bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective Analysis of Chinese Chronic Myeloid Leukemia Patients Who Have Stopped Tyrosine Kinase Inhibitors
Authors: Zhu Xiaojian , You Yong , Zhang Yicheng , Duan Minghui , Zhu Yu , Liu Bingcheng , Du Xin , Chen Suning
Published: October 2019

Background

Although life-long tyrosine kinase inhibitors (TKIs) therapy is still the consensus recommendation, TKIs discontinuation has yet been proven in part of the patients who sustain the long-term treatment-free remission (TFR) which has become a new endpoint and is an emerging goal in the management of chronic myeloid leukemia (CML) currently. In the last ten years, constant clinical trials have demonstrated that about 40%-50% patients with stable deep molecular response for a long period time stayed in TFR after stopping TKIs.

Methods

We retrospective analyzed 109 CML patients who have stopped TKIs in seven centers. They were included according to the unified standard. Rates of TFR were calculated by Kaplan-Meier analysis and stratified groups were compared with the log-rank test. COX univariate analysis was used to predict the potential factors on relapse after discontinuation.

Results

Clinical features of the 93 patients were included in this work. 39 of 93 patients lost major molecular remission (MMR) after a median follow-up of 15 months and the estimated TFR was 52.6%. 31 of 39 patients who met the definition of molecular relapse resumed TKIs treatment immediately and regained the response with an average time to MMR of 4.34 months (range, 1-12 months). No significant difference was found in median course of imatinib therapy between the TFR group and the relapse. Similarly, time to MMR, age, gender and Sokal risk also showed no difference between the two groups. History of withdrawal is the only statistically significant factor in this retrospective analysis.

Conclusion

In summary, this is the first report to prove that TKIs might be safely stopped in partial Chinese CML patients.

Disclosures

No relevant conflicts of interest to declare.
Inhibition of inositol kinase B controls acute and chronic graft-versus-host disease
Authors: Thangavelu Govindarajan , Du Jing , Paz Katelyn G. , Loschi Michael , Zaiken Michael C. , Flynn Ryan , Taylor Patricia A. , Kirchmeier Andrew Kemal , Panoskaltsis-Mortari Angela , Luznik Leo , MacDonald Kelli P. , Hill Geoffrey R. , Maillard Ivan , Munn David H. , Serody Jonathan S. , Murphy William J. , Miklos David , Cutler Corey S. , Koreth John , Antin Joseph H. , Soiffer Robert J. , Ritz Jerome , Dahlberg Carol , Miller Andrew T. , Blazar Bruce R.
Published: October 2019

T-cell activation leads to regulated increases in cytoplasmic calcium through inositol 1,4,5-triphosphate (IP3), a process balanced by phosphorylation and inactivation of IP3 by inositol 1,4,5-trisphosphate 3-kinase B (Itpkb). The investigators demonstrate that inhibition of Itpkb sustains increased intracellular Ca, leads to T-cell apoptosis, and inhibits graft-versus-host disease without impairing graft-versus-leukemia effects.
Comparison of the QuantiFERON-TB and tuberculin skin test for detection of latent tuberculosis infection in cancer patients in a developing country
Authors: Galindo Javier Leonardo , Galeano Adriana Catalina , Suarez-Zamora David Alfonso , Callejas Ana Milena , Caicedo-Verástegui Mónica Patricia , Londoño Darío , García-Herreros Luis Gerardo , Ospina-Serrano Aylen Vanessa , Saavedra Alfredo , Garcíaherreros Plutarco , Palacios Diana María , Baldión Margarita
Published: October 2019

Cancer patients have an increased risk of reactivation of latent tuberculosis infection. It is unknown which strategy on screening should be used in this population in developing countries. We aimed to determine the concordance between the tuberculin skin test (TST) and QuantiFERON®-TB (QFT) assay in order to diagnose latent tuberculosis infection in cancer patients.

We conducted a cross-sectional study of the agreement of diagnostic tests. Prevalence and agreement between tests were calculated. A logistic regression to assess predictors of discordance was performed. The accuracy of the TST to predict QFT results by a receiver operating characteristic (ROC) curve was evaluated.

We included 149 adults with cancer without active tuberculosis. Prevalence of latent tuberculosis infection was 21.5% (n=32), defined as positive results on either test. Test agreement was moderate for the diagnosis of latent tuberculosis infection (κ=0.43, 90% CI 0.26–0.6). No predictor was associated with the chance of discordant results. Agreement improved slightly using a cut-off point ≥8 mm (κ=0.5, 90% CI 0.35–0.66).

In a moderate-incidence setting, a moderate agreement was found between tests in cancer patients. Modification of the cut-off points of test results achieved marginally better agreement between the TST and QFT.
VarSight: prioritizing clinically reported variants with binary classification algorithms
Authors:   Undiagnosed Diseases Network, Holt James M. , Wilk Brandon , Birch Camille L. , Brown Donna M. , Gajapathy Manavalan , Moss Alexander C. , Sosonkina Nadiya , Wilk Melissa A. , Anderson Julie A. , Harris Jeremy M. , Kelly Jacob M. , Shaterferdosian Fariba , Uno-Antonison Angelina E. , Weborg Arthur , Worthey Elizabeth A.
Published: October 2019

Background

When applying genomic medicine to a rare disease patient, the primary goal is to identify one or more genomic variants that may explain the patient’s phenotypes. Typically, this is done through annotation, filtering, and then prioritization of variants for manual curation. However, prioritization of variants in rare disease patients remains a challenging task due to the high degree of variability in phenotype presentation and molecular source of disease. Thus, methods that can identify and/or prioritize variants to be clinically reported in the presence of such variability are of critical importance.

Methods

We tested the application of classification algorithms that ingest variant annotations along with phenotype information for predicting whether a variant will ultimately be clinically reported and returned to a patient. To test the classifiers, we performed a retrospective study on variants that were clinically reported to 237 patients in the Undiagnosed Diseases Network.

Results

We treated the classifiers as variant prioritization systems and compared them to four variant prioritization algorithms and two single-measure controls. We showed that the trained classifiers outperformed all other tested methods with the best classifiers ranking 72% of all reported variants and 94% of reported pathogenic variants in the top 20.

Conclusions

We demonstrated how freely available binary classification algorithms can be used to prioritize variants even in the presence of real-world variability. Furthermore, these classifiers outperformed all other tested methods, suggesting that they may be well suited for working with real rare disease patient datasets.
A modular steroid-inducible gene expression system for use in rice
Authors: Vlad Daniela , Abu-Jamous Basel , Wang Peng , Langdale Jane A.
Published: October 2019

Background

Chemically inducible systems that provide both spatial and temporal control of gene expression are essential tools, with many applications in plant biology, yet they have not been extensively tested in monocotyledonous species.

Results

Using Golden Gate modular cloning, we have created a monocot-optimized dexamethasone (DEX)-induciblepOp6/LhGR system and tested its efficacy in rice using the reporter enzyme β-glucuronidase (GUS). The system is tightly regulated and highly sensitive to DEX application, with 6 h of induction sufficient to induce high levels of GUS activity in transgenic callus. In seedlings, GUS activity was detectable in the root after in vitro application of just 0.01 μM DEX. However, transgenic plants manifested severe developmental perturbations when grown on higher concentrations of DEX. The direct cause of these growth defects is not known, but the rice genome contains sequences with high similarity to the LhGR target sequencelacO,suggesting non-specific activation of endogenous genes by DEX induction. These off-target effects can be minimized by quenching with isopropyl β-D-1-thiogalactopyranoside (IPTG).

Conclusions

Our results demonstrate that the system is suitable for general use in rice, when the method of DEX application and relevant controls are tailored appropriately for each specific application.
Construction of genetic linkage map and identification of a novel major locus for resistance to pine wood nematode in Japanese black pine (Pinus thunbergii)
Authors: Hirao Tomonori , Matsunaga Koji , Hirakawa Hideki , Shirasawa Kenta , Isoda Keiya , Mishima Kentaro , Tamura Miho , Watanabe Atsushi
Published: October 2019

Background

Pine wilt disease (PWD), which is caused by the pine wood nematode (PWN)Bursaphelenchus xylophilus, is currently the greatest threat to pine forests in Europe and East Asian countries including Japan. Constructing a detailed linkage map of DNA markers and identifying PWD resistance genes/loci lead to improved resistance inPinus thunbergii, as well as otherPinusspecies that are also susceptible to PWD.

Results

A total F1mapping population of 188 individuals derived from a cross between the PWD-resistantP. thunbergiivarieties ‘Tanabe 54’ (resistant rank 2 to PWD) and ‘Tosashimizu 63’ (resistant rank 4 to PWD) was inoculated with PWN, and was evaluated for disease symptoms. To perform linkage analysis for PWN resistance, a set of three maps was constructed; two parental maps generated using the integrated two-way pseudo-testcross method, and a consensus map with population-type cross-pollination. The linkage map of ‘Tanabe 54’ consisted of 167 loci, and covered 14 linkage groups (LGs), with a total genetic distance of 1214.6 cM. The linkage map of ‘Tosashimizu 63’ consisted of 252 loci, and covered 14 LGs, with a total genetic distance of 1422.1 cM. The integrated consensus map comprised 12 LGs with the basic chromosome number ofP. thunbergii, and a total genetic distance of 1403.6 cM. Results from quantitative trait loci (QTL) analysis using phenotype data and linkage maps indicated that PWN resistance is controlled by a single dominant allele, which was derived from the ‘Tanabe 54’ female parent. This major QTL was located on linkage group 3 and was designatedPWD1forPINE WILT DISEASE 1.

Conclusions

ThePWD1locus is a major resistance QTL located on thePinusconsensus LG03 that acts in a dominant manner to confer pine wood nematode resistance. Information from the present study will be useful forP. thunbergiibreeding programs to improve resistance to PWD, and also to help identify susceptibility genes inPinusspecies.
Serum uric acid and risk of cardiovascular mortality: a systematic review and dose-response meta-analysis of cohort studies of over a million participants
Authors: Rahimi-Sakak Fatemeh , Maroofi Mahsa , Rahmani Jamal , Bellissimo Nick , Hekmatdoost Azita
Published: October 2019

Background

Cardiovascular disease (CVD) is the leading cause of death worldwide. Some studies have suggested anassociation between serum uric acid levels and cardiovascular mortality; however, the results have not been summarized in a meta-analysis.

Methods

A comprehensive search of all related studies until April 2018was performed in MEDLINE/PubMed and Scopus databases DerSimonianand Laird random-effects models were used to combine hazard ratios (HRs) with 95% confidence intervals (CIs). Dose-response analysis was also carried out.

Results

Thirty-two studies containing forty-four arms with 1,134,073 participants reported association between uric acid and risk of CVD mortality were included in our analysis. Pooled results showed a significant positive association between uric acid levels and risk of CVD mortality (HR 1.45, 95% CI 1.33–1.58, I2 = 79%). Sub-group analysis showed this relationshipwasstronger in women compared to men. Moreover, there was a significant non-linear association between uric acid levels and the risk of CVD mortality (r = 0.0709, p = 0.001).

Conclusion

Our analysis indicates a positive dose-response association between SUA and CVD mortality risk.
The first case of Acrophialophora levis-induced severe pneumonia: a case report and literature review
Authors: Huang Junyun , Liu Zhiping
Published: October 2019

Background

In recent years, some rare fungi have been increasingly recognized as new human pathogens. Here we reported the first fatal case of human severe pneumonia complicated by multiple organ dysfunction caused by Acrophialophora levis infection. However, its pathogenic mechanism and risk factors are unknown. Acrophialophora genus has only reported in six cases of human infection worldwide, but it has not been reported previously in China.

Case presentation

A 71-year-old male patient with severe pneumonia complicated with multiple organ dysfunction caused by A. levis infection. The fungal identification was based on micromorphology and sequence analysis of the internal transcriptional spacer (ITS) of ribosomal RNA genes recovered from lower respiratory tract secretions. The microbial characteristics, sensitivity to antifungal drugs of this isolated A. levis were studied. Anti-infective regimen, liposomal amphotericin B combined with tegacycline, was used to prevent infection. The next day, the fever decreased, body temperature fluctuated between 36.5 and 37.8 degree, cough and sputum decreased, and sputum volume decreased, with oxygen uptake for 5 L/min, blood oxygen saturation over 95%. After 17 days of treatment, CT reexamination showed that the lesions in the right lung and left upper lung were absorbed and pleural effusion was reduced. The next 8 days, the patient asked to return to the local hospital for treatment. The local hospital stopped using liposomal amphotericin B because of the absence of liposomal amphotericin B, and died of respiratory failure 2 days later.

Conclusions

This study is the first to report the occurrence, risk factors, molecular determinants, microbial characteristics and susceptibility to antifungal agents of A. levis infection in China. In addition, six published cases of human infection with Acrophialophora were reviewed.
Increased activation of the pregenual anterior cingulate cortex to citalopram challenge in migraine: an fMRI study
Authors: Edes Andrea Edit , McKie Shane , Szabo Edina , Kokonyei Gyongyi , Pap Dorottya , Zsombok Terezia , Magyar Mate , Csepany Eva , Hullam Gabor , Szabo Adam Gyorgy , Kozak Lajos Rudolf , Bagdy Gyorgy , Juhasz Gabriella
Published: October 2019

Background

The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known. Thus, our aim was to investigate the relationship between acute increase of brain serotonin (5-HT) level and the activation changes of the ACC using pharmacological challenge MRI (phMRI) in migraine patients and healthy controls.

Methods

Twenty-seven pain-free healthy controls and six migraine without aura patients participated in the study. All participant attended to two phMRI sessions during which intravenous citalopram, a selective serotonin reuptake inhibitor (SSRI), or placebo (normal saline) was administered. We used region of interest analysis of ACC to compere the citalopram evoked activation changes of this area between patients and healthy participants.

Results

Significant difference in ACC activation was found between control and patient groups in the right pregenual ACC (pgACC) during and after citalopram infusion compared to placebo. The extracted time-series showed that pgACC activation increased in migraine patients compared to controls, especially in the first 8–10 min of citalopram infusion.

Conclusions

Our results demonstrate that a small increase in 5-HT levels can lead to increased phMRI signal in the pregenual part of the ACC that is involved in processing emotional aspects of pain. This increased sensitivity of the pgACC to increased 5-HT in migraine may contribute to recurring headache attacks and increased stress-sensitivity in migraine.
Determinants of prenatal care use and HIV testing during pregnancy: a population-based, cross-sectional study of 7080 women of reproductive age in Mozambique
Authors: Yaya Sanni , Oladimeji Olanrewaju , Oladimeji Kelechi Elizabeth , Bishwajit Ghose
Published: October 2019

Background

In low-income countries with poor coverage of healthcare services such as Mozambique, antenatal care serves as a vital tool for providing life-saving and cost-effective services for pregnant mothers. Nonetheless, many countries in Africa, including Mozambique, are struggling to attain an optimum level of antenatal care (at least 4 visits) utilisation among pregnant women. In the present study, we aimed to assess the sociodemographic and economic factors associated with antenatal care use in Mozambique.

Methods

Cross-sectional data from the latest round of Mozambique Demographic and Health Survey (2011) on women aged 15–49 years (n = 7080) were analysed. The outcome measures were early and adequate antenatal visit and HIV tests during the last pregnancy. Data were analysed using descriptive and multivariate regression methods. The predictor variables included various demographic (e.g. age, parity), empowerment (e.g. type of employment, household wealth status) and sociocultural factors (e.g. ethnicity, religion).

Results

Of the 7080 women whose data was analyzed, 15.3 and 60.1% had early and adequate ANC visits respectively while 75.4% received HIV test during ANC visits. The odds of early ANC visits were higher [OR = 1.300, 95%CI = 1.062,1.592] among women in the rural areas compared with those in the urban areas. However, participants in rural areas had lower odds [OR = 0.788, 0.687,0.902] of receiving HIV tests during ANC visits. Women in the urban areas with secondary [OR = 1.296, 95%CI = 1.007,1.666] and higher [OR = 1.663, 95%CI = 1.052,2.628] education had higher odds of having early ANC visit. Those in the higher wealth quintiles also had significantly increased odds of using all three types of ANC indicators, particularly for rural women in the highest wealth quintile [OR = 4.776, 95%CI = 1.250,18.24]. Being within the higher wealth quintiles was found to significantly increase the odds of using all three types of ANC indicators, particularly women from rural areas with highest wealth quintile [OR = 4.776, 95%CI = 1.250,18.24].

Conclusion

About two-fifth of the women in Mozambique are not using adequate antenatal care and about and a quarter do not take HIV tests during pregnancy. The sources of low and unequal use of these vital health services might be rooted in women’s socioeconomic status and cultural issues that require special policy and research attention.
Overexpression of iASPP is required for autophagy in response to oxidative stress in choriocarcinoma
Authors: Chan Ka-Kui , Wong Esther Shuk-Ying , Wong Ivy Tsz-Lo , Cheung Claire Ling-Yang , Wong Oscar Gee-Wan , Ngan Hextan Yuen-Sheung , Cheung Annie Nga-Yin
Published: October 2019

Background

Gestational trophoblastic disease (GTD) is a heterogeneous group of diseases developed from trophoblasts. ASPP (Ankyrin-repeat, SH3-domain and proline-rich region containing protein) family proteins, ASPP1 and ASPP2, have been reported to be dysregulated in GTD. They modulate p53 activities and are responsible for multiple cellular processes. Nevertheless, the functional role of the ASPP family inhibitory member, iASPP, is not well characterized in GTD.

Methods

To study the functional role of iASPP in GTD, trophoblastic tissues from normal placentas, hydatidiform mole (HM) and choriocarcinoma were used for immunohistochemistry, whereas siRNAs were used to manipulate iASPP expression in choriocarcinoma cell lines and study the subsequent molecular changes.

Results

We demonstrated that iASPP was overexpressed in both HM and choriocarcinoma when compared to normal placenta. Progressive increase in iASPP expression from HM to choriocarcinoma suggests that iASPP may be related to the development of trophoblastic malignancy. High iASPP expression in HM was also significantly associated with a high expression of autophagy-related protein LC3. Interestingly, iASPP silencing retarded the growth of choriocarcinoma through senescence instead of induction of apoptosis. LC3 expression decreased once iASPP was knocked down, suggesting a downregulation on autophagy. This may be due to iASPP downregulation rendered decrease in Atg5 expression and concomitantly hindered autophagy in choriocarcinoma cells. Autophagy inhibition per se had no effect on the growth of choriocarcinoma cells but increased the susceptibility of choriocarcinoma cells to oxidative stress, implying a protective role of iASPP against oxidative stress through autophagy in choriocarcinoma.

Conclusions

iASPP regulates growth and the cellular responses towards oxidative stress in choriocarcinoma cells. Its overexpression is advantageous to the pathogenesis of GTD. (266 words).
Myopic Laser-Assisted Subepithelial Keratectomy (LASEK) outcomes using three different excimer laser platforms: a retrospective observational study
Authors: Rodríguez-Pérez Isabel , Gros-Otero Juan , Teus Miguel A. , Cañones Rafael , García-González Montserrat
Published: October 2019

Background

To compare the visual and refractive outcomes after myopic LASEK using three different excimer lasers and standardized surgical and mitomycin C (MMC) application protocols.

Methods

In this retrospective, observational cohort study, we examined 122 eyes treated with Allegretto, 135 eyes treated with Esiris and 137 eyes treated with Technolas excimer lasers. All eyes were treated under the same surgical protocol, and a standardized MMC dosage was used. The three groups were refraction-matched, and both visual and refractive outcomes were evaluated at 1 and 7 days and 1 and 3 months after surgery.

Results

At 3 months postsurgery, Allegretto provided significantly better outcomes than Esiris and Technolas in terms of postoperative uncorrected distance visual acuity (UDVA) (1.11 ± 0.2 vs 1.01 ± 0.2 vs 0.98 ± 0.2) (P = 0.0001), corrected distance visual acuity (CDVA) (1.13 ± 0.2 vs 1.10 ± 0.1 vs 1.04 ± 0.2) (P = 0.0001), residual sphere (− 0.01 ± 0.2 vs + 0.29 ± 0.7 vs + 0.27 ± 0.6) (P = 0.0001), and efficacy index (0.99 ± 0.2 vs 0.90 ± 0.2 vs 0.91 ± 0.2) (P = 0.0004).

Conclusions

We found slightly better visual and refractive outcomes in the Allegretto group at 3 months post-op after LASEK with MMC to correct myopia.
Necrotizing enterocolitis after intravitreal bevacizumab in an infant with Incontinentia Pigmenti – a case report
Authors: Kunzmann S. , Ngyuen T. , Stahl A. , Walz J. M. , Nentwich M. M. , Speer C. P. , Ruf K.
Published: October 2019

Background

Incontinentia Pigmenti is a rare disease affecting multiple organs. Fifty of patients show affection of the eye with retinopathy and possible amaurosis being the worst outcome. Treatment has commonly been panretinal laser coagulation but intravitreal application of bevacizumab as VEGF-inhibitor has shown to effectively suppress retinal neovascularization.

Case presentation

A six-week-old female infant with Incontinentia Pigmenti developed a foudroyant necrotizing enterocolitis shortly after intravitreal injection of bevazicumab due to a retinopathy with impending tractional detachment of the left eye. Since the onset of abdominal symptoms occurred immediately after the intravitreal application, a link between the two events seemed likely. Sequential analyses of the VEGF serum concentrations showed a massive suppression of endogenous VEGF with only a very slow recovery over weeks. Such a severe systemic adverse event has not been reported after intravitreal treatment with bevacizumab in an infant.

Conclusion

This case report shows a relevant systemic uptake of bevacizumab after intravitreal application as suppressed VEGF levels show. There seems to be a connection between suppressed VEGF levels and the onset of necrotizing enterocolitis. Therefore, treatment with bevacizumab should be carefully considered and further research is needed to assess this drug’s safety profile.
Development of the Adjusted Wind Chill Equivalent Temperature (AWCET) for cold mortality assessment across a subtropical city: validation and comparison with a spatially-controlled time-stratified approach
Authors: Ho Hung Chak , Wong Man Sing , Abbas Sawaid , Zhu Rui
Published: October 2019

Background

Global warming has reduced the adaptability of the people living in subtropical regions to cope up with cold stress due to lengthening of hot days and shortening of transition period from hot to cold weather. However, existing studies on measuring cold stress are based on biometeorological indices designed for temperate regions. This may overestimate the impact of wind chill on mortality risk in subtropical cities.

Methods

This study developed an Adjusted Wind Chill Equivalent Temperature (AWCET) index. A spatially-controlled time-stratified approach was applied to evaluate the ability of AWCET for estimating cold mortality in subtropical cities, based on a mortality dataset (2008–2012) in Hong Kong.

Results

The use of AWCET could indicate increase in all-cause, cardiovascular, respiratory, and cancer-related mortality risk during the days with average temperature < = 1st [11.0 °C], <= 3rd [12.6 °C] and < = 5th [13.4 °C] percentiles. The results were stable and consistent based on both log-linear and curve-linear relationships between AWCET and mortality risk. AWCET was also compared with the New Wind Chill Equivalent Temperature (NWCET) designed for temperate regions, and has found that higher magnitude of mortality risk would be found when using AWCET for assessing all-cause and cause-specific mortality in Hong Kong, for days with average temperature < = 1st, <= 3rd and < = 5th percentiles.

Conclusions

AWCET is validated to be effective to access cold mortality in the context of subtropical cities. The use of AWCET may enhance the cold weather warning system in subtropical cities, as a supplementary tool to help demonstrating small administrative-level perceived temperature with volunteered geographic information.
The prevalence and increasing trends of overweight, general obesity, and abdominal obesity among Chinese adults: a repeated cross-sectional study
Authors: Chen Yongjie , Peng Qin , Yang Yu , Zheng Senshuang , Wang Yuan , Lu Wenli
Published: October 2019

Background

The prevalence of general and abdominal obesity has increased rapidly in China. The aims of this study were to estimate the dynamic prevalence of overweight, general obesity, and abdominal obesity and the distribution of body mass index (BMI) and waist circumference (WC) among Chinese adults.

Methods

Data were obtained from the China Health and Nutrition Survey (CHNS). According to the suggestions of the WHO for Chinese populations, overweight was defined as a 23 kg/m2 ≤ BMI < 27.5 kg/m2and general obesity as a BMI ≥ 27.5 kg/m2. Abdominal obesity was defined as a WC ≥ 90 cm for males and ≥ 80 cm for females. Grade 1, grade 2, and grade 3 obesity were defined as 27.5 kg/m2 ≤ BMI < 32.5 kg/m2, 32.5 kg/m2 ≤ BMI < 37.5 kg/m2, and BMI ≥ 37.5 kg/m2, respectively. Generalized estimation equations were used to estimate the prevalence and trends of overweight, general and abdominal obesity.

Results

This study included 12,543 participant. From 1989 to 2011, the median BMI of males and females increased by 2.65 kg/m2and 1.90 kg/m2, respectively; and WC increased by 8.50 cm and 7.00 cm, respectively. In 2011, the age-adjusted prevalence of overweight, general obesity, and abdominal obesity were 38.80% (95%CI: 37.95–39.65%), 13.99% (95%CI: 13.38–14.59%), and 43.15% (95%CI: 42.28–44.01%), respectively, and significantly increased across all cycles of the survey among all subgroups (allP < 0.0001). The age-adjusted prevalence of grade 1–3 obesity significantly increased in total sample and sex subgroups (allP < 0.0001). For all indicators, there were significant increases in annualORsamong all subgroups (allP < 0.0001), with the exception of grade 2 obesity. Significant differences were observed inORsacross the three age groups in males. AndORssignificantly decreased with age.

Conclusions

The age-adjusted prevalence of overweight, general obesity, and abdominal obesity significantly increased among Chinese adults from 1989 to 2011. The obesity population is trending toward an increased proportion of males and younger individuals in China.
Video-assisted thoracoscopic surgery versus muscle-sparing thoracotomy for non-small cell lung cancer: a systematic review and meta-analysis
Authors: Wang Zihuai , Pang Long , Tang Jiexi , Cheng Jiahan , Chen Nan , Zhou Jian , Liu Lunxu
Published: October 2019

Background

It has been widely accepted that video-assisted thoracoscopic surgery (VATS) lobectomy is superior to conventional open thoracotomy lobectomy in many aspects. However, the direct comparison between VATS and Muscle-sparing thoracotomy (MST) has not been widely conducted. We aimed to compare the perioperative outcomes in non-small cell lung cancer (NSCLC) patients following VATS and MST.

Methods

PubMed, EMBASE, the Cochrane Library and Web of Science were searched for relevant studies. The retrieval time was up to April 24, 2019. Studies investigating the comparison of video-assisted thoracoscopy and muscle-sparing thoracotomy were included in our meta-analysis. Odds ratio and mean differences with 95% confidential interval were applied to determine the effectiveness of dichotomous or continuous variables respectively.

Results

A total of 10 studies were included with 1514 patients. Compared with MST, the incidence of postoperative complications in VATS [OR = 0.54; 95%CI(0.4, 0.73); P < 0.001] and the hospital stay [MD = -1.5; 95%CI(− 2.28, − 0.73); P = 0.0001] decreased significantly, chest tube drainage time [MD = -0.71; 95%CI(− 1.18, − 0.24); P = 0.003] were shorter and the intraoperative blood loss [MD = − 43.87; 95%CI(− 73.66, − 14.08); P = 0.004] were less in VATS group. VATS also showed a relatively longer operative time [MD = 17.11; 95%CI(2.38, 31.85); P = 0.02]. However, no significant differences were observed in numbers of resected lymph nodes, postoperative mortality, postoperative pneumonia and postoperative bleeding.

Conclusion

Compared with MST, VATS was associated with lower incidence of postoperative complications, shorter length of hospital stay, less intraoperative blood loss and less chest tube drainage, which showed that VATS was a comparable method to MST. Meanwhile, these results should be further conformed by more randomized control trials.
Puerarin inhibits the osteoclastogenesis by inhibiting RANKL-dependent and –independent autophagic responses
Authors: Zhang Guoyou , Wang Yu , Tang Guoke , Ma Yuanzheng
Published: October 2019

Background

Puerarin exerts therapeutic effect on osteoporosis due to its inhibitory effect on the formation of osteoclasts. Puerarin is also widely established as an autophagy inhibitor. The study aimed to investigate the significance of autophagy in Puerarin-treated osteoclast formation.

Methods

Osteoclast precursors (OCPs) derived from bone marrow-derived macrophages (BMMs) were treated with Puerarin along with RANKL or without RANKL, and then the autophagic parameters of OCPs (including autophagic proteins, LC3 transformation, autophagosome or LC3-puncta) were observed through Western Blotting, Transmission Electron Microscopy and Immunofluorescence assays. Next, after using overexpression vectors of autophagic genes (Atg7, Atg5 and BECN1) to alter autophagy activity, OCP proliferation was measured by Ethynyl deoxyuridine (EdU) assays and Cell Counting Kit-8 (CCK-8) kit, and osteoclast differentiation was assessed by Tartrate-resistant acid phosphatase (TRAP) staining.

Results

The results showed that Puerarin could directly inhibit the autophagy and proliferation of OCPs. Importantly, overexpression of autophagic genes Atg5, Atg7 and BECN1 reversed Puerarin-inhibited OCP autophagy and proliferation. What’s more, RANKL could promote the autography of OCPs, which was recovered by Puerarin treatment. Interestingly, different from single-Puerarin treatment, we found that in the presence of RANKL, only BECN1 overexpression significantly reversed Puerarin-inhibited osteoclast differentiation and OCP autophagy.

Conclusion

In conclusion, Puerarin could inhibit the OCP autophagy in the presence or absence of RANKL, which blocked the OCP proliferation and osteoclast differentiation respectively. Moreover, BECN1 plays an essential role in Puerarin-inhibited osteoclastogenesis. Our study provides potential clue to further complete the intrinsic mechanism of Puerarin in treating osteoporosis.
Team-based learning (TBL): a community of practice
Authors: Burgess Annette , Haq Inam , Bleasel Jane , Roberts Chris , Garsia Roger , Randal Nicholas , Mellis Craig
Published: October 2019

Background

Rapid changes in medical practice have a large impact on the demands faced by educators in preparing students for future participation in a multifaceted healthcare workforce. Competencies required by today’s medical graduates encompass the ability to effectively collaborate, communicate and problem solve. The learning needs of medical students have also changed over time. Today’s medical students are highly interconnected, enjoying teamwork and collaborative practice, and desire continuous, explicit feedback. They want structured learning activities, with clear expectations, and enjoy a sense of accomplishment on their achievements. The conflation of these issues has seen many medical schools adopt the model of Team-based learning (TBL). Using the conceptual framework of communities of practice, we sought to qualitatively explore students’ and teachers’ experience of TBL in Year 1 of a graduate entry medical program.

Methods

Convenience sampling was used to select 169/350 (48%) Year 1 students who completed three TBL sessions. Each TBL session was facilitated by three senior clinicians. Following participation in the TBLs, students were invited to attend focus groups, and all facilitators (n = 9) were invited to attend interviews. A coding framework was developed to code the entire dataset, using the theoretical lens of communities of practice.

Results

34/169 (20%) of students attended focus groups. Three facilitators (3/9, 33%) were interviewed. Students and facilitators felt the structure and organisation of TBL made students accountable for their learning and team contributions. The combined expertise and clinical experience of facilitators, with immediate feedback helped groups to work both independently and collaboratively. Facilitators found working with their peers in the TBLs to be a rewarding experience.

Conclusions

The community of practice found in the TBL classes, provided an enriching and rewarding learning environment that motivated students to build on their basic knowledge and apply what had been learnt. The interactions of experienced, senior clinicians as facilitators, sharing their expertise within a clinical context, prompted effective student engagement in learning and understanding. Our change in curriculum design and pedagogy will assist in preparing medical students for demands of the increasingly complex healthcare systems in which they will work.
The relationship between perfectionism and symptoms of depression in medical school applicants
Authors: Bußenius Lisa , Harendza Sigrid
Published: October 2019

Background

The association between perfectionism and depression in the medical profession can ultimately influence physicians’ performance negatively. In medical students, especially maladaptive perfectionism is connected with distress and lower academic performance. The expression of perfectionism and symptoms of depression at the time of medical school application is not known. Therefore, we explored perfectionism and symptoms of depression in participants of multiple mini-interviews for medical school admission and investigated possible differences between applicants who were eventually admitted or rejected.

Methods

After the multiple mini-interviews admission procedure at Hamburg Medical School in August 2018, 146 applicants filled out a questionnaire including sociodemographic data and the following validated instruments: Multidimensional Perfectionism Scale by Hewitt and Flett (MPS-H), Multidimensional Perfectionism Scale by Frost (MPS-F), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and a 10-item version of the Big Five Inventory (BFI-10). The two groups of admitted and rejected applicants were compared and the correlation between symptoms of depression and perfectionism further explored.

Results

The admitted applicants were significantly more extrovert and had lower depression scores compared to the rejected applicants. In both groups, the composite scales of Adaptive Perfectionism (r = .21, p = .011) and Maladaptive Perfectionism (r = .43, p < .001) as well as their components correlated significantly with the PHQ-9 results. Maladaptive Perfectionism accounted for about 18% of variance in the PHQ-9 score.

Conclusions

Rejected medical school applicants who participated in a multiple mini-interviews admission procedure showed higher levels of depression symptoms than admitted applicants. The degree of depressive symptoms can be partly explained by Maladaptive Perfectionism scores. Since coping in medical school and in postgraduate medical education require robust mental health, perfectionism questionnaires could be an additional tool in medical school selection processes.
Are perceived bad working conditions and perceived workplace bullying associated with doctor visits? Results of the nationally representative German General Social Survey
Authors: Hajek André , König Hans-Helmut
Published: October 2019

Background

The reason for doctor visits associated with bad working conditions (and workplace bullying) remains unknown. Therefore, the aim of this study was to examine the association between perceived working conditions as well as workplace bullying and the number of doctor visits as well as the reason for seeing a doctor.

Methods

Data were derived from the German General Social Survey, a representative cross-section of the population in the year 2014. Self-reported doctor visits in the last 3 months were used as outcome measure. Self-rated working conditions (noise, bad air; time/performance pressure; bad working atmosphere; overtime; shifts/night work; hard physical labour) and workplace bullying were assessed. The reason for seeing a doctor was also recorded (acute illness; chronic illness; feeling unwell; requesting advice; visit to the doctor’s office without consulting the doctor (e.g., need to get a prescription); preventive medical check-up/vaccination). Regression analysis stratified by sex was conducted.

Results

Adjusting for various potential confounders, Poisson regressions showed that workplace bullying was associated with increased doctor visits in men, but not in women. Contrarily, time/performance pressure at work was only associated with increased doctor visits in women, but not in men. Furthermore, the probability of visiting the doctor for reasons of acute illness or feeling unwell increased with workplace bullying in men. The probability of visiting the doctor because of feeling unwell increased with time/performance pressure in women.

Conclusions

Our findings stress the association between adverse working conditions (workplace bullying as well as time/performance pressure at work) and doctor visits, with remarkable gender differences. Longitudinal studies are required to confirm the present findings and to obtain further insights into this relationship.
Plasma metabolomics and clinical predictors of survival differences in COPD patients
Authors: Pinto-Plata Victor , Casanova Ciro , Divo Miguel , Tesfaigzi Yohannes , Calhoun Vince , Sui Jing , Polverino Francesca , Priolo Carmen , Petersen Hans , de Torres Juan Pablo , Marin Jose Maria , Owen Caroline A. , Baz Rebeca , Cordova Elizabeth , Celli Bartolome
Published: October 2019

Background

Plasma metabolomics profile (PMP) in COPD has been associated with clinical characteristics, but PMP’s relationship to survival has not been reported. We determined PMP differences between patients with COPD who died an average of 2 years after enrollment (Non-survivors, NS) compared to those who survived (S) and also with age matched controls (C).

Methods

We studied prospectively 90 patients with severe COPD and 30 controls. NS were divided in discovery and validation cohorts (30 patients each) and the results compared to the PMP of 30 S and C. All participants completed lung function tests, dyspnea scores, quality of life, exercise capacity, BODE index, and plasma metabolomics by liquid and gas chromatography / mass spectometry (LC/MS, LC/MS2, GC/MS). Statistically, we used Random Forest Analysis (RFA) and Support Vector Machine (SVM) to determine metabolites that differentiated the 3 groups and compared the ability of metabolites vs. clinical characteristics to classify patients into survivors and non-survivors.

Results

There were 79 metabolites statistically different between S and NS [p < 0.05 and false discovery rate (q value) < 0.1]. RFA and SVM classification of COPD survivors and non-survivors had a predicted accuracy of 74 and 85% respectively. Elevation of tricyclic acid cycle intermediates branched amino acids depletion and increase in lactate, fructose and xylonate showed the most relevant differences between S vs. NS suggesting alteration in mitochondrial oxidative energy generation. PMP had similar predictive power for risk of death as information provided by clinical characteristics.

Conclusions

A plasma metabolomic profile characterized by an oxidative energy production difference between survivors and non-survivors was observed in COPD patients 2 years before death.
Identification of differentially expressed circRNAs and a novel hsa_circ_0000144 that promote tumor growth in gastric cancer
Authors: Wei Jianming , Wang Jinmiao , Gao Xibo , Qi Feng
Published: October 2019

Background

Circular RNAs (circRNAs) are involved in regulating tumor pathogenesis. The mechanism of circRNAs in gastric cancer (GC) is still unknown. Our study aimed to identify differentially expressed circRNAs and assess a novel circRNA (hsa_circ_0000144) in the proliferation, migration, and invasion in GC.

Methods

Gene ontology (GO) enrichment and analyses of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, pathway network, and the ceRNA regulatory network of hsa_circ_0000144 targeting miRNAs and mRNAs were performed with the help of bioinformatics using R language and Perl software. hsa_circ_0000144 expression and circRNA knockdown in GC cell lines were detected using quantitative PCR (qPCR) in vitro. Cell proliferation, migration, and invasion after circRNA knockdown were measured using the cell counting kit-8 assay and Transwell assay.

Results

The circRNA expression profile GSE78092 downloaded from the Gene Expression Omnibus database included three GC patients and three normal tissues. Thirty-two differentially expressed circRNAs comprised six upregulated circRNAs and 26 downregulated circRNAs. In particular, the ErbB signaling pathway, neurotrophin signaling pathway, cellular senescence, and pathways in bladder cancer and GC played the most important roles in the pathway network. The expression of hsa_circ_0000144 was upregulated in GC cell lines. Hsa_circ_0000144 knockdown suppressed tumor growth in vitro.

Conclusions

Hsa_circ_0000144 promotes GC cell proliferation, migration, and invasion, and the ceRNA regulatory network of hsa_circ_0000144 targeting miRNAs and mRNAs might be biomarkers for GC diagnosis and targeted therapy.
Potential Role of circPVT1 as a proliferative factor and treatment target in esophageal carcinoma
Authors: Zhong Rongrong , Chen Zhuozhi , Mo Ting , Li Zimo , Zhang Peng
Published: October 2019

Background

Many circRNAs have been reported to play important roles in cancer development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNAs in esophageal carcinoma (EC) remains unclear. In the current study, we investigated the potential role of circPVT1 in esophageal carcinoma.

Methods

Quantitative real-time PCR was performed to detect circPVT1 levels. CircPVT1-specific siRNA or plasmids were used to knock down or overexpression the target RNA. Hoechst Staining was implemented to evaluate the ratio of cell apoptosis. Transwell migration assays were carried out to study the effects of circPVT1 on esophageal squamous cell carcinoma cell invasion. RegRNA 2.0 was used for bioinformatics analysis. The expression levels of Pax-4, Pax-6, PPARα and PPAR-γ were assessed using Western blot.

Results

In the present study, we demonstrated a significant up-regulation of circPVT1 levels in EC tissues and cancer cell lines. The levels of circPVT1 decreased significantly when the cells were maintained to over-confluence. These results suggested a potential role for circPVT1 in cell proliferation. In addition, overexpressing circPVT1 in TE-10 cell promoted invasive ability of cancer cell. In contrast, siRNA knockdown of circPVT1 inhibited this phenomenon, leading to increased apoptosis levels of TE-10 cell. What’s more, miR-4663 had the effect of inhibiting tumor growth by downregulated Paxs and upregulated PPARs. Whereas, after the addition of circPVT1, this effect no longer worked, suggesting that circPVT1 may affect the malignancy of the tumor by affecting miRNA and regulating the levels of Paxs and PPARs.

Conclusions

Collectively, our study reveals a critical role for circPVT1 in esophageal carcinoma, which may provide new insights of this circRNA as a biomarker for the diagnosis and treatment target of EC.
Cervical kyphosis in asymptomatic populations: incidence, risk factors, and its relationship with health-related quality of life
Authors: Ao Shuang , Liu Yu , Wang Yu , Zhang Hao , Leng Hui
Published: October 2019

Background

Cervical kyphosis has been pointed out in asymptomatic populations. The purposes of this study were (1) to investigate the incidence of cervical kyphosis in asymptomatic populations, (2) to identify risk factors related to cervical kyphosis, and (3) to assess the relationship between cervical kyphosis and health-related quality of life (HRQOL).

Methods

A cohort of 235 asymptomatic volunteers’ records was retrospectively analyzed. Radiographic parameters of the coronal and sagittal planes were measured in the full-length spine x-ray. All patients were classified into two groups based on the cervical lordosis angle: cervical lordosis (CL) and cervical kyphosis (CK). HRQOL was evaluated by EQ-5D and SF-36 (PCS and MCS) questionnaires.

Results

CK was observed in 90 of 235 (38.3%) participants. There was a significant difference with regard to age between volunteers with CK and CL (32.23 ± 8.12 vs. 42.12 ± 6.14, p < 0.05). Several parameters had a significant relationship with CK, including TK, T1 slope, TIA, SVA, and CT. Logistic regression analysis identified age, TK, T1 slope, and SVA as independent risk factors of CK. In addition, there was a negative correlation between CK and the parameters of HRQOL (EQ-5D, − 0.63; PCS, − 0.68; MCS, − 0.59).

Conclusions

The incidence of CK in normal populations is 38.3%. Some spinal parameters are related to CK. CK is associated with the HRQOL.