bluuebunny/crossref_metadata_2025 huggingface dataset:
Postural control processes during standing and step initiation in autism spectrum disorder
Authors: Bojanek Erin K. , Wang Zheng , White Stormi P. , Mosconi Matthew W.
Published: January 2020

Background

Individuals with autism spectrum disorder (ASD) show a reduced ability to maintain postural stability, though motor control mechanisms contributing to these issues and the extent to which they are associated with other gross motor activities (e.g., stepping) are not yet known.

Methods

Seventeen individuals with ASD and 20 typically developing (TD) controls (ages 6–19 years) completed three tests of postural control during standing. During the neutral stance, individuals stood with their feet shoulder width apart. During the Romberg one stance, they stood with feet close together. During the circular sway, participants stood with feet shoulder width apart and swayed in a circular motion. The standard deviation (SD) of their center of pressure (COP) in the mediolateral (ML) and anteroposterior (AP) directions and the COP trajectory length were examined for each stance. We also assessed mutual information (MI), or the shared dependencies between COP in the ML and AP directions. Participants also completed a stepping task in which they stepped forward from one force platform to an adjacent platform. The amplitude and duration of anticipatory postural adjustments (APAs) were examined, as were the maximum lateral sway, duration, and velocity of COP adjustments following the initial step. We examined stepping variables using separate one-way ANCOVAs with height as a covariate. The relationships between postural control and stepping measures and ASD symptom severity were assessed using Spearman correlations with scores on the Autism Diagnostic Observation Schedule–Second Edition (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R).

Results

Individuals with ASD showed increased COP trajectory length across stance conditions (p = 0.05) and reduced MI during circular sway relative to TD controls (p = 0.02). During stepping, groups did not differ on APA amplitude (p = 0.97) or duration (p = 0.41), but during their initial step, individuals with ASD showed reduced ML sway (p = 0.06), reduced body transfer duration (p < 0.01), and increased body transfer velocity (p = 0.02) compared to controls. Greater neutral stance COPML variability (r = 0.55, p = 0.02) and decreased lateral sway (r = − 0.55, p = 0.02) when stepping were associated with more severe restricted and repetitive behaviors in participants with ASD.

Conclusions

We found that individuals with ASD showed reduced MI during circular sway suggesting a reduced ability to effectively coordinate joint movements during dynamic postural adjustments. Additionally, individuals with ASD showed reduced lateral sway when stepping indicating that motor rigidity may interfere with balance and gait. Postural control and stepping deficits were related to repetitive behaviors in individuals with ASD indicating that motor rigidity and key clinical issues in ASD may represent overlapping pathological processes.
Energy minimization for an electric bus using a genetic algorithm
Authors: Torabi Sina , Bellone Mauro , Wahde Mattias
Published: January 2020

Background and methods

This paper addresses, in simulation, energy minimization of an autonomous electric minibus operating in an urban environment. Two different case studies have been considered, each involving a total of 10 different 2?km bus routes and two different average speeds. In the proposed method, the minibus follows an optimized speed profile, generated using a genetic algorithm.

Results

In the first case study the vehicle was able to reduce its energy consumption by around 7 to 12% relative to a baseline case in which it maintains a constant speed between stops, with short acceleration and deceleration phases. In the second case study, involving mass variation (passengers entering and alighting) it was demonstrated that the number of round trips that can be completed on a single battery charge is increased by around 10% using the proposed method.
Exploring the experiences of the older adults who are brought to live in shelter homes in Karachi, Pakistan: a qualitative study
Authors: Cassum Laila Akber , Cash Keith , Qidwai Waris , Vertejee Samina
Published: January 2020

Background

The traditional joint family system in a culturally diverse Pakistani society shows great respect and care for older population by the families and their generations. However, in the recent years the phenomenon of population ageing in Pakistan is rapidly increasing due to demographic shift influencing life expectancy, along with changes in socio-cultural values. This transition has resulted in institutionalization of the elderly as an emerging shelter alternative. The aim of this study was to explore the experiences of the elderly people and to identify the reason which compelled them to reside in these shelter homes.

Method

A qualitative methodology, with a descriptive exploratory design, was adopted for the study. A purposive sample of 14 elderly males and females were selected, from two different shelter homes in Karachi, Pakistan. Semi-structured interviews were audio recorded and transcribed. Content analysis was done to extract the themes and comprehend the data.

Results

Content analysis revealed five major themes: the circumstances of leaving home, experiences, and challenges to wellbeing before entering the care facility, coping with challenges, and decision to live in a shelter home. The analysis discovered that the elderly were experiencing lack of physical, psychological, emotional, and financial support from their family and children. It also indicated that migration of children for better career and employment opportunities, entrance of women into the workforce, and insensitive behaviour of children, left the senior citizens neglected and helpless. The findings also uncovered the challenges of unemployment and family disputes that the elderly had to face made them dependent, distressed, helpless, and lonely resulting in both their apparently willing and forceful decision to reside in shelter homes.

Conclusion

The findings point to need for further investigation of the identified areas in this study through qualitative and quantitative researches. There is a dire need for increasing public awareness through the social, electronic, and print media, and providing capacity building training to HCPs for the care of the elderly. The lobbying group can act as a catalyst in persuading the government officials for the execution of a policy on retirement, day care and subsidized provision of health services for the betterment of the elderly.
An enhanced adaptive non-local means algorithm for Rician noise reduction in magnetic resonance brain images
Authors: Chen Kaixin , Lin Xiao , Hu Xing , Wang Jiayao , Zhong Han , Jiang Linhua
Published: January 2020

Background

The Rician noise formed in magnetic resonance (MR) imaging greatly reduced the accuracy and reliability of subsequent analysis, and most of the existing denoising methods are suitable for Gaussian noise rather than Rician noise. Aiming to solve this problem, we proposed fuzzy c-means and adaptive non-local means (FANLM), which combined the adaptive non-local means (NLM) with fuzzy c-means (FCM), as a novel method to reduce noise in the study.

Method

The algorithm chose the optimal size of search window automatically based on the noise variance which was estimated by the improved estimator of the median absolute deviation (MAD) for Rician noise. Meanwhile, it solved the problem that the traditional NLM algorithm had to use a fixed size of search window. Considering the distribution characteristics for each pixel, we designed three types of search window sizes as large, medium and small instead of using a fixed size. In addition, the combination with the FCM algorithm helped to achieve better denoising effect since the improved the FCM algorithm divided the membership degrees of images and introduced the morphological reconstruction to preserve the image details.

Results

The experimental results showed that the proposed algorithm (FANLM) can effectively remove the noise. Moreover, it had the highest peak signal-noise ratio (PSNR) and structural similarity (SSIM), compared with other three methods: non-local means (NLM), linear minimum mean square error (LMMSE) and undecimated wavelet transform (UWT). Using the FANLM method, the image details can be well preserved with the noise being mostly removed.

Conclusion

Compared with the traditional denoising methods, the experimental results showed that the proposed approach effectively suppressed the noise and the edge details were well retained. However, the FANLM method took an average of 13 s throughout the experiment, and its computational cost was not the shortest. Addressing these can be part of our future research.
Risk factors associated with hypertensive disorders in pregnancy in Nekemte referral hospital, from July 2015 to June 2017, Ethiopia: case-control study
Authors: Hinkosa Leta , Tamene Almaz , Gebeyehu Negeso
Published: January 2020

Background

Hypertension is the most common medical problem encountered in pregnancy and is a leading cause of perinatal and maternal morbidity and mortality. However, its magnitude and risk factors yet not adequately assessed at the study area.

Methods

Facility-based retrospective unmatched case-control study was conducted to identify risk factors associated with Hypertensive disorders of pregnancy in Nekemte Referral Hospital just two years back from study period July 1, 2015, to June 30, 2017. Bivariate logistic regression was considered for inclusion in to the multivariate logistic regression. Finally, multi varaite analysis were done to identify risk factors of hypertensive disorders of pregnancy.

Results

Among 6826 total delivery records from July 2015 –June 2017, 199 women developed hypertension during pregnancy. Among 199 women 153(76.9%) were pre-eclampsia/eclampsia,28(14.1%) were gestational hypertension, 14(0.7%) were superimposed hypertension and 4 (2.9%) were chronic hypertension.

Age ≥ 35 (AOR: 2.51, 95% CI: 1.08, 5.83), rural residential area (AOR: 1.79, 95% CI: 1.150, 2.799), prim gravida (AOR: 3.39, 95% CI: 2.16, 5.33), null parity (AOR: 4.35, 95% CI: 2.36, 8.03), positive history of abortion (AOR: 4.39, 95% CI: 1.64, 11.76), twin pregnancy (AOR: 3.78, 95% CI: 1.52, 9.39), lack of ANC follow up (AOR: 3.05, 95% CI: 1.56, 5.96) as well as positive pre-existing hypertension (AOR: 3.81, 95% CI: 1.69, 8.58), positive family history of hypertension (AOR: 5.04, 95% CI: 2.66, 9.56) and positive history of diabetes mellitus (AOR: 5.03, 95% CI: 1.59, 15.89) were risk factors for hypertensive disorders during pregnancy.

Conclusion

This study found that Women with hypertension during pregnancy have a greater risk of developing adverse pregnancy outcome as compared to normotensive pregnant women. so, identification of these risk factors would be useful for early diagnosis of hypertension disorders during pregnancy to give appropriate clinical monitoring and treatments and timely managing maternal and perinatal complications.
Knowledge on postnatal care among postpartum mothers during discharge in maternity hospitals in Asmara: a cross-sectional study
Authors: Beraki Ghirmay Ghebreigziabher , Tesfamariam Eyasu H. , Gebremichael Amanuel , Yohannes Berhanemeskel , Haile Kessete , Tewelde Shewit , Goitom Simret
Published: January 2020

Background

The early postnatal period is a dangerous time for both mother and baby where morbidity and mortality are highly prevalent if proper care is not done. Post natal care (PNC) knowledge has significant role in reducing such complications. In this study, the knowledge of postpartum mothers on PNC and its determinants were determined.

Methods

A cross-sectional quantitative study was conducted in postpartum mothers (PpM) who attended all maternal delivery services in Asmara. Data was collected by a structured questionnaire. All (n = 250) PpM who gave birth in December, 2017 were included in the study. Independent samples t-test and one way ANOVA were used to compare the scores in knowledge across categories of background characteristics using SPSS. Bonferroni post-hoc test was performed for variables that were found to be significant while using ANOVA tool. P-values less than 0.05 were considered as significant.

Results

The percentage of PpM who cited vaginal bleeding, as a maternal danger sign, and fever, as a baby danger sign, were 83.2 and 58.8%, respectively. The majority (96%) of PpM responded the correct answer on where to go if they note any danger signs. In addition, more than nine tenth of PpM correctly identified injectable contraceptives (92.7%) and oral contraceptive (91.5%). The percentages of knowledge in recognizing the necessary nutrients ranged from 87.6% for carbohydrates to 46% for minerals. The percentages of correct knowledge regarding first baby bath, frequency of breast feeding, umbilical care, duration of exclusive breast feeding, need and purpose of vaccine were 40.1, 81.9, 77.4, 94.8, and 99.2% respectively. The mean PNC knowledge score was 24.89/60. The score of knowledge on postnatal care was found to significantly differ across the categories of residence (p < 0.001) and ethnicity (p = 0.015). An increasing trend of knowledge score was observed with increase in age group (p < 0.001), educational level (p = 0.021), gravida (p < 0.001) and para (p < 0.001).

Conclusion

Considerable gaps in knowledge regarding postnatal care among postpartum mothers were evident. Special attention should be laid on rural residents, single/living together, junior/below in educational level, primigravida/para, non-Tigrigna ethnicity, and 17 to 25 years old mothers.
A root cause analysis of sub-optimal uptake and compliance to iron and folic acid supplementation in pregnancy in 7 districts of Zambia
Authors: Simuyemba Moses C. , Bwembya Phoebe A. , Chola Mumbi , Michelo Charles
Published: January 2020

Background

Iron and Folic Acid are two of the micronutrients recommended for pregnant women to support optimal maternal outcomes with regard to preventing anaemia and foetal birth defects. It is difficult to establish if women provided with iron and folic acid supplementation in Zambia benefit from it and how well it is implemented. The overall objective of this study was to determine the levels of uptake and compliance to iron and folic acid in pregnancy among women of child-bearing age in Zambia, with a focus on both supply and demand factors.

Methods

A cross sectional, mixed method study was done. Data was collected in August and September 2015 from six of the 14 districts in which Scaling Up Nutrition interventions were being undertaken as well as Lusaka district. A household survey covering 402 males and females of child-bearing age, 27 key informant interviews amongst key stakeholders and 12 focus group discussions at community level were conducted.

Results

Antenatal clinic attendance was almost universal (98.7%); the majority of both men (92.1%) and women (97.4%) had heard messages about iron and folic acid supplementation; the majority (96.5%) of women reported having taken iron and folic acid tablets during their last pregnancy, with 61.3% starting in the second trimester, 27.2% during the first trimester, and 7.7% in their third trimester. Eighty-five per cent (80.5%) of the women reported that they had taken all the tablets they were given with about 13.4% not taking all the tablets received.

Conclusions

Root cause analysis, using both qualitative and quantitative findings, showed that the main challenges faced were long distances to health facilities and high transport costs; some women not being reached with supplementation messaging; lack of formalised and uniform training around delivery of antenatal messages across health care workers; women not attending antenatal monthly to replenish supplements; and forgetfulness to take the drugs daily. While male involvement may be a supportive factor, it sometimes hinders women from accessing antenatal services. Results showed that both uptake and compliance to iron and folic acid supplementation in pregnancy in Zambia were sub-optimal.
Complete blood count-based inflammatory score (CBCS) is a novel prognostic marker for gastric cancer patients after curative resection
Authors: Lin Jian-Xian , Lin Jun-Peng , Xie Jian-Wei , Wang Jia-bin , Lu Jun , Chen Qi-Yue , Cao Long-long , Lin Mi , Tu Ruhong , Zheng Chao-Hui , Huang Chang-Ming , Li Ping
Published: January 2020

Background

We sought to investigate the prognostic value of complete blood count (CBC)-based biomarkers for patients with resectable gastric cancer (GC).

Methods

Patients with GC who underwent primary surgical resection between December 2008 and December 2013 were included. The estimated area under the curve (AUC) and multivariate Cox regression models were used to identify the best CBC-based biomarker. Time-dependent receiver operating characteristic (t-ROC) curve analysis was used to predict overall survival and compare the prognostic impact.

Results

In the 1810 patients analyzed, the median follow-up period was 51.0 months (range 1–101 months). Based on multivariate analysis, the lymphocyte-monocyte ratio (LMR) and hemoglobin (Hb) level were independent prognostic factors (both P < 0.05). Based on the LMR and Hb level, we established the CBC-based inflammatory score (CBCS). A higher CBCS was associated with older age, female sex, higher American Society of Anesthesiologists (ASA) score, proximal tumor location, larger tumor size, later stage and vascular involvement (all P < 0.05). Univariate analyses showed that a higher CBCS was also associated with worse overall survival (OS), which was consistent in each stage (all P < 0.05). Multivariate analysis revealed that the CBCS was a significant independent biomarker (P < 0.05). The AUC for the CBCS (0.627) was significantly higher than the AUCs for the LMR (0.573) and Hb level (0.605) (both P < 0.05). Furthermore, the t-ROC curve of the CBCS was superior to that of the prognostic nutritional index (PNI), systemic immune-inflammation index (SII), modified Glasgow prognostic score (mGPS) and C-reactive protein/albumin ratio (CRP/Alb) throughout the observation period.

Conclusion

The preoperative LMR and Hb level were optimal CBC-based biomarkers for predicting OS in GC patients after curative resection. Based on the LMR and Hb, we developed a novel and easily obtainable prognostic score called the CBCS, which may improve the prediction of clinical outcomes.
Major differences in follow-up practice of patients with colorectal cancer; results of a national survey in the Netherlands
Authors: Qaderi S. M. , Wijffels N. A. T. , Bremers A. J. A. , de Wilt J. H. W.
Published: January 2020

Background

The precise content and frequency of follow-up of patients with colorectal cancer (CRC) is variable and guideline adherence is low. The aim of this study was to assess the view of colorectal surgeons on their local follow-up schedule and to clarify their opinions about risk-stratification and organ preserving therapies. Equally important, adherence to the Dutch national guidelines was determined.

Methods

Colorectal surgeons were invited to complete a web-based survey about the importance and interval of clinical follow-up, CEA monitoring and the use of imaging modalities. Furthermore, the opinions regarding physical examination, risk-stratification, organ preserving strategies, and follow-up setting were assessed. Data were analyzed using quantitative and qualitative analysis methods.

Results

A total of 106 colorectal surgeons from 52 general and 5 university hospitals filled in the survey, yielding a hospital response rate of 74% and a surgeon response rate of 42%. The follow-up of patients with CRC was mainly done by surgeons (71%). The majority of the respondents (68%) did not routinely perform physical examination during follow-up of rectal patients. Abdominal ultrasound was the predominant modality used for detection of liver metastases (77%). Chest X-ray was the main modality for detecting lung metastases (69%). During the first year of follow-up, adherence to the minimal guideline recommendations was high (99–100%). The results demonstrate that, within the framework of the guidelines, some respondents applied a more intensive follow-up and others a less intensive schedule. The majority of the respondents (77%) applied one single follow-up imaging schedule for all patients that underwent treatment with curative intent.

Conclusions

Dutch colorectal surgeons’ adherence to minimal guideline recommendations was high, but within the guideline framework, opinions differed about the required intensity and content of clinical visits, the interval of CEA monitoring, and the importance and frequency of imaging techniques. This national survey demonstrates current follow-up practice throughout the Netherlands and highlights the follow-up differences of curatively treated patients with CRC.
A case of bilateral acute depigmentation of the Iris in one of two identical twins
Authors: Langevin Spencer , Gershkovich Alexandra , Marr Brian P.
Published: January 2020

Background

Bilateral Acute Depigmentation of the Iris (BADI) is a condition which was first described in a case series from Turkey by Tugal-Tutkin and Urgancioglu in (Graefes Arch Clin Exp Ophthalmol 244:742-6, 2006). The condition is characterized by bilateral acute depigmentation and discoloration of the iris stroma, pigment dispersion, and deposition of pigment in the angle. In our case we report a patient who developed BADI after receiving pitcher plant extract injections for chronic migraine, while her identical twin sister has normal iris architecture and pigmentation and never received any pitcher plant injections.

Case presentation

Patient is a 41-year-old female with history of pitcher plant extract injections to her face for chronic migraine, who later developed bilateral depigmentation of the iris. She did not have any signs of anterior segment uveitis or iridocyclitis. She has an identical twin sister who maintained normal iris pigmentation during the entire course.

Conclusions

Bilateral Acute depigmentation of the is a recently discovered condition described in the literature in Turkish patients (Tugal-Tutkun and Urgancioglu, Graefes Arch Clin Exp Ophthalmol 244:742-6, 2006; Tugal-Tutkun et al., Ophthalmology 116(8):1552-7, 2009). This condition affects mainly young females and is characterized by acute bilateral stromal depigmentation, without other pathologic ocular findings. These patients usually maintain normal vision and do not develop significant glaucoma from pigment collecting in the anterior chamber angle. This condition can be mistaken for Fuchs’ heterochromic iridocyclitis, pigment dispersion syndrome, pseudoexfoliation syndrome, and viral iridocyclitis. This is the first reported case in North America and is important for differentiation from the above pathologies. Our patient had a history of pitcher plant extract injections to the face but it is unclear if this is associated with our patient’s development of BADI. As awareness of this condition progresses, a possible etiology may be elucidated.
Inverted internal limiting membrane flap technique versus complete internal limiting membrane peeling in large macular hole surgery: a comparative study
Authors: Ramtohul Prithvi , Parrat Eric , Denis Danièle , Lorenzi Umberto
Published: January 2020

Background

To compare the anatomical and functional outcomes of the inverted internal limiting membrane (ILM) flap technique and the complete ILM removal in the treatment of large stage 4 macular hole (MH) > 400 μm and to evaluate reconstructive anatomical changes in foveal microstructure using spectral-domain optical coherence tomography.

Methods

This is a retrospective, consecutive, nonrandomized comparative study of patients affected by idiopathic, myopic or traumatic stage 4 MH (minimum diameter > 400 μm) treated with 25-gauge pars-plana vitrectomy with either complete ILM peeling (n = 23, Group 1) or inverted ILM flap technique (n = 23, Group 2), between August 2016 and August 2018. Main outcomes measured were the MH closure rate assessed by spectral-domain optical coherence tomography and the best-corrected visual acuity (BCVA) at six months. Foveal microstructure reconstructive changes were evaluated using SD-OCT to determine predictive factors of postoperative BCVA.

Results

Closure of MH was achieved in 16/23 cases of Group 1 (70%) and in 22/23 cases of the Group 2 (96%). Surgical failure was reported in 6 cases of Group 1 and 1 case of Group 2. The MH closure rate was significantly higher with the inverted ILM flap technique (P-value = 0.02). Average BCVA (LogMAR) changed from 1.04 ± 0.32 to 0.70 ± 0.31 in Group 1 and from 0.98 ± 0.22 to 0.45 ± 0.25 in Group 2 (P-value = 0.005) at 6 months. Improvement in BCVA (> 0.3 LogMAR units) was statistically higher in the Group 2 (P-value = 0.03). Restoration of foveal microstructure was significantly higher in the Group 2 at 6 months (52% vs 9%, P-value < 0.01). In Group 2, the integrity of the external limiting membrane at 3 months postoperatively was the only significant feature correlated with postoperative BCVA at 6 months (r = 0.562; P-Value = 0.01, forward stepwise regression analysis).

Conclusion

Inverted ILM flap technique is more effective than the classic ILM peeling for the closure of large stage 4 MHs > 400 μm, improving both anatomical and functional outcomes. Early recovery of the external limiting membrane at 3 months is a positive predictive value of postoperative BCVA 6 months after inverted ILM flap technique.
New insight into the informal patients’ payments on the evidence of literature: a systematic review study
Authors: Pourtaleb Arefeh , Jafari Mehdi , Seyedin Hesam , Akhavan Behbahani Ali
Published: January 2020

Background

Nowadays, a growing literature reveals how patients use informal payments to seek either better treatment or additional services, but little systematic review has been accomplished for synthesizing the main factors. The purpose of this study was to analyze the content of literatures to demonstrate the factors for informal patient payments.

Methods

In this systematic review study, PubMed, Web of Science, Wiley Online Library, Science Direct, Ovid, Scopus, and Iranian databases were investigated without time limitation for eligible English and Persian studies. Achieved data were analyzed using content analysis approach and MAXQDA 10 software.

Results

Themes related to informal payments in external context of health system were demographic features of health service consumers, patient’s personality features and social & cultural backgrounds of the community. Health system challenges’ themes were about stewardship weakness, and sustainable financing and social protection weakness. These were followed by human resources’ organizational behavior challenges, drugs, medical products, and services delivery provision process challenges and finally change management weakness for reducing and dealing with IPs.

Conclusion

It appears that improving the quality of health care services and accurate monitoring of delivery processes, along with performing some strategies for regulating payroll and medical tariffs, strict rules and regulations and improving health staff motivation, would be effective ways against informal payments. Improving the health insurance contribution, promoting transparency & accountability in health system especially in financing, identify precise control mechanism, using empower patient/public related approach, modifying community perception, reinforcing social resistance to unofficial payments and rebuilt lost social capital in health care are some of the other recommendations in this field. To practice these strategies, a comprehensive and systemic vision and approach is needed, however, the key point is that before applying any strategy the impact of this strategy on access, efficiency, equity, and other health systems’ goals and policies should be investigated due to the consideration.
Genome-wide analysis reveals the association between alternative splicing and DNA methylation across human solid tumors
Authors: Sun Xiaohui , Tian Yiping , Wang Jianming , Sun Zeyuan , Zhu Yimin
Published: January 2020

Background

Dysregulation of alternative splicing (AS) is a critical signature of cancer. However, the regulatory mechanisms of cancer-specific AS events, especially the impact of DNA methylation, are poorly understood.

Methods

By using The Cancer Genome Atlas (TCGA) SpliceSeq and TCGA data for ten solid tumor types, association analysis was performed to characterize the potential link between cancer-specific AS and DNA methylation. Functional and pathway enrichment analyses were performed, and the protein-protein interaction (PPI) network was constructed with the String website. The prognostic analysis was carried out with multivariate Cox regressions models.

Results

15,818 AS events in 3955 annotated genes were identified across ten solid tumor types. The different DNA methylation patterns between tumor and normal tissues at the corresponding alternative spliced exon boundaries were shown, and 51.3% of CpG sites (CpGs) revealed hypomethylated in tumors. Notably, 607 CpGs were found to be highly correlated with 369 cancer-specific AS events after permutation tests. Among them, the hypomethylated CpGs account for 52.7%, and the number of down-regulated exons was 173. Furthermore, we found 38 AS events in 35 genes could serve as new molecular biomarkers to predict patient survival.

Conclusions

Our study described the relationship between DNA methylation and AS events across ten human solid tumor types and provided new insights into intragenic DNA methylation and exon usage during the AS process.
Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis
Authors: Hartley Benjamin F. , Barnes Neil C. , Lettis Sally , Compton Chris H. , Papi Alberto , Jones Paul
Published: January 2020

Background

Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear.

Methods

This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox’s proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation.

Results

Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year.

Conclusions

The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations.
Chitotriosidase: a biomarker of activity and severity in patients with sarcoidosis
Authors: Bennett David , Cameli Paolo , Lanzarone Nicola , Carobene Loredana , Bianchi Nicola , Fui Annalisa , Rizzi Luigi , Bergantini Laura , Cillis Giuseppe , d’Alessandro Miriana , Mazzei Maria Antonietta , Refini Rosa Metella , Sestini Piersante , Bargagli Elena , Rottoli Paola
Published: January 2020

Background

Serum chitotriosidase is a promising biomarker that has shown high specificity and sensitivity in patients with sarcoidosis. The aim of this study was to investigate correlations between serum chitotriosidase, clinical phenotypes, disease localizations and different radiological lung involvement and to identify clinical features associated with over-expression of chitotriosidase in a large cohort of sarcoidosis patients.

Methods

Chitotriosidase activity was evaluated in a population of 694 consecutive patients (males 39%, age 55.8 ± 12.8 years). Clinical and respiratory functional characteristics, Clinical Outcome Scale (COS) classification, clinical phenotypes proposed by the GenPhenResA project, and radiological assessment, including CT scan, were collected. Serum sampling and clinical and functional assessments at follow-up were also included.

Results

Significantly higher chitotriosidase activity was observed in sarcoidosis patients than in healthy controls (p < 0.0001). Evidence of lung fibrosis with reticular abnormalities and traction bronchiectasis at High resolution CT, presence of multiple extrapulmonary sarcoid localizations and increased 24-h urinary excretion of calcium were associated with significantly higher chitotriosidase activity (p < 0.005). Patients with remitted or minimal disease had lower values of chitotriosidase than patients with persistent disease. At follow-up, patients who required an increase in steroid dose showed an increase in its activity.

Conclusions

Chitotriosidase is a reliable biomarker of sarcoidosis. It is increased in patients with sarcoidosis correlating with disease activity, severity and multiorgan dissemination. Steroid therapy tended to reduce chitotriosidase expression, however it responded in cases of disease relapse.
Ongoing challenges in pulmonary fibrosis and insights from the nintedanib clinical programme
Authors: Valenzuela Claudia , Torrisi Sebastiano Emanuele , Kahn Nicolas , Quaresma Manuel , Stowasser Susanne , Kreuter Michael
Published: January 2020

The approvals of nintedanib and pirfenidone changed the treatment paradigm in idiopathic pulmonary fibrosis (IPF), and increased our understanding of the underlying disease mechanisms. Nonetheless, many challenges and unmet needs remain in the management of patients with IPF and other progressive fibrosing interstitial lung diseases.

This review describes how the nintedanib clinical programme has helped to address some of these challenges. Data from this programme have informed changes to the IPF diagnostic guidelines, the timing of treatment initiation, and the assessment of disease progression. The use of nintedanib to treat patients with advanced lung function impairment, concomitant emphysema, patients awaiting lung transplantation and patients with IPF and lung cancer is discussed. The long-term use of nintedanib and an up-to-date summary of nintedanib in clinical practice are discussed. Directions for future research, namely emerging therapeutic options, precision medicine and other progressive fibrosing interstitial lung diseases, are described.

Further developments in these areas should continue to improve patient outcomes.
Proteome analysis guided genetic engineering of Corynebacterium glutamicum S9114 for tween 40-triggered improvement in l-ornithine production
Authors: Jiang Yan , Huang Ming-Zhu , Chen Xue-Lan , Zhang Bin
Published: January 2020

Background

l-ornithine is a valuable amino acid with a wide range of applications in the pharmaceutical and food industries. However, the production of l-ornithine by fermentation cannot compete with other methods, because of the low titers produced with this technique. Development of fermentation techniques that result in a high yield of l-ornithine and efficient strategies for improving l-ornithine production are essential.

Results

This study demonstrates that tween 40, a surfactant promoter of the production of glutamate and arginine, improves l-ornithine production titers in engineered C. glutamicum S9114. The intracellular metabolism under tween 40 triggered fermentation conditions was explored using a quantitative proteomic approach, identifying 48 up-regulated and 132 down-regulated proteins when compared with the control. Numerous proteins were identified as membrane proteins or functional proteins involved in the biosynthesis of the cell wall. Modulation of those genes revealed that the overexpression of CgS9114_09558 and the deletion of CgS9114_13845, CgS9114_02593, and CgS9114_02058 improved the production of l-ornithine in the engineered strain of C. glutamicum Orn8. The final strain with all the exploratory metabolic engineering manipulations produced 25.46 g/L of l-ornithine, and a yield of 0.303 g l-ornithine per g glucose, which was 30.6% higher than that produced by the original strain (19.5 g/L).

Conclusion

These results clearly demonstrate the positive effect of tween 40 addition on l-ornithine accumulation. Proteome analysis was performed to examine the impact of tween 40 addition on the physiological changes in C. glutamicum Orn8 and the results showed several promising modulation targets for developing l-ornithine-producing strains.
Inequity in inpatient services utilization: a longitudinal comparative analysis of middle-aged and elderly patients with the chronic non-communicable diseases in China
Authors: Fu Xian-zhi , Wang Lian-ke , Sun Chang-qing , Wang Dong-dong , He Jun-jian , Tang Qi-xin , Zhou Qian-yu
Published: January 2020

Background

Aging and the chronic non-communicable diseases (NCDs) challenge the Chinese government in the process of providing hospitalization services fairly and reasonably. The Chinese government has developed the basic medical insurance system to solve the problem of “expensive medical cost and difficult medical services” for vulnerable groups and alleviate the unfair phenomenon. However, few studies have confirmed its effect through longitudinal comparison. This study aimed to explore the trend in the inequity of inpatient use among middle-aged and elderly individuals with NCDs in China.

Methods

This longitudinal comparative study was based on CHARLS data in 2011, 2013 and 2015. Concentration index (CI) was used to measure the variation trend of inequity of inpatient services utilization, while the decomposition method of the CI was applied to measure the factors contributing to inequity in inpatient services utilization. The effect of each factor on the change of inequity in inpatient services utilization was divided into the change of the elasticity and the change of inequality using the Oaxaca-type decomposition method.

Results

The affluent middle-aged and elderly patients with NCDs used more inpatient services than poor groups. The per capita household consumption expenditure (PCE) and Urban Employee Basic Medical Insurance (UEBMI) contributed to the decline in pro-rich inequality of inpatient use, while the New Rural Cooperative Medical Scheme (NRCMS) contributed to the decline in pro-poor inequality of inpatient use.

Conclusions

There was a certain degree of pro-rich unfairness in the probability and frequency of inpatient services utilization for middle-aged and elderly individuals with NCDs in China. The decrease of pro-wealth contribution of PCE and UEBMI offset the decrease of pro-poor contribution of NRCMS, and improved the equity of inpatient services utilization, favoring poor people.
Beliefs about cannabis at the time of legalization in Canada: results from a general population survey
Authors: Cunningham John A.
Published: January 2020

Aims

Cannabis became a legally available drug in Canada in October of 2018. The objective of this study was to examine beliefs about cannabis use at the time of legalization among past year cannabis users, those who had used cannabis but not in the last year, and people who had never used cannabis.

Design and methods

A survey of 813 participants, 18 years and over, and identified using random digit dialing methods, was made of the Canadian general population. Among other items, participants were asked a series of questions about their beliefs regarding cannabis use and recovery.

Results

Compared to never and ever users, participants who used cannabis in the last year regarded cannabis as less of a societal problem (mean [SD] past year use = 3.8 [2.4] versus 6.4 [2.6] and 6.0 [2.4] respectively, p = .001), than people were less likely to become addicted to cannabis if they tried it (past year use = 13.3% versus 48.3% and 25.1%, p = .001), and a larger proportion believed that recovery from cannabis without treatment was likely (past year use = 40.8% versus 14.2% and 19.3%, p = .001). All groups were equally positive of the chances of recovering from cannabis addiction with treatment (p = .72).

Discussion and conclusion

Beliefs about cannabis use vary substantially between those who have used the drug in the past year and those who have not. Replication of the survey at a later date is merited in order to assess the ways in which beliefs about cannabis evolve after an extended period of cannabis being available as a legal drug.
Quality of life in children with infrequent congenital heart defects: cohort study with one-year of follow-up
Authors: Moreno-Medina Karen , Barrera-Castañeda Magally , Vargas-Acevedo Catalina , García-Torres Alberto E. , Ronderos Miguel , Huertas-Quiñones Manuel , Cabrera Silvana , Domínguez María Teresa , Sandoval Reyes Nestor , Dennis Rodolfo J.
Published: January 2020

Background

The evidence regarding patient related outcomes in children with infrequent congenital heart defects (I-CHD) is very limited. We sought to measure quality of life (QoL) in children with I-CHD, and secondarily, to describe QoL changes after one-year of follow-up, self-reported by children and through their caregivers’ perspective.

Methods

We assembled a cohort of children diagnosed with an I-CHD in a cardiovascular referral center in Colombia, between August 2016 and September 2018. At baseline and at one-year follow-up, a clinical psychology assessment was performed to establish perception of QoL. The Pediatric Quality of Life Inventory (PedsQL) 4.0 scale was used in both general and cardiac modules for patients and for their caregivers. We used a Mann-Whitney U test to compare scores for general and cardiac modules between patients and caregivers, while a Wilcoxon test was used to compared patients’ and caregivers’ baseline and follow-up scores. Results are presented as median and interquartile range.

Results

To date, QoL evaluation at one-year follow-up has been achieved in 112/157 patients (71%). Self-reported scores in general and cardiac modules were higher than the QoL perceived through their caregivers, both at baseline and after one-year of follow-up. When compared, there was no statistically significant difference in general module scores at baseline between patients (median = 74.4, IQR = 64.1–80.4) and caregivers scores (median = 68.4, IQR = 59.6–83.7), p = 0.296. On the contrary, there was a statistical difference in baseline scores in the cardiac module between patients (median = 79.6, IQR = 69.7–87.4) and caregivers (median = 73.6, IQR = 62.6–84.3), p = 0.019. At one-year of follow-up, scores for the general module between patients (median = 72.8, IQR = 59.2–85.9) and caregivers (median = 69.9, IQR = 58.1–83.7) were not statistically different (p = 0.332). Finally, a significant difference was found for cardiac module scores between patient (median = 75.0, IQR = 67.1–87.1) and caregivers (median = 73.1, IQR = 59.5–83.8), p = 0.034.

Conclusions

QoL in children with I-CHD can be compromised. However, children have a better perception of their QoL when compared with their caregivers’ assessments. To provide high-quality care, besides a thorough clinical evaluation, QoL directly elicited by the child should be an essential aspect in the integral management of I-CHD.
Classical complement cascade initiating C1q protein within neurons in the aged rhesus macaque dorsolateral prefrontal cortex
Authors: Datta Dibyadeep , Leslie Shannon N. , Morozov Yury M. , Duque Alvaro , Rakic Pasko , van Dyck Christopher H. , Nairn Angus C. , Arnsten Amy F. T.
Published: January 2020

Background

Cognitive impairment in schizophrenia, aging, and Alzheimer’s disease is associated with spine and synapse loss from the dorsolateral prefrontal cortex (dlPFC) layer III. Complement cascade signaling is critical in driving spine loss and disease pathogenesis. Complement signaling is initiated by C1q, which tags synapses for elimination. C1q is thought to be expressed predominately by microglia, but its expression in primate dlPFC has never been examined. The current study assayed C1q levels in aging primate dlPFC and rat medial PFC (mPFC) and used immunoelectron microscopy (immunoEM), immunoblotting, and co-immunoprecipitation (co-IP) to reveal the precise anatomical distribution and interactions of C1q.

Methods

Age-related changes in C1q levels in rhesus macaque dlPFC and rat mPFC were examined using immunoblotting. High-spatial resolution immunoEM was used to interrogate the subcellular localization of C1q in aged macaque layer III dlPFC and aged rat layer III mPFC. co-IP techniques quantified protein-protein interactions for C1q and proteins associated with excitatory and inhibitory synapses in macaque dlPFC.

Results

C1q levels were markedly increased in the aged macaque dlPFC. Ultrastructural localization found the expected C1q localization in glia, including those ensheathing synapses, but also revealed extensive localization within neurons. C1q was found near synapses, within terminals and in spines, but was also observed in dendrites, often near abnormal mitochondria. Similar analyses in aging rat mPFC corroborated the findings in rhesus macaques. C1q protein increasingly associated with PSD95 with age in macaque, consistent with its synaptic localization as evidenced by EM.

Conclusions

These findings reveal novel, intra-neuronal distribution patterns for C1q in the aging primate cortex, including evidence of C1q in dendrites. They suggest that age-related changes in the dlPFC may increase C1q expression and synaptic tagging for glial phagocytosis, a possible mechanism for age-related degeneration.