bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and genetic analysis of two wolfram syndrome families with high occurrence of wolfram syndrome and diabetes type II: a case report
Authors: Sobhani Maryam , Tabatabaiefar Mohammad Amin , Ghafouri-Fard Soudeh , Rajab Asadollah , Hojjat Asal , Kajbafzadeh Abdol-Mohammad , Noori-Daloii Mohammad Reza
Published: January 2020

Background

Mutations of the WFS1 gene are responsible for most cases of Wolfram syndrome (WS), a rare, recessively inherited neurodegenerative disorder characterized by juvenile-onset non-autoimmune diabetes mellitus and optic atrophy. Variants of WFS1 are also associated with non-syndromic hearing loss and type-2 diabetes mellitus (T2DM). Our study adds to literature significant associations between WS and T2DM.

Case presentation

In this study, we analyzed the clinical and genetic data of two families with high prevalence of WS and T2DM. Genetic linkage analysis and DNA sequencing were exploited to identify pathogenic variants. One novel pathogenic variant (c.2243-2244insC) and one known pathogenic (c.1232_1233delCT) (frameshift) variant were identified in exon eight of WFS1 gene.

Conclusions

The mutational and phenotypic spectrum of WS is broadened by our report of novel WFS1 mutation. Our results reveal the value of molecular analysis of WFS1 in the improvement of clinical diagnostics for WS. This study also confirms the role of WFS1 in T2DM.
Elevated matrix metalloproteinase 7 expression promotes the proliferation, motility and metastasis of tongue squamous cell carcinoma
Authors: Yuan Shuo , Lin Li-song , Gan Rui-Huan , Huang Li , Wu Xiao-ting , Zhao Yong , Su Bo-hua , Zheng Dali , Lu You-Guang
Published: January 2020

Background

Matrix metalloproteinase 7 (MMP7), as the smallest member of the matrix metalloproteinase family, has been verified to be implicated in cancer progression, especially metastasis. However, its expression pattern and function in tongue cancer is not clear.

Methods

The expression of MMP7 in human tongue squamous cell carcinoma (TSCC) specimens compared with their respective paired nontumour tissues by real-time PCR and immunohistochemical staining. The effect of MMP7 on the proliferation, apoptosis, migration, invasion of tongue cancer cells was tested in appropriate ways after MMP7 siRNA knockdown or overexpression. The effect of MMP7 on lymph node metastasis in vivo was analyzed using a high-metastasis orthotopic nude mouse tongue transplanted tumour model.

Results

We found markedly elevated expression of MMP7 in human TSCC specimens compared with their respective paired nontumour tissues, and this high expression was correlated with the patients’ lymph node metastasis. Furthermore, the results of molecular functional assays confirmed that MMP7 promotes cell proliferation, migration and invasion of TSCC cells. Knockdown of MMP7 inhibited lymph nodes metastasis in vivo.

Conclusions

MMP7 plays an oncogenic role in carcinogenesis and metastasis of tongue cancer, and may serve as a potential therapeutic target for tongue cancer.
Factors affecting current khat chewing among male adults 15–59 years in Ethiopia, 2016: a multi-level analysis from Ethiopian Demographic Health Survey
Authors: Akalu Temesgen Yihunie , Baraki Adhanom Gebreegziabher , Wolde Haileab Fekadu , Lakew Ayenew Molla , Gonete Kedir Abdela
Published: January 2020

Background

Regular khat chewing causes gingivitis, tooth loss, gastric disorders, cardiac complications, male impotence, sleeplessness, and several mental health problems. Based on the Ethiopian Demographic and Health Survey (EDHS) 2016, 12% of women and 27% of men have reported having ever chewed khat. Even though khat addiction is a major public health problem, studies that consider both individual level and community level factors are limited. Therefore, this study aimed to determine the prevalence and factors affecting current khat chewing among male adults in Ethiopia.

Methods

Data from EDHS, a community-based cross-sectional study conducted from January 18, 2016, to June 27, 2016, was used. A multistage stratified cluster sampling technique was used to select participants. Both descriptive and analytical statistics were done. Bi-variable and multivariable multilevel logistic regression analyses were performed to determine factors affecting current khat chewing. Adjusted Odds ratio (AOR) with 95% Confidence Interval (CI) for variables withP-value < 0.05 was used as a measure of association.

Result

A total of 12,595 male adults were included. The prevalence of current khat chewing was 23.61% (95% CI: 22.87, 24.36). Age 20–24 years; (AOR = 2.68, 95% CI: 2.02, 3.56), being uneducated (AOR = 1.62, 95% CI: 1.10, 2.39), professional/technical/managerial job (AOR = 3.59, 95% CI: 2.18, 5.91), Muslim religion (AOR = 18.30, 95% CI: 13.54, 24.74), poorest wealth index (AOR = 0.67, 95% CI: 0.51, 0.89), being divorced (AOR = 0.38, 95% CI: 0.21, 0.69), history of alcohol drinking in the last 30 days (AOR = 2.15, 95% CI: 1.69, 2.73), and history of cigarette smoking in the last 30 days (AOR = 14.92, 95% CI: 10.88, 20.47), and Amhara region (AOR = 0.07, 95% CI: 0.04, 0.14) were significantly associated with khat chewing.

Conclusion

Khat chewing remains high in Ethiopia with certain regional variations. The uneducated, older age, Alcohol and cigarette users, Muslims, and professional workers were at higher risk of khat chewing whereas the poorest wealth index and being divorced reduced its risk. Policymakers should consider a multi-faceted policy approach that accounts for regional variation and the identified risk factors to alleviate the problem.
District level inequality in reproductive, maternal, neonatal and child health coverage in India
Authors: Panda Basant Kumar , Kumar Gulshan , Awasthi Ashish
Published: January 2020

Background

As India already missed maternal and child health related millennium development goals, the maternal and child health outcomes are a matter of concern to achieve sustainable development goals (SDGs). This study is focused to assess the gap in coverage and inequality of various reproductive, maternal, neonatal and child health (RMNCH) indicators in 640 districts of India, using data from most recent round of National Family Health Survey.

Methods

A composite index named Coverage Gap Index (CGI) was calculated, as the weighted average of eight preventive maternal and child care interventions at different administrative levels. Bivariate and spatial analysis were used to understand the geographical diversity and spatial clustering in districts of India. A socio-economic development index (SDI) was also derived and used to assess the interlinkages between CGI and development. The ratio method was used to assess the socio-economic inequality in CGI and its component at the national level.

Results

The average national CGI was 26.23% with the lowest in Kerala (10.48%) and highest in Nagaland (55.07%). Almost half of the Indian districts had CGI above the national average and mainly concentrated in high focus states and north-eastern part. From the geospatial analysis of CGI, 122 districts formed hotspots and 164 districts were in cold spot. The poorest households had 2.5 times higher CGI in comparison to the richest households and rural households have 1.5 times higher CGI as compared to urban households.

Conclusion

Evidence from the study suggests that many districts in India are lagging in terms of CGI and prioritize to achieve the desired level of maternal and child health outcomes. Efforts are needed to reduce the CGI among the poorest and rural resident which may curtail the inequality.
Pleural fluid ADA activity in tuberculous pleurisy can be low in elderly, critically ill patients with multi-organ failure
Authors: Kim Sae Byol , Shin Beomsu , Lee Ji-Ho , Lee Seok Jeong , Lee Myoung Kyu , Lee Won-Yeon , Yong Suk Joong , Kim Sang-Ha
Published: January 2020

Background

Adenosine deaminase (ADA) activity is typically elevated in patients with tuberculous pleural effusion (TPE), but low ADA has occasionally been reported in patients with TPE. The characteristics of these patients are not well-known, and erroneous exclusion of the possibility of TPE can result in a delayed diagnosis. This study investigated the characteristics of patients with TPE who had low ADA activity.

Methods

We retrospectively reviewed patients with microbiologically or pathologically confirmed TPE between 2012 to 2018 in a tertiary hospital in South Korea. Patients were categorised into two groups: high ADA (≥40 IU/L) and low ADA (< 40 IU/L). Clinical characteristics and Sequential Organ Failure Assessment (SOFA) scores were compared between groups.

Results

A total of 192 patients with TPE were included; 36 (18.8%) had ADA < 40 IU/L with a mean ADA activity level of 20.9 (±9.2) IU/L. Patients with low ADA were older (75.3 vs. 62.0 years,p < 0.001) and had a lower mean lymphocyte percentage (47.6% vs. 69.9%,p < 0.001) than patients with high ADA. Patients in the low ADA group had a significantly higher mean SOFA score (2.31 vs. 0.68,p < 0.001), and patients with organ dysfunction were significantly more common in the low ADA group (p < 0.001). Patients with 2 or ≥ 3 organ dysfunctions constituted 19.4 and 13.9% of the patients in the low ADA group, whereas they constituted 7.1 and 1.3% of the patients in the high ADA group (p < 0.001). Multivariate logistic regression analyses showed that older age (odds ratio = 1.030, 95% confidence interval 1.002–1.060,p = 0.038) and a higher SOFA score (odds ratio = 1.598, 95% confidence interval 1.239–2.060,p < 0.001) were significantly associated with low ADA activity in patients with TPE.

Conclusions

ADA activity can be low in patients with TPE who are elderly, critically ill, and exhibit multiorgan failure. Low ADA activity cannot completely exclude the diagnosis of TPE, and physicians should exercise caution when interpreting pleural fluid exams.
Quantitative analysis of paraspinal muscle atrophy after oblique lateral interbody fusion alone vs. combined with percutaneous pedicle screw fixation in patients with spondylolisthesis
Authors: He Wei , He Da , Sun Yuqing , Xing Yonggang , Liu Mingming , Wen Jiankun , Wang Weiheng , Xi Yanhai , Tian Wei , Ye Xiaojian
Published: January 2020

Background

There is no available literature for comparison on muscle atrophy between the “stand-alone” oblique lateral interbody fusion (OLIF) and regular OLIF (i.e., combined with percutaneous pedicle screws fixation (PPSF) in patients with spondylolisthesis). This study aimed to identify changes in back muscle atrophy between the two surgeries.

Methods

This was a retrospective cohort study of patients who underwent OLIF or OLIF+PPSF at Beijing Jishuitan Hospital and Shanghai ChangZheng Hospital between 07/2014 and 10/2017. Computed tomography (CT) was used to measure functional cross-sectional area (FCSA) and fat infiltration percentage (FIP) of the multifidus and erector spinae before and 24 months after surgery.

Result

There were no differences in FCSA and FIP between OLIF (n = 32) and OLIF+PPSF (n = 41) groups before surgery. In the OLIF group, the multifidus and erector spinae FCSA and FIP did not change at 24 months (FCSA: multifidus: from 8.59 ± 1.76 to 9.39 ± 1.74 cm2, P = 0.072; erector spinae: from 13.32 ± 1.59 to 13.55 ± 1.31 cm2, P = 0.533) (FIP: multifidus: from 15.91 ± 5.30% to 14.38 ± 3.21%, P = 0.721; erector spinae: from 11.63 ± 3.05% to 11.22 ± 3.12%, P = 0.578). In the OLIF+PPSF group, the multifidus and erector spinae FCSA decreased (multifidus: from 7.72 ± 2.69 to 5.67 ± 1.71 cm2, P < 0.001; erector spinae: from 12.60 ± 2.04 to 10.15 ± 1.82 cm2, P < 0.001), while the FIP increased (multifidus: from 16.13 ± 7.01% to 49.38 ± 20.54%, P < 0.001; erector spinae: from 11.93 ± 3.22% to 22.60 ± 4.99%, P < 0.001). The differences of FCSA and FIP between the two groups at 24 months were significant (all P < 0.001). The patients in the standalone OLIF group had better VAS back pain, and JOA scores than the patients in the OLIF combined group (all P < 0.05) at 1 week and 3 months after surgery. There were two cases (4.9%) of adjacent segment degeneration in the OLIF combined group, while there was no case in the OLIF alone group.

Conclusions

Standalone OLIF had better clinical outcomes at 1 week and 3 months than OLIF+PPSF in patients with spondylolisthesis. OLIF may not result in paraspinal muscle atrophy at 24 months after surgery.
Modified C7 pedicle subtraction osteotomy for the correction of cervicothoracic kyphosis
Authors: Meng Yichen , Ma Jun , Shu Lun , Yin Jia , Gao Rui , Wang Ce , Zhou Xuhui
Published: January 2020

Background

Osteotomies in the cervical spine are technically challenging. The purpose of this study was to evaluate the feasibility of the modified pedicle subtraction osteotomy (PSO) technique at C7 to be used for the treatment of cervicothoracic kyphosis secondary to ankylosing spondylitis.

Methods

A total of 120 cervical spine computed tomography (CT) scans (of 82 male and 38 female patients) were evaluated. The scans were taken parallel to the middle sagittal plane and the sagittal plane intersecting the pedicles. Simulated osteotomy was performed by setting the apex of the wedge osteotomy at different points, and morphologic measurements were obtained. Seven patients with cervicothoracic kyphosis who underwent a modified PSO at C7 between May 2009 and June 2015 were retrospectively evaluated. The mean follow up was 32.9 months (range 21–54 months). Preoperative and postoperative chin-brow vertical angle (CBVA), sagittal vertical axis (SVA) and sagittal Cobb angle of the cervical region were reviewed. The outcomes were analyzed through various measures, which included the 36-Item Short Form Health Survey (SF-36) and a visual analog scale for neck pain.

Results

In this morphometric study, a modified PSO was performed on 87 patients (59 male and 28 female) with a reasonable ratio of 72.5%. In the case series, radiographic parameters and health-related quality-of-life measures were found to show significant postoperative improvement in all patients. No major complications occurred, and no implant failures were noted until the latest follow up.

Conclusions

The modified PSO is a safe and valid alternative to the classic PSO, allowing for excellent correction of cervical kyphosis and improvement in health-related quality-of-life measures.
Identifying risk factors for metastasis to the level VII lymph node in papillary thyroid carcinoma patients
Authors: Chen Jian , Zhang Deguang , Fang Liang , He Gaofei , Gao Li
Published: January 2020

Background

The level VI lymph nodes are anatomically connected to the level VII lymph nodes and papillary thyroid carcinoma (PTC) can metastasis to both regions. The aim of this study was to identify clinicopathologic factors associated with level VII lymph node metastasis.

Methods

Between March 2015 and September 2016, a total of 275 consecutive patients were operated on for PTC with prophylactic level VII dissection at the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, ZheJiang, China. Patients with PTC were performed via video-assisted approach. Multivariate logistic regression analysis was performed to evaluate the associations between clinicopathologic factors.

Results

Of the 275 subjects enrolled in this study, 79 patients (28.73%) showed lymph node metastasis to the level VII. The multivariate logistic regression analysis showed ultrasonography-positive lymph nodes (p < 0.001), the location of primary carcinoma (p = 0.002) and hashimoto thyroiditis (HT) (p = 0.04) were associated with level VII lymph node metastasis.

Conclusions

Based on the results of our study, we considered central-compartment lymph node dissection (CLND) as an integral strategy. On the basis of surgery safety, transcervical level VII lymph node dissection could be considered for PTC patients with high risk factors such as ultrasonography-positive lymph nodes, tumor located in middle and lower thirds of the thyroid lobe and the patients without HT. In future, prognostic significance of level VII lymph node dissection should be evaluated through long-term surveillance.
LncRNA CASC 2 is upregulated in aphthous stomatitis and predicts the recurrence
Authors: Lu Jiaping , Zhang Naizheng , Wu Chen
Published: January 2020

Background

Recurrent aphthous stomatitis (RAS) is a common oral disease with unknown molecular pathogenesis. Our preliminary microarray analysis revealed the altered expression of lncRNA Cancer Susceptibility Gene 2 (CASC2) in RAS. We therefore analyzed the role of CASC2 in RAS.

Methods

In this study, plasma samples were obtained from RAS patients and healthy participants. Plasma levels of CASC2 were measured by RT-qPCR. Plasma levels of IL-6 and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA). A follow-up study was performed to analyze the role of CASC2 in the recurrence of RAS.

Results

In the present study, we found that lncRNA Cancer Susceptibility Gene 2 (CASC2), as well as pro-inflammatory factors interleukin 6 (IL-6) and interleukin 18 (IL-18), were upregulated in plasma of RAS patients compared with healthy participants. Plasma levels of lncRNA CASC2 were positively correlated with plasma levels of IL-6 and IL-18 in RAS patients but not in healthy participants. Compared with pre-treatment levels, plasma levels of lncRNA CASC2, IL-6 and IL-18 were reduced after recovery. A follow-up study showed that patients with high levels of lncRNA CASC2 had a significantly higher recurrence rate.

Conclusion

LncRNA CASC 2 is upregulated in RAS and predicts the recurrence.
Evaluation of oral care protocols practice by dentists in Rio de Janeiro towards HIV/AIDS individuals
Authors: Silva-Boghossian Carina Maciel , Boscardini Brenda Azzariti Berrondo , Pereira Claudia Maria , Moreira Edson Jorge Lima
Published: January 2020

Background

The aim of this study was to evaluate the dentists’ knowledge and practice regarding HIV positive individuals’ oral care in Rio de Janeiro State.

Methods

Dentists from Rio de Janeiro State (n = 242) answered an electronic questionnaire on biosafety procedures, oral manifestations of AIDS, and knowledge of HIV infection. Collected information was stratified by gender, and data were analyzed using Chi-square and t tests.

Results

From the 14 oral manifestations investigated, oral candidiasis, necrotizing ulcerative gingivitis, and hairy leucoplakia were more associated with HIV, with no differences between the responses from men and women. Above 85% of the participants would be concerned about becoming infected with HIV after a needle/ sharp object injury and more than 80% of them were willing to be tested for HIV. However, significantly more women (98.8%), compared to men (91.3%), said they knew that HIV/ AIDS patients can contaminate dental care professionals, p = 0.007. There was a significant difference in the answers for the questions: “Are there special dental clinics for treatment of HIV/AIDS patients in Brazil?” (p = 0.044), and “Do the negative HIV tests surely indicate that the persons are free of viruses?” (p = 0.005). Significant differences between men and women were also observed regarding use of disposable mask (p = 0.01), and cap (p < 0.0001).

Conclusion

Most dentists who participated in the study presented a good knowledge on the care of HIV/ AIDS individuals, including biosafety protocols and in terms of the oral manifestations commonly associated to AIDS.
Evaluation of long-lasting indoor residual spraying of deltamethrin 62.5 SC-PE against malaria vectors in India
Authors: Sahu Sudhansu Sekhar , Thankachy Sonia , Dash Smrutidhara , Nallan Krishnamoorthy , Swaminathan Subramanian , Kasinathan Gunasekaran , Purushothaman Jambulingam
Published: January 2020

Background

Deltamethrin 62.5 polymer-enhanced suspension concentrate (SC-PE) is one of the World Health Organization-approved insecticides for indoor residual spraying and was recommended to evaluate its residual activity for determination of appropriate spray cycles in different eco-epidemiologic settings. In the current study, efficacy of deltamethrin 62.5 SC-PE was evaluated against vectors of malaria and its impact on malaria incidence in a Plasmodium falciparum hyper-endemic area in Koraput district, Odisha State, India.

Methods

The trial had two comparable arms, arm 1 with residual spraying of deltamethrin 62.5 SC-PE and arm 2 with deltamethrin 2.5% WP (positive control). Comparative assessment of the impact of each intervention arm on entomological (density, parity, infection and human blood index), epidemiological (malaria incidence) parameters, residual efficacy and adverse effects were evaluated.

Results

Both the arms were comparable in terms of entomological and epidemiological parameters. While, deltamethrin 62.5 SC-PE was found to be effective for 150 days in mud and wood surfaces and 157 days in cement surfaces; deltamethrin 2.5% was effective only for 105 days on mud surfaces and 113 days on cement and wood surfaces.

Conclusions

Deltamethrin 62.5 SC-PE had prolonged killing effectiveness up to 5 months. Hence, one round of IRS with deltamethrin 62.5 SC-PE would be sufficient to cover two existing malaria peak transmission seasons (July–August and October–November) in many parts of India.
Associations between dietary patterns and blood pressure in a sample of Australian adults
Authors: Margerison Claire , Riddell Lynnette J. , McNaughton Sarah A. , Nowson Caryl A.
Published: January 2020

Background

Investigating effects of whole diets on blood pressure (BP) can contribute to development of diet-based recommendations for health. Our aim was to assess the relationship between dietary patterns and BP in a sample of free-living Australian adults.

Methods

Usual dietary patterns of participants recruited to dietary intervention studies were assessed using factor analysis (two 24-h recalls). The mean of seven days of daily, seated BP measurements were used.

Results

Complete data from 251 participants (112 males; mean age 55.1(9.1) (SD) years; body mass index (BMI) 29.5(3.9) kg/m2) was included. Three dietary patterns were identified. Only Dietary Pattern 2 was positively associated with home systolic BP (β = 1.88, 95% CI 0.16, 3.60) after adjusting for age, sex, BMI, anti-hypertensive medication, smoking, education, physical activity and energy intake. This dietary pattern was characterised by high consumption of low-fibre bread, pasta, noodles and rice, meat dishes, poultry dishes and egg dishes, mixed cereal dishes, salted nuts and low consumption of milk and yoghurt (low-fat), vegetable juice, vegetables and high-fibre bread. Dietary Pattern 2 was also positively associated with intakes of energy (P = 0.002) and sodium (P = 0.005) and inversely associated with potassium intake (P = 0.002). After adjustment for energy, only the inverse association with potassium remained (P <  0.001).

Conclusions

In this sample of Australian adults, Dietary Pattern 2 was associated with higher BP and thus chronic disease risk, supporting the evidence that diets high in energy and sodium, and low in potassium from vegetables and dairy, are detrimental to cardiovascular health.
Item generation for a proxy health related quality of life measure in very young children
Authors: Verstraete Janine , Ramma Lebogang , Jelsma Jennifer
Published: January 2020

Background and aims

Very young children have a relatively high prevalence of morbidity and mortality. Health care and supportive technology has improved but may require difficult choices and decisions regarding the allocation of these resources in this age group. Cost-effective analysis (CEA) can inform these decisions and thus measurement of Health-Related Quality of Life (HRQoL) is becoming increasingly important. However, the components of HRQoL are likely to be specific to infants and young children. This study aimed to develop a bank of items to inform the possible development of a new proxy report instrument.

Methods

A review of the literature was done to define the concepts, generate items and identify measures that might be an appropriate starting point of reference. The items generated from the cognitive interviews and systematic review were subsequently pruned by experts in the field of HRQoL and paediatrics over two rounds of a Delphi study.

Results

Based on the input from the different sources, the greatest need for a new HRQoL measure was in the 0–3-year age group. The item pool identified from the literature consisted of 36 items which was increased to 53 items after the cognitive interviews. The ranking of items from the first round of the Delphi study pruned this pool to 28 items for consideration. The experts further reduced this pool to 15 items for consideration in the second round. The experts also recommended that items could be merged due to their similar nature or construct. This process allowed for further reduction of items to 11 items which showed content validity and no redundancy.

Conclusion

The need for an instrument to measure appropriate aspects of HRQoL in infants and young children became apparent as items included in existing measures did not cover the required spectrum. The identification of the final items was based on a sound conceptual model, acceptability to stakeholders and consideration of the observability of the item selected. The pruned item bank of 11 items needs to be subject to further testing with the target population to ensure validity and reliability before a new measure can be developed.
Identification of a small mutation panel of coding sequences to predict the efficacy of immunotherapy for lung adenocarcinoma
Authors: Li Ying , Jiang Wenbin , Li Tianhao , Li Mengyue , Li Xin , Zhang Zheyang , Zhang Sainan , Liu Yixin , Zhao Wenyuan , Gu Yunyan , Qi Lishuang , Ao Lu , Guo Zheng
Published: January 2020

Background

Immune checkpoint inhibitors are effective in some cases of lung adenocarcinoma (LUAD). Whole-exome sequencing has revealed that the tumour mutation burden (TMB) is associated with clinical benefits among patients from immune checkpoint inhibitors. Several commercial mutation panels have been developed for estimating the TMB regardless of the cancer type. However, different cancer types have different mutational landscapes; hence, this study aimed to develop a small cancer-type-specific mutation panel for high-accuracy estimation of the TMB of LUAD patients.

Methods

We developed a small cancer-type-specific mutation panel based on coding sequences (CDSs) rather than genes, for LUAD patients. Using somatic CDSs mutation data from 486 LUAD patients in The Cancer Genome Atlas (TCGA) database, we pre-selected a set of CDSs with mutation states significantly correlated with the TMB, from which we selected a CDS mutation panel with a panel-score most significantly correlated with the TMB, using a genetic algorithm.

Results

A mutation panel containing 106 CDSs of 100 genes with only 0.34 Mb was developed, whose length was much shorter than current commercial mutation panels of 0.80–0.92 Mb. The correlation of this panel with the TMB was validated in two independent LUAD datasets with progression-free survival data for patients treated with nivolumab plus ipilimumab and pembrolizumab immunotherapies, respectively. In both test datasets, survival analyses revealed that patients with a high TMB predicted via the 106-CDS mutation panel with a cut-point of 6.20 mutations per megabase, median panel score in the training dataset, had a significantly longer progression-free survival than those with a low predicted TMB (log-rankp = 0.0018, HR = 3.35, 95% CI 1.51–7.42; log-rankp = 0.0020, HR = 5.06, 95% CI 1.63–15.69). This small panel better predicted the efficacy of immunotherapy than current commercial mutation panels.

Conclusions

The small-CDS mutation panel of only 0.34 Mb is superior to current commercial mutation panels and can better predict the efficacy of immunotherapy for LUAD patients, and its low cost and time-intensiveness make it more suitable for clinical applications.
Real-world effectiveness of long-acting injections for reducing recurrent hospitalizations in patients with schizophrenia
Authors: Kim Hye Ok , Seo Gi Hyeon , Lee Boung Chul
Published: January 2020

Background

The comparative effectiveness of antipsychotic long-acting injections (LAIs) and oral medication is not clear due to various methodological problems.

Methods

To compare the effectiveness of LAIs and oral antipsychotics in preventing readmission in patients with schizophrenia, we performed a within-subject analysis of data collected from 75,274 patients hospitalized with schizophrenia over a 10-year period (2008–2017). Readmission rates were compared according to medication status (non-medication, oral medication alone, and LAI medication). Each admission episodes were compared according to medication status before admission.

Results

Total 132,028 episodes of admission were analyzed. During 255,664 person-years of total observation, 101,589 outcome events occurred. Comparing LAI to only oral medication, IRR was 0.71 (0.64–0.78, P < 0.001). IRR of LAI to only oral medication of first index admission was 0.74 (0.65–0.86). As hospitalization was repeated, IRR of second, third, and fourth or more index admission decreased 0.65 (0.53–0.79), 0.56 (0.43–0.76), and 0.42 (0.31–0.56), respectively.

Conclusions

LAI treatment reduced the readmission rate by 29% compared with oral medication in real-world settings. Moreover, LAIs reduced the readmission rate by 58% in patients with repeated admissions. The more readmissions, the greater the effect of LAIs in reducing the risk of re-hospitalization compared with oral antipsychotics.
Physicians’ brain drain - a gravity model of migration flows
Authors: Botezat Alina , Ramos Raul
Published: January 2020

Background

The past two decades have been marked by impressive growth in the migration of medical doctors. The medical profession is among the most mobile of highly skilled professions, particularly in Europe, and is also the sector that experiences the most serious labour shortages. However, surprisingly little is known about how medical doctors choose their destinations. In addition, the literature is scarce on the factors determining the sharp rise in the migration of doctors from Africa, Asia and Eastern and Southeastern Europe, and how the last economic crisis has shaped the migration flows of health professionals.

Methods

We use the new module on health worker migration provided by the Organisation for Economic Co-operation and Development (OECD) for 2000–2016 in order to examine the channels through which OECD countries attract foreign physicians from abroad. We estimate a gravity model using the Pseudo-Poisson Maximum Likelihood estimator.

Results

Our results reveal that a lower unemployment rate, good remuneration of physicians, an aging population, and a high level of medical technology at the destination are among the main drivers of physicians’ brain drain. Furthermore, an analysis of the mobility of medical doctors from a number of regions worldwide shows that individuals react differently on a country-wise basis to various determinants present in the destination countries. Physicians from African countries are particularly attracted to destination countries offering higher wages, and to those where the density of medical doctors is relatively low. Concurrently, a higher demand for healthcare services and better medical technology in the receiving country drives the inflow of medical doctors from Central and Eastern Europe, while Asian doctors seem to preferentially migrate to countries with better school systems.

Conclusions

This study contributes to a deeper understanding of the channels through which OECD countries attract foreign medical doctors from abroad. We find that, apart from dyadic factors, a lower unemployment rate, good remuneration of physicians, an aging population, and good medical infrastructure in the host country are among the main drivers of physicians’ brain drain. Furthermore, we find that utility from migration to specific countries may be explained by the heterogeneity of origin countries.
Early administration of fibrinogen concentrate is associated with improved survival among severe trauma patients: a single-centre propensity score-matched analysis
Authors: Itagaki Yuki , Hayakawa Mineji , Maekawa Kunihiko , Saito Tomoyo , Kodate Akira , Honma Yoshinori , Mizugaki Asumi , Yoshida Tomonao , Ohyasu Takayoshi , Katabami Kenichi , Wada Takeshi
Published: January 2020

Background

Fibrinogen plays an important role in haemostasis during the early phase of trauma, and low fibrinogen levels after severe trauma are associated with haemostatic impairment, massive bleeding, and poor outcomes. Aggressive fibrinogen supplementation may improve haemostatic function, as fibrinogen levels deteriorate before other routine coagulation parameters in this setting. Therefore, we evaluated whether early administration of fibrinogen concentrate (FC) was associated with improved survival in severe trauma patients.

Methods

This single-centre retrospective study evaluated patients with severe trauma (injury severity score ≥ 16) who were admitted to our emergency department between January 2010 and July 2018. The exclusion criteria included age < 18 years, cardiac arrest before emergency department arrival, cervical spinal cord injury not caused by a high-energy accident, and severe burn injuries. The FC and control groups included trauma patients who received and did not receive FC within 1 h after emergency department arrival, respectively. Propensity scores were used to balance the two groups based on the trauma and injury severity score (TRISS), heart rate at emergency department admission, and age. The primary outcome was the in-hospital survival rate.

Results

The propensity scoring model had a c-statistic of 0.734, the Hosmer-Lemeshow chi-squared value was 7.036 (degrees of freedom = 8), and the non-significant p value of 0.533 indicated a good model fit. The propensity score matching created 31 matched pairs of patients, who had appropriately balanced characteristics. The FC group had a significantly higher in-hospital survival rate than the control group (log-rank p = 0.013). The FC group also used significantly higher amounts of red blood cells and fresh frozen plasma within 6 h after emergency department admission. However, the two groups had similar transfusion amounts between 6 and 24 h after emergency department admission.

Conclusions

The present study revealed that early FC administration was associated with a favourable survival rate among severe trauma patients. Therefore, FC may be useful for the early management of trauma-induced coagulopathy and may improve outcomes in this setting.
The efficacy of dopamine versus epinephrine for pediatric or neonatal septic shock: a meta-analysis of randomized controlled studies
Authors: Wen Lingling , Xu Liangyin
Published: January 2020

Introduction

The efficacy of dopamine versus epinephrine for pediatric or neonatal septic shock remains controversial. We conduct a meta-analysis to explore the influence of dopamine versus epinephrine on shock reversal for pediatric or neonatal septic shock.

Methods

We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through July 2019 for randomized controlled trials (RCTs) assessing the efficacy and safety of dopamine versus epinephrine for pediatric or neonatal septic shock.

Results

Three RCTs are included in the meta-analysis. Overall for pediatric or neonatal septic shock, dopamine and epinephrine reveal comparable shock reversal within 1 h (risk ratios (RR) = 0.61; 95% CI = 0.16 to 2.31; P = 0.47), mortality (RR = 1.16; 95% CI = 0.87 to 1.55; P = 0.30), heart rate (standard mean differences (SMD) = 0.03; 95% CI = -0.28 to 0.34; P = 0.85), systolic blood pressure (SMD = -0.18; 95% CI = -0.69 to 0.33; P = 0.49), mean arterial pressure (SMD = -0.15; 95% CI = -1.64 to 1.34; P = 0.84) and adverse events (RR = 1.00; 95% CI = 0.94 to 1.07; P = 0.91).

Conclusions

Dopamine and epinephrine show the comparable efficacy for the treatment of pediatric or neonatal septic shock.
Efficacy of Ronopterin (VAS203) in Patients with Moderate and Severe Traumatic Brain Injury (NOSTRA phase III trial): study protocol of a confirmatory, placebo-controlled, randomised, double blind, multi-centre study
Authors:   on behalf of the NOSTRA Investigators, Tegtmeier Frank , Schinzel Reinhard , Beer Ronny , Bulters Diederik , LeFrant Jean-Yves , Sahuquillo Joan , Unterberg Andreas , Andrews Peter , Belli Antonio , Ibanez Javier , Lagares Alfonso , Mokry Michael , Willschke Harald , Flüh Charlotte , Schmutzhard Erich
Published: January 2020

Background

Traumatic brain injury is a leading cause of death and disability worldwide. The nitric oxide synthase inhibitor Ronopterin was shown to improve clinical outcome by enhancing neuroprotection in a phase IIa trial.

Methods/design

The NOSTRA phase III trial (Ronopterin in traumatic brain injury) is a multi-centre, prospective, randomised, double-blinded, placebo-controlled, phase III trial in Europe. It aims at determining whether the administration of Ronopterin compared to placebo improves neurological outcome in patients with moderate or severe traumatic brain injury at 6 months after injury. The trial is designed to recruit patients between 18 and 60 years of age with moderate or severe traumatic brain injury (Glasgow Coma Scale score ≥ 3) and requiring insertion of an intracranial pressure probe. Trial patients will receive a 48-h intravenous infusion of either Ronopterin or placebo starting at the earliest 6 h and at the latest 18 h after injury. The primary outcome will be the extended Glasgow Outcome Score (eGOS) at 6 months. Secondary outcomes will include the Quality of Life Index (QOLIBRI) at 6 months after the injury and the eGOS at 3 months after the injury. Additionally, effects on mortality, intracranial pressure and cerebral perfusion pressure are evaluated.

Discussion

The trial aims to provide evidence on the efficacy and safety of Ronopterin in patients with traumatic brain injury.

Trial registration

EudraCT, 2013–003368-29. Registered on 9 March 2016.

ClinicalTrials.gov, NCT02794168. Registered on 8 June 2016.

Protocol version 14.0 from 05 November 2018.
Preparation of high-capacity magnetic polystyrene sulfonate sodium material based on SI-ATRP method and its adsorption property research for sulfonamide antibiotics
Authors: Liu Huachun , Gong Bolin , Zhou Yanqiang , Sun Zhian , Wang Xiaoxiao , Zhao Shanwen
Published: January 2020

A novel polystyrene sulfonate sodium (PSS) magnetic material was prepared by surface-initiated atom transfer radical polymerization (SI-ATRP). The starting materials were brominated magnetic material as the carrier and macroinitiator, sodium styrene sulfonate (NaSS) as the monomer, and cuprous bromide/2,2′-dipyridyl as the catalyst system. The PSS material was characterized by Fourier transform infrared spectroscopy (FT-IR), elemental analysis, transmission electron microscope (TEM), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and a vibrating sample magnetometer (VSM). The adsorption properties of the material were then investigated on sulfa antibiotics. The kinetic and thermodynamic parameters were determined in adsorption of sulfamethazine (the smallest molecular-weight sulfonamide). The adsorption amount of sulfamerazine free acid (SMR) was found to increase with the initial concentration and temperature of SMR in solution. The adsorption effect was maximized at an initial concentration of 0.6 mmol/L. The static saturation adsorption capacity of the material was 33.53 mg/g, Langmuir and Freundlich equations exhibited good fit. The thermodynamic equilibrium equation is calculated as ΔG < 0, ΔH = 38.29 kJ/mol, ΔS > 0, which proves that the adsorption process is a process of spontaneous, endothermic and entropy increase. Kinetic studies show that the quasi-second-order kinetic equation can better fit the kinetic experimental results, which is consistent with the quasi-second-order kinetic model. The experimental results of kinetic studies were well fitted to a quasi-second-order kinetic equation. High performance liquid chromatography (HPLC) of an actual milk sample treated by the PSS magnetic material confirmed the strong adsorption of SMR from milk.
Identification and molecular characterization of Wolbachia strains in natural populations of Aedes albopictus in China
Authors: Hu Yaping , Xi Zhiyong , Liu Xiaobo , Wang Jun , Guo Yuhong , Ren Dongsheng , Wu Haixia , Wang Xiaohua , Chen Bin , Liu Qiyong
Published: January 2020

Background

Aedes albopictus is naturally infected with Wolbachia spp., maternally transmitted bacteria that influence the reproduction of hosts. However, little is known regarding the prevalence of infection, multiple infection status, and the relationship between Wolbachia density and dengue outbreaks in different regions. Here, we assessed Wolbachia infection in natural populations of Ae. albopictus in China and compared Wolbachia density between regions with similar climates, without dengue and with either imported or local dengue.

Results

To explore the prevalence of Wolbachia infection, Wolbachia DNA was detected in mosquito samples via PCR amplification of the 16S rRNA gene and the surface protein gene wsp. We found that 93.36% of Ae. albopictus in China were positive for Wolbachia. After sequencing gatB, coxA, hcpA, ftsZ, fbpA and wsp genes of Wolbachia strains, we identified a new sequence type (ST) of wAlbB (464/465). Phylogenetic analysis indicated that wAlbA and wAlbB strains formed a cluster with strains from other mosquitoes in a wsp-based maximum likelihood (ML) tree. However, in a ML tree based on multilocus sequence typing (MLST), wAlbB STs (464/465) did not form a cluster with Wolbachia strains from other mosquitoes. To better understand the association between Wolbachia spp. and dengue infection, the prevalence of Wolbachia in Ae. albopictus from different regions (containing local dengue cases, imported dengue cases and no dengue cases) was determined. We found that the prevalence of Wolbachia was lower in regions with only imported dengue cases.

Conclusions

The natural prevalence of Wolbachia infections in China was much lower than in other countries or regions. The phylogenetic relationships among Wolbachia spp. isolated from field-collected Ae. albopictus reflected the presence of dominant and stable strains. However, wAlbB (464/465) and Wolbachia strains did not form a clade with Wolbachia strains from other mosquitoes. Moreover, lower densities of Wolbachia in regions with only imported dengue cases suggest a relationship between fluctuations in Wolbachia density in field-collected Ae. albopictus and the potential for dengue invasion into these regions.
Oligotrophic bacterium Hymenobacter latericoloratus CGMCC 16346 degrades the neonicotinoid imidacloprid in surface water
Authors: Guo Leilei , Dai Zhiling , Guo Jingjing , Yang Wenlong , Ge Feng , Dai Yijun
Published: January 2020

The intensive and extensive application of imidacloprid in agriculture has resulted in water pollution and risks to aquatic invertebrates. However, pure bacteria remediation of imidacloprid in surface water environments has not been studied. Here, we isolated an imidacloprid-degrading bacterium from a water environment, examined its imidacloprid degradation in pure culture and surface water, sequenced its genome, and compared its Clusters of Orthologous Groups (COG) protein categorization with that for another imidacloprid-degrading bacterium. The isolate was an obligate oligotrophic bacterium, Hymenobacter latericoloratus CGMCC 16346, which degraded imidacloprid via hydroxylation by co-metabolism in pure culture. Resting cells degraded 64.4% of 100 mg/L imidacloprid in 6 days in the presence of co-substrate maltose, and growing culture degraded 40.8% of imidacloprid in 10 days. H. latericoloratus CGMCC 16346 degraded imidacloprid in surface water without co-substrate supplementation and retained imidacloprid-degrading activity after 30 days. The half-life of imidacloprid in surface water was decreased from 173.3 days in the control to 57.8 days by CGMCC 16346 inoculation. Genome sequencing and COG analysis indicated that carbohydrate metabolism and transport, cell wall/membrane biogenesis, and defense mechanisms are enriched in H. latericoloratus CGMCC 16346 compared with the copiotrophic imidacloprid-degrading Pseudoxanthomonas indica CGMCC 6648, indicating that H. latericoloratus CGMCC 16346 is adapted to live in oligotrophic water environments and biofilms. H. latericoloratus CGMCC 16346 is a promising bioremediation agent for elimination of imidacloprid contamination from surface water.
A novel trehalosamine isolated from Bacillus amyloliquefaciens and its antibacterial activities
Authors: Wang Ying , Zhao Bo , Liu Yaping , Mao Linjing , Zhang Xuanming , Meng Wu , Liu Kechun , Chu Jie
Published: January 2020

Bacillus amyloliquefaciens has been widely used as a probiotic in the field of biological control,and its antibacterial compounds plays an important role in the prevention and control of plant, livestock and poultry diseases. It has the advantages of green, safe and efficiency. This study aims to separate and purify active ingredient from Bacillus amyloliquefaciens GN59 and study its antibacterial activity. A novel compound was isolated from GN59 by column chromatography on silica gel and HPLC purification. The chemical structure was identified as α-d-glucopyranosyl-(1 → 1′)-3′-amino-3′-deoxy-β-d-glucopyranoside (a,β-3-trehalosamine) on the basis of spectroscopic analysis. This is the first report about a,β-3-trehalosamine isolated from biological resources on an antibiotic activity against pathogenic bacterium. The 3′-neotrehalosamine displayed antibacterial activity across a broad spectrum of microorganisms, including different gram-positive and gram-negative bacteria, with minimal inhibitory concentration (MIC) values ranging from 0.5 to 0.7 mg/mL. The results indicated that the 3′-neotrehalosamine from GN59 might be a potential candidate for bactericide.
Long non-coding RNAs as the critical factors during tumor progressions among Iranian population: an overview
Authors: Rahmani Zahra , Mojarrad Majid , Moghbeli Meysam
Published: January 2020

Background

Cancer is associated with various genetic and environmental risk factors. Beside the mutations or aberrant expression of protein-coding genes, the genetic deregulation of non-coding RNAs has also an important role during tumor progression and metastasis. Long non-coding RNAs (lncRNAs) are a class of ncRNAs larger than 200 nucleotides that may function as tumor-suppressor or oncogene.

Main body

There is a raising trend of cancer incidence among Iranian population during the last decades. Therefore, it is required to prepare a general population specific panel of genetic markers for the early detection of cancer in this population. The tissue-specific expression characteristics and high stability in body fluids highlight the lncRNAs as efficient diagnostic and prognostic noninvasive biomarkers in cancer. In present review we summarized all of the lncRNAs which have been reported until now in different tumors among Iranian patients.

Conclusions

This review paves the way of introducing a population based noninvasive diagnostic panel of lncRNAs for the early detection of tumor cells among Iranian population.