bluuebunny/crossref_metadata_2025 huggingface dataset:
Divergence, Convergence, and Therapeutic Implications: A Cell Biology Perspective of C9ORF72-ALS/FTD
Authors: Tang Xiaoqiang , Toro Arturo , T.G. Sahana , Gao Junli , Chalk Jessica , Oskarsson Björn E. , Zhang Ke
Published: June 2020

Ever since a GGGGCC hexanucleotide repeat expansion mutation inC9ORF72was identified as the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), three competing but nonexclusive hypotheses to explain how this mutation causes diseases have been proposed and are still under debate. Recent studies in the field have tried to understand how the repeat expansion disrupts cellular physiology, which has suggested interesting convergence of these hypotheses on downstream, functional defects in cells, such as nucleocytoplasmic transport disruption, membrane-less organelle defects, and DNA damage. These studies have not only provided an integrated view of the disease mechanism but also revealed novel cell biology implicated in neurodegeneration. Furthermore, some of the discoveries have given rise to new ideas for therapeutic development. Here, we review the research progress on cellular pathophysiology of C9ORF72-mediated ALS and FTD and its therapeutic implication. We suggest that the repeat expansion drives pathogenesis through a combination of downstream defects, of which some can be therapeutic targets.
Responding to health needs of women, children and adolescents within Syria during conflict: intervention coverage, challenges and adaptations
Authors: Akik Chaza , Semaan Aline , Shaker-Berbari Linda , Jamaluddine Zeina , Saad Ghada E. , Lopes Katherine , Constantin Joanne , Ekzayez Abdulkarim , Singh Neha S. , Blanchet Karl , DeJong Jocelyn , Ghattas Hala
Published: June 2020

Background

Women and children suffer disproportionately in armed-conflicts. Since 2011, the protracted Syrian crisis has fragmented the pre-existing healthcare system. Despite the massive health needs of women and children, the delivery of key reproductive, maternal, newborn, child and adolescent health and nutrition (RMNCAH&N) interventions, and its underlying factors are not well-understood in Syria. Our objective was to document intervention coverage indicators and their implementation challenges inside Syria during conflict.

Methods

We conducted 1) a desk review to extract RMNCAH&N intervention coverage indicators inside Syria during the conflict; and 2) qualitative interviews with decision makers and health program implementers to explore reasons behind provision/non-provision of RMNCAH&N interventions, and the rationale informing decisions, priorities, collaborations and implementation. We attempt to validate findings by triangulating data from both sources.

Results

Key findings showed that humanitarian organisations operating in Syria adopted a complex multi-hub structure, and some resorted to remote management to improve accessibility to certain geographic areas. The emergency response prioritised trauma care and infectious disease control. Yet, with time, humanitarian organisations successfully advocated for prioritising maternal and child health and nutrition interventions given evident needs. The volatile security context had implications on populations’ healthcare seeking behaviors, such as women reportedly preferring home births, or requesting Caesarean-sections to reduce insecurity risks. Additional findings were glaring data gaps and geographic variations in the availability of data on RMNCAH&N indicators. Adaptations of the humanitarian response included task-shifting to overcome shortage in skilled healthcare workers following their exodus, outreach activities to enhance access to RMNCAH&N services, and operating in ‘underground’ facilities to avoid risk of attacks.

Conclusion

The case of Syria provides a unique perspective on creative ways of managing the humanitarian response and delivering RMNCAH&N interventions, mainly in the multi-hub structure and use of remote management, despite encountered challenges. The scarcity of RMNCAH&N data is a tremendous challenge for both researchers and implementing agencies, as it limits accountability and monitoring, thus hindering the evaluation of delivered interventions.
Reduced free ubiquitin levels and proteasome activity in cultured neurons and brain tissues treated with amyloid beta aggregates
Authors: Park Chul-Woo , Jung Byung-Kwon , Ryu Kwon-Yul
Published: June 2020

Neurodegenerative diseases are characterized by progressive cognitive decline and the loss of neurons in the central nervous system; many are also characterized by abnormal aggregation of misfolded proteins. Ubiquitin (Ub) is a eukaryotic protein that plays pivotal roles in protein degradation and cellular signaling. Ubiquitinated aggregates are observed in neurodegenerative diseases; this ultimately results in reduced levels of available or free Ub. However, it remains unclear whether neurotoxicity arises from the aggregates or a deficiency of free Ub. To investigate this, we treated primary neurons of mouse embryonic brains with amyloid beta (Aβ) 42 and found that free Ub levels were decreased and cell viability was reduced in Aβ42-treated neurons. As reduced levels of free Ub are closely related to impaired function of the proteasome, we evaluated proteasome activity and found that proteasome activity was reduced upon treatment of primary neurons and mouse brain slices with Aβ42. Therefore, we conclude that proteotoxic stress from Aβ42 treatment reduced the levels of available Ub and decreased proteasome activity, resulting in inflammatory stress and apoptosis of neurons.
Does daily co administration of gonadotropins and letrozole during the ovarian stimulation improve IVF outcome for poor and sub optimal responders?
Authors: Shapira Moran , Orvieto Raoul , Lebovitz Oshrit , Nahum Ravit , Aizer Adva , Segev-Zahav Aliza , Haas Jigal
Published: June 2020

Background

Co-administration of letrozole during the first 5 days of ovarian stimulation was suggested to improve IVF outcomes in poor responders. We aimed to determine whether poor/sub-optimal responders might benefit from Letrozole co-treatment throughout the entire stimulation course.

Methods

We retrospectively reviewed the medical files of women who demonstrated poor (oocyte yield ≤3) and sub-optimal (4 ≤ oocyte yield ≤9) ovarian response during conventional multiple-dose antagonist stimulation protocols and were co-treated in a subsequent cycle with 5 mg Letrozole from the first day of stimulation until trigger day. A self-paired comparison between gonadotropins-only and gonadotropins-letrozole cycles was performed.

Results

Twenty-four patients were included. Mean patients’ age was 39.83 ± 4.60 and mean day-3-FSH was 12.77 ± 4.49 IU/m. Duration of stimulation and total gonadotropins dose were comparable between the two cycle groups. Peak estradiol levels were significantly lower in gonadotropins-letrozole cycles (2786.74 ± 2118.53 vs 1200.13 ± 535.98, p < 0.05). Number of retrieved oocytes (3.29 ± 2.15 vs 6.46 ± 3.20, p < 0.05), MII-oocytes (2.47 ± 1.65 vs 5.59 ± 3.20, p < 0.05), 2PN-embryos (1.78 ± 1.50, 4.04 ± 2.74, p < 0.05) and top-quality embryos (0.91 ± 0.97 vs. 2.35 ± 1.66, p < 0.05) were significantly higher in the gonadotropins-letrozole cycles. Clinical pregnancy rate in gonadotropins-letrozole cycles was 31.5%.

Conclusion

Letrozole co-treatment during the entire stimulation course improves ovarian response and IVF outcomes in poor/sub-optimal responders.
Management of decision of withholding and withdrawing life-sustaining treatments in French EDs
Authors: Douplat Marion , Fraticelli Laurie , Claustre Clement , Peiretti Alexandra , Serre Patrice , Bischoff Magali , Jacquin Laurent , Freyssenge Julie , Schott Anne-Marie , Tazarourte Karim , Frugier Soizic , Khoury Carlos E. L. ,   The LAT group, Grezard Maud , Antoine Jean-Damien , Dumont Odile , Lhuillier Elise , Pierro Luigi , Blain Stephane , Prost Celine , Sen-Brachet Piali , Khaldi Achraf
Published: June 2020

Background

Decisions of withholding or withdrawing life sustaining-treatments in emergency department are part of current practice but the decision-making process remains poorly described in the literature.

Study objective

We conducted a study in two phases, the first comprising a retrospective chart review study of patients dying in the ED and the second comprising survey study of health care workers at 10 urban emergency departments in France.

Method

In a first step, we analyzed medical records based on fifteen criteria of the decision-making process grouped into four categories: the collegiality, the traceability, the management and the communication as recommended by the international guidelines. In a second step, we conducted an auto-administrated survey to assess how the staff members (medical, paramedical) feel with the decision-making process.

Results

There were 273 deaths which occurred in the ED over the study period and we included 145 (53.1%) patients. The first-step analysis revealed that the traceability of the decision and the information given to patient or the relatives were the most reported points according to the recommendations. Three of the ten emergency departments had developed a written procedure. The collegial discussion and the traceability of the prognosis assessment were significantly increased in emergency department with a written procedure as well as management of pain, comfort care, and the communication with the patient or the relatives. In the second-step analysis, among the 735 staff members asked to take part in the survey, 287 (39.0%) answered. The medical and paramedical staff expressed difficult experience regarding the announcement and the communication with the patient and the relatives.

Conclusion

The management of the decision to withhold or withdraw life-sustaining treatments must be improved in emergency departments according to the guidelines. A standard written procedure could be useful in clinical practice despite the lack of experienced difference between centers with and without procedures.
Serum and fecal profiles of aromatic microbial metabolites reflect gut microbiota disruption in critically ill patients: a prospective observational pilot study
Authors: Chernevskaya Ekaterina , Beloborodova Natalia , Klimenko Natalia , Pautova Alisa , Shilkin Dmitrii , Gusarov Vitaliy , Tyakht Alexander
Published: June 2020

Background

High serum levels of certain aromatic microbial metabolites (AMM) are associated with severity and mortality in critically ill patients. Omics-based studies suggest gut dysbiosis and reduced microbiome diversity in critical conditions. However, the landscape of gut microbial metabolites is still to be outlined, not to mention the interplay correlation between the metabolome and gut microbiome in critically ill patients. The aim of this study was to analyze the association between serum and fecal levels of AMM and compare them with the composition of gut microbiota in critically ill patients in the acute and chronic stages.

Methods

In this prospective observational pilot study, we analyzed the temporal dynamics of the gut microbiome and the AMM spectrum across two distinct subgroups—acute critical ill (ACI) patients with nosocomial pneumonia and chronically critically ill (CCI) patients (9 subjects each group)—as well as performed comparison with 23 healthy volunteers. The AMM levels for each patient were measured using GC-MS in simultaneously taken serum and fecal samples (SFS). These parameters were compared with 16S rRNA fecal microbiome profiles.

Results

The observed proportions of bacterial taxa suggest a significant gut dysbiosis in the ACI and the CCI patients. Stronger imbalance in microbiome composition and dynamics observed in the ACI patients compared to the CCI ones resonates with a higher severity in the former group. The total levels of AMM in serum samples were higher for the ACI patients than for the CCI patients (3.7 (1.4–6.3) and 1.1 (1.0–1.6) μM, respectively; p = 0.0003). The qualitative composition of the SFS was also altered. We discovered significant associations between gut microbial taxa levels and metabolite concentrations in blood serum as well as in feces in each of the ACI and the CCI patients.

Conclusions

Aromatic microbial metabolite profiles in the gut and the serum are interlinked and reflect a disruption of the gut microbial community in critically ill patients.
Study protocol for prognosis and treatment strategy of peripheral persistent avascular retina after intravitreal anti-VEGF therapy in retinopathy of prematurity
Authors: Yu Ying , Wang Jianxun , Chen Feng , Chen Wensi , Jiang Nan , Xiang Daoman
Published: June 2020

Background

Prophylactic peripheral photocoagulation has been proposed to be applied to persistent, peripheral, avascular retina for retinopathy of prematurity (ROP) patients who have received an intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, there are doubts regarding the necessity of this prophylactic action regardless of fundus fluorescein angiography (FFA) results. The adverse prognosis for persistent avascular retina after anti-VEGF therapy in ROP patients is not well understood. The relationship between vascular leakage and an adverse prognosis is also unknown. Therefore, it would be of value to study the above issues to shape the treatment strategy of persistent avascular retina after intravitreal anti-VEGF therapy in ROP patients.

Methods/design

This is a prospective study of ROP patients with persistent avascular retina who have received anti-VEGF intravitreal therapy and have never received laser therapy. All the eyes being studied will be followed up and examined by FFA after anti-VEGF treatment and categorized into two groups, a leakage group and a non-leakage group according to the extent of vascular leakage from FFA results. The eyes being studied in the leakage group will be further randomized into two groups, a laser group and a non-laser group. A cohort study (observational) will be conducted on the non-leakage group and the non-laser group (with leakage) to investigate the incidence of an adverse prognosis for reactivation, retinal tear and retinal detachment; as well as to investigate the relationship between vascular leakage from FFA results and the abovementioned pathological changes. A randomized controlled study (experimental) will be conducted on the leakage group to compare the prognosis between the laser group and the non-laser group.

Discussion

The present study aims to investigate the occurrence rates of an adverse prognosis including reactivation, retinal tear and retinal detachment after anti-VEGF therapy in ROP patients with persistent avascular retina; to assess the relationship between vascular leakage from FFA results and the abovementioned pathological changes; to compare the prognosis of persistent avascular retina with or without prophylactic peripheral photocoagulation in these patients; to shape the treatment strategy and provide evidence for the indications of prophylactic photocoagulation.

Trial registration

Chinese Clinical Trial Registry (ChiCTR), ID: ChiCTR-ROC-17013253. Registered on 5 November 2017. http://www.chictr.org.cn/showproj.aspx?proj=22703
Quality, scope and reporting standards of randomised controlled trials in Irish Health Research: an observational study
Authors: Clyne Barbara , Boland Fiona , Murphy Norah , Murphy Edel , Moriarty Frank , Barry Alan , Wallace Emma , Devine Tatyana , Smith Susan M. , Devane Declan , Murphy Andrew , Fahey Tom
Published: June 2020

Background

Despite efforts to improve the accuracy and transparency of the design, conduct, and reporting of randomised controlled trials (RCTs), deficiencies remain. Such deficiencies contribute to significant, avoidable waste of health research investment and impede reproducibility. This study aimed to synthesise and critically analyse changes over time in the conduct and reporting of internationally published evidence on patient and/or population health-oriented RCTs conducted in one country.

Methods

This observational study drew on systematic review methods. We searched six databases for published RCTs (database inception to December 2018) where ≥ 80% of participants were recruited in the Republic of Ireland. RCTs of interventions targeted at patients, providers and/or policy makers intended to improve health, healthcare or health research were included. For each study, screening, data extraction and methodological quality appraisal were conducted by one member of the author team.

Results

From 17,560 titles and abstracts, 752 unique RCTs were published in 745 papers between 1968 and 2018, with a steady year-on-year increase since 1968. The number of participants was in the range of 2–8628. The majority were parallel design (86%) and classified as treatment evaluation. Of the 418 RCTs published since the introduction of mandatory clinical trial registration by the International Committee of Medical Journal Editors in 2005, 32% (n = 134) provided a trial registration number. This increased to 47% when taking studies published between 2013 and 2018 (n = 232). Since the 1996 publication of the CONSORT statement, 16% of included RCTs made specific reference to a standardised reporting guideline and this increased to 31% for more recent studies published between 2013 and 2018. Overall, 7% (n = 53) of studies referred to a published study protocol, increasing to 20% for studies published between 2013 and 2018.

Conclusion

Evidence from this single-country study of RCTs published in the international literature suggests that both the number overall, the number registered and the number referencing reporting guidelines have increased steadily over time. Despite widespread endorsement of reporting standards, reporting of RCTs remains suboptimal in domains such as compliance with the CONSORT statement and prospective trial registration. Researchers, funders and journal editors, nationally and internationally, should continue to focus on improving reporting and examining avoidable waste of health research investment.
Methods for assessment of patient adherence to removable orthoses used after surgery or trauma to the appendicular skeleton: a systematic review
Authors: Davies Gareth , Yeomans Daniel , Tolkien Zoe , Kreis Irene A. , Potter Shelley , Gardiner Matthew D. , Jain Abhilash , Henderson James , Blazeby Jane M.
Published: June 2020

Background

Patient adherence to treatment is a key determinant of outcome for healthcare interventions. Whilst non-adherence has been well evidenced in settings such as drug therapy, information regarding patient adherence to orthoses, particularly in the acute setting, is lacking. The aim of this systematic review was to identify, summarise, and critically appraise reported methods for assessing adherence to removable orthoses in adults following acute injury or surgery.

Methods

Comprehensive searches of the Ovid versions of MEDLINE, Embase, AMED, CINAHL, Central, the Cochrane Database of Systematic Reviews, and SPORTDiscus identified complete papers published in English between 1990 and September 2018 reporting measurement of adherence to orthoses in adults following surgery or trauma to the appendicular skeleton. Only primary studies with reference to adherence in the title/abstract were included to maintain the focus of the review. Data extraction included study design, sample size, study population, orthosis studied, and instructions for use. Details of methods for assessing adherence were extracted, including instrument/method used, frequency of completion, number of items (if applicable), and score (if any) used to evaluate adherence overall. Validity and reliability of identified methods were assessed together with any conclusions drawn between adherence and outcomes in the study.

Results

Seventeen papers (5 randomised trials, 10 cohort studies, and 2 case series) were included covering upper (n = 13) and lower (n = 4) limb conditions. A variety of methods for assessing adherence were identified, including questionnaires (n = 10) with single (n = 3) or multiple items (n = 7), home diaries (n = 4), and discussions with the patient (n = 3). There was no consistency in the target behaviour assessed or in the timing or frequency of assessment or the scoring systems used. None of the measures was validated for use in the target population.

Conclusions

Measurement and reporting of adherence to orthosis use is currently inconsistent. Further research is required to develop a measurement tool that provides a rigorous and reproducible assessment of adherence in this acute population.

Trial registration

PROSPERO: CRD42016048462. Registered on 17/10/2016.
Insecticide resistance, fitness and susceptibility to Zika infection of an interbred Aedes aegypti population from Rio de Janeiro, Brazil
Authors: dos Santos Carlucio Rocha , de Melo Rodovalho Cynara , Jablonka Willy , Martins Ademir Jesus , Lima José Bento Pereira , dos Santos Dias Luciana , da Silva Neto Mário Alberto Cardoso , Atella Georgia Correa
Published: June 2020

Background

Aedes aegypti is a vector of high relevance, since it transmits several arboviruses, including dengue, chikungunya and Zika. Studies on vector biology are usually conducted with laboratory strains presenting a divergent genetic composition from field populations. This may impair vector control policies that were based on laboratory observations employing only long maintained laboratory strains. In the present study we characterized a laboratory strain interbreed with Ae. aegypti collected from five different localities in Rio de Janeiro (Aedes Rio), for insecticide resistance (IR), IR mechanisms, fitness and Zika virus infection.

Methods

We compared the recently established Aedes Rio with the laboratory reference strain Rockefeller. Insecticide resistance (deltamethrin, malathion and temephos), activity of metabolic resistance enzymes and kdr mutation frequency were determined. Some life table parameters (longevity, blood-feeding, number and egg viability) and Zika virus susceptibility was also determined.

Results

Aedes Rio showed resistance to deltamethrin (resistance ratio, RR50 = 32.6) and temephos (RR50 = 7.0) and elevated activity of glutathione S-transferase (GST) and esterases (α-EST and pNPA-EST), but not acetylcholinesterase (AChE). In total, 92.1% of males genotyped for kdr presented a “resistant” genotype. Weekly blood-fed females from both strains, presented reduced mortality compared to sucrose-fed mosquitoes; however, Aedes Rio blood-fed females did not live as long (mean lifespan: Rockefeller = 70 ± 3.07; Aedes Rio = 53.5 ± 2.16 days). There were no differences between strains in relation to blood-feeding and number of eggs, but Aedes Rio eggs presented reduced viability (mean hatch: Rockefeller = 77.79 ± 1.4%; Aedes Rio = 58.57 ± 1.77%). Zika virus infection (plaque-forming unit, PFU) was similar in both strains (mean PFU ± SE: Aedes Rio: 4.53 × 104 ± 1.14 × 104 PFU; Rockefeller: 2.02 × 104 ± 0.71 × 104 PFU).

Conclusion

Selected conditions in the field, such as IR mechanisms, may result in pleiotropic effects that interfere in general physiology of the insect. Therefore, it is important to well characterize field populations to be tested in parallel with laboratory reference strains. This practice would improve the significance of laboratory tests for vector control methods.
Cerebral microvascular and microstructural integrity is regionally altered in patients with systemic lupus erythematosus
Authors: DiFrancesco Mark W. , Lee Gregory , Altaye Mekibib , Beebe Dean W. , Meyers-Eaton Jamie , Brunner Hermine I.
Published: June 2020

Background

To measure regional brain microvascular and microstructural changes in childhood-onset SLE (cSLE) using diffusion-weighted imaging (DWI) at multiple b values and investigate relationships of those measures with neurocognitive function and disease activity.

Methods

In this cross-sectional, case-control study, vascular volume fraction, effective diffusion, parenchymal diffusion, and blood flow parameters were regionally compared in cSLE patients and matched healthy controls. These markers of microvascular and microstructural integrity were derived by diffusion-weighted brain MRI and intravoxel incoherent motion (IVIM) modeling. Formal neurocognitive testing was completed focused on the domains of attention, visuoconstructional ability, working memory, and psychomotor speed. Test scores and measures of disease severity were regressed against regional microvascular integrity parameters among cSLE patients.

Results

Formal cognitive testing confirmed normal cognitive ability among all cSLE patients included in the analysis (n = 11). Nevertheless, reduction in blood volume fraction coincided with increased effective diffusion and flow parameters in cSLE patients vs. controls in posterior brain regions including the cuneus and precuneus. Regional microvascular measures correlated (|r| = 0.54–0.66) with neuropsychiatric scores and disease activity among cSLE patients.

Conclusions

There is imaging evidence, using IVIM, of degraded microvascular integrity in cSLE patients with normal cognitive ability. The observed regional changes correspond with posterior vascular border zones. These outcomes appear consistent with regional gray matter volume loss previously observed in cSLE patients with overt neurocognitive deficits, supporting the notion that adverse vascular changes precede loss of cognitive ability in cSLE. Longitudinal studies are needed to confirm the findings of this initial study.
Differential long-term retention of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis by age group from the FIRST registry
Authors: Kawabe Akio , Nakano Kazuhisa , Kubo Satoshi , Asakawa Takeshi , Tanaka Yoshiya
Published: June 2020

Background

The effectiveness and safety of biological disease-modifying antirheumatic drugs (bDMARDs) by age group (< 65, 65–74, and ≥ 75 years) are uncertain. We examined retention rates reflecting the effectiveness and safety of bDMARDs in actual clinical practice for clarifying optimal therapeutic strategies for rheumatoid arthritis (RA) by age groups.

Methods

Data of patients who were treated with tumor necrosis factor inhibitors (TNFi), abatacept (ABA), and tocilizumab (TCZ) between February 2011 and April 2017 were collected from a prospective observational registry of RA patients. A total of 1362 patients were enrolled, of which 695 were aged < 65 years, 402 were aged 65–74 years, and 265 were aged ≥ 75 years. Primary outcome was the drug retention rate in adjusted data using inverse probability of treatment weighting based on generalized propensity scores.

Results

In patients aged < 65 years, 3-year retention rates of TNFi, ABA, and TCZ were 43%, 47%, and 69%, respectively (ABA versus TCZ, p = 0.017; TNFi versus TCZ, p = 0.002). In patients aged 65–74 years, 3-year retention rates of TNFi, ABA, and TCZ were 44%, 53%, and 60%, respectively (TCZ versus TNFi, p = 0.034). In patients aged ≥ 75 years, 3-year retention rates for TNFi, ABA, and TCZ were 38%, 63%, and 58%, respectively (ABA versus TNFi, p = 0.017).

Conclusions

We found that the effectiveness and safety of TCZ were maximal in patients aged < 75 years and that patients aged ≥ 75 years might be suitable candidates for TCZ and ABA therapy. The use of therapeutic strategies appropriate to each age group might improve the outcomes of bDMARD therapy for RA.
Association of [1H]-MRS quantified liver fat content with glucose metabolism status
Authors: Wang Yun-Sheng , Ye Jun , Cao Yong-Hong , Zhang Rong , Han Xiao-Fang , Zou Ling-Ling , Kuang Lei , Zhang Ji , Lian Hu , Xia Jin-Xiang , Zhang Qiu , Dai Wu
Published: June 2020

Background

Previous literatures have implied that the liver fat deposition plays a crucial role in the development and progression of insulin resistance. In the present study, we aimed to investigate the association of liver fat content (LFC) with glucose metabolism status in the population of newly diagnosed type 2 diabetes mellitus (nT2DM), prediabetes mellitus (PDM) and normal controls (NC), and assessing if the LFC could as an indicator for the prediction of T2DM.

Methods

A total of 242 subjects (including 141 nT2DM patients, 48 PDM subjects and 53 NC) were enrolled. The levels of LFC were quantified by using the proton magnetic resonance spectroscopy ([1H]-MRS) technique. Clinical and laboratory parameters of study subjects were collected by medical records and biochemical detection. One-way ANOVA or nonparametric test (Kruskal–Wallis) was applied for intergroup comparisons; intergroup comparison was performed in using of Bonferroni multiple-significance-test correction.

Results

There were significantly increased LFC levels in nT2DM (14.72% ± 6.37%) than in PDM (9.62% ± 4.41%) and that of NC groups (5.11% ± 3.66%) (all p < 0.001). The prevalence of nonalcoholic fatty liver disease (NAFLD) was also found to be increased in nT2DM (91.48%) than in PDM (85.41%) and that of NC (32.07%) groups. Correlation analysis revealed that the increase of LFC positively associated with fast plasma glucose (FPG), 2 h plasma glucose (PG), Delta G30 and homeostatic model assessment of insulin resistance (HOMA-IR), negatively associated with Delta Ins30, Delta C30, Ins30/G30 AUC, CP30/G30 AUC, Ins AUC/G AUC, CP AUC/G AUC, homeostatic model assessment for β-cell function index (HOMA-β) and matsuda insulin sensitivity index (Matsuda ISI). Multilinear regression analysis showed that LFC, body mass index (BMI) and diastolic blood pressure (DBP) contributed for the prediction of HOMA-IR, and total cholesterol (TC), age, waist circumference (WC) and low-density lipoprotein cholesterol (LDL-C) were the significant contributors for HOMA-β.

Conclusions

Our study revealed an increased LFC level and prevalence of NAFLD in nT2DM than in PDM and that of NC groups, the increase of LFC was closely associated with insulin resistance and impaired glucose metabolism status, may be regarded as potential indicator contributing to the development and progression of T2DM.
Mesenchymal stem cell-derived exosomes improve motor function and attenuate neuropathology in a mouse model of Machado-Joseph disease
Authors: You Hua-Jing , Fang Shu-Bin , Wu Teng-Teng , Zhang Hongyu , Feng Yu-Kun , Li Xue-Jiao , Yang Hui-Hua , Li Ge , Li Xun-Hua , Wu Chao , Fu Qing-Ling , Pei Zhong
Published: June 2020

Background

Machado-Joseph disease is the most common autosomal dominant hereditary ataxia worldwide without effective treatment. Mesenchymal stem cells (MSCs) could slow the disease progression, but side effects limited their clinical application. Besides, MSC-derived exosomes exerted similar efficacy and have many advantages over MSCs. The aim of this study was to examine the efficacy of MSC-derived exosomes in YACMJD84.2 mice.

Methods

Rotarod performance was evaluated every 2 weeks after a presymptomatic administration of intravenous MSC-derived exosomes twice in YACMJD84.2 mice. Loss of Purkinje cells, relative expression level of Bcl-2/Bax, cerebellar myelin loss, and neuroinflammation were assessed 8 weeks following treatment.

Results

MSC-derived exosomes were isolated and purified through anion exchange chromatography. Better coordination in rotarod performance was maintained for 6 weeks in YACMJD84.2 mice with exosomal treatment, compared with those without exosomal treatment. Neuropathological changes including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation were also attenuated 8 weeks after exosomal treatment. The higher relative ratio of Bcl-2/Bax was consistent with the attenuation of loss of Purkinje cells.

Conclusions

MSC-derived exosomes could promote rotarod performance and attenuate neuropathology, including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation. Therefore, MSC-derived exosomes have a great potential in the treatment of Machado-Joseph disease.
Few-shot relation classification by context attention-based prototypical networks with BERT
Authors: Hui Bei , Liu Liang , Chen Jia , Zhou Xue , Nian Yuhui
Published: June 2020

Human-computer interaction under the cloud computing platform is very important, but the semantic gap will limit the performance of interaction. It is necessary to understand the semantic information in various scenarios. Relation classification (RC) is an import method to implement the description of semantic formalization. It aims at classifying a relation between two specified entities in a sentence. Existing RC models typically rely on supervised learning and distant supervision. Supervised learning requires large-scale supervised training datasets, which are not readily available. Distant supervision introduces noise, and many long-tail relations still suffer from data sparsity. Few-shot learning, which is widely used in image classification, is an effective method for overcoming data sparsity. In this paper, we apply few-shot learning to a relation classification task. However, not all instances contribute equally to the relation prototype in a text-based few-shot learning scenario, which can cause the prototype deviation problem. To address this problem, we propose context attention-based prototypical networks. We design context attention to highlight the crucial instances in the support set to generate a satisfactory prototype. Besides, we also explore the application of a recently popular pre-trained language model to few-shot relation classification tasks. The experimental results demonstrate that our model outperforms the state-of-the-art models and converges faster.
Using improved support vector regression to predict the transmitted energy consumption data by distributed wireless sensor network
Authors: Guo Ni , Gui Weifeng , Chen Wei , Tian Xin , Qiu Weiguo , Tian Zijian , Zhang Xiangyang
Published: June 2020

Massive energy consumption data of buildings was generated with the development of information technology, and the real-time energy consumption data was transmitted to energy consumption monitoring system by the distributed wireless sensor network (WSN). Accurately predicting the energy consumption is of importance for energy manager to make advisable decision and achieve the energy conservation. In recent years, considerable attention has been gained on predicting energy use of buildings in China. More and more predictive models appeared in recent years, but it is still a hard work to construct an accurate model to predict the energy consumption due to the complexity of the influencing factors. In this paper, 40 weather factors were considered into the research as input variables, and the electricity of supermarket which was acquired by the energy monitoring system was taken as the target variable. With the aim to seek the optimal subset, three feature selection (FS) algorithms were involved in the study, respectively: stepwise, least angle regression (Lars), and Boruta algorithms. In addition, three machine learning methods that include random forest (RF) regression, gradient boosting regression (GBR), and support vector regression (SVR) algorithms were utilized in this paper and combined with three feature selection (FS) algorithms, totally are nine hybrid models aimed to explore an improved model to get a higher prediction performance. The results indicate that the FS algorithm Boruta has relatively better performance because it could work well both on RF and SVR algorithms, the machine learning method SVR could get higher accuracy on small dataset compared with the RF and GBR algorithms, and the hybrid model called SVR-Boruta was chosen to be the proposed model in this paper. What is more, four evaluate indicators were selected to verify the model performance respectively are the mean absolute error (MAE), the mean squared error(MSE), the root mean squared error (RMSE), and the R-squared (R2), and the experiment results further verified the superiority of the recommended methodology.
The femoral trochlear anterior line is a better alternative intra-operative reference compared to femoral anterior tangent line for femoral rotation in both genders in total knee arthroplasty
Authors: Nam Ji-Hoon , Koh Yong-Gon , Kim Paul Shinil , Kang Kiwon , Kang Kyoung-Tak
Published: June 2020

Purpose

To determine the most reliable reference axis for the femoral component rotation in TKA patients by comparing the trochlear anterior line (TAL) and the femoral anterior tangent line (FAT). To evaluate the variability of each anatomic parameter in a Korean population.

Methods

Magnetic resonance images (MRIs) were taken for 500 patients (400 females and 100 males) with knee joint osteoarthritis who had Kellgren and Lawrence grade 3 and 4 prior to TKA in our institution between February 2016 and September 2017. It was investigated that whether significant differences in variance and gender exist for TAL and FAT.

Results

TAL and the FAT were internally rotated by 5.1° ± 3.1° and 6.8° ± 6.1°, respectively, about the Transepicondylar axis (TEA). Although no gender-related differences were found for the TAL, they were found for the FAT. The variance of the TAL with respect to the TEA was significantly smaller compared with that for the FAT and thus exhibited a more consistent distribution. In addition, such a trend was found for both genders.

Conclusions

The results show that the TAL is a favorable index for appropriate rotational alignment of the femoral component in TKA.
Understanding gold toxicity in aerobically-grown Escherichia coli
Authors: Muñoz-Villagrán C. , Contreras F. , Cornejo F. , Figueroa M. , Valenzuela-Bezanilla D. , Luraschi R. , Reinoso C. , Rivas-Pardo J. , Vásquez C. , Castro M. , Arenas F.
Published: June 2020

Background

There is an emerging field to put into practice new strategies for developing molecules with antimicrobial properties. In this line, several metals and metalloids are currently being used for these purposes, although their cellular effect(s) or target(s) in a particular organism are still unknown. Here we aimed to investigate and analyze Au3+ toxicity through a combination of biochemical and molecular approaches.

Results

We found that Au3+ triggers a major oxidative unbalance in Escherichia coli, characterized by decreased intracellular thiol levels, increased superoxide concentration, as well as by an augmented production of the antioxidant enzymes superoxide dismutase and catalase. Because ROS production is, in some cases, associated with metal reduction and the concomitant generation of gold-containing nanostructures (AuNS), this possibility was evaluated in vivo and in vitro.

Conclusions

Au3+ is toxic for E. coli because it triggers an unbalance of the bacterium’s oxidative status. This was demonstrated by using oxidative stress dyes and antioxidant chemicals as well as gene reporters, RSH concentrations and AuNS generation.
Genome wide meta-analysis of cDNA datasets reveals new target gene signatures of colorectal cancer based on systems biology approach
Authors: Ilyas Umair , Zaman Shahiq uz , Altaf Reem , Nadeem Humaira , Muhammad Syed Aun
Published: June 2020

Background

Colorectal cancer is known to be the most common type of cancer worldwide with high disease-related mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders.

Results

This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten publicly available microarray datasets were analyzed and seven potential biomarkers were identified from the list of differentially expressed genes having apvalue < 0.05. The expression profiling and the functional enrichment analysis revealed the role of these genes in cell communication, signal transduction, and immune response. The protein–protein interaction showed the functional association of the source genes (CTNNB1, NNMT, PTCH1, CALD1, CXCL14, CXCL8, and TNFAIP3) with the target proteins, such as AXIN, MAPK, IL6, STAT, APC, GSK3B, and SHH.

Conclusion

The integrated pathway analysis indicated the role of these genes in important physiological responses, such as cell cycle regulation, WNT, hedgehog, MAPK, and calcium signaling pathways during colorectal cancer. These pathways are involved in cell proliferation, chemotaxis, cellular growth, differentiation, tissue patterning, and cytokine production. The study shows the regulatory role of these genes in colorectal cancer and the pathways that can be effected after the dysregulation of these genes.
Influence of age and schooling in written discourse of healthy adults
Authors: Zanichelli Larissa , Fonseca Rochele Paz , Ortiz Karin Zazo
Published: June 2020

Background

Discourse production is a very complex cognitive task that requires the integration of several linguistic cognitive skills. Socio-demographic factors such as schooling can impact on cognitive tasks. This study investigated the impact of age and schooling in some macrolinguistic and microlinguistic aspects in the written discourse of healthy adults.

Methods

Individuals with no previous history of language, hearing, neurological, or psychiatric disorders were asked to write a story based on a figure that showed a “bank robbery.” A total of 463 graphic narrative were analyzed. The schooling was stratified into the following three bands: 5 to 8 years, 9 to 11 years and 12 or more, and the age ranged from 19 to 75 years.

Results

Individuals with high schooling (12 years or more) produced discourses with more information units, more coherent, and cohesive. The oldest group (60 to 75 years) needed more time to finish the written production.

Conclusion

The schooling influences some micro and macrolinguistic aspects in the written discourse production. A higher educational level provided a greater number of words as well as a higher number of information units, and the discourses produced are more coherent and cohesive. The age influenced only the time of discourse production.
Prevention of Colon Cancer Recurrence From Minimal Residual Disease: Computer Optimized Dose Schedules of Intermittent Apoptotic Adjuvant Therapy
Authors: Cockrell Chase , Teague Joseph , Axelrod David E.
Published: June 2020

PURPOSE

Adjuvant chemotherapy is used after surgery for stages II and III colorectal cancer to reduce recurrence. Nevertheless, recurrence may occur years later with the emergence of initially undetected minimal residual disease (MRD). Attempts to reduce recurrence by increasing the dose intensity and increasing the time of adjuvant therapy have been limited by the adverse effects of the recommended cytotoxic agents. The goals of this study were to suggest an alternative to the recommended cytotoxic agents and to determine optimal adjuvant therapy dose schedules that would reduce the percentage of recurrence at 5 years while retaining colon crypt function.

METHODS

A total of 84,400 dose schedules with different duration, interval between doses, and intensity of treatment were simulated with a high-performance computer. Simulated treatments used the drug sulindac, which had previously been used in primary prevention. With appropriate dose schedules, it can induce apoptosis at the crypt lumen surface while retaining crypt function. We used a computer model of cell dynamics in colon crypts that had been calibrated with measurements of human biopsy specimens. Proliferating mutant cells were assumed to emerge from MRD within crypts. Simulated outcomes included the recurrence percentage at 5 years and the retention of crypt function.

RESULTS

Optimal dose schedules were determined for adjuvant treatment of MRD that reduced the percentage of recurrence at 5 years of stages I, II, and III colon cancer to zero.

CONCLUSION

A new adjuvant therapy for colon cancer based upon optimum dose schedules of intermittent apoptotic treatment may prevent the recurrence of colon cancer from MRD and avoid the adverse effects of cytotoxic treatments.
Disparities in Cancer-Specific Survival Between Māori and Non-Māori New Zealanders, 2007-2016
Authors: Gurney Jason , Stanley James , McLeod Melissa , Koea Jonathan , Jackson Chris , Sarfati Diana
Published: June 2020

PURPOSE

While cancer survival is improving across most developed nations, those improvements are not shared equally within their population. Using high-quality national data, we have reviewed the extent to which cancer survival inequities are persisting for indigenous Māori compared with non-Māori New Zealanders and the extent to which these disparities are driven by deprivation, comorbidity, and stage of disease.

METHODS

Incident cases of cancer (2007-2016) were extracted from the New Zealand Cancer Registry and linked to mortality and hospitalization data. Descriptive, Kaplan-Meier, and Cox regression methods were used to compare survival outcomes between Māori and non-Māori.

RESULTS

Māori continue to have poorer survival than non-Māori for 23 of the 24 most common causes of Māori cancer death, with the extent of this disparity ranging from 12% to 156%. The magnitude of these disparities varies according to deprivation, comorbidity, and stage. Of note, there was a tendency for survival disparities to be largest among those with no comorbidity.

CONCLUSION

Māori continue to experience substantial cancer survival inequities. These observations are in keeping with reports from previous decades, which suggest that these disparities persist despite heightened attention. Reduction of the cancer burden on Māori and achievement of equitable survival outcomes require us to prevent cancer for Māori where we can, diagnose Māori patients early when we cannot, and once diagnosed, deliver equitable care to Māori patients at each step along the treatment path.
Overview of Breast Cancer and Implications of Overtreatment of Early-Stage Breast Cancer: An Indian Perspective
Authors: Bhattacharyya Gouri Shankar , Doval Dinesh C. , Desai Chirag J. , Chaturvedi Harit , Sharma Sanjay , Somashekhar S.P.
Published: June 2020

The prevalence and mortality of breast cancer is increasing in Asian countries, including India. With advances in medical technology leading to better detection and characterization of the disease, it has been possible to classify breast cancer into various subtypes using markers, which helps predict the risk of distant recurrence, response to therapy, and prognosis using a combination of molecular and clinical parameters. Breast cancer and its therapy, mainly surgery, systemic therapy (anticancer chemotherapy, hormonal therapy, targeted therapy, and immunotherapy), and radiation therapy, are associated with significant adverse influences on physical and mental health, quality of life, and the economic status of the patient and her family. The fear of recurrence and its devastating effects often leads to overtreatment, with a toxic cost to the patient financially and physically in cases in which this is not required. This article discusses some aspects of a breast cancer diagnosis and its impact on the various facets of the life of the patient and her family. It further elucidates the role of prognostic factors, the currently available biomarkers and prognostic signatures, and the importance of ethnically validating biomarkers and prognostic signatures.