Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and Safety of Berberine Alone or Combined with Statins for the Treatment of Hyperlipidemia: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.

To systematically evaluate the efficacy and safety of berberine for the treatment of hyperlipidemia, six electronic literature databases including SinoMed, CNKI, WanFang Data, PubMed, Embase and The Cochrane Library were searched to collect clinical randomized controlled trials (RCTs) of berberine alone or combined with statins for the treatment of hyperlipidemia from the inception to 8 March 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included RCTs. Then, meta-analysis was performed by using RevMan 5.3 software. A total of 11 RCTs involving 1386 patients were finally included. The results of meta-analysis showed that compared with the placebo group, berberine could significantly reduce the total cholesterol and low-density lipoprotein levels and elevate the high density lipoprotein level ( P<0.05 ). Compared with the simvastatin group, berberine was effective only in reducing the level of triglyceride ( MD=-0.37 , 95% CI: - 0.66, - 0.07, P=0.02 ). There, however, was no statistical significance between the BBR group and simvastatin group in the low density lipoprotein and high density lipoprotein levels. Compared with the simvastatin group, berberine plus simvastatin was more effective in reducing the level of triglyceride ( MD=-0.33 , 95% CI: - 0.46, - 0.20, P<0.00001 ) and total cholesterol ( MD=-0.36 , 95% CI: - 0.60, - 0.12, P=0.003 ). In terms of adverse reactions, the incidence of adverse reactions including transaminase elevation and muscle aches was lower in the berberine alone or combined with simvastatin group than that in the control group, while the instance of constipation was higher. This study suggests that berberine is effective for hyperlipidemia. The quality and quantity of included studies, however, were dissatisfactory, which might decrease the reliability of the results. Higher quality studies are needed to provide more high quality evidence.
Real-World Situation of Lateral Lymph Node Dissection for Rectal Cancer in Japan.

To the Editor—We appreciate the letter to the editor from Sakai and Higa concerning the lateral node dissection (LND) videos recently published in Diseases of the Colon & Rectum. Perhaps a few comments are pertinent here for the readership still considering this technique in their own clinical practice environment. First, the observation of “only” 7% lateral lymph node metastases in the JCOG2012 trial should not be seen as a reason for any decrease in the actual risk of lateral node metastases. Instead, the study population restricted to patients with “unsuspected” lateral node disease is perhaps the main reason for the low rates of metastatic disease compared with historically reported results. In fact, 7% of lateral node metastases among patients with unsuspected disease could have been considered rather high for most Western surgeons, provided very few would even have considered such an approach in the prophylactic setting. One should not forget that noninferiority of total mesorectal excision (TME) alone versus TME + prophylactic bilateral LND was not reached in this study. This suggests that, in Real-World Situation of Lateral Lymph Node Dissection for Rectal Cancer in Japan
Clinician Experiences and Attitudes Regarding Screening for Social Determinants of Health in a Large Integrated Health System

Background: Clinical screening for basic social needs—such as food and housing insecurity—is becoming more common as health systems develop programs to address social determinants of health. Clinician attitudes toward such programs are largely unexplored. Objective: To describe the attitudes and experiences of social needs screening among a variety of clinicians and other health care professionals. Research Design: Multicenter electronic and paper-based survey. Subjects: Two hundred fifty-eight clinicians including primarily physicians, social workers, nurses, and pharmacists from a large integrated health system in Southern California. Measures: Level of agreement with prompts exploring attitudes toward and barriers to screening and addressing social needs in different clinical settings. Results: Overall, most health professionals supported social needs screening in clinical settings (84%). Only a minority (41%) of clinicians expressed confidence in their ability to address social needs, and less than a quarter (23%) routinely screen for social needs currently. Clinicians perceived lack of time to ask (60%) and resources (50%) to address social needs as their most significant barriers. We found differences by health profession in attitudes toward and barriers to screening for social needs, with physicians more likely to cite time constraints as a barrier. Conclusions: Clinicians largely support social needs programs, but they also recognize key barriers to their implementation. Health systems interested in implementing social needs programs should consider the clinician perspective around the time and resources required for such programs and address these perceived barriers.
Risk factors associated with persistent airflow limitation in severe or difficult-to-treat asthma: insights from the TENOR study.

BACKGROUND The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study is among the largest to assess persistent airflow limitation and the first to evaluate a wide range of potential risk factors in high-risk patients with severe or difficult-to-treat asthma. A better understanding is needed regarding factors associated with persistent airway obstruction; this study was performed to determine demographic and clinical characteristics associated with persistent airflow limitation. METHODS Data from adult patients (>or= 18 years old) with severe or difficult-to-treat asthma were evaluated. Patients with COPD, obesity with a restrictive respiratory pattern, or a >or= 30 pack-year history of smoking were excluded. Patients with persistent airflow limitation (postbronchodilator FEV1/FVC ratio <or= 70% at two annual consecutive visits) and normal postbronchodilator FEV1/FVC ratio (75 to 85%) were compared. Multivariate analysis identified factors independently associated with persistent airflow limitation. RESULTS Of 1,017 patients, 612 patients (60%) showed evidence of persistent airflow limitation. Risk factors were as follows: older age (odds ratio [OR] per 10 years, 1.4; 95% confidence interval [CI], 1.3 to 1.6); male gender (OR, 4.5; 95% CI, 2.3 to 8.5); black ethnicity (OR, 2.2; 95% CI, 1.3 to 3.8); current or past smoking (OR, 3.9; 95% CI, 1.8 to 8.6; and OR, 1.6; 95% CI, 1.2 to 2.3, respectively); aspirin sensitivity (OR, 1.5; 95% CI, 1.0 to 2.4); and longer asthma duration (OR per 10 years, 1.6; 95% CI, 1.4 to 1.8). Protective factors were Hispanic ethnicity, higher education, family history of atopic dermatitis, pet(s) in the home, and dust sensitivity. CONCLUSIONS Persistent airflow limitation is prevalent in patients with severe or difficult-to-treat asthma and is associated with identifiable clinical and demographic characteristics.
Imidacloprid poisoning case series: potential for liver injury

Abstract Introduction: Imidacloprid is a commonly used neonicotinoid insecticide in Thailand. Limited reports suggest it may be associated with liver injury. Case series: A retrospective poison center case series identified 128 cases of imidacloprid ingestion from 2010–2016, of which four developed liver injury. Results: Three patients ingested soluble liquid concentrates and one ingested water-dispersible granules of imidacloprid. The estimated doses of ingestion ranged from 2–35 g. One patient developed cholestatic liver injury, two developed hepatocellular liver injury, and the remaining patient, who ingested the highest dose, developed a mixed pattern of liver injury. Median onset of liver injury was 5.5 days. Discussion: In prior case reports and animal studies, these cases suggest imidacloprid toxicity is associated with liver injury that may be delayed. This is consistent with our finding. The cases also demonstrated a possible dose-response relationship of imidacloprid ingestion with severity and type of liver injury. All findings suggested that imidacloprid might contribute to liver injury. Conclusion: We report four cases of liver injury, which are possibly related to ingestion of imidacloprid. In management, consideration should be given to repeating liver tests as an outpatient if initial tests are normal, with counseling on the possibility of delayed liver injury.
Autologous activated platelet-rich plasma injection into adult human ovary tissue: molecular mechanism, analysis, and discussion of reproductive response

In clinical infertility practice, one intractable problem is low (or absent) ovarian reserve which in turn reflects the natural oocyte depletion associated with advancing maternal age. The number of available eggs has been generally thought to be finite and strictly limited, an entrenched and largely unchallenged tenet dating back more than 50 years. In the past decade, it has been suggested that renewable ovarian germline stem cells (GSCs) exist in adults, and that such cells may be utilized as an oocyte source for women seeking to extend fertility. Currently, the issue of whether mammalian females possess such a population of renewable GSCs remains unsettled. The topic is complex and even agreement on a definitive approach to verify the process of ‘ovarian rescue’ or ‘re-potentiation’ has been elusive. Similarities have been noted between wound healing and ovarian tissue repair following capsule rupture at ovulation. In addition, molecular signaling events which might be necessary to reverse the effects of reproductive ageing seem congruent with changes occurring in tissue injury responses elsewhere. Recently, clinical experience with such a technique based on autologous activated platelet-rich plasma (PRP) treatment of the adult human ovary has been reported. This review summarizes the present state of understanding of the interaction of platelet-derived growth factors with adult ovarian tissue, and the outcome of human reproductive potential following PRP treatment.
Relation between Dietary Habits, Physical Activity, and Anthropometric and Vascular Parameters in Children Attending the Primary School in the Verona South District

The aim of this school-based study was to identify the possible association between diet and physical activity, as well as the anthropometric, vascular, and gluco-lipid parameters. We administered two validated questionnaires for diet and physical activity (Food Frequency questionnaire (FFQ), Children-Physical Activity Questionnaire (PAQ-C)) to children at four primary schools in Verona South (Verona, Italy). Specific food intake, dietary pattern, and physical activity level expressed in Metabolic Equivalent of Task (MET) and PAQ-C score were inserted in multivariate linear regression models to assess the association with anthropometric, hemodynamic, and gluco-lipid measures. Out of 309 children included in the study, 300 (age: 8.6 ± 0.7 years, male: 50%; Obese (OB): 13.6%; High blood pressure (HBP): 21.6%) compiled to the FFQ. From this, two dietary patterns were identified: “healthy” and “unhealthy”. Direct associations were found between (i) “fast food” intake, Pulse Wave Velocity (PWV), and (ii) animal-derived fat and capillary cholesterol, while inverse associations were found between vegetable, fruit, and nut intake and capillary glucose. The high prevalence of OB and HBP and the significant correlations between some categories of food and metabolic and vascular parameters suggest the importance of life-style modification politics at an early age to prevent the onset of overt cardiovascular risk factors in childhood.
Role of Mitochondrial DNA Damage in ROS-Mediated Pathogenesis of Age-Related Macular Degeneration (AMD)

Age-related macular degeneration (AMD) is a complex eye disease that affects millions of people worldwide and is the main reason for legal blindness and vision loss in the elderly in developed countries. Although the cause of AMD pathogenesis is not known, oxidative stress-related damage to retinal pigment epithelium (RPE) is considered an early event in AMD induction. However, the precise cause of such damage and of the induction of oxidative stress, including related oxidative effects occurring in RPE and the onset and progression of AMD, are not well understood. Many results point to mitochondria as a source of elevated levels of reactive oxygen species (ROS) in AMD. This ROS increase can be associated with aging and effects induced by other AMD risk factors and is correlated with damage to mitochondrial DNA. Therefore, mitochondrial DNA (mtDNA) damage can be an essential element of AMD pathogenesis. This is supported by many studies that show a greater susceptibility of mtDNA than nuclear DNA to DNA-damaging agents in AMD. Therefore, the mitochondrial DNA damage reaction (mtDDR) is important in AMD prevention and in slowing down its progression as is ROS-targeting AMD therapy. However, we know far less about mtDNA than its nuclear counterparts. Further research should measure DNA damage in order to compare it in mitochondria and the nucleus, as current methods have serious disadvantages.
Mutation Breeding in Tomato: Advances, Applicability and Challenges

Induced mutagenesis is one of the most effective strategies for trait improvement without altering the well-optimized genetic background of the cultivars. In this review, several currently accessible methods such as physical, chemical and insertional mutagenesis have been discussed concerning their efficient exploration for the tomato crop improvement. Similarly, challenges for the adaptation of genome-editing, a newly developed technique providing an opportunity to induce precise mutation, have been addressed. Several efforts of genome-editing have been demonstrated in tomato and other crops, exploring its effectiveness and convenience for crop improvement. Descriptive data compiled here from such efforts will be helpful for the efficient exploration of technological advances. However, uncertainty about the regulation of genome-edited crops is still a significant concern, particularly when timely trait improvement in tomato cultivars is needed. In this regard, random approaches of induced mutagenesis are still promising if efficiently explored in breeding applications. Precise identification of casual mutation is a prerequisite for the molecular understanding of the trait development as well as its utilization for the breeding program. Recent advances in sequencing techniques provide an opportunity for the precise detection of mutagenesis-induced sequence variations at a large scale in the genome. Here, we reviewed several novel next-generation sequencing based mutation mapping approaches including Mutmap, MutChromeSeq, and whole-genome sequencing-based mapping which has enormous potential to accelerate the mutation breeding in tomato. The proper utilization of the existing well-characterized tomato mutant resources combined with novel mapping approaches would inevitably lead to rapid enhancement of tomato quality and yield. This article provides an overview of the principles and applications of mutagenesis approaches in tomato and discusses the current progress and challenges involved in tomato mutagenesis research.
Social Determinants of Appropriate Treatment for Muscle-Invasive Bladder Cancer

Background: Racial disparities in guideline-based, appropriate treatment (ApT) may be a significant driving force for differences in survival for people with nonmetastatic muscle-invasive bladder cancer (MIBC). We hypothesize that receipt of ApT is influenced by factors such as race and socioeconomic status, irrespective of neighborhood-level differences in healthcare, variations in practice patterns, and clinical characteristics of patients with nonmetastatic MIBC. Methods: Within the National Cancer Database, we identified individuals diagnosed with MIBC between 2004 and 2013. Multivariable logistic regression and mixed effects modelling was used to examine predictors of ApT, clustered within institutions. Results: A total of 51,350 individuals had clinically staged nonmetastatic, lymph node–negative MIBC. Black individuals comprised 6.4% of the cohort. Mean age was 72.6 years (SD 11.6) with a male predominance (71.4%). Less than half received ApT (42.6%). Fewer black individuals received ApT compared with white individuals (37% vs. 43%, P < 0.001). When clustered by institution, the odds of ApT were 21% lower for black individuals [odds ratio (OR), 0.79; 95% confidence interval (CI), 0.73–0.87] compared with white individuals with nonmetastatic MIBC. When restricted to higher volume centers with more diverse populations, black individuals had 25% lower odds of ApT (OR, 0.75; 95% CI, 0.61–0.91; P < 0.01), compared with white counterparts. Conclusions: Racial disparities in treatment persisted after accounting for various clinical factors and social determinants of health. Future efforts should focus on addressing racial bias to improve disparities in bladder cancer treatment. Impact: If we are not delivering evidence-based care due to these biases (after accounting for access and biology), then it is expected that patients will experience inferior outcomes.
Synaptic Microtubule-Associated Protein EB3 and SRC Phosphorylation Mediate Structural and Behavioral Adaptations During Withdrawal From Cocaine Self-Administration

Addictive behaviors, including relapse, are thought to depend in part on long-lasting drug-induced adaptations in dendritic spine signaling and morphology in the nucleus accumbens (NAc). While the influence of activity-dependent actin remodeling in these phenomena has been studied extensively, the role of microtubules and associated proteins remains poorly understood. We report that pharmacological inhibition of microtubule polymerization in the NAc inhibited locomotor sensitization to cocaine and contextual reward learning. We then investigated the roles of microtubule end-binding protein 3 (EB3) and SRC kinase in the neuronal and behavioral responses to volitionally administered cocaine. In synaptoneurosomal fractions from the NAc of self-administering male rats, the phosphorylation of SRC at an activating site was induced after 1 d of withdrawal, while EB3 levels were increased only after 30 d of withdrawal. Blocking SRC phosphorylation during early withdrawal by virally overexpressing SRCIN1, a negative regulator of SRC activity known to interact with EB3, abolished the incubation of cocaine craving in both male and female rats. Conversely, mimicking the EB3 increase observed after prolonged withdrawal increased the motivation to consume cocaine in male rats. In mice, the overexpression of either EB3 or SRCIN1 increased dendritic spine density and altered the spine morphology of NAc medium spiny neurons. Finally, a cocaine challenge after prolonged withdrawal recapitulated most of the synaptic protein expression profiles observed at early withdrawal. These findings suggest that microtubule-associated signaling proteins such as EB3 cooperate with actin remodeling pathways, notably SRC kinase activity, to establish and maintain long-lasting cellular and behavioral alterations following cocaine self-administration. SIGNIFICANCE STATEMENT Drug-induced morphological restructuring of dendritic spines of nucleus accumbens neurons is thought to be one of the cellular substrates of long-lasting drug-associated memories. The molecular basis of these persistent changes has remained incompletely understood. Here we implicate for the first time microtubule function in this process, together with key players such as microtubule-bound protein EB3 and synaptic SRC phosphorylation. We propose that microtubule and actin remodeling cooperate during withdrawal to maintain the plastic structural changes initially established by cocaine self-administration. This work opens new translational avenues for further characterization of microtubule-associated regulatory molecules as putative drug targets to tackle relapse to drug taking.
Clinical Value of Measurement of Internal Auditory Canal in Pediatric Cochlear Implantation

Objectives: The aims of this study were to clarify the clinical value of the bony cochlear nerve canal (BCNC) and internal auditory canal (IAC) in children with bilateral sensorineural hearing loss (b-SNHL) and to reveal the correlation between these parameters and outcomes after cochlear implantation (CI). Methods: Ninety-four ears with b-SNHL that received CI and 100 ears with normal hearing were enrolled. Parameters of IAC and pre- and post-CI categories of auditory performance scores were analyzed. Results: The width of the BCNC and the width, height, and length of the IAC were shorter in the b-SNHL group. BCNC and IAC width were associated with b-SNHL. The calculated cutoff values for BCNC and IAC width were 2.055 mm in the BCNC and 4.245 mm in the IAC, setting the sensitivity to 90%. Patients with narrow BCNCs and IACs had significantly worse post-CI auditory performance. Conclusions: BCNC and IAC widths were narrower in children with b-SNHL than in normal-hearing children. Narrow BCNC and IAC width had a negative impact on post-CI outcomes. The proposed cutoff values for BCNC and IAC width were meaningful when predicting the auditory outcome after CI, especially considering both.
Human herpesvirus–encoded kinase induces B cell lymphomas in vivo

Kaposi’s sarcoma–associated herpesvirus (KSHV) is a gammaherpesvirus that is the etiological agent of the endothelial cell cancer Kaposi’s sarcoma (KS) and 2 B cell lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD). KSHV ORF36, also known as viral protein kinase (vPK), is a viral serine/threonine kinase. We previously reported that KSHV vPK enhances cell proliferation and mimics cellular S6 kinase to phosphorylate ribosomal protein S6, a protein involved in protein synthesis. We created a mouse model to analyze the function of vPK in vivo. We believe this is the first mouse tumor model of a viral kinase encoded by a pathogenic human virus. We observed increased B cell activation in the vPK transgenic mice compared with normal mice. We also found that, over time, vPK transgenic mice developed a B cell hyperproliferative disorder and/or a high-grade B cell non-Hodgkin lymphoma at a greatly increased incidence compared with littermate controls. This mouse model shows that a viral protein kinase is capable of promoting B cell activation and proliferation as well as augmenting lymphomagenesis in vivo and may therefore contribute to the development of viral cancers.
Leptin and Immunological Profile in Obesity and Its Associated Diseases in Dogs

Growing scientific evidence has unveiled increased incidences of obesity in domestic animals and its influence on a plethora of associated disorders. Leptin, an adipokine regulating body fat mass, represents a key molecule in obesity, able to modulate immune responses and foster chronic inflammatory response in peripheral tissues. High levels of cytokines and inflammatory markers suggest an association between inflammatory state and obesity in dogs, highlighting the parallelism with humans. Canine obesity is a relevant disease always accompanied with several health conditions such as inflammation, immune-dysregulation, insulin resistance, pancreatitis, orthopaedic disorders, cardiovascular disease, and neoplasia. However, leptin involvement in many disease processes in veterinary medicine is poorly understood. Moreover, hyperleptinemia as well as leptin resistance occur with cardiac dysfunction as a consequence of altered cardiac mitochondrial metabolism in obese dogs. Similarly, leptin dysregulation seems to be involved in the pancreatitis pathophysiology. This review aims to examine literature concerning leptin and immunological status in obese dogs, in particular for the aspects related to obesity-associated diseases.