The selective δ‐C(sp3)−H acetoxylation of N‐(SO2Py)‐protected amino acid derivatives has been accomplished by using palladium‐catalysis and PhI(OAc)2 (PIDA) as both terminal oxidant and acetoxy ...source. The distinct structural and electronic features of the SO2Py compared to more traditional carbonyl‐based directing groups is essential to override the otherwise more favourable competitive intramolecular C−H amination. The δ‐site selectivity predominates over traditionally more favorable 5‐membered cyclopalladation at competitive γ‐CH2. Experimental and DFT mechanistic studies provide important insights about the mechanism and the underlying factors controlling the chemo‐ and regioselectivity.
Selective δ‐C(sp3)−H acetoxylation of amino acid derivatives has been achieved by using palladium‐catalysis and PhI(OAc)2 (PIDA) as terminal oxidant and acetoxy source. The N‐SO2Py protecting/directing group plays a key role in enabling control of chemoselectivity (intermolecular C−O over intramolecular C−N bond formation) and regioselectivity (favoring δ‐CH3 over γ‐CH2 activation).
Herein, we report a protocol for the selective δ‐thiolation of aliphatic α‐amino acids catalyzed by a Pd(II)/Ag(I) system. This reaction employs disulfides as thiolating agents and N‐COPy as ...directing group, providing valuable non‐proteinogenic amino acid derivatives in moderate to good diastereoselectivities and yields. Remarkably, the method is also suitable for the late‐stage functionalization of a dipeptide. Experimental and DFT studies have provided significant insights into the mechanism and underlying factors controlling the selectivity of the process and determining the key role of the silver salt.
A light‐controlled method for cell release by means of surface modification with photolabile linkers is presented. This approach is applicable to any material, provided that the linker is properly ...designed, and provides direct control over the molecular interactions involved in cell adhesion.
Background Different risk-based colorectal cancer (CRC) screening strategies, such as the use of polygenic risk scores (PRS), have been evaluated to improve effectiveness of these programs. However, ...few studies have previously assessed its usefulness in a fecal immunochemical test (FIT)-based screening study. Methods A PRS of 133 single nucleotide polymorphisms was assessed for 3619 participants: population controls, screening controls, low-risk lesions (LRL), intermediate-risk (IRL), high-risk (HRL), CRC screening program cases, and clinically diagnosed CRC cases. The PRS was compared between the subset of cases (n = 648; IRL+HRL+CRC) and controls (n = 956; controls+LRL) recruited within a FIT-based screening program. Positive predictive values (PPV), negative predictive values (NPV), and the area under the receiver operating characteristic curve (aROC) were estimated using cross-validation. Results The overall PRS range was 110-156. PRS values increased along the CRC tumorigenesis pathway (Mann-Kendall P value 0.007). Within the screening subset, the PRS ranged 110-151 and was associated with higher risk-lesions and CRC risk (OR.sub.D10vsD1 1.92, 95% CI 1.22-3.03). The cross-validated aROC of the PRS for cases and controls was 0.56 (95% CI 0.53-0.59). Discrimination was equal when restricted to positive FIT (aROC 0.56), but lower among negative FIT (aROC 0.55). The overall PPV among positive FIT was 0.48. PPV were dependent on the number of risk alleles for positive FIT (PPVp10-p90 0.48-0.57). Conclusions PRS plays an important role along the CRC tumorigenesis pathway; however, in practice, its utility to stratify the general population or as a second test after a FIT positive result is still doubtful. Currently, PRS is not able to safely stratify the general population since the improvement on PPV values is scarce. Keywords: Polygenic risk score, Colorectal cancer, Screening, Positive fecal immunochemical test, Positive predictive value, Negative predictive value
The increase in life expectancy and long-lived individuals is a challenge for public health and provides an opportunity to understand the determinants of longevity. However, few studies have ...addressed the factors associated with the health status and quality of life in a long-lived individual population. We described the perceived health, clinical status, quality of life, and dependency for activities of daily living in a representative population in Castile and Leon, Spain.
A sample of 759 long-lived individuals aged 95 years and older was studied by the Health Sentinel Network of Castile and Leon (Spain) through a health examination and a structured questionnaire covering quality of life (EQ-5D-3), lifestyle habits, diet, working life and family health. A blood sample was taken for the study of biological and genetic markers. Chi Square and logistic regression OR with 95% confidence intervals were used to analyze the determinants of the long-lived individuals' health status. The significant level for the bivariate analysis was established at 0.05.
Perceived health was good, very good or excellent in 64.2%, while only 46.0% had a quality-of-life index above 0.5 (ranging from 0 to 1) and 44.1% maintained acceptable independence for activities of daily living. Quality-of-life index was higher in the oldest, (OR 7.98 2,32-27.41) above 100 years compared to those under 98, and men had better values for independence than women (OR 2.43 1.40-4.29). Cardiovascular diseases were the most prevalent (85.5%), but neurological and mental diseases and vision problems had the highest impact on quality of life and independence.
The long-lived individuals of Castile and Leon have a relatively well-preserved health status, although the perception of health is higher than that describing their quality of life and dependence. The quality of life was higher in the oldest age group and showed differences according to sex, with a better quality of life in men. Public health policies and programs should take in account the differences by sex and age as well as the prevention and control of the main conditions related with poor quality of life or dependence. Future research must include the interaction among genetic, socioeconomic, environmental, and other clinical factors in the quality of life and disability of long-lived individuals.
endoscopic submucosal dissection (ESD) in the Western setting remains a challenge. Therefore, other simplified techniques such as knife-assisted snare resection (KAR) have been reported to overcome ...this issue.
patients who underwent an ESD for the treatment of gastrointestinal neoplasms were included in a retrospective cross-sectional observational study. Factors associated with the end of ESD as a salvage p-KAR were identified and a logistic regression model was developed.
a total of 136 lesions in 133 patients were analyzed. Operator experience of under 50 cases and the combination of lesion size > 30 mm and colorectal location were independent predictive factors for switching to a salvage p-KAR according to the multivariate logistic regression analysis. We developed a risk scoring system based on these four variables (experience, size, location and the combination of size and location) with a receiver operating characteristic curve of 0.81 (95% CI: 0.74-0.89). The diagnostic accuracy of the score for a cut-off point ≥ 5 had a sensitivity of 0.79 (95% CI: 0.66-0.93) and a specificity of 0.71 (95% CI: 0.61-0.80).
a simple predictive score system that includes four preoperative factors accurately predicts ESD to finish as a p-KAR. A careful selection of cases considering these variables could be useful to achieve better outcomes in the Western setting.
Purpose
The objective of this study is to analyse the relative survival with breast cancer in women diagnosed after new treatments were generalised and to ascertain the current effect that tumour ...characteristics such as grade, stage or subtype have on survival as well as the new AJCC-pathological prognostic score.
Methods
The breast cancer MCC-Spain follow-up study is a prospective cohort study of 1685 incident breast cancer cases. Women between 20 and 85 years old were recruited between the years 2008 and 2013 in 18 hospitals located in 10 Spanish provinces and they have been followed until 2017/2018. Relative survival was estimated after 3, 5 and 8 years of follow-up using Ederer II method. In addition, Weibull regression adjusted by age, hospital, grade and stage was used to investigate prognosis factors.
Results
Among components of TNM staging system, tumour size greater than 50 mm (i.e. T3 or T4) more than doubled the risk of dying, while N3 nodal involvement and presence of metastasis had a huge effect on mortality. The AJCC pathological prognostic score strongly correlated with survival; thus, hazard ratios increased as the score rose, being 2.31, 4.00, 4.94, 7.92, 2.26, 14.9 and 58.9 for scores IB, IIA, IIB, IIIA, IIIB, IIIC and IV, respectively.
Conclusion
Both TNM staging and histological/molecular biomarkers are associated with overall survival in Spanish women with breast cancer; when both are combined in the AJCC pathological prognosis score, the prognostic value improved with risk indices that increased rapidly as the pathological prognosis score increased
In this paper, we present theoretical Stark widths and shifts calculated corresponding to 66 spectral lines of Sn iv. We use the Griem semi-empirical approach and the cowan computer code. For the ...intermediate coupling calculations, the standard method of least-squares fitting from experimental energy levels was used. Data are presented for an electron density of 1017 cm−3 and temperatures T = 1.1–5.0 (104 K). The matrix elements used in these calculations have been determined from 34 configurations of Sn iv: 4d10
ns(n = 5–10), 4d10
nd(n = 5–8), 4d95s2, 4d95p2, 4d95s5d, 4d85s5p2 and 4d105g for even parity and 4d10
np(n = 5–8), 4d10
nf (n = 4–6), 4d95snp(n = 5–8), 4d85s25p and 4d95snf (n = 4–10) for odd parity. Also, in order to test the matrix elements used in our calculations, we present calculated values of radiative lifetimes of 14 levels of Sn iv. There is good agreement between our calculations and the experimental radiative lifetimes obtained from the bibliography. The spectral lines of Sn iv are observed in UV spectra of HD 149499 B obtained with the Far Ultraviolet Spectroscopic Explorer, the Goddard High Resolution Spectrograph and the International Ultraviolet Explorer. Theoretical trends of the Stark broadening parameter versus the temperature for relevant lines are presented. Also our values of Stark broadening parameters have been compared with the data available in the bibliography.
Background
Self-management (SM) interventions are supportive interventions systematically provided by healthcare professionals, peers, or laypersons to increase the skills and confidence of patients ...in their ability to manage chronic diseases. We had two objectives: (1) to summarise the preferences and experiences of patients and their caregivers (informal caregivers and healthcare professionals) with SM in four chronic diseases and (2) to identify and describe the relevant outcomes for SM interventions from these perspectives.
Methods
We conducted a mixed-methods scoping review of reviews. We searched three databases until December 2020 for quantitative, qualitative, or mixed-methods reviews exploring patients’ and caregivers’ preferences or experiences with SM in type 2 diabetes mellitus (T2DM), obesity, chronic obstructive pulmonary disease (COPD), and heart failure (HF). Quantitative data were narratively synthesised, and qualitative data followed a three-step descriptive thematic synthesis. Identified themes were categorised into outcomes or modifiable factors of SM interventions.
Results
We included 148 reviews covering T2DM (
n
= 53 35.8%), obesity (
n
= 20 13.5%), COPD (
n
= 32 21.6%), HF (
n
= 38 25.7%), and those with more than one disease (
n
= 5 3.4%). We identified 12 main themes. Eight described the process of SM (disease progression, SM behaviours, social support, interaction with healthcare professionals, access to healthcare, costs for patients, culturally defined roles and perceptions, and health knowledge), and four described their experiences with SM interventions (the perceived benefit of the intervention, individualised care, sense of community with peers, and usability of equipment). Most themes and subthemes were categorised as outcomes of SM interventions.
Conclusion
The process of SM shaped the perspectives of patients and their caregivers on SM interventions. Their perspectives were influenced by the perceived benefit of the intervention, the sense of community with peers, the intervention’s usability, and the level of individualised care. Our findings can inform the selection of patient-important outcomes, decision-making processes, including the formulation of recommendations, and the design and implementation of SM interventions.
Background
Missed oesophageal cancer (MEC) at upper gastrointestinal endoscopy (UGE) is poorly documented.
Objective
The objectives of this study were: (1) to assess the rate, predictors and survival ...of MEC; (2) to compare MEC and non-MEC tumours.
Methods
This was a retrospective cohort study conducted at four tertiary centres. Oesophageal cancers (ECs) diagnosed between 2008 and 2015 were included. Patients with a premalignant condition (Barrett, achalasia), prior diagnosis of EC or oesophagogastric junction tumour of gastric origin were excluded. MEC was defined as EC detected within 36 months after negative UGE.
Results
123,395 UGEs were performed during the study period, with 502 ECs being diagnosed (0.4%). A total of 391 ECs were finally included. Overall MEC rate was 6.4% (95% confidence intervals (CI): 4.4–9.3%). The interval between negative and diagnostic UGE was less than 2 years in 84% of the cases. Multivariate analysis showed that a negative endoscopy was associated with proton pump inhibitor (PPI) therapy and less experienced endoscopists. MEC was smaller than non-MEC at diagnosis (25 versus 40 mm, p = 0.021), more often flat or depressed (p = 0.013) and less frequently diagnosed as metastatic disease (p = 0.013). Overall 2-year survival rate was similar for MEC (20%) and non-MEC (24.1%) (p = 0.95).
Conclusions
MEC accounted for 6.4% of all ECs and was associated with poor survival. High-quality UGE and awareness of MEC may help to reduce its incidence.
PDF
