bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular and Molecular Network Characteristics of TARM1-Related Genes in Mycobacterium tuberculosis Infections
Authors: Peng Li , Wu Hanxin , Zhu Liangyu , Song Jieqin , Ma Weijiang , Zhong Lei , Ma Weijie , Yang Rui , Huang Xun , Li Bingxue , Luo Suyi , Bao Fukai , Liu Aihua
Published: September 2024

Tuberculosis (TB) is a global infectious threat, and the emergence of multidrug-resistant TB has become a major challenge in eradicating the disease that requires the discovery of new treatment strategies. This study aimed to elucidate the immune infiltration and molecular regulatory network of T cell-interacting activating receptors on myeloid cell 1 (TARM1)-related genes based on a bioinformatics analysis. The GSE114911 dataset was obtained from the Gene Expression Omnibus (GEO) and screened to identify 17 TARM1-related differentially expressed genes (TRDEGs). Genes interacting with the TRDEGs were analyzed using a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A gene set enrichment analysis (GSEA) was used to identify the biological pathways significantly associated with a Mycobacterium tuberculosis (Mtb) infection. The key genes were obtained based on Cytoscape’s cytoHubba plug-in. Furthermore, protein–protein interaction (PPI) networks were analyzed through STRING, while mRNA–RNA-binding protein (RBP) and mRNA–transcription factor (TF) interaction networks were developed utilizing the StarBase v3.0 and ChIPBase databases. In addition, the diagnostic significance of key genes was evaluated via receiver operating characteristic (ROC) curves, and the immune infiltration was analyzed using an ssGSEA and MCPCounter. The key genes identified in the GSE114911 dataset were confirmed in an independent GSE139825 dataset. A total of seventeen TRDEGs and eight key genes were obtained in a differential expression analysis using the cytoHubba plug-in. Through the GO and KEGG analysis, it was found that these were involved in the NF-κB, PI3K/Akt, MAPK, and other pathways related to inflammation and energy metabolism. Furthermore, the ssGSEA and MCPCounter analysis revealed a significant rise in activated T cells and T helper cells within the Mtb infection group, which were markedly associated with these key genes. This implies their potential significance in the anti-Mtb response. In summary, our results show that TRDEGs are linked to inflammation, energy metabolism, and immune cells, offering fresh insights into the mechanisms underlying TB pathogenesis and supporting further investigation into the possible molecular roles of TARM1 in TB, as well as assisting in the identification of prospective diagnostic biomarkers.
Overcoming Challenges with Biochemical Studies of Selenocysteine and Selenoproteins
Authors: Cain Antavius , Krahn Natalie
Published: September 2024

Selenocysteine (Sec) is an essential amino acid that distinguishes itself from cysteine by a selenium atom in place of a sulfur atom. This single change imparts distinct chemical properties to Sec which are crucial for selenoprotein (Sec-containing protein) function. These properties include a lower pKa, enhanced nucleophilicity, and reversible oxidation. However, studying Sec incorporation in proteins is a complex process. While we find Sec in all domains of life, each domain has distinct translation mechanisms. These mechanisms are unique to canonical translation and are composed of Sec-specific enzymes and an mRNA hairpin to drive recoding of the UGA stop codon with Sec. In this review, we highlight the obstacles that arise when investigating Sec insertion, and the role that Sec has in proteins. We discuss the strategic methods implemented in this field to address these challenges. Though the Sec translation system is complex, a remarkable amount of information has been obtained and specialized tools have been developed. Continued studies in this area will provide a deeper understanding on the role of Sec in the context of proteins, and the necessity that we have for maintaining this complex translation machinery to make selenoproteins.
Regulation of Skeletal Development and Maintenance by Runx2 and Sp7
Authors: Komori Toshihisa
Published: September 2024

Runx2 (runt related transcription factor 2) and Sp7 (Sp7 transcription factor 7) are crucial transcription factors for bone development. The cotranscription factor Cbfb (core binding factor beta), which enhances the DNA-binding capacity of Runx2 and stabilizes the Runx2 protein, is necessary for bone development. Runx2 is essential for chondrocyte maturation, and Sp7 is partly involved. Runx2 induces the commitment of multipotent mesenchymal cells to osteoblast lineage cells and enhances the proliferation of osteoprogenitors. Reciprocal regulation between Runx2 and the Hedgehog, fibroblast growth factor (Fgf), Wnt, and parathyroid hormone-like hormone (Pthlh) signaling pathways and Dlx5 (distal-less homeobox 5) plays an important role in these processes. The induction of Fgfr2 (Fgf receptor 2) and Fgfr3 expression by Runx2 is important for the proliferation of osteoblast lineage cells. Runx2 induces Sp7 expression, and Runx2+ osteoprogenitors become Runx2+Sp7+ preosteoblasts. Sp7 induces the differentiation of preosteoblasts into osteoblasts without enhancing their proliferation. In osteoblasts, Runx2 is required for bone formation by inducing the expression of major bone matrix protein genes, including Col1a1 (collagen type I alpha 1), Col1a2, Spp1 (secreted phosphoprotein 1), Ibsp (integrin binding sialoprotein), and Bglap (bone gamma carboxyglutamate protein)/Bglap2. Bglap/Bglap2 (osteocalcin) regulates the alignment of apatite crystals parallel to collagen fibrils but does not function as a hormone that regulates glucose metabolism, testosterone synthesis, and muscle mass. Sp7 is also involved in Co1a1 expression and regulates osteoblast/osteocyte process formation, which is necessary for the survival of osteocytes and the prevention of cortical porosity. SP7 mutations cause osteogenesis imperfecta in rare cases. Runx2 is an important pathogenic factor, while Runx1, Runx3, and Cbfb are protective factors in osteoarthritis development.
The Impact of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Metabolic Rate in Drosophila melanogaster
Authors: Vecchie’ Denise , Wolter Julia M. , Perry Jesse , Jumbo-Lucioni Patricia , De Luca Maria
Published: September 2024

Evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) may increase metabolic rate by promoting thermogenesis, potentially through enhanced fat oxidation and improved insulin. More research is, however, needed to understand this intricate process. In this study, we used 22 lines from the Drosophila Genetic Reference Panel to assess the metabolic rate of virgin female and male flies that were either fed a standard medium or received lisinopril for one week or five weeks. We demonstrated that lisinopril affects the whole-body metabolic rate in Drosophila melanogaster in a genotype-dependent manner. However, the effects of genotypes are highly context-dependent, being influenced by sex and age. Our findings also suggest that lisinopril may increase the Drosophila metabolic rate via the accumulation of a bradykinin-like peptide, which, in turn, enhances cold tolerance by upregulating Ucp4b and Ucp4c genes. Finally, we showed that knocking down Ance, the ortholog of mammalian ACE in Malpighian/renal tubules and the nervous system, leads to opposite changes in metabolic rate, and that the effect of lisinopril depends on Ance in these systems, but in a sex- and age-specific manner. In conclusion, our results regarding D. melanogaster support existing evidence of a connection between ACEI drugs and metabolic rate while offering new insights into this relationship.
Prevalence of Fabry Disease in Patients on Dialysis in France
Authors: Sens Florence , Guittard Laure , Knebelmann Bertrand , Moranne Olivier , Choukroun Gabriel , de Précigout Valérie , Couchoud Cécile , Deleruyelle Isabelle , Lancelot Léa , Tran Thi Phuong Liên , Ghafari Thomas ,   FABRYDIAL Study Group, Juillard Laurent , Germain Dominique P.
Published: September 2024

Numerous prevalence studies on Fabry disease (FD, OMIM #301500) have been conducted in dialysis populations across the world with variable and controversial results. The FABRYDIAL study aimed to estimate the prevalence of FD in patients aged 18 to 74 years on chronic dialysis in France. This cross-sectional study was conducted in patients undergoing dialysis. One hundred and twenty-four dialysis centers participated. Patients with proven causes of nephropathy unrelated to FD were excluded. Alpha-galactosidase A activity was assayed in men, and both α-galactosidase A and lyso-Gb3 were assayed in women from dried blood spots. GLA gene sequencing was performed in case of abnormal values. If a variant was identified, a diagnosis validation committee was consulted for adjudication. Among the 6032 targeted patients, 3088 were included (73.6% of the eligible patients). Biochemical results were available for 2815 (1721 men and 1094 women). A genetic variant of GLA was identified in five patients: a benign c.937G>T/p.(Asp313Tyr) variant in two individuals, a likely benign c.427G>A/(p.Ala143Thr) variant, a likely benign c.416A>G/(p.Asn139Ser) variant, and a pathogenic c.1185dupG/p.Phe396Glyfs variant. Among the screened patients, the prevalence was 0.058% [0.010;0.328] in males, 0% [0.000;0.350] in females, and 0.035% [0.006;0.201] when both genders were pooled. Among all patients aged 18–74 years undergoing dialysis without a previously known cause of nephropathy unlinked to FD, the prevalence was 0.028% [0.006;0.121]. The prevalence of FD in a cohort of French dialysis patients was low. However, considering the prognostic impact of earlier diagnosis, signs of FD should be sought in patients with nephropathies of uncertain etiology.
Differential Expression of Mitogen-Activated Protein Kinase Signaling Pathways in the Human Choroid–Retinal Pigment Epithelial Complex Indicates Regional Predisposition to Disease
Authors: Hailey Dylan R. , Kanjilal Debolina , Koulen Peter
Published: September 2024

The retina is composed of neuronal layers that include several types of interneurons and photoreceptor cells, and separate underlying retinal pigment epithelium (RPE), Bruch’s membrane, and choroid. Different regions of the human retina include the fovea, macula, and periphery, which have unique physiological functions and anatomical features. These regions are also unique in their protein expression, and corresponding cellular and molecular responses to physiological and pathophysiological stimuli. Skeie and Mahajan analyzed regional protein expression in the human choroid–RPE complex. Mitogen-Activated Protein Kinase (MAPK) signaling pathways have been implicated in responses to stimuli such as oxidative stress and inflammation, which are critical factors in retina diseases including age-related macular degeneration. We, therefore, analyzed the Skeie and Mahajan, 2014, dataset for regional differences in the expression of MAPK-related proteins and discussed the potential implications in retinal diseases presenting with regional signs and symptoms. Regional protein expression data from the Skeie and Mahajan, 2014, study were analyzed for members of signaling networks involving MAPK and MAPK-related proteins, categorized by specific MAPK cascades, such as p38, ERK1/2, and JNK1/2, both upstream or downstream of the respective MAPK and MAPK-related proteins. We were able to identify 207 MAPK and MAPK-related proteins, 187 of which belonging to specific MAPK cascades. A total of 31 of these had been identified in the retina with two proteins, DLG2 and FLG downstream, and the other 29 upstream, of MAPK proteins. Our findings provide evidence for potential molecular substrates of retina region-specific disease manifestation and potential new targets for therapeutics development.
Freeze-Driven Adsorption of Oligonucleotides with polyA-Anchors on Au@Pt Nanozyme
Authors: Lapshinov Nikita E. , Pridvorova Svetlana M. , Zherdev Anatoly V. , Dzantiev Boris B. , Safenkova Irina V.
Published: September 2024

A promising and sought-after class of nanozymes for various applications is Pt-containing nanozymes, primarily Au@Pt, due to their easy preparation and remarkable catalytic properties. This study aimed to explore the freeze–thaw method for functionalizing Pt-containing nanozymes with oligonucleotides featuring a polyadenine anchor. Spherical gold nanoparticles ([Au]NPs) were synthesized and subsequently used as seeds to produce urchin-like Au@Pt nanoparticles ([Au@Pt]NPs) with an average diameter of 29.8 nm. The nanoparticles were conjugated with a series of non-thiolated DNA oligonucleotides, each consisting of three parts: a 5′-polyadenine anchor (An, with n = 3, 5, 7, 10; triple-branched A3, or triple-branched A5), a random sequence of 23 nucleotides, and a linear polyT block consisting of seven deoxythymine residues. The resulting conjugates were characterized using transmission electron microscopy, spectroscopy, dynamic light scattering, and emission detection of the fluorescent label at the 3′-end of each oligonucleotide. The stability of the conjugates was found to depend on the type of oligonucleotide, with decreased stability in the row of [Au@Pt]NP conjugates with A7 > A5 > 3A3 > 3A5 > A10 > A3 anchors. These [Au@Pt]NP–oligonucleotide conjugates were further evaluated using lateral flow test strips to assess fluorescein-specific binding and peroxidase-like catalytic activity. Conjugates with A3, A5, A7, and 3A3 anchors showed the highest levels of signals of bound labels on test strips, exceeding conjugates in sensitivity by up to nine times. These findings hold significant potential for broad application in bioanalytical systems.
Endocrine-Disrupting Chemicals and the Development of Diabetes Mellitus Type 1: A 5-Year Systematic Review
Authors: Keskesiadou Georgia-Nektaria , Tsokkou Sophia , Konstantinidis Ioannis , Georgaki Maria-Nefeli , Sioga Antonia , Papamitsou Theodora , Karachrysafi Sofia
Published: September 2024

Introduction: According to the Institute of Environmental Sciences, endocrine-disrupting chemicals (EDCs) are “natural or human-made chemicals that may mimic, block, or interfere with the body’s hormones, associated with a wide array of health issues”, mainly in the endocrine system. Recent studies have discussed the potential contribution of EDCs as risk factors leading to diabetes mellitus type 1 (T1DM), through various cellular and molecular pathways. Purpose: The purpose of this study was to investigate the correlation between the EDCs and the development of T1DM. Methodology: Thus, a 5-year systematic review was conducted to bring light to this research question. Using the meta-analysis and systematic review guideline protocol, a PRISMA flow diagram was constructed and, using the keywords (diabetes mellitus type 1) AND (endocrine-disrupting chemicals) in the databases PubMed, Scopus and ScienceDirect, the relevant data was collected and extracted into tables. Quality assessment tools were employed to evaluate the quality of the content of each article retrieved. Results: Based on the data collected and extracted from both human and animal studies, an association was found between T1DM and certain EDCs, such as bisphenol A (BPA), bisphenol S (BPS), persistent organic pollutants (POPs), phthalates and dioxins. Moreover, based on the quality assessments performed, using the Newcastle–Ottawa Scale and ARRIVE quality assessment tool, the articles were considered of high quality and thus eligible to justify the correlation of the EDCs and the development of T1DM. Conclusion: Based on the above study, the correlation can be justified; however, additional studies can be made focusing mainly on humans to understand further the pathophysiologic mechanism involved in this association.
Energy Metabolism Enhance Perylenequinone Biosynthesis in Shiraia sp. Slf14 through Promoting Mitochondrial ROS Accumulation
Authors: Wu Xueyi , Meng Xuan , Xiao Yiwen , Yang Huilin , Zhang Zhibin , Zhu Du
Published: September 2024

Perylenequinones (PQs) are important natural compounds that have been extensively utilized in recent years as agents for antimicrobial, anticancer, and antiviral photodynamic therapies. In this study, we investigated the molecular mechanisms regulating PQ biosynthesis by comparing Shiraia sp. Slf14 with its low PQ titer mutant, Slf14(w). The results indicated that the strain Slf14 exhibited a higher PQ yield, a more vigorous energy metabolism, and a more pronounced oxidation state compared to Slf14(w). Transcriptome analysis consistently revealed that the differences in gene expression between Slf14 and Slf14(w) are primarily associated with genes involved in redox processes and energy metabolism. Additionally, reactive oxygen species (ROS) were shown to play a crucial role in promoting PQ synthesis, as evidenced by the application of ROS-related inhibitors and promoters. Further results demonstrated that mitochondria are significant sources of ROS, which effectively regulate PQ biosynthesis in Shiraia sp. Slf14. In summary, this research revealed a noteworthy finding: the higher energy metabolism of the strain Slf14 is associated with increased intracellular ROS accumulation, which in turn triggers the activation and expression of gene clusters responsible for PQ synthesis.
Circular RNAs: Novel Players in Cancer Mechanisms and Therapeutic Strategies
Authors: Kim Jimi
Published: September 2024

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that have emerged as pivotal players in gene regulation. Our understanding of circRNAs has greatly expanded over the last decade, with studies elucidating their biology and exploring their therapeutic applications. In this review, we provide an overview of the current understanding of circRNA biogenesis, outline their mechanisms of action in cancer, and assess their clinical potential as biomarkers. Furthermore, we discuss circRNAs as a potential therapeutic strategy, including recent advances in circRNA production and translation, along with proof-of-concept preclinical studies of cancer vaccines.
MicroRNA Signature in an In Vitro Keratinocyte Model of Diabetic Wound Healing
Authors: Tsai Hsin-Chung , Chang Gary Ro-Lin , Tung Min-Che , Tu Min-Yu , Chen I-Chien , Liu Yu-Hsien , Cidem Abdulkadir , Chen Chuan-Mu
Published: September 2024

Treating diabetic wounds effectively remains a significant clinical challenge. Emerging studies suggest that microRNAs (miRNAs) play crucial roles in various physiological and pathological processes and hold promise as therapeutic tools. This study investigates the miRNA expression profile in keratinocytes using a cell model of diabetic wounds. Microarray analysis revealed that 43 miRNAs from wounded keratinocytes incubated under diabetic conditions (high glucose/hypoxia) exhibited a two-fold change in expression compared to those incubated under normal conditions (low glucose/normoxia). Quantitative RT-PCR confirmed significant differences in the expression of eight miRNAs, with miR-3138 and miR-3679-5p being further analyzed for their roles in keratinocyte migration. Transfection with a miR-3138 mimic and a miR-3679-5p inhibitor indicated that upregulation of miR-3138 and downregulation of miR-3679-5p enhance keratinocyte migration in both normal and diabetic wounds. Pathway and gene ontology (GO) analyses identified potential pathways and functional annotations associated with miR-3138 and miR-3679-5p in diabetic wound healing. Potential human gene targets of miR-3138 and miR-3679-5p were predicted using a three-way comparison of the TargetScan, miRDB, and DIANA databases. This study elucidates the miRNA expression signature of human keratinocytes in a diabetes-like environment, providing deeper insights into the pathogenesis of diabetic wounds.
Review of Applications of β-Cyclodextrin as a Chiral Selector for Effective Enantioseparation
Authors: Napiórkowska Ewa , Szeleszczuk Łukasz
Published: September 2024

The significance and necessity of separating enantiomers in food, pharmaceuticals, pesticides, and other samples remains constant and unrelenting. The successful chiral separation usually includes the application of a chiral auxiliary compound, known also as a chiral selector (CS), that forms complexes with enantiomers of different physicochemical properties, enabling efficient separation. While both native and substituted cyclodextrins (CDs) are commonly used as CSs, β-CD is undoubtedly the most popular one among them. This review includes recent advancements in the application of β-CD as a CS. While the theoretical background behind the enantioseparation is also part of this work, the main emphasis is put on the factors that affect the efficacy of this process such as temperature, pH, solvent, and the choice of other additives. Also, the different analytical methods: Nuclear Magnetic Resonance (NMR) spectroscopy, Capillary Electrophoresis (CE), fluorescence spectroscopy (FS), High-Performance Liquid Chromatography (HPLC), Isothermal Titration Calorimetry (ITC), and UV–vis spectroscopy, used for enantioseparation with the aid of β-CD as CS, are thoroughly compared. Also, since some of the chiral compounds have been studied in the context of their enantioseparation more than once, those works are compared and critically analyzed. In conclusion, while β-CD can be in most cases used as CS, the choice of the experimental conditions and method of analysis is crucial to achieve the success.
Chromate Affects Gene Expression and DNA Methylation in Long-Term In Vitro Experiments in A549 Cells
Authors: Fischer Franziska , Stößer Sandra , Wegmann Lisa , Veh Eva , Lumpp Tatjana , Parsdorfer Marlene , Schumacher Paul , Hartwig Andrea
Published: September 2024

Chromate has been shown to dysregulate epigenetic mechanisms such as DNA methylation, leading to changes in gene expression and genomic instability. However, most in vitro studies are limited to short incubation periods, although chronic exposure may be more relevant for both environmental and occupational exposure. In this study, human adenocarcinoma A549 cells were treated with 1, 2 or 5 µM chromate for 24 h and compared with incubations with 0.2, 0.5 or 1 µM chromate for 1 to 5 weeks. Chromium accumulated in a pronounced time- and concentration-dependent manner after short-term treatment, whereas a plateau of intracellular chromium content was observed after long-term treatment. While short-term treatment induced a G2 arrest of the cell cycle, this effect was not observed after long-term treatment at lower concentrations. The opposite was observed for global DNA methylation: while short-term treatment showed no effect of chromate, significant dose-dependent hypomethylation was observed in the long-term experiments. Time-dependent effects were also observed in a high-throughput RT-qPCR gene expression analysis, particularly in genes related to the inflammatory response and DNA damage response. Taken together, the results suggest specific differences in toxicity profiles when comparing short-term and long-term exposure to chromate in A549 cells.
Sustainable Design of Pavements: Predicting Pavement Service Life
Authors: Bhattacharya Subhendu , Taylor Richard , D’Melo Dawid , Campbell Connor
Published: September 2024

Pavement service life is an important factor that affects both the whole life cost and carbon footprint of a pavement. The service life of a pavement is affected by several different parameters which can be broadly classified into climate conditions, binder and mixture properties, pavement design, workmanship, and maintenance strategies. The current practice for determining service life of pavements involves the use of pavement design tools, which are used while constructing a new pavement or performing a reconstruction/resurfacing or pavement maintenance. In addition, field measurements using ground penetration radar, falling weight deflectometer, traffic speed deflectometer, and other techniques are also used to assess the condition of an existing pavement. The information from these measurements is then combined with pavement design software to predict potential pavement service life. The accuracy of the predicted pavement service life is affected by the associated uncertainties in the parameters that affect pavement life. The following paper presents various approaches that could be potentially used to determine the associated uncertainties in the estimation of pavement service life. The various uncertainty quantification techniques have been applied to a specific design, and the outcomes are discussed in this paper. The Monte Carlo simulation method, a system-level uncertainty quantification technique, can estimate a probabilistic pavement service life. The other uncertainty quantification schemes are software specific and provide probabilistic life factors by assumed statistical distributions. Hence, the Monte Carlo simulation technique could be one potential method that can be used for estimating a generalized pavement service utilizing predictions from various design software.
Mitigating the Threat of Invasive Mosquito Species Expansion: A Comprehensive Entomological Surveillance Study on Kastellorizo, a Remote Greek Island
Authors: Bisia Marina , Balatsos Georgios , Beleri Stavroula , Tegos Nikolaos , Zavitsanou Evangelia , LaDeau Shannon L. , Sotiroudas Vasilis , Patsoula Eleni , Michaelakis Antonios
Published: September 2024

The expansion of the tiger mosquito, a vector that can transmit diseases such as dengue, chikungunya, and Zika virus, poses a growing threat to global health. This study focuses on the entomological surveillance of Kastellorizo, a remote Greek island affected by its expansion. This research employs a multifaceted approach, combining KAP survey (knowledge, attitude, practices), mosquito collection using adult traps and human landing catches, and morphological and molecular identification methods. Results from questionnaires reveal community awareness and preparedness gaps, emphasizing the need for targeted education. Mosquito collections confirm the presence of the Aedes albopictus, Aedes cretinus, and Culex pipiens mosquitoes, highlighting the importance of surveillance. This study underscores the significance of community engagement in entomological efforts and proposes a citizen science initiative for sustained monitoring. Overall, this research provides essential insights for developing effective mosquito control programs in remote island settings, thereby emphasizing the importance of adopting a One Health approach to mitigate the spread of vector-borne diseases.
Ten-Year Results of the Fitmore® Hip Stem with a Focus on Varus/Valgus Alignment and Subsidence—A Retrospective Monocentric Analysis
Authors: Wanner Ronald , Butler Ransohoff Christopher , Wyss Tobias , Nötzli Hubert
Published: September 2024

Background: Hip arthroplasty is a common elective surgery worldwide, with rising numbers due to demographic changes and an emphasis on maintaining physical activity in the elderly. The development of new implant designs, especially shorter uncemented stems, has contributed to the advancement of minimally invasive implantation techniques. However, the long-term in vivo behaviour of these implants, particularly regarding subsidence, stability, and stress shielding, remains to be fully understood. Methods: This retrospective, monocentric cohort study analyses the long-term radiographic outcomes of the first 141 patients who underwent total hip arthroplasty with the Fitmore® Hip Stem between June 2007 and December 2008. It focuses on subsidence, stability, varus–valgus alignment, and the influence of patient-related, anatomical, and surgical factors on implant behaviour over a 10-year follow-up period. Results: The average change in varus/valgus alignment was 0.7° into varus and the average subsidence was 1.7 mm over 10 years, with most changes occurring within the first six weeks postoperatively. The varus–valgus alignment and subsidence did not significantly change after the first year, indicating stable osteointegration of the implant. Neither patient factors (gender, age) nor surgical and implant factors (implantation angle, approach, stem family, size, total offset) had a significant influence on the long-term behaviour of the implant. Conclusions: The Fitmore® Hip Stem shows highly reliable long-term stability and integration, unaffected by various patient, surgical, and implant factors, as confirmed by excellent register data. Nevertheless, monitoring of this and other new implants should be continued in order to determine implant behaviour, possible weaknesses, and indication limits at an early stage for the benefit of the patient.
The Impact of COVID-19 on Functional Capacity and Pulmonary Outcomes in the Hail Region: A Cross-Sectional Study
Authors: Althomali Omar W. , Hussain Shaik Daria , Kanwal Raheela , Amin Junaid , Acar Tolgahan , Abdelmoniem Ibrahim Ahmed , Hussein Hisham M. , Ansari Aisha , Alhammad Ayman A. , Shahid Ali Mohammad , Alqunun Ahmed , Alghamdi Wael
Published: September 2024

Background/Objectives: COVID-19, caused by the novel coronavirus SARS-CoV-2, has had a significant impact on life worldwide since its emergence in late 2019. The virus has caused a global pandemic, leading to widespread health, social, economic, and psychological effects. COVID-19 mainly affects the respiratory system. This study aimed to compare the functional capacity and pulmonary function outcomes between COVID-19 patients and individuals who have not been infected in the Hail region. Methods: Individuals of both genders above 18 years old who had been infected with COVID-19 in the previous 6 months or had never been infected were eligible to participate. Local hospitals and social media apps were used to recruit willing participants. Heart rate, pulse oxygen saturation, blood pressure, pulmonary function test, hand grip strength, and functional tests (6 min walk test, 30 s sit-to-stand test, and timed up and go test) were measured and compared between the groups. Statistical analysis was performed using SPSS Version 25. Results: Forty individuals affected with COVID-19 and forty-one healthy individuals were recruited. Our results showed that in individuals affected with COVID-19, scores on the minute ventilation, 30 s sit-to-stand, and 6 min walk tests were significantly lower than among healthy individuals. Other outcomes did not show any statistical differences between the groups. Conclusion: This study contributes to a greater understanding of the functional capacity status of individuals with COVID-19. Patients affected by COVID-19 may develop an impaired lung capacity and a decreased function capacity. These factors may negatively affect physical and cognitive health status. Future studies should evaluate the benefits of interventions with rehabilitation exercises following COVID-19. In light of the functional capacity and pulmonary function decline in individuals affected by COVID-19, interventions encompassing pulmonary and functional rehabilitation exercises are recommended to improve physical fitness and pulmonary function post-COVID-19.
Infectious Diseases-Approved Virtual Reality Goggles for Common Procedures in Pediatric Surgical Patients
Authors: Gilboa Pras Yarden , Indursky Atara , Gilboa Pras Shai , Schaffer Ortal , Niazov Eleonora , Zmora Osnat
Published: September 2024

Background/Objective: Virtual reality (VR) technology has been reported as effective in mitigating fear, anxiety, and pain in children undergoing various medical procedures. Our aim was to test the effectiveness of non-sponge-coated mobile phone-operated VR goggles approved by infectious diseases (ID) control in pediatric surgical patients. Methods: A prospective randomized trial in which pre-procedural and post-procedural heart rate, fear, and anxiety, and post-procedural pain were measured in pediatric surgical patients assigned to receive standard care versus standard care and VR goggles. The patients underwent line insertions, peripheral venipunctures for blood draws, drain removals, and wound care. Results: The control group and the intention-to-treat group were each randomly assigned twenty-four patients. Since eight patients who received VR goggles removed them prior to completion of the procedure, the study group included sixteen patients. In the study group, heart rate, fear, and anxiety scores were significantly lower after the procedure as compared to prior to the procedure. In the control group, these parameters were similar before and after the procedure. Post-procedural decrease in fear and anxiety was significant when comparing VR to control. However, despite better post-procedural physiological and emotional scores in the VR group as compared to control, the differences were not statistically significant. Pre-procedural anxiety was significantly higher in the study group. Conclusions: ID-approved VR goggles can reduce fear and anxiety associated with procedures commonly performed in pedicatric surgical patients. However, since increased baseline anxiety might be associated with VR, a higher benefit might be achieved if goggles were worn only by children who express a clear desire to use them.
In Silico Decoding of Parkinson’s: Speech & Writing Analysis
Authors: Ileșan Robert Radu , Ștefănigă Sebastian-Aurelian , Fleșar Radu , Beyer Michel , Ginghină Elena , Peștean Ana Sorina , Hirsch Martin C. , Perju-Dumbravă Lăcrămioara , Faragó Paul
Published: September 2024

Background: Parkinson’s disease (PD) has transitioned from a rare condition in 1817 to the fastest-growing neurological disorder globally. The significant increase in cases from 2.5 million in 1990 to 6.1 million in 2016, coupled with predictions of a further doubling by 2040, underscores an impending healthcare challenge. This escalation aligns with global demographic shifts, including rising life expectancy and a growing global population. The economic impact, notably in the U.S., reached $51.9 billion in 2017, with projections suggesting a 46% increase by 2037, emphasizing the substantial socio-economic implications for both patients and caregivers. Coupled with a worldwide demand for health workers that is expected to rise to 80 million by 2030, we have fertile ground for a pandemic. Methods: Our transdisciplinary research focused on early PD detection through running speech and continuous handwriting analysis, incorporating medical, biomedical engineering, AI, and linguistic expertise. The cohort comprised 30 participants, including 20 PD patients at stages 1–4 on the Hoehn and Yahr scale and 10 healthy controls. We employed advanced AI techniques to analyze correlation plots generated from speech and handwriting features, aiming to identify prodromal PD biomarkers. Results: The study revealed distinct speech and handwriting patterns in PD patients compared to controls. Our ParkinsonNet model demonstrated high predictive accuracy, with F1 scores of 95.74% for speech and 96.72% for handwriting analyses. These findings highlight the potential of speech and handwriting as effective early biomarkers for PD. Conclusions: The integration of AI as a decision support system in analyzing speech and handwriting presents a promising approach for early PD detection. This methodology not only offers a novel diagnostic tool but also contributes to the broader understanding of PD’s early manifestations. Further research is required to validate these findings in larger, diverse cohorts and to integrate these tools into clinical practice for timely PD pre-diagnosis and management.
Surgical Innovations to Protect Fertility from Oncologic Pelvic Radiation Therapy: Ovarian Transposition and Uterine Fixation
Authors: Yazdani Ariella , Sweterlitsch Katherine Moran , Kim Hanna , Flyckt Rebecca L. , Christianson Mindy S.
Published: September 2024

As oncologic therapy continues to advance, survivorship care has widened the realm of possibilities for quality-of-life improvements, including fertility preservation and restoration. We aim to summarize the current and future directions of fertility preservation techniques for patients facing gonadotoxic medical therapies who desire pregnancy after their condition is treated. This review of both ovarian and uterine transposition highlights the present roles, techniques, and fertility outcomes of the two fertility preservation treatment modalities designed to protect reproductive organs from harmful pelvic radiation. Current evidence shows that ovarian transposition preserves ovarian function for patients with localized pelvic radiation demonstrating the most successful return of fertility. Uterine transposition holds great promise for patients desiring to conceive and carry a full-term pregnancy after radiation therapy. With ongoing advancements in oncologic treatments leading to increased survival rates, fertility is increasingly becoming a key survivorship issue. Patients can anticipate counseling about these fertility preservation surgical techniques that protect both the ovaries as well as the uterus from harmful pelvic radiation.
COPD Patient’s Outcomes following Total Knee Arthroplasty—An Analysis of the National Inpatients Sampling (2016–2020)
Authors: Albagly Aviram , Kobo Ofer , Yonai Yaniv , Berkovich Yaron , Steinfeld Yaniv
Published: September 2024

Introduction: Total knee arthroplasty (TKA) is a common elective procedure aimed at improving patients’ quality of life. Patients undergoing this procedure can have a wide variety of comorbidities, including chronic obstructive pulmonary disease (COPD). Several studies demonstrated a higher risk of postoperative complications for this patient population. In this study, we examined the mortality risk of this group of patients, as well as the length of stay (LOS) and general costs. Methods: This study is a retrospective, case–control study. Using the National Inpatients Sampling (NIS) database, we defined a cohort of adults who received their inpatient primary TKA between 1 January 2016 and 31 December 2020. Preoperative variables include age, sex, race, primary payer, hospital location, and hospital type. Outcomes examined in this study include overall patient mortality as a primary outcome. Secondary outcomes include total LOS (in days) and inpatient costs in the United States (in USD). Results: A total of 2,835,499 patients who underwent TKA procedure in the United States were included. A total of 173,230 (6.1%) COPD patients were included in the COPD group. The mortality rate in the COPD group (0.1%) was more than three times higher than the control group (0.03%, p-value < 0.001). Patients in the COPD group had a longer in-hospital length of stay (2.76) compared to the control group (2.31, p-value < 0.001) and a higher treatment cost (average value of treatment per patient) (USD 69,386) compared to the control group (USD 64,446, p-value < 0.001). We also found higher mortality risk for patients older than 60 and patients of white ethnicity. Conclusion: COPD patients undergoing TKA have a higher mortality rate and this issue should be addressed in order to improve patient care and outcomes.
Efficacy of Postoperative Oral Nutritional Supplements in Geriatric Hip Fracture Patients Undergoing Total Hip Arthroplasty
Authors: Kim Chang-Hyun , Lee Byung-Ryul , Park Jong-Seok , Kim Jun-Bum , Kwon Sai-Won , Kim Woo-Jong , Jung Ki-Jin , Jang Byung-Woong , Hong Chang-Hwa
Published: September 2024

Background/Objectives: Geriatric hip fracture patients have an increased risk of malnutrition. Proper nutritional supply in the perioperative period is very important for their recovery. Oral nutritional supplements (ONSs) are recommended in geriatric hip fracture patients to improve dietary intake and prevent complications. This study aimed to evaluate the efficacy of postoperative ONSs after total hip arthroplasty in geriatric hip fracture patients. Methods: A retrospective study of elderly patients who underwent total hip arthroplasty for hip fracture was conducted. Data from patients who received ONSs postoperatively until hospital discharge (ONS group, n = 69) were compared with patients who did not receive ONSs (control group, n = 168). Laboratory test results, including serum protein and albumin levels, length of hospital stay, and the incidence of postoperative medical complications of the two groups, were analyzed. Results: Preoperative serum protein and albumin levels were significantly higher in the control group (p = 0.002 and p = 0.010, respectively). However, the degree of decline for both protein and albumin levels was significantly less in the ONS group (p < 0.001 for both). Serum albumin levels were significantly higher in the ONS group at postoperative two-week follow-up (p = 0.006). The length of hospital stay was shorter in the ONS group (p < 0.001). The incidence of postoperative delirium was significantly higher in the control group (p = 0.007). Conclusions: In geriatric hip fracture patients, postoperative ONSs can improve postoperative nutritional status, shorten the length of hospital stay, and reduce the incidence of postoperative delirium.
Association of Atrial Fibrillation and Cognitive Dysfunction: A Comprehensive Narrative Review of Current Understanding and Recent Updates
Authors: Passey Siddhant , Patel Jay , Patail Haris , Aronow Wilbert
Published: September 2024

Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. The prevalence of both AF and dementia is steadily rising and is expected to rise further in the coming decades. There is increasing evidence to suggest an association between AF and various degrees of cognitive dysfunction, from mild cognitive impairment to severe dementia. In this review, we aimed to discuss the epidemiological aspects, pathophysiological mechanisms, role of neuroimaging, impact of treatment modalities, and clinical and socioeconomic impact of this association. Numerous observational studies and meta-analyses have revealed this association to exist in AF patients with and without a history of stroke, and the association also persists after adjusting for shared risk factors such as hypertension and diabetes mellitus. Various pathophysiological mechanisms have been proposed for this association, including silent cerebral infarcts, cerebral microbleeds, cerebral hypoperfusion, inflammation, and atherosclerosis. While neuroimaging findings have been utilized to suggest some of these pathophysiological mechanisms, more studies are needed to further elucidate this and to determine the potential role of neuroimaging in altering anticoagulation and other treatment decisions. Anticoagulants have shown effectiveness in reducing the rate of cognitive decline in AF patients; however, their role in low-risk AF patients remains under investigation. Even though AF patients receiving catheter ablation may have post-operative cognitive dysfunction in the short term, long-term follow-up studies have shown an improvement in cognitive function following ablation. Cognitive decline in AF patients often occurs with greater functional decline and other psychosocial impairments such as depression and anxiety and future research on this association must incorporate aspects of social determinants of health and associated outcomes.
Risk Stratification and Management of Intermediate- and High-Risk Pulmonary Embolism
Authors: Mojaddedi Sanaullah , Jamil Javairia , Bishev Daniel , Essilfie-Quaye Kobina , Elgendy Islam Y.
Published: September 2024

Acute pulmonary embolism (PE) is a leading cause of mortality. Not only is PE associated with short-term mortality, but up to ~20% of patients might suffer from long-term consequences such as post-PE syndrome and chronic thromboembolic pulmonary hypertension. Current risk stratification tools poorly predict those who are at risk for short-term deterioration and those who develop long-term consequences. Traditionally, systemic thrombolysis has been considered the first-line therapy for patients with high-risk PE without contraindications; however, it comes with the risk of major bleeding (notably intracranial hemorrhage). The use of catheter-directed interventions (embolectomy or thrombolysis) has been increasing owing to their low bleeding risk; however, randomized trial data supporting their efficacy in improving clinical outcomes are limited. In this review, we highlight the evidence supporting the available advanced therapies for high- and intermediate-risk PE and summarize the ongoing trials which are evaluating these therapies.
Elevated HbA1c Levels Are Associated with a Risk of Pancreatic Cancer: A Case–Control Study
Authors: Grewe Steven , Jördens Markus S. , Roderburg Christoph , Leyh Catherine , Labuhn Simon , Luedde Tom , Krieg Sarah , Krieg Andreas , Loosen Sven H. , Kostev Karel
Published: September 2024

Background: The early diagnosis of pancreatic cancer (ICD-10 C25) can improve the patient’s prognosis. The association between pancreatic cancer and type 2 diabetes (T2D) is known, but not yet fully understood. It is, therefore, necessary to investigate the impact of hemoglobin A1c (HbA1c) serum levels on pancreatic cancer development and the potential intervention options. Methods: In the case–control study, patients from the German IQVIATM Disease Analyzer database aged ≥18 years with a diagnosis of pancreatic cancer (ICD-10 C25) and a diagnosis of T2D (ICD-10: E11) were included. The patients’ propensity score matched 1:5 with individuals without pancreatic cancer. Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Results: An elevated serum HbA1c prior to the index date was found to be significantly associated with an increased risk of a subsequent pancreatic cancer diagnosis for the mean HbA1c values of 6.5–8.4% (OR: 1.38; 95% CI: 1.22–1.57) as well as for mean HbA1c values ≥8.5% (OR: 1.41; 95% CI: 1.16–1.73). The only antihyperglycemic agent negatively associated with the subsequent pancreatic cancer diagnosis was the sodium–glucose cotransporter-2 (SGLT-2) inhibitor, with an odds ratio of 0.80 (95% confidence interval: 0.74–0.87 per year of therapy). This correlation was observed in both age- and sex-stratified subgroups. Conclusions: The data indicate that elevated serum HbA1c levels in patients with T2D are associated with an increased risk of pancreatic cancer development. It is possible that SGLT2 therapy may prove an effective means of reducing the risk of pancreatic cancer, thereby offering a potential avenue for the future reduction in pancreatic cancer incidence in patients with T2D.