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The diverse implant landscape, the rising and disparate costs of implants in public healthcare institutions (PHIs), and the limited application of health technology assessment (HTA) impede fair and sustainable implant subsidies in Singapore. This study described the Agency for Care Effectiveness (ACE) Implant Subsidy List (ISL) methodology and the key enablers for supporting government subsidy of clinically effective and cost-effective implants in Singapore.
Methods
A multi-tiered implant grouping scheme on the ISL was established by adapting overseas implant classifications, consulting clinicians, and conducting HTA evaluations, with subsidy extensions at the product group tier. Implants within a product group share similar biomechanical actions and patient outcomes and are subject to the same clinical criteria and pricing requirement. Implants on the ISL must be approved by the regulatory authority. Patients who meet the clinical criteria for ISL implants are eligible for subsidy. ACE conducted value-based pricing (VBP) and partnered with the public healthcare supply chain agency to harmonize PHI implant prices. The ISL is updated three times per year.
Results
Implants listed on the ISL were deemed clinically and cost effective. Underpinned by HTA principles, the implant grouping scheme promoted parsimonious classification, while allowing the creation of new product groups for implants offering superior benefits for patients. Reasonable prices set for the product groups aided affordability and cost sustainability. The ISL clinical criteria and standardized implant identifiers encouraged the appropriate use of subsidized implants and facilitated implementation. By ISL implementation in December 2023, ACE assessed 42,165 implants and listed 22,689 ISL implants spanning 143 product groups. Industry can apply for ISL listing three times per year, which keeps the ISL updated and relevant.
Conclusions
The ISL adopts a fit-for-purpose methodology to standardize implant classifications, enable scalable application of HTA, drive appropriate use of subsidized implants, and bring cost sustainability to the government subsidy of implants in Singapore. A strategic partnership with the public healthcare supply chain agency to concurrently establish national procurement contracts reduced disparate implant prices in PHIs and provided greater leverage for better implant prices.
This study aimed to investigate the effects of esketamine (Esk) combined with dexmedetomidine (Dex) on postoperative delirium (POD) and quality of recovery (QoR) in elderly patients undergoing thoracoscopic radical lung cancer surgery.
Methods
In this prospective, randomized, and controlled study, 172 elderly patients undergoing thoracoscopic radical lung cancer surgery were divided into two groups: the Esk + Dex group (n = 86) and the Dex group a (n = 86). The primary outcome was the incidence of POD within 7 days after surgery and the overall Quality of Recovery−15 (QoR − 15) scores within 3 days after surgery. Secondary outcomes included postoperative adverse reactions, extubation time, PACU stay, and hospitalization time. Serum levels of IL-6, IL-10, S100β protein, NSE, CD3+, CD4+, and CD8+ were detected from T0 to T5.
Results
Compared with the Dex group, the incidence of POD in the Esk + Dex group was significantly lower at 7 days after surgery (14.6% vs 30.9%; P = 0.013). The QoR − 15 score was significantly increased 3 days after surgery (P < 0.01). Levels of IL-6 and CD8+ were significantly decreased, and IL − 10 levels were significantly increased at T1-T2 (P < 0.05). At T1-T4, NSE levels were significantly decreased, while CD3+ and CD4+/CD8+ values were significantly increased (P < 0.01). At T1-T5, serum S100β protein concentration decreased significantly, and CD4+ value increased significantly (P < 0.01). The incidence of nausea/vomiting and hyperalgesia decreased significantly 48 hours after surgery (P < 0.01). The duration of extubation, PACU stay, and postoperative hospitalization were significantly shortened.
Conclusions
Esketamine combined with dexmedetomidine can significantly reduce the POD incidence and improve the QoR in patients undergoing thoracoscopic radical lung cancer surgery, which may be related to the improvement of cellular immune function.
Genetic mutations of fused in sarcoma (FUS) causing amyotrophic lateral sclerosis (ALS) may disrupt mRNA splicing events. For example, the FUS c.1394-2delA variant was reported in two western ALS patients, but its molecular mechanism is unclear. In this study, we aim to investigate FUS splice site mutations in Chinese ALS patients.
Methods:
Sanger sequencing was used to identify FUS splicing mutations in Chinese ALS patients. We combined a deep learning tool (SpliceAI), RNA sequencing, and RT-PCR/RT-qPCR to analyze the effect of FUS c.1394-2delA mutation on RNA splicing and expression. AlphaFold was used to predict the protein structure of mutant FUS. In transfected cell lines, we used immunofluorescence to assess cytoplasmic mislocalization of mutant FUS protein.
Results:
We identified a de novo FUS splice acceptor site mutation (c.1394-2delA, p. Gly466Valfs*14) in one Chinese sporadic ALS patient, which is linked to exon 14 skipping, and upregulated total FUS mRNA expression. The FUS splice site mutation was predicted to be translated into a truncated protein product at C-terminal. In vitro studies revealed that the FUS mutation increased cytoplasmic mislocalization in both HEK293T and SH-SY5Y cells.
Conclusions:
We identified a de novo FUS splicing mutation (c.1394-2delA, p. Gly466Valfs*14) in 1 out of 233 Chinese ALS patients. It caused abnormal RNA splicing, upregulated gene expression, truncated FUS translation, and cytosolic mislocalization. Our findings suggested that FUS splice site mutation is rare in Chinese ALS patients and extended our knowledge of molecular mechanisms of the FUS c.1394-2delA mutation.
Neuroimaging- and machine-learning-based brain-age prediction of schizophrenia is well established. However, the diagnostic significance and the effect of early medication on first-episode schizophrenia remains unclear.
Aims
To explore whether predicted brain age can be used as a biomarker for schizophrenia diagnosis, and the relationship between clinical characteristics and brain-predicted age difference (PAD), and the effects of early medication on predicted brain age.
Method
The predicted model was built on 523 diffusion tensor imaging magnetic resonance imaging scans from healthy controls. First, the brain-PAD of 60 patients with first-episode schizophrenia, 60 healthy controls and 21 follow-up patients from the principal data-set and 40 pairs of individuals in the replication data-set were calculated. Next, the brain-PAD between groups were compared and the correlations between brain-PAD and clinical measurements were analysed.
Results
The patients showed a significant increase in brain-PAD compared with healthy controls. After early medication, the brain-PAD of patients decreased significantly compared with baseline (P < 0.001). The fractional anisotropy value of 31/33 white matter tract features, which related to the brain-PAD scores, had significantly statistical differences before and after measurements (P < 0.05, false discovery rate corrected). Correlation analysis showed that the age gap was negatively associated with the positive score on the Positive and Negative Syndrome Scale in the principal data-set (r = −0.326, P = 0.014).
Conclusions
The brain age of patients with first-episode schizophrenia may be older than their chronological age. Early medication holds promise for improving the patient's brain ageing. Neuroimaging-based brain-age prediction can provide novel insights into the understanding of schizophrenia.
Sarcopenic obesity is regarded as a risk factor for the progression and development of non-alcoholic fatty liver disease (NAFLD). Since male sex is a risk factor for NAFLD and skeletal muscle mass markedly varies between the sexes, we examined whether sex influences the association between appendicular skeletal muscle mass to visceral fat area ratio (SVR), that is, an index of skeletal muscle mass combined with abdominal obesity, and the histological severity of NAFLD. The SVR was measured by bioelectrical impedance in a cohort of 613 (M/F = 443/170) Chinese middle-aged individuals with biopsy-proven NAFLD. Multivariable logistic regression and subgroup analyses were used to test the association between SVR and the severity of NAFLD (i.e. non-alcoholic steatohepatitis (NASH) or NASH with the presence of any stage of liver fibrosis). NASH was identified by a NAFLD activity score ≥5, with a minimum score of 1 for each of its categories. The presence of fibrosis was classified as having a histological stage ≥1. The SVR was inversely associated with NASH in men (adjusted OR 0·62; 95 % CI 0·42, 0·92, P = 0·017 for NASH, adjusted OR 0·65; 95 % CI 0·43, 0·99, P = 0·043 for NASH with the presence of fibrosis), but not in women (1·47 (95 % CI 0·76, 2·83), P = 0·25 for NASH, and 1·45 (95 % CI 0·74, 2·83), P = 0·28 for NASH with the presence of fibrosis). There was a significant interaction for sex and SVR (Pinteraction = 0·017 for NASH and Pinteraction = 0·033 for NASH with the presence of fibrosis). Our findings show that lower skeletal muscle mass combined with abdominal obesity is strongly associated with the presence of NASH only in men.
To establish optimal gestational weight gain (GWG) in Chinese pregnant women by Chinese-specific BMI categories and compare the new recommendations with the Institute of Medicine (IOM) 2009 guidelines.
Design:
Multicentre, prospective cohort study. Unconditional logistic regression analysis was used to evaluate the OR, 95 % CI and the predicted probabilities of adverse pregnancy outcomes. The optimal GWG range was defined as the range that did not exceed a 1 % increase from the lowest predicted probability in each pre-pregnancy BMI group.
Setting:
From nine cities in mainland China.
Participants:
A total of 3731 women with singleton pregnancy were recruited from April 2013 to December 2014.
Results:
The optimal GWG (ranges) by Chinese-specific BMI was 15·0 (12·8–17·1), 14·2 (12·1–16·4) and 12·6 (10·4–14·9) kg for underweight, normal weight and overweight pregnant women, respectively. Inappropriate GWG was associated with several adverse pregnancy outcomes. Compared with women gaining weight within our proposed recommendations, women with excessive GWG had higher risk for macrosomia, large for gestational age and caesarean section, whereas those with inadequate GWG had higher risk for low birth weight, small for gestational age and preterm delivery. The comparison between our proposed recommendations and IOM 2009 guidelines showed that our recommendations were comparable with the IOM 2009 guidelines and could well predict the risk of several adverse pregnancy outcomes.
Conclusions:
Inappropriate GWG was associated with higher risk of several adverse pregnancy outcomes. Optimal GWG recommendations proposed in the present study could be applied to Chinese pregnant women.
In this paper, the generation of relativistic electron mirrors (REMs) and the reflection of an ultra-short laser off this mirrors are discussed, applying two-dimensional particle-in-cell (2D-PIC) simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapidly expanding. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads the resonance between laser and REM. The reflected radiation near this interval and the corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, certain part of the reflected field could be selectively amplified or depressed, leading to the selectively adjusting of the corresponding spectra.
To evaluate the effects of gestational weight gain (GWG) in the first trimester (GWG-F) and the rate of gestational weight gain in the second trimester (RGWG-S) on gestational diabetes mellitus (GDM), exploring the optimal GWG ranges for the avoidance of GDM in Chinese women.
Design:
A population-based prospective study was conducted. Gestational weight was measured regularly in every antenatal visit and assessed by the Institute of Medicine (IOM) criteria (2009). GDM was assessed with the 75-g, 2-h oral glucose tolerance test at 24–28 weeks of gestation. Multivariable logistic regression was performed to assess the effects of GWG-F and RGWG-S on GDM, stratified by pre-pregnancy BMI. In each BMI category, the GWG values corresponding to the lowest prevalence of GDM were defined as the optimal GWG range.
Setting:
Southwest China.
Participants:
Pregnant women (n 1910) in 2017.
Results:
After adjusting for confounders, GWG-F above IOM recommendations increased the risk of GDM (OR; 95 % CI) among underweight (2·500; 1·106, 5·655), normal-weight (1·396; 1·023, 1·906) and overweight/obese women (3·017; 1·118, 8·138) compared with women within IOM recommendations. No significant difference was observed between RGWG-S and GDM (P > 0·05) after adjusting for GWG-F based on the previous model. The optimal GWG-F ranges for the avoidance of GDM were 0·8–1·2, 0·8–1·2 and 0·35–0·70 kg for underweight, normal-weight and overweight/obese women, respectively.
Conclusions:
Excessive GWG in the first trimester, rather than the second trimester, is associated with increased risk of GDM regardless of pre-pregnancy BMI. Obstetricians should provide more pre-emptive guidance in achieving adequate GWG-F.
Synaptotagmin 1 (Syt1) is an abundant and important presynaptic vesicle protein that binds Ca2+ for the regulation of synaptic vesicle exocytosis. Our previous study reported its localization and function on spindle assembly in mouse oocyte meiotic maturation. The present study was designed to investigate the function of Syt1 during mouse oocyte activation and subsequent cortical granule exocytosis (CGE) using confocal microscopy, morpholinol-based knockdown and time-lapse live cell imaging. By employing live cell imaging, we first studied the dynamic process of CGE and calculated the time interval between [Ca2+]i rise and CGE after oocyte activation. We further showed that Syt1 was co-localized to cortical granules (CGs) at the oocyte cortex. After oocyte activation with SrCl2, the Syt1 distribution pattern was altered significantly, similar to the changes seen for the CGs. Knockdown of Syt1 inhibited [Ca2+]i oscillations, disrupted the F-actin distribution pattern and delayed the time of cortical reaction. In summary, as a synaptic vesicle protein and calcium sensor for exocytosis, Syt1 acts as an essential regulator in mouse oocyte activation events including the generation of Ca2+ signals and CGE.
Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.
Hand, foot and mouth disease (HFMD) has spread widely and leads to high disease burden in many countries. However, relative transmissibility from male to female individuals remains unclear. HFMD surveillance database was built in Shenzhen City from 2013 to 2017. An intersex transmission susceptible–infectious–recovered model was developed to calculate the transmission relative rate among male individuals, among female individuals, from male to female and from female to male. Two indicators, ratio of transmission relative rate (Rβ) and relative transmissibility index (RTI), were developed to assess the relative transmissibility of male vs. female. During the study period, 270 347 HFMD cases were reported in the city, among which 16 were death cases with a fatality of 0.0059%. Reported incidence of total cases, male cases and female cases was 0.0057 (range: 0.0036–0.0058), 0.0052 (range: 0.0032–0.0053) and 0.0044 (range: 0.0026–0.0047), respectively. The difference was statistically significant between male and female (t = 3.046, P = 0.002). Rβ of male vs. female, female vs. female, from female to male vs. female and from male to female vs. female was 7.69, 1.00, 1.74 and 7.13, respectively. RTI of male vs. female, female vs. female, from female to male vs. female and from male to female vs. female was 3.08, 1.00, 1.88 and 1.43, respectively. Transmissibility of HFMD is different between male and female individuals. Male cases seem to be more transmissible than female.
Nitrogen is an essential element for biological activity, and nitrogen isotopic compositions of geological samples record information about both marine biological processes and environmental evolution. However, only a few studies of N isotopes in the early Cambrian have been published. In this study, we analysed nitrogen isotopic compositions, as well as trace elements and sulphur isotopic compositions of cherts, black shales, carbonaceous shales and argillaceous carbonates from the Daotuo drill core in Songtao County, NE Guizhou Province, China, to reconstruct the marine redox environment of both deep and surface seawater in the study area of the Yangtze shelf margin in the early Cambrian. The Mo–U covariation pattern of the studied samples indicates that the Yangtze shelf margin area was weakly restricted and connected to the open ocean through shallow water flows. Mo and U concentrations, δ15Nbulk and δ34Spy values of the studied samples from the Yangtze shelf margin area suggest ferruginous but not sulphidic seawater and low marine sulphate concentration (relatively deep chemocline) in the Cambrian Fortunian and early Stage 2; sulphidic conditions (shallow chemocline and anoxic photic zone) in the upper Cambrian Stage 2 and lower Stage 3; and the depression of sulphidic seawater in the middle and upper Cambrian Stage 3. Furthermore, the decreasing δ15N values indicate shrinking of the marine nitrate reservoir during the middle and upper Stage 3, which reflects a falling oxygenation level in this period. The environmental evolution was probably controlled by the changing biological activity through its feedback on the local marine environment.
Neurosyphilis (NS) may present with neuropsychiatric disorders characterized by cognitive impairment, personality disorders, and confusion, among others. Very few studies have focused on neuropsychiatric disorders secondary to NS in elderly people.
Method:
A retrospective chart review was performed to characterize the psychiatric findings, clinical signs and symptoms, laboratory findings, and brain magnetic resonance imaging results of ten elderly inpatients with NS.
Results:
In these ten patients, the most common presenting symptoms included a wide variety of psychiatric manifestations. The serum rapid plasma regain (RPR) and Treponema pallidum particle agglutination assay (TPPA) of the ten patients were positive, with positive CSF TPPA and RPR rates of 100% and 60%, respectively. In addition, 90% of the patients demonstrated abnormal imaging, including cerebral atrophy, infarct ischemic stroke, and hydrocephalus.
Conclusions:
Our findings support the importance of serological tests for syphilis as a routine component of the evaluation of patients with clinically evident neurological or psychiatric symptoms. If the serology is positive, all of the patients should be examined with a lumbar puncture. Moreover, psychiatric illnesses secondary to NS in the elderly also deserve medical attention.
The organic light-emitting (OLE) materials have attracted great interest due to their potential applications in sensors, biodetectors and OLE devices. However, highly efficient emission from organic solids is still a great challenge because of the aggregation-caused quenching effect. In this article, a three-dimensional (3D) organic-inorganic hybrid nanoparticle, based on polyhedral oligomeric silsesquioxane (POSS), was precisely fabricated via click chemistry with high yield, and its structure was characterized by Fourier transform infrared spectroscopy, 1H, and 29Si nuclear magnetic resonance spectroscopies, and Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry, respectively. The resultant 3D organic-inorganic nanohybrid showed significantly enhanced emission in solid film (Φfilm 80%) with a slight red-shift as compared with its organic counterpart, (Φfilm 14%), which exhibits a large red-shift in solid film, due to the deaggregation effect of POSS. Simultaneously, the resultant nanohybrid also exhibited good film formability, excellent spectrum and thermal stability (>250 °C) due to the introduction of POSS.
Total body fat mass (TBFM) and total body lean mass (TBLM) are the major components of the human body. Although these highly correlated phenotypic traits are frequently used to characterize obesity, the specific shared genetic factors that influence both traits remain largely unknown. Our study was aimed at identifying common quantitative trait loci (QTLs) contributing to both TBFM and TBLM. We performed a whole genome-linkage scan study in a large sample of 3255 subjects from 420 Caucasian pedigrees. Bivariate linkage analysis was carried out in both the entire sample and gender-specific subsamples. Several potentially important genomic regions that may harbour QTLs important for TBFM and TBLM were identified. For example, 20p12-11 achieved a LOD score of 2·04 in the entire sample and, in the male subsample, two genomic regions, 20p12 (LOD=2·08) and 3p26-25 (LOD=1·92), showed suggestive linkage. In addition, two-point linkage analyses for chromosome X showed suggestive linkages on Xp22 in the entire sample (LOD=2·14) and significant linkage on Xp22 in the female subsample (LOD=3·05). Complete pleiotropy was suggested for 20p12 and 3p26-25 in males. Our results suggest that QTLs on chromosomes 20p12, 3p26-25 and Xp22 may jointly influence TBFM and TBLM. Further fine mapping and gene identification studies for these pleiotropic effects are needed.
The construction of the sorghum (Sorghum bicolor L. Moench) molecular genetic linkage map started in the early 1990s. Molecular genetic maps with a high density of markers covering almost the entire sorghum genome have been completed and integration of a sorghum genetic and physical map is under way. The correlation between genetic linkage groups and relevant chromosomes was established and the locations of the important structures of chromosomes, such as centromeres, long and short arms, nucleolus organizer region (NOR), etc., have been identified on the linkage groups. Molecular cytogenetic mapping of each chromosome has been advanced substantially. With continuing progress in the field, sequencing of the full sorghum genome and study of sorghum functional genomics will be initiated soon.
We investigate the contact of bottom-contact pentacene-based thin-film transistors, with Au source/drain electrode. By separating the voltage drop at the contact from the source-drain voltage, the current-voltage characteristic of the injection contact is obtained. The contact characteristics are in a good agreement with a model of carrier injection from a metal electrode into a disordered hopping system.
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