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One sixth of human cancers harbor pathogenic germline variants, but few studies have established their functional contribution to cancer outcomes. Here, we developed a humanized mouse model harboring a common East Asian polymorphism, the BIM deletion polymorphism (BDP), which confers resistance to oncogenic kinase inhibitors through generation of non-apoptotic splice isoforms. However, despite its clear role in mediating bulk resistance in patients, the BDP's role in cancer stem and progenitor cells, which initiate disease and possess altered BCL-2 rheostats compared to differentiated tumor cells, remains unknown. To study the role of the BDP in leukemia initiation, we crossed the BDP mouse into a chronic myeloid leukemia (CML) model. We found that the BDP greatly enhanced the fitness of CML cells with a three-fold greater competitive advantage, leading to more aggressive disease. The BDP conferred almost complete resistance to cell death induced by imatinib in CML stem and progenitor cells (LSPCs). Using BH3 profiling, we identified a novel therapeutic vulnerability of BDP LSPCs to MCL-1 antagonists, which we confirmed in primary human LSPCs, and in vivo. Our findings demonstrate the impact of human polymorphisms on the survival of LSPCs and highlight their potential as companion diagnostics for tailored therapies., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods were performed in accordance with the relevant guidelines and regulations of Duke-NUS. This includes obtaining informed consent from all participants who provided primary cells under approved NUS IRB study #LN-20-058E., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Y-chromosome short tandem repeat (Y-STR) is an important type of genetic markers in the human genome, widely used in molecular anthropology and forensic genetics. However, most Y-STR studies has been focused on the length-based variations resulting from differences in the number of repeat units. Less attention was paid to sequence-based Y-STR variations. Consequently, sequence-based variation characteristics of Y-STRs in Chinese populations remain insufficiently studied. In this study, targeted sequencing of 42 Y-STR loci was performed for 331 Chinese Han males (with an average sequencing depth of 612 ×), unveiling a total of 387 sequence allele types and their frequencies in the population. Repeat pattern variations were observed in seven loci containing multiple repeat units. Across all sequenced repeat and flanking regions, 46 single-nucleotide substitutions and insertion/deletion variations were identified, including 13 mutations not recorded in the dbSNP database. Twenty-seven previously unreported sequence-based alleles were identified. Additionally, differences in Y-STRs between the Chinese Han population and three American populations (African Americans, Caucasians, and Hispanics) were revealed from sequence-based data analysis. In summary, this study provides a detailed summary of the sequence features of 42 Y-STRs in the Chinese Han population, improving our understanding of Y-STRs and providing basic data of sequence variations for the application of Y-STRs., 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 B.V. All rights reserved.)

As nitrogen analogues of iron-oxo species, high-valent iron-imido species have attracted great interest in the past decades. Fe V -alkylimido species are generally considered to be key reaction intermediates in Fe(III)-catalyzed C(sp 3 )─H bond aminations of alkyl azides but remain underexplored. Here, it is reported that iron-corrole (Cor) complexes can catalyze a wide range of intramolecular C─H amination reactions of alkyl azides to afford a variety of 5-, 6- and 7-membered N-heterocycles, including alkaloids and natural product derivatives, with up to 3880 turnover numbers (TONs) and excellent diastereoselectivity (>99:1 d.r.). Mechanistic studies including density functional theory (DFT) calculations and intermolecular hydrogen atom abstraction (HAA) reactions reveal key reactive Fe V -alkylimido intermediates. The [Fe V (Cor)(NAd)] (Ad = adamantyl) complex is independently prepared and characterized through electron paramagnetic resonance (EPR), resonance Raman (rR) measurement, and X-ray photoelectron spectroscopy (XPS). This complex is reactive toward HAA reactions with kinetic isotope effects (KIEs) similar to [Fe(Cor)]-catalyzed intramolecular C─H amination of alkyl azides., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Post-transplant or hematological cancer patients have a higher risk of mortality after infection with ancestral and early variants of severe acute respiratory syndrome (SARS)-CoV-2. Adoptive cell therapy (ACT) with virus-specific T cells (VSTs) could augment endogenous T cell immunity to avoid disease deterioration before viral clearance., Methods: We established a third-party SARS-CoV-2-specific T cell (COVID-T) bank in 2020 (NCT04351659) using convalescent and/or vaccinated donors. In a phase I/II study (NCT04457726), 13 adult and pediatric patients, acutely positive for SARS-CoV-2 and predicted to have a high chance of mortality, were recruited from September 2021 to February 2022. Twelve patients received a single dose of COVID-T cells, matched on at least 1 HLA., Results: A dose of either 75,000 or 150,000 IFN-γ+CD3+ cells/m 2 SARS-COV-2-specific T cells did not cause cytokine release syndrome, acute respiratory distress syndrome, or graft-versus-host disease. In the 8 patients who had detectable donor SARS-COV-2-specific T cells after ACT, none progressed to severe disease or died with COVID-19. In contrast, among the other four patients without evidence of donor micro-chimerism, two died of COVID-19., Conclusions: Long-acting third-party VSTs from convalescent or vaccinated donors could be expediently produced and might be clinically useful in future pandemics, particularly before global vaccination is implemented., Competing Interests: Declaration of competing interest W.L. is a part-time employee of Miltenyi Biotec. All authors declare no competing financial interests., (Copyright © 2024. Published by Elsevier Inc.)

The genetic lesions that drive acute megakaryoblastic leukemia (AMKL) have not been fully elucidated. To search for genetic alterations in AMKL, we performed targeted deep sequencing in 34 AMKL patient samples and 8 AMKL cell lines and detected frequent genetic mutations in the NOTCH pathway in addition to previously reported alterations in GATA-1 and the JAK-STAT pathway. Pharmacological and genetic NOTCH activation, but not inhibition, significantly suppressed AMKL cell proliferation in both in vitro and in vivo assays employing a patient-derived xenograft model. These results suggest that NOTCH inactivation underlies AMKL leukemogenesis. and NOTCH activation holds the potential for therapeutic application in AMKL., Competing Interests: Conflicts of Interest Disclosure The authors have nothing to disclose., (Copyright © 2024 International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

Eukaryotic cells are highly compartmentalized, requiring elaborate transport mechanisms to facilitate the movement of proteins between membrane-bound compartments. Most proteins synthesized in the endoplasmic reticulum (ER) are transported to the Golgi apparatus through COPII-mediated vesicular trafficking. Sar1, a small GTPase that facilitates the formation of COPII vesicles, plays a critical role in the early steps of this protein secretory pathway. Sar1 was characterized in yeast, animals and plants, but no Sar1 homolog has been identified and functionally analyzed in algae. Here we identified a putative Sar1 homolog (CrSar1) in the model green alga Chlamydomonas reinhardtii through amino acid sequence similarity. We employed site-directed mutagenesis to generate a dominant-negative mutant of CrSar1 (CrSar1DN). Using protein secretion assays, we demonstrate the inhibitory effect of CrSar1DN on protein secretion. However, different from previously studied organisms, ectopic expression of CrSar1DN did not result in collapse of the ER-Golgi interface in Chlamydomonas . Nonetheless, our data suggest a largely conserved role of CrSar1 in the ER-to-Golgi protein secretory pathway in green algae., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-546/coif). The authors have no conflicts of interest to declare.

Newly synthesized proteins are delivered to the apoplast via conventional or unconventional protein secretion in eukaryotes. In plants, proteins are secreted to perform various biological functions. Conserved from yeast to mammals, both conventional and unconventional protein secretion pathways have been revealed in plants. In the conventional protein secretion pathway, secretory proteins with a signal peptide are translocated into the endoplasmic reticulum and transported to the extracellular region via the endomembrane system. On the contrary, unconventional protein secretion pathways have been demonstrated to mediate the secretion of the leaderless secretory proteins. In this chapter, we summarize the updated findings and provide a comprehensive overview of protein secretion pathways in plants., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Riboregulators such as riboswitches and RNA thermometers provide simple, protein-independent tools to control gene expression at the post-transcriptional level. In bacteria, RNA thermometers regulate protein synthesis in response to temperature shifts. Thermometers outside of the bacterial world are rare, and in organellar genomes, no RNA thermometers have been identified to date. Here we report the discovery of an RNA thermometer in a chloroplast gene of the unicellular green alga Chlamydomonas reinhardtii. The thermometer, residing in the 5' untranslated region of the psaA messenger RNA forms a hairpin-type secondary structure that masks the Shine-Dalgarno sequence at 25°C. At 40°C, melting of the secondary structure increases accessibility of the Shine-Dalgarno sequence to initiating ribosomes, thus enhancing protein synthesis. By targeted nucleotide substitutions and transfer of the thermometer into Escherichia coli, we show that the secondary structure is necessary and sufficient to confer the thermometer properties. We also demonstrate that the thermometer provides a valuable tool for inducible transgene expression from the Chlamydomonas plastid genome, in that a simple temperature shift of the algal culture can greatly increase recombinant protein yields., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The importance of easy wayfinding in complex urban settings has been recognized in spatial planning. Empirical measurement and explicit representation of wayfinding, however, have been limited in deciding spatial configurations. Our study proposed and tested an approach to improving wayfinding by incorporating spatial analysis of urban forms in the Guangdong-Hong Kong-Macau Great Bay Area in China. Wayfinding was measured by an indicator of intelligibility using spatial design network analysis. Urban spatial configurations were quantified using landscape metrics to describe the spatial layouts of local climate zones (LCZs) as standardized urban forms. The statistical analysis demonstrated the significant associations between urban spatial configurations and wayfinding. These findings suggested, to improve wayfinding, 1) dispersing LCZ 1 (compact high-rise) and LCZ 2 (compact mid-rise) and 2) agglomerating LCZ 3 (compact low-rise), LCZ 5 (open mid-rise), LCZ 6 (open low-rise), and LCZ 9 (sparsely built). To our knowledge, this study is the first to incorporate the LCZ classification system into the wayfinding field, clearly providing empirically-supported solutions for dispersing and agglomerating spatial configurations. Our findings also provide insights for human-centered spatial planning by spatial co-development at local, urban, and regional levels., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Terminal Ru(v)-imido species are thought to be as reactive to group transfer reactions as their Ru(v)-oxo homologues, but are less studied. With the electron-rich corrole ligand, relatively stable and isolable Ru(v)-arylimido complexes [Ru( t Bu-Cor)(NAr)] (H 3 ( t Bu-Cor) = 5,15-diphenyl-10-( p-tert -butylphenyl)corrole, Ar = 2,4,6-Me 3 C 6 H 2 (Mes), 2,6-( i Pr) 2 C 6 H 3 (Dipp), 2,4,6-( i Pr) 3 C 6 H 2 (Tipp), and 3,5-(CF 3 ) 2 C 6 H 3 (BTF)) can be prepared from [Ru( t Bu-Cor)] 2 under strongly reducing conditions. This type of Ru(v)-monoarylimido corrole complex with S = ½ was characterized by high-resolution ESI mass spectrometry, X-band EPR, resonance Raman spectroscopy, magnetic susceptibility, and elemental analysis, together with computational studies. Under heating/light irradiation (xenon lamp) conditions, the complexes [Ru( t Bu-Cor)(NAr)] (Ar = Mes, BTF) could undergo aziridination of styrenes and amination of benzylic C(sp 3 )-H bonds with up to 90% product yields., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

As a fundamental metabolic pathway, autophagy plays important roles in plant growth and development, particularly under stress conditions. A set of autophagy-related (ATG) proteins is recruited for the formation of a double-membrane autophagosome. Among them, the essential roles of ATG2, ATG18, and ATG9 have been well established in plant autophagy via genetic analysis; however, the underlying molecular mechanism for ATG2 in plant autophagosome formation remains poorly understood. In this study, we focused on the specific role of ATG2 in the trafficking of ATG18a and ATG9 during autophagy in Arabidopsis (Arabidopsis thaliana). Under normal conditions, YFP-ATG18a proteins are partially localized on late endosomes and translocated to ATG8e-labeled autophagosomes upon autophagic induction. Real-time imaging analysis revealed sequential recruitment of ATG18a on the phagophore membrane, showing that ATG18a specifically decorated the closing edges and finally disassociated from the completed autophagosome. However, in the absence of ATG2, most of the YFP-ATG18a proteins are arrested on autophagosomal membranes. Ultrastructural and 3D tomography analysis showed that unclosed autophagosome structures are accumulated in the atg2 mutant, displaying direct connections with the endoplasmic reticulum membrane and vesicular structures. Dynamic analysis of ATG9 vesicles suggested that ATG2 depletion also affects the association between ATG9 vesicles and the autophagosomal membrane. Furthermore, using interaction and recruitment analysis, we mapped the interaction relationship between ATG2 and ATG18a, implying a possible role of ATG18a in recruiting ATG2 and ATG9 to the membrane. Our findings unveil a specific role of ATG2 in coordinating ATG18a and ATG9 trafficking to mediate autophagosome closure in Arabidopsis., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chronic arsenic exposure causes myocardial damage. The aim of this study is to investigate if oxidative stress and reduction in NO is involved in the myocardial damage induced by arsenic in drinking water. Rats were divided into a control group and different doses of sodium arsenite. With increasing sodium arsenite concentrations in drinking water, localised inflammatory foci and necrotic myocardial tissues were gradually observed. Compared to the control group, the activities and gene expression of antioxidant enzymes in arsenic-exposed rats decreased. NO content and the NOS activity as well as the expression of NOS mRNA in the myocardial tissue of exposed rats, decreased, and the extracellular NO content of cardiomyocytes treated with sodium arsenite also decreased. The rate of cell apoptosis induced by sodium arsenite decreased after treatment with sodium nitroprusside (an NO donor). In conclusion, arsenic exposure in drinking water can lead to myocardial injury and cardiomyocyte apoptosis through oxidative stress and a reduction in NO content., 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 B.V. All rights reserved.)

The genomes of cytoplasmic organelles (mitochondria and plastids) are maternally inherited in most eukaryotes, thus excluding organellar genomes from the benefits of sexual reproduction and recombination. The mechanisms underlying maternal inheritance are largely unknown. Here we demonstrate that two independently acting mechanisms ensure maternal inheritance of the plastid (chloroplast) genome. Conducting large-scale genetic screens for paternal plastid transmission, we discovered that mild chilling stress during male gametogenesis leads to increased entry of paternal plastids into sperm cells and strongly increased paternal plastid transmission. We further show that the inheritance of paternal plastid genomes is controlled by the activity of a genome-degrading exonuclease during pollen maturation. Our data reveal that (1) maternal inheritance breaks down under specific environmental conditions, (2) an organelle exclusion mechanism and a genome degradation mechanism act in concert to prevent paternal transmission of plastid genes and (3) plastid inheritance is determined by complex gene-environment interactions., (© 2023. The Author(s).)

Background: The impact of three-dimensional (3D) visualization on laparoscopic hepatectomy for hepatocellular carcinoma is largely unknown., Methods: A retrospective review with propensity-score matched analysis of 3D and two-dimensional (2D) laparoscopic hepatectomy performed in a tertiary hepatobiliary surgery center., Results: Since the availability of 3D laparoscopy, the proportion of laparoscopic major hepatectomies has significantly expanded (1.7% vs. 24.0%, p < 0.0001) and the percentage of difficult resections among patients who underwent laparoscopic hepatectomy has also increased (12.6% vs. 40.0%, p = 0.0001). A total of 305 patients (92 in the 3D group and 213 in the 2D group) underwent laparoscopic hepatectomy between 2002 and 2019. The 3D group had better liver function, larger tumors at more difficult locations, more major resections, and more difficult surgeries. After propensity score matching, 144 patients were analyzed (72 in both the 3D and 2D groups). Patients were comparable in terms of liver status, tumor status, and complexity of liver surgery. Operative time (218 vs. 218 mins, p = 0.50) and blood loss (0.2 vs. 0.2L, p = 0.49) were comparable between the two groups, however overall complications were higher in the 2D group (1.4 vs. 11.1%, p = 0.03). Patients who underwent 3D laparoscopic major hepatectomy had a shorter hospital stay than their comparable counterparts operated through an open approach (7 vs. 6 days, p = 0.003)., Conclusions: 3D visualization enhanced the feasibility of laparoscopic major hepatectomy and difficult laparoscopic liver resection. 3D resection was potentially associated with fewer operative morbidities and the 3D laparoscopic approach did not jeopardize the outcome of major hepatectomy., (© 2022. Society of Surgical Oncology.)

We review the anatomical limits of living donor liver transplantation. Graft size is the fundamental challenge in partial liver transplantation. Insufficient graft size leads to small-for-size syndrome, graft failure, and graft loss. However, smaller grafts can be used safely with surgical techniques to optimize outflow and modulate inflow, thereby minimizing portal hyperperfusion. Meanwhile, anatomical variations are common in the vascular and biliary systems. These variants pose additional challenges for vascular and biliary reconstruction. Recognition and appropriate management of these variants ensure donor safety and reduce recipient morbidity. The ultimate principle of partial liver transplantation is to ensure a sufficient graft volume with unimpeded outflow and reconstructable vascular and biliary systems. On this basis, the anatomical limits of living donor liver transplantation can be safely expanded., (Copyright © 2022 The Korean Society for Transplantation.)

Land use planning regulates surface hydrological processes by adjusting land properties with varied evapotranspiration ratios. However, a dearth of empirical spatial information hampers the regulation of place-specific hydrological processes. Therefore, this study proposed a Local Land Use Planning framework for EvapoTranspiration Ratio regulations (ETR-LLUP), which was tested for the developments of spatially-varied land use strategies in the Dongjiang River Basin (DRB) in Southern China. With the first attempt at integrating the Emerging Hot Spots Analysis (EHSA) with the Budyko framework, the spatiotemporal trends of evapotranspiration ratios based on evaporative index and dryness index, from 1992 to 2018, were illustrated. Then, representative land-cover types in each sub-basin were defined using Geographically Weighted Principal Component Analysis, in two wet years (1998 and 2016) and three dry years (2004, 2009, and 2018), which in turn were identified using the Standard Precipitation Index. Finally, Geographically Weighted Regressions (GWRs) were used to detect spatially-varied relationships between land-cover proportions and evaporative index in both dry and wet climates. Results showed that the DRB was consistently a water-limited region from 1992 to 2018, and the situation was getting worse. We also identified the upper DRB as hotspots for hydrological management. Forests and croplands experienced increasingly water stress compared to other vegetation types. More importantly, the spatial results of GWR models enabled us to adjust basin land use by 1) expanding and contracting a combination of 'mosaic natural vegetation' and 'broadleaved deciduous trees' in the western and eastern parts of the basin, respectively; and 2) increasing 'broadleaved evergreen trees' in the upstream parts of the basin. These spatially-varied land use strategies based on the ETR-LLUP framework allow for place-specific hydrological management during both dry and wet climates., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

It is uncertain whether tumour biology affects radical treatment for post-transplant hepatocellular carcinoma (HCC) oligo-recurrence, i.e. recurrence limited in numbers and locations amendable to radical therapy. We conducted a retrospective study on 144 patients with post-transplant HCC recurrence. Early recurrence within one year after transplant (HR 2.53, 95% CI 1.65−3.88, p < 0.001), liver recurrence (HR 1.74, 95% CI 1.12−2.68, p = 0.01) and AFP > 200 ng/mL upon recurrence (HR 1.62, 95% CI 1.04−2.52, p = 0.03) predicted mortality following recurrence. In patients with early recurrence and liver recurrence, radical treatment was associated with improved post-recurrence survival (early recurrence: median 18.2 ± 1.5 vs. 9.2 ± 1.5 months, p < 0.001; liver recurrence: median 28.0 ± 4.5 vs. 11.6 ± 2.0, p < 0.001). In patients with AFP > 200 ng/mL, improvement in survival did not reach statistical significance (median 18.2 ± 6.5 vs. 8.8 ± 2.2 months, p = 0.13). Survival benefits associated with radical therapy were reduced in early recurrence (13.6 vs. 9.0 months) and recurrence with high AFP (15.4 vs. 9.3 months) but were similar among patients with and without liver recurrence (16.9 vs. 16.4 months). They were also diminished in patients with multiple biological risk factors (0 risk factor: 29.0 months; 1 risk factor: 19.7 months; 2−3 risk factors: 3.4 months): The survival benefit following radical therapy was superior in patients with favourable biological recurrence but was also observed in patients with poor tumour biology. Treatment decisions should be individualised considering the oncological benefits, quality of life gain and procedural morbidity.

In selective macroautophagy/autophagy, cargo receptors are recruited to the forming autophagosome by interacting with Atg8 (autophagy-related 8)-family proteins and facilitate the selective sequestration of specific cargoes for autophagic degradation. In addition, Atg8 interacts with a number of adaptors essential for autophagosome biogenesis, including ATG and non-ATG proteins. The majority of these adaptors and receptors are characterized by an Atg8-family interacting motif (AIM) for binding to Atg8. However, the molecular basis for the interaction mode between ATG8 and regulators or cargo receptors in plants remains largely unclear. In this study, we unveiled an atypical interaction mode for Arabidopsis ATG8f with a plant unique adaptor protein, SH3P2 (SH3 domain-containing protein 2), but not with the other two SH3 proteins. By structure analysis of the unbound form of ATG8f, we identified the unique conformational changes in ATG8f upon binding to the AIM sequence of a plant known autophagic receptor, NBR1. To compare the binding affinity of SH3P2-ATG8f with that of ATG8f-NBR1, we performed a gel filtration assay to show that ubiquitin-associated domain of NBR1 outcompetes the SH3 domain of SH3P2 for ATG8f interaction. Biochemical and cellular analysis revealed that distinct interfaces were employed by ATG8f to interact with NBR1 and SH3P2. Further subcellular analysis showed that the AIM-like motif of SH3P2 is essential for its recruitment to the phagophore membrane but is dispensable for its trafficking in endocytosis. Taken together, our study provides an insightful structural basis for the ATG8 binding specificity toward a plant-specific autophagic adaptor and a conserved autophagic receptor. Abbreviations: ATG, autophagy-related; AIM, Atg8-family interacting motif; BAR, Bin-Amphiphysin-Rvs; BFA, brefeldin A; BTH, benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester; CCV, clathrin-coated-vesicle; CLC2, clathrin light chain 2; Conc A, concanamycin A; ER, endoplasmic reticulum; LDS, LIR docking site; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; LIR, LC3-interacting region; PE, phosphatidylethanolamine; SH3P2, SH3 domain containing protein 2; SH3, Src-Homology-3; UBA, ubiquitin-associated; UIM, ubiquitin-interacting motif.

We report high-speed, large dynamic range spectral domain interrogation of fiber-optic Fabry-Perot (FP) interferometric sensors. An optical interrogation system employing a piezoelectric FP tunable filter and an array of fiber-Bragg gratings for wavelength referencing is developed to acquire the reflection spectrum of FP sensors at a high interrogation speed with a wide wavelength range. A 98 nm wavelength interrogation range was obtained at the resonance frequency of ∼110 k H z of the FP tunable filter. At this frequency, the resolution of the FP cavity length measurement was 1.8 nm. To examine the performance of the proposed high-speed spectral domain interrogation scheme, two diaphragm-based fiber-tip FP sensors (a pressure sensor and acoustic sensor) were interrogated. The pressure measurement results show that the high-speed spectral domain interrogation method has the advantages of being robust to light intensity fluctuations and having a much larger dynamic range compared with the conventional intensity-based interrogation method. Moreover, owing to its capability of measuring the absolute FP cavity length, the proposed interrogation system mitigates the sensitivity drift that intensity-based interrogation often suffers from. The acoustic measurement results demonstrate that the high-speed spectral domain interrogation method is capable of high-frequency acoustic measurements of up to 20 kHz. This work will benefit many applications that require high-speed interrogation of fiber-optic FP interferometric sensors.

Background: Magnetic resonance (MR) elastography and proton density fat fraction (PDFF) are emerging techniques for non-invasive assessment of liver stiffness and steatosis, respectively. We investigated the role of MR metrics in pre-treatment prognostication of hepatocellular carcinoma (HCC)., Methods: Patients with newly diagnosed HCC were prospectively recruited. Pre-treatment MR elastography and PDFF were performed on tumor and non-tumor regions. HCC treatment was categorized as potentially curative (resection/ablation) or non-curative (locoregional/systemic therapy). HCC recurrence, liver-related complications (ascites/ variceal bleeding/ hepatic encephalopathy) and mortality were monitored., Results: Of the 158 recruited patients (mean age 62.9 years, 84.2% male, 82.9% viral hepatitis), 58.2% (n = 92) and 41.8% (n = 66) received potentially curative and non-curative therapy, respectively. Pre-treatment non-tumor liver stiffness independently predicted liver-related complications, regardless of treatment type (HR 1.384, 95% CI 1.067-1.796, p = 0.014). In the potentially curative therapy group, non-tumor stiffness and non-tumor PDFF were independently associated with HCC recurrence (HR 1.308, 95% CI 1.022-1.673 & HR 1.080, 95% CI 1.009-1.156 respectively, both p < 0.05); and non-tumor PDFF predicted mortality (HR 1.160, 95% CI 1.038-1.296, p = 0.009). In the non-curative group, tumor stiffness independently predicted liver-related complications (HR 1.299, 95% CI 1.023-1.651, p = 0.032), and a combination of tumor stiffness ≥ 5.7 kPa plus non-tumor stiffness ≥ 3.7 kPa was associated with a two-fold risk of liver-related complications (86.7% vs 40.0%, p < 0.001)., Conclusion: Pre-treatment MR elastography and PDFF over tumor and non-tumor regions demonstrated prognosticating roles in HCC. Simultaneous measurements of both metrics during conventional MR liver should be considered in the diagnostic workup of HCC., (© 2022. Asian Pacific Association for the Study of the Liver.)

Detection of a gravitational-wave signal of non-astrophysical origin would be a landmark discovery, potentially providing a significant clue to some of our most basic, big-picture scientific questions about the Universe. In this white paper, we survey the leading early-Universe mechanisms that may produce a detectable signal-including inflation, phase transitions, topological defects, as well as primordial black holes-and highlight the connections to fundamental physics. We review the complementarity with collider searches for new physics, and multimessenger probes of the large-scale structure of the Universe., Competing Interests: Conflict of interestThe author M.S. is Editor-in-Chief of the journal General Relativity and Gravitation; the article underwent a standard single-blind peer review process., (© The Author(s) 2022.)

This study verified whether radical treatment for hepatocellular carcinoma (HCC) oligo-recurrence after liver transplantation conveys survival benefits. A retrospective study of 144 patients with posttransplant HCC recurrence was performed. Propensity score matching was performed to adjust for baseline covariates between patients who received radical and palliative treatments. The primary endpoint was postrecurrence survival. A total of 50 patients (35%) received radical treatment for recurrence, and 76 (53%) and 18 (13%) patients received palliative and supportive treatments, respectively. Compared with the radical group, patients who received palliative treatment had more early recurrences (time from transplant 17 versus 11 months; P = 0.01) and more extensive disease in terms of tumor numbers (1 versus 4; P < 0.001), size of largest tumor (1.8 versus 2.5 cm; P = 0.046), numbers of involved organs (interquartile range [IQR], 1-1 versus 1-2; P = 0.02), and alpha-fetoprotein (AFP) level (7 versus 40 ng/mL; P = 0.01). Multivariate Cox regression analysis revealed that early recurrence (time from transplant hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03; P = 0.001), larger recurrent tumor (HR, 1.12; 95% CI, 1.03-1.23; P = 0.01), liver recurrence (HR, 1.84; 95% CI, 1.17-2.90; P = 0.01), and log 10 AFP level at recurrence (HR, 1.27; 95% CI, 1.07-1.52; P = 0.01) predicted poor survival. Mammalian target of rapamycin inhibitor (HR, 0.331; 95% CI, 0.213-0.548; P < 0.001) and radical treatment (HR, 0.342; 95% CI, 0.213-0.548; P < 0.001) were associated with improved survival. After 2-to-1 propensity score matching for covariates, the 50 patients who received curative treatment survived significantly longer than the 25 matched patients who received palliative treatment (median survival time, 30.9 ± 2.4 versus 19.5 ± 3.0 months; P = 0.01). Radical treatment conveys survival benefits to HCC oligo-recurrence after liver transplantation., (Copyright © 2021 American Association for the Study of Liver Diseases.)

Objective: The evidence for the beneficial effects of physical activity (PA) and potentially detrimental effects of long-term exposure to fine particulate matter (PM 2.5 ) on neurodegeneration diseases is accumulating. However, their joint effects remain unclear. We evaluated joint associations of habitual PA and PM 2.5 exposure with incident dementia in a longitudinal elderly cohort in Hong Kong., Methods: A total of 57,775 elderly participants (≥65 years) without dementia were enrolled during 1998-2001 and followed up till 2011. Their information on PA and other relevant covariates were collected at baseline (1998-2001) by a standard self-administered questionnaire, including PA volumes (high, moderate, low, and inactive) and types (aerobic exercise, traditional Chinese exercise, stretching exercise, walking slowly, and no exercise). Their annual mean PM 2.5 exposures at the residential address were estimated using a satellite-based spatiotemporal model. We then adopted the Cox proportional hazards model to examine the joint associations with the incidence of all-cause dementia, Alzheimer's diseases, and vascular dementia on additive and multiplicative scales., Results: During the follow-up period, we identified 1,157 incident cases of dementia, including 642 cases of Alzheimer's disease and 324 cases of vascular dementia. A higher PA level was associated with a lower risk of incident all-cause dementia (hazard ratio (HR) for the high-PA volume was 0.59 (95% CI, 0.47, 0.75), as compared with the inactive-PA), whereas a high level of PM 2.5 was related to the higher risk with an HR of 1.15 (95%CI: 1.00, 1.33) compared with the low-level of PM 2.5 . No clear evidence was observed of interaction between habitual PA (volume and type) and PM 2.5 inhalation to incident dementia on either additive or multiplicative scale., Conclusion: Habitual PA and long-term PM 2.5 exposure were oppositely related to incident dementia in the Hong Kong aged population. The benefits of PA remain in people irrespective of exposure to air pollution., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: There is limited evidence on the safety of immunotherapy use after liver transplantation and its efficacy in treating post-liver transplant hepatocellular carcinoma (HCC) recurrence., Aim: To assess the safety of immunotherapy after liver transplant and its efficacy in treating post-liver transplant HCC recurrence., Methods: A literature review was performed to identify patients with prior liver transplantation and subsequent immunotherapy. We reviewed the rejection rate and risk factors of rejection. In patients treated for HCC, the oncological outcomes were evaluated including objective response rate, progression-free survival (PFS), and overall survival (OS)., Results: We identified 25 patients from 16 publications and 3 patients from our institutional database (total n = 28). The rejection rate was 32% ( n = 9). Early mortality occurred in 21% ( n = 6) and was mostly related to acute rejection (18%, n = 5). Patients who developed acute rejection were given immunotherapy earlier after transplantation (median 2.9 years vs 5.3 years, P = 0.02) and their graft biopsies might be more frequently programmed death ligand-1-positive (100% vs 33%, P = 0.053). Their PFS (1.0 ± 0.1 mo vs 3.5 ± 1.1 mo, P = 0.02) and OS (1.0 ± 0.1 mo vs 19.2 ± 5.5 mo, P = 0.001) compared inferiorly to patients without rejection. Among the 19 patients treated for HCC, the rejection rate was 32% ( n = 6) and the overall objective response rate was 11%. The median PFS and OS were 2.5 ± 1.0 mo and 7.3 ± 2.7 mo after immunotherapy., Conclusion: Rejection risk is the major obstacle to immunotherapy use in liver transplant recipients. Further studies on the potential risk factors of rejection are warranted., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Coastal reservoirs are widely regarded as a viable solution to the water scarcity problem faced by coastal cities with growing populations. As a result of the accumulation of anthropogenic wastes and the alteration of hydroecological processes, these reservoirs may also become the emission hotspots of nitrous oxide (N 2 O). Hitherto, accurate global assessment of N 2 O emission suffers from the scarcity and low spatio-temporal resolution of field data, especially from small coastal reservoirs with high spatial heterogeneity and multiple water sources. In this study, we measured the surface water N 2 O concentrations and emissions at a high spatial resolution across three seasons in a subtropical coastal reservoir in southeastern China, which was hydrochemically highly heterogeneous because of the combined influence of river runoff, aquacultural discharge, industrial discharge and municipal sewage. Both N 2 O concentration and emission exhibited strong spatio-temporal variations, which were correlated with nitrogen loading from the river and wastewater discharge. The mean N 2 O concentration and emission were found to be significantly higher in the summer than in spring and autumn. The results of redundancy analysis showed that NH 4 + -N explained the greatest variance in N 2 O emission, which implied that nitrification was the main microbial pathway for N 2 O production in spite of the potentially increasing importance of denitrification of NO 3 - -N in the summer. The mean N 2 O emission across the whole reservoir was 107 μg m -2 h -1 , which was more than an order of magnitude higher than that from global lakes and reservoirs. Based on our results of Monte Carlo simulations, a minimum of 15 sampling points per km 2 would be needed to produce representative and reliable N 2 O estimates in such a spatially heterogeneous aquatic system. Overall, coastal reservoirs could play an increasingly important role in future climate change via their N 2 O emission to the atmosphere as water demand and anthropogenic pressure continue to rise., 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 © 2021 Elsevier B.V. All rights reserved.)

Precise staging is essential in the management of patients with recurrent hepatocellular carcinoma (HCC) after liver transplantation. There is no current consensus on the optimal staging strategy. We conducted this study to evaluate the performance of dual-tracer positron emission tomography-computed tomography (PET-CT) for this purpose and to investigate whether the results of dual-tracer PET-CT affected patient management., Methods: A retrospective study was conducted. Patients who underwent dual-tracer PET-CT for suspected or confirmed HCC recurrence after liver transplant were included. The lesion-based sensitivity and positive predictive value of dual-tracer PET-CT were determined., Results: Fifty-six patients and 189 recurrent tumors were included. The lesion-based sensitivity and positive predictive value of dual-tracer PET-CT were 94.7% and 90.4%, respectively. The sensitivity of dual-tracer PET-CT was better than the standard imaging in the surveillance protocol (82.5% versus 94.7%, P < 0.001), especially for detecting liver recurrence (71.0% versus 96.8%, P < 0.001). Half of the dual-tracer PET-CT detected additional recurrence (n = 26, 46.4%) and one-third led to a change in management (n = 19, 33.9%). Ten patients (17.9%) with inconclusive standard imaging had metabolic recurrence confirmed on PET-CT and treatment was commenced early. Four patients (7.1%) had revised locoregional treatment, and 5 (8.9%) had to withdraw from locoregional treatment after the detection of additional metastatic disease., Conclusions: Dual-tracer PET-CT is effective for staging posttransplant HCC recurrence. It often provides valuable information to guide clinical management., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Recent studies suggested that long-term exposure to fine particulate matter (PM 2.5 ) was related to a higher risk of dementia incidence or hospitalizations in western populations, but the evidence is limited in Asian cities. Here we explored the link between long-term PM 2.5 exposure and dementia incidence in the Hong Kong population and whether it varied by population sub-group. We utilized a Hong Kong Chinese cohort of 66,820 people aged ≥65 years who were voluntarily enrolled during 1998-2001 and were followed up to 2011. Prevalent dementia cases were excluded based on the face-to-face interview at baseline. We ascertained the first occurrence of hospitalization for all-cause dementia and major subtypes during the follow-up period. We assessed PM 2.5 concentrations using a satellite data-based model with a 1 × 1 km 2 resolution on the residential address. Cox proportional hazards models were adopted to estimate associations of annual mean PM 2.5 exposure with dementia incidence, adjusting for potential confounders. We identified 1183 incident cases of all-cause dementia during the follow-up period, of which 655 (55.4%) were cases of Alzheimer's disease, and 334 (28.2%) were those of vascular dementia. We found a positive association between annual mean PM 2.5 exposure and all-cause dementia incidence in the fully adjusted model. The estimated hazard ratio was 1.06 (95% confidence interval (CI): 1.00, 1.13) per every 3.8 μg/m 3 increase in annual mean PM 2.5 exposure. And the estimated HRs for Alzheimer's disease and vascular dementia were 1.03 (95% CI: 0.94, 1.12) and 1.09 (95% CI: 0.98, 1.22), respectively. We did not find effect modifications by age, sex, BMI, hypertension, diabetes, or heart disease on the associations. Results suggest that long-term exposure to PM 2.5 is associated with a higher risk of dementia incidence in the Asian population., 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 © 2020 Elsevier Ltd. All rights reserved.)

Coastal reservoirs are potentially CH 4 emission hotspots owing to their biogeochemical role as the sinks of anthropogenic carbon and nutrients. Yet, the fine-scale spatial variations in CH 4 concentrations and fluxes in coastal reservoirs remain poorly understood, hampering an accurate determination of reservoir CH 4 budgets. In this study, we examined the spatial variability of diffusive CH 4 fluxes and their drivers at a subtropical coastal reservoir in southeast China using high spatial resolution measurements of dissolved CH 4 concentrations and physicochemical properties of the surface water. Overall, this reservoir acted as a consistent source of atmospheric CH 4 , with a mean diffusive flux of 16.1 μmol m -2 h -1 . The diffusive CH 4 flux at the reservoir demonstrated considerable spatial variations, with the coefficients of variation ranging between 199 and 426% over the three seasons. The shallow water zone (comprising 23% of the reservoir area) had a disproportionately high contribution (56%) to the whole-reservoir diffusive CH 4 emissions. Moreover, the mean CH 4 flux in the sewage-affected sectors was significantly higher than that in the nonsewage-affected sectors. The results of bootstrap analysis further showed that increasing the sample size from 10 to 100 significantly reduced the relative standard deviation of mean diffusive CH 4 flux from 73.7 to 3.4%. Our findings highlighted the role of sewage in governing the spatial variations in reservoir CH 4 emissions and the importance of high spatial resolution data to improve the reliability of flux estimates for assessing the contribution of reservoirs to the regional and global CH 4 budgets.

Objectives: To determine whether the frequencies of SARS-CoV-2-specific T cells are sufficiently high in the blood of convalescent donors and whether it is technically feasible to manufacture clinical-grade products overnight for T-cell therapy and assessment of COVID-19 immunity., Methods: One unit of whole blood or leukapheresis was collected from each donor following standard blood bank practices. The leukocytes were stimulated using overlapping peptides of SARS-CoV-2, covering the immunodominant sequence domains of the S protein and the complete sequence of the N and M proteins. Thereafter, functionally reactive cells were enriched overnight using an automated device capturing IFNγ-secreting cells., Results: From 1 × 10 9 leukocytes, a median of 0.98 × 10 6 (range 0.56-2.95) IFNγ + T cells were produced from each of the six donors, suggesting a high frequency of SARS-CoV-2 reactive T cells in their blood, even though only one donor had severe COVID-19 requiring mechanical ventilation whereas the other five donors had minor symptoms. A median of 57% of the enriched T cells were IFNγ+ (range 20%-74%), with preferential enrichment of CD56+ T cells and effector memory T cells. TCRVβ-spectratyping confirmed distinctively tall oligoclonal peaks in final products. With just six donors, the probability that a recipient would share at least one HLA allele with one of the donors is >88% among Caucasian, >95% among Chinese, >97% among Malay, and >99% among Indian populations., Conclusions: High frequencies of rapid antigen-reactive T cells were found in convalescent donors, regardless of severity of COVID-19. The feasibility of clinical-grade production of SARS-CoV-2-specific T cells overnight for therapeutics and diagnostics is revealed., Competing Interests: WL is a part‐time advisor to Miltenyi Biomedicine., (© 2020 The Authors. Advances in Cell and Gene Therapy published by John Wiley & Sons Ltd.)

Background: Graft hepatocellular carcinoma (HCC) recurrence after liver transplant is more frequently encountered. Graft hepatectomy is technically challenging and is associated with high morbidity. Stereotactic body radiation therapy (SBRT) has been shown to be safe and effective for the treatment of primary HCC. However, its role in HCC recurrence in a liver graft remains unclear., Aim: To evaluate the safety and efficacy of SBRT for the treatment of graft HCC recurrence after liver transplantation., Methods: A retrospective study was conducted. From 2012 to 2018, 6 patients with intrahepatic HCC recurrence after liver transplant were treated with SBRT at Queen Mary Hospital, the University of Hong Kong. The primary outcome was time to overall disease progression and secondary outcomes were time to local progression and best local response, as assessed with the Modified response Evaluation Criteria for Solid Tumours criteria. Patients were monitored for treatment related toxicities and graft dysfunction., Results: A total of 9 treatment courses were given for 13 tumours. The median tumour size was 2.3 cm (range 0.7-3.6 cm). Two (22%) patients had inferior vena cava tumour thrombus. The best local treatment response was: 5 (55%) complete response, 1 (11%) partial response and 3 (33%) stable disease. After a median follow up duration of 15.5 mo, no local progression or mortality was yet observed. The median time to overall disease progression was 6.5 mo. There were 6 regional progression in the liver graft (67%) and 2 distant progression in the lung (22%). There was no grade 3 or above toxicity and there was no graft dysfunction after SBRT., Conclusion: SBRT appears to be safe in this context. Regional progression is the mode of failure., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP., (© 2020 by The American Society of Hematology.)

Numerous studies have indicated that ambient particulate matter is closely associated with increased risk of cardiovascular disease, yet the evidence for its association with renal disease remains underrecognized. We aimed to estimate the association between long-term exposure to fine particulate matter, defined as particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5), and mortality from renal failure (RF) among participants in the Elderly Health Service Cohort in Hong Kong, China, from 1998 to 2010. PM2.5 concentration at the residential address of each participant was estimated based on a satellite-based spatiotemporal model. We used Cox proportional hazards regression to estimate risks of overall RF and cause-specific mortality associated with PM2.5. After excluding 5,373 subjects without information on residential address or relevant covariates, we included 61,447 participants in data analyses. We identified 443 RF deaths during the 10 years of follow-up. For an interquartile-range increase in PM2.5 concentration (3.22 μg/m3), hazard ratios for RF mortality were 1.23 (95% confidence interval: 1.06, 1.43) among all cohort participants and 1.42 (95% confidence interval: 1.16, 1.74) among patients with chronic kidney disease. Long-term exposure to atmospheric PM2.5 might be an important risk factor for RF mortality in the elderly, especially among persons with existing renal diseases., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Extreme precipitation is a major issue for regional climate, hydrology, and safety of society. Our knowledge of extreme precipitation is poor because of difficulties in gauge observations and biases in regional and global datasets, in particular over the snow dominated regions. Here we investigate and report the distribution and magnitude of under-measured of the maximum daily total precipitation (herein daily maximum precipitation) due to biases in manual gauge observations in the high latitudes (over 45°N), using historical data during 1973-2004. We find remarkable patterns in under-measured of the long-term mean daily maximum precipitation and their association to regional climatic regimes. In contrast to relatively small and large-scale under-measured (<5 mm) of daily maximum rainfall, the biases in daily maximum snowfall are very serious, with the regional high values over 15 mm along the Ural Mountains and the coasts of east Asia, Greenland, in particular northern Eurasia coasts. The frequency distribution of observed daily maximum snowfall underestimate significantly the higher risk events over the high latitudes. Furthermore, defining the phase of extreme precipitation should be cautious over the northern regions, in particular the coasts. These results clearly demonstrate the urgent need to review and update precipitation datasets including recent automatic gauge observations and the knowledge of climate regimes and extremes over the broader northern regions., 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 © 2020 Elsevier B.V. All rights reserved.)

Background: Mammalian target of rapamycin (mTOR) inhibitors have been shown to reduce the risk of tumour recurrence after liver transplantation for hepatocellular carcinoma (HCC). However, their role in established post-transplant HCC recurrence is uncertain., Aim: To investigate whether mTOR inhibitor offers a survival benefit in post-transplant HCC recurrence., Methods: A retrospective study of 143 patients who developed HCC recurrence after liver transplantation was performed. They were divided into 2 groups based on whether they had received mTOR inhibitor-based immunosuppression. The primary endpoint was post-recurrence survival., Results: Seventy-nine (55%) patients received an mTOR inhibitor-based immunosuppressive regime, while 64 (45%) patients did not. The mTOR inhibitor group had a lower number of recurrent tumours (2 vs 5, P = 0.02) and received more active treatments including radiotherapy (39 vs 22%, P = 0.03) and targeted therapy (59 vs 23%, P < 0.001). The median post-recurrence survival was 21.0 ± 4.1 mo in the mTOR inhibitor group and 11.2 ± 2.5 mo in the control group. Multivariate Cox regression analysis confirmed that mTOR inhibitor therapy was independently associated with improved post-recurrence survival ( P = 0.04, OR = 0.482, 95%CI: 0.241-0.966). The number of recurrent tumours and use of other treatment modalities did not affect survival. No survival difference was observed between mTOR inhibitor monotherapy and combination therapy with calcineurin inhibitor., Conclusion: mTOR inhibitors prolonged survival after post-transplant HCC recurrence., Competing Interests: Conflict-of-interest statement: None of the authors has any conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The syntheses of [Ru VI (Por)(NAd)(O)] and [Ru VI (2,6-F 2 -TPP)(NAd) 2 ] have been described. [Ru VI (2,6-F 2 -TPP)(NAd)(O)] capable of catalysing aerobic epoxidation of alkenes has been characterised by X-ray crystallography with Ru[double bond, length as m-dash]NAd and Ru[double bond, length as m-dash]O bond distances being 1.778(5) Å and 1.760(4) Å (∠O-Ru-NAd: 174.37(19)°), respectively. Its first reduction potential is 740 mV cathodically shifted from that of [Ru VI (2,6-F 2 -TPP)(O) 2 ].

The regional water storage shifting causes nonstationary spatial distribution of droughts and flooding, leading to water management challenges, environmental degradation and economic losses. The regional water storage shifting is becoming evident due to the increasing climate variability. However, the previous studies for climate drivers behind the water storage shifting are not rigorously quantified. In this study, the terrestrial water storage (TWS) spatial shifting pattern during 2002-2017 over the China-India border area (CIBA) is developed using the Gravity Recovery and Climate Experiment (GRACE), suggesting that the Indus-Ganges-Brahmaputra basin (IGBB) was wetting while the central Qinghai-Tibet Plateau (QTP) was drying. Similar drying and wetting patterns were also found in the precipitation, snow depth, Palmer Drought Severity Index (PDSI) and potential evaporation data. Based on our newly proposed Indian monsoon (IM) and western North Pacific monsoon (WNPM) variation indices, the water shifting pattern over the CIBA was found to be affected by the weakening of the variation of IM and WNPM through modulating the regional atmospheric circulation. The weakening of IM and WNPM variations has shown to be attributed to the decreasing temperature gradient between the CIBA and the Indian Ocean, and possibly related to increasing regional temperatures associated with the increasing global temperature. As the global warming intensifies, it is expected that the regional TWS shifting pattern over the CIBA will be further exaggerated, stressing the need of advancing water resources management for local communities in the region., 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 © 2019 Elsevier B.V. All rights reserved.)

Background: Air quality alert programs have been introduced around the world to reduce the short term effects of air pollution on health. Hong Kong, a densely populated city in southern China with high levels of air pollution, introduced its first air quality health index (AQHI) on December 30th 2013. However, whether air quality alert program warnings, such as the AQHI, reduces morbidity is uncertain. Using a quasi-experimental design, we conducted the first evaluation of the AQHI in Hong Kong, focusing on cardiovascular morbidity in Hong Kong's elderly population., Method: Interrupted time series with Poisson segmented regression from 2010 to 2016 was used to detect any sudden or gradual changes in emergency hospital admissions for cardiovascular diseases (CVD), after the AQHI policy was implemented. To account for potential confounders, models were adjusted for air pollutants (NO 2 , SO 2 , PM 10 , O 3 ), temperature and humidity. The findings were validated using a negative control and three false policy periods. We also assessed effects on specific subtypes of CVD (hypertensive disease (HPD), acute myocardial infarction (AMI), heart failure, stroke and other CVD) and by sex., Results: From January 1st 2010 to December 31st, 2016, 375,672 hospital admissions for CVD occurred in Hong Kong's elderly population. Immediately after the policy HPD and AMI dropped by16% (relative risk (RR) 0.84, 95% confidence interval (CI): 0.78-0.91) and 15% (RR 0.85, 95% CI: (0.76-0.97)) respectively. There was no significant change for all CVD or other sub-types and no differences by sex., Conclusion: Hong Kong's AQHI helped reduced hospital admissions in the elderly for HPD and AMI but had no effect on overall emergency hospitalization for CVD. To maximize health benefits of the policy, at risk groups need to be able to follow the behavioral changes recommended by the AQHI warnings., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ruthenium porphyrin catalysed direct intermolecular amino-oxyarylation of alkenes including styrenes and 1,3-dienes to give primary amines with O-(2,4-dinitrophenyl)hydroxylamine as the amine source was achieved in moderate to good yields under mild reaction conditions. Spectroscopic analyses revealed that a ruthenium nitrido complex was the key reaction intermediate for the amino-oxyarylation reaction.

Aim: We construct a framework for mapping pattern and drivers of insect diversity at the continental scale and use it to test whether and which environmental gradients drive insect beta diversity., Location: Global; North and Central America; Western Europe., Time Period: 21st century., Major Taxa Studied: Insects., Methods: An informatics system was developed to integrate terrestrial data on insects with environmental parameters. We mined repositories of data for distribution, climatic data were retrieved (WorldClim), and vegetation parameters inferred from remote sensing analysis (MODIS Vegetation Continuous Fields). Beta diversity between sites was calculated and then modeled with two methods, Mantel test with multiple regression and generalized dissimilarity modeling., Results: Geographic distance was the main driver of insect beta diversity. Independent of geographic distance, bioclimate variables explained more variance in dissimilarity than vegetation variables, although the particular variables found to be significant were more consistent in the latter, particularly, tree cover. Tree cover gradients drove compositional dissimilarity at denser coverages, in both continental case studies. For climate, gradients in temperature parameters were significant in driving beta diversity more so than gradients in precipitation parameters., Main Conclusions: Although environmental gradients drive insect beta diversity independently of geography, the relative contribution of different climatic and vegetational parameters is not expected to be consistent in different study systems. With further incorporation of additional temporal information and variables, this approach will enable the development of a predictive framework for conserving insect biodiversity at the global scale., Competing Interests: None declared., (© 2019 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Since its introduction in 2012, associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has significantly expanded the pool of candidates for liver resection. It offers patients with insufficient liver function a chance of a cure. ALPPS is most controversial when its high morbidity and mortality is concerned. Operative mortality is usually a result of post-hepatectomy liver failure and can be minimized with careful patient selection. Elderly patients have limited reserve for tolerating the demanding operation. Patients with colorectal liver metastasis have normal liver and are ideal candidates. ALPPS for cholangiocarcinoma is technically challenging and associated with fair outcomes. Patients with hepatocellular carcinoma have chronic liver disease and limited parenchymal hypertrophy. However, in selected patients with limited hepatic fibrosis satisfactory outcomes have been produced. During the inter-stage period, serum bilirubin and creatinine level and presence of surgical complication predict mortality after stage II. Kinetic growth rate and hepatobiliary scintigraphy also guide the decision whether to postpone or omit stage II surgery. The outcomes of ALPPS have been improved by a combination of technical modifications. In patients with challenging anatomy, partial ALPPS potentially reduces morbidity, but remnant hypertrophy may compare unfavorably to a complete split. When compared to conventional two-stage hepatectomy with portal vein embolization or portal vein ligation, ALPPS offers a higher resection rate for colorectal liver metastasis without increased morbidity or mortality. While ALPPS has obvious theoretical oncological advantages over two-stage hepatectomy, the long-term outcomes are yet to be determined., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: On July 1st , 2015, Hong Kong became the first city in Asia to implement a policy regulating sulfur dioxide (SO 2 ) in shipping emissions. We conducted an accountability study assessing the improvement in ambient air quality and estimating the effect on health outcomes of the policy., Method: We used interrupted time series (ITS) with segmented regression to identify any change in ambient concentrations of SO 2 in contrast to other ambient pollutants (particulate matter <10 μm in diameter (PM 10 ), nitrogen dioxide (NO 2 ) and ozone (O 3 )) at 10 monitoring stations in Hong Kong from 2010 to 2017. We validated these findings using cumulative sum control (CUSUM) charts. We used a validated risk assessment model to estimate effects of changes in air quality on death for natural causes, cardiovascular and respiratory diseases., Results: Mean monthly concentrations of SO 2 fell abruptly at the monitoring station closest to the main shipping port (Kwai Chung (KC)) by -10.0 μgm 3 p-value = 0.0004, but not elsewhere. No such changes were evident for the other pollutants (PM 10 , NO 2 , O 3 ). CUSUM charts confirmed a change in July 2015. Estimated deaths avoided per year as a result of the policy were 379, 72, 30 for all natural causes, respiratory and cardiovascular diseases respectively., Conclusion: Implementation of the shipping emission policy in Hong Kong successfully reduced ambient SO 2 , with the potential to reduce mortality. However, to gain full benefits, restrictions on shipping emissions need to be implemented throughout the region., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Although numerous studies have demonstrated that the criteria air pollutants increased the risk of exacerbation of chronic obstructive pulmonary disease (COPD), few have explored the effects of ambient benzene and toluene on COPD., Objective: This study aimed to evaluate the short-term effects of ambient benzene and toluene on emergency COPD (eCOPD) hospitalizations., Methods: We obtained daily mean and maximum concentrations of benzene and toluene during April 1, 2011 - December 31, 2014 from the Hong Kong Environmental Protection Department, and daily counts of eCOPD hospitalizations from the Hospital Authority. Generalized additive distributed lag models were used to estimate the percentage excess risk (ER%) of eCOPD hospitalizations per interquartile range (IQR) increase in ambient benzene and toluene., Results: The ER% estimates of eCOPD hospitalizations post cumulative exposure of up to two days were 2.62% (95%CI: 0.17% to 5.13%) and 1.42% (0.16% to 2.69%), for per IQR increase of daily mean benzene (1.4μg/m 3 ) and toluene (4.6μg/m 3 ), respectively. People below the age of 65 had a significantly higher risk of eCOPD hospitalizations associated with daily maximum toluene than the elderly., Conclusions: Ambient benzene and toluene might be environmental stressors for acute exacerbations of COPD in the Hong Kong population., (Copyright © 2018. Published by Elsevier B.V.)

Introduction: Transcutaneous laryngeal ultrasound (TLUSG) is an innovative, non-invasive tool in detecting post-thyroidectomy vocal cord palsy (VCP). However, TLUSG failed to detect about 6-15% laryngoscopic examination (LE)-confirmed VCP. It is unclear whether the outcome of patients with VCP missed by TLUSG [false negative (FN)] is different from those with VCP diagnosed by TLUSG [true positive (TP)]. Therefore, this study aimed to compare the clinical outcome and prognosis between patients with FN results and TP results., Methods: Over 46 months, all consecutive patients undergoing thyroidectomy or endocrine-related neck procedure were recruited. They underwent pre-operative and post-operative voice assessments on symptoms, voice-specific questionnaire [voice handicap index questionnaire (VHI-30)], TLUSG and LE. For patients with post-operative vocal cord palsy, reassessment LE would be arranged at second, fourth, sixth and twelfth months post-operatively until VCP recovered., Results: In total, 1196 patients, including 74 post-thyroidectomy VCP, were recruited. For those with assessable vocal cords (VC), 58 VCP were correctly diagnosed by TLUSG (TP) and 10 VCP were missed by TLUSG (FN). Sensitivity and specificity of detecting a VCP by TLUSG were 85.3% and 94.7%, respectively. VHI-30 score was significantly increased after operation in TP group [31 (range - 6-105), p < 0.001] but not in FN group [20 (14-99), p = 0.089]. Comparing to TP group, VCP recovered earlier (69 vs. 125 days, p < 0.001) and less patients suffered from permanent VCP in patients with FN results. (34.5% vs. 0.0%, p = 0.027)., Conclusion: The VCP missed by TLUSG had a milder course of disease. Early recovery of VC function and non-permanent palsy were expected.

Background: Influenza and pneumococcal vaccine uptake in the older population aged 65 years or over of Hong Kong dramatically increased since the 2003 SARS outbreak. This study is aimed to evaluate the impact of increased coverage of influenza and pneumococcal vaccines by comparing the change of disease burden in the older population of Hong Kong, with the burden in the older population of Brisbane with relatively high vaccine coverage in the past fifteen years., Methods: Time series segmented regression models were applied to weekly numbers of cause-specific mortality or hospitalization of Hong Kong and Brisbane. Annual excess rates of mortality or hospitalization associated with influenza in the older population were estimated for the pre-SARS (reference period), post-SARS and post-pandemic period, respectively. The rate ratios (RRs) between these periods were also calculated to assess the relative change of disease burden., Results: Compared to the pre-SARS period, excess rates of mortality associated with influenza during the post-SARS period in Hong Kong decreased for cardiorespiratory diseases (RR = 0.90, 95% CI 0.80, 1.01), stroke (RR = 0.74, 95% CI 0.50, 1.09), and ischemic heart diseases (RR = 0.45, 95% CI 0.34, 0.58). The corresponding RRs in Brisbane were 0.79 (95% CI 0.54, 1.15), 0.33 (0.13, 0.80), and 1.09 (0.62, 1.90), respectively. Only the mortality of ischemic heart diseases showed a greater reduction in Hong Kong than in Brisbane. During the post-pandemic period, excess rates of all-cause mortality increased in Hong Kong, but to a lesser extent than in Brisbane (RR = 1.41 vs 2.39)., Conclusion: A relative decrease (or less of an increase) of influenza disease burden was observed in the older population of Hong Kong after increased coverage of influenza and pneumococcal vaccines in this population, as compared to those of Brisbane where vaccination rates remained stable. The lack of significant findings in some disease categories highlights the challenges of evaluating the benefits of vaccination at the population level.

A large number of liver transplants have been performed for hepatocellular carcinoma (HCC), and recurrence is increasingly encountered. The recurrence of HCC after liver transplantation is notoriously difficult to manage. We hereby propose multi-disciplinary management with a systematic approach. The patient is jointly managed by the transplant surgeon, physician, oncologist and radiologist. Immunosuppressants should be tapered to the lowest effective dose to protect against rejection. The combination of a mammalian target of rapamycin inhibitor with a reduced calcineurin inhibitor could be considered with close monitoring of graft function and toxicity. Comprehensive staging can be performed by dual-tracer positron emission tomography-computed tomography or the combination of contrast computed tomography and a bone scan. In patients with disseminated recurrence, sorafenib confers survival benefits but is associated with significant drug toxicity. Oligo-recurrence encompasses recurrent disease that is limited in number and location so that loco-regional treatments convey disease control and survival benefits. Intra-hepatic recurrence can be managed with graft resection, but significant operative morbidity is expected. Radiofrequency ablation and stereotactic body radiation therapy (SBRT) are effective alternative strategies. In patients with more advanced hepatic disease, regional treatment with trans-arterial chemoembolization or intra-arterial Yttrium-90 can be considered. For patients with extra-hepatic oligo-recurrence, loco-regional treatment can be considered if practical. Patients with more than one site of recurrence are not always contraindicated for curative treatments. Surgical resection is effective for patients with pulmonary oligo-recurrence, but adequate lung function is a pre-requisite. SBRT is a non-invasive and effective modality that conveys local control to pulmonary and skeletal oligo-recurrences., Competing Interests: Conflict-of-interest statement: None of the authors has any conflict of interest.