bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Sodium Dichloroacetate Alone and in Combination Therapies on Lung Tumor Growth and Metastasis
Authors: Al-Azawi Aya , Sulaiman Shahrazad , Arafat Kholoud , Yasin Javed , Nemmar Abderrahim , Attoub Samir
Published: November 2021

Metabolic reprogramming has been recognized as an essential emerging cancer hallmark. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been reported to have anti-cancer effects by reversing tumor-associated glycolysis. This study was performed to explore the anti-cancer potential of DCA in lung cancer alone and in combination with chemo- and targeted therapies using two non-small cell lung cancer (NSCLC) cell lines, namely, A549 and LNM35. DCA markedly caused a concentration- and time-dependent decrease in the viability and colony growth of A549 and LNM35 cells in vitro. DCA also reduced the growth of tumor xenografts in both a chick embryo chorioallantoic membrane and nude mice models in vivo. Furthermore, DCA decreased the angiogenic capacity of human umbilical vein endothelial cells in vitro. On the other hand, DCA did not inhibit the in vitro cellular migration and invasion and the in vivo incidence and growth of axillary lymph nodes metastases in nude mice. Treatment with DCA did not show any toxicity in chick embryos and nude mice. Finally, we demonstrated that DCA significantly enhanced the anti-cancer effect of cisplatin in LNM35. In addition, the combination of DCA with gefitinib or erlotinib leads to additive effects on the inhibition of LNM35 colony growth after seven days of treatment and to synergistic effects on the inhibition of A549 colony growth after 14 days of treatment. Collectively, this study demonstrates that DCA is a safe and promising therapeutic agent for lung cancer.
Genome-Wide Discovery of miRNAs with Differential Expression Patterns in Responses to Salinity in the Two Contrasting Wheat Cultivars
Authors: Zeeshan Muhammad , Qiu Cheng-Wei , Naz Shama , Cao Fangbin , Wu Feibo
Published: November 2021

Salinity is a serious environmental issue. It has a substantial effect on crop yield, as many crop species are sensitive to salinity due to climate change, and it impact is continuing to increase. Plant microRNAs (miRNAs) contribute to salinity stress response in bread wheat. However, the underlying molecular mechanisms by which miRNAs confer salt tolerance in wheat are unclear. We conducted a genome-wide discovery study using Illumina high throughput sequencing and comprehensive in silico analysis to obtain insight into the underlying mechanisms by which small RNAs confer tolerance to salinity in roots of two contrasting wheat cvv., namely Suntop (salt-tolerant) and Sunmate (salt-sensitive). A total of 191 microRNAs were identified in both cultivars, consisting of 110 known miRNAs and 81 novel miRNAs; 181 miRNAs were shared between the two cultivars. The known miRNAs belonged to 35 families consisted of 23 conserved and 12 unique families. Salinity stress induced 43 and 75 miRNAs in Suntop and Sunmate, respectively. Among them, 14 and 29 known and novel miRNAs were expressed in Suntop and 37 and 38 in Sunmate. In silico analysis revealed 861 putative target mRNAs for the 75 known miRNAs and 52 putative target mRNAs for the 15 candidate novel miRNAs. Furthermore, seven miRNAs including tae-miR156, tae-miR160, tae-miR171a-b, tae-miR319, tae-miR159a-b, tae-miR9657 and novel-mir59 that regulate auxin responsive-factor, SPL, SCL6, PCF5, R2R3 MYB, and CBL-CIPK, respectively, were predicted to contribute to salt tolerance in Suntop. This information helps further our understanding of how the molecular mechanisms of salt tolerance are mediated by miRNAs and may facilitate the genetic improvement of wheat cultivars.
Preoperative Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, and Mean Platelet Volume as Predictors of 1-Year Mortality in Patients Undergoing an Open Repair of Abdominal Aortic Aneurysms: A Retrospective Study
Authors: Ko Da Eun , Yoon Hei Jin , Nam Sang Beom , Song Suk Won , Lee Gisong , Ham Sung Yeon
Published: November 2021

Objectives: To investigate if preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), or mean platelet volume (MPV) could be used to predict 1-year mortality in patients undergoing open abdominal aortic aneurysm (AAA) repair. Methods: We retrospectively reviewed 382 patients who underwent open AAA repair between January 2008 and July 2019. We divided the patients into two groups based on 1-year mortality and compared the preoperative NLR, PLR, and MPV. The patients were then classified into tertiles based on their preoperative NLR (first tertile: <2.41 (n = 111); second tertile: 2.41 ≤ NLR ≤ 6.07 (n = 111); and third tertile: >6.07 (n = 112)). We compared the incidence of mortality and morbidity across the aforementioned tertiles. We performed a stepwise logistic regression analysis to evaluate the predictors for mortality. An additional subgroup analysis was performed by dividing the cases into non-ruptured and ruptured cases. Results: The preoperative NLR was significantly higher in the non-survivor group than in the survivor group (10.53 ± 7.60 vs. 5.76 ± 6.44, respectively, p = 0.003). The PLR and MPV were similar between the groups (145.35 ± 91.11 vs. 154.20 ± 113.19, p = 0.626, 9.38 ± 1.20 vs. 9.11 ± 1.39, p = 0.267, respectively). The incidence of 1-year mortality was 2.7%, 9.0%, and 14.3% in the first, second, and third NLR tertiles, respectively (p = 0.009). Higher NLR (odds ratio 1.085, 95% confidence interval 1.016–1.159, p = 0.015) and ruptured AAA (odds ratio 2.706, 95% confidence interval 1.097–6.673, p = 0.031) were the independent predictors of 1-year mortality in all patients. Moreover, the preoperative NLR was significantly higher in the ruptured AAA than in the non-ruptured AAA group (11.17 ± 7.90 vs. 4.10 ± 4.75, p < 0.001). In subgroup analysis, preoperative NLR (odds ratio 1.144, 95% confidence interval 1.031–1.271, p = 0.012) and PLR (odds ratio 0.986, 95% confidence interval 16 0.975–0.998, p = 0.017) was an independent predictor for 1-year mortality in ruptured cases. Conclusions: We demonstrated an independent relationship between the preoperative NLR and 1-year mortality in patients undergoing open AAA repair, besides PLR and MPV. Furthermore, the NLR and PLR had predictive power for 1-year mortality in ruptured cases.
Risk Factors for Pulmonary Embolism in Patients with Paralysis and Deep Venous Thrombosis
Authors: Keller Karsten , Wöllner Jens , Schmitt Volker H. , Ostad Mir A. , Sagoschen Ingo , Münzel Thomas , Espinola-Klein Christine , Hobohm Lukas
Published: November 2021

Background. Venous thromboembolism is a frequent complication and an important cause of death in patients with paralysis. We aimed to investigate predictors of pulmonary embolism (PE) and the impact of PE on the survival of patients with paralysis in comparison to those with deep venous thrombosis or thrombophlebitis (DVT). Methods: Patients were selected by screening the German nationwide inpatient sample (2005–2017) for paralysis, and were stratified for venous thromboembolism (VTE) and the VTE-sub-entity PE (ICD-code I26). Impact of PE on mortality and predictors for PE were analyzed. Results: Overall, 7,873,769 hospitalizations of patients with paralysis were recorded in Germany 2005–2017, of whom 1.6% had VTE and 7.0% died. While annual hospitalizations increased (2005: 520,357 to 2017: 663,998) (β 12,421 (95% CI 10,807 to 14,034), p < 0.001), in-hospital mortality decreased from 7.5% to 6.7% (β −0.08% (95% CI −0.10% to −0.06%), p < 0.001). When focusing on 82,558 patients with paralysis hospitalized due to VTE (51.8% females; 58.3% aged ≥ 70 years) in 2005–2017, in-hospital mortality was significantly higher in patients with paralysis and PE than in those with DVT only (23.8% vs. 6.3%, p < 0.001). Cancer (OR 2.18 (95% CI 2.09–2.27), p < 0.001), heart failure (OR 1.83 (95% CI 1.76–1.91), p < 0.001), COPD (OR 1.63 (95% CI 1.53–1.72), p < 0.001) and obesity (OR 1.42 (95% CI 1.35–1.50), p < 0.001) were associated with PE. PE (OR 4.28 (95% CI 4.07–4.50), p < 0.001) was a strong predictor of in-hospital mortality. Conclusions: In Germany, annual hospitalizations of patients with paralysis increased in 2005–2017, in whom VTE and especially PE substantially affected in-hospital mortality. Cancer, heart failure, COPD, obesity and acute paraplegia were risk factors of PE.
Cardiac Autonomic Dysfunction Is Associated with Severity of REM Sleep without Atonia in Isolated REM Sleep Behavior Disorder
Authors: You Sooyeoun , Won Kyoung Sook , Kim Keun Tae , Lee Hyang Woon , Cho Yong Won
Published: November 2021

123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy was performed to assess cardiac autonomic dysfunction and demonstrate its correlation with clinical and polysomnographic characteristics in patients with isolated rapid eye movement (REM) sleep behavior disorder. All subjects including 39 patients with isolated REM sleep behavior disorder and 17 healthy controls underwent MIBG cardiac scintigraphy for cardiac autonomic dysfunction assessment. The isolated REM sleep behavior disorder was confirmed by in-lab overnight polysomnography. A receiver operating curve was constructed to determine the cut-off value of the early and delayed heart-to-mediastinum ratio in patients with isolated REM sleep behavior disorder. Based on each cut-off value, a comparison analysis of REM sleep without atonia was performed by dividing isolated REM sleep behavior disorder patients into two groups. MIBG uptake below the cut-off value was associated with higher REM sleep without atonia. The lower heart-to-mediastinum ratio had significantly higher REM sleep without atonia (%), both with cut-off values of early (11.0 ± 5.6 vs. 29.3 ± 23.2%, p = 0.018) and delayed heart-to-mediastinum ratio (9.1 ± 4.3 vs. 30.0 ± 22.9%, p = 0.011). These findings indicate that reduced MIBG uptake is associated with higher REM sleep without atonia in isolated REM sleep behavior disorder.
Subclinical Signs of Retinal Involvement in Hereditary Angioedema
Authors: Triggianese Paola , Di Marino Matteo , Nesi Carolina , Greco Elisabetta , Modica Stella , Chimenti Maria , Conigliaro Paola , Mancino Raffaele , Nucci Carlo , Cesareo Massimo
Published: November 2021

To explore retinal abnormalities using spectral domain optical coherence tomography (SD-OCT) and OCT-angiography (OCT-A) in a highly selective cohort of patients with type I hereditary angioedema (HAE). This prospective case-control study included 40 type I HAE patients and 40 age-/sex-matched healthy subjects (HC). All participants underwent SD-OCT-scanning of retinal posterior pole (PP), peripapillary retinal nerve fiber layer (pRNFL), and optic nerve head (ONH). Superficial/deep capillary density was analyzed by OCT-A. A total of 80 eyes from 40 HAE and 40 eyes from HC were evaluated. The pRNFL was thicker in HAE than in HC in nasal superior (p < 0.0001) and temporal quadrants (p = 0.0005 left, p = 0.003 right). The ONH thickness in HAE patients was greater than in HC in the nasal (p = 0.008 left, p = 0.01 right), temporal (p = 0.0005 left, p = 0.003 right), temporal inferior (p = 0.007 left, p = 0.0008 right), and global (p = 0.005 left, p = 0.007 right) scans. Compared to HC, HAE showed a lower capillary density in both superficial (p = 0.001 left, p = 0.006 right) and deep (p = 0.008 left, p = 0.004 right) whole images, and superficial (p = 0.03 left) and deep parafoveal (p = 0.007 left, p = 0.005 right) areas. Our findings documented subclinical retinal abnormalities in type I HAE, supporting a potential role of the retinal assessment by SD-OCT/OCT-A as a useful tool in the comprehensive care of HAE patients.
Immunohistochemistry for Thymidine Kinase-1 (TK1): A Potential Tool for the Prognostic Stratification of Breast Cancer Patients
Authors: Fanelli Giuseppe Nicolò , Scarpitta Rosa , Cinacchi Paola , Fuochi Beatrice , Szumera-Ciećkiewicz Anna , De Ieso Katia , Ferrari Paola , Fontana Andrea , Miccoli Mario , Naccarato Antonio Giuseppe , Scatena Cristian
Published: November 2021

Breast cancer (BC) is the most frequent non-cutaneous malignancy in women. Histological grade, expression of estrogen and progesterone receptors (ER and PgR), overexpression/amplification of the human epidermal growth factor receptor 2 (HER2) oncogene, and proliferative activity measured with ki-67 provide important information on the biological features of BC and guide treatment choices. However, a biomarker that allows a more accurate prognostic stratification is still lacking. Thymidine kinase-1 (TK1), a ubiquitous enzyme involved in the pyrimidine nucleotide recovery pathway, is a cell-proliferation marker with potential prognostic and predictive impacts in BC. Eighty (80) cases of invasive BC with a long-term follow-up were retrospectively selected, and clinicopathological data were collected for each patient. TK1 tissue expression was evaluated immunohistochemically. Data suggested that TK1 expression levels are positively correlated with ER and PgR expression, and negatively correlated with HER2 status and the impact on patients’ distant recurrence-free survival (DRFS): in detail, among patients undergoing adjuvant chemotherapy, lower TK1 levels are correlated with better DRFS. Therefore, these results contribute to furthering the knowledge of TK1, suggesting a possible and important role of this enzyme as a biomarker in the stratification of BC patients.
Chemokine C-C Motif Ligand 7 (CCL7), a Biomarker of Atherosclerosis, Is Associated with the Severity of Alopecia Areata: A Preliminary Study
Authors: Waśkiel-Burnat Anna , Niemczyk Anna , Blicharz Leszek , Chmielińska Paulina , Zaremba Michał , Gąsecka Aleksandra , Filipiak Krzysztof J. , Olszewska Małgorzata , Rudnicka Lidia
Published: November 2021

Alopecia areata is an autoimmune, inflammatory form of non-scarring hair loss that may affect any hair-bearing area. Recently, an increased risk of cardiovascular disorders has been described in patients with alopecia areata. The aim of the study was to evaluate the serum concentrations of proinflammatory proteins associated with atherosclerosis (chemokine C-C motif ligand 4; CCL4, chemokine C-C motif ligand 7, CCL7; and sortilin, SORT1), and cardiovascular risk (myeloperoxidase, MPO; interleukin 1 receptor-like 1, IL1RL1; and growth differentiation factor 15, GDF15) in patients with alopecia areata without symptoms or prior cardiovascular disease in comparison with healthy controls. Sixty otherwise healthy patients with alopecia areata and twenty control subjects matched for age, gender, and body mass index (BMI) were enrolled in the study. No significant differences in the serum levels of MPO, IL1RL1, CCL4, CCL7, SORT1, and GDF15 were detected between patients with alopecia areata and healthy controls. A positive correlation was found between the serum concentration of CCL7 and the severity of alopecia areata (r = 0.281, p = 0.03), while GDF15 correlated with age at the disease onset (r = 0.509, p < 0.0001). The results of the present study suggest that the severity of alopecia areata may be associated with an increased risk of atherosclerosis.
Changes in Treatment Patterns and Globe Salvage Rate of Advanced Retinoblastoma in Korea: Efficacy of Intra-Arterial Chemotherapy
Authors: Lee Dong Hyun , Han Jung Woo , Hahn Seung Min , Kim Byung Moon , Lyu Chuhl Joo , Lee Sung Chul , Kim Dong Joon , Lee Christopher Seungkyu
Published: November 2021

(1) Background: To analyze changes in treatment patterns for advanced retinoblastoma over time and differences in globe salvage rates; (2) Methods: Retrospective, observational case-control study of 97 eyes of 91 patients with advanced retinoblastoma (Group D and E).; (3) Results: Patients were divided into two groups based on whether they were treated before or after intraarterial chemotherapy (IAC) was introduced in our center in 2010. Before 2010, primary treatment pattern was enucleation, which was performed in 57.6% of cases, whereas primary treatment pattern after 2010 was IAC combined with intravenous chemotherapy (IVC), which was performed in 78.1%. Intravitreal chemotherapy (IVitC) has been performed to treat vitreous and subretinal seeding since 2015. The 5-year globe salvage rate of IVC alone was 24.0% for Group D and 0% for Group E, whereas that of IVC–IAC was 50.4% for Group D and 49.7% for Group E. Whether IVitC was performed or not did not significantly contribute to globe salvage rate. There was one metastatic death in the IVC alone group.; (4) Conclusions: Primary treatment pattern changed from enucleation to IAC-based treatment, which can now save nearly half of eyes with advanced retinoblastoma with excellent safety profile and survival rate.
Implications of Transcranial Magnetic Stimulation as a Treatment Modality for Tinnitus
Authors: Denton Alexa J. , Finberg Ariel , Ashman Peter E. , Bencie Nathalie B. , Scaglione Tricia , Kuzbyt Brianna , Telischi Fred F. , Mittal Rahul , Eshraghi Adrien A.
Published: November 2021

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive, neuromodulating technique for brain hyperexcitability disorders. The objective of this paper is to discuss the mechanism of action of rTMS as well as to investigate the literature involving the application of rTMS in the treatment of tinnitus. The reviewed aspects of the protocols included baseline evaluation, the total number of sessions, frequency and the total number of stimuli, the location of treatment, and the outcome measures. Even with heterogeneous protocols, most studies utilized validated tinnitus questionnaires as baseline and outcome measures. Low frequency (1 Hz) stimulation throughout 10 consecutive sessions was the most widely used frequency and treatment duration; however, there was no consensus on the total number of stimuli necessary to achieve significant results. The auditory cortex (AC) was the most targeted location, with most studies supporting changes in neural activity with multi-site stimulation to areas in the frontal cortex (FC), particularly the dorsolateral prefrontal cortex (DLPFC). The overall efficacy across most of the reviewed trials reveals positive statistically significant results. Though rTMS has proven to impact neuroplasticity at the microscopic and clinical level, further studies are warranted to demonstrate and support the clinical use of rTMS in tinnitus treatment with a standardized protocol.
Low Branched Chain Amino Acids and Tyrosine in Thai Patients with Type 2 Diabetes Mellitus Treated with Metformin and Metformin-Sulfonylurea Combination Therapies
Authors: Sriboonvorakul Natthida , Pan-Ngum Wirichada , Poovorawan Kittiyod , Muangnoicharoen Sant , Quinn Lauren M. , Tan Bee K.
Published: November 2021

Type 2 diabetes mellitus (T2DM) is a growing public health challenge for Thailand (current prevalence ~10.0%). Amino acids offer novel biomarkers to predict risk of T2DM and indicate sub-optimal disease management, which could facilitate earlier treatment. We studied amino acid profiles in a Thai cohort comprising of individuals with T2DM (n = 65 single-drug-treated; n = 38 multi-drug-treated) compared to healthy controls (n = 104) using liquid chromatography-mass spectrometry. Age and BMI were significantly lower in the healthy controls compared to the single or multi-treated T2DM groups. The BCAA (leucine and valine) were significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p < 0.001) and isoleucine was significantly lower in the single-treated compared to the healthy controls (p = 0.014). These findings beg the question whether BCAAs supplementation be beneficial in T2DM patients treated with single or multi-drug therapy? Tyrosine was significantly lower in the single and multi-treated T2DM groups compared to healthy controls (p < 0.001 and p = 0.002), whereas phenylalanine was significantly higher in the multi-treated T2DM group compared to the single treated T2DM group (p = 0.045). We provide novel insights into the effects of diabetes treatments on these amino acids in insulin resistant states such as T2DM in a unique but understudied Thai population.
Marginal Bone Loss around Implants with Internal Hexagonal and Internal Conical Connections: A 12-Month Randomized Pilot Study
Authors: Galindo-Moreno Pablo , Concha-Jeronimo Ada , Lopez-Chaichio Lucia , Rodriguez-Alvarez Roque , Sanchez-Fernandez Elena , Padial-Molina Miguel
Published: November 2021

The aim of this study was to analyze the differences in terms of the marginal bone level (MBL) around implants with either an internal conical or an internal hexagonal implant–prosthesis connection. A randomized clinical trial included patients in need of a single implant-supported restoration. The implant–prosthesis connection was either internal conical or internal hexagonal while maintaining the same type of implant macro- and microarchitecture. Clinical and radiographical variables were registered up to 12 months of follow-up, including MBL. A total of 30 patients were included in the study. The main outcome variable, MBL 12 months after prosthesis delivery, was statistically different in both groups: −0.25 (0.12) vs. −0.70 (0.43) (conical vs. hexagonal; p = 0.033). Differences were also observed at the 3- and 6-month follow-up visits as well as for the MBL change from prosthesis delivery to the 12-month follow-up (−0.15 (0.13) vs. −0.56 (0.44); conical vs. hexagonal; p = 0.023). Correlations between MBL around the implants and radiographic measurements on the adjacent teeth, buccal bone to implant, tissue thickness or keratinized tissue were not significant neither globally nor when analyzed independently by group. In view of such results, it can be concluded that single-unit restorations with internal hexagonal-connection implants induce higher marginal bone loss after 12 months of follow-up from prosthesis delivery than internal conical-connection implants.
Predictive Modeling of Poor Outcome in Severe COVID-19: A Single-Center Observational Study Based on Clinical, Cytokine and Laboratory Profiles
Authors: Gorgojo-Galindo Óscar , Martín-Fernández Marta , Peñarrubia-Ponce María Jesús , Álvarez Francisco Javier , Ortega-Loubon Christian , Gonzalo-Benito Hugo , Martínez-Paz Pedro , Miramontes-González José Pablo , Gómez-Sánchez Esther , Poves-Álvarez Rodrigo , Jorge-Monjas Pablo , Tamayo Eduardo , Heredia-Rodríguez María , Tamayo-Velasco Álvaro
Published: November 2021

Pneumonia is the main cause of hospital admission in COVID-19 patients. We aimed to perform an extensive characterization of clinical, laboratory, and cytokine profiles in order to identify poor outcomes in COVID-19 patients. Methods: A prospective and consecutive study involving 108 COVID-19 patients was conducted between March and April 2020 at Hospital Clínico Universitario de Valladolid (Spain). Plasma samples from each patient were collected after emergency room admission. Forty-five serum cytokines were measured in duplicate, and clinical data were analyzed using SPPS version 25.0. Results: A multivariate predictive model showed high hepatocyte growth factor (HGF) plasma levels as the only cytokine related to intubation or death risk at hospital admission (OR = 7.38, 95%CI—(1.28–42.4), p = 0.025). There were no comorbidities included in the model except for the ABO blood group, in which the O blood group was associated with a 14-fold lower risk of a poor outcome. Other clinical variables were also included in the predictive model. The predictive model was internally validated by the receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.94, a sensitivity of 91.7% and a specificity of 95%. The use of a bootstrapping method confirmed these results. Conclusions: A simple, robust, and quick predictive model, based on the ABO blood group, four common laboratory values, and one specific cytokine (HGF), could be used in order to predict poor outcomes in COVID-19 patients.
Elderly Population with COVID-19 and the Accuracy of Clinical Scales and D-Dimer for Pulmonary Embolism: The OCTA-COVID Study
Authors: Quezada-Feijoo Maribel , Ramos Mónica , Lozano-Montoya Isabel , Sarró Mónica , Cabo Muiños Verónica , Ayala Rocío , Gómez-Pavón Francisco J. , Toro Rocío
Published: November 2021

Background: Elderly COVID-19 patients have a high risk of pulmonary embolism (PE), but factors that predict PE are unknown in this population. This study assessed the Wells and revised Geneva scoring systems as predictors of PE and their relationships with D-dimer (DD) in this population. Methods: This was a longitudinal, observational study that included patients ≥75 years old with COVID-19 and suspected PE. The performances of the Wells score, revised Geneva score and DD levels were assessed. The combinations of the DD level and the clinical scales were evaluated using positive rules for higher specificity. Results: Among 305 patients included in the OCTA-COVID study cohort, 50 had suspected PE based on computed tomography pulmonary arteriography (CTPA), and the prevalence was 5.6%. The frequencies of PE in the low-, intermediate- and high-probability categories were 5.9%, 88.2% and 5.9% for the Geneva model and 35.3%, 58.8% and 5.9% for the Wells model, respectively. The DD median was higher in the PE group (4.33 mg/L; interquartile range (IQR) 2.40–7.17) than in the no PE group (1.39 mg/L; IQR 1.01–2.75) (p < 0.001). The area under the curve (AUC) for DD was 0.789 (0.652–0.927). After changing the cutoff point for DD to 4.33 mg/L, the specificity increased from 42.5% to 93.9%. Conclusions: The cutoff point DD > 4.33 mg/L has an increased specificity, which can discriminate false positives. The addition of the DD and the clinical probability scales increases the specificity and negative predictive value, which helps to avoid unnecessary invasive tests in this population.
Chronotropic Incompetence in Non-Hospitalized Patients with Post-COVID-19 Syndrome
Authors: Jimeno-Almazán Amaya , Pallarés Jesús G. , Buendía-Romero Ángel , Martínez-Cava Alejandro , Courel-Ibáñez Javier
Published: November 2021

Patients recovering from COVID-19 commonly report persistence of dyspnea, exertional fatigue, and difficulties in carrying out their daily activities. However, the nature of these symptoms is still unknown. The purpose of the study was to identify limiting causes of cardiopulmonary origin for the performance of physical exercise in post-COVID-19 condition that could explain the symptomatic persistence of dyspnea or fatigue-related symptoms. Thirty-two non-hospitalized patients with post-COVID-19 condition (i.e., still presenting a chronic symptomatic phase lasting >90 days since debut of symptoms that lasted for at least 2 months and cannot be explained by an alternative diagnosis) completed a clinical examination including echocardiography, submaximal and maximal cardiorespiratory fitness tests (Ekblom-Bak and Bruce’s protocols), and a battery of validated questionnaires about fatigue and exercise intolerance. Four participants (12.5%) reported an abnormal cardiac response to exercise during the submaximal test, which aroused suspicion of the presence of chronotropic incompetence. All of them were confirmed with a positive diagnosis maximal exercise test after cardiology screening, even with a comprehensive clinical examination, resting ECG, and echocardiogram, without other findings. No statistical differences were found in any physiological variables or questionnaire values, between patients with positive and negative diagnoses. Chronotropic incompetence and other autonomic disorders may appear in patients with mild forms of COVID-19 presentation and may persist in the long term, being responsible for exercise intolerance after resolution of acute infection. Clinicians should be aware that chronotropic incompetence and other autonomic disorders may be a complication of COVID-19 and should consider appropriate diagnostic and therapeutic interventions in these patients, especially when early exercise-related fatigability is reported.
Can Cranioplasty Be Considered a Tool to Improve Cognitive Recovery Following Traumatic Brain Injury? A 5-Years Retrospective Study
Authors: Corallo Francesco , Lo Buono Viviana , Calabrò Rocco Salvatore , De Cola Maria Cristina
Published: November 2021

Cranioplasty (CP) is a neurosurgical intervention of skull repairing following a decompressive craniectomy. Unfortunately, the impact of cranioplasty on cognitive and motor function is still controversial. Fifteen TBI subjects aged 26–54 years with CP after decompressive craniectomy were selected in this observational retrospective study. As per routine clinical practice, a neuropsychological evaluation carried out immediately before the cranioplasty (Pre CP) and one month after the cranioplasty (T0) was used to measure changes due to CP surgery. This assessment was performed each year for 5 years after discharge in order to investigate long-term cognitive changes (T1-T5). Before cranioplasty, about 53.3% of subjects presented a mild to severe cognitive impairment and about 40.0% a normal cognition. After CP, we found a significant improvement in all neuropsychological test scores. The more significant differences in cognitive recovery were detected after four years from CP. Notably, we found significant differences between T4 and T0-T1, as well as between T5 and T0-T1-T2 in all battery tests. This retrospective study further suggests the importance of CP in the complex management of patients with TBI showing how these patients might improve their cognitive function over a long period after the surgical procedure.
Clinical Characteristics, Complications and Outcomes of Patients with Severe Acute Respiratory Distress Syndrome Related to COVID-19 or Influenza Requiring Extracorporeal Membrane Oxygenation—A Retrospective Cohort Study
Authors: Roedl Kevin , Kahn Ahmel , Jarczak Dominik , Fischer Marlene , Boenisch Olaf , de Heer Geraldine , Burdelski Christoph , Frings Daniel , Sensen Barbara , Nierhaus Axel , Braune Stephan , Yildirim Yalin , Bernhardt Alexander , Reichenspurner Hermann , Kluge Stefan , Wichmann Dominic
Published: November 2021

Extracorporeal membrane oxygenation (ECMO) represents a viable therapy option for patients with refractory acute respiratory distress syndrome (ARDS). Currently, veno-venous (vv) ECMO is frequently used in patients suffering from coronavirus disease 2019 (COVID-19). VV-ECMO was also frequently utilised during the influenza pandemic and experience with this complex and invasive treatment has increased worldwide since. However, data on comparison of clinical characteristics and outcome of patients with COVID-19 and influenza-related severe ARDS treated with vv-ECMO are scarce. This is a retrospective analysis of all consecutive patients treated with vv/(veno-arterial)va-ECMO between January 2009 and January 2021 at the University Medical Centre Hamburg-Eppendorf in Germany. All patients with confirmed COVID-19 or influenza were included. Patient characteristics, parameters related to ICU and vv/va-ECMO as well as clinical outcomes were compared. Mortality was assessed up to 90 days after vv/va-ECMO initiation. Overall, 113 patients were included, 52 (46%) with COVID-19 and 61 (54%) with influenza-related ARDS. Median age of patients with COVID-19 and influenza was 58 (IQR 53–64) and 52 (39–58) years (p < 0.001), 35% and 31% (p = 0.695) were female, respectively. Charlson Comorbidity Index was 3 (1–5) and 2 (0–5) points in the two groups (p = 0.309). Median SAPS II score pre-ECMO was 27 (24–36) vs. 32 (28–41) points (p = 0.009), and SOFA score was 13 (11–14) vs. 12 (8–15) points (p = 0.853), respectively. Median P/F ratio pre-ECMO was 64 (46–78) and 73 (56–104) (p = 0.089); pH was 7.20 (7.16–7.29) and 7.26 (7.18–7.33) (p = 0.166). Median days on vv/va-ECMO were 17 (7–27) and 11 (7–20) (p = 0.295), respectively. Seventy-one percent and sixty-nine percent had renal replacement therapy (p = 0.790). Ninety-four percent of patients with COVID-19 and seventy-seven percent with influenza experienced vv/va-ECMO-associated bleeding events (p = 0.004). Thirty-four percent and fifty-five percent were successfully weaned from ECMO (p = 0.025). Ninety-day mortality was 65% and 57% in patients with COVID-19 and influenza, respectively (p = 0.156). Median length of ICU stay was 24 (13–44) and 28 (16–14) days (p = 0.470), respectively. Despite similar disease severity, the use of vv/va-ECMO in ARDS related to COVID-19 and influenza resulted in similar outcomes at 90 days. A significant higher rate of bleeding complications and thrombosis was observed in patients with COVID-19.
Clinical Outcomes following Large Vessel Coronary Artery Perforation Treated with Covered Stent Implantation: Comparison between Polytetrafluoroethylene- and Polyurethane-Covered Stents (CRACK-II Registry)
Authors: Bartuś Jerzy , Januszek Rafał , Hudziak Damian , Kołodziejczak Michalina , Kuźma Łukasz , Tajstra Mateusz , Figatowski Tomasz , Pawłowski Tomasz , Gruz-Kwapisz Monika , Smolarek-Nicpoń Malwina , Skoczyńska Agnieszka , Tomasiewicz Brunon , Włodarczak Adrian , Kulczycki Jan , Plens Krzysztof , Jaguszewski Miłosz , Dobrzycki Sławomir , Ochała Andrzej , Gąsior Mariusz , Reczuch Krzysztof , Bartuś Stanisław , Wojakowski Wojciech , Wańha Wojciech
Published: November 2021

Data on the clinical outcomes comparing synthetic fluorocarbon polymer polytetrafluoroethylene- (PTFE, GraftMaster) and polyurethane- (Papyrus) covered stents (CSs) to seal coronary artery perforations (CAPs) are limited. We aimed to evaluate 30-day and 1-year clinical outcomes after PCI complicated by CAP and treated with CS. We assessed 106 consecutive patients with successful CAP sealing (122 CSs): GraftMaster (51 patients, 57 CSs) or Papyrus CS (55 patients, 65 CSs). The primary endpoint was the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiac death, target lesion revascularisation (TLR), and myocardial infarction (MI). The mean age of subjects was 69 ± 9.6 years (53.8% males). No significant differences were identified between the GraftMaster and Papyrus groups at the 30-day follow-up for MACE, cardiac death, MI and stent thrombosis (ST), while significantly lower rate of TLR and TVR (p = 0.02) were confirmed in the Papyrus group. At one year, differences remained similar between stents for MACE, a trend towards a lower rate of TLR (p = 0.07), MI (p = 0.08), and ST (p = 0.08), and higher for cardiac death (p = 0.07) was observed in the Papyrus group. This real-life registry of CAP illustrated that the use of Papyrus CS is associated with lower rates of TLR and TVR at 30-day follow-up in comparison to the GraftMaster CSs and no significant differences between both assessed CS at one year of follow-up.
Use of Coronary CT Angiography to Predict Obstructive Lesions in Patients with Chest Pain without Enzyme and ST-Segment Elevation
Authors: Kim June-sung , Kim Youn-Jung , Shin Yo Sep , Ahn Shin , Kim Won Young
Published: November 2021

It is challenging to rule out acute coronary syndrome among chest pain patients without both ST-segment elevation in electrocardiography and troponin elevation at emergency departments (ED). The purpose of this study was to develop a prediction model for rapidly determining the occurrence of significant stenosis in coronary computed tomography angiography (CCTA). Retrospective observational cohort study was conducted with 904 patients who had presented with chest pain without troponin elevation and ST-segment changes and underwent CCTA between January 2017 and December 2018. The primary endpoint was the presence of significant stenosis on CCTA, defined as narrowing above 70% diameter. The logistic regression model was used for development a new predictive model. One hundred and thirty-four patients (14.8%) were shown severe stenosis. The independent associated factors for significant stenosis were age ≥65 years, male, diabetes, history of acute coronary syndrome, and typical chest pain. Based these results, we developed a new prediction model. The area under the curve was 0.782 (95% confidence interval 0.742–0.822). Moreover, score of ≥5 was chosen as cut-off values with 86.6% sensitivity and 56.4% specificity. In conclusion, among chest pain patients without ST changes and troponin elevation, the new score will be helpful to identify potential candidate for CCTA such as patients with significant stenosis.
Heat Sterilization Effects on Polymeric, FDM-Optimized Orthopedic Cutting Guide for Surgical Procedures
Authors: Frizziero Leonardo , Santi Gian Maria , Leon-Cardenas Christian , Ferretti Patrich , Sali Merve , Gianese Francesco , Crescentini Nicola , Donnici Giampiero , Liverani Alfredo , Trisolino Giovanni , Zarantonello Paola , Stallone Stefano , Di Gennaro Giovanni Luigi
Published: November 2021

Improvements in software for image analysis have enabled advances in both medical and engineering industries, including the use of medical analysis tools to recreate internal parts of the human body accurately. A research analysis found that FDM-sourced elements have shown viability for a customized and reliable approach in the orthopedics field. Three-dimensional printing has allowed enhanced accuracy of preoperative planning, leading to reduced surgery times, fewer unnecessary tissue perforations, and fewer healing complications. Furthermore, using custom tools chosen for each procedure has shown the best results. Bone correction-related surgeries require customized cutting guides for a greater outcome. This study aims to assess the biopolymer-based tools for surgical operations and their ability to sustain a regular heat-sterilization cycle without compromising the geometry and fit characteristics for a proper procedure. To achieve this, a DICOM and FDM methodology is proposed for fast prototyping of the cutting guide by means of 3D engineering. A sterilization test was performed on HTPLA, PLA, and nylon polymers. As a result, the unique characteristics within the regular autoclave sterilization process allowed regular supplied PLA to show there were no significant deformations, whilst annealed HTPLA proved this material’s capability of sustaining repeated heat cycles due to its crystallization properties. Both of these proved that the sterilization procedures do not compromise the reliability of the part, nor the safety of the procedure. Therefore, prototypes made with a similar process as this proposal could be safely used in actual surgery practices, while nylon performed poorly because of its hygroscopic properties.
Colour and Texture Descriptors for Visual Recognition: A Historical Overview
Authors: Bianconi Francesco , Fernández Antonio , Smeraldi Fabrizio , Pascoletti Giulia
Published: November 2021

Colour and texture are two perceptual stimuli that determine, to a great extent, the appearance of objects, materials and scenes. The ability to process texture and colour is a fundamental skill in humans as well as in animals; therefore, reproducing such capacity in artificial (‘intelligent’) systems has attracted considerable research attention since the early 70s. Whereas the main approach to the problem was essentially theory-driven (‘hand-crafted’) up to not long ago, in recent years the focus has moved towards data-driven solutions (deep learning). In this overview we retrace the key ideas and methods that have accompanied the evolution of colour and texture analysis over the last five decades, from the ‘early years’ to convolutional networks. Specifically, we review geometric, differential, statistical and rank-based approaches. Advantages and disadvantages of traditional methods vs. deep learning are also critically discussed, including a perspective on which traditional methods have already been subsumed by deep learning or would be feasible to integrate in a data-driven approach.
Dynamic Pressure Test and Analysis of Marine Ballasted Centrifugal Pump under Rapid Changing Conditions
Authors: Zhu Zhipeng , Liu Houlin
Published: November 2021

Ship ballast pumps have stringent requirements for their transient characteristics. Here, the pneumatic control valve and programmable logic controller (PLC) are applied to realize the rapid reduction in flow rate for ballast pumps, and the dynamic pressure of steady and transient conditions and inner flow for the ballast pump are tested and analyzed. The results show that the dynamic pressure of each study scheme has cyclical increasing trends, however, the larger the amplitude of the flow rate reduction is, the greater the pressure increasing rate of the two measuring points. While the flow rate decreases to 0.4× Qd and 0.2× Qd, the rate of pressure increase is first fast and then slow. The dynamic pressure pulsation intensity is higher than the corresponding steady-state conditions after the transient conditions. With the increase in flow rate reduction, the characteristic frequencies of the dynamic pressure are 1APF (axial passing frequency) and 1BPF (blade passing frequency) and their harmonic frequency. The rapid decrease in flow rate causes the separation vortex in the impeller channel to be generated in advance, and the scale increases, which reduces the pulsation intensity of the pump outlet to prevent an increase in the level of broadband pulsation between 2APF and 1BPF.
PharmVIP: A Web-Based Tool for Pharmacogenomic Variant Analysis and Interpretation
Authors: Piriyapongsa Jittima , Sukritha Chanathip , Kaewprommal Pavita , Intarat Chalermpong , Triparn Kwankom , Phornsiricharoenphant Krittin , Chaosrikul Chadapohn , Shaw Philip J. , Chantratita Wasun , Mahasirimongkol Surakameth , Tongsima Sissades
Published: November 2021

The increasing availability of next generation sequencing (NGS) for personal genomics could promote pharmacogenomics (PGx) discovery and application. However, current tools for analysis and interpretation of pharmacogenomic variants from NGS data are inadequate, as none offer comprehensive analytic functions in a simple, web-based platform. In addition, no tools exist to analyze human leukocyte antigen (HLA) genes for determining potential risks of immune-mediated adverse drug reaction (IM-ADR). We describe PharmVIP, a web-based PGx tool, for one-stop comprehensive analysis and interpretation of genome-wide variants obtained from NGS platforms. PharmVIP comprises three main interpretation modules covering analyses of pharmacogenes involved in pharmacokinetics, pharmacodynamics and IM-ADR. The Guideline module provides Clinical Pharmacogenetics Implementation Consortium (CPIC) drug guideline recommendations based on the translation of genotypic data in genes having guidelines. The HLA module reports HLA genotypes, potential adverse drug reactions, and the relevant drug guidelines. The Pharmacogenes module is employed for prioritizing variants according to variant effect on gene function. Detailed, customizable reports are provided as exportable files and as an interactive web version. PharmVIP is a new integrated NGS workflow for the PGx community to facilitate discovery and clinical application.
Evaluation of the Predictive Role of Blood-Based Biomarkers in the Context of Suspicious Prostate MRI in Patients Undergoing Prostate Biopsy
Authors: Rajwa Pawel , Huebner Nicolai A. , Hostermann Dadjar I. , Grossmann Nico C. , Schuettfort Victor M. , Korn Stephan , Quhal Fahad , König Frederik , Mostafaei Hadi , Laukhtina Ekaterina , Mori Keiichiro , Motlagh Reza Sari , Yanagisawa Takafumi , Aydh Abdulmajeed , Bryniarski Piotr , Pradere Benjamin , Paradysz Andrzej , Baltzer Pascal A. , Grubmüller Bernhard , Shariat Shahrokh F.
Published: November 2021

The aim of this study was to assess the predictive value of pre-biopsy blood-based markers in patients undergoing a fusion biopsy for suspicious prostate magnetic resonance imaging (MRI). We identified 365 consecutive patients who underwent MRI-targeted and systematic prostate biopsy for an MRI scored Prostate Imaging–Reporting and Data System Version (PI-RADS) ≥ 3. We evaluated the neutrophil/lymphocyte ratio (NLR), derived neutrophil/lymphocyte ratio (dNLR), platelet/lymphocyte ratio (PLR), systemic immune inflammation index (SII), lymphocyte/monocyte ratio (LMR,) de Ritis ratio, modified Glasgow Prognostic Score (mGPS), and prognostic nutrition index (PNI). Uni- and multivariable logistic models were used to analyze the association of the biomarkers with biopsy findings. The clinical benefits of biomarkers implemented in clinical decision-making were assessed using decision curve analysis (DCA). In total, 69% and 58% of patients were diagnosed with any prostate cancer and Gleason Grade (GG) ≥ 2, respectively. On multivariable analysis, only high dNLR (odds ratio (OR) 2.61, 95% confidence interval (CI) 1.23–5.56, p = 0.02) and low PNI (OR 0.48, 95% CI 0.26–0.88, p = 0.02) remained independent predictors for GG ≥ 2. The logistic regression models with biomarkers reached AUCs of 0.824–0.849 for GG ≥ 2. The addition of dNLR and PNI did not enhance the net benefit of a standard clinical model. Finally, we created the nomogram that may help guide biopsy avoidance in patients with suspicious MRI. In patients with PI-RADS ≥ 3 lesions undergoing MRI-targeted and systematic biopsy, a high dNLR and low PNI were associated with unfavorable biopsy outcomes. Pre-biopsy blood-based biomarkers did not, however, significantly improve the discriminatory power and failed to add a clinical benefit beyond standard clinical factors.
Analysis of Rare Variants in Genes Related to Lipid Metabolism in Patients with Familial Hypercholesterolemia in Western Siberia (Russia)
Authors: Shakhtshneider Elena , Ivanoshchuk Dinara , Timoshchenko Olga , Orlov Pavel , Semaev Sergey , Valeev Emil , Goonko Andrew , Ladygina Nataliya , Voevoda Mikhail
Published: November 2021

The aim of this work was to identify genetic variants potentially involved in familial hypercholesterolemia in 43 genes associated with lipid metabolism disorders. Targeted high-throughput sequencing of lipid metabolism genes was performed (80 subjects with a familial-hypercholesterolemia phenotype). For patients without functionally significant substitutions in the above genes, multiplex ligation-dependent probe amplification was conducted to determine bigger mutations (deletions and/or duplications) in the LDLR promoter and exons. A clinically significant variant in some gene associated with familial hypercholesterolemia was identified in 47.5% of the subjects. Clinically significant variants in the LDLR gene were identified in 19 probands (73.1% of all variants identified in probands); in three probands (11.5%), pathogenic variants were found in the APOB gene; and in four probands (15.4%), rare, clinically significant variants were identified in genes LPL, SREBF1, APOC3, and ABCG5. In 12 (85.7%) of 14 children of the probands, clinically significant variants were detectable in genes associated with familial hypercholesterolemia. The use of clinical criteria, targeted sequencing, and multiplex ligation-dependent probe amplification makes it possible to identify carriers of rare clinically significant variants in a wide range of lipid metabolism genes and to investigate their influence on phenotypic manifestations of familial hypercholesterolemia.