bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of pruriceptors in enhancing sensitivity to pruritogens in a murine chronic compression model of dorsal root ganglion
Authors: Wang Tao , Tao Jin , Fang Yehong , Ma Chao 
Published: January 2021

AbstractChronic pruritus is a symptom that commonly observed in neurological diseases. It has been hypothesized that the chronic pruritus may result from sensitization of itch-signaling pathways but the mechanisms remain obscure. In this study, we established a mouse model of chronic compression of dorsal root ganglion (CCD) and injected various pruritogenic and algogenic agents intradermally to the calf skin ipsilateral to the compressed dorsal root ganglion (DRG). Compared to the naïve mice, a significant increase in itch-related behaviors was observed in the CCD mice after the injection of pruritogens including histamine and BAM8-22, but not after the injection of capsaicin, although all the above agents evoked enhanced pain-related behaviors toward the injected site. In addition, we investigated if pruritogen-evoked activities of DRG neurons were enhanced in this model. In vivo calcium imaging revealed that compressed DRG neurons exhibited enhanced responses to histamine and BAM8-22. Immunoflorescent staining also showed that the histamine receptor H1 and the capsaicin receptor TRPV1 were significantly upregulated in DRG neurons. Our findings indicated that the sensitization of primary pruriceptive neurons may underlie the enhanced itch sensation after chronic compression of DRG in the mice, and may play a role in chronic pruritus in neurological diseases.
Diabetes‐related foot disease in Australia: a systematic review of the prevalence and incidence of risk factors, disease and amputation in Australian populations
Authors: Zhang Yuqi , van Netten Jaap J. , Baba Mendel , Cheng Qinglu , Pacella Rosana , McPhail Steven M. , Cramb Susanna , Lazzarini Peter A. 
Published: January 2021

AbstractBackgroundDiabetes‐related foot disease (DFD) is a leading cause of global hospitalisation, amputation and disability burdens; yet, the epidemiology of the DFD burden is unclear in Australia. We aimed to systematically review the literature reporting the prevalence and incidence of risk factors for DFD (e.g. neuropathy, peripheral artery disease), of DFD (ulcers and infection), and of diabetes‐related amputation (total, minor and major amputation) in Australian populations.MethodsWe systematically searched PubMed and EMBASE databases for peer‐reviewed articles published until December 31, 2019. We used search strings combining key terms for prevalence or incidence, DFD or amputation, and Australia. Search results were independently screened for eligibility by two investigators. Publications that reported prevalence or incidence of outcomes of interest in geographically defined Australian populations were eligible for inclusion. Included studies were independently assessed for methodological quality and key data were extracted by two investigators.ResultsTwenty publications met eligibility and were included. There was high heterogeneity for populations investigated and methods used to identify outcomes. We found within diabetes populations, the prevalence of risk factors ranged from 10.0–58.8%, of DFD from 1.2–1.5%, and the incidence of diabetes‐related amputation ranged from 5.2–7.2 per 1000 person‐years. Additionally, the incidence of DFD‐related hospitalisation ranged from 5.2–36.6 per 1000 person‐years within diabetes populations. Furthermore, within inpatients with diabetes, we found the prevalence of risk factors ranged from 35.3–43.3%, DFD from 7.0–15.1% and amputation during hospitalisation from 1.4–5.8%.ConclusionsOur review suggests a similar risk factor prevalence, low but uncertain DFD prevalence, and high DFD‐related hospitalisation and amputation incidence in Australia compared to international populations. These findings may suggest that a low proportion of people with risk factors develop DFD, however, it is also possible that there is an underestimation of DFD prevalence in Australia in the few limited studies, given the high incidence of hospitalisation and amputation because of DFD. Either way, studies of nationally representative populations using valid outcome measures are needed to verify these DFD‐related findings and interpretations.
Novel PHOX2B germline mutation in childhood medulloblastoma: a case report
Authors: Ke Caiping , Shi Xiaoshun , Chen Allen Menglin , Li Chaoming , Jiang Bifeng , Huang Kailing , Zheng Zhouxia , Liu Yanhui , Chen Zhuona , Luo Yingjun , Lin Huaming , Zhang Jiexia 
Published: January 2021

Abstract
Background
Medulloblastoma is an aggressive brain tumor mostly found in children, few studies on pathogenic germline mutations predisposing this disease was reported.

Case presentation
We present an 11-year-old male with medulloblastoma, who harbors a de novo PHOX2B germline mutation as detected by whole exome sequencing (WES). Family history was negative. Sanger sequencing confirmed this mutation in peripheral blood, hair bulbs, urine and saliva. Identification of novel germline mutations is beneficial for childhood cancer screening.

Conclusions
This case revealed a de novo PHOX2B germline mutation as a potential cause of medulloblastoma in a child and suggests familial germline variant screening is useful when an affected family is considering having a second child.
Pair consensus decoding improves accuracy of neural network basecallers for nanopore sequencing
Authors: Silvestre-Ryan Jordi , Holmes Ian 
Published: January 2021

AbstractWe develop a general computational approach for improving the accuracy of basecalling with Oxford Nanopore’s 1D2 and related sequencing protocols. Our software PoreOver (https://github.com/jordisr/poreover) finds the consensus of two neural networks by aligning their probability profiles, and is compatible with multiple nanopore basecallers. When applied to the recently-released Bonito basecaller, our method reduces the median sequencing error by more than half.
Statistical analysis plan for management of hypertension and multiple risk factors to enhance cardiovascular health in Singapore: the SingHypertension pragmatic cluster randomized controlled trial
Authors:   for SingHypertension Study Group, Allen John C. , Halaand Benjamin , Shirore Rupesh M. , Jafar Tazeen H. 
Published: January 2021

Abstract
Introduction
Cardiovascular disease remains the leading cause of death in Singapore. Uncontrolled hypertension confers the highest attributable risk of CVD and remains a significant public health issue with sub-optimal blood pressure (BP) control rates. The aim of the trial is to evaluate the effectiveness and cost-effectiveness of a multicomponent intervention (MCI) versus usual care on lowering BP among adults with uncontrolled hypertension visiting primary care clinics in Singapore. This article describes the statistical analysis plan for the primary and secondary objectives related to intervention effectiveness.

Methods
The study is a cluster randomized trial enrolling 1000 participants with uncontrolled hypertension aged ≥ 40 years from eight primary care clinics in Singapore. The unit of randomization is the clinic, with eight clusters (clinics) randomized in a 1:1 ratio to either MCI or usual care. All participants will be assessed at baseline, 12 months, and 24 months with measurements of systolic and diastolic BP, antihypertensive and statin medication use, medication adherence, physical activity level, anthropometric parameters, smoking status, and dietary habits.
The primary objective of this study is to assess the effectiveness of MCI versus usual care on mean SBP at the 2-year follow-up. The primary outcome is SBP at 24 months.
SBP at baseline, 12, and 24 months will be modeled at the subject level using a likelihood-based, linear mixed-effects model repeated measures (MMRM) analysis with treatment group and follow-up as fixed effects, random cluster (clinic) effects, Gaussian error distribution, and adjustment to degrees of freedom using the Satterthwaite approximation. Secondary outcomes will be analyzed using a similar modeling approach incorporating generalized techniques appropriate for the type of outcome.

Discussion
The trial will allow us to determine whether the MCI has an impact on BP and cardiovascular risk factors over a 2-year follow-up period and inform recommendations for health planners in scaling up these strategies for the benefit of society at large. A pre-specified and pre-published statistical analysis plan mitigates reporting bias and data driven approaches.

Trial registration
ClinicalTrials.gov NCT02972619. Registered on 23 November 2016.
A late systemic and brain metastasis from subcutaneous leiomyosarcoma of the right forearm: a case report and review of the literature
Authors: Dietel Eric , Nestler Ulf , Nenning Hans , Eisenlöffel Christian , Stassart Ruth , Meixensberger Jürgen 
Published: January 2021

Abstract
Background
Leiomyosarcomas are rare malignant tumors which originate from smooth muscle cells and very seldom give rise to intracerebral metastases. Nearly all cases of intracranial metastases stem from leiomyosarcomas of the uterus. We present a 61-year-old Caucasian man who developed multiple intracranial and extracranial metastases from leiomyosarcoma of the right forearm, diagnosed and treated 9 years before the current presentation.

Case presentation
The Caucasian patient presented to the emergency department due to a progressive hemiparesis on the left side. Magnetic resonance imaging scans of the neurocranium showed multiple intracerebral masses with perifocal edema. One of these was located in the right parietal lobe, corresponding to the hemiparesis. The patient underwent microsurgical complete resection of the parietal mass and was subsequently subjected to further radiotherapy. Histopathological studies revealed metastasis of the former leiomyosarcoma.

Conclusions
Leiomyosarcomas represent a rare entity of mesenchymal tumors. Intracerebral metastasis of these tumors is even less frequent. This case shows the importance of long-term follow-up in patients with leiomyosarcoma.
On a multiple Hilbert-type integral inequality involving the upper limit functions
Authors: Zhong Jianhua , Yang Bicheng 
Published: January 2021

AbstractBy applying the weight functions, the idea of introducing parameters and the technique of real analysis, a new multiple Hilbert-type integral inequality involving the upper limit functions is given. The constant factor related to the gamma function is proved to be the best possible in a condition. A corollary about the case of the nonhomogeneous kernel and some particular inequalities are obtained.
A class of singular diffusion equations based on the convex–nonconvex variation model for noise removal
Authors: Dong Gang , Wu Boying 
Published: January 2021

AbstractThis paper focuses on the problem of noise removal. First, we propose a new convex–nonconvex variation model for noise removal and consider the nonexistence of solutions of the variation model. Based on the new variation method, we propose a class of singular diffusion equations and prove the of solutions and comparison rule for the new equations. Finally, experimental results illustrate the effectiveness of the model in noise reduction.
Interstitial lung abnormalities in patients with stage I non-small cell lung cancer are associated with shorter overall survival: the Boston lung cancer study
Authors: Hida Tomoyuki , Hata Akinori , Lu Junwei , Valtchinov Vladimir I. , Hino Takuya , Nishino Mizuki , Honda Hiroshi , Tomiyama Noriyuki , Christiani David C. , Hatabu Hiroto 
Published: January 2021

Abstract
Background
Interstitial lung abnormalities (ILA) can be detected on computed tomography (CT) in lung cancer patients and have an association with mortality in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study is to demonstrate the significance of ILA for mortality in patients with stage I NSCLC using Boston Lung Cancer Study cohort.

Methods
Two hundred and thirty-one patients with stage I NSCLC from 2000 to 2011 were investigated in this retrospective study (median age, 69 years; 93 males, 138 females). ILA was scored on baseline CT scans prior to treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA) by a sequential reading method. ILA score 2 was considered the presence of ILA. The difference of overall survival (OS) for patients with different ILA scores were tested via log-rank test and multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) including ILA score, age, sex, smoking status, and treatment as the confounding variables.

Results
ILA was present in 22 out of 231 patients (9.5%) with stage I NSCLC. The presence of ILA was associated with shorter OS (patients with ILA score 2, median 3.85 years [95% confidence interval (CI): 3.36 – not reached (NR)]; patients with ILA score 0 or 1, median 10.16 years [95%CI: 8.65 - NR]; P <  0.0001). In a Cox proportional hazards model, the presence of ILA remained significant for increased risk for death (HR = 2.88, P = 0.005) after adjusting for age, sex, smoking and treatment.

Conclusions
ILA was detected on CT in 9.5% of patients with stage I NSCLC. The presence of ILA was significantly associated with a shorter OS and could be an imaging marker of shorter survival in stage I NSCLC.
MRI texture feature repeatability and image acquisition factor robustness, a phantom study and in silico study
Authors: Shur Joshua , Blackledge Matthew , D’Arcy James , Collins David J. , Bali Maria , O’Leach Martin , Koh Dow-Mu 
Published: January 2021

Abstract
Purpose
To evaluate robustness and repeatability of magnetic resonance imaging (MRI) texture features in water and tissue phantom test-retest study.

Materials and methods
Separate water and tissue phantoms were imaged twice with the same protocol in a test-retest experiment using a 1.5-T scanner. Protocols were acquired to favour signal-to-noise ratio and resolution. Forty-six features including first order statistics and second-order texture features were extracted, and repeatability was assessed by calculating the concordance correlation coefficient. Separately, base image noise and resolution were manipulated in an in silico experiment, and robustness of features was calculated by assessing percentage coefficient of variation and linear correlation of features with noise and resolution. These simulation data were compared with the acquired data. Features were classified by their degree (high, intermediate, or low) of robustness and repeatability.

Results
Eighty percent of the MRI features were repeatable (concordance correlation coefficient > 0.9) in the phantom test-retest experiment. The majority (approximately 90%) demonstrated a strong or intermediate correlation with image acquisition parameter, and 19/46 (41%) and 13/46 (28%) of features were highly robust to noise and resolution, respectively (coefficient of variation < 5%). Agreement between the acquired and simulation data varied, with the range of agreement within feature classes between 11 and 92%.

Conclusion
Most MRI features were repeatable in a phantom test-retest study. This phantom data may serve as a lower limit of feature MRI repeatability. Robustness of features varies with acquisition parameter, and appropriate features can be selected for clinical validation studies.
The fertility assessment of normal cyclic Wistar rats following the administration of methanolic extract of Portulaca oleracea: an experimental study
Authors: Okafor Izuchukwu Azuka , Nnamah Uchenna Somtochukwu , Nnaka Jude 
Published: January 2021

AbstractBackgroundPurslane is a widely distributed shrub used for the treatment of different ailments. The increasing reproductive complications associated with herbal treatments have led to the need to critically evaluate the safety and/or reproductive potentials of commonly used plant extracts. This study investigated the reproductive effect of methanolic extracts of Portulaca oleracea (MEPO) in adult female Wistar rats.ResultsGroup C showed a significant decrease both in relative ovarian weight (p= 0.000), and relative uterine weight (p= 0.037), when compared with the control. There were no significant (p˃ 0.05) changes in the levels of follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol. When compared to the control, groups B and C showed abnormal estrous cycle and cycle arrest especially at the metestrus phase with mild congestion of a few blood vessels in the ovary and uterus.ConclusionsMEPO may possess some anti-fertility effect, as it disrupts the estrous cycle of adult female Wistar rats; although it has no major effect on the reproductive hormones, uterus, and ovarian histology of adult female Wistar rats. However, high dose consumption should be taken with precaution.
Patent urachus and bladder outflow obstruction—chance or consequence? A study of a cohort of patients with complete patent urachus presenting to a tertiary urological center and a review of literature
Authors: Taher Heba , Ramnarine Sharmila , Smeulders Naima , Desai Divyesh , Mushtaq Imran , Cuckow Peter , Cherian Abraham 
Published: January 2021

Abstract
Background
To explore the association between patent urachus and bladder outflow obstruction (BOO). A retrospective review of patient records over a 35-year period (1983–2018) with complete patent urachus was performed. Antenatal ultrasound findings were noted, and postnatal investigations included ultrasound (US), micturating cystourethrogram (MCUG), functional nuclear medicine scans (MAG3, DTPA, and DMSA), and serum creatinine. Associated anomalies and management in all patients were analyzed.

Results
Sixty-six patients with all types of urachal remnants were identified of whom only 16 had a patent urachus. All presented clinically with a discharging umbilicus, 10/16 confirmed on MCUG and 4 had umbilical cord cysts on antenatal US. Twenty-five percent had associated bladder outlet obstruction (BOO): etiologies included atresia of posterior urethra, congenital urethral hypoplasia, urethral atresia with prune belly syndrome, and sacrococcygeal teratoma. Vesicoureteral reflux (VUR) was confirmed in 37%, and four of them had bladder outlet obstruction (BOO).

Conclusion
With patent urachus, bladder outflow obstruction occurs in the minority. Based on our findings, we commend US and cystogram to document VUR. The isolated PU should be treated nonoperatively up to a year of age. Renal function should be checked with the finding of VUR. The etiopathogenesis of the condition remains uncertain.
Iron Overload in Functional Hyperandrogenism: In a Randomized Trial, Bloodletting Does Not Improve Metabolic Outcomes
Authors: Ortiz-Flores Andrés E , Martínez-García María Ángeles , Nattero-Chávez Lía , Álvarez-Blasco Francisco , Fernández-Durán Elena , Quintero-Tobar Alejandra , Escobar-Morreale Héctor F , Luque-Ramírez Manuel 
Published: January 2021

Abstract

Context
Functional hyperandrogenism may be associated with a mild increase in body iron stores. Iron depletion exerts a beneficial effect on metabolic endpoints in other iron overload states.

Objectives
(i) To determine the effect of iron depletion on the insulin sensitivity and frequency of abnormal glucose tolerance in patients with functional hyperandrogenism submitted to standard therapy with combined oral contraceptives (COC). ii) To assess the overall safety of this intervention.

Design
Randomized, parallel, open-label, clinical trial.

Setting
Academic hospital.

Patients
Adult women with polycystic ovary syndrome or idiopathic hyperandrogenism.

Intervention
After a 3-month run-in period of treatment with 35 μg ethinylestradiol plus 2 mg cyproterone acetate, participants were randomized (1:1) to 3 scheduled bloodlettings or observation for another 9 months.

Main outcome measures
Changes in insulin sensitivity index and frequency of prediabetes/diabetes, and percentage of women in whom bloodletting resulted in plasma hemoglobin &lt;120 g/L and/or hematocrit &lt;0.36.

Results
From 2015 to 2019, 33 women were included by intention-to-treat. During the follow-up, insulin sensitivity did not change in the whole group of women or between study arms [mean of the differences (MD): 0.0 (95%CI: −1.6 to 1.6)]. Women in the experimental arm showed a similar odds of having prediabetes/diabetes than women submitted to observation [odds ratio: 0.981 (95%CI: 0.712 to 1.351)]. After bloodletting, 4 (21.1%) and 2 women (10.5%) in the experimental arm had hemoglobin (Hb) levels &lt;120 g/L and hematocrit (Hct) values &lt;0.36, respectively, but none showed Hb &lt;110 g/L or Hct &lt;0.34.

Conclusions
Scheduled bloodletting does not improve insulin sensitivity in women with functional hyperandrogenism on COC.
Exposure to Propylthiouracil in the First Trimester of Pregnancy and Birth Defects: A Study at a Single Institution
Authors: Yoshihara Ai , Noh Jaeduk Yoshimura , Watanabe Natsuko , Fukushita Miho , Matsumoto Masako , Suzuki Nami , Hoshiyama Ayako , Suzuki Ai , Mitsumatsu Takako , Kinoshita Aya , Mikura Kentaro , Yoshimura Ran , Sugino Kiminori , Ito Koichi 
Published: January 2021

Abstract

Context
Medical treatment of Graves disease during the first trimester has been the subject of controversy ever since treatment with an antithyroid drug during the first trimester was reported to possibly be associated with an increased risk of birth defects in newborns.

Objective
We investigated whether the incidence of birth defects among newborns born to mothers with Graves disease (GD) treated with propylthiouracil (PTU) during the first trimester of pregnancy was higher than in a control group that was not exposed to any medication.

Methods
We reviewed the cases of 1913 women with GD who gave birth between January 1, 2015, and May 31, 2019. Detailed information concerning the outcome of pregnancy and the presence of birth defects was collected at the first visit after the delivery and again 1 year after delivery. We classified the mothers and infants into 3 groups according to the treatment the mother had received for GD in the first trimester of pregnancy: a group in which the mothers had been treated with PTU alone (PTU group), a group in which the mothers had not been treated with any medication (control group), and a group in which the mothers had received some other medical treatment, such as thiamazole, potassium iodide, or 2 or more drugs (other treatment group).

Results
The incidence of malformed infant births was 5.5% (30/541 infants) in the PTU group and 5.7% (27/ 475 infants) in the control group. There were no specific birth defects in the PTU group, and there were no significant differences between PTU dosages or maternal thyroid function according to whether mothers had delivered a child with a birth defect.

Conclusion
The results of our retrospective study showed that treatment with PTU during the first trimester of pregnancy did not increase the incidence of birth defects among newborns.
Synthetic Studies toward Aplysiasecosterol A: Concise Synthesis of the Tricyclic Core and Its Reactions for Introduction of the D Ring Fragment
Authors: Ohyoshi Takayuki , Tano Hikaru , Kigoshi Hideo 
Published: January 2021

Abstract
Aplysiasecosterol A, a 9,11-secosteroid, has a unique tricyclic γ-diketone skeleton including a hemiacetal. The concise and efficient synthesis of the tricyclic core was developed by using pseudo-desymmetrizing acetalization and acyl radical cyclization. Toward the total synthesis, an efficient method for the introduction of the D ring fragment was developed by using an organocuprate.