bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical Evaluation of Current Hypotheses for the Pathogenesis of Hypertrophic Cardiomyopathy
Authors: Ušaj Marko , Moretto Luisa , Månsson Alf
Published: February 2022

Hereditary hypertrophic cardiomyopathy (HCM), due to mutations in sarcomere proteins, occurs in more than 1/500 individuals and is the leading cause of sudden cardiac death in young people. The clinical course exhibits appreciable variability. However, typically, heart morphology and function are normal at birth, with pathological remodeling developing over years to decades, leading to a phenotype characterized by asymmetric ventricular hypertrophy, scattered fibrosis and myofibrillar/cellular disarray with ultimate mechanical heart failure and/or severe arrhythmias. The identity of the primary mutation-induced changes in sarcomere function and how they trigger debilitating remodeling are poorly understood. Support for the importance of mutation-induced hypercontractility, e.g., increased calcium sensitivity and/or increased power output, has been strengthened in recent years. However, other ideas that mutation-induced hypocontractility or non-uniformities with contractile instabilities, instead, constitute primary triggers cannot yet be discarded. Here, we review evidence for and criticism against the mentioned hypotheses. In this process, we find support for previous ideas that inefficient energy usage and a blunted Frank–Starling mechanism have central roles in pathogenesis, although presumably representing effects secondary to the primary mutation-induced changes. While first trying to reconcile apparently diverging evidence for the different hypotheses in one unified model, we also identify key remaining questions and suggest how experimental systems that are built around isolated primarily expressed proteins could be useful.
Discovery of Small Molecule Activators of Chemokine Receptor CXCR4 That Improve Diabetic Wound Healing
Authors: Xu Junwang , Hu Junyi , Idlett-Ali Shaquia , Zhang Liping , Caples Karly , Peddibhotla Satyamaheshwar , Reeves Morgan , Zgheib Carlos , Malany Siobhan , Liechty Kenneth W.
Published: February 2022

Diabetes produces a chronic inflammatory state that contributes to the development of vascular disease and impaired wound healing. Despite the known individual and societal impacts of diabetic ulcers, there are limited therapies effective at improving healing. Stromal cell-derived factor 1α (SDF-1α) is a CXC chemokine that functions via activation of the CXC chemokine receptor type 4 (CXCR4) receptor to recruit hematopoietic cells to locations of tissue injury and promote tissue repair. The expression of SDF-1α is reduced in diabetic wounds, suggesting a potential contribution to wound healing impairment and presenting the CXCR4 receptor as a target for therapeutic investigations. We developed a high-throughput β-arrestin recruitment assay and conducted structure–activity relationship (SAR) studies to screen compounds for utility as CXCR4 agonists. We identified CXCR4 agonist UCUF-728 from our studies and further validated its activity in vitro in diabetic fibroblasts. UCUF-728 reduced overexpression of miRNA-15b and miRNA-29a, negative regulators of angiogenesis and type I collagen production, respectively, in diabetic fibroblasts. In vivo, UCUF-728 reduced the wound closure time by 36% and increased the evidence of angiogenesis in diabetic mice. Together, this work demonstrates the clinical potential of small molecule CXCR4 agonists as novel therapies for pathologic wound healing in diabetes.
Numerical Study of the Influence of the Interaction Distance, the Polymeric Strips Pre-Tensioning, and the Soil–Polymeric Interaction on the Performance of Back-to-Back Reinforced Soil Walls
Authors: Brouthen Abdelaziz , Houhou Mohamed Nabil , Damians Ivan Puig
Published: February 2022

This study describes the results of a series of 2D finite element method (FEM) numerical models of 6 m high back-to-back reinforced soil walls using the geotechnical software PLAXIS. These structures are used to support embankments, especially for bridge abutment approaches. The quantitative influence of problem geometry, strip pre-tensioning, strip type, and surcharging on horizontal displacements, development of soil shear and plastic zones, lateral earth pressure, and reinforcement loads is presented. The numerical results demonstrate how this type of reinforced soil walls perform jointly at a certain distance of interaction between the two opposite walls. The walls of the two opposing sides clearly interact with each other when they are close enough and with an overlapping reinforcement layout. Pre-tensioning load can contribute to achieving vertical wall-facing alignment at the end of construction. Using perforated/holed strips, the tensile loads at the end of construction were reduced by about 30% due to the improved polymeric–soil interface strength and stiffness.
Evaluation of Methods to Collect Diurnal Culicidae (Diptera) at Canopy and Ground Strata, in the Atlantic Forest Biome
Authors: Deus Juliana Telles de , Mucci Luís Filipe , Lucheta Reginatto Simone , Pereira Mariza , Bergo Eduardo Sterlino , de Camargo-Neves Vera Lucia Fonseca
Published: February 2022

Hand-held insect nets are the standard method for capturing vector mosquitoes of sylvatic arboviruses; however, occupational risks and biases due to individual skill and attractiveness are important limitations. The use of chemical attractants and automatic traps could be an alternative to resolve these limitations. This study compares the yields achieved using nets with those employing electrical traps with CO2 and BG-Lure®, near the ground and in the canopy strata (6.0 and 8.0 m high). The study was conducted at the Cantareira State Park, which is in the Brazilian Atlantic Forest biome. In the 18 collections performed, 3570 specimens of 52 taxa were obtained. The most frequent species captured near the ground were Wyeomyia confusa and Limatus durhamii, whereas Sabethes albiprivus, Sabethes purpureus, and Haemagogus leucocelaenus were the most frequent in the canopy. The nets resulted in greater species richness and abundance, followed by the trap employing CO2. The combination of CO2 traps with BG-Lure® did not improve performance. The use of BG-Lure® alone resulted in low abundance and a low number of species. Our results demonstrate that the use of traps with CO2 can be complementary to collections with nets; however, for species of epidemiological interest such as those of the genera Haemagogus and Sabethes, especially in the canopy, the net remains the method of choice.
Emerging Trends and Challenges in Fog and Edge Computing for the Internet of Things
Authors: Confais Bastien , Parrein Benoît
Published: February 2022

Current network architectures such as Cloud computing are not adapted to provide an acceptable Quality of Service (QoS) to the large number of tiny devices that compose the Internet of Things (IoT) [...]
Evaluation of the Association between Fetal Cardiac Disorders with Choroid Plexus Cyst in Fetuses
Authors: Dakkali Mohammad Sedigh , Karimi Behnagh Arman , Ghasemi Assl Shakiba , Kimiaeifar Atiyeh , Radgoodarzi Mohammad
Published: February 2022

Choroid plexus cysts (CPCs) are often transient and benign findings observed in pregnancy screenings. This study aimed to examine the association between the frequency of congenital heart diseases and the detection of CPCs. In this prospective case-control study, pregnant mothers with no predisposing risk factors for the development of fetal cardiac abnormalities were eligible for entry. Based on the presence or absence of CPCs on ultrasound, the enrolled fetuses were divided into two groups. All patients (n = 100) underwent two-dimensional and color Doppler echocardiography to identify potential cardiac anomalies. Overall, CPCs were detected in 53 enrolled fetuses, and the remainder were enrolled as controls (n = 47). Pathological findings, such as echogenic intracardiac focus (EIF), ductal spasm, atrial septal defect (ASD), pericardial effusion, cardiomyopathy, and congenital heart disease were found in neither group. In the CPC group, two mild and six trivial cases of tricuspid regurgitation (TR) were detected. In the controls, five cases of trivial TR were identified. In conclusion, the presence of CPCs was not associated with significant functional or structural fetal cardiac abnormalities, which may be due to altered developmental mechanisms.
Consistency and Reliability Analyses of a Comprehensive Index for the Evaluation of Teeth Alignment Performance
Authors: Mapelli Andrea , Serafin Marco , Dolci Carolina , Gibelli Daniele , Caprioglio Alberto , Sforza Chiarella , Tartaglia Gianluca Martino
Published: February 2022

(1) Introduction: The purpose of this work was to describe a method and propose a novel accuracy index to assess orthodontic alignment performance. (2) Methods: Fifteen patients who underwent orthodontic treatment using directly printed clear aligners were recruited. The study sample included 12 maxillary and 10 mandibular arches, whose pre-treatment, predicted and post-treatment digital models were superimposed on the untreated posterior teeth by means of a best-fit surface-based registration, which was also used to transfer three anatomical landmarks, digitally labeled on the crown of each anterior moving tooth, from the pre-treatment to the predicted and post-treatment models. The Teeth Alignment Performance (TAP) index, quantifying how close the final landmarks were to their expected final position, was proposed as an accuracy index of both individual tooth and group of teeth movement, and its inter-examiner repeatability was tested. (3) Results: No systematic inter-rater discrepancy associated with TAP was observed (p > 0.05), not even when a slight systematic inter-rater difference in landmark labelling was detected (for the upper central incisors, p < 0.001). In addition, all Intra-class Correlation Coefficient (ICC) values showed excellent inter-rater agreement (>0.95), and the small Random Error of Measurement (REM), ranging from 1% for the arch TAP to 3% for the lower canine TAP, indicated that this accuracy index is highly repeatable. (4) Conclusions: The TAP index was proven to be comprehensive, consistent and reliable in assessing the performance of teeth alignment according to a digital plan. The proposed method is also suitable to be implemented in the clinical digital workflow.
Sexual Differences in Internet Gaming Disorder (IGD): From Psychological Features to Neuroanatomical Networks
Authors: Marraudino Marilena , Bonaldo Brigitta , Vitiello Benedetto , Bergui Giovanna C. , Panzica GianCarlo
Published: February 2022

Internet gaming disorder (IGD) has been included in the 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a condition in need of further study, and gaming disorder was recognized by the World Health Organization as a mental disorder in the International Classification of Disease (ICD-11) of 2018. IGD has different characteristics in the two sexes and is more prevalent in males than females. However, even if the female gamer population is constantly growing, the majority of available studies analyzed only males, or the data were not analyzed by sex. To better elucidate sex differences in IGD, we selectively reviewed research publications that evaluated IGD separately for males and females collected in approximately one hundred publications over the past 20 years. The available data in this narrative review indicate that IGD is strongly dimorphic by sex for both its psychological features and the involvement of different brain areas. Impulsivity, low self-control, anxiety, emotion dysregulation, and depression are some of the psychological features associated with IGD that show a sex dimorphism. At the same time, IGD and its psychological alterations are strongly correlated to dimorphic functional characteristics in relevant brain areas, as evidenced by fMRI. More research is needed to better understand sex differences in IGD. Animal models could help to elucidate the neurological basis of this disorder.
Comparison of Hybrid Posterior Fixation and Conventional Open Posterior Fixation Combined with Multilevel Lateral Lumbar Interbody Fusion for Adult Spinal Deformity
Authors: Endo Hirooki , Murakami Hideki , Yamabe Daisuke , Chiba Yusuke , Oikawa Ryosuke , Yan Hirotaka , Doita Minoru
Published: February 2022

We compared radiological and clinical outcomes between multilevel lateral lumbar interbody fusion (LLIF) + hybrid posterior fixation (PF) and multilevel LLIF + conventional open PF in patients with adult spinal deformity (ASD). Patients who underwent minimally invasive surgery for ASD in a single institution between 2014 and 2018 were retrospectively reviewed. Fifty-six patients (hybrid PF, 30; open PF, 26) who underwent ASD correction surgery were enrolled between 2014 and 2018. We evaluated patients’ demographics, clinical outcomes, and radiographical parameters in each group. There was significantly less estimated blood loss in the hybrid PF group (662.8 mL vs. 1088.8 mL; p = 0.012). The CRP level 7 days after surgery was significantly lower in the hybrid PF group (2.9 mg/dL vs. 4.3 mg/dL; p = 0.035). There was no significant difference between the two groups in other demographic variables, visual analog scores for back pain and leg pain, Oswestry Disability Index, coronal Cobb angle, lumbar lordosis, pelvic tilt, pelvic incidence–lumbar lordosis mismatch, and sagittal vertical axis. There was a significantly higher percentage of major complications in the open PF group (42.3% vs. 13.3%; p = 0.039). Thus, LLIF + hybrid PF for ASD corrective surgery may be comparable to LLIF + open PF in terms of clinical and radiographic outcomes.
Squamous Cell Carcinoma of the Vulva: A Survival and Epidemiologic Study with Focus on Surgery and Radiotherapy
Authors: Scampa Matteo , Kalbermatten Daniel F. , Oranges Carlo M.
Published: February 2022

Vulvar squamous cell carcinoma (SCC) is the most frequent vulvar neoplasia. While the primary role of surgery is widely accepted, large population studies are needed to compare survival between diverse treatment modalities and to identify independent prognostic factors to help council patients and guide oncological treatment. The U.S. National Cancer Index, Surveillance, Epidemiology and End Results (SEER) program data between 2000 and 2018 was screened for all squamous cell carcinoma affecting the vulva. Raw data was processed with IBM SPSS. Demographic, clinical-pathological and treatment data were studied. Overall survival (OS) was calculated using the Kaplan–Meier method and subgroups were compared using the log rank test. A multivariate cox regression was conducted to identify independent prognostic factors. A total of 11,360 patients were identified with a median age of 65. Median overall survival was 101 months. Surgery as a primary treatment is the therapeutic sequence associated with the best overall survival. Multivariate cox-regression did not meet proportional hazard assumption. Age, pathological grade, stage at diagnosis, treatment sequence and the use of chemotherapy were identified as independent prognostic factor. Surgery alone is the treatment sequence offering the best overall survival. Surgery should be offered to all eligible patients.
Related Factors of Anemia in Critically Ill Patients: A Prospective Multicenter Study
Authors: Juárez-Vela Raúl , Andrés-Esteban Eva María , Gea-Caballero Vicente , Sánchez-González Juan Luis , Marcos-Neira Pilar , Serrano-Lázaro Ainhoa , Tirado-Anglés Gabriel , Ruiz-Rodríguez Juan Carlos , Durante Ángela , Santolalla-Arnedo Iván , García-Erce José Antonio , Quintana-Díaz Manuel
Published: February 2022

Anemia is common in critically ill patients; almost 95% of patients admitted to intensive care units (ICUs) have hemoglobin levels below normal. Several causes may explain this phenomenon as well as the tendency to transfuse patients without adequate cause: due to a lack of adherence to protocols, lack of supervision, incomplete transfusion request forms, or a lack of knowledge about the indications, risks, and costs of transfusions. Daily sampling to monitor the coagulation parameters and the acid–base balance can aggravate anemia as the main iatrogenic factor in its production. We studied the association and importance of iatrogenic blood loss and other factors in the incidence of anemia in ICUs. We performed a prospective, observational, multicenter study in five Spanish hospitals. A total of 142 patients with a median age of 58 years (IQI: 48–69), 71.83% male and 28.17% female, were admitted to ICUs without a diagnosis of iatrogenic anemia. During their ICU stay, anemia appeared in 66.90% of the sample, 95 patients, (95% CI: 58.51–74.56%). Risk factors associated with the occurrence of iatrogenic anemia were arterial catheter insertion (72.63% vs. 46.81%, p-value = 0.003), venous catheter insertion (87.37% vs. 72.34%, p-value = 0.023), drainages (33.68% vs. 12. 77%, p-value = 0.038), and ICU stay, where the longer the stay, the higher the rate of iatrogenic anemia (p-value < 0.001). We concluded that there was a statistical significance in the production of iatrogenic anemia due to the daily sampling for laboratory monitoring and critical procedures in intensive care units. The implementation of patient blood management programs could address these issues.
Microcirculatory Alterations in Critically Ill Patients with COVID-19-Associated Acute Respiratory Distress Syndrome
Authors: Di Dedda Umberto , Ascari Alice , Fantinato Angela , Fina Dario , Baryshnikova Ekaterina , Ranucci Marco
Published: February 2022

Background: Presently, a number of specific observations have been performed on microcirculatory function in a coronavirus disease-19 (COVID-19) setting. We hypothesized that, in the critically ill, endothelial dysfunction secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the subsequent inflammation and coagulopathy may lead to microcirculatory alterations, further exacerbated by the hypoxemic state. A dysfunctional microcirculation may represent the hidden motor underlying the development of COVID-19’s clinical manifestations. Methods: A single center, prospective, observational study. We analyzed bedside sublingual microcirculation in twenty-four consecutive COVID-19-associated acute respiratory distress syndrome (ARDS) patients mechanically ventilated in an Intensive Care Unit (ICU), together with macro-hemodynamics, clinical parameters, echocardiography, and laboratory data at a single time-point after ICU admission. All participants were recruited between March and May 2020. Results: The microcirculatory pattern was characterized by increased values of total vessel density and perfused vessel density, a reduced value of proportion of perfused vessels and microvascular flow index, and high values of heterogeneity index. The duration of mechanical ventilation before microcirculation assessment was inversely associated with the proportion of perfused vessels (p = 0.023). Within the macro-hemodynamic parameters, the right ventricle end-diastolic diameter was inversely associated with proportion of perfused vessels and microvascular flow index (p = 0.039 and 0.014, respectively) and directly associated with the heterogeneity index (p = 0.033). Conclusions: In COVID-19-associated ARDS patients, the microcirculation showed impaired quality of flow parameters coupled with a high vessel density.
Impact of Glucocorticoid Cumulative Doses in a Real-Life Cohort of Patients Affected by Giant Cell Arteritis
Authors: Castan Paul , Dumont Anael , Deshayes Samuel , Boutemy Jonathan , Martin Silva Nicolas , Maigné Gwénola , Nguyen Alexandre , Gallou Sophie , Sultan Audrey , Aouba Achille , de Boysson Hubert
Published: February 2022

Objectives: To describe the impact of cumulative glucocorticoid (GC) doses on related adverse events (AEs) in giant cell arteritis (GCA) in a real-life setting. Methods: The medical charts of the last 139 consecutive GCA patients followed in a tertiary centre were retrospectively analysed. The cumulative GC doses were calculated, and the main GC-related AEs were collected during the follow-up. Results: After a median follow-up duration of 35.6 (2–111) months, the median cumulative GC dose in the 139 patients was 9184 (1770–24,640) mg, and 131 patients (94%) presented at least one GC-related AE. Infections (63%) were the most frequently reported GC-related AE, followed by metabolic events (63%), including weight gain in 51% of them. Cardiovascular and neuropsychiatric events occurred in 51% and 47% of patients, respectively. Osteoporotic fractures, muscular involvement, digestive events, geriatric deterioration, skin fragility, ophthalmologic complications and hypokalaemia were reported in <35% of patients. Cardiovascular events (p = 0.01), osteoporotic fractures (p = 0.004), cataract occurrence (p = 0.03), weight gain (p = 0.04) and infections (p = 0.01) were significantly associated with GC cumulative doses > 9 g. Longer GC durations were associated with cataract occurrence (p = 0.01), weight gain (p = 0.03) and all-grade infections (p = 0.048), especially herpes zoster occurrence (p = 0.003). Neuropsychiatric and metabolic events appeared within the first months after GC introduction, whereas herpes zoster recurred, and most cardiovascular AEs emerged after 1 year. Geriatric events, especially osteoporotic fractures, occurred 2 years after GC introduction. Conclusion: This study highlights how frequent GC-related AEs are and the impact of prolonged GC and cumulative doses.
New and Specialized Methods of Image Compression
Authors: Starosolski Roman
Published: February 2022

Due to the enormous amounts of images produced today, compression is crucial for consumer and professional (for instance, medical) picture archiving and communication systems [...]
Small Satellite Tools for High-Resolution Infrared Fire Monitoring
Authors: Fischer Christian , Halle Winfried , Säuberlich Thomas , Frauenberger Olaf , Hartmann Maik , Oertel Dieter , Terzibaschian Thomas
Published: February 2022

Space-borne infrared remote sensing specifically for the detection and characterization of fires has a long history in the DLR Institute of Optical Sensor Systems. In the year 2001, the first DLR experimental satellite, Bi-spectral Infrared Detection (BIRD), was launched after an intensive test period with cooled IR sensor systems on airborne systems. The main basis for the development of the FireBIRD mission with the two satellites, Technology Erprobungsträger No 1 (TET-1) and Bi-spectral-Infrared Optical System (BIROS), was the already space-proven sensor and satellite technology with successfully tested algorithms for fire detection and quantification in the form of the so-called fire radiation power (FRP). This paper summarizes the development principles for the IR sensor system of FireBIRD and the most critical design elements of the TET-1 and BIROS satellites, especially concerning the attitude control system—all very essential tools for high-resolution infrared fire monitoring. Key innovative tools necessary to increase the agility of small IR satellites are discussed.
Risk Factors, Clinical Characteristics, Management, and Outcomes of Musculoskeletal Fungal Infection at Thailand’s Largest National Tertiary Referral Center
Authors: Chokevittaya Piyaporn , Chayakulkeeree Methee , Katchamart Wanruchada
Published: February 2022

To investigate the risk factors, clinical characteristics, management, and outcomes of musculoskeletal fungal infection in Thai patients, patients aged ≥18 years definitively diagnosed with musculoskeletal fungal infection by culture and/or histopathology at Siriraj Hospital (Bangkok, Thailand) during 2002–2020 were retrospectively enrolled. Twenty-eight patients (median age: 58.5 years [range: 22–81], 57.1% male) with fungal osteomyelitis (n = 22), septic arthritis (n = 1), or fungal osteomyelitis with septic arthritis (n = 5) were included. Immunocompromised status was common (82%). Most patients had de novo infection from hematogenous spreading that usually presented at a single, non-contiguous site. The median symptom duration prior to diagnosis was 2 months. The tibia and knee were the most common site of osteomyelitis (30%) and septic arthritis (72%), respectively. The most common pathogens were Talaromyces marneffei and Cryptococcus neoformans. Organism identification from tissues at the affected sites was required in all cases. Most patients (82%) required combination surgery and systemic antifungal therapy. Among those with complete follow-up (23/28), 61% and 39% had complete and partial responses, respectively. Musculoskeletal fungal infection is an uncommon disease with insidious onset and non-specific manifestations that requires pathogen identification via tissue cultures and histopathologic studies. Combination surgery and systemic antifungal therapy yielded generally favorable outcomes.
Novel Myco-Coagulant Produced by Lentinus squarrosulus for Removal of Water Turbidity: Fungal Identification and Flocculant Characterization
Authors: Jebun Nessa , Alam Md Zahangir , Mamun Abdullah Al , Ahmad Raus Raha
Published: February 2022

Several river water fungal strains (RWF-1 to RWF-6) were isolated to investigate the potential of having coagulant properties from the metabolites produced by the fungus. The myco-coagulant produced from the liquid-state process was characterized and tested for flocculation of kaolin water. Molecular identification of the fungal strain isolated from river water and characterization of the myco-coagulant produced by the strain are presented in this paper. The genomic DNA of the fungal 18S ribosomal ribonucleic-acid (rRNA) and 28S rRNA genes were used and the species was identified as Lentinus squarrosulus strain 7-4-2 RWF-5. The characterization of myco-coagulant by Fourier-transform infrared spectroscopy (FTIR) showed that hydroxyl, carbonyl, amide and amine groups as principal functional groups were present in the new myco-coagulant. The mean zeta potential value of the myco-coagulant was −7.0 mV while the kaolin solution was −25.2 mV. Chemical analyses of the extracellular myco-coagulant revealed that it contained total sugar (5.17 g/L), total carbohydrate (237 mg/L), protein (295.4 mg/L), glucosamine (1.152 mg/L); and exhibited cellulase activity (20 units/L) and laccase activity (6.22 units/L). Elemental analyses of C, H, O, N and S showed that the weight fractions of each element in the myco-coagulant was 40.9, 6.0, 49.8, 1.7 and 1.4%, respectively. The myco-coagulant showed 97% flocculation activity at a dose of 1.8 mg/L, indicating good flocculation performance compared to that of polyaluminum chloride (PAC). The present work revealed that the fungal strain, L. squarrosulus 7-4-2 RWF-5 is able to produce cationic bio-coagulant. The flocculation mechanism of the novel myco-coagulant was a combination of polymer bridging and charge neutralization.
Genome Mining and Analysis of PKS Genes in Eurotium cristatum E1 Isolated from Fuzhuan Brick Tea
Authors: Guo Xiaoxiao , Chen Fusheng , Liu Jiao , Shao Yanchun , Wang Xiaohong , Zhou Youxiang
Published: February 2022

Eurotium cristatum as the dominant fungi species of Fuzhuan brick tea in China, can produce multitudinous secondary metabolites (SMs) with various bioactivities. Polyketides are a very important class of SMs found in E. cristatum and have gained extensive attention in recent years due to their remarkable diversity of structures and multiple functions. Therefore, it is necessary to explore the polyketides produced by E. cristatum at the genomic level to enhance its application value. In this paper, 12 polyketide synthase (PKS) genes were found in the whole genome of E. cristatum E1 isolated from Fuzhuan brick tea. In addition, the qRT-PCR results further demonstrated that these genes were expressed. Moreover, metabolic analysis demonstrated E. cristatum E1 can produce a variety of polyketides, including citreorosein, emodin, physcion, isoaspergin, dihydroauroglaucin, iso-dihydroauroglaucin, aspergin, flavoglaucin and auroglaucin. Furthermore, based on genomic analysis, the putative secondary metabolites clusters for emodin and flavoglaucin were proposed. The results reported here will lay a good basis for systematically mining SMs resources of E. cristatum and broadening its application fields.
Global Cutaneous Mucormycosis: A Systematic Review
Authors: Skiada Anna , Drogari-Apiranthitou Maria , Pavleas Ioannis , Daikou Eirini , Petrikkos George
Published: February 2022

Cutaneous mucormycosis is the third most common clinical type of mucormycosis. The signs and symptoms vary widely, and it is important to make the diagnosis as early as possible in order to achieve a better outcome. We present a systematic review of its epidemiology, clinical presentation, diagnosis, and treatment, analyzing cases published from 1958 until 2021. The review was conducted according to the PRISMA guidelines and included 693 cases from 485 articles from 46 countries. Most publications were from North America (256 cases, 36.9%) and Asia (216 cases, 31.2%). The most common risk factors were diabetes mellitus (20%) and hematological malignancies (15.7%). However, a large proportion of published cases (275, 39.6%) had no identified underlying disease. The most common mode of transmission was trauma (54%), and 108 (15.6%) cases were healthcare-associated. In this review, 291 (42.5%) patients had localized infection, and 90 (13%) had disseminated mucormycosis. In Europe, N. America and S. America, the most common genus was Rhizopus spp., while in Asia it was Apophysomyces spp. (34.7%). Treatment was performed with antifungals, mainly amphotericin B, and/or surgery. Mortality was significantly lower when both antifungals and surgery were applied (29.6%).
Dissecting the Association of Genetically Predicted Neuroticism with Coronary Artery Disease: A Two-Sample Mendelian Randomization Study
Authors: Yan Tao , Zhu Shijie , Xie Changming , Chen Xingyu , Zhu Miao , Weng Fan , Wang Chunsheng , Guo Changfa
Published: February 2022

Background: Observational studies on the association between neuroticism and coronary artery disease (CAD) are still rare, and the results of existing studies are not consistent. The present study aimed to explore causal associations of neuroticism with CAD. Methods: The summary-level data of GWAS for neuroticism and 12 items used to assess neuroticism were extracted from the UK Biobank, and included up to 380,506 participants. The general data for CAD were obtained from the CARDIoGRAMplusC4D consortium, which assembled 60,801 CAD patients and 123,504 non-cases. Single-nucleotide polymorphisms associated with neuroticism and 12 items at genome-wide significance were explored as instrumental variables. Two-sample Mendelian randomization (TSMR) analyses were performed to evaluate causal associations amongst the genetically predicted neuroticism and 12 items with CAD. Results: The present TSMR study did not reveal the genetic association of neuroticism with CAD. The calculated ORs for CAD using inverse-variance weighted, weighted median, and MR-Egger analysis were 1.12 (p-value = 0.187), 0.99 (p-value = 0.943), and 0.82 (p-value = 0.683), respectively. Further TSMR analysis of 12 dichotomous items for assessing neuroticism suggested that mood swings genetically increased the risk of CAD (OR = 1.67, p-value < 0.001). Conclusions: This study reported no genetically causal association of neuroticism with CAD. The present study also found that mood swings may genetically increase the risk of CAD. These findings may highlight the potential of mood control as a preventive measure for CAD.
Failure to Rescue (FTR) and Pitfalls in the Management of Complex Enteric Fistulas (CEF): From Rescue Surgery to Rescue Strategy
Authors: Cioffi Stefano Piero Bernardo , Chiara Osvaldo , Del Prete Luca , Bonomi Alessandro , Altomare Michele , Spota Andrea , Bini Roberto , Cimbanassi Stefania
Published: February 2022

Purpose: Complex enteric fistulas (CEF) represent general surgeons’ nightmare. This paper aims to explore the impact on failure-to-rescue (FTR) rate of a standardised and integrated surgical and critical care step-up approach. Methods: This was a retrospective observational cohort study. Patients treated for CEF from 2009 to 2019 at Niguarda Hospital were included. Each patient was approached following a three-step approach: study phase, sepsis control and strategy definition phase, and surgical rescue phase. Results: Sixteen patients were treated for CEF. Seven fistulas were classified as complex entero-cutaneous (ECF) and nine as entero-atmospheric fistula (EAF). Median number of surgical procedures for fistula control before definitive surgical attempt was 11 (IQR 2–33.5). The median time from culprit surgery and the first access at Niguarda Hospital to definitive surgical attempt were 279 days (IQR 231–409) and 120 days (IQR 34–231), respectively. Median ICU LOS was 71 days (IQR 28–101), and effective hospital LOS was 117 days, (IQR 69.5–188.8). Three patients (18.75%) experienced spontaneous fistula closure after conversion to simple ECF, whereas 13 (81.25%) underwent definitive surgery for fistula takedown. Surgical rescue was possible in nine patients. Nine patients underwent multiple postoperative revision for surgical complications. Four patients failed to be rescued. Conclusion: An integrated step-up rescue strategy is crucial to standardise the approach to CEF and go beyond the basic surgical rescue procedure. The definition of FTR is dependent from the examined population. CEF patients are a unique cluster of emergency general surgery patients who may need a tailored definition of FTR considering the burden of postoperative events influencing their outcome.
Smoking Obstructive Sleep Apnea: Arguments for a Distinctive Phenotype and a Personalized Intervention
Authors: Oțelea Marina Ruxandra , Trenchea Mihaela , Rașcu Agripina , Antoniu Sabina , Zugravu Corina , Busnatu Ștefan , Simionescu Anca Angela , Arghir Oana Cristina
Published: February 2022

Background: This is the first study that aims to define smoking, with obstructive sleep apnea (OSA), as a phenotype (SOSA). Moreover, we wanted to demonstrate the deleterious effects of the continuation of smoking on OSA. Methods: The cross-sectional study highlighted four dimensions of SOSA: the demographic and anthropometric features, the symptoms, the comorbidities, and the sleep study parameters. This study compared these characteristics between current smokers (CS), those who have never smoked (NS), and ex-smokers (ES) with OSA. Results: More men (83.95% in CS, versus 66.67% in NS) and an earlier onset of OSA (average age = 50.05 in CS, versus 52.26 in NS, p = 0.04) were recorded among CS. The distinguishing symptom of CS was daytime sleepiness, with an Epworth score that was significantly higher than in NS. Chronic obstructive pulmonary disease (COPD) was significantly more prevalent in CS (38.27%) than in NS (1.51%) (p < 0.001). The severity of OSA, consisting of a higher apnea-hypopnea index, a higher oxygen desaturation index, and a longer time spent below 90% oxygen saturation during sleep was significantly influenced by smoking. Conclusions: The SOSA phenotype includes younger male patients with a higher waist circumference, suggesting central obesity. They have a higher prevalence of COPD and a greater severity of OSA, in correlation with the number of pack-years of smoking.
European Ground Squirrels at the Edge: Current Distribution Status and Anticipated Impact of Climate on Europe’s Southernmost Population
Authors: Rammou Dimitra-Lida , Astaras Christos , Migli Despina , Boutsis George , Galanaki Antonia , Kominos Theodoros , Youlatos Dionisios
Published: February 2022

The European ground squirrel (Spermophilus citellus) is an endangered semifossorial small mammal of grassland/agricultural ecosystems. In the last few decades, the species’ population has declined throughout its range in Europe. The Greek populations represent the southernmost limit of the species’ range and are notably small, scattered, and located mainly in human-modified areas. The goal of the present research is to understand the environmental and anthropogenic variables associated with its distribution in the Mediterranean habitats, assess possible drivers of observed local extinctions, and propose conservation and land-use management actions in light of near-future climate change scenarios. We used presence records since 2000 across all known populations (107 colonies) and maximum entropy conditional probability models (MaxEnt) to calculate both the habitat suitability (bioclimatic variables) and habitat availability (anthropogenic/land-use variables) within the European ground squirrel’s historical range in northern Greece. We report a projected 39% to 94.3% decrease in habitat suitability by 2040–2060 due to climate change. Based on our findings, we provide guidance by proposing nascent conservation actions to protect the few existing colonies in Greece via improved land management practices and identify in situ climate refugia that could be prioritized as sites for future reintroductions.
Toxicity of Proton Therapy versus Photon Therapy on Salvage Re-Irradiation for Non-Small Cell Lung Cancer
Authors: Yang Kyungmi , Suh Yang-Gun , Shin Hyunju , Pyo Hongryull , Moon Sung Ho , Ahn Yong Chan , Oh Dongryul , Chung Eunah , Jo Kwanghyun , Noh Jae Myoung
Published: February 2022

This study evaluated the toxicity associated with radiation techniques on curative re-irradiation (re-RT) in patients with thoracic recurrence of non-small cell lung cancer (NSCLC). From 2011 to 2019, we retrospectively reviewed the data of 63 patients with salvage re-RT for in-field or marginal recurrence of NSCLC at two independent institutions. Re-RT techniques using X-ray beams and proton beam therapy (PBT) were also included. Re-RT had a 2-year overall survival (OS) and local progression-free survival of 48.0% and 52.0%, respectively. Fifteen patients experienced grade 3 or higher toxicity after re-RT. The complication rates were 18.2% (4/22) and 26.8% (11/41) in PBT patients and X-ray patients, respectively. Airway or esophageal fistulas occurred in seven patients (11.1%). Fistulas or severe airway obstruction occurred in patients with tumors adjacent to the proximal bronchial tree and esophagus, who underwent hypofractionated radiotherapy (RT) or concurrent chemotherapy, and with a higher dose exposure to the esophagus. In conclusion, salvage re-RT was feasible even in patients with local recurrence within the previous RT field. PBT showed similar survival outcomes and toxicity to those of other techniques. However, thoracic re-RT should be performed carefully considering tumor location and RT regimens such as the fraction size and concurrent chemotherapy.
Quantitative Assessment of Asbestos Fibers in Normal and Pathological Pleural Tissue—A Scoping Review
Authors: Caraballo-Arias Yohama , Caffaro Paola , Boffetta Paolo , Violante Francesco
Published: February 2022

Background: pleural mesothelioma is a rare cancer in the general population, but it is more common in subjects occupationally exposed to asbestos. Studies with asbestos fiber quantification in pleural tissue are scarce: for this reason, we aimed at undertaking a scoping review to summarize the evidence provided by studies in which asbestos fibers were determined by electron microscopy (SEM or TEM) in human pleural tissues, whether normal or pathologic. Materials and methods: A scoping review of articles that quantified asbestos fibers in human pleural tissue (normal or pathologic) by electron microscopy (SEM or TEM), in subjects with asbestos exposure (if any) was performed. Results: The 12 studies selected comprised 137 cases, out of which 142 samples were analyzed. Asbestos fibers were detected in 111 samples (78%) and were below the detectable limit in 31 samples (22%). The concentration of asbestos fibers detected in the positive samples was distributed from as low as 0.01 mfgdt (millions of fibers per gram of dry tissue) up to 240 mfgdt. However, the minimum concentration of fibers overlaps in the three types of tissues (normal pleura, pleural plaque, mesothelioma) in terms of magnitude; therefore, it is not possible to distinguish a definite pattern which differentiates one tissue from the other. Conclusions: The studies included were heterogeneous as to the representativeness of the samples and analytical techniques; the possibility of false negatives must be considered. It would be desirable to systematically search for asbestos fibers to fill the knowledge gap about the presence of asbestos fibers in normal or pathological pleural tissue in order to better understand the development of the different pleural diseases induced by this mineral.
Comparison of Clinical Efficacy and Safety between 70–150 µm and 100–300 µm Doxorubicin Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma
Authors: Yi Jung Woo , Hong Hyun Pyo , Kim Myung Sub , Shin Byung Seok , Kwon Heon-Ju , Kim Byung Ik , Sohn Won
Published: February 2022

Background: This study aimed to compare the efficacy and safety of 70–150 μm doxorubicin drug-eluting bead (DEB) transarterial chemoembolization (TACE) with those of 100–300 μm DEB-TACE as first-line treatment in patients with hepatocellular carcinoma (HCC). Methods: We retrospectively investigated 72 patients who underwent TACE with 70–150 μm DEBs (n = 40) or 100–300 μm DEBs (n = 32) for HCC in a tertiary center between March 2013 and May 2019. Initial treatment response and adverse events were assessed using the modified Response Evaluation Criteria in Solid Tumors and the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, respectively. Results: At the 2-month post-treatment assessment, the complete and objective response rates were 47.5% and 85.0%, respectively, for the 70–150 μm group and 34.4% and 81.3%, respectively, for the 100–300 μm group; however, the difference was not statistically significant (p > 0.05). In total, 65% patients in the 70–150 μm group and 59.4 % patients in the 100-300 μm group experienced at least one symptom of post-embolization syndrome after TACE; all symptoms were classified as grade 1 or 2. There was no significant difference between the two groups in terms of post-procedural laboratory changes such as changes in liver enzymes and bilirubin levels (p > 0.05). Laboratory toxicity of grade 3 occurred in three patients, all of which were transient elevation of liver enzyme levels. Hepatobiliary adverse events, such as bile duct injury, biloma, liver abscess, and hepatic infarction, were not observed in either treatment group. Conclusion: This study found no significant difference in tumor response between 70–150 μm and 100–300 μm DEB-TACE. Both groups showed favorable safety profiles, and the difference was not significant.
Palliative Sedation—The Last Resort in Case of Difficult Symptom Control: A Narrative Review and Experiences from Palliative Care in Switzerland
Authors: Camartin Cristian , Björkhem-Bergman Linda
Published: February 2022

Palliative sedation can be considered as “the last resort” in order to treat unbearable, refractory symptoms or suffering in end-of-life patients. The aim is symptom relief and not to induce death as in the case of euthanasia. The treatment might be one of the most challenging therapeutic options in the field of palliative care, involving both ethical and practical issues. Still, studies have shown that it is a safe and valuable treatment and in general does not shorten the life of the patient. Since patients in Switzerland have the legal option of assisted suicide, palliative sedation is an alternative that has become increasingly important. The use of palliative sedation was reported in 17.5% of all patients admitted to palliative care in Switzerland, making the country of those with the highest use of this treatment. The aim of this narrative review is to discuss ethical and practical issues in palliative sedation, with specific focus on experiences from Switzerland. Indications, ethical considerations, drugs of choice and duration are discussed. Decision making should be based on solid guidelines. When used correctly, palliative sedation is an important and useful tool in palliative care in order to provide good symptom relief.
Cytotoxicity of Acrylic Resins, Particulate Filler Composite Resin and Thermoplastic Material in Artificial Saliva with and without Melatonin
Authors: Cengiz Seda , Velioğlu Neslin , Cengiz Murat İnanç , Çakmak Özlü Fehiye , Akbal Ahmet Ugur , Çoban Ahmet Yılmaz , Özcan Mutlu
Published: February 2022

There is limited information on the effect of melatonin on the cytotoxicity of dental materials. The study evaluated the cytotoxic effects of heat- and auto-polymerized acrylic resin, particulate filler composite resin and a thermoplastic material on L-929 fibroblast cell viability at different incubation periods in artificial saliva without and with melatonin. Disk-shaped specimens were prepared according to each manufacturer’s instructions and divided into two groups to be stored either in artificial saliva (AS) and AS with melatonin (ASM). The measurements were performed using an MTT (3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide) assay, in which the L-929 mouse fibroblasts cell culture was used. For the MTT test, extracts were examined at 1, 24, 72 h and 1 and 2 weeks. Data were analyzed using 3-way ANOVA and Tukey’s tests. No significant difference was found between groups AS and ASM (F = 0.796; p = 0.373). Incubation period significantly affected all materials tested (p < 0.001). Storing resin-based materials in artificial saliva with melatonin solution for 24 h may reduce cytotoxic effects on the fibroblast cells for which the highest effect was observed. Soaking resin prosthesis or orthodontic appliances in artificial saliva with melatonin at least 24 h before intraoral use or rinsing medium containing melatonin may be recommended for decreasing the cytotoxicity of dental resin materials.
Experimental Investigation of Shear Keys for Adjacent Precast Concrete Box Beam Bridges
Authors: Ni Xiaojing , Anselme Ahehehinnou Ougbe , Wang Guannan , Xing Yuan , Xu Rongqiao
Published: February 2022

Longitudinal cracking in shear keys is one of the most frequently recurring problems in the adjacent precast concrete box beam bridges. The relative displacement across the shear key (RDSK) under loads has been used as a direct indicator for shear key cracking. Therefore, accurately simulating the interface between the shear key and beam or providing the correct relationship between shear transfer and RDSK is key to evaluating the damage of the shear key. In this study, the shear transfer properties of four types of composite specimens were studied by static displacement-controlled bi-shear (SDS), cyclic force-controlled bi-shear (CFS), and cyclic displacement-controlled bi-shear (CDS) tests. Two finite element models (FEMs) were established to calibrate and validate the interfacial material parameters. The results showed that adding reinforcement bars over the joints that connect the block and the overlay could improve the bearing capacity of the shear key. Formulae were proposed for the relation between shear force transfer and RDSK in engineering applications. The values of the interfacial material parameters used in the traction–separation model to simulate the interface between the shear key and beam were recommended.