) framework. In this context, the expansive learning processes revealed the potentiality of architectural students to become environmental facilitators for future design and planning projects to trigger sensitizing and comprehensive approaches. In these terms, architectural education prepares students to recognize and be aware of natural values, landscape narratives and the “barefoot” relationship between the landscape and the human being occupying and cultivating it.
A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression
Authors: Michalettou Theodora-Dafni , Michalopoulos Ioannis , Costes Sylvain V. , Hellweg Christine E. , Hada Megumi , Georgakilas Alexandros G.
Published: February 2021

The use of high linear energy transfer (LET) ionizing radiation (IR) is progressively being incorporated in radiation therapy due to its precise dose localization and high relative biological effectiveness. At the same time, these benefits of particle radiation become a high risk for astronauts in the case of inevitable cosmic radiation exposure. Nonetheless, DNA Damage Response (DDR) activated via complex DNA damage in healthy tissue, occurring from such types of radiation, may be instrumental in the induction of various chronic and late effects. An approach to elucidating the possible underlying mechanisms is studying alterations in gene expression. To this end, we identified differentially expressed genes (DEGs) in high Z and high energy (HZE) particle-, γ-ray- and X-ray-exposed healthy human tissues, utilizing microarray data available in public repositories. Differential gene expression analysis (DGEA) was conducted using the R programming language. Consequently, four separate meta-analyses were conducted, after DEG lists were grouped depending on radiation type, radiation dose and time of collection post-irradiation. To highlight the biological background of each meta-analysis group, functional enrichment analysis and biological network construction were conducted. For HZE particle exposure at 8–24 h post-irradiation, the most interesting finding is the variety of DNA repair mechanisms that were downregulated, a fact that is probably correlated with complex DNA damage formation. Simultaneously, after X-ray exposure during the same hours after irradiation, DNA repair mechanisms continue to take place. Finally, in a further comparison of low- and high-LET radiation effects, the most prominent result is that autophagy mechanisms seem to persist and that adaptive immune induction seems to be present. Such bioinformatics approaches may aid in obtaining an overview of the cellular response to high-LET particles. Understanding these response mechanisms can consequently aid in the development of countermeasures for future space missions and ameliorate heavy ion treatments.
Male Deep-Sea Shrimps Aristeus antennatus at Fishing Grounds: Growth and First Evaluation of Recruitment by Multilocus Genotyping
Authors: Abras Alba , García-Marín Jose-Luis , Heras Sandra , Vera Manuel , Agulló Melania , Planella Laia , Roldán María Inés
Published: February 2021

The population biology of the deep-sea shrimp Aristeus antennatus, as with other exploited demersal species, is usually studied using data from fishery statistics. Such statistical analyses have shown female-biased sex ratios during the spawning season in this species. Because the abundance of males increases at greater depths that are not exploited by fisheries (virgin grounds), knowledge on their recruitment is limited. Here, the growth and recruitment of A. antennatus males at fishing grounds was evaluated. This was achieved by integrating information on previously identified breeding behaviours and by tracing the young-of-year cohort through genotyping at 10 microsatellite loci. Using a codend and a codend cover with distinct meshed windows, four groups of males were collected in winter and in a subsequent spawning summer season. Summer collections were mostly composed of pre-adult males, reaching sizes that are to be expected from the growth of winter juveniles; however, many specimens also originated from nearby grounds. This result indicates the horizontal dispersal of male juveniles via intermediate and deep oceanographic currents. Such dispersal complements passive larval dispersal in surface waters, and contributes to the weak genetic divergence among regional fishing grounds. These features could be shared by other deep-sea crustacean and fish species, and should be considered for the sustainable exploitation of demersal fisheries.
Adiposity in Depression or Depression in Adiposity? The Role of Immune-Inflammatory-Microbial Overlap
Authors: Gawlik-Kotelnicka Oliwia , Strzelecki Dominik
Published: February 2021

Some of the most common and debilitating conditions are metabolic disorders (metabolic syndrome and non-alcoholic fatty liver disease) and depression. These conditions are also exacerbated by the fact that they often co-occur. Although the exact mechanisms underlying such relationships are poorly known, antipsychotic medication and antidepressant use, diet and physical activity, and lifestyle factors are believed to play a role; however, their high co-occurrence rate suggests a possible pathophysiological overlap. This paper reviews several possible bases for this overlap, including hypothalamic-pituitary-adrenal axis dysregulation, immune alterations with chronic inflammation, and oxidative stress. While it is entirely possible that changes in the microbiota may play a role in each of them, interventions based on the implementation of dietary and other lifestyle changes, supplementation with prebiotics or probiotics and faecal microbiota transplantation have failed to achieve conclusive results. A better characterization of the above associations may allow a more targeted approach to the treatment of both depressive and metabolic disorders. The paper also presents several practical applications for future studies.
Sarcopenic Obesity in Non-Alcoholic Fatty Liver Disease—The Union of Two Culprits
Authors: Emhmed Ali Saad , Nguyen Mindie H.
Published: February 2021

Non-alcoholic fatty liver disease (NAFLD) continues to rise and has become the most common cause of chronic liver disease among all ages and ethnicities. Metabolic disorders, such as obesity and insulin resistance, are closely associated with sarcopenia and NAFLD. Sarcopenic obesity is a clinical disorder characterized by the simultaneous loss of skeletal muscle and gain of adipose tissue. It is associated with worse outcomes in individuals with NAFLD. It is projected that NAFLD and sarcopenia will rise as the prevalence of obesity continues to increase at an unparallel rate. Recently, sarcopenia and sarcopenic obesity have gained considerable interest, but we still lack a well-defined definition and a management approach. Therefore, it is imperative to continue shining the light on this topic and better understand the underlying mechanism as well as treatment options. In this review article, we aimed to address the pathophysiology, impact, and outcomes of sarcopenic obesity on NAFLD.
Fly Ash with Ammonia: Properties and Emission of Ammonia from Cement Composites
Authors: Chyliński Filip , Goljan Anna , Michalik Agnieszka
Published: February 2021

The article presents the results of tests performed on fly ash with a high content of ammonium (up to 400 ppm) from the NOx reduction process. The main properties of fly ash were tested according to EN 450-1 and the results were compared with fly ash without ammonium. The comparison showed that fly ash with high concentration of ammonium suits the requirements of the European standard. Although the requirements do not limit the ammonium content, using such material as an additive for cement composites causes the emission of gaseous ammonium during mixing and from the final product. For this reason, the emission of ammonium from mortars containing fly ash were tested. The results have shown that using high ammonium fly ash might pollute indoor air and affect the health of users.
Microstructures and Macrosegregation of Al–Zn–Mg–Cu Alloy Billet Prepared by Uniform Direct Chill Casting
Authors: Zhou Li , Luo Yajun , Zhang Zhenlin , He Min , Xu Yinao , Zhao Yulei , Liu Sheng , Dong Lijun , Zhang Zhifeng
Published: February 2021

In this study, large-sized Al–Zn–Mg–Cu alloy billets were prepared by direct chill casting imposed with annular electromagnetic stirring and intercooling; a process named uniform direct chill casting. The effects of uniform direct chill casting on grain size and the alloying element distribution of the billets were investigated and compared with those of the normal direct chill casting method. The results show that the microstructures were refined and the homogeneity of the alloying elements distribution was greatly improved by imposing the annular electromagnetic stirring and intercooling. In uniform direct chill casting, explosive nucleation can be triggered, originating from the mold wall and dendrite fragments for grain refinement. The effects of electromagnetic stirring on macrosegregation are discussed with consideration of the centrifugal force that drives the movement of melt from the central part towards the upper-periphery part, which could suppress the macrosegregation of alloying elements. The refined grain can reduce the permeability of the melt in the mushy zone that can restrain macrosegregation.
Electrochemical Detection of Endosulfan Using an AONP-PANI-SWCNT Modified Glassy Carbon Electrode
Authors: Masibi Kgotla K. , Fayemi Omolola E. , Adekunle Abolanle S. , Al-Mohaimeed Amal M. , Fahim Asmaa M. , Mamba Bhekie B. , Ebenso Eno E.
Published: February 2021

This report narrates the successful application of a fabricated novel sensor for the trace detection of endosulfan (EDS). The sensor was made by modifying a glassy-carbon electrode (GCE) with polyaniline (PANI), chemically synthesized antimony oxide nanoparticles (AONPs), acid-functionalized, single-walled carbon nanotubes (fSWCNTs), and finally, the AONP-PANI-SWCNT nanocomposite. The electrochemical properties of the modified electrodes regarding endosulfan detection were investigated via cyclic voltammetry (CV) and square-wave voltammetry. The current response of the electrodes to EDS followed the trend GCE-AONP-PANI-SWCNT (−510 µA) > GCE-PANI (−59 µA) > GCE-AONPs (−11.4 µA) > GCE (−5.52 µA) > GCE-fSWCNTs (−0.168 µA). The obtained results indicated that the current response obtained at the AONP-PANI-SWCNT/GCE was higher with relatively low overpotential compared to those from the other electrodes investigated. This demonstrated the superiority of the AONP-PANI-SWCNT-modified GCE. The AONP-PANI-SWCNT/GCE demonstrated good electrocatalytic activities for the electrochemical reduction of EDS. The results obtained in this study are comparable with those in other reports. The sensitivity, limit of detection (LoD), and limit of quantification (LoQ) of AONP-PANI-SWCNT/GCE towards EDS was estimated to be 0.0623 µA/µM, 6.8 µM, and 20.6 µM, respectively. Selectivity, as well as the practical application of the fabricated sensor, were explored, and the results indicated that the EDS-reduction current was reduced by only 2.0% when interfering species were present, whilst average recoveries of EDS in real samples were above 97%.