bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycobacteriophage Alexphander Gene 94 Encodes an Essential dsDNA-Binding Protein during Lytic Infection
Authors: Chong Qui Emmanuel , Habtehyimer Feben , Germroth Alana , Grant Jason , Kosanovic Lea , Singh Ivana , Hancock Stephen P.
Published: July 2024

Mycobacteriophages are viruses that specifically infect bacterial species within the genera Mycobacterium and Mycolicibacterium. Over 2400 mycobacteriophages have been isolated on the host Mycolicibacterium smegmatis and sequenced. This wealth of genomic data indicates that mycobacteriophage genomes are diverse, mosaic, and contain numerous (35–60%) genes for which there is no predicted function based on sequence similarity to characterized orthologs, many of which are essential to lytic growth. To fully understand the molecular aspects of mycobacteriophage–host interactions, it is paramount to investigate the function of these genes and gene products. Here we show that the temperate mycobacteriophage, Alexphander, makes stable lysogens with a frequency of 2.8%. Alexphander gene 94 is essential for lytic infection and encodes a protein predicted to contain a C-terminal MerR family helix–turn–helix DNA-binding motif (HTH) and an N-terminal DinB/YfiT motif, a putative metal-binding motif found in stress-inducible gene products. Full-length and C-terminal gp94 constructs form high-order nucleoprotein complexes on 100–500 base pair double-stranded DNA fragments and full-length phage genomic DNA with little sequence discrimination for the DNA fragments tested. Maximum gene 94 mRNA levels are observed late in the lytic growth cycle, and gene 94 is transcribed in a message with neighboring genes 92 through 96. We hypothesize that gp94 is an essential DNA-binding protein for Alexphander during lytic growth. We proposed that gp94 forms multiprotein complexes on DNA through cooperative interactions involving its HTH DNA-binding motif at sites throughout the phage chromosome, facilitating essential DNA transactions required for lytic propagation.
Effects of Recombinant α1-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to 177Lu-Octreotate
Authors: Ytterbrink Charlotte , Shubbar Emman , Parris Toshima Z. , Langen Britta , Druid Malin , Schüler Emil , Strand Sven-Erik , Åkerström Bo , Gram Magnus , Helou Khalil , Forssell-Aronsson Eva
Published: July 2024

Recombinant α1-microglobulin (A1M) is proposed as a protector during 177Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but the radioprotective action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after 177Lu-octreotate and/or A1M administration. Mice were injected with 177Lu-octreotate and/or A1M, while control mice received saline or A1M vehicle solution. Bone marrow, kidney medulla, and kidney cortex were sampled after 24 h or 7 d. The differential protein expression was analyzed with tandem mass spectrometry. The dosimetric estimation was based on 177Lu activity in the kidney. PHLDA3 was the most prominent radiation-responsive protein in kidney tissue. In general, no statistically significant difference in the expression of radiation-related proteins was observed between the irradiated groups. Most canonical pathways were identified in bone marrow from the 177Lu-octreotate+A1M group. Altogether, a tissue-dependent proteomic response followed exposure to 177Lu-octreotate alone or together with A1M. Combining 177Lu-octreotate with A1M did not inhibit the radiation-induced protein expression early after exposure, and late effects should be further studied.
Deficiency of ValRS-m Causes Male Infertility in Drosophila melanogaster
Authors: Duan Xin , Wang Haolin , Cao Zhixian , Su Na , Wang Yufeng , Zheng Ya
Published: July 2024

Drosophila spermatogenesis involves the renewal of germline stem cells, meiosis of spermatocytes, and morphological transformation of spermatids into mature sperm. We previously demonstrated that Ocnus (ocn) plays an essential role in spermatogenesis. The ValRS-m (Valyl-tRNA synthetase, mitochondrial) gene was down-regulated in ocn RNAi testes. Here, we found that ValRS-m-knockdown induced complete sterility in male flies. The depletion of ValRS-m blocked mitochondrial behavior and ATP synthesis, thus inhibiting the transition from spermatogonia to spermatocytes, and eventually, inducing the accumulation of spermatogonia during spermatogenesis. To understand the intrinsic reason for this, we further conducted transcriptome-sequencing analysis for control and ValRS-m-knockdown testes. The differentially expressed genes (DEGs) between these two groups were selected with a fold change of ≥2 or ≤1/2. Compared with the control group, 4725 genes were down-regulated (dDEGs) and 2985 genes were up-regulated (uDEGs) in the ValRS-m RNAi group. The dDEGs were mainly concentrated in the glycolytic pathway and pyruvate metabolic pathway, and the uDEGs were primarily related to ribosomal biogenesis. A total of 28 DEGs associated with mitochondria and 6 meiosis-related genes were verified to be suppressed when ValRS-m was deficient. Overall, these results suggest that ValRS-m plays a wide and vital role in mitochondrial behavior and spermatogonia differentiation in Drosophila.
Survival Difference of Endometrial Cancer Patients with Peritoneal Metastasis Receiving Cytoreductive Surgery (CRS) with and without Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Systematic Review and Meta-Analysis
Authors: Panczel Ivan , Acs Miklos , Herold Magdolna , Madar-Dank Viktor , Piso Pompiliu , Schlitt Hans Jürgen , Dank Magdolna , Szasz Attila Marcell , Herold Zoltan
Published: July 2024

Although several studies have been completed to investigate the effect of cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in endometrial cancer with peritoneal metastasis (ECPM), a direct comparison was not performed previously. A meta-analysis was performed to investigate the suspected additional survival benefits of CRS plus HIPEC over CRS only. Twenty-one and ten studies with a total number of 1116 and 152 cases investigating CRS only and CRS plus HIPEC were identified, respectively. When all articles were analyzed, the 1-year survival rate was 17.60% higher for CRS plus HIPEC (82.28% vs. 64.68%; p = 0.0102). The same tendency was observed for the 2-year (56.07% vs. 36.95%; difference: 19.12%; p = 0.0014), but not for the 5-year (21.88% vs. 16.45%; difference: 5.43%; p = 0.3918) survival rates. The same clinical significance, but statistically less strong observations, could be made if only the studies published after 2010 were investigated (1-year survival rate: 12.08% and p = 0.0648; 2-year survival rate: 10.90% and p = 0.0988). CRS remains one of the core elements of ECPM treatment, but the addition of HIPEC to CRS can increase the positive clinical outcome, especially in the first 2 years.
Phylogenetics, Molecular Species Delimitation and Geometric Morphometrics of All Reddish-Brown Species in the Genus Neotriplax Lewis, 1887 (Coleoptera: Erotylidae: Tritomini)
Authors: Liu Jing , Xu Huixin , Wang Ziqing , Li Panpan , Yan Zihan , Bai Ming , Li Jing
Published: July 2024

To date, five species of reddish-brown Neotriplax have been described, but their highly similar body color and other phenotypic traits make accurate taxonomy challenging. To clarify species-level taxonomy and validate potential new species, the cytochrome oxidase subunit I (COI) was used for phylogenetic analysis and the geometric morphometrics of elytron, pronotum, and hind wing were employed to distinguish all reddish-brown Neotriplax species. Phylogenetic results using maximum likelihood and Bayesian analyses of COI sequences aligned well with the current taxonomy of the Neotriplax species group. Significant K2P divergences, with no overlap between intra- and interspecific genetic distances, were obtained in Neotriplax species. The automatic barcode gap discovery (ABGD), assemble species by automatic partitioning (ASAP), and generalized mixed Yule coalescent (GMYC) approaches concurred, dividing the similar species into eight molecular operational taxonomic units (MOTUs). Geometric morphometric analysis using pronotum, elytron, hind wing shape and wing vein patterns also validated the classification of all eight species. By integrating these analytical approaches with morphological evidence, we successfully delineated the reddish-brown species of Neotriplax into eight species with three new species: N. qinghaiensis sp. nov., N. maoershanensis sp. nov., and N. guangxiensis sp. nov. Furthermore, we documented the first record of N. lewisii in China. This study underscores the utility of an integrative taxonomy approach in species delimitation within Neotriplax and serves as a reference for the taxonomic revision of other morphologically challenging beetles through integrative taxonomy.
Genome-Wide Identification and Expression Pattern of Sugar Transporter Genes in the Brown Planthopper, Nilaparvata lugens (Stål)
Authors: Shangguan Xinxin , Yang Xiaoyu , Wang Siyin , Geng Lijie , Wang Lina , Zhao Mengfan , Cao Haohao , Zhang Yi , Li Xiaoli , Yang Mingsheng , Xu Kedong , Zheng Xiaohong
Published: July 2024

Sugar transporters play important roles in controlling carbohydrate transport and are responsible for mediating the movement of sugars into cells in numerous organisms. In insects, sugar transporters not only play a role in sugar transport but may also act as receptors for virus entry and the accumulation of plant defense compounds. The brown planthopper, Nilaparvata lugens, inflicts damage on rice plants by feeding on their phloem sap, which is rich in sugars. In the present study, we identified 34 sugar transporters in N. lugens, which were classified into three subfamilies based on phylogenetic analysis. The motif numbers varied from seven to eleven, and motifs 2, 3, and 4 were identified in the functional domains of all 34 NlST proteins. Chromosome 1 was found to possess the highest number of NlST genes, harboring 15. The gut, salivary glands, fat body, and ovary were the different tissues enriched with NlST gene expression. The expression levels of NlST2, 3, 4, 7, 20, 27, 28, and 31 were higher in the gut than in the other tissues. When expressed in a Saccharomyces cerevisiae hexose transporter deletion mutant (strain EBY.VW4000), only ApST4 (previously characterized) and NlST4, 28, and 31 were found to transport glucose and fructose, resulting in functional rescue of the yeast mutant. These results provide valuable data for further studies on sugar transporters in N. lugens and lay a foundation for finding potential targets to control N. lugens.
A Review of the Density, Biomass, and Secondary Production of Odonates
Authors: Rivas-Torres Anais , Cordero-Rivera Adolfo
Published: July 2024

Freshwater insects are highly significant as ecosystem service providers, contributing to provisioning services, supporting services, and cultural services. Odonates are dominant predators in many freshwater systems, becoming top predators in fishless ecosystems. One service that odonates provide is the export of matter and energy from aquatic to terrestrial ecosystems. In this study, we provide a review of the literature aiming to estimate the density, biomass, and secondary production of odonates and discuss to what extent this order of insects is relevant for the fertilization of terrestrial ecosystems. We found published data on 109 species belonging to 17 families of odonates from 44 papers. Odonata larvae are abundant in freshwater systems, with a mean density of 240.04 ± 48.01 individuals m−2 (±SE). Lentic habitats show much higher densities (104.40 ± 55.31 individuals m−2, N = 118) than lotic systems (27.12 ± 5.09, N = 70). The biomass estimations for odonates indicate values of 488.56 ± 134.51 mg m−2 y−1, with similar values in lentic and lotic habitats, which correspond to annual secondary productions of 3558.02 ± 2146.80 mg m−2 y−1. The highest biomass is found in dragonflies of the Aeshnidae, Corduliidae, and Gomphidae families. The available evidence suggests a significant potential contribution of Odonata to the exportation of material from water bodies to land. This is further strengthened by the ability of adult odonates to migrate and to colonize different types of water bodies.
Effects of Remimazolam versus Sevoflurane on Hemodynamics in Patients Undergoing Coil Embolization of Cerebral Aneurysm: A Prospective Randomized Controlled Trial
Authors: Ko Eunji , Je Lee Gyeong , Kim Jang Hun , Song Yeon Jae , Lim Choon Hak
Published: July 2024

Background: Cerebral aneurysm coil embolization is often performed under general anesthesia to prevent patient movement and sudden high blood pressure. However, the optimal anesthetic agent remains uncertain. This study aimed to determine whether maintaining anesthesia with remimazolam in patients undergoing coil embolization could avoid hypotension or hypertension compared to sevoflurane. Methods: Thirty-three adult patients participated in this single-blinded, randomized controlled trial. Patients in Group R were induced and maintained with remimazolam, whereas those in Group S received propofol and sevoflurane. Results: The use of remimazolam significantly reduced the incidence of intraoperative hypotension events (33.3% vs. 80.0%; p = 0.010) but did not change the incidence of hypertension events (66.7% vs. 73.3%; p = 0.690). Patients in Group R maintained a significantly higher range of maximal (100.2 ± 16.6 vs. 88.1 ± 13.5 mmHg; p = 0.037) and minimal (69.4 ± 6.6 vs. 63.4 ± 4.8 mmHg; p = 0.008) mean arterial blood pressure than those in Group S during the intervention. Conclusions: This is the first study to demonstrate the feasibility of maintaining general anesthesia with remimazolam in patients undergoing cerebral aneurysm coil embolization. The findings suggest that remimazolam may maintains better hemodynamic stability, reducing the incidence of hypotensive events without compromising patient safety.
Natural History of Visual Acuity and Microperimetry-Based Functional Outcome Measures of the Macula in Patients with Geographic Atrophy: A Retrospective Chart Review Study in Germany
Authors: Kohlhas Paul , Abdin Alaa Din , Aljundi Wissam , Mattern Ann-Isabel , Devenijn Machteld , Borchert Kathrin , Fricke Andreas , Viering Tammo , Wasem Jürgen , Seitz Berthold , Kaymak Hakan
Published: July 2024

Background/Objectives: Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) leading to the progressive and irreversible loss of visual function. Characteristics of GA include atrophic lesions resulting from the loss of photoreceptors, retinal pigment epithelium, and choriocapillaris. During GA progression, atrophic lesions typically advance from the macular periphery to the center, affecting foveal light sensitivity and visual acuity. This study analyzed changes in light sensitivity and visual acuity during the natural course of GA progression using the topographic analysis of structural and functional changes based on Early Treatment Diabetic Retinopathy Study (ETDRS) charts, multimodal imaging, and microperimetry assessment. Methods: Medical chart data of GA patients between 2014 and 2022 from the Internationale Innovative Ophthalmochirurgie GbR (I.I.O.) research center (Düsseldorf, Germany) were retrospectively analyzed. All patient eyes fulfilling the phase 3 OAKS study inclusion criteria were included and followed up for 60 months. The imputation of missing measurements and dropouts was performed by linear mixed models. Results: A total of 20 GA eyes from 13 GA patients were included in the study. At the index, 53.8% of patients had bilateral GA, with 70.0% of the eyes showing multifocal GA and 30.0% subfoveal encroachment (SFE). A total of 35.0% of the eyes had 2–5, and 15.0% over 20, areas of atrophy. Over time, the GA lesion size increased from 6.4 mm2 to 11.8 mm2 (1.08 mm2/year). After an average observation time of 2.9 years, 78.6% of the initially unaffected study eyes developed SFE. The percentage of study eyes without visual impairment decreased from 55.0% to 30.0%, with mean normal-luminance best-corrected visual acuity (NL-BCVA) reducing from 63.7 to 55.7 ETDRS letters. The share of absolute scotoma points in microperimetry assessment increased from 15.7% to 43.5% while overall average macular sensitivity declined from 15.7 dB to 7.4 dB. Conclusions: The substantial deterioration of macular outcomes and visual function was comprehensively detected. The results were a documentation of structural and functional aspects of the natural progression of GA for a 60-month follow-up, providing a typical outline for AMD patients with GA.
Incidence and Causes of Tubal Occlusion in Infertility: A Retrospective Cohort Study
Authors: Mayrhofer Daniel , Holzer Iris , Aschauer Judith , Selzer Clara , Parry John Preston , Ott Johannes
Published: July 2024

Background and Objectives: Fallopian tubal pathology is a primary risk factor for female infertility, with simple proximal disease and proximal disease extending more distally being more common than pure distal occlusion. Proximal tubal occlusion is often attributed to ascending events, such as pelvic inflammatory disease. Conversely, while distal occlusion can also be attributable to ascending pelvic inflammatory disease, it can also have a pelvic origin, such as through endometriosis and ruptured appendicitis. The aim of this study was to identify certain causes of infertility and their association with tubal occlusion. The focus was on the location of tubal occlusion, uni- versus bilateral occlusion, and other causes of infertility, including male factors. Methods: In a retrospective study cohort study, 373 women aged between 18 and 40 years, treated from 1 January 2017 to 31 December 2022, were included. Fallopian tube patency was tested using either hysterosalpingography, hysterosalpingo-contrast sonography, or laparoscopic chromopertubation. Results: In total, 95 of 373 women (25.5%) revealed at least one occluded tube, with unilateral occlusion being more common than bilateral occlusion (60/95, 63.2% vs. 35/95, 36.8%). The majority of tubal occlusions occurred proximally (86.2%). According to the adjusted multivariate regression models, the presence of hydrosalpinx (odds ratio, OR, 13.323, 95% confidence interval, CI: 2.679–66.253, p = 0.002), myomas (OR 2.108, 95%CI: 1.008–4.409; p = 0.048), and an abnormal sperm test result of the male partner (OR 2.105, 95%CI: 1.156–3.833; p = 0.015) were statistically significant associated factors for tubal occlusion. Conclusions: Fallopian tube patency testing is still of major relevance in fertility evaluation. The presence of uterine myomas, hydrosalpinges, and a male factor significantly increase the risk.
Long-Term Evaluation of Pulp Vitality Preservation in Direct and Indirect Pulp Capping: A Retrospective Clinical Study
Authors: Alovisi Mario , Baldi Andrea , Comba Allegra , Gamerro Roberta , Paolone Gaetano , Mandurino Mauro , Dioguardi Mario , Roggia Andrea , Scotti Nicola
Published: July 2024

Background: This retrospective clinical study aimed to assess dental pulp tissue reactions to direct and indirect pulp capping after 10 years of follow-up. Methods: A total of 276 permanent teeth with deep carious lesions were evaluated and divided into five groups: Group (1), direct pulp capping with Mineral Trioxide Aggregate cement; Group (2), direct pulp capping with a resin-based glass ionomer; Group (3), direct pulp capping with TheraCal; Group (4), indirect pulp capping with a three-step total-etch adhesive system; and Group (5), indirect pulp capping with a two-step self-etch adhesive system. Results: A 72.5% success rate was achieved overall. A statistically significant difference was found when comparing direct and indirect pulp capping with a success rate of 23.8% and 93.8%, respectively. For direct pulp-capping procedures, the area of pulp exposure was correlated with pulp necrosis (p = 0.035), while bleeding after exposure appeared independent (p = 0.053). Patient age was significantly related to the maintenance of pulp vitality (p = 0.013). A statistically significant correlation between the pulp-capping material and the occurrence of pulp necrosis was discovered (p = 0.017). For the indirect pulp-capping treatments, a significant correlation between patient age (p = 0.021) and the adhesive system (p = 0.019) with pulp necrosis was described. Conclusions: The pulp-capping material, patient age, and the width of the pulp exposure before the procedure should be carefully considered when performing direct pulp-capping treatments. The performance of the etch-and-rinse adhesive systems was superior to the self-etch system during the indirect pulp-capping procedures.
Comparative Uptake Patterns of Radioactive Iodine and [18F]-Fluorodeoxyglucose (FDG) in Metastatic Differentiated Thyroid Cancers
Authors: Diwanji Devan , Carrodeguas Emmanuel , Seo Youngho , Kang Hyunseok , Soe Myat Han , Chiang Janet M. , Zhang Li , Liu Chienying , Behr Spencer C. , Flavell Robert R.
Published: July 2024

Background: Metastatic differentiated thyroid cancer (DTC) represents a molecularly heterogeneous group of cancers with varying radioactive iodine (RAI) and [18F]-fluorodeoxyglucose (FDG) uptake patterns potentially correlated with the degree of de-differentiation through the so-called “flip-flop” phenomenon. However, it is unknown if RAI and FDG uptake patterns correlate with molecular status or metastatic site. Materials and Methods: A retrospective analysis of metastatic DTC patients (n = 46) with radioactive 131-iodine whole body scan (WBS) and FDG-PET imaging between 2008 and 2022 was performed. The inclusion criteria included accessible FDG-PET and WBS studies within 1 year of each other. Studies were interpreted by two blinded radiologists for iodine or FDG uptake in extrathyroidal sites including lungs, lymph nodes, and bone. Cases were stratified by BRAF V600E mutation status, histology, and a combination of tumor genotype and histology. The data were analyzed by McNemar’s Chi-square test. Results: Lung metastasis FDG uptake was significantly more common than iodine uptake (WBS: 52%, FDG: 84%, p = 0.04), but no significant differences were found for lymph or bone metastases. Lung metastasis FDG uptake was significantly more prevalent in the papillary pattern sub-cohort (WBS: 37%, FDG: 89%, p = 0.02) than the follicular pattern sub-cohort (WBS: 75%, FDG: 75%, p = 1.00). Similarly, BRAF V600E+ tumors with lung metastases also demonstrated a preponderance of FDG uptake (WBS: 29%, FDG: 93%, p = 0.02) than BRAF V600E− tumors (WBS: 83%, FDG: 83%, p = 1.00) with lung metastases. Papillary histology featured higher FDG uptake in lung metastasis (WBS: 39%, FDG: 89%, p = 0.03) compared with follicular histology (WBS: 69%, FDG: 77%, p = 1.00). Patients with papillary pattern disease, BRAF V600E+ mutation, or papillary histology had reduced agreement between both modalities in uptake at all metastatic sites compared with those with follicular pattern disease, BRAF V600E− mutation, or follicular histology. Low agreement in lymph node uptake was observed in all patients irrespective of molecular status or histology. Conclusions: The pattern of FDG-PET and radioiodine uptake is dependent on molecular status and metastatic site, with those with papillary histology or BRAF V600E+ mutation featuring increased FDG uptake in distant metastasis. Further study with an expanded cohort may identify which patients may benefit from specific imaging modalities to recognize and surveil metastases.
Work-Related Musculoskeletal Disorders: A Systematic Review and Meta-Analysis
Authors: Greggi Chiara , Visconti Virginia Veronica , Albanese Marco , Gasperini Beatrice , Chiavoghilefu Angela , Prezioso Caterina , Persechino Benedetta , Iavicoli Sergio , Gasbarra Elena , Iundusi Riccardo , Tarantino Umberto
Published: July 2024

Background: Musculoskeletal disorders (MSDs) involve muscles, nerves, tendons, joints, cartilage, and spinal discs. These conditions can be triggered by both the work environment and the type of work performed, factors that, in some cases, can also exacerbate pre-existing conditions. This systematic review aims to provide an overview of the impact that different work-related activities have on the musculoskeletal system. Methods: A global search of publications was conducted using the following international bibliographic web databases: PubMed and Web of Science. The search strategies combined terms for musculoskeletal disorders and workers. In addition, a meta-analysis was conducted to estimate the prevalence of MSDs within the healthcare sector. Results: A total of 10,805 non-duplicated articles were identified, and finally, 32 studies were reviewed in this article. Once the literature search was completed, occupational figures were categorized into healthcare, farming, industrial, and computer sectors. In the healthcare sector, the prevalence estimate for degenerative diseases of the lumbar spine was 21% (497 out of 2547 physicians and dentists) (95% CI, 17–26%), while for osteoarthritis of the hand, it was 37% (382 out of 1013 dentists) (95% CI, 23–51%). Conclusions: Musculoskeletal disorders significantly impair workers’ quality of life, especially in healthcare sector. These conditions are also associated with high costs for employers, such as absenteeism, lost productivity, and increased costs for healthcare, disability, and workers’ compensation.
Prediction of Osteoporotic Hip Fracture Outcome: Comparative Accuracy of 27 Immune–Inflammatory–Metabolic Markers and Related Conceptual Issues
Authors: Fisher Alexander , Fisher Leon , Srikusalanukul Wichat
Published: July 2024

Objectives: This study, based on the concept of immuno-inflammatory–metabolic (IIM) dysregulation, investigated and compared the prognostic impact of 27 indices at admission for prediction of postoperative myocardial injury (PMI) and/or hospital death in hip fracture (HF) patients. Methods: In consecutive HF patient (n = 1273, mean age 82.9 ± 8.7 years, 73.5% females) demographics, medical history, laboratory parameters, and outcomes were recorded prospectively. Multiple logistic regression and receiver-operating characteristic analyses (the area under the curve, AUC) were used to establish the predictive role for each biomarker. Results: Among 27 IIM biomarkers, 10 indices were significantly associated with development of PMI and 16 were indicative of a fatal outcome; in the subset of patients aged >80 years with ischaemic heart disease (IHD, the highest risk group: 90.2% of all deaths), the corresponding figures were 26 and 20. In the latter group, the five strongest preoperative predictors for PMI were anaemia (AUC 0.7879), monocyte/eosinophil ratio > 13.0 (AUC 0.7814), neutrophil/lymphocyte ratio > 7.5 (AUC 0.7784), eosinophil count < 1.1 × 109/L (AUC 0.7780), and neutrophil/albumin × 10 > 2.4 (AUC 0.7732); additionally, sensitivity was 83.1–75.4% and specificity was 82.1–75.0%. The highest predictors of in-hospital death were platelet/lymphocyte ratio > 280.0 (AUC 0.8390), lymphocyte/monocyte ratio < 1.1 (AUC 0.8375), albumin < 33 g/L (AUC 0.7889), red cell distribution width > 14.5% (AUC 0.7739), and anaemia (AUC 0.7604), sensitivity 88.2% and above, and specificity 85.1–79.3%. Internal validation confirmed the predictive value of the models. Conclusions: Comparison of 27 IIM indices in HF patients identified several simple, widely available, and inexpensive parameters highly predictive for PMI and/or in-hospital death. The applicability of IIM biomarkers to diagnose and predict risks for chronic diseases, including OP/OF, in the preclinical stages is discussed.
Cognitive Distortions as Barriers to Seeking Smoking Cessation Treatment: A Comparative Study
Authors: Arpacıoğlu Selim , Erzincan Erkal , Ergelen Mine , Arpacıoğlu Beyza , Paltun Salih Cihat , Yalçın Murat , Bilici Rabia
Published: July 2024

Background/Objectives: Despite the availability of effective pharmacotherapy and evidence-based treatments, a substantial proportion of smokers do not seek treatment. This study aims to explore the cognitive distortions associated with not seeking evidence-based smoking cessation treatment and to identify cognitive barriers. Methods: The research conducted in Istanbul between October and December 2017 employs a cross-sectional design and includes two groups: a treatment-seeking group comprising 156 patients diagnosed with tobacco use disorder and a non-treatment seeking group of 78 patients with tobacco use disorder who had never sought professional help for smoking cessation. A comprehensive data collection process was used, including sociodemographic information, cognitive distortion assessment using the cognitive distortions scale, a smoking-related cognitive distortions interview and the Fagerström Test for Nicotine Dependence. Results: While no significant sociodemographic differences were observed between the treatment-seeking and non-treatment-seeking groups, the study found that higher nicotine dependence was associated with a higher likelihood of seeking treatment. The treatment-seeking group displayed significantly higher levels of “all-or-nothing thinking” cognitive distortions related to smoking and smoking cessation. Conversely, the non-treatment-seeking group exhibited elevated levels of cognitive distortions such as “labeling”, “mental filtering”, “should statements” and “minimizing the positive” regarding receiving smoking cessation treatment. Conclusions: Understanding the cognitive distortions associated with treatment-seeking behavior for tobacco use disorder is crucial for developing targeted public-based interventions, public service announcements for tobacco use prevention and encouraging individuals to seek evidence-based treatment. Addressing these cognitive distortions can also potentially enhance the effectiveness of smoking cessation programs and reduce the global burden of tobacco-related diseases and mortality.
Assessment of Blood Flow Velocity in Retinal Vasculitis Using the Retinal Function Imager—A Pilot Study
Authors: Stuebiger Nicole , Lee Wen-Hsiang , Birtel Johannes , Druchkiv Vasyl , Davis Janet L. , DeBuc Delia Cabrera
Published: July 2024

Background: This pilot study aimed to evaluate the Retinal Function Imager (RFI) for visualizing retinal vasculature and assessment of blood flow characteristics in patients with retinal vasculitis. The RFI is a non-invasive imaging device measuring the blood flow velocity (BFV) in secondary and tertiary retinal vessels using hemoglobin as an intrinsic motion-contrast agent. Methods: To test the feasibility of the RFI for patients with retinal vasculitis, capillary perfusion maps (nCPMs) were generated from 15 eyes of eight patients (five females; mean age: 49 ± 12 years) with a mean uveitis duration of 74 ± 85 months. Five of these patients had birdshot chorioretinopathy, and three had primarily non-occlusive venous retinal vasculitis of unknown origin. To reflect that the BFV may be more reduced in patients with prolonged disease, patients were classified into a short-term (uveitis duration: 8–15 months) and a long-term uveitis group (uveitis duration: 60–264 months). Data were compared with healthy controls (16 eyes of 11 patients; mean age 45 ± 12 years; 8 females). Results: The mean BFV in the controls was 3.79 ± 0.50 mm/s in the retinal arteries and 2.35 ± 0.44 mm/s in the retinal veins, which was significantly higher compared to the retinal vasculitis group. Patients revealed an arterial BFV of 2.75 ± 0.74 mm/s (p < 0.001) and a venous BFV of 1.75 ± 0.51 mm/s (p = 0.016). In the short-term group, a trend towards a decreased venular and arteriolar BFV was seen, while a significant reduction was observed in the long-term group. The patients’ microvasculature anatomy revealed by the nCPMs appeared unevenly distributed and a lower number of blood vessels were seen, along with a lower degree of complexity of their branching patterns, when compared with controls. Conclusions: This study demonstrated a reduction in venular and arteriolar BFVs in patients with retinal vasculitis. BFV alterations were already observed in early disease stages and became more pronounced in progressed disease. Additionally, we showed that retinal microvasculature changes may be observed by nCPMs. Retinal imaging with the RFI may serve as a diagnostic and quantifying tool in retinal vasculitis.
Intra- and Early Post-Operative Factors Affecting Spinal Cord Ischemia in Patients Undergoing Fenestrated and Branched Endovascular Aortic Repair
Authors: Doering Allegra , Nana Petroula , Torrealba José I. , Panuccio Giuseppe , Trepte Constantin , Chindris Viorel , Kölbel Tilo
Published: July 2024

Background: Spinal cord ischemia (SCI) is a severe complication after fenestrated/branched endovascular repair (f/bEVAR). The underlying causes of SCI are still under investigation. This study aimed to evaluate intra- and early post-operative parameters that may affect SCI evolution. Methods: A single-center retrospective analysis was conducted including SCI patients with complete anesthesiologic records (1 January 2011 to 31 December 2023). Values of intra-operative glucose, hemoglobin, lactate, activated clotting time (ACT), and the need for transfusion were collected. The cohort was compared to a matched cohort of non-SCI patients. Results: Fifty-one patients with SCI and complete anesthesiologic records were included (mean age: 69.8 ± 6.2 years; 39.2% male). Intra-operative glucose value < 110 mg/dL (AUC: 0.73; sensitivity 91%, specificity of 83%) and hemoglobin value > 8.5 mg/dL (AUC: 0.61; sensitivity 83%, specificity 78%) were protective for Grade 3 SCI. Twenty-three patients with SCI were matched to 23 patients without SCI. SCI patients presented significantly higher glucose levels intra-operatively (glucose mean value: SCI 150 ± 46 mg/dL vs. non-SCI: 122 ± 30 mg/dL, p = 0.005). ACT (SCI 259 ± 31 svs. non-SCI 288 ± 28 s, p = 0.001), volume input (SCI 4030 ± 1430 mL vs. non-SCI 3020 ± 113 mL, p = 0.009), and need for transfusion (SCI: 52.5% vs. 4.3%, p < 0.001) were related to SCI. Higher glucose levels were detected among patients with SCI, at 24 (SCI: 142 ± 30 mg/dL vs. non-SCI: 118 ± 26 mg/dL, p=0.004) and 48 h (SCI: 140 ± 29 mg/dL vs. non-SCI: 112 ± 20 mg/dL, p < 0.001) post-operatively. Conclusions: SCI is a multifactorial complication after f/bEVAR. Intra-operative and early post-operative glucose levels may be related to SCI evolution. Targeted glucose < 110 mg/dL may be protective for Grade 3 SCI.
Influence of Neoadjuvant Therapy on Success of Endoscopic Vacuum Therapy in Anastomotic Leakage after Rectal Resection Because of Rectal Cancer
Authors: Strobel Rahel M. , Wellner Julia E. , Neumann Konrad , Otto Susanne D. , Eschlboeck Sophie M. , Seifarth Claudia , Schineis Christian H. W. , Beyer Katharina , Kreis Martin E. , Lauscher Johannes C.
Published: July 2024

Background: For locally advanced rectal cancer, neoadjuvant therapy (NT) is an established element of therapy. Endoscopic vacuum therapy (EVT) has been a relevant treatment option for anastomotic leakage after rectal resection since 2008. The aim was to evaluate the influence of NT on the duration and success of EVT in anastomotic leakage after rectal resection for rectal cancer. Methods: This was a monocentric, retrospective cohort study including patients who underwent rectal resection with primary anastomosis because of histologically proven carcinoma of the rectum in the Department for General and Visceral Surgery of Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin over a period of ten years (2012 to 2022). Results: Overall, 243 patients were included, of which 47 patients (19.3%) suffered from anastomotic leakage grade B with consecutive EVT. A total of 29 (61.7%) patients received NT and 18 patients (38.3%) did not. The median duration of EVT until the removal of the sponge did not differ between patients with and without NT: 24.0 days (95% CI 6.44–41.56) versus 20.0 days (95% CI 17.03–22.97); p = 0.273. The median duration from insertion of EVT until complete healing was 74.0 days with NT (95% CI 10.07–137.93) versus 62.0 days without NT (95% CI 45.99–78.01); p = 0.490. Treatment failure—including early persistence and late onset of recurrent anastomotic leakage—was evident in 27.6% of patients with NT versus 27.8% without NT; p = 0.989. Ostomy was reversed in 19 patients (79.2%) with NT compared to 11 patients (68.8%) without NT; p = 0.456. Overall, continuity was restored in 75% of patients in the long term after EVT. Conclusion: This trial comprised—to our knowledge—the largest study cohort to analyze the outcome of EVT in anastomotic leakage after rectal resection for rectal cancer. We conclude that neoadjuvant therapy neither prolongs EVT nor the time to healing from anastomotic leakage. The rates of treatment failure of EVT and permanent ostomy were not higher when neoadjuvant therapy was used.
A Real-World Safety Profile in Neurological, Skin, and Sexual Disorders of Anti-Seizure Medications Using the Pharmacovigilance Database of the Korea Adverse Event Reporting System (KAERS)
Authors: Kim Dajeong , Lee Sukhyang
Published: July 2024

(1) Background: The utilization of high-quality evidence regarding the safety of anti-seizure medications (ASMs) is constrained by the absence of standardized reporting. This study aims to examine the safety profile of ASMs using real-world data. (2) Methods: The data were collected from the Korea Adverse Event Reporting System Database (KAERS-DB) between 2012 and 2021. In total, 46,963 adverse drug reaction (ADR)–drug pairs were analyzed. (3) Results: At the system organ class level, the most frequently reported classes for sodium channel blockers (SCBs) were skin (37.9%), neurological (16.7%), and psychiatric disorders (9.7%). For non-SCBs, these were neurological (31.2%), gastrointestinal (22.0%), and psychiatric disorders (18.2%). The most common ADRs induced by SCBs were rash (17.8%), pruritus (8.2%), and dizziness (6.7%). Non-SCBs were associated with dizziness (23.7%), somnolence (13.0%), and nausea (6.3%). Rash, pruritus, and urticaria occurred, on average, two days later with SCBs compared to non-SCBs. Sexual/reproductive disorders were reported at a frequency of 0.23%. SCBs were reported as the cause more frequently than non-SCBs (59.8% vs. 40.2%, Fisher’s exact test, p < 0.0001). (4) Conclusions: Based on real-world data, the safety profiles of ASMs were identified. The ADRs induced by SCBs exhibited different patterns when compared to those induced by non-SCBs.
Evolution of Pulmonary Embolism Response Teams in the United States: A Review of the Literature
Authors: Pandya Vidish , Chandra Akhil Avunoori , Scotti Andrea , Assafin Manaf , Schenone Aldo L. , Latib Azeem , Slipczuk Leandro , Khaliq Asma
Published: July 2024

Pulmonary embolism (PE) is a significant cause of cardiovascular mortality, with varying presentations and management challenges. Traditional treatment approaches often differ, particularly for submassive/intermediate-risk PEs, because of the lack of clear guidelines and comparative data on treatment efficacy. The introduction of pulmonary embolism response teams (PERTs) aims to standardize and improve outcomes in acute PE management through multidisciplinary collaboration. This review examines the conception, evolution, and operational mechanisms of PERTs while providing a critical analysis of their implementation and efficacy using retrospective trials and recent randomized trials. The study also explores the integration of advanced therapeutic devices and treatment protocols facilitated by PERTs. PERT programs have significantly influenced the management of both massive and submassive PEs, with notable improvements in clinical outcomes such as decreased mortality and reduced length of hospital stay. The utilization of advanced therapies, including catheter-directed thrombolysis and mechanical thrombectomy, has increased under PERT guidance. Evidence from various studies, including those from the National PERT Consortium, underscores the benefits of these multidisciplinary teams in managing complex PE cases, despite some studies showing no significant difference in mortality. PERT programs have demonstrated potentials to reduce morbidity and mortality, streamlining the use of healthcare resources and fostering a model of sustainable practice across medical centers. PERT program implementation appears to have improved PE treatment protocols and innovated advanced therapy options, which will be further refined as they are employed in clinical practice. The continued expansion of the capabilities of PERTs and the forthcoming results from ongoing randomized trials are expected to further define and optimize management protocols for acute PEs.
Refractive Errors, Amplitude of Accommodation, and Myopia Progression in Kazakhstani Medical Students: 5-Year Follow-Up
Authors: Semenova Yuliya , Urazhanova Malika , Lim Lisa , Kaiyrzhanova Nazerke
Published: July 2024

Background/Objectives: this longitudinal study aimed to investigate the refractive errors, the amplitude of accommodation, and myopia progression in Kazakhstani medical students as they progressed from the first to the fifth course of their studies. Methods: A total of 696 students from Semey Medical University underwent non-cycloplegic and cycloplegic autorefraction in the first course, and 655 were available for examination in the fifth year of study. The amplitude of accommodation was measured before the instillation of cycloplegics using the push-up and push-down methods. A self-administered questionnaire was applied to evaluate the risk factors associated with myopia progression. Results: In the first course, the median spherical equivalent was −0.75 Diopters before cycloplegia and −0.25 Diopters after cycloplegia. In the fifth course, it constituted −1.125 Diopters before cycloplegia and −0.5 Diopters after cycloplegia. The proportion of students with myopia following cycloplegic refraction increased from 44.7% in the first course to 47.5% in the fifth course. The proportion of emmetropic students declined from 31.5% to 30.3%, and hyperopia decreased from 23.8% to 16.8%. The dioptric power of accommodative excess increased from 0.375 in the first year to 0.50 in the fifth year. The hours spent on near-work activities, such as reading books, writing, working at a computer, and using a mobile device, were significantly associated with a myopia progression of ≥0.5 Diopters. Conclusions: the findings of this study suggest implications for public health policy and educational practice.
Genes Related to Frontonasal Malformations Are Regulated by miR-338-5p, miR-653-5p, and miR-374-5p in O9-1 Cells
Authors: Iwaya Chihiro , Yu Sunny , Iwata Junichi
Published: July 2024

Frontonasal malformations are caused by a failure in the growth of the frontonasal prominence during development. Although genetic studies have identified genes that are crucial for frontonasal development, it remains largely unknown how these genes are regulated during this process. Here, we show that microRNAs, which are short non-coding RNAs capable of targeting their target mRNAs for degradation or silencing their expression, play a crucial role in the regulation of genes related to frontonasal development in mice. Using the Mouse Genome Informatics (MGI) database, we curated a total of 25 mouse genes related to frontonasal malformations, including frontonasal hypoplasia, frontonasal dysplasia, and hypotelorism. MicroRNAs regulating the expression of these genes were predicted through bioinformatic analysis. We then experimentally evaluated the top three candidate miRNAs (miR-338-5p, miR-653-5p, and miR-374c-5p) for their effect on cell proliferation and target gene regulation in O9-1 cells, a neural crest cell line. Overexpression of these miRNAs significantly inhibited cell proliferation, and the genes related to frontonasal malformations (Alx1, Lrp2, and Sirt1 for miR-338-5p; Alx1, Cdc42, Sirt1, and Zic2 for miR-374c-5p; and Fgfr2, Pgap1, Rdh10, Sirt1, and Zic2 for miR-653-5p) were directly regulated by these miRNAs in a dose-dependent manner. Taken together, our results highlight miR-338-5p, miR-653-5p, and miR-374c-5p as pathogenic miRNAs related to the development of frontonasal malformations.
Buffer Blocks as Wave Energy Dissipators: Flow Depth Reduction
Authors: Nageswaran Praba , Oetjen Jan , Harish S. , Sriram V. , Sundar V. , Schüttrumpf Holger
Published: July 2024

High-energy events such as tsunamis pose significant threats to coastal infrastructure and buildings, necessitating effective mitigation strategies to minimize damage. Compared to massive construction measures, buffer blocks are increasingly recognized as a potential solution for reducing the impact of such events. Understanding their effectiveness and optimizing their placement configurations is crucial for enhancing coastal resilience. The present study aims to experimentally evaluate the influence of buffer blocks on the depth of tsunami inundation. By comparing different configurations of buffer blocks, this study seeks to identify the most effective one for reducing the inundating flow depth. The laboratory tests revealed that the buffer blocks significantly influence flow depth and its characteristics. For ratios of flow depth to block height (R) below 1.5, the buffer blocks exhibited a delay in the arrival of the flow and effectively reduced the flow depths. However, for R values greater than 1.5, the effectiveness reduced as the flow began to overtop the obstructions. The increase in the flow depth at the buffer blocks was the least for a single-row configuration, while the multiple-row configurations with wider spacing offered higher flow resistance and increased the flow depths in front of the blocks. These findings suggest that strategically configured buffer blocks can substantially enhance coastal protection against high-energy flow events during natural coastal hazards. This study provides critical insights into the design and optimization of buffer block configurations, contributing to improved coastal infrastructure resilience and disaster mitigation strategies.
Biobanks as an Indispensable Tool in the “Era” of Precision Medicine: Key Role in the Management of Complex Diseases, Such as Melanoma
Authors: Valenti Alessandro , Falcone Italia , Valenti Fabio , Ricciardi Elena , Di Martino Simona , Maccallini Maria Teresa , Cerro Marianna , Desiderio Flora , Miseo Ludovica , Russillo Michelangelo , Guerrisi Antonino
Published: July 2024

In recent years, medicine has undergone profound changes, strongly entering a new phase defined as the “era of precision medicine”. In this context, patient clinical management involves various scientific approaches that allow for a comprehensive pathology evaluation: from preventive processes (where applicable) to genetic and diagnostic studies. In this scenario, biobanks play an important role and, over the years, have gained increasing prestige, moving from small deposits to large collections of samples of various natures. Disease-oriented biobanks are rapidly developing as they provide useful information for the management of complex diseases, such as melanoma. Indeed, melanoma, given its highly heterogeneous characteristics, is one of the oncologic diseases with the greatest clinical and therapeutic management complexity. So, the possibility of extrapolating tissue, genetic and imaging data from dedicated biobanks could result in more selective study approaches. In this review, we specifically analyze the several biobank types to evaluate their role in technology development, patient monitoring and research of new biomarkers, especially in the melanoma context.