bluuebunny/crossref_metadata_2025 huggingface dataset:
Copan Walk Away Specimen Processor (WASP) Automated System for Pathogen Detection in Female Reproductive Tract Specimens
Authors: Gao Jing , Chen Qiujing , Peng Yiqian , Jiang Nanyan , Shi Youhao , Ying Chunmei
Published: November 2021

Objective

Automation is increasingly being applied in clinical laboratories; however, preanalytical processing for microbiology tests and screening is still largely performed using manual methods owing to the complex procedures involved. To promote automation of clinical microbiology laboratories, it is important to assess the performance of automated systems for different specimen types separately. Therefore, the aim of this study was to explore the potential clinical application of the Copan Walk Away Specimen Processor (WASP) automated preanalytical microbiology processing system in the detection of pathogens in female reproductive tract specimens and its feasibility in optimizing diagnostic procedures.

Methods

Female reproductive tract specimens collected from pregnant women at their first obstetric check-up were inoculated into culture media using the Copan WASP automated specimen processing system and were also cultured using a conventional manual inoculation method. After 48 h of culture, the growth of colonies was observed, and the types of bacteria, number of colonies, and efficiency in isolating single colonies were compared between the automated and manual groups. The specimens collected from the WASP system using the Copan-ESwab sample collection tubes were further analyzed for the presence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Ureaplasmaurealyticum (UU) via fluorescence quantitative polymerase chain reaction (qPCR) and an immunochromatographic assay to investigate the feasibility of this method in optimizing detection of these common pathogens of the female reproductive tract.

Results

Compared with the manual culture method, the Copan WASP microbiology automation system detected fewer bacterial types (P<0.001) and bacterial colonies (P<0.001) but had a higher detection rate of single colonies (P<0.001). There was no significant difference in the detection rates of common pathogens encountered in clinical obstetrics and gynecology, including group B Streptococcus (GBS) (P=0.575) and Candida (P=0.917), between the two methods. Specimens collected in the Copan-ESwab tubes could be used for screening of GBS and CT via fluorescence-based qPCR but not with immunochromatography. However, UU and NG were not detected in any sample with either method; thus, further validation is required to determine the feasibility of the Copan system for screening these pathogens.

Conclusion

The Copan WASP microbiology automation system could facilitate the optimization of diagnostic procedures for detecting common pathogens of the female reproductive system, thereby reducing associated costs.
Emerging Non-statin Treatment Options for Lowering Low-Density Lipoprotein Cholesterol
Authors: Bardolia Chandni , Amin Nishita Shah , Turgeon Jacques
Published: November 2021

Low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for the development of atherosclerotic cardiovascular disease. Statins have been the gold standard for managing cholesterol levels and reducing the risks associated with atherosclerotic cardiovascular disease; however, many patients do not achieve their cholesterol goals or are unable to tolerate this drug class due to adverse drug events. Recent studies of non-statin cholesterol lowering drugs (i.e., ezetimibe, PCSK9 inhibitors) have demonstrated cardiovascular benefits; and new drugs [i.e., bempedoic acid (BDA), inclisiran] have produced promising results in pre-clinical and clinical outcome trials. This narrative review aims to discuss the place in therapy of ezetimibe, PCSK9 inhibitors, BDA, and inclisiran and describe their relative pharmacokinetic (PK) profiles, efficacy and safety as monotherapy and combination therapy, and cardiovascular benefit(s) when used for hypercholesterolemia.
The Prediction of Metastases of Lateral Cervical Lymph Node in Medullary Thyroid Carcinoma
Authors: Zhou Tian-Han , Zhao Ling-Qian , Zhang Yu , Wu Fan , Lu Kai-Ning , Mao Lin-Lin , Jiang Ke-Cheng , Luo Ding-Cun
Published: November 2021

Purpose

Development and validation of a nomogram for the prediction of lateral lymph node metastasis (LLNM) in medullary thyroid carcinoma (MTC).

Methods

We retrospectively reviewed the clinical features of patients with MTC in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017 and in our Department of Surgical Oncology, Hangzhou First People’s Hospital between 2009 and 2019. The log‐rank test was used to compare the difference in the Kaplan–Meier (K–M) curves in recurrence and survival. The nomogram was developed to predict the risk of LLNM in MTC patients. The prediction efficiency of the predictive model was assessed by area under the curve (AUC) and concordance index (C-index) and calibration curves. Decision curve analysis (DCA) was performed to determine the clinic value of the predictive model.

Result

A total of 714 patients in the SEER database and 35 patients in our department were enrolled in our study. Patients with LLNM had worse recurrence rate and cancer-specific survival (CSS) compared with patients without LLNM. Five clinical characteristics including sex, tumor size, multifocality, extrathyroidal extension, and distant metastasis were identified to be associated with LLNM in MTC patients, which were used to develop a nomogram. Our prediction model had satisfied discrimination with a C-index of 0.825, supported by both training set and internal testing set with a C-index of 0.825, and 0.816, respectively. DCA was further made to evaluate the clinical utility of this nomogram for predicting LLNM.

Conclusions

Male sex, tumor size >38mm, multifocality, extrathyroidal extension, and distant metastasis in MTC patients were significant risk factors for predicting LLNM.
Numerical Study on the Biomimetic Trailing Edge of a Turbine Blade Under a Wide Range of Outlet Mach Numbers
Authors: Wen Fengbo , Luo Yuxi , Wang Shuai , Wang Songtao , Wang Zhongqi
Published: November 2021

This study was carried out to investigate the loss mechanism of a blade with a harbor seal whisker structure on the trailing edge under different Mach numbers. The loss of high-pressure turbine blades with four different trailing edge geometries, including a prototype, an elliptical trailing edge (ETE), a sinusoidal trailing edge (STE), and a biomimetic trailing edge (BTE) at Mach numbers of 0.38–1.21 is studied. The delayed detached-eddy simulation method is used to predict the detailed flow of the four cascades. The result shows that, when the Mach number is less than 0.9, the BTE can effectively reduce the energy loss coefficient compared with the other three cases. As the Mach number increases, the three-dimensional characteristics of the wake behind the BTE weaken. The energy loss coefficient of the blade with the BTE is close to that of the blade with the ETE and STE when the Mach number is greater than 0.9. Besides this, by controlling the wake, the BTE can effectively suppress the dynamic movement of shock waves in the cascade at high Mach numbers.
The Brazilian Pareiasaur Revisited
Authors: Cisneros Juan C. , Dentzien-Dias Paula , Francischini Heitor
Published: November 2021

Provelosaurus americanus is the only known representative of the Pareiasauria in the Americas. This mid-size pareiasaur from the Rio do Rasto Formation of southern Brazil has been traditionally considered to be related to smaller forms from the South African Karoo known as the “dwarf pareiasaurs” of Lopingian age. P. americanus, however, co-existed with dinocephalians, which indicates a Guadalupian age. New fossils provide a nearly complete osteological account that forms the basis for a revised diagnosis and a test of phylogenetic relationships of P. americanus. Our results offer further support to the hypothesis that the Brazilian pareiasaur is the sister taxon of the Karoo “dwarf pareiasaurs,” being the earliest member of this group and one of the oldest pareiasaurs known so far. This is reinforced by a radiometric dating of the Morro Pelado Member of the Rio do Rasto Formation. In addition, the association of four individuals of various ontogenetic stages at the type locality supports some degree of social behavior in P. americanus.
Sex-Specific Stress Tolerance in Embryos of Lake Char (Salvelinus umbla)
Authors: Nusbaumer David , Garaud Laura , Ançay Laurie , Wedekind Claus
Published: November 2021

Salmonid fish have become important models in evolution and ecology, but possible effects of embryo or larval sex are mostly ignored, probably because morphological gonad formation starts only months after hatching and sexual maturation years later. However, recent gene expression studies and first observations in domestic strains suggest that sex-specific life histories could already start at an embryonic stage. Here we test this hypothesis in embryos and larvae of lake char (Salvelinus umbla). We sampled wild char and used their gametes to produce embryos of 40 different families. Embryos were raised singly in a stress or a non-stress environment until a late larval stage (stress was induced by allowing remainders of ovarian fluids to support microbial growth). Genetic markers were then used to sex the fish and reconstruct paternity (N= 1,463, including dead embryos). Primary sex ratio did not differ among families and was about 1:1. Female embryos hatched on average later and showed lower stress tolerance than male embryos. There were significant parental effects on offspring growth and mortality, but the sex differences in embryo performance were not family specific. We conclude that the sexes differ in their life history and susceptibilities to environmental stress already at embryonic stages. Environmental stress during incubation can therefore affect population sex ratio and hence population growth and genetics.
Eight in One: Hidden Diversity of the Bagrid Catfish Tachysurus albomarginatus s.l. (Rendhal, 1928) Widespread in Lowlands of South China
Authors: Shao Wei-Han , Cheng Jian-Li , Zhang E
Published: November 2021

There is increasing evidence that species diversity is underestimated in the current taxonomy of widespread freshwater fishes. The bagrid species T. albomarginatus s.l. is mainly distributed in the lowlands of South China, as currently identified. A total of 40 localities (including the type locality), which covers most of its known range, were sampled. Molecular phylogenetic analyses based on concatenated mtDNA and nuclear genes recover nine highly supported lineages clustering into eight geographic populations. The integration of molecular evidence, morphological data, and geographic distribution demonstrates the delineation of T. albomarginatus s.l. as eight putative species. Four species, namely, T. albomarginatus, T. lani, T. analis, and T. zhangfei sp. nov. and the T. similis complex are taxonomically recognized herein. Moreover, T. zhangfei sp. nov. comprises two genetically distinct lineages with no morphological and geographical difference. This study also reveals aspects of estimation of divergence time, distribution, and ecological adaption within the T. albomarginatus group. The unraveling of the hidden species diversity of this lowland bagrid fish highlights the need for not only the molecular scrutiny of widely distributed species of South China but also the adjustment of current biodiversity conservation strategies to protect the largely overlooked diversity of fishes from low-elevation rapids.
Circulating CitH3 Is a Reliable Diagnostic and Prognostic Biomarker of Septic Patients in Acute Pancreatitis
Authors: Pan Baihong , Li Yaozhen , Liu Yu , Wang Wei , Huang Gengwen , Ouyang Yang
Published: November 2021

Purpose

Acute pancreatitis (AP) is an inflammatory disease. AP starts with sterile inflammation and is often complicated with critical local or systemic infection or sepsis in severe cases. Septic AP activates peptidyl arginine deiminase (PAD) and citrullinates histone H3 (CitH3), leading to neutrophil extracellular trap (NET) formation. Investigating the role of NETs and underlying mechanisms in septic AP may facilitate developing diagnostic and therapeutic approaches. In this study, we sought to identify the expression of CitH3 in septic AP patients and to analyze the correlation of CitH3 concentration with NET components as well as clinical outcomes.

Methods

Seventy AP patients with or without sepsis (40 septic cases, 30 nonseptic cases) and 30 healthy volunteers were recruited in this study. Concentration of NET components (CitH3 and double-strain DNA) and key enzymes (PAD2/4) were measured. Clinical and laboratory characteristics of patients were recorded and analyzed.

Results

Levels of CitH3 were elevated significantly in septic AP patients compared with those in nonseptic AP and healthy volunteers. The area under the curve (AUC, 95% confidence interval) for diagnosing septic AP was 0.93 (0.86–1.003), and the cutoff was 43.05 pg/ml. Among septic AP cases (n = 40), the concentration of CitH3 was significantly increased in those who did not survive or were admitted to the intensive care unit, when compared with that in those who survived or did not require intensive care unit. Association analysis revealed that CitH3 concentration was positively correlated with PAD2, PAD4, dsDNA concentration, and Sequential Organ Failure Assessment scores.

Conclusion

CitH3 concentration increased in septic AP patients and was closely correlated with disease severity and clinical outcomes. CitH3 may potentially be a diagnostic and prognostic biomarker of septic AP.
Overview of a new Ocean Glider Navigation System: OceanGNS
Authors: von Oppeln-Bronikowski Nicolai , Zhou Mingxi , Bahadory Taimaz , de Young Brad
Published: November 2021

Ocean gliders are increasingly a platform of choice to close the gap between traditional ship-based observations and remote sensing from floats (e.g., Argo) and satellites. However, gliders move slowly and are strongly influenced by currents, reducing useful battery life, challenging mission planning, and increasing pilot workload. We describe a new cloud-based interactive tool to plan glider navigation called OceanGNS© (Ocean Glider Navigation System). OceanGNS integrates current forecasts and historical data to enable glider route–planning at varying scales. OceanGNS utilizes optimal route–planning by minimizing low current velocity constraints by applying a Dijkstra algorithm. The complexity of the resultant path is reduced using a Ramer-Douglas Pueckler model. Users can choose the weighting for historical and forecast data as well as bathymetry and time constraints. Bathymetry is considered using a cost function approach when shallow water is not desirable to find an optimal path that also lies in deeper water. Initial field tests with OceanGNS in the Gulf of St. Lawrence and the Labrador Sea show promising results, improving the glider speed to the destination 10–30%. We use these early tests to demonstrate the utility of OceanGNS to extend glider endurance. This paper provides an overview of the tool, the results from field trials, and a future outlook.
HOMO–LUMO Gaps and Molecular Structures of Polycyclic Aromatic Hydrocarbons in Soot Formation
Authors: Xu Yabei , Chu Qingzhao , Chen Dongping , Fuentes Andrés
Published: November 2021

A large number of PAH molecules is collected from recent literature. The HOMO-LUMO gap value of PAHs was computed at the level of B3LYP/6-311+G (d,p). The gap values lie in the range of 0.64–6.59 eV. It is found that the gap values of all PAH molecules exhibit a size dependency to some extent. However, the gap values may show a big variation even at the same size due to the complexity in the molecular structure. All collected PAHs are further classified into seven groups according to features in the structures, including the types of functional groups and the molecular planarity. The impact of functional groups, including –OH, –CHO, –COOH, =O, –O– and –CnHm on the bandgap is discussed in detail. The substitution of ketone group has the greatest reduction on the HOMO-LUMO gap of PAH molecules. Besides functional groups, we found that both local structure and the position of five-member rings make critical impacts on the bandgap via a detailed analysis of featured PAHs with unexpected low and high gap values. Among all these factors, the five-member rings forming nonplanar PAHs impact the gap most. Furthermore, we developed a machine learning model to predict the HOMO-LUMO gaps of PAHs, and the average absolute error is only 0.19 eV compared with the DFT calculations. The excellent performance of the machine learning model provides us an accurate and efficient way to explore the band information of PAHs in soot formation.
Abnormal Respiratory Sounds Classification Using Deep CNN Through Artificial Noise Addition
Authors: Zulfiqar Rizwana , Majeed Fiaz , Irfan Rizwana , Rauf Hafiz Tayyab , Benkhelifa Elhadj , Belkacem Abdelkader Nasreddine
Published: November 2021

Respiratory sound (RS) attributes and their analyses structure a fundamental piece of pneumonic pathology, and it gives symptomatic data regarding a patient's lung. A couple of decades back, doctors depended on their hearing to distinguish symptomatic signs in lung audios by utilizing the typical stethoscope, which is usually considered a cheap and secure method for examining the patients. Lung disease is the third most ordinary cause of death worldwide, so; it is essential to classify the RS abnormality accurately to overcome the death rate. In this research, we have applied Fourier analysis for the visual inspection of abnormal respiratory sounds. Spectrum analysis was done through Artificial Noise Addition (ANA) in conjunction with different deep convolutional neural networks (CNN) to classify the seven abnormal respiratory sounds—both continuous (CAS) and discontinuous (DAS). The proposed framework contains an adaptive mechanism of adding a similar type of noise to unhealthy respiratory sounds. ANA makes sound features enough reach to be identified more accurately than the respiratory sounds without ANA. The obtained results using the proposed framework are superior to previous techniques since we simultaneously considered the seven different abnormal respiratory sound classes.
Brief Postnatal Visual Deprivation Triggers Long-Lasting Interactive Structural and Functional Reorganization of the Human Cortex
Authors: Feng Yixuan , Collignon Olivier , Maurer Daphne , Yao Ke , Gao Xiaoqing
Published: November 2021

Patients treated for bilateral congenital cataracts provide a unique model to test the role of early visual input in shaping the development of the human cortex. Previous studies showed that brief early visual deprivation triggers long-lasting changes in the human visual cortex. However, it remains unknown if such changes interact with the development of other parts of the cortex. With high-resolution structural and resting-state fMRI images, we found changes in cortical thickness within, but not limited to, the visual cortex in adult patients, who experienced transient visual deprivation early in life as a result of congenital cataracts. Importantly, the covariation of cortical thickness across regions was also altered in the patients. The areas with altered cortical thickness in patients also showed differences in functional connectivity between patients and normally sighted controls. Together, the current findings suggest an impact of early visual deprivation on the interactive development of the human cortex.
Case Report: Bullous Lung Disease Following COVID-19
Authors: Pednekar Prachi , Amoah Kwesi , Homer Robert , Ryu Changwan , Lutchmansingh Denyse D.
Published: November 2021

More than 87% of patients report the persistence of at least one symptom after recovery from the Coronavirus disease 2019 (COVID-19). Dyspnea is one of the most frequently reported symptoms following severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection with persistent chest radiological abnormalities up to 3 months after symptom onset. These radiological abnormalities are variable and most commonly include ground-glass opacities, reticulations, mosaic attenuation, parenchymal bands, interlobular septal thickening, bronchiectasis, and fibrotic-like changes. However, in this case report, we describe findings of bullous lung disease as a complication of SARS CoV-2 infection. As the pandemic continues, there is a need to understand the multiple respiratory manifestations of post-acute sequelae of COVID-19. We, therefore, present this case to add to the current body of literature describing pulmonary disease as a consequence of SARS CoV-2 infection.
Leukotrienes Are Dispensable for Vaginal Neutrophil Recruitment as Part of the Immunopathological Response During Experimental Vulvovaginal Candidiasis
Authors: Yano Junko , White David J. , Sampson Anthony P. , Wormley Floyd L. , Fidel Paul L.
Published: November 2021

Recruitment of polymorphonuclear neutrophils (PMNs) into the vaginal lumen is the hallmark of an acute immunopathologic inflammatory response during vulvovaginal candidiasis (VVC) caused by Candida albicans. Recurrent VVC (RVVC) remains a chronic health burden in affected women worldwide despite the use of antifungal therapy. Based on the role leukotrienes (LTs) play in promoting inflammation, leukotriene receptor antagonists (LTRAs) targeted for LTB4 (etalocib) or LTC4, LTD4, and LTE4 (zafirlukast or montelukast) have been shown to reduce inflammation of epithelial tissues. An open-label pilot study using long-term regimens of zafirlukast in women with RVVC indicated the potential for some relief from recurrent episodes. To investigate this clinical observation further, we evaluated the effects of LT antagonistic agents and LT deficiency on the immunopathogenic response in a mouse model of VVC. Results showed that mice given daily intraperitoneal injections of individual LTRAs, starting 2days prior to vaginal inoculation with C. albicans and continuing through 14days post-inoculation, had no measurable reduction in PMN migration. The LTRAs were also ineffective in reducing levels of the hallmark vaginal inflammatory markers (S100A8, IL-1β) and tissue damage (LDH) associated with the immunopathogenic response. Finally, LT-deficient 5-lipoxygenase knockout mice showed comparable levels of vaginal fungal burden and PMN infiltration to wild-type mice following inoculation with a vaginal (ATCC 96113) or laboratory (SC5314) C. albicans isolate. These results indicate that despite some clinical evidence suggestive of off-target efficacy of LTRAs in RVVC, LTs and associated signaling pathways appear to be dispensable in the immunopathogenesis of VVC.
Activation and Role of Astrocytes in Ischemic Stroke
Authors: Shen Xin-Ya , Gao Zhen-Kun , Han Yu , Yuan Mei , Guo Yi-Sha , Bi Xia
Published: November 2021

Ischemic stroke refers to the disorder of blood supply of local brain tissue caused by various reasons. It has high morbidity and mortality worldwide. Astrocytes are the most abundant glial cells in the central nervous system (CNS). They are responsible for the homeostasis, nutrition, and protection of the CNS and play an essential role in many nervous system diseases’ physiological and pathological processes. After stroke injury, astrocytes are activated and play a protective role through the heterogeneous and gradual changes of their gene expression, morphology, proliferation, and function, that is, reactive astrocytes. However, the position of reactive astrocytes has always been a controversial topic. Many studies have shown that reactive astrocytes are a double-edged sword with both beneficial and harmful effects. It is worth noting that their different spatial and temporal expression determines astrocytes’ various functions. Here, we comprehensively review the different roles and mechanisms of astrocytes after ischemic stroke. In addition, the intracellular mechanism of astrocyte activation has also been involved. More importantly, due to the complex cascade reaction and action mechanism after ischemic stroke, the role of astrocytes is still difficult to define. Still, there is no doubt that astrocytes are one of the critical factors mediating the deterioration or improvement of ischemic stroke.
Clinical Analysis of Risk Factors of Postoperative Psychiatric Disorders in Patients With Adult Craniopharyngioma
Authors: Zhao Rui , Lu Pengwei , Fan Yanzhu , Li Chuzhong , Liu Chunhui , Zhao Peng , Cao Lei , Gao Hongwei , Gui Songbai
Published: November 2021

Objective: To analyze the risk factors relative to postoperative psychiatric disorders in adult patients with craniopharyngioma.

Methods: A retrospective case-control study design was used in this study. The Neuropsychiatric Inventory–Questionnaire (NPI-Q) assessment tool was used to assess psychiatric disorders in postoperative patients with craniopharyngioma at Beijing Tiantan Hospital from January 2018 to December 2020. The relationship between the psychiatric disorders and basic demographic data as well as several risk factors, such as the tumor characteristics (tumor location, tumor size, pathological finding of the tumor, etc.) and treatment-related factors (the extent of the resection), were analyzed.

Results: A total of 173 patients were included in this study. The prevalence of psychiatric disorders was 14.5% among adult craniopharyngioma patients. Irritability represented the most common type of psychological symptom (64%, n = 16), followed by agitation (36%, n = 9), and delusions (28%, n = 7). The risk factors relative to postoperative psychiatric disorders that were identified were a tumor volume larger than 7 cm3 (HR = 3.292, P = 0.042), tumor location (P = 0.003), hypothalamic invasion (HR = 9.766, P = 0.036), and gross-total resection (HR = 0.085, P = 0.042).

Conclusion: Neurocognitive assessment and intervention before and after surgery are important in patients with larger tumors, invading the third ventricle, and tumors with hypothalamic invasion. Prediction of these risk factors is essential for the treatment.
Microcontact Printing of Cholinergic Neurons in Organotypic Brain Slices
Authors: Steiner Katharina , Humpel Christian
Published: November 2021

Alzheimer's disease is a severe neurodegenerative disorder of the brain, characterized by beta-amyloid plaques, tau pathology, and cell death of cholinergic neurons, resulting in loss of memory. The reasons for the damage of the cholinergic neurons are not clear, but the nerve growth factor (NGF) is the most potent trophic factor to support the survival of these neurons. In the present study we aim to microprint NGF onto semipermeable 0.4 μm pore membranes and couple them with organotypic brain slices of the basal nucleus of Meynert and to characterize neuronal survival and axonal growth. The brain slices were prepared from postnatal day 10 wildtype mice (C57BL6), cultured on membranes for 2–6 weeks, stained, and characterized for choline acetyltransferase (ChAT). The NGF was microcontact printed in 28 lines, each with 35 μm width, 35 μm space between them, and with a length of 8 mm. As NGF alone could not be printed on the membranes, NGF was embedded into collagen hydrogels and the brain slices were placed at the center of the microprints and the cholinergic neurons that survived. The ChAT+ processes were found to grow along with the NGF microcontact prints, but cells also migrated. Within the brain slices, some form of re-organization along the NGF microcontact prints occurred, especially the glial fibrillary acidic protein (GFAP)+ astrocytes. In conclusion, we provided a novel innovative microcontact printing technique on semipermeable membranes which can be coupled with brain slices. Collagen was used as a loading substance and allowed the microcontact printing of nearly any protein of interest.
Current Strategies for Tumor Photodynamic Therapy Combined With Immunotherapy
Authors: Hua Jianfeng , Wu Pan , Gan Lu , Zhang Zhikun , He Jian , Zhong Liping , Zhao Yongxiang , Huang Yong
Published: November 2021

Photodynamic therapy (PDT) is a low invasive antitumor therapy with fewer side effects. On the other hand, immunotherapy also has significant clinical applications in the treatment of cancer. Both therapies, on their own, have some limitations and are incapable of meeting the demands of the current cancer treatment. The efficacy of PDT and immunotherapy against tumor metastasis and tumor recurrence may be improved by combination strategies. In this review, we discussed the possibility that PDT could be used to activate immune responses by inducing immunogenic cell death or generating cancer vaccines. Furthermore, we explored the latest advances in PDT antitumor therapy in combination with some immunotherapy such as immune adjuvants, inhibitors of immune suppression, and immune checkpoint blockade.
Case Report: A Novel Compound Heterozygous Mutation of the FRMD4A Gene Identified in a Chinese Family With Global Developmental Delay, Intellectual Disability, and Ataxia
Authors: Pan Yuhua , Guo Xiaoling , Zhou Xiaoqiang , Liu Yue , Lian Jingli , Yang Tingting , Huang Xiang , He Fei , Zhang Jian , Wu Buling , Xiong Fu , Yang Xingkun
Published: November 2021

Background: FERM domain-containing protein 4A (FRMD4A) is a scaffolding protein previously proposed to be critical in the regulation of cell polarity in neurons and implicated in human intellectual development.

Case Presentation: We report a case of a 3-year-old boy with corpus callosum anomaly, relative macrocephaly, ataxia, and unexplained global developmental delay. Here, compound heterozygous missense mutations in the FRMD4A gene [c.1830G>A, p.(Met610Ile) and c.2973G>C, p.(Gln991His)] were identified in the proband, and subsequent familial segregation showed that each parent had transmitted a mutation.

Conclusions: Our results have confirmed the associations of mutations in the FRMD4A gene with intellectual development and indicated that for patients with unexplained global developmental delay, the FRMD4A gene should be included in the analysis of whole exome sequencing data, which can contribute to the identification of more patients affected by this severe phenotypic spectrum.
Precision Medicine in Autoimmune Thyroiditis and Hypothyroidism
Authors: Ferrari Silvia Martina , Ragusa Francesca , Elia Giusy , Paparo Sabrina Rosaria , Mazzi Valeria , Baldini Enke , Benvenga Salvatore , Antonelli Alessandro , Fallahi Poupak
Published: November 2021

Autoimmune thyroid diseases (AITD) are T-cell-mediated organ specific autoimmune disorders, deriving from an altered response of the immune system that leads to the immune attack to the thyroid. Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are the two principal AITD clinical presentations. Hypothyroidism and thyrotoxicosis are, respectively, the clinical hallmarks of HT and GD. Patients with autoimmune thyroiditis are treated daily with synthetic L-thyroxine (L-T4) at the dose of 1.5–1.7 μg/kg. Various L-T4 formulations are commercially available (tablet, liquid solution, or soft gel capsule). L-T4 in tablets is generally prescribed to treat hypothyroidism, whereas the liquid formulation, or soft gel capsules, can be administered in hypothyroid patients in case of malabsorption or in patients in therapy with drugs interfering with L-T4 absorption. Furthermore, myoinositol has a crucial role in thyroid autoimmunity and function. Clinical studies reported a significant decline in TSH and antithyroid autoantibodies levels after treatment with myoinositol + selenium in patients with subclinical hypothyroidism and autoimmune thyroiditis. Moreover, thyroidectomy can be rarely recommended in patients with autoimmune thyroiditis, with cosmetic reasons for a goiter, or with important signs or symptoms of local compression, or nodular disease with a “suspicious” cytology for malignancy. Furthermore, a recent randomized trial suggested that total thyroidectomy can improve quality of life and fatigue, while medical therapy did not. In this review, we overview currently available evidence in personalized medicine in patients with autoimmune thyroiditis and hypothyroidism. Further research is needed in larger population to investigate the effect of these new treatments on quality of life.
Inter-Individual Variability of a High-Intensity Interval Training With Specific Techniques vs. Repeated Sprints Program in Sport-Related Fitness of Taekwondo Athletes
Authors: Ojeda-Aravena Alex , Herrera-Valenzuela Tomás , Valdés-Badilla Pablo , Cancino-López Jorge , Zapata-Bastias José , García-García José Manuel
Published: November 2021

This study investigated the effect of 4 weeks of high-intensity interval training (HIIT) with specific techniques (TS-G) vs. repeated sprints (RS-G) and analyzed the inter-individual variability [classified into responders (Rs) and non-responders (NRs)] on sport-related fitness in taekwondo (TKD) athletes. Athletes of both genders (n = 12) were randomly assigned into TS-G and RS-G groups. Both groups trained 3 days/week for 4 weeks [two blocks of three rounds of 2 min of activity (4-s of all-out efforts with 28-s dynamical pauses) with 1 min of recovery in between and 5 min between blocks] during their regular training. The related sport fitness assessments included squat jump (SJ), countermovement jump (CMJ), multiple frequency speed of kick test (FSKTMULT), specifically total kicks and Kick Decrement Index (KDI), and 20-m shuttle run (20MSR). Relevant results indicate a significant effect of the time factor in both groups for SJ performance and a significant decrease for KDI in RS-G. In addition, an improvement in performance according to the effect size analysis in the TS-G in total kicks, KDI, and 20MSR. Complementarily, a higher proportion of athlete Rs was reported in TS-G vs. RS-G for SJ (50% vs. 30.3%, respectively), CMJ, and total kicks (16.6% vs. 0%). In conclusion, the addition to the regular training of a HIIT with specific-techniques and repeated-sprints associated with intervals and similar structure of the combat during 4 weeks of training can improve the concentric characteristics of lower limb performance, although they were not the sufficient stimuli in the other components of TKD-related fitness.
Phylogenetic Analysis of the Plant U2 snRNP Auxiliary Factor Large Subunit A Gene Family in Response to Developmental Cues and Environmental Stimuli
Authors: Lu Shuai , Gao Cong , Wang Yongzhou , He Yingying , Du Junrong , Chen Moxian , Zhao Hua , Fang Hui , Wang Baohua , Cao Yunying
Published: November 2021

In all organisms, splicing occurs through the formation of spliceosome complexes, and splicing auxiliary factors are essential during splicing. U2AF65 is a crucial splicing cofactor, and the two typical RNA-recognition motifs at its center recognize and bind the polypyrimidine sequence located between the intron branch site and the 3′-splice site. U2AF65A is a member of the U2AF65 gene family, with pivotal roles in diseases in mammals, specifically humans; however, few studies have investigated plant U2AF65A, and its specific functions are poorly understood. Therefore, in the present study, we systematically identified U2AF65A in plant species from algae to angiosperms. Based on 113 putative U2AF65A sequences from 33 plant species, phylogenetic analyses were performed, followed by basic bioinformatics, including the comparisons of gene structure, protein domains, promoter motifs, and gene expression levels. In addition, using rice as the model crop, we demonstrated that the OsU2AF65A protein is localized to the nucleus and cytoplasm, and it is involved in responses to various stresses, such as drought, high salinity, low temperature, and heavy metal exposure (e.g., cadmium). Using Arabidopsis thaliana and rice mutants, we demonstrated that U2AF65A is involved in the accumulation of plant biomass, growth of hypocotyl upon thermal stimulation, and reduction of tolerance of high temperature stress. These findings offer an overview of the U2AF65 gene family and its stress response functions, serving as the reference for further comprehensive functional studies of the essential specific splicing cofactor U2AF65A in the plant kingdom.
Asymmetric Morphological Priming Among Inflected and Derived Verbs and Nouns in Greek
Authors: Loui Sofia , Protopapas Athanassios , Orfanidou Eleni
Published: November 2021

The present study examined differences between inflectional and derivational morphology using Greek nouns and verbs with masked priming (with both short and long stimulus onset asynchrony) and long-lag priming. A lexical decision task to inflected noun and verb targets was used to test whether their processing is differentially facilitated by prior presentation of their stem in words of the same grammatical class (inflectional morphology) or of a different grammatical class (derivational morphology). Differences in semantics, syntactic information, and morphological complexity between inflected and derived word pairs (both nouns and verbs) were minimized by unusually tight control of stimuli as permitted by Greek morphology. Results showed that morphological relations affected processing of morphologically complex Greek words (nouns and verbs) across prime durations (50–250ms) as well as when items intervened between primes and targets. In two of the four experiments (Experiments 1 and 3), inflectionally related primes produced significantly greater effects than derivationally related primes suggesting differences in processing inflectional versus derivational morphological relations, which may disappear when processing is less dependent on semantic effects (Experiment 4). Priming effects differed for verb vs. noun targets with long SOA priming (Experiment 3), consistent with processing differences between complex words of different grammatical class (nouns and verbs) when semantic effects are maximized. Taken together, results demonstrate that inflectional and derivational relations differentially affect processing complex words of different grammatical class (nouns and verbs). This finding indicates that distinctions of morphological relation (inflectional vs. derivational) are not of the same kind as distinctions of grammatical class (nouns vs. verbs). Asymmetric differences among inflected and derived verbs and nouns seem to depend on semantic effects and/or processing demands modulating priming effects very early in lexical processing of morphologically complex written words, consistent with models of lexical processing positing early access to morphological structure and early influence of semantics.
The Cambridge Cognitive and Psychiatric Assessment Kit (CamCOPS): A Secure Open-Source Client–Server System for Mobile Research and Clinical Data Capture
Authors: Cardinal Rudolf N. , Burchell Martin
Published: November 2021

CamCOPS is a free, open-source client–server system for secure data capture in the domain of psychiatry, psychology, and the clinical neurosciences. The client is a cross-platform C++ application, suitable for mobile and offline (disconnected) use. It allows touchscreen data entry by subjects/patients, researchers/clinicians, or both together. It implements a large and extensible range of tasks, from simple questionnaires to complex animated tasks. The client uses encrypted data storage and sends data via an encrypted network connection to a CamCOPS server. Individual institutional users set up and run their own CamCOPS server, so no data is transferred outside the hosting institution's control. The server, written in Python, provides clinically oriented and research-oriented views of tasks, including the tracking of changes over time. It provides an audit trail, export facilities (such as to an institution's primary electronic health record system), and full structured data access subject to authorization. A single CamCOPS server can support multiple research/clinical groups, each having its own identity policy (e.g., fully identifiable for clinical use; de-identified/pseudonymised for research use). Intellectual property rules regarding third-party tasks vary and CamCOPS has several mechanisms to support compliance, including for tasks that may be permitted to some institutions but not others. CamCOPS supports task scheduling and home testing via a simplified user interface. We describe the software, report local information governance approvals within part of the UK National Health Service, and describe illustrative clinical and research uses.
The Case for Co-production in Singapore's Mental Healthcare
Authors: Lee Ying Ying , Ang Suying , Tang Charmaine
Published: November 2021

For better or worse, there exists a power differential between psychiatrists and their patients in mental healthcare. Co-production was proposed to be the “third space” to offer truce between the professional-patient tension in mental healthcare. In Singapore, co-production is a new, but growing, approach to mental healthcare service delivery. In this commentary, we argue that co-production is not just a novel way to provide service, but a moral imperative. Recovery Colleges and its adoption in Singapore is discussed in some detail to highlight how co-production may be applied in practice.
Social Stigma Related to COVID-19 Disease Described by Primary and Secondary School Teachers and Adolescents Living With HIV in Western Kenya
Authors: Chory Ashley , Nyandiko Winstone , Ashimosi Celestine , Aluoch Josephine , Martin Roxanne , Biegon Whitney , Munyoro Dennis , Apondi Edith , Vreeman Rachel
Published: November 2021

Introduction: Understanding community members' knowledge, attitudes, and beliefs about the novel SARS-CoV-2 virus and the prevalence of associated stigma are critical steps for increasing accurate public health knowledge, encouraging uptake of preventative or mitigating health behaviors, and ultimately bringing the COVID-19 pandemic under control.

Methods: We conducted a one-time, phone-based assessment to assess the presence of perceived COVID-19 community stigma reported by Kenyan primary and secondary school teachers, as well as adolescents living with HIV. Participants were previously enrolled in an ongoing, cluster-randomized trial to evaluate the impact of multi-media teacher training on teachers' negative attitudes and beliefs around HIV. The SAFI Stigma Questionnaire, a validated tool to assess HIV-related stigma in this setting, was adapted to ask questions regarding the stigma and discrimination experienced or perceived during the COVID-19 pandemic.

Results: We enrolled 330 participants in this study, including 311 primary and secondary teachers (56% female, average age 36 years) and 19 adolescents living with HIV (57.89% female, average age 16.37 years). None of the adolescent participants reported witnessing or experiencing discrimination related to COVID-19, nor did they report losing financial and/or social support. In contrast, the teacher participants reported prominent social stigma experiences of various levels and related to COVID-19. Teachers in the intervention group, who had completed the multi-media training on HIV-related stigma, were significantly less likely to think that the community viewed COVID-19 as a dirty or shameful disease, and less likely to feel it was important to keep their COVID-19 infection a secret, compared to the teacher control group.

Conclusion: These findings suggest that COVID-19-related stigma may be prevalent in western Kenya and that interventions to reduce community-level stigma for HIV may also have a protective impact on other stigmatized infectious diseases such as COVID-19.
Trace Metal Lead Exposure in Typical Lip Cosmetics From Electronic Commercial Platform: Investigation, Health Risk Assessment and Blood Lead Level Analysis
Authors: Li Yanan , Fang Yanyan , Liu Zehua , Zhang Yahan , Liu Kangli , Jiang Luping , Yang Boyuan , Yang Yongdie , Song Yongwei , Liu Chaoyang
Published: November 2021

Lead (Pb) in lipstick products has become an increasing concern, which can cause safety problems to human body directly with diet. To investigate the Pb exposure and potential health risk level of typical popular lip cosmetics in Chinese e-commerce market, Python crawler was introduced to identify and select 34 typical popular lip cosmetics, including 12 lipsticks, 13 lip glosses, and 9 lip balms. And then this study used ICP-MS to determine the content of Pb. Furthermore, the ingestion health risk assessment method issued by United States Environmental Protection Agency (USEPA) and Monte Carlo simulation algorithm were applied to assess the probabilistic health risks of adults exposure. Finally, taking the possible exposure of children contacting with lip products, the health risk assessment of children blood Pb was carried out. The results showed that the concentration of Pb in lip products ranged from 0 to 0.5237 mg/kg, which was far lower than the limit set by various countries. The probabilistic non-carcinogenic risks and carcinogenic risks were 4.93 ×10−7~2.82 ×10−3 and 1.68 ×10−12~9.59 ×10−9, respectively, which were in an acceptable level. The results of blood Pb assessment suggested that the Pb content of lip cosmetics had no obvious influence on blood Pb concentration of children, and background Pb exposure is the main factor affecting children's blood Pb level (BLL). Overall, the samples of lip products are selected by Python crawler in this study, which are more objective and representative. This study focuses on deeper study of Pb, especially for the health risk assessment of blood Pb in children exposed to lip products. These results perhaps could provide useful information for the safety cosmetics usage for people in China and even the global world.
Spatial Analysis and Comparison of the Economic Burden of Common Diseases: An Investigation of 5.7 Million Rural Elderly Inpatients in Southeast China, 2010–2016
Authors: Tang Xuwei , Xie Xiaoxu , Rao Zhixiang , Zheng Zhenquan , Hu Chanchan , Li Shanshan , Hu Zhijian
Published: November 2021

Background: As China embraced an aging society, the burden of age-related diseases had increased dramatically. Knowledge about spatial distribution characteristics of disease burden and the influencing factors of medical expenditure is of great significance to the formulation of health policies. However, related research in rural China is still insufficient.

Methods: A total of 5,744,717 records of hospitalized rural elderly in southeast China were collected from 2010 to 2016. We described the temporal trends of hospitalization medical expenditure and the prevalence of catastrophic health expenses (CHE) in the rural elderly by common diseases. Then, geographical information tools were used for visualization of geographic distribution patterns of CHE, the ordinary least squares methods (OLS) and geographically weighted regression (GWR) were employed to examine the influencing factors of medical expenditure.

Results: The number of CHE hospitalizations and the total number of hospitalizations for the rural elderly people increased by 2.1 times and 2.2 times, respectively, from 2010 to 2016. Counties with a high prevalence of CHE were clustered in the eastern coastal area (Moran's I = 0.620, P < 0.001, General G < 0.001, P < 0.001). Unspecified transport accidents, cardiovascular disease, and essential hypertension were the top causes of CHE in the rural elderly. Adequate hospital beds (P < 0.05) and reasonable utilization and distribution of town-level (P < 0.001) and county-level hospitals (P < 0.001) may help reduce medical expenditures.

Conclusions: In the context of an aging society, the disease burden for the elderly in rural areas should arouse more attention. These findings highlight the importance of age-related disease prevention and the rational allocation of medical resources in rural areas.