bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simple dose-escalation regimen for hydroxychloroquine-induced hypersensitivity reaction in patients with systemic lupus erythematosus enabled treatment resumption
Authors: Takamasu E , Yokogawa N , Shimada K , Sugii S 
Published: October 2019

Objective This study aimed to investigate the risk factors of hydroxychloroquine (HCQ)-induced hypersensitivity in patients with systemic lupus erythematosus (SLE) and to propose a simple dose-escalation regimen in cases of mild HCQ-induced hypersensitivity. Methods We identified patients with SLE who started HCQ between 2009 and 2018 and cases of HCQ-induced hypersensitivity by reviewing the electronic medical charts. A simple dose-escalation regimen, starting at 40 mg/day with weekly increments of 40 mg/day to 200 mg/day, was used in patients with HCQ-induced hypersensitivity who did not require hospitalization or systemic steroid therapy. We then compared the clinical parameters of patients with and without HCQ-induced hypersensitivity and evaluated the success of our dose-escalation regimen. Results We enrolled 302 patients with SLE and identified 25 cases of HCQ-induced eruption (8.3%). The mean Naranjo score of these patients was 5.1 ± 1.4 (min 3, max 8), and all 25 patients received a ‘possible’ (9) or ‘probable’ (16) score. A mild, generalized, maculopapular rash occurred in 24 patients, and urticaria occurred in one patient at 24 days (interquartile range 15–40 days) after the start of treatment. The proportion of cyclophosphamide use, glucocorticoid consisting of prednisolone 20 mg/day or more, and initiation of SMX-TMP within 28 days were higher in patients with skin eruptions. On multivariate analysis, only cyclophosphamide use was identified as a risk factor of HCQ-induced hypersensitivity (odds ratio = 12.3 (95% confidential interval 1.4–14.3)). Thirteen of the 14 patients on the dose-escalation regimen (92.9%) tolerated continued HCQ treatment. One patient re-experienced eruptions on day 10 day after starting HCQ. Conclusions Mild late reactions are common in HCQ-induced hypersensitivity. A simpler dose-escalation regimen enables safe and easier reintroduction of HCQ but should not be applied to patients with immediate reactions or moderate late reactions.
Acceptability of risk-stratified breast screening: Effect of the order of presenting risk and benefit information
Authors: Ghanouni Alex , Waller Jo , Stoffel Sandro T , Vlaev Ivo , von Wagner Christian 
Published: October 2019

Objective To test whether reduced-frequency risk-stratified breast screening would be perceived more favourably by transposing the order of information on benefits and risks. Methods After reading vignettes describing non-stratified three-yearly screening and a risk-stratified alternative with five-yearly invitations for women at low risk, 698 women completed an online survey. Participants were allocated at random to information on screening benefits followed by risks, or vice versa, and asked to state preferences for either screening system. Participants also rated perceived magnitude of screening benefits and risks, and breast cancer susceptibility. Results Binomial logistic regression did not find order effects on preferences (p = 0.533) or perceived benefits of screening (p = 0.780). Perceived screening risks were greater when risks were presented first (p < 0.0005). Greater perceived susceptibility was associated with lower proportions preferring risk-stratified screening (15% vs. 39% in highest and lowest groups; p = 0.002), as were greater perceived screening benefits (e.g. 13% vs. 45% in highest and lowest groups; p < 0.0005). Conclusions No information order effect on preferences was observed. Information order did affect screening risk perceptions. Efforts to improve perceptions may need to be more intensive than those tested. Women perceiving themselves as high risk or perceiving greater benefits of screening may be particularly averse to less frequent screening.
Career choices for obstetrics and gynaecology: recent updates from 40 years of national surveys of UK medical graduates
Authors: Lambert Trevor W , Smith Fay , Goldacre Michael J 
Published: October 2019

Summary Objective To report doctors' early career choices for obstetrics and gynaecology, their eventual career destinations and factors influencing their career pathways. Design Multi-cohort multi-purpose national questionnaire surveys of medical graduates in selected graduation years between 1974 and 2015. Setting UK. Participants UK-trained medical graduates. Main outcome measures Career specialty choices; certainty about specialty choice; factors which influenced doctors' career choices; career specialty destinations 10 years after graduation. Results Obstetrics and Gynaecology was the first choice of career for 5.7% of post-2002 graduates in year 1, 4.3% in year 3 and 3.8% in year 5. A much higher percentage of women than men specified Obstetrics and Gynaecology as their first choice: in year 1, 7.7% of women and 2.3% of men did so. The gender gap has widened since the 1970s and 1980s. In recent years, of those who specified Obstetrics and Gynaecology as their first choice in year 1 after graduation, 48% were working in Obstetrics and Gynaecology in year 10 (63% of men, 45% of women). Looking backwards from career destinations, 85% of doctors working in Obstetrics and Gynaecology in year 10 had specified Obstetrics and Gynaecology as a first, second or third choice of preferred career in year 1. Conclusions Interest in Obstetrics and Gynaecology among UK graduates appears to be exceeding the demand for new specialists. Policy needs to address risks of over-production of trainees and ensure that some graduates interested in Obstetrics and Gynaecology consider alternative careers. The large gender imbalance should encourage consideration of the reasons for men choosing Obstetrics and Gynaecology in falling numbers.
Comparisons of two diaphragm ultrasound-teaching programs: a multicenter randomized controlled educational study
Authors: Garofalo Eugenio , Bruni Andrea , Pelaia Corrado , Landoni Giovanni , Zangrillo Alberto , Antonelli Massimo , Conti Giorgio , Biasucci Daniele Guerino , Mercurio Giovanna , Cortegiani Andrea , Giarratano Antonino , Vetrugno Luigi , Bove Tiziana , Forfori Francesco , Corradi Francesco , Vaschetto Rosanna , Cammarota Gianmaria , Astuto Marinella , Murabito Paolo , Bellini Valentina , Zambon Massimo , Longhini Federico , Navalesi Paolo , Bignami Elena 
Published: October 2019

Abstract
Background
This study aims to ascertain whether (1) an educational program is sufficient to achieve adequate Diaphragm Ultrasound (DUS) assessments on healthy volunteers and (2) combining a video tutorial with a practical session is more effective in making learners capable to obtain accurate DUS measurements, as opposed to sole video tutorial.

Results
We enrolledstep 1: 172 volunteers naïve to ultrasound. After watching a video tutorial, a questionnaire was administered and considered to be passed when at least 70% of the questions were correctly answered. Course participants who passed the theoretical test were randomized to either intervention or control group. Learners randomized to the interventional group underwent to a practical training, tutored by an expert, before accessing DUS examination. Participants randomized to the control group directly accessed DUS examination, without any practical training. DUS measurements by learners and tutors were recorded and checked for accuracy, according to predefined criteria. Detection of both acoustic windows and accurate DUS assessment was achieved by 83.7% learners of the intervention group while 3.5% only among controls (p < 0.0001). The subcostal view of the diaphragm was correctly identified by 92% and 65% learners in the intervention and control groups, respectively (p < 0.0001) while the apposition zone by 86% and 71% learners, respectively (p = 0.026). An accurate diaphragm displacement (DD) measurement was obtained by 91% and 45% learners in the intervention and control groups, respectively (p < 0.0001) while an accurate thickening fraction (TF) measurement by 99% and 21%, respectively (p < 0.0001). DD measurements by both groups of learners were significantly correlated with those assessed by expert tutors; however, a significant improvement of measurement accuracy was found in learners randomized to receive also the practical training, compared to controls.

Conclusions
A combined approach consisting of a theoretical module followed by a practical training is more effective in managing acoustic windows and performing accurate measurements when compared to an exclusively theoretical course.
Trial registration prospectively registered on clinicaltrials.gov (Identifier: NCT03704129; release date 17th October 2018).
Human amniotic mesenchymal stem cells improve the follicular microenvironment to recover ovarian function in premature ovarian failure mice
Authors: Liu Rongxia , Zhang Xiaoyu , Fan Zhenhai , Wang Yuying , Yao Guanping , Wan Xue , Liu Zulin , Yang Bing , Yu Limei 
Published: October 2019

Abstract

Background
Many adult women younger than 40 years old have premature ovarian failure (POF) and infertility. Previous studies confirmed that different tissue-derived stem cells could restore ovarian function and folliculogenesis in chemotherapy-induced POF mice. The aim of this study was to explore the therapeutic efficacy and underlying mechanisms of human amniotic mesenchymal stem cells (hAMSCs) transplantation for hydrogen peroxide-induced ovarian damage.

Methods
Bilateral ovaries of female mice were burned with 10% hydrogen peroxide to establish a POF model. After 24 h of treatment, hAMSCs and diethylstilbestrol were administered to POF mice by intraperitoneal injection and intragastric administration, respectively. After either 7 or 14 days, ovarian function was evaluated by the oestrus cycle, hormone levels, ovarian index, fertility rate, and ovarian morphology. The karyotype was identified in offspring by the G-banding technique. hAMSCs tracking, immunohistochemical staining, and real-time polymerase chain reaction (PCR) were used to assess the molecular mechanisms of injury and repair.

Results
The oestrus cycle was recovered after hAMSCs transplantation at 7 and 14 days. Oestrogen levels increased, while follicle-stimulating hormone levels decreased. The ovarian index, fertility rate, and population of follicles at different stages were significantly increased. The newborn mice had no obvious deformity and showed normal growth and development. The normal offspring mice were also fertile. The tracking of hAMSCs revealed that they colonized in the ovarian stroma. Immunohistochemical and PCR analyses indicated that changes in proteins and genes might affect mature follicle formation.

Conclusions
These results suggested that hAMSCs transplantation can improve injured ovarian tissue structure and function in oxidatively damaged POF mice. Furthermore, the mechanisms of hAMSCs are related to promoting follicular development, granulosa cell proliferation, and secretion function by improving the local microenvironment of the ovary.
Long noncoding RNA lnc-DILC stabilizes PTEN and suppresses clear cell renal cell carcinoma progression
Authors: Zhang Han , Wei Pengtao , Lv Wenwei , Han Xingtao , Yang Jinhui , Qin Shuaifeng 
Published: October 2019

AbstractBackgroundIncreasing evidence has indicated that long noncoding RNAs (lncRNAs) are crucial regulators affecting the progression of human cancers. Recently, lncRNA downregulated in liver cancer stem cells (lnc-DILC) was identified to function as a tumor suppressor inhibiting the tumorigenesis and metastasis in liver cancer and colorectal cancer. However, to date, little is known about the functional roles of lnc-DILC in modulating malignant phenotypes of clear cell renal cell carcinoma (ccRCC) cells.Methodslnc-DILC expression in human ccRCC tissues was detected by qRT-PCR. Overexpression and knockdown experiments were carried out to determine the effects of lnc-DILC on ccRCC cell proliferation, migration and invasion. To reveal the underlying mechanisms of lnc-DILC functions in ccRCC cells. RNA immunoprecipitation, RNA pull-down, in vivo ubiquitination, co-immunoprecipitation and western blot assays were performed.ResultsHere, we identified that lnc-DILC levels were dramatically downregulated in ccRCC tissues. Loss of lnc-DILC expression was correlated with larger tumor size, advanced tumor grade and lymph node metastasis, and also predicted worse prognosis in patients with ccRCC. Functionally, knockdown and overexpression experiments demonstrated that lnc-DILC inhibited cell proliferation, migration and invasion in ccRCC cells. Mechanistic investigation revealed that lnc-DILC bound to tumor suppressor PTEN and suppressed its degradation. lnc-DILC repressed the PTEN ubiquitination through blocking the interaction between PTEN and E3 ubiquitin ligase WWP2 and recruiting the deubiquitinase USP11 to PTEN. Moreover, we demonstrated that PTEN–AKT signaling was crucial for lnc-DILC-mediated suppressive effects.ConclusionsIn summary, our research revealed a novel mechanism by which lnc-DILC regulates PTEN stability via WWP2 and USP11, and shed light on potential therapeutic strategies by the restoration of lnc-DILC expression in patients with ccRCC.
Exploratory study on microRNA profiles from plasma-derived extracellular vesicles in Alzheimer’s disease and dementia with Lewy bodies
Authors: Gámez-Valero Ana , Campdelacreu Jaume , Vilas Dolores , Ispierto Lourdes , Reñé Ramón , Álvarez Ramiro , Armengol M. Pilar , Borràs Francesc E. , Beyer Katrin 
Published: October 2019

AbstractBackgroundBecause of the increasing life expectancy in our society, aging-related neurodegenerative disorders are one of the main issues in global health. Most of these diseases are characterized by the deposition of misfolded proteins and a progressive cognitive decline. Among these diseases, Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) are the most common types of degenerative dementia. Although both show specific features, an important neuropathological and clinical overlap between them hampers their correct diagnosis. In this work, we identified molecular biomarkers aiming to improve the misdiagnosis between both diseases.MethodsPlasma extracellular vesicles (EVs) -from DLB, AD and healthy controls- were isolated using size-exclusion chromatography (SEC) and characterized by flow cytometry, Nanoparticle Tracking Analysis (NTA) and cryo-electron microscopy. Next Generation Sequencing (NGS) and related bibliographic search was performed and a selected group of EV-associated microRNAs (miRNAs) was analysed by qPCR.ResultsResults uncovered two miRNAs (hsa-miR-451a and hsa-miR-21-5p) significantly down-regulated in AD samples respect to DLB patients, and a set of four miRNAs (hsa-miR-23a-3p, hsa-miR-126-3p, hsa-let-7i-5p, and hsa-miR-151a-3p) significantly decreased in AD respect to controls. The two miRNAs showing decreased expression in AD in comparison to DLB provided area under the curve (AUC) values of 0.9 in ROC curve analysis, thus suggesting their possible use as biomarkers to discriminate between both diseases. Target gene analysis of these miRNAs using prediction online tools showed accumulation of phosphorylation enzymes, presence of proteasome-related proteins and genes involved in cell death among others.ConclusionOur data suggest that plasma-EV associated miRNAs may reflect a differential profile for a given dementia-related disorder which, once validated in larger cohorts of patients, could help to improve the differential diagnosis of DLB versus AD.
Sustained preventive chemotherapy for soil-transmitted helminthiases leads to reduction in prevalence and anthelminthic tablets required
Authors: Mupfasoni Denise , Bangert Mathieu , Mikhailov Alexei , Marocco Chiara , Montresor Antonio 
Published: October 2019

Abstract

Background
The goal of soil-transmitted helminthiases (STH) control programmes is to eliminate STH-associated morbidity in the target population by reducing the prevalence of moderate- and heavy-intensity infections and the overall STH infection prevalence mainly through preventive chemotherapy (PC) with either albendazole or mebendazole. Endemic countries should measure the success of their control programmes through regular epidemiological assessments. We evaluated changes in STH prevalence in countries that conducted effective PC coverage for STH to guide changes in the frequency of PC rounds and the number of tablets needed.

Methods
We selected countries from World Health Organization (WHO)‘s Preventive Chemotherapy and Transmission control (PCT) databank that conducted ≥5 years of PC with effective coverage for school-age children (SAC) and extracted STH baseline and impact assessment data using the WHO Epidemiological Data Reporting Form, Ministry of Health reports and/or peer-reviewed publications. We used pooled and weighted means to plot the prevalence of infection with any STH and with each STH species at baseline and after ≥5 years of PC with effective coverage. Finally, using the WHO STH decision tree, we estimated the reduction in the number of tablets needed.

Results
Fifteen countries in four WHO regions conducted annual or semi-annual rounds of PC for STH for 5 years or more and collected data before and after interventions. At baseline, the pooled prevalence was 48.9% (33.1–64.7%) for any STH, 23.2% (13.7–32.7%) for Ascaris lumbricoides, 21.01% (9.7–32.3%) for Trichuris trichiura and 18.2% (10.9–25.5%) for hookworm infections, while after ≥5 years of PC for STH, the prevalence was 14.3% (7.3–21.3%) for any STH, 6.9% (1.3–12.5%) for A. lumbricoides, 5.3% (1.06–9.6%) for T. trichiura and 8.1% (4.0–12.2%) for hookworm infections.

Conclusions
Countries endemic for STH have made tremendous progress in reducing STH-associated morbidity, but very few countries have data to demonstrate that progress. In this study, the data show that nine countries should adapt their PC strategies and the frequency of PC rounds to yield a 36% reduction in drug needs. The study also highlights the importance of impact assessment surveys to adapt control strategies according to STH prevalence.
The time required to diagnose and treat lung cancer in Delhi, India: an updated experience of a public referral center
Authors: Vashistha Vishal , Choudhari Chandrashekhar , Garg Avneet , Gupta Aditi , Parthasarathy Gopanandan , Jain Deepali , Madan Karan , Hadda Vijay , Khilnani G. C. , Guleria Randeep , Mohan Anant 
Published: October 2019

Abstract

Background
Delays that postpone the evaluation and management of malignancy may lead to considerable morbidity. The primary objective of this study was to assess the time required to diagnose and treat lung cancer at an Indian public referral center that predominantly serves lower-income patients.

Methods
A review of patients diagnosed with lung cancer between January 2008 and December 2016 was completed. We computed the median time intervals and inter-quartile ranges between symptom onset, definitive diagnostic investigation, confirmed histologic diagnosis, and chemotherapy initiation. Median intervals were correlated with baseline demographics and disease characteristics using Kruskal-Wallis test.

Results
One thousand, three hundred and-seventy patients were selected. A majority (94.5%) with non-small cell lung cancer were diagnosed with advanced disease. After developing symptoms, patients required 101 [56–168] days to undergo a definitive diagnostic study, 107 [60–173] days to confirm a diagnosis, and 126 [85–196.8] days to initiate treatment. Patients who were previously treated for tuberculosis required more time to receive chemotherapy compared to those who were not (187 [134–261.5] days vs. 113 [75–180] days, p < 0.0001). A specialty Lung Cancer Clinic was implemented in 2012, and the mean referrals per month increased nearly four-fold (p < 0.0001), but the time required to administer treatment was not shortened.

Conclusion
Among lower-income Indian patients, the most prominent delays occur prior to diagnosis. Efforts should be directed toward encouraging physicians to maintain a high index of clinical suspicion and educating patients to report concerning symptoms as early as possible.
Clinical Presentation of Primary Hyperparathyroidism in Older Adults
Authors: Castellano Elena , Attanasio Roberto , Boriano Alberto , Borretta Giorgio 
Published: October 2019

Abstract

Background
The clinical presentation of primary hyperparathyroidism (PHPT) has changed greatly during the past few decades. Our aim was to evaluate whether the clinical presentation at diagnosis differed according to age.

Methods
We evaluated retrospectively a monocentric series of 462 consecutive patients with PHPT, dividing them according to a cutoff of 65 years of age.

Results
No differences were found in the mean serum PTH, calcium, or vitamin D levels. In older patients (n = 212; 45.9%), the urinary calcium levels were significantly lower (median, 205 mg/24 hour; interquartile range, 220 mg/24 hour) compared with those in younger patients (median, 308 mg/24 hour; interquartile range, 233 mg/24 hour). In addition, renal involvement was significantly less frequent (25% vs 49.2%), and bone involvement significantly more frequent (58% vs 44%) in older patients compared with younger patients. The clinical presentation was significantly different between the two age groups, with a lower frequency of symptomatic forms and a greater frequency of asymptomatic forms not meeting surgical criteria in the older patients (44.4% vs 57.2% and 18.4% vs 5.6%, respectively). Osteoporosis was significantly more frequent in the older adults than in their younger counterparts. The most affected bone site was the forearm in older adults and the lumbar spine in younger ones (50.3% and 50.5%, respectively).

Conclusion
The clinical presentation of PHPT differs according to age, and this difference can affect the selection of management modalities.
MicroRNA-19b restricts Wnt7b to the hem, which induces aspects of hippocampus development in the avian forebrain
Authors: Sindhu Suvimal Kumar , Udaykumar Niveda , Zaidi Mohd Ali Abbas , Soni Abhinav , Sen Jonaki 
Published: October 2019

ABSTRACT
The functions of the hippocampus are conserved between birds and mammals; however, it is not known whether similar mechanisms are responsible for its development in these two classes. In mammals, hippocampus development is known to be regulated by the hem organizer. Here, we have identified that, in birds, Wnt7b secreted from the hem is sufficient for inducing the expression of hippocampal markers. Furthermore, we have demonstrated that a microRNA, miR-19b, which is selectively excluded from the hem region, is necessary and sufficient for restricting the expression of Wnt7b to the hem. This study suggests that the role of the Wnt signal emanating from the hem is conserved between birds and mammals, and that a microRNA-based mechanism is crucial for determining the position of the hippocampus.
Can laboratory model systems instruct human limb regeneration?
Authors: Cox Ben D. , Yun Maximina H. , Poss Kenneth D. 
Published: October 2019

ABSTRACT
Regeneration has fascinated scientists since well before the 20th century revolutions in genetics and molecular biology. The field of regenerative biology has grown steadily over the past decade, incorporating advances in imaging, genomics and genome editing to identify key cell types and molecules involved across many model organisms. Yet for many or most tissues, it can be difficult to predict when and how findings from these studies will advance regenerative medicine. Establishing technologies to stimulate regrowth of a lost or amputated limb with a patterned replicate, as salamanders do routinely, is one of the most challenging directives of tissue regeneration research. Here, we speculate upon what research avenues the field must explore to move closer to this capstone achievement.