bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neutral Red Uptake Assay: Comments on the Results of the Istituto Superiore di Sanità in the EC/HO Validation Study
Authors: Stammati Annalaura , Zampaglioni Franco , Zanetti Cristiana
Published: August 2020

The neutral red uptake (NRU) assay was included, among others, in a validation study sponsored by the European Commission/British Home Office (EC/HO) study, for its reliability as an in vitro alternative to the Draize eye irritancy test. The test was performed in parallel by four laboratories (Istituto Superiore di Sanità [ISS], Microbiological Associates, Hatano Research Institute and Kurabo Industries) on 60 selected chemicals. The results obtained by the ISS are reported in this paper. A poor rank correlation was obtained between the in vivo endpoint and the ISS in vitro results for the full set of chemicals and for the subsets, with the exception of surfactants, by an independent statistics group. The same unsatisfactory results were obtained by the ISS group when the rank correlation was calculated for compounds divided into chemical groups. The performance of the NRU assay, as an alternative to the Draize eye irritancy test, is discussed.
Direct Determination of Glutathione S-transferase and Glucose-6-phosphate Dehydrogenase Activities in Cells Cultured in Microtitre Plates as Biomarkers for Oxidative Stress
Authors: García-Alfonso Concepción , Repetto Guillermo , Sanz Pilar , Repetto Manuel , López-Barea Juan
Published: August 2020

The enzymes glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G-6PDH) are implicated in the defence against oxidative stress. GST is mainly involved in the conjugation of electrophilic compounds with glutathione (GSH), although some of its isoenzymes display peroxidase activity. G-6PDH and glutathione reductase regenerate NADPH and GSH, respectively, to restore the reduced intracellular redox status following oxidative stress. Enzymatic assays for GST and G-6PDH were adapted and optimised to permit the direct in vitro determination of the effects of toxicants which induce oxidative stress in cells on microtitre plates, thereby avoiding the need to prepare cell-free extracts. To optimise the conditions of the enzymatic assays, GST activity’ was measured at substrate concentrations of 1–3mM GSH and 1–3mM 1-chloro-2,4-dinitrobenzene, while G-6PDH activity was measured at 7.5–37.5mM glucose-6-phosphate and 55–275mM NADP. Both enzymatic activities were directly proportional to cell number up to a density of 1 x 105 cells/well. The effects on GST and G-6PDH activities of three toxicants which induce oxidative stress — paraquat, iron (II) chloride and iron (III) chloride — were compared in cultured Vero cells to validate the new assays. Specific GST activity increased to 145% and 171% compared to the controls in cells treated with 5mM paraquat and 5mM iron (II) chloride, respectively, but was inhibited after exposure to 25mM iron (III) chloride. Specific G-6PDH activity increased to 136% compared to the control after exposure to 5mM paraquat, but was inhibited in cells exposed to 5mM iron (II) chloride and 25mM iron (III) chloride.
Toxicity and Cell Density Monitoring in Monolayer and Three-dimensional Cultures with the XTT Assay
Authors: Ponsoda Xavier , Gómez-Lechón Maria Jose , Castell Jose V.
Published: August 2020

The application of viability criteria (MTT and XTT tests) to monolayer cultures and immobilised cells in three-dimensional systems was investigated in order to assess cell viability and cell proliferation. The suitability and accuracy of these tests were compared with the conventional criteria (cellular protein and DNA content) used in monolayer cultures for the same purpose. The colorimetric assay based on the metabolic reduction of the tetrazolium salt XTT to a water-soluble formazan proved to be very useful, rapid and sensitive. This automated spectrophotometric enzymatic method, due to its lack of toxicity, also permits repeated nondestructive assays on a single cellular culture for the long-term monitoring of cytotoxicity, cell survival and cell proliferation, and can be performed in 96-well plates with minimal handling. This method could offer a solution for cellular density evaluation in complex cell cultures that do not permit visual examination; it is also the best choice for protein-based, three-dimensional systems such as collagen gels.
Magnetic Resonance Imaging of the Common Marmoset Head
Authors: Lee Vee-Meng , Burdett Newman G. , Carpenter T. Adrian , Herrod Nicholas J. , James Michael F. , Hall Laurance D.
Published: August 2020

This study evaluated the changes in the intrinsic magnetic resonance (MR) relaxation parameter values (T1; T2, proton density, magnetisation transfer and apparent diffusion coefficient) of the marmoset head, imaged before and after death. Knowing the absolute values of the MR parameters makes it possible to choose an imaging protocol for optimal structural differentiation. The changes between the ante-mortem and post-mortem MR parameters provide an insight into the changing biophysical microenvironment of the post-mortem brain, and allow some of the changes that occur in pathological conditions to be predicted. Diffusion-weighted MR imaging (MRI) was used to map quantitative apparent diffusion coefficient values, and to investigate diffusional anisotropy along the fibre tracts in pre-mortem and post-mortem brain tissue. A three-dimensional data set of the entire marmoset brain demonstrates the ability of three-dimensional MRI to differentiate internal brain structures. MRI is a non-invasive technique which, in principle, permits the same animal to be re-imaged serially and has the potential to probe in vivo brain structural and biophysical changes over an extended period of time. Serial imaging, where each animal acts as its own control, reduces the number of animals required to detect a significant change by minimising the effects of inter-subject variance. MRI therefore provides important scientific and ethical benefits.
The Use of Biomarkers as Alternatives to Current Animal Tests on Food Chemicals
Authors: Bottrill Krys
Published: August 2020

Recent developments in biomarkers relating to the interrelationship of diet, disease and health were surveyed. Most emphasis was placed on biomarkers of deleterious effects, since these are of greatest relevance to the subject of this review. The area of greatest activity was found to be that relating to biomarkers of mutagenic, genotoxic and carcinogenic effects. This is also one of the major areas of concern in considerations of the beneficial and deleterious effects of dietary components, and also the area in which regulatory testing requires studies of the longest duration. A degree of progress has also been made in the identification and development of biomarkers relating to certain classes of target organ toxicity. Biomarkers for other types of toxicity, such as immunotoxicity, neurotoxicity, reproductive toxicity and developmental toxicity, are less developed, and further investigation in these areas is required before a comprehensive biomarker strategy can be established. A criticism that recurs constantly in the biomarker literature is the lack of standardisation in the methods used, and the lack of reference standards for the purposes of validation and quality control. It is encouraging to note the growing acknowledgement of the need for validation of biomarkers and biomarker assays. Some validation studies have already been initiated. This review puts forward proposals for criteria to be used in biomarker validation. More discussion on this subject is required. It is concluded that the use of biomarkers can, in some cases, facilitate the implementation of the Three Rs with respect to the testing of food chemicals and studies on the effects of diet on health. The greatest potential is seen to be in the refinement of animal testing, in which biomarkers could serve as early and sensitive endpoints, in order to reduce the duration of the studies and also reduce the number of animals required. Biomarkers could also contribute to establishing a mechanistic basis for in vitro test systems and to facilitating their validation and acceptance. Finally, the increased information that could result from the incorporation of biomarker determinations into population studies could reduce the need for supplementary animal studies. This review makes a number of recommendations concerning the prioritisation of future activities on dietary biomarkers in relation to the Three Rs. It is emphasised, however, that further discussions will be required among toxicologists, epidemiologists and others researching the relationship between diet and health.
In Vitro Models for Studying Renal Stone Formation: A Clear Alternative
Authors: Grases Felix , Prieto Rafael M. , Costa-Bauzá Antonia
Published: August 2020

This paper discusses the limitations of using laboratory animals for direct in vivo observation of the development of renal stones. In fact, the majority of hypotheses related to mechanisms of stone formation have been based on the results of in vitro experiments. The relevance of in vitro experiments that allow the study of urolithiasis depends upon the degree of correspondence between the experimental conditions and those prevailing in the stone-forming kidney in vivo. For this reason, several in vitro experimental systems that attempt to reproduce the conditions found in vivo have been developed in order to study renal stone formation, which have been classified into two main groups: a) models to study papillary stone formation; and b) models to study “sedimentary” stone formation. These models are briefly described in this paper, and the information obtained was compared with that resulting from a study of the fine structure of real human renal calculi, in order to prove the validity of the models. It was concluded that the experimental in vitro models can closely reproduce the renal conditions under which human calculi are developed. This allows important data to be obtained about the aetiology of renal lithiasis, which is of great relevance to the development of effective treatments for this disease. Therefore, experimental in vitro models constitute a clear alternative to the use of laboratory animals.
Home-based balance pilot intervention for adults with visual impairments
Authors: Haibach-Beach Pamela , McNamera Scott , Lieberman Lauren
Published: August 2020

Older adults with visual impairments face many barriers to being physically active in their communities, which include their risk of suffering serious falls due to poor balance. Thus, the purpose of this study was to examine the effectiveness of a home-based intervention upon gait, balance, and well-being with older adults with visual impairments. A total of 17 adults with visual impairments above the age of 55 participated and were placed into either the experimental or the control group. All participants were assessed on well-being, balance, and gait. Experimental group participants attended balance workshops and received exercise equipment and a balance intervention manual. Following eight weeks, both groups were tested, and the experimental group was reassessed five months following the intervention. Four separate 2 × 2 mixed model analyses of variance (ANOVAs) were used to test for significant main effects and interactions related to their baseline and posttest scores for the four tests completed. Both groups improved their gait ( p = .006). Although not significant, the experimental group improved across the tests, and maintained their balance abilities scores 5 months after the intervention was delivered. A home-based exercise program can be an effective means for improving balance and gait in older adults with visual impairments.
Regional oxygen saturation change rate for detection of leg ischemia in minimally invasive cardiac surgery
Authors: Shikata Fumiaki , Nakamura Yoshitsugu , Okuzono Yasuhito , Uchigasaki Yuichi , Yamauchi Naoya
Published: August 2020

Introduction:

The criteria for placement of distal perfusion cannulas vary among reports. This cohort study aimed to establish a reproducible method to monitor critical leg ischemia during minimally invasive cardiac surgery.

Methods:

We included 121 patients who underwent minimally invasive cardiac surgery via right thoracotomy with right femoral arterial cannulation from 2015 to 2018. The change rate of regional oxygen saturation (ΔrSO2) was calculated as follows: rSO2 (baseline) − rSO2 (actual number)/rSO2 (baseline). Patients were divided into Group N (ΔrSO2 < 40%): 100/121 (83%) and Group H (ΔrSO2 > 40%, <10 minutes if >40%): 21/121 (17%). A distal perfusion cannula was placed when ΔrSO2 was >40% over 10 minutes.

Results:

No patients experienced significant leg ischemia. Significantly longer cardiopulmonary bypass and aortic cross-clamp times were observed in Group H than in Group N (cardiopulmonary bypass time, 129 ± 36 minutes (Group N) vs. 151 ± 34 minutes (Group H), p = 0.01). ΔrSO2 correlated positively with plasma creatine phosphokinase elevation (R = 0.40, p < 0.001) on postoperative day 1. Serum lactate on intensive care unit admission showed a significant positive correlation (R = 0.40, p < 0.001) with ΔrSO2.

Conclusion:

ΔrSO2 measurement by near-infrared spectroscopy can facilitate distal leg perfusion monitoring and assist surgeons in preventing critical leg ischemia during minimally invasive cardiac surgery.
A Failure of Political Communication Not a Failure of Bureaucracy: The Danger of Presidential Misinformation During the COVID-19 Pandemic
Authors: Hatcher William
Published: August 2020

President Trump’s communications during the novel coronavirus (COVID-19) pandemic violate principles of public health, such as practicing transparency and deferring to medical experts. Moreover, the president’s communications are dangerous and misleading, and his lack of leadership during the crisis limits the nation’s response to the problem, increases political polarization around public health issues of social distancing, and spreads incorrect information about health-related policies and medical procedures. To correct the dangerous path that the nation is on, the administration needs to adopt a more expert-centered approach to the crisis, and President Trump needs to practice compassion, empathy, and transparency in his communications.
Solitary plasmacytoma of the occipital bone: a case report
Authors: Wang Lei , Ren Nian-Jun , Cai Hao , Cheng Hao-Feng , Zhang Hai-Lin , Peng Xu-Bin , He Zheng-Wen
Published: August 2020

Solitary plasmacytoma (SP) of the skull is an uncommon clinical entity that is characterized by a localized proliferation of neoplastic monoclonal plasma cells. This case report describes a 50-year-old male that presented with a headache and an exophytic soft mass on the occiput. The diagnosis of SP was based on the pathological results and imaging examinations. The patient underwent occipital craniotomy, skull reconstruction and lower trapezius myocutaneous flap (LTMF) transplantation under general anaesthesia. The tumour was capsulized and extended to the subcutaneous and the subdural space through the dura mater with skull defects. The neoplasm of the occipital bone involved large areas of scalp and subcutaneous tissue, which resulted in a large postoperative scalp defect that was repaired using LTMF transplantation. All of the tumour was removed and the transplanted flap grew well. Follow-up at 5 months identified an aggressive mass lesion on the right frontal lobe. The patient received six cycles of the PAD chemotherapy regimen (bortezomib, doxorubicin and dexamethasone) and the lesion was significantly reduced. This case demonstrates that LTMF is an alternative approach for the repair of scalp and subcutaneous soft tissue defects caused by the excision of a large malignant tumour of the occipital region. Chemotherapy is the choice of treatment for neoplastic recurrence.
Differentiation of gastric glomus tumor from small gastric stromal tumor by computed tomography
Authors: Wang Jian , Liu Chang , Ao Weiqun , An Yongyu , Zhang Wenming , Niu Zhongfeng , Jia Yuzhu
Published: August 2020

Objective

This study was performed to investigate the value of computed tomography (CT) in the differentiation of gastric glomus tumors (GGTs) and small gastric stromal tumors (GSTs).

Methods

Fifty-nine patients with pathologically confirmed GGTs (n = 11) and GSTs (n = 48) from 2006 to 2019 were retrospectively evaluated. All patients’ preoperative CT imaging features were analyzed.

Results

The following features were significantly different between GGTs and small GSTs: location in the antrum, endophytic growth, heterogeneous enhancement in the arterial phase, CT value in the arterial phase of ≥60.7 Hounsfield units (HU), CT value in the portal phase of ≥87.6 HU, degree of enhancement in the arterial phase of ≥29.9 HU, and degree of enhancement in the portal phase of ≥49.0 HU. A model including four randomly selected features among these seven criteria was built to differentiate GGTs from small GSTs with a sensitivity and specificity of 90.9% (10/11) and 100% (48/48), respectively.

Conclusion

We identified seven features that are useful for differentiating GGTs from small GSTs. A combination of four of these seven criteria may increase the diagnostic accuracy.
A patient with glycogen storage disease type 0 and a novel sequence variant in GYS2: a case report and literature review
Authors: Arko Janez Jan , Debeljak Marusa , Tansek Mojca Zerjav , Battelino Tadej , Groselj Urh
Published: August 2020

Glycogen storage disease type 0 (GSD0) is an autosomal recessive disorder caused by a sequence variant in the GYS2 gene, leading to decreased or absent activity of hepatic glycogen synthase. With a frequency of less than 1 in 1,000,000 individuals, GSD0 represents only around 1% of all glycogen storage disease cases but it might be underrecognized. A 13-month-old girl of reportedly unrelated parents presented with a decreased level of consciousness, twitching in her left cheek, and munching. During a fasting test, hyperketotic hypoglycemia was found. A novel homozygous GYS2 gene sequence variant p.Thr445Arg was later confirmed by next-generation gene sequencing. After establishing a cornstarch- and protein-rich diet, the hypoglycemic episodes subsided and the patient’s neurocognitive development was normal. To date, only 39 patients with 24 disease-causing gene variants have been identified in GSD0, and we review their characteristics. Because of the heterogeneous phenotypes, GSD0 is an underdiagnosed disorder. In patients with hyperketotic hypoglycemia and postprandial hyperglycemia, GYS2 gene analysis should be performed.
Proposal of a Functional Impairment Symptom Scale for Concussion
Authors: McCarthy Matthew T. , Janse Sarah , Pizzimenti Natalie M. , Savino Anthony K. , Crosser Brian , Rose Sean C.
Published: August 2020

Clinicians currently administer patient-reported symptom scales to quantify and track concussion symptoms. These scales are based on subjective ratings without reference to the degree of functional impairment caused by the symptoms. Our objective was to develop a concussion symptom scale based on functional impairment and compare it to a widely used concussion symptom checklist. We conducted a retrospective chart review evaluating 133 patients age 9-22 with an acute concussion who completed 2 symptom checklists at their initial visit—the Sport Concussion Assessment Tool (SCAT-3) symptom evaluation (22 symptoms, 0-6 scale) and the proposed Functional Impairment Scale (22 symptoms, 0-3 scale related to degree of functional impairment). Mean total symptom score was 27.2±22.9 for Sport Concussion Assessment Tool–3 and 14.7±11.9 for the Functional Impairment Scale. Pearson correlation between the scales was 0.98 ( P < .001). Mean time from concussion to first visit was 6.9±6.2 days, and median clearance time after injury was 19 (95% CI 16-21) days. After adjusting for patient and injury characteristics, an increased score on each scale was associated with longer time to clearance (5-point increase in Sport Concussion Assessment Tool–3 hazard ratio 0.885, 95% CI 0.835-0.938, P < .001; 2.5-point increase in Functional Impairment Scale hazard ratio 0.851, 95% CI 0.802-0.902, P < .001). We propose a concussion symptom scale based on functional impairment that correlates strongly with the Sport Concussion Assessment Tool–3 scale, demonstrates a similar association with time to clearance, and may provide a more intuitive approach to monitoring how symptoms are affecting patients recovering from concussion. Future research should aim to validate this scale through a prospective longitudinal study.
“I Am Not a Hijra”: Class, Respectability, and the Emergence of the “New” Transgender Woman in India
Authors: Mount Liz
Published: August 2020

This article examines the mutual imbrication of gender and class that shapes how some transgender women seek incorporation into social hierarchies in postcolonial India. Existing literature demonstrates an association between transgender and middle-class-status in the global South. Through an 18-month ethnographic study in Bangalore from 2009 through 2016 with transgender women, NGO (nongovernmental organization) workers and activists, as well as textual analyses of media representations, I draw on “new woman” archetypes to argue that the discourses of empowerment and respectability that impacted middle-class cisgender women in late colonial, postcolonial and liberalized India also impact how trans women narrate their struggles and newfound opportunities. Trans woman identities are often juxtaposed to the identities of hijras, a recognized (yet socially marginal) group of working-class male-assigned gender-nonconforming people. Instead of challenging stereotypes of gender nonconformity most evident in the marginalization of hijras, some transgender women are at pains to highlight their difference from hijras. These trans women are from working-class backgrounds. It is partly their similarities in class location that propel trans women’s efforts to distinguish themselves from hijras. They employ the figure of the disreputable hijra to contain negative stereotypes associated with gender nonconformity, thus positioning their identities in proximity with middle-class respectable womanhood.
Cheaters, Liars, or Both? A New Classification of Dishonesty Profiles
Authors: Pascual-Ezama David , Prelec Drazen , Muñoz Adrián , Gil-Gómez de Liaño Beatriz
Published: August 2020

Experimental studies of dishonesty usually rely on population-level analyses, which compare the distribution of claimed rewards in an unsupervised, self-administered lottery (e.g., tossing a coin) with the expected lottery statistics (e.g., 50/50 chance of winning). Here, we provide a paradigm that measures dishonesty at the individual level and identifies new dishonesty profiles with specific theoretical interpretations. We found that among dishonest participants, (a) some did not bother implementing the lottery at all, (b) some implemented but lied about the lottery outcome, and (c) some violated instructions by repeating the lottery multiple times until obtaining an outcome they felt was acceptable. These results held both in the lab and with online participants. In Experiment 1 ( N = 178), the lottery was a coin toss, which permitted only a binary honest/dishonest response; Experiment 2 ( N = 172) employed a six-sided-die roll, which permitted gradations in dishonesty. We replicated some previous results and also provide a new, richer classification of dishonest behavior.
Functional interval observers for nonlinear fractional-order systems with time-varying delays and disturbances
Authors: Yen Dao Thi Hai , Huong Dinh Cong
Published: August 2020

This article considers the estimation problem for a class of uncertain fractional-order systems with time-varying delays and disturbances, in which the time-varying delays are present in the state, while the disturbances are present in the output. A new design method of functional interval observers is proposed. In contrast to interval observers currently available in the literature, which dealt with integer-order systems or fractional-order systems without time delays, the functional interval observers with fractional-order [Formula: see text] in this article can deal with fractional-order time-delay systems and integer-order time-delay systems (when [Formula: see text]). Existence conditions of functional interval observers for non-linear fractional-order systems with time-varying delays are established and they are formulated in terms of linear programmings. Two algorithms are provided for determining the functional interval observers. Illustrative examples of the functional interval observer application are presented.
Near infrared spectroscopy for rapid determination of solids content of amino resins
Authors: Gonçalves M , Paiva NT , Ferra JM , Martins J , Magalhães F , Carvalho L
Published: August 2020

Near infrared (NIR) spectroscopy is a fast and reliable technique for assessing properties of amino resins. One important property that defines the cost and performance of these resins is the solids content (SC). This work studied the prediction of SC of amino resins by combining NIR spectroscopy with partial least squares (PLS) regression. A total of 990 industrial NIR spectra of amino resins were obtained and split randomly by a ratio of 2/3 for calibration and 1/3 for validation. The best model achieved a root mean-square error of prediction (RMSEP) of 0.32% (m/m) and a coefficient of determination of prediction ([Formula: see text]) of 81%. standard normal variate (SNV) was found to be the NIR pre-processing that provided the best results for model construction. Addition of water to two amino resins showed that the NIR model does not respond to the water addition, despite water making great contribution to the SC value. An inference that can be obtained from this is that the NIR model of amino resins uses NIR properties of amino resins that relate to the SC and from there predict the most probable SC, instead of looking at all the components that affect the SC of amino resins.
Global Epidemiology of First 90 Days into COVID-19 Pandemic: Disease Incidence, Prevalence, Case Fatality Rate and Their Association with Population Density, Urbanisation and Elderly Population
Authors: Gupta Shivam , Kumar Patel Kamalesh , Sivaraman Shobana , Mangal Abha
Published: August 2020

As the COVID-19 pandemic marches exponentially, epidemiological data is of high importance to analyse the current situation and guide intervention strategies. This study analyses the epidemiological data of COVID-19 from 17 countries, representing 85 per cent of the total cases within first 90 days of lockdown in Wuhan, China. It follows a population-level observational study design and includes countries with 20,000 cases (or higher) as of 21 April 2020. We sourced the data for these 17 countries from worldometers. info, a digital platform being used by several media and reputed academic institutions worldwide. We calculated the prevalence, incidence, case fatality rate and trends in the epidemiology of COVID-19, and its correlation with population density, urbanisation and elderly population. The analysis represents 85 per cent ( N = 2,183,661) of all cases within the first 90 days of the pandemic. Across the analysed period, the burden of the pandemic primarily focused on high- and middle-income countries of Asia, Europe and North America. While the total number of cases and deaths are highest in USA, the prevalence, incidence and case fatality rates are higher in the European countries. The prevalence and incidence vary widely among countries included in the analysis, and the number of cases per million and the case fatality rate are correlated with the proportion of the elderly population and to a lesser extent with the proportion of the urban population.
Health System Response to COVID-19 and Future Pandemics
Authors: Narain Jai Prakash , Dawa Natasha , Bhatia Rajesh
Published: August 2020

The COVID-19 pandemic is a global health and economic crisis of a scale never witnessed before. Beginning in China, it has within a few months devastated many countries around the globe, requiring an unprecedented mobilisation of health systems. While the disease caused by this novel virus is generally mild and self-limiting, the risk of severe disease is disproportionately high among elderly and those with underlying medical conditions. In the absence of a vaccine or treatment, the public health strategies include: (a) preventing transmission through early detection and isolation, tracing contacts and quarantining them and implementation of measures such as social distancing and hand hygiene and (b) reducing mortality by augmenting clinical management and shielding the most vulnerable populations in the society. The pandemic is yet another reminder that we need to invest in public health, ramp up national capacities to detect a disease early and respond rapidly to emerging infections, strengthen and respect our national institutions and rely on evidence base for policymaking. It is high time that we paid heed to these lessons and strengthened without any further delay our health system capacity, as epidemics and pandemics of this nature will continue to challenge public health well into the future.
Coronavirus: A Framework to Decide Between National and Local Lockdown
Authors: Ladha Rani S.
Published: August 2020

This article offers a framework to help decide between national and local lockdown in response to the coronavirus pandemic. The approach is to find the optimum level of lockdown that balances the benefits (avoided ailments) of lockdown against its cost (arising from reduced economic output). With the path of the pathogen being unknown, India may have to consider a rolling lockdown: that is, open the economy which would probably risk a flare up of the virus due to increased human interaction, and before the virus hits a threshold shut down the economy to control the virus, and then open it again. This balancing act between opening and closing the economy is probably necessary till a remedy is found to deal with the virus. Finally, timely and reliable testing is the most preferred way because it can do two things at once: it can lower the transmission of ailments and make local lockdown far more viable by identifying critical areas and hotspots. Extensive testing would generate granular data of affected areas, which can limit application of rolling lockdown to the affected districts only. With the availability of granular data, the choice between national and local lockdown would become choice between district (say) and tehsil lockdown. The analysis below is framed in terms of national and local lockdown although it applies with respect to district and tehsil lockdown.
Genetics of Severe Acute Respiratory Syndrome Coronavirus-2 and Diagnosis of Coronavirus Disease-2019: An Overview
Authors: Sewda Anshuman , Dutt Gupta Shiv
Published: August 2020

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a positive sense, single-stranded RNA virus, responsible for the ‘coronavirus disease-2019’ (COVID-19) pandemic. SARS-CoV-2 belongs to the sarbecovirus (lineage-B) sub-genus within the betacoronavirus genus of the coronaviridae family. SARS-CoV-2 shares similarities with SARS-CoV, which was responsible for the 2003 SARS epidemic. SARS-CoV-2 binds with great affinity to the Angiotensin Converting Enzyme-2 receptors on human cells, and its ~30 kilobases long RNA genome hijacks the host machinery and compromises the host immune system with the help of accessory proteins, such as non-structural proteins, resulting in a widespread infection. The spike protein is responsible for the contagious nature of SARS-CoV-2 and, together with the nucleocapsid protein, elicits the host inflammatory response. Several real-time reverse transcriptase polymerase chain reaction (rRT-PCR) tests have been developed to confirm SARS-CoV-2 infection in suspected cases of COVID-19. Furthermore, rapid tests based on SARS-CoV-2-specific antigens and antibodies have been developed to conduct epidemiological surveillance of the hotspot regions that are worst affected by the COVID-19 pandemic. Until effective measures to prevent the occurrence or spread of COVID-19 pandemic are developed, containment measures are being taken, such as isolation of confirmed COVID-19 patients, quarantine of individuals who may have come in contact with a SARS-CoV-2 infected individual, community-wide social distancing, state/nation-wide lockdown, etc. Several vaccines and drugs are being tested that could target the viral structural proteins, non-structural proteins or associated SARS-CoV-2 sub-genomic RNA regions.
Tumor Biology is King: Secondary Tumors of the Thyroid From 2 Medical Centers in China
Authors: Wu Yu , Huang Kai , Zheng Xiangqian , Gao Ming , Liu Hui
Published: August 2020

Background:

We studied the clinical characteristics, diagnosis, treatment, and prognosis of secondary tumors of the thyroid (STTs) and analyzed this rare phenomenon based on our clinical experience.

Methods:

We reviewed 16 000 malignant thyroid tumors diagnosed at 2 medical centers in China from 1978 to 2018, including 55 patients with STTs.

Results:

The most frequent primary tumor sites included lung (21.8%), gastrointestinal (18.2%), breast (14.5%), and kidney (12.7%). The median age at STT diagnosis was 56 years. The time from diagnosis of primary tumor to metastases to the thyroid ranged from 0 to 108 months, with the longest interval being for renal cell carcinoma (RCC; mean: 49 months). There were 22 cases of single metastatic foci and 33 cases of multiple metastatic foci. At the time of STT diagnosis, 42 patients had multiple organ metastases and 13 patients had only thyroid metastases. Thyroid function was examined in 50 patients, including 23 with Hashimoto’s thyroiditis. Metastases were diagnosed histologically and confirmed by negative immunohistochemistry for thyroid markers. Twenty-one patients were treated with resection, including total thyroidectomy in 14 and unilateral lobectomy in 7. Thirty-four patients were treated without resection, but 2 were treated with tracheotomy. The median survival time of all patients with metastasis was 10 months (range: 1-96 months). Patients with primary RCC had the best prognosis (median survival time: 52 months), followed by patients with breast cancer (33 months). Patients who underwent thyroid surgery had a better prognosis than patients without thyroid surgery. Patients with single metastatic foci or single organ metastases had a better prognosis than patients with multiple metastatic foci or multiple organ metastases.

Conclusions:

Metastasis to the thyroid is a rare clinical phenomenon, and sometimes a diagnosis of STT is difficult; so, we need to pay more attention to it. While prognosis appears to be related to surgery or some characteristics of metastatic spread, these data suggest it is more complex. Tumor biology is king; in fact, prognosis was mainly related to the biological behavior of the primary tumor. We cannot only opt for surgery; thus, case selection is important, and the treatment strategy for STT patients should be determined individually according to their specific biological behaviors.
Better one or two? A systematic review of portable automated refractors
Authors: Samanta Anindya , Shetty Akaanksh , Nelson Patricia C
Published: August 2020

Introduction

More than 400 million people suffer from visual impairment globally, with more than half due to uncorrected refractive error. Autorefraction (AR) is the most common examination performed prior to prescribing glasses. As technology advances, so has the accuracy and number of portable autorefractors available. Portable technology has become acutely important with the coronavirus disease 2019 pandemic and the conversion of in-person clinical evaluations to remote telemedicine encounters. Patients and providers want to do as much as possible remotely. The aim of this study was to conduct a systematic literature review of the accuracy and effectiveness of available portable automated refractors compared to the current standard of care, subjective refraction (SR).

Methods

A literature search of PubMED, Embase and ClinicalTrials.gov 97 unique publications in English on portable autorefractors. Twelve studies comparing a portable AR device to at least one form of SR were systematically included in this review.

Results

There were four portable autorefractors (Netra, Quicksee, Retinomax and SVOne) studied against SR. There was high patient acceptance of glasses prescriptions by the Quicksee alone, with 87% subjects seeing the same or better than SR. Quicksee was more accurate than Netra and Retinomax. SVOne was preferred over Netra and outperformed Retinomax in multiple measures, despite Retinomax being the fastest test.

Discussion

There are numerous portable autorefractors available, but few were compared against SR. Quicksee and SVOne are the most accurate and patient-preferred devices. Quicksee was the most accurate, and it performed clinically the same as SR in some reports.
Public opinion and the politics of collateral consequence policies
Authors: Johnston Travis , Wozniak Kevin H
Published: August 2020

We analyze data from a national sample of the U.S. population to assess public support for policies that deny former offenders’ access to job training programs, food stamps, and public housing. We find that Americans generally oppose benefit restrictions, though support for these policies is higher among Republicans and people with higher levels of racial resentment. We also find that a legislator’s criminal justice reform positions generally do not significantly affect voters’ evaluation of him or her, and even voters with more punitive attitudes toward collateral consequence policies support legislators who advance particular kinds of reform proposals. These findings provide little evidence that any group of Americans would be mobilized to vote against a legislator who works to reform collateral consequence policies. We discuss the implications of these findings for American and comparative studies of the politics of punishment.
Evaluating academic and media nongovernmental organization partnerships for participatory data gathering
Authors: Heywood Emma , Ivey Beatrice , Meuter Sacha
Published: August 2020

This article discusses participatory methods for data gathering in the context of a partnership between a Swiss-based media development organization, Fondation Hirondelle, and a research team at the University of Sheffield. In 2018–2019, the partnership conducted fieldwork which focused on the impact of radio on women listeners in Niger. The project used participatory methods of data gathering in the form of workshops and focus group discussions (FGDs). The article examines the advantages and limitations of combining the practical experience of international development organizations and the in-depth research capabilities of academia. To triangulate this collaboration and to navigate the limitations of FGDs, the use of workshops is discussed as an important method for providing feedback among the radio practitioners and experts in Niger. The article examines the usefulness of combining these methods and reshaping their application to promote participatory research with radio audiences and practitioners.
Tilting at Windmills: Why Attacks on Repression Are Misguided
Authors: Brewin Chris R.
Published: August 2020

In the November 2019 issue of Perspectives, Otgaar et al. argued that the “memory wars” persist and that “the controversial issue of repressed memories is alive and well and may even be on the rise” (p. 1072). Their thesis overlooked the well-established consensus that recovered memories of trauma may be genuine, false, or a mixture of the two and instead focused on a disputed mechanism: unconscious repression. A formal cocitation analysis identified the major publications mentioning repressed memories, but none endorsed a theory of unconscious repression. Studies of beliefs about repressed memories by the general public and other groups do not support Otgaar et al.’s thesis either because these studies did not adequately assess the key ideas defining the theory of repression. Clinical evidence is consistent with recovered memories occurring in many different forms of therapy, including ones that do not use suggestive techniques or rely on the concept of repression. Thus, Otgaar et al. have proposed the existence of a problem for which little objective evidence can be found. Continuing theoretical uncertainties about the mechanisms responsible for forgetting are less important than the general recognition since the 1990s that suggestive therapy and attempts to exhume memories are hazardous and generally inappropriate.
Randomized phase II study of valproic acid in combination with bevacizumab and oxaliplatin/fluoropyrimidine regimens in patients with RAS-mutated metastatic colorectal cancer: the REVOLUTION study protocol
Authors: Avallone Antonio , Piccirillo Maria Carmela , Di Gennaro Elena , Romano Carmela , Calabrese Filomena , Roca Maria Serena , Tatangelo Fabiana , Granata Vincenza , Cassata Antonio , Cavalcanti Ernesta , Maurea Nicola , Maiolino Piera , Silvestro Lucrezia , De Stefano Alfonso , Giuliani Francesco , Rosati Gerardo , Tamburini Emiliano , Aprea Pasquale , Vicario Valeria , Nappi Anna , Vitagliano Carlo , Casaretti Rossana , Leone Alessandra , Petrillo Antonella , Botti Gerardo , Delrio Paolo , Izzo Francesco , Perrone Francesco , Budillon Alfredo
Published: August 2020

Background:

Despite effective treatments, metastatic colorectal cancer (mCRC) prognosis is still poor, mostly in RAS-mutated tumors, thus suggesting the need for novel combinatorial therapies. Epigenetic alterations play an important role in initiation and progression of cancers, including CRC. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with chemotherapy in the treatment of solid tumors. Owing to its HDACi activity and its safe use for epileptic disorders, valproic acid (VPA) is a good candidate for anticancer therapy that we have largely explored preclinically translating our findings in currently ongoing clinical studies. We have shown in CRC models that HDACi, including VPA, induces synergistic antitumor effects in combination with fluoropyrimidines. Furthermore, unpublished results from our group demonstrated that VPA induces differentiation and sensitization of CRC stem cells to oxaliplatin. Moreover, preclinical and clinical data suggest that HDACi may prevent/reverse anti-angiogenic resistance.

Methods/Design:

A randomized, open-label, two-arm, multicenter phase-II study will be performed to explore whether the addition of VPA to first line bevacizumab/oxaliplatin/fluoropyrimidine regimens (mFOLFOX-6/mOXXEL) might improve progression-free survival (PFS) in RAS-mutated mCRC patients. A sample size of 200 patients was calculated under the hypothesis that the addition of VPA to chemotherapy/bevacizumab can improve PFS from 9 to 12 months, with one-sided alpha of 0.20 and a power of 0.80. Secondary endpoints are overall survival, objective response rate, metastases resection rate, toxicity, and quality of life. Moreover, the study will explore several prognostic and predictive biomarkers on blood samples, primary tumors, and on resected metastases.

Discussion:

The “Revolution” study aims to improve the treatment efficacy of RAS-mutated mCRC through an attractive strategy evaluating the combination of VPA with standard cancer treatment. Correlative studies could identify novel biomarkers and could add new insight in the mechanism of interaction between VPA, fluoropyrimidine, oxaliplatin, and bevacizumab.

Trial Registration:

EudraCT: 2018-001414-15; ClinicalTrials.gov identifier: NCT04310176
Preparation and α-Glucosidase Inhibitory Activity of Gallic Acid-Dextran Conjugate
Authors: Ma Yuxiang , Liu Benguo
Published: August 2020

Phenolic acid-polysaccharide conjugates, produced in plant food and medicine processing, are thought to account for the α-glucosidase inhibitory activity of the final products. However, this speculation lacks experimental support because of the complexity of the plant system and the polysaccharide structure. In this study, with dextran (average molecular weight, 1000) as the skeleton, a gallic acid-dextran conjugate was synthesized and confirmed by ultraviolet, infrared, and nuclear magnetic resonance spectroscopic analysis for the first time. Furthermore, this gallic acid-dextran conjugate showed inhibition of α-glucosidase due to galloyl groups in a mixed competitive and noncompetitive inhibition mode, whose performance was superior to that of acarbose.
ACL Injuries Aren’t Just for Girls: The Role of Age in Predicting Pediatric ACL Injury
Authors: Bloom David A. , Wolfert Adam J. , Michalowitz Andrew , Jazrawi Laith M. , Carter Cordelia W.
Published: August 2020

Background:

Female athletes have a higher rate of anterior cruciate ligament (ACL) injuries than male athletes; however, the role of age in mediating this injury risk has not been explored. The purpose of this study was to characterize the relationship between age and sex in predicting ACL injury in the pediatric population.

Hypothesis:

Prepubescent boys are more likely to sustain an ACL injury than prepubescent girls.

Study Design:

Descriptive epidemiological study.

Level of Evidence:

Level 4.

Methods:

Data were collected from the Statewide Planning and Research Cooperative System database for the state of New York from 1996 to 2016. The database was queried for patients aged ≤19 years who had been diagnosed with an ACL tear using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 844.2 or the ICD-10 (10th Revision) codes S83.512A/S83.511A/S83.519A. Patient age and sex at time of ACL injury diagnosis were recorded. Chi-square analysis was used to compare the frequency of ACL injury between groups, with statistical significance set at P < 0.05.

Results:

A total of 20,128 patients aged ≤19 years were diagnosed with an ACL tear (10,830 males, 9298 females; male:female, 1.16:1). In all, 129 patients aged <12 years sustained an ACL tear (85 boys, 44 girls; male:female, 1.93:1), and 19,999 of those patients were aged 12 to 19 years (10,745 males, 9254 females; male:female, 1.16:1). Chi-square analysis demonstrated a significant relationship between sex and age group ( P < 0.006). Additional analysis revealed that female athletes were most at risk for ACL injury from ages 12 to 16 years, with 4025 male and 5095 female athletes sustaining ACL injuries in this group (male:female, 1:1.27; P < 0.0001).

Conclusion:

Prepubescent boys (aged <12 years) are more likely to sustain an ACL injury than same-aged female peers.

Clinical Relevance:

This study demonstrates that the risk of ACL injury varies with age and sex throughout childhood and adolescence, further guiding treatment and prevention for these pediatric athletes.