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Fulltext Perceptions, Expectations, and Experience of Physicians About Pharmacists and Pharmaceutical Care Services in Pakistan: Findings and Implications

Hayat K, Mustafa ZU, Godman B, Arshed M, Zhang J, Khan FU, et al.

Front Pharmacol, 2021;12:650137.
PMID: 34054528 DOI: 10.3389/fphar.2021.650137

Background: Optimal collaboration between pharmacists and other healthcare professionals such as physicians is integral in implementing pharmaceutical care. However, there are concerns regarding the role of pharmacists, especially among low- and middle-income countries. This study explored the perceptions, expectations, and experience of physicians working in various hospital settings of Punjab, Pakistan, about pharmacists and their roles. Methods: A self-administered questionnaire consisting of four sections was administered from October to December 2020. Descriptive and inferential statistics such as Kruskal-Wallis and Mann-Whitney tests were used for data analysis using SPSS. Results: Six hundred and seventy-eight physicians participated in this study with a response rate of 77.9%. Most of the physicians reported minimal to no interaction with pharmacists (n = 521, 76.8%). However, more than three-quarters of physicians (n = 660, 97.3%) accepted pharmacists as evidence-based sources of drug information. In addition, many physicians (n = 574, 84.7%) strongly agreed that pharmacists should attend patient care rounds to respond promptly to questions related to patient medication. A limited number of physicians (n = 124, 18.3%) assumed that pharmacists were advising their patients regarding the judicial use of their drugs. Median expectation and experience score had a significant association with age, experience, and education of physicians (P < 0.05). Conclusions: The perception of physicians was positive toward certain roles of pharmacists, coupled with high expectations. However, their experience was low, with most of the activities of pharmacists due to inadequate interprofessional coordination.
The role of competitive counterion adsorption on the electrolyte induced surface ordering in methyl ester sulfonate surfactants at the air-water interface

Xu H, Li P, Ma K, Welbourn RJL, Penfold J, Thomas RK, et al.

J Colloid Interface Sci, 2019 Jan 01;533:154-160.
PMID: 30153592 DOI: 10.1016/j.jcis.2018.08.061

The strong binding of Al3+ trivalent counterions to the anionic surfactants sodium polyethylene glycol monoalkyl ether sulfate and α-methyl ester sulfonate results in surface multilayer formation at the air-water interface. In contrast the divalent and monovalent counterions Ca2+ and Na+ result only in monolayer adsorption. Competitive counterion adsorption has been extensively studied in the context of surfactant precipitation and re-dissolution, but remains an important feature in understanding this surface ordering and how it can be manipulated. The α-methyl ester sulfonate surfactants are a promising class of anionic surfactants which have much potential for improved performance in many applications, greater tolerance to extreme solvent conditions such as water hardness, biocompatibility and sustainable production. Hence in this study we have used neutron reflectivity to extend previous studies on the surface ordering of the α-methyl ester sulfonate surfactant, sodium tetradecanoic 2-sulfo 1-methyl ester, in the presence of electrolyte to investigate the role of binary mixtures of electrolytes, AlCl3/CaCl2, and AlCl3/MgCl2. In the mixed electrolytes the evolution of the surface structure, from monolayer to multilayer with increasing AlCl3 concentration, is observed. It is broadly similar to that reported for the addition of only AlCl3. However with increasing CaCl2 concentration the structural evolution is shifted progressively to higher AlCl3 concentrations. Similar observations occur for the AlCl3/MgCl2 mixtures. However the presence of the MgCl2 results in an additional phenomenon; the partial co-adsorption of a more compact lamellar structure which exists until the highest AlCl3 concentrations. The results demonstrate the importance of the competitive adsorption of different counterions in driving and controlling the formation of surface multilayer structures with anionic surfactants. Furthermore it offers a facile route to the manipulation of these surface structures.
Impact of molecular structure, headgroup and alkyl chain geometry, on the adsorption of the anionic ester sulfonate surfactants at the air-solution interface, in the presence and absence of electrolyte

Wang Z, Li P, Ma K, Chen Y, Campana M, Penfold J, et al.

J Colloid Interface Sci, 2019 May 15;544:293-302.
PMID: 30861434 DOI: 10.1016/j.jcis.2019.03.011

The transition from monolayer to multilayer adsorption at the air-water interface in the presence of multivalent counterions has been demonstrated for a limited range of anionic surfactants which exhibit increased tolerance to precipitation in the presence of multivalent counterions. Understanding the role of molecular structure in determining the transition to surface ordering is an important aspect of the phenomenon. The focus of the paper is on the alkyl ester sulfonate, AES, surfactants; a promising group of anionic surfactants, with the potential for improved performance and biocompatibility. Neutron reflectivity measurements were made in aqueous solution and in the presence of NaCl, CaCl2, MgCl2 and AlCl3, for a range of alkyl ester sulfonate surfactants, in which the headgroup and alkyl chain geometries were manipulated. In the regions of monolayer adsorption changing the AES headgroup and alkyl chain geometries results in an increased saturation adsorption and in a more gradual decrease in the adsorption at low concentrations, consistent with a greater adsorption efficiency. Changing the AES headgroup and alkyl chain geometries also results in changes in the transition from monolayer adsorption to more ordered surface structures with the addition of AlCl3 and mixed multivalent electrolytes. A more limited surface layering is observed for the ethyl ester sulfonate, EES, with a C14 alkyl chain. Replacing the C14 alkyl chain with a C18 isostearic chain results in only monolayer adsorption. The results demonstrate the role and importance of the surfactant molecular structure in determining the nature of the surface adsorption in the presence of different electrolytes, and in the tendency to form extended surface multilayer structures.
Adsorption of Methyl Ester Sulfonate at the Air-Water Interface: Can Limitations in the Application of the Gibbs Equation be Overcome by Computer Purification?

Xu H, Li P, Ma K, Welbourn RJL, Penfold J, Roberts DW, et al.

Langmuir, 2017 09 26;33(38):9944-9953.
PMID: 28871785 DOI: 10.1021/acs.langmuir.7b02725

We describe a new laboratory synthesis of the α-methyl ester sulfonates based on direct sulfonation of the methyl ester by SO3 introduced from the vapor phase. This was used to synthesize a chain deuterated sample of αC14MES, which was then used to measure the surface excess of αC14MES directly at the air/water interface over a wide range of concentration using neutron reflection. The adsorption isotherm could be fitted to an empirical equation close to a Langmuir isotherm and gave a limiting surface excess of (3.4 ± 0.1) × 10-6 mol m-2 in the absence of added electrolyte. The neutron-measured surface excesses were combined with the integrated Gibbs equation to fit the variation in surface tension with concentration (σ-ln C curve). The fit was exact provided that we used a prefactor consistent with the counterion at the surface being an impurity divalent ion, as has previously been found for sodium diethylhexylsulfosuccinate (aerosol OT or AOT) and various perfluorooctanoates. The critical micelle concentration (CMC) was determined from this fit to be 2.4 ± 0.3 mM in the absence of electrolyte. In the presence of 100 mM NaCl, this contamination was suppressed and the σ-ln C curve could be fitted using the integrated Gibbs equation with the expected prefactor of 1. The new data were used to reinterpret measurements by Danov et al. on an unpurified sample of αC14MES for which computer refinement was used to try to eliminate the effects of the impurities.
Potential mechanism of perillaldehyde in the treatment of nonalcoholic fatty liver disease based on network pharmacology and molecular docking

Niu QQ, Xi YT, Zhang CR, Li XY, Li CZ, Wang HD, et al.

Eur J Pharmacol, 2024 Nov 06;985:177092.
PMID: 39510336 DOI: 10.1016/j.ejphar.2024.177092

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic metabolic liver diseases worldwide. Perillaldehyde (4-propyl-1-en-2-ylcyclohexene-1-aldehyde, PA) is a terpenoid compound extracted from Perilla, which has effective pharmacological activities such as anti-inflammatory, antidepressant, and anticancer. This study aimed to explore the pharmacological effects of PA in intervening with NAFLD and reveal its potential mechanisms. Firstly, we identified the core targets of PA intervention therapy for NAFLD through network pharmacology and molecular docking techniques. After that, in vitro animal experiments such as H&E and Masson staining, immunofluorescence, immunohistochemistry, and Western blot were conducted to validate the results network effectively pharmacology predicted. Network pharmacology analysis suggested that PPAR-α may be the core target of PA intervention in NAFLD. H&E and Masson staining showed that after low-dose (50 mg/kg) PA administration, there was a noticeable improvement in fat deposition in the livers of NAFLD mice, and liver tissue fibrosis was alleviated. Immunohistochemical and immunofluorescence analysis showed that low dose (50 mg/kg) PA could reduce hepatocyte apoptosis, decrease the content of pro-apoptosis protein Bax, and increase the expression of anti-apoptosis protein Bcl-2 in NAFLD mice. Western blot results confirmed that low-dose (50 mg/kg) PA could increase the expression of PPAR-α and inhibit the expression of NF-κB in NAFLD mice. Our study indicated that PA could enhance the activity of PPAR-α and reduce the level of NF-κB in NAFLD mice, which may positively affect the prevention of NAFLD.
The New Perspective of Alzheimer's Disease Research: Mechanism and Therapeutic Strategy of Neuronal Senescence

Niu Q, Li D, Zhang J, Piao Z, Xu B, Xi Y, et al.

Ageing Res Rev, 2024 Nov 18.
PMID: 39566741 DOI: 10.1016/j.arr.2024.102593

Alzheimer's disease (AD), commonly known as senile dementia, is a neurodegenerative disease with insidious onset and gradually worsening course. The brain is particularly sensitive to senescence, and neuronal senescence is an important risk factor for the occurrence of AD. However, the exact pathogenesis between neuronal senescence and AD has not been fully elucidated so far. Neuronal senescence is characterized by the permanent arrest of the cell cycle, and the changes in its structure, function, and microenvironment are closely related to the pathogenesis and progression of AD. In recent years, studies such as the Aβ cascade hypothesis and Tau protein phosphorylation have provided new strategies for the treatment of AD, but due to the complexity of the etiology of AD, there are still no effective treatment measures. This article aims to deeply analyze the pathogenesis between AD and neuronal senescence, and sort out various existing treatment methods, to provide new ideas and references for the clinical treatment of AD.
Fulltext Transmission Networks of HIV-1 Among Men Who Have Sex With Men in East and Southeast Asia

Tee KK, Kantor R, Sungkanuparph S, Takebe Y, Li P, Ditangco R, et al.

J Acquir Immune Defic Syndr, 2015 Sep 01;70(1):e28-30.
PMID: 25835606 DOI: 10.1097/QAI.0000000000000614
The structure of alkyl ester sulfonate surfactant micelles: The impact of different valence electrolytes and surfactant structure on micelle growth

Wang Z, Li P, Ma K, Chen Y, Penfold J, Thomas RK, et al.

J Colloid Interface Sci, 2019 Sep 05;557:124-134.
PMID: 31518834 DOI: 10.1016/j.jcis.2019.09.016

The ester sulfonate anionic surfactants are a potentially valuable class of sustainable surfactants. The micellar growth, associated rheological changes, and the onset of precipitation are important consequences of the addition of electrolyte and especially multi-valent electrolytes in anionic surfactants. Small angle neutron scattering, SANS, has been used to investigate the self-assembly and the impact of different valence electrolytes on the self-assembly of a range of ester sulfonate surfactants with subtly different molecular structures. The results show that in the absence of electrolyte small globular micelles form, and in the presence of NaCl, and AlCl3 relatively modest micellar growth occurs before the onset of precipitation. The micellar growth is more pronounced for the longer unbranched and branched alkyl chain lengths. Whereas changing the headgroup geometry from methyl ester to ethyl ester has in general a less profound impact. The study highlights the importance of relative counterion binding strengths and shows how the surfactant structure affects the counterion binding and hence the micelle structure. The results have important consequences for the response of such surfactants to different operational environments.
Fulltext Triptolide inhibits epithelial-mesenchymal transition phenotype through the p70S6k/GSK3/β-catenin signaling pathway in taxol-resistant human lung adenocarcinoma

Tian Y, Li P, Xiao Z, Zhou J, Xue X, Jiang N, et al.

Transl Lung Cancer Res, 2021 Feb;10(2):1007-1019.
PMID: 33718039 DOI: 10.21037/tlcr-21-145

Background: Chemotherapy is one of the primary treatments for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), however, chemoresistance develops over time and is a bottleneck to effective chemotherapy worldwide. Therefore, the development of new potent therapeutic agents to overcome chemoresistance is of utmost importance. Triptolide is a natural component extracted from Tripterygium Wilfordii, a Chinese plant; our study aimed to evaluate its anti-tumor effects in taxol-resistant human lung adenocarcinoma and investigate its molecular mechanisms of chemoresistance.
Methods: Triptolide's inhibition of cell viability was detected by sulforhodamine B (SRB) assay. Cell cycle was measured by flow cytometry and cell apoptosis was assessed by flow cytometry and western blot. Expression of β-catenin was analyzed by western blot and immunofluorescence (IF). The anti-tumor effects of triptolide were determined using a subcutaneous in-vivo model. Cell proliferation and apoptosis were evaluated by immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. The expression level of p-p70S6K and p-GSK-3α/β was evaluated by western blot and IHC.
Results: Triptolide inhibited cell proliferation, induced S-phase cell cycle arrest and apoptosis in taxol-resistant A549 (A549/TaxR) cells. Moreover, intraperitoneal injection of triptolide resulted in a significant delay of tumor growth without obvious systemic toxicity in mice. Additionally, triptolide reversed epithelial-mesenchymal transition (EMT) through repression of the p70S6K/GSK3/β-catenin signaling pathway.
Conclusions: Our study provides evidence that triptolide can reverse EMT in taxol-resistant lung adenocarcinoma cells and impairs tumor growth by inhibiting the p70S6K/GSK3/β-catenin pathway, indicating that triptolide has potential to be used as a new therapeutic agent for taxol-resistant lung adenocarcinoma.
α-Sulfo alkyl ester surfactants: Impact of changing the alkyl chain length on the adsorption, mixing properties and response to electrolytes of the tetradecanoate

Wang Z, Li P, Ma K, Chen Y, Yan Z, Penfold J, et al.

J Colloid Interface Sci, 2021 Mar 15;586:876-890.
PMID: 33309145 DOI: 10.1016/j.jcis.2020.10.122

HYPOTHESIS: The α-sulfo alkyl ester, AES, surfactants are a class of anionic surfactants which have potential for improved sustainable performance in a range of applications, and an important feature is their enhanced tolerance to precipitation in the presence of multivalent counterions. It is proposed that their adsorption properties can be adjusted substantially by changing the length of the shorter alkyl chain, that of the alkanol group in the ester.
EXPERIMENTS: Surface tension and neutron reflectivity have been used to investigate the variation in the adsorption properties with the shorter alkyl chain length (methyl, ethyl and propyl), the impact of NaCl on the adsorption, the tendency to form surface multilayer structures in the presence of AlCl3, and the effects of mixing the methyl ester sulfonate with the ethyl and propyl ester sulfonates on the adsorption.
FINDINGS: The variations in the critical micelle concentration, CMC, the adsorption isotherms, the saturation adsorption values, and the impact of NaCl illustrate the subtle influence of varying the shorter alkyl chain length of the surfactant. The non-ideal mixing of pairs of AES surfactants with different alkanol group lengths of the ester show that the extent of the non-ideality changes as the difference in the alkanol length increases. The surface multilayer formation observed in the presence of AlCl3 varies in a complex manner with the length of the short chain and for mixtures of surfactants with different chains lengths.
Fulltext Challenges in supportive cancer care: perspectives from the Asia Pacific and Middle East

Keefe D, Al Garni A, Villalon A, Hassan A, Kwong D, Li P, et al.

Support Care Cancer, 2016 11;24(11):4479-81.
PMID: 27543163 DOI: 10.1007/s00520-016-3381-1
Adsorption and self-assembly in methyl ester sulfonate surfactants, their eutectic mixtures and the role of electrolyte

Xu H, Li P, Ma K, Welbourn RJL, Doutch J, Penfold J, et al.

J Colloid Interface Sci, 2018 Apr 15;516:456-465.
PMID: 29408135 DOI: 10.1016/j.jcis.2018.01.086

The α-methyl ester sulfonate, MES, anionic surfactants are a potentially important class of sustainable surfactants for a wide range of applications. The eutectic-like Kraft point minimum in the C16 and C18-MES mixtures is an important feature of that potential. Understanding their individual adsorption properties and the surface mixing of the eutectic mixtures are key to their wider exploitation. Neutron reflectivity has been used to investigate the adsorption at the air-water interface of the C16 and C18-MES surfactants and the eutectic mixture of C16 and C18-MES, in aqueous solution and in electrolyte. The micelle mixing of the eutectic mixture is investigated using small angle neutron scattering. The adsorption isotherms for C14 to C18-MES are found to scale with their critical micelle concentration value. The surface and micelle compositions of the C16 and C18-MES eutectic mixture differ from the eutectic composition; with compositions in the limit of high concentrations richer in C16-MES. The mixing properties are described by the pseudo phase approximation with a repulsive interaction between the two surfactants. The impact of the multivalent ions Al3+ on the adsorption at the air-water interface results in a transition from monolayer to multilayer adsorption.
Fulltext Acupuncture Alleviates CUMS-Induced Depression-Like Behaviors by Restoring Prefrontal Cortex Neuroplasticity

Li P, Huang W, Chen Y, Aslam MS, Cheng W, Huang Y, et al.

Neural Plast, 2023;2023:1474841.
PMID: 37179843 DOI: 10.1155/2023/1474841

PURPOSE: To explore the therapeutic efficiency of acupuncture and the related molecular mechanism of neural plasticity in depression.
METHODS: Chronic unpredictable mild stress- (CUMS-) induced rats were established for the depression animal model. There were a total of four rat groups, including the control group, the CUMS group, the CUMS+acupuncture group, and the CUMS+fluoxetine group. The acupuncture group and the fluoxetine group were given a 3-week treatment after the modeling intervention. The researcher performed the open-field, elevated plus maze, and sucrose preference tests to evaluate depressive behaviors. The number of nerve cells, dendrites' length, and the prefrontal cortex's spine density were detected using Golgi staining. The prefrontal cortex expression, such as BDNF, PSD95, SYN, and PKMZ protein, was detected using the western blot and RT-PCR.
RESULTS: Acupuncture could alleviate depressive-like behaviors and promote the recovery of the neural plasticity functions in the prefrontal cortex, showing the increasing cell numbers, prolonging the length of the dendrites, and enhancing the spine density. The neural plasticity-related proteins in the prefrontal cortex, including BDNF, PSD95, SYN, and PKMZ, were all downregulated in the CUMS-induced group; however, these effects could be partly reversed after being treated by acupuncture and fluoxetine (P < 0.05).
CONCLUSION: Acupuncture can ameliorate depressive-like behaviors by promoting the recovery of neural plasticity functions and neural plasticity-related protein upregulation in the prefrontal cortex of CUMS-induced depressed rats. Our study provides new insights into the antidepressant approach, and further studies are warranted to elucidate the mechanisms of acupuncture involved in depression treatment.
Fulltext Acupuncture alleviates CUMS-induced depression-like behaviors of rats by regulating oxidative stress, neuroinflammation and ferroptosis

Shen J, Hao C, Yuan S, Chen W, Tong T, Chen Y, et al.

Brain Res, 2024 Mar 01;1826:148715.
PMID: 38142722 DOI: 10.1016/j.brainres.2023.148715

BACKGROUND: The treatment of depression with acupuncture has been documented. The mechanism behind acupuncture's curative and preventative effects is still unknown.
METHODS: The current study examined the effects of acupuncture on depression-like behaviors in a rat model of chronic unpredictable mild stress (CUMS), while also exploring its potential mechanisms. A total of six groups of rats were randomly assigned: control, CUMS, acupuncture, fluoxetine, acupoint catgut embedding and sham acupoint catgut embedding. Fluoxetine (2.1 mg/kg) and acupoint catgut embedding were used for comparative research to acupuncture. The modelling evaluation is measured by body weight and behavior tests. Western blotting and reverse transcription-polymerase chain reaction were used to detect the proteins and mRNA expression of Silent information regulator 1 (Sirt1)/ nuclear factor-erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1)/ Glutathione peroxidase 4 (GPX4) pathway in the hippocampus. The expression of oxidative stress (OS)-related proteins and inflammatory cytokines in the serum was detected with ELISA. Immunofluorescence showed microglia and astrocytes activity in the hippocampus.
RESULTS: Acupuncture and fluoxetine could alleviate CUMS-induced depression-like behaviors. Acupuncture was also found to effectively reverse the levels of MDA, SOD, GSH, GSH-PX and T-AOC, IL-1β, IL-6 and TNF-α in the serum of CUMS-induced rats. Rats with CUMS showed decreased levels of Sirt1, Nrf2, HO-1 and GPX4 in the hippocampus, while acupuncture treatment could partly reverse the diminished effects. In addition, acupuncture treatment significantly reduced the activation of hippocampal microglia and astrocytes in CUMS-induced rats.
CONCLUSION: The study's findings indicate that acupuncture has the potential to mitigate depression-like behaviors in rats induced with CUMS by mitigating OS and reducing neuroinflammation.
Anisotropic Heat Transfer in a Fibrous Membrane with Hierarchically Assembled 2D Materials

Du Y, Zhen F, Ding S, Zhong Y, Li P, Zhan K, et al.

ACS Appl Mater Interfaces, 2024 Nov 14.
PMID: 39540851 DOI: 10.1021/acsami.4c15588

Effective heat redistribution in specific directions is vital for advanced thermal management, significantly enhancing device performance by optimizing spatial heat configurations. We have designed and fabricated a hierarchical fibrous membrane that enables precise heat directing. By integrating hierarchical structure design with the anisotropic thermal conductivity of two-dimensional (2D) materials, we developed a fibrous membrane for anisotropic heat transfer. Such a structure is fabricated by aligning a 1D structured fiber in the 2D plane to achieve anisotropy at each scale level. The fiber units, where 2D nanosheets circumferentially and axially aligned, achieved a high axial thermal conductivity of 16.8 W·m-1·K-1 and advanced heat directing ability, confirmed by characterizations and simulations. The assembled membrane demonstrated an exceptional tensile strength (365 MPa) and high thermal conductivity (10.5 W·m-1·K-1) along the fiber axis. Our membranes are seen as a refined model for thermal management materials, combining the benefits of heat spreaders and thermal interface materials, thus being proficient in directing heat along programmed pathways. A practical wireless charging cooling demonstration illustrated this. Our methodology also proved versatile with different 2D fillers and various geometries. This research presents a method to achieve precise heat directing at the material's level, facilitating the systematic design of thermal management in electronics.
Magnetic resonance imaging of Asians with multiple sclerosis was similar to that of the West

Chong HT, Ramli N, Lee KH, Kim BJ, Ursekar M, Dayananda K, et al.

Can J Neurol Sci, 2006 Feb;33(1):95-100.
PMID: 16583730

Magnetic resonance imaging (MRI) of the brain is the most important paraclinical diagnostic test in multiple sclerosis (MS). The appearance of MRI in Asians with MS is not well defined. We retrospectively surveyed the first brain and spinal cord MRI in patients diagnosed to have MS, according to Poser's criteria in seven regions throughout Asia to define the MRI changes among Asians with MS. There were 101 patients with first brain, and 86 with first spinal cord MRI, 66 of whom had both. The brain MRI showed a mean of 17 lesions per patient in T2 weighted images, mostly asymptomatic. Almost all the lesions were in the white matter, particularly in the juxtacortical, deep and periventricular white matter. A third of the lesions were greater than 5 mm, 14% enhanced with gadolinium. There were more supratentorial than infratentorial lesions at a ratio of 7.5: 1. Ninety five percent of the spinal cord lesions were in cervical and thoracic regions, 34% enhanced with gadolinium. The lesions extended over a mean of 3.6 +/- 3.3 vertebral bodies in length. Fifty (50%) of the brain and 54 (63%) of the spinal MRI patients had the optic-spinal form of MS. The MRI of the optic-spinal and classical groups of patients were similar in appearance and distribution, except that the optic-spinal MS patients have fewer brain but longer and more severe spinal cord lesions. In conclusion, the brain and spinal cord MRI of Asian patients with MS was similar to that of the West, although, in this study, Asian MS patients had larger spinal cord lesions.
IDRiD: Diabetic Retinopathy - Segmentation and Grading Challenge

Porwal P, Pachade S, Kokare M, Deshmukh G, Son J, Bae W, et al.

Med Image Anal, 2020 01;59:101561.
PMID: 31671320 DOI: 10.1016/j.media.2019.101561

Diabetic Retinopathy (DR) is the most common cause of avoidable vision loss, predominantly affecting the working-age population across the globe. Screening for DR, coupled with timely consultation and treatment, is a globally trusted policy to avoid vision loss. However, implementation of DR screening programs is challenging due to the scarcity of medical professionals able to screen a growing global diabetic population at risk for DR. Computer-aided disease diagnosis in retinal image analysis could provide a sustainable approach for such large-scale screening effort. The recent scientific advances in computing capacity and machine learning approaches provide an avenue for biomedical scientists to reach this goal. Aiming to advance the state-of-the-art in automatic DR diagnosis, a grand challenge on "Diabetic Retinopathy - Segmentation and Grading" was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI - 2018). In this paper, we report the set-up and results of this challenge that is primarily based on Indian Diabetic Retinopathy Image Dataset (IDRiD). There were three principal sub-challenges: lesion segmentation, disease severity grading, and localization of retinal landmarks and segmentation. These multiple tasks in this challenge allow to test the generalizability of algorithms, and this is what makes it different from existing ones. It received a positive response from the scientific community with 148 submissions from 495 registrations effectively entered in this challenge. This paper outlines the challenge, its organization, the dataset used, evaluation methods and results of top-performing participating solutions. The top-performing approaches utilized a blend of clinical information, data augmentation, and an ensemble of models. These findings have the potential to enable new developments in retinal image analysis and image-based DR screening in particular.
Fulltext Corrigendum re "Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma" [Eur Urol 2017;72:747-54]

Machiela MJ, Hofmann JN, Carreras-Torres R, Brown KM, Johansson M, Wang Z, et al.

Eur Urol, 2018 Sep;74(3):e85-e86.
PMID: 29853305 DOI: 10.1016/j.eururo.2018.05.017
Fulltext Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma

Machiela MJ, Hofmann JN, Carreras-Torres R, Brown KM, Johansson M, Wang Z, et al.

Eur Urol, 2017 Nov;72(5):747-754.
PMID: 28797570 DOI: 10.1016/j.eururo.2017.07.015

BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.
OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.
DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.
RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13).
CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.
PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

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