A wide variety of pharmacological agents are used in the management of neuropsychiatric symptoms, which are common in Alzheimer's disease (AD), but results from randomised controlled trials (RCTs) on ...the efficacy and safety of these agents are conflicting.
To quantify the efficacy and safety of pharmacological treatment on neuropsychiatric symptoms in AD patients.
Systematic review and meta-analysis of RCTs comparing pharmacological agents with placebo on Neuropsychiatric Inventory (NPI) and safety outcomes in AD patients with neuropsychiatric symptoms.
Cholinesterase inhibitors (ChEIs) and atypical antipsychotics improved NPI total scores (ChEIs: standardised mean difference (SMD) -0.12; 95% CI -0.23 to -0.02; atypical antipsychotics: SMD -0.21; 95% CI -0.29 to -0.12), but antidepressants (95% CI -0.35 to 0.37) and memantine (95% CI -0.27 to 0.03) did not. However, ChEIs and atypical antipsychotics increased risk of dropouts due to adverse events (ChEIs: risk ratio (RR) 1.64; 95% CI 1.12 to 2.42; atypical antipsychotics: RR 2.24; 95% CI 1.53 to 3.26) and on incidence of adverse events (ChEIs: RR 1.08; 95% CI 1.01 to 1.17; atypical antipsychotics: RR 1.17; 95% CI 1.05 to 1.31). For typical antipsychotics, no study was included.
ChEIs and atypical antipsychotics could improve neuropsychiatric symptoms in AD patients, but with bad safety outcomes.
We study the CP violation in two-body nonleptonic decays of
B
c
meson. We concentrate on the decay channels which contain at least one excited heavy meson in the final states. Specifically, the ...following channels are considered:
B
c
→
c
c
¯
(
2
S
,
2
P
)
+
c
¯
q
(
1
S
,
1
P
)
,
B
c
→
c
c
¯
(
1
S
)
+
c
¯
q
(
2
S
,
2
P
)
,
B
c
→
c
c
¯
(
1
P
)
+
c
¯
q
(
2
S
)
,
B
c
→
c
c
¯
(
1
D
)
+
c
¯
q
(
1
S
,
1
P
)
, and
B
c
→
c
c
¯
(
3
S
)
+
c
¯
q
(
1
S
)
. The improved Bethe-Salpeter method is applied to calculate the hadronic transition matrix element. Our results show that some decay modes have large branching ratios, which is of the order of
10
-
3
. The CP violation effect in
B
c
→
η
c
(
1
S
)
+
D
(
2
S
)
,
B
c
→
η
c
(
1
S
)
+
D
0
∗
(
2
P
)
, and
B
c
→
J
/
ψ
+
D
∗
(
2
S
)
are most likely to be found. If the detection precision of the CP asymmetry in such channels can reach the
3
σ
level, at least
10
7
B
c
events are needed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
2,7‐dibromo‐9,9‐bis(perfluorohexylethyl propionate) fluorene was synthesized by Michael addition reaction using 2,7‐dibromofluorene and perfluorohexyl ethyl acrylate as the reactants. ...9,9‐Bis(perfluorohexylethyl propionate) fluorene copolymers were then synthesized by Suzuki coupling reaction with 2,7‐bis(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborane‐diyl)‐9,9 ‐dioctyl fluorene, 2,7‐dibromo‐9,9‐dioctyl fluorene and 2,7‐dibromo‐9,9‐bis(perfluorohexylethyl propionate) fluorene as the monomers. The fluorinated fluorene copolymers were characterized and investigated via Fourier infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance spectroscopy (1HNMR), ultraviolet absorption spectroscopy (UV–vis), cyclic voltammetry (CV) and photoluminance spectroscopy (PL). Because of the long fluorine‐containing alkyl side chain, the ultraviolet absorption peak of 9,9‐bis(perfluorohexylethyl propionate) fluorene is blue‐shifted compared with poly(9,9‐dioctylfluorene)(PF8). The LUMO energy level increases and the energy band gap of copolymers widens. Due to the self‐assembly of the long fluoroalkyl side chain, the photoluminance spectra of 9,9‐bis(perfluorohexylethyl propionate) fluorene copolymers exhibit a new excimer emission peak at 550 nm. The photoluminance stabilities of the copolymers under irradiation and humid conditions are significantly improved due to protective effect from the long fluoroalkyl side chain. After being irradiated under 500 W iodine tungsten lamp or kept under 70% relative humid conditions, the 9,9‐bis(perfluorohexylethyl propionate) fluorene copolymers showed much better photoluminance stability than that of poly(9,9‐dioctylfluorene) (PF8). These show that introducing long fluoroalkyl side chain into conjugated polymer main chain is a promising strategy to improve environmental stability of devices based on organic conjugated polymers.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Triggering receptor expressed on myeloid cells 2 (TREM2) gene is a recently identified susceptibility gene for Alzheimer's disease (AD), as its low-frequency variants increase the risk of this ...disease with an odds ratio similar to that of an APOE ɛ4 allele. To date, the expression and biologic functions of TREM2 under AD context remain largely unknown. Using APPswe/PS1dE9 mice, a transgenic model of AD, we showed that TREM2 was upregulated in microglia during disease progression. For the first time, we provided in vitro and in vivo evidence that this upregulation was attributed to the increased amyloid-β (Aβ)(1-42) levels in the brain. By knockdown and overexpression of TREM2 in cultured primary microglia, we revealed that TREM2 modulated microglial functions under AD context, as it facilitated Aβ(1-42) phagocytosis and inhibited Aβ(1-42)-triggered proinflammatory responses. Meanwhile, this modulation was dependent on DAP12, the adapter protein of TREM2. More importantly, overexpression of TREM2 in the brain of APPswe/PS1dE9 mice markedly ameliorated AD-related neuropathology including Aβ deposition, neuroinflammation, and neuronal and synaptic losses, which was accompanied by an improvement in spatial cognitive functions. Taken together, our data suggest that the upregulation of TREM2 serves as a compensatory response to Aβ(1-42) and subsequently protects against AD progression by modulation of microglia functions. These findings provide insights into the role of TREM2 in AD pathogenesis, and highlight TREM2 as a potential therapeutic target for this disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Introduction
This study aimed to assess whether biomarkers related to amyloid, tau, and neurodegeneration can accurately predict Alzheimer's disease (AD) neuropathology at autopsy in early and late ...clinical stages.
Methods
We included 100 participants who had ante mortem biomarker measurements and underwent post mortem neuropathological examination. Based on ante mortem clinical diagnosis, participants were divided into non‐dementia and dementia, as early or late clinical stages.
Results
Amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) amyloid beta (Aβ)42/phosphorylated tau (p‐tau)181 showed excellent performance in differentiating autopsy‐confirmed AD and predicting the risk of neuropathological changes in early and late clinical stages. However, CSF Aβ42 performed better in the early clinical stage, while CSF p‐tau181, CSF t‐tau, and plasma p‐tau181 performed better in the late clinical stage.
Discussion
Our findings provide important clinical information that, if using PET, CSF, and plasma biomarkers to detect AD pathology, researchers must consider their differential performances at different clinical stages of AD.
Highlights
Amyloid PET and CSF Aβ42/p‐tau181 were the most promising candidate biomarkers for predicting AD pathology.
CSF Aβ42 can serve as a candidate predictive biomarker in the early clinical stage of AD.
CSF p‐tau181, CSF t‐tau, and plasma p‐tau181 can serve as candidate predictive biomarkers in the late clinical stage of AD.
Combining APOE ε4 genotypes can significantly improve the predictive accuracy of AD‐related biomarkers for AD pathology.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Sustainable city has been a global concern in recent years, involving natural science and social science research. However, few studies have attempted to map the global research of sustainable city. ...This study aimed to reveal the global performance and development of sustainable city research during 1992 to 2016, using a bibliometric analysis based on Science Citation Index Expanded (SCI-EXPANDED) and Social Sciences Citation Index (SSCI) on Web of Science. Research performance, research emphases and trends were illustrated by bibliometric indicators and newly developed visualization tools, like Science of Science (Sci2), Gephi, and alluvial diagram. Sustainable city research in natural science and social science were well-matched in quantity, and had similar and different characteristics in terms of different investigated aspects. China ranked first in natural science research, while the USA was the leading country in social science research. More categories and clusters were involved in sustainable city field, indicating more interdisciplinary integration was undergoing. Energy and fuels in natural science field, and interdisciplinary applications mathematics in social science field started to attract more attention. Statistical analysis of words in title, author keywords, and KeyWords Plus has been investigated to monitor the development of sustainable city research. Finally, three critical issues in sustainable city research based on the clues by the analysis of these keywords were reviewed and discussed.
Mapping the evolution among categories of SCI-EXPANDED and SSCI publications during 1992–2016. Display omitted
•A bibliometric analysis was conducted to investigate sustainable city research in SCI and SSCI.•Sustainable city research in natural science and social science were well-matched in quantity.•China ranked first in SCI-EXPANDED, while the USA took the lead in SSCI.•More interdisciplinary integration was undergoing in both SCI and SSCI.•Climate change, China, and resilience in sustainable city research were reviewed and discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Central immunity components especially microglia in dementia have been well studied and corresponding immunotherapy gradually caught the attention. However, few studies focused on peripheral immunity ...and dementia. To address the issue, we examined the longitudinal association between incident dementia and peripheral immunity markers encompassing immune cell counts, and their derived ratios including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and lymphocyte-to-monocyte ratio (LMR), utilizing data of 361,653 participants from the UK Biobank (UKB). During a median follow-up of 8.99 years, 4239 participants developed dementia. The results revealed that increased innate immunity markers were associated with higher dementia risk (per SD increment hazard ratio HR; 95% confidence interval CI 1.14; 1.09-1.19 for neutrophils, 1.16; 1.11-1.20 for NLR and 1.11; 1.07-1.16 for SII), while increased adaptive immunity markers were associated with lower dementia risk (0.93; 0.90-0.97 for lymphocytes and 0.94; 0.90-0.98 for LMR). Our study pinpoints the differential role of innate and adaptive immunity in dementia incidence, which may provide some new perspectives in etiology and therapy of dementia.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Two recent studies have identified that a rare coding variant (p.R47H) in exon 2 of triggering receptor expressed on myeloid cells 2 ( TREM2 ) gene is associated with Alzheimer’s disease ...(AD) susceptibility in Caucasians. This association was not successfully replicated in Han Chinese, where this variant was rare or even absent. Previously, we re-sequenced TREM2 exon 2 to investigate whether additional rare variants conferred risk to AD in our cohort. Although several new variants had been identified, none of them was significantly associated with disease susceptibility. Here, to test whether TREM2 is truly a susceptibility gene of AD in Han Chinese, we extend our previous study by sequencing the other four exons of TREM2 in 988 AD patients and 1354 healthy controls. We provided the first evidence that a rare coding variant (p.H157Y) in TREM2 exon 3 conferred a considerable risk of AD in our cohort ( P corrected=0.02, OR=11.01, 95% CI: 1.38-88.05). This finding indicates that rare coding variants of TREM2 may play an important role in AD in Han Chinese.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Display omitted
► A bibliometric method was used to analyze top-cited articles in adsorption field. ► Five indicators were used to evaluate authors, institutions, and countries. ► Life citation cycle ...curves of highly cited articles were identified. ► The BET, Langmuir, M41S, PSOM and modified nudged elastic band method were popular.
The 126 most frequently cited articles published in the adsorption field between 1900 and 2011 were identified and characterized using the Science Citation Index (Expanded). The data analyzed cover a range of publication years, journals, Web of Science categories, authors, institutions, countries/territories, life citation cycle curves, and characteristics of frequently cited articles. The 126 most-frequently-cited articles were each cited an average of 1014 times, ranging from 502 to 9922 citations per article from 1918 to 2006; 80% of these articles were published after 1970. Fifty-five journals were represented, led by the Journal of the American Chemical Society, and followed by Science and Nature. Three categories out of the 35 Web of Science categories constituted 60% of the citations. The three categories were: physical chemistry, multidisciplinary chemistry, and multidisciplinary sciences. Thirteen of the authors contributed three or more articles. Harvard University, the Massachusetts Institute of Technology, and the University of Washington led the list of 107 institutions, while the United States led the list of 17 countries/territories, comprising more than half of the articles. Collaboration among the top authors was a frequent occurrence, while inter-institutional collaboration and national collaboration was not obvious among the topmost articles. Moreover, the citation patterns as a function of time varied widely among the topmost articles. As evidenced by citation life cycles, the well known BET and Langmuir isotherms have received considerable attention during the study period, and will probably continue to be popular in the adsorption field. Some emerging hotspots are likely to receive particular attention in the near future; these include the new family of “M41S” materials, pseudo-second-order kinetic models, and the nudged elastic band method.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Dysfunction of glial cell communication is involved in Alzheimer's disease (AD) pathogenesis, and the recent study reported that astrocytic secreted interleukin-3 (IL-3) participated in ...astrocyte-microglia crosstalk and restricted AD pathology in mice, but the effect of IL-3 on the pathological progression of AD in human is still unclear.
A total of 311 participants with cerebrospinal fluid (CSF) IL-3, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and AD biomarkers were included from the Alzheimer's disease Neuroimaging Initiative (ADNI). We assessed the associations of IL-3 with sTREM2 and AD biomarkers at baseline, and with cognitive change in longitudinal study. The mediation models were used to explore the potential mechanism of how IL-3 affects AD pathology.
We found that CSF IL-3 was significantly associated with CSF sTREM2 and CSF AD core biomarkers (Aβ42, p-tau, and t-tau) at baseline, and was also markedly related to cognitive decline in longitudinal analysis. Moreover, mediation analysis revealed that CSF IL-3 modulated the level of CSF sTREM2 and contributed to tau pathology (as measured by CSF p-tau/t-tau) and subsequent cognitive decline. In addition, Aβ pathology (as measured by CSF Aβ42) affected the development of tau pathology partly by modifying the levels of CSF IL-3 and CSF sTREM2. Furthermore, the effect of Aβ pathology on cognitive decline was partially mediated by the pathway from CSF IL-3 and CSF sTREM2 to tau pathology.
Our findings provide evidence to suggest that IL-3 is linked to sTREM2 and mediates the correlation between Aβ pathology to tau pathology. It indicates that IL-3 may be a major factor in the spreading from Aβ pathology to tau pathology to cognitive impairment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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