bluuebunny/crossref_metadata_2025 huggingface dataset:
A commentary on the carbon footprint of milk formula: harms to planetary health and policy implications
Authors: Smith Julie P.
Published: November 2019

Background

Infant formula requires mass production by the dairy industry, with plastic and other waste and degradation of land and waterways. Millions of babies, two thirds globally, now have milk formula, with breastfeeding in dramatic decline in Asia.

Economic cost externalities and commercial incentives

Economic thinking clarifies that markets are not perfect - price incentives can lead to excessive and inefficient environmental damage. Market prices paid to produce or use a commodity may not reflect its true resource costs. The ongoing global transition in infant and young child feeding (IYCF) toward milk formula use makes urgent the investigation of its environmental costs, including greenhouse gas (GHG) implications. Socially vulnerable populations are also particularly exposed to climate change risks, but have the least voice and agency.

The important role of public health advocacy

Few question the scale of the baby food industry, especially in major food exporting countries. Breastfeeding advocacy non-government organisations have led the investigations, and exposed the inequitable vulnerabilities. A ground-breaking study in 2016 showed emissions from just six Asia Pacific countries were equivalent to 6 billion miles of car travel. Each kilogram (kg) of milk formula generated 4 kg of (carbon dioxide (CO2) equivalent) greenhouse gas during production. Much of this was from unnecessary toddler formula. Recent research reveals that if looking at the full product lifecycle, including consumer use, GHG emissions per kg are actually three times higher than these pioneering estimates. Environment and health harms combined with economic evidence highlight the place for a strong public health response on this issue.

Conclusion

Formula feeding is a maladaptive practice in the face of contemporary global environmental and population health challenges. Breastfeeding protection, support and promotion helps to safeguard planetary and human health by minimising environmental harm. It is a beneficial response to concerns about disease burdens and climate change. Breastfeeding populations are more resilient in emergencies. Effective and cost-effective policies and interventions exist for increasing breastfeeding and reducing unnecessary use of formula. Implementing such measures presents a rare opportunity to both reduce the greenhouse gas problem and improve human nutrition, health, and health equity.
Free vascularized iliac bone flap based on deep circumflex iliac vessels graft for the treatment of osteonecrosis of femoral head
Authors: Lei Pengfei , Du Wei , Liu Hao , Wu Panfeng , Zhou Zhengbing , Yu Fang , Qing Liming , Pan Ding , Liu Rui , Zeng Lei , Cao Zheming , Ou Qifeng , Tang Juyu
Published: November 2019

Background

To investigate the feasibility and clinical efficacy of free vascularized iliac bone flap based on deep iliac circumflex vessels graft for the treatment of osteonecrosis of femoral head (ONFH) in young adults.

Methods

Eighteen patients (19 hips) undergoing ONFH were included from January 2016 to May 2017. After the debridement of the necrotic bones, the contralateral vascularized iliac bone flap was designed and harvested before grafting, in which the deep circumflex iliac vessels and the transverse branch (or ascending branch) of the lateral circumflex femoral artery and their accompanying veins were anastomosed. X-ray was obtained at 1, 3, 6, 9, and 12 months respectively for evaluation of the bone flap healing. Hip function was evaluated with Harris hip score at 18 months postoperatively.

Results

None of the patients is lost to follow-up. All the hips healed well except for four complications: one patient developed superficial wound infection, one patient had subcutaneous hematoma, and two patients developed anterolateral femoral cutaneous nerve injury. X-ray films at 12 months showed improvement in 13 hips (68.4%), five hips (26.3%) were unchanged, and one femoral head collapse with conversion to total hip arthroplasty (THA) at 14 months postoperatively (5.3%). Postoperative mean Harris hip scores were significantly improved compared to the preoperative results (P < 0.05).

Conclusion

Free vascularized iliac bone flap based on deep circumflex iliac vessels graft is an acceptable treatment option for young adult ONFH in mid-late stage with low conversion to THA rate at short-term follow-up.
Adult cognitive outcomes in phenylketonuria: explaining causes of variability beyond average Phe levels
Authors: Romani Cristina , Manti Filippo , Nardecchia Francesca , Valentini Federica , Fallarino Nicoletta , Carducci Claudia , De Leo Sabrina , MacDonald Anita , Palermo Liana , Leuzzi Vincenzo
Published: November 2019

Objective

The objective was to deepen the understanding of the causes of individual variability in phenylketonuria (PKU) by investigating which metabolic variables are most important for predicting cognitive outcomes (Phe average vs Phe variation) and by assessing the risk of cognitive impairment associated with adopting a more relaxed approach to the diet than is currently recommended.

Method

We analysed associations between metabolic and cognitive measures in a mixed sample of English and Italian early-treated adults with PKU (N = 56). Metabolic measures were collected through childhood, adolescence and adulthood; cognitive measures were collected in adulthood. Metabolic measures included average Phe levels (average of median values for each year in a given period) and average Phe variations (average yearly standard deviations). Cognition was measured with IQ and a battery of cognitive tasks.

Results

Phe variation was as important, if not more important, than Phe average in predicting adult outcomes and contributed independently. Phe variation was particularly detrimental in childhood. Together, childhood Phe variation and adult Phe average predicted around 40% of the variation in cognitive scores. Poor cognitive scores (> 1 SD from controls) occurred almost exclusively in individuals with poor metabolic control and the risk of poor scores was about 30% higher in individuals with Phe values exceeding recommended thresholds.

Conclusions

Our results provide support for current European guidelines (average Phe value = < 360 μmol/l in childhood; = < 600 μmo/l from 12 years onwards), but they suggest an additional recommendation to maintain stable levels (possibly Phe SD = < 180 μmol/l throughout life).

Public significance statements

We investigated the relationship between how well people with phenylketonuria control blood Phe throughout their life and their ability to carry out cognitive tasks in adulthood. We found that avoiding blood Phe peaks was as important if not more important that maintaining average low Phe levels. This was particularly essential in childhood. We also found that blood Phe levels above recommended European guidelines was associated with around 30% increase in the risk of poor cognitive outcomes.
Olaparib in the therapy of advanced ovarian cancer: first real world experiences in safety and efficacy from China
Authors: Ni Jing , Cheng Xianzhong , Zhou Rui , Xu Xia , Guo Wenwen , Chen Xiaoxiang
Published: November 2019

Purpose

Poly (ADP-ribose) polymerase (PARP) inhibitor, is a milestone in treatment of ovarian cancer. However, there is no real world study from China regarding the clinical outcome of the taking PARP inhibitor (PARPi), Olaparib(Lynparza™). The goal of this research is to evaluate the side effects and short-term efficacy in advanced ovarian cancer patients who administered Olaparib.

Methods

Patients with ovarian cancer, fallopian tube cancer and peritoneal cancer that treated with Olaparib in The Affiliated Cancer Hospital of Nanjing Medical University between September 2018 and June 2019 were recruited. The drug associated Adverse Events (AEs) were collected and short-term efficacy were analyzed by modified Response Evaluation Criteria in Solid Tumors (mRECIST) .

Results

Of all 28 enrolled patients, 92.9% were ovarian cancer, 7.1% were fallopian tube cancer, and 39.3% cases harbored germline BRCA-mutation. There were 6(21.4%) patients received Olaparib after multi-line chemotherapy, and 10 patients (35.7%) as second-line maintenance therapy and 2 patients (7.1%) as first-line maintenance therapy. There were still other 10 cases (35.7%) received Olaparib as exploratory therapy. Abdominal distention, decreased blood pressure, increased body hair, thirsty, burning sensation of stomach and leg swelling were newly reported AEs. Serious Adverse Events(SAEs) were usually managed by dose interruption or dose reduction, rather than discontinuation. 3 patients discontinued treatment, 8 patients received reduced dose of Olaparib, and 4 patients stopped therapy after the alleviation of AEs. Of all 28 enrolled cases, in monotherapy group, 1 of 6 patients achieved stable disease(SD) and also 2 patients achieved stable disease(SD) combined with anti-angiogenic drugs when disease progressed. 2 patients achieved complete remission(CR) and 3 patients were stable with exploratory therapy.

Conclusions

The AEs of Olaparib were all manageable. For the first time, we also identified several AEs such as abdominal distention, decreased blood pressure, increased body hair, thirsty, burning sensation of stomach and leg swelling during the follow-up which have not been reported. The short-term efficacy was observed in some exploratory cases that provided new potential indication to PARPi-related clinical trials.
High expression of NR1D1 is associated with good prognosis in triple-negative breast cancer patients treated with chemotherapy
Authors: Na Hyelin , Han Jinil , Ka Na-Lee , Lee Min-Ho , Choi Yoon-La , Shin Young Kee , Lee Mi-Ock
Published: November 2019

Background

Nuclear receptor subfamily 1, group D, member 1 (NR1D1) is a ligand-regulated nuclear receptor and transcriptional factor. Although recent studies have implicated NR1D1 as a regulator of DNA repair and proliferation in breast cancers, its potential as a therapeutic target for breast cancer has not been assessed in terms of clinical outcomes. Thus, this study aims to analyze NR1D1 expression in breast cancer patients and to evaluate its potential prognostic value.

Methods

NR1D1 expression was analyzed by immunohistochemistry using an anti-NR1D1 antibody in 694 breast cancer samples. Survival analyses were performed using the Kaplan–Meier method with the log-rank test to investigate the association of NR1D1 expression with clinical outcome.

Results

One hundred thirty-nine of these samples exhibited high NR1D1 expression, mostly in the nucleus of breast cancer cells. NR1D1 expression correlated significantly with histological grade and estrogen receptor status. Overall survival (OS) and disease-free survival (DFS) did not correlate significantly with NR1D1 expression in breast cancer patients regardless of whether they had received chemotherapy. Subgroup analysis performed according to molecular subtype of breast cancer showed a significant influence of high NR1D1 expression on OS (P = 0.002) and DFS (P = 0.007) in patients with triple-negative breast cancer (TNBC) treated with chemotherapy.

Conclusions

High NR1D1 expression level had a favorable impact on OS and DFS in patients with TNBC treated with chemotherapy. NR1D1 should be investigated further as a possible prognostic marker in TNBC patients receiving chemotherapeutic treatment and as a target in the development of chemotherapeutic approaches to treating TNBC.
Alcohol consumption, cigarette smoking, and familial breast cancer risk: findings from the Prospective Family Study Cohort (ProF-SC)
Authors:   kConFab Investigators, Zeinomar Nur , Knight Julia A. , Genkinger Jeanine M. , Phillips Kelly-Anne , Daly Mary B. , Milne Roger L. , Dite Gillian S. , Kehm Rebecca D. , Liao Yuyan , Southey Melissa C. , Chung Wendy K. , Giles Graham G. , McLachlan Sue-Anne , Friedlander Michael L. , Weideman Prue C. , Glendon Gord , Nesci Stephanie , Andrulis Irene L. , Buys Saundra S. , John Esther M. , MacInnis Robert J. , Hopper John L. , Terry Mary Beth
Published: November 2019

Background

Alcohol consumption and cigarette smoking are associated with an increased risk of breast cancer (BC), but it is unclear whether these associations vary by a woman’s familial BC risk.

Methods

Using the Prospective Family Study Cohort, we evaluated associations between alcohol consumption, cigarette smoking, and BC risk. We used multivariable Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence intervals (CI). We examined whether associations were modified by familial risk profile (FRP), defined as the 1-year incidence of BC predicted by Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), a pedigree-based algorithm.

Results

We observed 1009 incident BC cases in 17,435 women during a median follow-up of 10.4 years. We found no overall association of smoking or alcohol consumption with BC risk (current smokers compared with never smokers HR 1.02, 95% CI 0.85–1.23; consuming ≥ 7 drinks/week compared with non-regular drinkers HR 1.10, 95% CI 0.92–1.32), but we did observe differences in associations based on FRP and by estrogen receptor (ER) status. Women with lower FRP had an increased risk of ER-positive BC associated with consuming ≥ 7 drinks/week (compared to non-regular drinkers), whereas there was no association for women with higher FRP. For example, women at the 10th percentile of FRP (5-year BOADICEA = 0.15%) had an estimated HR of 1.46 (95% CI 1.07–1.99), whereas there was no association for women at the 90th percentile (5-year BOADICEA = 4.2%) (HR 1.07, 95% CI 0.80–1.44). While the associations with smoking were not modified by FRP, we observed a positive multiplicative interaction by FRP (pinteraction = 0.01) for smoking status in women who also consumed alcohol, but not in women who were non-regular drinkers.

Conclusions

Moderate alcohol intake was associated with increased BC risk, particularly for women with ER-positive BC, but only for those at lower predicted familial BC risk (5-year BOADICEA < 1.25). For women with a high FRP (5-year BOADICEA ≥ 6.5%) who also consumed alcohol, being a current smoker was associated with increased BC risk.
The Aquilegia genome reveals a hybrid origin of core eudicots
Authors: Aköz Gökçe , Nordborg Magnus
Published: November 2019

Background

Whole-genome duplications (WGDs) have dominated the evolutionary history of plants. One consequence of WGD is a dramatic restructuring of the genome as it undergoes diploidization, a process under which deletions and rearrangements of various sizes scramble the genetic material, leading to a repacking of the genome and eventual return to diploidy. Here, we investigate the history of WGD in the columbine genus Aquilegia, a basal eudicot, and use it to illuminate the origins of the core eudicots.

Results

Within-genome synteny confirms that columbines are ancient tetraploids, and comparison with the grape genome reveals that this tetraploidy appears to be shared with the core eudicots. Thus, the ancient gamma hexaploidy found in all core eudicots must have involved a two-step process: first, tetraploidy in the ancestry of all eudicots, then hexaploidy in the ancestry of core eudicots. Furthermore, the precise pattern of synteny sharing suggests that the latter involved allopolyploidization and that core eudicots thus have a hybrid origin.

Conclusions

Novel analyses of synteny sharing together with the well-preserved structure of the columbine genome reveal that the gamma hexaploidy at the root of core eudicots is likely a result of hybridization between a tetraploid and a diploid species.
Systemic and central nervous system metabolic alterations in Alzheimer’s disease
Authors: van der Velpen Vera , Teav Tony , Gallart-Ayala Héctor , Mehl Florence , Konz Ioana , Clark Christopher , Oikonomidi Aikaterini , Peyratout Gwendoline , Henry Hugues , Delorenzi Mauro , Ivanisevic Julijana , Popp Julius
Published: November 2019

Background

Metabolic alterations, related to cerebral glucose metabolism, brain insulin resistance, and age-induced mitochondrial dysfunction, play an important role in Alzheimer’s disease (AD) on both the systemic and central nervous system level. To study the extent and significance of these alterations in AD, quantitative metabolomics was applied to plasma and cerebrospinal fluid (CSF) from clinically well-characterized AD patients and cognitively healthy control subjects. The observed metabolic alterations were associated with core pathological processes of AD to investigate their relation with amyloid pathology and tau-related neurodegeneration.

Methods

In a case-control study of clinical and biomarker-confirmed AD patients (n = 40) and cognitively healthy controls without cerebral AD pathology (n = 34) with paired plasma and CSF samples, we performed metabolic profiling, i.e., untargeted metabolomics and targeted quantification. Targeted quantification focused on identified deregulated pathways highlighted in the untargeted assay, i.e. the TCA cycle, and its anaplerotic pathways, as well as the neuroactive tryptophan and kynurenine pathway.

Results

Concentrations of several TCA cycle and beta-oxidation intermediates were higher in plasma of AD patients, whilst amino acid concentrations were significantly lower. Similar alterations in these energy metabolism intermediates were observed in CSF, together with higher concentrations of creatinine, which were strongly correlated with blood-brain barrier permeability. Alterations of several amino acids were associated with CSF Amyloidβ1–42. The tryptophan catabolites, kynurenic acid and quinolinic acid, showed significantly higher concentrations in CSF of AD patients, which, together with other tryptophan pathway intermediates, were correlated with either CSF Amyloidβ1–42, or tau and phosphorylated Tau-181.

Conclusions

This study revealed AD-associated systemic dysregulation of nutrient sensing and oxidation and CNS-specific alterations in the neuroactive tryptophan pathway and (phospho)creatine degradation. The specific association of amino acids and tryptophan catabolites with AD CSF biomarkers suggests a close relationship with core AD pathology.

Our findings warrant validation in independent, larger cohort studies as well as further investigation of factors such as gender and APOE genotype, as well as of other groups, such as preclinical AD, to identify metabolic alterations as potential intervention targets.
The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury
Authors: Guan Fangxia , Huang Tuanjie , Wang Xinxin , Xing Qu , Gumpper Kristyn , Li Peng , Song Jishi , Tan Tao , Yang Greta Luyuan , Zang Xingxing , Zhang Jiewen , Wang Yuming , Yang Yunlei , Liu Yashi , Zhang Yanting , Yang Bo , Ma Jianjie , Ma Shanshan
Published: November 2019

Background

Traumatic brain injury (TBI) is a common neurotrauma leading to brain dysfunction and death. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold promise in the treatment of TBI. However, their efficacy is modest due to low survival and differentiation under the harsh microenvironment of the injured brain. MG53, a member of TRIM family protein, plays a vital role in cell and tissue damage repair. The present study aims to test whether MG53 preserves hUC-MSCs against oxidative stress and enhances stem cell survival and efficacy in TBI treatment.

Methods

In this study, we performed a series of in vitro and in vivo experiments in hUC-MSCs and mice to define the function of MG53 enhancing survival, neurogenesis, and therapeutic efficacy of stem cells in murine traumatic brain injury.

Results

We found that recombinant human MG53 (rhMG53) protein protected hUC-MSCs against H2O2-induced oxidative damage and stimulated hUC-MSC proliferation and migration. In a mouse model of contusion-induced TBI, intravenous administration of MG53 protein preserved the survival of transplanted hUC-MSCs, mitigated brain edema, reduced neurological deficits, and relieved anxiety and depressive-like behaviors. Co-treatment of MG53 and hUC-MSCs enhanced neurogenesis by reducing apoptosis and improving PI3K/Akt-GSK3β signaling.

Conclusion

MG53 enhances the efficacy of hUC-MSCs in the recovery of TBI, indicating that such adjunctive therapy may provide a novel strategy to lessen damage and optimize recovery for brain injury.
CD90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating AKT activation that influences adipose tissue and metabolic homeostasis
Authors: Pan Zhenzhen , Zhou Zixin , Zhang Huiying , Zhao Hui , Song Peixuan , Wang Di , Yin Jilong , Zhao Wanyi , Xie Zhaoxiang , Wang Fuwu , Li Yan , Guo Chun , Zhu Faliang , Zhang Lining , Wang Qun
Published: November 2019

Background

White adipose tissue includes subcutaneous and visceral adipose tissue (SAT and VAT) with different metabolic features. SAT protects from metabolic disorders, while VAT promotes them. The proliferative and adipogenic potentials of adipose-derived stem cells (ADSCs) are critical for maintaining adipose tissue homeostasis through driving adipocyte hyperplasia and inhibiting pathological hypertrophy. However, it remains to be elucidated the critical molecules that regulate different potentials of subcutaneous and visceral ADSCs (S-ADSCs, V-ADSCs) and mediate distinct metabolic properties of SAT and VAT. CD90 is a glycosylphosphatidylinositol-anchored protein on various cells, which is also expressed on ADSCs. However, its expression patterns and differential regulation on S-ADSCs and V-ADSCs remain unclear.

Methods

S-ADSCs and V-ADSCs were detected for CD90 expression. Proliferation, colony formation, cell cycle, mitotic clonal expansion, and adipogenic differentiation were assayed in S-ADSCs, V-ADSCs, orCD90-silenced S-ADSCs. Glucose tolerance test and adipocyte hypertrophy were examined in mice after silencing ofCD90in SAT.CD90expression and its association withCyclinD1andLeptinwere analyzed in adipose tissue from mice and humans. Regulation of AKT by CD90 was detected using a co-transfection system.

Results

Compared with V-ADSCs, S-ADSCs expressed high level of CD90 and showed increases in proliferation, mitotic clonal expansion, and adipogenic differentiation, together with AKT activation and G1-S phase transition.CD90silencing inhibited AKT activation and S phase entry, thereby curbing proliferation and mitotic clonal expansion of S-ADSCs. In vivoCD90silencing in SAT inhibited S-ADSC proliferation, which caused adipocyte hypertrophy and glucose intolerance in mice. Furthermore,CD90was highly expressed in SAT rather than in VAT in human and mouse, which had positive correlation withCyclinD1but negative correlation withLeptin.CD90 promoted AKT activation through recruiting its pleckstrin homology domain to plasma membrane.

Conclusions

CD90 is differentially expressed on S-ADSCs and V-ADSCs, and plays critical roles in ADSC proliferation, mitotic clonal expansion, and hemostasis of adipose tissue and metabolism. These findings identify CD90 as a crucial modulator of S-ADSCs and V-ADSCs to mediate distinct metabolic features of SAT and VAT, thus proposing CD90 as a valuable biomarker or target for evaluating ADSC potentials, monitoring or treating obesity-associated metabolic disorders.
Systematic comparison of hUC-MSCs at various passages reveals the variations of signatures and therapeutic effect on acute graft-versus-host disease
Authors: Zhao Qinjun , Zhang Leisheng , Wei Yimeng , Yu Hao , Zou Linglin , Huo Jiali , Yang Hongju , Song Baoquan , Wei Teng , Wu Dan , Zhang Wenxia , Zhang Lei , Liu Dengke , Li Zongjin , Chi Ying , Han Zhibo , Han Zhongchao
Published: November 2019

Background

Mesenchymal stem cells are heterogenous populations with hematopoietic supporting and immunomodulating capacities. Enormous studies have focused on their preclinical or clinical therapeutic effects, yet the systematic study of continuous in vitro passages on signatures and functions of UC-MSCs at both the cellular and molecular levels is still lacking.

Methods

In this study, to systematically evaluate the biological properties of MSCs at various passages, we analyzed biomarker expression, cell proliferation and apoptosis, chromosome karyotype, and tri-lineage differentiation potential. Subsequently, we took advantage of whole-exome sequencing to compare the somatic hypermutation of hUC-MSCs at P3, P6, and P15 including SNV and INDEL mutations. In addition, to explore the safety of the abovementioned hUC-MSCs, we performed metabolic pathway enrichment analysis and in vivo transplantation analysis. Furthermore, we cocultured the abovementioned hUC-MSCs with UCB-CD34+ HSCs to evaluate their hematopoietic supporting capacity in vitro. Finally, we transplanted the cells into acute graft-versus-host disease (aGVHD) mice to further evaluate their therapeutic effect in vivo.

Results

The hUC-MSCs at P3, P6, and P15 showed similar morphology, biomarker expression, and cytokine secretion. hUC-MSCs at P15 had advantages on adipogenic differentiation and some cytokine secretion such as IL-6 and VEGF, with disadvantages on cell proliferation, apoptosis, and osteogenic and chondrogenic differentiation potential. Based on the SNP data of 334,378 exons and bioinformatic analyses, we found the somatic point mutations could be divided into 96 subsets and formed 30 kinds of signatures but did not show correlation with risk of tumorigenesis, which was confirmed by the in vivo transplantation experiments. However, hUC-MSCs at P15 showed impaired hematologic supporting effect in vitro and declined therapeutic effect on aGVHD in vivo.

Conclusions

In this study, we systematically evaluated the biological and genetic properties of hUC-MSCs at various passages. Our findings have provided new references for safety and effectiveness assessments, which will provide overwhelming evidence for the safety of hUC-MSCs after continuous in vitro passages both at the cellular and molecular levels for the first time. Taken together, our studies could help understand the controversial effects of disease treatment and benefit the clinical research of UC-MSCs.
The effect of varying multidrug-resistence (MDR) definitions on rates of MDR gram-negative rods
Authors: Wolfensberger Aline , Kuster Stefan P. , Marchesi Martina , Zbinden Reinhard , Hombach Michael
Published: November 2019

Background

A multitude of definitions determining multidrug resistance (MDR) of Gram-negative organisms exist worldwide. The definitions differ depending on their purpose and on the issueing country or organization. The MDR definitions of the European Centre for Disease Prevention and Control (ECDC) were primarily chosen to harmonize epidemiological surveillance. The German Commission of Hospital Hygiene and Infection Prevention (KRINKO) issued a national guideline which is mainly used to guide infection prevention and control (IPC) measures. The Swiss University Hospital Zurich (UHZ) – in absentia of national guidelines – developed its own definition for IPC purposes. In this study we aimed to determine the effects of different definitions of multidrug-resistance on rates of Gram-negative multidrug-resistant organisms (GN-MDRO).

Methods

MDR definitions of the ECDC, the German KRINKO and the Swiss University Hospital Zurich were applied on a dataset comprising isolates of Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Pseudomonas aeruginosa, and Acinetobacter baumannii complex. Rates of GN-MDRO were compared and the percentage of patients with a GN-MDRO was calculated.

Results

In total 11′407 isolates from a 35 month period were included. For Enterobacterales and P. aeruginosa, highest MDR-rates resulted from applying the ‘ECDC-MDR’ definition. ‘ECDC-MDR’ rates were up to four times higher compared to ‘KRINKO-3/4MRGN’ rates, and up to six times higher compared to UHZ rates. Lowest rates were observed when applying the ‘KRINKO-4MRGN’ definitions. Comparing the ‘KRINKO-3/4MRGN’ with the UHZ definitions did not show uniform trends, but yielded higher rates for E. coli and lower rates for P. aeruginosa. On the patient level, the percentages of GN-MDRO carriers were 2.1, 5.5, 6.6, and 18.2% when applying the ‘KRINKO-4MRGN’, ‘UHZ-MDR’, ‘KRINKO-3/4MRGN’, and the ‘ECDC-MDR’ definition, respectively.

Conclusions

Different MDR-definitions lead to considerable variation in rates of GN-MDRO. Differences arise from the number of antibiotic categories required to be resistant, the categories and drugs considered relevant, and the antibiotic panel tested. MDR definitions should be chosen carefully depending on their purpose and local resistance rates, as definitions guiding isolation precautions have direct effects on costs and patient care.
Correction to: Abstracts from the 12th Asia Pacific Burn Congress
Authors:   Supplement Organiser: 12th Asia Pacific Burn Congress (12th APBC)
Published: November 2019

Following publication of the supplement Abstracts from the 12th Asia Pacific Burn Congress [1], all affiliations have been revised for legal reasons.
Serious infections in patients with self-reported psoriatic arthritis from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) treated with biologics
Authors: Ritchlin Christopher T. , Stahle Mona , Poulin Yves , Bagel Jerry , Chakravarty Soumya D. , Kafka Shelly , Srivastava Bhaskar , Langholff Wayne , Gottlieb Alice B.
Published: November 2019

Background

Patients with psoriatic arthritis (PsA) have increased risk of adverse events, including serious infections (SI), compared with psoriasis patients.

Methods

Patients eligible for, or receiving conventional systemic and biologic agents for psoriasis were followed prospectively using PSOLAR. Cohorts included: ustekinumab, tumor necrosis factor (TNF) inhibitors; infliximab; etanercept; adalimumab; non-biologic/methotrexate (MTX) (reference group); and non-biologic/non-MTX. Multivariate analyses using Cox hazard regression were used to identify factors associated with time to first SI. Rates of SI in PSOLAR psoriasis patients with self-reported PsA and possible risks with biologic therapy were evaluated.

Results

PSOLAR enrolled 4315 psoriasis patients with self-reported PsA. The overall population (N = 2401) included patients (n): 628 ustekinumab; 1413 TNF inhibitors; 258 infliximab; 481 etanercept; 674 adalimumab; 54 other biologics, 98 non-biologic/MTX; 208 non-biologic/non-MTX. Overall, 138 SI were reported with incidence rates per 100 patient-years as follows: a) ustekinumab: 1.00; b) TNF inhibitors: 2.22; c) infliximab: 2.12; d) etanercept: 2.58; e) adalimumab: 1.99; f) non-biologic/MTX: 3.01; g) and non-biologic/non-MTX: 2.31. Age, time-dependent disease activity Physician’s Global Assessment (PGA) of 4, 5, history of infection, and diabetes were associated with increased risk for SI (p < 0.05) in self-reported PsA patients. Biologic groups, other than ustekinumab, had numerically higher rates of SI.

Conclusions

PSOLAR psoriasis patients with self-reported PsA in the TNF inhibitors, infliximab, adalimumab, etanercept, and MTX cohorts had numerically higher SI rates than the ustekinumab cohort, although not statistically significant. Age, PGA 4, 5, history of infection, and diabetes were associated with an increased risk for SI, irrespective of biologic exposure.

Trial registration

NCT00508547; Registered July 30, 2007.
Integrating engineering in K-12 science education: spelling out the pedagogical, epistemological, and methodological arguments
Authors: Purzer Senay , Quintana-Cifuentes Jenny Patricia
Published: November 2019

This position paper is motivated by recent educational reform efforts that urge the integration of engineering in science education. We argue that it is plausible and beneficial to integrate engineering into formal K-12 science education. We illustrate how current literature, though often implicitly, discusses this integration from a pedagogical, epistemological, or methodological argumentative stance. From a pedagogical perspective, a historically dominant argument emphasizes how engineering helps make abstract science concepts more concrete. The epistemological argument is centered on how engineering is inherently interdisciplinary and hence its integrative role in support of scientific literacy and more broadly STEM literacy is natural. From a methodological perspective, arguments focus on the engineering design process, which is compatible with scientific inquiry and adaptable to answering different types of engineering questions. We call for the necessity of spelling out these arguments and call for common language as science and engineering educators form a research-base on the integration of science and engineering. We specifically provide and discuss specific terminology associated with four different models, each effectively used to integrate engineering into school science. We caution educators against a possible direction towards a convergence approach for a specific type of integrating engineering and science. Diversity in teaching models, more accurately represents the nature of engineering but also allows adaptations based on available school resources. Future synthesis can then examine student learning outcomes associated with different teaching models.
Science|Environment|Health – the emergence of a new pedagogy of complex living systems
Authors: Zeyer Albert , Dillon Justin
Published: November 2019

Science|Environment|Health (S|E|H) is an emerging science pedagogy for complex living systems. The name highlights a situation of mutual benefit between science education, environmental education and health education. The paper discusses a range of topics from the curriculum-focused origin of the S|E|H movement to the issues that concern S|E|H researchers today. These include, among others, the role of scientific knowledge in S|E|H decision making, medicine education as a paradigmatic example of S|E|H, complexity in S|E|H issues, the role of empathy in S|E|H, and the tension between societal and individual responsibility. In conclusion, it is argued that two insights are essential for current S|E|H work. First, living systems can be understood both in causal and empathetic terms, which makes S|E|H a powerful ‘science for all’ approach. Second, in living systems, there is always a trade-off between predictability and homeostasis. This brings S|E|H in a natural antagonism – but not in opposition – to STEM approaches.
Different lead locations guided by fluoroscopy and ECG parameters and their effect on patients functional status
Authors: MesbahTahaHassanin Mohamed , ShafieAmmar Ahmad , Abdullah Radwa M. , Khedr Mohammad Hassan
Published: November 2019

Background

Right ventricular apical pacing with the resultant left ventricular dyssynchrony often leads to depressed systolic function and heart failure. This study aimed at investigating the relation between various septal locations guided by ECG and fluoroscopy and the intermediate term functional capacity of the patients.

Results

Fifty patients who received a single lead pacemaker with assumed > 90% pacemaker dependency. Patients were randomized according to RV pacing site RV into group 1 “high septum” (n = 15), group 2 “mid septum” (n = 25), and group 3 “low septum” (n = 10) using QRS vector and duration as well as fluoroscopic parameters. Their clinical status was assessed 6 months after device implementation using 6-min walk test (6MWT).

The study showed that paced QRS complex duration itself has no significant difference between the different septal pacing locations (P-value 0.675), although its combination with the paced QRS complex vector can signify the optimal pacing site and 6MWT showed a significant difference among the groups in favor of group 1; group 1 (413.3 ± 148.5), group 2 (359.8 ± 124.6), and group 3 (276.0 ± 98.5) P value 0.04.

Conclusion

There was a significant difference found between the three septal pacing sites concerning the patient functional capacity with superiority of high septal location. By contrast, different septal sites showed no significant difference of the paced QRS complex duration. To optimize the pacing site in the septum, assessment of the paced QRS vector in leads I and III is of a great benefit especially when combined with paced QRS complex duration assessment.
Quaternion-based sparse tight frame for multicomponent signal recovery
Authors: Zhao Qiang , Du Qizhen , Yasin Qamar , Li Qingqing , Fu Liyun
Published: November 2019

Multicomponent noise attenuation often presents more severe processing challenges than scalar data owing to the uncorrelated random noise in each component. Meanwhile, weak signals merged in the noise are easier to degrade using the scalar processing workflows while ignoring their possible supplement from other components. For seismic data preprocessing, transform-based approaches have achieved improved performance on mitigating noise while preserving the signal of interest, especially when using an adaptive basis trained by dictionary-learning methods. We have developed a quaternion-based sparse tight frame (QSTF) with the help of quaternion matrix and tight frame analyses, which can be used to process the vector-valued multicomponent data by following a vectorial processing workflow. The QSTF is conveniently trained through iterative sparsity-based regularization and quaternion singular-value decomposition. In the quaternion-based sparse domain, multicomponent signals are orthogonally represented, which preserve the nonlinear relationships among multicomponent data to a greater extent as compared with the scalar approaches. We test the performance of our method on synthetic and field multicomponent data, in which component-wise, concatenated, and long-vector models of multicomponent data are used as comparisons. Our results indicate that more features, specifically the weak signals merged in the noise, are better recovered using our method than others.
Neonatal Severe Hyperparathyroidism: Novel Insights From Calcium, PTH, and the CASR Gene
Authors: Marx Stephen J , Sinaii Ninet
Published: November 2019

Context

Neonatal severe hyperparathyroidism (NSHPT) is rare and potentially lethal. It is usually from homozygous or heterozygous germline-inactivating CASR variant(s). NSHPT shows a puzzling range of serum calcium and parathyroid hormone (PTH) levels. Optimal therapy is unclear.

Evidence acquisition

We categorized genotype/phenotype pairings related to CASRs. For the 2 pairings in NSHPT, each of 57 cases of neonatal severe hyperparathyroidism required calcium, PTH, upper normal PTH, and dosage of a germline pathogenic CASR variant.

Evidence synthesis

Homozygous and heterozygous NSHPT are 2 among a spectrum of 9 genotype/phenotype pairings relating to CASRs and NSHPT. For the 2 NSHPT pairings, expressions differ in CASR allelic dosage, CASR variant severity, and sufficiency of maternofetal calcium fluxes. Homozygous dosage of CASR variants was generally more aggressive than heterozygous. Among heterozygotes, high-grade CASR variants in vitro were more pathogenic in vivo than low-grade variants. Fetal calcium insufficiency as from maternal hypoparathyroidism caused fetal secondary hyperparathyroidism, which persisted and was reversible in neonates. Among NSHPT pairings, calcium and PTH were higher in CASR homozygotes than in heterozygotes. Extreme hypercalcemia (above 4.5 mM; normal 2.2–2.6 mM) is a robust biomarker, occurring only in homozygotes (83% of that pairing). It could occur during the first week.

Conclusions

In NSHPT pairings, the homozygotes for pathogenic CASR variants show higher calcium and PTH levels than heterozygotes. Calcium levels above 4.5 mM among NSHPT are frequent and unique only to most homozygotes. This cutoff supports early and robust diagnosis of CASR dosage. Thereby, it promotes definitive total parathyroidectomy in most homozygotes.
Metformin and Risk of Alzheimer’s Disease Among Community-Dwelling People With Diabetes: A National Case-Control Study
Authors: Sluggett Janet K , Koponen Marjaana , Bell J Simon , Taipale Heidi , Tanskanen Antti , Tiihonen Jari , Uusitupa Matti , Tolppanen Anna-Maija , Hartikainen Sirpa
Published: November 2019

Context

Type 2 diabetes has been linked with an increased risk of Alzheimer’s disease (AD). Studies on the association between metformin use and AD have reported conflicting results.

Objective

To investigate whether metformin use modifies the association between diabetes and incident, clinically verified AD.

Design

Nested case-control study.

Setting

All community-dwelling people in Finland.

Participants

Cases were all community-dwelling Finns with AD diagnosed from 2005 to 2011 and with diabetes diagnosed ≥ 3 years before AD (n = 9862). Cases were matched with up to 2 control persons by age, sex, and diabetes duration (n = 19 550).

Main outcome measure

Cumulative metformin exposure was determined from reimbursed dispensings over a 10- to 16-year period. Adjusted odds ratios (aORs) were calculated using conditional logistic regression to estimate associations, with adjustment for potential confounders.

Results

A total of 7225 (73.3%) cases and 14528 (74.3%) controls received metformin at least once. Metformin use (ever use) was not associated with incident AD (aOR 0.99; 95% confidence interval [CI], 0.94–1.05). The adjusted odds of AD were lower among people dispensed metformin for ≥ 10 years (aOR 0.85; 95% CI, 0.76–0.95), those dispensed cumulative defined daily doses (DDDs) of < 1825–3650 (aOR 0.91; 95% CI, 0.84–0.98) and > 3650 DDDs (aOR 0.77; 95% CI, 0.67–0.88), and among persons dispensed an average of 2 g metformin daily (aOR 0.89; 95% CI, 0.82–0.96).

Conclusion

In this large national sample we found no evidence that metformin use increases the risk of AD. Conversely, long-term and high-dose metformin use was associated with a lower risk of incident AD in older people with diabetes.
A pilot study on dosimetric and radiomics analysis of urethral strictures following HDR brachytherapy as monotherapy for localized prostate cancer
Authors: Tsang Yat Man , Vignarajah Dinesh , Mcwilliam Alan , Tharmalingam Hannah , Lowe Gerry , Choudhury Ananya , Hoskin Peter
Published: November 2019

Objective:

A cohort of high dose-rate (HDR) monotherapy patients was analyzed to (i) establish the frequency of non-malignant urethral stricture; (ii) explore the relation between stricture formation with the dose distribution along the length of the urethra, and MRI radiomics features of the prostate gland.

Methods:

A retrospective review of treatment records of patients who received 19 Gy single fraction of HDR brachytherapy (BT) was carried out. A matched pair analysis used one control for each stricture case matched with pre-treatment International Prostate Symptom Score (IPSS) score, number of needles used and clinical target volume volume for each stricture case identified.

For all data sets, pre-treatment T  2 weighted MRI images were used to define regions of interests along the urethra and within the whole prostate gland. MRI textural radiomics features—energy, contrast and homogeneity were selected. Wilcoxon signed-rank test was performed to investigate significant differences in dosimetric parameters and MRI radiomics feature values between cases and controls.

Results:

From Nov 2010 to July 2017, there were 178 patients treated with HDR BT delivering 19 Gy in a single dose. With a median follow-up of 28.2 months, a total of 5/178 (3%) strictures were identified.

10 patients were included in the matched pair analysis. The urethral dosimetric parameters investigated were not statistically different between cases and controls (p > 0.05). With regards to MRI radiomics feature analysis, significant differences were found in contrast and homogeneity between cases and controls (p < 0.05). However, this did not apply to the energy feature (p = 0.28).

Conclusion:

In this matched pair analysis, no association between post-treatment stricture and urethral dosimetry was identified. Our study generated a preliminary clinical hypothesis suggesting that the MRI radiomics features of homogeneity and contrast of the prostate gland can potentially identify patients who develop strictures after HDR BT. Although the sample size is small, this warrants further validation in a larger patient cohort.

Advances in knowledge:

Urethral stricture has been reported as a specific late effect with prostate HDR brachytherapy. Our study reported a relatively low stricture rate of 3% and no association between post-treatment stricture and urethral dosimetry was identified. MRI radiomics features can potentially identify patients who are more prone to develop strictures.
Head position classification of medical imaging studies: an assessment and development of a protocol
Authors: Miller Courtney A. , Lee Yen , Avey Gregory D. , Vorperian Houri K.
Published: November 2019

Objectives

To determine the optimal approach to reliably classify head position of head and neck medical imaging studies as flexion, neutral or extension for use in craniofacial and orthodontic research.

Methods and material:

A prospective study scanned six participants in flexed, neutral and extended head positions. Additionally, a retrospective dataset of 46 CT studies were visually classified into six categories: flexion, neutral-flexion, neutral, neutral-extension, extension and flexion-extension. 14 landmarks were placed in the head and neck region of all studies to calculate 17 head position angle and distance measurements. Assessment of head position classification was performed for each measure, as well as all measures together using GUIDE forest.

Results:

No single measure was sufficient to reliably classify head position in both retrospective and prospective imaging studies. Therefore, this study developed a head position protocol that considers multiple measures using two hybrid predictive models, to classify head position. Compared to visual assessment of head position, this protocol classified the imaging studies into the four head position categories with 82% neutral sensitivity and 100% neutral precision where the three neutral groups (neutral-flexion, neutral and neutral-extension) were grouped together.

Conclusion:

This study established a novel head position classification protocol that uses multiple measures accounting for both head and neck positions to reliably classify head positions in imaging studies as: flexion, neutral or extension. Given the limitation that no single measure reliably classified head position, this protocol is strongly recommended to researchers who need to account for head position to reach valid conclusions.