bluuebunny/crossref_metadata_2025 huggingface dataset:
HLA-G/sHLA-G and HLA-G-Bearing Extracellular Vesicles in Cancers: Potential Role as Biomarkers
Authors: Li Peilong , Wang Nan , Zhang Yi , Wang Chuanxin , Du Lutao
Published: November 2021

As a non-classic major histocompatibility complex (MHC) class I molecule, human leukocyte antigen G (HLA-G) is expressed in fetal-maternal interface and immunoprivileged site only in healthy condition, and in pathological conditions such as cancer, it can bede novoexpressed. It is now widely accepted that HLA-G is a key molecule in the process of immune escape of cancer cells, which is ubiquitously expressed in the tumor environment. This raises the possibility that it may play an adverse role in tumor immunity. The expression level of HLA-G has been demonstrated to be highly correlated with clinical parameters in many tumors, and its potential significance in the diagnosis and prognosis of cancer has been postulated. However, because HLA-G itself has up to seven different subtypes, and for some subtypes, detected antibodies are few or absent, it is hard to evaluate the actual expression of HLA-G in tumors. In the present work, we described (a) the structure and three main forms of HLA-G, (b) summarized the mechanism of HLA-G in the immune escape of tumor cells, (c) discussed the potential role of HLA-G as a tumor marker, and reviewed (d) the methods for detecting and quantifying HLA-G.
Functional Trait Responses of Macrobenthos to Anthropogenic Pressure in Three Temperate Intertidal Communities
Authors: Dong Jian-Yu , Zhao Linlin , Yang Xiaolong , Sun Xin , Zhang Xiumei
Published: November 2021

With the increasing impact of human activities on marine ecosystems, there is a growing need to assess how the components of marine ecosystems (e.g., macrobenthos) respond to these anthropogenic pressures. In this work, the trait-based approach was used to assess the effects of anthropogenic pressures represented by the area of land-based aquaculture pond (Pond Area) and heavy metals on the macrobenthic communities in three intertidal zones[Aoshan Bay (AO), Wenquan River and Daren River (RW), and Xiaodao Bay (XD)] of Laoshan Bay, Shandong Peninsula, China. Compared with RW and XD, AO was under more pressure in terms of the average concentrations of heavy metals and total organic carbon (TOC) in sediments and also in the Pond Area. Fuzzy correspondence analysis (FCA) showed that there were significant differences in the composition of functional traits among the three regions (PERMANOVA; p < 0.05). In the highly polluted area, macrobenthic communities exhibited a combination of traits, such as relatively short life span, weak mobility, feeding on deposits, and more tolerant to organic matter, whereas in a less polluted area, they exhibited a combination of traits, such as relatively long life span, relatively high mobility, and more sensitivity to organic matter. The RDA results showed that the distribution of the trait modalities was significantly affected by heavy metals (Hg and Cd), TOC, Pond Area, and sampled location. Variation partitioning analysis (VPA) indicated that the shared influence of sediment-related pollution factors and Pond Area contributed most to the variance of the functional traits, which implied that human activities directly and/or indirectly lead to changes in functional traits of macrobenthic communities in the intertidal zones.
Microstructure and Mechanical Property Correlation Between Rotary Friction Welded Nitinol–Nitinol Joints
Authors: Rehman Ateekh Ur , Babu Nagumothu Kishore , Talari Mahesh Kumar , Usmani Yusuf Siraj , Al-Khalefah Hisham
Published: November 2021

In the present study, a rotary friction process was used to join nitinol in a similar welding combination. Macro- and microstructure characteristics of the weld zone were compared with adjacent zones and the base metal. The hardness and tensile properties of the joints were evaluated, and the results were discussed in relation to the weld microstructure. The weld macrostructure revealed a uniform flash around the circumference of the weld. The optical microstructure of the welded sample revealed fine recrystallized grains at the weld interface due to heavy deformation followed by dynamic recrystallization. The phase transformation behavior of the base metal and welded samples was studied by using a differential scanning calorimeter (DSC). The drift in phase transformation temperatures after rotary friction welding may be attributed to fine grain formation at the weld interface. Friction welded samples exhibited improved yield strength and hardness values compared to the base metal due to grain refinement at the weld interface.
High Temperature Chloride Corrosion Behavior of 904L:AlFeNiMoNb High-Entropy Alloy
Authors: Bai Lingyun , Peng Wenyi , Men Dandan , Zhu Jun , Wu Xuecheng , Shi Xiongtao , Xiang Junhuan , Deng Xiaohua , Wang Yuqing , Sun Zuxiang , Yu Siqi , Wei Xiang
Published: November 2021

In order to obtain high cost-effective coating materials working in chlorine-containing environment at high temperature, a 904L super austenitic alloy modified by an AlFeNiMoNb alloy (904L:AlFeNiMoNb) was obtained by vacuum arc melting process. The 904L:AlFeNiMoNb high-entropy alloy has a similar phase component with the AlFeNiMoNb alloy, but a more homogenous microstructure than that of the AlFeNiMoNb alloy. High-temperature chloride corrosion tests for 904L, AlFeNiMoNb, and 904L:AlFeNiMoNb high-entropy alloy were carried out under N2–2.6 vol.% CO2–1.3 vol.% O2–2,700 vppm HCl gaseous environment at 700°C and 800°C for 55 h, respectively. Due to the volatilization of FeCl2, weight change curves of the 904L alloy at 700°C and 800°C showed obvious weight loss. Especially at 800°C, the weight loss of the corroded 904L sample was 10 times that of the corroded sample at 700°C. Different from the weight loss situation of the 904L sample, both AlFeNiMoNb and 904L:AlFeNiMoNb high-entropy alloy showed small weight gains under the corrosion temperature of 700°C, while the latter gained half as much weight as the former. When the corrosion temperature was raised to 800°C, the AlFeNiMoNb and 904L:AlFeNiMoNb high-entropy alloy showed flat weight change curves with little weight loss. Weight loss for the AlFeNiMoNb and 904L:AlFeNiMoNb high-entropy alloy were 1.35138 and 0.0118 mg/cm2, respectively. The high temperature chloride corrosion resistance of 904L:AlFeNiMoNb high-entropy alloy is higher than that of 904L and AlFeNiMoNb at both 700°C and 800°C. Meanwhile, on the basis of the morphology and composition results of the corroded samples, combined with thermodynamic calculation, the high-temperature chloride corrosion mechanics of the tested alloys were discussed.
Genetic Variations and Clinical Features of NPHS1-Related Nephrotic Syndrome in Chinese Children: A Multicenter, Retrospective Study
Authors: Rong Liping , Chen Lizhi , Rao Jia , Shen Qian , Li Guomin , Liu Jialu , Mao Jianhua , Feng Chunyue , Wang Xiaowen , Wang Si , Kuang Xinyu , Huang Wenyan , Ma Qingshan , Liu Xiaorong , Ling Chen , Fu Rong , Gao Xiaojie , Ding Guixia , Yang Huandan , Han Mei , Huang Zhimin , Li Qian , Zhang Qiuye , Lin Yi , Jiang Xiaoyun , Xu Hong
Published: November 2021

Introduction: Few studies have addressed the genetic spectrum of NPHS1 variants in Chinese children with nephrotic syndrome. In this multicenter study, the clinical manifestations and features of NPHS1 variants in Chinese children with nephrotic syndrome were researched.

Method: Genotypical and phenotypical data from 30 children affected by NPHS1 variants were collected from a multicenter registration system in China and analyzed retrospectively.

Results: The patients were divided into two groups: congenital nephrotic syndrome (CNS [n = 24]) and non-CNS (early onset nephrotic syndrome [n = 6]). Renal biopsy was performed on four patients in the non-CNS group, revealing minimal change disease in three and focal segmental glomerulosclerosis in one. A total of 61 NPHS1 variants were detected, involving 25 novel variants. The “recurrent variants” included c.928G>A(p.Asp310Asn) in eight patients with CNS, followed by c.616C>A(p.Pro206Thr) in four, and c.2207T>C (p.Val736Ala) in three. Steroid treatment was applied in 29.2% (7/24)of the patients in the CNS group and 50% (3/6) of the patients in the non-CNS group. One patient in each group experienced complete remission but relapsed subsequently. Immunosuppressants were administered to three patients in the non-CNS group, eliciting an effective response. In the CNS group, three patients underwent renal transplantation and six died mainly from infection.

Conclusion: Variants of NPHS1 cause CNS and early childhood-onset nephrotic syndrome. NPHS1 variants in Chinese individuals with nephrotic syndrome (NS) were mainly compound heterozygous variants, and c.928G>A(p.Asp310Asn) in exon 8 may act as a recurrent variant in the Chinese population, followed by c.616C>A(p.Pro206Thr) in exon 6. Steroids and immunosuppressants may be effective in selected patients.
Developments in Fatty Acid-Derived Insect Pheromone Production Using Engineered Yeasts
Authors: Zhang Xiaoling , Miao Qin , Xu Xia , Ji Boyang , Qu Lingbo , Wei Yongjun
Published: November 2021

The use of traditional chemical insecticides for pest control often leads to environmental pollution and a decrease in biodiversity. Recently, insect sex pheromones were applied for sustainable biocontrol of pests in fields, due to their limited adverse impacts on biodiversity and food safety compared to that of other conventional insecticides. However, the structures of insect pheromones are complex, and their chemical synthesis is not commercially feasible. As yeasts have been widely used for fatty acid-derived pheromone production in the past few years, using engineered yeasts may be promising and sustainable for the low-cost production of fatty acid-derived pheromones. The primary fatty acids produced by Saccharomyces cerevisiae and other yeasts are C16 and C18, and it is also possible to rewire/reprogram the metabolic flux for other fatty acids or fatty acid derivatives. This review summarizes the fatty acid biosynthetic pathway in S. cerevisiae and recent progress in yeast engineering in terms of metabolic engineering and synthetic biology strategies to produce insect pheromones. In the future, insect pheromones produced by yeasts might provide an eco-friendly pest control method in agricultural fields.
Coronavirus Disease 2019: Clinics, Treatment, and Prevention
Authors: Burkert Francesco Robert , Lanser Lukas , Bellmann-Weiler Rosa , Weiss Günter
Published: November 2021

The coronavirus disease 2019 (COVID-19) pandemic, caused by a novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged at the end of 2019 in China and affected the entire world population, either by infection and its health consequences, or by restrictions in daily life as a consequence of hygiene measures and containment strategies. As of September 2021, more than 231,000.000 infections and 4,740.000 deaths due to COVID-19 have been reported. The infections present with varied clinical symptoms and severity, ranging from asymptomatic course to fatal outcome. Several risk factors for a severe course of the disease have been identified, the most important being age, gender, comorbidities, lifestyle, and genetics. While most patients recover within several weeks, some report persistent symptoms restricting their daily lives and activities, termed as post-COVID. Over the past 18months, we have acquired significant knowledge as reflected by an almost uncountable number of publications on the nature of the underlying virus and its evolution, host responses to infection, modes of transmission, and different clinical presentations of the disease. Along this line, new diagnostic tests and algorithms have been developed paralleled by the search for and clinical evaluation of specific treatments for the different stages of the disease. In addition, preventive non-pharmacological measures have been implemented to control the spread of infection in the community. While an effective antiviral therapy is not yet available, numerous vaccines including novel vaccine technologies have been developed, which show high protection from infection and specifically from a severe course or death from COVID-19. In this review, we tried to provide an up-to-date schematic of COVID-19, including aspects of epidemiology, virology, clinical presentation, diagnostics, therapy, and prevention.
Development and Characterization of a Reverse Genetics System for a Human-Derived Severe Fever With Thrombocytopenia Syndrome Virus Isolate From South Korea
Authors: Yun Seok-Min , Lee Tae-Young , Lim Hee-Young , Ryou Jungsang , Lee Joo-Yeon , Kim Young-Eui
Published: November 2021

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging, tick-borne Bandavirus that causes lethal disease in humans. As there are no licensed vaccines and therapeutics for SFTSV, there is an urgent need to develop countermeasures against it. In this respect, a reverse genetics (RG) system is a powerful tool to help achieve this goal. Herein, we established a T7 RNA polymerase-driven RG system to rescue infectious clones of a Korean SFTSV human isolate entirely from complementary DNA (cDNA). To establish this system, we cloned cDNAs encoding the three antigenomic segments into transcription vectors, with each segment transcribed under the control of the T7 promoter and the hepatitis delta virus ribozyme (HdvRz) sequences. We also constructed two helper plasmids expressing the nucleoprotein (NP) or viral RNA-dependent RNA polymerase (RdRp) under the control of the T7 promoter and the encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES). After co-transfection into BHK/T7-9 cells with three transcription and two helper plasmids, then passaging in Vero E6 or Huh-7 cells, we confirmed efficient rescue of the recombinant SFTSV. By evaluating the in vitro and in vivo virological properties of the parental and rescued SFTSVs, we show that the rescued virus exhibited biological properties similar to those of the parental virus. This system will be useful for identifying molecular viral determinants of SFTSV infection and pathogenesis and for facilitating the development of vaccine and antiviral approaches.
Malaria in Pregnancy: From Placental Infection to Its Abnormal Development and Damage
Authors: Chua Caroline Lin Lin , Khoo Sebastian Kah Ming , Ong Jun Long Ernest , Ramireddi Gaurav Kumar , Yeo Tsin Wen , Teo Andrew
Published: November 2021

Malaria remains a global health burden with Plasmodium falciparum accounting for the highest mortality and morbidity. Malaria in pregnancy can lead to the development of placental malaria, where P. falciparum-infected erythrocytes adhere to placental receptors, triggering placental inflammation and subsequent damage, causing harm to both mother and her infant. Histopathological studies of P. falciparum-infected placentas revealed various placental abnormalities such as excessive perivillous fibrinoid deposits, breakdown of syncytiotrophoblast integrity, trophoblast basal lamina thickening, increased syncytial knotting, and accumulation of mononuclear immune cells within intervillous spaces. These events in turn, are likely to impair placental development and function, ultimately causing placental insufficiency, intrauterine growth restriction, preterm delivery and low birth weight. Hence, a better understanding of the mechanisms behind placental alterations and damage during placental malaria is needed for the design of effective interventions. In this review, using evidence from human studies and murine models, an integrated view on the potential mechanisms underlying placental pathologies in malaria in pregnancy is provided. The molecular, immunological and metabolic changes in infected placentas that reflect their responses to the parasitic infection and injury are discussed. Finally, potential models that can be used by researchers to improve our understanding on the pathogenesis of malaria in pregnancy and placental pathologies are presented.
Serum Neurofilament Light Chain Levels and Myelin Oligodendrocyte Glycoprotein Antibodies in Pediatric Acquired Demyelinating Syndromes
Authors: Simone Marta , Palazzo Claudia , Mastrapasqua Mariangela , Bollo Luca , Pompamea Francesco , Gabellone Alessandra , Marzulli Lucia , Giordano Paola , De Giacomo Andrea , Frigeri Antonio , Ruggieri Maddalena , Margari Lucia
Published: November 2021

Introduction: The relationship between serum neurofilament light chain (sNfL) and myelin oligodendrocyte glycoprotein antibody (MOG-Ab) status has not been yet investigated in children with the acquired demyelinating syndrome (ADS).

Objective and Methods: The sNfL levels and MOG-Abs were measured by ultrasensitive single-molecule array and cell-based assay in a cohort of 37 children with ADS and negativity for serum anti-aquaporin 4 (AQP4) antibodies. The sNfL levels were compared in MOG-Ab+/MOG-Ab– and in two subgroups MOG-Ab+ with/without encephalopathy.

Results: About 40% ADS resulted in MOG-Ab+. MOG-Ab+ were younger at sampling (median = 9.8; range = 2.17–17.5 vs. 14.7/9–17; p = 0.002) with lower frequency of cerebrospinal fluid oligoclonal bands positivity (27% vs. 70%; p = 0.013) compared to MOG-Ab–. About 53% of MOG-Ab+ presented encephalopathy at onset, 1/22 of MOG-Ab– (p = 0.0006). Higher sNfL levels (p = 0.0001) were found in MOG-Ab+ (median/range = 11.11/6.8–1,129) and MOG-Ab– (median/range = 11.6/4.3–788) compared to age-matched controls (median/range = 2.98/1–4.53), without significant difference. MOG-Ab+ with encephalopathy resulted significantly younger at sampling (median/range: 4.5/2.17–11.17 vs. 14.16/9.8–17.5; p = 0.004), had higher sNfL levels (median/range:75.24/9.1–1,129 vs. 10.22/6.83–50.53; p = 0.04), and showed a trend for higher MOG-Ab titer (0.28/0.04–0.69 vs. 0.05/0.04–0.28; p = 0.1) in comparison to those without encephalopathy.

Discussion: We confirmed high sNfL levels in pediatric ADS independently from the MOG-Ab status. Encephalopathy at onset is associated more frequently with MOG Ab+ children with higher sNfL levels and MOG titer. These findings suggest a role of acute demyelination in association with axonal damage in the pathogenesis of encephalopathy in pediatric ADS.
Trunk Muscle Activation Patterns During Standing Turns in Patients With Stroke: An Electromyographic Analysis
Authors: Chen I-Hsuan , Liang Pei-Jung , Chiu Valeria Jia-Yi , Lee Shu-Chun
Published: November 2021

Recent evidence indicates that turning difficulty may correlate with trunk control; however, surface electromyography has not been used to explore trunk muscle activity during turning after stroke. This study investigated trunk muscle activation patterns during standing turns in healthy controls (HCs) and patients with stroke with turning difficulty (TD) and no TD (NTD). The participants with stroke were divided into two groups according to the 180° turning duration and number of steps to determine the presence of TD. The activation patterns of the bilateral external oblique and erector spinae muscles of all the participants were recorded during 90° standing turns. A total of 14 HCs, 14 patients with TD, and 14 patients with NTD were recruited. The duration and number of steps in the turning of the TD group were greater than those of the HCs, independent of the turning direction. However, the NTD group had a significantly longer turning duration than did the HC group only toward the paretic side. Their performance was similar when turning toward the non-paretic side; this result is consistent with electromyographic findings. Both TD and NTD groups demonstrated increased amplitudes of trunk muscles compared with the HC groups. Their trunk muscles failed to maintain consistent amplitudes during the entire movement of standing turns in the direction that they required more time or steps to turn toward (i.e., turning in either direction for the TD group and turning toward the paretic side for the NTD group). Patients with stroke had augmented activation of trunk muscles during turning. When patients with TD turned toward either direction and when patients with NTD turned toward the paretic side, the flexible adaptations and selective actions of trunk muscles observed in the HCs were absent. Such distinct activation patterns during turning may contribute to poor turning performance and elevate the risk of falling. Our findings provide insights into the contribution and importance of trunk muscles during turning and the association with TD after stroke. These findings may help guide the development of more effective rehabilitation therapies that target specific muscles for those with TD.
Very Early Cognitive Screening and Self-Reported Feeling of Fatigue Three Months After Stroke
Authors: Holmberg Josefin , Jondell Beatrice , Abzhandadze Tamar , Sunnerhagen Katharina S.
Published: November 2021

Stroke is a major cause of disability and the second leading cause of death worldwide. Post-stroke fatigue has been reported as one of the most limiting symptoms after a stroke. Early identification of risk factors for developing post-stroke fatigue is important for providing timely rehabilitation. A correlation has been found between fatigue and cognitive impairment after stroke, but 2 months after stroke at the earliest. In the present study, we examined whether cognitive function screening using the Montreal Cognitive Assessment (MoCA) very early after stroke could explain fatigue 3 months after stroke. A total of 311 stroke patients admitted to a comprehensive stroke unit in Sweden between 2011 and 2016 were included in this longitudinal study. Cognition was screened within 2 days after admission to the stroke unit. Data on self-reported feeling of fatigue were retrieved from Riksstroke’s 3-month follow-up form. The data were analyzed using binary logistic regression. We found that the cognitive function in an acute phase after stroke could not explain self-reported feeling of fatigue in a later stage. The correlation between cognitive impairment and fatigue that has been reported may be detectable no earlier than the subacute phase of stroke. As previous studies have shown that functional outcome, severity of stroke, and sex also correlate with fatigue after stroke, we controlled for these variables in our analysis. In line with previous studies, we found that female patients had higher odds of experiencing fatigue. This is something that health care professionals should be aware of when working with stroke patients.
Controlling Clinical States Governed by Different Temporal Dynamics With Closed-Loop Deep Brain Stimulation: A Principled Framework
Authors: Tinkhauser Gerd , Moraud Eduardo Martin
Published: November 2021

Closed-loop strategies for deep brain stimulation (DBS) are paving the way for improving the efficacy of existing neuromodulation therapies across neurological disorders. Unlike continuous DBS, closed-loop DBS approaches (cl-DBS) optimize the delivery of stimulation in the temporal domain. However, clinical and neurophysiological manifestations exhibit highly diverse temporal properties and evolve over multiple time-constants. Moreover, throughout the day, patients are engaged in different activities such as walking, talking, or sleeping that may require specific therapeutic adjustments. This broad range of temporal properties, along with inter-dependencies affecting parallel manifestations, need to be integrated in the development of therapies to achieve a sustained, optimized control of multiple symptoms over time. This requires an extended view on future cl-DBS design. Here we propose a conceptual framework to guide the development of multi-objective therapies embedding parallel control loops. Its modular organization allows to optimize the personalization of cl-DBS therapies to heterogeneous patient profiles. We provide an overview of clinical states and symptoms, as well as putative electrophysiological biomarkers that may be integrated within this structure. This integrative framework may guide future developments and become an integral part of next-generation precision medicine instruments.
Stepwise Covariance-Free Common Principal Components (CF-CPC) With an Application to Neuroscience
Authors: Riaz Usama , Razzaq Fuleah A. , Hu Shiang , Valdés-Sosa Pedro A.
Published: November 2021

Finding the common principal component (CPC) for ultra-high dimensional data is a multivariate technique used to discover the latent structure of covariance matrices of shared variables measured in two or more k conditions. Common eigenvectors are assumed for the covariance matrix of all conditions, only the eigenvalues being specific to each condition. Stepwise CPC computes a limited number of these CPCs, as the name indicates, sequentially and is, therefore, less time-consuming. This method becomes unfeasible when the number of variables p is ultra-high since storing k covariance matrices requires O(kp2) memory. Many dimensionality reduction algorithms have been improved to avoid explicit covariance calculation and storage (covariance-free). Here we propose a covariance-free stepwise CPC, which only requires O(kn) memory, where n is the total number of examples. Thus for n < < p, the new algorithm shows apparent advantages. It computes components quickly, with low consumption of machine resources. We validate our method CFCPC with the classical Iris data. We then show that CFCPC allows extracting the shared anatomical structure of EEG and MEG source spectra across a frequency range of 0.01–40 Hz.
Cox Regression Based Modeling of Functional Connectivity and Treatment Outcome for Relapse Prediction and Disease Subtyping in Substance Use Disorder
Authors: Zhai Tianye , Gu Hong , Yang Yihong
Published: November 2021

Functional magnetic resonance imaging (fMRI) has become one of the most widely used noninvasive neuroimaging technique in research of cognitive neurosciences and of neural mechanisms of neuropsychiatric/neurological diseases. A primary goal of fMRI-based neuroimaging studies is to identify biomarkers for brain-behavior relationship and ultimately perform individualized treatment outcome prognosis. However, the concern of inadequate validation and the nature of small sample sizes are associated with fMRI-based neuroimaging studies, both of which hinder the translation from scientific findings to clinical practice. Therefore, the current paper presents a modeling approach to predict time-dependent prognosis with fMRI-based brain metrics and follow-up data. This prediction modeling is a combination of seed-based functional connectivity and voxel-wise Cox regression analysis with built-in nested cross-validation, which has been demonstrated to be able to provide robust and unbiased model performance estimates. Demonstrated with a cohort of treatment-seeking cocaine users from psychosocial treatment programs with 6-month follow-up, our proposed modeling method is capable of identifying brain regions and related functional circuits that are predictive of certain follow-up behavior, which could provide mechanistic understanding of neuropsychiatric/neurological disease and clearly shows neuromodulation implications and can be used for individualized prognosis and treatment protocol design.
Examining Eating Attitudes and Behaviors in Collegiate Athletes, the Association Between Orthorexia Nervosa and Eating Disorders
Authors: Uriegas Nancy A. , Winkelmann Zachary K. , Pritchett Kelly , Torres-McGehee Toni M.
Published: November 2021

Purpose: Orthorexia nervosa (Orthorexia) is an eating attitude and behavior associated with a fixation on healthy eating, while eating disorders (EDs) are clinically diagnosed psychiatric disorders associated with marked disturbances in eating that may cause impairment to psychosocial and physical health. The purpose of this study was to examine risk for Orthorexia and EDs in student-athletes across sex and sport type and determine the association between the two.

Methods: Student-athletes (n = 1,090; age: 19.6 ± 1.4 years; females = 756; males = 334) completed a survey including demographics, the ORTO-15 test (<40 and <35 threshold values), the Eating Attitudes Test-26 (EAT-26; >20 score), and additional questions about pathogenic behaviors to screen for EDs.

Results: Using a <40 threshold value for the ORTO-15, 67.9% were at risk for Orthorexia, a more restrictive threshold value of <35 determined 17.7% prevalence across student-athletes with significant differences across sex [ <40: χ(1,1,090)2 = 4.914, p = 0.027; <35: χ(1,1,090)2 = 5.923, p = 0.015). Overall, ED risk (EAT-26 and/or pathogenic behavior use) resulted in a 20.9% prevalence, with significant differences across sex (χ2 = 11.360, p < 0.001) and sport-type category (χ2 = 10.312, p = 0.035). Multiple logistic regressions indicated a significant association between EAT-26 subscales scores and Orthorexia, and between Orthorexia positivity, ORTO-15 scores, and risk for EDs.

Conclusions: Risk for Orthorexia and ED is present in collegiate student-athletes. While healthy and balanced eating is important, obsessive healthy eating fixations may increase the risk for EDs in athletes. More education and awareness are warranted to minimize the risk for Orthorexia and EDs in student-athletes.
Elevated DNA Polymerase Delta 1 Expression Correlates With Tumor Progression and Immunosuppressive Tumor Microenvironment in Hepatocellular Carcinoma
Authors: Zhao Shuai , Wei Cuicui , Tang Haijia , Ding Han , Han Bing , Chen Shuxian , Song Xiaoling , Gu Qiang , Zhang Yichi , Liu Wangrui , Wang Jian
Published: November 2021

Background and Objective

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the DNA polymerase delta (POLD) family is significantly related to cancer prognosis. This study aimed to explore the significance of the POLD family in HCC via the DNA damage repair (DDR) pathway.

Methods

Data mining was conducted using bioinformatics methods. RNA sequencing and clinicopathological data were collected from The Cancer Genome Atlas, GTEx database and the Gumz Renal cohort. Statistical analyses were also performed in cancer samples (n>12,000) and the Affiliated Hospital of Youjiang Medical University for Nationalities (AHYMUN, n=107) cohort.

Results

The POLD family (POLD1–4) was identified as the most important functional component of the DDR pathway. Based on the analysis of independent cohorts, we found significantly elevated POLD expression in HCC compared with normal tissues. Second, we investigated the prognostic implication of elevated POLD1 expression in HCC and pan-cancers, revealing that increased POLD1 levels were correlated to worse prognoses for HCC patients. Additionally, we identified 11 hub proteins interacting closely with POLD proteins in base excision repair, protein-DNA complex and mismatch repair signaling pathways. Moreover, POLD1 mutation functioned as an independent biomarker to predict the benefit of targeted treatment. Importantly, POLD1 expression was associated with immune checkpoint molecules, including CD274, CD80, CD86, CTLA4, PDCD1 and TCGIT, and facilitated an immune-excluded tumor microenvironment. Additionally, we confirmed that elevated POLD1 expression was closely correlated with the aggressive progression and poor prognosis of HCC in the real-world AHYMUN cohort.

Conclusion

We identified a significant association between elevated POLD1 expression and poor patient survival and immune-excluded tumor microenvironment of HCC. Together, these findings indicate that POLD1 provides a valuable biomarker to guide the molecular diagnosis and development of novel targeted therapeutic strategies for HCC patients.
Myosteatosis Differentially Affects the Prognosis of Non-Metastatic Colon and Rectal Cancer Patients: An Exploratory Study
Authors: Pozzuto Lara , Silveira Marina Nogueira , Mendes Maria Carolina Santos , Macedo Lígia Traldi , Costa Felipe Osório , Martinez Carlos Augusto Real , Coy Cláudio Saddy Rodrigues , da Cunha Júnior Ademar Dantas , Carvalheira José Barreto Campello
Published: November 2021

Body composition performed by computed tomography (CT) impacts on cancer patients’ prognoses and responses to treatment. Myosteatosis has been related to overall survival (OS) and disease-specific survival in colorectal cancer (CRC); however, the independent impact of the association of myosteatosis with prognosis in colon cancer (CC) and rectal cancer (RC) is still unclear. CT was performed at the L3 level to assess body composition features in 227 patients with CRC. Clinical parameters were collected. Overall survival (OS) was the primary outcome, and the secondary outcome was disease-free survival (DFS). Skeletal muscle attenuation and intramuscular adipose tissue area were associated with DFS (p = 0.003 and p = 0.011, respectively) and OS (p < 0.001 and p < 0.001, respectively) in CC patients but not in RC patients. Only the skeletal muscle area was associated with better prognosis related to OS in RC patients (p = 0.009). When CC and RC were analyzed separately, myosteatosis influenced survival negatively in CC patients, worsening DFS survival (hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.07–6.82; p = 0.035) and OS (HR, 5.76; 95% CI, 1.31–25.40; p = 0.021). By contrast, the presence of myosteatosis did not influence DFS (HR, 1.02; 95% CI, 0.52–2.03; p = 0.944) or OS (HR, 0.76; 95% CI, 0.33–1.77; p = 0.529) in RC patients. Our study revealed the interference of myosteatosis in the therapy and survival of patients with CC but not in those with RC, strengthening the value of grouping the two types of cancer in body composition analyses.
Preliminary Safety and Efficacy of Proton Plus Carbon-Ion Radiotherapy With Concurrent Chemotherapy in Limited-Stage Small Cell Lung Cancer
Authors: Ma Ning-Yi , Chen Jian , Ming Xue , Jiang Guo-Liang , Lu Jiade J. , Wu Kai-Liang , Mao Jingfang
Published: November 2021

Objectives

This study aimed to investigate the tolerance and effect of proton plus carbon-ion radiotherapy with concurrent chemotherapy in limited-stage small cell lung cancer using the pencil beam scanning technique.

Materials and Methods

From March 2017 to April 2020, 25 patients with limited-stage small cell lung cancer treated with combined proton and carbon-ion radiotherapy were analyzed. The primary lesions and involved lymph nodes were irradiated using 2–4 portals. Proton and sequential carbon-ion beams were delivered with a median dose of 67.1 (range, 63–74.8) GyE as fraction doses of 2.0–2.2 GyE with proton beams in 20–23 fractions and 3.0–3.8 GyE with carbon ions in 5–8 fractions. Chemotherapy was delivered concurrently with radiotherapy in all patients.

Results

At the last follow-up, the 2-year overall and locoregional progression-free survival rates were 81.7% and 66.7%, respectively. Radiochemotherapy was well tolerated, with grade 1, 2, and 3 acute toxicities occurring in 12.0%, 68.0%, and 20.0% of patients, respectively. All grade 3 acute toxicities were hematologically related changes. One patient experienced grade 3 acute non-hematological toxicity in the esophagus, and one other patient had grade 3 bronchial obstruction accompanied by obstructive atelectasis as a late side effect.

Conclusion

Proton plus carbon-ion radiotherapy using pencil beam scanning yielded promising survival rates and tolerability in patients with limited-stage small cell lung cancer. A prospective clinical study is warranted to validate the therapeutic efficacy of particle radiotherapy in combination with chemotherapy in limited-stage small cell lung cancer.
Intraoperative Radiotherapy in Brain Malignancies: Indications and Outcomes in Primary and Metastatic Brain Tumors
Authors: Cifarelli Christopher P. , Jacobson Geraldine M.
Published: November 2021

Despite the continued controversy over defining an optimal delivery mechanism, the critical role of adjuvant radiation in the management of surgically resected primary and metastatic brain tumors remains one of the universally accepted standards in neuro-oncology. Local disease control still ranks as a significant predictor of survival in both high-grade glioma and treated intracranial metastases with radiation treatment being essential in maximizing tumor control. As with the emergence and eventual acceptance of cranial stereotactic radiosurgery (SRS) following an era dominated by traditional radiotherapy, evidence to support the use of intraoperative radiotherapy (IORT) in brain tumors requiring surgical intervention continues to accumulate. While the clinical trial strategies in treating glioblastoma with IORT involve delivery of a boost of cavitary radiation prior to the planned standard external beam radiation, the use of IORT in metastatic disease offers the potential for dose escalation to the level needed for definitive adjuvant radiation, eliminating the need for additional episodes of care while providing local control equal or superior to that achieved with SRS in a single fraction. In this review, we explore the contemporary clinical data on IORT in the treatment of brain tumors along with a discussion of the unique dosimetric and radiobiological factors inherent in IORT that could account for favorable outcome data beyond those seen in other techniques.
Understanding Monoclonal B Cell Lymphocytosis: An Interplay of Genetic and Microenvironmental Factors
Authors: Galigalidou Chrysi , Zaragoza-Infante Laura , Iatrou Anastasia , Chatzidimitriou Anastasia , Stamatopoulos Kostas , Agathangelidis Andreas
Published: November 2021

The term monoclonal B-cell lymphocytosis (MBL) describes the presence of a clonal B cell population with a count of less than 5 × 109/L and no symptoms or signs of disease. Based on the B cell count, MBL is further classified into 2 distinct subtypes: ‘low-count’ and ‘high-count’ MBL. High-count MBL shares a series of biological and clinical features with chronic lymphocytic leukemia (CLL), at least of the indolent type, and evolves to CLL requiring treatment at a rate of 1-2% per year, whereas ‘low-count’ MBL seems to be distinct, likely representing an immunological rather than a pre-malignant condition. That notwithstanding, both subtypes of MBL can carry ‘CLL-specific’ genomic aberrations such as cytogenetic abnormalities and gene mutations, yet to a much lesser extent compared to CLL. These findings suggest that such aberrations are mostly relevant for disease progression rather than disease onset, indirectly pointing to microenvironmental drive as a key contributor to the emergence of MBL. Understanding microenvironmental interactions is therefore anticipated to elucidate MBL ontogeny and, most importantly, the relationship between MBL and CLL.
The Hippo Signaling Pathway: The Trader of Tumor Microenvironment
Authors: Yang Duo , Zhang Na , Li Meihua , Hong Tao , Meng Wei , Ouyang Taohui
Published: November 2021

The Hippo pathway regulates cancer biology in many aspects and the crosstalk with other pathways complicates its role. Accumulated evidence has shown that the bidirectional interactions between tumor cells and tumor microenvironment (TME) are the premises of tumor occurrence, development, and metastasis. The relationship among different components of the TME constitutes a three-dimensional network. We point out the core position of the Hippo pathway in this network and discuss how the regulatory inputs cause the chain reaction of the network. We also discuss the important role of Hippo-TME involvement in cancer treatment.
Low Ligation Plus High Dissection Versus High Ligation of the Inferior Mesenteric Artery in Sigmoid Colon and Rectal Cancer Surgery: A Meta-Analysis
Authors: Yin Tzu-Chieh , Chen Yen-Cheng , Su Wei-Chih , Chen Po-Jung , Chang Tsung-Kun , Huang Ching-Wen , Tsai Hsiang-Lin , Wang Jaw-Yuan
Published: November 2021

Background

Whether high or low ligation of the inferior mesenteric artery (IMA) is superior in surgery for rectal and sigmoid colon cancers remains controversial. Although several meta-analyses have been conducted, the level of lymph node clearance was poorly defined. We performed a meta-analysis comparing high and low ligation of the IMA for sigmoid colon and rectal cancers, with emphasis on high dissection of the lymph node at the IMA root in all the included studies.

Methods

PubMed, MEDLINE, and EMBASE databases were searched to identify relevant articles published until 2020. The patient’s perioperative and oncologic outcomes were analyzed. Statistical analysis was performed using the statistical software RevMan version 5.4.

Results

A total of 17 studies, including four randomized controlled trials, published between 2011 and 2020 were selected. In total, 1,846 patients received low ligation of the IMA plus high dissection of lymph nodes (LL+HD), and 2,648 patients received high ligation of the IMA (HL). LL+HD was associated with low incidence of anastomotic leakage (p < 0.001), borderline long operative time (p = 0.06), and less yields of total lymph nodes (p = 0.03) but equivalent IMA root lymph nodes (p = 0.07); moreover, LL+HD exhibited non-inferior long-term oncological outcomes.

Conclusion

In comparison with HL, LL+HD was an effective and safe oncological procedure for sigmoid colon and rectal cancers. Therefore, to ligate the IMA below the level of the left colic artery with D3 high dissection for sigmoid colon and rectal cancers might be suggested once the surgeons are familiar with this technique.

Systematic Review Registration

INPLASY.com, identifier 202190029.
Successful Treatment of an Elderly Patient With Combined Small Cell Lung Cancer Receiving Anlotinib: A Case Report
Authors: Gan Yuying , Liu Pingli , Luo Tao
Published: November 2021

Combined small-cell lung cancer (C-SCLC) is a relatively rare subtype of SCLC and is defined by the combination of SCLC and any elements of non-small-cell lung carcinoma. Anlotinib is a novel oral multitarget tyrosine kinase inhibitor that led to significant improvements in progression-free survival and overall survival in third-line therapy of advanced SCLC in the ALTER1202 study. Antiangiogenic therapy with anlotinib in C-SCLC has not previously been reported. An 80-year-old man was admitted with a 20-day history of blood-stained sputum. Chest computed tomography revealed a soft mass (45 × 43 mm) in the right upper lobe and a mediastinal lymph node and additional lung lesions in the homo lung. Pathology confirmed C-SCLC after an ultrasound-guided percutaneous puncture biopsy of the right lung tumor. The elderly patient was given anlotinib monotherapy at a dose of 10 mg/day on days 1–14 of a 21-day cycle after providing informed consent, and the outcome was assessed as continued partial response. As of the last follow-up evaluation, the patient’s progression-free survival was more than 7 months, and the treatment showed satisfactory safety. Our findings provide direct evidence of the efficacy of anlotinib in an elderly patient with C-SCLC. More studies are needed to confirm our observations.
HK2 Is a Crucial Downstream Regulator of miR-148a for the Maintenance of Sphere-Forming Property and Cisplatin Resistance in Cervical Cancer Cells
Authors: Yang Hao , Hou Hui , Zhao Haiping , Yu Tianwei , Hu Yuchong , Hu Yue , Guo Junmei
Published: November 2021

The acquisition of cancer stem-like properties is believed to be responsible for cancer metastasis and therapeutic resistance in cervical cancer (CC). CC tissues display a high expression level of hexokinase 2 (HK2), which is critical for the proliferation and migration of CC cells. However, little is known about the functional role of HK2 in the maintenance of cancer stem cell-like ability and cisplatin resistance of CC cells. Here, we showed that the expression of HK2 is significantly elevated in CC tissues, and high HK2 expression correlates with poor prognosis. HK2 overexpression (or knockdown) can promote (or inhibit) the sphere-forming ability and cisplatin resistance in CC cells. In addition, HK2-overexpressing CC cells show enhanced expression of cancer stem cell-associated genes (including SOX2 and OCT4) and drug resistance-related gene MDR1. The expression of HK2 is mediated by miR-145, miR-148a, and miR-497 in CC cells. Overexpression of miR-148a is sufficient to reduce sphere formation and cisplatin resistance in CC cells. Our results elucidate a novel mechanism through which miR-148a regulates CC stem cell-like properties and chemoresistance by interfering with the oncogene HK2, providing the first evidence that dysregulation of the miR-148a/HK2 signaling plays a critical role in the maintenance of sphere formation and cisplatin resistance of CC cells. Our findings may guide future studies on therapeutic strategies that reverse cisplatin resistance by targeting this pathway.
Liver Involvement in SARS-CoV-2 Vertically Infected Newborn: A Case Report
Authors: Stolfi Ilaria , Conti Maria Giulia , Marciano Alessandra , Dito Lucia , Natale Fabio , Bartolucci Monica , Cellitti Raffaella , Regoli Daniela , Ticchiarelli Alessandra , Pangallo Ida , Pagano Federica , Ajassa Camilla , Brunelli Roberto , Terrin Gianluca
Published: November 2021

Neonatal SARS-CoV-2 infection can occur antenatally, peripartum, or postnatally. In the newborn, clinical manifestations may vary including fever and respiratory, gastrointestinal and neurological symptoms. Most commonly, they are subclinical. We herein present a case of vertical transmission of SARS-CoV-2 presenting with liver injury, characterized by an increase in serum transaminases.
Experiences Among School Personnel and School Nurses on Educational Adaptations for Students With CFS/ME: A Qualitative Interview Study
Authors: Similä Wenche Ann , Rø Torstein Baade , Nøst Torunn Hatlen
Published: November 2021

Introduction: Chronic fatigue syndrome (CFS/ME) is a disabling disease severely impacting school attendance, education, and social life in young students. Uncertainties surrounding CFS/ME etiology may impact the interpretation of CFS/ME in schools. Thus, school personnel need information from health care providers to make adequate adaptations to education and social life at school for these students.

Objectives: To explore teachers, counselors, and school nurses' experiences with adapting education for students with CFS/ME aged 13–19 in secondary and high schools.

Design: A qualitative study with focus group interviews and individual interviews performed face-to-face or digitally between November 2020 and March 2021. Data were analyzed using Systematic text condensation.

Participants: Six teachers, two counselors, and four school nurses in secondary and high school participated.

Results: Adapting education for students with CFS/ME was challenging, especially before the students received a diagnosis. The challenges were related to identifying the students' adaptational needs, maintaining a teacher-student relationship due to school absence, difficulties in maintaining continuity of education, and uncertainty regarding the diagnosis. Successful adaptations were related to quickly reacting to school absence, early referral to educational, psychological services, a close collaboration with the school management, and the development of digital teaching for students with CFS/ME. Interdisciplinary collaboration and a clear, constructive plan with adaptive measures, including maintained teacher-student communication and educational and social adaptations, may be useful in preventing the losses, young people, with CFS/ME experience.

Conclusion: Early interdisciplinary collaboration to adapt education and social life at school for students with CFS/ME, may support teachers, counselors, and school nurses in their efforts to adapt education and prevent losses related to academic and social development in students with CFS/ME.