bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Significance of Activated Monocytes in Patients with ST-Elevation Myocardial Infarction
Authors: Abo-Aly Mohamed , Shokri Elica , Chelvarajan Lakshman , Tarhuni Wadea M. , Tripathi Himi , Abdel-Latif Ahmed
Published: July 2023

Circulating monocytes have different subsets, including classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++), which play different roles in cardiovascular physiology and disease progression. The predictive value of each subset for adverse clinical outcomes in patients with coronary artery disease is not fully understood. We sought to evaluate the prognostic efficacy of each monocyte subset in patients with ST-elevation myocardial infarction (STEMI). We recruited 100 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). Blood samples were collected at the time of presentation to the hospital (within 6 h from onset of symptoms, baseline (BL)) and then at 3, 6, 12, and 24 h after presentation. Monocytes were defined as CD45+/HLA-DR+ and then subdivided based on the expression of CD14, CD16, CCR2, CD11b, and CD42. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, stent thrombosis, in-stent restenosis, and recurrent myocardial infarction. Univariate and multivariate Cox proportional hazards models, including baseline comorbidities, were performed. The mean age of our cohort was 58.9 years and 25% of our patients were females. Patients with high levels (above the median) of CD14+CD16++ monocytes showed an increased risk for the primary endpoint in comparison to patients with low levels; adjusted hazard ratio (aHR) for CD14+/CD16++ cells was 4.3 (95% confidence interval (95% CI) 1.2–14.8, p = 0.02), for CD14+/CD16++/CCR2+ cells was 3.82 (95% CI 1.06–13.7, p = 0.04), for CD14+/CD16++/CD42b+ cells was 3.37 (95% CI 1.07–10.6, p = 0.03), for CD14+/CD16++/CD11b+ was 5.17 (95% CI 1.4–18.0, p = 0.009), and for CD14+ HLA-DR+ was 7.5 (95% CI 2.0–28.5, p = 0.002). CD14++CD16−, CD14++CD16+, and their CD11b+, CCR2+, and CD42b+ aggregates were not significantly predictive for our composite endpoint. Our study shows that CD14+ CD16++ monocytes and their subsets expressing CCR2, CD42, and CD11b could be important predictors of clinical outcomes in patients with STEMI. Further studies with a larger sample size and different coronary artery disease phenotypes are needed to verify the findings.
Drug-Inducible Gene Therapy Effectively Reduces Spontaneous Seizures in Kindled Rats but Creates Off-Target Side Effects in Inhibitory Neurons
Authors: Sullivan Kyle A. , Vitko Iuliia , Blair Kathryn , Gaykema Ronald P. , Failor Madison J. , San Pietro Jennifer M. , Dey Deblina , Williamson John M. , Stornetta Ruth L. , Kapur Jaideep , Perez-Reyes Edward
Published: July 2023

Over a third of patients with temporal lobe epilepsy (TLE) are not effectively treated with current anti-seizure drugs, spurring the development of gene therapies. The injection of adeno-associated viral vectors (AAV) into the brain has been shown to be a safe and viable approach. However, to date, AAV expression of therapeutic genes has not been regulated. Moreover, a common property of antiepileptic drugs is a narrow therapeutic window between seizure control and side effects. Therefore, a long-term goal is to develop drug-inducible gene therapies that can be regulated by clinically relevant drugs. In this study, a first-generation doxycycline-regulated gene therapy that delivered an engineered version of the leak potassium channel Kcnk2 (TREK-M) was injected into the hippocampus of male rats. Rats were electrically stimulated until kindled. EEG was monitored 24/7. Electrical kindling revealed an important side effect, as even low expression of TREK M in the absence of doxycycline was sufficient to cause rats to develop spontaneous recurring seizures. Treating the epileptic rats with doxycycline successfully reduced spontaneous seizures. Localization studies of infected neurons suggest seizures were caused by expression in GABAergic inhibitory neurons. In contrast, doxycycline increased the expression of TREK-M in excitatory neurons, thereby reducing seizures through net inhibition of firing. These studies demonstrate that drug-inducible gene therapies are effective in reducing spontaneous seizures and highlight the importance of testing for side effects with pro-epileptic stressors such as electrical kindling. These studies also show the importance of evaluating the location and spread of AAV-based gene therapies in preclinical studies.
Abscisic Acid Regulates Carbohydrate Metabolism, Redox Homeostasis and Hormonal Regulation to Enhance Cold Tolerance in Spring Barley
Authors: Guo Junhong , Beemster Gerrit T. S. , Liu Fulai , Wang Zongming , Li Xiangnan
Published: July 2023

Abscisic acid (ABA) plays a vital role in the induction of low temperature tolerance in plants. To understand the molecular basis of this phenomenon, we performed a proteomic analysis on an ABA-deficit mutant barley (Az34) and its wild type (cv Steptoe) under control conditions (25/18 °C) and after exposure to 0 °C for 24 h. Most of the differentially abundant proteins were involved in the processes of photosynthesis and metabolisms of starch, sucrose, carbon, and glutathione. The chloroplasts in Az34 leaves were more severely damaged, and the decrease in Fv/Fm was larger in Az34 plants compared with WT under low temperature. Under low temperature, Az34 plants possessed significantly higher activities of ADP-glucose pyrophosphorylase, fructokinase, monodehydroascorbate reductase, and three invertases, but lower UDP-glucose pyrophosphorylase activity than WT. In addition, concentrations of proline and soluble protein were lower, while concentration of H2O2 was higher in Az34 plants compared to WT under low temperature. Collectively, the results indicated that ABA deficiency induced modifications in starch and sucrose biosynthesis and sucrolytic pathway and overaccumulation of reactive oxygen species were the main reason for depressed low temperature tolerance in barley, which provide novel insights to the response of barley to low temperature under future climate change.
Normoferremia in Patients with Acute Bacterial Infections—A Hitherto Unexplored Field of the Dichotomy between CRP and Ferritin Expression in Patients with Hyper Inflammation and Failure to Increase Ferritin
Authors: Levinson Tal , Feigin Eugene , Berliner Shlomo , Shenhar-Tsarfaty Shani , Shapira Itzhak , Rogowski Ori , Zeltzer David , Goldiner Ilana , Shtark Moshe , Katz Shalhav Malka , Wasserman Asaf
Published: July 2023

Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin. The estimated time between symptom onset and the procurement of blood tests was also measured. 225 patients had a median ferritin level of 109.9 ng/mL [IQR 85.1, 131.7] and a median CRP level of 248.4 mg/L [IQR 221, 277.5]. An infectious inflammatory process was identified in 195 patients. Ferritin levels were relatively low in comparison with the CRP in each group, divided according to time from symptom onset until the procurement of blood tests. The discrepancy between high CRP and low ferritin suggests that these two acute phase response proteins utilize different pathways, resulting in a failure to increase ferritin concentrations in a documented state of hyperinflammation. A new entity of normoferremic inflammation accounts for a significant percentage of patients with acute bacterial infections, which enables bacteria to better survive the inflammation and serves as a new “inflammatory stamp”.
The Role of Estrogen Receptors in Health and Disease
Authors: Pakdel Farzad
Published: July 2023

Many biological and physiological events, including growth, development, and metabolism of reproductive and non-reproductive tissues in men and women, are regulated by estrogens and estrogen receptors (ERs) [...]
Enhanced Levels of Glycosphingolipid GM3 Delay the Progression of Diabetic Nephropathy
Authors: Naito Shokichi , Nakayama Kenichi , Kawashima Nagako
Published: July 2023

We recently found that albuminuria levels in patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) inversely correlate with glycosphingolipid GM3 expression levels in glomerular podocytes. Moreover, we showed enhanced expression of GM3 via activation of the GM3 synthase gene upon administration of valproic acid (VPA) is effective in suppressing albuminuria and podocyte injury in mice with anti-nephrin antibody-induced podocytopathy. However, the therapeutic effect of GM3 on diabetic nephropathy, which is the most common underlying disease in patients undergoing dialysis and with podocyte injury, remains unclear. Here, we investigated the therapeutic effect of enhanced GM3 expression via VPA on podocyte injury using streptozotocin-induced diabetic nephropathy model mice. Administration of VPA clearly decreased levels of albuminuria and glomerular lesions and inhibited the loss of podocytes and expansion in the mesangial area. Furthermore, we found that albuminuria levels in patients with diabetic nephropathy inversely correlate with the expression of GM3 in podocytes. These results indicate that maintaining GM3 expression in podocytes by administration of VPA may be effective in treating not only podocyte injury, such as MCD and FSGS, but also the late stage of diabetic nephropathy.
Metal Nanomaterials and Hydrolytic Enzyme-Based Formulations for Improved Antifungal Activity
Authors: Lyagin Ilya , Aslanli Aysel , Domnin Maksim , Stepanov Nikolay , Senko Olga , Maslova Olga , Efremenko Elena
Published: July 2023

Active research of metal-containing compounds and enzymes as effective antifungal agents is currently being conducted due to the growing antifungal resistance problem. Metals are attracting special attention due to the wide variety of ligands that can be used for them, including chemically synthesized and naturally obtained variants as a result of the so-called “green synthesis”. The main mechanism of the antifungal action of metals is the triggering of the generation and accumulation of reactive oxygen species (ROS). Further action of ROS on various biomolecules is nonspecific. Various hydrolytic enzymes (glucanases and proteases), in turn, exhibit antifungal properties by affecting the structural elements of fungal cells (cell walls, membranes), fungal quorum sensing molecules, fungal own protective agents (mycotoxins and antibiotics), and proteins responsible for the adhesion and formation of stable, highly concentrated populations in the form of biofilms. A wide substrate range of enzymes allows the use of various mechanisms of their antifungal actions. In this review, we discuss the prospects of combining two different types of antifungal agents (metals and enzymes) against mycelial fungi and yeast cells. Special attention is paid to the possible influence of metals on the activity of the enzymes and the possible effects of proteins on the antifungal activity of metal-containing compounds.
Derivation of Human Extraembryonic Mesoderm-like Cells from Primitive Endoderm
Authors: Farkas Karin , Ferretti Elisabetta
Published: July 2023

In vitro modeling of human peri-gastrulation development is a valuable tool for understanding embryogenetic mechanisms. The extraembryonic mesoderm (ExM) is crucial in supporting embryonic development by forming tissues such as the yolk sac, allantois, and chorionic villi. However, the origin of human ExM remains only partially understood. While evidence suggests a primitive endoderm (PrE) origin based on morphological findings, current in vitro models use epiblast-like cells. To address this gap, we developed a protocol to generate ExM-like cells from PrE-like cell line called naïve extraembryonic endoderm (nEnd). We identified the ExM-like cells by specific markers (LUM and ANXA1). Moreover, these in vitro-produced ExM cells displayed angiogenic potential on a soft matrix, mirroring their physiological role in vasculogenesis. By integrating single-cell RNA sequencing (scRNAseq) data, we found that the ExM-like cells clustered with the LUM/ANXA1-rich cell populations of the gastrulating embryo, indicating similarity between in vitro and ex utero cell populations. This study confirms the derivation of ExM from PrE and establishes a cell culture system that can be utilized to investigate ExM during human peri-gastrulation development, both in monolayer cultures and more complex models.
Molecular Biology and Therapeutic Targets of Primitive Tracheal Tumors: Focus on Tumors Derived by Salivary Glands and Squamous Cell Carcinoma
Authors: Marchioni Alessandro , Tonelli Roberto , Samarelli Anna Valeria , Cappiello Gaia Francesca , Andreani Alessandro , Tabbì Luca , Livrieri Francesco , Bosi Annamaria , Nori Ottavia , Mattioli Francesco , Bruzzi Giulia , Marchioni Daniele , Clini Enrico
Published: July 2023

Primary tracheal tumors are rare, constituting approximately 0.1–0.4% of malignant diseases. Squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) account for about two-thirds of these tumors. Despite most primary tracheal cancers being eligible for surgery and/or radiotherapy, unresectable, recurrent and metastatic tumors may require systemic treatments. Unfortunately, the poor response to available chemotherapy as well as the lack of other real therapeutic alternatives affects the quality of life and outcome of patients suffering from more advanced disease. In this condition, target therapy against driver mutations could constitute an alternative to chemotherapy, and may help in disease control. The past two decades have seen extraordinary progress in developing novel target treatment options, shifting the treatment paradigm for several cancers such as lung cancer. The improvement of knowledge regarding the genetic and biological alterations, of major primary tracheal tumors, has opened up new treatment perspectives, suggesting the possible role of biological targeted therapies for the treatment of these rare tumors. The purpose of this review is to outline the state of knowledge regarding the molecular biology, and the preliminary data on target treatments of the main primary tracheal tumors, focusing on salivary-gland-derived cancers and squamous cell carcinoma.
Implications of Physical Exercise on Episodic Memory and Anxiety: The Role of the Serotonergic System
Authors: Illesca-Matus Ricardo , Ardiles Nicolás M. , Munoz Felipe , Moya Pablo R.
Published: July 2023

There is a growing interest in investigating the effects of physical exercise on cognitive performance, particularly episodic memory. Similarly, an increasing number of studies in recent decades have studied the effects of physical activity on mood and anxiety disorders. Moreover, the COVID-19 pandemic has raised awareness of the importance of regular physical activity for both mental and physical health. Nevertheless, the exact mechanisms underlying these effects are not fully understood. Interestingly, recent findings suggest that the serotonergic system may play a key role in mediating the effects of physical exercise on episodic memory and anxiety. In this review, we discuss the impact of physical exercise on both episodic memory and anxiety in human and animal models. In addition, we explore the accumulating evidence that supports a role for the serotonergic system in the effects of physical exercise on episodic memory and anxiety.
Macrophages Provide Essential Support for Erythropoiesis, and Extracellular ATP Contributes to a Erythropoiesis-Supportive Microenvironment during Repeated Psychological Stress
Authors: Momčilović Sanja , Bogdanović Andrija , Milošević Maja S. , Mojsilović Slavko , Marković Dragana C. , Kočović Dušica M. , Vignjević Petrinović Sanja
Published: July 2023

Psychological stress is a significant contributor to various chronic diseases and affects multiple physiological processes including erythropoiesis. This study aimed to examine the tissue-specific contributions of macrophages and extracellular ATP, as a signal of disturbed tissue homeostasis, to erythropoiesis under conditions of repeated psychological stress. Adult male BALB/c mice were subjected to 2 h daily restraint stress for seven consecutive days. Clodronate-liposomes were used to deplete resident macrophages from the bone marrow and spleen two days prior to the first restraint procedure, as well as newly recruited macrophages, every third day for the duration of the experiment. Repeated stress induced a considerable increase in the number of erythroid progenitor cells as well as in the percentage of CD71+/Ter119+ and CD71−/Ter119+ cells in the bone marrow and spleen. Macrophage depletion completely abolished the stimulative effect of repeated stress on immature erythroid cells, and prevented stress-induced increases in ATP levels, P2X7 receptor (P2X7R) expression, and ectonucleotidase CD39 activity and expression in the bone marrow and spleen. The obtained results demonstrate the stimulative effects of repeated stress on erythroid cells, extracellular ATP levels, P2X7R expression, CD39 activity and expression within the bone marrow and spleen, as well as the essential role of macrophages in stress-induced changes.
Challenges and Future Trends in Atopic Dermatitis
Authors: Gatmaitan Julius Garcia , Lee Ji Hyun
Published: July 2023

Atopic dermatitis represents a complex and multidimensional interaction that represents potential fields of preventive and therapeutic management. In addition to the treatment armamentarium available for atopic dermatitis, novel drugs targeting significant molecular pathways in atopic dermatitis biologics and small molecules are also being developed given the condition’s complex pathophysiology. While most of the patients are expecting better efficacy and long-term control, the response to these drugs would still depend on numerous factors such as complex genotype, diverse environmental triggers and microbiome-derived signals, and, most importantly, dynamic immune responses. This review article highlights the challenges and the recently developed pharmacological agents in atopic dermatitis based on the molecular pathogenesis of this condition, creating a specific therapeutic approach toward a more personalized medicine.
CdS Nanoparticles Supported by Cobalt@Carbon-Derived MOFs for the Improved Adsorption and Photodegradation of Ciprofloxacin
Authors: Li Mi , Fang Qin , Lai Yan , Chen Luying , Fu Qiucheng , He Jiao , Chen Yongjuan , Jiang Liang , Yan Zhiying , Wang Jiaqiang
Published: July 2023

The design and synthesis of efficient photocatalysts that promote the degradation of organic pollutants in water have attracted extensive attention in recent years. In this work, CdS nanoparticles are grown in situ on Co@C derived from metal–organic frameworks. The resulting hierarchical CdS/Co@C nanostructures are evaluated in terms of their adsorption and photocatalytic ciprofloxacin degradation efficiency under visible-light irradiation. The results show that, apart from offering a large surface area (55.69 m2·g−1), the prepared material can effectively suppress the self-agglomeration of CdS and enhance the absorption of visible light. The CdS/Co@C-7 composite containing 7% wt Co@C has the highest photodegradation rate, and its activity is approximately 4.4 times greater than that of CdS alone. Moreover, this composite exhibits remarkable stability after three successive cycles of photocatalysis. The enhanced photocatalytic performance is largely ascribed to the rapid separation of electron–hole pairs and the effective electron transfer between CdS and Co@C, which is confirmed via electrochemical experiments and photoluminescence spectra. The active substance capture experiment and the electron spin resonance technique show that h+ is the main active entity implicated in the degradation of CIP, and accordingly, a possible mechanism of CIP photocatalytic degradation over CdS/Co@C is proposed. In general, this work presents a new perspective on designing novel photocatalysts that promote the degradation of organic pollutants in water.
Small RNA and Degradome Sequencing Reveal Roles of miRNAs in the Petal Color Fading of Malus Crabapple
Authors: Rong Hao , Han Xin , Xin Yue , Ni Zhouxian , Zhang Wangxiang , Xu Li’an
Published: July 2023

The Malus crabapple is an important woody ornamental plant. The fading of petals during its development significantly affects their ornamental value. Petal color is related to anthocyanin content and miRNAs play an important role in the post-transcriptional regulation of anthocyanin synthesis. However, the mechanisms underlying miRNA regulation of petal fading have rarely been studied. Transcriptome and small RNA sequencing of petals from the blooming phases of Malus. ‘Indian Summer’ varieties S1 (small bud), S2 (initial-flowering), and S3 (late-flowering) allowed us to identify 230 known miRNAs and 17 novel miRNAs, including 52 differentially expressed miRNAs which targeted 494 genes and formed 823 miRNA–target pairs. Based on the target gene annotation results, miRNA–target pairs were screened that may be involved in the fading process of Malus crabapple petals through three different pathways: anthocyanin synthesis, transport, and degradation, involving mcr-miR858-MYB1\MYB5 and mcr-miR396-McCHI inhibiting anthocyanin synthesis; mcr-miR167, mcr-miR390, mcr-miR535, and mcr-miR858 inhibiting anthocyanin transport from the cytoplasm to the vacuole by targeting ABC transporter genes (ABCB, ABCC, ABCD, and ABCG); and mcr-miR398 targeting the superoxide dismutase genes (CZSOD2 and CCS) to accelerate anthocyanin degradation. These findings offer a novel approach to understanding the mechanism of petal fading and serve as a reference for other plants with floral fading.
Epithelial–Mesenchymal Transition (EMT)
Authors: Manfioletti Guidalberto , Fedele Monica
Published: July 2023

Epithelial–mesenchymal transition (EMT) is a cellular process involved in many physiological and pathological conditions [...]
Genome-Wide Identification of WRKY Gene Family and Functional Characterization of CcWRKY25 in Capsicum chinense
Authors: Zhang Liping , Wu Dan , Zhang Wei , Shu Huangying , Sun Peixia , Huang Chuang , Deng Qin , Wang Zhiwei , Cheng Shanhan
Published: July 2023

Pepper is renowned worldwide for its distinctive spicy flavor. While the gene expression characteristics of the capsaicinoid biosynthesis pathway have been extensively studied, there are already a few reports regarding transcriptional regulation in capsaicin biosynthesis. In this study, 73 WRKYs were identified in the genome of Capsicum chinense, and their physicochemical traits, DNA, and protein sequence characteristics were found to be complex. Combining RNA-seq and qRT-PCR data, the WRKY transcription factor CA06g13580, which was associated with the accumulation tendency of capsaicinoid, was screened and named CcWRKY25. CcWRKY25 was highly expressed in the placenta of spicy peppers. The heterologous expression of CcWRKY25 in Arabidopsis promoted the expression of genes PAL, 4CL1, 4CL2, 4CL3, CCR, and CCoAOMT and led to the accumulation of lignin and flavonoids. Furthermore, the expression of the capsaicinoid biosynthesis pathway genes (CBGs) pAMT, AT3, and KAS was significantly reduced in CcWRKY25-silenced pepper plants, resulting in a decrease in the amount of capsaicin. However, there was no noticeable difference in lignin accumulation. The findings suggested that CcWRKY25 could be involved in regulating capsaicinoid synthesis by promoting the expression of genes upstream of the phenylpropanoid pathway and inhibiting CBGs’ expression. Moreover, the results highlighted the role of CcWRKY25 in controlling the pungency of pepper and suggested that the competitive relationship between lignin and capsaicin could also regulate the spiciness of the pepper.
Identification of a Putative SARS-CoV-2 Main Protease Inhibitor through In Silico Screening of Self-Designed Molecular Library
Authors: Liu Nanxin , Yang Zeyu , Liu Yuying , Dang Xintao , Zhang Qingqing , Wang Jin , Liu Xueying , Zhang Jie , Pan Xiaoyan
Published: July 2023

There have been outbreaks of SARS-CoV-2 around the world for over three years, and its variants continue to evolve. This has become a major global health threat. The main protease (Mpro, also called 3CLpro) plays a key role in viral replication and proliferation, making it an attractive drug target. Here, we have identified a novel potential inhibitor of Mpro, by applying the virtual screening of hundreds of nilotinib-structure-like compounds that we designed and synthesized. The screened compounds were assessed using SP docking, XP docking, MM-GBSA analysis, IFD docking, MD simulation, ADME/T prediction, and then an enzymatic assay in vitro. We finally identified the compound V291 as a potential SARS-CoV-2 Mpro inhibitor, with a high docking affinity and enzyme inhibitory activity. Moreover, the docking results indicate that His41 is a favorable amino acid for pi-pi interactions, while Glu166 can participate in salt-bridge formation with the protonated primary or secondary amines in the screened molecules. Thus, the compounds reported here are capable of engaging the key amino acids His41 and Glu166 in ligand-receptor interactions. A pharmacophore analysis further validates this assertion.
A 43 Bp-Deletion in the F3′H Gene Reducing Anthocyanins Is Responsible for Keeping Buds Green at Low Temperatures in Broccoli
Authors: Yu Huifang , Wang Jiansheng , Shen Yusen , Sheng Xiaoguang , Shaw Ranjan Kumar , Branca Ferdinando , Gu Honghui
Published: July 2023

Most broccoli cultivars or accessions exhibit green buds under appropriate growth conditions, which turn purple at cold temperatures. However, certain cultivars consistently maintain green buds both during normal growth and at cold temperatures. In this study, we used BSA-seq (bulked segregation analysis-sequencing), along with fine mapping and transcriptome analysis to identify a candidate gene (flavonoid 3′-hydroxylase, F3′H) responsible for reducing anthocyanin accumulation in the mutant GS and HX-16 broccoli (Brassica oleracea L. var. italica), which could retain green buds even at low temperatures. A 43-bp deletion was detected in the coding sequence (CDS) of the F3′H gene in HX-16 and the mutant GS, which significantly decreased F3′H expression and the accumulation of cyanidin and delphinidin in the mutant GS. Furthermore, the expression of F3′H was upregulated at low temperatures in the wild line PS. Our results demonstrated the efficacy of utilizing the 43-bp InDel (Insertion–Deletion) in predicting whether buds in B. oleracea L. will turn purple or remain green at cold temperatures across forty-two germplasm materials. This study provides critical genetic and molecular insights for the molecular breeding of B. oleracea and sheds light on the molecular mechanisms underlying the effect of low temperatures on bud color in broccoli.
Quantitative Threshold Determination of Auditory Brainstem Responses in Mouse Models
Authors: Tanaka Kenji , Ohara Shuma , Matsuzaka Tadaaki , Matsugaki Aira , Ishimoto Takuya , Ozasa Ryosuke , Kuroda Yukiko , Matsuo Koichi , Nakano Takayoshi
Published: July 2023

The auditory brainstem response (ABR) is a scalp recording of potentials produced by sound stimulation, and is commonly used as an indicator of auditory function. However, the ABR threshold, which is the lowest audible sound pressure, cannot be objectively determined since it is determined visually using a measurer, and this has been a problem for several decades. Although various algorithms have been developed to objectively determine ABR thresholds, they remain lacking in terms of accuracy, efficiency, and convenience. Accordingly, we proposed an improved algorithm based on the mutual covariance at adjacent sound pressure levels. An ideal ABR waveform with clearly defined waves I–V was created; moreover, using this waveform as a standard template, the experimentally obtained ABR waveform was inspected for disturbances based on mutual covariance. The ABR testing was repeated if the value was below the established cross-covariance reference value. Our proposed method allowed more efficient objective determination of ABR thresholds and a smaller burden on experimental animals.
The Relationship between Mental Health and Loneliness in the Elderly during the COVID-19 Pandemic
Authors: Sadatnia Mahsa , Jalali Amir , Tapak Laili , Shamsaei Farshid
Published: July 2023

Background and Aim: The coronavirus pandemic has had a negative impact on the health and well-being of communities and individuals around the world. One of the concerns about the COVID-19 epidemic is the impact of social isolation due to social distancing on the mental health of older adults. This study aimed to investigate the relationship between mental health and loneliness among seniors during the COVID-19 pandemic. Materials and Methods: In this cross-sectional study, 211 retirees of Kermanshah University of Medical Sciences were selected by available sampling method in 2021. Data were collected through the Demographic, Mental Health Questionnaire (GHQ-28) and the Adult Social and Emotional Feeling Questionnaire (SELSA-S). Data were analyzed using paired t-test, one-way analysis of variance, covariance, and chi-squared tests. The significance level was considered 0.05. Results: The mean age of participants was 71.26 years and the results showed a significant relationship between feeling lonely and mental health (r = 0.535, p = 0.001). There were statistically significant relationships between mental health and social functioning (r = −0.204, p ≥ 0.001) and depression (r = 0.501, p = 0.001) and also between mental health and three subscales of loneliness: romantic loneliness (r = 0.001, p = 0.001), social loneliness (r = 0.493, p = 0.001), and family loneliness (r = 0.289, p = 0.001). Conclusion: Feeling lonely during the coronavirus disease pandemic has a negative effect on the mental health of older adults; therefore, it is necessary for mental health professionals to improve the mental health of the elderly with proper planning and interventions.
Antifungal Drug-Drug Interactions with Commonly Used Pharmaceutics in European Pediatric Patients with Acute Lymphoblastic Leukemia
Authors: Sienkiewicz-Oleszkiewicz Beata , Salamonowicz-Bodzioch Małgorzata , Słonka Justyna , Kałwak Krzysztof
Published: July 2023

Leukemia is one of the leading childhood malignancies, with acute lymphoblastic leukemia (ALL) being the most common type. Invasive fungal disease is a concerning problem also at pediatric hemato-oncology units. Available guidelines underline the need for antifungal prophylaxis and give recommendations for proper treatment in various clinical scenarios. Nonetheless, antifungal agents are often involved in drug-drug interaction (DDI) occurrence. The prediction of those interactions in the pediatric population is complicated because of the physiological differences in adults, and the lack of pharmacological data. In this review, we discuss the potential DDIs between antifungal agents and commonly used pharmaceutics in pediatric hemato-oncology settings, with special emphasis on the use of liposomal amphotericin B and ALL treatment. We obtained information from Micromedex® and Drugs.com® interaction checking databases and checked the EudraVigilance® database to source the frequency of severe adverse drug reactions that resulted from antifungal drug interactions. Several major DDIs were identified, showing a favorable safety profile of echinocandins and liposomal amphotericin B. Interestingly, although there are numerous available drug interaction checking tools facilitating the identification of potential serious DDIs, it is important to use more than one tool, as the presented searching results may differ between particular checking programs.
Importance of Demographic and Clinical Features in Evaluating the Severity of COVID-19 in Hospitalized Patients: A Serbian Retrospective Study in the First Pandemic Year
Authors: Aritonovic Pribakovic Jelena , Peric Milica , Milenkovic Aleksandra , Janicevic Aleksandra , Hadzistevic Snezana , Ilic Aleksandra , Stojanovic-Tasic Mirjana , Bulatovic Kristina , Rasic Dragisa , Mitic Jadranka
Published: July 2023

The aim of this study is to determine the demographic and initial clinical characteristics of patients with COVID-19 and their importance in evaluating the severity of the disease. A retrospective study included patients suffering from COVID-19 who were hospitalized at The Department of Infectious Disease of the Clinical Hospital Center Pristina—Gracanica from the beginning of the pandemic until the end of 2020. We compared the symptoms of the disease, radiographic findings of pneumonia, laboratory parameters, duration of symptoms before admission, the difference in the need for certain therapies, and the presence of comorbidities between non-severe and severe groups of patients. Patients with a severe disease were statistically significantly older. Hypertension was significantly associated with severe clinical conditions. Radiographic findings of bilateral pneumonia on admission were much more frequent among the severe group, and these patients’ need for oxygen support was significantly higher. Lower neutrophil and higher lymphocyte counts were statistically significant in the non-severe group. Biochemical parameters at admission also showed statistical significance between the examined groups. Based on our research, we can conclude that a complete overview of the patient, including demographic and laboratory parameters as perhaps the most significant attributes, can help doctors in the timely clinical assessment of patients and, thus, in the timely application of adequate therapeutic protocols in the treatment of COVID-19.
Ketamine Clinical Use on the Pediatric Critically Ill Infant: A Global Bibliometric and Critical Review of Literature
Authors: Maia Mary Lucy Ferraz , Pantoja Lucas Villar Pedrosa Silva , Da Conceição Brenda Costa , Machado-Ferraro Kissila Márvia , Gonçalves Jackeline Kerlice Mata , Dos Santos-Filho Paulo Monteiro , Lima Rafael Rodrigues , Fontes-Junior Enéas Andrade , Maia Cristiane Socorro Ferraz
Published: July 2023

The developing central nervous system is vulnerable to several stimuli, especially psychotropic drugs. Sedation procedures during the developmental period are frequent in pediatric intensive care units (PICUs), in which the use of the sedative agent is still a challenge for the PICU team. Ketamine has been indicated for sedation in critically ill children with hemodynamic and ventilatory instabilities, but the possible neurobehavioral consequences related to this use are still uncertain. Here, we performed a bibliometric analysis with conventional metrics and a critical review of clinical findings to reveal a gap in the literature that deserves further investigation. We revealed that only 56 articles corresponded to the inclusion criteria of the study. The United States of America emerges as the main country within the scope of this review. In addition, professional clinical societies play a key role in the publications of scientific clinical findings through the specialist journals, which encourages the sharing of research work. The co-occurrence of keywords evidenced that the terms “sedation”, “ketamine”, and “pediatric” were the most frequent. Case series and review articles were the most prevalent study design. In the critical evaluation, the scarce studies highlight the need of use and post-use monitoring, which reinforces the importance of additional robust clinical studies to characterize the possible adverse effects resulting from ketamine anesthetic protocol in critically ill children.
Primary Immunodeficiencies: Pathogenetic Advances, Diagnostic and Management Challenges
Authors: Costagliola Giorgio , Consolini Rita
Published: July 2023

The field of immunology is rapidly progressing, with new monogenic disorders being discovered every year [...]
Impact of Alcohol Dehydrogenase 7 Polymorphism and Alcohol Consumption on Risk of Head and Neck Squamous Cell Carcinoma: A Korean Case-Control Study
Authors: Lee Dong-Won , Ji Yong-Bae , Song Chang-Myeon , Kim Jeong-Kyu , Lee Seung-Hwan , Tae Kyung
Published: July 2023

Background: Head and neck squamous cell carcinoma (HNSCC) is closely associated with alcohol consumption and individual genetic susceptibility, such as single nucleotide polymorphism (SNP) of alcohol dehydrogenase (ADH). This study aimed to investigate the association of ADH7 SNPs with the risk of HNSCC. Methods: We analyzed ADH7 rs1573496C>G, rs3737482T>C, rs1154460G>A, and rs284787T>C SNPs in 250 patients with HNSCC and 322 controls in the Korean populations. Genotyping was conducted using the TaqMan assay. Linkage disequilibrium and haplotypes were analyzed. Results: The odds ratios (OR) and 95% confidence intervals (CI) of the CT and CC genotypes of ADH7 rs3737482T>C were 0.48 (0.29–0.78) and 0.69 (0.49–0.96), indicating a significantly decreased risk. In SNP of rs1154460G>A, the OR and 95% CI of the AA genotype was 1.63 (1.11–2.40), showing a significant increase in the risk. Furthermore, SNPs of ADH7 rs3737482T>C and ADH7 rs1154460G>A exhibit synergistic interactions with alcohol composition on the risk of HNSCC. None of the haplotypes were associated with the risk of HNSCC. Conclusions: ADH7 rs3737482T>C and rs1154460G>A SNPs are associated with the risk of development of HNSCC in Koreans. They could serve as molecular biological markers to screen high-risk groups for HNSCC.
VEGF Detection via Impedance Spectroscopy on Surface Functionalized Interdigitated Biosensor
Authors: Lin Yue-Der , Zida Serge Ismael , Yang Chu-Chun , Khung Yit Lung
Published: July 2023

Vascular endothelial growth factor (VEGF), a clinically important biomarker, often plays a key role in angiogenesis, would healing, tumor growth, lung development, and in retinal diseases. Hence, detecting and quantifying VEGF is deemed medically important in clinical diagnosis for many diseases. In this report, a simple yet highly cost-effective platform was proposed for VEGF protein detection using commercially available interdigitated sensors that are surface modified to present DNA optimally for VEGF capture. The dielectric characteristics between the fingers of the sensor were modulated by the negatively charged aptamer-VEGF capture, and the impedance was estimated using an impedance analyzer. Impedance-spectra tests were compared among pristine unmodified surfaces, functionalized monolayer surfaces, and aptamer-grafted surfaces in order to evaluate the efficacy of VEGF detection. From our results, the sensitivity experiments as conducted showed the ability of the interdigitated sensor to detect VEGF at a low concentration of 5 pM (200 pg/mL). The specificity of the functionalized sensor in detecting VEGF was further examined by comparing the impedance to platelet-derived growth factor, and the results confirm the specificity of the sensor. Finally, the Nyquist plot of impedance spectra was also presented to help data visualization and the overall performance of the device was found to be a highly suitable template for a smart biosensor for the detection of VEGF.
Deep Learning-Based Approaches for Oil Spill Detection: A Bibliometric Review of Research Trends and Challenges
Authors: Vasconcelos Rodrigo N. , Lima André T. Cunha , Lentini Carlos A. D. , Miranda José Garcia V. , de Mendonça Luís F. F. , Lopes José M. , Santana Mariana M. M. , Cambuí Elaine C. B. , Souza Deorgia T. M. , Costa Diego P. , Duverger Soltan G. , Franca-Rocha Washington S.
Published: July 2023

Oil spill detection and mapping using deep learning (OSDMDL) is crucial for assessing its impact on coastal and marine ecosystems. A novel approach was employed in this study to evaluate the scientific literature in this field through bibliometric analysis and literature review. The Scopus database was used to evaluate the relevant scientific literature in this field, followed by a bibliometric analysis to extract additional information, such as architecture type, country collaboration, and most cited papers. The findings highlight significant advancements in oil detection at sea, with a strong correlation between technological evolution in detection methods and improved remote sensing data acquisition. Multilayer perceptrons (MLP) emerged as the most prominent neural network architecture in 11 studies, followed by a convolutional neural network (CNN) in 5 studies. U-Net, DeepLabv3+, and fully convolutional network (FCN) were each used in three studies, demonstrating their relative significance too. The analysis provides insights into collaboration, interdisciplinarity, and research methodology and contributes to the development of more effective policies, strategies, and technologies for mitigating the environmental impact of oil spills in OSDMDL.
Communicating about the Counterinsurgency Program in the Philippines: Local Government Communication Practices
Authors: Silvallana Daniel Fritz V. , Hagling Misraim Grace
Published: July 2023

Government agencies play a critical role in addressing societal issues and rely on effective communication strategies to inform and engage the public. However, research on government communication practices in the Philippines is limited. To bridge this gap, this study aims to explore the Philippine government’s communication practices and the influence of environmental attributes on communication efforts regarding the counterinsurgency program. Drawing on the government public relations model, a qualitative research approach was employed to gain in-depth insights into the experiences and perspectives of local information officers. The study utilized semi-structured interviews as the primary data collection method. By engaging local government communicators in the Philippines, the study identified four major themes: common media strategies, pressure to meet public information needs, lack of financial resources, and the impact of external legal frameworks. The findings revealed that government communicators employ various media strategies and face significant pressure to meet public information needs. Furthermore, the study highlights the intersection of external legal frameworks with other environmental constraints, such as politics and professional development, impacting government communication practices. This paper contributes to the limited scholarship on government communication practices in the Philippines, offering preliminary insights into the complex dynamics of government communication to address societal challenges.
Evaluation of the Safety of Percutaneous Sensory Nerve Stimulation in Patients with Head and Neck Cancer Receiving Chemoradiotherapy
Authors: Hamamoto Takao , Sato Yuki , Yumii Kohei , Chikuie Nobuyuki , Taruya Takayuki , Horibe Yuichiro , Ishino Takashi , Ueda Tsutomu , Takeno Sachio , Yoshimura Kenichi
Published: July 2023

Chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck cancer; however, CRT may cause post-treatment dysphagia. Transcutaneous electrical sensory stimulation (TESS), developed in recent years for swallowing rehabilitation, is used at many medical facilities. Although TESS has been used for dysphagia in several fields, its safety and efficacy in patients with head and neck cancer remain to be clarified. Therefore, this study evaluated the safety of TESS in ten patients with head and neck cancers undergoing CRT. Swallowing rehabilitation intervention and TESS implementation were performed for all patients during CRT. Non-blood-toxicity adverse events (AEs), such as dermatitis and mucositis, occurred during CRT; however, the severity was less than grade 3. No patient experienced pain due to TESS. As survival time analysis using the Kaplan–Meier method for interferential current device implementation rates revealed a feasibility of 100% for up to 60 Gy and a feasibility of 78% for up to 70 Gy, TESS may be feasible until 70 Gy. This study confirmed the feasibility and safety of TESS in the head and neck region during CRT. Although the precise mechanism of TESS on dysphagia remains unclear, its continued use has great potential for improving sensory disturbance.
Centers of Endemism and The Potential of Zoos and Botanical Gardens in Conservation of Endemics
Authors: Hobohm Carsten , Barker Nigel
Published: July 2023

Knowledge about ecological conditions and processes in centers of endemism (CoEs) is still limited with respect to various systematic groups of organisms, ecosystem types, ecological conditions, and ecosystem services. We review the characterization, identification, and meaning of CoEs. Endemics play an increasing and prominent role in nature conservation monitoring and management and in the organization of zoos, aquaria, and botanical gardens. We examine the importance of different groups of organisms and indicators for the characterization of endemic-rich regions, e.g., with regard to the richness of endemics per region and degree of endemism, the importance of heterogeneity in space, continuity in time, isolation, and ex situ management for the survival of endemic species. Currently, conversion of land cover and land use change are the most important causes of biodiversity decline and extinction risk of endemic and endangered species. These are followed by climate change, including severe weather, and then natural processes such as volcanism, landslides, or tsunamis. For conservation purposes, the management of regional land use, zoos, aquaria, botanical gardens, and social aspects of the diversity of endemics and CoEs have to be taken into account as well. We find that the ex situ representation of endemics in general is limited, and conservation networks in this regard can be improved. We need better answers to questions about the relationship between ecoregions, CoEs and regional awareness of endemism, which is linked with human culture including aesthetics, well-being, health, and trade.
Erosion and Sediment Transport Modeling: A Systematic Review
Authors: Andualem Tesfa Gebrie , Hewa Guna A. , Myers Baden R. , Peters Stefan , Boland John
Published: July 2023

Soil erosion and sediment transport have significant consequences, including decreased agricultural production, water quality degradation, and modification to stream channels. Understanding these processes and their interactions with contributing factors is crucial for assessing the environmental impacts of erosion. The primary objective of this review is to identify a suitable soil erosion and sediment transport model for catchment-scale application. The study considers various model selection processes, including model capability and the spatial and temporal domains for assessing spatiotemporal distributions. The review acknowledges the limitations, uncertainties, and unrealistic assumptions associated with soil erosion and sediment transport models. Models are usually developed with a particular objective, which demands an assessment of capabilities, spatial, and temporal applicability, and catchment-scale applicability. Distributed models are often preferred for catchment-scale applications, as they can adequately account for spatial variations in erosion potential and sediment yield, aiding in the evaluation of erosion-contributing elements and planning erosion control measures. Based on the findings of this study, the authors encourage utilizing models (such as Soil and Water Assessment Tool (SWAT) or Automated Geospatial Watershed Assessment Tool (AGWA)) that can forecast net erosion as a function of sediment output for catchment erosion and sediment yield modeling. This review helps researchers and practitioners involved in erosion and sediment modeling by guiding the selection of an appropriate model type based on specific modeling purposes and basin scale. By choosing appropriate models, the accuracy and effectiveness of sediment yield estimation and erosion control measures can be improved.