bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuralgic amyotrophy and hepatitis E infection: 6 prospective case reports
Authors: Garofoli Romain , Seror Paul , Zauderer Jennifer , Roren Alexandra , Guerini Henri , Rannou François , Drapé Jean-Luc , Nguyen Christelle , Lefèvre-Colau Marie-Martine 
Published: November 2020

IntroductionHepatitis E virus (HEV) represents the main cause of enterically transmitted hepatitis worldwide. It is known that neuralgic amyotrophy (NA) is one of the most frequent neurological manifestations of HEV. However, clinical, electrodiagnostic (EDX) and MRI characteristics, as well as long-term follow-up of HEV-related NA have not been fully described yet.Case reportsWe describe longitudinally clinical, EDX, biological and MRI results of six cases of HEV-associated NA, diagnosed from 2012 to 2017. Patients were between the ages of 33 and 57 years old and had a positive HEV serology. Clinical patterns showed the whole spectrum of NA, varying from extensive multiple mononeuropathy damage to single mononeuropathy. EDX results showed that the patients totalised 26 inflammatory mononeuropathies (1 to 8 per patient). These involved classical nerves such as suprascapular (6/6 cases), long thoracic (5/6 cases) and accessory spinal nerves (2/6 cases) and, some less frequent more distal nerves like anterior interosseous nerve (3/6 cases), as well as some unusual ones such as the lateral antebrachial cutaneous nerve (1/6 case), sensory fibres of median nerve (1/6 case) and phrenic nerves (1/6 case). After 2 to 8 years, all nerves had clinically recovered (muscle examination above 3/5 on MRC scale for all muscles except in one patient).DiscussionHEV should be systematically screened when NA is suspected, whatever the severity, if the onset is less than 4 months (before IgM HEV-antibodies disappear) and appears to be frequently associated with severe clinical and EDX pattern, without increasing the usual recovery time.
A High-Content Screen Identifies Drugs That Restrict Tumor Cell Extravasation across the Endothelial Barrier
Authors: Hilfenhaus Georg , Mompeón Ana , Freshman Jonathan , Prajapati Divya P. , Hernandez Gloria , Freitas Vanessa M. , Ma Feiyang , Langenbacher Adam D. , Mirkov Snezana , Song Dana , Cho Byoung-Kyu , Goo Young Ah , Pellegrini Matteo , Chen Jau-Nian , Damoiseaux Robert , Iruela-Arispe M. Luisa 
Published: November 2020

Abstract

Metastases largely rely on hematogenous dissemination of tumor cells via the vascular system and significantly limit prognosis of patients with solid tumors. To colonize distant sites, circulating tumor cells must destabilize the endothelial barrier and transmigrate across the vessel wall. Here we performed a high-content screen to identify drugs that block tumor cell extravasation by testing 3,520 compounds on a transendothelial invasion coculture assay. Hits were further characterized and validated using a series of in vitro assays, a zebrafish model enabling three-dimensional (3D) visualization of tumor cell extravasation, and mouse models of lung metastasis. The initial screen advanced 38 compounds as potential hits, of which, four compounds enhanced endothelial barrier stability while concurrently suppressing tumor cell motility. Two compounds niclosamide and forskolin significantly reduced tumor cell extravasation in zebrafish, and niclosamide drastically impaired metastasis in mice. Because niclosamide had not previously been linked with effects on barrier function, single-cell RNA sequencing uncovered mechanistic effects of the drug on both tumor and endothelial cells. Importantly, niclosamide affected homotypic and heterotypic signaling critical to intercellular junctions, cell–matrix interactions, and cytoskeletal regulation. Proteomic analysis indicated that niclosamide-treated mice also showed reduced levels of kininogen, the precursor to the permeability mediator bradykinin. Our findings designate niclosamide as an effective drug that restricts tumor cell extravasation through modulation of signaling pathways, chemokines, and tumor–endothelial cell interactions.

Significance:
A high-content screen identified niclosamide as an effective drug that restricts tumor cell extravasation by enhancing endothelial barrier stability through modulation of molecular signaling, chemokines, and tumor–endothelial cell interactions.
Could HPV Testing on Self-collected Samples Be Routinely Used in an Organized Cervical Screening Program? A Modeled Analysis
Authors: Smith Megan A. , Hall Michaela T. , Saville Marion , Brotherton Julia M.L. , Simms Kate T. , Lew Jie-Bin , Bateson Deborah , Skinner S. Rachel , Kelaher Margaret , Canfell Karen 
Published: November 2020

Abstract

Background:
Cervical screening on self-collected samples has mainly been considered for targeted use in underscreened women. Updated evidence supports equivalent sensitivity of PCR-based human papillomavirus (HPV) testing on self-collected and clinician-collected samples.

Methods:
Using a well-established model, we compared the lifetime impact on cancer diagnoses and deaths resulting from cervical screening using self-collected samples only, with and without the existing restriction in Australia to women aged 30+ years and ≥2 years overdue, compared with the mainstream program of 5-yearly HPV screening on clinician-collected samples starting at 25 years of age. We conservatively assumed sensitivity of HPV testing on self-collected relative to clinician-collected samples was 0.98. Outcomes were estimated either in the context of HPV vaccination (“routinely vaccinated cohorts;” uptake as in Australia) or in the absence of HPV vaccination (“unvaccinated cohorts”).

Results:
In unvaccinated cohorts, the health benefits of increased participation from self-collection outweighed the worst case (2%) loss of relative test sensitivity even if only 15% of women, who would not otherwise attend, used it (“additional uptake”). In routinely vaccinated cohorts, population-wide self-collection could be marginally (0.2%–1.0%) less effective at 15% additional uptake but 6.2% to 12.4% more effective at 50% additional uptake. Most (56.6%–65.0%) of the loss in effectiveness in the restricted self-collection pathway in Australia results from the requirement to be 2 or more years overdue.

Conclusions:
Even under pessimistic assumptions, any potential loss in test sensitivity from self-collection is likely outweighed by improved program effectiveness resulting from feasible levels of increased uptake.

Impact:
Consideration could be given to offering self-collection more widely, potentially as an equal choice for women.
See related commentary by Lim, p. 245
Systemic Effects of Radiation Therapy-Induced Abscopal Responses in Patients with Advanced Lung Cancer
Authors: D’Andrea Mark A. , Reddy G. Kesava 
Published: November 2020

<b><i>Background:</i></b> Out-of-field tumor regression effects of radiation therapy (abscopal response) have been sporadically observed in the past, but they have only recently gained significant importance due to the use of innovative high-precision radiation delivery devices for the treatment of various cancers including non-small cell lung cancer (NSCLC). In this study, we provide a detailed overview of the current state of knowledge and clinical experience of radiation therapy-induced abscopal effects in patients with advanced NSCLC. <b><i>Summary:</i></b> Peer-reviewed published clinical evidence on the abscopal effect of radiation therapy was collected using electronic databases such as MEDLINE via PubMed and Google Scholar. The clinical data on the abscopal effect of radiation therapy were reviewed and the outcomes have been summarized. Most studies describing the abscopal effects of radiation therapy in patients with advanced NSCLC have been in the form of either case reports or small cohort studies. Although the exact molecular mechanisms for the abscopal effect are yet to be established, current evidence indicates that tumor cell destruction induced by local radiation therapy releases tumor antigens, which stimulate the immune system of the host to activate the body’s immune effector cells systemically and trigger the regression of distant nonirradiated cancer cells. These off-target antitumor effects of radiation therapy provide an opportunity to explore the use of the radiation therapy in combination with novel immunotherapy agents to maximize treatment outcomes in patients with advanced NSCLC and other cancers. <b><i>Key Message:</i></b> The findings suggest that radiation therapy has the ability to induce abscopal effects with an increased potential to boost these effects when it is used in combination with immunotherapy for the treatment of patients with advanced NSCLC and other cancers. Clinical trials investigating radiation therapy-induced abscopal effects may lead to a dramatic change in its use especially when it is combined with immunotherapy for the treatment of patients with advanced NSCLC.
On the Contemporary Relevance of Dependency Perspective: a Critical Appraisal
Authors: Özekin Muhammed Kürşad 
Published: November 2020

Abstract
Is dependency theory dead as an explanation of underdevelopment today? Today, a broad consensus answers this question in the affirmative. In contrast to this commonly-held contention, this study counter-argues that despite the need of refinement to account for the recent changes that have taken place in global economy, a certain strand of dependency analyses still maintains validity, and offers inspirations for those wanting to address limits and prospects of capitalist development. The study first critically surveys the barrage of criticisms levied against the dependency school, since any revisiting of this archaic line of thought might be quite easily subjected to an outright dismissal beforehand. Then, the study reveals that the conceptualization of dependency as elaborated by historical-structural dependency analyses still maintains validity, and when wisely applied to the new conditions, offers a basilar IPE framework to address the limits, prospects, and divergent patterns of development in today’s Global South.
Accessing the Right to Basic Education in South Africa: Four Years after the Ratification of the Covenant on Economic, Social, and Cultural Rights
Authors: Makapela Sicelo , Tanga Pius 
Published: November 2020

Abstract
This article examines access to the right to basic education enshrined in the South African Constitution. Underpinned by the human rights-based approach, the study employed survey questionnaires and in-depth interviews as methods of data collection. The results of the study revealed that the majority of the survey respondents contend that the post-apartheid state has fulfilled the right to basic education only to a small extent notwithstanding the existence of pre-schools, primary, and secondary schools located within a reasonable walking distance from the communities. Preference for the three classes was not equally distributed in the population, X2 (2, N= 500) = 99.68, p < 0.05. On the contrary, the majority of government participants interviewed rated the post-apartheid state fulfillment of the right to basic education in the Buffalo City Metropolitan Municipality as fair. Overall, all the government participants had a moderate view regarding the fulfillment of the right.
The Coping Mechanisms Employed by Grandparent-Headed Families in Addressing Juvenile Delinquency in Hill Crest, Alice Township, Eastern Cape Province
Authors: Mugedya Samuel , Kang’ethe Simon M , Nomngcoyiya Thanduxolo 
Published: November 2020

Abstract
Literature studies have shown that older persons face an array of challenges, among them parenting a delinquent grandchild. This study adopted both a qualitative approach and paradigm, supported by an explorative and a descriptive case study design. The study sampled eleven participants, and data were collected using in-depth interviews and focus group discussions with grandparents, a community committee member, and probation officers. Measures employed by grandparent households in tandem with the Department of Social Development were unearthed. These included, but were not limited to, corporal punishment, seeking assistance from relatives, seeking assistance from social workers, and creating attachment. This article recommends that the government prioritize the grandparents’ vulnerability to the dangers of parenting difficult children, either by freeing them from such a harmful environment, or putting measures in place to manage children in conflict with the law, with special attention to grandparent-headed households.
View. The Dutch Critical Care Triage Guideline on Covid-19: Not Necessarily Discriminatory
Authors: den Exter André 
Published: November 2020

Abstract
Recently, the Dutch Medical Doctors Association (Federatie Medisch Specialisten en de Koninklijke Nederlandsche Maatschappij tot bevordering der Geneeskunst) drafted the ‘Covid-19 triage guideline ICU admission’ that has age cut-offs that deprioritise or exclude the elderly. Such an age limit for intensive care unit (ICU) admission in case of a national emergency seems discriminatory, and thus, is it inappropriate to use, or not? The question is whether age in itself can be considered as an acceptable selection criterion.
Differences in Opioid Overdose Mortality Rates Among Middle-Aged Adults by Race/Ethnicity and Sex, 1999-2018
Authors: Hoopsick Rachel A. , Homish Gregory G. , Leonard Kenneth E. 
Published: November 2020

Objectives The types of opioids abused in the United States have changed from prescription opioids to heroin to fentanyl. However, the types of opioids abused may differ by demographic factors, especially among middle-aged adults. We examined national trends in opioid overdose mortality rates among middle-aged adults by race/ethnicity and sex. Methods Using 1999-2018 data from the Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research database, we examined overdose mortality rates per 100 000 population in 2018 among adults aged 45-64 that involved natural and semisynthetic opioids, heroin, synthetic opioids (excluding methadone), and methadone. We tested for significant differences in mortality rates by race/ethnicity and sex. We plotted drug-specific trends by race/ethnicity and sex from 1999 to 2018. Results In 2018, non-Hispanic White adults had the highest rates per 100 000 population of natural and semisynthetic overdose mortality (men: 8.7; women: 7.9; P < .001), and non-Hispanic Black adults had the highest rates of heroin (men: 17.7; women: 5.4; P < .001) and synthetic opioid (men: 36.0; women: 11.2; P < .001) overdose mortality. Men had significantly higher overdose mortality rates than women did for deaths involving natural and semisynthetic opioids, heroin, and synthetic opioids, but not methadone. From 1999 to 2018, mortality rates increased sharply for heroin and synthetic opioids, increased modestly for natural and semisynthetic opioids, and decreased for methadone. The greatest increases were among non-Hispanic Black men for heroin overdose (3.3 in 1999 to 17.7 in 2018) and synthetic opioid overdose (0.1 in 1999 to 36.0 in 2018). Conclusions Policy making should consider unique subgroup risks and alternative trajectories of opioid use other than people being prescribed opioids, developing opioid use disorder, subsequently moving to heroin, and then to fentanyl.
A Systematic Review of Basic Science and Animal Studies on the Use of Doxycycline to Reduce the Risk of Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Rupture/Transection
Authors: Kraeutler Matthew J. , Aliberti Gianna M. , Scillia Anthony J. , McCarty Eric C. , Mulcahey Mary K. 
Published: November 2020

Background: Posttraumatic osteoarthritis (PTOA) after injury to the anterior cruciate ligament (ACL) is common. Purpose: To perform a systematic review of basic science and animal studies to determine the effect of doxycycline treatment on the prevention of PTOA after ACL rupture/transection. Study Design: Systematic review. Methods: A systematic review was performed by searching the PubMed, Cochrane Library, and Embase databases to identify basic science and animal studies evaluating the effect of doxycycline treatment on the prevention of PTOA of the knee joint after ACL/cranial cruciate ligament (CCL) injury. The search phrase used was “doxycycline cruciate ligament.” Inclusion criteria were basic science and animal studies evaluating the effect of oral administration of doxycycline in ACL/CCL-deficient animals with or without a control group. Results: Seven studies met inclusion criteria and were included in this systematic review. Five studies were performed in dogs, 1 in rabbits, and 1 in mice. Overall, the effects of doxycycline treatment on the prevention of PTOA after ACL/CCL rupture/transection were mixed. In dogs, no significant effects of doxycycline treatment were found in terms of matrix metalloproteinase (MMP) activity, while a mouse study found significantly lower MMP-13 expression on the tibia in doxycycline-treated animals, suggesting that doxycycline may protect against proteoglycan loss and decrease osteoarthritis progression. Cartilage nitric oxide concentrations were lower in doxycycline-treated dogs compared with untreated dogs, suggesting decreased cartilage degradation among doxycycline-treated dogs, although there were no significant effects on cartilage stromelysin levels with no significant effects in terms of physiological remodeling or catabolism of cartilage. Bone formation or resorption was not found to be affected by doxycycline treatment. One study demonstrated a substantial beneficial effect of doxycycline on gross morphology of the medial femoral condyle. Doxycycline was found to conserve bone strain energy density and appeared to limit subchondral bone loss in 1 study. Conclusion: Based on the limited available animal studies, doxycycline appears to demonstrate some benefits in the prevention of PTOA after ACL/CCL rupture/transection. Additional studies are needed to further characterize the potential benefits, side effects, dosage, and duration of this treatment after ACL injury in human patients.
Real-world single-center experience with direct-acting antivirals for improvement of the liver fibrosis after chronic hepatitis C treatment
Authors: Lee Sun Hee , Shin Hyun Phil , Lee Joung Il 
Published: November 2020

Background Recently, new direct-acting antivirals (DAAs) are known to eradicate chronic hepatitis C (CHC) virus infection and prevent the progression of liver fibrosis. Liver fibrosis may predispose to liver cirrhosis or hepatocellular carcinoma. We investigated the effect of DAAs on liver fibrosis using non-invasive methods, and evaluated the correlations of these methods. Methods We retrospectively analyzed 68 patients with CHC who were treated with DAAs and reached sustained virologic response at 12 weeks post-treatment from January 2016 to October 2018. The degree of liver fibrosis was assessed using serum biomarkers, such as AST-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. Liver stiffness was assessed using two-dimensional shear-wave elastography (2 D-SWE). The pre- and post-treatment serum biomarker levels and SWE findings were evaluated and compared. Results A total of 68 patients with CHC were enrolled. The median age was 58 years (52.3–73 years) and 37 patients (54.4%) were female. After treatment, the median APRI was decreased from 0.701 to 0.328 (P < 0.0001), and the median FIB-4 was decreased from 2.355 to 1.860 (P < 0.0001). The median kPa in 2 D-SWE significantly reduced from 6.85 to 5.66 (P = 0.013). APRI and FIB-4 were significantly correlated pre- and post-treatment; however, the correlation between the serum biomarkers and 2 D-SWE was partially significant. Conclusion The serum fibrosis biomarkers and liver stiffness on 2 D-SWE were shown to be improved after the treatment with DAAs. Further research including larger number of patients is needed to compare the efficacy of each evaluating method.
Non-alcoholic fatty liver disease (NAFLD) and the cardiovascular disease (CVD) risk categories in primary care: is there an association?
Authors: Miptah Hayatul Najaa , Ramli Anis Safura , Mohamad Mariam , Hashim Hilwati , Tharek Zahirah 
Published: November 2020

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is an emerging novel cardiovascular disease (CVD) risk factor. It’s prevalence is increasing globally. However, there is paucity in the evidence showing the association between NAFLD and CVD risk in primary care setting. Therefore, the objectives of this study were to determine the prevalence and factors associated with NAFLD among patients with ≥1 risk factor for NAFLD or CVD attending primary care clinics.

Methodology
A cross sectional study was conducted in two clinics at a university primary care centre. Patients aged ≥18 years with ≥1 risk factor for NAFLD or CVD were recruited. Participants with history of established liver disease or chronic alcohol use were excluded. Socio-demographics, clinical related data, anthropometric measurements and blood investigation results were recorded in a proforma. Diagnosis of NAFLD was made using abdominal ultrasound. The 10-year CVD risk was calculated using the general Framingham Risk Score (FRS). Multiple logistic regression (MLogR) was performed to identify independent factors associated with NAFLD.

Results
A total of 263 participants were recruited. The mean age was 52.3 ± 14.7 years old. Male and female were equally distributed. Majority of the participants were Malays (79.8%). The overall prevalence of NAFLD was 54.4% (95%CI 48,60%). Participants in the high FRS category have higher prevalence of NAFLD (65.5%), followed by those in the moderate category (55.4%) and the low category (46.3%), p = 0.025. From MLogR, independent factors associated with NAFLD were being employed (OR = 2.44, 95%CI 1.26,4.70, p = 0.008), obesity with BMI ≥27.5 (OR = 2.89, 95%CI 1.21,6.91, p = 0.017), elevated fasting glucose ≥5.6 mmol/L (OR = 2.79, 95%CI 1.44,5.43, p = 0.002), ALT ≥34 U/L (OR = 3.70, 95%CI 1.85,7.44, p < 0.001) and high FRS category (OR = 2.82, 95%CI 1.28,6.23, p = 0.010).

Conclusion
NAFLD is highly prevalent among patients with ≥1 risk factor for NAFLD or CVD in these primary care clinics. Patients who were obese, have elevated fasting glucose, elevated ALT and in the high FRS category were more likely to have NAFLD. This study underscores the importance of targeted screening for NAFLD in those with risk factors in primary care. Aggressive intervention must be executed in those with NAFLD in order to reduce CVD complications and risk of progression.