bluuebunny/crossref_metadata_2025 huggingface dataset:
VEGFR Inhibitors for Uterine Metastatic Perivascular Epithelioid Tumors (PEComa) Resistant to mTOR Inhibitors. A Case Report and Review of Literature
Authors: Liapi Aikaterini , Mathevet Patrice , Herrera Fernanda G. , Hastir Delfyne , Sarivalasis Apostolos
Published: March 2021

Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms. PI3K/AKT/mTOR pathway upregulation is critical for their pathogenesis and is often associated with TSC1/TSC2 inactivation. Although first line mTOR inhibitors are an effective treatment, metastatic PEComas eventually progress. A 53-year-old woman presented a 4-month history of post-menopausal vaginal bleeding. Clinical and radiological examination detected a uterine mass and a single S1 bone lesion. The patient underwent a radical hysterectomy and bone biopsy. The anatomopathological evaluation concluded to an oligo-metastatic uterine PEComa. The tumor harbored a heterozygous deletion of 9q34 that contains the TSC1 gene. Concerning the primary lesion, the resection was complete and the single bone metastasis was treated with radiotherapy. Three months later, the patient presented bone, lung and subcutaneous metastatic progression. An everolimus and denosumab treatment was initiated. After 2 years of treatment, a clinically significant bone, lung and subcutaneous progression was detected. Following a literature review of the possible therapeutic options, we initiated a second line treatment by pazopanib. This treatment resulted in regression of the subcutaneous lesions and stability of lung and bone metastases. In this challenging, rare setting, our report suggests single agent, anti-angiogenic, tyrosine kinase inhibitor to be effective as second line treatment of metastatic uterine PEComa progressing on mTOR inhibitors.
Comparison of Caudal Block vs. Penile Block vs. Intravenous Fentanyl Only in Children Undergoing Penile Surgery: A Prospective, Randomized, Double Blind Study
Authors: Ekstein Margaret , Weinbroum Avi A. , Ben-Chaim Jacob , Amar Eyal , Schvartz Reut , Klein Yifat , Bar-Yosef Yuval
Published: March 2021

Objectives: Penile surgery is commonly performed in pediatric surgical centers. There is no consensus regarding which analgesic method is most effective in controlling pain in these children.

Methods: Consecutive children between 4 months and 16 years of age who underwent elective penile surgery were recruited. After inhaled induction of anesthesia, children were randomized to one of three methods of intraoperative analgesia: caudal block, IV fentanyl titrated to surgical response and spontaneous respiration, or dorsal penile nerve block (DPNB). All patients were given inhaled agents; fentanyl was added if either block was insufficient. Demographic data, analgesic use and pain scores were recorded by a blinded investigator in the PACU and ward. Pain scores, analgesic requirement, and recovery parameters of returning to normal activity level, eating, and voiding post-operatively for up to 4 days, were compared.

Results: 116 children were recruited. Pain scores in the post anesthesia care unit were significantly lower in the DPNB and caudal block groups compared to the fentanyl group for the first 30 postoperative min. Pain scores and analgesic use were subsequently similar among the three groups for the rest of the study period. There was no statistical difference in time to eat, return to normal activity or in parental satisfaction scores among the groups. There was a trend toward earliest time to void in the DPNB group.

Conclusions: Regional blocks most effectively controlled pain for 30 min after surgery. The choice of intra-operative analgesia protocol had no effect on later pain and recovery parameters.
Quantitative Chemical Proteomics Reveals Resveratrol Inhibition of A549 Cell Migration Through Binding Multiple Targets to Regulate Cytoskeletal Remodeling and Suppress EMT
Authors: Chen Xiao , Wang Yutong , Tian Jing , Shao Yurou , Zhu Bo , Wang Jigang , Hua Zichun
Published: March 2021

Resveratrol (RSV), a health-promoting natural product, has been shown to affect various cellular processes in tumor cells. However, the specific protein targets of RSV and the mechanism of action (MOA) of its anticancer effect remain elusive. In this study, the pharmacological activity of RSV was first evaluated in A549 cells, and the results showed that RSV significantly inhibited A549 cell migration but did not affect cell viability. To elucidate the underlying mechanism, a quantitative chemical proteomics approach was employed to identify the protein targets of RSV. A total of 38 target proteins were identified, and proteomic analysis showed that the targets were mainly involved in cytoskeletal remodeling and EMT, which were verified by subsequent in vitro and in vivo assays. In conclusion, RSV inhibits A549 cell migration by binding to multiple targets to regulate cytoskeletal remodeling and suppress EMT.
Neuroprotective Effect of Astragaloside IV on Cerebral Ischemia/Reperfusion Injury Rats Through Sirt1/Mapt Pathway
Authors: Shi Yi-Hua , Zhang Xi-Le , Ying Peng-Jie , Wu Zi-Qian , Lin Le-Le , Chen Wei , Zheng Guo-Qing , Zhu Wen-Zong
Published: March 2021

Background: Ischemic stroke is a common disease with poor prognosis, which has become one of the leading causes of morbidity and mortality worldwide. Astragaloside IV (AS-IV) is the main bioactive ingredient of Astragali Radix (which has been used for ischemic stroke for thousands of years) and has been found to have multiple bioactivities in the nervous system. In the present study, we aimed to explore the neuroprotective effects of AS-IV in rats with cerebral ischemia/reperfusion (CIR) injury targeting the Sirt1/Mapt pathway.

Methods: Sprague–Dawley rats (male, 250–280 g) were randomly divided into the Sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, AS-IV group, MCAO/R + EX527 (SIRT1-specific inhibitor) group, and AS-IV + EX527 group. Each group was further assigned into several subgroups according to ischemic time (6 h, 1 d, 3 d, and 7 days). The CIR injury was induced in MCAO/R group, AS-IV group, MCAO/R + EX527 group, and AS-IV + EX527 group by MCAO surgery in accordance with the modified Zea Longa criteria. Modified Neurological Severity Scores (mNSS) were used to evaluate the neurological deficits; TTC (2,3,5-triphenyltetrazolium chloride) staining was used to detect cerebral infarction area; Western Blot was used to assess the protein levels of SIRT1, acetylated MAPT (ac-MAPT), phosphorylated MAPT (p-MAPT), and total MAPT (t-MAPT); Real-time Quantitative Polymerase Chain Reaction (qRT-PCR) was used in the detection of Sirt1 and Mapt transcriptions.

Results: Compared with the MCAO/R group, AS-IV can significantly improve the neurological dysfunction (p < 0.05), reduce the infarction area (p < 0.05), raise the expression of SIRT1 (p < 0.05), and alleviate the abnormal hyperacetylation and hyperphosphorylation of MAPT (p < 0.05). While compared with the AS-IV group, AS-IV + EX527 group showed higher mNSS scores (p < 0.05), more severe cerebral infarction (p < 0.05), lower SIRT1 expression (p < 0.01), and higher ac-MAPT and p-MAPT levels (p < 0.05).

Conclusion: AS-IV can improve the neurological deficit after CIR injury in rats and reduce the cerebral infarction area, which exerts neuroprotective effects probably through the Sirt1/Mapt pathway.
Palmul-Tang, a Korean Medicine, Promotes Bone Formation via BMP-2 Pathway in Osteoporosis
Authors: Choi La Yoon , Kim Mi Hye , Nam Yeon Kyung , Kim Ju Hee , Cho Hea-Young , Yang Woong Mo
Published: March 2021

Osteoporosis is a common skeletal disease in post-menopausal women. Palmul-tang, an herbal medicine, has been treated for gynecological disease such as anemia, anorexia, anti-fatigue, unspecified menstruation and female infertility in East Asia. In this study, ameliorative effects of Palmul-tang soft extracts (PMT), a Korean Medicine, on osteoporosis were investigated. Ovariectomized (OVX) osteoporotic ICR mice were intragastrically administrated PMT for 4 weeks. The level of bone mineral density (BMD) was analyzed in bone tissues by dual X-ray absorptiometry. The bone medullary cavity and deposition of collagen were investigated by histological analysis. In addition, the BMP-2 signaling-related molecules, osteoblastic differentiation and formation markers, were determined in femoral tissues. The levels of BMD and bone mineral content were significantly increased in tibia, femurs and LV by treatment of PMT. PMT replenished bone marrow cavity and increased collagen deposition in bone marrow cells of femur. In addition, administration of PMT recovered serum ALP, bALP, osteocalcin and calcium levels in osteoporotic mice. Moreover, PMT treatment up-regulated the expressions of BMP-2, RUNX2 and OSX with its downstream factors, ALP, OPN and BSP-1, in the femoral tissues. Taken together, PMT restored the bone minerals and improvement of bone integrity by bone-forming BMP-2 signaling pathway. These results demonstrate that PMT could be an ameliorative agent for osteoporosis.
Signal Fingerprinting as a Novel Diagnostic Tool to Identify Conduction Inhomogeneity
Authors: Ye Ziliang , van Schie Mathijs S. , de Groot Natasja M. S.
Published: March 2021

Background

Inhomogeneous intra-atrial conduction facilitates both initiation and perpetuation of atrial fibrillation (AF) and is reflected in electrogram (EGM) morphology.

Objective

The primary objective of this study is to investigate regional differences in features of different EGM types during sinus rhythm (SR) and to design a patient-specific signal fingerprint, which quantifies the severity and extensiveness of inhomogeneity in conduction.

Methods

Patients (N = 189, 86% male; mean age 65 ± 9 years) undergoing coronary artery bypass grafting (CABG) underwent high-resolution mapping of the right atrium (RA), left atrium (LA), and pulmonary vein area (PVA) including Bachmann’s bundle (BB). EGMs during 5 s of SR were classified as single potentials (SPs), short double potentials (SDPs, interval between deflections < 15 ms), long double potentials (LDPs, deflection interval > 15 ms), or fractionated potentials (FPs, ≥3 deflections). Of all SPs, differences in relative R- and S-wave amplitude were calculated (R/S ratios). Time difference between first and last deflection was determined (fractionation duration, FD) and potentials with amplitudes < 1.0 mV were labeled as low-voltage. Conduction block (CB) was defined as a difference in local activation time (LAT) between adjacent electrodes of ≥12 ms.

Results

A total of 1,763,593 EGMs (9,331 ± 3,336 per patient) were classified (Table 1).

Conclusion

The signal fingerprint, consisting of quantified EGM features, including the R/S ratio of SPs, the relative frequency distribution of unipolar voltages, the proportion of low-voltage areas, the proportion of the different types of EGMs, and durations of LDP and FDP, may serve as a diagnostic tool to determine the severity and extensiveness of conduction inhomogeneity. Further studies are required to determine whether the signal fingerprint can be used to identify patients at risk for AF onset or progression.
Comparative Metabolite and Gene Expression Analyses in Combination With Gene Characterization Revealed the Patterns of Flavonoid Accumulation During Cistus creticus subsp. creticus Fruit Development
Authors: Aničić Neda , Patelou Efstathia , Papanikolaou Antigoni , Kanioura Anthi , Valdesturli Camilla , Arapitsas Panagiotis , Skorić Marijana , Dragićević Milan , Gašić Uroš , Koukounaras Athanasios , Kostas Stefanos , Sarrou Eirini , Martens Stefan , Mišić Danijela , Kanellis Angelos
Published: March 2021

Cistus creticus L. subsp. creticus (rockrose) is a shrub widespread in Greece and the Mediterranean basin and has been used in traditional medicine as herb tea for colds, for healing and digestive hitches, for the treatment of maladies, as perfumes, and for other purposes. Compounds from its flavonoid fraction have recently drawn attention due to antiviral action against influenza virus and HIV. Although several bioactive metabolites belonging to this group have been chemically characterized in the leaves, the genes involved in their biosynthesis in Cistus remain largely unknown. Flavonoid metabolism during C. creticus fruit development was studied by adopting comparative metabolomic and transcriptomic approaches. The present study highlights the fruit of C. creticus subsp. creticus as a rich source of flavonols, flavan-3-ols, and proanthocyanidins, all of which displayed a decreasing trend during fruit development. The majority of proanthocyanidins recorded in Cistus fruit are B-type procyanidins and prodelphinidins, while gallocatechin and catechin are the dominant flavan-3-ols. The expression patterns of biosynthetic genes and transcription factors were analyzed in flowers and throughout three fruit development stages. Flavonoid biosynthetic genes were developmentally regulated, showing a decrease in transcript levels during fruit maturation. A high degree of positive correlations between the content of targeted metabolites and the expression of biosynthetic genes indicated the transcriptional regulation of flavonoid biosynthesis during C. creticus fruit development. This is further supported by the high degree of significant positive correlations between the expression of biosynthetic genes and transcription factors. The results suggest that leucoanthocyanidin reductase predominates the biosynthetic pathway in the control of flavan-3-ol formation, which results in catechin and gallocatechin as two of the major building blocks for Cistus proanthocyanidins. Additionally, there is a decline in ethylene production rates during non-climacteric Cistus fruit maturation, which coincides with the downregulation of the majority of flavonoid- and ethylene-related biosynthetic genes and corresponding transcription factors as well as with the decline in flavonoid content. Finally, functional characterization of a Cistus flavonoid hydroxylase (F3′5′H) was performed for the first time.
Transcriptomic Profiling of Apple Calli With a Focus on the Key Genes for ALA-Induced Anthocyanin Accumulation
Authors: Zheng Jie , Liu Longbo , Tao Huihui , An Yuyan , Wang Liangju
Published: March 2021

The red color is an attractive trait of fruit and determines its market acceptance. 5-Aminolevulinic acid (ALA), an eco-friendly plant growth regulator, has played a universal role in plant secondary metabolism regulation, particularly in flavonoid biosynthesis. It has been widely reported that ALA can up-regulate expression levels of several structural genes related to flavonoid metabolism and anthocyanin accumulation. However, the molecular mechanisms behind ALA-induced expression of these genes are complicated and still far from being completely understood. In this study, transcriptome analysis identified the differentially expressed genes (DEGs) associated with ALA-induced anthocyanin accumulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the flavonoid biosynthesis (ko00941) pathway was significantly enhanced in the ALA-treated apple calli at 24, 48, and 72 h after the treatment. Expression pattern revealed that ALA up-regulated the expression of the structural genes related to not only anthocyanin biosynthesis (MdCHS, MdCHI, MdF3’H, MdDFR, MdANS, and MdUFGT) but also anthocyanin transport (MdGST and MdMATE). Two R2R3-MYB transcription factors (MdMYB10 and MdMYB9), which are the known positive regulators of anthocyanin biosynthesis, were significantly induced by ALA. Gene overexpression and RNA interference assays demonstrated that MdMYB10 and MdMYB9 were involved in ALA-induced anthocyanin biosynthesis. Moreover, MdMYB10 and MdMYB9 might positively regulate the transcription of MdMATE8 by binding to the promoter region. These results indicate that MdMYB10 and MdMYB9 modulated structural gene expression of anthocyanin biosynthesis and transport in response to ALA-mediated apple calli coloration at the transcript level. We herein provide new details regarding transcriptional regulation of ALA-induced color development.
Clinical Psychology Services for Patients Hospitalized Due to COVID-19 During the Pandemic in Northern Italy: From Isolation to Rehabilitation
Authors: Callus Edward , Bertoldo Enrico Giuseppe , Fiolo Valentina , Pagliuca Silvana , Baroni Barbara
Published: March 2021

The objective of this paper is to describe the organization and modality of provision of clinical psychology services for those patients who had to be hospitalized due to COVID-19 during the pandemic in Northern Italy. The IRCCS Policlinico San Donato hospital in Milan was converted into a COVID-19 center in March 2020, and all the staff, including the Clinical Psychology Service Team, were diverted to assist these patients. A description is given of how the service was organized and the modalities which were utilized to assist the patients. Following the pertinent ministerial decrees, guidelines, and relevant literature, the patients were followed up through telehealth (via phone, smartphone, or tablet with audio or audio-visual calls). A COVID-19 rehabilitation unit was later opened in April 2020, where all patients were seen and followed up by the Clinical Psychology team, the last patient being discharged at the end of June. Details are given about the type of services provided during the hospitalization at the different points in time. At admittance and subsequent isolation, patients indicated by the medical and nursing staff, and those who specifically requested it, were given psychological support. Patients transferred to the COVID-19 rehabilitation unit were all evaluated for anxiety, depression, posttraumatic stress disorder, and sleep disorders both on admission and at discharge when possible.
Evolution of Prospective Secondary Education Economics Teachers’ Personal and Emotional Metaphors
Authors: Mellado Lucía , Parte Laura , Sánchez-Herrera Susana , Bermejo María Luisa
Published: March 2021

This study examines personal and emotional metaphors of prospective economics teachers about the roles they themselves as teachers and their pupils would play by analysing their drawings and responses to open questions. This is a longitudinal study that analyses the evolution of future instructors using two periods: before and after their teaching practicum. Metaphors are categorised into four classes: behaviourist/transmissive, cognitivist/constructivist, situative/socio-historical, and self-referential. The categories for emotions are primary or social and positive, negative, or neutral. The results show that the highest percentage of metaphors for the teacher’s role in both questionnaires were cognitivist/constructivist. Comparison of the findings before and after the teaching practicum revealed no changes in most of the participants’ metaphors and associated models. The analysis also reveals that among those who change, the tendency is to evolve towards more pupil-centred metaphors and associated models. The most common pupil metaphors are behaviourist and cognitivist, increasing after the practicum. Finally, most of the emotions expressed are positive and social, also increasing after the practicum.
The “Missing 6 dB” Revisited: Influence of Room Acoustics and Binaural Parameters on the Loudness Mismatch Between Headphones and Loudspeakers
Authors: Denk Florian , Kohnen Michael , Llorca-Bofí Josep , Vorländer Michael , Kollmeier Birger
Published: March 2021

Generations of researchers observed a mismatch between headphone and loudspeaker presentation: the sound pressure level at the eardrum generated by a headphone has to be about 6 dB higher compared to the level created by a loudspeaker that elicits the same loudness. While it has been shown that this effect vanishes if the same waveforms are generated at the eardrum in a blind comparison, the origin of the mismatch is still unclear. We present new data on the issue that systematically characterize this mismatch under variation of the stimulus frequency, presentation room, and binaural parameters of the headphone presentation. Subjects adjusted the playback level of a headphone presentation to equal loudness as loudspeaker presentation, and the levels at the eardrum were determined through appropriate transfer function measurements. Identical experiments were conducted at Oldenburg and Aachen with 40 normal-hearing subjects including 14 that passed through both sites. Our data verify a mismatch between loudspeaker and binaural headphone presentation, especially at low frequencies. This mismatch depends on the room acoustics, and on the interaural coherence in both presentation modes. It vanishes for high frequencies and broadband signals if individual differences in the sound transfer to the eardrums are accounted for. Moreover, small acoustic and non-acoustic differences in an anechoic reference environment (Oldenburg vs. Aachen) exert a large effect on the recorded loudness mismatch, whereas not such a large effect of the respective room is observed across moderately reverberant rooms at both sites. Hence, the non-conclusive findings from the literature appear to be related to the experienced disparity between headphone and loudspeaker presentation, where even small differences in (anechoic) room acoustics significantly change the response behavior of the subjects. Moreover, individual factors like loudness summation appear to be only loosely connected to the observed mismatch, i.e., no direct prediction is possible from individual binaural loudness summation to the observed mismatch. These findings – even though not completely explainable by the yet limited amount of parameter variations performed in this study – have consequences for the comparability of experiments using loudspeakers with conditions employing headphones or other ear-level hearing devices.
Designing Exhibits to Support Relational Learning in a Science Museum
Authors: Jee Benjamin D. , Anggoro Florencia K.
Published: March 2021

Science museums aim to provide educational experiences for both children and adults. To achieve this goal, museum displays must convey scientifically-relevant relationships, such as the similarities that unite members of a natural category, and the connections between scientific models and observable objects and events. In this paper, we explore how research on comparison could be leveraged to support learning about such relationships. We describe how museum displays could promote educationally-relevant comparisons involving natural specimens and scientific models. We also discuss how these comparisons could be supported through the design of a display—in particular, by using similarity, space, and language to facilitate relational thinking for children and their adult companions. Such supports may be pivotal given the informal nature of learning in museums.
Six Weeks of Basketball Combined With Mathematics in Physical Education Classes Can Improve Children's Motivation for Mathematics
Authors: Wienecke Jacob , Hauge Jesper , Nielsen Glen , Mouritzen Kristian , Damsgaard Linn
Published: March 2021

This study investigated whether 6 weeks of basketball combined with mathematics once a week in physical education lessons could improve children's motivation for mathematics. Seven hundred fifty-seven children (mean age = 10.4 years, age range: 7–12 years) were randomly selected to have either basketball combined with mathematics once a week (BM) or to have basketball sessions without mathematics (CON). Children in BM and CON motivation for classroom-based mathematics were measured using the Academic Self-Regulation Questionnaire (SRQ-A) before (T0) and after the intervention (T1). Among the BM, levels of intrinsic motivation, feelings of competence, and autonomy were measured using the Post-Experimental Intrinsic Motivation Inventory (IMI) questionnaire acutely after a basketball session combined with mathematics and immediately after a session of classroom-based mathematics. BM had significantly higher acute levels of perceived autonomy (+14.24%, p < 0.0001), competencies (+6.33%, p < 0.0001), and intrinsic motivation (+16.09%, p < 0.0001) during basketball sessions combined with mathematics compared to when having classroom-based mathematics. A significant decrease in the mean for intrinsic motivation was observed from T0 to T1 for CON (−9.38%, p < 0.001), but not for BM (−0.39%, p = 0.98). BM had a more positive development in intrinsic motivation compared to CON from T0 to T1 (p = 0.006), meaning that BM had a positive influence on children's intrinsic motivation for classroom-based mathematics. This study indicates that basketball combined with mathematics is an intrinsically motivating way to practice mathematics, which also has a positive influence on children's general intrinsic motivation for mathematics in the classroom.
Effect of Intelligence Mindsets on Math Achievement for Chinese Primary School Students: Math Self-Efficacy and Failure Beliefs as Mediators
Authors: Su Aoxue , Wan Shuya , He Wei , Dong Lianchun
Published: March 2021

This study examined the relationship of intelligence mindsets to math achievement for primary school students in the Chinese educational context, as well as the mediating function of math self-efficacy and failure beliefs in this relationship. Participants included 466 fifth graders (231 boys and 235 girls) from two Chinese primary schools. Results indicated that boys had significantly higher mean levels of growth mindsets and math self-efficacy than girls, whereas boys had no statistically significant differences to girls on failure beliefs and math grade. Further, intelligence mindsets had a significant positive effect on math achievement, and failure beliefs and math self-efficacy played a full mediating role in the relationship between intelligence mindsets and math achievement. Moreover, intelligence mindsets affected math achievement through the chain mediating role of failure beliefs and math self-efficacy. These above findings contribute to advance our knowledge about the underlying mechanisms through which intelligence mindsets affect math achievement, which are of great significance to students' growth and current educational practice.
Occupational Burnout Among Frontline Health Professionals in a High-Risk Area During the COVID-19 Outbreak: A Structural Equation Model
Authors: Li Dan , Wang YuanYuan , Yu Hui , Duan Zhizhou , Peng Ke , Wang Nan , Zhou Qiang , Hu Xudong , Fang Ke , Wilson Amanda , Ou Jianjun , Wang Xiaoping
Published: March 2021

Background: The outbreak of coronavirus disease 2019 (COVID-19) resulted in a substantial workload and stress for frontline health professionals in high-risk areas. Little research has investigated the mechanism of occupational burnout among the frontline health professionals located in the center of the epidemic in Wuhan, China.

Methods: A total of 199 frontline health professionals from Wuhan Jinyintan Hospital completed the cross-sectional survey. Mechanisms of occupational burnout (according to the Maslach Burnout Inventory–General Survey, MBI-GS) among the health professionals in Jinyintan Hospital during the COVID-19 outbreak were examined using a structural equation model (SEM).

Results: The levels of the three burnout dimensions (emotional exhaustion, cynicism, and professional efficacy) were high at 34.2, 50.8, and 35.2%, respectively. Frontline health professionals in this stressful period reported significantly greater emotional exhaustion (p < 0.001) and job-related cynicism (p < 0.001), but no significant difference in professional efficacy (p = 0.449), when compared to employees in a large multinational company. The SEM results revealed that both acute stress symptoms and psychosomatic symptoms significantly predicted the emotional exhaustion and occupation cynicism dimensions of burnout.

Conclusion: The study reveals the occupational burnout mechanism of frontline health professionals during the COVID-19 peak at the time of the outbreak. This study provides an important contribution to understanding the future psychological interventions necessary for frontline health professionals during an epidemic crisis.
The Mediation Effect of Hyperarousal Symptoms on the Relationship Between Childhood Physical Abuse and Suicidal Ideation of Patients With PTSD
Authors: Kwon Aeran , Lee Hyun Seo , Lee Seung-Hwan
Published: March 2021

Objective: This study examined the relationship of childhood physical abuse, posttraumatic stress disorder (PTSD), depression, and suicide in patients with PTSD through path analysis.

Materials and Methods: A total of 114 patients with PTSD (36 men and 78 women) were recruited and completed psychological assessments including the Childhood Trauma Questionnaire, the scale for suicidal ideation, the clinician-administered PTSD scale for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the PTSD checklist, and the Hospital Anxiety and Depression Scale. Structural equation modeling was used to evaluate the results. We developed a model including childhood physical abuse experience as the causal variable, suicidal ideation as a result variable, and PTSD and depression as mediation variables. PTSD symptoms were divided into four clusters [intrusion, avoidance, negative cognition and mood, and altered arousal and reactivity (hyperarousal)] to determine predictive power for suicide.

Results: PTSD symptoms fully mediated the relationship between childhood physical abuse and suicidal ideation. Furthermore, PTSD symptoms fully mediated the relationship between childhood physical abuse and depression. Among the PTSD symptoms, hyperarousal was the only symptom cluster that mediated the relationship between childhood physical abuse and suicidal ideation. The symptom clusters of negative cognition and mood as well as hyperarousal mediated the relationship between childhood physical abuse and depression.

Conclusions: This study presents a link between childhood physical abuse and current symptoms in patients with PTSD, and highlights specific PTSD symptom clusters (i.e., hyperarousal, negative cognition and mood) that may increase the risk for psychopathology later in life.
Neural Autoantibodies in Cerebrospinal Fluid and Serum in Clinical High Risk for Psychosis, First-Episode Psychosis, and Healthy Volunteers
Authors: Bien Christian G. , Rohleder Cathrin , Mueller Juliane K. , Bien Corinna I. , Koethe Dagmar , Leweke F. Markus
Published: March 2021

The pathophysiological role of neural autoantibodies in acute psychotic disorders is receiving increased attention. However, there is still an ongoing debate, whether predominantly psychotic manifestations of autoimmune encephalitides exist that may remain undetected and, thus, untreated. Furthermore, it is discussed if such conditions can be diagnosed based on serum antibody results or if a reliable diagnosis requires additional cerebrospinal fluids (CSF) results. In this study, we screened pairs of serum and CSF samples from antipsychotic-naïve individuals with first-episode schizophrenic psychosis (FEP, n = 103), clinical high risk for psychosis (CHR, n = 47), and healthy volunteers (HV, n = 40) for eight different antibodies against various antigens that have been shown to be associated with autoimmune encephalitides: N-methyl-D-aspartate receptor (NMDAR, NR1 subunits only), glutamic acid decarboxylase (GAD65), leucine-rich glioma inactivated protein 1 (LGI1), contactin-associated protein-like 2 protein (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit 1, AMPAR subunit 2, γ-aminobutyric acid-B receptors (GABABR), and glycine receptors. All patients were within the norm with regards to a careful neurological examination, a magnetic resonance imaging (MRI) of the brain, an electroencephalogram (EEG), and routine blood pathology. All CSF samples were autoantibody-negative. In three serum samples of individuals with FEP, we detected low-titer CASPR2 immunoglobulin (Ig) G antibodies (≤1:160, n = 2) and non-IgG antibodies against NMDAR (n = 1) (overall serum-autoantibody prevalence in FEP: 2.91%). However, the IgG titers were below the laboratory cut-off defined for positivity, and non-IgG antibodies are of no clinical relevance. This suggests that there were no cases of autoimmune encephalitis in our cohort. Our results highlight the importance and the high specificity of CSF analysis to reliably detect autoantibodies. They confirm the hypothesis that pure psychotic manifestations of antibody-associated autoimmune encephalitides without any additional neuropsychiatric findings are very rare. However, special attention must be paid to those presenting with atypical mental illnesses with additional neurological symptoms, evidence of clinically-significant cognitive involvement, profound sleep-wake perturbations, seizures, electroencephalographic, or magnetic resonance imaging pathologies to be able to identify cases with autoimmune-mediated psychiatric syndromes.
Reaching Thousands of Children in Low Income Communities With High-Quality ECED Services: A Journey of Perseverance and Creativity
Authors: Mesa Nathalia , Nores Milagros , Vega Hilda
Published: March 2021

This paper describes a creative and bold way in which a local NGO addressed increasing access and quality of ECED services in Colombia. This case study on Fundacion Carulla's aeioTU early childhood innovation in Colombia contributes to understanding the possibilities for the private sector to spark innovation, and the importance of an open and collaborative strategy in contributing to the ECED sector at large. The critical role of monitoring and evaluation in the provision of services is highlighted. This guided key decisions on different growth phases. After a decade of work, Fundacion Carulla-aeioTU has shown capacity to effectively support children's development in low-income settings through their participation in quality programming. Furthermore, this case study also describes how the organization, having proven its capacity to provide high-quality services directly to children, decided to innovate and bring about different solutions to reach and support other stakeholders in the early childhood development ecosystem.
Epistemic Injustice in Brain Studies of (Trans)Gender Identity
Authors: Llaveria Caselles Eric
Published: March 2021

This study undertakes an analysis of the conceptualization of gender identity in neuroscientific studies of (trans)gender identity that contrast the brains of cisgender and transgender participants. The analysis focuses on instances of epistemic injustice that combine scientific deficiencies and the exclusion of relevant bodies of knowledge. The results of a content analysis show how the ignoring of biosocial, developmental, mosaicist, contextualist, and depathologizing approaches leads to internal conceptual inconsistencies, hermeneutical deficiencies and the upholding of questionable paradigms in the research field. Interviews with researchers involved in these brain studies reveal targeted and diffuse forms of testimonial injustice against alternative approaches, promoted by the hierarchical arrangements of research teams in combination with the careerist and economic logic of research. The analysis points to the exclusion of critical epistemologies of science and the historical oppression of trans people as epistemic agents as the underlying hermeneutical deficiencies.
The Covid-19 Pandemics: why Intersectionality Matters
Authors: Maestripieri Lara
Published: March 2021

Covid-19 has been a disrupting event in contemporary social life but is far from being a great equaliser. Preliminary studies have put in evidence how different social groups faced a differentiated risk of contagion and coped differently with the various consequences of the emergency. Evidence shows how minorities and migrants face disproportionally higher risks of contagion than the white upper and middle class, and how vulnerable communities are more exposed to deaths and the rapid spread of the virus. At the same time, societies are coping with social distancing measures and their disruptive social and economic consequences, which have a more significant impact on the most vulnerable segments of societies: women, children, low-income classes and ethnic minorities. This article argues that an intersectional framework allows an understanding of what is occurring in the current pandemic, both in terms of its social determinants and social consequences. To open the black box of inequality, intersectional scholars analyze the intersections of multiple structures of inequalities (such as gender, age, class, ethnicity), which have a multiplying effect when disadvantaged positions intersect in the same individual. Covid-19 is a clear example of an intersectional phenomenon: the impact of individual and community exposure to Covid-19 is the results of multiple and interrelating structures of inequality. Up to now, research in social sciences has underestimated the role of intersectionality in analyzing the social and economic consequences of this pandemic.
Interferon-γ Response of Mycobacterium avium subsp. paratuberculosis Infected Goats to Recombinant and Synthetic Mycobacterial Antigens
Authors: Köhler Heike , Liebler-Tenorio Elisabeth , Hughes Valerie , Stevenson Karen , Bakker Douwe , Willemsen Peter , Bay Sylvie , Ganneau Christelle , Biet Franck , Vordermeier H. Martin
Published: March 2021

Despite its potential for early diagnosis of Mycobacterium avium subsp. paratuberculosis (MAP) infection, the IFN-γ release assay is not used routinely, because of low specificity of the established crude antigen preparation Johnin (PPDj). Limited data are available assessing the potential of MAP-derived protein and lipopeptide antigens to replace PPDj in assays for goats, while cattle and sheep have been studied more extensively. Furthermore, MAP infection is claimed to interfere with the diagnosis of bovine tuberculosis when other crude antigen preparations (PPDb, PPDa) are applied. In this study, the diagnostic potential of MAP-derived recombinant protein antigens, synthetic MAP lipopentapeptides and of Mycobacterium bovis-specific peptide cocktails was assessed compared to crude mycobacterial antigen preparations in experimentally infected goats. Goats were inoculated with MAP, or Mycobacterium avium subsp. hominissuis (MAH) as surrogate for environmental mycobacteria, non-exposed animals served as controls. Mycobacterium avium Complex-specific antibody and PPDj-induced IFN-γ responses were monitored in vivo. Infection status was assessed by pathomorphological findings and bacteriological tissue culture at necropsy 1 year after inoculation. The IFN-γ response to 13 recombinant protein antigens of MAP, two synthetic MAP lipopentapeptides and three recombinant peptide cocktails of Mycobacterium bovis was investigated at three defined time points after infection. At necropsy, MAP or MAH infection was confirmed in all inoculated goats, no signs of infection were found in the controls. Antibody formation was first detected 3–6 weeks post infection (wpi) in MAH-inoculated and 11–14 wpi in the MAP-inoculated goats. Maximum PPDj-induced IFN-γ levels in MAH and MAP exposed animals were recorded 3–6 and 23–26 wpi, respectively. Positive responses continued with large individual variation. Antigens Map 0210c, Map 1693c, Map 2020, Map 3651cT(it), and Map 3651c stimulated increased whole blood IFN-γ levels in several MAP-inoculated goats compared to MAH inoculated and control animals. These IFN-γ levels correlated with the intensity of the PPDj-induced responses. The two synthetic lipopentapeptides and the other MAP-derived protein antigens had no discriminatory potential. Stimulation with Mycobacterium bovis peptide cocktails ESAT6-CFP10, Rv3020c, and Rv3615c did not elicit IFN-γ production. Further work is required to investigate if test sensitivity will increase when mixtures of the MAP-derived protein antigens are applied.
HDAC Inhibition Induces Cell Cycle Arrest and Mesenchymal-Epithelial Transition in a Novel Pleural-Effusion Derived Uterine Carcinosarcoma Cell Line
Authors: Stockhammer Paul , Okumus Özlem , Hegedus Luca , Rittler Dominika , Ploenes Till , Herold Thomas , Kalbourtzis Stavros , Bankfalvi Agnes , Sucker Antje , Kimmig Rainer , Aigner Clemens , Hegedus Balazs
Published: March 2021

Objective: Uterine carcinosarcoma (UCS) is a rare but highly aggressive malignancy with biphasic growth pattern. This morphology can be attributed to epithelial-mesenchymal transition (EMT) that often associates with tumor invasion and metastasis. Accordingly, we analyzed a novel patient-derived preclinical model to explore whether EMT is a potential target in UCS.

Methods: A novel UCS cell line (PF338) was established from the malignant pleural effusion of a 59-year-old patient at time of disease progression. Immunohistochemistry was performed in primary and metastatic tumor lesions. Oncogenic mutations were identified by next-generation sequencing. Viability assays and cell cycle analyses were used to test in vitro sensitivity to different standard and novel treatments. E-cadherin, β-catenin and pSMAD2 expressions were measured by immunoblot.

Results: Whereas immunohistochemistry of the metastatic tumor showed a predominantly sarcomatous vimentin positive tumor that has lost E-cadherin expression, PF338 cells demonstrated biphasic growth and carried mutations in KRAS, PIK3CA, PTEN and ARID1A. PF338 tumor cells were resistant to MEK- and TGF-β signaling-inhibition but sensitive to PIK3CA- and PARP-inhibition and first-line chemotherapeutics. Strikingly, histone deacetylase (HDAC) inhibition markedly reduced cell viability by inducing a dose-dependent G0/1 arrest and led to mesenchymal-epithelial transition as evidenced by morphological change and increased E-cadherin and β-catenin expression.

Conclusions: Our data suggest that HDAC inhibition is effective in a novel UCS cell line by interfering with both viability and differentiation. These findings emphasize the dynamic manner of EMT/MET and epigenetics and the importance of molecular profiling to pave the way for novel therapies in UCS.
Optimization of the Multi-Facility Location Problem Using Widely Available Office Software
Authors: Němec Petr , Stodola Petr
Published: March 2021

Multi-facility location problem is a type of task often solved (not only) in logistics. It consists in finding the optimal location of the required number of centers for a given number of points. One of the possible solutions is to use the principle of the genetic algorithm. The Solver add-in, which uses the evolutionary method, is available in the Excel office software. It was used to solve the benchmark in 4 levels of difficulty (from 5 centers for 25 points to 20 centers for 100 points), and one task from practice. The obtained results were compared with the results obtained by the metaheuristic simulated annealing method. It was found that the results obtained by the evolutionary method are sufficiently accurate. Their accuracy depends on the complexity of the task and the performance of the HW used. The advantage of the proposed solution is easy availability and minimal requirements for user knowledge.
Unlocking the Patterns of the Tunisian Durum Wheat Landraces Genetic Structure Based on Phenotypic Characterization in Relation to Farmer’s Vernacular Name
Authors: Robbana Cyrine , Kehel Zakaria , Ammar Karim , Guzmán Carlos , Naceur M’Barek Ben , Amri Ahmed
Published: March 2021

During the 1970s, Tunisian durum wheat landraces were replaced progressively by modern cultivars. These landraces are nowadays maintained by smallholder farmers in some ecological niches and are threatened gradually by extinction resulting in the narrowing of the genetic diversity. This study aims to investigate patterns of phenotypic variability using twelve quantitative traits in a panel of 189 durum wheat landraces and seven checks, based on farmer’s population name attribution and genetic structure. Our results showed high phenotypic variability among and within landraces and checks for ten out of twelve studied traits. The principal components analysis showed similar grouping using farmers name attribution and genetic structure using K = 6. These results confirmed the identification of a new gene pool in the oases of Tunisia, represented by the sub-population Jenah Zarzoura and the robustness and high relationships between phenotypic and genome-wide genetic structure using DArTseq method. These findings will enhance the conservation efforts of these landraces and their use in breeding efforts at national and international levels to adapt to dry conditions.
Assessment of the Behavioural Response of Korean Water Deer (Hydropotes inermis argyropus) to Different Fence Heights
Authors: Park Hee-Bok , Woo Donggul , Choi Tae Young , Hong Sungwon
Published: March 2021

Fences have been widely implemented to reduce the risk of wildlife–vehicle collisions, wildlife disease spread, and crop damage. To manufacture fences, it is imperative to assess the behavioural responses of the target species. Here, we investigated the success rate of fences and classified eight behavioural responses of Korean water deer (Hydropotes inermis argyropus) to different fence heights. We explored the association of 801 behavioural responses and defined a threshold based on 40 events by applying non-metric multidimensional scaling and a binary logistic generalised linear mixed model. With fences lower and higher than 1.2 m, recession and rest were the dominant behaviours, respectively, before the deer crossed the fences by performing vertical and running jumps. Considering all independent events, 0.9 m was the marginal threshold, with highly variable outliers over this value. Placing exit pathways for deer and eliminating possible resting areas outside fences are essential for reducing the number of successful jump attempts. The optimal fence height could differ based on conditional factors; however, we recommend a height of 1.5 m considering the cost and roadkill risk. In conclusion, exploring and classifying the behavioural responses of the target species may be critical for establishing appropriate fence protocols.
Prevalence of Select Intestinal Parasites in Alabama Backyard Poultry Flocks
Authors: Carrisosa Miranda , Jin Shanhao , McCrea Brigid A. , Macklin Kenneth S. , Dormitorio Teresa , Hauck Rüdiger
Published: March 2021

Keeping chickens as backyard pets has become increasingly popular in the United States in recent years. However, biosecurity is generally low in backyard flocks. As a consequence, they can serve as reservoirs for various pathogens that pose a risk for commercial poultry or human health. Eighty-four fecal samples, 82 from chickens and two from turkeys, from 64 backyard flocks throughout the state of Alabama were collected in the summers of 2017 and 2018. Coccidia oocysts were seen in 64.1% of flocks with oocyst counts in most samples below 10,000 oocysts per gram. Eggs of Ascaridia spp. or Heterakis gallinarum were observed in 20.3% of the flocks, and eggs of Capillaria spp. in 26.6% of the flocks. Egg counts were low, rarely exceeding 1000 eggs per gram. DNA extracted directly from fecal samples was investigated by PCR for other relevant parasites. The results showed that 4.7% of flocks were positive for Histomonas meleagridis, 18.8% of flocks for Tetratrichomonas gallinarum, 18.8% of flocks for Cryptosporidium spp. and 87.5% of flocks for Blastocystis spp. The results will help to provide information that can be used to design outreach programs to improve health and wellbeing of birds in backyard flocks.