bluuebunny/crossref_metadata_2025 huggingface dataset:
Indigenous Border Migrants and (Im)Mobility Policies in Chile in Times of COVID-19
Authors: Piñones-Rivera Carlos , Liberona Nanette , Arancibia Rodrigo , Jiménez Verónica
Published: August 2022

The commodification of healthcare and the structural violence towards the migrant population in the Chilean system materialize in a series of structural barriers to accessing healthcare. In the face of this structural vulnerability, cross-border health mobility is one of the primary resources of indigenous border migrants living in the Tarapacá region (Chile). This involves crossing the border of both people (specialists/patients) and objects (such as ritual supplies or biomedicines), which play a crucial role as, in many cases, it is the only way to satisfy their healthcare needs. The security-orientated geopolitics of border closure (Plan Frontera Segura) has been reinforced by immobility policies linked to the COVID-19 pandemic. While doing so leaves people without the fundamental resource of healthcare mobility or obliges them to cross the border via unauthorized crossings, exposing them to criminalization and abuse by different agents of violence (the military, people smugglers, etc.). In this paper, we will offer a description of these processes of (im)mobility, analyzing their conformation both by the current policies of the Chilean State and by the notorious deficiency in indigenous and migrant rights, denouncing the material impact they have on the health/illness/care process of indigenous migrants.
Households’ Direct Economic Burden Associated with Chronic Non-Communicable Diseases in Saudi Arabia
Authors: Almalki Ziyad S. , Alahmari Abdullah K. , Alqahtani Nasser , Alzarea Abdulaziz Ibrahim , Alshehri Ahmed M. , Alruwaybiah Abdulrahman M. , Alanazi Bader A. , Alqahtani Abdulhadi M. , Ahmed Nehad J.
Published: August 2022

Households’ economic burden associated with chronic non-communicable diseases (NCDs) is a deterrent to healthcare access, adversely impacting patients’ health. Therefore, we investigated the extent of out-of-pocket (OOP) spending among individuals diagnosed with chronic NCDs among household members in Riyadh, Saudi Arabia. Face-to-face interviews were conducted among households in Riyadh Province from the beginning of January 2021 to the end of June 2021. The respondents were asked to record OOP spending throughout the past three months in their health. A generalized linear regression model was used to determine the effects of several factors on the level of OOP spending. A total of 39.6% of the households studied had at least one member with a chronic NCD. Diabetes patients spent an average of SAR 932 (USD 248), hypertension patients SAR 606 (USD 162), and hypothyroid patients SAR 402 (USD 107). It was shown that households with older and more educated members had greater OOP spending. Households with an employed head of household, more family members, higher SES status, health insurance coverage, and urban residency had significantly higher OOP expenditure. The burden of OOP spending for chronic NCD households remains high, with some disparities. The research offers important information for decision making to lower OOP cost among NCD households.
Sustainability Performance and the Cost of Capital
Authors: Gonçalves Tiago , Dias João , Barros Victor
Published: August 2022

This study examines the association between firms’ environmental, social, and governance (ESG) performance and the cost of capital for the largest European firms listed on the STOXX Euro 600 in a large panel from 2002 to 2018. We find that ESG is priced by both debt and equity markets, although in different directions. While better ESG performance is associated with a lower cost of equity, the relationship is positive regarding the cost of debt. We also account for industry idiosyncrasies. The relationship with the cost of equity is penalized for firms lagging in ESG performance compared with industry peers, and the industry median corporate sustainability performance score is around optimal to balance the cost of equity and cost of debt. We also find that ESG is not influential in shaping firms’ cost of capital in periods of financial and sovereign crises. Overall, in the same research setting, we find that the channels of firms’ cost of capital composition behave differently in response to changes in sustainability performance.
Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist’s Decision on Systemic Therapy in a Real-World Setting
Authors: Erber Ramona , Angeloni Miriam , Stöhr Robert , Lux Michael P. , Ulbrich-Gebauer Daniel , Pelz Enrico , Bankfalvi Agnes , Schmid Kurt W. , Walter Robert F. H. , Vetter Martina , Thomssen Christoph , Mayr Doris , Klauschen Frederick , Sinn Peter , Sotlar Karl , Stering Katharina , Stenzinger Albrecht , Wunderle Marius , Fasching Peter A. , Beckmann Matthias W. , Hoffmann Oliver , Kimmig Rainer , Harbeck Nadia , Wuerstlein Rachel , Ferrazzi Fulvia , Hartmann Arndt
Published: August 2022

In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna® subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna® (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen’s kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna® Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna® testing classified as Prosigna® Luminal A at high / intermediate risk or upgraded to Prosigna® Luminal B.
Adult Exposure to Di-N-Butyl Phthalate (DBP) Induces Persistent Effects on Testicular Cell Markers and Testosterone Biosynthesis in Mice
Authors: Källsten Liselott , Almamoun Radwa , Pierozan Paula , Nylander Erik , Sdougkou Kalliroi , Martin Jonathan W. , Karlsson Oskar
Published: August 2022

Studies indicate that phthalates are endocrine disruptors affecting reproductive health. One of the most commonly used phthalates, di-n-butyl phthalate (DBP), has been linked with adverse reproductive health outcomes in men, but the mechanisms behind these effects are still poorly understood. Here, adult male mice were orally exposed to DBP (10 or 100 mg/kg/day) for five weeks, and the testis and adrenal glands were collected one week after the last dose, to examine more persistent effects. Quantification of testosterone, androstenedione, progesterone and corticosterone concentrations by liquid chromatography-mass spectrometry showed that testicular testosterone was significantly decreased in both DBP treatment groups, whereas the other steroids were not significantly altered. Western blot analysis of testis revealed that DBP exposure increased the levels of the steroidogenic enzymes CYP11A1, HSD3β2, and CYP17A1, the oxidative stress marker nitrotyrosine, and the luteinizing hormone receptor (LHR). The analysis further demonstrated increased levels of the germ cell marker DAZL, the Sertoli cell markers vimentin and SOX9, and the Leydig cell marker SULT1E1. Overall, the present work provides more mechanistic understanding of how adult DBP exposure can induce effects on the male reproductive system by affecting several key cells and proteins important for testosterone biosynthesis and spermatogenesis, and for the first time shows that these effects persist at least one week after the last dose. It also demonstrates impairment of testosterone biosynthesis at a lower dose than previously reported.
Unifying Different Cancer Theories in a Unique Tumour Model: Chronic Inflammation and Deaminases as Meeting Points
Authors: Hernández-Camarero Pablo , López-Ruiz Elena , Marchal Juan Antonio , Perán Macarena
Published: August 2022

The increase in cancer incidences shows that there is a need to better understand tumour heterogeneity to achieve efficient treatments. Interestingly, there are several common features among almost all types of cancers, with chronic inflammation induction and deaminase dysfunctions singled out. Deaminases are a family of enzymes with nucleotide-editing capacity, which are classified into two main groups: DNA-based and RNA-based. Remarkably, a close relationship between inflammation and the dysregulation of these molecules has been widely documented, which may explain the characteristic intratumor heterogeneity, both at DNA and transcriptional levels. Indeed, heterogeneity in cancer makes it difficult to establish a unique tumour progression model. Currently, there are three main cancer models—stochastic, hierarchic, and dynamic—although there is no consensus on which one better resembles cancer biology because they are usually overly simplified. Here, to accurately explain tumour progression, we propose interactions among chronic inflammation, deaminases dysregulation, intratumor genetic heterogeneity, cancer phenotypic plasticity, and even the previously proposed appearance of cancer stem-like cell populations in the edges of advanced solid tumour masses (instead of being the cells of origin of primary malignancies). The new tumour development model proposed in this study does not contradict previously accepted models and it may open up a window to interesting therapeutic approaches.
Repair of Retinal Degeneration by Human Amniotic Epithelial Stem Cell–Derived Photoreceptor–like Cells
Authors: Li Jinying , Qiu Chen , Zhou Jiayi , Wei Yang , Yuan Weixin , Liu Jia , Cui Wenyu , Huang Jianan , Qiu Cong , Guo Lihe , Yu Luyang , Ge Zhen
Published: August 2022

The loss of photoreceptors is a major event of retinal degeneration that accounts for most cases of untreatable blindness globally. To date, there are no efficient therapeutic approaches to treat this condition. In the present study, we aimed to investigate whether human amniotic epithelial stem cells (hAESCs) could serve as a novel seed cell source of photoreceptors for therapy. Here, a two–step treatment with combined Wnt, Nodal, and BMP inhibitors, followed by another cocktail of retinoic acid, taurine, and noggin induced photoreceptor–like cell differentiation of hAESCs. The differentiated cells demonstrated the morphology and signature marker expression of native photoreceptor cells and, intriguingly, bore very low levels of major histocompatibility complex (MHC) class II molecules and a high level of non–classical MHC class I molecule HLA–G. Importantly, subretinal transplantation of the hAESCs–derived PR–like cells leads to partial restoration of visual function and retinal structure in Royal College of Surgeon (RCS) rats, the classic preclinical model of retinal degeneration. Together, our results reveal hAESCs as a potential source of functional photoreceptor cells; the hAESCs–derived photoreceptor–like cells could be a promising cell–replacement candidate for therapy of retinal degeneration diseases.
Expression Profiling and MicroRNA Regulatory Networks of Homeobox Family Genes in Sugarcane Saccharum spontaneum L.
Authors: Li Yihan , Wang Yongjun , Feng Xiaoxi , Hua Xiuting , Dou Meijie , Yao Wei , Zhang Muqing , Zhang Jisen
Published: August 2022

Homeobox (HB) genes play important roles in plant growth and development processes, particularly in the formation of lateral organs. Thus, they could influence leaf morphogenesis and biomass formation in plants. However, little is known about HBs in sugarcane, a crucial sugar crop, due to its complex genetic background. Here, 302 allelic sequences for 104 HBs were identified and divided into 13 subfamilies in sugarcane Saccharum spontaneum. Comparative genomics revealed that whole-genome duplication (WGD)/segmental duplication significantly promoted the expansion of the HB family in S. spontaneum, with SsHB26, SsHB63, SsHB64, SsHB65, SsHB67, SsHB95, and SsHB96 being retained from the evolutionary event before the divergence of dicots and monocots. Based on the analysis of transcriptome and degradome data, we speculated that SsHB15 and SsHB97 might play important roles in regulating sugarcane leaf morphogenesis, with miR166 and SsAGO10 being involved in the regulation of SsHB15 expression. Moreover, subcellular localization and transcriptional activity detection assays demonstrated that these two genes, SsHB15 and SsHB97, were functional transcription factors. This study demonstrated the evolutionary relationship and potential functions of SsHB genes and will enable the further investigation of the functional characterization and the regulatory mechanisms of SsHBs.
Impairment in the Intestinal Morphology and in the Immunopositivity of Toll-like Receptor-4 and Other Proteins in an Autistic Mouse Model
Authors: Franco Caterina , Gianò Marzia , Favero Gaia , Rezzani Rita
Published: August 2022

Autism spectrum disorder (ASD) identifies a neurodevelopmental disease defined by social impairments and repetitive or stereotyped behaviors. The etiology of ASD remains unclear; it primarily affects the brain, but a link between gastrointestinal (GI) diseases, inflammatory mucosal pathology and this disorder has been suggested. In particular, a central role seems to be played by an imbalance in pro-and anti-inflammatory cytokines, oxidative stress, and apoptosis. Toll-like receptor 4 (TLR4) is a protein of innate immunity responsible for the regulation and maintenance of intestinal homeostasis. Through histochemical and immunohistochemical evaluations we analyzed the intestinal morphology and the immunopositivity of TLR4 and of other pro-inflammatory and apoptotic proteins in BTBR T+Itpr3tf/J mice. Morphological data showed that the mucosal tunica presented longer intestinal villi. The length of the villi and the epithelial surface determine the exchanges of the intestinal mucosa with luminal contents, modifying the microbiota composition. The biochemical and immunohistochemical results indicated a close relationship among the increase of TLR4 and the activation of NF-kB subunits (p65 and p50) and pro-inflammatory and apoptotic proteins, such as cyclooxygenase-2, interleukin-1β, inducible nitric oxide synthase, tumor nuclear factor—alpha, caspase-3, caspase-8. These preliminary results require more in-depth study but they suggest the TLR4 signaling pathway as a possible target for therapeutic approaches to reduce GI disorders in ASD.
Lithium Enhances Hippocampal Glucose Metabolism in an In Vitro Mice Model of Alzheimer’s Disease
Authors: Gherardelli Camila , Cisternas Pedro , Inestrosa Nibaldo C.
Published: August 2022

Impaired cerebral glucose metabolism is an early event that contributes to the pathogenesis of Alzheimer’s disease (AD). Importantly, restoring glucose availability by pharmacological agents or genetic manipulation has been shown to protect against Aβ toxicity, ameliorate AD pathology, and increase lifespan. Lithium, a therapeutic agent widely used as a treatment for mood disorders, has been shown to attenuate AD pathology and promote glucose metabolism in skeletal muscle. However, despite its widespread use in neuropsychiatric disorders, lithium’s effects on the brain have been poorly characterized. Here we evaluated the effect of lithium on glucose metabolism in hippocampal neurons from wild-type (WT) and APPSwe/PS1ΔE9 (APP/PS1) mice. Our results showed that lithium significantly stimulates glucose uptake and replenishes ATP levels by preferential oxidation of glucose through glycolysis in neurons from WT mice. This increase was also accompanied by a strong increase in glucose transporter 3 (Glut3), the major carrier responsible for glucose uptake in neurons. Similarly, using hippocampal slices from APP-PS1 mice, we demonstrate that lithium increases glucose uptake, glycolytic rate, and the ATP:ADP ratio in a process that also involves the activation of AMPK. Together, our findings indicate that lithium stimulates glucose metabolism and can act as a potential therapeutic agent in AD.
Water-Soluble Chalcogenide W6-Clusters: On the Way to Biomedical Applications
Authors: Gassan Alena D. , Ivanov Anton A. , Pozmogova Tatiana N. , Eltsov Ilia V. , Kuratieva Natalia V. , Mironov Yuri V. , Shestopalov Michael A.
Published: August 2022

Despite the great potential of octahedral tungsten cluster complexes in fields of biomedical applications such as X-ray computed tomography or angiography, there is only one example of a water-soluble W6Q8-cluster that has been reported in the literature. Herein we present the synthesis and a detailed characterization including X-ray structural analysis, NMR, IR, UV–Vis spectroscopies, HR-MS spectrometry, and the electrochemical behavior of two new cluster complexes of the general formula W6Q8L6 with phosphine ligands containing a hydrophilic carboxylic group, which makes the complexes soluble in an aqueous medium. The hydrolytic stability of the clusters’ aqueous solutions allows us to investigate for the first time the influence of W6-clusters on cell viability. The results obtained clearly demonstrate their very low cytotoxicity, comparable to the least-toxic clusters presented in the literature.
diaPASEF Proteomics and Feature Selection for the Description of Sputum Proteome Profiles in a Cohort of Different Subtypes of Lung Cancer Patients and Controls
Authors: Arenas-De Larriva María del Sol , Fernández-Vega Alejandro , Jurado-Gamez Bernabe , Ortea Ignacio
Published: August 2022

The high mortality, the presence of an initial asymptomatic stage and the fact that diagnosis in early stages reduces mortality justify the implementation of screening programs in the populations at risk of lung cancer. It is imperative to develop less aggressive methods that can complement existing diagnosis technologies. In this study, we aimed to identify lung cancer protein biomarkers and pathways affected in sputum samples, using the recently developed diaPASEF mass spectrometry (MS) acquisition mode. The sputum proteome of lung cancer cases and controls was analyzed through nano-HPLC–MS using the diaPASEF mode. For functional analysis, the results from differential expression analysis were further analyzed in the STRING platform, and feature selection was performed using sparse partial least squares discriminant analysis (sPLS-DA). Our results showed an activation of inflammation, with an alteration of pathways and processes related to acute-phase, complement, and immune responses. The resulting sPLS-DA model separated between case and control groups with high levels of sensitivity and specificity. In conclusion, we showed how new-generation proteomics can be used to detect potential biomarkers in sputum samples, and ultimately to discriminate patients from controls and even to help to differentiate between different cancer subtypes.
Norepinephrine Inhibits Lipopolysaccharide-Stimulated TNF-α but Not Oxylipin Induction in n-3/n-6 PUFA-Enriched Cultures of Circumventricular Organs
Authors: Pflieger Fabian Johannes , Wolf Jacqueline , Feldotto Martin , Nockher Andreas , Wenderoth Tatjana , Hernandez Jessica , Roth Joachim , Ott Daniela , Rummel Christoph
Published: August 2022

Sensory circumventricular organs (sCVOs) are pivotal brain structures involved in immune-to-brain communication with a leaky blood–brain barrier that detect circulating mediators such as lipopolysaccharide (LPS). Here, we aimed to investigate the potential of sCVOs to produce n-3 and n-6 oxylipins after LPS-stimulation. Moreover, we investigated if norepinephrine (NE) co-treatment can alter cytokine- and oxylipin-release. Thus, we stimulated rat primary neuroglial sCVO cultures under n-3- or n-6-enriched conditions with LPS or saline combined with NE or vehicle. Supernatants were assessed for cytokines by bioassays and oxylipins by HPLC-MS/MS. Expression of signaling pathways and enzymes were analyzed by RT-PCR. Tumor necrosis factor (TNF)α bioactivity and signaling, IL-10 expression, and cyclooxygenase (COX)2 were increased, epoxide hydroxylase (Ephx)2 was reduced, and lipoxygenase 15-(LOX) was not changed by LPS stimulation. Moreover, LPS induced increased levels of several n-6-derived oxylipins, including the COX-2 metabolite 15d-prostaglandin-J2 or the Ephx2 metabolite 14,15-DHET. For n-3-derived oxylipins, some were down- and some were upregulated, including 15-LOX-derived neuroprotectin D1 and 18-HEPE, known for their anti-inflammatory potential. While the LPS-induced increase in TNFα levels was significantly reduced by NE, oxylipins were not significantly altered by NE or changes in TNFα levels. In conclusion, LPS-induced oxylipins may play an important functional role in sCVOs for immune-to-brain communication.
Efficacy of Nerve-Derived Hydrogels to Promote Axon Regeneration Is Influenced by the Method of Tissue Decellularization
Authors: Kuna Vijay Kumar , Lundgren Andre , Anerillas Luis Oliveros , Kelk Peyman , Brohlin Maria , Wiberg Mikael , Kingham Paul J. , Novikova Ludmila N. , Andersson Gustav , Novikov Lev N.
Published: August 2022

Injuries to large peripheral nerves are often associated with tissue defects and require reconstruction using autologous nerve grafts, which have limited availability and result in donor site morbidity. Peripheral nerve-derived hydrogels could potentially supplement or even replace these grafts. In this study, three decellularization protocols based on the ionic detergents sodium dodecyl sulfate (P1) and sodium deoxycholate (P2), or the organic solvent tri-n-butyl phosphate (P3), were used to prepare hydrogels. All protocols resulted in significantly decreased amounts of genomic DNA, but the P2 hydrogel showed the best preservation of extracellular matrix proteins, cytokines, and chemokines, and reduced levels of sulfated glycosaminoglycans. In vitro P1 and P2 hydrogels supported Schwann cell viability, secretion of VEGF, and neurite outgrowth. Surgical repair of a 10 mm-long rat sciatic nerve gap was performed by implantation of tubular polycaprolactone conduits filled with hydrogels followed by analyses using diffusion tensor imaging and immunostaining for neuronal and glial markers. The results demonstrated that the P2 hydrogel considerably increased the number of axons and the distance of regeneration into the distal nerve stump. In summary, the method used to decellularize nerve tissue affects the efficacy of the resulting hydrogels to support regeneration after nerve injury.
The Effect of Isosaponarin Derived from Wasabi Leaves on Glutamate Release in Rat Synaptosomes and Its Underlying Mechanism
Authors: Lu Cheng-Wei , Yeh Kun-Chieh , Chiu Kuan-Ming , Lee Ming-Yi , Lin Tzu-Yu , Wang Su-Jane
Published: August 2022

Excessive glutamate release is known to be involved in the pathogenesis of neurological diseases, and suppression of glutamate release from nerve terminals is considered to be a treatment strategy. In this study, we investigated whether isosaponarin, a flavone glycoside isolated from wasabi leaves, could affect glutamate release in rat cerebral cortex nerve terminals (synaptosomes). The release of glutamate was evoked by the K+ channel blocker 4-aminopyridine (4-AP) and measured by an online enzyme-coupled fluorimetric assay. Isosaponarin produced a concentration-dependent inhibition of 4-AP-evoked glutamate release with a half-maximum inhibition of release value of 22 μM. The inhibition caused by isosaponarin was prevented by eliminating extracellular Ca2+ or by using bafilomycin A1, an inhibitor of synaptic vesicle exocytosis. Isosaponarin decreased intrasynaptosomal rises in Ca2+ levels that were induced by 4-AP, without affecting the synaptosomal membrane potential. The isosaponarin-induced inhibition of glutamate release was significantly prevented in synaptosomes that were pretreated with a combination of the calcium channel blockers ω-conotoxin GVIA (N-type) and ω-agatoxin IVA (P/Q-types). The protein kinase C (PKC) pan-inhibitor GF109203X and the Ca2+-dependent PKC inhibitor Go6976 abolished the inhibition of glutamate release by isosaponarin, while the Ca2+-independent PKC inhibitor rottlerin did not show any effect. The results from immunoblotting assays also showed that isosaponarin lowered PKC, PKCα, synaptosomal-associated protein of 25 kDa (SNAP-25), and myristoylated alanine-rich C-kinase substrate (MARCKS) phosphorylation induced by 4-AP. In addition, FM1-43-labeled synaptic vesicles in synaptosomes showed that treatment with isosaponarin resulted in an attenuation of the 4-AP-induced decrease in fluorescence intensity that is consistent with glutamate release. Transmission electron microscopy of synaptosomes also provided evidence that isosaponarin altered the number of synaptic vesicles. These results indicate that isosaponarin suppresses the Ca2+-dependent PKC/SNAP-25 and MARCKS pathways in synaptosomes, causing a decrease in the number of available synaptic vesicles, which inhibits vesicular glutamate release from synaptosomes.
NIR-Triggered Generation of Reactive Oxygen Species and Photodynamic Therapy Based on Mesoporous Silica-Coated LiYF4 Upconverting Nanoparticles
Authors: Ho Tsung-Han , Yang Chien-Hsin , Jiang Zheng-En , Lin Hung-Yin , Chen Yih-Fung , Wang Tzong-Liu
Published: August 2022

To date, the increase in reactive oxygen species (ROS) production for effectual photodynamic therapy (PDT) treatment still remains challenging. In this study, a facile and effective approach is utilized to coat mesoporous silica (mSiO2) shell on the ligand-free upconversion nanoparticles (UCNPs) based on the LiYF4 host material. Two kinds of mesoporous silica-coated UCNPs (UCNP@mSiO2) that display green emission (doped with Ho3+) and red emission (doped with Er3+), respectively, were successfully synthesized and well characterized. Three photosensitizers (PSs), merocyanine 540 (MC 540), rose bengal (RB), and chlorin e6 (Ce6), with the function of absorption of green or red emission, were selected and loaded into the mSiO2 shell of both UCNP@mSiO2 nanomaterials. A comprehensive study for the three UCNP@mSiO2/PS donor/acceptor pairs was performed to investigate the efficacy of fluorescence resonance energy transfer (FRET), ROS generation, and in vitro PDT using a MCF-7 cell line. ROS generation detection showed that as compared to the oleate-capped and ligand-free UCNP/PS pairs, the UCNP@mSiO2/PS nanocarrier system demonstrated more pronounced ROS generation due to the UCNP@mSiO2 nanoparticles in close vicinity to PS molecules and a higher loading capacity of the photosensitizer. As a result, the three LiYF4 UCNP@mSiO2/PS nanoplatforms displayed more prominent therapeutic efficacies in PDT by using in vitro cytotoxicity tests.
Myoglobin–Pyruvate Interactions: Binding Thermodynamics, Structure–Function Relationships, and Impact on Oxygen Release Kinetics
Authors: Adepu Kiran Kumar , Bhandari Dipendra , Anishkin Andriy , Adams Sean H. , Chintapalli Sree V.
Published: August 2022

Myoglobin (Mb), besides its roles as an oxygen (O2) carrier/storage protein and nitric oxide NO scavenger/producer, may participate in lipid trafficking and metabolite binding. Our recent findings have shown that O2 is released from oxy-Mb upon interaction with lactate (LAC, anerobic glycolysis end-product). Since pyruvate (PYR) is structurally similar and metabolically related to LAC, we investigated the effects of PYR (aerobic glycolysis end-product) on Mb using isothermal titration calorimetry, circular dichroism, and O2-kinetic studies to evaluate PYR affinity toward Mb and to compare the effects of PYR and LAC on O2 release kinetics of oxy-Mb. Similar to LAC, PYR interacts with both oxy- and deoxy-Mb with a 1:1 stoichiometry. Time-resolved circular dichroism spectra revealed that there are no major conformational changes in the secondary structures of oxy- or deoxy-Mb during interactions with PYR or LAC. However, we found contrasting results with respect to binding affinities and substrate preference, where PYR has higher affinity toward deoxy-Mb when compared with LAC (which prefers oxy-Mb). Furthermore, PYR interaction with oxy-Mb releases a significantly lower amount of O2 than LAC. Taken together, our findings support the hypothesis that glycolytic end-products play a distinctive role in the Mb-rich tissues by serving as novel regulators of O2 availability, and/or by impacting other activities related to oxy-/deoxy-Mb toggling in resting vs. exercised or metabolically activated conditions.
Multitargeting the Action of 5-HT6 Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer’s Disease: Can It Work from a Molecular Point of View?
Authors: Czarnota-Łydka Kinga , Kucwaj-Brysz Katarzyna , Pyka Patryk , Haberek Wawrzyniec , Podlewska Sabina , Handzlik Jadwiga
Published: August 2022

In view of the unsatisfactory treatment of cognitive disorders, in particular Alzheimer’s disease (AD), the aim of this review was to perform a computer-aided analysis of the state of the art that will help in the search for innovative polypharmacology-based therapeutic approaches to fight against AD. Apart from 20-year unrenewed cholinesterase- or NMDA-based AD therapy, the hope of effectively treating Alzheimer’s disease has been placed on serotonin 5-HT6 receptor (5-HT6R), due to its proven, both for agonists and antagonists, beneficial procognitive effects in animal models; however, research into this treatment has so far not been successfully translated to human patients. Recent lines of evidence strongly emphasize the role of kinases, in particular microtubule affinity-regulating kinase 4 (MARK4), Rho-associated coiled-coil-containing protein kinase I/II (ROCKI/II) and cyclin-dependent kinase 5 (CDK5) in the etiology of AD, pointing to the therapeutic potential of their inhibitors not only against the symptoms, but also the causes of this disease. Thus, finding a drug that acts simultaneously on both 5-HT6R and one of those kinases will provide a potential breakthrough in AD treatment. The pharmacophore- and docking-based comprehensive literature analysis performed herein serves to answer the question of whether the design of these kind of dual agents is possible, and the conclusions turned out to be highly promising.
Identification of Myocardial Insulin Resistance by Using Liver Tests: A Simple Approach for Clinical Practice
Authors: Herance José Raúl , Martín-Saladich Queralt , Velásquez Mayra Alejandra , Hernandez Cristina , Aparicio Carolina , Ramirez-Serra Clara , Ferrer Roser , Giralt-Arnaiz Marina , González-Ballester Miguel Ángel , Pericàs Juan M. , Castell-Conesa Joan , Aguadé-Bruix Santiago , Simó Rafael
Published: August 2022

Background: We report that myocardial insulin resistance (mIR) occurs in around 60% of patients with type 2 diabetes (T2D) and was associated with higher cardiovascular risk in comparison with patients with insulin-sensitive myocardium (mIS). These two phenotypes (mIR vs. mIS) can only be assessed using time-consuming and expensive methods. The aim of the present study is to search a simple and reliable surrogate to identify both phenotypes. Methods: Forty-seven patients with T2D underwent myocardial [18F]FDG PET/CT at baseline and after a hyperinsulinemic–euglycemic clamp (HEC) to determine mIR were prospectively recruited. Biochemical assessments were performed before and after the HEC. Baseline hepatic steatosis index and index of hepatic fibrosis (FIB-4) were calculated. Furthermore, liver stiffness measurement was performed using transient elastography. Results: The best model to predict the presence of mIR was the combination of transaminases, protein levels, FIB-4 score and HOMA (AUC = 0.95; sensibility: 0.81; specificity: 0.95). We observed significantly higher levels of fibrosis in patients with mIR than in those with mIS (p = 0.034). In addition, we found that patients with mIR presented a reduced glucose uptake by the liver in comparison with patients with mIS. Conclusions: The combination of HOMA, protein, transaminases and FIB-4 is a simple and reliable tool for identifying mIR in patients with T2D. This information will be useful to improve the stratification of cardiovascular risk in T2D.
Sustainable Mobility as a Service: Demand Analysis and Case Studies
Authors: Musolino Giuseppe
Published: August 2022

Urban mobility is evolving today towards the concept of Mobility as a Service (MaaS). MaaS allows passengers to use different transport services as a single option, by using a digital platform. Therefore, according to the MaaS concept, the mobility needs of passengers are the central element of the transport service. The objective of this paper is to build an updated state-of-the-art of the main disaggregated and aggregated variables connected to travel demand in presence of MaaS. According to the above objective, this paper deals with methods and case studies to analyze passengers’ behaviour in the presence of MaaS. The methods described rely on the Transportation System Models (TSMs), in particular with the travel demand modelling component. The travel demand may be estimated by means of disaggregated, or sample, surveys (e.g., individual choices) and of aggregate surveys (e.g., characteristics of the area, traffic flows). The surveys are generally supported by Information Communication System (ICT) tools, such as: smartphones; smartcards; Global Position Systems (GPS); points of interest. The analysis of case studies allows to aggregate the existing scientific literature according to some criteria: the choice dimension of users (e.g., mode, bundle and path, or a combination of them); the characteristics of the survey (e.g., revealed preferences or stated preferences); the presence of behavioural theoretical background and of calibrated choice model(s).
The Media in the Construction of Reality in the Context of Colombian Social Nonconformity
Authors: Barrios-Rubio Andrés , Fajardo Valencia Gloria Consuelo
Published: August 2022

Introduction: Convergence of linguistics and semiotics materializes in the text not only the conceptual content that is expressed through codes, but the message also underlies the realism of the communicative intentions of the issuing agent in a specific context and the value of the interactions of the actors of the communicative act. Methodology: The vision of reality that is established in the collective imaginary must be analyzed from the interpretation of society and culture, the laws of operation and their constituent parts. For this, this research approached two newspapers of national circulation, five general radio channels of national coverage, and two television newscasts of private channels, and through the use of quantitative instruments, the posts, tweets or videos were reviewed in order to analyze the constituent elements of the discourse—text, images, hashtags, or keywords—which are appreciated from the syntactic and semantic perspectives (structural) and pragmatics (functional). Results: The communication process in its social context denotes the intervention of nonlinguistic elements of sociocultural order that demarcate the generation and interpretation of the meanings and senses of linguistic expressions. Discussion: The linguistic structure offers conditions for communication, but any generation and transmission of meanings is a product of the intention of the subjects who use it for specific purposes and in specific communicative situations within a social context. Conclusions: Intensive use of digital technology and social networks naturalized a relationship of proximity and familiarity in the communication process, satisfaction of needs in the multiplicity of information that is created and distributed in the network bundled to mobile devices and the political and social ecosystem of the nation.
Intelligent Remote Photoplethysmography-Based Methods for Heart Rate Estimation from Face Videos: A Survey
Authors: Premkumar Smera , Hemanth Duraisamy Jude
Published: August 2022

Over the last few years, a rich amount of research has been conducted on remote vital sign monitoring of the human body. Remote photoplethysmography (rPPG) is a camera-based, unobtrusive technology that allows continuous monitoring of changes in vital signs and thereby helps to diagnose and treat diseases earlier in an effective manner. Recent advances in computer vision and its extensive applications have led to rPPG being in high demand. This paper specifically presents a survey on different remote photoplethysmography methods and investigates all facets of heart rate analysis. We explore the investigation of the challenges of the video-based rPPG method and extend it to the recent advancements in the literature. We discuss the gap within the literature and suggestions for future directions.
Short-Chain Acid Additives to Control PbI2 Crystallization in Hybrid Perovskite Films
Authors: Dionigi Chiara , Calabrese Gabriele , Ruani Giampiero , Milita Silvia
Published: August 2022

The quality and the performance of hybrid perovskite (HP)’s films strongly depend on the complete conversion into MAPbI3 of a spin-coated solution of methylammonium iodide (MAI) and PbI2. Highly crystalline PbI2 on a substrate limits such a conversion and, consequently, the HP’s solar cell performances. We investigate for the first time the use of short-chain organic acids as additives in a non-complexing solvent like γ-butyrolactone (GBL), that can retard retard the crystallization of PbI2. Based on XRD analyses of the spin coated films, the acetic acid is the most effective additive in retarding the PbI2 crystallization, making Pb2+ available for a subsequent reaction with MAI. These results open a new experimental path for fabricating perovskite films by single or sequential step methods involving acid additives.
Pyrethroid Susceptibility in Stomoxys calcitrans and Stomoxys indicus (Diptera: Muscidae) Collected from Cattle Farms in Southern Thailand
Authors: Lorn Sokchan , Klakankhai Warin , Nusen Pitunart , Sumarnrote Anchana , Tainchum Krajana
Published: August 2022

The susceptibility to six pyrethroid insecticides (permethrin, deltamethrin, alpha-cypermethrin, cypermethrin, lambda-cyhalothrin, and bifenthrin), each at the recommended concentration, was evaluated for two stable fly species—Stomoxys calcitrans (Linnaeus, 1758) and Stomoxys indicus Picard, 1908 (Diptera: Muscidae)—through tarsal contact using a World Health Organization (WHO) cone bioassay procedure. The field populations of S. calcitrans were collected from the Songkhla and Phattalung provinces, while S. indicus were collected from the Phattalung and Satun provinces in Thailand. The stable flies were exposed to insecticide-treated filter paper for 30 min, and their knockdown counts at 30 min and 60 min and mortality counts at 12 h and 24 h were recorded. The S. calcitrans and S. indicus Songkhla and Phattalung populations were moderately susceptible to pyrethroids, as indicated by the 24 h mortality. Nonetheless, the Satun population of S. indicus was completely susceptible to permethrin, with 100% mortality, and showed the lowest susceptibility to deltamethrin and bifenthrin. The results indicate the generally low susceptibility of stable flies to pyrethroids in the southern provinces of Thailand.
Left Atrial Anterior Wall Scar-Related Atrial Tachycardia in Patients after Catheter Ablation or Cardiac Surgery: Electrophysiological Characteristics and Ablation Strategy
Authors: Wang Hao , Xi Siqi , Chen Jindong , Gan Tian , Huang Weiye , He Ben , Zhao Liang
Published: August 2022

Background: The mechanisms of atrial tachycardia (AT) related to the left atrial anterior wall (LAAW) are complex and can be challenging to map in patients after catheter ablation for atrial fibrillation (AF) or cardiac surgery. We aimed to investigate the electrophysiological characteristics AT and to devise an ablation strategy. Methods and Results: We identified 31 scar-related LAAW reentrant ATs in 22 patients after catheter ablation for AF or cardiac surgery. Activation maps of the left atrium (LA) or both atria were obtained using a high-density mapping system, and the precise mechanism and critical area for each AT were analyzed. Patients were followed up regularly in a clinic. After analyzing the activation and propagation of each AT, the scar-related LAAW ATs were classified into three types, based on mechanisms related to: (1) LAAW conduction gap(s) in 19 LA macro-reentrant ATs; (2) LAAW epicardial connection(s) in 11 LA or bi-atrial ATs; and (3) LAAW local micro-reentry in 1 LAAW AT. Multiple ATs were identified in seven patients. Effective ablation (termination or circuit change of AT) was obtained in 30 ATs by targeting the critical area identified by the mapping system. During 16.0 ± 7.6 months follow-up, recurrent AT occurred in two patients. Conclusions: Three mechanisms of scar-related AT of LAAW were identified, most of which were related to LAAW conduction gaps. Notably, epicardial AT or bi-atrial AT comprised a nonnegligible proportion. A high-density mapping system could make it possible to determine the accurate mechanism of AT and serve as a guide following ablation.
Social Disparities in Outpatient and Inpatient Management of Pediatric Supracondylar Humerus Fractures
Authors: Modest Jacob M. , Brodeur Peter G. , Kim Kang W. , Testa Edward J. , Gil Joseph A. , Cruz Aristides I.
Published: August 2022

Socioeconomic status, race, and insurance status are known factors affecting adult orthopaedic surgery care, but little is known about the influence of socioeconomic factors on pediatric orthopaedic care. The purpose of this study was to determine if demographic and socioeconomic related factors were associated with surgical management of pediatric supracondylar humerus fractures (SCHFs) in the inpatient versus outpatient setting. Pediatric patients (<13 years) who underwent surgery for SCHFs were identified in the New York Statewide Planning and Research Cooperative System database from 2009–2017. Inpatient and outpatient claims were identified by International Classification of Diseases-9-Clinical Modification (CM) and ICD-10-CM SCHF diagnosis codes. Claims were then filtered by ICD-9-CM, ICD-10-Procedural Classification System, or Current Procedural Terminology codes to isolate SCHF patients who underwent surgical intervention. Multivariable logistic regression analysis was performed to determine the effect of patient factors on the likelihood of having inpatient management versus outpatient management. A total of 7079 patients were included in the analysis with 4595 (64.9%) receiving inpatient treatment and 2484 (35.1%) receiving outpatient treatment. The logistic regression showed Hispanic (OR: 2.386, p < 0.0001), Asian (OR: 2.159, p < 0.0001) and African American (OR: 2.095, p < 0.0001) patients to have increased odds of inpatient treatment relative to White patients. Injury diagnosis on a weekend had increased odds of inpatient management (OR: 1.863, p = 0.0002). Higher social deprivation was also associated with increased odds of inpatient treatment (OR: 1.004, p < 0.0001). There are disparities among race and socioeconomic status in the surgical setting of SCHF management. Physicians and facilities should be aware of these disparities to optimize patient experience and to allow for equal access to care.
Test Performance Characteristics of Dynamic Liver Enzyme Trends in the Prediction of Choledocholithiasis
Authors: Lei Yang , Lethebe B. , Wishart Erin , Bazerbachi Fateh , Elmunzer B. , Thosani Nirav , Buxbaum James , Chen Yen-I , Bass Sydney , Cole Martin , Turbide Christian , Brenner Darren , Heitman Steven , Mohamed Rachid , Forbes Nauzer
Published: August 2022

(1) Background: Various methods to predict the presence or absence of choledocholithiasis (CDL) have been proposed. We aimed to assess the performance characteristics of dynamic liver enzyme trends in the prediction of CDL. (2) Methods: This was a single-center retrospective cohort study. All adult in-patients undergoing endoscopy for suspected CDL between 1 January 2012 and 7 October 2018 were identified, with patients with prior cholecystectomy, prior sphincterotomy, or indwelling biliary prostheses were excluded. Available laboratory parameters within 72 h preceding the procedure were recorded, allowing for the assessment of trends. Dynamic enzyme trends were defined as any increase or decrease by 30% and 50% within 72 h of the index procedure. (3) Results: A total of 878 patients were included. Mean age was 61.8 years, with 58.6% female. Increases in alkaline phosphatase (ALP) of at least 30% or 50% were both specific for the presence of CDL, with specificities of 82.7% (95% CI 69.7–91.8%) and 88.5% (95% CI 76.6–95.6%), respectively. Decreases in bilirubin or ALP of at least 50% were highly specific for the absence of CDL, with specificities of 91.7% (95% CI 85.7–95.8%) and 100.0% (97.2–100.0%), respectively. (4) Conclusions: Several liver enzyme trends appear to be specific for the absence or presence of stones; in particular, significant decreases in total bilirubin or ALP of at least 30–50% over the prior 72 h appear to be especially predictive of an absence of intraductal findings during endoscopy.
Diagnosis of Cardiac Surgery-Associated Acute Kidney Injury: State of the Art and Perspectives
Authors: Casanova Alfredo G. , Sancho-Martínez Sandra M. , Vicente-Vicente Laura , Ruiz Bueno Patricia , Jorge-Monjas Pablo , Tamayo Eduardo , Morales Ana I. , López-Hernández Francisco J.
Published: August 2022

Diagnosis of cardiac surgery-associated acute kidney injury (CSA-AKI), a syndrome of sudden renal dysfunction occurring in the immediate post-operative period, is still sub-optimal. Standard CSA-AKI diagnosis is performed according to the international criteria for AKI diagnosis, afflicted with insufficient sensitivity, specificity, and prognostic capacity. In this article, we describe the limitations of current diagnostic procedures and of the so-called injury biomarkers and analyze new strategies under development for a conceptually enhanced diagnosis of CSA-AKI. Specifically, early pathophysiological diagnosis and patient stratification based on the underlying mechanisms of disease are presented as ongoing developments. This new approach should be underpinned by process-specific biomarkers including, but not limited to, glomerular filtration rate (GFR) to other functions of renal excretion causing GFR-independent hydro-electrolytic and acid-based disorders. In addition, biomarker-based strategies for the assessment of AKI evolution and prognosis are also discussed. Finally, special focus is devoted to the novel concept of pre-emptive diagnosis of acquired risk of AKI, a premorbid condition of renal frailty providing interesting prophylactic opportunities to prevent disease through diagnosis-guided personalized patient handling. Indeed, a new strategy of risk assessment complementing the traditional scores based on the computing of risk factors is advanced. The new strategy pinpoints the assessment of the status of the primary mechanisms of renal function regulation on which the impact of risk factors converges, namely renal hemodynamics and tubular competence, to generate a composite and personalized estimation of individual risk.