bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prescription of Drug Ontology 2.0 (PDRO): More Than the Sum of Its Parts
Authors: Ethier Jean-François , Goyer François , Fabry Paul , Barton Adrien
Published: November 2021

While drugs and related products have profoundly changed the lives of people around the world, ongoing challenges remain, including inappropriate use of a drug product. Inappropriate uses can be explained in part by ambiguous or incomplete information, for example, missing reasons for treatments, ambiguous information on how to take a medication, or lack of information on medication-related events outside the health care system. In order to fully assess the situation, data from multiple systems (electronic medical records, pharmacy and radiology information systems, laboratory management systems, etc.) from multiple organizations (outpatient clinics, hospitals, long-term care facilities, laboratories, pharmacies, registries, governments) on a large geographical scale is needed. Formal knowledge models like ontologies can help address such an information integration challenge. Existing approaches like the Observational Medical Outcomes Partnership are discussed and contrasted with the use of ontologies and systems using them for data integration. The PRescription Drug Ontology 2.0 (PDRO 2.0) is then presented and entities that are paramount in addressing this problematic are described. Finally, the benefits of using PDRO are discussed through a series of exemplar situation.
Neurosurgical Care during the COVID-19 Pandemic in Central Germany: A Retrospective Single Center Study of the Second Wave
Authors: Sander Caroline , Dercks Nikolaus von , Fehrenbach Michael Karl , Wende Tim , Stehr Sebastian , Winkler Dirk , Meixensberger Jürgen , Arlt Felix
Published: November 2021

The healthcare system has been placed under an enormous burden by the SARS-CoV-2 (COVID-19) pandemic. In addition to the challenge of providing sufficient care for COVID-19 patients, there is also a need to ensure adequate care for non-COVID-19 patients. We investigated neurosurgical care in a university hospital during the pandemic. We examined the second wave of the pandemic from 1 October 2020 to 15 March 2021 in this retrospective single-center study and compared it to a pre-pandemic period from 1 October 2019 to 15 March 2020. Any neurosurgical intervention, along with patient- and treatment-dependent factors, were recorded. We also examined perioperative complications and unplanned readmissions. A statistical comparison of the study groups was performed. We treated 535 patients with a total of 602 neurosurgical surgeries during the pandemic. This compares to 602 patients with 717 surgeries during the pre-pandemic period. There were 67 fewer patients (reduction to 88.87%) admitted and 115 fewer surgeries (reduction to 83.96%) performed, which were essentially highly elective procedures, such as cervical spinal stenosis, intracranial neurinomas, and peripheral nerve lesions. Regarding complication rates and unplanned readmissions, there was no significant difference between the COVID-19 pandemic and the non-pandemic patient group. Operative capacities were slightly reduced to 88% due to the pandemic. Nevertheless, comprehensive emergency and elective care was guaranteed in our university hospital. This speaks for the sufficient resources and high-quality processes that existed even before the pandemic.
Acceptance of the COVID-19 Vaccine by Foreigners in South Korea
Authors: Achangwa Chiara , Lee Tae-Jun , Lee Moo-Sik
Published: November 2021

Vaccination against COVID-19 is an important strategy for its control. Assessing the willingness to accept the COVID-19 vaccine in different subgroups is important for an inclusive vaccination program design. Our aim was to determine the COVID-19 vaccine acceptance rate and associated factors among foreigners in South Korea. An online cross-sectional study was carried out from May to June 2021. In this study, 710 individuals participated and most were aged between 26 and 29 (36.1%) years. Overall, 70.8% were willing to receive the vaccine. Males were less likely to accept the vaccine than females (OR: 0.5; 95% CI: 0.4–0.7, p < 0.001). Single people were more likely to receive the vaccine than those who were married (OR: 1.4; 95% CI: 0.9–2.0, p = 0.04). Other factors associated with willingness to accept COVID-19 vaccine were; vaccine convenience (OR: 1.7; 95% CI: 1.2–2.3, p = 0.002), doctors’ recommendation (OR: 2.8; 95% CI: 2.0–3.9, p < 0.001), vaccine price (OR: 1.7; 95% CI: 1.2–2.3, p = 0.003), vaccine effectiveness (OR: 8.3; 95% CI: 5.8–12.1, p < 0.001), vaccine importance (OR: 7.9; 95% CI: 4.6–14.1, p < 0.001), and vaccine safety (OR: 6.9; 95% CI: 4.5–10.8, p < 0.001). Providing more information on vaccine safety and effectiveness is required to increase vaccine acceptance.
Occurrence of Professional Burnout and Severity of Depressive Symptoms among Cardiac Nurses: A Cross-Sectional Study
Authors: Larysz Anna , Prokopowicz Anna , Zakliczyński Michał , Uchmanowicz Izabella
Published: November 2021

Nurses with depression are not only likely to suffer themselves, but it may have an impact on their coworkers and potentially the quality of care they provide. This study aimed to determine the prevalence of depression and its association with burnout in cardiac nurses. A group of 400 cardiac nurses (361 women and 39 men) was enrolled. The standardized tools such as Maslach Burnout Inventory (MBI), Beck Depression Inventory (BDI), and Patient Health Questionaire-9 (PHQ-9) were used. A high level of professional burnout regarding emotional exhaustion was observed in 53.3% of nurses, high depersonalization in 52.5%, and low personal accomplishment in 72.8%. PHQ-9 and BDI were shown to correlate significantly and positively with all three MBI subscales (p < 0.05). High depressive symptoms and occupational burnout were correlated with depression (p < 0.05). In conclusion, nurses were found to have high levels of depression and professional burnout, which may have resulted in a negative impact on the quality of patient care. Identification of burnout in cardiac nurses is necessary to consider interventions to prevent stress and depression.
The Management of Agriculture Plastic Waste in the Framework of Circular Economy. Case of the Almeria Greenhouse (Spain)
Authors: Castillo-Díaz Francisco José , Belmonte-Ureña Luis Jesús , Camacho-Ferre Francisco , Tello-Marquina Julio César
Published: November 2021

In recent decades, ecosystems have suffered diverse environmental impacts caused by anthropogenic activities, including the dumping of plastic waste. This situation has prompted the European Union to introduce a new policy based on the circular economy. In this study, the present state and future perspectives on the generation and treatment of plastic waste in the intensive agriculture of Almeria (Spain) are analyzed. This activity generates 1503.6 kg·ha−1·year−1, on average, of plastic waste with an approximate treatment cost of 0.25 €/kg. The present study shows that the volume of plastic waste from intensive agriculture in Almeria is constantly increasing (48,948.2 tons in 2020/21) and it is suggested that the current management system does not meet the needs of the sector. Although it presents great opportunities for improvement under the framework of the circular economy. Furthermore, this work reports a direct relationship between the price of the raw materials needed for the production of plastic and the volume of recycled plastics. For this reason, it would be advisable for the administration to consider the implementation of a tax rebate system for the sector and specifically when the petroleum derivatives used to manufacture plastic are less expensive, and the recycling option is not so attractive.
NTRK Gene Fusion Detection in Atypical Spitz Tumors
Authors: Cappellesso Rocco , Nozzoli Filippo , Zito Marino Federica , Simi Sara , Castiglione Francesca , De Giorgi Vincenzo , Cota Carlo , Senetta Rebecca , Scognamiglio Giosuè , Anniciello Anna Maria , Cesinaro Anna Maria , Mandalà Mario , Gianatti Andrea , Valente Maria Gabriella , Valeri Barbara , Sementa Angela Rita , Ricci Costantino , Corti Barbara , Roviello Giandomenico , Dei Tos Angelo Paolo , Franco Renato , Massi Daniela
Published: November 2021

Atypical Spitz tumors (AST) deviate from stereotypical Spitz nevi for one or more atypical features and are now regarded as an intermediate category of melanocytic tumors with uncertain malignant potential. Activating NTRK1/NTRK3 fusions elicit oncogenic events in Spitz lesions and are targetable with kinase inhibitors. However, their prevalence among ASTs and the optimal approach for their detection is yet to be determined. A series of 180 ASTs were screened with pan-TRK immunohistochemistry and the presence of NTRK fusions was confirmed using FISH, two different RNA-based NGS panels for solid tumors, and a specific real time RT-PCR panel. Overall, 26 ASTs showed pan-TRK immunostaining. NTRK1 fusions were detected in 15 of these cases showing cytoplasmic immunoreaction, whereas NTRK3 was detected in one case showing nuclear immunoreaction. Molecular tests resulted all positive in only two ASTs (included the NTRK3 translocated), RNA-based NGS and real time RT-PCR were both positive in three cases, and FISH and real time RT-PCR in another two cases. In seven ASTs NTRK1 fusions were detected only by FISH and in two cases only by real time RT-PCR. The frequency of NTRK fusions in ASTs is 9%, with a clear prevalence of NTRK1 compared to NTRK3 alterations. Pan-TRK immunohistochemistry is an excellent screening test. Confirmation of NTRK fusions may require the use of different molecular techniques.
Hygiene Hypothesis as the Etiology of Kawasaki Disease: Dysregulation of Early B Cell Development
Authors: Lee Jong-Keuk
Published: November 2021

Kawasaki disease (KD) is an acute systemic vasculitis that occurs predominantly in children under 5 years of age. Despite much study, the etiology of KD remains unknown. However, epidemiological and immunological data support the hygiene hypothesis as a possible etiology. It is thought that more sterile or clean modern living environments due to increased use of sanitizing agents, antibiotics, and formula feeding result in a lack of immunological challenges, leading to defective or dysregulated B cell development, accompanied by low IgG and high IgE levels. A lack of B cell immunity may increase sensitivity to unknown environmental triggers that are nonpathogenic in healthy individuals. Genetic studies of KD show that all of the KD susceptibility genes identified by genome-wide association studies are involved in B cell development and function, particularly in early B cell development (from the pro-B to pre-B cell stage). The fact that intravenous immunoglobulin is an effective therapy for KD supports this hypothesis. In this review, I discuss clinical, epidemiological, immunological, and genetic studies showing that the etiopathogenesis of KD in infants and toddlers can be explained by the hygiene hypothesis, and particularly by defects or dysregulation during early B cell development.
Intrabody Targeting HIF-1α Mediates Transcriptional Downregulation of Target Genes Related to Solid Tumors
Authors: Hu Yaozhong , Romão Ema , Vincke Cécile , Brys Lea , Elkrim Yvon , Vandevenne Marylène , Liu Changxiao , Muyldermans Serge
Published: November 2021

Uncontrolled growth of solid tumors will result in a hallmark hypoxic condition, whereby the key transcriptional regulator of hypoxia inducible factor-1α (HIF-1α) will be stabilized to activate the transcription of target genes that are responsible for the metabolism, proliferation, and metastasis of tumor cells. Targeting and inhibiting the transcriptional activity of HIF-1 may provide an interesting strategy for cancer therapy. In the present study, an immune library and a synthetic library were constructed for the phage display selection of Nbs against recombinant PAS B domain protein (rPasB) of HIF-1α. After panning and screening, seven different nanobodies (Nbs) were selected, of which five were confirmed via immunoprecipitation to target the native HIF-1α subunit. The inhibitory effect of the selected Nbs on HIF-1 induced activation of target genes has been evaluated after intracellular expression of these Nbs in HeLa cells. The dramatic inhibition of both intrabody formats on the expression of HIF-1-related target genes has been confirmed, which indicated the inhibitory efficacy of selected Nbs on the transcriptional activity of HIF-1.
Dendritic Cells and Cancer Immunotherapy: The Adjuvant Effect
Authors: Nava Sara , Lisini Daniela , Frigerio Simona , Bersano Anna
Published: November 2021

Dendritic cells (DCs) are immune specialized cells playing a critical role in promoting immune response against antigens, and may represent important targets for therapeutic interventions in cancer. DCs can be stimulated ex vivo with pro-inflammatory molecules and loaded with tumor-specific antigen(s). Protocols describing the specific details of DCs vaccination manufacturing vary widely, but regardless of the employed protocol, the DCs vaccination safety and its ability to induce antitumor responses is clearly established. Many years of studies have focused on the ability of DCs to provide overall survival benefits at least for a selection of cancer patients. Lessons learned from early trials lead to the hypothesis that, to improve the efficacy of DCs-based immunotherapy, this should be combined with other treatments. Thus, the vaccine’s ultimate role may lie in the combinatorial approaches of DCs-based immunotherapy with chemotherapy and radiotherapy, more than in monotherapy. In this review, we address some key questions regarding the integration of DCs vaccination with multimodality therapy approaches for cancer treatment paradigms.
L-dopa-Dependent Effects of GLP-1R Agonists on the Survival of Dopaminergic Cells Transplanted into a Rat Model of Parkinson Disease
Authors: Elabi Osama F. , Davies Jeffrey S. , Lane Emma L.
Published: November 2021

Cell therapy is a promising treatment for Parkinson’s disease (PD), however clinical trials to date have shown relatively low survival and significant patient-to-patient variability. Glucagon Like Peptide-1 receptor (GLP-1R) agonists have potential neuroprotective effects on endogenous dopaminergic neurons. This study explores whether these agents could similarly support the growth and survival of newly transplanted neurons. 6-OHDA lesioned Sprague Dawley rats received intra-striatal grafts of dopaminergic ventral mesencephalic cells from embryonic day 14 Wistar rat embryos. Transplanted rats then received either saline or L-dopa (12 mg/kg) administered every 48 h prior to, and following cell transplantation. Peripheral GLP-1R agonist administration (exendin-4, 0.5 μg/kg twice daily or liraglutide, 100 μg/kg once daily) commenced immediately after cell transplantation and was maintained throughout the study. Graft survival increased under administration of exendin-4, with motor function improving significantly following treatment with both exendin-4 and liraglutide. However, this effect was not observed in rats administered with L-dopa. In contrast, L-dopa treatment with liraglutide increased graft volume, with parallel increases in motor function. However, this improvement was accompanied by an increase in leukocyte infiltration around the graft. The co-administration of L-dopa and exendin-4 also led to indicators of insulin resistance not seen with liraglutide, which may underpin the differential effects observed between the two GLP1-R agonists. Overall, there may be some benefit to the supplementation of grafted patients with GLP-1R agonists but the potential interaction with other pharmacological treatments needs to be considered in more depth.
New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues
Authors: Pike John Wesley , Meyer Mark B.
Published: November 2021

Recent studies of transcription have revealed an advanced set of overarching principles that govern vitamin D action on a genome-wide scale. These tenets of vitamin D transcription have emerged as a result of the application of now well-established techniques of chromatin immunoprecipitation coupled to next-generation DNA sequencing that have now been linked directly to CRISPR-Cas9 genomic editing in culture cells and in mouse tissues in vivo. Accordingly, these techniques have established that the vitamin D hormone modulates sets of cell-type specific genes via an initial action that involves rapid binding of the VDR–ligand complex to multiple enhancer elements at open chromatin sites that drive the expression of individual genes. Importantly, a sequential set of downstream events follows this initial binding that results in rapid histone acetylation at these sites, the recruitment of additional histone modifiers across the gene locus, and in many cases, the appearance of H3K36me3 and RNA polymerase II across gene bodies. The measured recruitment of these factors and/or activities and their presence at specific regions in the gene locus correlate with the emerging presence of cognate transcripts, thereby highlighting sequential molecular events that occur during activation of most genes both in vitro and in vivo. These features provide a novel approach to the study of vitamin D analogs and their actions in vivo and suggest that they can be used for synthetic compound evaluation and to select for novel tissue- and gene-specific features. This may be particularly useful for ligand activation of nuclear receptors given the targeting of these factors directly to genetic sites in the nucleus.
Τhe Greek Variant in APP Gene: The Phenotypic Spectrum of APP Mutations
Authors: Kalampokini Stefania , Georgouli Despoina , Patrikiou Eleni , Provatas Antonios , Valotassiou Varvara , Georgoulias Panagiotis , Spanaki Cleanthe , Hadjigeorgiou Georgios M. , Xiromerisiou Georgia
Published: November 2021

Mutations in the gene encoding amyloid precursor protein (APP) cause autosomal dominant inherited Alzheimer’s disease (AD). We present a case of a 68-year-old female who presented with epileptic seizures, neuropsychiatric symptoms and progressive memory decline and was found to carry a novel APP variant, c.2062T>G pLeu688Val. A comprehensive literature review of all reported cases of AD due to APP mutations was performed in PubMed and Web of Science databases. We reviewed 98 studies with a total of 385 cases. The mean age of disease onset was 51.3 ± 8.3 (31–80 years). Mutations were most often located in exons 17 (80.8%) and 16 (12.2%). The most common symptoms were dementia, visuospatial symptoms, aphasia, epilepsy and psychiatric symptoms. Mutations in the β-amyloid region, and specifically exon 17, were associated with high pathogenicity and a younger age of disease onset. We describe the second reported APP mutation in the Greek population. APP mutations may act variably on disease expression and their phenotype is heterogeneous.
Efficacy of 5% Dextrose Water Injection for Peripheral Entrapment Neuropathy: A Narrative Review
Authors: Wu Yung-Tsan , Wu Chueh-Hung , Lin Jui-An , Su Daniel , Hung Chen-Yu , Lam Stanley K. H.
Published: November 2021

Current non-surgical treatment for peripheral entrapment neuropathy is considered insignificant and unsustainable; thus, it is essential to find an alternative novel treatment. The technique of perineural injection therapy using 5% dextrose water has been progressively used to treat many peripheral entrapment neuropathies and has been proven to have outstanding effects in a few high-quality studies. Currently, the twentieth edition of Harrison’s Principles of Internal Medicine textbook recommends this novel injection therapy as an alternative local treatment for carpal tunnel syndrome (CTS). Hence, this novel approach has become the mainstream method for treating CTS, and other studies have revealed its clinical benefit for other peripheral entrapment neuropathies. In this narrative review, we aimed to provide an insight into this treatment method and summarize the current studies on cases of peripheral entrapment neuropathy treated by this method.
Albumin–Hyaluronan Interactions: Influence of Ionic Composition Probed by Molecular Dynamics
Authors: Bełdowski Piotr , Przybyłek Maciej , Raczyński Przemysław , Dedinaite Andra , Górny Krzysztof , Wieland Florian , Dendzik Zbigniew , Sionkowska Alina , Claesson Per M.
Published: November 2021

The lubrication mechanism in synovial fluid and joints is not yet fully understood. Nevertheless, intermolecular interactions between various neutral and ionic species including large macromolecular systems and simple inorganic ions are the key to understanding the excellent lubrication performance. An important tool for characterizing the intermolecular forces and their structural consequences is molecular dynamics. Albumin is one of the major components in synovial fluid. Its electrostatic properties, including the ability to form molecular complexes, are closely related to pH, solvation, and the presence of ions. In the context of synovial fluid, it is relevant to describe the possible interactions between albumin and hyaluronate, taking into account solution composition effects. In this study, the influence of Na+, Mg2+, and Ca2+ ions on human serum albumin–hyaluronan interactions were examined using molecular dynamics tools. It was established that the presence of divalent cations, and especially Ca2+, contributes mostly to the increase of the affinity between hyaluronan and albumin, which is associated with charge compensation in negatively charged hyaluronan and albumin. Furthermore, the most probable binding sites were structurally and energetically characterized. The indicated moieties exhibit a locally positive charge which enables hyaluronate binding (direct and water mediated).
Assessment of the Effects of Dietary Vitamin D Levels on Olanzapine-Induced Metabolic Side Effects: Focus on the Endocannabinoidome-Gut Microbiome Axis
Authors: Abolghasemi Armita , Manca Claudia , Iannotti Fabio A. , Shen Melissa , Leblanc Nadine , Lacroix Sébastien , Martin Cyril , Flamand Nicolas , Di Marzo Vincenzo , Silvestri Cristoforo
Published: November 2021

Vitamin D deficiency is associated with poor mental health and dysmetabolism. Several metabolic abnormalities are associated with psychotic diseases, which can be compounded by atypical antipsychotics that induce weight gain and insulin resistance. These side-effects may be affected by vitamin D levels. The gut microbiota and endocannabinoidome (eCBome) are significant regulators of both metabolism and mental health, but their role in the development of atypical antipsychotic drug metabolic side-effects and their interaction with vitamin D status is unknown. We studied the effects of different combinations of vitamin D levels and atypical antipsychotic drug (olanzapine) exposure on whole-body metabolism and the eCBome-gut microbiota axis in female C57BL/6J mice under a high fat/high sucrose (HFHS) diet in an attempt to identify a link between the latter and the different metabolic outputs induced by the treatments. Olanzapine exerted a protective effect against diet-induced obesity and insulin resistance, largely independent of dietary vitamin D status. These changes were concomitant with olanzapine-mediated decreases in Trpv1 expression and increases in the levels of its agonists, including various N-acylethanolamines and 2-monoacylglycerols, which are consistent with the observed improvement in adiposity and metabolic status. Furthermore, while global gut bacteria community architecture was not altered by olanzapine, we identified changes in the relative abundances of various commensal bacterial families. Taken together, changes of eCBome and gut microbiota families under our experimental conditions might contribute to olanzapine and vitamin D-mediated inhibition of weight gain in mice on a HFHS diet.
Human Periodontal Ligament Stem Cell and Umbilical Vein Endothelial Cell Co-Culture to Prevascularize Scaffolds for Angiogenic and Osteogenic Tissue Engineering
Authors: Zhao Zeqing , Sun Yaxi , Qiao Qingchen , Zhang Li , Xie Xianju , Weir Michael D. , Schneider Abraham , Xu Hockin H. K. , Zhang Ning , Zhang Ke , Bai Yuxing
Published: November 2021

(1) Background: Vascularization remains a critical challenge in bone tissue engineering. The objective of this study was to prevascularize calcium phosphate cement (CPC) scaffold by co-culturing human periodontal ligament stem cells (hPDLSCs) and human umbilical vein endothelial cells (hUVECs) for the first time; (2) Methods: hPDLSCs and/or hUVECs were seeded on CPC scaffolds. Three groups were tested: (i) hUVEC group (hUVECs on CPC); (ii) hPDLSC group (hPDLSCs on CPC); (iii) co-culture group (hPDLSCs + hUVECs on CPC). Osteogenic differentiation, bone mineral synthesis, and microcapillary-like structures were evaluated; (3) Results: Angiogenic gene expressions of co-culture group were 6–9 fold those of monoculture. vWF expression of co-culture group was 3 times lower than hUVEC-monoculture group. Osteogenic expressions of co-culture group were 2–3 folds those of the hPDLSC-monoculture group. ALP activity and bone mineral synthesis of co-culture were much higher than hPDLSC-monoculture group. Co-culture group formed capillary-like structures at 14–21 days. Vessel length and junction numbers increased with time; (4) Conclusions: The hUVECs + hPDLSCs co-culture on CPC scaffold achieved excellent osteogenic and angiogenic capability in vitro for the first time, generating prevascularized networks. The hPDLSCs + hUVECs co-culture had much better osteogenesis and angiogenesis than monoculture. CPC scaffolds prevacularized via hPDLSCs + hUVECs are promising for dental, craniofacial, and orthopedic applications.
Connections between Immune-Derived Mediators and Sensory Nerves for Itch Sensation
Authors: Toyama Sumika , Tominaga Mitsutoshi , Takamori Kenji
Published: November 2021

Although histamine is a well-known itch mediator, histamine H1-receptor blockers often lack efficacy in chronic itch. Recent molecular and cellular based studies have shown that non-histaminergic mediators, such as proteases, neuropeptides and cytokines, along with their cognate receptors, are involved in evocation and modulation of itch sensation. Many of these molecules are produced and secreted by immune cells, which act on sensory nerve fibers distributed in the skin to cause itching and sensitization. This understanding of the connections between immune cell-derived mediators and sensory nerve fibers has led to the development of new treatments for itch. This review summarizes current knowledge of immune cell-derived itch mediators and neuronal response mechanisms, and discusses therapeutic agents that target these systems.
Auxin Metabolite Profiling in Isolated and Intact Plant Nuclei
Authors: Skalický Vladimír , Vojtková Tereza , Pěnčík Aleš , Vrána Jan , Juzoń Katarzyna , Koláčková Veronika , Sedlářová Michaela , Kubeš Martin F. , Novák Ondřej
Published: November 2021

The plant nucleus plays an irreplaceable role in cellular control and regulation by auxin (indole-3-acetic acid, IAA) mainly because canonical auxin signaling takes place here. Auxin can enter the nucleus from either the endoplasmic reticulum or cytosol. Therefore, new information about the auxin metabolome (auxinome) in the nucleus can illuminate our understanding of subcellular auxin homeostasis. Different methods of nuclear isolation from various plant tissues have been described previously, but information about auxin metabolite levels in nuclei is still fragmented and insufficient. Herein, we tested several published nucleus isolation protocols based on differential centrifugation or flow cytometry. The optimized sorting protocol leading to promising yield, intactness, and purity was then combined with an ultra-sensitive mass spectrometry analysis. Using this approach, we can present the first complex report on the auxinome of isolated nuclei from cell cultures of Arabidopsis and tobacco. Moreover, our results show dynamic changes in auxin homeostasis at the intranuclear level after treatment of protoplasts with free IAA, or indole as a precursor of auxin biosynthesis. Finally, we can conclude that the methodological procedure combining flow cytometry and mass spectrometry offers new horizons for the study of auxin homeostasis at the subcellular level.
N-Methyl-d-aspartic Acid (NMDA) Receptor Is Involved in the Inhibitory Effect of Ketamine on Human Sperm Functions
Authors: Chen Ying , Xu Wenqing , Yuan Yuan , Chen Houyang , Zheng Shuangyan , He Yuanqiao , Luo Tao
Published: November 2021

Ketamine, which used to be widely applied in human and animal medicine as a dissociative anesthetic, has become a popular recreational drug because of its hallucinogenic effect. Our previous study preliminarily proved that ketamine could inhibit human sperm function by affecting intracellular calcium concentration ([Ca2+]i). However, the specific signaling pathway of [Ca2+]i induced by ketamine in human sperm is still not clear yet. Here, the N-methyl-d-aspartic acid (NMDA) receptor was detected in the tail region of human sperm. Its physiological ligand, NMDA (50 μM), could reverse ketamine’s inhibitory effect on human sperm function, and its antagonist, MK801 (100 μM), could restrain the effect of NMDA. The inhibitory effect caused by 4 mM ketamine or 100 μM MK801 on [Ca2+]i, which is a central factor in the regulation of human sperm function, could also be recovered by 50 μM NMDA. The results suggest that the NMDA receptor is probably involved in the inhibitory effect of ketamine on human sperm functions.
Extracellular Vesicles of Adipose-Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons
Authors: Chen Shih-Heng , Chen Zhi-Yu , Lin Ya-Hsuan , Chen Shih-Hsien , Chou Pang-Yun , Kao Huang-Kai , Lin Feng-Huei
Published: November 2021

Healing of ruptured tendons remains a clinical challenge because of its slow progress and relatively weak mechanical force at an early stage. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have therapeutic potential for tissue regeneration. In this study, we isolated EVs from adipose-derived stem cells (ADSCs) and evaluated their ability to promote tendon regeneration. Our results indicated that ADSC-EVs significantly enhanced the proliferation and migration of tenocytes in vitro. To further study the roles of ADSC-EVs in tendon regeneration, ADSC-EVs were used in Achilles tendon repair in rabbits. The mechanical strength, histology, and protein expression in the injured tendon tissues significantly improved 4 weeks after ADSC-EV treatment. Decorin and biglycan were significantly upregulated in comparison to the untreated controls. In summary, ADSC-EVs stimulated the proliferation and migration of tenocytes and improved the mechanical strength of repaired tendons, suggesting that ADSC-EV treatment is a potential highly potent therapeutic strategy for tendon injuries.
The Use of Information and Communication Technology (ICT) in the Implementation of Instructional Supervision and Its Effect on Teachers’ Instructional Process Quality
Authors: Wiyono Bambang Budi , Wedi Agus , Ulfa Saida , Putra Arda Purnama
Published: November 2021

This study aimed to explore communication techniques based on the information and communication technology (ICT) used in the implementation of instructional supervision to determine their effect on the teacher’s learning process and find effective techniques to improve the quality of the teacher’s learning process. This research was conducted in Blitar City with a sample of 60 teachers through a random sampling technique. The data collection technique used a rating scale, checklist, and open-form questionnaire. Descriptive statistics were used to describe the data, while the Pearson product-moment correlation techniques and multiple regression were used to test the research hypotheses. The results show that the most widely used ICT-based communication techniques are WhatsApp, Google Meet, Zoom, Skype, and Google Forms. These are followed by email, video-recording, and audio-recording techniques. The use of ICT is still rare. There is a significant relationship between the use of ICT in instructional supervision and the quality of the teacher’s teaching-learning process, except when using telephones and televisions. ICT techniques are most commonly used for synchronous communication, followed by use for sharing information, and recording activities. The use of ICT in instructional supervision simultaneously affects the teacher’s instructional process.
Cytochrome c: Using Biological Insight toward Engineering an Optimized Anticancer Biodrug
Authors: Delinois Louis J. , De León-Vélez Omar , Vázquez-Medina Adriana , Vélez-Cabrera Alondra , Marrero-Sánchez Amanda , Nieves-Escobar Christopher , Alfonso-Cano Daniela , Caraballo-Rodríguez Delvin , Rodriguez-Ortiz Jael , Acosta-Mercado Jemily , Benjamín-Rivera Josué A. , González-González Kiara , Fernández-Adorno Kysha , Santiago-Pagán Lisby , Delgado-Vergara Rafael , Torres-Ávila Xaiomy , Maser-Figueroa Andrea , Grajales-Avilés Gladimarys , Méndez Glorimar I. Miranda , Santiago-Pagán Javier , Nieves-Santiago Miguel , Álvarez-Carrillo Vanessa , Griebenow Kai , Tinoco Arthur D.
Published: November 2021

The heme protein cytochrome c (Cyt c) plays pivotal roles in cellular life and death processes. In the respiratory chain of mitochondria, it serves as an electron transfer protein, contributing to the proliferation of healthy cells. In the cell cytoplasm, it activates intrinsic apoptosis to terminate damaged cells. Insight into these mechanisms and the associated physicochemical properties and biomolecular interactions of Cyt c informs on the anticancer therapeutic potential of the protein, especially in its ability to subvert the current limitations of small molecule-based chemotherapy. In this review, we explore the development of Cyt c as an anticancer drug by identifying cancer types that would be receptive to the cytotoxicity of the protein and factors that can be finetuned to enhance its apoptotic potency. To this end, some information is obtained by characterizing known drugs that operate, in part, by triggering Cyt c induced apoptosis. The application of different smart drug delivery systems is surveyed to highlight important features for maintaining Cyt c stability and activity and improving its specificity for cancer cells and high drug payload release while recognizing the continuing limitations. This work serves to elucidate on the optimization of the strategies to translate Cyt c to the clinical market.
Post-Acute Sequelae of COVID-19 and Cardiovascular Autonomic Dysfunction: What Do We Know?
Authors: Bisaccia Giandomenico , Ricci Fabrizio , Recce Vittoria , Serio Antonio , Iannetti Giovanni , Chahal Anwar A. , Ståhlberg Marcus , Khanji Mohammed Yunus , Fedorowski Artur , Gallina Sabina
Published: November 2021

Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID syndrome, is emerging as a major health issue in patients with previous SARS-CoV-2 infection. Symptoms commonly experienced by patients include fatigue, palpitations, chest pain, dyspnea, reduced exercise tolerance, and “brain fog”. Additionally, symptoms of orthostatic intolerance and syncope suggest the involvement of the autonomic nervous system. Signs of cardiovascular autonomic dysfunction appear to be common in PASC and are similar to those observed in postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. In this review, we report on the epidemiology of PASC, discuss current evidence and possible mechanisms underpinning the dysregulation of the autonomic nervous system, and suggest nonpharmacological and pharmacological interventions to treat and relieve symptoms of PASC-associated dysautonomia.
Primary Failure to an Anti-TNF Agent in Inflammatory Bowel Disease: Switch (to a Second Anti-TNF Agent) or Swap (for Another Mechanism of Action)?
Authors: Gisbert Javier P. , Chaparro María
Published: November 2021

Background: About a third of patients with inflammatory bowel disease do not respond to anti-tumour necrosis factor (anti-TNF) therapy, which is challenging. Aim: To review the current data on the two main strategies when facing primary non-response to an anti-TNF agent in inflammatory bowel disease: changing to a second anti-TNF (switching) or to a drug with another mechanisms of action (swapping). Methods: We performed a bibliographic search to identify studies reporting on efficacy of any biologic treatment after primary anti-TNF non-response. Results: The efficacy of a second anti-TNF is lower when the reason to withdraw the first one is primary failure. Nevertheless, switching to another anti-TNF even after primary failure may still be effective in some patients. Both vedolizumab and ustekinumab have generally been shown to be less effective in anti-TNF exposed patients. However, despite primary anti-TNF failure, patients may respond to vedolizumab or ustekinumab in a limited but considerable number of cases. The cause for swapping (primary vs. secondary anti-TNF failure) seems to have limited effect on vedolizumab efficacy. Primary anti-TNF non-response seems to be a clearer predictor of treatment failure for ustekinumab. Unfortunately, the two main strategies to treat specifically a patient with primary non-response to an anti-TNF agent—switching to a second anti-TNF or swapping for vedolizumab/ustekinumab—have not been properly compared. Conclusion: The data reviewed in the present study clearly emphasise the imperative need to carry out head-to-head randomised trials in patients exposed to anti-TNF agents in general, and specifically in those with primary non-response to these agents.
Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes
Authors: Malaise Olivier , Paulissen Geneviève , Deroyer Céline , Ciregia Federica , Poulet Christophe , Neuville Sophie , Plener Zelda , Daniel Christophe , Gillet Philippe , Lechanteur Chantal , Brondello Jean-Marc , de Seny Dominique , Malaise Michel
Published: November 2021

Osteoarthritis (OA) is recognized as being a cellular senescence-linked disease. Intra-articular injections of glucocorticoids (GC) are frequently used in knee OA to treat synovial effusion but face controversies about toxicity. We investigated the influence of GC on cellular senescence hallmarks and senescence induction in fibroblast-like synoviocytes (FLS) from OA patients and mesenchymal stem cells (MSC). Methods: Cellular senescence was assessed via the proliferation rate, β-galactosidase staining, DNA damage and CKI expression (p21, p16INK4A). Experimental senescence was induced by irradiation. Results: The GC prednisolone did not induce an apparent senescence phenotype in FLS, with even higher proliferation, no accumulation of β-galactosidase-positive cells nor DNA damage and reduction in p21mRNA, only showing the enhancement of p16INK4A. Prednisolone did not modify experimental senescence induction in FLS, with no modulation of any senescence parameters. Moreover, prednisolone did not induce a senescence phenotype in MSC: despite high β-galactosidase-positive cells, no reduction in proliferation, no DNA damage and no CKI enhancement was observed. Conclusions: We provide reassuring in vitro data about the use of GC regarding cellular senescence involvement in OA: the GC prednisolone did not induce a senescent phenotype in OA FLS (the proliferation ratio was even higher) and in MSC and did not worsen cellular senescence establishment.
Health-Related Quality of Life Issues Experienced by Thoracic and Breast Sarcoma Patients: A Rare and Understudied Group
Authors: van Eck Ilse , den Hollander Dide , Lidington Emma , Hentschel Leopold , Eichler Martin , Salah Samer , Singer Susanne , Pinto Monica , Fauske Lena , Fiore Marco , Nixon Ioanna , Constantinidou Anastasia , Desar Ingrid M. E. , Bonenkamp Johannes J. , van Houdt Winan J. , Reuvers Milou J. P. , Haas Rick L. M. , Bruland Øyvind S. , Kasper Bernd , van der Graaf Winette T. A. , Husson Olga
Published: November 2021

Thoracic and breast sarcomas constitute a rare subgroup within the sarcoma population. There is limited knowledge about their health-related quality of life (HRQoL) and a valid disease-specific HRQoL instrument is lacking. This qualitative study aimed to investigate the HRQoL issues experienced by a small group of thoracic and breast sarcoma patients. Semi-structured interviews with 19 thoracic and four breast sarcoma patients were conducted and thematically analysed. Physical issues mentioned by both groups were fatigue, sleep disturbances, pain, wound infections, and symptoms related to chemotherapy and radiotherapy. Tightness in the back and restrictions in performing tasks above arm height were specific physical issues for breast sarcoma patients, whereas respiratory problems were only mentioned by thoracic sarcoma patients. Body image issues, changes in mood, fear of recurrence, and living with uncertainty were important mental health issues for both subgroups. Social issues in both groups included challenges in work and relationships, financial difficulties, loss of independence, and limitations in social activities. The identified physical, mental, and social health challenges can significantly impact thoracic and breast sarcoma patients’ HRQoL. Results of this qualitative study will guide personalised supportive care for breast and thoracic sarcoma patients and help in determining the best possible HRQoL measurement strategy for sarcoma patients with different primary sarcoma locations.
What We Know about the Long-Term Risks of Hysterectomy for Benign Indication—A Systematic Review
Authors: Madueke-Laveaux Obianuju Sandra , Elsharoud Amro , Al-Hendy Ayman
Published: November 2021

Hysterectomy is the most common treatment option in women with uterine fibroids, providing definitive relief from the associated burdensome symptoms. As with all surgical interventions, hysterectomy is associated with risk of complications, short-term morbidities, and mortality, all of which have been described previously. However, information on the potential long-term risks of hysterectomy is only recently becoming available. A systematic literature review was performed to identify studies published between 2005 and December 2020 evaluating the long-term impact of hysterectomy on patient outcomes. A total of 29 relevant studies were identified. A review of the articles showed that hysterectomy may increase the risk of cardiovascular events, certain cancers, the need for further surgery, early ovarian failure and menopause, depression, and other outcomes. It is important to acknowledge that the available studies examine possible associations and hypotheses rather than causality, and there is a need to establish higher quality studies to truly evaluate the long-term consequences of hysterectomy. However, it is of value to consider these findings when discussing the benefits and risks of all treatment options with patients with uterine fibroids to allow for preference-based choices to be made in a shared decision-making process. This is key to ensuring that patients receive the treatment that best meets their individual needs.
Compatibilization of Starch/Synthetic Biodegradable Polymer Blends for Packaging Applications: A Review
Authors: Gunawardene Oneesha H. P. , Gunathilake Chamila , Amaraweera Sumedha M. , Fernando Nimasha M. L. , Wanninayaka Darshana B. , Manamperi Asanga , Kulatunga Asela K. , Rajapaksha Suranga M. , Dassanayake Rohan S. , Fernando Chakrawarthige A. N. , Manipura Aruna
Published: November 2021

The health and environmental concerns of the usage of non-biodegradable plastics have driven efforts to explore replacing them with renewable polymers. Although starch is a vital renewable polymer, poor water resistivity and thermo-mechanical properties have limited its applications. Recently, starch/synthetic biodegradable polymer blends have captured greater attention to replace inert plastic materials; the question of ‘immiscibility’ arises during the blend preparation due to the mixing of hydrophilic starch with hydrophobic polymers. The immiscibility issue between starch and synthetic polymers impacts the water absorption, thermo-mechanical properties, and chemical stability demanded by various engineering applications. Numerous studies have been carried out to eliminate the immiscibility issues of the different components in the polymer blends while enhancing the thermo-mechanical properties. Incorporating compatibilizers into the blend mixtures has significantly reduced the particle sizes of the dispersed phase while improving the interfacial adhesion between the starch and synthetic biodegradable polymer, leading to fine and homogeneous structures. Thus, Significant improvements in thermo-mechanical and barrier properties and water resistance can be observed in the compatibilized blends. This review provides an extensive discussion on the compatibilization processes of starch and petroleum-based polymer blends.
Scale-Resolving Simulations of a Circular Cylinder Subjected to Low Mach Number Turbulent Inflow
Authors: Lidtke Artur K. , Klapwijk Maarten , Lloyd Thomas
Published: November 2021

Inflow turbulence is relevant for many engineering applications relating to noise generation, including aircraft wings, landing gears, and non-cavitating marine propellers. While modelling of this phenomenon is well-established for higher Mach number aerospace problems, lower Mach number applications, which include marine propellers, still lack validated numerical tools. For this purpose, simplified cases for which extensive measurement data are available can be used. This paper investigates the effect of inflow turbulence on a circular cylinder at a Reynolds number of 14,700, a Mach number of 0.029, and with inflow turbulence intensities ranging between 0% and 22%. In the present work focus is put on the hydrodynamics aspect, with the aim of addressing radiated noise in a later study. The flow is simulated using the partially averaged Navier Stokes equations, with turbulence inserted using a synthetic inflow turbulence generator. Results show that the proposed method can successfully replicate nearfield pressure variations and relevant flow features in the wake of the body. In agreement with the literature, increasing inflow turbulence intensity adds broadband frequency content to all the presented fluctuating flow quantities. In addition, the applied variations in inflow turbulence intensity result in a major shift in flow dynamics around a turbulence intensity of 15%, when the dominant effect of von Kármán vortices on the dominant flow dynamics becomes superseded by freestream turbulence.
The Effect of Monochromatic LED Light Wavelengths and Photoperiods on Botrytis cinerea
Authors: Rasiukevičiūtė Neringa , Brazaitytė Aušra , Vaštakaitė-Kairienė Viktorija , Kupčinskienė Asta , Duchovskis Pavelas , Samuolienė Giedrė , Valiuškaitė Alma
Published: November 2021

Botrytis cinerea is a ubiquitous necrotrophic pathogen causing grey mould in economically important crops. Light effect in horticulture is undeniable and fungi also react to light. Selected specific light-emitting diodes (LEDs) and photoperiods can be used for fungal pathogen inhibition. This study aimed to evaluate how LED light wavelengths and photoperiods affect the growth parameters of B. cinerea. The morphological (mycelium appearance, sclerotia distribution) and phenotypic (conidia presence and size, mycelium growth rate, recovery) characteristics of the fungal pathogen B. cinerea were evaluated under royal blue 455 nm, blue 470 nm, cyan 505 nm, yellow 590 nm, and red 627 nm LED lights at various photoperiods (4, 8, 12, 16, 20, 24 h). The results revealed that the light conditions and photoperiods influenced the B. cinerea morphological and phenotypic characteristics. Overall, the highest B. cinerea inhibition was under yellow (590 nm) LED light at 4 and 8 h photoperiods. Conidia did not form under blue 455 nm at 8, 16, 20, and 24 h photoperiods. Therefore, it can be assumed that the phenotypic and morphological features of B. cinerea depend on the specific photoperiod and LED light wavelength. The results allowed an exploration of original research approaches, raised new scientific questions for further investigation, and suggested new green plant protection solutions.