bluuebunny/crossref_metadata_2025 huggingface dataset:
AllesTM: predicting multiple structural features of transmembrane proteins
Authors: Hönigschmid Peter , Breimann Stephan , Weigl Martina , Frishman Dmitrij
Published: June 2020

Background

This study is motivated by the following three considerations: a) the physico-chemical properties of transmembrane (TM) proteins are distinctly different from those of globular proteins, necessitating the development of specialized structure prediction techniques, b) for many structural features no specialized predictors for TM proteins are available at all, and c) deep learning algorithms allow to automate the feature engineering process and thus facilitate the development of multi-target methods for predicting several protein properties at once.

Results

We present AllesTM, an integrated tool to predict almost all structural features of transmembrane proteins that can be extracted from atomic coordinate data. It blends several machine learning algorithms: random forests and gradient boosting machines, convolutional neural networks in their original form as well as those enhanced by dilated convolutions and residual connections, and, finally, long short-term memory architectures. AllesTM outperforms other available methods in predicting residue depth in the membrane, flexibility, topology, relative solvent accessibility in its bound state, while in torsion angles, secondary structure and monomer relative solvent accessibility prediction it lags only slightly behind the currently leading technique SPOT-1D. High accuracy on a multitude of prediction targets and easy installation make AllesTM a one-stop shop for many typical problems in the structural bioinformatics of transmembrane proteins.

Conclusions

In addition to presenting a highly accurate prediction method and eliminating the need to install and maintain many different software tools, we also provide a comprehensive overview of the impact of different machine learning algorithms and parameter choices on the prediction performance.

AllesTM is freely available at https://github.com/phngs/allestm.
Intraoperative hypotension is associated with increased postoperative complications in patients undergoing surgery for pheochromocytoma-paraganglioma: a retrospective cohort study
Authors: Li Nan , Kong Hao , Li Shuang-Ling , Zhu Sai-Nan , Zhang Zheng , Wang Dong-Xin
Published: June 2020

Background

Dramatic hemodynamic fluctuation occurs frequently during surgery for pheochromocytoma or paraganglioma. However, the criteria of intraoperative hemodynamic instability vary widely, and most of them were defined arbitrarily but not according to patients’ prognosis. The objective was to analyze the relationship between different thresholds and durations of intraoperative hyper−/hypotension and the risk of postoperative complications in patients undergoing surgery for pheochromocytoma or paraganglioma.

Methods

This was a retrospective single-center cohort study performed in a tertiary care hospital from January 1, 2005 to December 31, 2017. Three hundred twenty-seven patients who underwent surgery for pheochromocytoma or paraganglioma, of which the diagnoses were confirmed by postoperative pathologic examination, were enrolled. Those who were less than 18 years, underwent surgery involving non-tumor organs, or had incomplete data were excluded. The primary endpoint was a composite of the occurrence of AKI or other complications during hospital stay after surgery. Multivariate Logistic regression models were used to analyze the association between different thresholds and durations of intraoperative hyper−/hypotension and the development of postoperative complications.

Results

Forty three (13.1%) patients developed complications during hospital stay after surgery. After adjusting for confounding factors, intraoperative hypotension, defined as systolic blood pressure (SBP) of ≤95 mmHg for ≥20 min (OR 3.211; 99% CI 1.081–9.536;P = 0.006), SBP of ≤90 mmHg for ≥20 min (OR 3.680; 98.8% CI 1.107–12.240;P = 0.006), SBP of ≤85 mmHg for ≥10 min (OR 3.975; 98.3% CI 1.321–11.961;P = 0.003), and SBP of ≤80 mmHg for ≥1 min (OR 3.465; 95% CI 1.484–8.093;P = 0.004), were associated with an increased risk of postoperative complications. On the other hand, intraoperative hypertension was not significantly associated with the development of postoperative complications.

Conclusions

For patients undergoing surgery for pheochromocytoma or paraganglioma, intraoperative hypotension is associated with increased postoperative complications; and the harmful effects are level- and duration-dependent. The effects of intraoperative hypertension need to be studied further.
Short-course Rifaximin therapy efficacy and lactulose hydrogen breath test in Chinese patients with diarrhea-predominant irritable bowel syndrome
Authors: Zhuang Xiaojun , Tian Zhenyi , Luo Mei , Xiong Lishou
Published: June 2020

Background

Gut microbiota alterations including small intestinal bacterial overgrowth (SIBO) might play a role in pathogenesis of irritable bowel syndrome (IBS). Rifaximin could effectively and safely improve IBS symptoms. The aim of this study was to investigate the effect of rifaximin on Gastrointestinal (GI) symptoms, quality of life (QOL) and SIBO eradication in Chinese IBS-D patients.

Methods

This study included 78 IBS-D patients defined by the Rome IV criteria. Patients received 400 mg rifaximin twice daily for 2 weeks and 10-week follow-up. GI symptoms were assessed at week 0, 2, 4, 8 and 12. QOL and lactulose hydrogen breath test (LHBT) results were estimated at week 0 and 4.

Results

All participants showed significant improvements in GI symptom subdomains after rifaximin treatment (all P < 0.05), which could maintain at least 10 weeks of follow-up. Additionally, QOL scores were increased with concomitant improvement of clinical symptoms (all P < 0.05). The 45 rifaximin-responsive patients (57.7%) achieved significantly greater GI-symptom improvement than non-responders (all P < 0.05). No GI symptoms were associated with SIBO (all P > 0.05). SIBO normalization after rifaximin treatment measured by LHBT was found in 44.4% (20/45) of patients with SIBO before treatment.

Conclusion

A short course (2 weeks) of rifaximin improved GI symptoms and QOL in Chinese IBS-D patients whether they had SIBO or not. However, the efficacy of rifaximin could not be explained by the successful eradication of SIBO. Further studies on the therapeutic mechanisms of rifaximin in IBS are urgently needed.
Multimorbidity patterns, polypharmacy and their association with liver and kidney abnormalities in people over 65 years of age: a longitudinal study
Authors: Villén Noemí , Guisado-Clavero Marina , Fernández-Bertolín Sergio , Troncoso-Mariño Amelia , Foguet-Boreu Quintí , Amado Ester , Pons-Vigués Mariona , Roso-Llorach Albert , Violán Concepción
Published: June 2020

Background

The implementation of individual clinical practice guidelines in patients with multimorbidity often results in polypharmacy. Our aim was to analyse medication use according to longitudinal multimorbidity patterns (MP) and determine during a 5-year period (2012–16) which MP are associated with abnormal liver and kidney function in primary care patients over 65 years of age living in Catalonia.

Methods

Design: Longitudinal study (years 2012 to 2016) based on the electronic health records contained in Information System for Research in Primary Care database of the Catalan Institute of Health (SIDIAP). Variables: age, sex, MP, medication and polypharmacy (drug exposure obtained from the Pharmacy Invoice Registry). Medicines were classified in accordance with the Anatomical Therapeutic Chemical Classification System (ATC). Glomerular filtration rate was used to determine abnormal kidney function, and serum levels of alkaline phosphatase, alanine transaminase and gamma-glutamyl transpeptidase were used to diagnose abnormal liver function. Statistics: For medication use in MP, we calculated annual mean packages of each drug in each MP, and observed/expected ratios were obtained by dividing mean packages in the cluster by mean packages of the same drug in the overall population. Logistic regression models were fitted to estimate the association between MP at baseline and abnormal kidney and liver function tests during follow up.

Results

Nine hundred sixteen thousand six hundred nineteen patients were included, and 743,827 completed the follow up. We identified one polypharmacy profile per MP, and concluded that the most prescribed drugs in each pattern corresponded to the diseases overrepresented in that specific MP. The median of drugs ranged from 3 (Cluster 1 - Non-Specific) to 8 (Cluster 10 - Multisystem Pattern). Abnormal kidney function was most commonly observed in the Cluster 4 - Cardio-Circulatory and Renal (Odds Ratio [OR] 2.19; Confidence interval [CI] 95% 2.15–2.23) and Cluster 3 - Minority Metabolic Autoimmune-Inflammatory (OR 2.16; CI 95% 2.12–2.20) MP. A higher risk of abnormal liver function was observed in the Cluster 8 - Digestive (OR 3.39; CI 95% 3.30–3.49), and Cluster 4 - Cardio-Circulatory and Renal (OR 1.96; CI 95% 1.91–2.02) MP.

Conclusions

A higher risk of abnormal kidney and liver function was observed in specific MP. The long-term characterisation of MP and polypharmacy illustrates the burden of chronic multimorbidity and polypharmacy in the elderly population.
Simulating transmission of ESKAPE pathogens plus C. difficile in relevant clinical scenarios
Authors: Weber Katharina L. , LeSassier Danielle S. , Kappell Anthony D. , Schulte Kathleen Q. , Westfall Nicole , Albright Nicolette C. , Godbold Gene D. , Palsikar Veena , Acevedo Carlos A. , Ternus Krista L. , Hewitt F. Curtis
Published: June 2020

Background

The prevalence of healthcare-acquired infections (HAI) and rising levels of antimicrobial resistance places significant economic and public health burdens on modern healthcare systems. A group of highly drug resistant pathogens known as the ESKAPE pathogens, along with C. difficile, are the leading causes of HAIs. Interactions between patients, healthcare workers, and environmental conditions impact disease transmission. Studying pathogen transfer under varying contact scenarios in a controlled manner is critical for understanding transmission and disinfectant strategies. In lieu of human subject research, this method has the potential to contribute to modeling the routes of pathogen transmission in healthcare settings.

Methods

To overcome these challenges, we have developed a method that utilizes a synthetic skin surrogate to model both direct (skin-to-skin) and indirect (skin-to fomite-to skin) pathogen transfer between infected patients and healthy healthcare workers. This surrogate material includes a background microbiome community simulating typical human skin flora to more accurately mimic the effects of natural flora during transmission events.

Results

We demonstrate the ability to modulate individual bacterial concentrations within this microbial community to mimic bacterial concentrations previously reported on the hands of human subjects. We also explore the effect of various decontamination approaches on pathogen transfer between human subjects, such as the use of handwashing or surface disinfectants. Using this method, we identify a potential outlier, S. aureus, that may persist and retain viability in specific transfer conditions better than the overall microbial community during decontamination events.

Conclusions

Our work describes the development of an in vitro method that uses a synthetic skin surrogate with a defined background microbiota to simulate skin-to-skin and skin-to fomite-to skin contact scenarios. These results illustrate the value of simulating a holistic microbial community for transfer studies by elucidating differences in different pathogen transmission rates and resistance to common decontamination practices. We believe this method will contribute to improvements in pathogen transmission modeling in healthcare settings and increase our ability to assess the risk associated with HAIs, although additional research is required to establish the degree of correlation of pathogen transmission by skin or synthetic alternatives.
Myasthenia gravis with anti-muscle-specific tyrosine kinase antibodies during therapy for multiple myeloma: a case report
Authors: Sakano Shoko , Matsuyama Hirofumi , Ishikawa Hidehiro , Shindo Akihiro , Ii Yuichiro , Matsuura Keita , Mizutani Minoru , Kawada Norikazu , Tomimoto Hidekazu
Published: June 2020

Background

The onset of myasthenia (MG) gravis with anti-muscle-specific tyrosine kinase (MuSK) antibodies most commonly peaks in the fourth decade of life, and MG with MuSK antibodies (MuSK-MG) rarely coexists with a malignant tumor. To date, MuSK-MG has not been reported in multiple myeloma (MM).

Case presentation

A 60-year-old male with MM who was receiving treatment with bortezomib and thalidomide presented diplopia, ptosis, and limb weakness. A diagnosis of MM with Bence-Jones proteinuria was established when he was 56 years old, and he received chemotherapy with four courses of bortezomib and dexamethasone. Although he received thalidomide as maintenance therapy, it was discontinued a year before hospital admission because of sensory neuropathy as a side effect. Six months before hospital admission, he developed mild diplopia. One month before admission, his chemotherapy was interrupted because of viral infection and fatigability. Then he developed neck weakness and bilateral ptosis. A diagnosis of MuSK-MG was made based on neurological and serological examinations. According to the previous relevant literature, this is the first report of MuSK-MG in a patient with MM.

Conclusions

In patients with MM, the possibility of co-existing of autoimmune disease, including MuSK-MG, should be considered. This case emphasizes the need to still consider testing for anti-MuSK antibodies in older MM patients where there is clinical suspicion for possible MG despite negative anti-acetylcholine receptor antibodies and lacking classic MuSK MG phenotype at onset.
Pharmacological treatment of increased vascular risk and cognitive performance in middle-aged and old persons: six-year observational longitudinal study
Authors: van Eersel Marlise E. A. , Visser Sipke T. , Joosten Hanneke , Gansevoort Ron T. , Slaets Joris P. J. , Izaks Gerbrand J.
Published: June 2020

Background

Lowering vascular risk is associated with a decrease in the prevalence of cardiovascular disease and dementia. However, it is still unknown whether lowering of vascular risk with pharmacological treatment preserves cognitive performance in general. Therefore, we compared the change in cognitive performance in persons with and without treatment of vascular risk factors.

Methods

In this longitudinal observational study, 256 persons (mean age, 58 years) were treated for increased vascular risk during a mean follow-up period of 5.5 years (treatment group), whereas 1678 persons (mean age, 50 years) did not receive treatment (control group). Cognitive performance was three times measured during follow-up using the Ruff Figural Fluency Test (RFFT) and Visual Association Test (VAT), and calculated as the average of standardized RFFT and VAT score per participant. Because treatment allocation was nonrandomized, additional analyses were performed in demographic and vascular risk-matched samples and adjusted for propensity scores.

Results

In the treatment group, mean (SD) cognitive performance changed from − 0.30 (0.80) to − 0.23 (0.80) to 0.02 (0.87), and in control group, from 0.08 (0.77) to 0.24 (0.79) to 0.49 (0.74) at the first, second and third measurement, respectively (ptrend < 0.001). After adjustment for demographics and vascular risk, the change in cognitive performance during follow-up was not statistically significantly different between the treatment and control group: mean estimated difference, − 0.10 (95%CI − 0.21 to 0.01; p = 0.08). Similar results were found in matched samples and after adjustment for propensity score.

Conclusion

Change in cognitive performance during follow-up was similar in treated and untreated persons. This suggests that lowering vascular risk preserves cognitive performance.
Changes in choroidal thickness in advanced diabetic retinopathy treated with pan-retinal photocoagulation using a pattern scanning laser versus a conventional laser
Authors: Park Nari , Lee In Gul , Kim Jee Taek
Published: June 2020

Background

To compare the effect of pan-retinal photocoagulation (PRP) using pattern scanning or conventional laser on subfoveal choroidal thickness (SFChT).

Methods

Thirty-eight patients (64 eyes) with advanced diabetic retinopathy (DR) who underwent PRP using pattern scanning or conventional laser were included. Changes in SFChT were compared with baseline values at 1, 3, 6, and 12 months after PRP using swept-source optical coherence tomography.

Results

The conventional laser group showed a statistically significant decrease in SFChT at 1, 3, 6, and 12 months after PRP (P < 0.001). SFChT was significantly decreased at 3 (P = 0.025), 6 (P = 0.004), and 12 (P < 0.001) months after treatment in the pattern laser group.

Conclusion

Eyes with advanced DR showed a significant reduction in SFChT over 12 months regardless of the type of laser used; however, the reduction was sooner after conventional laser than after pattern laser.
Gender difference in the association between education and schizophrenia in Chinese adults
Authors: Luo Yanan , Pang Lihua , Zhao Yihao , Guo Chao , Zhang Lei , Zheng Xiaoying
Published: June 2020

Background

Improving education level was evidenced to decrease the risk of schizophrenia, but whether this strength of education role depends on gender is not. This study aimed to investigate whether there was gender difference in the association between education and schizophrenia in Chinese adults.

Methods

Data were obtained from the Second China National Sample Survey on Disability in 2006, including 1,909,205 participants aged 18 years or older. Schizophrenia was ascertained according to the International Statistical Classification of Diseases, Tenth Revision. Logistics regression models were fitted to examine the combined effect of gender and education on schizophrenia.

Results

The lifetime prevalence of schizophrenia in female groups was higher than in male groups, with 0.44% (95%CI: 0.42–0.45%) and 0.36% (95%CI: 0.35–0.37%), respectively. Compared with schizophrenia male patients, more females with schizophrenia experienced severe or extreme difficulty in understanding and communicating. However, more males with schizophrenia suffered from severe or extreme difficulty in the function of daily activities. The combined effect of education and schizophrenia was statistically significant, indicating that, as the level of education increased, schizophrenia risk of females decreased faster than the risk of males.

Conclusions

This study showed that additional years of education associated with lower risk of schizophrenia, and this association was stronger in females than in males. As education elevated, the risk of schizophrenia decreased more for women than for men. The findings indicate that improving education level may have an effect on reducing the gender disparities in mental health of China. Actions to prevent schizophrenia and address its gender disparities will require attention to the improving educational opportunities.
Declining trend in HIV new infections in Guangxi, China: insights from linking reported HIV/AIDS cases with CD4-at-diagnosis data
Authors: Sun Xiaodan , Yang Wenmin , Tang Sanyi , Shen Mingwang , Wang Tianyang , Zhu Qiuying , Shen Zhiyong , Tang Shuai , Chen Huanhuan , Ruan Yuhua , Xiao Yanni
Published: June 2020

Background

The Guangxi Zhuang Autonomous Region bears a relatively high burden of HIV/AIDS infection. The number of accumulatively reported HIV/AIDS cases in Guangxi is the third highest among 31 provinces or Autonomous Region from 2004 to 2007, changed to the second highest between 2011 and 2013, then returned to the third highest again after 2014. We aim to estimate the new infections and evaluate the real-time HIV epidemic in Guangxi, China, in order to reveal the rule of HIV transmission.

Methods

Firstly, the number of annually reported HIV and AIDS cases, as well as the number of cases linked with CD4 data are extracted from the HIV/AIDS information system in China. Secondly, two CD4-staged models are formulated by linking the with-host information on CD4 level to between-host transmission and surveillance data. Thirdly, new HIV infections, diagnosis rates and undiagnosed infections over time are estimated by using Bayesian method and Maximum Likelihood Estimation method.

Results

The data reveal that the newly reported cases have been decreasing since 2011, while lots of cases are identified at late CD4 stage. The data fitted results indicate that both models can describe the trend of the epidemic well. The estimation results show that the new and undiagnosed infections began to decrease from the period2006 - 2008. However, the diagnosis probabilities/rates keep at a very low level, and there are still a large number of infections undiagnosed, most of which have a large probability to be identified at late CD4 stage.

Conclusions

Our findings suggest that HIV/AIDS epidemic in Guangxi has been controlled to a certain extent, while the diagnosis rate still needs to be improved. More attentions should be paid to identify infections at their early CD4 stages. Meanwhile, comprehensive intervention measures should be continually strengthened in avoid of the rebound of new infections.
High level of vaccination and protection against hepatitis B with low rate of HCV infection markers among hospital health care personnel in north of Iran: a cross-sectional study
Authors: Hiva Saffar , Negar Khoshayand , Mohammad-Reza Parsaei , Gholam-Reza Ghorbani , Mohsen Aarabi , Ali-Asghar Nadi Ghara , Mohammed-Jafar Saffar
Published: June 2020

Background

hepatitis B virus (HBV) and C virus (HCV) are among the leading causes of mortality worldwide. Health care personnel (HCP) are subjected to increased risk of these infections. Therefore, HBV vaccination and post-vaccination serologic testing (PVST) are recommended for them. Our objectives in this study were investigate how well the vaccination guidelines for hospital HCPs were implemented. Moreover, the prevalence rates of HBV and HCV infections were calculated. To determine the presence of immunological memory, vaccinated personnel negative to antibody against HB surface antigen with one dose of HB vaccine were boosted.

Methods

From 1 July to 30 November 2017, a cross-sectional study among HCPs working in public hospitals were conducted. All HCPs from various professional categories potentially at risk of exposure to contaminated sources were included. The information was gathered via interview and self-administered questionnaire. The questions were focused on the demographic characteristics, HB vaccination and immunity status and time elapsed since initial vaccination series, and frequency of needelstick injuries during the past 12 months of their work. Moreover, the prevalence rate of HBV and HCV infections were calculated. To determine the presence of immunological memory, subjects negative to HBV seromarkers received a booster dose of the vaccine.

Results

A total of 186 out of 766 participants were male and nurses comprised 71% of personnel. Although all HCP were vaccinated, 84% of them completed the course and less than 5% of them received PVST. According to the results, 0.78, 4.6, and 83% were serologically positive to HBV surface antigen, antibodies against HBV core, and S antigens, respectively. Approximately, 91% of seronegative participants responded to a booster dose and only 0.91% of the personnel was anti-HCV positive.

Conclusion

Most HCP received full HBV vaccination course. Although a minority did PVST, the HBV vaccine-induced long-term protection and HB vaccine booster were not required. Therefore, policies should be made to increase the rate PVST after immunization. According to the results, the HCV infection rate was low and thus pre-recruitment screening was not necessary.
Epidemiology of Epstein-Barr virus infection and infectious mononucleosis in the United Kingdom
Authors: Kuri Ashvin , Jacobs Benjamin Meir , Vickaryous Nikki , Pakpoor Julia , Middeldorp Jaap , Giovannoni Gavin , Dobson Ruth
Published: June 2020

Background

Epstein-Barr Virus (EBV) is a ubiquitous gamma-herpesvirus with which ~ 95% of the healthy population is infected. EBV infection has been implicated in a range of haematological malignancies and autoimmune diseases. Delayed primary EBV infection increases the risk of subsequent complications. Contemporaneous seroepidemiological data is needed to establish best approaches for successful vaccination strategies in the future.

Methods

We conducted a sero-epidemiological survey using serum samples from 2325 individuals between 0 and 25 years old to assess prevalence of detectable anti-EBV antibodies. Second, we conducted a retrospective review of Hospital Episode Statistics to examine changes in Infectious Mononucleosis (IM) incidence over time. We then conducted a large case-control study of 6306 prevalent IM cases and 1,009,971 unmatched controls extracted from an East London GP database to determine exposures associated with IM.

Results

1982/2325 individuals (85.3%) were EBV seropositive. EBV seropositivity increased more rapidly in females than males during adolescence (age 10–15). Between 2002 and 2013, the incidence of IM (derived from hospital admissions data) increased. Exposures associated with an increased risk of IM were lower BMI, White ethnicity, and not smoking.

Conclusions

We report that overall EBV seroprevalence in the UK appears to have increased, and that a sharp increase in EBV seropositivity is seen in adolescent females, but not males. The incidence of IM requiring hospitalisation is increasing. Exposures associated with prevalent IM in a diverse population include white ethnicity, lower BMI, and never-smoking, and these exposures interact with each other. Lastly, we provide pilot evidence suggesting that antibody responses to vaccine and commonly encountered pathogens do not appear to be diminished among EBV-seronegative individuals. Our findings could help to inform vaccine study designs in efforts to prevent IM and late complications of EBV infection, such as Multiple Sclerosis.
Activation of FoxO1/SIRT1/RANKL/OPG pathway may underlie the therapeutic effects of resveratrol on aging-dependent male osteoporosis
Authors: Ameen Omnia , Yassien Rania I. , Naguib Yahya M.
Published: June 2020

Background

Age-dependent male osteoporosis remains a poorly studied medical problem despite its significance. It is estimated that at least 1 of 5 men will suffer from osteoporotic consequences. Given that multiple mechanisms are involved in the process of senescence, much attention has been given to compounds with polymodal actions. To challenge such a health problem, we tested here the therapeutic potential of resveratrol in male osteoporosis. We also studied the possible molecular mechanisms that may underlie resveratrol effects.

Methods

Thirty male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control (3–4 months old weighing 150–200 g receiving vehicle), aged (18–20 months old, weighing 350–400 g and receiving vehicle), and resveratrol treated aged (18–20 months old, weighing 350–400 g and receiving resveratrol 20 mg/kg/day for 6 weeks) groups. Assessment of serum calcium, phosphate, bone specific alkaline phosphatase, inflammatory cytokines, oxidative stress markers, and rat femur gene expression of FoxO1, SIRT1, RANKL and OPG proteins was carried out. Histopathological assessment of different levels of rat femur was also performed.

Results

Age-dependent osteoporosis resulted in significant increase in serum levels of phosphate, bone specific alkaline phosphatase, hsCRP, IL-1β, IL-6, TNF-α, MDA, NO, and RANKL gene expression. However, there was significant decrease in serum level of GSH, and gene expression of FoxO1, SIRT1 and OPG. Osteoporotic changes were seen in femur epiphysis, metaphysis and diaphysis. Resveratrol restored significantly age-dependent osteoporotic changes.

Conclusion

We concluded that resveratrol can play an important role in the prevention of male osteoporosis. Resveratrol can counter the molecular changes in male osteoporosis via anti-inflammatory, anti-oxidant and gene modifying effects.
Casein phosphopeptide combined with fluoride enhances the inhibitory effect on initial adhesion of Streptococcus mutans to the saliva-coated hydroxyapatite disc
Authors: Wang Xiaodie , Liu Limin , Zhou Xiaoyan , Huo Yongbiao , Gao Jinlong , Gu Haijing
Published: June 2020

Background

Recent preventive strategies for dental caries focus on targeting the mechanisms underlying biofilm formation, including the inhibition of bacterial adhesion. A promising approach to prevent bacterial adhesion is to modify the composition of acquired salivary pellicle. This in vitro study investigated the effect and possible underlying mechanism of pellicle modification by casein phosphopeptide (CPP) onStreptococcus mutans(S. mutans) initial adhesion, and the impact of fluoride on the efficacy of CPP.

Methods

The salivary pellicle-coated hydroxyapatite (s-HA) discs were treated with phosphate buffered saline (negative control), heat-inactivated 2.5% CPP (heat-inactivated CPP), 2.5% CPP (CPP) or 2.5% CPP supplemented with 900 ppm fluoride (CPP + F). After cultivation ofS. mutansfor 30 min and 2 h, the adherent bacteria were visualized by scanning electron microscopy (SEM) and quantitatively evaluated using the plate count method. Confocal laser scanning microscopy (CLSM) was used to evaluate the proportions of total and deadS. mutans. The concentrations of total, free, and bound calcium and fluoride in the CPP and fluoride-doped CPP solutions were determined. The water contact angle and zeta potential of s-HA with and without modification were measured. The data were statistically analyzed using one-way ANOVA followed by a Turkey post hoc multiple comparison test.

Results

Compared to the negative control group, the amount of adherentS. mutanssignificantly reduced in the CPP and CPP + F groups, and was lowest in the CPP + F group. CLSM analysis showed that there was no statistically significant difference in the proportion of deadS. mutansbetween the four groups. Water contact angle and zeta potential of s-HA surface significantly decreased in the CPP and CPP + F groups as compared to the negative control group, and both were lowest in the CPP + F group.

Conclusions

Pellicle modification by CPP inhibitedS. mutansinitial adhesion to s-HA, possibly by reducing hydrophobicity and negative charge of the s-HA surface, and incorporating fluoride into CPP further enhanced the anti-adhesion effect.
Pediatric outpatient utilization by differing Medicaid payment models in the United States
Authors: Canares Therese L. , Friedman Ari , Rodean Jonathan , Burns Rebecca R. , Berkowitz Deena , Hall Matt , Alpern Elizabeth , Montalbano Amanda
Published: June 2020

Background

In the United States (US), Medicaid capitated managed care costs are controlled by optimizing patients’ healthcare utilization. Adults in capitated plans utilize primary care providers (PCP) more than emergency departments (ED), compared to fee-for-service (FFS). Pediatric data are lacking. We aim to determine the association between US capitated and FFS Medicaid payment models and children’s outpatient utilization.

Methods

This retrospective cohort compared outpatient utilization between two payment models of US Medicaid enrollees aged 1–18 years using Truven’s 2014 Marketscan Medicaid database. Children enrolled > 11 months were included, and were excluded for eligibility due to disability/complex chronic condition, lack of outpatient utilization, or provider capitation penetration rate < 5% or > 95%. Negative binomial and logistic regression assessed relationships between payment model and number of visits or odds of utilization, respectively.

Results

Of 711,008 children, 66,980(9.4%) had FFS and 644,028(90.6%) had capitated plans. Children in capitated plans had greater odds of visits to urgent care, PCP-acute, and PCP-well-child care (aOR 1.21[95%CI 1.15–1.26]; aOR 2.07[95%CI 2.03–2.13]; aOR 1.86 [95%CI 1.82–1.91], respectively), and had lower odds of visits to EDs and specialty care (aOR 0.82 [95%CI 0.8–0.83]; aOR 0.61 [95%CI 0.59–0.62], respectively), compared to FFS.

Conclusions

The majority of children in this US Medicaid population had capitated plans associated with higher utilization of acute care, but increased proportion of lower-cost sites, such as PCP-acute visits and UC. Health insurance programs that encourage capitated payment models and care through the PCP may improve access to timely acute care in lower-cost settings for children with non-complex chronic conditions.
Child maltreatment and cardiovascular disease: quantifying mediation pathways using UK Biobank
Authors: Ho Frederick K. , Celis-Morales Carlos , Gray Stuart R. , Petermann-Rocha Fanny , Lyall Donald , Mackay Daniel , Sattar Naveed , Minnis Helen , Pell Jill P.
Published: June 2020

Background

Child maltreatment is associated with cardiovascular disease (CVD), but mediation pathways have not been fully elucidated. The aim of the current study was to determine and quantify the underlying pathways linking child maltreatment and CVD.

Methods

We conducted a retrospective cohort study using the UK Biobank. The number and types of child maltreatment, including abuse and neglect, were recalled by the participants. Lifestyle, biological, physical, and mental health factors measured at baseline were explored as potential mediators. Incident CVD was ascertained through record linkage after baseline measurement. Age, sex, ethnicity, area-based deprivation, and education level were adjusted for as confounders. Cox proportional hazard models were conducted to test for associations between child maltreatment and incident CVD.

Results

A total of 152,040 participants who completed the child maltreatment assessment were included in the analyses, and one third reported at least one type of child maltreatment. There was a dose-response relationship between the number of maltreatment types and incident CVD. On average, each additional type of child maltreatment was associated with an 11% (95% CI 8–14%, P < 0.0001) increased risk of CVD. The majority (56.2%) of the association was mediated through depressive symptoms, followed by smoking (14.7%), high-density lipoprotein cholesterol (8.7%), and sleep duration (2.4%).

Conclusion

Child maltreatment is associated with incident CVD through a combination of mental health, lifestyle, and biological pathways. Therefore, in addition to interventions to reduce the occurrence of child maltreatment, attention should be targeted at promoting healthy lifestyles and preventing, identifying, and treating depression among children and adults who have previously been maltreated.
Using health facility deaths to estimate population causes of neonatal and child mortality in four African countries
Authors: Kalter Henry D. , Perin Jamie , Amouzou Agbessi , Kwamdera Gift , Adewemimo Wasilat Adeyinka , Nguefack Félicitée , Roubanatou Abdoulaye-Mamadou , Black Robert E.
Published: June 2020

Background

Verbal autopsy is the main method used in countries with weak civil registration systems for estimating community causes of neonatal and 1–59-month-old deaths. However, validation studies of verbal autopsy methods are limited and assessment has been dependent on hospital-based studies, with uncertain implications for its validity in community settings. If the distribution of community deaths by cause was similar to that of facility deaths, or could be adjusted according to related demographic factors, then the causes of facility deaths could be used to estimate population causes.

Methods

Causes of neonatal and 1–59-month-old deaths from verbal/social autopsy (VASA) surveys in four African countries were estimated using expert algorithms (EAVA) and physician coding (PCVA). Differences between facility and community deaths in individual causes and cause distributions were examined using chi-square and cause-specific mortality fractions (CSMF) accuracy, respectively. Multinomial logistic regression and random forest models including factors from the VASA studies that are commonly available in Demographic and Health Surveys were built to predict population causes from facility deaths.

Results

Levels of facility and community deaths in the four countries differed for one to four of 10 EAVA or PCVA neonatal causes and zero to three of 12 child causes. CSMF accuracy for facility compared to community deaths in the four countries ranged from 0.74 to 0.87 for neonates and 0.85 to 0.95 for 1–59-month-olds. Crude CSMF accuracy in the prediction models averaged 0.86 to 0.88 for neonates and 0.93 for 1–59-month-olds. Adjusted random forest prediction models increased average CSMF accuracy for neonates to, at most, 0.90, based on small increases in all countries.

Conclusions

There were few differences in facility and community causes of neonatal and 1–59-month-old deaths in the four countries, and it was possible to project the population CSMF from facility deaths with accuracy greater than the validity of verbal autopsy diagnoses. Confirmation of these findings in additional settings would warrant research into how medical causes of deaths in a representative sample of health facilities can be utilized to estimate the population causes of child death.
SNHG16 promotes tumorigenesis and cisplatin resistance by regulating miR-338-3p/PLK4 pathway in neuroblastoma cells
Authors: Xu Zhaoying , Sun Yongfa , Wang Danfeng , Sun Huifang , Liu Xiaojun
Published: June 2020

Background

Long noncoding RNA small nucleolar RNA host gene 16 (lncRNA SNHG16) has been revealed to be involved in the tumorigenesis of neuroblastoma. However, the role of SNHG16 in regulating cisplatin sensitivity in neuroblastoma remains largely unknown.

Methods

The expression of SNHG16, microRNA (miR)-338-3p and polo-like kinase 4 (PLK4) mRNA was measured using quantitative real-time polymerase chain reaction. The protein levels of PLK4, multidrug resistance protein 1 (MRP1), multidrug-resistance gene 1-type p-glycoprotein (P-gp) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related proteins were detected by Western blot. The half maximal inhibitory concentration (IC50) value, cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8 assays or Transwell assay. Apoptotic cells were measured by Flow cytometry. The interaction between miR-338-3p and SNHG16 or PLK4 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assay. In vivo experiments were conducted through the murine xenograft model.

Results

SNHG16 was up-regulated, while miR-338-3p was down-regulated in cisplatin-resistant neuroblastoma tissues and cells. SNHG16 silencing weakened cisplatin resistance, reflected by the reduction of IC50 value, down-regulation of MRP-1 and P-gp protein expression, suppression of proliferation, migration and invasion, as well as enhancement of apoptosis in SNHG16 deletion cisplatin-resistant neuroblastoma cells. Besides that, SNHG16 could regulate PLK4 expression by sponging miR-338-3p and SNHG16/miR-338-3p/PLK4 axis could affect the activation of PI3K/AKT pathway in cisplatin-resistant neuroblastoma cells. MiR-338-3p inhibition attenuated SNHG16 deletion-mediated impairment on cisplatin resistance and PLK4 overexpression reversed the decrease of cisplatin-resistance induced by miR-338-3p re-expression. Furthermore, SNHG16 knockdown contributed to the anti-tumor effect of cisplatin in neuroblastoma in vivo.

Conclusion

SNHG16 contributed to the tumorigenesis and cisplatin resistance in neuroblastoma possibly through miR-338-3p/PLK4 pathway, indicating a novel insight for overcoming chemoresistance in neuroblastoma patients.
miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6
Authors: An Yunhe , Zhang Jun , Cheng Xiaoyan , Li Baoming , Tian Yanjie , Zhang Xiaoli , Zhao Fangqi
Published: June 2020

Background

The aberrant expression of microRNA-454 (miR-454) has been confirmed to be involved in the development of cancers. However, the functional role of miR-454 in the progression of ovarian cancer remains unclear.

Methods

The expression of miR-454 in ovarian cancer cells and serum of ovarian cancer patients was detected by RT-PCR. CCK8, colony formation, transwell, and flow cytometry assays were conducted to assess the effects of miR-454 on ovarian cancer cell proliferation, migration, invasion, and apoptosis, respectively. Dual-luciferase reporter assay was used to confirm the targeting relationship between miR-454 and E2F6. The expression pattern of E2F6 in ovarian cancer tissues was detected using immunohistochemistry (IHC) assay. The relative expression of related proteins was examined using western blot analysis.

Results

miR-454 was markedly down-regulated by hypoxia in ovarian cancer cells. Compared with normal samples, the expression of miR-454 was up-regulated in the serum of ovarian cancer patients, and correlated with the clinicopathological stages of ovarian cancer. Next, we found that miR-454 overexpression inhibited the proliferation, migration and invasion of OVCAR3 and SKOV3 cells, as well as promoted apoptosis. In addition, the Akt/mTOR and Wnt/β-catenin signaling pathway were inhibited by miR-454 in ovarian cancer cells. Mechanically, bioinformatic analysis and dual-luciferase reporter assay confirmed that E2F6 was a direct target of miR-454 and negatively regulated by miR-454 in ovarian cancer cells. Moreover, IHC analysis showed that E2F6 was highly expressed in ovarian cancer tissues. Finally, we found that the increasing cell proliferation and migration triggered by E2F6 overexpression were abolished by miR-454 overexpression.

Conclusion

Taken together, these results highlight the role of miR-454 as a tumor suppressor in ovarian cancer cells by targeting E2F6, indicating that miR-454 may be a potential diagnostic biomarker and therapeutic target for ovarian cancer.
Identification of methylation-driven genes related to the prognosis of papillary renal cell carcinoma: a study based on The Cancer Genome Atlas
Authors: Liu Zeyu , Wan Yuxiang , Yang Ming , Qi Xuewei , Dong Zhenzhen , Huang Jinchang , Xu Jingnan
Published: June 2020

Background

Aberrant DNA methylation patterns are involved in the pathogenesis of papillary renal cell carcinoma (pRCC). This study aimed to investigate the potential of methylation-driven genes as biomarkers in determining the prognosis of pRCC by bioinformatics analysis.

Methods

DNA methylation and transcriptome profiling data were downloaded from The Cancer Genome Atlas database. Methylation-driven genes (MDGs) were obtained using MethylMix R package. A Cox regression model was used to screen for pRCC prognosis-related MDGs, and a linear risk model based on MDG methylation profiles was constructed. A combined methylation and gene expression survival analysis was performed to further explore the prognostic value of MDGs independently.

Results

A total of 31 MDGs were obtained. Univariate and multivariate Cox regression analysis identified eight genes (CASP1, CD68, HOXD3, HHLA2, HOXD9, HOXA10-AS, TMEM71, and PLA2G16), which were used to construct a predictive model associated with overall survival in pRCC patients. Combined DNA methylation and gene expression survival analysis revealed that C19orf33, GGT6, GIPC2, HHLA2, HOXD3, HSD17B14, PLA2G16, and TMEM71 were significantly associated with patients’ survival.

Conclusion

Through the analysis of MDGs in pRCC, this study identified potential biomarkers for precision treatment and prognosis prediction, and provided the basis for future research into the molecular mechanism of pRCC.
Wrist-worn wearables based on force myography: on the significance of user anthropometry
Authors: Delva Mona Lisa , Lajoie Kim , Khoshnam Mahta , Menon Carlo
Published: June 2020

Background

Force myography (FMG) is a non-invasive technology used to track functional movements and hand gestures by sensing volumetric changes in the limbs caused by muscle contraction. Force transmission through tissue implies that differences in tissue mechanics and/or architecture might impact FMG signal acquisition and the accuracy of gesture classifier models. The aim of this study is to identify if and how user anthropometry affects the quality of FMG signal acquisition and the performance of machine learning models trained to classify different hand and wrist gestures based on that data.

Methods

Wrist and forearm anthropometric measures were collected from a total of 21 volunteers aged between 22 and 82 years old. Participants performed a set of tasks while wearing a custom-designed FMG band. Primary outcome measure was the Spearman’s correlation coefficient (R) between the anthropometric measures and FMG signal quality/ML model performance.

Results

Results demonstrated moderate (0.3 ≤|R| < 0.67) and strong (0.67 ≤ |R|) relationships for ratio of skinfold thickness to forearm circumference, grip strength and ratio of wrist to forearm circumference. These anthropometric features contributed to 23–30% of the variability in FMG signal acquisition and as much as 50% of the variability in classification accuracy for single gestures.

Conclusions

Increased grip strength, larger forearm girth, and smaller skinfold-to-forearm circumference ratio improve signal quality and gesture classification accuracy.
Diffuse reflectance spectroscopy for breach detection during pedicle screw placement: a first in vivo investigation in a porcine model
Authors: Swamy Akash , Spliethoff Jarich W. , Burström Gustav , Babic Drazenko , Reich Christian , Groen Joanneke , Edström Erik , Elmi-Terander Adrian , Racadio John M. , Dankelman Jenny , Hendriks Benno H. W.
Published: June 2020

Background

The safe and accurate placement of pedicle screws remains a critical step in open and minimally invasive spine surgery, emphasizing the need for intraoperative guidance techniques. Diffuse reflectance spectroscopy (DRS) is an optical sensing technology that may provide intraoperative guidance in pedicle screw placement.

Purpose

The study presents the first in vivo minimally invasive procedure using DRS sensing at the tip of a Jamshidi needle with an integrated optical K-wire. We investigate the effect of tissue perfusion and probe-handling conditions on the reliability of fat fraction measurements for breach detection in vivo.

Methods

A Jamshidi needle with an integrated fiber-optic K-wire was gradually inserted into the vertebrae under intraoperative image guidance. The fiber-optic K-wire consisted of two optical fibers with a fiber-to-fiber distance of 1.024 mm. DRS spectra in the wavelength range of 450 to 1600 nm were acquired at several positions along the path inside the vertebrae. Probe-handling conditions were varied by changing the amount of pressure exerted on the probe within the vertebrae. Continuous spectra were recorded as the probe was placed in the center of the vertebral body while the porcine specimen was sacrificed via a lethal injection.

Results

A typical insertion of the fiber-optic K-wire showed a drop in fat fraction during an anterior breach as the probe transitioned from cancellous to cortical bone. Fat fraction measurements were found to be similar irrespective of the amount of pressure exerted on the probe (p = 0.65). The 95% confidence interval of fat fraction determination was found in the narrow range of 1.5–3.6% under various probe-handling conditions. The fat fraction measurements remained stable during 70 min of decreased blood flow after the animal was sacrificed.

Discussions

These findings indicate that changes in tissue perfusion and probe-handling conditions have a relatively low measureable effect on the DRS signal quality and thereby on the determination of fat fraction as a breach detection signal.

Conclusions

Fat fraction quantification for intraoperative pedicle screw breach detection is reliable, irrespective of changes in tissue perfusion and probe-handling conditions.