bluuebunny/crossref_metadata_2025 huggingface dataset:
PERAN SULTAN DAYANU IKHSANUDDIN DALAM PENYEBARAN AGAMA ISLAM DI BARATA KULISUSU: 1597-1631
Authors: Hidhayati Rini , Hayari Hayari
Published: April 2022

Artikel ini mengkaji tentang peran Sultan Dayanu Ikhsanuddin dalam  penyebaran agama Islam di  Barata Kulisusu: 1597-1631 dengan tujuan untuk: (1) Mengetahui proses masuknya Agama Islam di Barata Kulisusu (2) Mengetahui peran Sultan Dayanu Ikhsanuddin dalam menyebarkan agama Islam di Barata Kulisusu (3) Mengetahui dampak penyebaran agama Islam terhadap kehidupan masyarakat di Barata Kulisusu. Metode yang digunakan dalam penelitian ini adalah metode sejarah yang terdiri dari lima tahapan yakni: (1) Pemilihan topik, (2) Heuristik sumber, (3) Verifikasi sumber, (4) Interpretasi, dan (5) Historiografi. Hasil penelitian menunjukkan, (1) Masuknya agama Islam di Barata Kulisusu pada masa Sultan Dayanu Ikhsanuddin dibawa oleh Syekh Gau Malanga/Buraku. Terjadinya proses islamisasi di Barata Kulisusu ketika Syekh Gau Malanga/Buraku mulai mengikuti ajaran dan menikah dengan masyarakat pribumi. Pernihakan Syekh Gau Malanga/Buraku mendapat kepercayaan dari masyarakat terutama dari anggota keluarga dan kerabat dekat istrinya. Posisi inilah yang digunakan Syekh Gau Malanga/Buraku untuk menanamkan ajaran Islam pada masyarakat Kulisusu secara perlahan-lahan sampai akhirnya Islam menjadi agama yang dianut masyarakat Kulisusu. (2) Peran Sultan Dayanu Ikhsanuddin dalam penyebaran Islam di Barata Kulisusu melaui jalur pernikahan dengan Wa Ode Bilahi (3) Penyebaran agama Islam memiliki dampak dalam kehidupan masyarakat Kulisusu yaitu: sosial, politik, serta ekonomi.
The Role of Organizational Commitment and Organization Culture Toward Job Performance
Authors: Tuti Setyorini  , Janri Delastriani Manafe  , Indawati Jauhar Nino
Published: April 2022

This study seeks to find out the factors that affect lecturers’ performance in Indonesia. Data were collected through a questionnaire participated by 178 active lecturers at the State Polytechnic of Kupang. The present study is important since it may give solutions to enhance the performance of Kupang State Polytechnic lecturers. Data analysis was conducted using the principles of Structural Equation Modeling (SEM). The results of this study demonstrated that there are direct and indirect influences of organizational culture and commitment toward lecturer performance as mediated by Organizational Citizenship Behavior (OCB). This shows the importance of OCB as a situational factor that can improve the performance of teaching staff in an educational institution.

 

AbstrakPenelitian ini menyelidiki faktor-faktor yang berpengaruh terhadap kinerja dosen di Indonesia. Pengumpulan data dilakukan dengan kuesioner dengan 178 dosen aktif Politeknik Negeri Kupang sebagai responden. Penelitian ini penting karena dapat memberikan solusi bagi peningkatan kinerja dosen di Politeknik Negeri Kupang. Data dianalisa dengan menggunakan Structural Equation Modeling (SEM). Secara langsung maupun tidak langsung terdapat pengaruh dari budaya dan komitmen organisasi terhadap kinerja dosen yang diperantarai oleh Organizational Citizenship Behavior (OCB). Penelitian ini mengetengahkan pentingnya OCB sebagai faktor situasional yang dapat meningkatkan kinerja tenaga pengajar di suatu lembaga pendidikan.
Identification of Recombinant Chimpanzee Adenovirus C68 Degradation Products Detected by AEX-HPLC
Authors: Powers Thomas W. , Mullins Elise K. , Zhang Kun , Binder Joseph J. , Friese Olga , Runnels Herbert A. , Thompson Lawrence C.
Published: April 2022

Physicochemical tests represent important tools for the analytical control strategy of biotherapeutics. For adenoviral modalities, anion-exchange high performance liquid chromatography (AEX-HPLC) represents an important methodology, as it is able to simultaneously provide information on viral particle concentration, product purity and surface charge in a high-throughput manner. During product development of an adenoviral-based therapeutic, an accelerated stability study was performed and showed changes in each of the AEX-HPLC reportable attributes. These changes also correlated with a decrease in product infectivity prompting a detailed characterization of the impurity and mechanism of the surface charge change. Characterization experiments identified the impurity to be free hexon trimer, suggesting that capsid degradation could be contributing to both the impurity and reduced particle concentration. Additional mass spectrometry characterization identified deamidation of specific hexon residues to be associated with the external surface charge modification observed upon thermal stress conditions. To demonstrate a causal relationship between deamidation and surface charge changes observed by AEX-HPLC, site-directed mutagenesis experiments were performed. Through this effort, it was concluded that deamidation of asparagine 414 was responsible for the surface charge alteration observed in the AEX-HPLC profile but was not associated with the reduction in infectivity. Overall, this manuscript details critical characterization efforts conducted to enable understanding of a pivotal physicochemical test for adenoviral based therapeutics.
Coherent Control of Molecular Dissociation by Selective Excitation of Nuclear Wave Packets
Authors: López Peña Hugo A. , Shusterman Jacob M. , Ampadu Boateng Derrick , Lao Ka Un , Tibbetts Katharine Moore
Published: April 2022

We report on pump-probe control schemes to manipulate fragmentation product yields in p-nitrotoluene (PNT) cation. Strong field ionization of PNT prepares the parent cation in the ground electronic state, with coherent vibrational excitation along two normal modes: the C–C–N–O torsional mode at 80 cm−1 and the in-plane ring-stretching mode at 650 cm−1. Both vibrational wave packets are observed as oscillations in parent and fragment ion yields in the mass spectrum upon optical excitation. Excitation with 650 nm selectively fragments the PNT cation into C7H7+, whereas excitation with 400 nm selectively produces C5H5+ and C3H3+. In both cases the ion yield oscillations result from torsional wave packet excitation, but 650 and 400 nm excitation produce oscillations with opposite phases. Ab initio calculations of the ground and excited electronic potential energy surfaces of PNT cation along the C–C–N–O dihedral angle reveal that 400 nm excitation accesses an allowed transition from D0 to D6 at 0° dihedral angle, whereas 650 nm excitation accesses a strongly allowed transition from D0 to D4 at a dihedral angle of 90°. This ability to access different electronic excited states at different locations along the potential energy surface accounts for the selective fragmentation observed with different probe wavelengths. The ring-stretching mode, only observed using 800 nm excitation, is attributed to a D0 to D2 transition at a geometry with 90° dihedral angle and elongated C–N bond length. Collectively, these results demonstrate that strong field ionization induces multimode coherent excitation and that the vibrational wave packets can be excited with specific photon energies at different points on their potential energy surfaces to induce selective fragmentation.
The Voices of Primary School Boys and Girls on Human Rights and Their Historical Agency
Authors: López Martínez Manuel José , Jiménez Martínez Mᵃ Dolores
Published: April 2022

The teaching of History in primary school must integrate education for active global citizenship in the face of inequalities and social injustice caused by the constant violation of human rights in the present. The transformative framework at school promotes global citizenship from a humanizing perspective and a respect for diversity. All of this comes in a context marked by the effects of the capitalist economic dimension of globalization, which translates into a crisis in the exercising of fundamental democratic values. Below, we show the first-phase results of educational research comprising a qualitative exploratory study that investigates what primary school students think about and know. The participants come from a public school in the city of Almería, south-eastern Spain. Given the volume of information obtained from the semi-structured group interviews conducted on a total of 126 students (male and female) and seven teachers at the school, a qualitative content analysis has been carried out to extract relevant meaning regarding the research objectives; these focused on what the students know and feel about human rights, social problems and injustices, and the role of girls and boys throughout history. Hearing, listening to and recognizing the voices of primary school boys and girls has provided us, first of all, with ethical cues to design professional teacher development experiences in line with the new times of change and uncertainty, from the framework of a critical teaching of the contents of school history. Secondly, it has guided us in the configuration of training opportunities to cover the weaknesses caused by the democratic deficit and strengthen democracy by increasing child citizen participation. In this way, we hope to contribute to the education of a global citizenry that is more critical and committed to the common good in collective decision-making in an interconnected world.
New Insights in PRRT: Lessons From 2021
Authors: Puliani Giulia , Chiefari Alfonsina , Mormando Marilda , Bianchini Marta , Lauretta Rosa , Appetecchia Marialuisa
Published: April 2022

Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs has been used for over two decades for the treatment of well-differentiated neuroendocrine tumors (NETs), and the publication of the NETTER-1 trials has further strengthened its clinical use. However, many aspects of this treatment are still under discussion. The purpose of this review is to collect and discuss the new available evidence, published in 2021, on the use of 177Lu-Oxodotreotide (DOTATATE) or 90Y-Edotreotide (DOTATOC) in adult patients with NETs focusing on the following hot topics: 1) PRRT use in new clinical settings, broaden its indications; 2) the short- and long-term safety; and 3) the identification of prognostic and predictive factors. The review suggests a possible future increase of PRRT applications, using it in other NETs, as a neoadjuvant treatment, or for rechallenge. Regarding safety, available studies, even those with long follow-up, supported the low rates of adverse events, even though 1.8% of treated patients developed a second malignancy. Finally, there is a lack of prognostic and predictive factors for PRRT, with the exception of the crucial role of nuclear imaging for both patient selection and treatment response estimation.
Seasonal Changes in an Afromontane Forest Bird Community in Tanzania
Authors: Dinesen Lars , Lehmberg Thomas , Romdal Tom S. , Sonne Jesper , Hansen Louis A.
Published: April 2022

Seasonal variation in the composition of avian communities is poorly documented in African montane forests. Using field observations, mist-netting data (63,424 NMH), recording of mixed-species flocks (160 flocks noted), and of the feeding ecology of greenbuls (757 observations), we document marked seasonal changes in a bird community in an East African montane forest (1,340–2,130 m) in the Udzungwa Mountains in south-central Tanzania. This mountain range contains the largest remaining forests in the Eastern Arc Mountains in Tanzania, part of a key global biodiversity hotspot. Our analysis is based on data in the dry and wet season from about 12 months of fieldwork. Field observation data combined with mist-net data demonstrate noticeable seasonal changes in certain species’ abundances, indicating (i) seasonal movements out of the montane forest during the dry season and (ii) movements of part of the populations for other species. Our mist-net results show a significant difference in species abundances between the two seasons driven by 16 species. We also document significant changes in diet for two species of greenbuls, which shift feeding behavior from arthropods in the wet season to include a larger proportion of fruit in their dry season diet. Our results further show that birds are more active in mixed-species flocks in the dry season, with a significantly higher average number of species and of individuals in the dry season, i.e., 11.3 (±0.52 SE) species, 32.3 (±1.76 SE) individuals] compared to the wet season 9.7 (±0.78 SE) species, 20.8 (±1.85 SE) individuals]. One of two very distinctive types of mixed-species flocks – confined to the understory – exists only in the dry season. We discuss these changes to seasonal variability in climate, i.e., temperature and precipitation.
The Role of RNA-Binding Protein HuR in Lung Cancer by RNA Sequencing Analysis
Authors: Ye Xiong , Fu Qiang , Xiao Hui
Published: April 2022

Background: The overexpression of human antigen R (HuR) has been proven in various types of cancer and is associated with the poor survival lung cancer patients. HuR overexpression stabilizes the mRNA of tumor-promoting genes by binding with 3′-UTR AU-rich elements. However, the role of HuR in the proliferation of lung cancer is unclear.

Methods: HuR expression was assessed using immunohistochemistry of tumor tissue samples from ten patients with lung cancer and ten patients with benign lung disease. Gene, protein, mRNA, and lncRNA changes in A549 HuR knockdown (KD) cells were assessed by single-cell RNA sequencing analysis. Furthermore, cell proliferation, migration, and invasion were determined by Cell Counting Kit-8 (CCK-8) assays and Transwell assays with or without Matrigel. The cell cycle was assessed by propidium iodide staining. The protein level, mRNA level and half-life of PLK1 were detected by western blotting and RT-qPCR.

Results: In clinical patients, the expression of HuR was significantly higher in lung cancer patients than in patients with benign lung disease. RNA sequencing analysis of A549 HuR knockdown cells revealed that the main function of HuR was related to ribonucleoprotein complex biogenesis. HuR was found to regulate signaling pathways mainly related to the spliceosome, RNA transport and the cell cycle. HuR KD suppressed the proliferation, migration and invasion of A549 cells, indicating its promotive role in these processes.

Conclusion: These results demonstrate that HuR plays an important role in the progression of lung cancer.
Advances in Pathogenesis, Progression, Potential Targets and Targeted Therapeutic Strategies in SARS-CoV-2-Induced COVID-19
Authors: Zhou Hong , Ni Wei-Jian , Huang Wei , Wang Zhen , Cai Ming , Sun Yan-Cai
Published: April 2022

As the new year of 2020 approaches, an acute respiratory disease quietly caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. Subsequently, COVID-19 broke out on a global scale and formed a global public health emergency. To date, the destruction that has lasted for more than two years has not stopped and has caused the virus to continuously evolve new mutant strains. SARS-CoV-2 infection has been shown to cause multiple complications and lead to severe disability and death, which has dealt a heavy blow to global development, not only in the medical field but also in social security, economic development, global cooperation and communication. To date, studies on the epidemiology, pathogenic mechanism and pathological characteristics of SARS-CoV-2-induced COVID-19, as well as target confirmation, drug screening, and clinical intervention have achieved remarkable effects. With the continuous efforts of the WHO, governments of various countries, and scientific research and medical personnel, the public’s awareness of COVID-19 is gradually deepening, a variety of prevention methods and detection methods have been implemented, and multiple vaccines and drugs have been developed and urgently marketed. However, these do not appear to have completely stopped the pandemic and ravages of this virus. Meanwhile, research on SARS-CoV-2-induced COVID-19 has also seen some twists and controversies, such as potential drugs and the role of vaccines. In view of the fact that research on SARS-CoV-2 and COVID-19 has been extensive and in depth, this review will systematically update the current understanding of the epidemiology, transmission mechanism, pathological features, potential targets, promising drugs and ongoing clinical trials, which will provide important references and new directions for SARS-CoV-2 and COVID-19 research.
The Nutritional Intervention of Resveratrol Can Effectively Alleviate the Intestinal Inflammation Associated With Celiac Disease Induced by Wheat Gluten
Authors: Yu Tian , Xie Yiting , Yuan Juanli , Gao Jinyan , Xiao Zhiwen , Wu Yong , Chen Hongbing
Published: April 2022

Background and Aims

Wheat gluten is a critical trigger for celiac disease, often causing inflammatory lesions and oxidative stress damage in the intestines of patients. In daily life, it is difficult for celiac disease patients to strictly avoid the dietary intake of gluten, which makes complementary preventive therapy particularly urgent. As such, we investigated the alleviating effects of resveratrol in vivo and in vitro models of celiac disease.

Methods

We established in vivo and in vitro models of gluten protein-induced celiac disease. The intervention effect of resveratrol was defined well based on relevant indicators of inflammation, immunity and oxidative stress, and its possible involvement in signaling pathways and genes were also identified.

Results

Resveratrol was effective in reducing intestinal oxidative stress and inflammatory damage induced by wheat gluten in both cell and mouse models for celiac disease. We identified correlations between the genes (Fgf15, Nr0b2, Aire and Ubd) and signaling pathways (PPAR, AMPK and FoxO) in which resveratrol performed critical roles.

Conclusions

Resveratrol contributed to regulate development of autoimmunity through up-regulation of Aire and Ubd genes and promote nutrient absorption in intestine through down-regulation of Fgf15 and Nr0b2 genes, as well as played a role in regulating complex response system of oxidative stress, inflammatory response and immune response in intestine by activating PPAR, AMPK and FoxO signaling pathways, thus effectively alleviating the intestinal symptoms of celiac disease.
Dragonfly Neurons Selectively Attend to Targets Within Natural Scenes
Authors: Evans Bernard John Essex , O’Carroll David Charles , Fabian Joseph Mahandas , Wiederman Steven D.
Published: April 2022

Aerial predators, such as the dragonfly, determine the position and movement of their prey even when both are moving through complex, natural scenes. This task is likely supported by a group of neurons in the optic lobe which respond to moving targets that subtend less than a few degrees. These Small Target Motion Detector (STMD) neurons are tuned to both target size and velocity, whilst also exhibiting facilitated responses to targets traveling along continuous trajectories. When presented with a pair of targets, some STMDs generate spiking activity that represent a competitive selection of one target, as if the alternative does not exist (i.e., selective attention). Here, we describe intracellular responses of CSTMD1 (an identified STMD) to the visual presentation of targets embedded within cluttered, natural scenes. We examine CSTMD1 response changes to target contrast, as well as a range of target and background velocities. We find that background motion affects CSTMD1 responses via the competitive selection between features within the natural scene. Here, robust discrimination of our artificially embedded “target” is limited to scenarios when its velocity is matched to, or greater than, the background velocity. Additionally, the background’s direction of motion affects discriminability, though not in the manner observed in STMDs of other flying insects. Our results highlight that CSTMD1’s competitive responses are to those features best matched to the neuron’s underlying spatiotemporal tuning, whether from the embedded target or other features in the background clutter. In many scenarios, CSTMD1 responds robustly to targets moving through cluttered scenes. However, whether this neuronal system could underlie the task of competitively selecting slow moving prey against fast-moving backgrounds remains an open question.
Ultra-High-Field MRI in the Diagnosis and Management of Gliomas: A Systematic Review
Authors: Shaffer Annabelle , Kwok Susanna S. , Naik Anant , Anderson Aaron T. , Lam Fan , Wszalek Tracey , Arnold Paul M. , Hassaneen Wael
Published: April 2022

Importance:

Gliomas, tumors of the central nervous system, are classically diagnosed through invasive surgical biopsy and subsequent histopathological study. Innovations in ultra-high field (UHF) imaging, namely 7-Tesla magnetic resonance imaging (7T MRI) are advancing preoperative tumor grading, visualization of intratumoral structures, and appreciation of small brain structures and lesions.

Objective

Summarize current innovative uses of UHF imaging techniques in glioma diagnostics and treatment.

Methods

A systematic review in accordance with PRISMA guidelines was performed utilizing PubMed. Case reports and series, observational clinical trials, and randomized clinical trials written in English were included. After removing unrelated studies and those with non-human subjects, only those related to 7T MRI were independently reviewed and summarized for data extraction. Some preclinical animal models are briefly described to demonstrate future usages of ultra-high-field imaging.

Results

We reviewed 46 studies (43 human and 3 animal models) which reported clinical usages of UHF MRI in the diagnosis and management of gliomas. Current literature generally supports greater resolution imaging from 7T compared to 1.5T or 3T MRI, improving visualization of cerebral microbleeds and white and gray matter, and providing more precise localization for radiotherapy targeting. Additionally, studies found that diffusion or susceptibility-weighted imaging techniques applied to 7T MRI, may be used to predict tumor grade, reveal intratumoral structures such as neovasculature and microstructures like axons, and indicate isocitrate dehydrogenase 1 mutation status in preoperative imaging. Similarly, newer imaging techniques such as magnetic resonance spectroscopy and chemical exchange saturation transfer imaging can be performed on 7T MRI to predict tumor grading and treatment efficacy. Geometrical distortion, a known challenge of 7T MRI, was at a tolerable level in all included studies.

Conclusion

UHF imaging has the potential to preoperatively and non-invasively grade gliomas, provide precise therapy target areas, and visualize lesions not seen on conventional MRI.
Overexpression of CDCA8 Predicts Poor Prognosis and Promotes Tumor Cell Growth in Prostate Cancer
Authors: Wan Shun , He Yang , Zhang Bin , Yang Zhi , Du Fang-Ming , Zhang Chun-Peng , Fu Yu-Qiang , Mi Jun
Published: April 2022

Human cell division cycle-related protein 8 (CDCA8) is an essential component of the vertebrate chromosomal passenger complex (CPC). CDCA8 was confirmed to play a role in promoting malignant tumor progression. However, the exact function of CDCA8 in the development and progression of prostate cancer (PCa) remains unclear. In this study, the database GSE69223 was downloaded by the gene expression omnibus (GEO) database, as well as CDCA8 expression differences in multiple tumor tissues and normal tissues were detected by The Cancer Genome Atlas (TCGA), TIMER, Oncomine, and Ualcan databases. Kaplan-Meier and Cox regression methods were used to analyze the correlation between CDCA8 expression and prognosis in PCa. We confirmed the expression of CDCA8 in PCa tissues by HPA. We also analyzed the association of CDCA8 expression with PCa clinical characteristics in the TCGA database. To further understand the role of CDCA8 in PCa, we assessed the effects of CDCA8 on PCa cell growth, proliferation, and migration in vitro studies. As a result, CDCA8 was significantly overexpressed in PCa cells compared with normal prostate cells. High CDCA8 expression predicts poor prognosis in PCa patients, and CDCA8 expression was higher in high-grade PCa. In addition, silencing of CDCA8 significantly inhibited PCa cell proliferation and migration. In summary, CDCA8 promoted the proliferation and migration of PCa cells.
Long-Term Results of a Phase 2 Study of Definitive Chemoradiation Therapy Using S-1 for Esophageal Squamous Cell Carcinoma Patients Who Were Elderly or With Serious Comorbidities
Authors: Chen Yun , Zhu Zhengfei , Zhao Weixin , Liu Qi , Zhang Junhua , Deng Jiaying , Ai Dashan , Lu Saiquan , Jiang Liuqing , Tseng Ihsuan , Jia Huixun , Zhao Kuaile
Published: April 2022

Background

The optimal evidence-based management for the subsets of locally advanced esophageal squamous cell carcinoma (ESCC) patients who rejected or were intolerant to intravenous chemotherapy due to old age or serious comorbidities is currently lacking. This study aimed to assess the safety and local control rate (LCR) of S-1 (tegafur–gimeracil–oteracil potassium) combined with radiotherapy in these subsets of ESCC patients.

Methods

Locally advanced ESCC patients who rejected or were intolerant to intravenous chemotherapy due to age >75 years or serious comorbidities were enrolled in a prospective, single-arm, phase 2 trial. The patients were treated with definitive concurrent chemoradiotherapy with S-1, which was administered orally twice daily for 28 days. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end-point was the 3-year LCR.

Results

One hundred five ESCC patients were recruited between March 2013 and October 2015. At the median follow-up of 73.1 months (IQR 65.5–81.4 months), 3-year LCR was 61.1%, and 1, 3, and 5-year overall survival was 77.9, 42.3, and 24.8% respectively. For safety analysis, ≥grade 3 acute adverse events included thrombocytopenia (6.7%), leukopenia (2.9%), anemia (1.0%), anorexia (1.0%), fatigue (10.5%), hiccup (1.0%), pneumonitis (4.8%), and esophagitis (3.8%). Two patients (1.9%) died of late esophageal hemorrhage, and one patient (1.0%) died of late radiation-induced pneumonitis.

Conclusion

S-1 is a promising regimen in concurrent chemoradiotherapy with low toxicity and a favorable LCR in ESCC patients who rejected or were intolerant to intravenous chemotherapy due to old age or serious comorbidities.

Clinical Trial Registration

ClinicalTrials.gov, NCT01831531.
Cerebrospinal Fluid Histamine Levels in Healthy Children and Potential Implication for SIDS: Observational Study in a French Tertiary Care Hospital
Authors: Plancoulaine Sabine , Guyon Aurore , Inocente Clara-Odilia , Germe Philippine , Zhang Min , Robert Philippe , Lin Jian-Sheng , Franco Patricia
Published: April 2022

Objective

A defect of the waking systems could constitute a factor of vulnerability for sudden infant death syndrome (SIDS). A decrease in orexin levels, which promotes wakefulness and activates histaminergic neurons (another hypothalamic wake-promoting system) has already been demonstrated between 2 and 6 months. This work aims to study the levels of histamine (HA), tele-methylhistamine (t-MeHA), its direct metabolite, and t-MeHA/HA ratio in the cerebrospinal fluid (CSF) of healthy children, to evaluate the maturation of the histaminergic system and its possible involvement in SIDS.

Methods

Seventy Eight French children between 0 and 20 years (48.7% boys) were included, all of whom had a clinical indication for lumbar puncture, but subsequently found to be normal. Measurements of HA and t-MeHA in CSF were performed by reverse phase liquid chromatography coupled to mass spectrometry detection. Statistical analyses were performed using Spearman correlations and Non-parametric pairwise ranking tests.

Results

A negative correlation was found between age and CSF HA (r = −0.44, p < 10−4) and t-MeHA (r = −0.70, p < 10−4) levels. In pairwise comparisons, no difference in CSF HA and t-MeHA levels was observed between youngest age groups (i.e., 0–2 mo vs. 3–6 mo), but CSF HA and t-MeHA levels were significantly lower in older children (i.e., >6 mo vs. 0–6 mo). The CSF HA decrease with age was only observed in boys, who also presented global lower CSF HA levels than girls.

Conclusion

CSF HA and t-MeHA levels decrease with age in boys, and global levels are lower in boys than in girls. These results reveal changes in histaminergic transmission and metabolism during maturation. Whether lower CSF histamine values in boys compared to girls could contribute to their higher risk of SIDS warrants further research.
Application of Argon Plasma Coagulation for Gastrointestinal Angiodysplasia in Children— Experience From a Tertiary Center
Authors: Yeh Pai-Jui , Le Puo-Hsien , Chen Chien-Chang , Chao Hsun-Chin , Lai Ming-Wei
Published: April 2022

Background

Argon plasma coagulation (APC) has been applied in adults to treat various diseases, including vascular lesions in the gastrointestinal (GI) tract. However, angiodysplasia (AD) is an uncommon cause of pediatric GI bleeding, while the experience of treating AD with APC was rarely reported.

Methods

Five children with AD in the GI tract successfully treated with APC were reviewed.

Results

Three of the five patients were girls, and the age at diagnosis ranged from 1.5 months to 10.5 years of age. One patient with gastric AD manifested with tarry stool, and the rest had colonic AD, which caused various degrees of bloody stool. Three patients had evident anemia. All patients received an endoscopic diagnosis, and two had compatible findings in radiographic exams. Each patient underwent one APC treatment session, and none encountered procedure-related complications or re-bleeding.

Conclusion

AD can be an etiology of GI bleeding even in neonates. APC is an effective and safe therapy for symptomatic AD in children.
Cinobufacini Injection Inhibits the Proliferation of Triple-Negative Breast Cancer Through the Pin1–TAZ Signaling Pathway
Authors: Kong Lu , Liu Xu , Yu Bing , Yuan Ye , Zhao Qianru , Chen Yuru , Qu Bin , Du Xue , Tian Xiaoxuan , Shao Rui , Wang Yu
Published: April 2022

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC), which is characterized by the total absence of human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and estrogen receptor (ER) expression. Cinobufacini injection (CI) is the aqueous extract from the dry skin of Bufo gargarizans, which is broadly used for the treatment of malignant tumors. However, the potential mechanism of CI against TNBC has not been fully revealed. In this study, we found that CI inhibited the proliferation of MDA-MB-231 and 4T1 cells in a time- and dose-dependent manner. RNA-seq data showed that downregulated and upregulated genes were mainly enriched in biological processes related to tumor cell proliferation, including cell cycle arrest and regulation of apoptosis signaling pathways. Indeed, after CI treatment, the protein level of CDK1 and Bcl-2/Bax decreased, indicating that CI induced the cell cycle of MDA-MB-231 arrest in the G2/M phase and increased the rate of apoptosis. Meanwhile, CI significantly inhibited the growth of tumor in vivo, and RNA-seq data showed that the TAZ signaling pathway played a vital role after CI treatment. Both immunohistochemistry and Western blot analysis confirmed the downregulation of Pin1 and TAZ, caused by CI treatment. Furthermore, the bioinformatics analysis indicated that Pin1 and TAZ were indeed elevated in TNBC patients, with poor staging, classification, and patient survival rate. In conclusion, CI effectively inhibited the proliferation of TNBC in vitro and in vivo and induced their apoptosis and cycle arrest through the Pin1–TAZ pathway.
Efficacy of Systemic Biologic Drugs in Pediatric Psoriasis: Evidence From Five Selected Randomized Clinical Trials
Authors: Di Lernia Vito , Macca Laura , Peterle Lucia , Ingrasciotta Ylenia , Trifirò Gianluca , Guarneri Claudio
Published: April 2022

Background: Psoriasis is a chronic, immune-mediated skin disease that may occur at any age. Prevalence in children ranges between 0.5 and 1.0% across Europe. Approximately 10–20% of paediatric psoriasis patients are moderate-to-severe in severity and may require the use of systemic therapy.

Objective: Recently, newer targeted, systemic therapies have been licensed for treatment of moderate-to-severe paediatric psoriasis. The objective of this study was to evaluate the short-term efficacy of available antipsoriatic systemic drugs in children with a narrative synthesis of key efficacy from randomized clinical trials.

Methods: A systematic review of literature was performed on Medline and embase databases and the Cochrane Central Register of Controlled Trials. Randomized clinical trials investigating the efficacy of treatments licensed by the US Food and Drug Administration and/or the European Medicines Agency for paediatric and adolescent psoriatic population were retrieved and analyzed. Data from this literature review was assessed in line with GRADE (grading of recommendations, assessment, development and evaluations). The short-term (12-16 weeks) clinical efficacy from baseline was evaluated according to the Psoriasis Area and Severity Index (PASI) 75 and 90 compared to baseline. Illustrative comparative risks, relative risk (RR) and the number needed to treat (NNT) for response on PASI 75 and PASI 90 were extracted.

Results: A total of five relevant studies were identified on two TNF-alpha blockers (etanercept and adalimumab), the IL12/23 inhibitor ustekinumab and two IL-17 inhibitors (ixekizumab, secukinumab). Comparators were placebo (3 studies), placebo and etanercept (1 study) methotrexate (1 study). All examined drugs resulted efficacious. The probability to achieve PASI 75 and PASI 90 was higher for the IL-12/23 and IL-17 inhibitors. Overall, the anti-IL17s and the anti-IL12/23 antibodies showed a more favourable NNT for PASI 75, whereas IL-17 inhibitors for PASI 90.

Conclusion: The approved biological therapies may be beneficial for the treatment of moderate to severe plaque psoriasis in children and adolescents. Since psoriasis is a chronic and often challenging condition with no definitive solution, systematic evaluations of long-term efficacy, drug survival and adverse effects may help careful, individualized, patient-centered clinical decision making.
Single Dose Comparative Bioavailability Study of Lisdexamfetamine Dimesylate as Oral Solution Versus Reference Hard Capsules in Healthy Volunteers
Authors: Rizea-Savu Simona , Duna Simona Nicoleta , Panagiotopoulos Dimitrios , Sandulovici Roxana Colette
Published: April 2022

Lisdexamfetamine is an inactive prodrug of dexamfetamine that is used for the second-line treatment of attention-deficit/hyperactivity disorder (ADHD) and moderate to severe binge eating disorder (BED). Once in the blood, the prodrug is hydrolyzed in erythrocyte cytosol, thus releasing the active dexamfetamine. We here present a fully validated HPLC-MS/MS analytical method for simultaneous determination of lisdexamfetamine and dexamfetamine in human plasma and the first published comparative bioavailability study of lisdexamfetamine including a GMP finished product formulated as oral solution. The Test (T)/Reference (R) ratios for the geometric means (%) of the primary pharmacokinetic (PK) parameters and their corresponding two-sided 90% confidence intervals (CIs) were contained within the predefined regulatory limits of 80.00–125.00% for both lisdexamfetamine and dexamfetamine. While for the lisdexamfetamine prodrug, PK results for the two formulations were slightly different due to the distinct dissolution state at administration, the PK parameters calculated for dexamfetamine were almost identical. A potential explanation of this phenomenon, already described in literature, is that biotransformation of lisdexamfetamine by red blood cells (rather than its release within the gastrointestinal tract) is the process controlling the rate of dexamfetamine delivery.
Superalkalis for the Activation of Carbon Dioxide: A Review
Authors: Srivastava Harshita , Srivastava Ambrish Kumar
Published: April 2022

The activation of carbon dioxide is essential not only for global carbon balance but also for its conversion into fuel. As CO2 is highly stable, it is quite challenging to activate or reduce CO2. Recently, the ability of superalkalis to easily transfer an electron to CO2 has been proposed in several studies. The superalkalis are species possessing lower ionization energy than alkali atoms. These are hypervalent species, having an excess of electrons. Owing to this, they possess strong reducing power and cause the linear structure of CO2 to bend by transferring an electron to it. Herein, we present a comprehensive account of the single-electron reduction and activation of CO2 by various kinds of superalkalis. This review also includes a novel strategy for the capture and storage of CO2 by superalkali.
Ventricular-Vascular Uncoupling in Heart Failure: Effects of Arterial Baroreflex-Induced Sympathoexcitation at Rest and During Exercise
Authors: Mannozzi Joseph , Al-Hassan Mohamed-Hussein , Kaur Jasdeep , Lessanework Beruk , Alvarez Alberto , Massoud Louis , Bhatti Tauheed , O’Leary Donal S.
Published: April 2022

Autonomic alterations in blood pressure are primarily a result of arterial baroreflex modulation of systemic vascular resistance and cardiac output on a beat-by-beat basis. The combined central and peripheral control by the baroreflex likely acts to maintain efficient energy transfer from the heart to the systemic vasculature; termed ventricular-vascular coupling. This level of control is maintained whether at rest or during exercise in healthy subjects. During heart failure, the ventricular-vascular relationship is uncoupled and baroreflex dysfunction is apparent. We investigated if baroreflex dysfunction in heart failure exacerbated ventricular-vascular uncoupling at rest, and during exercise in response to baroreceptor unloading by performing bilateral carotid occlusions in chronically instrumented conscious canines. We observed in healthy subjects that baroreceptor unloading caused significant increases in effective arterial elastance (Ea) at rest (1.2 ± 0.3 mmHg/ml) and during exercise (1.3 ± 0.2 mmHg/ml) that coincided with significant increases in stroke work (SW) (1.5 ± 0.2 mmHg/ml) and (1.6 ± 0.2 mmHg/ml) suggesting maintained ventricular-vascular coupling. Heart Failure significantly increased the effect of baroreceptor unloading on Ea at rest (3.1 ± 0.7 mmHg/ml) and during exercise (2.3 ± 0.5 mmHg/ml) whereas no significant increases in stroke work occurred, thus signifying further ventricular-vascular uncoupling. We believe that the enhanced ventricular-vascular uncoupling observed during baroreceptor unloading only worsens the already challenged orthostatic and exercise tolerance and thereby contributes to poor exercise performance and quality of life for heart failure patients.
The Endophyte Trichoderma asperellum M2RT4 Induces the Systemic Release of Methyl Salicylate and (Z)-jasmone in Tomato Plant Affecting Host Location and Herbivory of Tuta absoluta
Authors: Agbessenou Ayaovi , Akutse Komivi S. , Yusuf Abdullahi A. , Khamis Fathiya M.
Published: April 2022

The use of endophytic fungi has dramatically increased plant performance through the enhancement of plant protection against abiotic and biotic stressors. We previously demonstrated that the endophytic fungus Trichoderma asperellum M2RT4 improves tomato defenses against the tomato leafminer Tuta absoluta through the reduction of oviposition, leafmining, pupation, and adult emergence. However, the underlying mechanism by which the presence of this endophytic fungus within tomato host plant affects T. absoluta host selection and life-history traits is unknown. We tested the behavioral responses of T. absoluta in Y-tube olfactometer bioassays and found that females preferred non-inoculated tomato plants against those inoculated by endophytes. Additionally, T. absoluta females were not attracted to non-inoculated infested nor to inoculated-infested tomato plants. Chemical analysis revealed the emission of methyl salicylate in inoculated tomato plant and an increase in the amounts of monoterpenes emitted from non-inoculated infested plants. Additionally, we found that upon herbivory, T. asperellum M2RT4 modulates tomato plant chemistry through the production of (Z)-jasmone thus activating both salicylic and jasmonic acid defense pathways. Further, T. absoluta females were attracted to monoterpernes including α-pinene, 2-carene, and β-phellandrene but repelled by methyl salicylate. Methyl salicylate could therefore be considered as a good semiochemical-based candidate for sustainable T. absoluta management using a “push-pull” approach. However, in dose-response bioassays, females of T. absoluta did not show any preference to the four component-blend (α-pinene, 2-carene, β-phellandrene, and methyl salicylate). (Z)-jasmone-treated tomato leaflets significantly reduced the leafmining activity of the pest at the concentration of 10 ng/μL and causing the highest larval mortality rate (83%) with the shortest LT50 (1.73 days) 7 days post-treatment. T. asperellum M2RT4 effect on herbivore performance was then (Z)-jasmone-mediated. These findings expand our understanding of how the endophytic fungus T. asperellum M2RT4 could mediate chemical interactions between T. absoluta and its host plant which are potentially important for development of environmentally friendly T. absoluta management programs.
Protein Biofortification in Lentils (Lens culinaris Medik.) Toward Human Health
Authors: Salaria Sonia , Boatwright Jon Lucas , Thavarajah Pushparajah , Kumar Shiv , Thavarajah Dil
Published: April 2022

Lentil (Lens culinaris Medik.) is a nutritionally dense crop with significant quantities of protein, low-digestible carbohydrates, minerals, and vitamins. The amino acid composition of lentil protein can impact human health by maintaining amino acid balance for physiological functions and preventing protein-energy malnutrition and non-communicable diseases (NCDs). Thus, enhancing lentil protein quality through genetic biofortification, i.e., conventional plant breeding and molecular technologies, is vital for the nutritional improvement of lentil crops across the globe. This review highlights variation in protein concentration and quality across Lens species, genetic mechanisms controlling amino acid synthesis in plants, functions of amino acids, and the effect of antinutrients on the absorption of amino acids into the human body. Successful breeding strategies in lentils and other pulses are reviewed to demonstrate robust breeding approaches for protein biofortification. Future lentil breeding approaches will include rapid germplasm selection, phenotypic evaluation, genome-wide association studies, genetic engineering, and genome editing to select sequences that improve protein concentration and quality.
Incidence of Coffee Leaf Rust in Vietnam, Possible Original Sources and Subsequent Pathways of Migration
Authors: Le Cham Thi Mai , Okane Izumi , Ono Yoshitaka , Tsuda Yoshiaki , Yamaoka Yuichi
Published: April 2022

This research focused on the incidence and population genetics of coffee leaf rust (CLR) fungus, Hemileia vastatrix, to estimate the possible original source(s) and subsequent migration pathways of wind-borne and human-aided spores in three main coffee production regions (Northwest, Central Highlands, and Southeast) in Vietnam. In southern Vietnam (Central Highlands and Southeast), Coffea canephora covers the majority area, while Catimor lines of C. arabica accounts for 95% of the coffee plantations in northwestern Vietnam. Field surveys conducted at eighty-five plantations, show coffee leaf samples infected by the rust fungus across forty-one plantations. Catimor varieties exhibited high levels of susceptibility with severe rust symptoms, while robusta varieties had varying degrees of susceptibility. We analyzed 863−869 base pairs of internal transcribed spacer (ITS) region from 83 samples (41 sequences from Vietnam, 2 from Thailand, and the remaining 40 from American countries); and fifty-two haplotypes consisting of 123 polymorphic sites were detected. Although the analysis of molecular variance (AMOVA) indicates significant genetic differentiation in the H. vastatrix populations in Vietnam, there was no clear genetic structure with respect to the three geographic areas surveyed. Based on the haplotype network, NeighborNet analysis, and geographical distribution patterns of the haplotypes, five haplotypes were identified as early established, from which most other haplotypes in Vietnam were derived. The early established haplotypes were found in the highest frequency in Northwest Vietnam. This finding corresponds to the earliest record of CLR in Vietnam. The phylogenetic network analysis also illustrated that H. vastatrix had expanded from the northwest to southern Vietnam. Pairwise genetic distance analysis and the geophylogenetic tree also suggests that CLR was first established in the Northwest. In addition, some scattered individuals on the principal coordinate analysis (PCoA) diagram and several separated haplotypes in the phylogenetic networks indicated that other branches of CLR in Vietnam were initiated in the Central Highlands. Hemileia vastatrix from these branches have been spreading in southern Vietnam.
Associations of Changes in Religiosity With Flourishing During the COVID-19 Pandemic: A Study of Faith Communities in the United States
Authors: Jacobi Christopher Justin , Cowden Richard G. , Vaidyanathan Brandon
Published: April 2022

This study explored the extent to which perceived changes in religiosity from before to during the COVID-19 pandemic are associated with flourishing. Participants from a diverse set of faith communities in two United States metropolitan regions (N = 1,480) completed an online survey between October and December 2020. The survey included items capturing perceived changes in four dimensions of religiosity (i.e., importance of religion, frequency of prayer, frequency of religious service attendance, and sense of connectedness to one’s faith community) and a multidimensional measure of flourishing. Based on multilevel regressions, results indicated that self-reported decreases in each dimension of religiosity were associated with lower overall flourishing. This pattern of findings was largely similar for the domains of flourishing, with some variation in the strength of associations that emerged. An increase in frequency of religious service attendance was associated with lower overall flourishing and lower scores on selected domains of flourishing (e.g., mental and physical health), indicating possible evidence of religious coping. Faith communities might have to find ways of supporting members during the challenging COVID-19 period to prevent long-term declines in flourishing.
“It Is My Choice to Control Myself!”: Testing the Mediating Roles of Expectancy and Value in the Association Between Perceived Choice and Self-Control Success
Authors: Chow Tak Sang , Hui Chin Ming , Siu Tiffany Sok U.
Published: April 2022

Past research suggested that when individuals feel that it is their free choice to perform a task, they are more likely to succeed. However, little has been known about the effect of perceived choice of self-control and the psychological processes underlying the benefits of this perception in everyday contexts. To fill this gap, a 7-day experience sampling study (115 college students and 1,725 reported episodes of self-control) was conducted to test whether confidence in sustaining the current self-control activity (expectancy) and perceived value of current self-control (value) could mediate the link between perceived choice and success in the current self-control activity. The results of multilevel analysis suggested that the perceived choice can boost self-control success by increasing expectancy and value of self-control. These findings add mechanistic understanding of the effect of perceived choice on self-control success.