bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility and Challenges for Sequential Treatments in ALK-Rearranged Non-Small-Cell Lung Cancer
Authors: Elsayed Mei , Bozorgmehr Farastuk , Kazdal Daniel , Volckmar Anna-Lena , Sültmann Holger , Fischer Jürgen R. , Kriegsmann Mark , Stenzinger Albrecht , Thomas Michael , Christopoulos Petros
Published: April 2021

Background

Anaplastic lymphoma kinase-rearranged non-small-cell lung cancer (ALK+ NSCLC) is a model disease for use of targeted therapies (TKI), which are administered sequentially to maximize patient survival.

Methods

We retrospectively analyzed the flow of 145 consecutive TKI-treated ALK+ NSCLC patients across therapy lines. Suitable patients that could not receive an available next-line therapy (“attrition”) were determined separately for various treatments, based on the approval status of the respective targeted drugs when each treatment failure occurred in each patient.

Results

At the time of analysis, 70/144 (49%) evaluable patients were still alive. Attrition rates related to targeted treatments were approximately 25-30% and similar for administration of a second-generation (2G) ALK inhibitor (22%, 17/79) or any subsequent systemic therapy (27%, 27/96) after crizotinib, and for the administration of lorlatinib (27%, 6/22) or any subsequent systemic therapy (25%, 15/61) after any 2G TKI. The rate of chemotherapy implementation was 67% (62/93). Both administration of additional TKI (median overall survival [mOS] 59 vs. 41 months for multiple vs. one TKI lines, logrank p=0.002), and chemotherapy (mOS 41 vs. 16 months, logrank p<0.001) were significantly associated with longer survival. Main reason for patients foregoing any subsequent systemic treatment was rapid clinical deterioration (n=40/43 or 93%) caused by tumor progression. In 2/3 of cases (29/43), death occurred under the first failing therapy, while in 11/43 the treatment was switched, but the patient did not respond, deteriorated further, and died within 8 weeks.

Conclusions

Despite absence of regulatory obstacles and no requirement for specific acquired mutations, 25-30% of ALK+ NSCLC patients forego subsequent systemic therapy due to rapid clinical deterioration, in several cases (approximately 1/3) associated with an ineffective first next-line choice. These results underline the need for closer patient monitoring and broader profiling in order to support earlier and better directed use of available therapies.
Molecular Dynamics Studies of Therapeutic Liquid Mixtures and Their Binding to Mycobacteria
Authors: Monteiro Hugo , Santos Filipa , Paiva Alexandre , Duarte Ana Rita C. , Ferreira Ricardo J.
Published: April 2021

Tuberculosis is an highly contagious disease still considered by the WHO as one of most infectious diseases worldwide. The therapeutic approach, used to prevent and treat tuberculosis targets the Mycobacterium tuberculosis complex, comprises a combination of drugs administrated for long periods of time, which, in many cases, could cause several adverse effects and, consequently, low compliance of the patient to the treatment and drug-resistance. Therefore, therapeutic liquid mixtures formulated with anti-tuberculosis drugs and/or adjuvants in tuberculosis therapy are an interesting approach to prevent toxic effects and resistance to anti-tuberculosis drugs. The herein formulated therapeutic liquid mixtures, including ethambutol, arginine, citric acid and water under different molar ratios, were studied through a molecular dynamics approach to understand how ethambutol and arginine could be stabilized by the presence of citric acid and/or water in the mixture. To gain insights on how the uptake of these mixtures into the mycobacteria cell may occur and how a mycobacterial ABC transporter could contribute to this transport, multiple simultaneous ligand docking was performed. Interactions between citric acid and ethambutol involving the carboxyl and hydroxyl groups of citric acid with the amines of ethambutol were identified as the most critical ones. Water molecules present in the mixture provides the necessary network of hydrogen bonds that stabilize the mixture. Molecular docking additionally provided an interesting hypothesis on how the different mixture components may favor binding of ethambutol to an ABC importer. The data presented in this work helps to better understand these mixtures as well as to provide cues on the mechanisms that allow them to cross the mycobacterial cell membrane.
Population Pharmacokinetics and Initial Dose Optimization of Sirolimus Improving Drug Blood Level for Seizure Control in Pediatric Patients With Tuberous Sclerosis Complex
Authors: Chen Xiao , Wang Dongdong , Zhu Lin , Lu Jinmiao , Huang Yidie , Wang Guangfei , Zhu Yiqing , Ye Qiaofeng , Wang Yi , Xu Hong , Li Zhiping
Published: April 2021

The purposes of this study were to explore the population pharmacokinetics and initial dose optimization of sirolimus improving drug blood level for seizure control in pediatric patients with tuberous sclerosis complex (TSC). Eighty pediatric patients diagnosed with TSC-related epilepsy were included for analysis. Sirolimus concentrations, physiological and biochemical indexes, and drug combination were collected to build a nonlinear mixed effect (NONMEM) model. Initial dose optimization was simulated by the Monte Carlo method. The weight and concomitant medication of oxcarbazepine affected sirolimus clearance. Without oxcarbazepine, for once-daily sirolimus regimen, the doses of 0.07, 0.06, 0.05, 0.04, and 0.03 mg/kg/day were recommended for weights of 5–7.5, 7.5–11.5, 11.5–19, 19–40, and 40–70 kg, respectively; for twice-daily sirolimus regimen, the doses of 0.05, 0.04, and 0.03 were recommended for weights of 5–8, 8–20, and 20–70 kg, respectively. With oxcarbazepine, for once-daily sirolimus regimen, the doses of 0.09, 0.08, 0.07, 0.06, 0.05, and 0.04 mg/kg/day were recommended for weights of 5–7.5, 7.5–10, 10–13.5, 13.5–20, 20–35, and 35–70 kg, respectively; for twice-daily sirolimus regimen, the doses of 0.06, 0.05, 0.04, and 0.03 were recommended for weights of 5–7, 7–14.5, 14.5–38, and 38–70 kg, respectively. The present study was the first to establish a population pharmacokinetic model of sirolimus improving drug blood level for seizure control in pediatric patients with TSC and recommend the initial dosage regimen.
Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19
Authors: Sukhatme Vikas P. , Reiersen Angela M. , Vayttaden Sharat J. , Sukhatme Vidula V.
Published: April 2021

Fluvoxamine is a well-tolerated, widely available, inexpensive selective serotonin reuptake inhibitor that has been shown in a small, double-blind, placebo-controlled, randomized study to prevent clinical deterioration of patients with mild coronavirus disease 2019 (COVID-19). Fluvoxamine is also an agonist for the sigma-1 receptor, through which it controls inflammation. We review here a body of literature that shows important mechanisms of action of fluvoxamine and other SSRIs that could play a role in COVID-19 treatment. These effects include: reduction in platelet aggregation, decreased mast cell degranulation, interference with endolysosomal viral trafficking, regulation of inositol-requiring enzyme 1α-driven inflammation and increased melatonin levels, which collectively have a direct antiviral effect, regulate coagulopathy or mitigate cytokine storm, which are known hallmarks of severe COVID-19.
Fenofibrate (a PPAR-α Agonist) Administered During Ethanol Withdrawal Reverts Ethanol-Induced Astrogliosis and Restores the Levels of Glutamate Transporter in Ethanol-Administered Adolescent Rats
Authors: Villavicencio-Tejo Francisca , Flores-Bastías Osvaldo , Marambio-Ruiz Lucas , Pérez-Reytor Diliana , Karahanian Eduardo
Published: April 2021

High-ethanol intake induces a neuroinflammatory response, which has been proposed as responsible for the maintenance of chronic ethanol consumption. Neuroinflammation decreases glutamate transporter (GLT-1) expression, increasing levels of glutamate that trigger dopamine release at the corticolimbic reward areas, driving long-term drinking behavior. The activation of peroxisome proliferator-activated receptor alpha (PPARα) by fibrates inhibits neuroinflammation, in models other than ethanol consumption. However, the effect of fibrates on ethanol-induced neuroinflammation has not yet been studied. We previously reported that the administration of fenofibrate to ethanol-drinking rats decreased ethanol consumption. Here, we studied whether fenofibrate effects are related to a decrease in ethanol-induced neuroinflammation and to the normalization of the levels of GLT-1. Rats were administered ethanol on alternate days for 4 weeks (2 g/kg/day). After ethanol withdrawal, fenofibrate was administered for 14 days (50 mg/kg/day) and the levels of glial fibrillary acidic protein (GFAP), phosphorylated NF-κB-inhibitory protein (pIκBα) and GLT-1, were quantified in the prefrontal cortex, hippocampus, and hypothalamus. Ethanol treatment increased the levels of GFAP in the hippocampus and hypothalamus, indicating a clear astrocytic activation. Similarly, ethanol increased the levels of pIκBα in the three areas. The administration of fenofibrate decreased the expression of GFAP and pIκBα in the three areas. These results indicate that fenofibrate reverts both astrogliosis and NF-κB activation. Finally, ethanol decreased GLT-1 expression in the prefrontal cortex and hippocampus. Fenofibrate normalized the levels of GLT-1 in both areas, suggesting that its effect in reducing ethanol consumption could be due to the normalization of glutamatergic tone.
Injection-Based Management of Osteoarthritis of the Knee: A Systematic Review of Guidelines
Authors: Pavone Vito , Vescio Andrea , Turchetta Matteo , Giardina Serena Maria Chiara , Culmone Annalisa , Testa Gianluca
Published: April 2021

Osteoarthritis (OA) is a leading cause of disability among older adults. Numerous pharmaceutical and nonpharmaceutical interventions have been described. Intra-articular injections are commonly the first line treatment. There are several articles, reporting the outcome of corticosteroids (CS), hyaluronic acid (HA) and platelet rich plasma (PRP). The aim of the study is to highlight the usefulness, indication and efficacy of the intra-articular injection of principal drugs. CSs have been shown to reduce the severity of pain, but care should be taken with repeated injections because of potential harm. HA reported good outcomes both for pain reduction and functional improvement. Different national societies guidelines do not recommend the PRP intra-articular injection in the management of knee OA for lack of evidence. In conclusion, the authors affirm that there is some evidence that intra-articular steroids are efficacious, but their benefit may be relatively short lived (<4 weeks). Most of the positive outcome were limited to the studies or part of the studies that considered the injection of high molecular weight as visco-supplementation, with a course of two to four injections a year.
Application of Proteomics and Metabonomics to Reveal the Molecular Basis of Atractylodis Macrocephalae Rhizome for Ameliorating Hypothyroidism Instead of Hyperthyroidism
Authors: Chen Jing , Dou Peiyuan , Xiao Hang , Dou Deqiang , Han Xueying , Kuang Haixue
Published: April 2021

As the treatments of diseases with Chinese herbs are holistic and characterized by multiple components, pathways, and targets, elucidating the efficacy of Chinese herbs in treating diseases, and their molecular basis, requires a comprehensive, network-based approach. In this study, we used a network pharmacology strategy, as well as in vivo proteomics and metabonomics, to reveal the molecular basis by which Atractylodis macrocephalae rhizome (AMR) ameliorates hypothyroidism. Eighteen main compounds from AMR and its fractions (volatile oil fraction, crude polysaccharides fraction, lactones fraction, oligosaccharide fraction, and atractyloside fraction) were identified by HPLC, and their targets were screened using the TCMSP database and Swiss Target Prediction. Disease targets were gathered from the TTD, CTD and TCMSP databases. Hub targets were screened by different plug-ins, such as Bisogene, Merge, and CytoNCA, in Cytoscape 3.7.1 software and analyzed for pathways by the DAVID database. Hypothyroidism and hyperthyroidism pharmacological models were established through systems pharmacology based on proteomic and metabolomic techniques. Finally, AMR and its fractions were able to ameliorate the hypothyroidism model to different degrees, whereas no significant improvements were noted in the hyperthyroidism model. The lactones fraction and the crude polysaccharides fraction were considered the most important components of AMR for ameliorating hypothyroidism. These amelioration effects were achieved through promoting substance and energy metabolism. In sum, the integrative approach used in this study demonstrates how network pharmacology, proteomics, and metabolomics can be used effectively to elucidate the efficacy, molecular basis, and mechanism of action of medicines used in TCM.
Dietary Supplementation With Chlorogenic Acid Derived From Lonicera macranthoides Hand-Mazz Improves Meat Quality and Muscle Fiber Characteristics of Finishing Pigs via Enhancement of Antioxidant Capacity
Authors: Wang Wenlong , Wen Chaoyue , Guo Qiuping , Li Jianzhong , He Shanping , Yin Yulong
Published: April 2021

Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in nature, is regarded as a potential feed additive to promote animal health and enhance the meat products’ quality via its various biological properties. The current study aims: (1) to determine whether dietary CGA supplementation improves meat quality and muscle fiber characteristics, and (2) to ascertain whether the corresponding improvement is associated with enhancing the antioxidant capacity of the finishing pigs. Thirty-two (Large × White × Landrace) finishing pigs with an average initial body weight of 71.89 ± 0.92 kg were allotted to 4 groups, and each was fed diets supplemented with 0, 0.02, 0.04, or 0.08% (weight/weight) of CGA. The meat quality traits, muscle fiber characteristics, and the serum and muscle antioxidant capacity were assessed. Results suggested that, compared with the control group, dietary CGA supplementation at a level of 0.04% significantly decreased the b∗ value and distinctly increased the inosinic acid content of longissimus dorsi (LD) and biceps femoris (BF) muscles (P < 0.01). Moreover, dietary supplementation with 0.04% of CGA markedly improved the amino acid composition of LD and BF muscles, as well as augmented the mRNA abundance of Nrf-2, GPX-1, MyoD, MyoG, and oxidative muscle fiber (I and IIa) in LD muscle (P < 0.05). This result indicates that a diet supplemented with 0.04% of CGA promotes myogenesis and induces a transformation toward more oxidative muscle fibers in LD muscle, subsequently improving meat quality. Besides, dietary supplementation with 0.02% and 0.04% of CGA notably enhanced the serum GSH-PX level (P < 0.01). Considering all these effects are closely related to the alteration of antioxidant activities of the finishing pigs, the underlying metabolism is likely connected to the boosting of their antioxidant capacity induced by dietary CGA.
Multifaceted Roles of Adipose Tissue-Derived Exosomes in Physiological and Pathological Conditions
Authors: Liu Yunnan , Wang Chen , Wei Mengying , Yang Guodong , Yuan Lijun
Published: April 2021

Adipose tissue functions importantly in the bodily homeostasis and systemic metabolism, while obesity links to multiple disorders. Beyond the canonical hormones, growth factors and cytokines, exosomes have been identified to play important roles in transmission of information from adipose tissue to other organs. Exosomes are nanoscale membrane vesicles secreted by donor cells, and transfer the genetic information to the recipient cells where the encapsulated nucleic acids and proteins are released. In this review, we elaborate the recent advances in the biogenesis and profiling of adipose tissue derived exosomes, and their physiological and pathological effects on different organs. Moreover, the potential significance of the exosomes as therapeutic vehicles or drugs is also discussed.
Nitrogen Fertilization Influences the Quantity, Composition, and Tissue Association of Foliar Phenolics in Strawberries
Authors: Narvekar Ashwini Sushil , Tharayil Nishanth
Published: April 2021

Unlike quantitative changes, the compositional changes of plant phenolics and changes in their tissue association as influenced by the nutrient supply are less well understood. We evaluated the quantity, composition, and tissue association of phenolics in leaves of two Fragaria ananassa cultivars in response to different levels of nitrogen (N) fertilization using global metabolomic approaches. Influence of N supply on phenolic content in both cultivars was similar, but the magnitude of this response was compound specific. Ellagitannins, the most abundant class of phenolic oligomers, were less responsive to the applied N treatments, whereas proanthocyanidins, the less abundant class of phenolic oligomers, exhibited higher fold change. Within mono-phenolics, the hydroxycinnamates were more abundant but showed lower fold change than the hydroxybenzoates. Among flavonoids, the hydroxylated flavonols showed higher abundances than the flavones, with a preferential accumulation of dihydroxylated flavonol at lower N levels. Furthermore, glycosylated flavonols were higher than the acylated forms. The extractable fraction of phenolics was more influenced by the N treatment than the fiber-bound fraction. The extensive compositional modification of phenolics and a greater response of non-bound fractions in response to N rates highlight the potential to use precise management of N supply as an effective strategy to enhance the bioactive compounds in crops.
Understanding the Sorghum–Colletotrichum sublineola Interactions for Enhanced Host Resistance
Authors: Abreha Kibrom B. , Ortiz Rodomiro , Carlsson Anders S. , Geleta Mulatu
Published: April 2021

Improving sorghum resistance is a sustainable method to reduce yield losses due to anthracnose, a devastating disease caused by Colletotrichum sublineola. Elucidating the molecular mechanisms of sorghum–C. sublineola interactions would help identify biomarkers for rapid and efficient identification of novel sources for host-plant resistance improvement, understanding the pathogen virulence, and facilitating resistance breeding. Despite concerted efforts to identify resistance sources, the knowledge about sorghum–anthracnose interactions remains scanty. Hence, in this review, we presented an overview of the current knowledge on the mechanisms of sorghum-C. sublineola molecular interactions, sources of resistance for sorghum breeding, quantitative trait loci (QTL), and major (R-) resistance gene sequences as well as defense-related genes associated with anthracnose resistance. We summarized current knowledge about C. sublineola populations and its virulence. Illustration of the sorghum-C. sublineola interaction model based on the current understanding is also provided. We highlighted the importance of genomic resources of both organisms for integrated omics research to unravel the key molecular components underpinning compatible and incompatible sorghum–anthracnose interactions. Furthermore, sorghum-breeding strategy employing rapid sorghum germplasm screening, systems biology, and molecular tools is presented.
Identification, Expression, and Interaction Analysis of Ovate Family Proteins in Populus trichocarpa Reveals a Role of PtOFP1 Regulating Drought Stress Response
Authors: Wang Hemeng , Chen Jin-Gui , Chang Ying
Published: April 2021

Ovate family proteins (OFPs) are a family of plant growth regulators that play diverse roles in many aspects of physiological processes. OFPs have been characterized in various plant species including tomato, Arabidopsis, and rice. However, little is known about OFPs in woody species. Here, a total of 30 PtOFP genes were identified from the genome of Populus trichocarpa and were further grouped into four subfamilies based on their sequence similarities. Gene expression analysis indicated that some members of the PtOFP gene family displayed tissue/organ-specific patterns. Analysis of cis-acting elements in the promoter as well as gene expression by hormone treatment revealed putative involvement of PtOFPs in hormonal response. Furthermore, PtOFP1 (Potri.006G107700) was further experimentally demonstrated to act as a transcriptional repressor. Yeast two-hybrid assay showed physical interactions of PtOFP1 with other proteins, which suggests that they might function in various cellular processes by forming protein complexes. In addition, overexpression of PtOFP1 in Arabidopsis conferred enhanced tolerance to PEG-induced drought stress at seedling stage, as well as a higher survival rate than the wild type at mature stage. These results provide a systematic analysis of the Populus OFP gene family and lay a foundation for functional characterization of this gene family.
The Interpersonal Neurobiology of Intersubjectivity
Authors: Schore Allan N.
Published: April 2021

In 1975, Colwyn Trevarthen first presented his groundbreaking explorations into the early origins of human intersubjectivity. His influential model dictates that, during intimate and playful spontaneous face-to-face protoconversations, the emotions of both the 2–3-month-old infant and mother are nonverbally communicated, perceived, mutually regulated, and intersubjectively shared. This primordial basic interpersonal interaction is expressed in synchronized rhythmic-turn-taking transactions that promote the intercoordination and awareness of positive brain states in both. In this work, I offer an interpersonal neurobiological model of Trevarthen’s intersubjective protoconversations as rapid, reciprocal, bidirectional visual-facial, auditory-prosodic, and tactile-gestural right brain-to-right brain implicit nonverbal communications between the psychobiologically attuned mother and the developing infant. These co-constructed positive emotional interactions facilitate the experience-dependent maturation of the infant’s right brain, which is in an early critical period of growth. I then address the central role of interpersonal synchrony in intersubjectivity, expressed in a mutual alignment or coupling between the minds and bodies of the mother and infant in face-to-face protoconversations, as well as how these right brain-to-right brain emotional transmissions generate bioenergetic positively charged interbrain synchrony within the dyad. Following this, I offer recent brain laterality research on the essential functions of the right temporoparietal junction, a central node of the social brain, in face-to-face nonverbal communications. In the next section, I describe the ongoing development of the protoconversation over the 1st year and beyond, and the co-creation of a fundamental energy-dependent, growth-promoting social emotional matrix that facilitates the emergence of the highly adaptive human functions of mutual play and mutual love. In the final section, I discuss the clinical applications of this interpersonal neurobiological model of intersubjectivity, which has a long history in the psychotherapy literature. Toward that end, I offer very recent paradigm-shifting hyperscanning research that simultaneously measures both the patient and therapist during a psychotherapeutic interaction. Using the Trevarthen’s two-person intersubjective model, this research demonstrates changes in both brains of the therapeutic dyad and the critical role of nonverbal communications in an emotionally-focused psychotherapy session. These studies specifically document interbrain synchronization between the right temporoparietal junction of the patient and the right temporoparietal junction of the clinician, a right brain-to-right brain nonverbal communication system in the co-constructed therapeutic alliance. Lastly, I discuss the relationship between the affect communicating functions of the intersubjective motivational system and the affect regulating functions of the attachment motivational system.
Specific Autobiographical Recall Mediates Impact of Cognition and Depression on Independence Function and Well-Being in Older Adults
Authors: Holland Carol A. , Boukouvalas Alexis , Clarkesmith Danielle , Cooke Richard
Published: April 2021

Autobiographical memory specificity has been associated with cognitive function, depression, and independence in older adults. This longitudinal study of 162 older adults moving to active supported living environments tracks changes in the role of the ability to recall specific autobiographical memory as a mediator between underlying cognitive function, or depression, and outcome perceived health or independence (e.g., Instrumental Activities of Daily Living, IADLs), across 18 months, as compared with controls not moving home. Clear improvements across time in autobiographical specificity were seen for residents but not controls, supporting the role of a socially active environment, and confirmed by correlation with number of activities reported in diaries, although the impact of diary activities on the effect of time on autobiographical specificity was not found. The role of autobiographical specificity in mediating general cognition and outcome functional limitations was clear for social limitations at 12 and 18 months, but its role in mediating effects of executive function and perceived health persisted throughout. The role of specificity in mediating between depression and perceived health, IADLs, and Functional Limitations persisted throughout. Analysis examining autobiographical specificity and depression as joint mediators between cognition and independence showed a forward effect such that higher specificity scores reduced the negative mediation effect of depression on independence. Finally, data showed the reduction of many of these mediations over time, supporting the role of autobiographical memory in times of change in a person's social situation. Data support potential autobiographical memory intervention development.
Core-Symptom-Defined Cortical Gyrification Differences in Autism Spectrum Disorder
Authors: Ning Mingmin , Li Cuicui , Gao Lei , Fan Jingyi
Published: April 2021

Autism spectrum disorder (ASD) is a heterogeneous disease that is characterized by abnormalities in social communication and interaction as well as repetitive behaviors and restricted interests. Structural brain imaging has identified significant cortical folding alterations in ASD; however, relatively less known is whether the core symptoms are related to neuroanatomical differences. In this study, we aimed to explore core-symptom-anchored gyrification alterations and their developmental trajectories in ASD. We measured the cortical vertex-wise gyrification index (GI) in 321 patients with ASD (aged 7–39 years) and 350 typically developing (TD) subjects (aged 6–33 years) across 8 sites from the Autism Brain Imaging Data Exchange I (ABIDE I) repository and a longitudinal sample (14 ASD and 7 TD, aged 9–14 years in baseline and 12–18 years in follow-up) from ABIDE II. Compared with TD, the general ASD patients exhibited a mixed pattern of both hypo- and hyper- and different developmental trajectories of gyrification. By parsing the ASD patients into three subgroups based on the subscores of the Autism Diagnostic Interview—Revised (ADI-R) scale, we identified core-symptom-specific alterations in the reciprocal social interaction (RSI), communication abnormalities (CA), and restricted, repetitive, and stereotyped patterns of behavior (RRSB) subgroups. We also showed atypical gyrification patterns and developmental trajectories in the subgroups. Furthermore, we conducted a meta-analysis to locate the core-symptom-anchored brain regions (circuits). In summary, the current study shows that ASD is associated with abnormal cortical folding patterns. Core-symptom-based classification can find more subtle changes in gyrification. These results suggest that cortical folding pattern encodes changes in symptom dimensions, which promotes the understanding of neuroanatomical basis, and clinical utility in ASD.
Neural Correlates of Mentalizing in Individuals With Clinical High Risk for Schizophrenia: ALE Meta-Analysis
Authors: Vucurovic Ksenija , Caillies Stéphanie , Kaladjian Arthur
Published: April 2021

Psychotic disorder refers to a spectrum of disorders that have multiple etiologies, due to the complex interaction of biological and genetic vulnerability with familial and cultural factors. A clinical high risk (CHR) for schizophrenia is defined as the presence of brief, attenuated, or intermittent psychotic symptoms in non-schizophrenic individuals. The transition to schizophrenia appears significantly more frequent in this at-risk population than in the general population. Moreover, the ability to attribute mental states to others, known as mentalizing or theory of mind, and its neural correlates found in individuals with CHR are similar to those described in patients with schizophrenia. We have therefore explored neurofunctional correlates of mentalizing in individuals with CHR vs. healthy controls, in order to identify the differences in brain activation. A neural coordinate-based activation likelihood estimation meta-analysis of existing neuroimaging data revealed that three regions displayed decreased activation in individuals with CHR, compared with healthy controls: the right temporoparietal junction, the right middle temporal gyrus, and the left precuneus. These results, combined with those in the literature, further support the hypothesis that abnormal activation of posterior brain regions involved in mentalizing correlates with psychotic symptoms in help-seeking individuals.
Are There Familial Patterns of Symptom Dimensions in Obsessive-Compulsive Disorder?
Authors: Balachander Srinivas , Meier Sandra , Matthiesen Manuel , Ali Furkhan , Kannampuzha Anand Jose , Bhattacharya Mahashweta , Kumar Nadella Ravi , Sreeraj Vanteemar S. , Ithal Dhruva , Holla Bharath , Narayanaswamy Janardhanan C. , Arumugham Shyam Sundar , Jain Sanjeev , Reddy YC Janardhan , Viswanath Biju
Published: April 2021

Background:Obsessive-compulsive disorder (OCD) is a heterogeneous illness, and emerging evidence suggests that different symptom dimensions may have distinct underlying neurobiological mechanisms. We aimed to look for familial patterns in the occurrence of these symptom dimensions in a sample of families with at least two individuals affected with OCD.

Methods:Data from 153 families (total number of individuals diagnosed with DSM-5 OCD = 330) recruited as part of the Accelerator Program for Discovery in Brain Disorders using Stem Cells (ADBS) was used for the current analysis. Multidimensional Item Response Theory (IRT) was used to extract dimensional scores from the Yale-Brown Obsessive-Compulsive Scale (YBOCS) checklist data. Using linear mixed-effects regression models, intra-class correlation coefficients (ICC), for each symptom dimension, and within each relationship type were estimated.

Results:IRT yielded a four-factor solution with Factor 1 (Sexual/Religious/Aggressive), Factor 2 (Doubts/Checking), Factor 3 (Symmetry/Arranging), and Factor 4 (Contamination/Washing). All except for Factor 1 were found to have significant ICCs, highest for Factor 3 (0.41) followed by Factor 4 (0.29) and then Factor 2 (0.27). Sex-concordant dyads were found to have higher ICC values than discordant ones, for all the symptom dimensions. No major differences in the ICC values between parent-offspring and sib-pairs were seen.

Conclusions:Our findings indicate that there is a high concordance of OCD symptom dimensions within multiplex families. Symptom dimensions of OCD might thus have significant heritability. In view of this, future genetic and neurobiological studies in OCD should include symptom dimensions as a key parameter in their analyses.
A Multi-Criteria Framework for Pandemic Response Measures
Authors: Ekenberg Love , Mihai Adriana , Fasth Tobias , Komendantova Nadejda , Danielson Mats
Published: April 2021

In managing the COVID-19 pandemic, several compelling narratives seem to have played a significant role in the decision-making processes regarding which risk mitigation and management measures to implement. Many countries were to a large extent unprepared for such a situation, even though predictions about a significant probability for a pandemic to occur existed, and national governments of several countries often acted in an uncoordinated manner, which resulted in many inconsistencies in the disaster risk reduction processes. Limited evidence has also made room for strategic narratives meant to persuade the public of the chosen set of actions, even though the degree of uncertainty regarding the outcomes of these was high, further complicating the situation. In this article, we assume a normative standpoint regarding rhapsodic decision making and suggest an integrated framework for a more elaborated decision analysis under the ambiguity of how to contain the virus spread from a policy point of view, while considering epidemiologic estimations and socioeconomic factors in a multi-stakeholder-multi-criteria context based on a co-creative work process for eliciting attitudes, perceptions, as well as preferences amongst relevant stakeholder groups. The framework, applied in our paper on Romania for demonstrative purposes, is used for evaluating mitigation measures for catastrophic events such as the COVID-19 situation, to mobilize better response strategies for future scenarios related to pandemics and other hazardous events, as well as to structure the production and analysis of narratives on the current pandemic effects.
An Overview of Systematic Reviews of Acupuncture for Infertile Women Undergoing in vitro Fertilization and Embryo Transfer
Authors: Wang Xia , Wang Yan , Wei Shaobin , He Bisong , Cao Yihong , Zhang Nannan , Li Maoya
Published: April 2021

Background: Currently, more and more subfertility couples are opting for combined acupuncture to improve the success rate of in vitro fertilization and embryo transfer (IVF-ET). However, the efficacy and safety of acupuncture in IVF-ET is still highly controversial.

Objectives: The purpose of this overview is to summarize evidence of essential outcomes of systematic reviews (SRs) of acupuncture in IVF-ET and evaluate their methodological quality.

Methods: We conducted a comprehensive literature search for relevant SRs in eight databases from inception to July 31, 2020, without language restriction. We evaluated the methodological quality of the included SRs by using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), which was the latest available assessment tool. The Risk of Bias in Systematic Review (ROBIS) tool was used to assess the risk of bias in SRs. We assessed the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) score to determine the strength of evidence. We excluded the overlapping randomized controlled trials (RCTs) and performed a re-meta-analysis of the primary RCTs.

Results: This review included 312 original RCT studies and 65,388 participants. By using AMSTAR-2, we found that the methodological quality of 16 SRs was critically low, because they had more than one critical weakness. Our reviews showed that although the GRADE for quality of evidence profile was suboptimal, acupuncture seemed to be beneficial in increasing the pregnancy rate. Our re-meta-analysis suggested that acupuncture was superior to sham acupuncture in improving the clinical pregnancy rate (CPR) of IVF-ET with substantial heterogeneity (RR = 1.31, 95% CI: 1.13–1.52, p = 0.0004, I2 = 66%). No statistical difference was observed regarding the outcomes of live birth rate (LBR), ongoing pregnancy rate (OPR), biochemical pregnancy rate (BPR), and miscarriage rate (MR) between two groups. When compared with no adjunctive treatment groups, acupuncture improved CPR (RR = 1. 25, 95% CI: 1.11–1.42, p = 0.0003) and OPR (RR = 1. 38, 95% CI: 1.04–1.83, p = 0.03). Acupuncture was more superior than no adjunctive treatment in reducing MR (OR = 1.42, 95% CI: 1.03–1.95, p = 0.03) and BPR (RR = 1.19, 95% CI: 1.02–1.37, p = 0.02).

Conclusions: Although the evidence of acupuncture in IVF-ET is insufficient, acupuncture appears to be beneficial to increase the clinical pregnancy rate in women undergoing IVF-ET. However, there are severe heterogeneity and methodological quality defects, which limit the reliability of results. Further, high-quality primary studies are still needed.
Public Stigma Toward Female and Male Opium and Heroin Users. An Experimental Test of Attribution Theory and the Familiarity Hypothesis
Authors: Sattler Sebastian , Zolala Farzaneh , Baneshi Mohammad Reza , Ghasemi Javad , Amirzadeh Googhari Saber
Published: April 2021

Drug abuse and addiction exist around the world. People addicted to drugs such as opium or heroin often encounter dehumanizing discriminatory behaviors and health-care systems that are reluctant to provide services. Experiencing discrimination often serves as a barrier to receiving help or finding a home or work. Therefore, it is important to better understand the mechanisms that lead to the stigmatization of drug addiction and who is more prone to stigmatizing behaviors. There is also a dearth of research on whether different patterns of stigma exist in men and women. Therefore, this study investigated factors affecting gender-specific stigmatization in the context of drug addiction. In our vignette study (NMensample= 320 andNWomensample= 320) in Iran, we experimentally varied signals and signaling events regarding a person with drug addiction (i.e.,NVignettes= 32 per sample), based on Attribution Theory, before assessing stigmatizing cognitions (e.g., blameworthiness), affective responses (e.g., anger), and discriminatory inclinations (e.g., segregation) with the Attribution Questionnaire. We also tested assumptions from the Familiarity Hypothesis by assessing indicators of respondents' familiarity with drug addiction (e.g., knowledge about addiction). Results, for example, show higher stigma if the person used “harder” drugs, displayed aggressive behavior, or had a less controllable drug urge. Self-attributed knowledge about addiction or prior drug use increased some forms of stigma, but diminished others. These findings only partially converged between men and women. We suggest that anti-stigma initiatives should consider information about the stigmatized person, conditions of the addiction, and characteristics of stigmatizers.
Does Economic Support Have an Impact on the Health Status of Elderly Patients With Chronic Diseases in China? - Based on CHARLS (2018) Data Research
Authors: Tang Shaoliang , Xu Yun , Li Zhengjun , Yang Tongling , Qian David
Published: April 2021

Objective: The economic support of elderly patients with chronic diseases may affect their health status. This study assessed the impact of economic support on the health status of elderly patients with chronic diseases in China and explored the relationship between regional economic differences and the impact of economic support on health status.

Methods: This study used the data of 3,416 elderly patients with chronic diseases from the China Health and Retirement Longitudinal Study (CHARLS) in 2018. Logit model and stepwise regression method were used to analyze and compare the influence of economic support on self-rated health, mental health, and activities of daily living (ADL) of elderly patients with chronic diseases. Sub-regional comparison was used for the research of regional differences in the impact of economic support on health.

Results: we find that economic support has a positive effect on the health status of elderly patients with chronic diseases in China. Socioeconomic support has a positive effect on self-rated health and mental health of elderly patients with chronic diseases, and the effect on activities of daily living (ADL) is no longer significant after the gradual inclusion of control variables. Family economic support has no significant impact on the health dimensions of elderly patients with chronic diseases. With respect to regional differences, socioeconomic support can improve mental health in central China and improve self-rated health in western China, while it can improve overall health status in eastern China. The influence of family economic support on different health dimensions in different regions is still insignificant.

Conclusions: The health status of elderly patients with chronic diseases is affected by socioeconomic support in China. In order to improve the health of elderly patients with chronic diseases, it is necessary to increase socioeconomic support. Meanwhile, it is also essential to pay attention to the differences in economic support between different regions and increase the socioeconomic support for elderly patients with chronic diseases in undeveloped regions so as to improve their health status.
Review: Influences of Semiconductor Metal Oxide Properties on Gas Sensing Characteristics
Authors: Saruhan Bilge , Lontio Fomekong Roussin , Nahirniak Svitlana
Published: April 2021

Semiconductor metal oxides (SMOxs) are widely used in gas sensors due to their excellent sensing properties, abundance, and ease of manufacture. The best examples of these sensing materials are SnO2 and TiO2 that have wide band gap and offer unique set of functional properties; the most important of which are electrical conductivity and high surface reactivity. There has been a constant development of SMOx sensor materials in the literature that has been accompanied by the improvement of their gas-sensitive properties for the gas detection. This review is dedicated to compiling of these efforts in order to mark the achievements in this area. The main material-specific aspects that strongly affect the gas sensing properties and can be controlled by the synthesis method are morphology/nanostructuring and dopants to vary crystallographic structure of MOx sensing material.
Binary Gravitational Perturbations and Their Influence on the Habitability of Circumstellar Planets
Authors: Pilat-Lohinger Elke , Bazsó Ákos
Published: April 2021

In order to assess the habitability of planets in binary star systems, not only astrophysical considerations regarding stellar and atmospheric conditions are needed, but orbital dynamics and the architecture of the system also play an important role. Due to the strong gravitational perturbations caused by the presence of the second star, the study of planetary orbits in double star systems requires special attention. In this context, we show the important role of the main gravitational perturbations (resonances) and review our recently developed methods which allow a quick determination of locations of secular resonances (SRs) in binary stars for circumstellar planetary motion where a giant planet has to move exterior to the habitable zone (HZ). These methods provide the basis for our online-tool ShaDoS which allows a quick check of circumstellar HZs regarding secular perturbations. It is important to know the locations of SRs since they can push a dynamically quiet HZ into a high-eccentricity state which will change the conditions for habitability significantly. Applications of SHaDoS to the wide binary star HD106515 AB and the tight system HD41004 AB reveal a quiet HZ for both systems. However, the study of these systems indicates only for the tight binary star a possible change of the HZ's dynamical state if the orbital parameters change due to new observational data.
Highlights of Discoveries for δ Scuti Variable Stars From the Kepler Era
Authors: Guzik Joyce Ann
Published: April 2021

The NASAKeplerand follow-on K2 mission (2009–2018) left a legacy of data and discoveries, finding thousands of exoplanets, and also obtaining high-precision long time-series data for hundreds of thousands of stars, including many types of pulsating variables. Here we highlight a few of the ongoing discoveries fromKeplerdata on δ Scuti pulsating variables, which are core hydrogen-burning stars of about twice the mass of the Sun. We discuss many unsolved problems surrounding the properties of the variability in these stars, and the progress enabled byKeplerdata in using pulsations to infer their interior structure, a field of research known as asteroseismology.
Case Report: Bowel Occlusion Following the Use of Barbed Sutures in Abdominal Surgery. A Single-Center Experience and Literature Review
Authors: Stabile Guglielmo , Romano Federico , De Santo Davide , Sorrentino Felice , Nappi Luigi , Cracco Francesco , Ricci Giuseppe
Published: April 2021

Introduction: A high level of surgical ability is required to perform endoscopic knot tying. Barbed sutures help in avoiding this procedure, thus reducing intraoperative time and lowering blood loss and hospitalization time when compared to traditional sutures. Some cases of bowel occlusion following the use of barbed sutures have been described in literature. All of them are characterized by the entanglement of an intestinal loop in wire barbs with bowel occlusion symptoms.

Case Presentation: We report two more cases which occurred in our Institute in 2020 and review those which have been reported in the literature by searching on Pubmed, Scopus, and Embase. We used the search terms: “Barbed,” ”Suture,” “Bowel,” and ”Obstruction.” We examined in the literature the surgical procedures, the type of complications, the time to onset of the complications, and the type of barbed suture.

Discussion: Twenty-two cases in total were reported in the literature from 2011 to 2020, and bowel complications were largely subsequent to interventions such as hernia surgical repair and myomectomy. In order to take advantage of barbed sutures while minimizing the risk of adverse events, such as intestinal occlusion, some precautions may be considered, such as the shortening of thread tails and use of antiadhesive barriers. Moreover, performing a few stitches backwards when ending the suture might be a useful suggestion. Further studies in this field may be useful in order to assess whether it might be better avoiding barbed suture application on serosal tissues to prevent bowel damage.
Potential Pain in Fish and Decapods: Similar Experimental Approaches and Similar Results
Authors: Elwood Robert W.
Published: April 2021

I review studies that examined the possibility of pain experience in fish and note how they provided guidance on general methods that could be applied to other animals such as decapod crustaceans. The fish studies initially reported the occurrence of prolonged rocking movements in trout and rubbing of their lips if they were injected with acetic acid. Subsequent studies examined the role of morphine in reducing these activities and examined shifts in attention when responding to noxious stimuli. Various studies take up these themes in decapods. The results reported for the two taxonomic groups are remarkably similar and indicate that responses of both go beyond those expected of mere nociceptive reflex. Thus, the idea of pain cannot be dismissed by the argument that fish and decapods respond only by reflex. The responses of both clearly involve central processing, and pain experience, although not proven for either, is a distinct possibility. These studies have been the subjects of highly critical opinion pieces and these are examined and rebutted. The conclusion is that both fish and decapods should be awarded consideration for their welfare.