bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Hippotherapy on Health-Related Quality of Life in Caregivers of Children with Cerebral Palsy: A Pilot Quasi-Experimental Study in Japan
Authors: Mutoh Tomoko , Mutoh Tatsushi , Kurosaki Hiromi , Taki Yasuyuki
Published: December 2023

Background: Despite accumulating data regarding the beneficial effects of hippotherapy on gait and balance skills in children with cerebral palsy (CP), its effects on caregivers’ quality of life (QOL) are limited, presumably due to a lack of reliable and valid measurement tools. This study aims to evaluate the impact of hippotherapy on the health-related QOL of primary caregivers using the Japanese version of the Cerebral Palsy Quality of Life for Children (CP QOL) questionnaire. Methods: A quasi-experimental design embedded within our existing cohort was utilized. A total of 29 children with CP (range 4–12 years) and their caregivers participated in either a weekly hippotherapy or recreation (usual care) program for 1 year. In addition to gait-related measurements (Gross Motor Function Measure [GMFM]-E) of children, CP QOL-evidenced determinants of the caregivers’ health-related QOL and well-being were compared before and after the intervention. Results: In addition to improvements in children’s GMFM-E scores, hippotherapy improved CP QOL domains related to participation and physical health, children’s emotional well-being, and parents’ overall health (p < 0.05). Linear regression analysis showed a positive relationship between the children’s GMFM-E scores and their caregivers’ health domains in participants who received hippotherapy (r2 = 0.404; p = 0.011). Conclusions: Hippotherapy has a beneficial effect on the physical and mental well-being and satisfaction of Japanese parents caring for children with CP.
Empowering Healthcare through Precision Medicine: Unveiling the Nexus of Social Factors and Trust
Authors: Tan Bian Ted Nicholas , Khan Md. Irfanuzzaman , Saleh Md. Abu , Wangchuk Dawa , Talukder Md. Jakir Hasan , Kinght-Agarwal Catherine R.
Published: December 2023

This study investigated the impact of social factors on the acceptance of precision medicine (PM) using a quantitative survey grounded in the Unified Theory of Acceptance and Use of Technology (UTAUT) framework. The findings revealed that social influence has a significantly positive effect on PM acceptance, while the influence of social media is found to be insignificant. Performance expectancy emerged as the most influential factor, demonstrating a significant relationship with PM acceptance. Trust plays a crucial moderating role, mitigating the impact of social factors on PM acceptance. While exploring the mediating effects of trust, we identified a significant mediation effect for social influence and performance expectancy on PM acceptance. However, the mediation effect of social media influence is insignificant. These findings highlight the importance of trust in shaping decisions regarding PM acceptance. These findings have significant implications for healthcare practitioners and policymakers aiming to promote the adoption of precision medicine in clinical practice.
The Search of a Molecular “Swiss Knife” for Chloroplast Genomic Editing
Authors: Dorogova Natalya V. , Sidorchuk Yuriy V.
Published: December 2023

In recent years, genome editing methods have become an integral part of the genetic engineering toolset that allows for making targeted changes to plant genomes, both in the case of single-gene mutations and multiplex modifications. These technologies were mostly proven effective for editing nuclear genomes. However, plastids, the best-known example of which is chloroplasts, have their own genome (plastome), which is also available for various genetic manipulations, including editing. Despite the fact that the modification of plastomes represents a very promising task for modern biotechnology, the structure of plastids and the peculiarities of their genome organization require the specific adaptation of genome editing methods. This applies to both the design of genetic constructs and methods of their delivery to plastids. The article provides an overview of the current state of research in the field of plastid genome editing with chloroplasts taken as an example. We consider the possibilities of using programmable genome-editing technologies, analyze their effectiveness, limitations, and problems caused by the structural features of these organelles, and their genome organization. We discuss the results of the first successful experiments in this field and try to assess the prospects for the development of tools and methods for increasing the efficiency and the specificity of this biotechnological platform.
Effect of Osmolytes on Photoassembly of Functionally Active Mn4CaO5 Cluster in Mn-Depleted Photosystem II Preparations Isolated from Spinach Leaves
Authors: Yanykin Denis V. , Kazantseva Dina V. , Khorobrykh Andrey A.
Published: December 2023

The effect of osmolytes (trehalose, sucrose, betaine, D-glucose and hydroxyectoine) on the photoassembly of the functionally active inorganic core of the water-oxidizing complex (Mn4CaO5 cluster) in Mn-depleted PSII preparations (apo-WOC-PSII) was investigated. It was revealed that the efficiency of the photoassembly of the Mn4CaO5 cluster was considerably (three times) increased in the presence of 1 M disaccharides (trehalose or sucrose) in contrast to other osmolytes. It was found that the osmolytes (especially trehalose or sucrose) improved the redox interaction of exogenous Mn2+ with apo-WOC-PSII, enhanced the protective effect of Mn2+ against the photoinhibition of apo-WOC-PSII, protected CaCl2-treated PSII preparations against thermoinactivation, and stabilized the water-oxidizing complex and electron transport from QA to QB in native PSII preparations during heat treatment. It is suggested that the ability of osmolytes to enhance the efficiency of the photoassembly of a Mn4CaO5 cluster depends on their effect on the following key processes: the redox interaction of Mn2+ with apo-WOC-PSII; the stability of apo-WOC-PSII to photoinhibition during the photoactivation procedure; and the stabilization of both the newly assembled functionally active Mn4CaO5 cluster and the electron transfer from QA to QB.
Prioritizing Patient Safety: Analysis of the Procurement Process of Infusion Pumps in Spain
Authors: Herrero Laura , Sánchez-Santiago Blanca , Cano Marina , Sancibrian Ramon , Ratwani Raj , Peralta Galo
Published: December 2023

To understand whether patient safety and human factors are considered in healthcare technology procurement, we analyzed the case of infusion pumps as their use critically affects patient safety. We reviewed infusion pump procurements in the Spanish Public Sector Procurement Database. Sixty-three batches in 29 tenders for supplying 12.224 volumetric and syringe infusion pumps and consumables for an overall budget of EUR 30.4 M were identified and reviewed. Concepts related to “ease of use” were identified in the selection requirements of 35 (55.6%) batches, as part of the criteria for the selection of pumps in 23 (36.5%) batches, related to “intuitiveness” in the selection requirements of 35 (55.6%) batches, and in the criteria in 10 (15.9%) batches. No method to evaluate the ease of use, intuitiveness, or usability was mentioned. A review of the procurement teams responsible for the evaluation of the tenders showed no reported human factors or patient safety expertise. We conclude that infusion pump procurement considers usability as a relevant criterion for selection. However, no human factor experts nor specific methods for evaluation of the technology in this field are usually defined. Potential room for refining the selection of healthcare technology to improve patient safety is detected.
Impact of Motivational Workshop on Financial Inclusion of Rural People in Bangladesh: Evidence from Randomized Controlled Trial
Authors: Morshed Md Monzur , Maharjan Keshav Lall
Published: December 2023

Despite the expansion of financial institutions and the proliferation of mobile financial services, reaching the unbanked and bringing them under formal financial services has become a policy concern in many developing countries. Due to the lack of financial accounts, unbanked people prefer informal, risky, and inconvenient mechanisms for receiving, sending, and transferring money. Previous studies rely much on common interventions like no account maintenance and opening fees, easy documentation processes, and money subsidies for opening financial accounts. This study aims to examine the impact of the motivational workshop on opening savings accounts through causality among the unbanked people in a setting where the respondents are unbanked despite having all the requirements and many institutional offers to open savings accounts. We encouraged the unbanked people through a one-hour-long motivational workshop to open savings accounts. Based on our cross-sectional data and randomized controlled trial experiment among the 505 unbanked rural people at Dhubil union under Sirajganj in Bangladesh, we have evidence that motivational workshop positively impacts opening accounts by 32.33 percent. However, the account opening rate differs in terms of respondent’s preference for financial institutions. Our study also finds that unbanked people have the highest preference for mobile financial services for opening accounts resulting in 15.33 percent. The result of this study has some policy implications for adopting effective strategies for universal financial access in many developing countries.
Inflammatory and Prothrombotic Biomarkers Contribute to the Persistence of Sequelae in Recovered COVID-19 Patients
Authors: Garcia-Larragoiti Nallely , Cano-Mendez Alan , Jimenez-Vega Yeny , Trujillo Mercedes , Guzman-Cancino Patricia , Ambriz-Murillo Yesenia , Viveros-Sandoval Martha Eva
Published: December 2023

The presence of long COVID (LC) following SARS-CoV-2 infection is a common condition that affects the quality of life of patients and represents a diagnostic challenge due to the diversity of symptoms that may coexist. We still do not have accurate information regarding the pathophysiological pathways that generate the presence of LC, and so it is important to know the inflammatory and immunothrombotic biomarker profiles and their implications in order to characterize risk subgroups and establish early therapeutic strategies. We performed the determination of inflammatory and immunothrombotic biomarkers in volunteers with previous diagnoses of SARS-CoV-2. The inflammatory biomarkers were analyzed in plasma by flow cytometry, and we analyzed the von Willebrand factor (vWF) in the plasma samples using ELISA. The clinical variables and the presence or absence of long COVID symptoms were then analyzed. IL-6, sCD40L, p-Selectin, PSGL-1, PAI-1, tPA, D-Dimer, TF, and Factor IX levels were elevated in the groups with LC, especially in the subgroup of patients with metabolic syndrome (MetS). VWF levels were found to be increased in patients with sequelae and MetS. Our results confirmed the persistence of an active immunothrombotic state, and so it is important to identify the population at risk in order to provide adequate clinical follow-up.
Synthesis of 1,3,4-Thiadiazole Derivatives and Their Anticancer Evaluation
Authors: Stecoza Camelia Elena , Nitulescu George Mihai , Draghici Constantin , Caproiu Miron Teodor , Hanganu Anamaria , Olaru Octavian Tudorel , Mihai Dragos Paul , Bostan Marinela , Mihaila Mirela
Published: December 2023

Thiadiazole derivatives have garnered significant attention in the field of medicinal chemistry due to their diverse pharmacological activities, including anticancer properties. This article presents the synthesis of a series of thiadiazole derivatives and investigates their chemical characterization and potential anticancer effects on various cell lines. The results of the nuclear magnetic resonance (NMR) analyses confirmed the successful formation of the target compounds. The anticancer potential was evaluated through in silico and in vitro cell-based assays using LoVo and MCF-7 cancer lines. The assays included cell viability, proliferation, apoptosis, and cell cycle analysis to assess the compounds’ effects on cancer cell growth and survival. Daphnia magna was used as an invertebrate model for the toxicity evaluation of the compounds. The results revealed promising anticancer activity for several of the synthesized derivatives, suggesting their potential as lead compounds for further drug development. The novel compound 2g, 5-[2-(benzenesulfonylmethyl)phenyl]-1,3,4-thiadiazol-2-amine, demonstrated good anti-proliferative effects, exhibiting an IC50 value of 2.44 µM against LoVo and 23.29 µM against MCF-7 after a 48-h incubation and little toxic effects in the Daphnia test.
Insight into the Binding of Argon to Cyclic Water Clusters from Symmetry-Adapted Perturbation Theory
Authors: Rock Carly A. , Tschumper Gregory S.
Published: December 2023

This work systematically examines the interactions between a single argon atom and the edges and faces of cyclic H2O clusters containing three–five water molecules (Ar(H2O)n=3–5). Full geometry optimizations and subsequent harmonic vibrational frequency computations were performed using MP2 with a triple-ζ correlation consistent basis set augmented with diffuse functions on the heavy atoms (cc-pVTZ for H and aug-cc-pVTZ for O and Ar; denoted as haTZ). Optimized structures and harmonic vibrational frequencies were also obtained with the two-body–many-body (2b:Mb) and three-body–many-body (3b:Mb) techniques; here, high-level CCSD(T) computations capture up through the two-body or three-body contributions from the many-body expansion, respectively, while less demanding MP2 computations recover all higher-order contributions. Five unique stationary points have been identified in which Ar binds to the cyclic water trimer, along with four for (H2O)4 and three for (H2O)5. To the best of our knowledge, eleven of these twelve structures have been characterized here for the first time. Ar consistently binds more strongly to the faces than the edges of the cyclic (H2O)n clusters, by as much as a factor of two. The 3b:Mb electronic energies computed with the haTZ basis set indicate that Ar binds to the faces of the water clusters by at least 3 kJ mol−1 and by nearly 6 kJ mol−1 for one Ar(H2O)5 complex. An analysis of the interaction energies for the different binding motifs based on symmetry-adapted perturbation theory (SAPT) indicates that dispersion interactions are primarily responsible for the observed trends. The binding of a single Ar atom to a face of these cyclic water clusters can induce perturbations to the harmonic vibrational frequencies on the order of 5 cm−1 for some hydrogen-bonded OH stretching frequencies.
Injectable Xenogeneic Dental Pulp Decellularized Extracellular Matrix Hydrogel Promotes Functional Dental Pulp Regeneration
Authors: Yuan Shengmeng , Yang Xueting , Wang Xiuting , Chen Jinlong , Tian Weidong , Yang Bo
Published: December 2023

The present challenge in dental pulp tissue engineering scaffold materials lies in the development of tissue-specific scaffolds that are conducive to an optimal regenerative microenvironment and capable of accommodating intricate root canal systems. This study utilized porcine dental pulp to derive the decellularized extracellular matrix (dECM) via appropriate decellularization protocols. The resultant dECM was dissolved in an acid pepsin solution to form dECM hydrogels. The analysis encompassed evaluating the microstructure and rheological properties of dECM hydrogels and evaluated their biological properties, including in vitro cell viability, proliferation, migration, tube formation, odontogenic, and neurogenic differentiation. Gelatin methacrylate (GelMA) hydrogel served as the control. Subsequently, hydrogels were injected into treated dentin matrix tubes and transplanted subcutaneously into nude mice to regenerate dental pulp tissue in vivo. The results showed that dECM hydrogels exhibited exceptional injectability and responsiveness to physiological temperature. It supported the survival, odontogenic, and neurogenic differentiation of dental pulp stem cells in a 3D culture setting. Moreover, it exhibited a superior ability to promote cell migration and angiogenesis compared to GelMA hydrogel in vitro. Additionally, the dECM hydrogel demonstrated the capability to regenerate pulp-like tissue with abundant blood vessels and a fully formed odontoblast-like cell layer in vivo. These findings highlight the potential of porcine dental pulp dECM hydrogel as a specialized scaffold material for dental pulp regeneration.
Elevated IL-1β and Comparable IL-1 Receptor Antagonist Levels Are Characteristic Features of L-PRP in Female College Athletes Compared to Male Professional Soccer Players
Authors: Mochizuki Tomoharu , Ushiki Takashi , Suzuki Katsuya , Sato Misato , Ishiguro Hajime , Suwabe Tatsuya , Watanabe Satoshi , Edama Mutsuaki , Omori Go , Yamamoto Noriaki , Kawase Tomoyuki
Published: December 2023

Autologous platelet-rich plasma (PRP) therapy has been becoming popular for the treatment of musculotendinous injuries among athletes. However, for individual and practical variations, clinical success is hardly predictable. To overcome this difficulty, we have been exploring possible criterion candidates for monitoring its clinical effectiveness. In this study, we focused on sex-based differences in young elite athletes and compared the biochemical compositions of their PRP. Leukocyte-rich PRP (L-PRP) was manually prepared from blood samples collected from male professional soccer players (mPSPs) (n = 25) and female college athletes (fCAs) (n = 36). Platelet-derived growth factor-BB (PDGF-BB), transforming-growth factor-β1 (TGFβ1), platelet factor-4 (PF4), interleukin-1β (IL-1β), and IL-1 receptor antagonist (IL-1RA) were quantified using an enzyme-linked immunosorbent assay. The levels of PDGF-BB, TGFβ1, and PF4 in L-PRP were significantly higher in mPSPs than in fCAs. Conversely, IL-1β and IL-1RA were detected at significantly and slightly higher levels, respectively, in fCAs than in mPSPs. Our findings suggest that, even though L-PRP from fCAs may have lower potential to induce cell growth and differentiation than that of mPSPs, due to the latter’s higher capacity to control inflammation, it does not necessarily imply that PRP treatment in fCAs is less effective. Thus, these cytokine levels should be checked before PRP therapy.
Phenotype–Genotype Correlations in Three Different Cases of Adult-Onset Genetic Focal Segmental Glomerulosclerosis
Authors: Kalmár Tibor , Turkevi-Nagy Sándor , Bitó László , Kaiser László , Maróti Zoltán , Jakab Dániel , Letoha Annamária , Légrády Péter , Iványi Béla
Published: December 2023

This study highlights the importance of a combined diagnostic approach in the diagnosis of rare diseases, such as adult-onset genetic FSGS. We present three adult patient cases evaluated with kidney biopsy for proteinuria, chronic kidney disease, and hypertension, which were suggestive of adult-onset genetic FSGS. Renal biopsy samples and formalin-fixed, paraffin-embedded fetal kidneys were evaluated using standard light microscopical stainings, direct immunofluorescence on cryostat sections, and electron microscopy. Clinical exome sequencing was performed for each case, and 45 FSGS-related genes were analyzed. Identifying mutations in the PAX2, ACTN4, and COL4A5 genes have prompted a re-evaluation of the previous histopathological examinations. The PAX2 mutation led to a thinner nephrogenic zone and decreased number of glomeruli, resulting in oligohydramnios during fetal development and oligomeganephronia and adaptive focal-segmental glomerulosclerosis in adulthood. The ACTN4 mutation caused distinct electron-dense aggregates in podocyte cell bodies, while the COL4A5 mutation led to segmental sclerosis of glomeruli with marked interstitial fibrosis and tubular atrophy. The identification of specific mutations and their histopathological consequences can lead to a better understanding of the disease and its progression, as well as potential treatment options.
Tissue Injury Protection: The Other Face of Anticoagulant Treatments in the Context of Ischemia and Reperfusion Injury with a Focus on Transplantation
Authors: Carré Julie , Kerforne Thomas , Hauet Thierry , Macchi Laurent
Published: December 2023

Organ transplantation has enhanced the length and quality of life of patients suffering from life-threatening organ failure. Donors deceased after brain death (DBDDs) have been a primary source of organs for transplantation for a long time, but the need to find new strategies to face organ shortages has led to the broadening of the criteria for selecting DBDDs and advancing utilization of donors deceased after circulatory death. These new sources of organs come with an elevated risk of procuring organs of suboptimal quality. Whatever the source of organs for transplant, one constant issue is the occurrence of ischemia–reperfusion (IR) injury. The latter results from the variation of oxygen supply during the sequence of ischemia and reperfusion, from organ procurement to the restoration of blood circulation, triggering many deleterious interdependent processes involving biochemical, immune, vascular and coagulation systems. In this review, we focus on the roles of thrombo-inflammation and coagulation as part of IR injury, and we give an overview of the state of the art and perspectives on anticoagulant therapies in the field of transplantation, discussing benefits and risks and proposing a strategic guide to their use during transplantation procedures.
Yolkin, a Polypeptide Complex from Egg Yolk, Affects Cytokine Levels and Leukocyte Populations in Broiler Chicken Blood and Lymphoid Organs after In Ovo Administration
Authors: Szczypka Marianna , Lis Magdalena , Kuczkowski Maciej , Bobrek Kamila , Pawlak Aleksandra , Zambrowicz Aleksandra , Gaweł Andrzej , Obmińska-Mrukowicz Bożena
Published: December 2023

Yolkin is a polypeptide complex isolated from hen egg yolk that exhibits immunomodulating properties. The aim of the present study was to determine whether in-ovo-delivered yolkin affects leukocyte populations and cytokine levels in broiler chickens. The experiment was carried out on eggs from Ross 308 broiler breeder birds. Yolkin was administered in ovo on the 18th day of incubation, once, at the following three doses: 1, 10, or 100 µg/egg. The immunological parameters were assessed in 1-, 7-, 14-, 21-, 28-, 35-, and 42-day-old birds kept under farming conditions and routinely vaccinated. The leukocyte populations were determined in the thymus, spleen, and blood. The cytokine (IL-1β, IL-2, IL-6, and IL-10) levels were determined in the plasma of the broiler chickens. Each experimental group included eight birds. The most pronounced effect of yolkin was an increase in the population of T cells, both CD4+ and CD8+, mainly in the blood. This effect on the lymphocyte subsets may be valuable regarding chicken immune responses, mainly against T-dependent antigens, during infection or after vaccination.
Rice OsANN9 Enhances Drought Tolerance through Modulating ROS Scavenging Systems
Authors: Jia Yangyang , Gu Xiangyang , Chai Jiaxin , Yao Xiaohong , Cheng Shoutao , Liu Lirui , He Saiya , Peng Yizhuo , Zhang Qian , Zhu Zhengge
Published: December 2023

Drought is a critical abiotic stress which leads to crop yield and a decrease in quality. Annexins belong to a multi-gene family of calcium- and lipid-binding proteins and play diverse roles in plant growth and development. Herein, we report a rice annexin protein, OsANN9, which in addition to regular annexin repeats and type-II Ca2+ binding sites, also consists of a C2H2-type zinc-finger domain. We found that the expression of OsANN9 was upregulated by polyethylene glycol (PEG) or water-deficient treatment. Moreover, plants that overexpressed OsANN9 had increased survival rates under drought stress, while both OsANN9-RNAi and osann9 mutants showed sensitivity to drought. In addition, the overexpression of OsANN9 increased superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities, which regulate reactive oxygen species homeostasis. Collectively, these findings indicate that OsANN9 may function as a positive regulator in response to drought stress by modulating antioxidant accumulation. Interestingly, the setting rates of osann9 mutant rice plants significantly decreased in comparison to wild-type plants, suggesting that OsANN9 might be involved in other molecular mechanisms in the rice seed development stage.
DNAJC30 Gene Variants Are a Frequent Cause of a Rare Disease: Leber Hereditary Optic Neuropathy in Polish Patients
Authors: Skorczyk-Werner Anna , Tońska Katarzyna , Maciejczuk Aleksandra , Nowomiejska Katarzyna , Korwin Magdalena , Ołdak Monika , Wawrocka Anna , Krawczyński Maciej R.
Published: December 2023

Leber hereditary optic neuropathy (LHON) is a rare disorder causing a sudden painless loss of visual acuity in one or both eyes, affecting young males in their second to third decade of life. The molecular background of the LHON is up to 90%, genetically defined by a point mutation in mitochondrial DNA. Recently, an autosomal recessive form of LHON (LHONAR1, arLHON) has been discovered, caused by biallelic variants in the DNAJC30 gene. This study provides the results of the DNAJC30 gene analysis in a large group of 46 Polish patients diagnosed with LHON, together with the clinical characterization of the disease. The c.152A>G (p.Tyr51Cys) substitution in the DNAJC30 gene was detected in all the patients as homozygote or compound heterozygote. Moreover, we identified one novel variant, c.293A>G, p.(Tyr98Cys), as well as two ultra-rare DNAJC30 variants: c.293A>C, p.(Tyr98Ser), identified to date only in one individual affected with LHONAR1, and c.130_131delTC (p.Ser44ValfsTer8), previously described only in two patients with Leigh syndrome. The patients presented here represent the largest group of subjects with DNAJC30 gene mutations described to date. Based on our data, the autosomal recessive form of LHON caused by DNAJC30 gene mutations is more frequent than the mitochondrial form in Polish patients. The results of our study suggest that Sanger sequencing of the single-exon DNAJC30 gene should be a method of choice applied to identify a molecular background of clinically confirmed LHON in Polish patients. This approach will help to reduce the costs of molecular testing.
Translation Fidelity and Respiration Deficits in CLPP-Deficient Tissues: Mechanistic Insights from Mitochondrial Complexome Profiling
Authors: Key Jana , Gispert Suzana , Koepf Gabriele , Steinhoff-Wagner Julia , Reichlmeir Marina , Auburger Georg
Published: December 2023

The mitochondrial matrix peptidase CLPP is crucial during cell stress. Its loss causes Perrault syndrome type 3 (PRLTS3) with infertility, neurodegeneration, and a growth deficit. Its target proteins are disaggregated by CLPX, which also regulates heme biosynthesis via unfolding ALAS enzymes, providing access for pyridoxal-5′-phosphate (PLP). Despite efforts in diverse organisms with multiple techniques, CLPXP substrates remain controversial. Here, avoiding recombinant overexpression, we employed complexomics in mitochondria from three mouse tissues to identify endogenous targets. A CLPP absence caused the accumulation and dispersion of CLPX-VWA8 as AAA+ unfoldases, and of PLPBP. Similar changes and CLPX-VWA8 co-migration were evident for mitoribosomal central protuberance clusters, translation factors like GFM1-HARS2, the RNA granule components LRPPRC-SLIRP, and enzymes OAT-ALDH18A1. Mitochondrially translated proteins in testes showed reductions to <30% for MTCO1-3, the mis-assembly of the complex IV supercomplex, and accumulated metal-binding assembly factors COX15-SFXN4. Indeed, heavy metal levels were increased for iron, molybdenum, cobalt, and manganese. RT-qPCR showed compensatory downregulation only for Clpx mRNA; most accumulated proteins appeared transcriptionally upregulated. Immunoblots validated VWA8, MRPL38, MRPL18, GFM1, and OAT accumulation. Co-immunoprecipitation confirmed CLPX binding to MRPL38, GFM1, and OAT, so excess CLPX and PLP may affect their activity. Our data mechanistically elucidate the mitochondrial translation fidelity deficits which underlie progressive hearing impairment in PRLTS3.
Artemisia annua L. Polyphenols Enhance the Anticancer Effect of β-Lapachone in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells
Authors: Jung Eun Joo , Kim Hye Jung , Shin Sung Chul , Kim Gon Sup , Jung Jin-Myung , Hong Soon Chan , Kim Choong Won , Lee Won Sup
Published: December 2023

Recent studies suggest that the anticancer activity of β-lapachone (β-Lap) could be improved by different types of bioactive phytochemicals. The aim of this study was to elucidate how the anticancer effect of β-Lap is regulated by polyphenols extracted from Korean Artemisia annua L. (pKAL) in parental HCT116 and oxaliplatin-resistant (OxPt-R) HCT116 colorectal cancer cells. Here, we show that the anticancer effect of β-Lap is more enhanced by pKAL in HCT116-OxPt-R cells than in HCT116 cells via a CCK-8 assay, Western blot, and phase-contrast microscopy analysis of hematoxylin-stained cells. This phenomenon was associated with the suppression of OxPt-R-related upregulated proteins including p53 and β-catenin, the downregulation of cell survival proteins including TERT, CD44, and EGFR, and the upregulation of cleaved HSP90, γ-H2AX, and LC3B-I/II. A bioinformatics analysis of 21 proteins regulated by combined treatment of pKAL and β-Lap in HCT116-OxPt-R cells showed that the enhanced anticancer effect of β-Lap by pKAL was related to the inhibition of negative regulation of apoptotic process and the induction of DNA damage through TERT, CD44, and EGFR-mediated multiple signaling networks. Our results suggest that the combination of pKAL and β-Lap could be used as a new therapy with low toxicity to overcome the OxPt-R that occurred in various OxPt-containing cancer treatments.
In Vitro and In Vivo Imaging-Based Evaluation of Doxorubicin Anticancer Treatment in Combination with the Herbal Medicine Black Cohosh
Authors: Płoska Agata , Wozniak Marcin , Hedhli Jamila , Konopka Christian J. , Skondras Antonios , Matatov Sarah , Stawarz Andrew , Schuh Sarah , Czerwinski Andrzej , Dobrucki Lawrence W. , Kalinowski Leszek , Dobrucki Iwona T.
Published: December 2023

As a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts was used to determine the influence of BC and DOX administration on tumor growth and metabolism. The number of apoptotic cells after incubation with both DOX and BC was significantly increased (~100%) compared to the control. Treatment with DOX altered the potential of MCF-7 cells to form colonies; however, coincubation with BC did not affect this process. In vivo, PET-CT imaging showed that combined treatment of DOX and BC induced a significant reduction in both metabolic activity (29%) and angiogenesis (32%). Both DOX and BC treatments inhibited tumor growth by 20% and 12%, respectively, and combined by 57%, vs. control. We successfully demonstrated that BC increases cytotoxic effects of DOX, resulting in a significant reduction in tumor size. Further studies regarding drug transport and tumor growth biomarkers are necessary to establish the underlying mechanism and potential clinical use of BC in breast cancer patients.
Abnormal Cholesterol Metabolism and Lysosomal Dysfunction Induce Age-Related Hearing Loss by Inhibiting mTORC1-TFEB-Dependent Autophagy
Authors: Lee Yun Yeong , Ha Jungho , Kim Young Sun , Ramani Sivasubramanian , Sung Siung , Gil Eun Sol , Choo Oak-Sung , Jang Jeong Hun , Choung Yun-Hoon
Published: December 2023

Cholesterol is a risk factor for age-related hearing loss (ARHL). However, the effect of cholesterol on the organ of Corti during the onset of ARHL is unclear. We established a mouse model for the ARHL group (24 months, n = 12) and a young group (6 months, n = 12). Auditory thresholds were measured in both groups using auditory brainstem response (ABR) at frequencies of 8, 16, and 32 kHz. Subsequently, mice were sacrificed and subjected to histological analyses, including transmission electron microscopy (TEM), H&E, Sudan Black B (SBB), and Filipin staining, as well as biochemical assays such as IHC, enzymatic analysis, and immunoblotting. Additionally, mRNA extracted from both young and aged cochlea underwent RNA sequencing. To identify the mechanism, in vitro studies utilizing HEI-OC1 cells were also performed. RNA sequencing showed a positive correlation with increased expression of genes related to metabolic diseases, cholesterol homeostasis, and target of rapamycin complex 1 (mTORC1) signaling in the ARHL group as compared to the younger group. In addition, ARHL tissues exhibited increased cholesterol and lipofuscin aggregates in the organ of Corti, lateral walls, and spiral ganglion neurons. Autophagic flux was inhibited by the accumulation of damaged lysosomes and autolysosomes. Subsequently, we observed a decrease in the level of transcription factor EB (TFEB) protein, which regulates lysosomal biosynthesis and autophagy, together with increased mTORC1 activity in ARHL tissues. These changes in TFEB and mTORC1 expression were observed in a cholesterol-dependent manner. Treatment of ARHL mice with atorvastatin, a cholesterol synthesis inhibitor, delayed hearing loss by reducing the cholesterol level and maintaining lysosomal function and autophagy by inhibiting mTORC1 and activating TFEB. The above findings were confirmed using stress-induced premature senescent House Ear Institute organ of Corti 1 (HEI-OC1) cells. The findings implicate cholesterol in the pathogenesis of ARHL. We propose that atorvastatin could prevent ARHL by maintaining lysosomal function and autophagy by inhibiting mTORC1 and activating TFEB during the aging process.
Bioactive Compounds for Combating Oxidative Stress in Dermatology
Authors: Turcov Delia , Zbranca-Toporas Anca , Suteu Daniela
Published: December 2023

There are extensive studies that confirm the harmful and strong influence of oxidative stress on the skin. The body’s response to oxidative stress can vary depending on the type of reactive oxygen species (ROS) or reactive nitrogen species (RNS) and their metabolites, the duration of exposure to oxidative stress and the antioxidant capacity at each tissue level. Numerous skin diseases and pathologies are associated with the excessive production and accumulation of free radicals. title altered Both categories have advantages and disadvantages in terms of skin structures, tolerability, therapeutic performance, ease of application or formulation and economic efficiency. The effect of long-term treatment with antioxidants is evaluated through studies investigating their protective effect and the improvement of some phenomena caused by oxidative stress. This article summarizes the available information on the presence of compounds used in dermatology to combat oxidative stress in the skin. It aims to provide an overview of all the considerations for choosing an antioxidant agent, the topics for further research and the answers sought in order to optimize therapeutic performance.
Soluble CD137: A Potential Prognostic Biomarker in Critically Ill Patients
Authors: Räth Ulrich , Mester Patricia , Schwarz Herbert , Schmid Stephan , Müller Martina , Buechler Christa , Pavel Vlad
Published: December 2023

T cell depletion and functional impairment are characteristics of sepsis. CD137 is a costimulatory receptor on activated T cells, while soluble CD137 (sCD137) inhibits CD137 signaling. This study found elevated sCD137 levels in the plasma of patients with systemic inflammatory response syndrome (SIRS), sepsis, or septic shock compared to healthy controls. The sCD137 levels negatively correlated with the C-reactive protein and positively with procalcitonin and interleukin-6. There was no difference in sCD137 levels based on ventilation, dialysis, or vasopressor treatment. Patients with SARS-CoV-2, Gram-positive, or Gram-negative bacterial infections had similar sCD137 levels as noninfected individuals. Notably, higher plasma sCD137 levels were observed in non-survivors compared to survivors in both the SIRS/sepsis group and the SARS-CoV-2 subgroup. In conclusion, plasma sCD137 levels are associated with severe illness and survival in critically ill patients.
The Interplay between Helicobacter pylori and Gut Microbiota in Non-Gastrointestinal Disorders: A Special Focus on Atherosclerosis
Authors: Candelli Marcello , Franza Laura , Cianci Rossella , Pignataro Giulia , Merra Giuseppe , Piccioni Andrea , Ojetti Veronica , Gasbarrini Antonio , Franceschi Francesco
Published: December 2023

The discovery of Helicobacter pylori (H. pylori) in the early 1980s by Nobel Prize winners in medicine Robin Warren and Barry Marshall led to a revolution in physiopathology and consequently in the treatment of peptic ulcer disease. Subsequently, H. pylori has also been linked to non-gastrointestinal diseases, such as autoimmune thrombocytopenia, acne rosacea, and Raynaud’s syndrome. In addition, several studies have shown an association with cardiovascular disease and atherosclerosis. Our narrative review aims to investigate the connection between H. pylori infection, gut microbiota, and extra-gastric diseases, with a particular emphasis on atherosclerosis. We conducted an extensive search on PubMed, Google Scholar, and Scopus, using the keywords “H. pylori”, “dysbiosis”, “microbiota”, “atherosclerosis”, “cardiovascular disease” in the last ten years. Atherosclerosis is a complex condition in which the arteries thicken or harden due to plaque deposits in the inner lining of an artery and is associated with several cardiovascular diseases. Recent research has highlighted the role of the microbiota in the pathogenesis of this group of diseases. H. pylori is able to both directly influence the onset of atherosclerosis and negatively modulate the microbiota. H. pylori is an important factor in promoting atherosclerosis. Progress is being made in understanding the underlying mechanisms, which could open the way to interesting new therapeutic perspectives.
Functional and Potential Therapeutic Implication of MicroRNAs in Pancreatic Cancer
Authors: Pal Amartya , Ojha Anushka , Ju Jingfang
Published: December 2023

The alarmingly low five-year survival rate for pancreatic cancer presents a global health challenge, contributing to about 7% of all cancer-related deaths. Late-stage diagnosis and high heterogeneity are the biggest hurdles in treating pancreatic cancer. Thus, there is a pressing need to discover novel biomarkers that could help in early detection as well as improve therapeutic strategies. MicroRNAs (miRNAs), a class of short non-coding RNA, have emerged as promising candidates with regard to both diagnostics and therapeutics. Dysregulated miRNAs play pivotal roles in accelerating tumor growth and metastasis, orchestrating tumor microenvironment, and conferring chemoresistance in pancreatic cancer. The differential expression profiles of miRNAs in pancreatic cancer could be utilized to explore novel therapeutic strategies. In this review, we also covered studies on recent advancements in various miRNA-based therapeutics such as restoring miRNAs with a tumor-suppressive function, suppressing miRNA with an oncogenic function, and combination with chemotherapeutic drugs. Despite several challenges in terms of specificity and targeted delivery, miRNA-based therapies hold the potential to revolutionize the treatment of pancreatic cancer by simultaneously targeting multiple signaling pathways.
The Dynamics of OXA-23 β-Lactamase from Acinetobacter baumannii
Authors: Arrigoni Roberto , Ballini Andrea , Santacroce Luigi , Palese Luigi Leonardo
Published: December 2023

Antibiotic resistance is a pressing topic, which also affects β-lactam antibiotic molecules. Until a few years ago, it was considered no more than an interesting species from an academic point of view, Acinetobacter baumanii is today one of the most serious threats to public health, so much so that it has been declared one of the species for which the search for new antibiotics, or new ways to avoid its resistance, is an absolute priority according to WHO. Although there are several molecular mechanisms that are responsible for the extreme resistance of A. baumanii to antibiotics, a class D β-lactamase is the main cause for the clinical concern of this bacterial species. In this work, we analyzed the A. baumanii OXA-23 protein via molecular dynamics. The results obtained show that this protein is able to assume different conformations, especially in some regions around the active site. Part of the OXA-23 protein has considerable conformational motility, while the rest is less mobile. The importance of these observations for understanding the functioning mechanism of the enzyme as well as for designing new effective molecules for the treatment of A. baumanii is discussed.
Building a Multimodal Classifier of Email Behavior: Towards a Social Network Understanding of Organizational Communication
Authors: Shah Harsh , Jaidka Kokil , Ungar Lyle , Fagan Jesse , Grosser Travis
Published: December 2023

Within organizational settings, communication dynamics are influenced by various factors, such as email content, historical interactions, and interpersonal relationships. We introduce the Email MultiModal Architecture (EMMA) to model these dynamics and predict future communication behavior. EMMA uses data related to an email sender’s social network, performance metrics, and peer endorsements to predict the probability of receiving an email response. Our primary analysis is based on a dataset of 0.6 million corporate emails from 4320 employees between 2012 and 2014. By integrating features that capture a sender’s organizational influence and likability within a multimodal structure, EMMA offers improved performance over models that rely solely on linguistic attributes. Our findings indicate that EMMA enhances email reply prediction accuracy by up to 12.5% compared to leading text-centric models. EMMA also demonstrates high accuracy on other email datasets, reinforcing its utility and generalizability in diverse contexts. Our findings recommend the need for multimodal approaches to better model communication patterns within organizations and teams and to better understand how relationships and histories shape communication trajectories.
MulticloudFL: Adaptive Federated Learning for Improving Forecasting Accuracy in Multi-Cloud Environments
Authors: Stefanidis Vasilis-Angelos , Verginadis Yiannis , Mentzas Gregoris
Published: December 2023

Cloud computing and relevant emerging technologies have presented ordinary methods for processing edge-produced data in a centralized manner. Presently, there is a tendency to offload processing tasks as close to the edge as possible to reduce the costs and network bandwidth used. In this direction, we find efforts that materialize this paradigm by introducing distributed deep learning methods and the so-called Federated Learning (FL). Such distributed architectures are valuable assets in terms of efficiently managing resources and eliciting predictions that can be used for proactive adaptation of distributed applications. In this work, we focus on deep learning local loss functions in multi-cloud environments. We introduce the MulticloudFL system that enhances the forecasting accuracy, in dynamic settings, by applying two new methods that enhance the prediction accuracy in applications and resources monitoring metrics. The proposed algorithm’s performance is evaluated via various experiments that confirm the quality and benefits of the MulticloudFL system, as it improves the prediction accuracy on time-series data while reducing the bandwidth requirements and privacy risks during the training process.
The Outcome of under 10 mm Single-Incision Surgery Using a Non-Specialized Volar Plate in Distal Radius Fractures: A Retrospective Comparative Study
Authors: Huang Chang-Yu , Lee Chia-Che , Chen Chih-Wei , Hu Ming-Hsiao , Wu Kuan-Wen , Wang Ting-Ming , Wang Jyh-Horng , Tseng Tzu-Hao
Published: December 2023

Background: The distal radius fracture is a common orthopedic injury. We aimed to share the surgical steps and investigate the outcomes of treating distal radius fractures with wounds ≤10 mm using a globally accessible locking plate. Methods: We collected 46 patients who underwent surgery via a <10 mm wound, with a control group consisting of 40 patients who underwent conventional procedures. Both groups were treated using the same volar plate. We compared the radiographic reduction quality, including volar tilt angle, radial inclination angle, and ulna variance. Additionally, clinical outcomes, such as pain assessed using VAS, Q-Dash score, and PRWE, were evaluated. Patient satisfaction with the wound was also analyzed. The follow-up time for the clinical outcomes was 24.2 ± 13.47 months. Results: There were no differences in the quality of reduction in parameters such as the volar tilt angle (p = 0.762), radial inclination angle (p = 0.986), and ulna variance (p = 0.166). Both groups exhibited comparable results in pain VAS (p = 0.684), Q-Dash score (p = 0.08), and PRWE (p = 0.134). The ≤10 mm incision group displayed an increase in satisfaction with the wound (p < 0.001). Conclusions: Treating distal radius fractures with a <10 mm wound using a non-specialized locking plate is a feasible approach. It does not compromise the quality of fracture reduction or functional scores and improves wound satisfaction.
Efficacy, Safety and Outcomes of the Laparoscopic Management of Cesarean Scar Ectopic Pregnancy as a Single Therapeutic Approach: A Case Series
Authors: Salem Wehbe Georges , Amara Inesse Ait , Nisolle Michelle , Badr Dominique A. , Timmermans Marie , Karampelas Stavros
Published: December 2023

A standardized consensus for the management of cesarean scar pregnancy (CSP) is lacking. The study objective is to evaluate the efficacy, safety and outcomes of the laparoscopic management of CSP as a single therapeutic surgical approach without being preceded by vascular pretreatment or vasoconstrictors injection. This is a retrospective bi-centric study, a case series. Eight patients with a future desire to conceive underwent the laparoscopic treatment of unruptured CSPs. Surgery consisted of “en bloc” excision of the deficient uterine scar with the adherent tissue of conception, followed by immediate uterine repair. The data collected for each patient was age, gestity, parity, number of previous c-sections, pre-pregnancy isthmocele-related symptoms, gestational age, fetal cardiac activity, initial β-human chorionic gonadotropin levels, intra-operative blood loss, blood transfusion, operative time and the postoperative complications, evaluated according to Clavien–Dindo classification. The CSP was successfully removed in all patients by laparoscopy. The surgical outcomes were favorable. All patients with histories of isthmocele-related symptoms reported postoperative resolution of symptoms. The median residual myometrium thickness increased significantly from 1.2 mm pre-operatively to 8 mm 3 to 6 months after surgery. The laparoscopic management seems to be an appropriate treatment of CSP when performed by skilled laparoscopic surgeons. It can be safely proposed as a single surgical therapeutic approach. Larger series and further prospective studies are needed to confirm this observation and to affirm the long-term gynecological and obstetrical outcomes of this management.