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Adonis El Salloukh,1,* Murad Khan,2,* Patrick Watts,1 Phillip M Newton,3 Gwyn Samuel Williams4 1Ophthalmology Department, University Hospital of Wales, Cardiff, Wales, UK; 2Birmingham and Midlands Eye Centre, Birmingham, England, UK; 3Neuroscience and Medical Education, Swansea University, Wales, UK; 4Ophthalmology Department, Singleton Hospital, Swansea, Wales, UK*These authors contributed equally to this workCorrespondence: Murad Khan, Birmingham and Midlands Eye Centre, City Hospital, Dudley Road, Birmingham, B18 7QH, UK, Email muradatherkhan@gmail.comPurpose: Mental workload is a recognised concept in medicine, and cognitive overload may lead to complications in surgery, including cataract surgery. A better understanding of what factors contribute to this can potentially improve patient safety and decrease surgeon stress. Simulated cataract surgery is now an essential part of training and a safe environment for exploring the effects of cognitive load upon performance. We used the EyeSi cataract surgery simulator to assess the effects of distraction on surgical performance and on ophthalmology trainees and consultants undertaking cataract surgery.Patients and Methods: Consultant and trainee cataract surgeons undertook a simulated list of six cases each, of which half were allowed to proceed without extraneous cognitive load with distraction and half were not. Blood pressure and pulse measurements were taken at three intervals in each of the six cases, as well as surgical scores on the simulator recorded for each case.Results: Distraction did not statistically significantly affect the scores, blood pressure or pulse measurements of either the 10 trainees or 10 consultants. Consultants performed more poorly than trainees overall (P = 0.0229) and suffered more serious errors that returned a score of zero for an individual stage (P = 0.0074).Conclusion: Consultant cataract surgeons performed worse than trainees on the EyeSi simulator, raising questions over whether simulation is as true to reality as has been suggested. An important finding is that ophthalmic training curricula around the world have been adapted in order to include simulated cataract surgery as an essential component of training new ophthalmic surgeons.Keywords: simulation, cataract surgery, ophthalmology

Asif Jan,1,2 Abdullah R Alanzi,3 Ramzi A Mothana,3 Jun-Ya Kaimori,4 Syed Shaukat Ali,5 Tahir Muhammad,6,7 Muhammad Saeed,8 Rani Akbar,9 Mehtab Khan10 1Department of Pharmacy, University of Peshawar, Peshawar, 25000, Pakistan; 2District Headquarter Hospital (DHQH) Charsadda, Charsadda, 24430, Pakistan; 3Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, 1151, Saudi Arabia; 4Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan; 5Department of Pharmacy, University of Malakand, Malakand, Pakistan; 6Molecular Neuropsychiatry & Development (Mind) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, 43964, Canada; 7Institute of Medical Science, University of Toronto, Toronto, ON, 43964, Canada; 8Department of Pharmacy, Qurtaba University of Science and Technology, Peshawar, 25000, Pakistan; 9Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan, 23200, Pakistan; 10Department of Biology, Faculty of Science, University of Moncton, Moncton, NB, E1A 3E9, CanadaCorrespondence: Asif Jan, Email asif.research1@gmail.comIntroduction: Despite the availability of various antihypertensive medications, the response to these medications varies among individuals. Understanding how individual genetic variations affect drugs treatment outcomes is a key area of focus in precision medicine. This study investigated the correlation between single nucleotide polymorphisms (SNPs) in selected genes (CACNA1C, CACNA1D, ABCB1, ACE, ADBR2, and NOS1AP) and the blood pressure (BP) control by amlodipine.Methods: Four hundred individuals of Pashtun ethnicity undergoing amlodipine treatment for hypertension were included in the present study and divided into the controlled (BP less than 140/90 mmHg) and uncontrolled (BP greater than 140/90 mmHg) hypertension groups. Blood samples (3 mL) were collected from each participant, and DNA was extracted using the Kit method. Ten SNPs in amlodipine pharmacogenes were selected and genotyped using real-time PCR with the TaqMan® system. Logistic regression model was used to determine the association between SNPs and the amlodipine BP response.Results: Notable association were observed between SNP rs2239050/CACNA1C and amlodipine blood pressure response, with GG genotype carriers demonstrating a better response (P=0.004) than individuals carrying CC or CG genotypes. SNP rs312481/CACNA1D also exhibited a positive pharmacogenetic association, Individuals with the GG genotype showing a considerable reduction in BP (P=0.021) compared to participants with AA or GA genotypes. In case of SNP rs429/ACE individuals carrying TA genotype were less likely to achieve BP control (P=0.002) than AA genotype carriers.Conclusion: Our finding suggests that the SNPs rs2239050/CACNA1C, rs312481/CACNA1D and rs429/ACE influence amlodipine blood pressure response in patients with hypertension. It is recommended that prior knowledge of amlodipine associated pharmacogenetic variants is important that could improve its treatment outcomes in hypertensive patients.Keywords: pharmacogenomics, hypertension, genetic markers, personalized medicine, amlodipine, Pashtun, Pakistan

Memona Khan,* Khaoula Cherni,* Rawdha Dekhili, Jolanda Spadavecchia CNRS, UMR 7244, NBD-CSPBAT, Laboratory of Chemistry, Structures and Properties of Biomaterials and Therapeutic Agents University Paris 13, Sorbonne Paris Nord, Bobigny, France*These authors contributed equally to this workCorrespondence: Rawdha Dekhili; Jolanda Spadavecchia, Email rawdhadekhilichimiste@gmail.com; jolanda.spadavecchia@univ-paris13.fr; jolanda.spadavecchia@gmail.comIntroduction: The aim of this study is focused on the development of theranostic hybrid nanovectors based on gold-doxorubicin (DOX)-gemcitabine (GEM) complexes and their active targeting with Galectin-1 (Gal-1) as a promising therapeutic and prognostic marker in cancer.Methods: For this purpose, a gold salt (HAuCl4) interacts with antitumor drugs (DOX; GEM) by chelation and then stabilizes with dicarboxylic acid-terminated polyethylene glycol (PEG) as a biocompatible surfactant. The proposed methodology is fast and reproducible, and leads to the formation of a hybrid nanovector named GEM@DOX IN PEG-AuNPs, in which the chemo-biological stability was improved. All synthetic chemical products were evaluated using various spectroscopic techniques (Raman and UV–Vis spectroscopy) and transmission electron microscopy (TEM).Results: To conceive a therapeutic application, our hybrid nanovector (GEM@DOX IN PEG-AuNPs) was conjugated with the Galectin-1 protein (Gal-1) at different concentrations to predict and specifically recognize cancer cells. Gal-1 interacts with GEM@DOX in PEG-AuNPs, as shown by SPR and Raman measurements. We observed both dynamic variation in the plasmon position (SPR) and Raman band with Gal-1 concentration.Discussion: We identified that GEM grafted electrostatically onto DOX IN PEG-AuNPs assumes a better chemical conformation, in which the amino group (NH3+) reacts with the carboxylic (COO−) group of PEG diacide, whereas the ciclopenthanol group at position C-5’ reacts with NH3+ of DOX.Conclusion: This study opens further way in order to built “smart nanomedical devices” that could have a dual application as therapeutic and diagnostic in the field of nanomedicine and preclinical studies associated.Keywords: gold-complex, gemcitabine, doxorubicin, galectin-1 protein, Raman spectroscopy, nanovector, diagnostic, biomarkers

Mohsin Khan,1,* Syed Khalid Perwez,2,* Rahul Paul Gaddam,2 Rabuni Aiswarya,2 Mohammed Abrar Basha,3 Abhradeep Malas,4 Shafiul Haque,5– 7 Faraz Ahmad4 1Department of Commerce, School of Social Science and Languages, Vellore Institute of Technology, Vellore, India; 2VIT Business School, Vellore Institute of Technology, Vellore, India; 3School of Life Sciences, B.S Abdur Rahman Crescent Institute of Science & Technology, Chennai, India; 4Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, India; 5Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia; 6Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon; 7Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates*These authors contributed equally to this workCorrespondence: Faraz Ahmad, Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, 632014, India, Tel +91 8969 66 8060, Email faraz.ahmad@vit.ac.inPurpose: While previous studies have suggested close association of psychological variables of students withtheir higher-order cognitive abilities, such studies have largely been lacking for third world countries like India, with their unique socio-economic-cultural set of challenges. We aimed to investigate the relationship between psychological variables (depression, anxiety and stress) and cognitive functions among Indian students, and to predict cognitive performance as a function of these variables.Patients and Methods: Four hundred and thirteen university students were systematically selected using purposive sampling. Widely used and validated offline questionnaires were used to assess their psychological and cognitive statuses. Correlational analyses were conducted to examine the associations between these variables. An Artificial Neural Network (ANN) model was applied to predict cognitive levels based on the scores of psychological variables.Results: Correlational analyses revealed negative correlations between emotional distress and cognitive functioning. Principal Component Analysis (PCA) reduced the dimensionality of the input data, effectively capturing the variance with fewer features. The feature weight analysis indicated a balanced contribution of each mental health symptom, with particular emphasis on one of the symptoms. The ANN model demonstrated moderate predictive performance, explaining a portion of the variance in cognitive levels based on the psychological variables.Conclusion: The study confirms significant associations between emotional statuses of university students with their cognitive abilities. Specifically, we provide evidence for the first time that in Indian students, self-reported higher levels of stress, anxiety, and depression are linked to lower performance in cognitive tests. The application of PCA and feature weight analysis provided deeper insights into the structure of the predictive model. Notably, use of the ANN model provided insights into predicting these cognitive domains as a function of the emotional attributes. Our results emphasize the importance of addressing mental health concerns and implementing interventions for the enhancement of cognitive functions in university students.Keywords: depression anxiety stress score, DASS, Montreal Cognitive Assessment, MoCA, college students, artificial neural network, predictive performance, Indian, developing economies, feature reduction, feature weights

This article features the buoyancy-driven electro-magnetohydrodynamic micropolar nanomaterial flow subjected to motile microorganisms. The flow is engendered via an elongating surface, and the energy relation includes heat source generation, magnetohydrodynamics, and radiation. A Buongiorno nanomaterial model (which includes thermophoretic and Brownian diffusions) together with chemical reaction and bioconvection aspects is pondered. The nonlinear governing expressions are transfigured into a dimensionless system, and the dimensionless expressions are computed using the numerical differential-solve scheme. Graphical analyses are conducted to examine the liquid flow, microrotation velocity, microorganism concentration, and temperature in relation to secondary variables. It is observed that a higher Hartman number has an opposite influence on temperature and velocity profiles. A rise in material variables engenders a decline in microrotation velocity. The temperature is enhanced through radiation. The concentration shows conflicting trends for both thermophoretic and random factors. The presence of motile microorganisms reduces the bioconvection Lewis and Peclet numbers.

The Marangoni convective phenomena have a unique impact on industries and medical tools. These phenomena are more prominent in the presence of dual nanoparticles (NPs) over base fluids such as blood that are surrounded by a thin interfacial nanolayer, an important feature to control the physical and thermal properties of the NP. In this problem, we have analysed the thermo-solutal Marangoni convective Darcy-Forchheimer flow of nanomaterials with the impact of the interfacial nanolayer. The results of the system of an exponential heat source, non-linear radiation, joule heating, and activation energy are discussed. An appropriate transition is applied to rationalise the substantially paired and nonlinear governing equations and then processed by the Galerkin finite element method (G-FEM). The impression of different governing parameters on the governing systems in conjunction with entropy and Bejan number is demonstrated through graphical and tabular form. Graphs are drawn with an evaluation of general and hybrid nanofluids (HNFs) and different nanolayer thicknesses of NPs. Activation energy and chemical reaction parameters restrict the Sherwood number, and the same is observed for the Nusselt number with an increase in the Brinkman and Eckert numbers. The thickness of the interfacial nanolayer of the NPs restricts the entropy generation of the system, while the entropy is higher for the HNF than the nanofluid. An opposite feature was observed for the Bejan number.

Léa El Haddad,1 Mainur Khan,1 Rania Soufny,1 David Mummy,2 Bastiaan Driehuys,2 Wissam Mansour,3 Priya S Kishnani,4 Mai K ElMallah1 1Division of Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA; 2Department of Radiology, Duke University Medical Center, Durham, NC, USA; 3Division of Pulmonary and Sleep Medicine, Department of Medicine, Duke University Medical Center, Durham, NC, USA; 4Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USACorrespondence: Mai K ElMallah, Division of Pulmonary and Sleep Medicine, Department of Pediatrics, Duke University Medical Center, Box 2644, Durham, NC, 27710, USA, Tel +1-919-684-3577, Email mai.elmallah@duke.eduAbstract: Pompe disease (PD) is a neuromuscular disorder caused by a deficiency of acid alpha-glucosidase (GAA) – a lysosomal enzyme responsible for hydrolyzing glycogen. GAA deficiency leads to accumulation of glycogen in lysosomes, causing cellular disruption. The severity of PD is directly related to the extent of GAA deficiency – if no or minimal GAA is produced, symptoms are severe and manifest in infancy, known as infantile onset PD (IOPD). If left untreated, infants with IOPD experience muscle hypotonia and cardio-respiratory failure leading to significant morbidity and mortality in the first year of life. In contrast, late-onset PD (LOPD) patients have more GAA activity and present later in life, but also have significant respiratory function decline. Despite FDA-approved enzyme replacement therapy, respiratory insufficiency remains a major cause of morbidity and mortality, emphasizing the importance of early detection and management of respiratory complications. These complications include impaired cough and airway clearance, respiratory muscle weakness, sleep-related breathing issues, and pulmonary infections. This review aims to provide an overview of the respiratory pathology, monitoring, and management of PD patients. In addition, we discuss the impact of novel approaches and therapies on respiratory function in PD.Keywords: Pompe disease, respiratory complications, respiratory monitoring, respiratory therapy

AbstractFocused Ultrasound (FUS) is emerging as a promising primary and adjunct therapy for the treatment of cancer. This includes histotripsy, which is a noninvasive, non-ionizing, non-thermal ultrasound guided ablation modality. As histotripsy has progressed from bench-to-bedside, it has become evident that this therapy has benefits beyond local tumor ablation. Specifically, histotripsy has the potential to shift the local tumor microenvironment from immunologically ‘cold’ to ‘hot’. This is associated with the production of damage associated molecular patterns, the release of a selection of proinflammatory mediators, and the induction of inflammatory forms of cell death in cells just outside of the treatment zone. In addition to the induction of this innate immune response, histotripsy can also improve engagement of the adaptive immune system and promote systemic anti-tumor immunity targeting distal tumors and metastatic lesions. These tantalizing observations suggest that, in settings of widely metastatic disease burden, selective histotripsy of a limited number of accessible tumors could be a means of maximizing responsiveness to systemic immunotherapy. More work is certainly needed to optimize treatment strategies that best synergize histotripsy parameters with innate and adaptive immune responses. Likewise, rigorous clinical studies are still necessary to verify the presence and repeatability of these phenomena in human patients. As this technology nears regulatory approval for clinical use, it is our expectation that the insights and immunomodulatory mechanisms summarized in this review will serve as directional guides for rational clinical studies to validate and optimize the potential immunotherapeutic role of histotripsy tumor ablation.

Environmental remediation of toxic organic pollutants on catalytic degradation has gained much attention. Organic dyes and fossil fuels as pollutants are the two major problems nowadays. The efficient and targeted eradication of organic dye from water systems is a critical global concern for the treatment of both drinking water and wastewater. In this study, ZnO–ZnS–CdO–CdS quaternary core–shell nanocomposites (NCs) were synthesized using Ricinus communis as a stabilizing agent and hydrazine hydrate as a reducing agent. UV-visible spectroscopy and photoluminescence confirmed the formation of NCs. Fourier transform infrared spectroscopy confirmed the presence of functional groups, while scanning electron microscopy analysis revealed that the morphology of nanomaterials was spherical and poly distributed. X-ray powder diffraction confirmed the crystalline nature of prepared samples. The prepared nanocatalysts were used in the production of hydrogen gas from green sources of the Brassica campestris leaf extract and the degradation of Congo red and methyl red dyes. Overall, the photocatalytic performance of NCs and their design was successful. The prepared catalysts were not only active in the degradation of a single substrate but also in the degradation of a mixture of dyes.

Abstract Ferric ions can bind strongly with dissolved organic matter (DOM), including humic acids (HA), fulvic acids (FA), and protein-like substances, whereas isolation of Fe-DOM precipitates (Fe-DOMP) and their biochemical characteristics remain unclear. In this work FeCl3 was used to isolate DOM components from various sources, including river, lake, soil, cow dung, and standard tryptophan and tyrosine, through precipitation at pH 7.5–8.5. The Fe-DOMP contribute to total DOM by approximately 38.6–93.8% of FA, 76.2% of HA and 25.0–30.4% of tryptophan and tyrosine, whilst fluorescence spectra allowed to monitor/discriminate the various DOM fractions in the samples. The relative intensity of the main infrared peaks such as 3406‒3383 cm−1 (aromatic OH), 1689‒1635 cm−1 (‒COOH), 1523–1504 cm−1 (amide) and 1176–1033 cm−1 (‒S=O) show either to decline or disappear in Fe‒DOMP. These results suggest the occurrence of Fe bonds with various functional groups of DOM, indicating the formation of π–d electron bonding systems of different strengths in Fe‒DOMP. The novel method used for isolation of Fe-DOMP shows promising in opening a new frontier both at laboratory and industrial purposes. Furthermore, results obtained may provide a better understanding of metal–organic complexes involved in the regulation of the long-term stabilization/sequestration of DOM in soils and waters.

More than 24,000 species of helminth parasitize wild birds worldwide, and this number is expanding as interest in wildlife parasitology increases. The objective of the current study was to update the baseline of helminthological surveys conducted on chukar partridges (Alectoris chukar) in northern Pakistan. After reviewing the available literature, a parasite-host association checklist was developed. Nematodes (53.8 %) were the most commonly reported parasite, followed by cestodes (15.3 %) and trematodes (15.3 %) respectively.

Memona Khan,1 Hui Liu,2 Pasquale Sacco,3,4 Eleonora Marsich,3,4 Xiaowu Li,2 Nadia Djaker,1 Jolanda Spadavecchia1 1CNRS, UMR 7244, NBD-CSPBAT, Laboratory of Chemistry, Structures and Properties of Biomaterials and Therapeutic Agents University Paris13, Sorbonne Paris Nord, Bobigny, France; 2Department of Hepatobiliary Surgery, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases& Carson International Cancer Center, Shenzhen University General Hospital & Shenzhen University Clinical Medical Academy Center, Shenzhen University, Shenzhen, People’s Republic of China; 3Department of Life Sciences, University of Trieste, Trieste, I-34127, Italy; 4Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, I-34129, ItalyCorrespondence: Nadia Djaker; Jolanda Spadavecchia, CNRS, UMR 7244, NBD-CSPBAT, Laboratory of Chemistry, Structures and Properties of Biomaterials and Therapeutic Agents University Paris13, Sorbonne Paris Nord, Bobigny, France, Email nadia.djaker@univ-paris13.fr; jolanda.spadavecchia@univ-paris13.frIntroduction: The realization of MRI contrast agents through chemical protocols of functionalization is a strong domain of research. In this work, we developed and formulated a novel hybrid gold nanoparticle system in which a gold salt (HAuCl4) is combined with dotarem, an MRI contrast agent (DOTA) by chelation (Method IN) and stabilized by a lactose-modified chitosan polymer (CTL; Chitlac) to form DOTA IN-CTL AuNPs.Result and Discussion: The authors demonstrate the biological efficiency of these nanoparticles in the case of three cell lines: Mia PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line). DOTA IN-CTL AuNPs are stable under physiological conditions, are nontoxic, and are very efficient as PTT agents. The highlights, such as high stability and preliminary MRI in vitro and in vivo models, may be suitable for diagnosis and therapy.Conclusion: We proved that DOTA IN-CTL AuNPs have several advantages: i) Biological efficacy on three cell lines: MIA PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line); ii) high stability, and no-toxicity; iii) high efficiency as a PPT agent. The study conducted on MRI in vitro and in vivo models will be suitable for diagnosis and therapy.Keywords: nanotheranostic, MRI, hybrid nanoparticles, dotarem, biomedical applications

Anjiya Shaikh,1,* Maria Khan,2,* Faisal Waseem Ismail3 1Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA; 2Department of Medicine, Aga Khan University, Karachi, Sindh, Pakistan; 3Section of Gastroenterology, Department of Medicine, Aga Khan University, Karachi, Sindh, Pakistan*These authors contributed equally to this workCorrespondence: Faisal Waseem Ismail, Department of Medicine, Aga Khan University, Karachi, Sindh, Pakistan, Tel +92-3009214175, Email faisal.ismail@aku.eduObjective: Telemedicine is being widely implemented in the COVID-19 pandemic to avoid infection risk. However, its effectiveness has not been evaluated, especially in developing countries, where it is invaluable for healthcare access. This study assesses physicians’ and patients’ perspectives of the usefulness and challenges of telemedicine in the gastroenterology department to identify its pitfalls.Methods: A cross-sectional telephonic survey was conducted on patients presenting to the gastroenterology department at a tertiary care hospital in Pakistan. An online survey was sent to physicians in the department.Results: A total of 160 patients participated, with a mean age 49.8 years, and 42.8% (n=68) males. There were 23.8% (n=38) initial visits and 76.3% (n=122) follow-ups. More than 85% of patients agreed telemedicine saved cost and time, 46.5% (n=74) said it improved healthcare access, and 76.3% (n=122) wanted to use it again. More than 80% were satisfied with the physician-patient interaction. Of the 7 physicians who participated, most felt telemedicine was inadequately facilitated, but felt comfortable with technology. Most felt it did not negatively affect healthcare, but thought it was complex for patients and that lack of physical interaction is a limitation. Nearly half were in favor of continuing its use after the pandemic.Conclusion: Telemedicine is an effective alternative to in-person visits. Patients find it convenient, with adequate interaction. Physicians have reservations that need addressal, such as poor administration. Most patients and half of physicians are welcome to using telemedicine in the post-COVID era.Keywords: telemedicine, gastroenterology, teleconsultation

Summary: Background: The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods: In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings: In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1–9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3–25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation: There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained. Funding: Bill & Melinda Gates Foundation.

In the current study, pure and manganese-doped superparamagnetic iron oxide nanoparticles (Mn-doped SPIONPs) were successfully prepared by a green approach using a fresh aqueous extract of Asparagus officinalis as a reducing and stabilizing agent. Magnetic behaviors of pure and Mn-doped SPIONPs were measured at room temperature against various field strengths by a vibrating sample magnetometer (VSM). The saturation magnetization was in the range of 5.39–2.07 emu. Absorption at 340 nm in the UV-visible spectrum confirmed the presence of iron oxide nanoparticles (IONPs). The presence of plant extract as a capping agent was confirmed by Fourier transform infrared (FTIR) spectroscopy. The crystalline nature of IONPs was confirmed by X-ray diffraction. A gradual increase in size was observed with increasing concentration of Mn. The synthesized materials were applied successfully as sorbent for the effective removal of lead ions (Pb(ii)). Experimental results of adsorption were also analyzed by Langmuir and Freundlich isotherm equations at different temperatures. The results suggested that sorption processes were spontaneous, and the synthesized SPIONPs displayed PbII removal capacity at higher loadings with q m of 21.3 and 29.56 mg·g−1 for undoped and 7% Mn-doped IOPNs, respectively, as compared to the commercial activated carbon.

Background: Glutathione (GSH) is a principle thiol-containing tripeptide (cysteine, glutamic acid and glycine) antioxidant against free radicals and other harmful oxidants in cellular defence. The alpha-2-macroglobulin (α2M) is large tetrameric zinc-binding glycoprotein which inhibits proteinases regardless of their specificity and catalytic mechanism. Materials and Methods: The interaction of GSH was analyzed with α2M including the structural and functional alterations in α2M using various biochemical and biophysical methods. UV-visible and fluorescence spectroscopy were used to study the binding of α2M with GSH and Fourier transform infrared (FT-IR) spectroscopy was explored to study the structural change induced in α2M. Results: The results suggest that exposure of α2M to GSH decreases the antiproteolytic potential as suggested by the amidase assay. The UV-spectroscopic study showed the formation of α2M-GSH complex and fluorescence analysis showed significant quenching in fluorescence intensity of α2M suggesting GSH binding and structural alteration in the protein. FT-IR spectroscopy was explored to study the structural change induced in α2M which suggest that the secondary structure of α2M changes upon complex formation. Conclusion: Our studies show that interaction of α2M with photoilluminated GSH results in functional and conformational changes of the protein. Keywords: glutathione, GSH, alpha-2-macroglobulin, photo-illumination, ITC, FTIR

Mukhtiar Ahmad,1,* Mehran Khan,2,* Rizwan Asif,3,* Nuzhat Sial,4,* Usman Abid,5,* Tahira Shamim,6 Zahid Hameed,7 Muhammad Junaid Iqbal,8,* Uroosa Sarfraz,8 Hina Saeed,1,* Zara Asghar,2 Madeeha Akram,2 Qamar Ullah,9 Qurat ul Ain Younas,10 Laraib Rauf,11 Alishba Hadi,1 Sajida Maryam,12 Yasir Hameed,1 Muhammad Rashid Khan,13,* Eman Tariq,14 Saba Saeed15,* 1Department of Biochemistry and Biotechnology, Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Department of Pharmacy, Islamia University of Bahawalpur, Bahawalpur, Pakistan; 3Department of Microbiology, Government College University Faisalabad, Faisalabad, Pakistan; 4Department of Zoology, Islamia University of Bahawalpur, Bahawalpur, Pakistan; 5Department of Pharmaceutics, Bahauddin Zakariya University, Multan, Pakistan; 6University College of Conventional Medicine, Islamia University of Bahawalpur, Bahawalpur, Pakistan; 7Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan; 8Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan; 9Department of Livestock and Dairy Development, Peshawar, Pakistan; 10Department of Zoology, Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan; 11Department of Healthcare Management, Riphah International University, Islamabad, Pakistan; 12Arid Agriculture University, Rawalpindi, Pakistan; 13University College of Eastern Medicine, Islamia University of Bahawalpur, Bahawalpur, Pakistan; 14Department of Chemistry, University of Swabi, Swabi, Pakistan; 15Department of Zoology, University of the Punjab, Lahore, Pakistan*These authors contributed equally to this workCorrespondence: Yasir Hameed, Department of Biochemistry and Biotechnology, Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan, Email Yasirhameed2011@gmail.comIntroduction: In light of the increased demand for reliable cancer-associated biomarkers and ANLN oncogenic potential, the present study aimed to investigate ANLN’s role in 24 human cancers.Methods: The UALCAN, Kaplan–Meier (KM) plotter, TNM Plot, GENT2, GEPIA, HPA, cBioPortal, STRING, Enrichr, TIMER, Cytoscape, DAVID, MuTarget, and CTD online databases and bioinformatic tools were used in this study.Results: In three of the cancers analyzed, ANLN expression was downregulated in tumor tissue, while it was overexpressed in the 21 other types of tumor tissue relative to controls. In CESC, ESCA, HNSC, and KIRC patients, ANLN overexpression was correlated with shorter overall survival, relapse-free survival, and metastasis. This suggests that ANLN is significantly involved in the development and progression of these four cancers. Further expression analysis revealed upregulation of ANLN in CESC, ESCA, HNSC, and KIRC patients with different clinical characteristics, regardless of the heterogeneity barrier. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that ANLN-associated genes were coexpressed with ANLN and were included in diverse BP, MF, and KEGG terms. Moreover, some interesting correlations were also documented between ANLN expression and its promoter-methylation level, genetic alterations, other mutant genes, and CD8+ T- and CD4+ T-cell infiltration. Moreover, we also identified ANLN-associated transcription factors, miRNAs, and chemotherapeutic drugs.Conclusion: This pan-cancer study revealed the novel diagnostic and prognostic role of ANLN across four cancers, regardless of heterogeneity.Keywords: cancer, ANLN, diagnostic, prognostic, biomarker

Abdullah AL-Harbi,1– 3 Tammam Alanazi,1 Hazim Alghamdi,1 Meshal Alberreet,1 Abdulaziz Alkewaibeen,1 Abdulrahman Alkhalifah,1 Aamir Omair,1,4 Mohammad Khan,1– 3 Hamdan AL-Jahdali1– 3 1College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 2Department of Medicine, Pulmonary Division, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia; 3King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 4Department of Medical education, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaCorrespondence: Abdullah AL-HarbiDepartment of Medicine, Pulmonary Division, Ministry of National Guard-Health Affairs, P.O. Box 22490, MC 1443, Riyadh, 11426, Saudi Arabia, Email harbia7@ngha.med.sa; draalharbi@yahoo.comBackground: Insomnia is commonly reported in patients with asthma. However, the prevalence of insomnia and its relationship to asthma control have not been established.Objective: To determine the prevalence of insomnia in adults with asthma and to evaluate the association between insomnia and level of asthma control.Methods: This is a cross-sectional study of 200 patients recruited from pulmonary clinics at a tertiary care center. Adults (age ≥ 16 years) diagnosed with asthma by the primary treating physician were recruited over a 6-month period from December 2018 to May 2019. Asthma and insomnia severity were assessed using the Asthma Control Test and Insomnia Severity Index (ISI).Results: The mean age of participants was 51± 17 years, and 67% were female. Insomnia (ISI score ≥ 10) was present in 46.5% of the participants. The severity of insomnia was inversely related to the level of asthma control: moderate-to-severe insomnia was more frequent in patients with uncontrolled asthma (43%) than in those with partially controlled asthma (25%) or well-controlled asthma (12%) (P < 0.05 for all comparisons).Conclusion: Insomnia is common among patients with asthma, especially those with suboptimal asthma control. Further investigations are required to more fully understand the complex relationship between asthma and insomnia.Keywords: prevalence, asthma, insomnia, asthma control, Insomnia Severity Index

Muhammad Khan,1,2 Zhihong Zhao,3 Xianming Li,1 Guixiang Liao1 1Department of Oncology, Shenzhen People’s Hospital, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2Department of Oncology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 3Department of Nephrology, Shenzhen People’s Hospital, Second Clinical Medicine Centre, Jinan University, Shenzhen, People’s Republic of ChinaCorrespondence: Guixiang Liao; Xianming LiDepartment of Radiation Oncology, Shenzhen People’s Hospital, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of ChinaEmail liaoguixiang@163.com; chenlhnfy@163.comBackground: Whole-brain radiotherapy (WBRT) remains an essential modality of treatment for brain metastases (BMs) derived from non-small cell lung cancer (NSCLC) patients and anti-PD-1 therapy has demonstrated intracranial responses in these patients. We aimed to evaluate if the combination of the two treatments could yield additive efficacy.Methods: A retrospective review of our institution’s database was carried out to identify NSCLC patients with BMs who had been treated with anti-PD1 therapy and/or WBRT between 2015 and 2020. Patient characteristics, main outcomes, including progression-free survival (PFS) and overall survival (OS), and factors affecting these outcomes were analyzed. SPSS 24 was used for statistical analysis. Appropriate statistical tests were employed according to the type of data.Results: Overall, 21 NSCLC BM patients were identified that had received WBRT. Of these, ten had been additionally treated with anti-PD1 therapy within 30 days of WBRT initiation. Median PFS was 3 (95% CI 0.8– 5.1) months with WBRT alone versus 11 (95% CI 6.3– 15.6) months with combined treatment. Risk of disease progression was 71% lower with the combined approach (HR 0.29, 95% CI 0.11– 0.80; p=0.016). A trend toward improved OS was also observed with the combined approach (HR 0.33, 95% CI 0.08– 1.12; p=0.107). Concurrent treatment (p=0.028) and male sex (p=0.052) were associated with improved PFS, while OS was associated only with age (p=0.02).Conclusion: Concurrent WBRT and anti-PD1 therapy may delay progression and improve survival in BM patients with confirmed EGFR- and ALK-negative NSCLC histology. Prospective studies are warranted to validate and elucidate on the additive effect of the two modalities.Keywords: brain metastasis, BM, whole-brain radiation therapy, WBRT, non–small cell lung cancer, NSCLC, immune checkpoint blockade, ICB, combination, combined therapy

Sheryl Ker,1,&ast; Jennifer Hsu,2,&ast; Anisha Balani,1,&ast; Sankha Subhra Mukherjee,1 A John Rush,3– 5 Mehreen Khan,2 Sara Elchehabi,2 Seth Huffhines,2 Dustin DeMoss,2,6 Miguel E Rentería,1 Joydeep Sarkar1 1Holmusk Technologies, Inc., New York, NY, USA; 2John Peter Smith Health Network, Fort Worth, TX, USA; 3Department of Psychiatry, Duke-National University of Singapore (NUS), Singapore; 4Duke University School of Medicine, Durham, NC, USA; 5Texas Tech Health Sciences Center, Odessa, TX, USA; 6University of North Texas Health Science Center/Texas Christian University, Fort Worth, TX, USA&ast;These authors contributed equally to this workCorrespondence: Miguel E Rentería; Joydeep SarkarHolmusk Technologies, Inc., 4th Floor, 54 Thompson St, New York, NY, 10012, USAEmail miguel.renteria@holmusk.com; joydeep.sarkar@holmusk.comPurpose: To describe attrition patterns of opioid use disorder (OUD) patients treated with buprenorphine (BUP) and to assess how clinical, sociodemographic, or BUP medication dosing features are associated with attrition.Patients and Methods: Electronic health records of adults (16+ year-olds) with OUD treated with BUP from 23 different substance use or mental health care programs across 11 US states were examined for one year following BUP initiation in inpatient (IP), intensive outpatient (IOP), or outpatient (OP) settings. Treatment attrition was declared at > 37 days following the last recorded visit. Survival analyses and predictive modelling were used.Results: Retention was consistently 2– 3 times higher following BUP initiation in OP (n = 2409) than in IP/IOP (n = 2749) settings after 2 (50% vs 25%), 6 (27% vs 9%) and 12 months (14% vs 4%). Retention was higher for females, whites (vs blacks), and those with less severe OUD, better global function, or not using non-psychotropic medications. Comorbid substance use, other psychiatric disorders, and the number of psychotropic medications were variously related to retention depending on the setting in which BUP was initiated. Predictive modelling revealed that a higher global assessment of functioning and a smaller OUD severity based on the Clinical Global Impression – Severity led to longer retentions, a higher initial BUP dose led to higher retention in a few cases, an OP setting of BUP initiation led to longer retentions, and a lower total number of psychotropic and non-psychotropic medications led to longer retentions. These were the most important parameters in the model, which identified 75.2% of patients who left BUP treatment within three months post-initiation, with a precision of 90.5%.Conclusion: Of all the OUD patients who began BUP, 50– 75% left treatment within three months, and most could be accurately identified. This could facilitate patient-centered management to better retain OUD patients in BUP treatment.Keywords: opioids, buprenorphine, buprenorphine dosing, treatment engagement, treatment retention, treatment dropout, predictors

Muhammad Khan,1,2 Xianming Li,1 Maosheng Yan,1 Zihuang Li,1 Hongli Yang,1 Guixiang Liao1 1Department of Oncology, Shenzhen People’s Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of ChinaCorrespondence: Guixiang LiaoDepartment of Oncology, Shenzhen People’s Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of ChinaTel +86 755 22942401Email liaoguixiang@163.comPurpose: Glioblastoma (GBM) shows frequent relapse and is highly resistant to treatment; therefore, it is considered fatal. Various vaccination protocols that have been tested in patients with GBM, which is the most common and aggressive primary brain tumor, have indicated safety and efficacy, to some extent, when used alone or in combination with standard of care. Recently, neoantigen-based personalized vaccines have shown tremendous immunogenicity and safety in GBM. We aimed to systematically review the medical literature for clinical trials to evaluate the efficacy and safety of neoantigen-based personalized vaccines for newly diagnosed GBM.Methods: We conducted a literature search for clinical trials on PubMed, Cochrane Library, China National Knowledge Infrastructure, and ClinicalTrials.gov until March 20, 2021. The primary outcomes of interest were immunogenicity and safety of the therapy. Efficacy outcomes, such as progression-free survival and overall survival, were secondary outcomes of interest.Results: Two clinical trials involving 24 patients were included in this review. High immunogenicity was observed in both studies. The GAPVAC-101 trial reported 50% APVAC1-induced and 84.7% APVAC2-induced immunogenicity with CD8+ and CD4+ T cell responses in 92% (12/13) and 80% (8/10) immune responders, respectively. Two out of five patients showed CD4+ and CD8+ T cell responses in the study by Keskin et al. Dexamethasone use had limited immunogenicity in a trial by Keskin et al (6/8). No serious treatment-related adverse events were reported.Conclusion: Actively personalized vaccines aimed at unmutated peptides and neoantigens for patients with GBM are safe and highly immunogenic, particularly when administered in combination. Larger studies are warranted to investigate the role.Keywords: glioblastoma, GBM, active immunotherapy, personalized peptide vaccination, neoantigen, immunogenicity, safety

Background and objectives: The enucleation of the pulmonary hydatid cyst is followed by individual closure of bronchial air leaks and obliteration of the residual pericystic cavity by capitonnage, either by circumferential or interrupted transverse suture. The objective of the study was to compare the surgical outcome of transverse and circumferential capitonnage in terms of postoperative recovery course, residual cavitations, air leaks, cavitatory or pleural collections and the recurrence of primary disease after enucleation of the pulmonary hydatid cyst. Methods: Patients with pulmonary hydatid cyst were included in the study and divided into two groups. Each group consisted of 30 patients. Patients of Group-1 underwent enucleation of the hydatid cyst followed by closure of bronchial air leaks with classical circumferential closure of the cavity and patients of Group-2 had enucleation of the hydatid cyst and closure of the cavity by transverse capitonnage. Results: Ten cases (33.33%) of Group-1 had hospital stay for more than 5 days compared to 4(13.33%) in Group-2 (p=0.03). Out of 30 patients who had undergone circumferential closure of the hydatid cavity, 5 (16.67%) patients had residual cavitatory fluid collection while there was none in the other group. In Group-1, 7 (23.3%) cases had reactionary intrapleural fluid collection compared to 2 (6.6%) in Group-2 (p=0.035). After 3 months of follow-up, 4 patients in circumferential capitonnage had mild haemoptysis and 1 had aspergilloma while no such complication occurred in any patient in the transverse capitonnage group. No recurrence of cyst occurred in any case in both groups. Conclusion: There was a considerable advantage of transverse capitonnage of the hydatid lung cavity after enucleation in terms of short hospital stay, minimal or no reactionary intrapleural or intra cavitatory collections and less air leaks. IMC J Med Sci 2021; 15(2): 002 *Correspondence: Farooq Ahmad Ganie, Department of Cardiovascular and Thoracic Surgery, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar -190011, J & K, India. E-mail: farooq.ganie@yamil.com

Mohammad Azam Ansari,1 Sultan Akhtar,2 Mohd Ahmar Rauf,3 Mohammad N Alomary,4 Sami AlYahya,4 Saad Alghamdi,5 MA Almessiere,2,6 Abdulhadi Baykal,7 Firdos Khan,8 Syed Farooq Adil,9 Mujeeb Khan,9 Mohammad Rafe Hatshan9 1Department of Epidemic Disease Research, Institute for Research & Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia; 2Department of Biophysics, Institute for Research & Medical Consultation (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia; 3Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA; 4National Centre for Biotechnology, King Abdulaziz City for Science and Technology (KACST), Riyadh, 11442, Saudi Arabia; 5Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia; 6Department of Physics, College of Science, Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia; 7Department of Nanomedicine Research, Institute for Research & Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia; 8Department of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, 31441, Saudi Arabia; 9Department of Chemistry, College of Science, King Saud University, Riyadh, 11451, Kingdom of Saudi ArabiaCorrespondence: Mohammad Azam Ansari; Syed Farooq Adil Email maansari@iau.edu.sa; sfadil@ksu.edu.saBackground: The constant rise of microbial biofilm formation and drug resistance to existing antimicrobial drugs poses a significant threat to community health around the world because it reduces the efficacy and efficiency of treatments, increasing morbidity, mortality, and health-care expenditures. As a result, there is an urgent need to develop novel antimicrobial agents that inhibit microbial biofilm formation.Methods: The [Ni0.4Cu0.2Zn0.4](Fe2-xDyx)O4(x≤ 0.04) (Ni-Cu-Zn) nano spinel ferrites (NSFs) have been synthesized by the sol–gel auto-combustion process and were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive x-ray (EDX) and transmission electron microscopy (TEM). The antimicrobial, antibiofilm and antiproliferative activities of Ni-Cu-Zn NSFs were also examined.Results: The XRD pattern confirms the secondary phase DyFeO3 and Fe2O3 for substituted Dy3+ samples, and the crystallite size ranged from 10 to 19 nm. TEM analysis of NSFs revealed that the particles were cube-shaped and 15nm in size. NSFs exhibited significant antimicrobial, antibiofilm and antiproliferative activity. At concentration of 1 mg/mL, it was found that the NSFs (ie, x=0.0, x=0.01, x=0.02, x=0.03 and x=0.04) inhibit biofilm formation by 27.6, 26.2, 58.5, 33.3 and 25% for methicillin-resistant Staphylococcus aureus (MRSA) and 47.5, 43.5, 48.6, 58.3 and 26.6% for Candida albicans, respectively. SEM images demonstrate that treating MRSA and C. albicans biofilms with NSFs significantly reduces cell adhesion, colonization and destruction of biofilm architecture and extracellular polymeric substances matrices. Additionally, SEM and TEM examination revealed that NSFs extensively damaged the cell walls and membranes of MRSA and C. albicans. Huge ultrastructural alteration such as deformation, disintegration and separation of cell wall and membrane from the cells was observed, indicating significant loss of membrane integrity, which eventually led to cell death. Furthermore, it was observed that NSF inhibited the cancer cell growth and proliferation of HCT-116 in a dose-dependent manner.Conclusion: The current study demonstrated that the synthesized Ni-Cu-Zn NSFs could be used to develop potential antimicrobial surface coatings agents for a varieties of biomedical-related materials and devices in order to prevent the biofilms formation and their colonization. Furthermore, the enhanced antiproliferative properties of manufactured SNFs suggest a wide range of biomedical applications.Keywords: biomedical application, nano spinel ferrites, MRSA, Candida albicans, biofilm, ultrastructural alteration

Memona Khan,1 Sarah Boumati,2 Celia Arib,1 Amadou Thierno Diallo,1 Nadia Djaker,1 Bich-thuy Doan,2 Jolanda Spadavecchia1 1CNRS, UMR 7244, CSPBAT, Laboratoire de Chimie, Structures et Propriétés de Biomatériaux et d’Agents Thérapeutiques, Université Sorbonne Paris Nord, Bobigny, 93000, France; 2CNRS UMR 8060, iCLeHS, Synthèse, Electrochimie, Imagerie et Systèmes Analytiques Pour le Diagnostic SEISAD, Chimie ParisTech, Université PSL, Paris, 75231, FranceCorrespondence: Bich-thuy DoanCNRS, UMR 8060, iCLeHS, Synthèse, Electrochimie, Imagerie et Systèmes Analytiques Pour le Diagnostic SEISAD, Chimie ParisTech, PSL University, 11 Rue Pierre et Marie Curie, Paris Cedex 05, Paris, 75231, FranceEmail bich-thuy.doan@chimieparistech.psl.euJolanda SpadavecchiaCNRS, UMR 7244, CSPBAT, Laboratoire de Chimie, Structures et Propriétés de Biomatériaux et d’Agents Thérapeutiques, Sorbonne Paris Nord University, 1 rue chablis, Bobigny, 93000, FranceEmail jolanda.spadavecchia@gmail.comIntroduction: In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl4) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl3 * 6 H2O) to form DOX IN-Gd-AuNRs compared with DOX ON-Gd-AuNRs in which the drug was grafted onto the bimetallic pegylated nanoparticle surface by electrostatic adsorption.Material and Method: The physical and chemical evaluation was performed by spectroscopic analytical techniques (Raman spectroscopy, UV-Visible and transmission electron microscopy (TEM)). Magnetic features at 7T were also measured. Photothermal abilities were assessed. Cytotoxicity studies on MIA PaCa-2, human pancreatic carcinoma and TIB-75 hepatocytes cell lines were carried out to evaluate their biocompatibility and showed a 320 fold higher efficiency for DOX after encapsulation.Results: Exhaustive physicochemical characterization studies were conducted showing a mid size of 20 to 40 nm diameters obtained with low polydispersity, efficient synthesis using seed mediated synthesis with chelation reaction with high scale-up, long duration stability, specific doxorubicin release with acidic pH, strong photothermal abilities at 808 nm in the NIR transparency window, strong magnetic r1 relaxivities for positive MRI, well adapted for image guided therapy and therapeutical purpose in biological tissues.Conclusion: In this paper, we have developed a novel theranostic nanoparticle composed of gadolinium complexes to gold ions, with a PEG biopolymer matrix conjugated with antitumoral doxorubicin, providing multifunctional therapeutic features. Particularly, these nano conjugates enhanced the cytotoxicity toward tumoral MIAPaCa-2 cells by a factor of 320 compared to doxorubicin alone. Moreover, MRI T1 features at 7T enables interesting positive contrast for bioimaging and their adapted size for potential passive targeting to tumors by Enhanced Permeability Retention. Given these encouraging antitumoral and imaging properties, this bimetallic theranostic nanomaterial system represents a veritable promise as a therapeutic entity in the field of medicinal applications.Keywords: hybrid nanorods, doxorubicin, MRI, MIAPaCa-2 cells, hyperthermia

Manik Chandra Shill,1 Asim Kumar Bepari,1 Mahi Khan,1 Zarin Tasneem,1 Tania Ahmed,1 Md Asif Hasan,1 Md Jahir Alam,1 Murad Hossain,1 Md Ashrafur Rahman,1 Shazid Md Sharker,1 Masum Shahriar,2 Ghazi Muhammad Sayedur Rahman,1 Hasan Mahmud Reza1 1Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka, 1229, Bangladesh; 2Department of Pharmacy, Jahangirnagar University, Savar, BangladeshCorrespondence: Manik Chandra Shill; Hasan Mahmud RezaDepartment of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka, 1229, BangladeshEmail manik.shill@northsouth.edu; hasan.reza@northsouth.eduIntroduction: Hypoglycemia in diabetes mellitus (DM) correlates with hepatic impairment, nephropathy, lipid abnormalities, and oxidative stress and subsequently complicates the disease pathogenesis. Medicinal plants have been used for the management of diabetes since ancient times. In this study, we explored the potentials of Colocasia affinis (CA), a plant known to possess anti-allergic and anti-inflammatory activities, as a remedy for diabetes and related complications.Methods: We induced diabetes in rats using a single intraperitoneal dose (65 mg/kg) of streptozotocin (STZ). We next treated the rats with an ethanolic extract of leaves of CA to reveal its antidiabetic and organ-protective potentials. Biomarkers of diabetes, inflammation, and oxidative stress were measured using biochemical and histopathological analysis. We also performed molecular docking for three major phytochemicals (kaempferol, myricetin, and rosmarinic acid) of CA.Results: Oral administration of the CA leaves extract at 250 mg/kg and 500 mg/kg doses decreased blood glucose level significantly (p< 0.05) in STZ-induced diabetic rats. The extract also considerably attenuated plasma HbA1c levels and normalized blood lipids, glycogen, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Additionally, treatment with the extract improved kidney complications by decreasing serum creatinine and blood urea nitrogen (BUN) levels. Furthermore, CA leaves extract normalized nitric oxide (NO) and advance oxidative protein products (AOPP) in diabetic rats. The extract also showed significant improvement of the antioxidant enzymes glutathione dismutase (GSH) and superoxide dismutase (SOD) at a dose of 500 mg/kg. Besides, histological investigation demonstrated attenuation of inflammation of the vital organs, including the liver and the kidney. In silico studies revealed that three major phytochemicals (kaempferol, myricetin, and rosmarinic acid) of the ethanolic extract of leaves of CA can inhibit several molecular targets of diabetes and inflammation.Conclusion: Collectively, our results demonstrated the therapeutic potentials of CA for the mitigation of diabetes and diabetic complications.Keywords: diabetes mellitus, Colocasia affinis, antidiabetic potentials, vital organs protection, oxidative stress markers

The current study was conducted to assess the potential of ginger rhizome extract (Zingiber officinale) for the synthesis of silver nanoparticles (AgNPs) through the green method and its mitigating activity against pathogenic bacterial strains. AgNPs were synthesized through a simple one-step approach and characterized by UV-Visible (UV-Vis) spectroscopy, powder X-ray diffraction (PXRD), transmission electronic microscopy (TEM), and energy dispersive X-rays spectroscopy (EDS). PXRD and TEM results of AgNPs showed the face central cubic structures and predominantly spherical structures with a size of 6.5 nm. EDS analysis confirms the elemental silver in nanoparticles. Moreover, the impact of the pH, as well as temperature, during the synthesis of AgNPs has also been investigated. At 25°C and pH 5, there was no significant peak for AgNPs in the absorption spectra. However, with an increase in temperature from 25°C to 85°C and pH 5 to pH 11, particles started attaining the spherical shape of different sizes due to an increase in the reduction rate. The AgNPs displayed effective results against selected pathogenic strains, Pseudomonas aeruginosa (MTCC 424), Methicillin-resistant Staphylococcus aureus (ATCC 43300), and fungus Candida albicans (KACC 30003). The prepared AgNPs exhibited excellent antioxidant activity and catalytic reduction of methyl orange with the pseudo-first-order rate constant of 3.9 × 10−3.

Abdullah AL-Harbi,1– 3 Majed AL-Ghamdi,1– 3 Mohammad Khan,1– 3 Sulaiman AL-Rajhi,1,3,4 Hamdan AL-Jahdali1– 3 1College of Medicine, King Saud University for Health Sciences, Riyadh, Saudi Arabia; 2Department of Medicine, Pulmonary Division, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia; 3King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 4Department of Medical Imaging, Ministry of National Guard-Health Affairs, Riyadh, Saudi ArabiaCorrespondence: Abdullah AL-HarbiDepartment of Medicine, Pulmonary Division, Ministry of National Guard-Health Affairs, King Abdulaziz Medical City, PO Box 22490, MC 1443, Riyadh 11426, Saudi ArabiaEmail harbia7@ngha.med.saObjective: The aim of this study was to assess the clinical characteristics and outcomes of patients with post‐tuberculosis (post-TB) bronchiectasis. We also evaluated the performance of various multidimensional severity score systems to predict mortality, future exacerbation, and hospitalization.Methods: We conducted a prospective observational cohort study to evaluate the etiology of bronchiectasis in 301 patients. Patients fell into three groups: post-TB (129 [43%]), idiopathic (76 [25%]), and other (96 [32%]) etiologies of bronchiectasis. Four multidimensional grading scales, including the Bronchiectasis Severity Index (BSI), the FACED score, and two derivative versions of the FACED score, Exacerbation (Exa-FACED and E-FACED), were calculated and compared for each patient.Results: Patients with post-TB bronchiectasis were predominantly female (61%) with a mean age of 68± 11 years. Moreover, 26% of post-TB bronchiectasis patients were colonized with Pseudomonas aeruginosa. At baseline, patients with post-TB bronchiectasis were older, had higher severity scores, and were more likely to have experienced severe exacerbations that required hospitalization compared to patients with idiopathic bronchiectasis or bronchiectasis arising from other causes. During follow-up, 52% of patients required hospitalization, 58% had frequent (≥ 2 per year) acute exacerbations, and the overall 5-year mortality rate was 30%. Five-year survival was efficiently predicted by each of the grading scales. Although the modified variations of the FACED outperformed the original FACED scale in predicting forthcoming frequent acute exacerbations and hospitalization, the BSI outperformed all three systems in this regard.Conclusion: Patients with post-TB bronchiectasis had higher severity scores than patients with idiopathic bronchiectasis or bronchiectasis arising from other causes. In addition, all scoring systems performed adequately in 5-year mortality projections. BSI and the modified versions of the FACED outperformed the FACED in predicting forthcoming exacerbations and hospitalizations.Keywords: bronchiectasis, post-TB bronchiectasis, Bronchiectasis Severity Index, BSI, FACED score, acute exacerbation, hospitalization, Exacerbation-FACED score, Exa-FACED score, E-FACED score

David Zargaran,1 Alexander Zargaran,2 Mansoor Khan3 1Department of Medicine, Imperial College London, London, UK; 2Department of Medicine, King’s College London, London, UK; 3Brighton and Sussex University Hospitals, Brighton, UKCorrespondence: David Zargaran Email david.zargaran@imperial.ac.ukBackground: Retro-hepatic inferior vena cava (RHIVC) injuries resulting from blunt or penetrating abdominal trauma are rare but devastating events that remain a considerable challenge to even the most experienced doctors, which continue to carry a considerable mortality.Aim: To establish a better understanding of the management of RHIVC injuries and to identify any adjuncts or operative methods that were associated with an increased survival.Methods: A systematic review of the MEDLINE database was conducted using Medical Search Headings and exploded keywords and phrases. Studies were screened and subjected to inclusion/exclusion criteria. Data were extracted in a methodical manner collecting population demographics, morbidity, mortality and operative intervention, where provided. Operative strategies were compared and discussed.Results: An initial search identified 483 articles. Following duplicate removal and abstract screening, 85 full-text articles were assessed with 25 meeting the desired criteria and were, therefore, included in the systematic review. Key operative strategies and complications were identified and discussed.Conclusion: The wide variety of operative interventions in the management of RHIVC liver injuries described attest to the increased efforts to improve outcomes. The overall improvement in mortality can be noted since the earlier descriptions reported mortality approaching 100% compared to the 52% reported in this review. An algorithm has been proposed based on these findings and our experiences for the management of RHIVC injuries.Keywords: trauma, liver, hepatic

Abstract Background Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cell-mediated immune responses (T-CMI) of elderly adults to a vaccine intended for intramuscular (IM) administration would be attenuated when deposited into SC fat, independent of confounding conditions. Results Fifty-two healthy, community dwelling elderly adults (65–82 years), seronegative for HBV, were enrolled in the SENIEUR protocol as a strictly healthy population. These seniors were randomized to receive a licensed alum-adjuvanted recombinant HBV vaccine either SC or IM, with the inoculum site verified by imaging. The response rates, defined as hepatitis B surface antibodies (HBsAb) ≥10 IU/L, were significantly lower in the elderly than in young adults, a group of 12, healthy, 21–34-year-old volunteers. Moreover, elderly participants who received the vaccine IM were significantly more likely to be responders than those immunized SC (54% versus 16%, p = 0.008). The low seroconversion rate in the IM group progressively declined with increasing age, and responders had significantly lower HBsAb titers and limited isotype responses. Moreover, T-CMI (proliferation and cytokine production) were significantly reduced in both percentage of responders and intensity of the response for both Th1 and Th2 subsets in the elderly. Conclusions Our data demonstrate the blunted immunogenicity of SC inoculation as measured by peak titers and response rates. Further, the qualitative and quantitative deficits in B- and T-CMI responses to primary alum adjuvanted protein antigens persisted even in strictly healthy elderly populations with verified IM placement compared to younger populations. Clinical trial registration ClinicalTrials.gov , NCT04162223 . Registered 14 November 2019. Retrospectively registered.

Abstract In this work, grain boundary (GB) potential barrier ( Δφ GB), dopant density (Pnet), and filled trap state density (PGB,trap) were manipulated at the nanoscale by exposing the fabricated perovskite films to various relative humidity (RH) environments. Spatial mapping of surface potential in the perovskite film revealed higher positive potential at GBs than inside the grains. The average Δφ GB, Pnet, and PGB,trap in the perovskite films decreased from 0% RH to 25% RH exposure, but increased when the RH increased to 35% RH and 45% RH. This clearly indicated that perovskite solar cells fabricated at 25% RH led to the lowest average GB potential, smallest dopant density, and least filled trap states density. This is consistent with the highest photovoltaic efficiency of 18.16% at 25% RH among the different relative humidities from 0% to 45% RH.

The study aims in the development of functionally graded epoxy-based layered composites dispersed with B4C and lead particles. The development route adopted for the composites is a novel route called layered molding and curing. Various compositions of single and trilayered composites were prepared through the abovementioned route. The samples prepared were subjected to mechanical and tribological studies, and the results were reported in this article. It is found that the mechanical properties of the single-layered composites consisting of 20% lead and 20% B4C show superior characteristics than those of the samples with increased addition of lead. However, the trilayered samples with lead core showcased excellent mechanical properties. On the other hand, the wear rate and mass loss of the trilayered samples with B4C cladding show minimum wear rate than the samples with lead cladding. Furthermore, the coefficient of friction of the samples also showcases the better performance of single-layered samples with 20% lead. The worn surface analysis done through scanning electron microscopy and stereo zoom microscopy reveals the reason for the low specific wear rate of 20% lead sample as the self-hindrance of wear debris evolved during the wear study.

This work investigates the efficacy of deep learning (DL) for classifying C100 superconducting radio-frequency (SRF) cavity faults in the Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab. CEBAF is a large, high-power continuous wave recirculating linac that utilizes 418 SRF cavities to accelerate electrons up to 12 GeV. Recent upgrades to CEBAF include installation of 11 new cryomodules (88 cavities) equipped with a low-level RF system that records RF time-series data from each cavity at the onset of an RF failure. Typically, subject matter experts (SME) analyze this data to determine the fault type and identify the cavity of origin. This information is subsequently utilized to identify failure trends and to implement corrective measures on the offending cavity. Manual inspection of large-scale, time-series data, generated by frequent system failures is tedious and time consuming, and thereby motivates the use of machine learning (ML) to automate the task. This study extends work on a previously developed system based on traditional ML methods (Tennant and Carpenter and Powers and Shabalina Solopova and Vidyaratne and Iftekharuddin, Phys. Rev. Accel. Beams, 2020, 23, 114601), and investigates the effectiveness of deep learning approaches. The transition to a DL model is driven by the goal of developing a system with sufficiently fast inference that it could be used to predict a fault event and take actionable information before the onset (on the order of a few hundred milliseconds). Because features are learned, rather than explicitly computed, DL offers a potential advantage over traditional ML. Specifically, two seminal DL architecture types are explored: deep recurrent neural networks (RNN) and deep convolutional neural networks (CNN). We provide a detailed analysis on the performance of individual models using an RF waveform dataset built from past operational runs of CEBAF. In particular, the performance of RNN models incorporating long short-term memory (LSTM) are analyzed along with the CNN performance. Furthermore, comparing these DL models with a state-of-the-art fault ML model shows that DL architectures obtain similar performance for cavity identification, do not perform quite as well for fault classification, but provide an advantage in inference speed.

Aouidat F, Boumati S, Khan M, Tielens F, Doan BT, Spadavecchia J. Int J Nanomedicine. 2019;14:9309–9324. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. The authors raised concerns regarding errors that had been made during the calculation of the size of the nanostructures shown in Figure 2. The sizes reported in the histograms of Figure 2; a1, a2 and a3 were incorrect due to miscalculations that occurred during analysis of the gold core and polymer shells of the spherical nanostructures represented in TEM images of Figure 2A. The authors provided the editor with data from the original study and requested to remove the incorrect histograms and replace them. However, the Editor determined that this part of the article was integral to the study and the admission of these errors, because of the miscalculation, meant the data was unreliable and would not accept the correction proposed by the authors. The Editor requested for the article to be retracted and the authors were notified but do not agree with this decision. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

RNA sequencing (RNAseq) is a recent technology that profiles gene expression by measuring the relative frequency of the RNAseq reads. RNAseq read counts data is increasingly used in oncologic care and while radiology features (radiomics) have also been gaining utility in radiology practice such as disease diagnosis, monitoring, and treatment planning. However, contemporary literature lacks appropriate RNA-radiomics (henceforth, radiogenomics) joint modeling where RNAseq distribution is adaptive and also preserves the nature of RNAseq read counts data for glioma grading and prediction. The Negative Binomial (NB) distribution may be useful to model RNAseq read counts data that addresses potential shortcomings. In this study, we propose a novel radiogenomics-NB model for glioma grading and prediction. Our radiogenomics-NB model is developed based on differentially expressed RNAseq and selected radiomics/volumetric features which characterize tumor volume and sub-regions. The NB distribution is fitted to RNAseq counts data, and a log-linear regression model is assumed to link between the estimated NB mean and radiomics. Three radiogenomics-NB molecular mutation models (e.g., IDH mutation, 1p/19q codeletion, and ATRX mutation) are investigated. Additionally, we explore gender-specific effects on the radiogenomics-NB models. Finally, we compare the performance of the proposed three mutation prediction radiogenomics-NB models with different well-known methods in the literature: Negative Binomial Linear Discriminant Analysis (NBLDA), differentially expressed RNAseq with Random Forest (RF-genomics), radiomics and differentially expressed RNAseq with Random Forest (RF-radiogenomics), and Voom-based count transformation combined with the nearest shrinkage classifier (VoomNSC). Our analysis shows that the proposed radiogenomics-NB model significantly outperforms (ANOVA test, p < 0.05) for prediction of IDH and ATRX mutations and offers similar performance for prediction of 1p/19q codeletion, when compared to the competing models in the literature, respectively.

Gliomas are primary brain tumors that originate from glial cells. Classification and grading of these tumors is critical to prognosis and treatment planning. The current criteria for glioma classification in central nervous system (CNS) was introduced by World Health Organization (WHO) in 2016. This criteria for glioma classification requires the integration of histology with genomics. In 2017, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) was established to provide up-to-date recommendations for CNS tumor classification, which in turn the WHO is expected to adopt in its upcoming edition. In this work, we propose a novel glioma analytical method that, for the first time in the literature, integrates a cellularity feature derived from the digital analysis of brain histopathology images integrated with molecular features following the latest WHO criteria. We first propose a novel over-segmentation strategy for region-of-interest (ROI) selection in large histopathology whole slide images (WSIs). A Deep Neural Network (DNN)-based classification method then fuses molecular features with cellularity features to improve tumor classification performance. We evaluate the proposed method with 549 patient cases from The Cancer Genome Atlas (TCGA) dataset for evaluation. The cross validated classification accuracies are 93.81% for lower-grade glioma (LGG) and high-grade glioma (HGG) using a regular DNN, and 73.95% for LGG II and LGG III using a residual neural network (ResNet) DNN, respectively. Our experiments suggest that the type of deep learning has a significant impact on tumor subtype discrimination between LGG II vs. LGG III. These results outperform state-of-the-art methods in classifying LGG II vs. LGG III and offer competitive performance in distinguishing LGG vs. HGG in the literature. In addition, we also investigate molecular subtype classification using pathology images and cellularity information. Finally, for the first time in literature this work shows promise for cellularity quantification to predict brain tumor grading for LGGs with IDH mutations.

Fatima Aouidat,1 Sarah Boumati,2 Memona Khan,1 Frederik Tielens,3 Bich-Thuy Doan,2 Jolanda Spadavecchia1 1CNRS, UMR 7244, CSPBAT, Laboratory of Chemistry, Structures and Properties of Biomaterials And Therapeutic Agents University Paris 13, Sorbonne Paris Cité, Bobigny, France; 2UTCBS – Chimie ParisTech – University Paris Descartes - CNRS UMR 8258 – INSERM U1022 Equipe “Synthesis, Electrochemistry, Imaging and Analytical Systems for Diagnostics” SEISAD, Paris, France; 3General Chemistry (ALGC), Vrije University of Brussel (Free University Brussels-VUB), Brussel, BelgiumCorrespondence: Jolanda Spadavecchia Email jolanda.spadavecchia@univ-paris13.frIntroduction: The development of biopolymers for the synthesis of Gd(III) nanoparticles, as therapeutics, could play a key role in nanomedicine. Biocompatible polymers are not only used for complex monovalent biomolecules, but also for the realization of multivalent active targeting materials as diagnostic and/or therapeutic hybrid nanoparticles. In this article, it was reported for the first time, a novel synthesis of Gd(III)–biopolymer–Au(III) complex, acting as a key ingredient of core-shell gold nanoparticles (Gd(@AuNPs).Material and methods: The physical and chemical evaluation was carried out by spectroscopic analytical techniques (Raman spectroscopy, UV-visible and TEM). The theoretical characterization by DFT (density functional theory) analysis was carried out under specific conditions to investigate the interaction between the Au and the Gd precursors, during the first nucleation step. Magnetic features with relaxivity measurements at 7T were also performed as well as cytotoxicity studies on hepatocyte cell lines for biocompatibility studies. The in vivo detailed dynamic biodistribution studies in mice to characterize the potential applications for biology as MRI contrast agents were then achieved.Results: Physical–chemical evaluation confirms the successful design and reaction supposed. Viabilities of TIB-75 (hepatocytes) cells were evaluated using Alamar blue cytotoxic tests with increasing concentrations of nanoparticles. In vivo biodistribution studies were then accomplished to assess the kinetic behavior of the nanoparticles in mice and characterize their stealthiness property after intravenous injection.Conclusion: We demonstrated that Gd@AuNPs have some advantages to display hepatocytes in the liver. Particularly, these nanoconjugates give a good cellular uptake of several quantities of Gd@NPs into cells, while preserving a T1 contrast inside cells that provide a robust in vivo detection using T1-weighted MR images. These results will strengthen the role of gadolinium as complex to gold in order to tune Gd(@AuNPs) as an innovative diagnostic agent in the field of nanomedicine.Keywords: Gd-gold complex, theoretical study, MRI, relaxivity, biodistribution

The solution of nonlinear mathematical models has much importance and in soliton theory its worth has increased. In the present article, we have investigated the Caudrey-Dodd-Gibbon and Pochhammer-Chree equations, to discuss the physics of these equations and to attain soliton solutions. The exp(−ϕ(ζ ))-expansion technique is used to construct solitary wave solutions. A wave transformation is applied to convert the problem into the form of an ordinary differential equation. The drawn-out novel type outcomes play an essential role in the transportation of energy. It is noted that in the study, the approach is extremely reliable and it may be extended to further mathematical models signified mostly in nonlinear differential equations.

Zil Goldstein,1 Musaub Khan,2 Tamar Reisman,1 Joshua D Safer11Center for Transgender Medicine and Surgery at Mount Sinai, Mount Sinai Health System and Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; 2New York Medical College, Valhalla, NY USAIntroduction: Venous thromboembolism (VTE) is a potential risk of estrogen therapy. However, data show an improvement in the quality of life for transgender people who use feminizing hormone therapy. With few transgender-specific data, guidance may be drawn from cisgender (nontransgender) data, with a focus on hormonal birth control and postmenopausal hormone replacement therapy (HRT). The aim of this review is to examine the degree to which routes of administration, patient comorbidities, and type of hormone utilized affect the safety of estrogen therapy.Methods: We identified 6,349 studies by searching PubMed with the terms “transgender”, “estrogen”, “VTE”, and “HRT”. Of these, there were only 13 studies between 1989 and 2018 that investigated the effects of hormone therapy, including types of estrogens used, in transgender women and men.Results: The data suggest that the route of hormone administration, patient demographics, and patient comorbidities all affect estrogen’s link with VTE. For example, avoiding ethinyl estradiol might make the use of hormone therapy in trans feminine individuals safer than oral birth control. Data from both cis and trans groups suggest additional VTE risk associated with the use of progestins. While transdermal estrogens dosed up to 0.1 mg/day or below appear lower risk for VTE than other forms of estrogen, it is unclear whether this is related to the delivery method or a dose effect. Finally, even if the risk from exogenous estrogen use remains significant statistically, the absolute clinical risk remains low.Conclusion: Clinicians should avoid the use of ethinyl estradiol. Additionally, data suggest that progestins should be avoided for transgender individuals. Further study of the relationship between estrogen use and the risk of VTE will serve to inform the safest care strategies for transgender individuals.Keywords: transgender, estrogen therapy, venous thromboembolism