bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic self-medication in Afghanistan: first report
Authors: Roien Rohullah , Mousavi Sayed Hamid , Athaie Mohammad Arif , Mohaqiq Mahdi , Delshad Mohammad Hossein , pourhaji fatemeh
Published: April 2020

Introduction: The purpose of this study was to find, the prevalence of self-medication with antibiotics, and antibiotics used for self-treated disease.Methods: this cross-sectional study was carried out among 385 participants in 12 community pharmacies located in 4 different regions of Kabul from May to November 2017. Standard questionnaire based on similar studies was designed and distributed among participants. Data was collected and analyzed in SPSS 16.0.Results: out of 385 participants (61.29% male and 38.70% female) 282 persons (73.25%) had practiced antibiotic self-medication during last year. The common reasons for antibiotic self-medication was economic problems (26.95%), lack of time (22.69%), comfortability (21.63%), lack of confidence on health care system (17.37%), and poor access to health care facilities (11.34%). Conditions like cough (28.01%), common cold (14.89%), respiratory infections (13.47%), sore throat (12.41%) and diarrhea (7.44%) were commonly self-medicated with antibiotics. penicillins (25.17%), metronidazole (15.60%), ceftriaxone (14.18%), tetracycline (10.28%), Azithromycin (9.21%), cefixime (7.09%), ciprofloxacin (6.73%) were mostly used for self-medication. 93 (32.97%) respondents had experienced side effects during antibiotic self-medication. Conclusions: The prevalence of antibiotic self-medication is very high (75.53%) in Kabul and this widespread antibiotic use has increased the risk of antibiotic resistance. Awareness and Strict rules for selling antibiotics without prescription should be developed and implemented to improve the rational use of antibiotics. Only pharmacists or professional peoples should be permitted to work in pharmacies. The quality, accessibility and cost of health care services should be enhanced in order to improve patient’ satisfaction in health care system.
Recurrent recurrence of positive SARS-CoV-2 RNA in a COVID-19 patient
Authors: Cao Shugang , Wu Aimei , Li Jiaxia , Li Yuancheng , Xia Mingwu , Wu Juncang
Published: April 2020

Background: Coronavirus disease 2019 (COVID-19) is a highly infectious disease. A small proportion of discharged patients may become positive again for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, even if they meet the discharge criteria. Herein, we report a rare COVID-19 patient with recurrent recurrence of positive SARS-CoV-2 RNA.Case presentation: A 68-year-old man was admitted due to fever, muscle pain, and fatigue. He was initially diagnosed with COVID-19 according to two consecutive positive results for SARS-CoV-2 RNA plus clinical symptoms and chest CT findings, and was discharged from hospital when meeting the discharge criteria, including two consecutive negative results. He was tested positive for SARS-CoV-2 RNA twice during the quarantine and was hospitalized again. He was asymptomatic then, but IgG and IgM were both positive. He was discharged in the context of four consecutive negative test results for SARS-CoV-2 RNA after antiviral treatment. However, he was tested positive once again on the 3rd and 4th day after the second discharge, although still asymptomatic. IgG and IgM were still positive. After antiviral treatment, the results of SARS-CoV-2 RNA were negative in three consecutive retests, and he was finally discharged and quarantined for further surveillance. Conclusion: This case suggests that a small proportion of convalescent patients may become positive again for SARS-CoV-2 RNA and be a virus carrier.
From complex to simple : hierarchical free-energy landscape renormalized in deep neural networks
Authors: Yoshino Hajime
Published: April 2020

We develop a statistical mechanical approach based on the replica method to study the design space of deep and wide neural networks constrained to meet a large number of training data. Specifically, we analyze the configuration space of the synaptic weights and neurons in the hidden layers in a simple feed-forward perceptron network for two scenarios: a setting with random inputs/outputs and a teacher-student setting. By increasing the strength of constraints,~i.e. increasing the number of training data, successive 2nd order glass transition (random inputs/outputs) or 2nd order crystalline transition (teacher-student setting) take place layer-by-layer starting next to the inputs/outputs boundaries going deeper into the bulk with the thickness of the solid phase growing logarithmically with the data size.
This implies the typical storage capacity of the network grows exponentially fast with the depth.
In a deep enough network, the central part remains in the liquid phase.
We argue that in systems of finite width N, the weak bias field can remain in the center and plays the role of a symmetry-breaking field that connects the opposite sides of the system. The successive glass transitions bring about a hierarchical free-energy landscape with ultrametricity, which evolves in space: it is most complex close to the boundaries but becomes renormalized into progressively simpler ones in deeper layers. These observations provide clues to understand why deep neural networks operate efficiently. Finally, we present some numerical simulations of learning which reveal spatially heterogeneous glassy dynamics truncated by a finite width N effect.
Effects of antecedent soil water content on infiltration and erosion processes on loessial slopes under simulated rainfall
Authors: Ma Lan , Li Junyou , Liu Jingjing
Published: April 2020

Soil texture and antecedent soil water content (ASWC) are primary factors governing hillslope hydrological and erosion processes. We used simulated rainfall to investigate the runoff and erosion processes on sloped plots with three loessial soils and analyzed the effects of soil texture and ASWC on the hydrological processes. The results demonstrated that the average infiltration rate decreased with increasing clay content (i.e., Ansai (AS) loamy sand > Fuxian (FX) clay loam > Yangling (YL) clay). ASWC had little effect on infiltration processes for the YL clay but exerted a significant influence on infiltration for the FX and AS soils; this implies that infiltration models for loamy soils must consider the effects of ASWC. The Horton model was found to describe infiltration processes in these loessial soils better than the Kostiakov or Philip models. The YL clay yielded much less sediment than the FX and AS soils, and its sediment yield rate gradually decreased with the rainfall duration. There was a negative relationship between clay content and sediment yield under high ASWC, but no clear relation under low ASWC. These erosion differences derived from the splash erosion for the YL clay, and the depressions or rills occurred on the loamy soil plots.
A new backwash strategy for reducing the cost of an immersed ultrafiltration system by restricting cake layer breakage
Authors: Qu Fangshu , Li Xiaolian , He Junguo , Pan Zhihui , Zhao Yan , Rong Hongwei , Li Guibai , Yu Huarong
Published: April 2020

Ultrafiltration (UF) is increasingly used for potable water treatment, but membrane fouling necessitates the application of periodical backwash, which increases running cost. A new backwash strategy, in which air scouring was only applied with sludge water discharging, was proposed to improve backwash performance in a water plant using UF. Four gravity-driven UF systems were simultaneously run at increasing air scouring intervals (3–24hours) and sludge water discharging intervals (12–24hours). The membrane fluxes were monitored to assess membrane fouling and the mix solution turbidity was also monitored to investigate deposition of particles. The results indicated that membrane fouling was not aggravated by the extension of air scouring and sludge water discharging intervals. Water backwash on its own induced a shift of particle deposition from the membrane surface to the bottom of the membrane tank due to limited cake layer breakage, enabling the extension of sludge water discharging intervals. For the gravity-driven system investigated, the running cost, including energy, water and chemical demand, was reduced by 16.67% as the air scouring and sludge water discharging intervals increased from 3hours to 24hours and from 12hours to 24hours, respectively.
Towards a better understanding of microalgae natural flocculation mechanisms to enhance flotation harvesting efficiency
Authors: Demir Irem , Besson Alexandre , Guiraud Pascal , Formosa-Dague Cécile
Published: April 2020

In microalgae harvesting, flocculation is usually a compulsory preliminary step to further separation by sedimentation or flotation. For some microalgae species, and under certain growth conditions, flocculation can occur naturally. Natural flocculation presents many advantages as it does not require the addition of any flocculants to the culture medium and shows high efficiency rate. But because natural flocculation is so specific to the species and conditions, and thanks to the knowledge accumulated over the last years on flocculation mechanisms, researchers have developed strategies to induce this natural harvesting. In this review, we first decipher at the molecular scale the underlying mechanisms of natural flocculation and illustrate them by selected studies from the literature. Then we describe the developed strategies to induce natural flocculation that include the use of biopolymers, chemically modified or not, or involve mixed species cultures. But all these strategies need the addition of external compounds or microorganism which can present some issues. Thus alternative directions to completely eliminate the need for an external molecule, through genetic engineering of microalgae strains, are presented and discussed in the third part of this review.
Don Juan María Osuna (1785-1851) native of san Vicente Ferrer and first alcalde of the pueblo of San Diego
Authors: Farris Glenn
Published: April 2020

This article explores various documents other sources of information regarding the life and origins of Juan Maria Osuna, who became in 1835 the first elected mayor of the pueblo of San Diego. There have been some questions as to Osuna's place of birth; the article attempts to resolve the problem.
Demografía y economía de una capital estatal. Mexicali, Baja California
Authors: Estrella Valenzuela Gabriel , Ranfla González Arturo
Published: April 2020

Este trabajo tiene como objetivo central, identificar de manera general los sectores de actividad econórnica en los que la ciudad de Mexicali presenta un grado de especialización respecto del conjunto del estado de Baja California. Para lograr ese objetivo, en la primera sección se señalan las características generales que han definido las tendencias del comportamiento demográfico de esta zona del país a lo largo del siglo xx, con el propósito de hacer evidente el nexo que ha estado presente entre las modlilidades que ha asumido el desarrollo económico de Mexicali y las fluctuaciones que se han observado en los componentes de su dinámica poblacional. En la segunda sección del trabajo, se aborda la evaluación de la especialización de la estructura económica de Mexicali, en términos de la capacidad de generación de empleos y del tipo de empleos generados. En este caso, se recurre a la perspectiva analítica de la "base económica", dado que interesa destacar el papel que ha desempeñado la contigüidad a la frontera con los Estados Unidos, respecto de las posibilidades -pretéritas y actuales- de desarrollo de la econonúa de esta localidad a través de su capacidad de respuesta a la demanda externa de bienes y servicios.
Contexto de la política tarifaria residencial del sector eléctrico y estimación de la función consumo eléctrico residencial: El caso de Mexicali, Baja California (1990-1992)
Authors: Sández Pérez Agustín
Published: April 2020

En este artículo se plantean diversos aspectos de la problemática del consumo eléctrico en el noroeste del país, y particulannente en Mexicali, Baja California. Se resalta la especificidad de la demanda en la regi6n; donde se requiere de un replanteamiento de su estilo de desarrollo orientado hacia un uso racional de la energía eléctrica. Asimismo, se subraya la necesidad de revisar mecanismos que pennitan financiar el crecimiento del sector eléctrico. Basado en diversas fuentes y en los resultados de la Encuesta sobre el grado de adecuaci6n ambiental de la vivienda y consumo eléctrico en Mexicali, se estudian las características del consumo eléctrico residencial y su relación con el nivel socioeconómico de los usuarios. Se expone también el contexto de las políticas en dicho sector y la problemática en la detenninación de tarifas eléctricas. Finalmente, se analiza el modelo de la funci6n consumo eléctrico residencial, que para el caso de estudio, presenta un importante contenido  estacional.
Sindicatos en Ciudad Juárez: Historia y debilidad sindical
Authors: Quintero Ramírez Cirila
Published: April 2020

Este trabajo analiza la evoluci6n del sindicalismo juarense en tres décadas de industria maquiladora. Postula como idea central, la existencia de un debilitamiento sindical en las rnaquiladoras debido a dos factores centrales: la ausencia de una trayectoria sindical en la regi6n y la persistencia de actividades econ6micas dependientes de los vaivenes de la economía estadounidense en Ciudad Juárez, y la existencia de un faccionalismo inter e intrasindical de las principales centrales obreras de la localidad, que ha permitido la derrota no sólo de los movimientos oficiales sino independientes. La debilidad sindical también ha conducido a una politica de apatía, conformismo y de alta colaboraci6n con los empresarios, que ha convertido al sindicalismo juarense en una expresión de un sindicalismo subordinado, que legitima su estancia en las maquiladoras más por su vinculación con los empresarios que con sus agremiados. Este alÚculo permite vislumbrar dos escenarios futuros en la localidad juarense: la acentuación de esta conducta sindical, o bien, la desaparición de los sindicatos en las maquiladoras.
De la ética católica a la ética de la pobreza: Hacia una tesis sobre las ideas y creencias religiosas como factor de rezago socioeconómico en la población mexicana de los Estados Unidos
Authors: Arriaga Martínez Rafael
Published: April 2020

En este artículo pretendemos fundamentar una tesis cuya proposición mayor postula la posibilidad de determinar la influencia de las ideas y creencias religiosas en la conducta económica de los mexicanos residentes en los Estados Unidos. Como concepto clave de la discusión, aquí la religión es defmida de acuerdo con uno de los corolarios de la visión weberiana de la misma, a saber, como vehículo ético susceptible de frenar o estimular el ascenso social de los grupos sociales. Es pues, en tomo a estos dos enunciados, que hemos concatenado la mayor parte de la base teórica, conceptual y metodológica desplegada en este trabajo.
Effects of coronary computer tomography angiography screening on smoking habits in asymptomatic individuals with family history of premature coronary heart disease
Authors: Shah Nadim , Almteiri Mohamed Abdulla Alraqabani , Noaman Samer , Cox Nicholas , Wong Chiew , Kelly Anne-Maree , Soon Kean
Published: April 2020

Background:

The Screening for Asymptomatic Coronary Heart disease in the Siblings of young
Myocardial Infarction patients study (SACHSMI) investigated the association
between index myocardial infarction patient sibling(s) and obstructive coronary heart
disease as detected by coronary computer tomography angiography (CCTA). The
results of SACHSMI described a statistically significant association between smoking
and prevalence of stenosis detected by CCTA. Data is lacking, however, regarding
CCTA screening effects on smoking habits of young individuals.

Methods:

Fifty asymptomatic siblings of prospectively identified index myocardial infarction
patients, aged 55 years or younger, were screened. These 50 sibling participants
were shown and explained their CCTA results. The participants were followed using
telephone call at 1 and 12 months after screening to assess any change in their
smoking habits. The primary outcome of interest was to identify any change in
smoking habit among the participants of the SACHSMI study undergoing CCTA 1
and 12 months post scanning.

Results:

Of the 50 participants, 20 (40%) had a history of smoking. One month post CCTA, 12
(60%; 95% confidence interval (CI): 36% to 81%) participants either stopped
smoking (7/20 (35%; 95% CI: 15% to 59%)) or reduced (5/20 (25%; 95% CI: 9% to
49%)) the number of cigarettes smoked daily. At 12 months post CCTA, 11 (55%;
95% CI: 32% to 77%) participants either stopped smoking (6/20 (30%; 95% CI: 12%

to 54%)) or reduced (5/20 (25%; 95% CI: 9% to 49%)) the number of cigarettes
smoked daily.

Conclusions:

Screening individuals with family history of premature CHD via CCTA may have the
additional benefit of reducing smoking in the short term.
A Role for the Adenosine ADORA2B Receptor in Midazolam Induced Cognitive Dysfunction
Authors: Gile Jennifer , Oyama Yoshimasa , Shuff Sydney , Eckle Tobias
Published: April 2020

Background:

We recently reported a role for the circadian rhythm protein Period 2 (PER2) in midazolam
induced cognitive dysfunction. Based on previous studies showing a critical role for the adenosine A2B receptor
(ADORA2B) in PER2 regulation, we hypothesized that hippocampal ADORA2B is crucial for cognitive
function.

Methods:

Midazolam treated C57BL/6J mice were analyzed for Adora2b hippocampal mRNA expression levels,
and spontaneous T-maze alternation was determined in Adora2b-/- mice. Using the specific ADORA2B agonist
BAY-60-6583 in midazolam treated C57BL/6J mice, we analyzed hippocampal Per2 mRNA expression levels
and spontaneous T-maze alternation. Finally, Adora2b-/- mice were assessed for mRNA expression of markers for
inflammation or cognitive function in the hippocampus.

Results:

Midazolam treatment significantly downregulated Adora2b or Per2 mRNA in the hippocampus of
C57BL/6J mice, and hippocampal PER2 protein expression or T-maze alternation was significantly reduced in
Adora2b-/- mice. ADORA2B agonist BAY-60-6583 restored midazolam mediated reduction in spontaneous alternation
in C57BL/6J mice. Analysis of hippocampal Tnf-α or Il-6 mRNA levels in Adora2b-/- mice did not reveal
an inflammatory phenotype. However, C-fos, a critical component of hippocampus-dependent learning and memory,
was significantly downregulated in the hippocampus of Adora2b-/- mice.

Conclusion:

These results suggest a role of ADORA2B in midazolam induced cognitive dysfunction. Further, our
data demonstrate that BAY-60-6583 treatment restores midazolam induced cognitive dysfunction, possibly via
increases of Per2. Additional mechanistic studies hint towards C-FOS as another potential underlying mechanism
of memory impairment in Adora2b-/- mice. These findings suggest the ADORA2B agonist as a potential therapy
in patients with midazolam induced cognitive dysfunction.
Therapeutic Effects of Micronutrient Supplements on Sperm Parameters: Fact or Fiction?
Authors: Dimitriadis Fotios , Tsounapi Panagiota , Zachariou Athanasios , Kaltsas Aris , Sokolakis Ioannis , Hatzichristodoulou Georgios , Symeonidis Evangelos N. , Kotsiris Dimitrios , Gabales Melinda R. , Vlachopoulou Evlalia , Takenaka Atsushi , Sofikitis Nikolaos
Published: April 2020

Background:

Despite the limited evidence about the effect of micronutrient supplementation on the
semen quality, many micronutrient supplements have been used to improve male fertility. Approximately, 40%-
50% of male infertility cases in general and up to 80% in men with idiopathic infertility cases are caused by oxidative
stress and decreased level of seminal total antioxidant capacity.

Objective:

To investigate the beneficial effects of micronutrient supplementation on sperm concentration, motility
and morphology.

Methods:

A Pub Med, Google Scholar, Embase data, web of Science and Cochrane Library
database extensive research of the randomized controlled studies utilizing micronutrient vitamins
and supplements was performed.

Results:

The existent international literature is rather heterogeneous and a definitive is difficult to be drawn.
Several micronutrients have beneficial effects on sperm parameters. Rational use of micronutrients might be
helpful for infertile patients.

Conclusion:

Further randomized, controlled clinical trials are required to elucidate the efficacy and safety of
micronutrients and propose proper protocols for their use. A well-rounded, balanced diet is more preferable than
the widespread use of micronutrient supplements beyond the recommended doses. Future studies should concern
the pregnancy rate as a primary outcome in their designs. Further research should be done to determine the appropriate
antioxidant compounds, the duration of the treatment, as well as a certain dose of antioxidants in clinical
practices. The pre-treatment evaluation of the seminal oxidative status is also an important parameter to proceed
with micronutrient supplementation without the risk of reductive stress. Under these conditions, supplements
could support the quality of sperm and help to alleviate male infertility.
Multilevel Characterization of Antibody-Ligand Conjugates by CESI-MS
Authors: Fonslow Bryan , Jarvas Gabor , Szigeti Marton , Guttman Andras
Published: April 2020

Aims:

To demonstrate the capabilities of our new capillary electrophoresis –
mass spectrometry method, which facilitates highly accurate relative quantitation of
modification site occupancy of antibody-ligand (e.g., antibody-drug) conjugates.

Background:

Antibody-drug conjugates play important roles in medical discovery for
imaging and therapeutic intervention. The localization and stoichiometry of the
conjugation can affect the orientation, selectivity, specificity, and strength of molecular
interactions, influencing biochemical function.

Objective:

To demonstrate the option to analyze the localization and stoichiometry of
antibody-ligand conjugates by using essentially the same method at all levels including
ligand infusion, peptide mapping, as well as reduced and intact protein analysis.

Materials and Methods:

Capillary electrophoresis coupled with electrospray ionization
mass spectrometry was used to analyze the antibody-ligand conjugates.

Results:

We identified three prevalent ligand conjugation sites with estimated
stoichiometries of 73, 14, and 6% and an average ligand-antibody ratio of 1.37,
illustrating the capabilities of CE-ESI-MS for rapid and efficient characterization of
antibody-drug conjugates.

Conclusion:

The developed multilevel analytical method offers a comprehensive way to
determine the localization and stoichiometry of antibody-drug conjugates for molecular
medicinal applications. In addition, a significant advantage of the reported approach is
the small, hydrophilic, unmodified peptides well separated from the neutrals, which is not
common with other liquid phase separation methods such as LC.
Pathogenic Mechanisms of a Stroke-like attack Elicited by Epidural Steroid Injection Therapy
Authors: He Zhen
Published: April 2020

Background:

The pathogenic mechanisms involved in a disastrous scenario, following epidural steroid injections (ESI), remain unclarified. Intra-arterial injection of steroids with needlepenetrating vascular injury would be the culprit, as particulate medicine elicits a brain or spinal cord stroke-like attack.

Methods:

On the other hand, the limited experimental approaches simulating an accidental steroid intra-arterial injection for ESI conflicted in their results: hemorrhage vs. ischemia.

Results:

This article dissects the potential pathogenic mechanisms at a neurovascular unit. Noticeably, a schematic representation provides an explanation of how emboli formed by particulate steroids elicit either hemorrhagic, or ischemic lesion.

Conclusion:

In addition, the development of a rat model with intravertebral artery steroid injection is a proposal to address the unmet need in evaluating steroids and vascular injury in ESI.
Synthesis of some 1H-1,5-benzodiazepine Series Containing Chromene Ring from α,β-Unsaturated Ketones of 6-Acetyl-5-Hydroxy-4-Methylcoumarin
Authors: Toan Duong Ngoc , Thanh Nguyen Dinh , Truong Mai Xuan , Thao Nguyen Minh
Published: April 2020

Background:

Reaction of α,β-unsaturated ketones with o-phenylenediamine afforded corresponding
2,3-dihydro-1H-1,5-benzodiazepines.

Objective:

α,β-Unsaturated ketones of 6-acetyl-5-hydroxy-4-methylcoumarin are precursors for synthesis of
2,3-dihydro-1H-1,5-benzodiazepines by a reaction with o-phenylenediamine.

Methods:

Enones of 6-acetyl-5-hydroxy-4-methylcoumarin were prepared from this ketone and (un)substituted
benzaldehydes in the presence of piperidine, triethylamine, or pyridine as a catalyst in absolute ethanol with
1:1 molar ratios, respectively. 2',3'-Dihydro-1H-1',5'-benzodiazepines were synthesized by using the reaction
of these enones with o-phenylenediamine in absolute ethanol in the presence of glacial acetic acid as a catalyst.
Their biological activities were evaluated using the disk diffusion method.

Results:

Seven new 2',3'-dihydro-1H-1',5'-benzodiazepines were obtained and their structures were confirmed
by thin-layer chromatography, IR, NMR and MS spectra. Some synthesized benzodiazepines showed antibacterial
and antifungal activities against Escherichia coli (Gram-(−) bacterium), Staphylococus epidermidis
(Gram-(+) bacterium). Candida albicans (fungus).

Conclusion:

The formation of enones from 6-acetyl-5-hydroxy-4-methylcoumarin and (un)substituted benzaldehydes
could be catalyzed by piperidine, triethylamine, pyridine to afford similar yields. 2',3'-dihydro-1H-
1',5'-benzodiazepines have been synthesized from the aforementioned enones and o-phenylenediamine.
Kinetics and Computational Evaluation of Eugenol and Vanillic Acid on Inhibition of a Potential Enzyme of a Nosocomial Pathogen that Promotes Struvite Formation
Authors: Jagannathan Venkataseshan , Venkatesan Arthi , Viswanathan Pragasam
Published: April 2020

Background:

Struvite/infection stone is one of the major clinical burdens in urinary tract
infections that is caused by the ureolytic behavior of pathogenic bacteria.

Objective:

The current strategy for treating infective stones is mostly antibiotic therapy, which ends
in promoting resistance to the organisms. Hence in the present study, we investigated two phytocompounds,
eugenol (an allyl-substituted guaiacol) and vanillic acid (a phenolic acid) that are found to be
effective in inhibiting the urease enzyme of a nosocomial pathogen Proteus mirabilis.

Methods:

The enzyme was purified to apparent homogeneity and the kinetic parameters were studied
in the presence and in the absence of eugenol and vanillic acid. Molecular docking and simulation
were done to understand the level of protein-ligand interactions and the interacting residues.

Results:

Kinetic parameters obtained from the Michaelis-Menten plot show that both eugenol and
vanillic acid exhibit non-competitive inhibition of urease enzyme in a dose-dependent manner. In silico
studies showed that eugenol and vanillic acid have almost similar binding affinities to the regulatory
pocket of the modeled protein. Dynamics and simulation results indicate that the interaction of
ligands with the ARG373 residue of the protein provides a stable bound conformation.

Conclusion:

Overall, our results suggest that both the phytocompounds eugenol and vanillic acid
have a potential application as a new therapy for the inhibition of urease enzyme that could possibly
replace the complexions related to struvite stone formation.
Cucurbitacin IIb from Ibervillea sonorae Induces Apoptosis and Cell Cycle Arrest via STAT3 Inhibition
Authors: Torres-Moreno Heriberto , Marcotullio Maria C. , Velazquez Carlos , Arenas-Luna Víctor M. , Hernández-Gutiérrez Salomón , Robles-Zepeda Ramón E.
Published: April 2020

Background:

Cucurbitacin IIb (CIIb) from Ibervillea sonorae has a high capacity to suppress cancer
cell proliferation and induce apoptosis. This study investigated the molecular mechanisms related to the antiproliferative
and apoptosis induction capacity of CIIb in HeLa cells.

Materials and Methods:

The cell viability and anti-proliferative effect of CIIb were evaluated by using the
trypan blue exclusion assay. The effect of CIIb on the mitochondrial membrane potential was determined by
flow cytometry using JC-1. The activity of caspase-3 and caspase-9 was evaluated by flow cytometry using
commercial kits. The effect of CIIb on the cell cycle was investigated using Fluorescence-Activated Cell Sorting
(FACS) analysis. Western blot analysis was used to evaluate both the inhibitory effect of CIIb on the
STAT3 signaling pathway and cyclin –B1, and DNA damage by the comet assay.

Results:

CIIb triggers disruption of the mitochondrial membrane potential (Δψm) and consequently activated
the caspases -3 and -9, as a result of the activation of the intrinsic pathway of the apoptosis. Likewise, the CIIbinduced
cell cycle was arrested in S and G2/M after 24h of treatment. CIIb also reduced the expression of
STAT3 and cyclin –B1. Finally, CIIb produced an antiproliferative effect at 48 and 72 h, inducing DNA damage.

Conclusion:

These results demonstrate CIIb-induced apoptosis and cell cycle arrest in HeLa through the inhibition
of STAT3.
Possible Enhancement of Photodynamic Therapy (PDT) Colorectal Cancer Treatment when Combined with Cannabidiol
Authors: Nkune Nkune W. , Kruger Cherie A. , Abrahamse Heidi
Published: April 2020

:

Colorectal cancer (CRC) has a high mortality rate and is one of the most difficult diseases to manage due to tumour resistance and metastasis. The treatment of choice for CRC is reliant on the phase and time of diagnosis. Despite several conventional treatments available to treat CRC (surgical excision, chemo-, radiation- and immune-therapy), resistance is a major challenge, especially if it has metastasized. Additionally, these treatments often cause unwanted adverse side effects and so it remains imperative to investigate, alternative combination therapies.
Photodynamic Therapy (PDT) is a promising treatment modality for the primary treatment of CRC, since it is non-invasive, has few side effects and selectively damages only cancerous tissues, leaving adjacent healthy structures intact. PDT involves three fundamentals: a Photosensitizer (PS) drug localized in tumour tissues, oxygen and light. Upon PS excitation using a specific wavelength of light, an energy transfer cascade occurs, that ultimately yields cytotoxic species, which in turn induces cell death. Cannabidiol (CBD) is a cannabinoid compound derived from the Cannabis sativa plant, which is found to exert anticancer effects on CRC through different pathways, inducing apoptosis and so inhibits tumour metastasis and secondary spread.
This review paper highlights current conventional treatment modalities for CRC and their limitations, as well as discusses the necessitation for further investigation into unconventional active nanoparticle targeting PDT treatments for enhanced primary CRC treatment. This can be administered in combination with CBD, to prevent CRC secondary spread and so enhance the synergistic efficacy of CRC treatment outcomes, with less side effects.
AN ASSESSMENT OF HOUSING AFFORDABILITY INDEX AT DISTRICTS LEVEL IN KELANTAN
Authors: Mohamed Osman Mariana , Zainudin Farah Eleena , Rabe Noor Suzilawati , Hitam Mizan , Abdullah Muhammad Faris
Published: April 2020

The purpose of this paper is to assess the housing affordability level in every district in Kelantan. The goal of this study is to determine the affordability level and the affordable housing price in every district in Kelantan. In order to determine the housing affordability level, the Price-to-Income Ratio approach or known as median multiple is used in this study. The study found that the overall affordable leve in Kelantan from 2012, 2014 to 2016 has increased from 4.5 to 4.8 to 5.4 which clearly showed the level worsen over the years. In term of afforadablee housing price, the Kelantan median house price for 2016 was RM199,900 but using median multiple calculation using the income data, the maximum affordable house price should be within RM 110,844, which clearly showed that the current housing prices is severely unafforable for Kelantan State.
THE IMPACT OF PERSONALITY AND LIFESTYLE ON INTERACTION WITH NATURE
Authors: Abu Bakar Aisyah , Mohamed Osman Mariana , Hitam Mizan
Published: April 2020

Awareness on the complex interdepending systems between individuals and their contexts is a fundamental understanding of sustainable well-being. Collectivist beliefs and biospheric values translate the normative behaviours when environmental decisions are being made. Issue: Existing research has limited empirical evidence on the impact of personality and lifestyle (PL) on interaction with nature (IN) for Malaysia. Purpose: This paper aims to verify the statistical predictability of IN based on PL. Approach: Multiple Correlation and Multiple Linear Regression were carried out to assess linear associations and parameters of linear equations to predict IN components based on PL items. Findings: IN components were predictable by the majority of the PL items and ‘feeling affected by the environmental loss of other countries’ was the strongest predictor of IN.
NEIGHBOURHOOD QUALITY ASSESSMENT: A VIEW OF TENURE OWNERSHIP AND MOBILITY DECISIONS IN PENANG, MALAYSIA
Authors: Abdul Fattah Hamizah , Badarulzaman Nurwati , Ali Kausar
Published: April 2020

Most people have experienced a crucial moment of decision during their life course, that of whether to stay over or to move out of their house and neighbourhood. Residential mobility refers to mobility thoughts and intentions, as well as the actual moving behaviours among the residents, which are often triggered by feelings of dissatisfactions, state of disequilibrium or mismatch between the present housing needs and consumption, and the desired housing preferences. Residential mobility is postulated to be influenced by many factors, notably family life cycle (infant to elderly phase), tenure ownership (house owner or renter), housing profile (dwelling features) and quality of the neighbourhood. There is limited study on tenure ownership and factors of neighbourhood quality that can affect mobility decision and residential mobility behaviour. Hence, this study examines mobility decisions based on tenure ownership and neighbourhood quality including physical, social and economic attributes among residents of housing schemes in Penang Island, Malaysia. A questionnaire survey of 717 respondents living in low, medium and high cost housing in the study area revealed that dwelling features, neighbourhood facilities, environment, social interaction and attachment are the major considerations and preferences affecting residential mobility behaviours among residents. The study findings provide insights and guidance on planning for better neighbourhoods to satisfy residents’ needs and enhance quality of life.
PERFORMANCE DIMENSIONS OF SRI LANKAN HOTEL INDUSTRY
Authors: Kaluthanthri Prathap , Osmadi Atasya
Published: April 2020

The mixed nature of industrial and service dimension of a hotel including pure service (room service), stock management service (beverage and vendors product), and in-house processing (Food at the restaurant) crafts are a unique business setting for a hotel. In consequence, it creates a challenging task for monitoring the alignment of the strategic plan of the hotel. Hence, the performance of a hotel needs to be measured through a three-dimensional perspective which covers (i) nature of pure service, (ii) product, and (iii) service-product. The measure of the three-dimensional perspective requires empirically validated hotel-specific performance measurement system. The study reviews experts’ views on performance measurement dimensions for the hotel industry in Sri Lanka based on the Analytic Hierarchy Process (AHP). Performance dimensions identified through literature review evaluated by a panel of experts consists of academics, seniors and middle-level management of hotels, government and travel advisory officials, and opinion leaders. The results of AHP on performance dimensions were re-confirmed by applying Content Validity Ratio (CVR) analysis. The AHP order of performance dimensions begins with Competitiveness followed by Finance, Quality, Innovation, Flexibility, Resource utilization, Environment, and Supplier Performance respective. The CVR on AHP order confirmed 6 dimensions on performance measurement for Sri Lankan hotel industry as final selection leaving out environmental and supplier performance from the list of performance dimensions.
DO DURATION OF STAY AND PARK VISITATION MATTER? AN EVALUATION OF PARK DISTANCE
Authors: Abdul Malek Nurhayati , Nashar Amanina
Published: April 2020

Among ways to keep up with healthy lifestyle include physical activities. Recent statistics by the Ministry of Health (2016) indicated a drastic increase in the prevalence of non-communicable disease from 1990 to 2016 and the number is expected to increase or remain high. In response to the issue, the Eleventh Malaysia Plan 2016-2020 was formulated to improve Malaysians’ wellbeing by providing ample open spaces to encourage an active lifestyle. This paper aims to investigate the association of proximity to neighbourhood park and its level of utilisation. 680 respondents were involved in the questionnaire survey conducted at 7 selected neighbourhood parks. The output of the Pearson Correlation evinced that proximity to neeighborhood parks was highly associated to the level of park utilisation. There was a strong and positive relationships between (i) park distance and numbers of visitations (r = 0.841,n = 680,p = 0.000< 0.01), (ii) park distance and length of stay (r = 0.803, n = 680, p = 0.000< 0.01), and (iii) number of visitations and length of stay (r = 0.644, n = 680,p = 0.000< 0.01). The results also indicated that that the longer the distance of the park from home, the longer the time spent at the park. Whereas, the shorter the distance of the park from home, the higher the utilisation of the park.
Fluid Administration in Emergency Room Limited by Lung Ultrasound in Patients with Sepsis: Protocol for a Prospective Phase II Multicenter Randomized Controlled Trial
Authors: Mohamed Mouhand F H , Malewicz Nathalie M , Zehry Hanan Ibrahim , Hussain Dina A Monim , Barouh Judah Leão , Cançado Adriana V , Silva Jeancarllo Sousa , Suwileh Salah , Carvajal Jose Retamal
Published: April 2020

Background

Sepsis remains a major health challenge with high mortality. Adequate volume administration is fundamental for a successful outcome. However, individual fluid needs differ between patients due to varying degrees of systemic vasodilation, circulatory flow maldistribution, and increased vascular permeability. The current fluid resuscitation practice has been questioned. Fluid overload is associated with higher mortality in sepsis. A sign of fluid overload is extravascular lung water, seen as B lines in lung ultrasound. B lines correlate inversely with oxygenation (measured by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen ie, PaO2/FiO2). Thus, B lines seen by bedside ultrasound may have a role in guiding fluid therapy.

Objective

We aim to evaluate if fluid administration guided by lung ultrasound in patients with sepsis in emergency departments will lead to better oxygenation and patient outcomes than those in the standard therapy.

Methods

A phase II, multicenter, randomized, open-label, parallel-group, superiority trial will be performed. Patients will be recruited at emergency departments of the participating centers. A total of 340 patients will be randomly allocated to the intervention or standard-of-care group (30mL/kg). The intervention group will receive ultrasound-guided intravenous fluid until 3 B lines appear. The primary outcome will be oxygenation (measured as PaO2/FiO2 ratio) at 48 hours after starting intravenous fluid administration. Secondary outcomes will be patients’ outcome parameters, including oxygenation after 15 mL/kg fluid at 6, 12, 24, and 48 hours; sepsis progress through Sequential Organ Failure Assessment (SOFA) scores; pulmonary edema evaluation; and 30-day mortality.

Results

The trial will be conducted in accordance with the Declaration of Helsinki. Institutional review board approval will be sought after the participating sites are selected. The protocol will be registered once the institutional review board approval is granted. The trial duration is expected to be 1.5-2.5 years. The study is planned to be performed from 2021 to 2022, with enrollment starting in 2021. First results are expected in 2022. Informed written consent will be obtained before the patient’s enrollment in the study. An interim analysis and data monitoring will ensure the patient safety. The results will be published in a peer-reviewed journal and discussed at international conferences.

Conclusions

This is a protocol for a randomized control trial that aims to evaluate the role of bedside ultrasound in guiding fluid therapy in patients with sepsis via B lines evaluation.

International Registered Report Identifier (IRRID)

PRR1-10.2196/15997
Detecting and Filtering Immune-Related Adverse Events Signal Based on Text Mining and Observational Health Data Sciences and Informatics Common Data Model: Framework Development Study
Authors: Yu Yue , Ruddy Kathryn , Mansfield Aaron , Zong Nansu , Wen Andrew , Tsuji Shintaro , Huang Ming , Liu Hongfang , Shah Nilay , Jiang Guoqian
Published: April 2020

Background

Immune checkpoint inhibitors are associated with unique immune-related adverse events (irAEs). As most of the immune checkpoint inhibitors are new to the market, it is important to conduct studies using real-world data sources to investigate their safety profiles.

Objective

The aim of the study was to develop a framework for signal detection and filtration of novel irAEs for 6 Food and Drug Administration–approved immune checkpoint inhibitors.

Methods

In our framework, we first used the Food and Drug Administration’s Adverse Event Reporting System (FAERS) standardized in an Observational Health Data Sciences and Informatics (OHDSI) common data model (CDM) to collect immune checkpoint inhibitor-related event data and conducted irAE signal detection. OHDSI CDM is a standard-driven data model that focuses on transforming different databases into a common format and standardizing medical terms to a common representation. We then filtered those already known irAEs from drug labels and literature by using a customized text-mining pipeline based on clinical text analysis and knowledge extraction system with Medical Dictionary for Regulatory Activities (MedDRA) as a dictionary. Finally, we classified the irAE detection results into three different categories to discover potentially new irAE signals.

Results

By our text-mining pipeline, 490 irAE terms were identified from drug labels, and 918 terms were identified from the literature. In addition, of the 94 positive signals detected using CDM-based FAERS, 53 signals (56%) were labeled signals, 10 (11%) were unlabeled published signals, and 31 (33%) were potentially new signals.

Conclusions

We demonstrated that our approach is effective for irAE signal detection and filtration. Moreover, our CDM-based framework could facilitate adverse drug events detection and filtration toward the goal of next-generation pharmacovigilance that seamlessly integrates electronic health record data for improved signal detection.
Flattening the Mental Health Curve: COVID-19 Stay-at-Home Orders Are Associated With Alterations in Mental Health Search Behavior in the United States (Preprint)
Authors: Jacobson Nicholas C , Lekkas Damien , Price George , Heinz Michael V , Song Minkeun , O’Malley A James , Barr Paul J
Published: April 2020

BACKGROUND

The coronavirus disease (COVID-19) has led to dramatic changes worldwide in people’s everyday lives. To combat the pandemic, many governments have implemented social distancing, quarantine, and stay-at-home orders. There is limited research on the impact of such extreme measures on mental health.

OBJECTIVE

The goal of this study was to examine whether stay-at-home orders produced differential changes in mental health symptoms using internet search queries on a national scale.

METHODS

In the United States, individual states vary in their adoption of measures to reduce the spread of COVID-19; as of March 23, 2020, 11 of the 50 states had issued stay-at-home orders. The staggered rollout of stay-at-home measures across the United States allows us to investigate whether these measures impact mental health by exploring variations in mental health search queries across the states. This paper examines the changes in mental health search queries on Google between March 16-23, 2020, across each state and Washington, DC. Specifically, this paper examines differential changes in mental health searches based on patterns of search activity following issuance of stay-at-home orders in these states compared to all other states. The participants were all the people who searched mental health terms in Google between March 16-23. Between March 16-23, 11 states underwent stay-at-home orders to prevent the transmission of COVID-19. Outcomes included search terms measuring anxiety, depression, obsessive-compulsive, negative thoughts, irritability, fatigue, anhedonia, concentration, insomnia, and suicidal ideation.

RESULTS

Analyzing over 10 million search queries using generalized additive mixed models, the results suggested that the implementation of stay-at-home orders are associated with a significant flattening of the curve for searches for suicidal ideation, anxiety, negative thoughts, and sleep disturbances, with the most prominent flattening associated with suicidal ideation and anxiety.

CONCLUSIONS

These results suggest that, despite decreased social contact, mental health search queries increased rapidly prior to the issuance of stay-at-home orders, and these changes dissipated following the announcement and enactment of these orders. Although more research is needed to examine sustained effects, these results suggest mental health symptoms were associated with an immediate leveling off following the issuance of stay-at-home orders.
A Global Digital Citizen Science Policy to Tackle Pandemics Like COVID-19 (Preprint)
Authors: Katapally Tarun R
Published: April 2020

UNSTRUCTURED

The coronavirus disease (COVID-19) pandemic is an extremely complex existential threat that requires cohesive societal effort to address health system inefficiencies. When our society has faced existential crises in the past, we have banded together by using the technology at hand to overcome them. The COVID-19 pandemic is one such threat that requires not only a cohesive effort, but also enormous trust to follow public health guidelines, maintain social distance, and share necessities. However, are democratic societies with civil liberties capable of doing this? Mobile technology has immense potential for addressing pandemics like COVID-19, as it gives us access to big data in terms of volume, velocity, veracity, and variety. These data are particularly relevant to understand and mitigate the spread of pandemics such as COVID-19. In order for such intensive and potentially intrusive data collection measures to succeed, we need a cohesive societal effort with full buy-in from citizens and their representatives. This article outlines an evidence-based global digital citizen science policy that provides the theoretical and methodological foundation for ethically sourcing big data from citizens to tackle pandemics such as COVID-19.