bluuebunny/crossref_metadata_2025 huggingface dataset:
Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments
Authors: Dawalibi Ahmad , Alosaimi Amal Ahmed , Mohammad Khalid S.
Published: July 2024

Bone metastases, a common and debilitating consequence of advanced cancers, involve a complex interplay between malignant cells and the bone microenvironment. Central to this interaction are interleukins (ILs), a group of cytokines with critical roles in immune modulation and inflammation. This review explores the dualistic nature of pro-inflammatory and anti-inflammatory interleukins in bone metastases, emphasizing their molecular mechanisms, pathological impacts, and therapeutic potential. Pro-inflammatory interleukins, such as IL-1, IL-6, and IL-8, have been identified as key drivers in promoting osteoclastogenesis, tumor proliferation, and angiogenesis. These cytokines create a favorable environment for cancer cell survival and bone degradation, contributing to the progression of metastatic lesions. Conversely, anti-inflammatory interleukins, including IL-4, IL-10, and IL-13, exhibit protective roles by modulating immune responses and inhibiting osteoclast activity. Understanding these opposing effects is crucial for developing targeted therapies aimed at disrupting the pathological processes in bone metastases. Key signaling pathways, including NF-κB, JAK/STAT, and MAPK, mediate the actions of these interleukins, influencing tumor cell survival, immune cell recruitment, and bone remodeling. Targeting these pathways presents promising therapeutic avenues. Current treatment strategies, such as the use of denosumab, tocilizumab, and emerging agents like bimekizumab and ANV419, highlight the potential of interleukin-targeted therapies in mitigating bone metastases. However, challenges such as therapeutic resistance, side effects, and long-term efficacy remain significant hurdles. This review also addresses the potential of interleukins as diagnostic and prognostic biomarkers, offering insights into patient stratification and personalized treatment approaches. Interleukins have multifaceted roles that depend on the context, including the environment, cell types, and cellular interactions. Despite substantial progress, gaps in research persist, particularly regarding the precise mechanisms by which interleukins influence the bone metastatic niche and their broader clinical implications. While not exhaustive, this overview underscores the critical roles of interleukins in bone metastases and highlights the need for continued research to fully elucidate their complex interactions and therapeutic potential. Addressing these gaps will be essential for advancing our understanding and treatment of bone metastases in cancer patients.
Squamous Cell Carcinoma in Never Smokers: An Insight into SMARCB1 Loss
Authors: Patel Akshay J. , Hemead Hanan , Jesani Hannah , Bille Andrea , Taniere Philippe , Middleton Gary
Published: July 2024

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) constituting 85% of cases. Among NSCLCs, squamous cell carcinoma (SqCC) is strongly associated with smoking. However, lung cancer in never smokers (LCINS) represents approximately 25% of lung cancer cases globally and shows increasing incidence, particularly in East Asia. LCINS-SqCC is less well-characterized, especially regarding its genomic alterations and their impact on clinical outcomes. We conducted a retrospective analysis over a 20-year period (July 2003–July 2023) at two major tertiary centers in the UK. The cohort included 59 patients with LCINS-SqCC who underwent radical surgical resection. Data collected included demographic information, comorbidities, histopathological details, and outcome metrics such as disease-free and overall survival. Molecular sequencing of tumor specimens was performed to identify genomic aberrations. The cohort had a median age of 71 years (IQR 62–77) and a median BMI of 25.4 (IQR 22.8–27.8), with a slight male predominance (53%). The majority of patients (93%) had a preoperative MRC of 1–2. Recurrent disease was observed in 23 patients (39%), and 32 patients (54%) had died at a median follow-up of 3 years. Median disease-free survival was 545 days (IQR 132–1496), and overall survival was 888 days (IQR 443–2071). Preoperative creatinine levels were higher in patients who experienced recurrence (p = 0.037). Molecular analysis identified biallelic SMARCB1 loss in two younger patients, associated with rapid disease progression despite R0 resection. These patients’ tumors were PDL1-negative, TTF-1-negative, and positive for cytokeratin, CD56, and p40. SMARCB1-deficient SqCC in never smokers represents a highly aggressive variant with poor disease-free survival, highlighting the importance of integrating advanced molecular diagnostics in clinical practice. This study underscores the necessity for personalized treatment strategies, including targeted therapies such as EZH2 inhibitors and immune checkpoint blockade, to address the unique molecular pathways in SMARCB1-deficient cancers. Further clinical trials are essential to optimize therapeutic approaches for this challenging subgroup of lung cancer.
Discordant ALK Status in Non-Small Cell Lung Carcinoma: A Detailed Reevaluation Comparing IHC, FISH, and NGS Analyses
Authors: Tobiášová Katarína , Barthová Martina , Janáková Ľuboslava , Lešková Katarína , Farkašová Anna , Loderer Dušan , Grendár Marián , Plank Lukáš
Published: July 2024

ALK detection was performed on 2813 EGFR-unmutated NSCLC cases by simultaneous use of immunohistochemistry (VENTANA® anti-ALK D5F3, Roche Molecular Systems, Inc., Rotkreuz, Switzerland) and fluorescence in situ hybridization with the ALK break apart and the ALK/EML4 fusion probe (ZytoVision, Bremerhaven, Germany). A total of 33 cases were positive discordant (FISH-positive, IHC-negative) and 17 cases were negative discordant (FISH-negative, IHC-positive). This study’s aim was to reevaluate the methods used and compare discordant samples to positive concordant samples in order to ellucidate the differences. FISH signal variants were examined and compared. Positive discordant cases featured one pattern of ALK rearrangement in 41.4%, two patterns in 48.3%, and three patterns in 10.3% of analysed samples, with a higher variability of detected patterns and a higher number of ALK copy gains. Positive concordant cases displayed one pattern of rearrangement in 82%, two patterns in 17.8%, and three patterns in 0.6% of analysed samples. The association between number of patterns and concordance/discordance was statistically significant (p < 0.05). Eleven positive discordant and two negative concordant cases underwent NGS analysis, which resulted in identification of ALK fusion in one positive discordant and two negative discordant cases. Positive protein expression regardless of FISH result correlated more with a positive NGS result compared to samples with a positive FISH result with negative protein expression. FISH analysis was able to detect atypical or heterogenous patterns of rearrangement in a proportion of cases with negative protein expression, which may be associated with more extensive genetic alterations rather than true ALK rearrangement.
A Novel De Novo Missense Mutation in KIF1A Associated with Young-Onset Upper-Limb Amyotrophic Lateral Sclerosis
Authors: Bernard Emilien , Cluse Florent , Bohic Adrien , Hermier Marc , Raoul Cédric , Leblanc Pascal , Guissart Claire
Published: July 2024

We investigate the etiology of amyotrophic lateral sclerosis (ALS) in a 35-year-old woman presenting with progressive weakness in her left upper limb. Prior to sequencing, a comprehensive neurological work-up was performed, including neurological examination, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Six months before evaluation, the patient experienced weakness and atrophy in her left hand, accompanied by brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Trio genome sequencing identified a likely pathogenic de novo variant in the KIF1A gene (NM_001244008.2): c.574A>G, p.(Ile192Val). Pathogenic variants in KIF1A have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). This report describes a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS.
The Many Faces of Hypusinated eIF5A: Cell Context-Specific Effects of the Hypusine Circuit and Implications for Human Health
Authors: Nakanishi Shima , Cleveland John L.
Published: July 2024

The unique amino acid hypusine [Nε-(4-amino-2-hydroxybutyl)lysine] is exclusively formed on the translational regulator eukaryotic initiation factor 5A (eIF5A) via a process coined hypusination. Hypusination is mediated by two enzymes, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH), and hypusinated eIF5A (eIF5AHyp) promotes translation elongation by alleviating ribosome pauses at amino acid motifs that cause structural constraints, and it also facilitates translation initiation and termination. Accordingly, eIF5AHyp has diverse biological functions that rely on translational control of its targets. Homozygous deletion of Eif5a, Dhps, or Dohh in mice leads to embryonic lethality, and heterozygous germline variants in EIF5A and biallelic variants in DHPS and DOHH are associated with rare inherited neurodevelopmental disorders, underscoring the importance of the hypusine circuit for embryonic and neuronal development. Given the pleiotropic effects of eIF5AHyp, a detailed understanding of the cell context-specific intrinsic roles of eIF5AHyp and of the chronic versus acute effects of eIF5AHyp inhibition is necessary to develop future strategies for eIF5AHyp-targeted therapy to treat various human health problems. Here, we review the most recent studies documenting the intrinsic roles of eIF5AHyp in different tissues/cell types under normal or pathophysiological conditions and discuss these unique aspects of eIF5AHyp-dependent translational control.
Promotion of Bone Formation in a Rat Osteoporotic Vertebral Body Defect Model via Suppression of Osteoclastogenesis by Ectopic Embryonic Calvaria Derived Mesenchymal Stem Cells
Authors: Yu Yerin , Lee Somin , Bock Minsung , An Seong Bae , Shin Hae Eun , Rim Jong Seop , Kwon Jun-oh , Park Kwang-Sook , Han Inbo
Published: July 2024

Osteoporotic vertebral compression fractures (OVCFs) are the most prevalent fractures among patients with osteoporosis, leading to severe pain, deformities, and even death. This study explored the use of ectopic embryonic calvaria derived mesenchymal stem cells (EE-cMSCs), which are known for their superior differentiation and proliferation capabilities, as a potential treatment for bone regeneration in OVCFs. We evaluated the impact of EE-cMSCs on osteoclastogenesis in a RAW264.7 cell environment, which was induced by the receptor activator of nuclear factor kappa-beta ligand (RANKL), using cytochemical staining and quantitative real-time PCR. The osteogenic potential of EE-cMSCs was evaluated under various hydrogel conditions. An osteoporotic vertebral body bone defect model was established by inducing osteoporosis in rats through bilateral ovariectomy and creating defects in their coccygeal vertebral bodies. The effects of EE-cMSCs were examined using micro-computed tomography (μCT) and histology, including immunohistochemical analyses. In vitro, EE-cMSCs inhibited osteoclast differentiation and promoted osteogenesis in a 3D cell culture environment using fibrin hydrogel. Moreover, μCT and histological staining demonstrated increased new bone formation in the group treated with EE-cMSCs and fibrin. Immunostaining showed reduced osteoclast activity and bone resorption, alongside increased angiogenesis. Thus, EE-cMSCs can effectively promote bone regeneration and may represent a promising therapeutic approach for treating OVCFs.
Distinctive Deposition Patterns of Sporadic Transthyretin-Derived Amyloidosis in the Atria: A Forensic Autopsy-Based Study
Authors: Ichimata Shojiro , Hata Yukiko , Yoshida Koji , Hirono Keiichi , Nishida Naoki
Published: July 2024

Left-to-right differences in the histopathologic patterns of transthyretin-derived amyloid (ATTR) deposition in the atria of older adults have not yet been investigated. Hence, this study evaluated heart specimens from 325 serial autopsy subjects. The amount of ATTR deposits in the seven cardiac regions, including both sides of atria and atrial appendages, was evaluated semiquantitatively. Using digital pathology, we quantitatively evaluated the immunohistochemical deposition burden of ATTR in the myocardium. We identified 20 sporadic ATTR cardiac amyloidosis cases (nine males). All patients had ATTR deposition in the left atrial regions of the myocardium. In the semiquantitative analysis, 14 of the 20 cases showed more severe ATTR deposition on the left atrial regions than on the right side, with statistically significant differences in the pathology grading (p < 0.01 for both the atrium and atrial appendage). Quantitative analysis further supported the difference. Moreover, six had ATTR deposition in the epineurium and/or neural fibers of the atria. Cluster analysis revealed that ATTR deposition in the myocardium was significantly more severe in males than in females. The heterogeneous distribution of amyloid deposits between atria revealed in this study may impair the orderly transmission of the cardiac conduction system and induce arrhythmias, which may be further aggravated by additional neuropathy in the advanced phase. This impairment could be more severe among males. These findings emphasize that atrial evaluation is important for individuals with sporadic ATTR cardiac amyloidosis, particularly for early detection.
Role of ATG4 Autophagy-Related Protein Family in the Lower Airways of Patients with Stable COPD
Authors: Nucera Francesco , Di Stefano Antonino , Ricciardolo Fabio Luigi Massimo , Gnemmi Isabella , Pizzimenti Cristina , Monaco Francesco , Tuccari Giovanni , Caramori Gaetano , Ieni Antonio
Published: July 2024

Autophagy is a complex physiological pathway mediating homeostasis and survival of cells degrading damaged organelles and regulating their recycling. Physiologic autophagy can maintain normal lung function, decrease lung cellular senescence, and inhibit myofibroblast differentiation. It is well known that autophagy is activated in several chronic inflammatory diseases; however, its role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and the expression of autophagy-related genes (ATGs) in lower airways of COPD patients is still controversial. The expression and localization of all ATG proteins that represented key components of the autophagic machinery modulating elongation, closure, and maturation of autophagosome membranes were retrospectively measured in peripheral lungs of patients with stable COPD (n = 10), control smokers with normal lung function (n = 10), and control nonsmoking subjects (n = 8) using immunohistochemical analysis. These results show an increased expression of ATG4 protein in alveolar septa and bronchiolar epithelium of stable COPD patients compared to smokers with normal lung function and non-smoker subjects. In particular, the genes in the ATG4 protein family (including ATG4A, ATG4B, ATG4C, and ATG4D) that have a key role in the modulation of the physiological autophagic machinery are the most important ATGs increased in the compartment of lower airways of stable COPD patients, suggesting that the alteration shown in COPD patients can be also correlated to impaired modulation of autophagic machinery modulating elongation, closure, and maturation of autophagosomes membranes. Statistical analysis was performed by the Kruskal–Wallis test and the Mann–Whitney U test for comparison between groups. A statistically significant increased expression of ATG4A (p = 0.0047), ATG4D (p = 0.018), and ATG5 (p = 0.019) was documented in the bronchiolar epithelium as well in alveolar lining for ATG4A (p = 0.0036), ATG4B (p = 0.0054), ATG4C (p = 0.0064), ATG4D (p = 0.0084), ATG5 (p = 0.0088), and ATG7 (p = 0.018) in patients with stable COPD compared to control groups. The ATG4 isoforms may be considered as additional potential targets for the development of new drugs in COPD.
Functional Characterization of JcSWEET12 and JcSWEET17a from Physic Nut
Authors: Wu Pingzhi , Wu Youting , Yu Zhu , Jiang Huawu , Wu Guojiang , Chen Yaping
Published: July 2024

Physic nut (Jatropha curcas L.) has attracted extensive attention because of its fast growth, easy reproduction, tolerance to barren conditions, and high oil content of seeds. SWEET (Sugar Will Eventually be Exported Transporter) family genes contribute to regulating the distribution of carbohydrates in plants and have great potential in improving yield and stress tolerance. In this study, we performed a functional analysis of the homology of these genes from physic nut, JcSWEET12 and JcSWEET17a. Subcellular localization indicated that the JcSWEET12 protein is localized on the plasma membrane and the JcSWEET17a protein on the vacuolar membrane. The overexpression of JcSWEET12 (OE12) and JcSWEET17a (OE17a) in Arabidopsis leads to late and early flowering, respectively, compared to the wild-type plants. The transgenic OE12 seedlings, but not OE17a, exhibit increased salt tolerance. In addition, OE12 plants attain greater plant height and greater shoot dry weight than the wild-type plants at maturity. Together, our results indicate that JcSWEET12 and JcSWEET17a play different roles in the regulation of flowering time and salt stress response, providing a novel genetic resource for future improvement in physic nut and other plants.
Light-Induced Charge Separation in Photosystem I from Different Biological Species Characterized by Multifrequency Electron Paramagnetic Resonance Spectroscopy
Authors: Bindra Jasleen K. , Malavath Tirupathi , Teferi Mandefro Y. , Kretzschmar Moritz , Kern Jan , Niklas Jens , Utschig Lisa M. , Poluektov Oleg G.
Published: July 2024

Photosystem I (PSI) serves as a model system for studying fundamental processes such as electron transfer (ET) and energy conversion, which are not only central to photosynthesis but also have broader implications for bioenergy production and biomimetic device design. In this study, we employed electron paramagnetic resonance (EPR) spectroscopy to investigate key light-induced charge separation steps in PSI isolated from several green algal and cyanobacterial species. Following photoexcitation, rapid sequential ET occurs through either of two quasi-symmetric branches of donor/acceptor cofactors embedded within the protein core, termed the A and B branches. Using high-frequency (130 GHz) time-resolved EPR (TR-EPR) and deuteration techniques to enhance spectral resolution, we observed that at low temperatures prokaryotic PSI exhibits reversible ET in the A branch and irreversible ET in the B branch, while PSI from eukaryotic counterparts displays either reversible ET in both branches or exclusively in the B branch. Furthermore, we observed a notable correlation between low-temperature charge separation to the terminal [4Fe-4S] clusters of PSI, termed FA and FB, as reflected in the measured FA/FB ratio. These findings enhance our understanding of the mechanistic diversity of PSI’s ET across different species and underscore the importance of experimental design in resolving these differences. Though further research is necessary to elucidate the underlying mechanisms and the evolutionary significance of these variations in PSI charge separation, this study sets the stage for future investigations into the complex interplay between protein structure, ET pathways, and the environmental adaptations of photosynthetic organisms.
The New Face of Dynamic Mutation—The CAA [CAG]n CAA CAG Motif as a Mutable Unit in the TBP Gene Causative for Spino-Cerebellar Ataxia Type 17
Authors: Hoffman-Zacharska Dorota , Sulek Anna
Published: July 2024

Since 1991, several genetic disorders caused by unstable trinucleotide repeats (TNRs) have been identified, collectively referred to as triplet repeat diseases (TREDs). They share a common mutation mechanism: the expansion of repeats (dynamic mutations) due to the propensity of repeated sequences to form unusual DNA structures during replication. TREDs are characterized as neurodegenerative diseases or complex syndromes with significant neurological components. Spinocerebellar ataxia type 17 (SCA17) falls into the former category and is caused by the expansion of mixed CAA/CAG repeats in the TBP gene. To date, a five-unit organization of this region [(CAG)3 (CAA)3] [(CAG)n] [CAA CAG CAA] [(CAG)n] [CAA CAG], with expansion in the second [(CAG)n] unit being the most common, has been proposed. In this study, we propose an alternative organization scheme for the repeats. A search of the PubMed database was conducted to identify articles reporting both the number and composition of GAC/CAA repeats in TBP alleles. Nineteen reports were selected. The sequences of all identified CAG/CAA repeats in the TBP locus, including 67 cases (probands and b relatives), were analyzed in terms of their repetition structure and stability in inheritance, if possible. Based on the analysis of three units [(CAG)3 (CAA)2] [CAA (CAG)n CAA CAG] [CAA (CAG)n CAA CAG], the organization of repeats is proposed. Detailed analysis of the CAG/CAA repeat structure, not just the number of repeats, in TBP-expanded alleles should be performed, as it may have a prognostic value in the prediction of stability/instability during transmission and the possible anticipation of the disease.
MiR-223-3p in Cancer Development and Cancer Drug Resistance: Same Coin, Different Faces
Authors: Barbagallo Davide , Ponti Donatella , Bassani Barbara , Bruno Antonino , Pulze Laura , Akkihal Shreya A. , George-William Jonahunnatha N. , Gundamaraju Rohit , Campomenosi Paola
Published: July 2024

MicroRNAs (miRNAs) are mighty post-transcriptional regulators in cell physiology and pathophysiology. In this review, we focus on the role of miR-223-3p (henceforth miR-223) in various cancer types. MiR-223 has established roles in hematopoiesis, inflammation, and most cancers, where it can act as either an oncogenic or oncosuppressive miRNA, depending on specific molecular landscapes. MiR-223 has also been linked to either the sensitivity or resistance of cancer cells to treatments in a context-dependent way. Through this detailed review, we highlight that for some cancers (i.e., breast, non-small cell lung carcinoma, and glioblastoma), the oncosuppressive role of miR-223 is consistently reported in the literature, while for others (i.e., colorectal, ovarian, and pancreatic cancers, and acute lymphocytic leukemia), an oncogenic role prevails. In prostate cancer and other hematological malignancies, although an oncosuppressive role is frequently described, there is less of a consensus. Intriguingly, NLRP3 and FBXW7 are consistently identified as miR-223 targets when the miRNA acts as an oncosuppressor or an oncogene, respectively, in different cancers. Our review also describes that miR-223 was increased in biological fluids or their extracellular vesicles in most of the cancers analyzed, as compared to healthy or lower-risk conditions, confirming the potential application of this miRNA as a diagnostic and prognostic biomarker in the clinic.
The Diel Activity Pattern of Haemaphysalis longicornis and Its Relationship with Climatic Factors
Authors: Noh Byung-Eon , Kim Gi-hun , Lee Hak Seon , Kim Hyunwoo , Lee Hee-Il
Published: July 2024

Haemaphysalis longicornis is one of the most medically important carriers of various pathogens. Although H. longicornis is an important vector, only basic ecological and biological information has been obtained, primarily focusing on its abundance and distribution. This study determined the most active time and meteorological conditions for the diel activity of H. longicornis. The diel activity pattern of H. longicornis was the highest between 10:00 and 14:00, and the lowest between 22:00 and 02:00. The major activity temperature of H. longicornis was between 25 °C and 40 °C, with the highest activity at 35 °C. The relative humidity was between 30% and 70% during the active period. Temperature had the highest correlation with diel activity (R = 0.679), followed by humidity (R = −0.649) and light intensity (R = 0.572). Our results provide basic information for the development of tick-borne disease vector control programs and tick surveillance.
Safe Transition from Open to Total Minimally Invasive Esophagectomy for Cancer Utilizing Process Management Methodology
Authors: Bjelovic Milos , Gunjic Dragan , Babic Tamara , Veselinovic Milan , Djukanovic Marija , Potkonjak Dario , Milosavljevic Vladimir
Published: July 2024

Background: The global shift from open esophagectomy (OE) to minimally invasive esophagectomy (MIE) for treating esophageal cancer is well-established. Recent data indicate that transitioning from hybrid minimally invasive esophagectomy (hMIE) to total minimally invasive esophagectomy (tMIE) can be challenging due to concerns about higher leakage rates and lower lymph node counts, especially at the beginning of the learning curve. This study aimed to demonstrate that a safe transition from OE to tMIE for cancer is possible using process management methodology. Methods: A step-change approach was adopted in process management planning, with hMIE serving as an intermediate step between OE and tMIE. This single-center, case–control study included 150 patients who underwent the Ivor Lewis procedure with curative intent for esophageal cancer. Among these patients, 50 underwent OE, 50 hMIE (laparoscopic procedure followed by conventional right thoracotomy), and 50 tMIE (laparoscopic and thoracoscopic approach). A preceptored training scheme was implemented during execution, and treatment results were monitored and controlled to ensure a safe transition. Results: During the transition, the tMIE group was not worse than the hMIE and OE groups regarding operation duration (p = 0.135), overall postoperative complications (p = 0.020), anastomotic leakage rates (p = 0.773), 30-day mortality (p = 1.0), and oncological outcomes (based on R status (p = 0.628) and 2-year survival (p = 0.967)). Additionally, the tMIE group showed superior results in terms of major postoperative pulmonary complications (p = 0.004) and ICU stay duration (p < 0.001). Conclusions: Utilizing managerial methodology and practice in surgery, as a bridge between interdisciplinary and transdisciplinary approaches, demonstrated that transitioning from OE to tMIE, with hMIE as an intermediate step, is safe and feasible without compromising outcomes.
Clinical Characteristics and Outcomes of Extrapulmonary Nontuberculous Mycobacterial Infections in a Tertiary-Care Hospital: A Retrospective Study
Authors: Kim Seulki , Kim A Reum , Bae Moonsuk , Lim Seungjin , Lee Su Jin
Published: July 2024

Background/Objectives: The incidence of nontuberculous mycobacterial (NTM) infections has increased globally; however, the clinical manifestations and optimal treatment strategies for extrapulmonary NTM infections remain poorly defined. This study assessed the clinical manifestations and treatment outcomes of extrapulmonary NTM infections. Methods: Data from adult patients with suspected extrapulmonary NTM infections at a tertiary-care hospital from 2009–2022 were categorized into NTM disease and isolation groups. Diagnosis of NTM disease relied on stringent criteria, whereas isolation required NTM isolation without meeting the criteria for infection. Results: Among 75 patients evaluated, 32 (42%) were diagnosed with NTM disease and 43 (57%) with NTM isolation. History of immunosuppressant use within the past 3 months (p = 0.070) and injection (p = 0.001) were more frequent in the disease group. The median interval from symptom onset to evaluation was 106.6 and 20 days in the disease and isolation groups, respectively. The prevalence of positive NTM polymerase chain reaction results (36.4%, p = 0.003) and acid-fast bacillus staining (39.1%, p < 0.001) was significantly higher in the disease group than in the isolation group. Mycobacterium intracellulare (21.9%), M. abscessus (15.6%), M. chelonae (9.4%), and M. fortuitum complex (9.4%) were the most frequently identified species. Of the 27 patients in the disease group who received treatment, 13 improved, four experienced treatment failure, seven were lost to follow-up, and three died during treatment, with one death directly attributable to NTM disease. Conclusions: NTM disease exhibits a spectrum of clinical manifestations. Accurate diagnosis is crucial for initiating effective treatment.
The Usefulness of Virtual Reality in Symptom Management during Chemotherapy in Lung Cancer Patients: A Quasi-Experimental Study
Authors: Mitello Lucia , Marti Flavio , Mauro Lucia , Siano Ludovica , Pucci Antonello , Tarantino Concetta , Rocco Gennaro , Stievano Alessandro , Iacorossi Laura , Anastasi Giuliano , Ferrara Rosaria , Marucci Anna Rita , Varrassi Giustino , Giannarelli Diana , Latina Roberto
Published: July 2024

Background: Virtual reality (VR) emerges as a promising non-pharmacological intervention for managing symptoms and providing distraction during chemotherapy. This study aims to assess VR’s effectiveness on cancer-related symptoms, vital signs, and the patients’ perception of chemotherapy in lung cancer patients. Methods: A quasi-experimental study was conducted on 100 patients. Participants were allocated into an intervention group (n = 55), which experienced immersive VR, and a comparison group (n = 45), which received usual care. Data were collected through questionnaires and checklists, including feedback on the VR experience, pain, vital signs, and common cancer symptoms, assessed through the Edmonton Symptom Assessment Scale. Results: VR had a significant impact on reducing the perception of chemotherapy length. Patients reported high levels of satisfaction and tolerability. No adverse events were observed. VR did not have significant influence on pain intensity or vital signs. The only exceptions were oxygen saturation, where a significant difference (p = 0.02) was reported, and the perception of chemotherapy duration. Conclusions: As a non-pharmacological intervention, VR proves to be beneficial in minimizing the perceived length of chemotherapy sessions for lung cancer patients, enhancing their overall treatment experience. The intervention was found to be a safe, feasible, and well-accepted distraction technique. Future research should explore VR’s potential effects on a wider range of symptoms and evaluate its impact on long-term outcomes.
Navigating Life with Posterior Urethral Valves—Sexual Health and Lower Urinary Tract Symptoms
Authors: Zöhrer Pirmin I. , Vauth Franziska , Jaekel Anke K. , Rösch Wolfgang H. , Hofmann Aybike
Published: July 2024

Background: Quality of life (QoL) is crucial for young adults with posterior urethral valves (PUV). This study investigates the impact of lower urinary tract symptoms (LUTS) on their quality of life and sexual health, including self-efficacy. Methods: Patients aged 16 and older treated for PUV completed four validated questionnaires (Sexual Self-Efficacy Scale (SSES-E), ICIQ MLUTS, ICIQ MLUTSsex, ICIQ LUTSqol) and an individual health questionnaire. Results: Eighteen (52.9%) patients responded, with a median age of 23 years (IQR 18–26). Three had terminal renal failure; two were transplanted. Thirteen urinated naturally; five used a stoma. Sixteen had mild and two had moderate LUTS. Fifteen patients completed the SSES-E, scoring an average of 80, similar to the healthy cohort (83). Renal failure or catheterization did not significantly affect the overall score. In the ICIQ MLUTSsex, patients reported no significant impact of LUTS on sexuality. However, those with moderate LUTS had lower self-efficacy than those with mild symptoms (mean 75 vs. 84). Conclusions: Although quality of life and sexual function do not appear to be significantly impaired, LUTS are common and appear to be associated with a decreased SSE in our cohort. This should be particularly considered during the transition to adult care.
Oleic Acid and Linoleic Acid Enhances the Biocontrol Potential of Metarhizium rileyi
Authors: Wang Guang , Zhang Xu , Du Guangzu , Wang Wenqian , Yao Yunhao , Jin Sitong , Cai Haosheng , Peng Yuejin , Chen Bin
Published: July 2024

Metarhizium rileyi is a wide spread insect fungi with a good biocontrol potentiality to various pests, particularly noctuid insects. However, it is characterized by its slow growth, its sensitivity to abiotic stress, and the slow speed of kill to pests, which hinder its use compared with other entomopathogenic fungi. In this study, the responses of M. rileyi to eight types of lipids were observed; among the lipids, oleic acid and linoleic acid significantly promoted the growth and development of M. rileyi and enhanced its stress tolerances and virulence. An additional mechanistic study demonstrated that exogenous oleic acid and linoleic acid significantly improved the conidial germination, appressorium formation, cuticle degradation, and cuticle infection, which appear to be largely dependent on the up-regulation of gene expression in growth, development, protective, and cuticle-degrading enzymes. In conclusion, exogenous oleic acid and linoleic acid enhanced the stress tolerances and virulence of M. rileyi via protecting conidial germination and promoting cuticle infection. These results provide new insights for the biopesticide development of M. rileyi.
Breast Cancer Detection and Analytics Using Hybrid CNN and Extreme Learning Machine
Authors: Sureshkumar Vidhushavarshini , Prasad Rubesh Sharma Navani , Balasubramaniam Sathiyabhama , Jagannathan Dhayanithi , Daniel Jayanthi , Dhanasekaran Seshathiri
Published: July 2024

Early detection of breast cancer is essential for increasing survival rates, as it is one of the primary causes of death for women globally. Mammograms are extensively used by physicians for diagnosis, but selecting appropriate algorithms for image enhancement, segmentation, feature extraction, and classification remains a significant research challenge. This paper presents a computer-aided diagnosis (CAD)-based hybrid model combining convolutional neural networks (CNN) with a pruned ensembled extreme learning machine (HCPELM) to enhance breast cancer detection, segmentation, feature extraction, and classification. The model employs the rectified linear unit (ReLU) activation function to enhance data analytics after removing artifacts and pectoral muscles, and the HCPELM hybridized with the CNN model improves feature extraction. The hybrid elements are convolutional and fully connected layers. Convolutional layers extract spatial features like edges, textures, and more complex features in deeper layers. The fully connected layers take these features and combine them in a non-linear manner to perform the final classification. ELM performs classification and recognition tasks, aiming for state-of-the-art performance. This hybrid classifier is used for transfer learning by freezing certain layers and modifying the architecture to reduce parameters, easing cancer detection. The HCPELM classifier was trained using the MIAS database and evaluated against benchmark methods. It achieved a breast image recognition accuracy of 86%, outperforming benchmark deep learning models. HCPELM is demonstrating superior performance in early detection and diagnosis, thus aiding healthcare practitioners in breast cancer diagnosis.
Novel Surgical Technique for Total Knee Arthroplasty Integrating Kinematic Alignment and Real-Time Elongation of the Ligaments Using the NextAR System
Authors: Sabatini Luigi , Ascani Daniele , Vezza Daniele , Massè Alessandro , Cacciola Giorgio
Published: July 2024

This study introduces an innovative surgical approach for total knee arthroplasty (TKA) that combines kinematic alignment (KA) principles with real-time elongation of the knee ligaments through the range of motion, using augmented reality (AR). The novelty of the surgical technique lies in the possibility of enhancing the decision-making process to perform the cut on the tibia as for the KA caliper technique developed by Dr. Stephen Howell. The NextAR is a CT-based AR system that offers the possibility of performing three-dimensional surgical preoperative planning and an accurate execution in the surgical room through single-use infrared sensors, smart glasses, and a control unit. During the preoperative planning, the soft tissue is not considered and only the alignment based on bony reference is ensured. Thanks to the possibility of measuring in real time the elongation of the knee collateral lateral ligaments, the system assists the surgeon in optimizing the cut on the tibia after an accurate resurfacing of the femur as described in the KA surgical technique. The implant used in this novel approach is a medial pivot design (Medacta GMK Sphere) that allows the restoration of the physiological behavior of the software tissue and natural knee kinematics. In conclusion, this novel technique offers a promising approach to TKA, allowing personalized treatment tailored to each patient’s unique anatomy and soft tissue characteristics. The integration of KA and real-time soft tissue analysis provided by NextAR enhances surgical precision and outcomes, potentially improving patient satisfaction and functional results.
Mapping the Functional Structure of Urban Agglomerations at the Block Level: A New Spatial Classification That Goes beyond Land Use
Authors: Ai Bin , Lai Zhenlin , Ma Shifa
Published: July 2024

The functional structure of territorial space is an important factor for analyzing the interaction between humans and nature. However, the classification of remote sensing images struggles to distinguish between multiple functions provided by the same land use type. Therefore, we propose a framework to combine multi-source data for the recognition of dominant functions at the block level. Taking the Guangdong–Hong Kong–Macau Greater Bay Area (GBA) as a case study, its block-level ‘production–living–ecology’ functions were interpreted. The whole GBA was first divided into different blocks and its total, average, and proportional functional intensities were then calculated. Each block was labeled as a functional type considering the attributes of human activity and social information. The results show that the combination of land use/cover data, point of interest identification, and open street maps can efficiently separate the multiple and mixed functions of the same land use types. There is a great difference in the dominant functions of the cities in the GBA, and the spatial heterogeneity of their mixed functions is closely related to the development of their land resources and socio-economy. This provides a new perspective for recognizing the spatial structure of territorial space and can give important data for regulating and optimizing landscape patterns during sustainable development.
Adaptation and Validation of a Modified Broth Microdilution Method for Screening the Anti-Yeast Activity of Plant Phenolics in Apple and Orange Juice Models
Authors: Staš Jan , Houdkova Marketa , Banout Jan , Duque-Dussán Eduardo , Roubík Hynek , Kokoska Ladislav
Published: July 2024

Yeasts are the usual contaminants in fruit juices and other beverages, responsible for the decrease in the quality and shelf-life of such products. Preservatives are principally added to these beverages to enhance their shelf-life. With the increasing consumer concern towards chemical food additives, plant-derived antimicrobials have attracted the attention of researchers as efficient and safer anti-yeast agents. However, the methods currently used for determining their anti-yeast activity are time- and material-consuming. In this study, the anti-yeast effect of plant phenolic compounds in apple and orange juice food models using microtiter plates has been evaluated in order to validate the modified broth microdilution method for screening the antimicrobial activity of juice preservative agents. Among the twelve compounds tested, four showed a significant in vitro growth-inhibitory effect against all tested yeasts (Saccharomyces cerevisiae, Zygosaccharomyces bailii, and Zygosaccharomyces rouxii) in both orange and apple juices. The best results were obtained for pterostilbene in both juices with minimum inhibitory concentrations (MICs) ranging from 32 to 128 μg/mL. Other compounds, namely oxyresveratrol, piceatannol, and ferulic acid, exhibited moderate inhibitory effects with MICs of 256–512 μg/mL. Furthermore, the results indicated that differences in the chemical structures of the compounds tested significantly affected the level of yeast inhibition, whereas stilbenes with methoxy and hydroxy groups produced the strongest effect. Furthermore, the innovative assay developed in this study can be used for screening the anti-yeast activity of juice preservative agents because it saves preparatory and analysis time, laboratory supplies, and manpower in comparison to the methods commonly used.
Synthesis and Characterization of Novel Indazole–Sulfonamide Compounds with Potential MAPK1 Inhibitory Activity for Cancer Treatment
Authors: Saghdani Nassima , Chihab Abdelali , El Brahmi Nabil , El Kazzouli Saïd
Published: July 2024

Indazoles are a very important group of nitrogen-containing heterocycles with a wide range of biological and medicinal applications. These properties make them highly attractive for drug development, particularly when combined with sulfonamides to enhance their medicinal potential. In this work, we synthesized an indazole-based sulfonamide, namely the 1-((2-chloro-5-methoxyphenyl)sulfonyl)-5-nitro-1H-indazole (3). The reduction of the nitro group of 5-nitroindazole (1) to its corresponding amine was also performed to yield compound (4). Both compounds’ structures were elucidated using various spectroscopic techniques such as 1H NMR, 13C NMR, infrared (IR), and high-resolution mass spectrometry (HRMS). Our molecular docking studies suggest that compounds (3) and (4) have a strong affinity for MAPK1, indicating their potential as cancer treatments.
Compressive Behavior of Novel Additively Manufactured Ti-6Al-4V Lattice Structures: Experimental and Numerical Studies
Authors: Aljaberi Mohammed Hussein Kadhim , Aghdam Mohammad M. , Goudarzi Taha , Al-Waily Muhannad
Published: July 2024

This paper presents novel configurations for additively manufactured lattice structures, including helical and elliptic designs, in addition to the pyramid base model. Functionally graded versions of the pyramid and elliptic lattice structures are developed by considering desirable relative densities in each layer. The lattice structures were manufactured using Ti-6Al-4V powder in a three-dimensional selective laser melting printer. The averaged porosities are 0.86, 0.91, 0.916, 0.93 and 0.74 for pyramid, functionally graded pyramid, elliptic, functionally graded elliptic and helical, respectively. The mechanical behavior of the lattice structures was characterized through compression tests using a universal testing machine and computationally analyzed using finite element code. The results indicate that the elliptic and functionally graded elliptic lattices have elastic moduli of 0.76 and 0.67 GPa, while the yield strengths are 41.32 and 32.24 MPa, respectively, in comparison to cancellous bone. Moreover, pyramid, functionally graded pyramid, and helical lattices show relatively lower elastic moduli of 0.57, 0.65 and 0.41 GPa and higher yield strengths of 54.1, 52.15 and 61.02 MPa, respectively. This could be an indication that they are fit for cortical bones. All samples have low elastic moduli coupled with high yield strengths. This could reduce or eliminate stress shielding, making them suitable for some load-bearing bio-inspired applications. A comparative study utilizing experimental and numerical models was conducted to evaluate the performance of the proposed designs.
Strain Measurement during Quasi-Static and Cyclic Loads in AL-6XN Material Using Digital Image Correlation Technique
Authors: Ramírez-Acevedo Donovan , Ambriz Ricardo Rafael , García Christian Jesús , Mendoza Cesar , Jaramillo David
Published: July 2024

A customized digital image correlation (DIC) system was implemented to monitor the strain produced in a cold-rolled AL-6XN stainless steel plate, 3.0 mm thick, subjected to quasi-static and cyclic loading tests. A comparison of the DIC strain measurements was made against those provided by conventional extensometers. Furthermore, the DIC system was used to monitor the fatigue crack initiation in low-cycle fatigue tests. The true stress–strain behavior for the AL-6XN material was properly captured by the DIC measurements. For low-cycle fatigue tests (strain control), the strain mapping generated by DIC allowed for identifying zones with higher strain than the nominal strain amplitude applied (εa) since the first stages of the fatigue life (FL). These zones become potential fatigue crack initiation sites.
Optimization and Modelling of the Physical and Mechanical Properties of Grass Fiber Reinforced with Slag-Based Composites Using Response Surface Methodology
Authors: Ma Jiale , He Long , Wu Zhixin , Hou Jiarui
Published: July 2024

The construction industry’s high energy consumption and carbon emissions negatively impact the ecological environment; large-scale construction projects consume much energy and emit a significant amount of CO2 into the atmosphere. Statistics show that 30% of energy loss and 40% of solid waste in the construction industry are generated during construction. Therefore, reducing emissions during construction has significant research potential and value. Many scholars have recently studied eco-friendly building materials to facilitate the use of high-carbon emission materials like cement. Adding fibers to composite materials has become a research hotspot among these studies. Although adding fibers to composite materials has many advantages, it mainly reduces the compressive strength of the composite material. This research used the response surface methodology (RSM) to optimize the raw material ratios and thus improve the performance of plant fiber composite materials. Single-factor experiments were conducted to analyze the effects of grass size, grass content, and quicklime content on the composite materials’ compressive strength, flexural strength, and water absorption. The influencing factors and levels for the response surface experiment were determined based on the results of the single-factor analysis. Using the response surface methodology (RSM), a second-order polynomial regression model was established to analyze the interaction effects of the three factors on the composite materials’ compressive strength, flexural strength, and water absorption rate. The optimal ratio was determined: the optimized options for grass size, grass content, and quicklime content are 2.0 mm, 8.2 g, and 38 g, respectively. The actual values of compressive strength, flexural strength, and water absorption rate of the composite materials made according to the predicted ratio are 11.425 MPa, 2.145 MPa, and 21.89%, respectively, with a relative error of 8% between the actual and predicted values. X-ray diffraction and scanning electron microscopy were also used to reveal the factors contributing to the relatively high strength of the optimized samples.