bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicentre, phase II study of eribulin in combination with S-1 in patients with advanced breast cancer
Authors: Iwasa Tsutomu , Tsurutani Junji , Watanabe Satomi , Kato Ryoji , Mizuno Yutaka , Kojima Yasuyuki , Takashima Tsutomu , Matsunami Nobuki , Morimoto Takashi , Yamamura Jun , Ohtani Shoichiro , Tanabe Yuko , Yoshinami Tetsuhiro , Takano Toshimi , Komoike Yoshifumi , Nakagawa Kazuhiko
Published: October 2019

Background

We previously reported the synergistic effect of S-1 and eribulin in preclinical models. In addition, our phase I study revealed the recommended dose for the phase II study of the combination therapy in advanced breast cancer (ABC) patients pre-treated with anthracycline and taxane. Our current study reports on the efficacy and safety of the combined use of eribulin and S-1 in patients with ABC and poor prognosis.

Methods

Patients with breast cancer who received prior anthracycline- and/or taxane-based therapy were assigned to receive a combination therapy of eribulin (1.4 mg/m2 on days 1 and 8, every 21 days) and S-1 (65 mg/m2, on days 1 to 14, every 21 days) for advanced/metastatic disease. All patients had at least one clinicopathological factor such as being oestrogen receptor negative, Human Epidermal Growth Factor Receptor 2 (HER2) receptor negative, presence of visceral involvement, presence of three or more metastatic sites, or having a disease-free interval shorter than 2 years. The primary endpoint was the independent-reviewer assessed objective response rate (ORR). Secondary endpoints were clinical benefit rate, disease control rate, progression-free survival (PFS), and overall survival (OS).

Results

This study enrolled 33 patients. Confirmed ORR was 33.3% (95% CI: 17.3 to 52.8). Median PFS was 7.5 months (95% CI: 4.0 to 14.3). Median OS time was not reached during the current experimental periods. The most common grade 3/4 adverse event was neutropenia (68.8%).

Conclusions

The combination of eribulin and S-1 is safe and effective for treatment in patients with ABC and poor prognosis.

Trial registration

Current Controlled Trials UMIN000015049, date of registration: September 5th 2014.
Poorly differentiated neuroendocrine rectal carcinoma with uncommon immune-histochemical features and clinical presentation with a subcutaneous metastasis, treated with first line intensive triplet chemotherapy plus bevacizumab FIr-B/FOx regimen: an experience of multidisciplinary management in clinical practice
Authors:   on behalf of Oncology Network ASL1 Abruzzo, Bruera Gemma , Giuliani Antonio , Romano Lucia , Chiominto Alessandro , Di Sibio Alessandra , Mastropietro Stefania , Cosenza Pierluigi , Ricevuto Enrico , Schietroma Mario , Carlei Francesco
Published: October 2019

Background

Neuroendocrine tumors (NETs) are heterogeneous, widely distributed tumors arising from neuroendocrine cells. Gastrointestinal (GI)-NETs are the most common and NETs of the rectum represent 15, 2% of gastrointestinal malignancies. Poorly differentiated neuroendocrine carcinomas of the GI tract are uncommon. We report a rare case of poorly differentiated locally advanced rectal neuroendocrine carcinoma with nodal and a subcutaneous metastasis, with a cytoplasmic staining positive for Synaptophysin and Thyroid Transcription Factor-1.

Case presentation

A 72-year-old male presented to hospital, due to lumbar, abdominal, perineal pain, and severe constipation. A whole-body computed tomography scan showed a mass of the right lateral wall of the rectum, determining significant reduction of lumen caliber. It also showed a subcutaneous metastasis of the posterior abdominal wall. Patient underwent a multidisciplinary evaluation, diagnostic and therapeutic plan was shared and defined. The pathological examination of rectal biopsy and subcutaneous nodule revealed features consistent with small-cell poorly differentiated neuroendocrine carcinoma. First line medical treatment with triplet chemotherapy and bevacizumab, according to FIr-B/FOx intensive regimen, administered for the first time in this young elderly patient affected by metastatic rectal NEC was highly active and tolerable, as previously reported in metastatic colo-rectal carcinoma (MCRC). A consistent rapid improvement in clinical conditions were observed during treatment. After 6 cycles of treatment, CT scan and endoscopic evaluation showed clinical complete response of rectal mass and lymph nodes; patient underwent curative surgery confirming the pathologic complete response at PFS 9 months.

Discussion and conclusions

This case report of a locally advanced rectal NEC with an unusual subcutaneous metastasis deserves further investigation of triplet chemotherapy-based intensive regimens in metastatic GEP NEC.
STAT3 induces G9a to exacerbate HER3 expression for the survival of epidermal growth factor receptor-tyrosine kinase inhibitors in lung cancers
Authors: Chang Yi-Fang , Lim Ken-Hong , Chiang Ya-Wen , Sie Zong-Lin , Chang Jungshan , Ho Ai-Sheng , Cheng Chun-Chia
Published: October 2019

Background

HER3 mediates drug resistance against epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), resulting in tumor relapse in lung cancers. Previously, we demonstrated that EGFR induces HER3 overexpression, which facilitates the formation of cancer stem-like tumorspheres. However, the cellular mechanism through which EGFR regulates HER3 expression remains unclear. We hypothesized that EGFR downstream of STAT3 participates in HER3 expression because STAT3 contributes to cancer stemness and survival of EGFR-TKI resistant cancers.

Methods

First, RNAseq was used to uncover potential genes involved in the formation of lung cancer HCC827-derived stem-like tumorspheres. EGFR-positive lung cancer cell lines, including HCC827, A549, and H1975, were individually treated with a panel containing 172 therapeutic agents targeting stem cell-associated genes to search for potential agents that could be applied against EGFR-positive lung cancers. In addition, gene knockdown and RNAseq were used to investigate molecular mechanisms through which STAT3 regulates tumor progression and the survival in lung cancer.

Results

BBI608, a STAT3 inhibitor, was a potential therapeutic agent that reduced the cell viability of EGFR-positive lung cancer cell lines. Notably, the inhibitory effects of BBI608 were similar with those associated with YM155, an ILF3 inhibitor. Both compounds reduced G9a-mediated HER3 expression. We also demonstrated that STAT3 upregulated G9a to silence miR-145-5p, which exacerbated HER3 expression in this study.

Conclusions

The present study revealed that BBI608 could eradicate EGFR-positive lung cancers and demonstrated that STAT3 enhanced the expression of HER3 through miR-145-5p repression by G9a, indicating that STAT3 is a reliable therapeutic target against EGFR-TKI-resistant lung cancers.
Correction to: Running on a high: parkrun and personal well-being
Authors: Grunseit Anne , Richards Justin , Merom Dafna
Published: October 2019

It was highlighted that the original article [1] contained an error in the proportions reported in the Results, at the Representativeness of registered parkrunners section.
Retroperitoneal abscess with pylephlebitis caused by lumbar acupuncture: a case report
Authors: Lee Hayemin , Sung Kiyoung , Cho Jinbeom
Published: October 2019

Background

Retroperitoneal abscess (RA) is an unusual life-threatening disease that has insidious and occult presentations. Although the incidence of this disease is low, diagnosis and treatment are challenging due to its nonspecific presentation and the complex anatomy of the retroperitoneal space. Recently, we experienced one case of a RA with extensive thrombophlebitis of the portal venous system.

Case presentation

An 80-year-old male presented to the emergency room with symptoms and signs of septic shock; however, the decision making for diagnosis and treatment was difficult, as no clinical and radiological evidence supported key findings regarding the origin of sepsis. Although this patient eventually recovered after surgical drainage, we suggested that more straightforward diagnostic and treatment procedures were required in this patient to avoid possible critical complications. Through a retrospective review of operative findings, patient history, and microbiology, we found that the RA in this patient was caused by lumbar acupuncture, which is usually performed for the management of chronic back pain with long needles.

Conclusion

Early surgical intervention should be considered for RA whenever the patient does not respond to broad-spectrum antibiotic treatment. Acupuncture is a possible cause of otherwise unexplained soft tissue infections, such as RA, especially in Asian countries.
Sustained density of neuroendocrine cells with aging precedes development of prostatic hyperplasia in spontaneously hypertensive rats
Authors: Kyoda Yuki , Ichihara Koji , Hashimoto Kohei , Kobayashi Ko , Fukuta Fumimasa , Masumori Naoya
Published: October 2019

Background

Neuroendocrine (NE) cells may have an impact on the development and initial growth of benign prostatic hyperplasia (BPH) according to previous human studies.

Methods

To explore the relationship of NE cells and BPH development, we compared the density of NE cells and also prostatic weight in spontaneously hypertensive rats (SHR), which develop by aging, and Wistar-Kyoto rats (WKY) as control. The total weights of the epithelium and stroma in the ventral lobes of 8-, 12, 16-, 28- and 56-week-old SHR and WKY were calculated using Image J software. NE cells in the ventral prostatic ducts (VPd) were quantified using immunohistochemical staining for serotonin.

Results

Although there was no significant difference in the estimated total weight of the epithelium and stroma in the ventral lobes adjusted by body weight (ES weight) between the two groups at 8, 12 and 16 weeks of age, ES weight was significantly greater in the SHR group than in the WKT group at 28 and 56 weeks. The density of NE cells in the VPd decreased with aging in the WKY group, whereas it was sustained until 16 weeks and then decreased with aging in the SHR group. The difference in the density between the two groups was most marked at 16 weeks of age.

Conclusion

In the natural history of BPH, NE cells may play an important role in the initial development of BPH because sustained density of NE cells in the VPd precedes the development of prostatic hyperplasia.
Burnout among postgraduate doctors in Colombo: prevalence, associated factors and association with self-reported patient care
Authors: Fernando Beminihennedige Minuri S. , Samaranayake Dulani Lakmali
Published: October 2019

Background

Postgraduate doctors are prone to burnout due to occupational and educational stressors. Sri Lankan situation is unknown. This study determines burnout among postgraduate doctors in Colombo: Prevalence, associated factors, and association with self-reported patient care.

Methods

A cross-sectional study was conducted among 278 postgraduate doctors from eight specialties working in Colombo district, attached to the main postgraduate training institute for medical professionals. A self-administered questionnaire was used. It comprised of the Copenhagen Burnout Inventory and an author-developed questionnaire, which was used to assess, associated factors and self-reported patient care. Prevalence of burnout was calculated. Associations were analysed using chi-square and binary logistic regression.

Results

The response rate was 88.1% (n = 245). The prevalence of personal, work-related and client-related burnout was 41.6% (95% CI = 35.5–47.8%), 30.6% (95% CI = 24.8–36.4%), 8.9% (95% CI = 5.4–12.5%) respectively.

Personal burnout was positively associated with, the trainee being a female, having a chronic disease, being involved in frequent unhealthy habits, having doctor parents, having home–work demands and having emotional demands. It was negatively associated with, having frequent healthy habits, being satisfied with skill development opportunities, and frequent use of deep studying. Work-related burnout was positively associated with, female gender, being involved in frequent unhealthy habits, having home–work demands and having emotional demands. It was negatively associated with, frequent use of deep methods of studying. Client-related burnout was positively associated with having emotional demands and negatively associated with being satisfied with training.

The frequent self-reported, suboptimal patient-care practices: poor communication, poor clinical practice, poor response to patient’s needs and poor communication during handing over were associated positively with client-related burnout.

Conclusions

Most postgraduate doctors in Colombo have high personal and work-related burnout but client-related burnout is less. The factors associated with burnout need to be addressed by the programme managers of the postgraduate courses. Preventive measures should be introduced to reduce burnout among future postgraduate trainees of Colombo.
How do researchers acquire and develop notions of research integrity? A qualitative study among biomedical researchers in Switzerland
Authors: Satalkar Priya , Shaw David
Published: October 2019

Background

Structured training in research integrity, research ethics and responsible conduct of research is one strategy to reduce research misconduct and strengthen reliability of and trust in scientific evidence. However, how researchers develop their sense of integrity is not fully understood. We examined the factors and circumstances that shape researchers’ understanding of research integrity.

Methods

This study draws insights from in-depth, semi-structured interviews with 33 researchers in the life sciences and medicine, representing three seniority levels across five research universities in Switzerland.

Results

The results of this study indicate that early education, moral values inculcated by the family and participation in team sports were the earliest influences on notions of honesty, integrity and fairness among researchers. Researchers’ personality traits, including degree of ambition and internal moral compass, were perceived as critical in determining the importance they attributed to conducting research with high ethical standards. Positive and negative experiences in early research life also had a significant impact on their views regarding research integrity. Two thirds of the study participants had not received any formal training in research integrity. Their awareness of training opportunities at their institutions was also limited.

Conclusion

Age-appropriate development of honesty and integrity starts as early as primary education. Research integrity training should be offered from the bachelors level and continue throughout the entire professional life of researchers. Although these courses may not imbue researchers with integrity itself, they are essential to improving the research culture, reinforcing integrity norms, and discouraging researchers who lack personal integrity from engaging in research misconduct.
Association between physician adoption of a new oral anti-diabetic medication and Medicare and Medicaid drug spending
Authors: Metes Ilinca D. , Xue Lingshu , Chang Chung-Chou H. , Huskamp Haiden A. , Gellad Walid F. , Lo-Ciganic Wei-Hsuan , Choudhry Niteesh K. , Richards-Shubik Seth , Guclu Hasan , Donohue Julie M.
Published: October 2019

Background

In the United States, there is well-documented regional variation in prescription drug spending. However, the specific role of physician adoption of brand name drugs on the variation in patient-level prescription drug spending is still being investigated across a multitude of drug classes. Our study aims to add to the literature by determining the association between physician adoption of a first-in-class anti-diabetic (AD) drug, sitagliptin, and AD drug spending in the Medicare and Medicaid populations in Pennsylvania.

Methods

We obtained physician-level data from QuintilesIMS Xponent™ database for Pennsylvania and constructed county-level measures of time to adoption and share of physicians adopting sitagliptin in its first year post-introduction. We additionally measured total AD drug spending for all Medicare fee-for-service and Part D enrollees (N = 125,264) and all Medicaid (N = 50,836) enrollees with type II diabetes in Pennsylvania for 2011. Finite mixture model regression, adjusting for patient socio-demographic/clinical characteristics, was used to examine the association between physician adoption of sitagliptin and AD drug spending.

Results

Physician adoption of sitagliptin varied from 44 to 99% across the state’s 67 counties. Average per capita AD spending was $1340 (SD $1764) in Medicare and $1291 (SD $1881) in Medicaid. A 10% increase in the share of physicians adopting sitagliptin in a county was associated with a 3.5% (95% CI: 2.0–4.9) and 5.3% (95% CI: 0.3–10.3) increase in drug spending for the Medicare and Medicaid populations, respectively.

Conclusions

In a medication market with many choices, county-level adoption of sitagliptin was positively associated with AD spending in Medicare and Medicaid, two programs with different approaches to formulary management.
Correction to: Increase of catastrophic health expenditure while it does not have socio-economic anymore; finding from a district on Tehran after recent extensive health sector reform
Authors: Kazemi-galougahi Mohammad Hassan , Dadgar Elham , Kavosi Zahra , Majdzadeh Reza
Published: October 2019

In the original publication of this article [1], the title should be revised as blow:
A systematic review and meta-analyses of risk factors associated with lameness in dairy cows
Authors: Oehm Andreas W. , Knubben-Schweizer Gabriela , Rieger Anna , Stoll Alexander , Hartnack Sonja
Published: October 2019

Background

Lameness in dairy cows has been an ongoing concern of great relevance to animal welfare and productivity in modern dairy production. Many studies have examined associations between various factors related to housing, management, and the individual animal and the occurrence of lameness. The objective of this systematic review was to answer the research question “what are risk factors associated with lameness in dairy cows that are housed in free stall barns or tie stall facilities”. Furthermore, we performed a synthesis of current evidence on certain risk factors by means of a meta-analysis to illustrate the strength of their association with bovine lameness.

Results

Following pre-defined procedures and inclusion criteria in accordance with the PRISMA statement, two observers independently included 53 articles out of a pool of 1941 articles which had been retrieved by a broad literature research in a first step. 128 factors that have been associated with lameness were identified in those papers. Meta-analyses were conducted for five factors presented in six different studies: Body condition score, presence of claw overgrowth, days in milk, herd size, and parity. Results indicated that a body condition score of ≤2.5/5 is associated with increased odds of lameness. A higher risk of being lame was found for the presence of claw overgrowth, the first 120 days in milk, larger herd sizes, and increasing parity. Throughout the study, we encountered profound difficulties in retrieving data and information of sufficient quality from primary articles as well as in recovering comparable studies.

Conclusions

We learned that an abundance of literature on bovine lameness exists. To adequately address a problem of this importance to both animal welfare and economic viability, solid evidence is required in the future to develop effective intervention strategies. Therefore, a consistent working definition of lameness and specific risk factors should be an option to consider.
Genome-wide discovery and characterization of long noncoding RNAs in patients with multiple myeloma
Authors: Lu Minqiu , Hu Ying , Wu Yin , Zhou Huixing , Jian Yuan , Tian Ying , Chen Wenming
Published: October 2019

Background

Long noncoding RNAs (lncRNAs) are involved in a wide range of biological processes in tumorigenesis. However, the role of lncRNA expression in the biology, prognosis, and molecular classification of human multiple myeloma (MM) remains unclear, especially the biological functions of the vast majority of lncRNAs. Recently, lncRNAs have been identified in neoplastic hematologic disorders. Evidence has accumulated on the molecular mechanisms of action of lncRNAs, providing insight into their functional roles in tumorigenesis. This study aimed to characterize potential lncRNAs in patients with MM.

Methods

In this study, the whole-transcriptome strand-specific RNA sequencing of samples from three newly diagnosed patients with MM was performed. The whole transcriptome, including lncRNAs, microRNAs, and mRNAs, was analyzed. Using these data, MM lncRNAs were systematically analyzed, and the lncRNAs involved in the occurrence of MM were identified.

Results

The results revealed that MM lncRNAs had distinctive characteristics different from those of other malignant tumors. Further, the functions of a set of lncRNAs preferentially expressed in MM were verified, and several lncRNAs were identified as competing endogenous RNAs. More importantly, the aberrant expression of certain lncRNAs, including maternally expressed gene3, colon cancer–associated transcript1, and coiled-coil domain-containing 26, as well as some novel lncRNAs involved in the occurrence of MM was established. Further, lncRNAs were related to some microRNAs, regulated each other, and participated in MM development.

Conclusions

Genome-wide screening and functional analysis enabled the identification of a set of lncRNAs involved in the occurrence of MM. The interaction exists among microRNAs and lncRNAs.
Histone methyltransferase SUV39H2 regulates cell growth and chemosensitivity in glioma via regulation of hedgehog signaling
Authors: Wang Ran , Cheng Lilin , Yang Xi , Chen Xin , Miao Yifeng , Qiu Yongming , Zhou Zhiyi
Published: October 2019

Background

Malignant glioma is one of the essentially incurable tumors with chemoresistance and tumor recurrence. As a histone methyltransferase, SUV39H2 can trimethylate H3K9. SUV39H2 is highly expressed in many types of human tumors, while the function of SUV39H2 in the development and progression of glioma has never been elucidated.

Methods

RT-qPCR and IHC were used to test SUV39H2 levels in glioma tissues and paired normal tissues. The clinical relevance of SUV39H2 in glioma was analyzed in a public database. Colony formation assays, CCK-8 assays, and flow cytometry were conducted to explore the role of SUV39H2 in the growth of glioma cells in vitro. A cell line-derived xenograft model was applied to explore SUV39H2’s role in U251 cell proliferation in vivo. Sphere formation assays, RT-qPCR, flow cytometry, and IF were conducted to illustrate the role of SUV39H2 in the stemness and chemosensitivity of glioma. Luciferase reporter assays and WB were applied to determine the function of SUV39H2 in Hh signaling.

Results

SUV39H2 was highly expressed in glioma tissues relative to normal tissues. SUV39H2 knockdown inhibited cell proliferation and stemness and promoted the chemosensitivity of glioma cells in vitro. In addition, SUV39H2 knockdown also significantly inhibited glioma cell growth in vivo. Moreover, we further uncovered that SUV39H2 regulated hedgehog signaling by repressing HHIP expression.

Conclusions

Our findings delineate the role of SUV39H2 in glioma cell growth and chemosensitivity as a pivotal regulator of the hedgehog signaling pathway and may support SUV39H2 as a potential target for diagnosis and therapy in glioma management.
The health profile of newly-arrived refugee women and girls and the role of region of origin: using a population-based dataset in California between 2013 and 2017
Authors: Sudhinaraset May , Cabanting Nuny , Ramos Marisa
Published: October 2019

Background

There has been an increasing number of refugee women globally; yet, there is little recent data describing the health profile of refugee women by region of origin in the United States. It is important to monitor the health status of women by region of origin to provide needed targeted interventions.

Methods

We analyzed the Refugee Health Electronic Information System (RHEIS), a population-based dataset that included 14,060 female refugees who entered California between October 3, 2013 and February 15, 2017. We assessed differences in health status by region of origin.

Results

Almost one out of three women experienced a traumatic event. Women from Africa and Latin America and the Caribbean experienced higher levels of trauma compared to other regions, including sexual assault, physical, and weapon assault. More than half of women and girls (56.6%) reported experiences of persecution, with Southeast Asians reporting the highest levels. Among women of reproductive age, 7.0% of women were currently pregnant at the time of arrival to the US, 19.0% ever had a spontaneous abortion, and 8.6% reported ever having an abortion. One in three women from Africa reported female genital cutting. Moreover, 80.0% of women reported needing language assistance at the time of their health assessment.

Conclusions

Refugee women and girls experience high levels of trauma and persecution, suggesting the need for trauma-informed care. Those working with refugee women, such as resettlement agencies and health providers, should be equipped with information about antenatal care, nutrition, and pregnancy to newly arrived women. Lastly, differences in health status by region of origin indicate a need for tailored interventions and linguistically appropriate health information.
The impact of patient-reported outcome (PRO) data from clinical trials: a systematic review and critical analysis
Authors: Rivera Samantha Cruz , Kyte Derek G. , Aiyegbusi Olalekan Lee , Slade Anita L. , McMullan Christel , Calvert Melanie J.
Published: October 2019

Background

Patient-reported outcomes (PROs) are commonly collected in clinical trials and should provide impactful evidence on the effect of interventions on patient symptoms and quality of life. However, it is unclear how PRO impact is currently realised in practice. In addition, the different types of impact associated with PRO trial results, their barriers and facilitators, and appropriate impact metrics are not well defined. Therefore, our objectives were: i) to determine the range of potential impacts from PRO clinical trial data, ii) identify potential PRO impact metrics and iii) identify barriers/facilitators to maximising PRO impact; and iv) to examine real-world evidence of PRO trial data impact based on Research Excellence Framework (REF) impact case studies.

Methods

Two independent investigators searched MEDLINE, EMBASE, CINAHL+, HMIC databases from inception until December 2018. Articles were eligible if they discussed research impact in the context of PRO clinical trial data. In addition, the REF 2014 database was systematically searched. REF impact case studies were included if they incorporated PRO data in a clinical trial.

Results

Thirty-nine publications of eleven thousand four hundred eighty screened met the inclusion criteria. Nine types of PRO trial impact were identified; the most frequent of which centred around PRO data informing clinical decision-making. The included publications identified several barriers and facilitators around PRO trial design, conduct, analysis and report that can hinder or promote the impact of PRO trial data. Sixty-nine out of two hundred nine screened REF 2014 case studies were included. 12 (17%) REF case studies led to demonstrable impact including changes to international guidelines; national guidelines; influencing cost-effectiveness analysis; and influencing drug approvals.

Conclusions

PRO trial data may potentially lead to a range of benefits for patients and society, which can be measured through appropriate impact metrics. However, in practice there is relatively limited evidence demonstrating directly attributable and indirect real world PRO-related research impact. In part, this is due to the wider challenges of measuring the impact of research and PRO-specific issues around design, conduct, analysis and reporting. Adherence to guidelines and multi-stakeholder collaboration is essential to maximise the use of PRO trial data, facilitate impact and minimise research waste.

Trial registration

Systematic Review registration PROSPERO CRD42017067799.
Effects of a reimbursement change and travel times on the delivery of private and public radiology services in Norway: a register-based longitudinal study of Norwegian claims data
Authors: Mokienko Anastasia
Published: October 2019

Background

The variation in the impact of the 2008 reimbursement change for Norwegian radiology providers, depending on the travel times to private and public providers in different municipalities, was examined. The activity-based fund allocation for radiology providers was reduced from approximately 50% to 40%, which was compensated by an increased basic grant. The hypothesis was that the Norwegian population would be affected by the reimbursement change unevenly depending on their distances to different types of the providers.

Methods

The study of the effect of the reimbursement change and travel time difference between private and public radiology providers in Norway (Time_difference) on the number of the services was performed using fixed-effects regressions applied to panel data at the municipality level with monthly observations for the period 2007–2010.

Results

After the reimbursement change, the number of private services decreased more than the number of public services. Private services declined after 2008, but the absolute value of the effect was smaller as the Time_difference became greater. The number of public services increased as the Time_difference grew. The total number of services decreased until the Time_difference was equal to 40 min and increased for time differences greater than 40 min.

Conclusions

The messages for policymakers are as follows. Populations that only had private providers nearby were more affected by the reimbursement change in terms of a reduced number of services. The reimbursement change contributed to the reallocation of patients from private to public providers. The difference between the centralities of municipalities in their consumption patterns was reduced and the difference between different Regional Health Authorities was increased due to the reimbursement change.
PYCR1 interference inhibits cell growth and survival via c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathway in hepatocellular cancer
Authors: Zhuang Juhua , Song Yanan , Ye Ying , He Saifei , Ma Xing , Zhang Miao , Ni Jing , Wang Jiening , Xia Wei
Published: October 2019

Background

Liver cancer is the second leading causes of cancer-related death globally. Pyrroline-5-carboxylate reductase 1 (PYCR1) plays a critical role in metabolic profiles of tumors. Therefore, it is necessary to explore the mechanisms of PYCR1 on cell growth and survival in hepatocellular carcinoma (HCC).

Methods

Protein and mRNA expression levels of PYCR1 in 140 pairs of tumor and adjacent normal liver tissues of HCC patients were analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Expressions of PYCR1 were inhibited in BEL-7404 cells and SMMC-7721 cells using gene interference technology. The cell proliferation was detected by Celigo and MTT assay. The colony formation assay was also performed. The cell apoptosis was measured by flow cytometric assay. The effect of PYCR1 interference on tumor growth was observed by xenograft nude mice assay in vivo. The downstream pathway of PYCR1 interference was searched by microarray and bioinformatics analysis, and validated by qRT-PCR and western blot.

Results

PYCR1 levels were significantly up-regulated in HCC tumor tissues than adjacent normal liver tissues in both protein and mRNA levels (P < 0.01). In vitro, the cell proliferation was significantly slower in shPYCR1 group than shCtrl group in BEL-7404 and SMMC-7721 cells (P < 0.001). The colony number was significantly smaller after PYCR1 interference (P < 0.01). The percentage of apoptosis cells significantly increased in shPYCR1 group (P < 0.01). In vivo, PYCR1 interference could obviously suppress tumor growth in xenograft nude mice. The volume and weight of tumors were significantly smaller via PYCR1 interference. The c-Jun N-terminal kinase (JNK) signaling pathway significantly altered, and insulin receptor substrate 1 (IRS1) were significantly down-regulated by PYCR1 interference in both mRNA and protein levels (P < 0.001).

Conclusion

PYCR1 interference could inhibit cell proliferation and promote cell apoptosis in HCC through regluting JNK/IRS1 pathway. Our study will provide a drug target for HCC therapy and a potential biomarker for its diagnosis or prognosis.
Validation of three mental health scales among pregnant women in Qatar
Authors: Roof Katherine A. , James-Hawkins Laurie , Abdul Rahim Hanan F. , Yount Kathryn M.
Published: October 2019

Objectives

The objective of this study is to validate three mental health scales in a targeted sample of pregnant Arab women living in Qatar: the Kuwait University Anxiety Scale, the Perceived Stress Scale, and the Edinburgh Postnatal Depression Scale.

Methods

Random split-half exploratory factor analysis and confirmatory factor analyses (n = 336;n = 331), conducted separately, were used to evaluate scale dimensionality, factor loadings, and factor structure of the KUAS, the PSS, and the EPDS.

Results

Fit statistics for the three scales suggested adequate fit to the data and estimated factor loadings were positive, similar in magnitude, and were significant. The final CFA model for the KUAS supported a 19-item, two factor structure. CFA models also confirmed 8- and 10-item, single-factor structures for the PSS and EPDS, respectively.

Conclusions

The validation of scales for these aspects of mental health in Arab pregnant women is critical to ensure appropriate screening, identification, and treatment to reduce the risk of sequelae in women and their children. Findings offer a useful comparison to mental-health scale validations in other Arab contexts.
The prevalence of Toxoplasma gondii in mice living in Danish indoor sow herds
Authors: Nielsen Stine Thorsø , Westergaard Isabella Linde , Guldbech Grith Kirkhoff , Nielsen Henrik Vedel , Johansen Maria Vang
Published: October 2019

Background

Toxoplasma gondii is found worldwide, and consumption of undercooked meat is considered a significant risk factor for human infections. In Denmark, little is known about the distribution of T. gondii, but a recent study revealed a seroprevalence of 34% in Danish indoor sows. The present cross-sectional study aimed to investigate the role of mice for the transmission of T. gondii in Danish indoor sow herds.

Results

In total, 56 sow herds were visited, 137 mice were caught by snap traps from 32 farms, and 52 cat faecal samples were collected from 22 farms. Eight percent of the mice were positive for T. gondii DNA, representing 11% of the farms. Significant associations were found between the presence of T. gondii-positive mice and both open feed systems (P= 0.041) and extra rodent control on the farm (P= 0.024). All cat faecal samples were deemed negative for T. gondii by light microscopy examination and real-time polymerase chain reaction analysis.

Conclusion

Mice captured inside Danish sow herds were found to be infected with T. gondii and may thus contribute to the transmission of T. gondii to sows, which may explain the high seroprevalence found in Danish pigs.
Report on advances for pediatricians in 2018: allergy, cardiology, critical care, endocrinology, hereditary metabolic diseases, gastroenterology, infectious diseases, neonatology, nutrition, respiratory tract disorders and surgery
Authors: Caffarelli Carlo , Santamaria Francesca , Mastrorilli Carla , Santoro Angelica , Iovane Brunella , Petraroli Maddalena , Gaeta Valeria , Di Pinto Rosita , Borrelli Melissa , Bernasconi Sergio , Corsello Giovanni
Published: October 2019

This review reported notable advances in pediatrics that have been published in 2018. We have highlighted progresses in allergy, cardiology, critical care, endocrinology, hereditary metabolic diseases, gastroenterology, infectious diseases, neonatology, nutrition, respiratory tract disorders and surgery. Many studies have informed on epidemiologic observations. Promising outcomes in prevention, diagnosis and treatment have been reported. We think that advances realized in 2018 can now be utilized to ameliorate patient care.
Field-captured Aedes vexans (Meigen, 1830) is a competent vector for Rift Valley fever phlebovirus in Europe
Authors: Birnberg Lotty , Talavera Sandra , Aranda Carles , Núñez Ana I. , Napp Sebastian , Busquets Núria
Published: October 2019

Background

Aedes vexans(Meigen) is considered a nuisance species in central Europe and the Mediterranean region. It is an anthropophilic and mammalophilic floodwater mosquito involved in the transmission of several arboviruses. Rift Valley fever (RVF) is a relevant mosquito-borne zoonosis, affecting mainly humans and ruminants, that causes severe impact in public health and economic loses. Due to globalization and climate change, the European continent is threatened by its introduction. The main purpose of the present study was to evaluate the vector competence of a European field-collectedAe. vexanspopulation.

Methods

Aedes vexansfield-collected larvae were reared in the laboratory under field-simulated conditions. To assess the vector competence for Rift Valley fever phlebovirus (RVFV) transmission, adult F0 females were exposed to infectious blood meals containing the 56/74 RVFV strain. Additionally, intrathoracic inoculations with the same virus strain were performed to evaluate the relevance of the salivary gland barriers. Natural circulation of alphavirus, flavivirus and phlebovirus was also tested.

Results

To our knowledge, an autochthonousAe. vexanspopulation was experimentally confirmed as a competent vector for RVFV for the first time. This virus was capable of infecting and disseminating within the studiedAe. vexansmosquitoes. Moreover, infectious virus was isolated from the saliva of disseminated specimens, showing their capacity to transmit the virus. Additionally, a natural infection with a circulating Mosquito flavivirus was detected. The co-infection with the Mosquito flavivirus seemed to modulate RVFV infection susceptibility in field-collectedAe. vexans, but further studies are needed to confirm its potential interference in RVFV transmission.

Conclusions

Our results show that field-collected EuropeanAe. vexanswould be able to transmit RVFV in case of introduction into the continent. This should be taken into consideration in the design of surveillance and control programmes.
Prevalence of sickle cell disease and sickle cell trait among children admitted to Al Fashir Teaching Hospital North Darfur State, Sudan
Authors: Adam Mudathir A. , Adam Nassreldeen K. , Mohamed Babiker A.
Published: October 2019

Objective

It is estimated that 50% to 90% of infants born with (SCA) in sub-Saharan Africa die before 5 years old. Northern Darfur State at western Sudan region has a multiethnic population with a high frequency of sickle cell anaemia, but little about it is published. This study aimed to determine the prevalence of sickle cell anaemia among children admitted to Al Fashir Teaching Hospital in Al Fashir, Northern Darfur State, Sudan.

Results

The prevalence of sickle cell disease by haemoglobin electrophoresis among these 400 children patients was 59 (14.8%). Sickle cell trait patients were 11.3% and Sickle cell disease positive patients were 3.5%. Individuals with SCA have consistently low blood Hb concentration, normal MCV and high mean WBC’s. Individuals with sickle cell trait had haematological parameters near to those of normal individuals.
Ontology patterns for the representation of quality changes of cells in time
Authors: Burek Patryk , Scherf Nico , Herre Heinrich
Published: October 2019

Background

Cell tracking experiments, based on time-lapse microscopy, have become an important tool in biomedical research. The goal is the reconstruction of cell migration patterns, shape and state changes, and, comprehensive genealogical information from these data. This information can be used to develop process models of cellular dynamics. However, so far there has been no structured, standardized way of annotating and storing the tracking results, which is critical for comparative analysis and data integration. The key requirement to be satisfied by an ontology is the representation of a cell’s change over time. Unfortunately, popular ontology languages, such as Web Ontology Language (OWL), have limitations for the representation of temporal information. The current paper addresses the fundamental problem of modeling changes of qualities over time in biomedical ontologies specified in OWL.

Results

The presented analysis is a result of the lessons learned during the development of an ontology, intended for the annotation of cell tracking experiments. We present, discuss and evaluate various representation patterns for specifying cell changes in time. In particular, we discuss two patterns of temporally changing information: n-ary relation reification and 4d fluents. These representation schemes are formalized within the ontology language OWL and are aimed at the support for annotation of cell tracking experiments. We analyze the performance of each pattern with respect to standard criteria used in software engineering and data modeling, i.e. simplicity, scalability, extensibility and adequacy. We further discuss benefits, drawbacks, and the underlying design choices of each approach.

Conclusions

We demonstrate that patterns perform differently depending on the temporal distribution of modeled information. The optimal model can be constructed by combining two competitive approaches. Thus, we demonstrate that both reification and 4d fluents patterns can work hand in hand in a single ontology. Additionally, we have found that 4d fluents can be reconstructed by two patterns well known in the computer science community, i.e. state modeling and actor-role pattern.
Harm reduction drug policy in Israel: what has been accomplished and what still needs to be done?
Authors: Bonny-Noach Hagit
Published: October 2019

The leading formal drug policy in Israel is the traditional approach of abstinence, probation, and punitive measures based on three main pillars: Enforcement, Treatment and Rehabilitation, and Prevention. However, under the treatment pillar, Israel has adopted a number of harm reduction services, focused mostly on people who use heroin and people who inject drugs. These include Methadone Maintenance Treatment, Buprenorphine Maintenance Treatment, and Needle and Syringe Exchange Programs. More specialized services are designated mostly for people who use drugs, who frequent the largest open drug scene in Tel-Aviv. These include a health clinic, an emergency apartment for female addict sex-workers, and a ‘First Step’ center. Even so, the harm reduction approach has remained controversial, stigmatized, and is considered a sub-category for total-abstinence treatment in Israel. This paper follows the evolution of harm reduction interventions in Israel among people who use drugs and sheds light on the lack of a comprehensive, well-planned, formal national harm reduction drug policy. Additionally, this article expresses concern over the uncertain future of Israel’s comprehensive and balanced drug treatment policies caused by the structural changes in abolishing the Israel Anti-Drug Authority, the statutory authority and central body in Israel that promoted and coordinated all national policies related to treatment and harm reduction.

Conclusions

Although it is a major challenge to translate worldwide evidence and research findings into action and social change, recommendations are offered to implement a comprehensive harm reduction drug policy led by a multidisciplinary group of policy-makers across all areas of drug policy. These focus on expanding and developing more services for Opioid Maintenance Therapy patients and people who inject drugs as well as a national effort to reduce high levels of stigma and discrimination against them, encompassing other common substances and focusing on populations such as adolescents and young adults that engage in other types of substance use such as cannabis, amphetamine-type stimulants, and hallucinogens.
Molecular and phenotypic characterization of clinical isolates belonging to a KPC-2-producing strain of ST15 Klebsiella pneumoniae from a Vietnamese pediatric hospital
Authors: Berglund Björn , Hoang Ngoc Thi Bich , Tärnberg Maria , Le Ngai Kien , Nilsson Maud , Khu Dung Thi Khanh , Svartström Olov , Welander Jenny , Nilsson Lennart E. , Olson Linus , Dien Tran Minh , Le Hai Thanh , Larsson Mattias , Hanberger Håkan
Published: October 2019

Background

Carbapenem-resistant Klebsiella pneumoniae are becoming increasingly common in hospital settings worldwide and are a source of increased morbidity, mortality and health care costs. The global epidemiology of carbapenem-resistant K. pneumoniae is characterized by different strains distributed geographically, with the strain ST258 being predominant in Europe and USA, and ST11 being most common in East Asia. ST15 is a less frequently occurring strain but has nevertheless been reported worldwide as a source of hospital outbreaks of carbapenem-resistant K. pneumoniae.

Methods

In this study, whole-genome sequencing and antimicrobial susceptibility testing was used to characterize 57 clinical isolates of carbapenem-resistant K. pneumoniae belonging to a strain of ST15, which were collected at a Vietnamese pediatric hospital from February throughout September 2015.

Results

Aside from the carbapenem resistance gene blaKPC-2, which was carried by all isolates, prevalence of resistance genes to other antibiotics including aminoglycosides, macrolides, quinolones, fosfomycin and trimethoprim, was also high. All isolates were multidrug-resistant. Susceptibility was highest to ceftazidime/avibactam (96%), gentamicin (91%) and tigecycline (82%). Notably, the colistin resistance rate was very high (42%). Single-nucleotide polymorphism analysis indicated that most isolates belonged to a single clone.

Conclusions

The diverse variety of antibiotic resistance genes and the high antibiotic resistance rates to last-resort antibiotics such as carbapenems and colistin, is indicative of a highly adaptable strain. This emphasizes the importance of implementation of infection controls measures, continued monitoring of antibiotic resistance and prudent use of antibiotics to prevent further selection of resistant strains and the emergence of pan-resistant clones.
Correction to: Gilteritinib: a novel FLT3 inhibitor for acute myeloid leukemia
Authors: Zhao Juanjuan , Song Yongping , Liu Delong
Published: October 2019

The original article [1] contains an error in the legend of Fig. 1 whereby it is incorrectly stated that MEC stands for ‘mitoprostate cancer using magnetic resonance imagingxantrone, etoposide, cyclophosphamide’. Correction to: Biomark Res (2019) 7:19. https://doi.org/10.1186/s40364-019-0170-2