bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasonic Characteristics of Medullary Thyroid Carcinoma
Authors: Lei Rongqiang , Wang Zongle , Qian Linxue 
Published: April 2021

Abstract
The aim of this study was to evaluate the differences in ultrasonic features of patients with medullary thyroid carcinoma (MTC), papillary thyroid carcinoma (PTC), and benign thyroid nodules. This study included 53 cases of MTC, 151 cases of PTC, and 200 cases of benign thyroid nodule which were pathologically confirmed. There were no significant differences in sex and thyroid gland involvement among the MTC, PTC, and benign thyroid nodule groups. The age among the 3 groups was statistically different (P = 0.002). The TNM stage of MTC was significantly higher than that of PTC (P < 0.001). Compared with PTC, the lesion size, shape, margin, echogenicity, internal nodule component, and blood flow were significantly different in MTC (P < 0.001, P < 0.001, P < 0.001, P < 0.001, P = 0.045, P < 0.001). However, there were no differences in the form of calcification and cervical lymph node involvement between the 2 groups (P = 0.671, P = 0.128). Except for the lesion size and shape (P = 0.068, P = 0.444), MTC group have significant differences in the grade of Thyroid Imaging Reporting and Data System, lesion margin, echogenicity, internal nodule component, calcification, cervical lymph node, and blood flow compared with benign thyroid nodule group (P < 0.001, P = 0.014, P = 0.032, P < 0.001, P < 0.001, P < 0.001). Our data indicate that ultrasound have important value in preoperative diagnosis of MTC. The ultrasonic features of MTC include relatively large nodules, aspect ratio less than 1, smooth edge, solid hypoechoic, microcalcification, and rich blood flow. It is necessary to combine multiple ultrasonic features for the differential diagnosis of MTC, PTC, and benign thyroid nodules.
Neoadjuvant Cytoreductive Treatment With BRAF/MEK Inhibition of Prior Unresectable Regionally Advanced Melanoma to Allow Complete Surgical Resection, REDUCTOR
Authors: Blankenstein Stéphanie A. , Rohaan Maartje W. , Klop Willem Martin C. , van der Hiel Bernies , van de Wiel Bart A. , Lahaye Max J. , Adriaansz Sandra , Sikorska Karolina , van Tinteren Harm , Sari Aysegül , Grijpink-Ongering Lindsay G. , van Houdt Winan J. , Wouters Michel W. J. M. , Blank Christian U. , Wilgenhof Sofie , van Thienen Johannes V. , van Akkooi Alexander C. J. , Haanen John B. A. G. 
Published: April 2021

Objective:
To evaluate the potency of short-term neoadjuvant cytoreductive therapy with dabrafenib plus trametinib (BRAF and MEK inhibitor) to allow for radical surgical resection in patients with unresectable locally advanced melanoma.

Summary Background Data:
Approximately 5% of stage III melanoma patients presents with unresectable locally advanced disease, making standard of care with resection followed by adjuvant systemic therapy impossible. Although neoadjuvant targeted therapy has shown promising results in resectable stage III melanoma, its potency to enable surgical resection in patients with primarily unresectable locally advanced stage III melanoma is still unclear.

Methods:
In this prospective, single-arm, phase II trial, patients with unresectable BRAF-mutated locally advanced stage IIIC or oligometastatic stage IV melanoma were included. After 8 weeks of treatment with dabrafenib and trametinib, evaluation by positron emission tomography/computed tomography and physical examination were used to assess sufficient downsizing of the tumor to enable resection. The primary objective was the percentage of patients who achieved a radical (R0) resection.

Results:
Between August 2014 and March 2019, 21 patients (20/21 stage IIIC American Joint Committee on Cancer staging manual 7th edition) were included. Planned inclusion of 25 patients was not reached due to slow accrual and changing treatment landscape. Despite this, the predefined endpoint was successfully met. In 18/21 (86%) patients a resection was performed, of which 17 were R0 resections. At a median follow-up of 50 months (interquartile range 37.7–57.1 months), median recurrence-free survival was 9.9 months (95% confidence interval 7.52-not reached) in patients undergoing surgery.

Conclusions:
This prospective, single-arm, open-label phase II trial, shows neoadjuvant dabrafenib plus trametinib as a potent cytoreductive treatment, allowing radical resection of metastases in 17/21 (81%) patients with prior unresectable locally advanced melanoma.
Neuromodulation techniques for cancer pain management
Authors: Magee David J. , Schutzer-Weissmann John , Pereira Erlick A.C. , Brown Matthew R.D. 
Published: April 2021

Purpose of review
Advanced pain management techniques may be indicated in 5–15% of cancer patients. Despite this, a recent review identified that, over the course of 1 year in England, only 458 patients received a procedure intended to provide analgesia and only 30 patients had intrathecal drug delivery (ITDD) devices implanted. This article describes the emerging evidence for ITDD in cancer pain and provides a narrative review of other neuromodulatory techniques (including spinal cord stimulation, peripheral nerve stimulation and acupuncture), approaches that might be employed to address this area of significant unmet clinical need.

Recent findings
Numerous studies have been published within the last year reporting positive outcomes associated with ITDD in cancer pain management. Neuromodulation represents an important strategy in the management of persistent pain. Whilst the nonmalignant pain evidence-base is rapidly growing, it remains sparse for cancer pain management. The growing cohort of cancer survivors may significantly benefit from neuromodulatory techniques.

Summary
ITDD and other neuromodulatory techniques for cancer pain management appear underutilised in the UK and offer the prospect of better treatment for cancer patients with refractory pain or intolerable side-effects from systemic analgesics.
Clinical practice guidelines for cancer pain: problems and solutions
Authors: Farquhar-Smith Paul 
Published: April 2021

Purpose of review
Clinical practice guidelines (CPGs) should allow practitioners to follow the best evidence-based management for patients. The increasing specialisation of medicine and pain medicine has increased the number of CPGs, but practitioners are still facing contradictory advice that can be difficult to implement and follow.

Recent findings
A recent comprehensive metareview of 25 reviews have highlighted that the same issues of quality, barriers to implementation and difficulties in applicability are as prevalent as they were years ago when assessment tools (e.g. AGREE II) and recommendations for CPG development were introduced. There remains a lack of consistency of recommendations and quality of evidence for CPGs in cancer pain that impedes the ability to provide the ‘best’ management for patients.

Summary
Even the most renowned and apparently high-quality CPGs in many specialities, including cancer pain, still are potentially deficient especially in terms of applicability, implementation, and transparency of conflicts of interest. Despite the increased scrutiny, in part related to the opioid crisis, the situation has not changed. The development of CPGs should engender collaboration with multiple stakeholder groups and focus on transparency and facilitating implementation.
A Machine Learning Perspective on Causes of Suicides and identification of Vulnerable Categories using Multiple Algorithms
Authors: Shreemali Jitendra , Chakrabarti Prasun , Chakrabarti Tulika , Poddar Sandeep , Sipple Daniel , Kateb Babak , Nami Mohammad 
Published: April 2021

AbstractBackgroundSuicides represent a social tragedy with long term impact for the family. Given the growing incidence of suicides, a better understanding of factors causing it and addressing them has emerged as a social imperative.Material and MethodsThis study analyzed suicide data for three decades (1987-2016) and was carried out in two phases. Machine Learning Models run after pre-processing the suicide data included Neural network, Regression, Random Forest, XG Boost Tree, CHAID, Generalized Linear, Random Trees, Tree-AS and Auto Numeric Model.Results and ConclusionAnalysis of findings suggested that the key predictors for suicide are Age, Gender, and Country. In the second phase, data from happiness reports were merged with suicide data to check if Country-specific factors impact the list or order of key predictors. While the key predictors remain the same, Country-specific factors like Generosity, Health and Trust impact the suicide rate in the Country.
Refining “long-COVID” by a prospective multimodal evaluation of patients with long-term symptoms related to SARS-CoV-2 infection
Authors: Scherlinger Marc , Felten Renaud , Gallais Floriane , Nazon Charlotte , Chatelus Emmanuel , Pijnenburg Luc , Mengin Amaury , Gras Adrien , Vidailhet Pierre , Arnould-Michel Rachel , Bibi-Triki Sabrina , Carapito Raphaël , Trouillet-Assant Sophie , Perret Magali , Belot Alexandre , Bahram Seiamak , Arnaud Laurent , Gottenberg Jacques-Eric , Fafi-Kremer Samira , Sibilia Jean 
Published: April 2021

AbstractBackgroundCOVID-19 long-haulers or “long-COVID” represent 10% of COVID-19 patients and remain understudied.MethodsIn this prospective study, we recruited 30 consecutive patients seeking medical help for persistent symptoms (> 30 days) attributed to COVID-19. All reported a viral illness compatible with COVID-19. The patients underwent a multi-modal evaluation including clinical, psychological, virological, specific immunological assays and were followed longitudinally.ResultsThe median age was 40 [interquartile range: 35-54] and 18 (60%) were female. After a median time of 152 [102-164] days after symptom onset, fever, cough and dyspnea were less frequently reported as compared with the initial presentation, but paresthesia and burning pain emerged in 18 (60%) and 13 (43%) patients, respectively. The clinical examination was unremarkable in all patients although the median fatigue and pain visual analogic scales were 7 [5-8] and 5 [2-6], respectively.Extensive biological studies were unremarkable, as were multiplex cytokine and ultra-sensitive interferon-a2 measurements. At this time, nasopharyngeal swab and stool RT-PCR were negative for all tested patients. Using SARS-CoV-2 serology and IFN-γ ELISPOT, we found evidence of a previous SARS-CoV-2 infection in 50% (15/30) of patients, with objective evidence of lack or waning of immune response in two. Finally, psychiatric evaluation showed that 11 (36.7%), 13 (43.3%) and 9 (30%) patients had a positive screening for anxiety, depression and post-traumatic stress disorder, respectively.ConclusionsHalf of patients seeking medical help for long-COVID lack SARS-CoV-2 immunity. The presence of SARS-CoV-2 immunity did not cluster clinically or biologically long haulers, who reported severe fatigue, altered quality of life, and exhibited psychological distress.Key pointsAmong 30 consecutive patients reporting persistent symptoms (median 6 months) self-attributed to COVID-19, pain, fatigue and disability were reported in virtually all patients.More than one third of patients suffer from psychological disorders such as anxiety, depression and/or post-traumatic stress disorder, regardless of SARS-CoV-2 immunity.At the time of evaluation, only 50% of patients had cellular and/or humoral sign of a past SARS-CoV-2, and serology positivity varied depending of the kit used.Exhaustive clinical, biological and immunological evaluations failed to find an alternative diagnosis, or to identify specific cytokine signature including type I interferon.
Long-Term Acceptability of Hygiene, Face Covering, and Social Distancing Interventions to Prevent Exacerbations in people living with Airways Diseases
Authors: Hurst John R , Cumella Andrew , Niklewicz Camila Nagoda , Philip Keir EJ , Singh Victoria , Hopkinson Nicholas S 
Published: April 2021

AbstractIntroductionThere has been a substantial reduction in admissions to hospital with exacerbations of airways diseases during the COVID-19 pandemic, likely because measures introduced to prevent the spread of SARS-CoV-2 also reduced transmission of other respiratory viruses. The acceptability to patients of continuing such interventions beyond the pandemic as a measure to prevent exacerbations is not known.MethodAn online survey of people living with respiratory disease was created by the Asthma UK – British Lung Foundation Partnership. People were asked what infection control measures they expected to continue themselves, and what they thought should be policy for the population more generally in the future, once the COVID-19 pandemic had subsided.Results4442 people completed the survey: 3627 with asthma, 258 with bronchiectasis and 557 with COPD. Regarding personal behaviour, 79.5% would continue increased handwashing, 68.6% social distancing indoors, 46.9% would continue to wear a face covering in indoor public places (45.7% on public transport), and 59.3% would avoid friends and family who were unwell with a respiratory infection. 45.6% wanted healthcare professionals to continue wearing a mask when seeing patients. 60.7% thought that face coverings should continue to be worn by everyone in indoor public spaces during the ‘flu season. Women and older people were, in general, more cautious.ConclusionPeople living with airways diseases are supportive of infection control measures to reduce the risk of exacerbations and such measures should be considered for inclusion in guidelines. Further research to refine understanding of the most effective approaches is needed.
Case fatality rates for COVID-19 are higher than case fatality rates for motor vehicle accidents for individuals over 40 years of age
Authors: Puranik Arjun , Niesen Michiel J.M. , Lindemer Emily , Lenehan Patrick , Cristea-Platon Tudor , Pawlowski Colin , Soundararajan Venky 
Published: April 2021

AbstractThe death toll of the COVID-19 pandemic has been unprecedented, due to both the high number of SARS-CoV-2 infections and the seriousness of the disease resulting from these infections. Here, we present mortality rates and case fatality rates for COVID-19 over the past year compared with other historic leading causes of death in the United States. Among the risk categories considered, COVID-19 is the third leading cause of death for individuals 40 years old and over, with an overall annual mortality rate of 325 deaths per 100K individuals, behind only cancer (385 deaths per 100K individuals) and heart disease (412 deaths per 100K individuals). In addition, for individuals 40 years old and over, the case fatality rate for COVID-19 is greater than the case fatality rate for motor vehicle accidents. In particular, for the age group 40-49, the relative case fatality rate of COVID-19 is 1.5 fold (95% CI: [1.3, 1.7]) that of a motor vehicle accident, demonstrating that SARS-CoV-2 infection may be significantly more dangerous than a car crash for this age group. For older adults, COVID-19 is even more dangerous, and the relative case fatality rate of COVID-19 is 29.4 fold (95% CI: [23.2, 35.7]) that of a motor vehicle accident for individuals over 80 years old. On the other hand, motor vehicle accidents have a 4.5 fold (95% CI: [3.9, 5.1]) greater relative case fatality rate compared to COVID-19 for the age group of 20-29 years. These results highlight the severity of the COVID-19 pandemic especially for adults above 40 years of age and underscore the need for large-scale preventative measures to mitigate risks for these populations. Given that FDA-authorized COVID-19 vaccines have now been validated by multiple studies for their outstanding real-world effectiveness and safety, vaccination of all individuals who are over 40 years of age is one of the most pressing public health priorities of our time.
Post-acute COVID-19 sequelae in cases managed in the community or hospital in the UK: a population based study
Authors: Whittaker Hannah R , Gulea Claudia , Koteci Ardita , Kallis Constantinos , Morgan Ann D , Iwundu Chukwuma , Weeks Mark , Gupta Rikisha , Quint Jennifer K 
Published: April 2021

AbstractObjectiveTo compare post-COVID-19 sequelae between hospitalised and non-hospitalised individualsDesignPopulation-based cohort studySetting1,383 general practices in England contributing to Clinical Practice Research Database AurumParticipants46,687 COVID-19 cases diagnosed between 1st August to 17th October 2020 (45.4% male; mean age 40), either hospitalised within two weeks of diagnosis or non-hospitalised, and followed-up for a maximum of three months.Main outcome measuresEvent rates of new symptoms, diseases, prescriptions and healthcare utilisation in hospitalised and non-hospitalised individuals, with between-group comparison using Cox regression. Outcomes compared at 6 and 12 months prior to index date, equating to first UK wave and pre-pandemic. Non-hospitalised group outcomes stratified by age and sex.Results45,272 of 46,687 people were non-hospitalised; 1,415 hospitalised. Hospitalised patients had higher rates of 13/26 symptoms and 11/19 diseases post-COVID-19 than the community group, received more prescriptions and utilised more healthcare. The largest differences were noted for rates per 100,000 person-weeks [95%CI] of breathlessness: 536 [432 to 663] v. 85 [77 to 93]; joint pain: 295 [221 to 392] v. 168 [158 to 179]; diabetes: 303 [225 to 416] v. 36 [32 to 42], hypertension: 244 [178 to 344] v. 47 [41 to 53]. Although low, rates of chest tightness, tinnitus and lung fibrosis were higher in the community group. 4.2% (1882/45,272) of the community group had a post-acute burden, most frequently reporting anxiety, breathlessness, chest pain and fatigue. In those non-hospitalised, age and sex differences existed in outcome rates. Healthcare utilisation in the community group increased 28.5% post-COVID-19 relative to pre-pandemic.ConclusionsPost-COVID-19 sequelae differ between hospitalised and non-hospitalised individuals, with age and sex-specific differences in those non-hospitalised. Most COVID-19 cases managed in the community do not report ongoing issues to healthcare professionals. Post-COVID-19 follow-up and management strategies need to be tailored to specific groups.
Can a second booster dose be delayed in patients who have had COVID-19?
Authors: Taubel Jorg , Spencer Christopher S , Freier Anne , Camilleri Dorothée , Garitaonandia Ibon , Lorch Ulrike 
Published: April 2021

AbstractVaccination forms a key part of public health strategies to control the spread of SARS-CoV-2 globally. In the UK, two vaccines (BNT162b2-mRNA produced by Pfizer, and ChAdOx-1-S produced by Oxford-AstraZeneca) have been licensed to date, and their administration is prioritised according to individual risk. This study forms part of a longitudinal assessment of participants ‘SARS-CoV-2-specific antibody levels before and after vaccination. Our results confirm that there is little quantitative difference in the antibody titres achieved by the two vaccines. Our results also suggest that individuals who have previously been infected with SARS-CoV-2 achieve markedly higher antibody titres than those who are immunologically naïve. This finding is useful to inform vaccine prioritisation strategies in the future: individuals with no history of SARS-CoV-2 infection should be prioritised for a second vaccine inoculation.
The Balancing Role of Distribution Speed against Varying Efficacy Levels of COVID-19 Vaccines under Variants
Authors: Kim Daniel , Keskinocak Pınar , Pekgün Pelin , Yildirim Inci 
Published: April 2021

ABSTRACTMutations in SARS-CoV-2 raised concerns about diminishing vaccine effectiveness against COVID-19 caused by particular variants. Even with high initial efficacy, if a vaccine’s efficacy drops significantly against variants, or if it cannot be distributed quickly, it is uncertain whether the vaccine can provide better health outcomes than other vaccines. Hence, we evaluated the trade-offs between the speed of distribution vs. efficacy against infection of multiple vaccines when variants emerge by utilizing a Susceptible-Infected-Recovered-Deceased (SIR-D) model and assessing the level of infection attack rate (IAR). Our results show that speed is a key factor to a successful immunization strategy to control the COVID-19 pandemic even when the emerging variants may reduce the efficacy of a vaccine. Due to supply-chain challenges, the accessibility and distribution of the vaccines have been hindered in many regions, especially in low-income countries, while the second or third wave of the pandemic has occurred due to the variants. Understanding the tradeoffs between speed and efficacy and distributing vaccines that are available as quickly as possible are crucial to eradicate the pandemic before new variants spread.
Metabolic Preference Assay for Rapid Diagnosis of Bloodstream Infections
Authors: Rydzak Thomas , Groves Ryan A. , Zhang Ruichuan , Pushpker Rajnigandha , Mapar Maryam , Lewis Ian A. 
Published: April 2021

AbstractBloodstream infections (BSIs) cause >500,000 infections and >80,000 deaths per year in North America. The length of time between the onset of symptoms and administration of appropriate antimicrobials is directly linked to mortality rates. It currently takes 2-5 days to identify BSI pathogens and measure their susceptibility to antimicrobials – a timeline that directly contributes to preventable deaths. To address this, we developed a rapid metabolic preference assay (MPA) that uses the pattern of metabolic fluxes observed in ex-vivo microbial cultures to identify common pathogens and determine their antimicrobial susceptibility profiles. In a head-to-head race with a leading platform (VITEK 2) used in diagnostic laboratories, MPA decreased testing timelines from 40 hours to under 20. If put into practice, this assay could reduce septic shock mortality and reduce the use of broad spectrum antibiotics.One Sentence SummaryMetabolomics enables rapid diagnosis of BSIs.