bluuebunny/crossref_metadata_2025 huggingface dataset:
Strengthening sleep–autonomic interaction via acoustic enhancement of slow oscillations
Authors: Grimaldi Daniela , Papalambros Nelly A , Reid Kathryn J , Abbott Sabra M , Malkani Roneil G , Gendy Maged , Iwanaszko Marta , Braun Rosemary I , Sanchez Daniel J , Paller Ken A , Zee Phyllis C
Published: February 2019

Slow-wave sleep (SWS) is important for overall health since it affects many physiological processes including cardio-metabolic function. Sleep and autonomic nervous system (ANS) activity are closely coupled at anatomical and physiological levels. Sleep-related changes in autonomic function are likely the main pathway through which SWS affects many systems within the body. There are characteristic changes in ANS activity across sleep stages. Notably, in non-rapid eye-movement sleep, the progression into SWS is characterized by increased parasympathetic activity, an important measure of cardiovascular health.

Experimental manipulations that enhance slow-wave activity (SWA, 0.5–4 Hz) can improve sleep-mediated memory and immune function. However, effects of SWA enhancement on autonomic regulation have not been investigated. Here, we employed an adaptive algorithm to deliver 50 ms sounds phase-locked to slow-waves, with regular pauses in stimulation (~5 s ON/~5 s OFF), in healthy young adults. We sought to determine whether acoustic enhancement of SWA altered parasympathetic activity during SWS assessed with heart rate variability (HRV), and evening-to-morning changes in HRV, plasma cortisol, and blood pressure.

Stimulation, compared with a sham condition, increased SWA during ON versus OFF intervals. This ON/OFF SWA enhancement was associated with a reduction in evening-to-morning change of cortisol levels and indices of sympathetic activity. Furthermore, the enhancement of SWA in ON intervals during sleep cycles 2–3 was accompanied by an increase in parasympathetic activity (high-frequency, HRV). Together these findings suggest that acoustic enhancement of SWA has a positive effect on autonomic function in sleep. Approaches to strengthen brain–heart interaction during sleep could have important implications for cardiovascular health.
“The Miracle Tablet Maybe”: Legalization of the Pill and Women’s Childbearing and Career Decisions
Authors: Finseraas Henning , Skorge Øyvind Søraas
Published: February 2019

A substantial literature argues that the legalization of the birth control pill in the United States reduced fertility and enhanced career investments. This study questions whether the broader effects hold across contexts. We use administrative data to study the Norwegian legalization of the pill and find effects on teenage motherhood but not on subsequent career outcomes. Using survey data, we show that the pill's impact on fertility is largest for women with an early sexual debut; nevertheless, broader effects of pill usage are still absent. Our study indicates that the pill cannot explain the rise of Norwegian women's economic empowerment.
Maintenance Olaparib in Patients With Newly Diagnosed Advanced Ovarian Cancer
Authors: Moore Kathleen , Colombo Nicoletta , Scambia Giovanni , Kim Byoung-Gie , Oaknin Ana , Friedlander Michael , Lisyanskaya Alla , Floquet Anne , Leary Alexandra , Sonke Gabe S. , Gourley Charlie , Banerjee Susana , Oza Amit , González-Martín Antonio , Aghajanian Carol , Bradley William , Mathews Cara , Liu Joyce , Lowe Elizabeth S. , Bloomfield Ralph , DiSilvestro Paul
Published: February 2019

(Abstracted from N Engl J Med 2018;379:2495–2505)

Standard-of-care therapy for patients newly diagnosed with advanced ovarian cancer consists of frontline cytoreductive surgery and adjuvant platinum chemotherapy. Approximately 70% of these patients have a relapse within 3 years.
Effect of High Dose Folic Acid Supplementation in Pregnancy on Pre-eclampsia (FACT): Double Blind, Phase III, Randomised Controlled, International, Multicentre Trial
Authors: Wen Shi Wu , White Ruth Rennicks , Rybak Natalie , Gaudet Laura M. , Robson Stephen , Hague William , Simms-Stewart Donnette , Carroli Guillermo , Smith Graeme , Fraser William D. , Wells George , Davidge Sandra T. , Kingdom John , Coyle Doug , Fergusson Dean , Corsi Daniel J. , Champagne Josee , Sabri Elham , Ramsay Tim , Mol Ben Willem J. , Oudijk Martijn A. , Walker Mark C.
Published: February 2019

(Abstracted from BMJ 2018;362:k3478)

Preeclampsia is a serious medical condition, affecting approximately 3% to 5% of pregnancies, accounting for more than 35,000 maternal deaths annually worldwide and an important factor in maternal morbidity. Preeclampsia affects multiple organ systems and leads to an increased risk of other severe maternal and neonatal complications in pregnancy.
Rare Autosomal Trisomies: Important and Not So Rare
Authors: Scott Fergus , Bonifacio Michael , Sandow Rhiannon , Ellis Katie , Smet Maria-Elisabeth , McLennan Andrew
Published: February 2019

(Abstracted from Prenatal Diagn 2018;38(10):765–771)

Noninvasive prenatal testing (NIPT) analyzes cell-free DNA (cfDNA) in maternal plasma, which is a combination of DNA from maternal cells and from placental cytotrophoblast. The technique of massively parallel sequencing (MPS) sequences and counts large numbers of unique, single-locus DNA fragments and assigns them to the chromosome of origin.
Cherchez la femme: Maternal Incidental Findings Can Explain Discordant Prenatal Cell-free DNA Sequencing Results
Authors: Bianchi Diana W.
Published: February 2019

(Abstracted from Genet Med 2018;20:910–917)

Maternal plasma DNA sequencing has been offered as an alternative to biochemical and sonographic screening tests for fetal aneuploidy since 2011. The circulating cell-free DNA (cfDNA) fragments in the peripheral blood sample of a pregnant woman derive from 3 tissues: placenta, maternal bone marrow, and the fetus (or fetuses).
TRPA1 Sensitization Produces Hyperalgesia to Heat but not to Cold Stimuli in Human Volunteers
Authors: Weyer-Menkhoff Iris , Lötsch Jörn
Published: February 2019

Background:

Transient receptor potential ion channels play a role in thermal hyperalgesia and are among targets of novel analgesics. However, a role of TRPA1 in either heat or cold hyperalgesia is controversial. In this study, changes in thermal sensitivity were assessed following topical application of a specific sensitizer of TRPA1 and compared with the effects of sensitizers of TRPV1 and TRPM8.

Methods:

Employing a randomized cross-over design, thermal thresholds were assessed in 16 pain-free volunteers before and at 20 minutes after topical application of cinnamaldehyde, capsaicin or menthol stimulating TRPA1, TRPV1, or TRPM8, respectively. Cold or warm detection thresholds and cold or heat pain thresholds were assessed according to the standardized quantitative sensory testing protocol proposed by the German Research Network on Neuropathic Pain.

Results:

The effects of different irritants displayed a cluster structure. Hyperalgesia was induced by capsaicin and cinnamaldehyde on heat pain thresholds and by menthol on cold pain thresholds (Cohen d=2.2035, 0.9932, and 1.256, respectively). A second cluster comprised large effects directed toward hyposensitization, such as cold hyposensitization induced by capsaicin and cinnamaldehyde, or small or absent hyposensitizing effects.

Conclusions:

The observation that the TRPA1 irritant cinnamaldehyde induced heat hyperalgesia at an effect sizes comparable with that of capsaicin attributes TRPA1 a role in human heat-induced pain. Results suggest the inclusion of heat pain as a major efficacy measure in human experimental studies of the effects of TRPA1 antagonists and the development of TRPA1 antagonists for clinical pain settings involving heat hyperalgesia.
Use of Topical Rho Kinase Inhibitors in the Treatment of Fuchs Dystrophy After Descemet Stripping Only
Authors: Macsai Marian S. , Shiloach Mira
Published: February 2019

Purpose:

Fuchs corneal dystrophy (FD) is a common cause of endothelial keratoplasty. Recently, a series of FD cases treated with Descemet stripping only (DSO) demonstrated recovery of the central endothelium without transplantation of donor cells. Ripasudil, a rho kinase inhibitor, has been shown to promote corneal endothelial wound healing in animal models. This study prospectively evaluated the use of ripasudil in patients undergoing DSO for FD.

Methods:

Enrolled patients underwent DSO with or without cataract surgery, performed by 1 surgeon. On the first postoperative day, patients were assigned to topical ripasudil 0.4% (Glanatec) 4 times a day for 2 months or no ripasudil and followed up monthly for the first 6 months and then at 9 and 12 months after surgery. Endothelial cell density (ECD) and pachymetry were evaluated at each postoperative visit.

Results:

Eighteen patients were enrolled, including 8 women and 1 man in each group. Overall, patients who underwent DSO with ripasudil recovered vision more quickly (4.6 vs. 6.5 weeks, P < 0.01). In addition, the ripasudil group had a statistically significantly higher average ECD at 3, 6, and 12 months. The patients in the DSO observation group had a 10% decrease in peripheral ECD when comparing counts before surgery with counts 12 months after surgery (P < 0.05). In the DSO ripasudil group, there was no significant difference between peripheral ECD at preoperative baseline versus 12 months after surgery.

Conclusions:

DSO with topical rho kinase inhibitors may be an alternative treatment for patients with FD and a peripheral ECD greater than 1000 cells/mm2.
Hyper IgE syndrome associated with novel and recurrent STAT3 mutations
Authors: Deng Ying , Li Tong , Xie Xiaoqin , Xia Dengmei , Ding Li , Xiang Hongmei , Ma Jessie J. , Li Wei
Published: February 2019

Rationale:

Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency presenting as two forms including autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES), which are mainly caused by mutations in STAT3 and DOCK8, respectively. To date, only about 500 cases have been reported worldwide including 37 cases in China. The spectrum and prevalence of mutations and molecular pathogenesis in HIES remain poorly understood.

Patient concerns:

Here we reported two Chinese children presenting clinical manifestations of HIES.

Diagnosis:

Based on medical history, clinical manifestations, and laboratory findings, a diagnosis of HIES was made for both children. Targeted next-generation sequencing (NGS) identified a novel heterozygous deletion of 15 bp (c.1960_1974del, p.G654_D658del or alternatively c.1966_1980del, and p.G656_D660del), and a recurrent missense mutation (c.1144C>T, p.R382W) in STAT3 in the two patients, respectively.

Interventions:

The two patients have been given the successful treatment of skin infections with cefaclor.

Outcomes:

Both patients have been under follow-up for more than 6 months, with no signs of recurrent infections.

Lessons:

Our results extend the spectrum of STAT3 mutations associated with ADHIES and highlight the value of targeted NGS in confirming diagnosis of genetic disorders.
Association between carotid artery stenosis and peripheral artery disease
Authors: Jung Hyuk Jae , Lee Sang Su , Kim Hyun Yul , Park Byung Soo , Kim Dong il , Nam Kyoung Jin , Roh Ji Eun , Choo Ki Seok
Published: February 2019

We aimed to investigate the association between carotid artery stenosis and peripheral artery disease (PAD) by screening carotid ultrasonography (CUS).

From January 2012 to December 2015, 231 consecutive patients who had undergone preoperative CUS for PAD were included in this study. A radiologist assessed the degree of internal carotid artery (ICA) stenosis by using the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Severe (>70%) ICA stenosis was evaluated based on the type of vascular surgery, PAD lesion, and ankle-brachial index (ABI). Data were analyzed using multiple logistic regression analysis and the χ
2 test.

Among 231 PAD patients, multilevel lesions revealed significantly higher incidence of severe ICA stenosis than iliac and infrainguinal lesion (22.5% vs 9.4% vs 8%: P = .016). Age (odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.00–1.12: P = .035), chronic kidney disease (CKD, OR: 6.19, 95% CI: 2.04–45.04: P = .013), and cerebral vascular disease (CVD, OR: 4.08, 95% CI: 1.13–16.46: P = .037) were significant risk factors of severe ICA stenosis in multivariate analysis. Prevalence of severe ICA stenosis according to ABI in PAD was not significant.

Preoperative screening by CUS provides valuable information onasymptomatic carotid artery stenosis (ACAS) that can identify severe ACAS patients who are at high risk of stroke and to consider more intensive management of carotid disease in PAD patients. CUS can be a useful noninvasive preoperative screening imaging tool for PAD patients with multilevel lesions, aged > 65 years old, with CKD and CVD.
Glutathione-S-transferases M1/T1 gene polymorphisms and male infertility risk in Chinese populations
Authors: Hu Chun-Yan , Lu Dong-Liang , Wu Tao , Cheng Shu-Lin , Wu Tian-tian , Wang Shu , Zhang Tao
Published: February 2019

Background:

A meta-analysis was applied to evaluate the associations between the glutathione-S-transferases (GSTs) M1/T1 gene polymorphisms and male infertility in Chinese populations.

Methods:

A comprehensive search for articles was conducted from PubMed, Web of Science, Embase, China biology medical literature database (CBM), China National Knowledge Infrastructure (CNKI), VIP, and Chinese literature database(Wang fang) up to April 30, 2018. All of the statistical analyses were performed using Review Manager 5.3 and Stata 14.0.

Results:

Ten studies on GSTM1 gene polymorphism involving 3302 cases and 1959 controls, and ten studies on GSTT1 gene polymorphism involving 3048 cases and 1861 controls were included in this meta-analysis. Overall, the null genotype of GSTM1/GSTT1 was significantly related to male infertility risk in Chinese populations (GSTM1, OR = 1.35, 95% CI: 1.02–1.78; GSTT1, OR = 1.40, 95% CI: 1.15–1.70). In subgroup analyses stratified by infertility type, significant association was observed between GSTT1 null genotype and male infertility in both nonobstructive azoospermia (NOA) and oligoasthenozoospermia (OAT). However, the GSTM1 null genotype was associated with OAT, but not NOA in Chinese populations. The sensitivity analysis confirmed the reliability and stability of the meta-analysis.

Conclusion:

Our meta-analysis supports that the GSTM1/GSTT1 null genotype might contribute to individual susceptibility to male infertility in Chinese populations.
Application of a combined model with seasonal autoregressive integrated moving average and support vector regression in forecasting hand-foot-mouth disease incidence in Wuhan, China
Authors: Zou Jiao-Jiao , Jiang Gao-Feng , Xie Xiao-Xu , Huang Juan , Yang Xiao-Bing
Published: February 2019

Hand-foot-mouth disease (HFMD) is a serious public health problem with increasing cases and substantial financial burden in China, especially in Wuhan city. Hence, there is an urgent need to construct a model to predict the incidence of HFMD that could make the prevention and control of this disease more effective.

The incidence data of HFMD of Wuhan city from January 2009 to December 2016 were used to fit a combined model with seasonal autoregressive integrated moving average (SARIMA) model and support vector regression (SVR) model. Then, the SARIMA-SVR hybrid model was constructed. Subsequently, the fitted SARIMA-SVR hybrid model was applied to obtain the fitted HFMD incidence from 2009 to 2016. Finally, the fitted SARIMA-SVR hybrid model was used to forecast the incidence of HFMD of the year 2017. To assess the validity of the model, the mean square error (MSE) and mean absolute percentage error (MAPE) between the actual values and predicted values of HFMD incidence (2017) were calculated.

From 2009 to 2017, a total of 107636 HFMD cases were reported in Wuhan City, Hubei Province, and the male-to-female ratio is 1.60:1. The age group of 0 to 5 years old accounts for 95.06% of all reported cases and scattered children made up the large proportion (accounted for 56.65%). There were 2 epidemic peaks, from April to July and September to December, respectively, with an emphasis on the former. High-prevalence areas mainly emerge in Dongxihu District, Jiangxia District, and Hongshan District. SARIMA (1,0,1)(0,0,2)[12] is the optimal model given with a minimum Akaike information criterion (AIC) (700.71), then SVR model was constructed by using the optimum parameter (C = 100000, =0.00001, =0.01). The forecasted incidences of single SARIMA model and SARIMA-SVR hybrid model from January to December 2017 match the actual data well. The single SARIMA model shows poor performance with large MSE and MAPE values in comparison to SARIMA-SVR hybrid model.

The SARIMA-SVR hybrid model in this study showed that accurate forecasting of the HFMD incidence is possible. It is a potential decision supportive tool for controlling HFMD in Wuhan, China.
Intracranial endodermal cyst presenting with nonobstructive hydrocephalus
Authors: Fujii Yoshiko , Nagaishi Masaya , Nakae Ryuta , Takigawa Tomoji , Tanaka Yoshihiro , Suzuki Kensuke
Published: February 2019

Rationale:

Endodermal cysts are rare benign lesions in the central nervous system. Their common symptoms include headache and neck pain caused by mass effect or inflammatory reaction. We report the case of an elderly woman with intracranial endodermal cyst who presented with nonobstructive hydrocephalus.

Patient concerns:

A 78-year-old woman presented with acute deterioration of consciousness caused by acute hydrocephalus. She subsequently underwent ventriculoperitoneal shunt placement. Eighteen months after this operation, she developed numbness of extremities and gait and progressive cognitive disturbances.

Diagnosis:

Initially, the endodermal cyst could not be recognized, but it became clinically evident in the craniocervical junction after ventriculoperitoneal shunt placement. MRI revealed multiple cystic lesions in the pontomedullary cistern. Postoperative pathology confirmed the diagnosis of endodermal cyst.

Interventions:

Subtotal resection of the cystic lesion was performed. Intra-operatively, multiple cysts containing a milky white fluid were noted and the medullary surface including the median and lateral apertures of the fourth ventricle were covered by thick, cloudy arachnoid membrane.

Outcomes:

Although the numbness of extremities improved after the surgery, she remained bedridden due to deterioration in cognitive function and generalized muscle weakness. The patient developed recurrence 2 months after the surgery; however, no additional surgery was performed owing to her poor general condition.

Lessons:

Endodermal cysts rarely present with nonobstructive hydrocephalus caused by recurrent meningitis. In such cases, the lesions are often invisible on initial diagnostic imaging, and complete resection of the lesions is typically difficult because of strong adhesion between the cyst walls and contiguous vital structures.
Metallic artifact reduction by evaluation of the additional value of iterative reconstruction algorithms in hip prosthesis computed tomography imaging
Authors: Neroladaki Angeliki , Martin Steve Philippe , Bagetakos Ilias , Botsikas Diomidis , Hamard Marion , Montet Xavier , Boudabbous Sana
Published: February 2019

To evaluate iterative metal artifact reduction (iMAR) technique in images data of hip prosthesis on computed tomography (CT) and the added value of advanced modeled iterative reconstruction (ADMIRE) compared with standard filtered back projection (FBP).

Twenty-eight patients addressed to CT examinations for hip prosthesis were included prospectively. Images were reconstructed with iMAR algorithm in addition to FBP and ADMIRE techniques. Measuring image noise assessed objective image quality and attenuation values with standardized region of interest (ROI) in 4 predefined anatomical structures (gluteus medius and rectus femoris muscles, inferior and anterior abdominal fat, and femoral vessels when contrast media was present). Subjective image quality was graded on a 5-point Likert scale, taking into account the size of artifacts, the metal–bone interface and the conspicuity of pelvic organs, and the diagnostic confidence.

Improvement in overall image quality was statistically significant using iMAR (P<.001) compared with ADMIRE and FBP. ADMIRE did not show any impact in image noise, attenuation value, or global quality image. iMAR showed a significant decrease in image noise in all ROIs (Hounsfield Unit) as compared with FBP and ADMIRE. Interobserver agreement was high in all reconstructions (FBP, FBP+iMAR, ADMIRE, and ADMIRE + iMAR) more than 0.8. iMAR reconstructions showed emergence of new artifacts in bone–metal interface.

iMAR algorithm allows a significant reduction of metal artifacts on CT images with unilateral or bilateral prostheses without additional value of ADMIRE. It improves the analysis of surrounding tissue but potentially generates new artifacts in bone–metal interface.
Comparison of the immunogenicity and safety of 3 inactivated hepatitis A vaccines in Korean children aged 12 to 18 months
Authors: Hong Seung Soo , Choi Ui Yoon , Ma Sang Hyuk , Lee Soo Young , Han Seung Beom , Kim Kyung-Hyo , Kang Jin Han , Kim Jong-Hyun
Published: February 2019

Several approved inactivated hepatitis A (HA) vaccines are available in Korea. These have been shown to be immunogenic and safe in European children; however, their immunogenicity and safety have not been investigated among Korean children. We aimed to compare the immunogenicity and safety of the most commonly used HA vaccines in ethnic Korean children aged 12 to 18 months.

In this open-label, randomized, prospective, multicenter study, 108 children were enrolled and randomized to receive a pediatric form of Avaxim, Epaxal, or Havrix. The 2nd dose was administered after an interval of 6 months. Anti-HA virus (HAV) immunoglobulin (Ig) G was measured to assess geometric mean concentrations (GMCs) and seropositvity rates (≥20 mIU/mL anti-HAV IgG). To assess safety, local solicited adverse events (AEs), systemic solicited AEs, unsolicited AEs, and serious AEs (SAEs) were graded.

Among the 108 participants enrolled, 37, 34, and 37 received Avaxim, Epaxal, and Havrix, respectively. After administration of 2 doses, the seropositivity rates in the Avaxim, Epaxal, and Havrix groups were all 100% (95% confidence intervals [CIs]: 99.0–100, 98.9–100, and 99.0–100, respectively; P < .001). The anti-HAV GMCs in the Avaxim, Epaxal, and Havrix groups were 5868.4 (95% CI: 4237.2–8126.6), 1962.1 (95% CI: 1298.0–2965.9), and 2232.9 mIU/mL (95% CI: 1428.4–3490.4), respectively, after administration of 2 doses (P < .001). There were no significant differences in the proportions of participants reporting local solicited AEs, systemic solicited AEs, unsolicited AEs, and SAEs among the 3 vaccine groups after the 1st and 2nd doses. All local solicited and unsolicited AEs were grade 1 or 2. Grade 3 systemic solicited AE occurred in 5.4% and 2.9% of the participants in the Havrix group after the 1st and 2nd doses, respectively. SAEs after the 1st and 2nd doses were reported in 2 participants and 1 participant, respectively, but none was assessed as being related to vaccination.

The results indicate that these vaccines were safe and immunogenic in ethnic Korean children. The results have contributed to the establishing of an HA vaccination policy in Korea and will be informative to countries that plan to initiate vaccination programs against HAV.
Prosthetic valve thrombosis – association of genetic polymorphisms of VKORC1, CYP2C9 and CYP4F2 genes
Authors: SR Kalpana , G Bharath , Jain Simran , Moorthy Nagaraja , Manjunath Satvic C. , Christopher Rita
Published: February 2019

Prosthetic Valve Thrombosis (PVT), in spite of the advances in the valve design and the material used, remains a serious complication of mechanical cardiac valve replacement. The factors influencing the development of PVT are: thrombogenicity of the valve, hemodynamics of the transprosthetic blood flow and ineffective anticoagulation. Genetic polymorphism of the genes VKORC1 (-1639 G > A and 1173 C > T), CYP2C9 (∗2 & ∗3 alleles) and CYP4F2 (1347 G > A) are known to influence the anticoagulant dose-effect response. Since there has not been any earlier study on the direct influence of gene polymorphism on the development of PVT, we investigated into this association.

Genotyping for the genes VKORC1, CYP2C9 and CYP4F2 was carried out by conventional PCR-RFLP method for 91 consecutive PVT patients. Subjects of our earlier study served as controls (n = 136).

Female patients and patients with smaller prosthetic valve size were more prone to developing PVT (68%, n = 62). Patients bearing A allele of CYP4F2 1347 G > A polymorphism exhibited a fivefold increased risk of PVT (OR = 5.022 (1.39–18.04), P = .013). G allele of VKORC1 when analyzed in combination of genotypes showed a fourteen fold increased risk for developing PVT (OR = 14.25 (5.52–36.77), P = 0.001). CYP2C9 (∗2&∗3) gene polymorphism did not show any significant association with PVT (OR = 1.54 (0.128 – 18.82), P = .731).

Patients bearing A allele of CYP4F2 showed an increased risk of developing PVT in our case – control study.
The different effects of adefovir dipivoxil and telbivudine on the prognosis of hepatitis b virus-related hepatocellular carcinoma patients after curative resection
Authors: He Linye , Xia Zijing , Shen Junyi , Zhang Xiaoyun , Peng Wei , Li Chuan , Wen Tianfu
Published: February 2019

Numerous studies suggested that antiviral therapy could reduce the recurrence in hepatocellular carcinoma (HCC) patients after hepatectomy. The impact of nucleotide and nucleoside analogues on prognosis of chronic hepatitis B (CHB) related HCC remains to be explored. We aimed to investigate the role of the telbivudine and adefovir dipivoxil on the prognosis of CHB-related HCC patients after hepatectomy.

One hundred eighty-eight CHB-related patients who received hepatectomy from February 2010 to February 2017 were divided into telbivudine (LdT) and adefovir dipivoxil (ADV) groups. The characteristics and survival information of both groups were retrospectively compared and analyzed.

One hundred eleven and 77 patients received telbivudine and adefovir dipivoxil monotherapy, respectively. Alanine aminotransferase (ALT), total bilirubin level, status of hepatitis B e antigen (HBeAg), serum HBV-DNA level were compared between groups. OS and DFS in ADV-treatment group were significantly better than it in LdT-treatment group (P < .05). In the subgroups analysis, we found that ADV treatment was significantly associated with better DFS and OS among patients with cirrhosis, HBeAg-negative patients, or those with detectable HBV-DNA.

CHB-related HCC patients receiving long-term ADV-treatment had a better OS and DFS than patients receiving LdT-treatment after hepatectomy.
Prognostic significance of inflammation-based indexes in patients with stage III/IV colorectal cancer after adjuvant chemoradiotherapy
Authors: Yang Jing , Guo Xinli , Wu Tong , Niu Kaifan , Ma Xuelei
Published: February 2019

Inflammation-based indexes such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation indexes (SII) have been reported to be associated with prognosis in cancer patients.

The aim of this study was to estimate the prognostic significance of inflammation-based indexes such as NLR, PLR, LMR, and SII in stage III/IV colorectal cancer (CRC) patients undertaking adjuvant chemoradiotherapy (CRT).

Two hundred twenty stage III/IV CRC patients were enrolled in this study. Inflammatory indexes were defined as follows: NLR = absolute neutrophil counts/absolute lymphocyte counts; PLR = absolute platelet counts/absolute lymphocyte counts; LMR = absolute lymphocyte counts/absolute monocyte counts; SII = absolute neutrophil counts × absolute platelet counts/absolute lymphocyte counts. The correlations between indexes and prognosis were evaluated using the Cox proportional hazard model.

The results of univariate analysis demonstrated that NLR, PLR, and SII were significantly associated with progression-free survival (PFS) and overall survival (OS). Multivariate analysis showed that SII (P = .030) was an independent predictor of PFS, and NLR (P = .047) was an independent prognostic factor of OS.

Those inflammation-based indexes could provide a convenient and secure method to predict the outcomes of stage III/IV CRC patients receiving adjuvant CRT.
Pulmonary vascular involvement of IgG4-related disease
Authors: Zhou Yong , Shao Lingyan , Ruan Wenjing , Jin Joy , Xu Hangdi , Ying Kejing , Wu Xiaohong
Published: February 2019

Background:

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized, immune-mediated chronic fibrotic inflammation that can involve almost all organs, causing tumefaction and dysfunction. Its presence in pulmonary circulation is underestimated and has not yet been investigated.

Objectives:

We describe a representative IgG4-RD patient with pulmonary artery stenosis and pulmonary embolism, leading to reversible pulmonary hypertension. Literature review of IgG4-RD with pulmonary circulation involvement was conducted.

Data sources:

References for this review were identified through searches via PubMed, EBSCO, and Web of Science for published articles before November 2016.

Results:

There were 15 published cases of IgG4-RD with pulmonary vascular involvement, 3 with pulmonary arteritis, 2 with pulmonary artery aneurysm, 3 with pulmonary artery stenosis, 1 with obliterative phlebitis, and 1 with pulmonary embolism. Possible immunity and inflammation mechanisms were summarized.

Conclusions:

IgG4-RD with pulmonary vascular involvement is rare. Echocardiogram and contrast-enhanced chest CT are helpful to screen the disease. Clinical manifestations were found from asymptomatic to dyspnea or even syncope. And nearly all cases had more than 1 organ affected, with significantly increased serum IgG4 levels. PET/CT aided in identifying affected organs and determining candidate biopsy sites. More awareness is urged to evaluate the pulmonary vascular manifestations of this disease.
Efficacy of methotrexate, doxorubicin, and cisplatin for osteosarcoma
Authors: Tang Qing-xi , Wang Lu-Chuan , Wang Yu , Gao Hong-da , Hou Zhi-ling
Published: February 2019

Background:

This systematic review will address the efficacy and safety of methotrexate, doxorubicin, and cisplatin (MAP) for the treatment of patients with osteosarcoma.

Methods:

We will retrieve the studies from the following 9 electronic databases: Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Information, and Wanfang Data. Two independent researchers will screen and select the relevant papers for eligibility after the search strategies have been conducted. All articles up to the present in any language, region will be considered in this study. A systematic review and data synthesis will be performed of randomized controlled trials of MAP for the treatment of patients with osteosarcoma. The primary outcome includes event-free survival. The secondary outcomes consist of overall survival, quality of life, and toxicity. In addition, 2 independent researchers will extract data, and will assess the quality of included studies by using Cochrane risk of bias tool. Results data will be pooled and meta-analysis will be conducted if >2 eligible studies will be included.

Results:

This systematic review will evaluate the efficacy and safety of MAP for the treatment of patients with osteosarcoma.

Conclusion:

The findings of this study will summarize the up-to-date evidence of MAP for osteosarcoma, and may provide the guidance for the clinical practice, as well as the health policy maker.

PROSPERO registration number:

PROSPERO CRD42018120004.
Prognostic value of serum albumin for patients with acute aortic dissection
Authors: Gao Yongli , Li Dongze , Cao Yu , Zhu Xingyu , Zeng Zhi , Tang Li
Published: February 2019

Serum albumin (SA) is associated with inflammation and thrombosis, which are involved in acute aortic dissection (AAD). Our aim was to investigate the effect of SA level on survival in patients with AAD.

We analyzed 777 patients with AAD. The patients were divided into hypoalbuminemia and non-hypoalbuminemia groups according to their AAD Stanford classification. Multivariable Cox regression was used to investigate the association between SA levels and in-hospital mortality in type A and B AAD.

A total of 103 (13.3%) patients died in-hospital. The in-hospital mortality in type A and B patients with hypoalbuminemia was higher compared to those without (type A: 34.2% vs 13.9%, P <.001; type B: 7.9% vs 1.6%, P = .001). Kaplan–Meier analysis showed that survival was significantly lower in patients with hypoalbuminemia compared to those without, regardless of AAD type (type A: log-rank χ2 = 14.71; P <.001; Type B: log-rank χ2 = 10.42; P = .001). After adjusting for confounding factors, hypoalbuminemia was an independent predictor of in-hospital mortality in patients with either type A (HR, 2.492; 95% confidence interval [CI], 1.247–4.979; P = .010) or type B (HR, 8.729; 95% CI, 1.825–41.736; P = .007).

SA is independently associated with increased in-hospital mortality in both type A and B AAD.
Drain Management Following Distal Pancreatectomy
Authors: Seykora Thomas F. , Liu Jason B. , Maggino Laura , Pitt Henry A. , Vollmer Charles M.
Published: February 2019

Objective:

To explore contemporary drain management practices and examine the impact of early removal following distal pancreatectomy (DP).

Background:

Despite accruing evidence supporting its benefit following pancreatoduodenectomy, early drain removal after DP has yet to be explored.

Methods:

The American College of Surgeons’ National Surgical Quality Improvement Program (ACS-NSQIP) was queried for elective DPs from 2014 to 2017. When possible, data were linked to survey responses regarding drain management from hepato-pancreato-biliary (HPB) surgeons in the ACS-NSQIP HPB Collaborative conducted in 2017. The independent association between timing of drain removal and patients’ outcomes was investigated through multivariable analyses and propensity-score matching.

Results:

Of 5581 DPs identified, 4708 (84.4%) patients received intraoperative drains and early removal (≤ POD3) was performed in 716 (15.2%). Drain fluid amylase was recorded on POD1 for 1285 (27.3%) patients who received drains. The overall rates of death or serious morbidity (DSM) and clinically-relevant fistula (CR-POPF) were 19.5% and 17.0%. Early removal demonstrated significantly better outcomes when compared to late removal and no drain placement for: DSM, CR-POPF, delayed gastric emptying, percutaneous drainage, length of stay, and readmission. On multivariable analysis, early removal demonstrated reduced odds of developing DSM (OR = 0.41, 95% CI = 0.26–0.65) and CR-POPF (OR = 0.33, 95% CI = 0.18–0.61) compared to no drain placement, while late removal displayed increased odds for CR-POPF (OR = 2.15, 95% CI = 1.27–3.61) when compared to no drain placement. After propensity-score matching, early removal was associated with reduced odds for CR-POPF (OR = 0.35, 95% CI = 0.17–0.73).

Conclusion:

Although not yet widely implemented, early drain removal after distal pancreatectomy is associated with better outcomes. This study demonstrates the potential benefits of early removal and provides a substrate to define best practices and improve the quality of care for DP.
Alzheimer’s Environmental and Genetic Risk Scores are Differentially Associated With General Cognitive Ability and Dementia Severity
Authors: Andrews Shea J. , McFall G. Peggy , Dixon Roger A. , Cherbuin Nicolas , Eramudugolla Ranmalee , Anstey Kaarin J.
Published: February 2019

Purpose:

We investigated the association of the Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI) and an Alzheimer disease (AD) genetic risk score (GRS) with cognitive performance.

Methods:

The ANU-ADRI (composed of 12 risk factors for AD) and GRS (composed of 25 AD risk loci) were computed in 1061 community-dwelling older adults. Participants were assessed on 11 cognitive tests and activities of daily living. Structural equation modeling was used to evaluate the association of the ANU-ADRI and GRS with: (1) general cognitive ability (g), (2) dementia-related variance in cognitive performance (δ), and (3) verbal ability (VA), episodic memory (EM), executive function (EF), and processing speed (PS).

Results:

A worse ANU-ADRI score was associated with poorer performance in “g” [β (SE)=−0.40 (0.02),P<0.001], δ [−0.40 (0.04),P<0.001], and each cognitive domain [VA=−0.29 (0.04),P<0.001; EM=−0.34 (0.03),P<0.001; EF=−0.38 (0.03),P<0.001; and PS=−0.40 (0.03),P<0.001]. A worse GRS was associated with poorer performance in δ [−0.08 (0.03),P=0.041] and EM [−0.10 (0.03),P=0.035].

Conclusions:

The ANU-ADRI was broadly associated with worse cognitive performance, including general ability and dementia severity, validating its further use in early dementia risk assessment.
Prevalence of Mild Cognitive Impairment Among Older People in Kazakhstan and Potential Risk Factors
Authors: Tsoy Radmila T. , Turuspekova Saule T. , Klipitskaya Nina K. , Mereke Alibek , Cumming Robert G.
Published: February 2019

Background:

There have been no epidemiological studies of mild cognitive impairment (MCI) in Central Asia.

Objective:

The objective of this study was to describe the prevalence of, and risk factors for, MCI in an urban population in Kazakhstan.

Methods:

Adults aged 60 years and over were randomly selected from registers of 15 polyclinics in Almaty. Of 790 eligible people, 668 agreed to participate (response rate 85%). Subjects were screened using the Montreal Cognitive Assessment (MoCA). Those who scored 26 or lower on the MoCA were assessed by a multidisciplinary team and a diagnosis of normal cognition, MCI or dementia was made.

Results:

The median MoCA score was 22 and the prevalence of MCI was 30%. MoCA scores were lower, and MCI prevalence was higher, among those with less education and those with older age. There was no difference in MoCA scores or MCI prevalence by sex or ethnic group (Kazakh or Russian). High blood pressure, older age, and lower education were associated with increased odds of MCI in crude analyses but only age and education remained statistically significant in an adjusted logistic regression model.

Conclusions:

The prevalence of MCI in Kazakhstan is high. Higher levels of education may lead to lower prevalence of MCI in the future.
Epigenetic inhibitors sensitize DLBCL cells to rituximab and doxorubicin
Authors: Facciotto Chiara , Casado Julia , Turunen Laura , Leivonen Suvi-Katri , Tumiati Manuela , Rantanen Ville , Kauppi Liisa , Lehtonen Rainer , Leppä Sirpa , Wennerberg Krister , Hautaniemi Sampsa
Published: February 2019

Primary therapy for diffuse large B-cell lymphoma (DLBCL) is an immunochemotherapy regimen comprising rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). While R-CHOP cures 60% of the patients with DLBCL, those who do not respond or relapse have dismal prognosis, and effective treatment strategies are needed. Due to the plastic nature of the epigenome and its fundamental role in regulating cell identity, we hypothesized that reprogramming the epigenome can overcome resistance to R-CHOP. We developed a novel drug screening protocol to identify epigenetic modifiers that sensitize DLBCL cell lines to immunochemotherapy. Of the herein tested 60 epigenetic compounds, we identified several histone deacetylase (HDAC) and histone methyltransferase (HMT) inhibitors that acted synergistically with immunochemotherapy. We show that sensitization through HDAC and HMT inhibitors is achieved by dysregulating homologous recombination, a central DNA repair pathway, as well as by disrupting the cell cycle and affecting the apoptotic pathway. Epigenetic inhibitors are well-tolerated, which together with our findings support their use in combination with immunochemotherapy in patients with primary refractory and relapsed DLBCL.
Progranulin deficiency leads to reduced glucocerebrosidase activity
Authors: Zhou Xiaolai , Paushter Daniel H. , Pagan Mitchell D. , Kim Dongsung , Lieberman Raquel L. , Overkleeft Herman S. , Sun Ying , Smolka Marcus B. , Hu Fenghua
Published: February 2019

Mutation in theGRNgene, encoding the progranulin (PGRN) protein, shows a dose-dependent disease correlation, wherein haploinsufficiency results in frontotemporal lobar degeneration (FTLD) and complete loss results in neuronal ceroid lipofuscinosis (NCL). Although the exact function of PGRN is unknown, it has been increasingly implicated in lysosomal physiology. Here we report that PGRN interacts with the lysosomal enzyme, glucocerebrosidase (GBA), and is essential for proper GBA activity. GBA activity is significantly reduced in tissue lysates from PGRN-deficient mice. This is further evidence that reduced lysosomal hydrolase activity may be a pathological mechanism in cases of GRN-related FTLD and NCL.
Intrinsic temporal tuning of neurons in the optic tectum is shaped by multisensory experience
Authors: Busch Silas E. , Khakhalin Arseny S.
Published: February 2019

Homeostatic intrinsic plasticity is often described as an adjustment of neuronal excitability to maintain stable spiking output. Here we report that intrinsic plasticity in the tectum of Xenopus tadpoles also supports temporal tuning, wherein neurons independently adjust spiking responses to fast and slow patterns of synaptic activation. Using the dynamic clamp technique, and five different types of visual, acoustic, and multisensory conditioning, we show that in tadpoles exposed to light flashes, tectal neurons became selective for fast synaptic inputs, while neurons exposed to looming and multisensory stimuli remained responsive to longer inputs. We also report a homeostatic co-tuning between synaptic and intrinsic temporal properties in tectal cells, as neurons that naturally received fast synaptic inputs tended to be most responsive to long-lasting synaptic conductances, and the other way around. These results expand our understanding of plasticity in the brain, and inform future work on the mechanisms of sensorimotor transformation.

Significance statement

With the recent explosion of work in neural connectivity reconstruction and biologically inspired deep learning, most researchers concentrate on the topology of connections between neurons, rather than on differences in neuronal tuning. Here we show that in a sensory network in Xenopus tadpoles, different neurons are tuned, and respond stronger, to either short or long synaptic inputs. This tuning tended to be opposite to the actual dynamics of synaptic inputs each cell received, such that neurons that normally receive shorter inputs generated stronger spiking in response to longer testing currents, and the other way around. This observation shows that even in networks that don’t generate oscillations, neurons reshape their temporal selectivity, to optimize their impact on distributed calculations.
Firing rate distributions in spiking networks with heterogeneous connectivity
Authors: Vegué Marina , Roxin Alex
Published: February 2019

Meanfield theory for networks of spiking neurons based on the so-called diffusion approximation has been used to calculate certain measures of neuronal activity which can be compared with experimental data. This includes the distribution of firing rates across the network. However, the theory in its current form applies only to networks in which there is relatively little heterogeneity in the number of incoming and outgoing connections per neuron. Here we extend this theory to include networks with arbitrary degree distributions. Furthermore, the theory takes into account correlations in the in-degree and out-degree of neurons, which would arise e.g. in the case of networks with hub-like neurons. Finally, we show that networks with broad and postively correlated degrees can generate a large-amplitude sustained response to transient stimuli which does not occur in more homogeneous networks.
The isotopic N turnover rate as a proxy to evaluate in the long-term the protein turnover in growing ruminants
Authors: Cantalapiedra-Hijar Gonzalo , Fouillet Hélène , Chantelauze Céline , Khodorova Nadezda , Bahloul Lahlou , Ortigues-Marty Isabelle
Published: February 2019

Protein turnover is an energy-consuming process essential for ensuring the maintenance of living organisms. Gold standard methods for protein turnover measurement are based on intravenous infusions of stable isotopes. Although accurate they have inherent drawbacks precluding their generalization for large farm animals and during long time periods. We proposed here a non-invasive proxy of the whole-body fractional protein degradation (WBFPDR; protein turnover for a growing animal) in the long term and in a large number of beef cattle. The proxy is based on the rate at which urine-N and plasma proteins are progressively depleted in 15N after a slight decrease in the isotopic N composition of diet (i.e. diet-switch). We aimed to test the ability of this proxy to adequately discriminate the WBFPDR of 36 growing-fattening young bulls assigned to different dietary treatments known to impact the protein turnover rate: the protein content and amino acid profile. To achieve this objective, the experimental diets were enriched with 15N labeled-urea during 35 days while the animals were adapted to diets. After stopping the 15N labeled-urea administration the animals were thereafter sampled for spot urines (n = 13) and blood (n = 10) over 5 months and analyzed for their 15N enrichments in total N and plasma proteins, respectively. Adequately fitting the 15N kinetics in plasma proteins and urines required mono- and bi-exponential models, respectively, and the model parameters were compared across dietary conditions using a non-linear mixed effect model. The single 15N depletion rate found in plasma proteins represented their fractional synthesis rate, whereas the slowest depletion rate found in urines was interpreted as a proxy of the WBFPDR. The proxy here tested in urines suggested different WBFPDR values between Normal vs High protein diets but not between balanced vs unbalanced methionine diets. In contrast, the proxy tested in plasma indicated that both dietary conditions affected the fractional synthesis rate of plasma proteins. We consider that the rate at which urines are progressively 15N-depleted following an isotopic diet-switch could be proposed as a non-invasive proxy of the long-term whole-body fractional protein degradation rate for large farm animals.