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The Coronavirus pandemic caused by the novel SARS-CoV-2 has significantly impacted human health and the economy, especially in countries struggling with financial resources for medical testing and treatment, such as Brazils case, the third most affected country by the pandemic. In this scenario, machine learning techniques have been heavily employed to analyze different types of medical data, and aid decision making, offering a low-cost alternative. Due to the urgency to fight the pandemic, a massive amount of works are applying machine learning approaches to clinical data, including complete blood count (CBC) tests, which are among the most widely available medical tests. In this work, we review the most employed machine learning classifiers for CBC data, together with popular sampling methods to deal with the class imbalance. Additionally, we describe and critically analyze three publicly available Brazilian COVID-19 CBC datasets and evaluate the performance of eight classifiers and five sampling techniques on the selected datasets. Our work provides a panorama of which classifier and sampling methods provide the best results for different relevant metrics and discuss their impact on future analyses. The metrics and algorithms are introduced in a way to aid newcomers to the field. Finally, the panorama discussed here can significantly benefit the comparison of the results of new ML algorithms.
Comparison of machine learning techniques to handle imbalanced COVID-19 CBC datasets
BACKGROUND: Clinical and economic comparisons of therapies for plaque psoriasis are regularly updated following each new devel- opment in the field. With the recent availability of a novel accessory (Multi Micro DoseTM [MMD®] tip) for the 308nm excimer laser (XTRAC®, Strata Skin Sciences, Horsham, PA), which can determine and deliver an optimal therapeutic dose (OTDTM) of ultraviolet-B light in an improved protocol, the need for comparative health-economic assessment recurs. To this end, a comprehensive evaluation of treatment-related costs was undertaken from the payer perspective. Results show that outcomes are influenced by many factors; most importantly, the severity and extent of disease, treatment selection, and patient preference, as well as compliance, adherence, and persistence with care. Among study comparators, the 308nm excimer laser – XTRAC – with its latest MMD enhancement, is safe and delivers incremental clinical benefits with the potential for significant cost savings. These benefits are particularly relevant today in the context of SARS-CoV-2 virus and the COVid-19 pandemic. J Drugs Dermatol. 2020;19(11):1101-1108. doi:10.36849/JDD.2020.5510.
Therapies for Psoriasis: Clinical and Economic Comparisons
Studies describing reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay-based infection control strategies (LAMP-based ICSs) for coronavirus disease 2019 (COVID-19) are limited. We reviewed the medical records of cases in which RT-LAMP was performed. Standard ICSs and LAMP-based ICSs were implemented during the study period. The strategies were intended to impose longer periods of infection control precautions (ICPs) for specific patients, such as those with a history of exposure to COVID-19 patients and/or bilateral ground glass opacities (bGGO) on chest computed tomography (CT). Of 212 patients, which included 13 confirmed COVID-19 patients in the diagnostic cohort, exposure to COVID-19 patients (P <0.0001) and chest CT bGGO (P = 0.0022) were identified as significant predictors of COVID-19. In the 173 hospitalized patients in which the results of the first RT-LAMP were negative, the duration of ICPs was significantly longer in patients with exposure to COVID-19 and/or a high clinical index of suspicion and patients with bGGO than in the remaining patients (P = 0.00046 and P = 0.0067, respectively). Additionally, no confirmed COVID-19 cases indicating nosocomial spread occurred during the study period. Establishing a comprehensive system that combines rational LAMP-based ICSs with standard ICSs might be useful for preventing nosocomial spread.
Reverse Transcription Loop-Mediated Isothermal Amplification Assay-Based Infection Control Strategies for COVID-19 in a Hospital Under the State of Emergency in Tokyo, Japan in Spring 2020
BACKGROUND: Sorafenib, a multi-kinase inhibitor approved for treatment of advanced renal cell carcinoma and other malignancies, has been shown as a modulator for dendritic cells. This study was designed to examine the effects of sorafenib on macrophages, the major ontogeny of innate immunity. MATERIALS AND METHODS: Macrophages were derived from sorted CD14(+) monocytes of human peripheral blood mononuclear cells. Cell viability and surface antigens were examined by trypan blue analysis. Autophagy was characterized by light microscopy and transmission electron microscopy for morphology, Western blotting for microtubule associated light chain protein 3B (LC-3B) I lipidation, and acridine orange staining for acidic component vacuoles. Soluble factors contained in culture medium and serum were measured by ELISA. RESULTS: We found that sorafenib inhibited the viability of macrophages accompanied by morphological changes characteristic of autophagy. This autophagy-inducing effect was validated by LC3B-I lipidation and autophagosome accumulation. The surface antigen expression and the function of activated macrophages were inhibited by sorafenib, including the expression of co-stimulatory molecule CD80, phagocytosis, and the production of reactive oxygen species. The secretion of IL-10, but not IL-6, TNF- nor TGF-, was reduced by sorafenib. CONCLUSION: Sorafenib, in addition to being a cancer targeted therapeutic agent, can induce autophagy and modulate the function of human macrophages.
Sorafenib induces autophagy and suppresses activation of human macrophage
Nuclear localization of cytoplasmic RNA virus proteins mediated by intrinsic nuclear localization signal (NLS) plays essential roles in successful virus replication. We previously reported that NLS mutation in the matrix (M) protein obviously attenuates the replication and pathogenicity of Newcastle disease virus (NDV), but the attenuated replication mechanism remains unclear. In this study, we showed that M/NLS mutation not only disrupted Ms nucleocytoplasmic trafficking characteristic but also impaired viral RNA synthesis and transcription. Using TMT-based quantitative proteomics analysis of BSR-T7/5 cells infected with the parental NDV rSS1GFP and the mutant NDV rSS1GFP-M/NLSm harboring M/NLS mutation, we found that rSS1GFP infection stimulated much greater quantities and more expression changes of differentially expressed proteins involved in host cell transcription, ribosomal structure, posttranslational modification, and intracellular trafficking than rSS1GFP-M/NLSm infection. Further in-depth analysis revealed that the dominant nuclear accumulation of M protein inhibited host cell transcription, RNA processing and modification, protein synthesis, posttranscriptional modification and transport; and this kind of inhibition could be weakened when most of M protein was confined outside the nucleus. More importantly, we found that the function of M protein in the cytoplasm effected the inhibition of TIFA expression in a dose-dependent manner, and promoted NDV replication by down-regulating TIFA/TRAF6/NF-B-mediated production of cytokines. It was the first report about the involvement of M protein in NDV immune evasion. Taken together, our findings demonstrate that NDV replication is closely related to the nucleocytoplasmic trafficking of M protein, which accelerates our understanding of the molecular functions of NDV M protein.
TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein
Children with fragile X syndrome and William Beuren syndrome share several socio-communicative deficits. In both populations, around 30/35% of individuals meets criteria for autism spectrum disorder on gold standard instruments. Notwithstanding, few studies have explored feasibility and validity of therapy for socio-communicative deficits in individuals with these genetic conditions. In this study, we present preliminary data on a pilot RCT aimed to verify the effectiveness of cooperative parent-mediated therapy for socio-communicative deficits in a transdiagnostic perspective in a small sample of 12 participants. Our preliminary data showed that the experimental group had significant improvement in one socio-communicative skill (responsivity) and in clinical global impression, while the control group in an adaptive measure of socialization and word production. Implications of these results are then discussed.
Cooperative Parent-Mediated Therapy in Children with Fragile X Syndrome and Williams Beuren Syndrome: A Pilot RCT Study of a Transdiagnostic Intervention-Preliminary Data
OBJECTIVE To determine if a specific population of patients with a daily persistent headache from onset have underlying nutcracker physiology and to propose a pathogenesis model for their headaches utilizing a novel MRI protocol. BACKGROUND A single case report of a daily persistent headache associated with nutcracker syndrome was recently published. As the left renal vein has a connection to the spinal lumbar veins and secondarily to the spinal epidural venous plexus, one could hypothesize that renal vein compression could lead to persistent headache by altering spinal and cerebral venous pressure with secondary alterations in CSF pressure. The authors have published on a series of patients with a unique subtype of daily persistent headache from onset that appears to be caused by an abnormal reset of CSF pressure to an elevated state. The goal of the present study was to look for the presence of nutcracker physiology in this unique patient subgroup and to propose a pathogenesis model utilizing a novel MRI protocol to evaluate for retrograde lumbar vein flow and regional spinal epidural venous plexus congestion. MATERIALS AND METHODS Case series of patients with a daily persistent headache from onset, head pressure, and whose headaches worsened in the Trendelenburg position. Patients were imaged with a 3 T MRI in the supine position from the lower diaphragm to the top of the pelvis with a dynamic angiogram centered over the left L2 lumbar vein. RESULTS 12 patients were studied of which 8 were positive for left renal vein compression, lumbar vein dilation and early spinal epidural venous plexus enhancement. All were women. Mean age of headache onset was 39 years. Six of the 8 patients had a lumbar puncture, and all had a normal opening pressure. All improved with CSF volume removal although pain resolution lasted from hours to 6 months. The patient's headaches were marked by holocranial pressure and the majority displayed migrainous associated symptoms although none had a prior headache history. They did not complain of typical symptoms or signs of nutcracker syndrome. CONCLUSION We suggest that patients with a daily persistent headache from onset who worsen in the Trendelenburg position may have underlying nutcracker physiology. From our imaging findings, it can be hypothesized that left renal vein compression leads to retrograde flow through the valveless lumbar vein which then leads to spinal epidural venous congestion and subsequently causes congestion of the cerebral venous system leading to an elevation of CSF pressure and to a daily headache. What appears to be unique about these patients is that a daily headache is their only manifestation of nutcracker physiology.
Nutcracker phenomenon with a daily persistent headache as the primary symptom: Case series and a proposed pathogenesis model based on a novel MRI technique to evaluate for spinal epidural venous congestion.
COVID-19 is taking a mental toll on students as they plan for college, but college admission counselors say connections can ease uncertainty A survey released in late July by Junior Achievement (JA) indicated that among students from 13-17 years of age, two-thirds were worried about attending school in-person this fall, with nearly 40 percent having said they were "extremely concerned" or "very concerned " About 70 percent said their parents are worried About one quarter of the young people responding said they were concerned "that their dreams won't come true," and a similar number felt they might not be able to have job or career that will pay enough
Amplified Anxiety
Abstract (249 words) Background Zimbabwe suffers from regular outbreaks of typhoid fever (TF), worse since 2017. Most cases were in Harare and a vaccination campaign with Typhoid Conjugate Vaccine (TCV) was conducted in March 2019. The vaccine effectiveness (VE) was assessed against culture-confirmed S. Typhi in children six months to 15 years and in individuals six months to 45 years in Harare. Methods A matched case-control study was conducted in three urban suburbs of Harare targeted by the TCV vaccination campaign. Suspected TF cases were enrolled prospectively in four health facilities and were matched to facility (1:1) and community (1:5) controls. Findings Of 504 suspected cases from July 2019 to March 2020, 148 laboratory-confirmed TF cases and 153 controls confirmed-negative were identified. One hundred and five (47 aged six months to 15 years) cases were age, sex, and residence matched with 105 facility-based controls while 96 cases were matched 1:5 by age, sex, and immediate-neighbour with 229 community controls. The adjusted VE against confirmed TF was 75% (95%CI: 1-94, p=0.049) compared to facility controls, and 84% (95%CI: 57-94, p<0.001) compared to community controls in individuals six months to 15 years. The adjusted VE against confirmed TF was 46% (95%CI: 26-77, p=0.153) compared to facility controls, and 67% (95%CI: 35-83, p=0.002) compared to community controls six months to 45 years old. Interpretation This study confirms that one vaccine dose of TCV is effective to control TF in children between six months and 15 years old in an African setting.
Effectiveness of Typhoid Conjugate Vaccine in Zimbabwe used in response to an outbreak among children and young adults: a matched case control study
The coronavirus disease 2019 (COVID-19) may cause cytokine storm and respiratory illness such as pneumonia and progressive respiratory failure. Tocilizumab (TCZ), a monoclonal antibody that targets the interleukin-6 (IL-6) receptor, was approved as an alternative treatment for severe COVID-19 patients despite limited real-world clinical data in China. In the present study, we will discuss and evaluate the treatment response of TCZ therapy in patients with COVID-19. The clinical characteristics, treatment, laboratory parameters of IL-6, C-reactive protein (CRP), lymphocyte counts before and after TCZ therapy, and clinical outcomes in the 13 patients with COVID-19 were retrospectively evaluated according to the related medical records. The results showed that 13 patients with COVID-19 were totally included in this study. One of them was moderately ill, 8 were seriously ill, and 4 were critically ill. Eleven patients received TCZ administration once, while the other 2 patients received it twice. The median level of IL-6 before TCZ administration was 27.91 (7.42C210.90) pg/mL. Serum IL-6 level tended to further spike firstly and then gradually decreased after TCZ therapy in 10 patients. A persistent and dramatic increase of IL-6 was observed in 2 patients who were finally dead. The CRP levels of 76.92% (10/13) of the patients were above the normal range before the start of TCZ therapy and gradually declined after the TCZ treatment. No. 1 and No. 10 patients finally died accompanied by the corresponding lymphocyte counts persistently dropping. No. 13 patient became exacerbated possibly due to inducing severe bacterial infection after TCZ treatment, while the other 10 patients showed clinical improvement. In summary, the study revealed that TCZ may have a certain therapeutic effect on severe COVID-19 patients with a risk of the cytokine storm. It is necessary to further evaluate the efficacy and safety of TCZ by rigorous randomized controlled trial in the next step.
Tocilizumab, an Exploratory Treatment for Severe COVID-19 Patients
There is increasing evidence of a link between the coronavirus disease 2019 (COVID-19) and venous and arterial thrombotic events Here, we report a 60-year-old male patient with severe COVID-19 who developed extensive arterial thromboses and limb ischemia despite being on therapeutic-dose anticoagulation While the exact mechanism for such events is unknown, our report highlights the importance of maintaining a high degree of suspicion in critically ill patients Further research should focus on the mechanistic pathways along with the optimal anticoagulation and/or antithrombotic strategy
Limb Ischemia due to Extensive Arterial Thrombosis in the Absence of Venous Occlusion as an Unusual Complication of Critical Illness from COVID-19
The field of international public health and the contribution of international organizations to its development is described. The growth and elaboration of the field of international public health law in the last decade and a half is one of the most notable developments in global health policy. In this new era of global health governance, international law has an important, albeit limited, role to play in promoting and coordinating international cooperation and national action to protect and promote global health. Particular attention is paid to the global health impact of international law developed under the auspices of the World Health Organization and the World Trade Organization.
International Law and Public Health Policy
Pulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from previous coronavirus infections, such as the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome, as well as current clinical evidence from the Coronavirus disease 2019 (COVID-19), support that SARS-CoV-2 infection may lead to PF, seriously impacting patient prognosis and quality of life. Therefore, effective prevention and treatment of PF will improve patient prognosis and reduce the overall social and economic burdens. Stem cells, especially mesenchymal stem cells (MSCs) have many great advantages, including migration to damaged lung tissue and secretion of various paracrine factors, thereby regulating the permeability of endothelial and epithelial cells, reducing inflammatory response, promoting tissue repair and inhibiting bacterial growth. Clinical trials of MSCs for the treatment of acute lung injury, PF and severe and critically ill COVID-19 are ongoing. The purpose of this study is to systematically review preclinical studies, explored the effectiveness of MSCs in the treatment of bleomycin (BLM)-induced pulmonary fibrosis and analyze the potential mechanism, combined with clinical trials of current MSCs for idiopathic pulmonary fibrosis (IPF) and COVID-19, so as to provide support for clinical research and transformation of MSCs. Searching PubMed and Embase (? 2021.4) identified a total of 36 preclinical studies of MSCs as treatment of BLM-induced acute lung injury and PF in rodent models. Most of the studies showed the MSCs treatment to reduce BLM-induced lung tissue inflammatory response, inflammatory cell infiltration, inflammatory cytokine expression, extracellular matrix production and collagen deposition, and to improve Ashcroft score. The results of present studies indicate that MSCs may serve as a potential therapeutic modality for the treatment of PF, including viral-induced PF and IPF.
Effectivity of mesenchymal stem cells for bleomycin-induced pulmonary fibrosis: a systematic review and implication for clinical application
The study evaluated the interlinkages and diversification opportunities in the context of emerging bond markets from 2007:1 to 2020:5, using the vector autoregressive (VAR) model and sub\period analyses to compare BRIC (2007:1C2010:11) and BRICS (2010:12C2020:5) regimes. As indicated by the breaking unit\root test, dummies for the global financial crisis and COVID\19 were incorporated in the analyses. VAR results showed that the Indian bond market responds positively to the previous change in the Chinese bond market during the BRIC era while BRICS bond markets are mostly uninfluenced by prior behavior patterns of one another. These suggested that the diversification opportunity has been increased following the admission of South Africa to the league. In addition, variance decomposition and impulse response provide proofs to suggest that BRICS bond markets are more exogenous and independent compared to what is obtained during the BRIC period. Consequently, the authors concluded that the BRICS bloc has provided greater diversification opportunities for emerging markets bondholders in the recent past. ? 2022 by Emerald Publishing Limited.
Interlinkages and diversification opportunities among emerging bond markets: Bric and brics comparison
BACKGROUND The SILK intracranial stent is a Conformit Europenne mark-approved endovascular device. This flow-diversion device is being used in Europe for intracranial aneurysm treatment by aneurysm occlusion. The device construct creates an intracranial bypass conduit that reconstructs the parent vessel while maintaining patency of the perforating arteries and branch arteries. The investigators report the first two patients in which the SILK stent was used for intracranial aneurysms in the United States. CASE DESCRIPTION Two patients, one with a symptomatic giant posterior communicating artery aneurysm and one with a symptomatic fusiform vertebrobasilar junction and basilar artery aneurysm, were treated at two separate institutions with the device. A total of three SILK stents were placed in these patients. In the first patient, a single device was sufficient to cause immediate angiographic stasis within the posterior communicating artery aneurysm. However, reversal of anticoagulation and antiplatelet therapy was required due to a spontaneous bleed from an intercostal artery, and this led to in-stent thrombosis and major stroke. In the second patient, the placement of two devices resulted in immediate stasis of the basilar artery aneurysm. The patient remained on antiplatelet therapy and was discharged without complication. His follow-up angiogram at approximately 2 months showed complete occlusion of the aneurysm with parent vessel reconstruction. In both patients, immediate stasis was identified, and no immediate neurological complications occurred. However, in one patient, a complication occurred that was related to reversal of/cessation of antiplatelet therapy. CONCLUSION In this initial U.S. experience with SILK flow-diversion devices, these devices were deployed easily and immediate flow stasis in the aneurysm was achieved. Further evaluation of this device is needed at multiple centers with adequately trained and experienced operators.
SILK flow-diverting device for intracranial aneurysms.
IMPORTANCE: Visual screening for oral cancer has been found to be useful in a large randomized clinical trial in Kerala, India, showing substantial reduction in mortality. To address the shortage of medical personnel in resource-deficient regions, using the services of community health workers has been proposed as a strategy to fill the gap in human resources in health care. OBJECTIVE: To assess the feasibility of community health workers in screening and early detection of oral cancer using a mobile application capturing system. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study using a household sample was conducted in 10 areas of Gautam Budhnagar district, Uttar Pradesh, India, from January 31, 2020, to March 31, 2021, to assess the feasibility of identification of oral lesions by community health workers using a mobile phone application compared with diagnosis by trained dentists in a screening clinic. Men and women aged 30 years or older as well as tobacco users younger than 30 years were eligible for screening. INTERVENTIONS: Screening by trained community health workers vs dentists. RESULTS: A total of 1200 participants were screened by the community health workers during their home visits; of these, 1018 participants (526 [51.7%] men; mean [SD] age, 35 [16] years) were also referred and screened by the dentists a clinic. There was near-perfect agreement ( = 0.9) between the findings of the community health workers and the dentists in identifying the positive or negative cases with overall sensitivity of 96.69% (95% CI, 94.15%-98.33%) and specificity of identification of 98.69% (95% CI, 97.52%-99.40%). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, trained community health workers were able after initial supervision by qualified dentists to perform oral cancer screening programs. These findings suggest that community health workers can perform this screening in resource-constrained settings.
Feasibility of Training Community Health Workers in the Detection of Oral Cancer
BACKGROUND Cancer and cardiovascular disease (CVD) are independently associated with adverse outcomes in patients with COVID-19. However, outcomes in patients with COVID-19 with both cancer and comorbid CVD are unknown. METHODS This retrospective study included 2,476 patients who tested positive for SARS-CoV-2 at 4 Massachusetts hospitals between March 11 and May 21, 2020. Patients were stratified by a history of either cancer (n=195) or CVD (n=414) and subsequently by the presence of both cancer and CVD (n=82). We compared outcomes between patients with and without cancer and patients with both cancer and CVD compared with patients with either condition alone. The primary endpoint was COVID-19-associated severe disease, defined as a composite of the need for mechanical ventilation, shock, or death. Secondary endpoints included death, shock, need for mechanical ventilation, need for supplemental oxygen, arrhythmia, venous thromboembolism, encephalopathy, abnormal troponin level, and length of stay. RESULTS Multivariable analysis identified cancer as an independent predictor of COVID-19-associated severe disease among all infected patients. Patients with cancer were more likely to develop COVID-19-associated severe disease than were those without cancer (hazard ratio [HR], 2.02; 95% CI, 1.53-2.68; P<.001). Furthermore, patients with both cancer and CVD had a higher likelihood of COVID-19-associated severe disease compared with those with either cancer (HR, 1.86; 95% CI, 1.11-3.10; P=.02) or CVD (HR, 1.79; 95% CI, 1.21-2.66; P=.004) alone. Patients died more frequently if they had both cancer and CVD compared with either cancer (35% vs 17%; P=.004) or CVD (35% vs 21%; P=.009) alone. Arrhythmias and encephalopathy were also more frequent in patients with both cancer and CVD compared with those with cancer alone. CONCLUSIONS Patients with a history of both cancer and CVD are at significantly higher risk of experiencing COVID-19-associated adverse outcomes. Aggressive public health measures are needed to mitigate the risks of COVID-19 infection in this vulnerable patient population.
Outcomes of COVID-19 in Patients With a History of Cancer and Comorbid Cardiovascular Disease.
Almost 13 months have passed since the World Health Organization (WHO) declared the coronavirus disease 19 (COVID-19) pandemic, caused by the SARS-CoV-2, on March 11th, 2020. During this period, we have realized that the most effective weapon we have to prevent SARS-CoV-2 infection, or to make it less aggressive, is vaccines. Currently, according to the WHO document "Draft landscape of COVID-19 candidate vaccines," there are 275 vaccines in development against the virus, although at the moment there are four preparations in distribution in the United States and in Europe. The characteristics of these vaccines are quite different from each other and may even be unfamiliar in the medical field. In particular, among dermatologists, knowledge of vaccines is of fundamental importance, especially in atopic dermatitis. Atopic patients are aware of having a predisposition to develop allergies, and so they are asking dermatologists about the safety of the vaccines currently available against the SARS-CoV-2. This article provides an up-to-date overview of this topic by reviewing current literature and sharing our personal experience.
Vaccines for COVID-19 in patients with atopic dermatitis: three things every dermatologist should know
Cyclodextrins (CDs) and cyclodextrin (CD)-based polymers are well-known complexing agents. One of their distinctive features is to increase the quantity of a drug in a solution or improve its delivery. However, in certain instances, the activity of the solutions is increased not only due to the increase of the drug dose but also due to the drug complexation. Based on numerous studies reviewed, the drug appeared more active in a complex form. This review aims to summarize the performance of CDs and CD-based polymers as activity enhancers. Accordingly, the review is divided into two parts, i.e., the effect of CDs as active drugs and as enhancers in antimicrobials, antivirals, cardiovascular diseases, cancer, neuroprotective agents, and antioxidants.
Cyclodextrin Monomers and Polymers for Drug Activity Enhancement
COVID\19 results in the suspension of life all over the world. Universities suspended their academic activities except for online courses for undergrad and grad students. However, PhD students in both biochemistry and molecular biology fields must hold their experiments at the laboratories. Even under these extreme circumstances, the academic journey of a master's or PhD student should not be stopped; on contrary, they need to use these times to improve their knowledge related to their fields. Therefore, they can turn this COVID\19 crisis into an opportunity for themselves.
Commentary: Challenges for PhD students during COVID\19 pandemic: Turning crisis into an opportunity