bluuebunny/crossref_metadata_2025 huggingface dataset:
Newborn Neurobehavior Is Related to Later Neurodevelopment and Social Cognition Skills in Extremely Preterm-Born Children: A Prospective Longitudinal Cohort Study
Authors: Aho Leena , Metsäranta Marjo , Lönnberg Piia , Wolford Elina , Lano Aulikki
Published: September 2021

Objective: The aim of this study was to evaluate the ability of the neonatal neurobehavioral characteristics to act as an indicator for later neurodevelopment and neurocognitive performance.

Methods: Sixty-six infants born extremely preterm (<28 gestational weeks) were followed until 6.5 years. Neurobehavior at term age was assessed by the behavior subscale of the Hammersmith Neonatal Neurological Examination (HNNE) using dichotomic rating, optimal, and non-optimal. The Griffiths Mental Developmental Scales (GMDS) at 2 years, and the Wechsler Intelligence Scales at 6.5 years, and a Neuropsychological Assessment at 6.5 years were used to assess neurodevelopment and neurocognitive performance including social cognition skills.

Results: An optimal auditory orientation at term age was associated with better developmental quotients (DQ) in Personal–Social, and Hearing–Language GMDS subscale at 2 years (p < 0.05). An optimal visual alertness was associated with better Total (p < 0.01), Locomotor (p < 0.001), and Eye–Hand Coordination (p < 0.01) DQs at 2 years, and with sensorimotor function (p < 0.001) and social perception (p < 0.01) tests at 6.5 years.

Conclusion: The neurobehavioral characteristics of newborns might serve as a precursor of social cognition skills and the HNNE behavior subscale offers a tool to identify infants at risk for later deficits in neurodevelopment and social cognition.
Ephemerality in Social Media: Unpacking the Personal and Social Characteristics of Time Limit Users on WeChat Moments
Authors: Zhang Yun , Wang Hongyan , Luo Chuan , Chen Siyu
Published: September 2021

Social media platforms increasingly give users the option of ephemerality through settings that delete or hide posted content after a set period of time. Many individuals apply these settings to manage their posting history and, in turn, reduce concerns about self-presentation. Despite the growing popularity of this feature, few studies have empirically explored it. This study examines the Time Limit setting on WeChat Moments as an example and investigates how users using the Time Limit setting differ from nonusers in terms of personal characteristics (demographics, personality traits, psychological factors, and previous behavioral patterns) and social characteristics (audience size and audience diversity). Compared with nonusers, users using Time Limit setting scored significantly higher on posting frequency and privacy setting use and scored significantly lower on audience size. We also examine how personal and social characteristics vary between user groups with different degrees of ephemerality (i.e., low, medium, or high). Our findings show that users using the Time Limit setting who scored higher on measures of life changes, self-monitoring, posting frequency, and audience size and lower on perceived stress were more likely to opt for the low (i.e., 6months) rather than the medium (i.e., 1month) or high (i.e., 3days) degree of ephemerality. Our work contributes to the understanding of ephemerality settings on social media platforms and provides insights that help practitioners design more effective platforms.
Emotional Intelligence and Prosocial Behavior in College Students: A Moderated Mediation Analysis
Authors: Wang Haiying , Wu Shuang , Wang Weichen , Wei Chao
Published: September 2021

This study examined the relationship between emotional intelligence (EI) and prosocial behavior (PSB) and constructed a model for their interaction by examining the mediating effect of social support (SS) and the moderating effect of self-esteem (SE) in this relationship. A total of 742 college students aged from 18 to 20 in Northeast China (Mage =19.42 ± 0.53 years) completed a survey measuring the Emotional Intelligence Scale, Prosocial Tendencies Measurement Scale—Chinese Version, Perceived Social Support Scale, and Self-Esteem Scale. The results showed that: (1) EI positively predicted PSB; (2) SS partially mediated the relationship between EI and PSB; and (3) SE moderated the direct effect of EI on PSB and the relationship between SS and PSB. That is, when the SE of college students was higher, the effect of SS in promoting PSB was enhanced. Therefore, our results suggested that under the influence of both internal and external factors, there is an indirect effect of EI on PSB. This finding may potentially provide a theoretical basis for designing college students' mental health courses and cultivating PSB in college.
Valuation of Lost Productivity in Caregivers: A Validation Study
Authors: Gelfand Aaron , Sou Julie , Sawatzky Rick , Prescott Katrina , Pearce Alison , Anis Aslam H. , Lee Christine , Zhang Wei
Published: September 2021

Objective

This study aimed to: (a) adapt the previously validated Valuation of Lost Productivity (VOLP) questionnaire for people with health problems, to a caregiver version to measure productivity losses associated with caregiving responsibilities, and (b) evaluate measurement feasibility and validity of an online version of the caregiver VOLP questionnaire.

Methods

A mixed methods design was utilized. Qualitative methods, such as reviewing existing questionnaires that measured caregiver work productivity losses and performing one-on-one interviews with caregivers, were used for VOLP adaptation and online conversion. Quantitative methods were used to evaluate feasibility and validity of the online VOLP. The Work Productivity and Activity Impairment (WPAI) questionnaire for caregivers was included to compare its absenteeism and presenteeism outcomes and their correlations with VOLP outcomes.

Results

When adapting the VOLP for caregivers, our qualitative analysis showed the importance of adding three major components: caregiving time, work productivity loss related to volunteer activities and caregivers’ lost job opportunities. A total of 383 caregivers who completed online survey were included in our final quantitative analysis. We found small Spearman rank correlations between VOLP and WPAI, observing a larger correlation between their absenteeism [r = 0.49 (95% confidence interval: 0.37–0.60)] than their presenteeism [r = 0.36 (0.24–0.47)]. Correlations between VOLP outcomes and total caregiving hours were larger for absenteeism [r = 0.38 (0.27–0.47)] than presenteeism [r = 0.22 (0.10–0.34)]. Correlations between WPAI outcomes and total caregiving hours were smaller for absenteeism [r = 0.27 (0.15–0.38)] than presenteeism [r = 0.35 (0.23–0.46)].

Conclusion

The study provides evidence of the feasibility and preliminary validity evidence of the adapted VOLP caregiver questionnaire in measuring productivity losses due to caregiving responsibilities, when compared with the results for WPAI and the results from the previous patient-VOLP validation study.
Are Family Physical Activity Habits Passed on to Their Children?
Authors: Zovko Vinko , Djuric Sasa , Sember Vedrana , Jurak Gregor
Published: September 2021

Studies of the familial association of physical activity (PA) and sedentary behavior (SB) have increased in recent years. However, there is a lack of studies that have objectively examined the correlates between parents, grandparents, and childrens' PA. Therefore, the purpose of this study was to measure PA using accelerometers to determine the extent to which PA and SB correlate among parents, grandparents, and children. A sample of 169 children between 11 and 14 years (77 boys and 97 girls), 225 parents (98 males and 127 females), and 52 grandparents (16 males and 36 females) were recruited for the current study. Accelerometers RM42 (UKK Terveyspalvelut Oy, Tampere, Finland) were used to determine PA levels of children, parents, and grandparents. Epoch length was 6 s. Mothers' moderate-to-vigorous PA (MVPA) was associated with children's MVPA (p < 0.05). After adjusting for age, BMI (child), and educational status, the results remain the same. Results of linear regression analyses for boys' sedentary time showed that fathers' sedentary time was significantly associated with boys (p < 0.01), but not with girls. The association of grandmothers' and grandfathers' MVPA activity with that of children showed that grandparents' MVPA, when adjusted for age, BMI, and educational status, was not a significant predictor (p > 0.05) of children's MVPA (total sample). In contrast, grandfathers' sedentary behavior was a significant predictor (β = 0.269; p < 0.05) of children's sedentary behavior (total sample). The results of the current study suggest that parental involvement in PA, particularly by mothers, is important for children's PA and, accordingly, healthy outcomes.
Implications of Sensory Processing and Attentional Differences Associated With Autism in Academic Settings: An Integrative Review
Authors: Mallory Courtney , Keehn Brandon
Published: September 2021

The impact of classroom environments on student engagement and academic performance is well-documented. Autism spectrum disorder (ASD) is associated with atypical sensory processing and attentional impairments, which may lead to challenges in successfully accessing educational material within these settings. These symptoms may help explain why students with ASD show discrepancies between intellectual ability and academic performance. Given the increasing number of students with ASD present in classrooms, understanding strengths and weaknesses in sensory processing and attention is necessary in order to design better classroom environments and develop more efficacious accommodations and interventions to support optimal student success. Therefore, the objectives of this review are to provide a brief review of the current literature on sensory processing and attention in ASD, survey how sensory and attentional functions affect academic outcomes in both neurotypical and ASD learners, and suggest potential accommodations/interventions for students with ASD based on these findings.
Transition Between Sensitive Delusion of Reference and Mood Disorder: A Case Report
Authors: Esposito Cecilia Maria , Fiorentini Alessio , Callari Antonio , Galeazzi Gian Maria , Brambilla Paolo
Published: September 2021

The Sensitive Delusion of Reference is a clinical entity described by Ernst Kretschmer and never integrated into mainstream nosographic systems. It represents the possibility of developing psychosis starting from a personality characterized by sensitivity, scrupulousness, and fear of judgment of others. The presentation of the following clinical case highlights how the overlap between this clinical entity and mood disorders leads to characteristic psychopathology, which has not been sufficiently detailed. In particular, the delusions, which always starts from the idea of reference and the shame in the face of the judgment of others, takes on characteristics of guilt during the depressive phases and persecutory themes during the activation phases. This clinical observation, which obviously needs to be confirmed on a larger scale, encourages a renewed interest in the concept of Kretschmer's Sensitive Delusion of Reference and creates the possibility of intersecting multiple psychopathological levels, for a more complete perspective on the individual case.
Natural Language Processing as an Emerging Tool to Detect Late-Life Depression
Authors: DeSouza Danielle D. , Robin Jessica , Gumus Melisa , Yeung Anthony
Published: September 2021

Late-life depression (LLD) is a major public health concern. Despite the availability of effective treatments for depression, barriers to screening and diagnosis still exist. The use of current standardized depression assessments can lead to underdiagnosis or misdiagnosis due to subjective symptom reporting and the distinct cognitive, psychomotor, and somatic features of LLD. To overcome these limitations, there has been a growing interest in the development of objective measures of depression using artificial intelligence (AI) technologies such as natural language processing (NLP). NLP approaches focus on the analysis of acoustic and linguistic aspects of human language derived from text and speech and can be integrated with machine learning approaches to classify depression and its severity. In this review, we will provide rationale for the use of NLP methods to study depression using speech, summarize previous research using NLP in LLD, compare findings to younger adults with depression and older adults with other clinical conditions, and discuss future directions including the use of complementary AI strategies to fully capture the spectrum of LLD.
Emerging Concepts and Evidence in Telematics Novel Approaches or Treatments for Spasticity Management After Botulinum Injection
Authors: Bascuñana-Ambrós Helena , Nadal-Castells Mª Josep , Ramírez-Mirabal Eliot , Beranuy-Rodriguez Marta , Pintor-Ojeda Alberto , Perrot-González Jean-Claude
Published: September 2021

There is a strong recommendation for the use of intramuscular botulinum toxin in patients with persistent or progressive spasticity affecting one or more joints and who have an identifiable therapeutic target. After a botulinum toxin injection, a stretching intervention improves the results of the treatment, and it should be performed by patients and/or caregivers after being trained by a therapist. Adherence to this recommendation remains low once the therapist stops following the patient. The COVID-19 pandemic has increased the use of telemedicine with different approaches to treat patients. There has been an increased use of motivational applications, with virtual reality software and real-life videos, which provide a gaming experience that increases adherence. There are programs with synchronous telehealth exercises guided by physical therapists or software with sensor-based technology that shows the range of motion (ROM) and strength of the muscles of a particular joint. These new approaches to patient follow-up appear to increase adherence to exercise because they need to be “watched and controlled” is achieved.
Menstrual Hygiene Management—Knowledge, Attitudes, and Practices Among Female College Students in Bhutan
Authors: Tshomo Tashi , Gurung Mongal Singh , Shah Safieh , Gil-Cuesta Julita , Maes Peter , Wangdi Rinchen , Tobden Jamba
Published: September 2021

Background:Girls and women face substantial menstrual hygiene management (MHM) challenges in low- and middle-income countries. These challenges are related to inadequate knowledge and insufficient water, sanitation, and hygiene (WASH) facilities. Currently, the literature on MHM among college-attending women in Bhutan is scarce. We aimed to explore the knowledge, attitudes, and practices (KAP) of female college students from all the 10 government colleges of Bhutan, documenting the conditions of available MHM facilities, from August to September 2018.

Methods:A cross-sectional KAP survey was conducted with a random sample of female students from all years and a random sample of MHM facilities at each college and hostel. A questionnaire was adapted from a similar study conducted with school students in Bhutan. Socio-demographics, overall KAP findings, and differences in KAP between first and final year students were analyzed; college and hostel toilets were self-reported and directly observed.

Results:In the survey, 1,010 participants completed the self-administered questionnaire. The comprehensive knowledge of menstruation was found to be low (35.5%) among participants. Half of the participants (50.3%) reported their mother as the source of information, and 35.1% of the participants agreed that women should not enter a shrine during menstruation. It was also reported that approximately 4% of median monthly pocket money was spent on the absorbents, and 96.9% of absorbents were wrapped before disposal. Half of the participants (55.1%) reported that their daily activities were affected due to menstruation, and 24.2% of the female students missed college due to dysmenorrhea. One-fifth of the participants (21.3%) reported unavailability of water in college, 80.1% of the participants reported absence of soap for hand washing, and 24.1% described no bins for disposal. The participants also reported that in 33.7% of hostel toilets, the door locks were missing. The direct observations also had similar findings.

Conclusions:Female students living in hostels during college years lose considerable resources during their formative years of learning, such as time, energy, and money, due to issues of menstruation management. Although the overall understanding of menstruation was low, the MHM practices of our participants scored highly, and the vast majority of them asked for a platform to discuss menstruation. Despite some agreement with menstrual taboos (e.g., visiting shrine), only 5.1% of the participants were uncomfortable conversing about MHM. Improved public health knowledge, psychosocial/medical support, and WASH infrastructure with freely available menstrual products could lead to more effective MHM practices among female college students.
Unpacking Adaptive Capacity to Flooding in Urban Environments: Social Capital, Social Vulnerability, and Risk Perception
Authors: Bixler R. Patrick , Paul Sandeep , Jones Jessica , Preisser Matthew , Passalacqua Paola
Published: September 2021

To effectively cope with the impacts of climate change and increase urban resilience, households and neighborhoods must adapt in ways that reduce vulnerability to climate-related natural hazards. Communities in the United States and elsewhere are exposed to more frequent extreme heat, wildfires, cyclones, extreme precipitation, and flooding events. Whether and how people respond to increased hazard exposure (adaptive behavior) is widely recognized to be driven by their capacity to adapt, perception of the risk, and past experiences. Underlying these important dimensions, however, is social context. In this paper, we examine how social capital and social vulnerability shape risk perception and household flood mitigation actions. The study, based on a metropolitan-wide survey of households in Austin, Texas, USA, suggests that bonding social capital (personal networks, neighborhood cohesion, and trust) is positively related to mitigation behavior and that social vulnerability is negatively related to risk perception. Importantly, our research demonstrates a positive and significant effect of social capital on adaptive behavior even when controlling for social vulnerability of a neighborhood. This suggests that policies and programs that strengthen the social connectedness within neighborhoods can increase adaptive behaviors thus improving community resilience to flood events.
How Do You Test a Rat’s Memory?
Authors: Wright David W.
Published: September 2021

Brain injury often impairs a person’s ability to remember. To find new drugs that improve memory after a brain injury, scientist must rely on experiments in animals such as rats. But how do you test the memory in rats? One way is to use a pool of colored water, called the Morris water maze. In this maze, rats have to “remember” where to go to get out of the water. The more a rat’s memory has improved, the quicker it finds its way out of the water (rats do not like being in water). This test can also be used to compare two different drug treatments. It is an important tool for new drug discovery.
Antiviral Effectivity of Favipiravir Against Peste Des Petits Ruminants Virus Is Mediated by the JAK/STAT and PI3K/AKT Pathways
Authors: Zhang Weifeng , Deng Hualong , Liu Yanfen , Chen Shaohong , Liu You , Zhao Yuntao
Published: September 2021

Peste des petits ruminants virus (PPRV), belonging to the genus Morbillivirus in the family Paramyxoviridae, causes severe infectious disease in small ruminants and has been rapidly spreading in many parts of Africa, the Middle East, and Asia. Although vaccination is considered to be an effective means of controlling PPR, the heat-sensitive nature of the vaccines against PPRV greatly limits their application in areas with a hot climate. In the present study, we investigated the anti-PPRV effects of favipiravir and sought to identify the underlying mechanisms in vitro using the Vero cell line. MTT assays, Western blotting, indirect immunofluorescence assays, virus plaque formation assays, and qRT-PCR were used to assess the effects of favipiravir on the life cycle of PPRV and the expression of RNA-dependent RNA polymerase (RdRp). Additionally, the expression levels of JAK1, STAT1, phosphorylated (p)-STAT1, PI3K, AKT, and p-AKT, as well as those of signaling molecules acting downstream of the JAK/STAT and PI3K/AKT signaling pathways, were determined by Western blotting and qRT-PCR. The results indicated that, in PPRV-infected, favipiravir-treated Vero cells, the attachment, invasion, replication, and release of PPRV were significantly inhibited, as was the expression of RdRp, when compared with that in untreated PPRV-infected cells. Furthermore, in favipiravir-treated cells, the expression of JAK1 and STAT1 was downregulated, whereas that of p-STAT1 was significantly upregulated. Similarly, the expression levels of PKR, IRF9, ISG54, and MxA proteins that are associated with innate antiviral activity in host cells were also markedly increased. Moreover, with favipiravir treatment, the expression of PI3K and p-AKT and the p-AKT/AKT ratio were significantly decreased, whereas the expression of AKT was noticeably upregulated. The expression of GSK3, NF-κB p65, p-NF-κB p65, and BAD was also increased with favipiravir treatment, while the expression of CREB, p-CREB, p-GSK3, and Bcl-2 was slightly decreased. In addition, all the p-GSK3/GSK3, p-CREB/CREB, p-NF-κB/NF-κB, and p-BAD/BAD ratios were significantly reduced in favipiravir-treated cells. These results implied that the antiviral effectivity of favipiravir against PPRV is mediated by the JAK/STAT and PI3K/AKT pathways and that favipiravir has potential for use as an effective antiviral agent against PPRV.
Dog Pulling on the Leash: Effects of Restraint by a Neck Collar vs. a Chest Harness
Authors: Shih Hao-Yu , Phillips Clive J. C. , Mills Daniel S. , Yang Yifei , Georgiou Fillipe , Paterson Mandy B. A.
Published: September 2021

Leash pulling is a concern for dog owners and can be detrimental to the health and welfare of dogs. Neck-collars and back-connection harnesses are popular restraint types. Harnesses have been proposed as a better and more considerate option for canine health and welfare. Anecdotally, dogs pull more when wearing a back-connection harness; however, there is no scientific evidence for this perception. This study aimed to investigate how strongly dogs pull on the lead to achieve a food treat or toy under restraint by a neck-collar versus a back-connection harness. A within-subject counterbalanced design was used for the study, involving 52 shelter dogs. A customised canine leash tension metre was connected to the collar or harness to record the pulling of the dogs, including measuring the maximal and mean leash tension, and the time spent pulling. In addition, dog behaviours were recorded using two cameras from two separate directions. The maximal and mean leash tension and the pulling time were greater under restraint by harness when attracting dogs with food treats. No significant difference between harness and collar was found in potential stress-related behaviours (e.g. tail and ear positions, lip-licking, and panting). However, dogs looked at the experimenter more often when restrained by harness than collar in the food treat attraction test. No significant difference was detected between harness and collar with respect to leash tension and stress-related behaviours in the toy attraction test. These findings suggest that dogs tend to pull stronger and more steadily when wearing a back-connection harness compared to a neck collar to reach the food treat but not the toy.
RNA Profiles of the Korat Chicken Breast Muscle with Increased Carnosine Content Produced through Dietary Supplementation with β-Alanine or L-Histidine
Authors: Kubota Satoshi , Promkhun Kasarat , Sinpru Panpradub , Suwanvichanee Chanadda , Molee Wittawat , Molee Amonrat
Published: September 2021

Korat chicken (KRC) is a slow-growing chicken bred in Thailand, whose meat exhibits a unique toughness. A previous study produced KRC breast meat containing high carnosine content through dietary supplementation with β-alanine or L-histidine; however, the KRC that were fed an L-histidine-supplemented diet produced meat that was significantly more tender. Herein, we performed RNA-Seq to identify candidate genes involved in the regulation of carnosine content and meat toughness. Total RNA was isolated from five female KRC breast muscles in each treatment group that KRC fed diets without supplementation, supplemented with β-alanine or L-histidine. Compared to the non-supplemented group, we identified 118 and 198 differentially expressed genes (DEGs) in the β-alanine or L-histidine supplementation groups, respectively. Genes potentially related to meat tenderness—i.e., those regulating myosin, collagen, intramuscular fat, and calpain—were upregulated (LOC107051274, ACSBG1, and CAPNS2) and downregulated (MYO7B, MYBPH, SERPINH1, and PGAM1). However, carnosine synthase gene was not identified. Functional enrichment analysis identified pathways affected by dietary supplementation, including the insulin signaling pathway (β-alanine supplementation) and the insulin resistance and adipocytokine signaling pathways (L-histidine supplementation). The FoxO signaling pathway was identified as a regulatory network for both supplementation groups. The identified genes can be used as molecular markers of meat tenderness in slow-growing chickens.
Design of Optimized Energy Management Strategy for All-Wheel-Drive Electric Vehicles
Authors: Dou Haishi , Zhang Youtong , Fan Likang
Published: September 2021

The performance of the all-wheel-drive electric vehicle is inseparable from the energy management strategy (EMS). An outstanding EMS could extend the cycling mileage, coordinating the power output of the battery and exerts the advantage of the motor comprehensively. However, the current EMS has poor performance in real-time, and this paper proposes the dynamic programming coordination strategy (DPCS) to solve the problem. Firstly, the EMS based on a rule-based control strategy (RBCS) is applied in a different driving cycle. Secondly, the dynamic programming algorithm (DP) is proposed in the process. The DPCS cooperated the advantage of RBCS and DP, extracting the boundary parameters along with the demand power and vehicle speed. Finally, the number of motors joined in the driving condition is elucidated and the method obtains the optimal torque split ratio through a partly-known driving cycle. By incorporating the thought of a basis of rules, the DPCS determines the torque of each motor that confirm the motor working in an efficient range that incorporates the mind of dynamic programming. The method is validated through the simulation. The results show that the strategy can significantly improve the mileage of the driving cycle, with comprehensive performance in energy distribution and utilization.
Novel Fuzzy Controller for a Standalone Electric Vehicle Charging Station Supplied by Photovoltaic Energy
Authors: Zaid Sherif A. , Albalawi Hani , Alatawi Khaled S. , El-Rab Hassan W. , El-Shimy Mohamed E. , Lakhouit Abderrahim , Alhmiedat Tareq A. , Kassem Ahmed M.
Published: September 2021

The electric vehicle (EV) is one of the most important and common parts of modern life. Recently, EVs have undergone a big development thanks to the advantages of high efficiency, negligible pollution, low maintenance, and low noise. Charging stations are very important and mandatory services for electric vehicles. Nevertheless, they cause high stress on the electric utility grid. Therefore, renewable energy-sourced charging stations have been introduced. They improve the environmental issues of the electric vehicles and support remote area operation. This paper proposes the application of fuzzy control to an isolated charging station supplied by photovoltaic power. The system is modeled and simulated using Matlab/Simulink. The simulation results indicate that the disturbances in the solar insolation do not affect the electric vehicle charging process at all. Moreover, the controller perfectly manages the stored energy to compensate for the solar energy variations. Additionally, the system response with the fuzzy controller is compared to that with the PI controller. The comparison shows that the fuzzy controller provides an improved response.
Atmospheric NO2 Distribution Characteristics and Influencing Factors in Yangtze River Economic Belt: Analysis of the NO2 Product of TROPOMI/Sentinel-5P
Authors: Liu Xian , Yi Guihua , Zhou Xiaobing , Zhang Tingbin , Lan Yan , Yu Daijun , Wen Bo , Hu Jiao
Published: September 2021

Nitrogen dioxide (NO2) has a great influence on atmospheric chemistry. Scientifically identifying the temporal-spatial characteristics of NO2 distribution and their driving factors will be of realistic significance to atmospheric governance in the Yangtze River Economic Belt (YREB). Based on the NO2 data derived from the TROPOspheric Monitoring Instrument (TROPOMI) onboard the Sentinel-5 satellite (2017~present), spatial autocorrelation analysis, standard deviation ellipse (SDE), and geodetectors were used to systematically analyze the spatial-temporal evolution and driving factors of tropospheric NO2 vertical column density (NO2 VCD) in the YREB from 2019 to 2020. The results showed that the NO2 VCD in the YREB was high in winter and autumn and low in spring and summer (temporal distribution), and high in the northeast and low in the southwest (spatial distribution), with significant spatial agglomeration. High-value agglomeration zones were collectively and stably distributed in the east region, while low-value zones were relatively dispersed. The explanatory power of each potential factor for the NO2 VCD showed regional and seasonal variations. Surface pressure was found to be a core influencing factor. Synergistic effects of factors presented bivariate enhancement or nonlinear enhancement, and interaction between any two factors strengthened the explanatory power of a single factor for the NO2 VCD.
Primary Amoebic Meningoencephalitis by Naegleria fowleri: Pathogenesis and Treatments
Authors: Güémez Andrea , García Elisa
Published: September 2021

Naegleria fowleri is a free-living amoeba (FLA) that is commonly known as the “brain-eating amoeba.” This parasite can invade the central nervous system (CNS), causing an acute and fulminating infection known as primary amoebic meningoencephalitis (PAM). Even though PAM is characterized by low morbidity, it has shown a mortality rate of 98%, usually causing death in less than two weeks after the initial exposure. This review summarizes the most recent information about N. fowleri, its pathogenic molecular mechanisms, and the neuropathological processes implicated. Additionally, this review includes the main therapeutic strategies described in case reports and preclinical studies, including the possible use of immunomodulatory agents to decrease neurological damage.
Characterization of a Compound Heterozygous SLC2A9 Mutation That Causes Hypouricemia
Authors: Yoon Jaeho , Cachau Raul , David Victor A. , Thompson Mary , Jung Wooram , Jee Sun-Ha , Daar Ira O. , Winkler Cheryl A. , Cho Sung-Kweon
Published: September 2021

Renal hypouricemia is a rare genetic disorder. Hypouricemia can present as renal stones or exercise-induced acute renal failure, but most cases are asymptomatic. Our previous study showed that two recessive variants of SLC22A12 (p.Trp258*, pArg90His) were identified in 90% of the hypouricemia patients from two independent cohorts: the Korean genome and epidemiology study (KoGES) and the Korean Cancer Prevention Study (KCPS-II). In this work, we investigate the genetic causes of hypouricemia in the rest of the 10% of unsolved cases. We found a novel non-synonymous mutation of SLC2A9 (voltage-sensitive uric acid transporter) in the whole-exome sequencing (WES) results. Molecular dynamics prediction suggests that the novel mutation p.Met126Val in SLCA9b (p.Met155Val in SLC2A9a) hinders uric acid transport through a defect of the outward open geometry. Molecular analysis using Xenopus oocytes confirmed that the p.Met126Val mutation significantly reduced uric acid transport but does not affect the SLC2A9 protein expression level. Our results will shed light on a better understanding of SLC2A9-mediated uric acid transport and the development of a uric acid-lowering agent.
Physical Therapy Exercises for Sleep Disorders in a Rehabilitation Setting for Neurological Patients: A Systematic Review and Meta-Analysis
Authors: Tramontano Marco , De Angelis Sara , Galeoto Giovanni , Cucinotta Maria Carmela , Lisi Danilo , Botta Riccardo Maria , D’ippolito Mariagrazia , Morone Giovanni , Buzzi Maria Gabriella
Published: September 2021

Background: Sleep occupies one-third of human life and is essential for health and for emotional, physical, and cognitive well-being. Poor or insufficient sleep is associated with a wide range of dysfunctions that involve different body systems, such as the endocrine, metabolic, and immune systems, thus compromising the higher cortical functions, cognitive performance, mood, and post-physical activity recovery. The present systematic review and meta-analysis aimed to explore the effectiveness of physical therapy exercises on sleep disorders in patients with neurological disorders. Our systematic review identified 10 articles that investigated the effects of physical therapy on sleep disorders in patients with neurological disorders, 6 of which were included in the meta-analysis. Results suggest that physical therapy exercises are a safe and useful strategy for managing sleep disorders in neurorehabilitation.
The Unfolded Protein Response Is Associated with Cancer Proliferation and Worse Survival in Hepatocellular Carcinoma
Authors: Patel Ankit , Oshi Masanori , Yan Li , Matsuyama Ryusei , Endo Itaru , Takabe Kazuaki
Published: September 2021

Hepatocellular carcinoma is a leading cause of cancer death worldwide. The unfolded protein response (UPR) has been revealed to confer tumorigenic capacity in cancer cells. We hypothesized that a quantifiable score representative of the UPR could be used as a biomarker for cancer progression in HCC. In this study, a total of 655 HCC patients from 4 independent HCC cohorts were studied to examine the relationships between enhancement of the UPR and cancer biology and patient survival in HCC utilizing an UPR score. The UPR correlated with carcinogenic sequence and progression of HCC consistently in two cohorts. Enhanced UPR was associated with the clinical parameters of HCC progression, such as cancer stage and multiple parameters of cell proliferation, including histological grade, mKI67 gene expression, and enrichment of cell proliferation-related gene sets. The UPR was significantly associated with increased mutational load, but not with immune cell infiltration or angiogeneis across independent cohorts. The UPR was consistently associated with worse survival across independent cohorts of HCC. In conclusion, the UPR score may be useful as a biomarker to predict prognosis and to better understand HCC.
Photodynamic Therapy: A Compendium of Latest Reviews
Authors: Algorri José Francisco , Ochoa Mario , Roldán-Varona Pablo , Rodríguez-Cobo Luís , López-Higuera José Miguel
Published: September 2021

Photodynamic therapy (PDT) is a promising therapy against cancer. Even though it has been investigated for more than 100 years, scientific publications have grown exponentially in the last two decades. For this reason, we present a brief compendium of reviews of the last two decades classified under different topics, namely, overviews, reviews about specific cancers, and meta-analyses of photosensitisers, PDT mechanisms, dosimetry, and light sources. The key issues and main conclusions are summarized, including ways and means to improve therapy and outcomes. Due to the broad scope of this work and it being the first time that a compendium of the latest reviews has been performed for PDT, it may be of interest to a wide audience.
The CDH1 c.1901C>T Variant: A Founder Variant in the Portuguese Population with Severe Impact in mRNA Splicing
Authors: Barbosa-Matos Rita , Leal Silva Rafaela , Garrido Luzia , Aguiar Ana Cerqueira , Garcia-Pelaez José , André Ana , Seixas Susana , Sousa Sónia Passos , Ferro Luísa , Vilarinho Lúcia , Gullo Irene , Devezas Vitor , Oliveira Renata , Fernandes Susana , Costa Susy Cabral , Magalhães André , Baptista Manuela , Carneiro Fátima , Pinheiro Hugo , Castedo Sérgio , Oliveira Carla
Published: September 2021

Hereditary diffuse gastric cancer (HDGC) caused by CDH1 variants predisposes to early-onset diffuse gastric (DGC) and lobular breast cancer (LBC). In Northern Portugal, the unusually high number of HDGC cases in unrelated families carrying the c.1901C>T variant (formerly known as p.A634V) suggested this as a CDH1-founder variant. We aimed to demonstrate that c.1901C>T is a bona fide truncating variant inducing cryptic splicing, to calculate the timing of a potential founder effect, and to characterize tumour spectrum and age of onset in carrying families. The impact in splicing was proven by using carriers’ RNA for PCR-cloning sequencing and allelic expression imbalance analysis with SNaPshot. Carriers and noncarriers were haplotyped for 12 polymorphic markers, and the decay of haplotype sharing (DHS) method was used to estimate the time to the most common ancestor of c.1901C>T. Clinical information from 58 carriers was collected and analysed. We validated the cryptic splice site within CDH1-exon 12, which was preferred over the canonical one in 100% of sequenced clones. Cryptic splicing induced an out-of-frame 37bp deletion in exon 12, premature truncation (p.Ala634ProfsTer7), and consequently RNA mediated decay. The haplotypes carrying the c.1901C>T variant were found to share a common ancestral estimated at 490 years (95% Confidence Interval 445–10,900). Among 58 carriers (27 males (M)–31 females (F); 13–83 years), DGC occurred in 11 (18.9%; 4M–7F; average age 33 ± 12) and LBC in 6 females (19.4%; average age 50 ± 8). Herein, we demonstrated that the c.1901C>T variant is a loss-of-function splice-site variant that underlies the first CDH1-founder effect in Portugal. Knowledge on this founder effect will drive genetic testing of this specific variant in HDGC families in this geographical region and allow intrafamilial penetrance analysis and better estimation of variant-associated tumour risks, disease age of onset, and spectrum.
The Race for Hydroxamate-Based Zirconium-89 Chelators
Authors: Feiner Irene V. J. , Brandt Marie , Cowell Joseph , Demuth Tori , Vugts Daniëlle , Gasser Gilles , Mindt Thomas L.
Published: September 2021

Metallic radionuclides conjugated to biological vectors via an appropriate chelator are employed in nuclear medicine for the diagnosis (imaging) and radiotherapy of diseases. For the application of radiolabeled antibodies using positron emission tomography (immunoPET), zirconium-89 has gained increasing interest over the last decades as its physical properties (t1/2 = 78.4 h, 22.6% β+ decay) match well with the slow pharmacokinetics of antibodies (tbiol. = days to weeks) allowing for late time point imaging. The most commonly used chelator for 89Zr in this context is desferrioxamine (DFO). However, it has been shown in preclinical studies that the hexadentate DFO ligand does not provide 89Zr-complexes of sufficient stability in vivo and unspecific uptake of the osteophilic radiometal in bones is observed. For clinical applications, this might be of concern not only because of an unnecessary dose to the patient but also an increased background signal. As a consequence, next generation chelators based on hydroxamate scaffolds for more stable coordination of 89Zr have been developed by different research groups. In this review, we describe the progress in this research field until end of 2020, including promising examples of new candidates of chelators currently in advanced stages for clinical translation that outrun the performance of the current gold standard DFO.
Combining APR-246 and HDAC-Inhibitors: A Novel Targeted Treatment Option for Neuroblastoma
Authors: Müller Michael , Rösch Lisa , Najafi Sara , Gatzweiler Charlotte , Ridinger Johannes , Gerloff Xenia F. , Jones David T. W. , Baßler Jochen , Kreth Sina , Stainczyk Sabine , Frese Karen , Meder Benjamin , Westermann Frank , Milde Till , Peterziel Heike , Witt Olaf , Oehme Ina
Published: September 2021

APR-246 (Eprenetapopt/PRIMA-1Met) is a very potent anti-cancer drug in clinical trials and was initially developed as a p53 refolding agent. As an alternative mode of action, the elevation of reactive oxygen species (ROS) has been proposed. Through an in silico analysis, we investigated the responses of approximately 800 cancer cell lines (50 entities; Cancer Therapeutics Response Portal, CTRP) to APR-246 treatment. In particular, neuroblastoma, lymphoma and acute lymphocytic leukemia cells were highly responsive. With gene expression data from the Cancer Cell Line Encyclopedia (CCLE; n = 883) and patient samples (n = 1643) from the INFORM registry study, we confirmed that these entities express low levels of SLC7A11, a previously described predictive biomarker for APR-246 responsiveness. Combining the CTRP drug response data with the respective CCLE gene expression profiles, we defined a novel gene signature, predicting the effectiveness of APR-246 treatment with a sensitivity of 90% and a specificity of 94%. We confirmed the predicted APR-246 sensitivity in 8/10 cell lines and in ex vivo cultures of patient samples. Moreover, the combination of ROS detoxification-impeding APR-246 with approved HDAC-inhibitors, known to elevate ROS, substantially increased APR-246 sensitivity in cell cultures and in vivo in two zebrafish neuroblastoma xenograft models. These data provide evidence that APR-246, in combination with HDAC-inhibitors, displays a novel potent targeted treatment option for neuroblastoma patients.
Review of Myeloma Therapies and Their Potential for Oral and Maxillofacial Side Effects
Authors: Beaumont Sophie , Harrison Simon , Er Jeremy
Published: September 2021

Myeloma is a common haematological malignancy in which adverse skeletal related events are frequently seen. Over recent years, treatment for myeloma has evolved leading to improved survival. Antiresorptive therapy is an important adjunct therapy to reduce the risk of bone fractures and to improve the quality of life for myeloma patients; however, this has the potential for unwanted side effects in the oral cavity and maxillofacial region. Osteonecrosis of the jaw related to antiresorptive medications and other myeloma therapies is not uncommon. This review serves to highlight the risk of osteonecrosis of the jaw for myeloma patients, with some suggestions for prevention and management.
Hybrid Formation and Fusion of Cancer Cells In Vitro and In Vivo
Authors: Hass Ralf , von der Ohe Juliane , Dittmar Thomas
Published: September 2021

The generation of cancer hybrid cells by intra-tumoral cell fusion opens new avenues for tumor plasticity to develop cancer stem cells with altered properties, to escape from immune surveillance, to change metastatic behavior, and to broaden drug responsiveness/resistance. Genomic instability and chromosomal rearrangements in bi- or multinucleated aneuploid cancer hybrid cells contribute to these new functions. However, the significance of cell fusion in tumorigenesis is controversial with respect to the low frequency of cancer cell fusion events and a clonal advantage of surviving cancer hybrid cells following a post-hybrid selection process. This review highlights alternative processes of cancer hybrid cell development such as entosis, emperipolesis, cannibalism, therapy-induced polyploidization/endoreduplication, horizontal or lateral gene transfer, and focusses on the predominant mechanisms of cell fusion. Based upon new properties of cancer hybrid cells the arising clinical consequences of the subsequent tumor heterogeneity after cancer cell fusion represent a major therapeutic challenge.
Albumin Might Attenuate Bacteria-Induced Damage on Kupffer Cells for Patients with Chronic Liver Disease
Authors: Lin Hao , Fan Yuhui , Wieser Andreas , Zhang Jiang , Regel Ivonne , Nieß Hanno , Mayerle Julia , Gerbes Alexander L. , Steib Christian J.
Published: September 2021

Chronic liver diseases (CLDs) are complex diseases that cause long-term inflammation and infection, which in turn accelerate their development. The usage of albumin in patients with CLDs has been debated for years. Human serum albumin (HSA) plays a key role in immunomodulation during the process of CLDs. The correlation between albumin and C-reactive protein (CRP) in CLD patients was analyzed by linear regression with the Pearson statistic. The damage of THP-1 and primary cells was evaluated by measuring the lactate dehydrogenase (LDH) in the supernatant. Immunofluorescence staining was performed to determine underlying pathways in Kupffer cells (KCs). Albumin negatively correlated with infection in patients with CLDs. In vitro experiments with THP-1 cells and KCs showed that albumin reduced LDH release after stimulation with bacterial products, while no differences in hepatic stellate cells (HSCs) and sinusoidal endothelial cells (SECs) were detected. Moreover, immunofluorescence staining revealed an increase of p-ERK and p-NF-kB p65 density after albumin treatment of KCs stimulated by bacterial products. In conclusion, albumin could assist CLD patients in alleviating inflammation caused by bacterial products and might be beneficial to patients with CLDs by securing KCs from bacteria-induced damage, providing a compelling rationale for albumin therapy in patients with CLDs.
Corneal Epithelial Stem Cells–Physiology, Pathophysiology and Therapeutic Options
Authors: Ruan Yue , Jiang Subao , Musayeva Aytan , Pfeiffer Norbert , Gericke Adrian
Published: September 2021

In the human cornea, regeneration of the epithelium is regulated by the stem cell reservoir of the limbus, which is the marginal region of the cornea representing the anatomical and functional border between the corneal and conjunctival epithelium. In support of this concept, extensive limbal damage, e.g., by chemical or thermal injury, inflammation, or surgery, may induce limbal stem cell deficiency (LSCD) leading to vascularization and opacification of the cornea and eventually vision loss. These acquired forms of limbal stem cell deficiency may occur uni- or bilaterally, which is important for the choice of treatment. Moreover, a variety of inherited diseases, such as congenital aniridia or dyskeratosis congenita, are characterized by LSCD typically occurring bilaterally. Several techniques of autologous and allogenic stem cell transplantation have been established. The limbus can be restored by transplantation of whole limbal grafts, small limbal biopsies or by ex vivo-expanded limbal cells. In this review, the physiology of the corneal epithelium, the pathophysiology of LSCD, and the therapeutic options will be presented.