bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: adult onset diabetes with partial pancreatic agenesis and congenital heart disease due to a de novo GATA6 mutation
Authors: Sanchez-Lechuga Begona , Saqlain Muhammad , Ng Nicholas , Colclough Kevin , Woods Conor , Byrne Maria 
Published: April 2020

AbstractBackgroundMutations in GATA6 are the most frequent cause of pancreatic agenesis. Most cases present with neonatal diabetes mellitus.Case presentationThe case was a female born after an uncomplicated pregnancy and delivery in a non-consanguineous family (3.59 kg, 70th percentile). Severe cardiac malformations were diagnosed at two and a half months old. No hyperglycaemic episodes were recorded in the neonatal period. Diabetes was diagnosed at 21 years due to the detection of incidental glycosuria. She had a low but detectable C-peptide level at diagnosis. Anti-GAD and Islet-cell antibodies were negative and she failed oral hypoglycaemic therapy and was started on insulin. Abdominal MRI revealed the absence of most of the neck, body, and tail of pancreas with normal pancreas elastase levels. Criteria for type 1 or type 2 diabetes were not fulfilled, therefore a next generation sequencing (NGS) panel was performed. A novel heterozygous pathogenic GATA6 mutation (p.Tyr235Ter) was identified. The GATA6 variant was not detected in her parents, implying that the mutation had arisen de novo in the proband.ConclusionRarely GATA6 mutations can cause adult onset diabetes. This report highlights the importance of screening the GATA6 gene in patients with adult-onset diabetes, congenital cardiac defects and pancreatic agenesis with no first-degree family history of diabetes. It also emphasizes the importance of genetic counselling in these patients as future offspring will be at risk of inheriting the variant and developing GATA6 anomalies.
Synergistic enhancement of efficacy of platinum drugs with verteporfin in ovarian cancer cells
Authors: Dasari Venkata Ramesh , Carey David J. , Gogoi Radhika 
Published: April 2020

AbstractBackgroundEpithelial ovarian cancers (EOCs) comprises the majority of malignant ovarian neoplasms. Combination treatment with chemotherapeutic agents seems to be a promising strategy in ovarian cancer (OVCA) patients in order to overcome drug resistance. In this in vitro study, we investigated the therapeutic efficacy of verteporfin (VP) alone and in combination with cisplatin (CDDP), carboplatin (CP) and paclitaxel (Taxol). The main objectives of this study are to determine the nature of interactions between VP and CDDP/CP/Taxol and to understand the mechanism of action of VP in OVCA cells.MethodsThe efficacy of VP on cell proliferation, cytotoxicity, invasion and clonogenic capacity was assayed in CDDP-sensitive (COV504, OV-90) and CDDP-resistant (A2780Cis) cell lines. The cytotoxic effects of drugs either alone or in combination were evaluated using MTT assay and Cell Viability Blue assay. The effects of drugs on the metabolic functions were studied using matrigel invasion assay and clonogenic assay. Immunoblot analysis was carried out to investigate changes in YAP and cell cycle genes. Changes in the cytokines due to drug treatments were analyzed using a cytokine array.ResultsTreatment with VP inhibited cell proliferation, invasion and increased cytotoxicity of OVCA cells. We observed that VP chemosensitized CDDP-resistant cells, even at lower doses. When added either in constant or non-constant ratios, VP produced synergistic effects in combination with CDDP/CP/Taxol. A cytokine array identified upregulation of cytokines in OVCA cells that were inhibited by VP treatment.ConclusionsEither in cisplatin-resistant cell lines or cisplatin-sensitive cell lines, VP proves to be more efficient in inhibiting cell proliferation and inducing cytotoxicity. Our results suggest that novel combinations of VP with CDDP or CP or Taxol might be an attractive therapeutic strategy to enhance OVCA chemosensitivity. The fact that lower doses of VP are effective in chemosensitizing the CDDP-resistant cells, might ultimately lead to the development of an innovative combination therapy for the treatment of OVCA patients.
Clinical performance evaluation of the Idylla™ EGFR Mutation Test on formalin-fixed paraffin-embedded tissue of non-small cell lung cancer
Authors: Delgado-García Mercedes , Weynand Birgit , Gómez-Izquierdo Lourdes , Hernández María José , Blanco Ángela María , Varela Mar , Matias-Guiu Xavier , Nadal Ernest , Márquez-Lobo Bélgica , Alarcão Ana , de Álava Enrique , Biscuola Michele 
Published: April 2020

AbstractBackgroundDetection of epidermal growth factor receptor (EGFR)mutations in exons 18–21 is recommended in all patients with advanced Non-small-cell lung carcinoma due to the demonstrated efficiency of the standard therapy with tyrosine kinase inhibitors inEGFR-mutated patients. Therefore, choosing a suitable technique to testEGFRmutational status is crucial to warrant a valid result in a short turnaround time using the lowest possible amount of tissue material.The Idylla™EGFRMutation Test is a simple, fast and reliable method designed for the detection ofEGFRmutations from formalin-fixed paraffin-embedded samples.The aim of this study was the Clinical Performace Evaluation of the Idylla™ EGFR Mutation Test on the Idylla™ System.MethodsEGFRmutational status was determined on 132 archived formalin-fixed paraffin-embedded tissue sections with Idylla™ technology. Results were compared with the results previously obtained by routine method in the reference lab (Therascreen®EGFRRGQ PCR v2, Qiagen in Molecular Pathology lab, Hospital Universitario Virgen del Rocío de Sevilla).ResultsThe overall agreement between results obtained with the Idylla™EGFRMutation Test and the Comparator test method was 95.38% (with 1-sided 95% lower limit of 91.7%) showing Positive Diagnostic Agreement of 93.22% and Negative Diagnostic Agreement of 97.18%, with a Limit Of Detection ≤5%.ConclusionsThe Idylla™EGFRMutation Test passed its clinical validity performance characteristics for accuracy.
Value of digital mammography in predicting lymphovascular invasion of breast cancer
Authors: Liu Zhuangsheng , Li Ruqiong , Liang Keming , Chen Junhao , Chen Xiangmeng , Li Xiaoping , Li Ronggang , Zhang Xin , Yi Lilei , Long Wansheng 
Published: April 2020

Abstract
Background
Lymphovascular invasion (LVI) has never been revealed by preoperative scans. It is necessary to use digital mammography in predicting LVI in patients with breast cancer preoperatively.

Methods
Overall 122 cases of invasive ductal carcinoma diagnosed between May 2017 and September 2018 were enrolled and assigned into the LVI positive group (n = 42) and the LVI negative group (n = 80). Independent t-test and χ2 test were performed.

Results
Difference in Ki-67 between the two groups was statistically significant (P = 0.012). Differences in interstitial edema (P = 0.013) and skin thickening (P = 0.000) were statistically significant between the two groups. Multiple factor analysis showed that there were three independent risk factors for LVI: interstitial edema (odds ratio [OR] = 12.610; 95% confidence interval [CI]: 1.061–149.922; P = 0.045), blurring of subcutaneous fat (OR = 0.081; 95% CI: 0.012–0.645; P = 0.017) and skin thickening (OR = 9.041; 95% CI: 2.553–32.022; P = 0.001).

Conclusions
Interstitial edema, blurring of subcutaneous fat, and skin thickening are independent risk factors for LVI. The specificity of LVI prediction is as high as 98.8% when the three are used together.
“Objectively terrifying”: a qualitative study of youth’s experiences of transitions out of child and adolescent mental health services at age 18
Authors: Cleverley Kristin , Lenters Lindsey , McCann Emma 
Published: April 2020

Abstract
Background
Mental health issues presenting in childhood often persist into adulthood, usually requiring youth to transition from child and adolescent mental health services to adult mental health services at 18 years. Discontinuity of care during this transition period is well-documented and can leave youth vulnerable to adverse mental health outcomes. There is growing recognition of the need to improve transition-related care for youth leaving the child and adolescent mental health system. However, the perspectives and experiences of youth have not always been forefront in these discussions, and in particular, the perspectives of youth in the pre-transition period. This study qualitatively explores transition-related knowledge and experiences of youth both prior-to and after transition.

Methods
A purposive sample of youth aged 16–19 years was recruited from two child and adolescent mental health programs. Youth were enrolled as part of a longitudinal follow-up study and had the opportunity to opt into this study. Interviews were transcribed and coded using NVivo11 software. Main themes were distilled through descriptive analysis following the principles of directed content analysis. The study followed the principles of participatory action research, engaging youth with lived experience navigating transitions in each stage of the study.

Results
In-depth, semi-structured interviews were conducted with 14 pre-transition and 8 post-transition youth. All youth reported having either a mood and/or anxiety disorder for which the majority were receiving treatment at the time of the interview. The participants’ experiences were distilled into six major themes. Youth advocated for being considered partners in transition planning and to have increased control over transition-related decisions. Youth also made specific recommendations on how to improve continuity of care during the transition process.

Conclusions
Transition planning should be individualized for each youth based on their developmental needs, transition readiness and ongoing mental health needs. Transition pathways, co-designed with youth and caregivers, should be developed to guide providers in transition best practices. Obtaining both the pre- and post-transition experiences of youth is crucial for developing a more complete of understanding of youth perspectives and implementing guidelines that improve transition quality and experiences.
Exposure to ambient fine particulate matter is associated with changes in fasting glucose and lipid profiles: a nationwide cohort study
Authors: Shin Woo-young , Kim Jung-ha , Lee Gyeongsil , Choi Seulggie , Kim Seong Rae , Hong Yun-Chul , Park Sang Min 
Published: April 2020

Abstract
Background
Ambient fine particulate matter is a rising concern for global public health. It was recently suggested that exposure to fine particulate matter may contribute to the development of diabetes and dyslipidaemia. This study aims to examine the potential associations of ambient particulate matter exposure with changes in fasting glucose and lipid profiles in Koreans.

Method
We used the data from the National Health Insurance Service–National Sample Cohort (NHIS-NSC), a nationwide database representative of the Korean population. A total of 85,869 individuals aged ≥20 years were included. Multiple regression analyses were conducted to assess the associations between exposure to particulate matter and changes in fasting glucose and lipid profiles at 2-year intervals after adjusting for confounders.

Results
Significant associations were observed between an increase in interquartile range for particulate matter < 2.5 μm in diameter (PM2.5) and elevated levels of fasting glucose and low-density lipoprotein cholesterol (p for trend = 0.015 and 0.010, respectively), while no association for particulate matter sized 2.5–10 μm in diameter (PM10–2.5) was noted after adjusting for the other covariates. Sub-group analyses showed stronger associations in individuals who were older (≥60 years) or physically inactive.

Conclusions
Fine particulate matter exposure affects worsening fasting glucose and low-density lipoprotein cholesterol levels, with no evidence of an association for coarse particulate matter.
Child and adolescent injury burden in the eastern mediterranean region: Findings from the Global Burden of Disease 1990-2017
Authors: Al-Hajj Samar , El Bcheraoui Charbel , Daoud Farah , Khalil Ibrahim , Moradi-Lakeh Maziar , Abu-Raddad Laith J. , Hamadeh Randa R. , Mokdad Ali 
Published: April 2020

AbstractBackgroundChild and adolescent injury is one of the leading causes of child death globally with a large proportion occurring in Low- and Middle-Income Countries (LMICs). Similarly, the Eastern Mediterranean Region (EMR) countries borne a heavy burden that largely impact child and adolescent safety and health in the region. We aim to assess child and adolescent injury morbidity and mortality and estimate its burden in the Eastern Mediterranean Region based on findings from the Global Burden of Disease (GBD), Injuries and Risk Factors study 2017.MethodsData from the Global Burden of Disease GBD 2017 were used to estimate injury mortality for children aged 0–19, Years of Life Lost (YLLs), Years lived with Disability (YLDs) and Disability Adjusted Life Years (DALYs) by age and sex from 1990 to 2017.ResultsIn 2017, an estimated 133,117 (95% UI 122,587-143,361) children died in EMR compared to 707,755 (95% UI 674401.6–738,166.6) globally. The highest rate of injury deaths was reported in Syria at 183.7 (95% UI 181.8–185.7) per 100,000 population. The leading cause of injury deaths was self-harm and interpersonal violence followed by transport injury. The primary cause of injury DALYs in EMR in 2017 was self-harm and interpersonal violence with a rate of 1272.95 (95% UI 1228.9 – 1319.2) almost 3-times the global rate.ConclusionAlmost 19% of global child injury related deaths occur in the EMR. Concerted efforts should be integrated to inform policies and adopt injury preventive strategies to reduce injury burden and promote child and adolescent health and well-being in EMR countries.
Does the medical insurance system really achieved the effect of poverty alleviation for the middle-aged and elderly people in China? Characteristics of vulnerable groups and failure links
Authors: Ma Meiyan , Li Ye , Wang Nianshi , Wu Qunhong , Shan Linghan , Jiao Mingli , Fu Xuelian , Li Heng , Sun Tao , Yi Bin , Tian Wanxin , Xia Qi , Shi Baoguo , Hao Yanhua , Yin Hui , Ning Ning , Gao Lijun , Liang Libo , Wang Jiahui 
Published: April 2020

Abstract
Background
We examined the physiological, household, and spatial agglomeration characteristics of the health poverty population in China. We identified weak links that affect the implementation of the medical insurance and further improve its effectiveness for health poverty alleviation.

Methods
A national representative sample from the China Health and Retirement Longitudinal Study (CHARLS) was analyzed. The WHO recommended method was adopted to calculate catastrophic health expenditure (CHE) and impoverishment by medical expenses (IME). We created a binary indicator for IME as the outcome variable and applied the treatment-effect model to analyze the determinants of IME.

Results
The incidence of IME was 7.2% of the overall population, compared to 20.3% of the sample households trapped in CHE. The incidence of IME enrolled in insurance schemes was 7.4% higher than that of uninsured families (4.8%). Economic level, living area, family size, age of household head, having hospitalized members, and participating in insurance were statistically significant for the occurrence of IME.

Conclusions
The original poverty-promoting policies has not reached the maximum point of convergence with China’s current demand for health. The overlapped health vulnerabilities exacerbated the risk of poverty among the elderly and households with high health needs and utilization. In addition, the medical insurance schemes have proven to be insufficient for protection against economic burden of poor households. So, special health needs, age, and household capacity to pay should be comprehensively considered while strengthening the connection between the disease insurance scheme with supplementary insurance.
The effect of cash transfers on mental health – new evidence from South Africa
Authors: Ohrnberger Julius , Fichera Eleonora , Sutton Matt , Anselmi Laura 
Published: April 2020

Abstract
Background
Mental health and poverty are strongly interlinked. There is a gap in the literature on the effects of poverty alleviation programmes on mental health. We aim to fill this gap by studying the effect of an exogenous income shock generated by the Child Support Grant, South Africa’s largest Unconditional Cash Transfer (UCT) programme, on mental health.

Methods
We use biennial data on 10,925 individuals from the National Income Dynamics Study between 2008 and 2014. We exploit the programme’s eligibility criteria to estimate instrumental variable Fixed Effects models.

Results
We find that receiving the Child Support Grant improves adult mental health by 0.822 points (on a 0–30 scale), 4.1% of the sample mean.

Conclusion
Our findings show that UCT programmes have strong mental health benefits for the poor adult population.
Determinants of empirical antipseudomonal antibiotic prescription for adults with pneumonia in the emergency department
Authors: Angrill Nuria , Gallego Miguel , Font Juli , Vallés Jordi , Morón Anisi , Monsó Eduard , Rello Jordi 
Published: April 2020

Abstract
Background
Antipseudomonal antibiotics should be restricted to patients at risk of Pseudomonas aeruginosa infection. However, the indications in different guidelines on community-acquired pneumonia (CAP) are discordant. Our objectives were to assess the prevalence of antipseudomonal antibiotic prescriptions and to identify determinants of empirical antibiotic choices in the emergency department.

Methods
Observational, retrospective, one-year cohort study in hospitalized adults with pneumonia. Antibiotic choices and clinical and demographic data were recorded on a standardized form. Antibiotics with antipseudomonal activity were classified into two groups: a) β-lactam antipseudomonals (β-APS), including carbapenems, piperacillin / tazobactam or cefepime (in monotherapy or combination) and b) monotherapy with antipseudomonal quinolones.

Results
Data were recorded from 549 adults with pneumonia, with Pseudomonas aeruginosa being isolated in only nine (1.6%). Most (85%) prescriptions were compliant with SEPAR guidelines and 207 (37%) patients received antibiotics with antipseudomonal activity (14% β-APS and 23% levofloxacin). The use of β-APS was independently associated with ICU admission (OR 8.16 95% CI 3.69–18.06) and prior hospitalization (OR 6.76 95% CI 3.02–15.15), while levofloxacin was associated with negative pneumococcal urine antigen tests (OR 3.41 95% CI 1.70–6.85) but negatively associated with ICU admission (OR 0.26 95% CI 0.08–0.86). None of these factors were associated with P aeruginosa episodes. In univariate analysis, prior P aeruginosa infection/colonization (2/9 vs 6/372, p = 0.013), severe COPD (3/9 vs 26/372, p = 0.024), multilobar involvement (7/9 vs 119/372, p = 0.007) and prior antibiotic (6/9 vs 109/372, p = 0.025) were significantly associated with P aeruginosa episodes.

Conclusions
Antipseudomonal prescriptions were common, in spite of the very low incidence of Pseudomonas aeruginosa. The rationale for prescription was influenced by both severity-of-illness and pneumococcal urine antigen test (levofloxacin) and prior hospitalization and ICU admission (β-APS). However, these factors were not associated with P aeruginosa episodes. Only prior P aeruginosa infection/colonization and severe COPD seem to be reliable indicators in clinical practice.
Comprehensive genomic profiling aids in understanding the lesion origins of a patient with six synchronous invasive lung adenocarcinomas: a case study
Authors: Song Yang , Jia Ziqi , Wu Pancheng , Wang Weiwei , Ou Qiuxiang , Bao Hua , Yu Man , Wu Xue , Liu Peng , Liang Naixin , Zhang Shuyang , Li Shanqing 
Published: April 2020

Abstract
Background
Synchronous multiple primary lung cancers (sMPLC) are rare forms of lung cancer, and their diagnosis remains as a significant challenge. Distinguishing sMPLC from advanced disease is important as their prognoses and therapeutic management vary dramatically.

Case presentation
The patient was a 56-year-old Chinese male who exhibited six synchronous invasive adenocarcinomas at diagnosis [T2(6)N0M0], and who achieved durable clinical benefit under adjuvant chemotherapy for 41 months following wedge resection and lobectomy. Whole-exome sequencing revealed that two lesions (L4 and L6) in the left upper lobe of the patient’s lung shared 28 nonsynonymous mutations; thus, suggesting that the lesions may have arisen from a common ancestor at the early stages of tumorigenesis, and spread into distinct histologic subtypes. Moreover, while L5 was in the same lobe as L4 and L6, it represented a distinct lineage as it did not share any mutations with other lesions. Notably, the BRAF V600E oncogenic mutation was exclusive to L5. In addition, the KRAS G12C mutation was identified in three lesions (L1-L3) located in the right lung, which may have resulted from convergent evolution.

Conclusion
We report a patient with six synchronous invasive adenocarcinomas who demonstrated durable clinical benefits under adjuvant chemotherapy following surgical treatment. While cancer staging is one of the many challenges associated with sMPLC, the data generated through next-generation sequencing can provide information on lesion origins, and thus, advance the era of precision medicine.
Surgical management of bilateral hip fractures in a patient with fibrodysplasia ossificans progressiva treated with the RAR-γ agonist palovarotene: a case report
Authors: Singh Sukhmani , Kidane Joseph , Wentworth Kelly L. , Motamedi Daria , Morshed Saam , Schober Andrew E. , Hsiao Edward C. 
Published: April 2020

Abstract
Background
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder marked by painful, recurrent flare-ups and heterotopic ossification (HO) in soft and connective tissues, which can be idiopathic or provoked by trauma, illness, inflammation, or surgery. There are currently no effective treatments for FOP, or for patients with FOP who must undergo surgery. Palovarotene, an investigational retinoic acid receptor-γ agonist, offers a potential avenue to prevent HO formation.

Case presentation
The patient is a 32 year-old male, who at age 29 enrolled in a study evaluating palovarotene to prevent HO formation in FOP. One year after starting palovarotene, he fell resulting in a left intertrochanteric fracture. He underwent intramedullary nailing of the femur shaft with screw placement at the distal femur. After surgery, he received palovarotene at 20 mg/day for 4 weeks, then 10 mg/day for 8 weeks. Imaging 12 weeks after surgery showed new bridging HO at the site of intramedullary rod insertion and distal screw.
Nine months after the left hip fracture, the patient had a second fall resulting in a subdural hematoma, left parietal bone fracture, and right intertrochanteric fracture. He underwent intramedullary nailing of the right hip, in a modified procedure which did not require distal screw placement. Palovarotene 20 mg/day was started at fracture occurrence and continued for 4 weeks, then reduced to 10 mg/day for 8 weeks. HO also formed near the insertion site of the intramedullary rod. No HO developed at the right distal intramedullary rod. After each fracture, the patient had prolonged recurrent flare-ups around the hips.

Conclusion
Surgery is only rarely considered in FOP due to the high risks of procedural complications and potential for inducing HO. This case emphasizes the risks of increased flare activity and HO formation from injury and surgery in patients with FOP. The efficacy of HO prevention by palovarotene could not be assessed; however, our observation that palovarotene can be administered in an individual with FOP following surgery with no negative impact on clinical fracture healing, osteointegration, or skin healing will help facilitate future trials testing the role of palovarotene as a therapy for HO.