bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation landscape of germline and somatic BRCA1/2 in patients with high-grade serous ovarian cancer
Authors: Eoh Kyung Jin , Kim Hye Min , Lee Jung-Yun , Kim Sunghoon , Kim Sang Wun , Kim Young Tae , Nam Eun Ji 
Published: March 2020

Abstract
Background
Poly (ADP-ribose) polymerase inhibitors targeting BRCA1/2 mutations are available for treating patients with high-grade serous ovarian cancer. These treatments may be more appropriately directed to patients who might respond if the tumor tissue is additionally tested by next-generation sequencing with a multi-gene panel and Sanger sequencing of a blood sample. In this study, we compared the results obtained using the next-generation sequencing multi-gene panel to a known germline BRCA1/2 mutational state determined by conventional Sanger sequencing to evaluate the landscape of somatic mutations in high-grade serous ovarian cancer tumors.

Methods
Cancer tissue from 98 patients with high-grade serous ovarian cancer who underwent Sanger sequencing for germline BRCA1/2 analysis were consecutively analyzed for somatic mutations using a next-generation sequencing 170-gene panel.

Results
Twenty-four patients (24.5%) showed overall BRCA1/2 mutations. Seven patients (7.1%) contained only somatic BRCA1/2 mutations with wild-type germline BRCA1/2, indicating acquired mutation of BRCA1/2. Three patients (3.1%) showed reversion of germline BRCA1 mutations. Among the 14 patients (14.3%) with both germline and somatic mutations in BRCA1/2, two patients showed different variations of BRCA1/2 mutations. The next-generation sequencing panel test for somatic mutation detected other pathogenic variations including RAD51D and ARID1A, which are possible targets of poly (ADP-ribose) polymerase inhibitors. Compared to conventional Sanger sequencing alone, next-generation sequencing-based tissue analysis increased the number of candidates for poly (ADP-ribose) polymerase inhibitor treatment from 17.3% (17/98) to 26.5% (26/98).

Conclusions
Somatic mutation analysis by next-generation sequencing, in addition to germline BRCA1/2 mutation analysis, should become the standard of care for managing women with high-grade serous ovarian cancer to widen the indication of poly (ADP-ribose) polymerase inhibitors.
High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection
Authors: Ito Takahiro , Kuriyama Naohisa , Kozuka Yuji , Komatsubara Haruna , Ichikawa Ken , Noguchi Daisuke , Hayasaki Aoi , Fujii Tekehiro , Iizawa Yusuke , Kato Hiroyuki , Tanemura Akihiro , Murata Yasuhiro , Kishiwada Masashi , Mizuno Shugo , Usui Masanobu , Sakurai Hiroyuki , Isaji Shuji 
Published: March 2020

Abstract
Background
Tumor budding (TB) is used as an indicator of poor prognosis in various cancers. However, studies on TB in perihilar cholangiocarcinoma are still limited. We examined the significance of TB in resected perihilar cholangiocarcinoma with or without neoadjuvant therapy.

Methods
Seventy-eight patients who underwent surgical resection at our institution for perihilar cholangiocarcinoma from 2004 to 2017, (36 with neoadjuvant therapy), were enrolled in this study. TB was defined as an isolated cancer cell or clusters (< 5 cells) at the invasive front and the number of TB was counted using a 20 times objective lens. Patients were classified into two groups according to TB counts: low TB (TB < 5) and high TB (TB ≥5).

Results
In this 78 patient cohort, high TB was significantly associated with advanced tumor status (pT4: 50.0% vs 22.2%, p = 0.007, pN1/2: 70.8% vs 39.6%, p = 0.011, M1: 20.8% vs 1.9%) and higher histological grade (G3: 25.0% vs 5.7%, p = 0.014). Disease specific survival (DSS) in high TB was significantly inferior compared to that in low TB group (3-y DSS 14.5% vs 67.7%, p < 0.001). Interestingly, DSS in high TB showed similar to survival in unresected patients. In addition, high TB was also associated with advanced tumor status and poor prognosis in patients with neoadjuvant therapy. Multivariate analysis identified high TB as an independent poor prognostic factors for DSS (HR: 5.206, p = 0.001).

Conclusion
This study demonstrated that high TB was strongly associated with advanced tumor status and poor prognosis in resected perihilar cholangiocarcinoma patients. High TB can be a novel poor prognostic factor in resected perihilar cholangiocarcinoma regardless of neoadjuvant therapy.
Hemiplegic (unilateral) cerebral palsy in northern Stockholm: clinical assessment, brain imaging, EEG, epilepsy and aetiologic background factors
Authors: Tillberg Elsa , Isberg Bengt , Persson Jonas K. E. 
Published: March 2020

Abstract
Background
The purpose of this study was to describe clinical presentation, epilepsy, EEG, extent and site of the underlying cerebral lesion with special reference towards aetiologic background factors in a population-based group of children with hemiplegic cerebral palsy.

Methods
Forty-seven children of school- age, fulfilling the SPCE (Surveillance of Cerebral palsy in Europe)-criteria of hemiplegic cerebral palsy, identified via the Swedish cerebral palsy register, were invited and asked to participate in the study.

Results
Fifteen boys and six girls participated. Of the sixteen children born at term, five had no risk factors for cerebral palsy. Two out of five preterm children presented additional risk factors. Debut of motor impairment was observed in the first year of life in sixteen children. Age at diagnosis varied from 2 months to 6 years. Epilepsy was common and associated with grey- and white matter injury.

Conclusions
Recognizing the importance of risk factors for cerebral palsy, any child with these risk factors should be offered a check-up by a paediatrician or a paediatric neurologist. Thereby reducing diagnostic delay. Epilepsy is common in hemiplegic cerebral palsy and associated with grey- and white matter injury in this cohort.
Pharmacotherapy of restricted/repetitive behavior in autism spectrum disorder:a systematic review and meta-analysis
Authors: Yu Yanjie , Chaulagain Ashmita , Pedersen Sindre Andre , Lydersen Stian , Leventhal Bennett L. , Szatmari Peter , Aleksic Branko , Ozaki Norio , Skokauskas Norbert 
Published: March 2020

Abstract
Background
This paper is a systematic review and meta-analysis of the efficacy of available medications for the treatment of restricted/repetitive behavior (RRBs) in Autism Spectrum Disorder (ASD).

Method
We searched MEDLINE, Embase, PsycINFO, The Cochrane Library (Cochrane Database of Systematic Reviews (CDRS), the Cochrane Central Register of Controlled Trials (CENTRAL), database of Abstracts of Reviews of Effects (DARE)), Scopus, Epistimonikos, Clinicaltrials.gov, and included all randomized controlled trials published after 1993 that were directed at RRBs in patients with ASD of all ages. We extracted the relevant data from the published studies with a predefined data extraction form and assessed the risk of bias. The primary outcomes were change in restricted/repetitive behavior. We performed a meta-analysis using the random effect model and included studies with given mean and standard deviation. This study is registered with PROSPERO number CRD42018092660).

Results
We identified 14 randomized controlled trials that met initial inclusion criteria. After closer inspection, nine trials – involving 552 patients in total – were included in the final analysis. The meta-analysis found no significant difference between medications (including fluvoxamine, risperidone, fluoxetine, citalopram, oxytocin, N-Acetylcysteine, buspirone) and placebo in the treatment of RRBs in ASD (P = 0.20). Similarly, the sub-group meta-analysis also showed no significant difference between Selective Serotonin Reuptake Inhibitor (SSRIs) and placebo in the treatment of RRBs in ASD (P = 0.68). There was no evidence of publication bias.

Conclusion
This meta-analysis finds little support for the routine use of medications to treat restricted/repetitive behaviors in Autism Spectrum Disorder. Further research of large, balanced trials with precise assessment tools and long-term follow-up are needed.

Trial registration
The study protocol is registered in PROSPERO (Reference number: CRD42018092660).
Effectiveness of the female condom in preventing HIV and sexually transmitted infections: a systematic review and meta-analysis
Authors: Wiyeh Alison B. , Mome Ruth K. B. , Mahasha Phetole W. , Kongnyuy Eugene J. , Wiysonge Charles S. 
Published: March 2020

Abstract
Background
The effectiveness of female condoms for preventing HIV and sexually transmitted infections (STIs) remains inconclusive. We examined the effects of female condoms on the acquisition of HIV and STIs.

Methods
We searched four databases, two trial registries, and reference lists of relevant publications in October 2018 and updated our search in February 2020. We screened search output, evaluated study eligibility, and extracted data in duplicate; resolving differences through discussion. We calculated the effective sample size of cluster randomised trials using an intra-cluster correlation coefficient of 0·03. Data from similar studies were combined in a meta-analysis. We performed a non-inferiority analysis of new condoms relative to marketed ones using a non-inferiority margin of 3%. We assessed the certainty of evidence using GRADE.

Results
We included fifteen studies of 6921 women. We found that polyurethane female condoms (FC1) plus male condoms may be as effective as male condoms only in reducing HIV acquisition (1 trial, n = 149 women, RR 0.07, 95%CI 0.00–1.38; low-certainty evidence). However, the use of FC1 plus male condoms is superior to male condoms alone in reducing the acquisition of gonorrhoea (2 trials, n = 790, RR 0.59, 95%CI 0.41–0.86; high-certainty evidence) and chlamydia (2 trials, n = 790, RR 0.67, 95%CI 0.47–0.94; high-certainty evidence). Adverse events and failure rates of FC1 were very low and decreased during follow up. Although the functionality of newer female condoms (Woman’s, Cupid, Pheonurse, Velvet, and Reddy) may be non-inferior to FC2, there were no available studies assessing their efficacy in preventing HIV and STIs.

Conclusion
The use of female plus male condoms is more effective than use of male condoms only in preventing STIs and may be as effective as the male condom only in preventing HIV. There is a need for well conducted studies assessing the effects of newer female condoms on HIV and STIs.

PROSPERO registration number
CRD42018090710
A case report: white cord syndrome following anterior cervical discectomy and fusion: importance of prompt diagnosis and treatment
Authors: Jun Deuk Soo , Baik Jong-Min , Lee Seung-Kwan 
Published: March 2020

Abstract
Background
Objective: White cord syndrome is extremely rare and search of the literature has revealed very few cases. Postoperative MR scan revealed hyperintense intrinsic cord signal changes within cord ischemia and edema. It is thought to be caused by reperfusion injury of the spinal cord. This is called white cord syndrome. This report is very rare case of ‘White Cord Syndrome’ with paraplegia after anterior cervical discectomy and fusion (ACDF).

Case presentation
A 49-year-old woman presented with neck pain lasting for several months and second and third finger radiating pain. Severe cervical herniated intervertebral disc findings could be identified at C6–7 level on C-spine MRI. ACDF C6–7 surgery was performed. Immediately after the operation, physical examination revealed paraplegia and emergency MRI was performed. On MR images, T2 high signal myelopathy suspected as reperfusion injury at C6–7 level, and emergency surgery was performed under diagnosis of white cord syndrome. After the emergency operation, the paraplegic problem was gradually resolved. Before discharge, motor power and sensory deficit of bilateral lower extremity were fully recovered.

Conclusion
Surgeons should explain the possibility of white cord syndrome before cervical decompression surgery and should perform a neurological examination immediately after surgery. We recommend that the importance of early recognition and prompt treatment of white cord syndrome.
Bizarre parosteal osteochondromatous proliferation co-occurring with a metatarsal fatigue fracture: a case report
Authors: Yao Ruoyu , Goh En Lin , Fan Zhaoxiang , Wu Xuequn , Feng Yanqi 
Published: March 2020

Abstract
Background
Bizarre parosteal osteochondromatous proliferation (BPOP) is a relatively rare benign extraperiosteal osteochondroma-like proliferative lesion that shares similarities with malignant tumours in terms of morphology. The aetiology of BPOP has yet to be determined and there are no previous reports of BPOP associated with fracture.

Case presentation
A 57-year-old woman presented with a one-month history of pain and swelling in her right foot, which were worsened by activity and improved with rest. Physical examination revealed a hard, non-mobile mass measuring 1.5 cm × 1.5 cm on the dorsal aspect of the third metatarsal of the right foot. There was overlying erythema and tenderness on palpation. Computed tomography (CT) of the right foot demonstrated a fracture of the neck of the third metatarsal, osteolysis at the fracture site and soft tissue swelling. Bone scintigraphy revealed increased tracer uptake suggesting abnormal bone metabolism at the neck of the third metatarsal. Surgical excision of the lesion was performed. Histopathology and immunohistochemistry confirmed the diagnosis of BPOP.

Conclusion
BPOP is a rare benign lesion that is commonly misdiagnosed. Differential diagnosis is mainly achieved through imaging and histopathological assessment.
Free vitamin D correlate better with bone mineral density and thoracolumbar junction osteoporotic vertebral fractures than serum vitamin D
Authors: chhantyal Kishor , He Lei , Mo Jian , Yin Mingyu , He Tianwei , Chen Yuyong , Yang Yang , Zhang Liangming , Rong Limin 
Published: March 2020

Abstract
Background
Vitamin D deficiency has long been studied as a risk factor for osteoporosis. However, the association between serum vitamin D status, bone mineral density (BMD) and the incidence of vertebral fractures (OVFs) remain controversial. It is believed that free portion of the circulating vitamin D carries the metabolic activities of vitamin D. Therefore, the aim of the present study is to analyse if free vitamin D correlates with BMD and osteoporotic fragile vertebral fractures in the elderly population.

Methods
A total of 90 consecutive patients, including 81 female and 9 male patients, aged > 48 years, were included in this cross sectional study between March and July of 2018. Total vitamin D (total 25(OH)D), free vitamin D (free 25(OH)D), calcium and phosphorus were measured. BMD was measured using dual energy X-ray absorptiometry (DEXA) and osteoporotic vertebral fracture was assessed using plain radiograph. Multiple linear regression was performed to find out the association between total vitamin D, free vitamin D and BMD at various sites. To evaluate the association with osteoporotic vertebral multivariate logistic regression model was used.

Results
The mean total vitamin D and free vitamin D were 25.1 ± 10.2 and 6.1 ± 1.7 respectively. Free vitamin D had a linear correlation with total vitamin D (R2 = 0.69). While free vitamin D had a positive correlation with lumbar BMD roles (p < 0.05), total vitamin D didn’t have any association with BMD at any site. Of the total patients, 62 patients (68.9%) had thoracolumbar junction OVFs. Free vitamin D level correlated with the prevalence of OVFs as well as lumbar osteoporosis (p < 0.05). However, there was no statistical correlation between serum vitamin D status and the OVFs.

Conclusions
Free vitamin D was significantly related to the occurrence of thoracolumbar junction OVFs and lumbar BMD, which assumed to be a positive predictor for fracture and osteoporosis prevention. However, total serum vitamin D levels did not have any association with BMD at different sites as well as fragile vertebral fracture.

Trial registration
The study is registered at clinicaltrials.gov NCT03605173.
Methodology of the health economic evaluation of the Feel4Diabetes-study
Authors:   on behalf of the Feel4Diabetes research group, Willems Ruben , Pil Lore , Lambrinou Christina-Paulina , Kivelä Jemina , Wikström Katja , Gonzalez-Gil Esther M. , De Miguel-Etayo Pilar , Nánási Anna , Semánová Csilla , Van Stappen Vicky , Cardon Greet , Tsochev Kaloyan , Iotova Violeta , Chakarova Nevena , Makrilakis Konstantinos , Dafoulas George , Timpel Patrick , Schwarz Peter , Manios Yannis , Annemans Lieven 
Published: March 2020

AbstractBackgroundThe clinical and economic burden of type 2 diabetes mellitus on society is rising. Effective and efficient preventive measures may stop the increasing prevalence, given that type 2 diabetes mellitus is mainly a lifestyle-driven disease. The Feel4Diabetes-study aimed to tackle unhealthy lifestyle (unhealthy diet, lack of physical activity, sedentary behaviour, and excess weight) of families with a child in the first grades of elementary school. These schools were located in regions with a relatively low socio-economic status in Belgium, Bulgaria, Finland, Greece, Hungary and Spain. Special attention was paid to families with a high risk of developing type 2 diabetes mellitus.MethodsThe aim of this paper is to describe the detailed methodology of the intervention’s cost-effectiveness analysis. Based on the health economic evaluation of the Toybox-study, both a decision analytic part and a Markov model have been designed to assess the long-term (time horizon of 70 year with one-year cycles) intervention’s value for money. Data sources used for the calculation of health state incidences, transition probabilities between health states, health state costs, and health state utilities are listed. Intervention-related costs were collected by questionnaires and diaries, and attributed to either all families or high risk families only.ConclusionsThe optimal use of limited resources is pivotal. The future results of the health economic evaluation of the Feel4Diabetes-study will contribute to the efficient use of those resources.
When a child dies: a systematic review of well-defined parent-focused bereavement interventions and their alignment with grief- and loss theories
Authors: Kochen Eline M. , Jenken Floor , Boelen Paul A. , Deben Laura M. A. , Fahner Jurrianne C. , van den Hoogen Agnes , Teunissen Saskia C. C. M. , Geleijns Karin , Kars Marijke C. 
Published: March 2020

AbstractBackgroundThe availability of interventions for bereaved parents have increased. However, most are practice based. To enhance the implementation of bereavement care for parents, an overview of interventions which are replicable and evidence-based are needed. The aim of this review is to provide an overview of well-defined bereavement interventions, focused on the parents, and delivered by regular health care professionals. Also, we explore the alignment between the interventions identified and the concepts contained in theories on grief in order to determine their theoretical evidence base.MethodA systematic review was conducted using the methods PALETTE and PRISMA. The search was conducted in MEDLINE, Embase, and CINAHL. We included articles containing well-defined, replicable, paediatric bereavement interventions, focused on the parent, and performed by regular health care professionals. We excluded interventions on pathological grief, or interventions performed by healthcare professionals specialised in bereavement care. Quality appraisal was evaluated using the risk of bias, adapted risk of bias, or COREQ. In order to facilitate the evaluation of any theoretical foundation, a synthesis of ten theories about grief and loss was developed showing five key concepts: anticipatory grief, working models or plans, appraisal processes, coping, and continuing bonds.ResultsTwenty-one articles were included, describing fifteen interventions. Five overarching components of intervention were identified covering the content of all interventions. These were: the acknowledgement of parenthood and the child’s life; establishing keepsakes; follow-up contact; education and information, and; remembrance activities. The studies reported mainly on how to conduct, and experiences with, the interventions, but not on their effectiveness. Since most interventions lacked empirical evidence, they were evaluated against the key theoretical concepts which showed that all the components of intervention had a theoretical base.ConclusionsIn the absence of empirical evidence supporting the effectiveness of most interventions, their alignment with theoretical components shows support for most interventions on a conceptual level. Parents should be presented with a range of interventions, covered by a variety of theoretical components, and aimed at supporting different needs. Bereavement interventions should focus more on the continuous process of the transition parents experience in readjusting to a new reality.Trial registrationThis systematic review was registered in Prospero (registration number:CRD42019119241).
First referral to an integrated onco-palliative care program: a retrospective analysis of its timing
Authors: Barth Claire , Colombet Isabelle , Montheil Vincent , Huillard Olivier , Boudou-Rouquette Pascaline , Tlemsani Camille , Alexandre Jérôme , Goldwasser François , Vinant Pascale 
Published: March 2020

Abstract
Background
Palliative care (PC) referral is recommended early in the course of advanced cancer. This study aims to describe, in an integrated onco-palliative care program (IOPC), patient’s profile when first referred to this program, timing of this referral and its impact on the trajectory of care at end-of-life.

Methods
The IOPC combined the weekly onco-palliative meeting (OPM) dedicated to patients with incurable cancer, and/or the clinical evaluation by the PC team. Oncologists can refer to the multidisciplinary board of the OPM the patients for whom goals and organization of care need to be discussed. We analyzed all patients first referred at OPM in 2011–2013. We defined the index of precocity (IP), as the ratio of the time from first referral to death by the time from diagnosis of incurability to death, ranging from 0 (late referral) to 1 (early referral).

Results
Of the 416 patients included, 57% presented with lung, urothelial cancers, or sarcoma. At first referral to IOPC, 76% were receiving antitumoral treatment, 63% were outpatients, 56% had a performance status ≤2 and 46% had a serum albumin level > 35 g/l. The median [1st-3rd quartile] IP was 0.39 [0.16–0.72], ranging between 0.53 [0.20–0.79] (earliest referral, i.e. close to diagnosis of incurability, for lung cancer) to 0.16 [0.07–0.56] (latest referral, i.e. close to death relatively to length of metastatic disease, for prostate cancer). Among 367 decedents, 42 (13%) received antitumoral treatment within 14 days before death, and 157 (43%) died in PC units.

Conclusions
The IOPC is an effective organization to enable early integration of PC and decrease aggressiveness of care near the end-of life. The IP is a useful tool to model the timing of referral to IOPC, while taking into account each cancer types and therapeutic advances.