Background & Aims Risk for colorectal cancer (CRC) can be greatly reduced through screening. To aid in the development of screening strategies, we refined models designed to determine risk of CRC by ...incorporating information from common genetic susceptibility loci. Methods By using data collected from more than 12,000 participants in 6 studies performed from 1990 through 2011 in the United States and Germany, we developed risk determination models based on sex, age, family history, genetic risk score (number of risk alleles carried at 27 validated common CRC susceptibility loci), and history of endoscopic examinations. The model was validated using data collected from approximately 1800 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, conducted from 1993 through 2001 in the United States. Results We identified a CRC genetic risk score that independently predicted which patients in the training set would develop CRC. Compared with determination of risk based only on family history, adding the genetic risk score increased the discriminatory accuracy from 0.51 to 0.59 ( P = .0028) for men and from 0.52 to 0.56 ( P = .14) for women. We calculated age- and sex-specific 10-year CRC absolute risk estimates based on the number of risk alleles, family history, and history of endoscopic examinations. A model that included a genetic risk score better determined the recommended starting age for screening in subjects with and without family histories of CRC. The starting age for high-risk men (family history of CRC and genetic risk score, 90%) was 42 years, and for low-risk men (no family history of CRC and genetic risk score, 10%) was 52 years. For men with no family history and a high genetic risk score (90%), the starting age would be 47 years; this is an intermediate value that is 5 years earlier than it would be for men with a genetic risk score of 10%. Similar trends were observed in women. Conclusions By incorporating information on CRC risk alleles, we created a model to determine the risk for CRC more accurately. This model might be used to develop screening and prevention strategies.
Accumulating evidence has suggested that the epithelial–mesenchymal transition (EMT) is a pathway that potentially leads to podocyte depletion and proteinuria in diabetic nephropathy (DN). Therefore, ...this study was designed to investigate the protective effects of forkhead transcription factor O1 (FOXO1) on podocyte EMT, under high-glucose (HG) conditions in vitro and under diabetic conditions in vivo. The results showed that HG-induced podocyte EMT was associated with FOXO1 inactivation, which was accompanied by activation of the transforming growth factor (TGF)-β1/SMAD3/integrin-linked kinase (ILK) pathway. Accordingly, constitutive FOXO1 activation suppressed the TGF-β1/Smad3/ILK pathway and partially reversed EMT, similar to the effects observed after treatment with SIS3 or QLT0267, which are selective inhibitors of TGF-β1-dependent SMAD3 phosphorylation and ILK, respectively. In addition, lentiviral-mediated FOXO1 overexpression in the kidneys of diabetic mice considerably increased FOXO1 expression and activation, while decreasing proteinuria and renal pathological injury. These data suggested that forced FOXO1 activation inhibited HG-induced podocyte EMT and ameliorated proteinuria and renal injury in diabetic mice. Our findings further highlighted that FOXO1 played a protective role against diabetes in mice and may potentially be used as a novel therapeutic target for treating diabetic nephropathy.
Primary caregivers of children with type 1 diabetes mellitus (T1DM) are prone to negative emotions. This study explored the anxiety status of the caregivers and analyzed the related factors. In this ...prospective study, 245 primary caregivers of T1DM children who were reexamined in the outpatient clinic of Children’s Hospital affiliated to Zhengzhou University between April 2020 and Sep 2022 were surveyed with a questionnaire and the Hamilton Anxiety Rating Scale (HAMA). The detection rate of anxiety symptoms in T1DM primary caregivers was 21.2%, with a total score of HAMA score of 11.74 ± 2.50. There were significant differences between the anxiety and non-anxiety groups in treatment method, HbA1C to standard (≤7.0%), severe hypoglycemia in the last 1 year and the number of adolescent cases (χ2 = 15.798, p = 0.000; χ2 = 4.197, p = 0.040; χ2 = 5.291, p = 0.021; χ2 = 14.279, p = 0.000). Multivariable logistic regression analysis showed that insulin pump treatment, HbA1C to standard (≤7.0%) and adolescence were associated with anxiety in primary caregivers (OR = 4.040, 95%CI 1.969–8.289, p = 0.000; OR = 0.472, 95%CI 0.237–0.955, p = 0.037; OR = 2.952, 95%CI 1.495–5.831, p = 0.002). Pediatric endocrine care should pay more attention to the anxiety of the caregivers of adolescent T1DM children treated with insulin pumps while helping the children manage their disease.
The accumulation of plastic wastes in landfills and the environment threatens our environment and public health, while leading to the loss of potential carbon resources. The urgent necessary lies in ...developing an energy‐saving and environmentally benign approach to upgrade plastic into value‐added chemicals. Artificial photosynthesis holds the ability to realize plastic upcycling by using endless solar energy under mild conditions, but remains in the initial stage for plastic upgrading. In this review, we aim to look critically at the photocatalytic conversion of plastic wastes from the perspective of resource reutilization. To begin with, we present the emerging conversion routes for plastic wastes and highlight the advantages of artificial photosynthesis for processing plastic wastes. By parsing photocatalytic plastic conversion process, we demonstrate the currently available routes for processing plastic, including plastic photodegradation, tandem decomposition of plastic and CO2 reduction, selective plastic oxidation, as well as photoreforming of plastic. This review concludes with a personal perspective for potential advances and emerging challenges in photocatalytic plastic conversion.
Artificial photosynthesis offers an efficient approach towards plastic disposal under mild conditions, while contributing to the utilization of the carbon resource in plastic wastes via the conversion from plastics to value‐added products. Moreover, the pathway to obtain the desired chemicals can be easily tuned via rational design of high‐performance photocatalytic systems.
Background and aims
Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer and is associated with an increased lifetime risk of gastric and duodenal cancers of 8–16% and 7%, ...respectively; therefore, we aim to describe an esophagogastroduodenoscopy (EGD) surveillance program for upper gastrointestinal (GI) precursor lesions and cancer in LS patients.
Methods
Patients who either had positive genetic testing or met clinical criteria for LS who had a surveillance EGD at our institution from 1996 to 2017 were identified. Patients were included if they had at least two EGDs or an upper GI cancer detected on the first surveillance EGD. EGD and pathology reports were extracted manually.
Results
Our cohort included 247 patients with a mean age of 47.1 years (SD 12.6) at first EGD. Patients had a mean of 3.5 EGDs (range 1–16). Mean duration of follow-up was 5.7 years. Average interval between EGDs was 2.3 years. Surveillance EGD detected precursor lesions in 8 (3.2%) patients, two (0.8%) gastric cancers and two (0.8%) duodenal cancers. Two interval cancers were diagnosed: a duodenal adenocarcinoma was detected 2 years, 8 months after prior EGD and a jejunal adenocarcinoma was detected 1 year, 9 months after prior EGD.
Conclusions
Our data suggest that surveillance EGD is a useful tool to help detect precancerous and cancerous upper GI lesions in LS patients. To our knowledge, this is the first study to examine a program of surveillance EGDs in LS patients. More data are needed to determine the appropriate surveillance interval.
Purpose
The aim of this study is to describe the demographics and clinical features of patients with young onset (YO) CRC.
Methods
A retrospective review of patients with CRC diagnosed between ages ...20 and 49 years was evaluated at the Memorial Sloan Kettering Cancer Center from 1/2004 to 6/2019. We excluded those with a hereditary CRC syndrome, inflammatory bowel disease, or prior CRC diagnosis.
Patient demographics; presenting symptoms; medical, surgical, and smoking history; family history of cancer; tumor characteristics; and pathology were obtained from the electronic medical record.
Results
We identified 3856 YO CRC patients (median age CRC diagnosis 43; 52.5% male). A total of 59.1% were overweight or obese (32.2% and 26.9%, respectively). Most (90.1%) had no family history of CRC in a first-degree relative; 56.3% of patients reported being never smokers; 5.2% had diabetes. The most common presenting symptoms were rectal bleeding (47.7%), abdominal pain/bloating (33.1%), and change in bowel habits (24.7%). The majority presented with left-sided cancers (77.3%), at late-stage disease (68.4% at stages 3 or 4).
Conclusion
Most YO CRC patients presented with rectal bleeding or abdominal pain, left-sided cancers, and later-stage disease and had no family history of CRC in a first-degree relative. Over half were overweight and obese and were more likely to have never smoked. More data are needed to better understand YO CRC risk factors and to help identify high-risk populations who may benefit from earlier screening.
Recently near-ground remote sensing using unmanned aerial vehicles (UAV) witnessed wide applications in obtaining field information. In this research, four Rapideye satellite images and eight RGB ...images acquired from UAV were used from early June to the end of July, 2015 covering two experimental winter wheat fields, in order to monitor wheat canopy growth status and analyze the correlation among satellite images based normalized difference vegetation index (NDVI) with UAV's RGB images based visible-band difference vegetation index (VDVI) and ground variables of the sampled grain protein contents. Firstly, through image interpretation of UAV's multi-temporal RGB images with fine spatial resolution, the wheat canopy color changes could be intuitively and clearly monitored. Subsequently, by monitoring the changes of satellite images based NDVI as well as VDVI values and UAV's RGB images based VDVI values, the conclusions were made that these three vegetation indices demonstrated the same and synchronized trend of increasing at the early stage of wheat growth season, reaching up to peak values at the same timing, and starting to decrease since then. The results of the correlation analysis between NDVI of satellite images and sampled grain protein contents show that NDVI has good predicative capability for mapping grain protein content before ripening growth stage around June7, 2015, while the reliability of using satellite image based NDVI to predict grain protein contents becomes worse as ripening stage approaches. The regression analysis between UAV's RGB image based VDVI and satellite image based VDVI as well as NDVI showed good coefficients of determination. It is concluded that it is feasible and practical to temporally complement satellite remote sensing by using UAV's RGB images based vegetation indices to monitor wheat growth status and to map within-field spatial variations of grain protein contents for small scale farmlands.
Endometrial cancer (EC) incidence is on the rise. Although early-onset endometrial cancer (EOEC; age at diagnosis <50 years) is relatively uncommon, the incidence of EOEC has been reportedly ...increasing in recent decades. However, the rising EOEC has not been thoroughly described with regard to the racial and ethnic disparities and compared with late-onset EC (age at diagnosis ≥50 years). We used the Cancer in North America (CiNA) Analytic File, 1995-2018, from the North American Association of Central Cancer Registries, which allowed us to examine trends in invasive EC incidence by racial and ethnic groups and by age at diagnosis. We found striking differences for demographic and tumor characteristics as well as racial and ethnic patterns and time trends in EC incidence between EOEC and late-onset EC. The faster increases in EOEC incidence rates, especially among non-White women, mirror similar observations in other cancers, pointing to a possible link with rising obesity epidemic in younger generations.
The qualitative analysis of a three-species reaction-diffusion model with a modified Leslie-Gower scheme under the Neumann boundary condition is obtained. The existence and the stability of the ...constant solutions for the ODE system and PDE system are discussed, respectively. And then, the priori estimates of positive steady states are given by the maximum principle and Harnack inequality. Moreover, the nonexistence of nonconstant positive steady states is derived by using Poincaré inequality. Finally, the existence of nonconstant positive steady states is established based on the Leray-Schauder degree theory.
Background
Dissection of the regulatory pathways that control skeletal muscle development and atrophy is important for the treatment of muscle wasting. Long noncoding RNA (lncRNA) play important ...roles in various stages of muscle development. We previously reported that Synaptopodin‐2 (SYNPO2) intron sense‐overlapping lncRNA (SYISL) regulates myogenesis through an interaction with enhancer of zeste homologue 2 (EZH2). However, it remains unclear whether SYISL homologues exist in humans and pigs, and whether the functions and mechanisms of these homologues are conserved among species.
Methods
Bioinformatics, cell fractionation, and quantitative real‐time polymerase chain reaction (qRT‐PCR) analyses were used for the identification and molecular characterization of SYISL homologues in humans and pigs. Effects on myogenesis and muscle atrophy were determined via loss‐of‐function or gain‐of‐function experiments using C2C12 myoblasts, myogenic progenitor cells, dexamethasone (DEX), and aging‐induced muscle atrophy models. RNA pulldown, RNA immunoprecipitation, dual luciferase reporting, and co‐transfection experiments were used to explore the mechanisms of SYISL interactions with proteins and miRNAs.
Results
We identified SYISL homologues in humans (designated hSYISL) and pigs (designated pSYISL). Functional experiments demonstrated that hSYISL and pSYISL regulate myogenesis through interactions with EZH2. Interestingly, we showed that SYISL functions to regulate muscle atrophy and sarcopenia through comparative analysis. SYISL is significantly up‐regulated after muscle atrophy (P < 0.01); it significantly promotes muscle atrophy in DEX‐induced muscle atrophy models (P < 0.01). SYISL knockdown or knockout alleviates muscle atrophy and sarcopenia in DEX‐induced and aged mice. The tibialis anterior (TA) muscle weight of 3‐month‐old wild‐type (WT) mice decreased by 33.24% after DEX treatment (P < 0.001), while the muscle weight loss of 3‐month‐old SYISL knockout mice was only 18.20% after DEX treatment (P < 0.001). SYISL knockout in 18‐month‐old WT mice significantly increased the weights of quadriceps (Qu), gastrocnemius (Gas), and TA muscles by 10.45% (P < 0.05), 13.95% (P < 0.01), and 24.82% (P < 0.05), respectively. Mechanistically, SYISL increases the expression levels of the muscle atrophy genes forkhead box protein O3a (FoxO3a), muscle ring finger 1 (MuRF1), and muscle atrophy‐related F‐box (Atrogin‐1) via sponging of miR‐23a‐3p/miR‐103‐3p/miR‐205‐5p and thus promotes muscle atrophy. Additionally, we verified that human SYISL overexpression in muscles of 18‐month‐old WT mice significantly decreased the weights of Gas, Qu, and TA muscles by 7.76% (P < 0.01), 12.26% (P < 0.05), and 13.44% (P < 0.01), respectively, and accelerates muscle atrophy through conserved mechanisms.
Conclusions
Our results identify SYISL as a conserved lncRNA that modulates myogenesis in mice, pigs, and humans. We also demonstrated its previously unknown ability to promote muscle atrophy.
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