bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysmetabolic Iron Overload in Metabolic Syndrome
Authors: Sachinidis Alexandros , Doumas Michael , Imprialos Konstantinos , Stavropoulos Konstantinos , Katsimardou Alexandra , Athyros Vasilios G. 
Published: January 2020

Background:
We sought to determine the association of dysmetabolic iron overload syndrome (DIOS)
with metabolic syndrome (MetS).

Methods:
Several studies have shown that DIOS is associated with Mets, mainly through the pathogenesis of its
components: type 2 diabetes mellitus (T2DM), essential hypertension, non-alcoholic fatty liver disease (NAFLD)
and polycystic ovary syndrome (POS).

Results:
Serum ferritin levels increase proportionally according to the degree of insulin resistance (IR) and the
number of components of Mets. Moreover, DIOS predicts the onset of T2DM and NAFLD. Dysregulation of iron
metabolism in DIOS is due to a multifactorial and dynamic process triggered by an unhealthy diet, facilitated by
environmental and genetic cofactors, and resulting in a bidirectional relation between the liver and visceral adipose
tissue (VAT). Iron removal combined with a healthy diet improved both insulin sensitivity and beta-cell function,
but had no significant effect on blood glucose; however, phlebotomy therapy might be considered with
conflicting results.

Conclusion:
Iron overload is closely associated with metabolic syndrome and its components; however, it remains
under-appreciated in everyday clinical practice. Diet and lifestyle modification offer some clinical benefit;
however, it is not adequate for successful management of the disease. The results of phlebotomy remain controversial,
underlying the necessity of further efforts in this field.
Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review
Authors: Shahcheraghi Seyed H. , Tchokonte-Nana Venant , Lotfi Marzieh , Lotfi Malihe , Ghorbani Ahmad , Sadeghnia Hamid R. 
Published: January 2020

:
Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90%
of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of
oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis
of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth
factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved
in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic
functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In
addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy,
and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by
invasion and migration, is an important tool in designing effective therapeutic interventions. This review will
investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.
Experimental Models for the Discovery of Novel Anticonvulsant Drugs: Focus on Pentylenetetrazole-Induced Seizures and Associated Memory Deficits
Authors: Alachkar Alaa , Ojha Shreesh K. , Sadeq Adel , Adem Abdu , Frank Annika , Stark Holger , Sadek Bassem 
Published: January 2020

:
Epilepsy is a chronic neurological disorder characterized by irregular, excessive neuronal excitability,
and recurrent seizures that affect millions of patients worldwide. Currently, accessible antiepileptic drugs (AEDs)
do not adequately support all epilepsy patients, with around 30% patients not responding to the existing therapies.
As lifelong epilepsy treatment is essential, the search for new and more effective AEDs with an enhanced safety
profile is a significant therapeutic goal. Seizures are a combination of electrical and behavioral events that can
induce biochemical, molecular, and anatomic changes. Therefore, appropriate animal models are required to
evaluate novel potential AEDs. Among the large number of available animal models of seizures, the acute pentylenetetrazole
(PTZ)-induced myoclonic seizure model is the most widely used model assessing the anticonvulsant
effect of prospective AEDs, whereas chronic PTZ-kindled seizure models represent chronic models in which the
repeated administration of PTZ at subconvulsive doses leads to the intensification of seizure activity or enhanced
seizure susceptibility similar to that in human epilepsy. In this review, we summarized the memory deficits accompanying
acute or chronic PTZ seizure models and how these deficits were evaluated applying several behavioral
animal models. Furthermore, major advantages and limitations of the PTZ seizure models in the discovery of
new AEDs were highlighted. With a focus on PTZ seizures, the major biochemicals, as well as morphological
alterations and the modulated brain neurotransmitter levels associated with memory deficits have been illustrated.
Moreover, numerous medicinal compounds with concurrent anticonvulsant, procognitive, antioxidant effects,
modulating effects on several brain neurotransmitters in rodents, and several newly developed classes of compounds
applying computer-aided drug design (CADD) have been under development as potential AEDs. The
article details the in-silico approach following CADD, which can be utilized for generating libraries of novel
compounds for AED discovery. Additionally, in vivo studies could be useful in demonstrating efficacy, safety,
and novel mode of action of AEDs for further clinical development.
Mesenchymal Stem Cell-Conditioned Medium Rescues LPS-Impaired ENaC Activity in Mouse Trachea via WNK4 Pathway
Authors: Hou Yapeng , Zhou Zhiyu , Liu Hongfei , Zhang Honglei , Ding Yan , Cui Yong , Nie Hongguang 
Published: January 2020

Background:
Airway epithelium plays an essential role in maintaining the homeostasis and function of
respiratory system as the first line of host defense. Of note, epithelial sodium channel (ENaC) is one of the victims
of LPS-induced airway injury. Regarding the great promise held by mesenchymal stem cells (MSCs) for
regenerative medicine in the field of airway injury and the limitations of cell-based MSCs therapy, we focused on
the therapeutic effect of MSCs conditioned medium (MSCs-CM) on the ENaC activity in mouse tracheal epithelial
cells.

Methods:
Ussing chamber apparatus was applied to record the short-circuit currents in primary cultured mouse
tracheal epithelial cells, which reflects the ENaC activity. Expressions of α and γ ENaC were measured at the
protein and mRNA levels by western blot and real-time PCR, respectively. The expression of with-no-lysinekinase-
4 (WNK4) and ERK1/2 were measured at protein levels, and the relationship between WNK4 and ERK1/2
was determined by WNK4 knockdown.

Results:
MSCs-CM restored the LPS-impaired ENaC activity, as well as enhanced the mRNA and protein expressions
of ENaC in primary cultured mouse tracheal epithelial cells. Meanwhile, WNK4 and ERK1/2, both
negative-regulators of ENaC, were suppressed accordingly after the administration of MSCs-CM in LPS-induced
airway injury. After WNK4 gene was knocked down by siRNA, the level of ERK1/2 phosphorylation decreased.

Conclusion:
In light of the key role of ENaC in fluid reabsorption and the beneficial effects of MSCs-CM in the
injury of airway epithelium, our results suggest that MSCs-CM is effective in alleviating LPS-induced ENaC
dysfunction through WNK4-ERK1/2 pathway, which will provide a potent direction for the therapy of airway
injury.
Gut Dysbiosis Dysregulates Central and Systemic Homeostasis via Suboptimal Mitochondrial Function: Assessment, Treatment and Classification Implications
Authors: Anderson George , Maes Michael 
Published: January 2020

:
The gut and mitochondria have emerged as two important hubs at the cutting edge of research
across a diverse array of medical conditions, including most psychiatric conditions. This article highlights
the interaction of the gut and mitochondria over the course of development, with an emphasis on
the consequences for transdiagnostic processes across psychiatry, but with relevance to wider medical
conditions. As well as raised levels of circulating lipopolysaccharide (LPS) arising from increased gut
permeability, the loss of the short-chain fatty acid, butyrate, is an important mediator of how gut dysbiosis
modulates mitochondrial function. Reactive cells, central glia and systemic immune cells are also
modulated by the gut, in part via impacts on mitochondrial function in these cells. Gut-driven alterations
in the activity of reactive cells over the course of development are proposed to be an important determinant
of the transdiagnostic influence of glia and the immune system. Stress, including prenatal stress,
also acts via the gut. The suppression of butyrate, coupled to raised LPS, drives oxidative and nitrosative
stress signalling that culminates in the activation of acidic sphingomyelinase-induced ceramide. Raised
ceramide levels negatively regulate mitochondrial function, both directly and via its negative impact on
daytime, arousal-promoting orexin and night-time sleep-promoting pineal gland-derived melatonin.
Both orexin and melatonin positively regulate mitochondria oxidative phosphorylation. Consequently,
gut-mediated increases in ceramide have impacts on the circadian rhythm and the circadian regulation of
mitochondrial function. Butyrate, orexin and melatonin can positively regulate mitochondria via the disinhibition
of the pyruvate dehydrogenase complex, leading to increased conversion of pyruvate to acetyl-
CoA. Acetyl-CoA is a necessary co-substrate for the initiation of the melatonergic pathway in mitochondria
and therefore the beneficial effects of mitochondria melatonin synthesis on mitochondrial function.
This has a number of treatment implications across psychiatric and wider medical conditions, including
the utilization of sodium butyrate and melatonin.

:
Overall, gut dysbiosis and increased gut permeability have significant impacts on central and systemic
homeostasis via the regulation of mitochondrial function, especially in central glia and systemic immune
cells.
The Value of Neuroimaging Techniques in the Translation and Transdiagnostic Validation of Psychiatric Diagnoses - Selective Review
Authors: Todeva-Radneva Anna , Paunova Rositsa , Kandilarova Sevdalina , St. Stoyanov Drozdstoy 
Published: January 2020

:Psychiatric diagnosis has long been perceived as more of an art than a science since its foundations lie within the observation, and the self-report of the patients themselves and objective diagnostic biomarkers are lacking. Furthermore, the diagnostic tools in use not only stray away from the conventional medical framework but also remain invalidated with evidence-based concepts. However, neuroscience, as a source of valid objective knowledge has initiated the process of a paradigm shift underlined by the main concept of psychiatric disorders being “brain disorders”. It is also a bridge closing the explanatory gap among the different fields of medicine via the translation of the knowledge within a multidisciplinary framework.:The contemporary neuroimaging methods, such as fMRI provide researchers with an entirely new set of tools to reform the current status quo by creating an opportunity to define and validate objective biomarkers that can be translated into clinical practice. Combining multiple neuroimaging techniques with the knowledge of the role of genetic factors, neurochemical imbalance and neuroinflammatory processes in the etiopathophysiology of psychiatric disorders is a step towards a comprehensive biological explanation of psychiatric disorders and a final differentiation of psychiatry as a well-founded medical science.:In addition, the neuroscientific knowledge gained thus far suggests a necessity for directional change to exploring multidisciplinary concepts, such as multiple causality and dimensionality of psychiatric symptoms and disorders. A concomitant viewpoint transition of the notion of validity in psychiatry with a focus on an integrative validatory approach may facilitate the building of a collaborative bridge above the wall existing between the scientific fields analyzing the mind and those studying the brain.
Cumulative HIV Viremia Copy-Years and Hypertension in People Living with HIV
Authors: Xu Yunan , Chen Xinguang , Wijayabahu Akemi , Zhou Zhi , Yu Bin , Spencer Emma C. , Cook Robert L. 
Published: January 2020

Background:
Evidence regarding the association between HIV viral load (VL) and hypertension
is inconsistent. In this study, we investigated the relationship using viremia copy-years
(VCY), a cumulative measure of HIV plasma viral burden.

Methods:
Data were analyzed for 686 PLWH in the Florida Cohort Study, who had at least five
years of VL data before the baseline. VL data were extracted from Enhanced HIV/AIDS Reporting
System (eHARS) and used to define peak VL (pVL), recent VL (rVL), and undetectable VL (uVL:
rVL<50copies/mL). A five-year VCY (log10 copy × years/mL) before the baseline investigation,
was calculated and divided into 5 groups (≤2.7, 2.8-3.7, 3.8-4.7, 4.8-5.7 and >5.7) for analysis. Hypertension
was determined based on hypertension diagnosis from medical records. Multivariable logistic
regression was used for association analysis.

Results:
Of the total sample, 277 (40.4%) participants were hypertensive. Compared to the participants
with lowest VCY (≤2.7 log10 copy × years/mL), the odds ratios (OR) and 95% confidence interval
[95% CI] for hypertension of the remaining four groups, in order, were 1.91 [1.11, 3.29], 1.91
[1.03, 3.53], 2.27 [1.29, 3.99], and 1.25 [0.65, 2.42], respectively, controlling for confounders. The
association was independent of pVL, rVL, and uVL, each of which was not significantly associated
with hypertension.

Conclusion:
Persistent HIV infection is a risk factor for hypertension among PLWH. Information
provided by VCY is more effective than single time-point VL measures in investigating HIV infection-
hypertension relationship. The findings of this study support the significance of continuous viral
suppression in hypertension prevention among PLWH.
Analysis of Collective Human Intelligence for Diagnosis of Pigmented Skin Lesions Harnessed by Gamification Via a Web-Based Training Platform: Simulation Reader Study
Authors: Rinner Christoph , Kittler Harald , Rosendahl Cliff , Tschandl Philipp 
Published: January 2020

Background
The diagnosis of pigmented skin lesion is error prone and requires domain-specific expertise, which is not readily available in many parts of the world. Collective intelligence could potentially decrease the error rates of nonexperts.

Objective
The aim of this study was to evaluate the feasibility and impact of collective intelligence for the detection of skin cancer.

Methods
We created a gamified study platform on a stack of established Web technologies and presented 4216 dermatoscopic images of the most common benign and malignant pigmented skin lesions to 1245 human raters with different levels of experience. Raters were recruited via scientific meetings, mailing lists, and social media posts. Education was self-declared, and domain-specific experience was tested by screening tests. In the target test, the readers had to assign 30 dermatoscopic images to 1 of the 7 disease categories. The readers could repeat the test with different lesions at their own discretion. Collective human intelligence was achieved by sampling answers from multiple readers. The disease category with most votes was regarded as the collective vote per image.

Results
We collected 111,019 single ratings, with a mean of 25.2 (SD 18.5) ratings per image. As single raters, nonexperts achieved a lower mean accuracy (58.6%) than experts (68.4%; mean difference=−9.4%; 95% CI −10.74% to −8.1%; P<.001). Collectives of nonexperts achieved higher accuracies than single raters, and the improvement increased with the size of the collective. A collective of 4 nonexperts surpassed single nonexperts in accuracy by 6.3% (95% CI 6.1% to 6.6%; P<.001). The accuracy of a collective of 8 nonexperts was 9.7% higher (95% CI 9.5% to 10.29%; P<.001) than that of single nonexperts, an improvement similar to single experts (P=.73). The sensitivity for malignant images increased for nonexperts (66.3% to 77.6%) and experts (64.6% to 79.4%) for answers given faster than the intrarater mean.

Conclusions
A high number of raters can be attracted by elements of gamification and Web-based marketing via mailing lists and social media. Nonexperts increase their accuracy to expert level when acting as a collective, and faster answers correspond to higher accuracy. This information could be useful in a teledermatology setting.
Nonmedical Factors and Health-Related Quality of Life in CKD in India
Authors: Modi Gopesh K. , Yadav Ashok K. , Ghosh Arpita , Kamboj Kajal , Kaur Prabhjot , Kumar Vivek , Bhansali Shobhit , Prasad Narayan , Sahay Manisha , Parameswaran Sreejith , Varughese Santosh , Gang Sishir , Singh Shivendra , Sircar Dipankar , Gopalakrishnan Natarajan , Jaryal Ajay , Vikrant Sanjay , Agarwal Seema Baid , Jha Vivekanand 
Published: January 2020

Background and objectives
Patient-reported outcomes have gained prominence in the management of chronic noncommunicable diseases. Measurement of health-related quality of life is being increasingly incorporated into medical decision making and health care delivery processes.

Design, setting, participants, & measurements
The Indian Chronic Kidney Disease Study is a prospective cohort of participants with mild to moderate CKD. Baseline health-related quality of life scores, determined by the standardized Kidney Disease Quality of Life 36 item instrument, are presented for the inception cohort (n=2919). Scores are presented on five subscales: mental component summary, physical component summary, burden, effect of kidney disease, and symptom and problems; each is scored 0–100. The associations of socioeconomic and clinical parameters with the five subscale scores and lower quality of life (defined as subscale score <1 SD of the sample mean) were examined. The main socioeconomic factors studied were sex, education, occupation, and income. The key medical factors studied were age, eGFR, diabetes, hypertension, and albuminuria.

Results
The mean (SD) subscale scores were physical component summary score, 43±9; mental component summary score, 48±10; burden, 61±33; effects, 87±13; and symptoms, 90±20. Among the socioeconomic variables, women, lower education, and lower income were negatively associated with reduced scores across all subscales. For instance, the respective β-coefficients (SD) for association with the physical component summary subscale were −2.6 (−3.4 to −1.8), −1.5 (−2.2 to −0.7), and −1.6 (−2.7 to −0.5). Medical factors had inconsistent or no association with subscale scores. The quality of life scores also displayed regional variations.

Conclusions
In this first of its kind analysis from India, predominantly socioeconomic factors were associated with quality of life scores in patients with CKD.
Kajian literatur: Dampak perubahan iklim terhadap timbulnya penyakit tular nyamuk terutama Limfatik Filariasis
Authors: Novita Risqa 
Published: January 2020

Lingkungan memberikan kontribusi terbesar sebesar 45% terhadap status kesehatan seseorang dibandingkan faktor lainnya seperti perilaku sebesar 30%, pelayanan kesehatan sebesar 20% dan keturunan sebesar 5%. Kondisi kesehatan lingkungan di Indonesia masih rendah, yang dibuktikan dengan rendahnya pencapaian indikator kesehatan lingkungan dan masih menjadi masalah kesehatan tertinggi yang disebabkan oleh kondisi lingkungan yang buruk. Perubahan iklim menimbulkan peningkatan mosquito borne diseases terutama penyakit Limfatik Filariasis yang ditularkan oleh nyamuk Aedes sp, Anopheles sp, Culex sp dan Mansonia sp. Tujuan penulisan review artikel ini adalah untuk mengetahui dampak perubahan iklim dengan kejadian mosquito borne diseases, terutama Limfatik Filariasis. Studi ini berupa review dari literatur di Google dan Pubmed yang dicari melalui pencarian kata kunci yaitu kesehatan lingkungan, perubahan iklim, mosquito borne diseases dan Limfatik Filariasis. Berdasarkan analisis terhadap literatur diketahui bahwa kesehatan lingkungan merupakan suatu standar yang harus dicapai untuk terciptanya kesehatan manusia. Variabel perubahan iklim yang berpengaruh terhadap perkembangan nyamuk perantara Limfatik filariasis adalah temperatur dan presipitasi. Temperatur sebesar 33.50C dan presipitasi 600 mm optimal untuk perkembangan nyamuk. Kesimpulan. Perubahan iklim dapat berpengaruh terhadap kejadian penyakit mosquito borne diseases terutama Limfatik Filariasis. Nyamuk perantara Limfatik filariasis bersifat ektoterm yang bergantung dengan perubahan iklim.
Kata kunci : Kesehatan lingkungan, Limfatik Filariasis, mosquito borne diseases, perubahan iklim
PENINGKATAN PRODUKTIVITAS PADI HIBRIDA MELALUI PEMBERIAN PUPUK N DENGAN SISTEM RATUN DI LAHAN PASANG SURUT
Authors: Gribaldi Gribaldi , Nurlaili Nurlaili , Danial Ekawati 
Published: January 2020

Penelitian bertujuan untuk mengetahui peningkatan produktivitas padi hibrida dengan sistem ratun pada beberapa dosis dan aplikasi pupuk N di Lahan pasang surut. Penelitian dilaksanakan pada bulan April - Agustus 2019 di Lahan Percobaan Dinas Pertanian Kabupaten Banyuasin, dengan menggunakan Rancangan Acak Kelompok Faktorial (RAKF) yang diulang tiga kali. Faktor faktor yang diteliti terdiri dari; Perlakuan dosis pupuk (N): dosis 90 kg N/ha (N1), dosis 135 kg N/ha (N2). Perlakuan aplikasi pupuk (A): aplikasi pupuk ½ dosis saat tanam + ½ dosis fase primordia (A1); aplikasi pupuk 1/3 dosis saat tanam + 1/3 dosis fase primordia + 1/3 dosis saat panen (A2), aplikasi pupuk 1/3 dosis saat tanam + 1/3 dosis fase primordia + 1/6 dosis saat panen + 1/6 dosis pada 21 hari setelah panen (A3). Hasil penelitian menunjukan, dosis dan aplikasi pupuk N berpengaruh terhadap peningkatan produktivitas padi hibrida di lahan pasang surut, Peningkatan produktivitas padi hibrida pada beberapa dosis dan aplikasi pupuk N berkisar 37.3-63.2 persen. Peningkatan produktivitas tertinggi didapat pada perlakuan pemupukan dosis 135 kgN/ha dan aplikasinya 1/3 dosis saat tanam+1/3 dosis saat primordia dan 1/3 dosis saat panen, yaitu sebesar 63,2 persen atau dengan hasil gabah sebesar 7,28 ton/ha.
Kuliah Lapangan Terpadu Berbasis Inkuiri untuk Meningkatkan Penguasaan Konsep Mahasiswa Pendidikan Biologi
Authors: Ibrahim Yusuf 
Published: January 2020

Kuliah lapangan merupakan pengalaman belajar penting bagi mahasiswa calon guru biologi. Tujuan dari penelitian ini adalah untuk mengetahui peningkatan penguasaan konsep mahasiswa melalui pengalaman belajar kuliah lapangan terpadu berbasis inkuiri. Subjek penelitian dalam penelitian ini adalah mahasiswa calon guru biologi di salah satu iniversitas swasta di kota Bandung (n=30). Instrumen yang digunakan dalam penelitian ini adalah tes penguasaan konsep. Metodologi penelitian yang digunakan dalam penelitian ini adalah metode kuasi ekperimen dengan desain one group postes postes design. Hasil penelitian menunjukan bahwa implementasi pengalaman belajar kuliah lapangan terpadu berbasis inkuiri dapat meningkatkan penguasaan konsep mahasiswa calon guru biologi (N-gain=0,62). Pengalaman belajar melalui kuliah lapangan terpadu berbasis inkuiri dapat membantu mahasiswa meningkatkan penguasaan konsepnya.