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Purpose: To adapt the Rotator Cuff Quality of Life (RC-QOL) questionnaire into traditional Chinese (Chi-RC-QOL) and to evaluate the validity and reliability in patients suffering from rotator cuff pathologies in Hong Kong. Methods: The Chi-RC-QOL will be constructed using the forward-translation followed by the backward-translation method. Thirty consecutive patients with clinically and radiologically confirmed rotator cuff pathology were recruited. Descriptive statistics will be followed by validity assessment using comparison with the Constant Shoulder (CS) score, University of California Los Angeles (UCLA) Shoulder Rating Scale, and Western Ontario Rotator Cuff (WORC) score. Parametric data will be tested using Pearson's correlation coefficient for the total scores. Reliability was assessed using a test–retest interval of 30 min. The Cronbach's α and intraclass correlation coefficient were calculated. Results: Cronbach's α and internal consistency scores were high for all parts of the Chi-RC-QOL, with Cronbach's α ranging between 0.89 and 0.98. Internal consistency scores range from 0.82 to 0.92, which can be regarded as an excellent correlation. Test–retest reliability was excellent for all parts of the Chi-RC-QOL with good absolute reliability. Chi-RC-QOL correlates well with the CS score, UCLA Shoulder Rating Scale, and the WORC score, with all being statistically significant. Conclusions: The current study adapted the RC-QOL to traditional Chinese version. The analysis confirmed the validity and reliability of the Chi-RC-QOL questionnaire. Level of Evidence: III. [ABSTRACT FROM AUTHOR]

Unlabelled: INTRODUCTION (PURPOSE OF THE STUDY): The objective of this study was to assess whether dual-time-point (18)F-fluoro-2-deoxyglucose ((18)F-FDG)-PET/CT imaging improved the evaluation of suspected malignancy and if there was any resulting change in management. Methods: A total of 53 patients with suspected malignancy were investigated by performing two static acquisitions started at mean times t = 64 and t = 155 min after the tracer injection. The total number of malignant lesions was 133 and the total number of benign lesions was 61. Visual and semiquantitative analysis was performed on both the early and delayed images. Results: Overall, there was a significant improvement (P < 0.001) in the sensitivity of delayed imaging (94%) compared with early imaging (77%) in detecting malignant lesions, without a reduction in specificity. In 10 patients, 13 malignant lesions were undetected on early imaging alone but detected on delayed imaging. In seven patients, 10 malignant lesions were incorrectly classified as 'likely benign' on early imaging but correctly reported as 'likely malignant' on delayed imaging. Management was altered in 2 out of 17 patients. Overall, delayed imaging altered management in 2 out of 53 studied patients. Dual-time-point (18)FDG-PET/CT imaging was useful in differentiating malignant from benign intra-abdominal lesions but did not improve the evaluation of pulmonary lesions. Conclusions: (18)F-FDG-PET/CT imaging should be performed as late as reasonably possible after tracer administration in order to increase tumour-to-background contrast and thereby improve the sensitivity of demonstrating additional sites of disease. Dual-time-point (18)FDG-PET/CT may be of benefit in the evaluation of intra-abdominal lesions but does not improve the overall evaluation of pulmonary lesions. [ABSTRACT FROM AUTHOR]

Eliza Lai Yi Wong1, Jean Woo2, Elsie Hui3, Carrie Chan2, Wayne LS Chan2, Annie Wai Ling Cheung11School of Public Health and Primary Care, The Chinese University of Hong Kong, 2School of Public Health and Primary Care, Division of Geriatrics, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, 3Medical and Geriatric Unit, Shatin Hospital, HK SAR, Hong Kong, People’s Republic of ChinaBackground: Care of diabetes mellitus in the elderly requires an additional perspective to take into account impaired cognitive function, physical function, low level of education, and difficulty making lifestyle changes. Existing services tend to be driven by the views of tertiary and secondary care staff, rather than those of primary care staff and elderly patients. This study aimed to explore the attitudes and preferences of elderly patients with diabetes mellitus towards primary care (clinical care and community program).Method: Elderly patients with diabetes mellitus aged 60 years or above were recruited from governmental diabetes mellitus clinics and diabetes mellitus specific community centers. Three focus group discussions of 14 diabetic elderly patients were conducted and their perspectives on the new service model were assessed. Participants were interviewed according to an open-ended discussion guide which includes the following items: comments on existing clinic follow up and community program, motivation for joining the community program, and suggestions on further clinical services and community service program development.Results: Incapability of the current health service to address their special needs was a common concern in three focus group discussions. The majority highlighted the benefits of the new service program, that is, self-care knowledge and skill, attitudes to living with diabetes mellitus, and supportive network. Key facilitators included experiential learning, a group discussion platform, and goal setting with patients.Conclusions: This study is the first qualitative study to explore the views of elderly diabetic patients’ on their self-care needs. Elderly people with diabetes mellitus in this study identified bad experiences of clinical follow-up; benefit from the community program; and recommendations for the future development of primary care. Study findings revealed a number of discrepancies between elderly diabetic patients’ needs and existing health services in Hong Kong. The study findings provide health practitioners, researchers and educators with an additional perspective on the provision of quality of care for elderly diabetic patients in the community.Keywords: primary care, diabetes, self-care

Recently, owing to their special spatial structures, peptide-based macrocycles have shown tremendous promise and aroused great interest in multidisciplinary research ranging from potent antibiotics against resistant strains to functional biomaterials with novel properties. Besides traditional monocyclic peptides, many fascinating polycyclic and remarkable higher-order cyclic, spherical and cylindric peptidic systems have come into the limelight owing to breakthroughs in various chemical ( e.g. , native chemical ligation and transition metal catalysis), biological ( e.g. , post-translational enzymatic modification and genetic code reprogramming), and supramolecular ( e.g. , mechanically interlocked, metal-directed folding and self-assembly via noncovalent interactions) macrocyclization strategies developed in recent decades. In this tutorial review, diverse state-of-the-art macrocyclization methodologies and techniques for peptides and peptidomimetics are surveyed and discussed, with insights into their practical advantages and intrinsic limitations. Finally, the synthetic-technical aspects, current unresolved challenges, and outlook of this field are discussed.

Background: Sarcopenia or skeletal muscle depletion is a poor prognostic factor for gastric cancer (GC). However, existing cutoff values of skeletal muscle index (SMI) for defining sarcopenia have been found to have limitations when clinically applied. This study aimed to determine the optimal cutoff for SMI to predict severe toxicities of chemotherapy and overall survival (OS) in patients with advanced GC., Methods: Patients with metastatic gastric adenocarcinoma who received first-line palliative chemotherapy between January 2014 and December 2021 at Queen Mary Hospital, Hong Kong, were included in this study. The SMI was determined via a pre-chemotherapy computed tomography scan. Optimal cutoff points of SMI were identified by recursive partitioning analysis. Univariate and multivariate analyses evaluating risk factors of severe chemotherapy toxicities and OS were also performed., Results: A total of 158 patients (male: 108 (68.4%), median age: 65.3) were included. The SMI cutoff to define low SMI was ≤33 cm2/m2 for males and ≤28 cm2/m2 for females; 30 patients (19.0%) had low SMI. Patients with low SMI had a higher incidence of hematological toxicities (63.3% vs 32.0%, P = .001) and non-hematological toxicities (66.7% vs 36.7%, P = .003). Multivariable analysis indicated that low SMI and low serum albumin (≤28 g/L) were independent predictive factors of hematological toxicity, while low SMI and neutrophil-lymphocyte ratio ≥5 were predictive factors of non-hematological toxicity. Moreover, patients with low SMI had a significantly shorter OS (P = .011), lower response rate to chemotherapy (P = .045), and lower utilization of subsequent lines of treatment (P < .001)., Conclusions: Using pre-chemotherapy SMI cutoff (≤33 cm2/m2 for males and 28 cm2/m2 for females) one can identify individuals with a higher risk of severe chemotherapy toxicities and worse prognosis., (© The Author(s) 2024. Published by Oxford University Press.)

Background and Aim: LIVERSTAT is an artificial intelligence-based noninvasive test devised to screen for and provide risk stratification for metabolic dysfunction-associated fatty liver disease (MAFLD) by using simple blood biomarkers and anthropometric measurements. We aimed to study LIVERSTAT in patients with MAFLD and to explore its role for the diagnosis of advanced fibrosis., Methods: This is a retrospective study of data from MAFLD patients who underwent a liver biopsy. Patients with type 2 diabetes who underwent transient elastography and had liver stiffness measurement (LSM) < 5 kPa were included as patients with no fibrosis. Among these patients, controlled attenuation parameter <248 dB/m was considered as no steatosis. The LIVERSTAT results were generated based on a proprietary algorithm, blinded to the histological and LSM data., Results: The data for 350 patients were analyzed (mean age 53 years, 45% male, advanced fibrosis 22%). The sensitivity, specificity, positive predictive value, negative predictive value, and misclassification rate of LIVERSTAT to diagnose advanced fibrosis were 90%, 50%, 30%, 95%, and 42%, respectively. The corresponding rates for Fibrosis-4 score (FIB4) were 56%, 83%, 44%, 89%, and 22%, respectively. When LSM was used as a second test, the corresponding rates for LIVERSTAT were 60%, 97%, 76%, 94%, and 8%, respectively, while the corresponding rates for FIB4 were 38%, 99%, 83%, 89%, and 11%, respectively., Conclusion: LIVERSTAT had a higher negative predictive value compared with FIB4 and a lower misclassification rate compared with FIB4 when used in a two-step approach in combination with LSM for the diagnosis of advanced fibrosis., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Paleoclimate model simulations provide reference data to help interpret the geological record and offer a unique opportunity to evaluate the performance of current models under diverse boundary conditions. Here, we present a dataset of 35 climate model simulations of the warm early Eocene Climatic Optimum (EECO; ~ 50 million years ago) and corresponding preindustrial reference experiments. To streamline the use of the data, we apply standardised naming conventions and quality checks across eight modelling groups that have carried out coordinated simulations as part of the Deep-Time Model Intercomparison Project (DeepMIP). Gridded model fields can be downloaded from an online repository or accessed through a new web application that provides interactive data exploration. Local model data can be extracted in CSV format or visualised online for streamlined model-data comparisons. Additionally, processing and visualisation code templates may serve as a starting point for advanced analysis. The dataset and online platform aim to simplify accessing and handling complex data, prevent common processing issues, and facilitate the sharing of climate model data across disciplines., (© 2024. The Author(s).)

GORAB is a key regulator of Golgi vesicle transport and protein glycanation. Loss of GORAB function in gerodermia osteodysplastica (GO) causes shortening of glycosaminoglycan chains, leading to extracellular matrix disorganization that results in wrinkled skin, osteoporosis and elevated TGF-β signaling. In this study, we investigated the role of TGF-β-signaling, oxidative stress, and resulting cellular senescence in the osteoporosis phenotype of GO. Treatment of Gorab Prx1 conditional knockouts with the TGF-β neutralizing antibody 1D11 rescued the trabecular bone loss, indicating that TGF-β overactivation causes osteoporosis in GO. Using an inducible knockout system, we demonstrated that TGF-β dysregulation was not a cell-intrinsic effect of GORAB inactivation, but a consequence of a disorganized extracellular matrix. Enhanced TGF-β signaling caused elevated Nox4 expression in Gorab Prx1 mutants and in GO patients' fibroblasts, resulting in overproduction of mitochondrial superoxide. The resulting oxidative stress was detected in GORAB null cells and also in wildtype bystander cells. The same effect was observed in zebrafish after TALEN-mediated gorab inactivation, indicating that the pathway is evolutionarily conserved. Treating Gorab Prx1 mutants with the antioxidant N-acetylcysteine ameliorated the osteoporosis phenotype. TGF-β induced oxidative stress coincided with accumulation of DNA damage and elevated expression of senescence markers. Inactivation of Cdkn2a in the Gorab Prx1 rescued the osteoporosis phenotype. Reduced colony formation and altered subpopulations of bone marrow stromal cells were normalized upon inactivation of Cdkn2a, thus further demonstrating the relevance of cellular senescence in the pathogenesis. Our results shed light on the causative role of a TGF-β-Nox4-senescence axis and therapeutic strategies for GO., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

Competing Interests: None declared.

The moiré potential in rotationally misfit two-dimensional (2D) heterostructures has been used to build artificial exciton and electron lattices, which have become platforms for realizing exotic electronic phases. Here, we demonstrate a different approach to create a superlattice potential in 2D crystals by using the near field of an array of polar molecules. A bilayer of titanyl phthalocyanine (TiOPc), consisting of alternating out-of-plane dipoles, is deposited on monolayer MoS 2 . Time-resolved two-photon photoemission spectroscopy reveals a pair of interlayer exciton states with an energy difference of ∼0.1 eV, which is consistent with the electrostatic potential modulation induced by the TiOPc bilayer as determined by density functional theory calculations. Because the symmetry and the period of this potential superlattice can be changed readily by using molecules of different shapes and sizes, molecule/2D heterostructures can be promising platforms for designing artificial exciton and electron lattices.

Organic photovoltaics (OPVs) based on non-fullerene acceptors (NFAs) have achieved a power conversion efficiency close to 20%. These NFA OPVs can generate free carriers efficiently despite a very small energy level offset at the donor/acceptor interface. Why these NFAs can enable efficient charge separation (CS) with low energy losses remains an open question. Here, the CS process in the PM6:Y6 bulk heterojunction is probed by time-resolved two-photon photoemission spectroscopy. It is found that the CS, the conversion from bound charge transfer (CT) excitons to free carriers, is an endothermic process with an enthalpy barrier of 0.15 eV. The CS can occur spontaneously despite being an endothermic process, which implies that it is driven by entropy. It is further argued that the morphology of the PM6:Y6 film and the anisotropic electron delocalization restrict the electron and hole wavefunctions within the CT exciton such that they can primarily contact each other through point-like junctions. This configuration can maximize the entropic driving force., (© 2024 Wiley‐VCH GmbH.)

We investigate the properties of ultrathin 3,4,9,10-perylenetetracarboxylic diimide (PTCDI) films using a combination of tip-enhanced photoluminescence and unsupervised machine learning. We expose nanoscale spectral heterogeneities that can be understood on the basis of the interplay between vibronic effects, intermolecular excitons, and intramolecular excitons in PTDCI films.

Objectives: To examine the diagnostic performance of the FRAIL Scale for frailty screening with reference to the Fried phenotype and investigate its association with health outcomes in older cancer survivors., Data Source: In this cross-sectional quantitative study, participants were post-treatment cancer survivors aged 65 or above. Measurements included the FRAIL Scale, Fried phenotype, Geriatric Depression Scale-15 item, Modified Barthel Inventory, and EORTC Core Quality of Life Questionnaire. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of the FRAIL Scale with reference to the Fried phenotype. Health outcomes associated with being frail as estimated by the FRAIL Scale and Fried phenotype were also examined using regressions., Results: Based on 293 older cancer survivors, the area under curve (AUC) of the FRAIL Scale was 0.79, and the optimal cut-off of 1 yielded a sensitivity of 92% and specificity of 41%. According to regression results, the FRAIL Scale was modified by adding an item on time since cancer treatment completion (AUC = 0.81), and using a cut-off of 2 for older cancer survivors, which yielded a sensitivity of 74% and specificity of 67%. The modified FRAIL Scale was associated with depressive symptoms, functional independence, fatigue, dyspnea, physical functioning, and role functioning., Conclusions: The modified FRAIL Scale is proposed for use in older cancer survivors, and a cut-off of 2 should be used., Implications for Nursing Practice: The modified FRAIL Scale can serve as a brief screening tool for identifying frailty among older cancer survivors in practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Despite the large binding energy of charge transfer (CT) excitons in type-II organic/2D heterostructures, it has been demonstrated that free carriers can be generated from CT excitons with a long lifetime. Using a model fluorinated zine phthalocyanine (F 8 ZnPc)/monolayer-WS 2 interface, we find that CT excitons can dissociate spontaneously into free carriers despite it being an enthalpy-uphill process. Specifically, it is observed that CT excitons can gain an energy of 250 meV in 50 ps and dissociate into free carriers without any applied electric field. This observation is surprising because excited electrons typically lose energy to the environment and relax to lower energy states. We hypothesize that this abnormal enthalpy-uphill CT exciton dissociation process is driven by entropy gain. Kinetically, the entropic driving force can also reduce the rate for the reverse process - the conversion of free electron-hole pairs back to CT excitons. Hence, this mechanism can potentially explain the very long carrier lifetime observed in organic/2D heterostructures.

Purpose: This study aimed (1) to estimate the prevalence of cognitive frailty, (2) to identify factors associated with cognitive frailty and (3) to examine the association of cognitive frailty with health-related quality of life (HRQOL) in older cancer survivors., Methods: This was a cross-sectional study. Participants were aged 65 or above, diagnosed with cancer and had completed cancer treatment. Measures on physical frailty, cognitive functioning and HRQOL were administered. Multiple linear regression models were used to examine the association of cognitive frailty with HRQOL., Results: Among 293 recruited participants, 18.8% had a cognitive functioning decline, 8.9% were physically frail and 8.2% were cognitively frail. Regular exercise (OR = 0.383, p = .035) and shorter time since treatment completion were associated with less likelihood of cognitive frailty (OR = 1.004, p = .045). Cognitive frailty was significantly associated with global health status (β = -0.116; p = .044), physical functioning (β = -0.177; p = .002), social functioning (β = -0.123; p = .035) and fatigue symptoms (β = 0.212; p < .001) after adjusting for potential confounding variables., Conclusions: Cognitive frailty, found in 8.2% of older cancer survivors, is associated with various dimensions of HRQOL. Longitudinal research examining the trajectory and impact of cognitive frailty on more diverse health outcomes in older cancer survivors is warranted. The findings improve service providers' knowledge of cognitive frailty in older cancer survivors and inform surveillance and care for geriatric cancer survivorship., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Aims: Type 2 diabetes (T2D) and chronic hepatitis B infection (CHB) are risk factors of HCC. Sodium glucose co-transporter 2 inhibitors (SGLT2i) inhibit HCC oncogenesis in preclinical studies. However, clinical studies are lacking. This study aimed to evaluate the impact of SGLT2i use on incident HCC using a territory-wide cohort of exclusively patients with co-existing T2D and CHB., Approach and Results: Patients with co-existing T2D and CHB between 2015 and 2020 were identified from the representative electronic database of the Hong Kong Hospital Authority. Patients with and without SGLT2i use were 1:1 matched by propensity score for their demographics, biochemistry results, liver-related characteristics, and background medications. Cox proportional hazards regression model was used to assess the association between SGLT2i use and incident HCC. A total of 2,000 patients with co-existing T2D and CHB (1,000 in each SGLT2i and non-SGLT2i group; 79.7% on anti-HBV therapy at baseline) were included after propensity-score matching. Over a follow-up of 3,704 person-years, the incidence rates of HCC were 1.39 and 2.52 cases per 100 person-year in SGLT2i and non-SGLT2i groups, respectively. SGLT2i use was associated with a significantly lower risk of incident HCC (HR 0.54, 95%CI: 0.33-0.88, p =0.013). The association remained similar regardless of sex, age, glycemic control, diabetes duration, presence of cirrhosis and hepatic steatosis, timing of anti-HBV therapy, and background antidiabetic agents including dipeptidyl peptidase-4 inhibitors, insulin, or glitazones (all p interaction>0.05)., Conclusions: Among patients with co-existing T2D and CHB, SGLT2i use was associated with a lower risk of incident HCC., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Mouse models are a critical tool for studying human diseases, particularly developmental disorders 1 . However, conventional approaches for phenotyping may fail to detect subtle defects throughout the developing mouse 2 . Here we set out to establish single-cell RNA sequencing of the whole embryo as a scalable platform for the systematic phenotyping of mouse genetic models. We applied combinatorial indexing-based single-cell RNA sequencing 3 to profile 101 embryos of 22 mutant and 4 wild-type genotypes at embryonic day 13.5, altogether profiling more than 1.6 million nuclei. The 22 mutants represent a range of anticipated phenotypic severities, from established multisystem disorders to deletions of individual regulatory regions 4,5 . We developed and applied several analytical frameworks for detecting differences in composition and/or gene expression across 52 cell types or trajectories. Some mutants exhibit changes in dozens of trajectories whereas others exhibit changes in only a few cell types. We also identify differences between widely used wild-type strains, compare phenotyping of gain- versus loss-of-function mutants and characterize deletions of topological associating domain boundaries. Notably, some changes are shared among mutants, suggesting that developmental pleiotropy might be 'decomposable' through further scaling of this approach. Overall, our findings show how single-cell profiling of whole embryos can enable the systematic molecular and cellular phenotypic characterization of mouse mutants with unprecedented breadth and resolution., (© 2023. The Author(s).)

Aromatase inhibitors (Ais) are used as adjuvant endocrine therapy for oestrogen receptor-positive (ER+ve) post-menopausal breast cancer patients. Ais, by inhibiting the enzyme aromatase, block the conversion of androgen to oestrogen, reducing oestrogen levels. Resistance to Ais limits their clinical utilisation. Here, we show that overexpression of BQ323636.1 (BQ), a novel splice variant of nuclear co-repressor NCOR2, is associated with resistance to the non-steroidal aromatase inhibitor anastrozole in ER+ve post-menopausal breast cancer. Mechanistic study indicates that BQ overexpression enhances androgen receptor (AR) activity and in the presence of anastrozole, causes hyper-activation of AR signalling, which unexpectedly enhanced cell proliferation, through increased expression of CDK2, CDK4, and CCNE1. BQ overexpression reverses the effect of anastrozole in ER+ve breast cancer in an AR-dependent manner, whilst co-treatment with the AR antagonist bicalutamide recovered its therapeutic effect both in vitro and in vivo. Thus, for BQ-overexpressing breast cancer, targeting AR can combat anastrozole resistance. Clinical study of 268 primary breast cancer samples of ER+ve patients who had been treated with non-steroidal Ais showed 32.5% (38/117) of cases with combined high nuclear expression of BQ and AR, which were found to be significantly associated with Ai resistance. Non-steroidal Ai-treated patients with high nuclear expression of both BQ and AR had poorer overall, disease-specific, and disease-free survival. These findings suggest the importance of assessing BQ and AR expression status in the primary ER+ve breast tumour prior to Ai treatment. This may save patients from inappropriate treatment and enable effective therapy to be given at an early stage. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)