bluuebunny/crossref_metadata_2025 huggingface dataset:
The Knowledge Status of Coastal and Marine Ecosystem Services - Challenges, Limitations and Lessons Learned From the Application of the Ecosystem Services Approach in Management
Authors: Carrasco De La Cruz Pedro Manuel
Published: May 2021

The concept of ecosystem services (ES), first introduced in 1970’s, gained mainstream attention in 2005, when the Millennium Ecosystem Assessment formally proposed a definition for it. In spite of this attention, many aspects about the ES concept have remained controversial to date, i.e., their classification, value, generation, link to human well-being, and supportive role as management tool. This review explores the knowledge status of ecosystem services, focusing on those services generated in coastal and marine environments (CMES). A knowledge gap and an underdevelopment of tools to assess CMES is evident in the literature, especially when compared to the progress done in the assessment of land ES. Possible explanations reside on the yet small proportion that the research done on CMES represents for the ecosystem service framework (ESF), in part due to the intrinsic challenges of researching the marine environment, also due to the limited availability of spatial data on marine ecosystems. Nevertheless, the ES concept is getting more attention toward policy-makers and stakeholders, leading to the implementation of an ecosystem services approach (ESA) to the management and protection of CMES. Six lessons are rescued from the literature to improve the ESA: (1) integration of the ESA in a science-policy process; (2) more simplicity for the CMES prediction models; (3) move toward empowering of stakeholders; (4) integration of the value pluralism of CMES with less focus on money; (5) the link of ES to Human Well-being must not been forgotten; and (6) communication of results and social literacy are key.
Modeling Bacterial Adhesion to Unconditioned Abiotic Surfaces
Authors: Spengler Christian , Maikranz Erik , Santen Ludger , Jacobs Karin
Published: May 2021

Understanding bacterial adhesion as a first step toward biofilm formation is of fundamental interests in many applications. While adhesion to abiotic surfaces is directly relevant for some applications, it also provides a controlled reference setting to study details of the adhesion process in general. This review describes the traditional approaches from contact mechanics and colloidal science, which treat the bacterium–substratum interaction in a continuous manner. We will discuss its shortcomings and provide an introduction to different approaches, which understand the adhesion process as a result of individual stochastic interactions of many macromolecules with the substratum.
Prediction of Contact and Lubrication Characteristics of Micro-textured Surface Under Thermal Line Contact EHL
Authors: Zhao Jiang , Li Zhengminqing , Zhang Hong , Zhu Rupeng
Published: May 2021

In this study, a method combining numerical surface generation technology and three-dimensional hot-line contact EHL is employed to evaluate the contact characteristics of micro-textured surfaces under high-load line contact. Based on numerical simulation, the film thickness, film pressure, friction coefficient and surface flashing temperature of the virtual texture surface with different cross-sectional shapes and sizes are studied. On this basis, the subsurface stress at the contact point is calculated by the DC-FFT algorithm. The results show that, compared with a smooth surface, the micro-textures of different shapes all increase the average oil film thickness of the surface and reduce the friction coefficient, but at the same time lead to an increase in the contact stress of the surface. By changing the width and depth of the texture, the maximum film pressure has changed by 11.4 and 18.5%, respectively.
A Composite Perforated Partitioned Sandwich Panel With Corrugation for Underwater Low-Frequency Sound Absorption
Authors: Wang Junyi , Hu Jiaming , Chen Yun
Published: May 2021

Underwater acoustic wave absorption and control play an important role in underwater applications. Various types of underwater acoustic metamaterials have been proposed in recent years with the vigorous development of acoustic metamaterials. Compared with airborne sound, underwater sound waves have a longer wavelength and much smaller propagation loss, making them more difficult to control. In addition, given that the acoustic impedance of water is much greater than that of air, numerous conventional materials and structures are not suited to underwater use. In this paper, we propose a composite structure based on an excellent broadband low-frequency sound absorber of air using aluminum mixed with rubber. Our composite structure possesses broadband low-frequency (<1,000 Hz) sound absorption underwater, omnidirectional high sound absorption coefficient under the oblique incidence (0–75°), and pressure resistance. It has promising applications for underwater acoustic wave control and contributes to the design of underwater acoustic metamaterials.
Prognostic Significance of the Fission1/Parkin Ratio for Sepsis: A Prospective Cohort Study
Authors: Huang Wei , Wang Xiaoting , Zhang Hongmin , Wang Guangjian , Liu Dawei
Published: May 2021

Introduction: Fission1 (Fis1) and parkin are key proteins related to mitochondrial fission and mitophagy, respectively. This study aimed to assess the prognostic value of the Fis1/parkin ratio as a biomarker in patients with sepsis.

Methods: Consecutive patients with sepsis (n = 133) or simple infection (n = 24) were enrolled within 24 h of arrival at the intensive care unit (ICU). Serum levels of Fis1, parkin, mitofusin2 (Mfn2), and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) were measured by enzyme-linked immunosorbent assay (ELISA) upon ICU admission. Clinical parameters and standard laboratory test data were also collected. All patients received follow-up for at least 28 days.

Results: Patients with sepsis presented with significantly decreased serum levels of parkin, Mfn2, and PGC-1α, but an increased serum Fis1 level and Fis1/parkin, Fis1/Mfn2, and Fis1/PGC-1α ratios at ICU admission. Relative to patients with simple infections, the ratios were remarkably elevated in septic patients—particularly septic shock patients. The area under the receiver operating characteristic (ROC) curve of the Fis1/parkin ratio was greater than that of Fis1, parkin, Mfn2, and PGC-1α levels as well as that of the Fis1/Mfn2 and Fis1/PGC-1α ratios for prediction of 28-day mortality due to sepsis. All of the ratios were significantly higher in non-survivors than survivors at the 28-day follow-up examination. Fis1/parkin ratio was found to be an independent predictor of 28-day mortality in patients with sepsis.

Conclusions: The Fis1/parkin ratio is valuable for risk stratification in patients with sepsis and is associated with poor clinical outcomes for sepsis in the ICU.
Antifungal Activity of Minocycline and Azoles Against Fluconazole-Resistant Candida Species
Authors: Tan Jingwen , Jiang Shaojie , Tan Lihua , Shi Haiyan , Yang Lianjuan , Sun Yi , Wang Xiuli
Published: May 2021

Candida species are the most common fungal pathogens to infect humans, and can cause life-threatening illnesses in individuals with compromised immune systems. Fluconazole (FLU) is the most frequently administered antifungal drug, but its therapeutic efficacy has been limited by the emergence of drug-resistant strains. When co-administered with minocycline (MIN), FLU can synergistically treat clinical Candida albicans isolates in vitro and in vivo. However, there have been few reports regarding the synergistic efficacy of MIN and azoles when used to treat FLU-resistant Candida species, including Candida auris. Herein, we conducted a microdilution assay wherein we found that MIN and posaconazole (POS) showed the best in vitro synergy effect, functioning against 94% (29/31) of tested strains, whereas combinations of MIN+itraconazole (ITC), MIN+voriconazole (VOR), and MIN+VOR exhibited synergistic activity against 84 (26/31), 65 (20/31), and 45% (14/31) of tested strains, respectively. No antagonistic activity was observed for any of these combinations. In vivo experiments were conducted in Galleria mellonella, revealing that combination treatment with MIN and azoles improved survival rates of larvae infected with FLU-resistant Candida. Together, these results highlight MIN as a promising synergistic compound that can be used to improve the efficacy of azoles in the treatment of FLU-resistant Candida infections.
Evaluation of Metagenomic-Enabled Antibiotic Resistance Surveillance at a Conventional Wastewater Treatment Plant
Authors: Majeed Haniyyah J. , Riquelme Maria V. , Davis Benjamin C. , Gupta Suraj , Angeles Luisa , Aga Diana S. , Garner Emily , Pruden Amy , Vikesland Peter J.
Published: May 2021

Wastewater treatment plants (WWTPs) receive a confluence of sewage containing antimicrobials, antibiotic resistant bacteria, antibiotic resistance genes (ARGs), and pathogens and thus are a key point of interest for antibiotic resistance surveillance. WWTP monitoring has the potential to inform with respect to the antibiotic resistance status of the community served as well as the potential for ARGs to escape treatment. However, there is lack of agreement regarding suitable sampling frequencies and monitoring targets to facilitate comparison within and among individual WWTPs. The objective of this study was to comprehensively evaluate patterns in metagenomic-derived indicators of antibiotic resistance through various stages of treatment at a conventional WWTP for the purpose of informing local monitoring approaches that are also informative for global comparison. Relative abundance of total ARGs decreased by ∼50% from the influent to the effluent, with each sampling location defined by a unique resistome (i.e., total ARG) composition. However, 90% of the ARGs found in the effluent were also detected in the influent, while the effluent ARG-pathogen taxonomic linkage patterns identified in assembled metagenomes were more similar to patterns in regional clinical surveillance data than the patterns identified in the influent. Analysis of core and discriminatory resistomes and general ARG trends across the eight sampling events (i.e., tendency to be removed, increase, decrease, or be found in the effluent only), along with quantification of ARGs of clinical concern, aided in identifying candidate ARGs for surveillance. Relative resistome risk characterization further provided a comprehensive metric for predicting the relative mobility of ARGs and likelihood of being carried in pathogens and can help to prioritize where to focus future monitoring and mitigation. Most antibiotics that were subject to regional resistance testing were also found in the WWTP, with the total antibiotic load decreasing by ∼40–50%, but no strong correlations were found between antibiotics and corresponding ARGs. Overall, this study provides insight into how metagenomic data can be collected and analyzed for surveillance of antibiotic resistance at WWTPs, suggesting that effluent is a beneficial monitoring point with relevance both to the local clinical condition and for assessing efficacy of wastewater treatment in reducing risk of disseminating antibiotic resistance.
Effects of Field Fumigation and Inoculation With the Pecan Truffle (Tuber lyonii) on the Fungal Community of Pecan (Carya illinoinensis) Seedlings Over 5 Years
Authors: Grupe Arthur C. , Jusino Michelle A. , Mujic Alija B. , Spakes-Richter Brantlee , Bonito Gregory , Brenneman Tim , Smith Matthew E.
Published: May 2021

Truffle fungi are esteemed for their aromatic qualities and are among the most widely cultivated edible ectomycorrhizal fungi. Here we document a successful method for establishing Tuber lyonii, the pecan truffle, on pecan (Carya illinoinensis) seedlings in a field setting. We assessed the impacts of soil fumigation and varying concentrations of truffle spore inoculum on the ectomycorrhizal fungal and the complete fungal communities as well as the colonization of T. lyonii on pecan roots at three nurseries in Georgia, United States. To identify fungal communities on pecan seedlings, we performed high-throughput amplicon sequencing of the fungal ITS1 rDNA region. Our 5-year long field experiment demonstrates that fumigation and inoculation together resulted in the highest persistence of T. lyonii on pecan roots. While fungal OTU numbers fluctuated over the years of our experiments, there was no statistical support to demonstrate diversification of communities when Shannon diversity metrics were used. However, we did find that older seedlings were less likely to be dominated by T. lyonii compared to younger ones, suggesting successional changes in the fungal community over time. This suggests that transplanting inoculated seedlings after 2 or 3 years post-inoculation is optimal for future truffle propagation efforts. Our results demonstrate that T. lyonii can be established in situ with methods that are compatible with current pecan nursery industry practices and that fungal communities on pecan seedlings vary depending on the experimental treatments used during planting. While the pecan truffle is not yet widely cultivated, our results provide insights for future large-scale cultivation of this and perhaps other Tuber species.
Using Metabolomics to Differentiate Player Positions in Elite Male Basketball Games: A Pilot Study
Authors: Khoramipour Kayvan , Gaeini Abbas Ali , Shirzad Elham , Gilany Kambiz , Chamari Karim , Sandbakk Øyvind
Published: May 2021

Purpose: The current study compared metabolic profiles and movement patterns between different player positions and explored relationships between indicators of internal and external loads during elite male basketball games.

Methods: Five main players from 14 basketball teams (n = 70) were selected as subjects and defined as backcourt (positions 1–3) or frontcourt (positions 4–5) players. Video-based time motion analysis (VBTMA) was performed based on players’ individual maximal speeds. Movements were classified into high and low intensity running with and without ball, high and low intensity shuffling, static effort and jumps. Saliva samples were collected before and after 40-min basketball games with metabolomics data being analyzed by multivariate statistics. Independent t-tests were used to compare VBTMA.

Results: Frequency, duration, and distance of high and low intensity running and -shuffling were higher in backcourt players, whereas static effort duration and frequency as well as jump frequency were higher in frontcourt players (all p ≤ 0.05). The levels of taurine, succinic acid, citric acid, pyruvate, glycerol, acetoacetic acid, acetone, and hypoxanthine were higher in backcourt players, while lactate, alanine, 3-methylhistidine were higher and methionine was lower in frontcourt players (all p < 0.05). High intensity running with ball was significantly associated by acetylecholine, hopoxanthine, histidine, lactic acid and leucine in backcourt players (p < 0.05).

Conclusion: We demonstrate different metabolic profiles of backcourt and frontcourt players during elite male basketball games; while aerobic metabolic changes are more present in backcourt players, frontcourt players showed lager changes in anaerobic metabolic pathways due to more static movements.
CXCR2 May Serve as a Useful Index of Disease Activity in Interstitial Lung Disease Associated With Primary Sjögren’s Syndrome
Authors: Zhu Xiaofang , Lu Saisai , Zhu Lixia , Yu Mengjiao , Wei Tingting , Zhu Xiaochun , Chen Dan , Chen Chengshui
Published: May 2021

Background: Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by typical autoantibody production and lymphocytic-mediated exocrine gland damage. Interstitial lung disease (ILD) is a common complication of pSS and can be associated with a poor prognosis. However, the pathogenesis of ILD in pSS is still unclear.

Methods: In this study, we used RNA sequencing to investigate the gene-expression profile of the minor salivary glands (MSGs) from 36 patients with ILD-pSS and 128 patients with non-ILD-pSS.

Results: In the remarkably enriched chemokine-mediated signaling pathway, C-X-C motif chemokine receptor 2 (CXCR2), a receptor for interleukin-8, which participates in the activation of neutrophils, was found to be significantly elevated in both MSG and plasma from pSS patients with vs. without ILD (p < 0.001). Furthermore, the CXCR2 expression level in MSG and plasma was significantly associated with the diffusing capacity of the lungs for carbon monoxide, erythrocyte sedimentation rate, and EULAR Sjögren’s Syndrome disease Activity Index in ILD-pSS.

Conclusion: Therefore, with its potential role in ILD progression in patients with pSS and its strong association with clinical manifestations of the disease, CXCR2 may serve as a useful index for disease activity in ILD associated with pSS.
The Small Ones Matter—sHsps in the Bacterial Chaperone Network
Authors: Obuchowski Igor , Karaś Piotr , Liberek Krzysztof
Published: May 2021

Small heat shock proteins (sHsps) are an evolutionarily conserved class of ATP-independent chaperones that form the first line of defence during proteotoxic stress. sHsps are defined not only by their relatively low molecular weight, but also by the presence of a conserved α-crystallin domain, which is flanked by less conserved, mostly unstructured, N- and C-terminal domains. sHsps form oligomers of different sizes which deoligomerize upon stress conditions into smaller active forms. Activated sHsps bind to aggregation-prone protein substrates to form assemblies that keep substrates from irreversible aggregation. Formation of these assemblies facilitates subsequent Hsp70 and Hsp100 chaperone-dependent disaggregation and substrate refolding into native species. This mini review discusses what is known about the role and place of bacterial sHsps in the chaperone network.
Vitamin D, Chronic Migraine, and Extracranial Pain: Is There a Link? Data From an Observational Study
Authors: Rebecchi Valentina , Gallo Daniela , Princiotta Cariddi Lucia , Piantanida Eliana , Tabaee Damavandi Payam , Carimati Federico , Gallazzi Marco , Clemenzi Alessandro , Banfi Paola , Candeloro Elisa , Tanda Maria Laura , Mauri Marco , Versino Maurizio
Published: May 2021

Several studies focused on the role of vitamin D (vitD) in pain chronification. This study focused on vitD level and pain chronification and extension in headache disorders. Eighty patients with primary headache underwent neurological examination, laboratory exams, including serum calcifediol 25(OH)D, and headache features assessment along with three questionnaires investigating depression, anxiety, and allodynia. The 86.8% of the population had migraine (48% episodic and 52% chronic). The 44.1% of patients had extracranial pain, and 47.6% suffered from allodynia. A vitD deficit, namely a serum 25(OH)D level <20 ng/ml, was detectable in 46.1% of the patients, and it occurred more frequently (p = 0.009) in patients suffering from chronic migraine (CM)–medication overuse migraine (MOH) (62.9%) than in episodic migraine (EM, 25.7%) or tension-type headache (TTH, 11.4%). The occurrence of extracranial pain and allodynia was higher in the CM-MOH than in the EM and in the TTH groups but was not related to the co-occurrence of vitD deficiency (Fisher's exact test p = 0.11 and p = 0.32, respectively). Our findings show that 25(OH)D deficit is also related to chronic headache, probably because of vitD anti-inflammatory and tolerogenic properties, reinforcing the idea of a neuroinflammatory mechanism underpinning migraine chronification.
Pridopidine for the Improvement of Motor Function in Patients With Huntington's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Chen Shujun , Liang Tianyu , Xue Tao , Xue Shouru , Xue Qun
Published: May 2021

Background: Huntington's disease (HD) is a progressive neurodegenerative disorder. Generally, it is characterized by deficits in cognition, behavior, and movement. Recent studies have shown that pridopidine is a potential and effective drug candidate for the treatment of HD. In the present study, we performed a meta-analysis to evaluate the efficacy and safety of pridopidine in HD.

Methods: The MEDLINE, EMBASE, CENTRAL, and Clinicaltrials.gov databases were searched for randomized controlled trials (RCTs) which had that evaluated pridopidine therapy in HD patients.

Results: We pooled data from 1,119 patients across four RCTs. Patients in the pridopidine group had a significantly lower Unified Huntington's Disease Rating Scale (UHDRS)-modified Motor Score (mMS) (MD −0.79, 95% CI = −1.46 to −0.11, p = 0.02) than those in the placebo group. Additionally, no differences were observed in the UHDRS-Total Motor Score (TMS) (MD −0.91. 95% CI = −2.03 to 0.21, p = 0.11) or adverse events (RR 1.06, 95% CI = 0.96 to 1.16, p = 0.24) in the pridopidine and placebo groups. In the subgroup analysis, the short-term (≤12 weeks) and long-term (>12 weeks) subgroups exhibited similar efficacy and safety with no statistical significance in TMS, mMS, or adverse events. However, TMS (MD −1.50, 95% CI = −2.87 to −0.12, p = 0.03) and mMS (MD −1.03, 95% CI = −1.87 to −0.19, p = 0.02) were observed to be improved significantly when the dosage of pridopidine ≥90 mg/day. Additionally, pridopidine (≥90 mg/day) increased total adverse events (RR 1.11, 95% CI = 1.00 to 1.22, p = 0.04) compared with placebo. On this basis, we analyzed the incidence of various adverse events when the dosage was ≥90 mg/day. Nonetheless, these results were within the acceptable threshold, although patients developed symptoms, such as nasopharyngitis and insomnia.

Conclusion: Pridopidine improved mMS and had no statistical significance in association with TMS or adverse events. Pridopidine (≥90 mg/day) improved TMS and mMS but increased adverse events, such as nasopharyngitis and insomnia. More RCTs were expected to assess pridopidine in HD.
Cervicocephalic Spotty Calcium for the Prediction of Coronary Atherosclerosis in Patients With Acute Ischemic Stroke
Authors: Zheng Chong , Yan Shaozhen , Fu Fan , Zhao Cheng , Guo Daode , Wang Zhichao , Lu Jie
Published: May 2021

Purpose: To investigate the characteristics of cervicocephalic spotty calcium (SC) and coronary atherosclerosis in patients with acute ischemic stroke (AIS) and to assess the predictive value of SC for coronary atherosclerosis using combined coronary and cervicocephalic CTA.

Materials and Methods: Patients with AIS (n = 70) confirmed by brain MRI or CT and patients with asymptomatic carotid atherosclerosis (n = 58) confirmed by carotid ultrasonography were enrolled in our study. Subjects in both groups underwent combined coronary and cervicocephalic CTA. SC was used to evaluate cervicocephalic atherosclerosis. Coronary artery stenosis (CAS) ≥ 50% by segment and coronary artery calcium score (CACS) were used to evaluate coronary atherosclerosis. The SC frequency and the difference in coronary atherosclerosis between the two groups were compared, and the correlation between SC and coronary atherosclerosis was analyzed. Independent factors for CAS ≥ 50% were assessed via logistic regression analysis. Receiver operating characteristic curve analysis was performed to evaluate the added value of SC for predicting CAS ≥ 50%.

Results: Both SC and the CACS were significantly higher in the Stroke group than in the Control group (total SC count: 6.83 ± 4.34 vs. 2.98 ± 2.87, P < 0.05; CACS: 477.04 ± 798.01 vs. 136.31 ± 205.65, P < 0.05). There were significant differences in the presence of CAS ≥ 50% (61.4 vs. 27.6%, P < 0.001). SC and coronary atherosclerosis were significantly correlated for both the CACS and CAS ≥ 50% (r = 0.746 and 0.715, respectively; P < 0.001). SC was an independent predictor for CAS ≥ 50%.

Conclusion: SC correlates significantly with the CACS and could serve as an independent predictor of CAS ≥ 50% in patients with AIS, which suggests that combined cerebrovascular and cardiovascular assessments are of importance for such patients.
Clinical Review and Prognostic Analysis of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionate Receptor-Associated Encephalitis
Authors: Wang Kemo , Shi Yanting , Du Qianwen , Zhang Ran-ran , Wu Huaikuan , Qiao Shan , Liu Xuewu
Published: May 2021

Purpose: Autoimmune encephalitis (AE) is a heterogeneous neurological autoimmune disorder associated with cognitive and psychiatric symptoms. It can be divided into several subtypes based on autoantibodies. Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis (AMPAR-E) is one of the recently discovered AE subtypes, usually manifesting limbic encephalitis and with a good prognosis. Considering AMPAR-E has been described for the first time, only a few cases with similar antibodies have been reported clinically. We aimed to clarify the clinical course and prognosis of the disease in the light of previous reports.

Patients and Methods: We collected data on the diagnosis and treatment of six cases of AMPAR-E, diagnosed at the Qilu Hospital of Shandong University in the past 5 years. We retrospectively analyzed the clinical characteristics of the patients and performed a follow-up of the disease.

Results: The patients often presented with limbic encephalitis, which sometimes coexisted with tumors. In addition, immunotherapy had a significant effect on the disease. The clinical outcome was related to factors such as the age of onset, timing of treatment, and presence of tumors.

Conclusion: In conclusion, specific antibody tests should be performed as early as possible in suspected cases. Clinicians should actively administer immunotherapy and the management of the co-tumor. In addition, repeat antibody tests and image examinations following discharge from the hospital guide the maintenance protocol of immunotherapy.
Iterative Restoration of the Fringe Phase (REFRASE) for QSM
Authors: Lindemeyer Johannes , Worthoff Wieland A. , Shymanskaya Aliaksandra , Shah N. Jon
Published: May 2021

In quantitative susceptibility mapping (QSM), reconstructed results can be critically biased by misinterpreted or missing phase data near the edges of the brain support originating from the non-local relationship between field and susceptibility. These data either have to be excluded or corrected before further processing can take place. To address this, our iterative restoration of the fringe phase (REFRASE) approach simultaneously enhances the accuracy of multi-echo phase data QSM maps and the extent of the area available for evaluation. Data loss caused by strong local phase gradients near the surface of the brain support is recovered within the original phase data using harmonic and dipole-based fields extrapolated from a robust support region toward an extended brain mask. Over several iterations, phase data are rectified prior to the application of further QSM processing steps. The concept is successfully validated on numerical phantoms and brain scans from a cohort of volunteers. The increased extent of the mask and improved numerical stability within the segmented globus pallidus confirm the efficacy of the presented method in comparison to traditional evaluation.
Do Impairments in Visual Functions Affect Skiing Performance?
Authors: Stalin Amritha , Creese Marieke , Dalton Kristine Nicole
Published: May 2021

Nordic and alpine skiing-related visual tasks such as identifying hill contours, slope characteristics, and snow conditions increase demands on contrast processing and other visual functions. Prospective observational studies were conducted to assess the relationships between skiing performance and a broad range of visual functions in nordic and alpine skiers with vision impairments. The study hypothesized that contrast sensitivity (CS), visual acuity (VA), and visual field (VF) would be predictive of skiing performance. Binocular static VA, CS, light sensitivity, glare sensitivity, glare recovery, dynamic VA, translational and radial motion perception, and VF were assessed in elite Para nordic (n = 26) and Para alpine (n = 15) skiers. Skiing performance was assessed based on skiers’ raw race times. Performance on the visual function tests was compared with skiing performances using Kendall’s correlations (with and without Bonferroni–Holm corrections) and linear multivariable regressions (p < 0.05 considered significant). None of the vision variables were significantly correlated with performance in Para nordic or Para alpine skiing after Bonferroni–Holm corrections were applied. Before applying the corrections, VF extent (ρ = -0.37, p = 0.011), and static VA (ρ = 0.26, p = 0.066) demonstrated the strongest correlations with Para nordic skiing performance; in Para alpine skiing, static VA and CS demonstrated the strongest correlations with downhill (static VA: ρ = 0.54, p = 0.046, CS: ρ = -0.50, p = 0.06), super G (static VA: ρ = 0.50, p = 0.007, CS: ρ = -0.51, p = 0.017), and giant slalom (static VA: ρ = 0.57, p = 0.01, CS: ρ = -0.46, p = 0.017) performance. Dynamic VA and VF were significantly associated with downhill (ρ = 0.593, p = 0.04) and slalom (ρ = -0.49, p = 0.013) performances, respectively. Static VA was a significant predictor of giant slalom [(F(3,11) = 24.71, p < 0.001), and R of 0.87], super G [(F(3,9) = 17.34, p = 0.002), and R of 0.85], and slalom [(F(3,11) = 11.8, p = 0.002), and R of 0.80] performance, but CS and VF were not. Interestingly, static VA and CS were highly correlated in both Para nordic (ρ = -0.60, p < 0.001) and Para alpine (ρ = -0.80, p < 0.001) skiers. Of the vision variables, only static VA and VF were associated with skiing performance and should be included as the in Para nordic and Para alpine classifications. The strong correlations between static VA and CS in these skiers with vision impairment may have masked relationships between CS and skiing performance.
Drug Response-Related DNA Methylation Changes in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder
Authors: Zhou Jiaqi , Li Miao , Wang Xueying , He Yuwen , Xia Yan , Sweeney John A. , Kopp Richard F. , Liu Chunyu , Chen Chao
Published: May 2021

Pharmacotherapy is the most common treatment for schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Pharmacogenetic studies have achieved results with limited clinical utility. DNA methylation (DNAm), an epigenetic modification, has been proposed to be involved in both the pathology and drug treatment of these disorders. Emerging data indicates that DNAm could be used as a predictor of drug response for psychiatric disorders. In this study, we performed a systematic review to evaluate the reproducibility of published changes of drug response-related DNAm in SCZ, BD and MDD. A total of 37 publications were included. Since the studies involved patients of different treatment stages, we partitioned them into three groups based on their primary focuses: (1) medication-induced DNAm changes (n = 8); (2) the relationship between DNAm and clinical improvement (n = 24); and (3) comparison of DNAm status across different medications (n = 14). We found that only BDNF was consistent with the DNAm changes detected in four independent studies for MDD. It was positively correlated with clinical improvement in MDD. To develop better predictive DNAm factors for drug response, we also discussed future research strategies, including experimental, analytical procedures and statistical criteria. Our review shows promising possibilities for using BDNF DNAm as a predictor of antidepressant treatment response for MDD, while more pharmacoepigenetic studies are needed for treatments of various diseases. Future research should take advantage of a system-wide analysis with a strict and standard analytical procedure.
A Nomogram for Predicting Multiple Metastases in Metastatic Colorectal Cancer Patients: A Large Population-Based Study
Authors: Ge Yuhang , Xiang Renshen , Ren Jun , Song Wei , Lu Wei , Fu Tao
Published: May 2021

Objectives

The present study aims to discover the risk factors of multiple metastases and develop a functional nomogram to forecast multiple metastases in metastatic colorectal cancer (mCRC) patients.

Methods

mCRC cases were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Survival times between multiple metastases and single metastasis were compared using Kaplan–Meier analysis and log-rank tests. Risk factors for multiple metastases were determined by univariate and multivariate logistic regression analyses, and a nomogram was developed to forecast the probability of multiple metastases in mCRC patients. We assessed the nomogram performance in terms of discrimination and calibration, including concordance index (C-index), area under the curve (AUC), and decision curve analysis (DCA). Bootstrap resampling was used as an internal verification method, and at the same time we select external data from Renmin Hospital of Wuhan University as independent validation sets.

Results

A total of 5,302 cases were included in this study as training group, while 120 cases were as validation group. The patients with single metastasis and multiple metastases were 3,531 and 1,771, respectively. The median overall survival (OS) and cancer-specific survival (CSS) for patients with multiple metastases or single metastasis were 19 vs. 31 months, and 20 vs. 33 months, respectively. Based on the univariate and multivariate analyses, clinicopathological characteristics were associated with number of metastasis and were used to establish nomograms to predict the risk of multiple metastases. The C-indexes and AUC for the forecast of multiple metastases were 0.715 (95% confidence interval (CI), 0.707–0.723), which showed the nomogram had good discrimination and calibration curves of the nomogram showed no significant bias from the reference line, indicating a good degree of calibration. In the validation group, the AUC was 0.734 (95% CI, 0.653–0.834), and calibration curve also showed no significant bias, indicating the favorable effects of our nomogram.

Conclusions

We developed a new nomogram to predict the risk of multiple metastases. The nomogram shows the good prediction effect and can provide assistance for clinical diagnosis and treatment.
Case Report: High-Level MET Amplification as a Resistance Mechanism of ROS1-Tyrosine Kinase Inhibitors in ROS1-Rearranged Non-Small Cell Lung Cancer
Authors: Yang Jiangping , Zhou Ping , Yu Min , Zhang Yan
Published: May 2021

Background

Although C-ros oncogene 1 (ROS1) targeted therapies have demonstrated remarkable efficacy in ROS1-rearranged non-small cell lung cancer (NSCLC), patients inevitably develop resistance to ROS1-tyrosine kinase inhibitors (TKIs). Commonly acquired resistance mechanisms include a second mutation of the ROS1 kinase domain and activation of bypass signaling pathways. However, MMNG HOS Transforming gene (MET) amplification has not been reported as a novel mechanism of ROS1-TKIs resistance.

Case Presentation

We report a case of a 62-year-old man diagnosed with ROS1-rearranged metastatic lung adenocarcinoma, who received first-line treatment with crizotinib for 19 months. During the course of disease, the primary lung tumor was under control while the brain metastasis progressed despite the treatment with lorlatinib. The biopsy and genetic tests of the metastatic brain tumor showed a high level of MET amplification (32 copies). However, fluorescence in situ hybridization of the primary cancer showed no MET amplification, suggesting that MET amplification may be associated with an acquired resistance to ROS1-TKIs.

This case suggested that MET amplification could be explored as a potential mechanism for developing ROS1-TKIs resistance. Combination treatment with highly potent and selective MET-TKIs warrants further investigations.
Ancient Adversary – HERV-K (HML-2) in Cancer
Authors: Dervan Eoin , Bhattacharyya Dibyangana D. , McAuliffe Jake D. , Khan Faizan H. , Glynn Sharon A.
Published: May 2021

Human endogenous retroviruses (HERV), ancient integrations of exogenous viruses, make up 8% of our genome. Long thought of as mere vestigial genetic elements, evidence is now accumulating to suggest a potential functional role in numerous pathologies including neurodegenerative diseases, autoimmune disorders, and multiple cancers. The youngest member of this group of transposable elements is HERV-K (HML-2). Like the majority of HERV sequences, significant post-insertional mutations have disarmed HERV-K (HML-2), preventing it from producing infectious viral particles. However, some insertions have retained limited coding capacity, and complete open reading frames for all its constituent proteins can be found throughout the genome. For this reason HERV-K (HML-2) has garnered more attention than its peers. The tight epigenetic control thought to suppress expression in healthy tissue is lost during carcinogenesis. Upregulation of HERV-K (HML-2) derived mRNA and protein has been reported in a variety of solid and liquid tumour types, and while causality has yet to be established, progressively more data are emerging to suggest this phenomenon may contribute to tumour growth and metastatic capacity. Herein we discuss its potential utility as a diagnostic tool and therapeutic target in light of the current in vitro, in vivo and clinical evidence linking HERV-K (HML-2) to tumour progression.
Doxorubicin-Induced Cognitive Impairment: The Mechanistic Insights
Authors: Du Jiajia , Zhang Aoxue , Li Jing , Liu Xin , Wu Shuai , Wang Bin , Wang Yanhong , Jia Hongyan
Published: May 2021

Chemotherapy can significantly prolong the survival of patients with breast cancer; Nevertheless, the majority of patients receiving chemotherapy such as doxorubicin may have cognitive deficits that manifest as impairments in learning, reasoning, attention, and memory. The phenomenon of chemotherapy-induced cognitive decline is termed as chemotherapy-related cognitive impairment (CRCI) or chemo-brain. Doxorubicin (DOX), a commonly used drug in adjuvant chemotherapy for patients with breast cancer, has been reported to induce chemo-brain through a variety of mechanisms including DNA damage, oxidative stress, inflammation, dysregulation of apoptosis and autophagy, changes in neurotransmitter levels, mitochondrial dysfunction, glial cell interactions, neurogenesis inhibition, and epigenetic factors. These mechanisms do not operate independently but are inter-related, coordinately contributing to the development of chemo-brain. Here we review the relationships of these mechanisms and pathways in attempt to provide mechanistic insights into the doxorubicin-induced cognitive impairment.
Sex-Specific Temporal Trends in Overweight and Obese Among Schoolchildren From 2009 to 2018: An Age Period Cohort Analysis
Authors: Chang Yung-Chieh , Hsieh Wan-Hua , Huang Sen-Fang , Hsiao Hsinyi , Wang Ying-Wei , Chu Chia-Hsiang , Wen Shu-Hui
Published: May 2021

Background: Our study examined the age, period, and cohort effects on overweight and obesity in children using a 10-year dataset collected from schoolchildren in Hualien, Taiwan.

Methods: We used data from the annual health checkup of a total of 94,661 schoolchildren in primary schools and junior high schools in Hualien from 2009 to 2018. Children were defined as overweight or obese by the gender- and age-specific norm of the body mass index. We conducted the age-period-cohort (APC) analysis in boys and girls separately.

Results: From 2009 to 2018, the rates of children overweight and obese were 12.78 and 14.23%, respectively. Boys had higher rates of overweight and obesity than girls (29.73 vs. 24.03%, P < 0.001). Based on APC analysis results, positive age effect existed regardless of gender. The risk of overweight or obesity of children aged 9 or 12 years was significantly higher compared to the average rate. As for period effect, a fluctuating downward trend in overweight was evident in 2016, and a similar trend in obesity was seen in 2017 across gender groups. The birth cohort of 2007 to 2009 had a significant higher proportion of overweight and obese than other birth cohorts. This indicated that the proportion of children overweight and obese in the young generation is higher than that in the old generation.

Conclusion: An increased risk of children overweight or obese was associated with age and later birth cohort. For the period effect, the trend in the prevalence of overweight and obesity fluctuated downward slowly from 2016 to 2017.
The Leukodystrophy Spectrum in Saudi Arabia: Epidemiological, Clinical, Radiological, and Genetic Data
Authors: Alfadhel Majid , Almuqbil Mohammed , Al Mutairi Fuad , Umair Muhammad , Almannai Mohammed , Alghamdi Malak , Althiyab Hamad , Albarakati Rayyan , Bashiri Fahad A. , Alshuaibi Walaa , Ba-Armah Duaa , Saleh Mohammed A. , Al-Asmari Ali , Faqeih Eissa , Altuwaijri Waleed , Al-Rumayyan Ahmed , Balwi Mohammed Ali , Ababneh Faroug , Alswaid Abdulrahman Faiz , Eyaid Wafaa M. , Almontashiri Naif A. M. , Alhashem Amal , Hundallah Khalid , Bertoli-Avella Aida , Bauer Peter , Beetz Christian , Alrifai Muhammad Talal , Alfares Ahmed , Tabarki Brahim
Published: May 2021

Background: Leukodystrophies (LDs) are inherited heterogeneous conditions that affect the central nervous system with or without peripheral nerve involvement. They are individually rare, but collectively, they are common. Thirty disorders were included by the Global Leukodystrophy Initiative Consortium (GLIA) as LDs.

Methods: We conducted a retrospective chart review of a consecutive series of patients diagnosed with different types of LD from four large tertiary referral centers in Riyadh, Saudi Arabia. Only those 30 disorders defined by GLIA as LDs were included.

Results: In total, 83 children from 61 families were identified and recruited for this study. The male-to-female ratio was 1.5:1, and a consanguinity rate of 58.5% was observed. An estimated prevalence of 1:48,780 or 2.05/100,000 was observed based on the clinical cohort, whereas a minimum of 1:32,857 or 3.04/100,000 was observed based on the local genetic database. The central region of the country exhibited the highest prevalence of LDs (48.5%). The most common LD was metachromatic leukodystrophy (MLD), and it accounted for 25.3%. The most common disorder based on carrier frequency was AGS. Novel variants were discovered in 51% of the cases, but 49% possessed previously reported variants. Missense variants were high in number and accounted for 73% of all cases. Compared with other disorders, MLD due to saposin b deficiency was more common than expected, Pelizaeus-Merzbacher-like disease was more prevalent than Pelizaeus-Merzbacher disease, and X-linked adrenoleukodystrophy was less common than expected. The mortality rate among our patients with LD was 24%.

Conclusion: To the best of our knowledge, this is the largest cohort of patients with LD from Saudi Arabia. We present epidemiological, clinical, radiological, and genetic data. Furthermore, we report 18 variants that have not been reported previously. These findings are of great clinical and molecular utility for diagnosing and managing patients with LD.
Risk Factors for Mortality in Neonatal Gastric Perforation: A Retrospective Cohort Study
Authors: Huang Yao , Lu Qi , Peng Nan , Wang Li , Song Yan , Zhong Qin , Yuan Peng
Published: May 2021

Background: Neonatal gastric perforation is a rare but life-threatening issue. The aim of this study was to describe the clinical characteristics and prognosis of patients with neonatal gastric perforation and identify predictive factors for poor prognosis.

Methods: This was a retrospective cohort study of patients with neonatal gastric perforation treated in a tertiary pediatric public hospital between April 2009 and October 2020. The enrolled patients were divided into survival and non-survival groups. Demographic information, clinical characteristics, laboratory and imaging features, and outcomes were collected from the electronic medical record. Univariate and multivariate logistic regression analyses were performed to obtain the independent factors associated with death risk. Additionally, we separated this population into two groups (pre-term and term groups) and explored the mortality predictors of these two groups, respectively.

Results: A total of 101 patients with neonatal gastric perforation were included in this study. The overall survival rate was 70.3%. Seventy-one (70.3%) were pre-term neonates, and sixty-two (61.4%) were low-birth-weight neonates. The median age of onset was 3 days (range: 1–11 days). Abdominal distension [98 (97.0%) patients] was the most common symptom, followed by lethargy [78 (77.2%) patients], shortness of breath [60 (59.4%) patients] and vomiting [34 (33.7%) patients]. Three independent mortality risk factors were identified: shock (OR, 3.749; 95% CI, 1.247–11.269; p = 0.019), serum lactic acid > 2.5 mmol/L (5.346; 1.727–16.547; p = 0.004) and platelet count <150 × 109/L (3.510; 1.115–11.053; p = 0.032). There was a borderline significant association between sclerema neonatorum and total mortality (4.827; 0.889–26.220; p = 0.068). In pre-term infants, serum lactic acid > 2.5 mmol/L and platelet count <150 × 109/L remained independent risk factors for death. In term infants, the incidence of shock, coagulopathy, pH < 7.3, serum lactic acid > 2.5 mmol/L, and hyponatremia were statistically different between non-survival and survival groups.

Conclusion: Shock, hyperlactatemia, and thrombocytopenia are independently associated with an increased risk of death in patients with neonatal gastric perforation. Identification of modifiable risk factors during the critical periods of life will contribute to the development of effective prevention and intervention strategies of neonatal gastric perforation.
New Horizons in Short Children Born Small for Gestational Age
Authors: Netchine Irène , van der Steen Manouk , López-Bermejo Abel , Koledova Ekaterina , Maghnie Mohamad
Published: May 2021

Children born small for gestational age (SGA) comprise a heterogeneous group due to the varied nature of the cause. Approximately 85–90% have catch-up growth within the first 4 postnatal years, while the remainder remain short. In later life, children born SGA have an increased risk to develop metabolic abnormalities, including visceral adiposity, insulin resistance, and cardiovascular problems, and may have impaired pubertal onset and growth. The third “360° European Meeting on Growth and Endocrine Disorders” in Rome, Italy, in February 2018, funded by Merck KGaA, Germany, included a session that examined aspects of short children born SGA, with three presentations followed by a discussion period, on which this report is based. Children born SGA who remain short are eligible for GH treatment, which is an approved indication. GH treatment increases linear growth and can also improve some metabolic abnormalities. After stopping GH at near-adult height, metabolic parameters normalize, but pharmacological effects on lean body mass and fat mass are lost; continued monitoring of body composition and metabolic changes may be necessary. Guidelines have been published on diagnosis and management of children with Silver-Russell syndrome, who comprise a specific group of those born SGA; these children rarely have catch-up growth and GH treatment initiation as early as possible is recommended. Early and moderate pubertal growth spurt can occur in children born SGA, including those with Silver-Russell syndrome, and reduce adult height. Treatments that delay puberty, specifically metformin and gonadotropin releasing hormone analogs in combination with GH, have been proposed, but are used off-label, currently lack replication of data, and require further studies of efficacy and safety.