bluuebunny/crossref_metadata_2025 huggingface dataset:
Embryoid Body Test: A Simple and Reliable Alternative Developmental Toxicity Test
Authors: Hwang Inho , Jeung Eui-Bae
Published: December 2024

The increasing emphasis on animal welfare and ethics, as well as the considerable time and cost involved with animal testing, have prompted the replacement of many aspects of animal testing with alternative methods. In the area of developmental toxicity, the embryonic stem cell test (EST) has played a significant role. The EST evaluates toxicity using mouse embryonic stem cells and somatic cells and observes the changes in heartbeat after cardiac differentiation. Nevertheless, the EST is a relatively complex testing process, and an in vitro test requires a long duration. Several attempts have been made to develop a more straightforward testing method than the EST, with improved reproducibility and accuracy, leading to the development of the embryoid body test (EBT). Unlike the EST, which involves cardiac differentiation stages, the EBT verifies toxicity by measuring the changes in the area of the embryoid body. Despite its short testing period and simple procedure, the EBT offers high accuracy and reproducibility and is fully validated through two rounds of validation, making it ready for practical application. The EBT is expected to play a crucial role in the rapidly increasing demand for alternative methods to animal testing, particularly for screening early developmental toxicity.
Evolution of Theories on Doxorubicin-Induced Late Cardiotoxicity-Role of Topoisomerase
Authors: Szponar Jaroslaw , Ciechanski Erwin , Ciechanska Magda , Dudka Jaroslaw , Mandziuk Sławomir
Published: December 2024

Doxorubicin (DOX) has been widely used as a cytotoxic chemotherapeutic. However, DOX has a number of side effects, such as myelotoxicity or gonadotoxicity, the most dangerous of which is cardiotoxicity. Cardiotoxicity can manifest as cardiac arrhythmias, myocarditis, and pericarditis; life-threatening late cardiotoxicity can result in heart failure months or years after the completion of chemotherapy. The development of late cardiomyopathy is not yet fully understood. The most important question is how DOX reprograms the cardiomyocyte, after which DOX is excreted from the body, initially without symptoms. However, clinically overt cardiomyopathy develops over the following months and years. Since the 1980s, DOX-induced disorders in cardiomyocytes have been thought to be related to oxidative stress and dependent on the Fe/reactive oxygen species (ROS) mechanism. That line of evidence was supported by dexrazoxane (DEX) protection, the only Food and Drug Administration (FDA)-approved drug for preventing DOX-induced cardiomyopathy, which complexes iron. Thus, the hypothesis related to Fe/ROS provides a plausible explanation for the induction of the development of late cardiomyopathy via DOX. However, in subsequent studies, DEX was used to identify another important mechanism in DOX-induced cardiomyopathy that is related to topoisomerase 2β (Top2β). Does the Top2β hypothesis explain the mechanisms of the development of DOX-dependent late heart failure? Several of these mechanisms have been identified to date, proving the involvement of Top2β in the regulation of the redox balance, including oxidative stress. Thus, the development of late cardiomyopathy can be explained based on mechanisms related to Top2β. In this review, we highlight free radical theory, iron imbalance, calcium overload, and finally, a theory based on Top2β.
The Balance of Ketoacids α-Ketoglutarate and α-Ketoglutaramate Reflects the Degree of the Development of Hepatoencephalopathy in Rats
Authors: Shurubor Yevgeniya I. , Keskinov Anton A. , Yudin Vladimir S. , Krasnikov Boris F.
Published: December 2024

Hepatoencephalopathy (HE) is a liver disease that can lead to brain pathology and the impairment of human cognitive abilities. The objective assessment of HE disease severity is difficult due to the lack of reliable diagnostic markers. This paper examines the background to the emergence of HE markers and provides a brief overview of research results indicating the diagnostic value of potential markers isolated from a wide range of metabolites analyzed. It has been suggested that metabolites of the glutamate–glutamine (Glu-Gln) cycle, α-ketoglutarate (αKG), and α-ketoglutaramate (αKGM) can act as such markers of HE. The informative value of these markers was revealed during a comparative analysis of the distribution of αKG and αKGM in samples of the blood plasma and tissues (liver, kidneys, and brain) of rats exposed to the strong hepatotoxin thioacetamide (TAA). A comparative analysis of the balance of αKG and αKGM, as well as their ratio (αKG/αKGM) in the examined samples of blood plasma and animal tissues in these models, revealed their diagnostic value for assessing the severity of HE and/or monitoring the recovery process.
BCAT1 Associates with DNA Repair Proteins KU70 and KU80 and Contributes to Regulate DNA Repair in T-Cell Acute Lymphoblastic Leukemia (T-ALL)
Authors: Tosello Valeria , Rompietti Chiara , Papathanassiu Adonia E. , Arrigoni Giorgio , Piovan Erich
Published: December 2024

Increased expression of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) often correlates with tumor aggressiveness and drug resistance in cancer. We have recently reported that BCAT1 was overexpressed in a subgroup of T-cell acute lymphoblastic (T-ALL) samples, especially those with NOTCH1 activating mutations. Interestingly, BCAT1-depleted cells showed pronounced sensitivity to DNA-damaging agents such as etoposide; however, how BCAT1 regulates this sensitivity remains uncertain. Here, we provide further clues on its chemo-sensitizing effect. Indeed, BCAT1 protein regulates the non-homologous end joining (c-NHEJ) DNA repair pathway by physically associating with the KU70/KU80 heterodimer. BCAT1 inhibition during active repair of DNA double-strand breaks (DSBs) led to increased KU70/KU80 acetylation and impaired c-NHEJ repair, a dramatic increase in DSBs, and ultimately cell death. Our results suggest that, in T-ALL, BCAT1 possesses non-metabolic functions that confer a drug resistance mechanism and that targeting BCAT1 activity presents a novel strategy to improve chemotherapy response in T-ALL patients.
Proteasome Inhibitors Induce Apoptosis in Ex Vivo Cells of T-Cell Prolymphocytic Leukemia
Authors: Gasparini Vanessa Rebecca , Rampazzo Elisa , Barilà Gregorio , Buratin Alessia , Buson Elena , Calabretto Giulia , Vicenzetto Cristina , Orsi Silvia , Tonini Alessia , Teramo Antonella , Trentin Livio , Facco Monica , Semenzato Gianpietro , Bortoluzzi Stefania , Zambello Renato
Published: December 2024

Finding an effective treatment for T-PLL patients remains a significant challenge. Alemtuzumab, currently the gold standard, is insufficient in managing the aggressiveness of the disease in the long term. Consequently, numerous efforts are underway to address this unmet clinical need. The rarity of the disease limits the ability to conduct robust clinical trials, making in silico, ex vivo, and in vivo drug screenings essential for designing new therapeutic strategies for T-PLL. We conducted a drug repurposing analysis based on T-PLL gene expression data and identified proteasome inhibitors (PIs) as a promising new class of compounds capable of reversing the T-PLL phenotype. Treatment of ex vivo T-PLL cells with Bortezomib and Carfilzomib, two PI compounds, supported this hypothesis by demonstrating increased apoptosis in leukemic cells. The current lack of a suitable in vitro model for the study of T-PLL prompted us to perform similar experiments in the SUP-T11 cell line, validating its potential by showing an increased apoptotic rate. Taken together, these findings open new avenues for investigating the molecular mechanisms underlying the efficacy of PI in T-PLL and expand the spectrum of potential therapeutic strategies for this highly aggressive disease.
The Impact of Comorbid Sleep-Disordered Breathing on Hospitalization Risk Related to Diabetes and Atherosclerotic Disease: A Retrospective Cohort Analysis
Authors: Hlynsson Hlynur Davíð , Ong Jason C. , Day Joseph , Kauss Thomas , Montazeri Kristófer , Hertzberg Jeffrey , Wickwire Emerson , Hankla Rebecca M. , Finnsson Eysteinn , Ágústsson Jón Skírnir , Riney Heidi
Published: December 2024

Objective: To determine the relationship between comorbid sleep-disordered breathing (SDB) and hospitalization rates related to diabetes mellitus (DM) and atherosclerotic disease (AD). Methods: This study used a retrospective cohort design from a large medical claims database with 5 years of data between 2018 and 2022. The presences of SDB, DM, and AD were identified using International Classification of Diseases (ICD-10) and relevant Current Procedural Terminology (CPT) codes. Hospitalizations related to DM and AD were identified primarily using Place of Service (POS) code 21. Propensity-score matching was first used on data from the entire 5-year period to select matched controls (unadjusted n = 883,910, adjusted n = 888,619) compared to those diagnosed with SDB (n = 519,818) on hospitalization rates during the concurrent 5-year period. A second analysis used propensity-score matching on data from year 1 only to select matched controls (unadjusted n = 248,848, adjusted n = 260,298) compared to those diagnosed with SDB in year 1 (n = 193,671) on hospitalization outcomes in the subsequent 4-year period. Results: Odds ratios (ORs) revealed a significant association between SDB diagnosis and hospitalizations related to DM (OR 1.23–1.71), AD (OR: 1.08–1.34), and either condition (OR 1.17–1.49) in both analyses. Post hoc analysis revealed sex differences in the relationship between SDB and future hospitalizations, with females showing a pattern of significantly elevated risk across all future hospitalization outcomes (OR: 1.25–1.44), whereas males were found to have a significant relationship between SDB diagnosis and future DM hospitalization only (OR 1.10). Conclusions: These findings provide real-world evidence that comorbid SDB increases the risk for hospitalizations related to chronic cardiometabolic conditions. Sex is a potential moderator of this relationship and should be further explored.
Meniscal Extrusion Correlates with Symptom Severity in Knee Osteoarthritis: An Ultrasound and Magnetic Resonance Imaging Analysis of 100 Patients
Authors: Tortorella Fabio , Boffa Angelo , Di Martino Alessandro , Andriolo Luca , Facchini Giancarlo , Di Carlo Maddalena , Miceli Marco , Zaffagnini Stefano , Filardo Giuseppe
Published: December 2024

Purpose: The aim of this study was to investigate how meniscal extrusion, assessed either with ultrasounds or magnetic resonance (MR), correlates with clinical symptoms in knee osteoarthritis (OA). Methods: One hundred patients with symptomatic knee OA were enrolled (60.3 ± 9.7 years). Patients underwent MR evaluation and ultrasound analyses (clinostatic and orthostatic positions). Patients were clinically evaluated through IKDC, KOOS, WOMAC, VAS, and Tegner scores. Correlation analyses were performed between meniscal extrusion extent and clinical scores. Lower (<4 mm) and higher extrusion (≥4 mm) groups were also compared. Results: The identification of low/high extrusion was 56/44 (MR) and 45/55 (ultrasounds) for patients with medial meniscus and 72/28 (MR) and 57/43 (ultrasounds) for patients with lateral meniscus. Meniscal extrusion correlated with symptoms (p < 0.05) with worse clinical findings in patients with higher extrusion, particularly for the lateral meniscus. For the medial meniscus, more differences were found between lower and higher extrusion groups with ultrasounds than MR, especially in the orthostatic position, while for the lateral meniscus, similar trends were documented with both methods. Conclusions: Extrusion of both menisci correlates with knee OA symptoms, with a stronger correlation for the lateral meniscus. Ultrasounds performed in the standing position identify more patients with meniscal extrusion and correlate better than MR with clinical findings.
A Pilot Study to Evaluate the Minimally Invasive Burn Care for Small, Deep Partial-Thickness Burns of the Hands and Feet Using Enzyme Debridement and Autologous Skin Cell Spray
Authors: Aoki Kohei , Komiya Takako , Yamashita Kento , Shimada Kazuki , Fujii Miki , Matsumura Hajime
Published: December 2024

Background/Objectives: We treated deep partial-thickness burns of the hands and feet in four cases using a combination of NexoBrid and ReCell autologous cell regeneration techniques, without conventional split-thickness skin graft, with good results following debridement of the eschar. Methods: We report cases of patients treated with a combination of the NexoBrid and ReCell techniques between 1 August 2023 and 31 July 2024. The degree of debridement and the time to complete wound closure were evaluated. Scar quality was assessed using the Vancouver Scar Scale (VSS). Results: Four patients aged 0–28 years with an average total burn surface area of 1.2% were treated on two hands and two feet, with an average follow-up of 12 months; no additional surgical treatment was needed. The mean VSS score was 0.25. The patients were satisfied with the aesthetic appearance of their hands and feet, and no complications, such as hypertrophic scars, were observed. We also developed separate algorithms for sedation and analgesia management for adults and children. Conclusions: Using ReCell alone following debridement of small burn wounds with NexoBrid resulted in early wound closure with good scar condition and cosmetic appearance.
Comparative Analysis of Outcomes in Adult Spinal Deformity Patients with Proximal Junctional Kyphosis or Failure Initially Fused to Upper Versus Lower Thoracic Spine
Authors: Onafowokan Oluwatobi O. , Lafage Renaud , Tretiakov Peter , Smith Justin S. , Line Breton G. , Diebo Bassel G. , Daniels Alan H. , Gum Jeffrey L. , Protopsaltis Themistocles S. , Hamilton David Kojo , Buell Thomas , Soroceanu Alex , Scheer Justin , Eastlack Robert K. , Mullin Jeffrey P. , Mundis Gregory , Hosogane Naobumi , Yagi Mitsuru , Anand Neel , Okonkwo David O. , Wang Michael Y. , Klineberg Eric O. , Kebaish Khaled M. , Lewis Stephen , Hostin Richard , Gupta Munish Chandra , Lenke Lawrence G. , Kim Han Jo , Ames Christopher P. , Shaffrey Christopher I. , Bess Shay , Schwab Frank J. , Lafage Virginie , Burton Douglas , Passias Peter G.
Published: December 2024

Background: Patients with proximal junctional kyphosis (PJK) or failure (PJF) may demonstrate disparate outcomes and recovery when fused to the upper (UT) versus lower (LT) thoracic spine. Few studies have distinguished the reoperation and recovery abilities of patients with PJK or PJF when fused to the upper (UT) versus lower (LT) thoracic spine. Methods: Adult spine deformity patients ≥ 18 yrs with preoperative and 5-year (5Y) data fused to the sacrum/pelvis were included. The rates of PJK, PJK revision, and radiographic PJF were compared between patients with upper instrumented vertebra (UIV) in the upper thoracic spine (UT; T1-T7) and lower thoracic spine (LT; T8-L1). Mean differences were assessed via analyses of covariance, factoring in any differences between cohorts at baseline and any use of PJF prophylaxis. Backstep logistic regressions assessed predictors of achieving Smith et al.’s Best Clinical Outcomes (BCOs) and complications, controlling for similar covariates. Results: A total of 232 ASD patients were included (64.2 ± 10.2 years, 78% female); 36.3% were UT and 63.7% were LT. Postoperatively, the rates of PJK for UT were lower than LT at 1Y (34.6 vs. 50.4%, p = 0.024), 2Y (29.5 vs. 49.6% (p = 0.003), and 5Y (48.7 vs. 62.8%, p = 0.048), with comparable rates of PJF. In total, 4.0% of UT patients underwent subsequent reoperation, compared to 13.0% of LT patients (p = 0.025). A total of 6.0% of patients had recurrent PJK, and 3.9% had recurrent PJF (both p > 0.05). After reoperation, UT patients reported higher rates of improvement in the minimum clinically important difference for ODI by 2Y (p = 0.007) and last follow-up (p < 0.001). While adjusted regression revealed that, for UT patients, the minimization of construct extension was predictive of achieving BCOs by last follow-up (model p < 0.001), no such relationship was identified in LT patients. Conclusions: Patients initially fused to the lower thoracic spine demonstrate an increased incidence of PJK and lower rates of disability improvement, but are at a lessened risk of neurologic complications if reoperation is required.
Early Prediction of Gestational Diabetes Mellitus and Insulin Therapy Requirement Using First-Trimester PAPP-A and Free β-hCG MoMs Levels: A Retrospective Case–Control Study
Authors: Balkaş Gülay , Çelen Şevki
Published: December 2024

Objectives: To evaluate the association between gestational diabetes mellitus (GDM), including insulin-dependent GDM with pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) and free beta human chorionic gonadotropin (free β-hCG) MoM levels, and to assess their potential as predictive risk factors. Methods: This retrospective study included 2588 women with singleton pregnancies who underwent combined first-trimester screening, along with the 50 g glucose challenge test (GCT) and a 100 g oral glucose tolerance test (OGTT) between 24 and 28 weeks of gestation. Patients were initially divided into four groups based on the glucose screening results, and PAPP-A and free β-hCG MoMs were compared between these groups. GDM cases managed by diet were then compared with those requiring insulin therapy. Results: Of the study population, 132 women (5.10%) were diagnosed with GDM, 112 (84.8%) managed their glycemia with dietary changes, while 20 (15.2%) required insulin therapy. PAPP-A levels were significantly lower in the GDM group compared to the control group (p < 0.001). In addition, the insulin-dependent GDM group had significantly lower PAPP-A levels than the diet-controlled group (p < 0.001). No significant differences were observed in the free β-hCG MoM levels between the groups (p = 0.292). Receiver operating characteristic analysis identified 0.815 as the optimal PAPP-A cut-off value for predicting GDM, with a sensitivity of 61.4%, specificity of 61.6%, and an area under the curve (AUC) of 0.649 (95% CI: 0.595–0.703). For insulin-dependent GDM, the same threshold yielded an AUC of 0.621 (95% CI: 0.563–0.679), with a sensitivity of 58.6% and a specificity of 59.7%. Conclusions: Low serum PAPP-A MoM levels are significantly associated with the development of GDM, including insulin-dependent cases. Although PAPP-A alone may not be a definitive predictive marker for GDM, low levels could support the recommendation for early screening as part of a broader diagnostic approach.
Robot-Assisted Pyelolithotomy in Pelvic Kidney
Authors: Mahmud Husny , Shvero Asaf , Kleinmann Nir , Dotan Zohar A. , Zilberman Dorit E.
Published: December 2024

Background/Objectives: Pelvic kidney is a congenital anomaly characterized by the kidney’s failure to ascend to its normal anatomical location during early embryonic development. This anomaly complicates traditional surgical approaches for renal calculi due to the kidney’s atypical positioning and associated anatomical challenges. We sought to summarize our experience with robotic-assisted pyelolithotomy (RPPK) for pelvic kidney stones. Methods: A retrospective review of patients who underwent RPPK was conducted between 2014 and 2023. Demographic data on stone characteristics, operative details, and postoperative outcomes were analyzed. Results: Four patients (three male; mean age—51.2 years with a range of 45–54; mean BMI—26.6 with a range of 22.3–32.2) underwent RPPK. All had a right-sided pelvic kidney; two had prior failed ureteroscopy. The mean stone diameter was 27.7 mm (range: 17–35); the mean density was 1207.5 HU (range: 905–1500). The mean operative time was 265 min (range: 200–323); the time from incision to closure was 142.2 min (range: 95–225). No ureteral stents or drains were used. Blood loss was negligible. The mean hospital stay was 2.2 days. No immediate complications were recorded. The mean follow-up was 11.75 months (range: 3–30). Conclusions: RPPK is safe and effective for managing pelvic kidney stones. Challenging renal anatomy stone size and density are not obstacles to the robotic approach unlike other fragmentation methods
Whole-Body Cold Stimulation Improves Cardiac Autonomic Control Independently of the Employed Temperature
Authors: Solaro Nadia , Giovanelli Luca , Bianchi Laura , Piterà Paolo , Verme Federica , Malacarne Mara , Pagani Massimo , Fontana Jacopo Maria , Capodaglio Paolo , Lucini Daniela
Published: December 2024

Background/Objectives: The autonomic nervous system (ANS) is considered one of the mechanisms mediating the benefits of whole-body cold stimulation (WBC). Nevertheless, different treatment protocols, different methodologies employed to assess the ANS, and, in particular, difficulties in interpreting the numerous variables obtained represent important barriers to understanding the effects of WBC on the ANS. The present study aimed to explore the effects of WBC on cardiac autonomic control (CAR) as assessed using a single composite percentile-ranked proxy of autonomic balance (ANSI), considering two different WBC temperatures and the same WBC protocol. Methods: Heart rate variability (HRV) was employed to assess the ANS in 23 subjects with obesity who underwent 10 WBC sessions, studied before and after 2 min WBC at −55 °C (15 subjects) or 2 min WBC at −110 °C (8 subjects) both at the first session (T1) and the last one (T10). To overcome some important barriers in data interpretation and age/sex bias, we considered the Autonomic Nervous System Index (ANSI), a single composite percentile-ranked proxy of autonomic control. Results: We observed an improvement in CAR independently of the employed temperature. Both treatments, without distinction, caused a significant increase in the ANSI post-WBC treatment both at T1 and T10 and a significant betterment of the total power of the RR interval variability from pre- to post-treatment at T1 and overall from T1 to T10. Conclusions: WBC was capable of inducing an immediate change in the ANS control (pre- vs. post-treatment both at T1 and T10) and a long-term modulation in cardiac autonomic control (T1-pre vs. T10-pre).
The Role of Radioiodine Therapy in Differentiated Thyroid Cancer Arising from Struma Ovarii: A Systematic Review
Authors: Bellini Pietro , Dondi Francesco , Zilioli Valentina , Gatta Elisa , Cavadini Maria , Cappelli Carlo , Viganò Gian Luca , Bertagna Francesco
Published: December 2024

Background: Struma ovarii (SO) is an ovarian teratoma with the presence of ectopic thyroid tissue. Differentiated thyroid cancer (DTC) in SO is a rare finding. Management of DTC in SO is currently not clearly established. We performed a systematic review of the literature to assess the role of 131I radiometabolic therapy in the treatment of DTC in SO. Methods: a wide literature search in the Scopus, PubMed/MEDLINE, and Web of Science databases was made to find published articles regarding the treatment of patients with DTC and SO. The quality assessment of studies was performed by QUADAS-2 evaluation. Results: eleven studies were included in the systematic review. All of them were retrospective studies and/or case series, and two of them also included a review of the literature. Most of the studies describe cases of DTC in SO treated by total thyroidectomy (TT) and subsequent radioiodine (RAI) therapy, especially in patients with distant metastases and/or concomitant thyroid cancer. However, the majority of patients apparently did not require radiometabolic therapy. Conclusions: TT and subsequent RAI therapy is usually performed in metastatic disease, not recommended in patients with intraovarian disease without risk factors, and it appeared possible but not mandatory in patients with risk factors.
Glucagon-like Peptide-1 Receptor Agonists and Diabetic Kidney Disease: From Bench to Bed-Side
Authors: Abdelrahman Aly M. , Awad Alaa S. , Hasan Irtiza , Abdel-Rahman Emaad M.
Published: December 2024

Glucagon-like peptide-1 (GLP-1) receptor agonists are currently available for the management of type 2 diabetes mellitus. They have been shown to help with diabetic kidney diseases through multiple mechanisms. In this review, we will shed light on the different mechanisms of action through which GLP-1 receptor agonists may achieve their roles in renal protection in diabetics, both in animal and human studies, as well as review the renal outcomes when using these drugs and their safety profile in diabetic patients.
Characteristics of Helicopter Emergency Medical Services (HEMS) Interventions for Burn Patients—A Four-Year Retrospective Analysis
Authors: Wejnarski Arkadiusz , Leszczyński Piotr Konrad , Biadun Maja , Malm Maria , Mitura Kryspin , Sholokhova Daryna , Rzońca Patryk , Gałązkowski Robert , Marzec Leszek
Published: December 2024

Background: The World Health Organization (WHO) estimates that 180,000 patients die from burns every year, which is considered a serious public health issue. Patients with burns require immediate pre-hospital care and transport to specialized treatment facilities. The aim of this study was to outline the profile of the burn patient from the perspective of the Polish Medical Air Rescue (PMAR), as well as to analyze the medical procedures being implemented. Methods: The study includes 2154 interventions by air emergency medical teams (AEMS) which provided aid for burn patients. The analysis covered the period from 2018 to 2022, including nationwide data made available from the IT systems of the PMAR. Statistical design was used, allowing for correlations of variables, at a significance level of p < 0.05. Results: Patients’ ages ranged from 1 month to 96 years (mean 35.05; SD ± 26.88). Adult patients (n = 1409; 65.41%) constituted the vast majority. The number of interventions to children below 1-year-old was noticeable (n = 394; 18.29%). Men were the most likely to suffer burns, up to three times more often than women (n = 1574, 73.07% vs. n = 570, 26.46%. T29—burns to multiple body areas (n = 890)—and T21—burns to the trunk (n = 255)—were most frequently reported as diagnoses according to the ICD-10 classification. A statistically significant association was found between age group and ICD-10 diagnosis (p < 0.001). The vast majority of patients were transported from the scene directly to Burn Treatment Centers (n = 1373; 63.74%). Treatment of pain by helicopter emergency medical services (HEMS) crews appeared to be effective (p < 0.001), and other interventions consisted of administering medications—ketamine (23.72%), rocuronium bromide (15.78%), propofol (14.02%)—and procedures such as sedation (30.87%), as well as intubation (13.42%) and mechanical ventilation (13.23%). Conclusions: The burn patient profile indicates men with a mean age of 35 years. Nevertheless, HEMS crews often carry out missions to infants and newborns. The most common diagnosis was extensive body burns. In 63.74% of the missions, patients were transported to the Burn Treatment Center. The HEMS crews implement effective pharmacological analgesia, and handle rescue medications and procedures to stabilize the patient’s condition.
Pregnancy Outcomes and Maternal Characteristics in Women with Pregestational and Gestational Diabetes: A Population-Based Study in Spain, 2016–2022
Authors: López-de-Andrés Ana , Jimenez-Garcia Rodrigo , Carabantes-Alarcon David , Cuadrado-Corrales Natividad , Bodas-Pinedo Andrés , Moreno-Sierra Jesús , Jimenez-Sierra Ana , Zamorano-Leon José J.
Published: December 2024

Background/Objectives: The objective of this study was to compare trends in the incidence of deliveries and in obstetric interventions and outcomes in women with and without type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM). Methods: This was an observational study using the Spanish National Hospital Discharge Database (2016–2022). Results: A total of 1,995,953 deliveries were recorded between 2016 and 2022 (6495 mothers with T1DM, 5449 with T2DM, and 124,172 with GDM). The incidence of T1DM and GDM increased over time, although it remained stable in women with T2DM. Women with T2DM were more likely to have obstetric comorbid conditions (72.93%) than women with GDM (63.04%), women with T1DM (59.62%), and women who did not have diabetes (45.3%). Pre-eclampsia, previous cesarean delivery, and arterial hypertension were the most prevalent conditions in all types of diabetes. The highest frequency of cesarean delivery was recorded for women with T1DM (55.04%), followed by women with T2DM (44.94%), and those with GDM (28.13%). The probability of cesarean delivery was 2.38, 1.79, and 1.19 times greater for T1DM, T2DM, and GDM, respectively, than for women who did not have diabetes. The adjusted rate for severe maternal morbidity was significantly higher for women with T1DM (RR 2.31; 95%CI 2.02–2.63) and T2DM (RR 1.58; 95%CI 1.34–1.87) than for women without diabetes. Conclusions: The incidence of deliveries in women with T2DM remained unchanged between 2016 and 2022; the incidence of deliveries increased in women with T1DM and GDM. The prevalence of comorbidity and obstetric factors increased over time in women with T1DM and GDM.
A Protocol Investigation Comparing Transcatheter Repair with the Standard Surgical Procedure for Secondary Mitral Regurgitation
Authors: Nappi Francesco , Avtaar Singh Sanjeet Singh , Salsano Antonio , Nassif Aubin , Shingu Yasushige , Wakasa Satoru , Fiore Antonio , Spadaccio Cristiano , EL-Dean Zein
Published: December 2024

Background: Secondary mitral regurgitation (SMR) is characterized by a pathological process impacting the left ventricle (LV) as opposed to the mitral valve (MV). In the absence of structural alterations to the MV, the expansion of the LV or impairment of the papillary muscles (PMs) may ensue. A number of technical procedures are accessible for the purpose of determining the optimal resolution for MR. Nevertheless, there is a dearth of rigorous data to facilitate a comparative analysis of MV replacement, MV repair (including subvalvular repair), and transcatheter mitral valve interventions (TMV-Is). The objective of this investigation is to evaluate and compare the efficacy and clinical outcomes of transcatheter mitral valve repair (TMV-r) utilizing the edge-to-edge mitral valve repair (TEER) procedure in comparison to conventional surgical mitral valve interventions (S-SMVis) in patients with secondary mitral regurgitation. Methods and analysis: A consortium of five cardiac surgery institutions from four European states and Japan have joined forces to establish a multicenter observational registry, designated TEERMISO. Patients who underwent technical procedures for SMR between January 2007 and December 2023 will be enrolled consecutively into the TEERMISO registry. The investigation team evaluated the comparative efficacy of replacement and repair techniques, utilizing both the standard surgical methodology and the transcatheter intervention. The primary clinical outcome will be the degree of left ventricular remodeling, as assessed by the left ventricular end-diastolic volume index, at 10 years. The forthcoming research will assess a variety of secondary endpoints, among which all-cause mortality will be the primary endpoint. Subsequent assessments will be made in the following order: functional status, hospitalization, neurocognition, physiological measures (echocardiographic assessment), occurrence of adverse clinical incidents, and reoperation. Ethics and dissemination: The multicenter design of the database is anticipated to reduce the potential for bias associated with institutional caseload and surgical experience. All participating centers possess an established mitral valve protocol that facilitates comprehensive follow-up and management of any delayed mitral complications following replacement surgery or surgical repair of the secondary mitral regurgitation. The data collected will provide insights into the impact of diverse surgical approaches on standard mitral valve surgery and TEER. This will facilitate the evaluation of LV remodeling over the course of long-term post-procedural follow-up. Trial Registration: ClinicalTrials.gov ID: NCT05090540; IRB ID: 202201143
Dental Considerations in Children with Inherited Bleeding Disorders and Inhibitors: A Systematic Review
Authors: Vujkov Sanja , Bajkin Branislav , Blagojević Duška , Nešković Isidora , Komšić Jelena , Tadić Ana , Petrović Bojan
Published: December 2024

Background/Objectives: This systematic review evaluates the effectiveness of various hematological treatment protocols and local hemostatic measures in preventing oral bleeding and other complications during and after dental treatments in children with inherited bleeding disorders and inhibitors. Methods: This study was registered in the PROSPERO database. The comprehensive search strategy for this systematic review was conducted across five databases, namely, PubMed, Google Scholar, Web of Science, Scopus, and Cochrane Library. The search was aimed at identifying relevant literature published from January 2000 up to February 2024. Eligible studies included those with various designs, such as randomized controlled trials (RCTs), observational studies, cohort studies, case–control studies, and cross-sectional studies. Data extraction was carried out systematically, and relevant information on study characteristics, interventions, treatment protocols, local measures, complications, and outcomes was collected. Results: The systematic review included a total of five studies, encompassing participants ranging from ages of 2 to 18 years. These studies varied in their scope, with some focusing on hemophilia A with inhibitors while others addressed broader inherited bleeding disorders. The interventions examined included various prophylactic and treatment measures such as Emicizumab, recombinant factor VIIa, and local hemostatic measures. The study outcomes primarily assessed the efficacy of these interventions in preventing postoperative bleeding and improving quality of life. Emicizumab has significantly shifted the treatment paradigm for children with inherited bleeding disorders and inhibitors. This prophylactic treatment has been associated with a marked reduction in the frequency of bleeding episodes, fewer hospital admissions for bleeding management, and enhanced participation in daily activities. Conclusions: This review highlights gaps in the management of dental care in children with inherited bleeding disorders and inhibitors. It underscores the need for standardized protocols that integrate new prophylactic treatments such as Emicizumab. Our findings suggest that adopting updated protocols can significantly reduce bleeding complications during dental procedures.
Three-Dimensional Printing of Hydrogel Blend Tissue Engineering Scaffolds with In Situ Delivery of Anticancer Drug for Treating Melanoma Resection-Induced Tissue Defects
Authors: Chen Xiao-Die , Zhang Xin-Yang , Zhu Han-Qi , Lu Helen H. , Wang Min
Published: December 2024

Surgery is considered the gold standard for treating melanoma, but the high recurrence rate after surgery still remains as a major challenge. Therefore, using doxorubicin (DOX) as a model drug, this study investigated the 3D printing of anticancer drug-loaded hydrogel blend scaffolds for inhibiting post-operation melanoma recurrence and for promoting tissue regeneration. Three-dimensional printing could successfully produce methacrylate-modified chitosan (CSMA) and methylcellulose (MC) hydrogel blend scaffolds. Polymer blend inks exhibited satisfactory printability, and the printed porous scaffolds showed good biocompatibility and mechanical properties. Three-dimensionally printed DOX-loaded hydrogel scaffolds displayed controlled drug release, which may effectively prevent/impede tumor recurrence after surgery. Furthermore, combining 3D printing and bioprinting, DOX-loaded and rat bone marrow mesenchymal stem cell (rBMSC)-laden scaffolds were created for assessing local DOX delivery on healthy tissues. Within the 14-day culture period, rBMSCs encapsulated in multilayered scaffolds that were incorporated with DOX displayed rejuvenated cell viability. The 3D printed and bioprinted dual purpose hydrogel scaffolds have the promise of combating tumor recurrence and providing structural support for tissue regeneration.
Computer Vision-Based Gait Recognition on the Edge: A Survey on Feature Representations, Models, and Architectures
Authors: Salcedo Edwin
Published: December 2024

Computer vision-based gait recognition (CVGR) is a technology that has gained considerable attention in recent years due to its non-invasive, unobtrusive, and difficult-to-conceal nature. Beyond its applications in biometrics, CVGR holds significant potential for healthcare and human–computer interaction. Current CVGR systems often transmit collected data to a cloud server for machine learning-based gait pattern recognition. While effective, this cloud-centric approach can result in increased system response times. Alternatively, the emerging paradigm of edge computing, which involves moving computational processes to local devices, offers the potential to reduce latency, enable real-time surveillance, and eliminate reliance on internet connectivity. Furthermore, recent advancements in low-cost, compact microcomputers capable of handling complex inference tasks (e.g., Jetson Nano Orin, Jetson Xavier NX, and Khadas VIM4) have created exciting opportunities for deploying CVGR systems at the edge. This paper reports the state of the art in gait data acquisition modalities, feature representations, models, and architectures for CVGR systems suitable for edge computing. Additionally, this paper addresses the general limitations and highlights new avenues for future research in the promising intersection of CVGR and edge computing.
Hydrodynamic Modelling of Severn Bore and Its Dependence on Ocean Tide and River Discharge
Authors: Che Bowen , Hu Hao , Ma Jun , Liang Dongfang
Published: December 2024

Owing to the high tidal range, the Severn Estuary and Bristol Channel have the potential to generate huge amounts of renewable electricity for the UK. During the flood tide, the surging water travels upstream to form the Severn Bore. This study explores the dynamics of the Severn Bore through hydrodynamic modelling, analyzing how the tidal amplitude, mean water level, and river discharge affect the bore’s intensity, reach, and sustainability. The Delft3D simulations show that the downstream tidal amplitude plays a critical role. Tides with an amplitude of less than 6 m will lead to the disappearance of the Severn Bore. The mean water level also significantly influences the bore’s propagation, with a 1.5 m drop resulting in a 15 km retreat of the bore. A high river discharge rate weakens the bore’s intensity and reduces its reach. These findings underscore the need for careful planning in tidal energy development within the Severn Estuary. Excessive exploitation of tidal energy can be detrimental to the Severn Bore and the ecological function of the estuary.
Analyzing Archive Transit Multibeam Data for Nodule Occurrences
Authors: Mussett Mark E. , Naar David F. , Caress David W. , Conrad Tracey A. , Graham Alastair G. C. , Kaufmann Max , Maia Marcia
Published: December 2024

We show that analyzing archived and future multibeam backscatter and bathymetry data, in tandem with regional environmental parameters, can help to identify polymetallic nodule fields in the world’s oceans. Extensive archived multibeam transit data through remote areas of the world’s oceans are available for data mining. New multibeam data will be made available through the Seabed 2030 Project. Uniformity of along- and across-track backscatter, backscatter intensity, angular response, water depth, nearby ground-truth data, local slope, sedimentation rate, and seafloor age provide thresholds for discriminating areas that are permissive to nodule presence. A case study of this methodology is presented, using archived multibeam data from a remote section of the South Pacific along the Foundation Seamounts between the Selkirk paleomicroplate and East Pacific Rise, that were collected during the 1997 Foundation–Hotline expedition on R/V Atalante. The 12 kHz Simrad EM12D multibeam data and the other forementioned data strongly suggest that a previously unknown nodule occurrence exists along the expedition transit. We also compare the utility of three different backscatter products to demonstrate that scans of printed backscatter maps can be a useful substitute for digital backscatter mosaics calculated using primary multibeam data files. We show that this expeditious analysis of legacy multibeam data could characterize benthic habitat types efficiently in remote deep-ocean areas, prior to more time-consuming and expensive video and sample acquisition surveys. Additionally, utilizing software other than specialty sonar processing programs during this research allows an exploration of how multibeam data products could be interrogated by a broader range of scientists and data users. Future mapping, video, and sampling cruises in this area would test our prediction and investigate how far it might extend to the north and south.
An Improved D* Lite-Based Dynamic Route Planning Algorithm for Ships in Arctic Waters
Authors: Xu Tie , Yang Haoran , Ma Jun , Xiong Kun , Hu Qinyou
Published: December 2024

The ice conditions in Arctic waters are complex and variable, requiring ships to dynamically adjust their routes to ensure safe and efficient navigation. Traditional dynamic path planning algorithms struggle to address the extensive variability of Arctic ice conditions. To tackle this issue, this paper improves the D* Lite algorithm by leveraging the gradual and convergent nature of Arctic ice condition changes. The original algorithm’s local update and path extraction rules are modified to prevent chain updates triggered by minor localized changes, thereby reducing the frequency of updates in non-critical areas. By simulating dynamic route planning for ships in Arctic waters during both the freezing and melting periods, the improved D* Lite algorithm was compared with the original D* Lite algorithm and a global update algorithm in terms of voyage distance, risk coefficient, planning time, and the number of node updates. The computational results demonstrate that the improved D* Lite algorithm achieves planning results very similar to those of the original D* Lite algorithm and the global update algorithm at the lowest update cost, significantly enhancing the safety and efficiency of dynamic route planning for ships in Arctic waters.
Functional Characterization of FgAsp, a Gene Coding an Aspartic Acid Protease in Fusarium graminearum
Authors: Li Ping , Fu Zhizhen , Wang Mengru , Yang Tian , Li Yan , Ma Dongfang
Published: December 2024

Aspartic proteases (APs), hydrolases with aspartic acid residues as catalytic active sites, are closely associated with processes such as plant growth and development and fungal and bacterial pathogenesis. F. graminearum is the dominant pathogenic fungus that causes Fusarium head blight (FHB) in wheat. However, the relationship of APs to the growth, development, and pathogenesis of F. graminearum is not clear. Therefore, we selected the FGSG_09558 gene, whose function annotation is aspartate protease, for further study. In this study, FGSG_09558 was found to contain a conserved structural domain and signal peptide sequence of aspartic acid protease and was therefore named FgAsp. The function of FgAsp in F. graminearum was investigated by constructing the knockout and complementation mutants of this gene. The results showed that with respect to the wild type (PH-1), the knockout mutant showed a significant reduction in mycelial growth, asexual spore production, and sexual spore formation, highlighting the key role of FgAsp in the growth and development of F. graminearum. In addition, the mutants showed a significant reduction in the virulence and accumulation level of deoxynivalenol (DON) content on maize whiskers, wheat germ sheaths, and wheat ears. DON, as a key factor of virulence, plays an important role in the F. graminearum infection of wheat ears, suggesting that FgAsp is involved in the regulation of F. graminearum pathogenicity by affecting the accumulation of the DON toxin. FgAsp had a significant effect on the ability of F. graminearum to utilize various sugars, especially arabinose. In response to the stress, hydrogen peroxide inhibited the growth of the mutant most significantly, indicating the important function of FgAsp in the strain’s response to environmental stress. Finally, FgAsp plays a key role in the regulation of F. graminearum growth and development, pathogenicity, and environmental stress response.
Effects of the Interaction of Salinity and Rare Earth Elements on the Health of Mytilus galloprovincialis: The Case of Praseodymium and Europium
Authors: Leite Carla , Russo Tania , Polese Gianluca , Soares Amadeu M. V. M. , Pretti Carlo , Pereira Eduarda , Freitas Rosa
Published: December 2024

The growing use of products containing rare earth elements (REEs) may lead to higher environmental emissions of these elements, which can potentially enter aquatic systems. Praseodymium (Pr) and europium (Eu) are widely used REEs with various applications. However, their ecotoxicological impacts remain largely unexplored, with poorly understood risks to wildlife. Moreover, organisms also face environmental stressors like salinity fluctuations, and the nature of the interaction between salinity variations and contaminants is not yet clear. Therefore, this study aimed to evaluate the influence of salinity shifts on the impacts of Pr and Eu on adult mussels and the sperm of the species Mytilus galloprovincialis after 28 days and 30 min of exposure, respectively. To do so, biochemical and histopathological alterations were evaluated in adults, while biochemical and physiological changes were analysed in sperm. Additionally, the Integrated Biological Index (IBR) was calculated to understand the overall impact of each treatment. The results showed that adult mussels were most affected when exposed to the combination of high salinity and each element, which altered the behaviour of defence mechanisms causing redox imbalance and cellular damage. On the other hand, sperm demonstrated sensitivity to specific REE-salinity combinations, particularly Pr at lower salinity and Eu at higher salinity. These specific treatments elicited changes in sperm motility and velocity: Pr 20 led to a higher production of O2− and a decrease in velocity, while Eu 40 resulted in reduced motility and an increase in irregular movement. At both lower and higher salinity levels, exposure to Eu caused similar sensitivities in adults and sperm, reflected by comparable IBR scores. In contrast, Pr exposure induced greater alterations in sperm than in adult mussels at lower salinity, whereas the reverse was observed at higher salinity. These findings suggest that reproductive success and population dynamics could be modulated by interactions between salinity levels and REE pollution, highlighting the need for further investigation into how REEs and environmental factors interact. This study offers valuable insights to inform policymakers about the potential risks of REE contamination, emphasising the importance of implementing environmental regulations and developing strategies to mitigate the impact of these pollutants.