bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital left lobe megaly of liver resembling splenic pathology: a diagnostic dilemma confirmed bySPECT-CT of liver-spleen scan
Authors: Bhattacharjee Puja , Mandal Tapati , Quddus Sharmin , Mutsuddi Pupree , Akhter Papia , Islam Md Azharul , Md Ismail - , Siddique Abu Bakker , Islam Reajul , Haque Jasmine Ara
Published: March 2021

Liver scintigraphy is a specialized nuclear medicine imaging technique used to diagnose hepatic pathological conditions as well as to assess the function of the liver. Itis also used to follow the progress of treatment of certain diseases. This procedure may be referred as liver-spleen scan because the spleen is alsoevaluateddue to its proximity and close functional relationship to liver.SPECT-CT correlation along with planar images increases the specificity of the test and can guide the physicians to rule outdiagnostic dilemma regarding certain hepatic & splenic diseases. Here, we present a case where the patient was initially suspected tohave splenomegaly with splenic hematomabut finally confirmedas unusuallyenlarged left lobe of liverand normal sized spleen with SPECT-CT of liver-spleen scan.

Bangladesh J. Nuclear Med. 22(2): 161-165, Jul 2019
Environmental changes and general health condition
Authors: Islam Nabhira Aftabi Binte , Uddin Nasir , Sultana Hafiza
Published: March 2021

Background: The environment directly affects health status and plays a major role in quality of life, years of healthy life lived, and health disparities. Humans impact the physical environment in many ways, like over population, pollution, burning fossil fuels, and deforestation. The study was conducted to assess environmental changes and the general health condition.

Methods: It was a cross-sectional study. To assess environmental  changes  and  general  health  condition of dental second year student and data were collected by checklist. Respondents were selected purposively. Data were collected on 8th September 2019 at Marks medical college dental unit. Samples were second year dental students, who were presented in class on that date.

Results: Distribution of the respondents according to sex, 64.5% were female and 35.5% male.  Majority  of the student (51.6%) were come from outside of the Dhaka. 45.2% respondents were lived in Dhaka by born. 80.6% respondents lived with their family. It was alarming that 83.9% respondents never did physical exercise and only 16.1% did sometimes physical exercise. 61.3% respondent admired that they have hair loss, 16.1% has no problems in skin but others has problems. 51 .6% has dust, 1 2.9% has food allergy. 6.5 % has frequently exposure of diarrhea diseases. Often 67.7% has been suffered by headache. Reason of seasonal changes  29%  respondents suffered by itching. 77.4% and 83 .9% respondents were affected by anxiety and depression. 77.4% respondent has knowledge about weather change in our country as well as whole world.

Conclusion: General health condition maybe changed for multiple causes. Environment is one of the strong factors. The relation between environmental temperature and health has been known for a very long time.

JOPSOM 2020; 39(1): 73-77
Life style change and reverse cholesterol transport in obese women
Authors: Králová Lesná I , Suchánek P , Kovář J , Poledne R
Published: March 2021

HDL cholesterol resp. apolipoprotein A1 concentrations are tools
to estimate individual CVD risk, although only a part of HDL
particles participate in reverse cholesterol transport (RCT). This
discrepancy was analyzed in life style change based on increase
of physical activity and dietary counseling. Efflux of cholesterol
from pre-labeled macrophages to plasma acceptors of tested
individuals was used as an RCT measure. Changes of lipoprotein
parameters, glucose, fasting insulin concentrations and RCT were
analyzed in 15 obese women after 9-week intervention consisted
of 5 sessions of increased physical activity per week. Controlled
increase in physical activity for 9 weeks induced a decrease of
body weight averaging 9 kg (ranged from 2.3 to 15.5 kg). The
intervention leads to significant decreases of triglycerides,
apoprotein A1 and apoprotein B concentration, whereas total
cholesterol, LDL cholesterol and HDL cholesterol did not change
significantly. The increase of RCT was not significant, but there
was highly significant negative correlation between individual
decrease of body weight and an increase of RCT. Significant
increase of RCT was found in 13 persons with a weight reduction
more than 3.5 kg. Substantial weight loss is necessary to
increase RCT.
DIagnosys: An Analytical Framework for the Identification of Elementary School Students with Intellectual Disability
Authors: Tafla Tally Lichtensztejn , Brunoni Decio , Carreiro Luiz Renato Rodrigues , Seabra Alessandra Gotuzo , Silva Leandro Augusto da , Bastos Daiane Cristina de Souza , Rossi Ana Claudia , Santos Pedro Henrique Araujo dos , Teixeira Maria Cristina Triguero Veloz
Published: March 2021

The identification of mild Intellectual Disability (ID) usually occurs late when the demands intrinsic to literacy reveal the typical signs to the educators. The study had two phases. The first phase aimed at developing a computation system (framework), named DIagnosys, an instrument designed to help educators identify students with characteristics compatible with ID, and to describe the operational, tactical, and strategic levels. The second phase verified the framework predictive sensitivity, using an artificial intelligence algorithm. For that purpose, the framework was applied in 51 teachers and their 1,758 students of 2nd and 4th grade, and their respective parents. We collected data using a checklist of signs compatible with ID, the Brief Problem Monitor (teacher and parent versions), the Wechsler Abbreviated Scale of Intelligence, and medical evaluation. The statistical analysis using a Confusion Matrix showed an accuracy of 82 and 95% for teacher and parent checklists, respectively. The decision-making model showed high indexes of sensitivity, providing evidence that teachers can be protagonists of the teaching-learning process mobilizing the parents to use the health care services.
Serum Lipid Levels and Treatment Outcomes in Women Undergoing Assisted Reproduction: A Retrospective Cohort Study
Authors: Cai Wang-Yu , Luo Xi , Chen Erxidi , Lv Houyi , Fu Kaiyou , Wu Xiao-Ke , Xu Jian
Published: March 2021

Objective

To evaluate associations between serum lipid levels and treatment outcomes in women undergoing assisted reproduction.

Materials and Methods

The study included 2011 women who underwent in vitro fertilization/intracytoplasmic sperm injection with fresh embryo transfer. Serum lipid evaluation included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Ovarian stimulation outcomes included endometrial thickness and the number of oocytes retrieved, and reproductive outcomes included live birth, clinical pregnancy, and miscarriage.

Results

Higher HDL-C quartiles were associated with more oocytes retrieved. Lower TC (quartile 1 odds ratio [OR] 1.59 [1.21–2.08], quartile 3 OR 1.36 [1.04–1.77]), LDL-C (quartile 1 OR 1.41 [1.07–1.86]), and TG (quartile 2 OR 1.39 [1.06–1.84]) were independently associated with clinical pregnancy after adjusting for potential confounders. Lower LDL-C (quartile 1 OR 2.22 [1.58–3.13], quartile 2 OR 1.78 [1.27–2.50], quartile 3 OR 1.51 [1.07–2.13]), TC (quartile 1 OR 1.39 [1.00–1.93]), TG (quartile 1 OR 1.44 [1.03–2.03], quartile 2 OR 1.46 [1.04–2.04], quartile 3 OR 1.44 [1.04–1.99]), and higher HDL-C (quartile 2 OR 0.71 [0.51–0.99]) were independently associated with live birth. Higher LDL-C (quartile 1 OR 0.44 [0.30–0.66], quartile 2 OR 0.49 [0.33–0.73], quartile 3 OR 0.63 [0.43–0.94]) and lower HDL-C (quartile 1 OR 1.60 [1.07–2.39]) were independently associated with miscarriage.

Conclusions

Serum lipid levels were associated with treatment outcomes in women undergoing assisted reproduction.
UV-B Radiation Tolerance and Temperature-Dependent Activity Within the Entomopathogenic Fungal Genus Metarhizium in Brazil
Authors: Couceiro Joel da Cruz , Fatoretto Maíra Blumer , Demétrio Clarice Garcia Borges , Meyling Nicolai Vitt , Delalibera Ítalo
Published: March 2021

Metarhizium comprises a phylogenetically diverse genus of entomopathogenic fungi. In Brazil, Metarhizium anisopliae s.str. subclade Mani 2 is predominantly isolated from insects, while M. robertsii and M. brunneum mostly occur in the soil environment. Solar radiation and high temperatures are important abiotic factors that can be detrimental to fungal propagules. We hypothesized that among 12 Brazilian isolates of Metarhizium spp., M. anisopliae Mani 2 (n = 6), being adapted to abiotic conditions of the phylloplane, is more tolerant to UV light and high temperatures than M. robertsii (n = 3) and M. brunneum (n = 3). Inoculum of each isolate was exposed to UV-B for up to 8 h and viability evaluated 48 h later. After 8 h under UV-B, most of the isolates had germination rates below 5%. Discs of mycelia were incubated at different temperatures, and diameter of colonies were recorded for 12 days. Mycelia of M. robertsii isolates grew faster at 33 °C, while M. anisopliae and M. brunneum grew most at 25 °C. Dry conidia were incubated at 20, 25 or 40 °C for 12 days, and then viabilities were examined. At 40 °C, conidia of five M. anisopliae isolates were the most tolerant. In the three experiments, considerable intra- and inter-specific variability was detected. The results indicate that conclusions about tolerance to these abiotic factors should be made only at the isolate level.
Integrated Transcriptomic and Epigenetic Study of PCOS: Impact of Map3k1 and Map1lc3a Promoter Methylation on Autophagy
Authors: Qin Yulan , Li Ting , Zhao Hui , Mao Zhanrui , Ding Chunxia , Kang Yani
Published: March 2021

Polycystic ovary syndrome (PCOS) is a prevalent heterogeneous endocrine and metabolic disorder in women of reproductive age. Epigenetic mechanisms contribute to the development of PCOS. Nevertheless, the role of DNA methylation in the development of PCOS remains unclear. To investigate the molecular mechanisms underlying the hyperandrogenic phenotype of PCOS, dihydrotestosterone (DHT)-induced prenatally androgenized (PNA) mice were used to mimic this phenotype. Ovarian samples from PNA and control mice were subjected to methyl-CpG-binding domain (MBD)-seq and RNA-seq, and validation was conducted using methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (RT-qPCR). Immunohistochemical analysis (using anti-LC3II antibody) and transmission electron microscopy were conducted using ovarian tissue sections (which included granulosa cells) from PNA and control mice. There were 857 genes with differentially methylated promoter regions and 3,317 differentially expressed genes (DEGs) in the PNA mice compared to the control mice. Downregulation of Dnmt1 (which encodes DNA methyltransferase 1), accompanied by global hypomethylation, was observed in the PNA mice compared to the control mice. The promoter regions of Map3k1 (which encodes MEKK1) and Map1lc3a (which encodes LC3II) were hypomethylated, accompanied by upregulation of Map3k1 and Map1lc3a mRNA expression. The autophagy profiling results showed that LC3II protein expression and autophagosomes were significantly increased in the granulosa cells of PNA mice. Additionally, the mRNA expression of genes related to the mitogen-activated protein kinase (MAPK)/p53 pathway (Mapk14, Mapkapk3, and Trp53) and the autophagy-related gene Becn1 were significantly increased. DHT could change the DNA methylation and transcription level of Map3k1 and lead to an activation of autophagy in granulosa cells. These observations indicated that the change in autophagy may be driven by MAPK/p53 pathway activation, which may have been caused by DHT-induced transcriptional, and the methylation level changed of the key upstream gene Map3k1. Our study provides a novel genetic basis and new insights regarding the pathogenesis of PCOS.
Generation of Transgenic Mice that Conditionally Overexpress Tenascin-C
Authors: Yonebayashi Saori , Tajiri Kazuko , Hara Mari , Saito Hiromitsu , Suzuki Noboru , Sakai Satoshi , Kimura Taizo , Sato Akira , Sekimoto Akiyo , Fujita Satoshi , Okamoto Ryuji , Schwartz Robert J. , Yoshida Toshimichi , Imanaka-Yoshida Kyoko
Published: March 2021

Tenascin-C (TNC) is an extracellular matrix glycoprotein that is expressed during embryogenesis. It is not expressed in normal adults, but is up-regulated under pathological conditions. Although TNC knockout mice do not show a distinct phenotype, analyses of disease models using TNC knockout mice combined with in vitro experiments revealed the diverse functions of TNC. Since high TNC levels often predict a poor prognosis in various clinical settings, we developed a transgenic mouse that overexpresses TNC through Cre recombinase-mediated activation. Genomic walking showed that the transgene was integrated into and truncated the Atp8a2 gene. While homozygous transgenic mice showed a severe neurological phenotype, heterozygous mice were viable, fertile, and did not exhibit any distinct abnormalities. Breeding hemizygous mice with Nkx2.5 promoter-Cre or α-myosin heavy chain promoter Cre mice induced the heart-specific overexpression of TNC in embryos and adults. TNC-overexpressing mouse hearts did not have distinct histological or functional abnormalities. However, the expression of proinflammatory cytokines/chemokines was significantly up-regulated and mortality rates during the acute stage after myocardial infarction were significantly higher than those of the controls. Our novel transgenic mouse may be applied to investigations on the role of TNC overexpression in vivo in various tissue/organ pathologies using different Cre donors.
Tertiary Lymphoid Structure-B Cells Narrow Regulatory T Cells Impact in Lung Cancer Patients
Authors: Germain Claire , Devi-Marulkar Priyanka , Knockaert Samantha , Biton Jérôme , Kaplon Hélène , Letaïef Laïla , Goc Jérémy , Seguin-Givelet Agathe , Gossot Dominique , Girard Nicolas , Validire Pierre , Lefèvre Marine , Damotte Diane , Alifano Marco , Lemoine François M. , Steele Keith E. , Teillaud Jean-Luc , Hammond Scott A. , Dieu-Nosjean Marie-Caroline
Published: March 2021

The presence of tertiary lymphoid structures (TLS) in the tumor microenvironment is associated with better clinical outcome in many cancers. In non-small cell lung cancer (NSCLC), we have previously showed that a high density of B cells within TLS (TLS-B cells) is positively correlated with tumor antigen-specific antibody responses and increased intratumor CD4+ T cell clonality. Here, we investigated the relationship between the presence of TLS-B cells and CD4+ T cell profile in NSCLC patients. The expression of immune-related genes and proteins on B cells and CD4+ T cells was analyzed according to their relationship to TLS-B density in a prospective cohort of 56 NSCLC patients. We observed that tumor-infiltrating T cells showed marked differences according to TLS-B cell presence, with higher percentages of naïve, central-memory, and activated CD4+ T cells and lower percentages of both immune checkpoint (ICP)-expressing CD4+ T cells and regulatory T cells (Tregs) in the TLS-Bhigh tumors. A retrospective study of 538 untreated NSCLC patients showed that high TLS-B cell density was even able to counterbalance the deleterious impact of high Treg density on patient survival, and that TLS-Bhigh Treglow patients had the best clinical outcomes. Overall, the correlation between the density of TLS-Bhigh tumors with early differentiated, activated and non-regulatory CD4+ T cell cells suggest that B cells may play a central role in determining protective T cell responses in NSCLC patients.
An Inverted Management Strategy for the Fishery of Endangered Marine Species
Authors: Pinheiro Hudson T. , Nunes Jose A. C. C. , Coni E. O. C. , Almeida E. C. G. , Sampaio C. L. S. , Ferreira Carlos E. L. , Meirelles Pedro M. , Hostim-Silva M. , Pereira Pedro H. C. , Giglio Vinicius J. , Gasparini J. L. , Rocha L. A. , Ferreira Camilo M.
Published: March 2021

Overfishing is notorious for triggering population collapses and disrupting marine biological functioning worldwide. To counter such a threat, policy-makers have created and implemented multiple management strategies, but most were incapable to prevent the decline of several key species. Here, we discuss a new management strategy in force since June 2019 in Brazil that aims to deter the overfishing of parrotfish species of the genera Scarus and Sparisoma. This innovative strategy, here referred to as inverted management, allows the capture of endangered parrotfish species inside management areas, such as partially protected marine areas—MPAs, but bans it elsewhere. This initiative is supposed to be built in a partnership among the government, scientists, managers, and fishers. If implemented correctly, endangered species would recover in the much larger area outside MPAs, and fishers would benefit from the conservation-value of the scarce and valued product. However, to succeed, the strategy depends on the adoption of a series of challenging management rules that are not currently being enforced along an extensive coastline. So far, few MPAs have incorporated rules for endangered species in their management plan, and those that have done so have no plans or the means to enforce them. Therefore, fishing of endangered species is currently ongoing without any management or monitoring in the entire Brazilian coast. Concerned with the challenges to develop plans to recover populations of endangered species faced by Brazilian managers, we suggest wide communication and a ban on the fisheries until management plans are implemented. Additionally, we suggest that the effectiveness of the inverted management strategy for parrotfishes should be assessed before it’s applied to other endangered species.
Differential Effects of Serum Lipoprotein-Associated Phospholipase A2 on Periventricular and Deep Subcortical White Matter Hyperintensity in Brain
Authors: Jiang Junying , Gao Yuanyuan , Zhang Rui , Wang Lin , Zhao Xiaoyuan , Dai Qi , Zhang Wei , Xu Xiujian , Chen Xuemei
Published: March 2021

Background and Purpose: Serum level of lipoprotein-associated phospholipase A2 (Lp-PLA2) was associated with white matter hyperintensity (WMH). There were differences in the anatomical structure and pathophysiological mechanism between periventricular WMH (PVWMH) and deep subcortical WMH (DSWMH). In this study, we aimed to investigate the effects of serum Lp-PLA2 on the PVWMH and DSWMH.

Methods: In total, 711 Chinese adults aged ≥45 years with cranial magnetic resonance imaging (MRI) were recruited in this cross-sectional study, who had received physical examinations in the Department of Neurology, the Affiliated Jiangning Hospital of Nanjing Medical University due to dizziness and headaches between January 2016 and July 2019. Enzyme linked immunosorbent assay (ELISA) was utilized to determine the serum Lp-PLA2. Fazekas scale was used to measure the severity of PVWMH (grade 0–3) and DSWMH (grade 0–3) on MRI scans. Ordinal regression analysis was carried out to investigate the relationship between serum Lp-PLA2 and PVWMH or DSWMH.

Results: Finally, 567 cases were included in this study. The average level of serum Lp-PLA2 was 213.35±59.34 ng/ml. There were statistical differences in the age, hypertension, diabetes mellitus, atrial fibrillation, lacunar infarction, Lp-PLA2 grade, creatinine, Hcy, and H-CRP (P < 0.05) in PVWMH groups. Ordinal regression analysis indicated that there was a lower risk of PVWMH in the patients with normal and moderately elevated serum Lp-PLA2 compared with those with significantly elevated serum Lp-PLA2 after adjusting age, hypertension, diabetes mellitus, atrial fibrillation, lacunar infarction, Cr, Hcy, and H-CRP. In addition, PVWMH was correlated to advanced age, hypertension, diabetes mellitus, and lacunar infarction. After adjusting for confounding factors, DSWMH was correlated to advanced age and lacunar infarction. There was no correlation between serum Lp-PLA2 and DSWMH.

Conclusions: Serum Lp-PLA2 was closely associated with the pathogenesis of PVWMH rather than DSWMH. There might be different pathological mechanisms between PVWMH and DSWMH.
Individualizing Therapy in CIDP: A Mini-Review Comparing the Pharmacokinetics of Ig With SCIg and IVIg
Authors: Beydoun Said R. , Sharma Khema R. , Bassam Bassam A. , Pulley Michael T. , Shije Jeffrey Z. , Kafal Ayman
Published: March 2021

Immunoglobulin (Ig) therapy is a first-line treatment for CIDP, which can be administered intravenously (IVIg) or subcutaneously (SCIg) and is often required long term. The differences between these modes of administration and how they can affect dosing strategies and treatment optimization need to be understood. In general, the efficacy of IVIg and SCIg appear comparable in CIDP, but SCIg may offer some safety and quality of life advantages to some patients. The differences in pharmacokinetic (PK) profile and infusion regimens account for many of the differences between IVIg and SCIg. IVIg is administered as a large bolus every 3–4 weeks resulting in cyclic fluctuations in Ig concentration that have been linked to systemic adverse events (AEs) (potentially caused by high Ig levels) and end of dose “wear-off” effects (potentially caused by low Ig concentration). SCIg is administered as a smaller weekly, or twice weekly, volume resulting in near steady-state Ig levels that have been linked to continuously maintained function and reduced systemic AEs, but an increase in local reactions at the infusion site. The reduced frequency of systemic AEs observed with SCIg is likely related to the avoidance of high Ig concentrations. Some small studies in immune-mediated neuropathies have focused on serum Ig data to evaluate its potential use as a biomarker to aid clinical decision-making. Analyzing dose data may help understand how establishing and monitoring patients' Ig concentration could aid dose optimization and the transition from IVIg to SCIg therapy.
Screen Fast, Screen Faster: A Pilot Study to Screen for Depressive Symptoms Using the Beck Depression Inventory Fast Screen in Parkinson's Disease With Mild Cognitive Impairment
Authors: Elben Saskia , Dimenshteyn Karina , Trenado Carlos , Folkerts Ann-Kristin , Ophey Anja , Sulzer Patricia , Becker Sara , Schmidt Nele , Tödt Inken , Witt Karsten , Liepelt-Scarfone Inga , Yilmaz Rezzak , Kalbe Elke , Wojtecki Lars
Published: March 2021

Objective: Depressive symptoms have a high prevalence in patients with Parkinson's disease (PD) and are associated with cognitive dysfunction. Especially in PD with mild cognitive impairment (MCI), a time-efficient and valid instrument for the assessment of depression primarily focusing on psychological symptoms and disregarding confounding somatic symptoms is needed. We performed an examination of the psychometric properties of the Beck Depression Inventory II (BDI-II) and the Beck Depression Inventory Fast Screen (BDI-FS).

Methods: The sample consisted of 64 patients [22 females and 42 males, mean age: 67.27 years (SD = 7.32)]. Depressive symptoms were measured in a cohort of PD patients with MCI. For the BDI-II and BDI-FS the psychometric concepts of internal consistency, convergent validity and diagnostic agreement were assessed.

Results: Patients gave higher ratings on test items addressing somatic symptoms than those addressing non-somatic ones. The correlation between the absolute total scores of the BDI-II and the BDI-FS was significant (r = 0.91, p < 0.001), which indicated convergent validity. The Cronbach's alpha values indicated adequate internal consistencies for both measures (BDI-II: 0.84; BDI-FS: 0.78). There was a higher than chance level agreement of diagnoses of the two questionnaires, measured by Cohen's kappa (0.58, p < 0.001). The agreements between previous diagnosis of depression and the diagnoses of the BDI-II/BDI-FS were also significantly higher than chance level (BDI-II: 0.34, p = 0.007, BDI-FS: 0.39, p = 0.002). Additional AUC analysis across different cutoffs showed that performance of BDI-FS was better than BDI-II, supporting the observation of an equivalent or better performance of BDI-FS than BDI-II. Importantly, AUC analysis confirmed that a cutoff = 4 for BDI-FS was suitable in the considered sample of patients with PD-MCI.

Discussion: In a cohort of PD-MCI, the BDI-FS demonstrates adequate psychometric properties in comparison to the BDI-II and can be used as a screening measure for assessing depression in cognitively impaired PD patients, focusing solely on psychological symptoms. Still, further research is needed to validate this instrument.
Friend vs. Foe: Cognitive and Affective Empathy in Women With Different Hormonal States
Authors: Kimmig Ann-Christin Sophie , Wildgruber Dirk , Wendel Sina-Maria Ute , Sundström-Poromaa Inger , Derntl Birgit
Published: March 2021

Empathy is crucial for social functioning as well as social coherence. It can be influenced by modulatory factors such as familiarity and liking (i.e., emotional closeness). Furthermore, there are first hints that hormonal status may modulate affective but not cognitive empathy in women. The aim of this study was to investigate potential separate as well as combined modulatory effects of emotional closeness and hormonal status on female cognitive and affective empathy. Three hormonal status groups of women (n = 62) were studied: (1) naturally-cycling (NC) women in the early follicular phase (fNC), (2) NC women during periovulatory phase (oNC), and (3) oral contraceptive (OC) users. All women underwent a newly developed empathy task (i.e., Tübinger Empathy Test, TET) presenting textual descriptions of positive and negative emotional scenes relating to three different perspectives (i.e., self vs. friend vs. enemy/disliked person). Regardless of hormonal status, empathic responses were higher for the friend compared to the enemy perspective for both empathy components. However, cognitive empathy was less affected by varying emotional closeness toward the target person than affective empathy. Hormonal status modulated only affective empathy. OC users showed significantly less affective empathy toward the enemy compared to the fNC women. Overall, affective empathy seems more sensitive to modulatory effects of emotional closeness and hormonal status than cognitive empathy. Possible implications of this current investigation for future research on empathy and OC use, contraceptive education as well as for other clinical applications are discussed.
[18F]F13640, a 5-HT1A Receptor Radiopharmaceutical Sensitive to Brain Serotonin Fluctuations
Authors: Colom Matthieu , Vidal Benjamin , Fieux Sylvain , Redoute Jérôme , Costes Nicolas , Lavenne Franck , Mérida Inés , Irace Zacharie , Iecker Thibaud , Bouillot Caroline , Billard Thierry , Newman-Tancredi Adrian , Zimmer Luc
Published: March 2021

Introduction

Serotonin is involved in a variety of physiological functions and brain disorders. In this context, efforts have been made to investigate the in vivo fluctuations of this neurotransmitter using positron emission tomography (PET) imaging paradigms. Since serotonin is a full agonist, it binds preferentially to G-protein coupled receptors. In contrast, antagonist PET ligands additionally interact with uncoupled receptors. This could explain the lack of sensitivity to serotonin fluctuations of current 5-HT1A radiopharmaceuticals which are mainly antagonists and suggests that agonist radiotracers would be more appropriate to measure changes in neurotransmitter release. The present study evaluated the sensitivity to endogenous serotonin release of a recently developed, selective 5-HT1A receptor PET radiopharmaceutical, the agonist [18F]F13640 (a.k.a. befiradol or NLX-112).

Materials and Methods

Four cats each underwent three PET scans with [18F]F13640, i.e., a control PET scan of 90 min, a PET scan preceded 30 min before by an intravenous injection 1 mg/kg of d-fenfluramine, a serotonin releaser (blocking challenge), and a PET scan comprising the intravenous injection of 1 mg/kg of d-fenfluramine 30 min after the radiotracer injection (displacement challenge). Data were analyzed with regions of interest and voxel-based approaches. A lp-ntPET model approach was implemented to determine the dynamic of serotonin release during the challenge study.

Results

D-fenfluramine pretreatment elicited a massive inhibition of [18F]F13640 labeling in regions known to express 5-HT1A receptors, e.g., raphe nuclei, hippocampus, thalamus, anterior cingulate cortex, caudate putamen, occipital, frontal and parietal cortices, and gray matter of cerebellum. Administration of d-fenfluramine during PET acquisition indicates changes in occupancy from 10% (thalamus) to 31% (gray matter of cerebellum) even though the dissociation rate of [18F]F13640 over the 90 min acquisition time was modest. The lp-ntPET simulation succeeded in differentiating the control and challenge conditions.

Conclusion

The present findings demonstrate that labeling of 5-HT1A receptors with [18F]F13640 is sensitive to serotonin concentration fluctuations in vivo. Although the data underline the need to perform longer PET scan to ensure accurate measure of displacement, they support clinical development of [18F]F13640 as a tool to explore experimental paradigms involving physiological or pathological (neurological or neuropsychiatric pathologies) fluctuations of extracellular serotonin.
Survival Benefit of Crossover Administration of Regorafenib and Trifluridine/Tipiracil Hydrochloride for Patients With Metastatic Colorectal Cancer: Exploratory Analysis of a Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study (REGOTAS)
Authors: Chida Keigo , Kotani Daisuke , Moriwaki Toshikazu , Fukuoka Shota , Masuishi Toshiki , Takashima Atsuo , Kumekawa Yosuke , Kajiwara Takeshi , Yamazaki Kentaro , Komoda Masato , Makiyama Akitaka , Denda Tadamichi , Hatachi Yukimasa , Suto Takeshi , Sugimoto Naotoshi , Enomoto Masanobu , Ishikawa Toshiaki , Kashiwada Tomomi , Ando Koji , Yuki Satoshi , Okita Yoshihiro , Kusaba Hitoshi , Sakai Daisuke , Okamoto Koichi , Tamura Takao , Yamashita Kimihiro , Gosho Masahiko , Shimada Yasuhiro
Published: March 2021

Background: The survival benefits of regorafenib (REG) and trifluridine/tipiracil hydrochloride (TFTD) have been demonstrated in chemorefractory patients with metastatic colorectal cancer (mCRC). However, the effects of crossover administration of REG and TFTD on patient survival remain unclear. The present study evaluated the association between exposure to REG and TFTD and overall survival (OS) in patients with mCRC using data from the REGOTAS study.

Patients and Methods: We analyzed patients registered in the REGOTAS study, which retrospectively compared the efficacy and safety of use of REG or TFTD as later-line chemotherapy for chemorefractory mCRC patients. We compared the survival outcomes of cohort A (treated using both REG and TFTD) and cohort B (treated using either REG or TFTD).

Results: A total of 550 patients (cohort A, n = 252; cohort B, n = 298) met the inclusion criteria. The median OS was significantly increased in cohort A compared with cohort B [9.6 months (95% confidence interval (CI), 8.9–10.9 months) vs. 5.2 months (95% CI, 4.4–6.0 months), P < 0.001]. Multivariate analysis revealed that cohort A was independently associated with a significant increase in OS [A vs. B: Hazard ratios (HR), 0.58; 95% CI, 0.47–0.72; P < 0.001]. Subgroup analysis adjusted using multivariate Cox model revealed a consistently better trend in most subgroups for cohort A compared with cohort B.

Conclusions: Our study revealed prolonged survival in patients treated with REG and TFTD. Therefore, all active agents, including REG and TFTD, should be made available to mCRC patients.
Value of Adaptive Trials and Surrogate Endpoints for Clinical Decision-Making in Rare Cancers
Authors: Krendyukov Andriy , Singhvi Sanjay , Zabransky Markus
Published: March 2021

Despite high-level endorsement, the number of adaptive Phase II/III trials in rare cancers needs to be improved, with better understanding of their value for clinical decisions in daily practice. This paper describes approaches to trial design in rare cancers, which has been supplemented by a search of ClinicalTrials.gov for adaptive trial designs in rare cancer. In addition, an online survey of 3,200 oncologists was conducted. Practicing physicians were questioned on the importance of different evidence levels, types of adaptive trial design, and categories of surrogate endpoints for clinical decision making. The results of the online survey revealed that evidence from Phase II/III trials with an adaptive design and relatively small sample size was considered high value in rare cancer by 97% of responders, similar to the randomized controlled trial rating (82%). Surrogate clinical endpoints were considered valuable alternatives to overall survival by 80% of oncologists. Preferred adaptive designs were futility analysis, interim analysis, adaptive sample size, and adaptive randomization. In conclusion, rare cancer oncologists rate evidence from adaptive clinical trials with as high a value and importance for clinical decision making processes as conventional randomized controlled trials. All stakeholders have a vested interest in advances in clinical trial designs to ensure efficient and timely development of innovative medicinal products to allow more patients faster access to the pivotal treatment.
Case Report: 18F-FDG PET-CT for Diagnosing Prosthetic Device-Related Infection in an Infant With CHD
Authors: Kawamura Junpei , Ueno Kentaro , Taimura Eri , Matsuba Tomoyuki , Imoto Yutaka , Jinguji Megumi , Kawano Yoshifumi
Published: March 2021

Patients who have undergone cardiac surgery using prosthetic devices have an increased risk of developing prosthetic device-related infection and mediastinitis. However, accurate diagnosis of prosthetic device-related infection can be difficult to evaluate and treat with antibiotic therapy alone. In recent years, 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) has made promising contributions to detect infective endocarditis, pacemaker infections, or other inflammations. Nevertheless, 18F-FDG PET-CT for congenital heart disease (CHD) with device infection has been sparsely reported. We present an infantile girl diagnosed with pulmonary atresia with a ventricular septal defect who underwent replacement of the right ventricle-to-pulmonary artery (RV-PA) conduit for improvement cyanosis. She developed high fever and was diagnosed with mediastinitis and bacteremia by Pseudomonas aeruginosa (P. aeruginosa) on postoperative day 4. Mediastinal drainage and 6 weeks of antibiotic therapy improved her condition, but bacteremia flared up on postoperative day 56. Despite a long course of antibiotic therapy, she had two more recurrences of bacteremia with the detection of P. aeruginosa. Echocardiography and chest contrast CT showed no evidence of vegetation and mediastinitis. On postoperative day 115, 18F-FDG PET-CT revealed an accumulation on the RV-PA conduit (SUV max 3.4). Finally, she developed an infectious ventricular pseudo-aneurysm on postoperative day 129 and underwent aneurysm removal and RV-PA conduit replacement on postoperative day 136. Our case showed the importance of 18F-FDG PET-CT for diagnosing specific localization of prosthetic device-related infection which is hard to detect using other imaging techniques. It can be a useful diagnostic tool for infantile patients with CHD with cardiac prosthetic devices and improve subsequent clinical treatments.
Safety and Feasibility of Antibiotic De-escalation in Critically Ill Children With Sepsis – A Prospective Analytical Study From a Pediatric ICU
Authors: Battula Vasudha , Krupanandan Ravi Kumar , Nambi P. Senthur , Ramachandran Bala
Published: March 2021

Introduction: De-escalation is the key to balance judicious antibiotic usage for life-threatening infections and reducing the emergence of antibiotic resistance caused by antibiotic overuse. Robust evidence is lacking regarding the safety of antibiotic de-escalation in culture negative sepsis.

Materials and Methods: Children admitted to the PICU during the first 6 months of 2019 with suspected infection were included. Based on the clinical condition, cultures and septic markers, antibiotics were de-escalated or continued at 48–72 h. Outcome data like worsening of primary infection, acquisition of hospital acquired infection, level of ICU support and mortality were captured.

Results: Among the 360 admissions, 247 (68.6%) children received antibiotics. After excluding 92 children, 155 children with 162 episodes of sepsis were included in the study. Thirty four episodes were not eligible for de-escalation. Among the eligible group of 128 episodes, antibiotics were de-escalated in 95 (74.2%) and continued in 33 (25.8%). The primary infection worsened in 5 (5.2%) children in the de-escalation group and in 1 (3%) in non de-escalation group [Hazard ratio: 2.12 (95%CI: 0.39–11.46)]. There were no significant differences in rates of hospital acquired infection, mortality or length of ICU stay amongst the groups. Blood cultures and assessment of clinical recovery played a major role in de-escalation of antibiotics and the clinician's hesitation to de-escalate in critically ill culture negative children was the main reason for not de-escalating among eligible children.

Conclusion: Antibiotic de-escalation appears to be a safe strategy to apply in criticallly ill children, even in those with negative cultures.
Combination of Botulinum Toxin and minocycline Ameliorates Neuropathic Pain Through Antioxidant Stress and Anti-Inflammation via Promoting SIRT1 Pathway
Authors: Yu Zhi , Liu Jiayu , Sun Le , Wang Yusheng , Meng Hongmei
Published: March 2021

Neuropathic pain (NP) is one of the intractable complications of spinal cord injury (SCI), with poor prognosis and seriously affects the quality of life of patients. This study aims to determine the treatment effect and mechanism of multimodal therapies in a rat model of SCI-induced NP by combining treatment with the anti-inflammatory agent minocycline (MC) and botulinum toxin (BoNT). The combined utilization alleviated SCI-induced NP and reduced apoptosis, inflammation, and oxidative stress of SCI by activating SIRT1 and dampening pAKT, P53, and p-NF-KB. BoNT with a concentration of 0.1 nm and MC with a concentration of 20 uM were selected for the experiment in the primary microglia and astrocytes treated with LPS. It was found that the combination of BoNT and MC obviously inhibits the inflammatory response and oxidative stress of glial cells, and notably activates SIRT1 and restrains pAKT, P53, and p-NF-KB. Therefore, in the treatment of SCI-induced NP, the combination of BoNT and MC markedly improves the therapeutic effect of NP by promoting the SIRT1 expression, thereby inactivating NF-KB, P53, and PI3K/AKT signaling pathway, inhibiting inflammation and oxidative stress as well as relieving SCI-induced NP.
Preparation and Release Profiles in Vitro/Vivo of Galantamine Pamoate Loaded Poly (Lactideco-Glycolide) (PLGA) Microspheres
Authors: Du Liping , Liu Shankui , Hao Guizhou , Zhang Li , Zhou Miaomiao , Bao Yueqing , Ding Bing , Sun Qinyong , Zhang Guimin
Published: March 2021

Patient’s poor compliance and the high risk of toxic effects limit the clinical use of galantamine hydrobromide. To overcome these drawbacks, the sustained-release galantamine pamoate microspheres (GLT-PM-MS) were successfully developed using an oil/water emulsion solvent evaporation method in this study. Physicochemical properties of GLT-PM-MS were carefully characterized, and the in vitro and in vivo drug release behaviors were well studied. Results showed that the morphology of optimized microspheres were spherical with smooth surfaces and core-shell interior structure. Mean particle size, drug loading and entrapment efficiency were 75.23 ± 1.79 μm, 28.01 ± 0.81% and 87.12 ± 2.71%, respectively. The developed GLT-PM-MS were found to have a sustained release for about 24 days in vitro and the plasma drug concentration remained stable for 17 days in rats. These results indicated that GLT-PM-MS could achieve the sustained drug release purpose and be used in clinical trial.
XMD-17-51 Inhibits DCLK1 Kinase and Prevents Lung Cancer Progression
Authors: Yang Wei-Qiang , Zhao Wei-Jun , Zhu Liu-Lian , Xu Shuai-Jun , Zhang Xue-Lin , Liang Yong , Ding Xiao-Fei , Kiselyov Alexander , Chen Guang
Published: March 2021

Doublecortin-like kinase 1 (DCLK1) is a cancer stem cell marker that is highly expressed in various types of human cancer, and a protein kinase target for cancer therapy that is attracting increasing interest. However, no drug candidates targeting DCLK1 kinase have been developed in clinical trials to date. XMD-17-51 was found herein to possess DCLK1 kinase inhibitory activities by cell-free enzymatic assay. In non-small cell lung carcinoma (NSCLC) cells, XMD-17-51 inhibited DCLK1 and cell proliferation, while DCLK1 overexpression impaired the anti-proliferative activity of XMD-17-51 in A549 cell lines. Consequently, XMD-17-51 decreased Snail-1 and zinc-finger-enhancer binding protein 1 protein levels, but increased those of E-cadherin, indicating that XMD-17-51 reduces epithelial-mesenchymal transition (EMT). Furthermore, sphere formation efficiency was significantly decreased upon XMD-17-51 treatment, and XMD-17-51 reduced the expression of stemness markers such as β-catenin, and pluripotency factors such as SOX2, NANOG and OCT4. However, the percentage of ALDH+ cells was increased significantly following treatment with XMD-17-51 in A549 cells, possibly due to EMT inhibition. In combination, the present data indicated that XMD-17-51 inhibited DCLK1 kinase activity in a cell-free assay with an IC50 of 14.64 nM, and decreased DCLK1 protein levels, cell proliferation, EMT and stemness in NSCLC cell lines. XMD-17-51 has the potential to be a candidate drug for lung cancer therapy.
Exploring the Dimensions of Smartphone Distraction: Development, Validation, Measurement Invariance, and Latent Mean Differences of the Smartphone Distraction Scale (SDS)
Authors: Throuvala Melina A. , Pontes Halley M. , Tsaousis Ioannis , Griffiths Mark D. , Rennoldson Mike , Kuss Daria J.
Published: March 2021

Background: Distraction is a functional emotion regulation strategy utilized to relieve emotional distress. Within the attention economy perspective, distraction is increasingly associated with digital technology use, performance impairments and interference with higher-order cognitive processes. Research on smartphone distraction and its association with problematic smartphone use is still scarce and there is no available psychometric assessment tool to assess this cognitive and emotive process parsimoniously.

Method: The present study reports the development and evaluation of the psychometric properties of the Smartphone Distraction Scale (SDS) through exploratory and confirmatory factor analysis, construct validity, gender invariance, and latent mean differences. The study was conducted in a sample of British university students (N = 1,001; M = 21.10 years, SD = 2.77).

Results: The 16-item SDS was best conceptualized in a four-factor model solution comprising attention impulsiveness, online vigilance, emotion regulation, and multitasking. Construct validity was established using relevant psychosocial and mental health measures, with SDS scores being moderately associated with deficient self-regulation and problematic social media use. Gender measurement invariance was achieved at the configural, metric, and scalar levels, and latent mean differences indicated that females had significantly higher means than males across all four SDS latent factors.

Discussion: The SDS presents with several strengths, including its theoretical grounding, relatively short length, and sound psychometric properties. The SDS enables the assessment of distraction, which appears to be one of the pathways to problematic smartphone use facilitating overuse and overreliance on smartphones for emotion regulation processes. The assessment of distraction in relation to problematic use in vulnerable populations may facilitate interventions that could encourage metacognition and benefit these groups by allowing sustained productivity in an increasingly disrupted work and social environment.
Systematic Review of Potential Occupational Respiratory Hazards Exposure Among Sewage Workers
Authors: Muzaini Kamarulzaman , Yasin Siti Munira , Ismail Zaliha , Ishak Ahmad Razali
Published: March 2021

Background: Sewage workers have a higher risk of exposure to various potential occupational respiratory hazards found in sewage plants. Although previous studies discuss occupational respiratory hazard concentration impacting sewage workers' respiratory health, the results are scarce and mixed. Hence, there is a need to identify the potential respiratory hazards in sewage plants so as to clarify the short- and long-term respiratory health effects. Therefore, this systematic review (SR) aims to critically review previous studies investigating potential respiratory hazards found at sewage plants and their effects on sewage workers' respiratory health.

Methods: An SR was conducted using PubMed, EBSCO Medline, Web of Science, Scopus, and Google Scholar on peer-reviewed studies published between January 1994 and October 2020 evaluating the impact of potential exposure to respiratory hazards and its effects on respiratory health among sewage workers. “Sewage treatment plant,” “respiratory hazards,” and “respiratory health effects” were the three main search terms chosen in this SR. The inclusion criteria were (1) studies on potential occupational respiratory hazard exposure among sewage workers, (2) manuscripts written in English, and (3) studies published in the peer-reviewed literature. The human observational studies' quality was assessed using the Effective Public Health Practice Project Quality Assessment Tool.

Results: We identified 5,660 articles through an initial database search. Only 26 items met the inclusion criteria and were included in this review; 15 human observational studies and 11 environmental assessment studies were conducted in the sewage industries. Most of the human observational studies were rated as moderate quality, two studies were rated as weak quality, and one study with strong quality was identified. Hydrogen sulfide, bioaerosols, particulate matter 2.5 (PM 2.5), and volatile organic compounds (VOC) were found to be potential respiratory hazards. Most of the risks contributed to adverse outcomes on the sewage workers' respiratory health with some inconsistent findings on the relationship between respiratory hazard exposure and respiratory health effects.

Conclusion: Our review finds that, although this area is of great importance, quality studies are still lacking. There is a need for additional studies to clarify the effects of respiratory hazard exposure on sewage workers and respiratory health, especially PM 2.5 and VOC.