Redox Reorganization: Aluminium Promoted 1,5-Hydride Shifts Allow the Controlled Synthesis of Multisubstituted Cyclohexenes.

An efficient synthesis of cyclohexenes has been achieved from easily accessible tetrahydropyrans via a tandem 1,5-hydride shift-aldol condensation. We discovered that readily available aluminium reagents, e.g. Al2 O3 or Al(Ot Bu)3 are essential for this process, promoting the 1,5-hydride shift with complete regio- and enantiospecificity (in stark contrast to results obtained under basic conditions). The mild conditions, coupled with multiple methods available to access the tetrahydropyran starting materials makes this a versatile method with exceptional functional group tolerance. A wide range of cyclohexenes (>40 examples) have been prepared, many in enantiopure form, showing our ability to selectively install a substituent at each position around the newly forged cyclohexene ring. Experimental and computational studies revealed that aluminium serves a dual role in facilitating the hydride shift, activating both the alkoxide nucleophile and the electrophilic carbonyl group.

A Rapid, Simple, Inexpensive, and Mobile Colorimetric Assay COVID-19-LAMP for Mass On-Site Screening of COVID-19.

To control the COVID-19 pandemic and prevent its resurgence in areas preparing for a return of economic activities, a method for a rapid, simple, and inexpensive point-of-care diagnosis and mass screening is urgently needed. We developed and evaluated a one-step colorimetric reverse-transcriptional loop-mediated isothermal amplification assay (COVID-19-LAMP) for detection of SARS-CoV-2, using SARS-CoV-2 isolate and respiratory samples from patients with COVID-19 (n = 223) and other respiratory virus infections (n = 143). The assay involves simple equipment and techniques and low cost, without the need for expensive qPCR machines, and the result, indicated by color change, is easily interpreted by naked eyes. COVID-19-LAMP can detect SARS-CoV-2 RNA with detection limit of 42 copies/reaction. Of 223 respiratory samples positive for SARS-CoV-2 by qRT-PCR, 212 and 219 were positive by COVID-19-LAMP at 60 and 90 min (sensitivities of 95.07% and 98.21%) respectively, with the highest sensitivities among nasopharyngeal swabs (96.88% and 98.96%), compared to sputum/deep throat saliva samples (94.03% and 97.02%), and throat swab samples (93.33% and 98.33%). None of the 143 samples with other respiratory viruses were positive by COVID-19-LAMP, showing 100% specificity. Samples with higher viral load showed shorter detection time, some as early as 30 min. This inexpensive, highly sensitive and specific COVID-19-LAMP assay can be useful for rapid deployment as mobile diagnostic units to resource-limiting areas for point-of-care diagnosis, and for unlimited high-throughput mass screening at borders to reduce cross-regional transmission.

PLD4 is a genetic determinant to systemic lupus erythematosus and involved in murine autoimmune phenotypes.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterised by autoantibody production and widespread inflammation damaging many organs. Previous genome-wide association studies (GWASs) have revealed over 80 genetic determinants of SLE, but they collectively explain a fraction of the heritability, and only a few were proven in vivo for the involvement in SLE. We conducted a meta-analysis of SLE GWAS in the Japanese population, followed by functional analyses of a susceptibility gene with use of mutant mice. METHODS: We conducted a meta-analysis of two GWASs comprising a total of 1363 cases and 5536 controls using the 1000 Genome Project data as an imputation reference. Enrichment analyses for functional annotations were conducted. We examined Phospholipase D4 (Pld4) mutant mice to assess functional involvement of a genetic determinant. RESULTS: We found a total of 14 significant loci, which included rs2582511 in AHNAK2/PLD4 recently reported in a Chinese study and a novel locus of rs143181706 in MAMLD1 (p=7.9×10-11 and 3.7×10-8, respectively). PLD4 risk allele was associated with anti-dsDNA antibody production. Enrichment analysis of genetic signals revealed involvement of a wide range of immune-related cells and pathways. Pld4 mutant mice revealed remarkably low body weight. The mice demonstrated autoimmune phenotypes compatible with SLE, including splenomegaly and lymphadenopathy, expansion of B cells and hypersecretion of BAFF and production of autoantibodies especially anti-nuclear antibody and anti-dsDNA antibody. CONCLUSIONS: We found a novel susceptibility gene to SLE. Pld4 mutant mice revealed autoimmune phenotypes suggesting functional involvement of PLD4 with the basics of SLE.

Polarization-selective ultra-broadband super absorber.

While a broadband metamaterial perfect absorber (MPA) has been implemented and proposed intensively in recent years, an ultra-broadband perfect absorber with polarization selectivity has not been realized in literature. In this work, we propose a configuration of polarization-selective (PS) MPA with ultra-wide absorption bandwidth. The aluminum wire grid is integrated on top of the ultrathin-metal-dielectric stacking. The transverse electric (TE) wave is blocked due to the requirement of zero tangential electric field at the metal surface. The transverse magnetic field can pass the aluminum wire-grids because the normal electric field can be supported by the surface charge density at the metal surface, and full absorption of the TM wave is accomplished by the metal-dielectric stacking beneath. Theoretical calculation using rigorously coupled wave analysis demonstrates the wavelength selectivity from λ = 1.98µm to λ = 11.74µm where the TE absorption is <0.04 while TM absorption is >0.95, using 300 nm thick aluminum (Al) wire grid with 16-pair SiO2/Ti stacking. Additionally, the design is wavelength scalable by adjusting the dielectric thickness (tSiO2) and the wire grid period (P) and height (t). The experimental result is demonstrated using Al grids and Ti/SiO2, and the measured result fully supports the calculated prediction.

Communication challenges experienced by migrants with cancer: A comparison of migrant and English-speaking Australian-born cancer patients.

OBJECTIVES: Understanding the difficulties faced by different migrant groups is vital to address disparities and inform targeted health-care service delivery. Migrant oncology patients experience increased morbidity, mortality and psychological distress, with this tentatively linked to language and communication difficulties. The objective of this exploratory study was to investigate the communication barriers and challenges experienced by Arabic, Greek and Chinese (Mandarin and Cantonese) speaking oncology patients in Australia. METHODS: This study employed a cross-sectional design using patient-reported outcome survey data from migrant and English-speaking Australian-born patients with cancer. Patients were recruited through oncology clinics and Australian state cancer registries. Data were collected regarding patient clinical and demographic characteristics and health-care and communication experiences. Data from the clinics and registries were combined for analysis. RESULTS: Significant differences were found between migrant groups in demographic characteristics, communication and health-care experiences, and information and care preferences. Chinese patients cited problems with understanding medical information, the Australian health-care system, and communicating with their health-care team. Conversely, Arabic- and Greek-speaking patients reported higher understanding of the health-care system, and less communication difficulties. CONCLUSIONS: Our study findings suggest that migrant groups differ from each other in their health communication expectations and requirements. Lower education and health literacy of some groups may play a role in poorer health outcomes. Public health interventions and assistance provided to migrants should be tailored to the specific needs and characteristics of that language or cultural group. Future research directions are discussed.

Omnidirectional, polarization-independent, ultra-broadband metamaterial perfect absorber using field-penetration and reflected-wave-cancellation.

In this work, we present the result of nickel (Ni)-based metamaterial perfect absorbers (MPA) with ultra-broadband close-to-one absorbance. The experimental broadband characteristic is significantly improved over the past effort on metamaterial perfect absorbers. An in-depth physical picture and quantitative analysis is presented to reveal the physical origin of its ultrabroadband nature. The key constituent is the cancellation of the reflected wave using ultra-thin, moderate-extinction metallic films. The ultra-thin metal thickness can reduce the reflection as the optical field penetrates through the metallic films. This leads to minimal reflection at each ultra-thin metal layer, and light is penetrating into the Ni/SiO2 stacking. More intuitively, when the layer thickness is much smaller than the photon wavelength, the layer is essentially invisible to the photons. This results in absorption in the metal thin-film through penetration while there is minimal reflection by the metal film. More importantly, the experimental evidence for omni-directionality and polarization-insensitivity are established for the proposed design. Detailed measurement is conducted. Due to the ultrathin metal layers and the satisfactory tolerance in dielectric thickness, the broadband absorption has minimal degradation at oblique incidence. Such a wide angle, polarization-insensitive, ultra-broadband MPA can be very promising in the future, and the optical physics using sub-skin-depth metal film can also facilitate miniaturized high-performance nano-photonic devices.

"I might not have cancer if you didn't mention it": a qualitative study on information needed by culturally diverse cancer survivors.

BACKGROUND: Immigrants from culturally and linguistically diverse (CALD) backgrounds diagnosed with cancer face multiple challenges with health systems foreign to them. There is scarce understanding about their needs following cancer treatment in the survivorship phase. Unmet needs were examined in immigrant Chinese and Greek cancer survivors in order to assist development of relevant and useful information resources for these CALD groups. METHODS: Qualitative descriptive design was used. Adult cancer survivors, whose native language was Mandarin, Cantonese or Greek, were recruited through ethnic cancer support groups and cancer specialists in two Australian cities. Six focus groups were conducted, two in each native language group. Recorded responses were transcribed, translated into English, and thematically analysed. RESULTS: Thirty-nine CALD cancer survivors participated from Greek (11), Cantonese (14) and Mandarin (14) backgrounds. Thematic findings included as follows: ongoing cancer-related stressors, cancer misunderstandings, coping strategies, 'survivor' seldom reflects self-appraisal, and additional CALD survivorship information needed. Immigrant cancer survivors may prefer 'recovery' to 'survivorship' descriptors and need information similar to Caucasian cancer survivors alongside as follows: resources for navigating health care, financial and community entitlements; caregiver-directed information to enhance their support; explanations about differences in health care approaches between survivors' original and adopted countries; and acknowledgment of survivorship diversity within CALD groups. CONCLUSIONS: Immigrant cancer survivors' additional requirements to native survivors likely reflect challenges in dealing with foreign environments and varied levels of acculturation within group members. Identification of immigrant cancer survivorship issues may support development of targeted resources for promoting survivors' self-care and capacity for finding, choosing, and using existing support options.

Migrant health in cancer: outcome disparities and the determinant role of migrant-specific variables.

BACKGROUND: Multiethnic societies face challenges in delivering evidence-based culturally competent health care. This study compared health-related quality of life and psychological morbidity in a hospital-based sample of first-generation migrants and Australian-born Anglo cancer patients, controlling for potential confounders related to migrant status. Further, it explored the relative contribution of ethnicity versus migrant-related variables. METHODS: Eligible participants, recruited via 16 oncology clinics in Australia, included those over the age of 18, diagnosed with cancer (any type or stage) within the previous 12 months and having commenced treatment at least 1 month previously. RESULTS: In total, 571 migrant patients (comprising 145 Arabic, 248 Chinese, and 178 Greek) and a control group of 274 Anglo-Australian patients participated. In multiple linear regression models adjusted for age, sex, education, marital status, socioeconomic status, time since diagnosis, and type of cancer, migrants had clinically significantly worse health-related quality of life (HRQL; 3.6-7.3 points on FACT-G, p < .0001), higher depression and anxiety (both p < .0001), and higher incidence of clinical depression (p < .0001) and anxiety (p = .003) than Anglo-Australians. Understanding the health system (p < .0001 for each outcome) and difficulty communicating with the doctor (p = .04 to .0001) partially mediated the impact of migrancy. In migrant-only analyses, migrant-related variables (language difficulty and poor understanding of the health system), not ethnicity, predicted outcomes. CONCLUSION: Migrants who develop cancer have worse psychological and HRQL outcomes than Anglo-Australians. Potential targets for intervention include assistance in navigating the health system, translated information, and cultural competency training for health professionals.

Experimentally-implemented genetic algorithm (Exp-GA): toward fully optimal photovoltaics.

The geometry and dimension design is the most critical part for the success in nano-photonic devices. The choices of the geometrical parameters dramatically affect the device performance. Most of the time, simulation is conducted to locate the suitable geometry, but in many cases simulation can be ineffective. The most pronounced examples are large-area randomized patterns for solar cells, light emitting diode (LED), and thermophtovoltaics (TPV). The large random pattern is nearly impossible to calculate and optimize due to the extended CPU runtime and the memory limitation. Other scenarios that numerical simulations become ineffective include three-dimensional complex structures with anisotropic dielectric response. This leads to extended simulation time especially for the repeated runs during its geometry optimization. In this paper, we show that by incorporating genetic algorithm (GA) into real-world experiments, shortened trial-and-error time can be achieved. More importantly, this scheme can be used for many photonic design problems that are unsuitable for simulation-based optimizations. Moreover, the experimentally implemented genetic algorithm (Exp-GA) has the additional advantage that the resultant objective value is a real one rather than a theoretical one. This prevents the gaps between the modeling and the fabrication due to the process variation or inaccurate numerical models. Using TPV emitters as an example, 22% enhancement in the mean objective value is achieved.

Approaching conversion limit with all-dielectric solar cell reflectors.

Metallic back reflectors has been used for thin-film and wafer-based solar cells for very long time. Nonetheless, the metallic mirrors might not be the best choices for photovoltaics. In this work, we show that solar cells with all-dielectric reflectors can surpass the best-configured metal-backed devices. Theoretical and experimental results all show that superior large-angle light scattering capability can be achieved by the diffuse medium reflectors, and the solar cell J-V enhancement is higher for solar cells using all-dielectric reflectors. Specifically, the measured diffused scattering efficiency (D.S.E.) of a diffuse medium reflector is >0.8 for the light trapping spectral range (600nm-1000nm), and the measured reflectance of a diffuse medium can be as high as silver if the geometry of embedded titanium oxide(TiO(2)) nanoparticles is optimized. Moreover, the diffuse medium reflectors have the additional advantage of room-temperature processing, low cost, and very high throughput. We believe that using all-dielectric solar cell reflectors is a way to approach the thermodynamic conversion limit by completely excluding metallic dissipation.

Aperiodic and randomized dielectric mirrors: alternatives to metallic back reflectors for solar cells.

Dielectric mirrors have recently emerged for solar cells due to the advantages of lower cost, lower temperature processing, higher throughput, and zero plasmonic absorption as compared to conventional metallic counterparts. Nonetheless, in the past, efforts for incorporating dielectric mirrors into photovoltaics were not successful due to limited bandwidth and insufficient light scattering that prevented their wide usage. In this work, it is shown that the key for ultra-broadband dielectric mirrors is aperiodicity, or randomization. In addition, it has been proven that dielectric mirrors can be widely applicable to thin-film and thick wafer-based solar cells to provide for light trapping comparable to conventional metallic back reflectors at their respective optimal geometries. Finally, the near-field angular emission plot of Poynting vectors is conducted, and it further confirms the superior light-scattering property of dielectric mirrors, especially for diffuse medium reflectors, despite the absence of surface plasmon excitation. The preliminary experimental results also confirm the high feasibility of dielectric mirrors for photovoltaics.

The versatile designs and optimizations for cylindrical TiO2-based scatterers for solar cell anti-reflection coatings.

The anti-reflection coating(ARC) based on dielectric nano-particles has been recently proposed as a new way to achieve the low reflectance required for solar cell front surfaces. In this scenario, the Mie modes associated with the dielectric nano-particles are utilized to facilitate photon forward scattering. In this work, versatile designs together with systematically optimized geometry are examined, for the ARCs based on dielectric scatterers. It is found that the Si3N4-TiO2 or SiO2-TiO2 stack is capable of providing low reflectance while maintaining a flat and passivated ARC-semiconductor interface which can be beneficial for reduced interface recombination and prevent V(OC) degradation associated with topography on the active materials. It is also confirmed that the plasmonic nano-particles placed at the front side of solar cells is not a preferred scheme, even with thorough geometrical optimization. At the ultimate design based on mixed graded index(GI) Mie-scattering, the averaged reflectance can be as low as 0.25%. Such a low reflectance is currently only achievable by ultra-long silicon nano-tips, but silicon nano-tips introduce severe surface recombination. On the other hand, the mixed GI Mie design preserves a flat and passivated ARC-silicon interface, with total thickness reduced to 279.8 nm, much thinner than 1.6 µm for silicon nanotips. In addition, the light trapping capability of mixed GI Mie design is much better than silicon nanotips. In fact, when compared to the state-of-art TiO2 light trapping anti-reflection coating, the mixed GI Mie design provides same light trapping capability while providing much lower reflectance.

An optimized surface plasmon photovoltaic structure using energy transfer between discrete nano-particles.

Surface plasmon enhancement has been proposed as a way to achieve higher absorption for thin-film photovoltaics, where surface plasmon polariton(SPP) and localized surface plasmon (LSP) are shown to provide dense near field and far field light scattering. Here it is shown that controlled far-field light scattering can be achieved using successive coupling between surface plasmonic (SP) nano-particles. Through genetic algorithm (GA) optimization, energy transfer between discrete nano-particles (ETDNP) is identified, which enhances solar cell efficiency. The optimized energy transfer structure acts like lumped-element transmission line and can properly alter the direction of photon flow. Increased in-plane component of wavevector is thus achieved and photon path length is extended. In addition, Wood-Rayleigh anomaly, at which transmission minimum occurs, is avoided through GA optimization. Optimized energy transfer structure provides 46.95% improvement over baseline planar cell. It achieves larger angular scattering capability compared to conventional surface plasmon polariton back reflector structure and index-guided structure due to SP energy transfer through mode coupling. Via SP mediated energy transfer, an alternative way to control the light flow inside thin-film is proposed, which can be more efficient than conventional index-guided mode using total internal reflection (TIR).

Reducing disparity in outcomes for immigrants with cancer: a qualitative assessment of the feasibility and acceptability of a culturally targeted telephone-based supportive care intervention.

PURPOSE: Australia has one of the most culturally diverse populations in the world. Immigrant cancer patients' poorer outcomes compared to English-speaking patients confirm the need for culturally sensitive supportive care interventions. The aims of this study were (1) to identify cultural sensitivities that are important to the acceptability of a telephone-based supportive care intervention and (2) to identify cultural barriers and facilitators to intervention participation. METHODS: Patients and carers attending Chinese or Arabic cancer support groups were recruited. Two focus groups comprising 12 patients and 4 carers, and two telephone interviews were conducted in the participants' own language. A semi-structured interview format was utilised to determine potential cultural sensitivities that may influence the intervention delivery format as well as patients' willingness to participate in telephone-based supportive care interventions. Content analysis confirmed similar themes across groups. RESULTS: The intervention was viewed favourably as a means of providing information and support in the patient's language. Cultural considerations included assurances of confidentiality, as cancer is not openly discussed within communities. An initial face-to-face contact was highlighted as the most important factor facilitating participation. Participants also recommended the inclusion of patient-initiated calls as part of the intervention. CONCLUSIONS: This study provides cultural insights relevant to the development of a culturally sensitive telephone-based supportive care intervention for Arabic- and Chinese-speaking cancer patients. Participants highlighted the need for face-to-face contact and inclusion of patient-initiated calls as important methodological considerations.

High-quality single-cell transcriptomics from ovarian histological sections during folliculogenesis.

High-quality, straightforward single-cell RNA sequencing (RNA-seq) with spatial resolution remains challenging. Here, we developed DRaqL (direct RNA recovery and quenching for laser capture microdissection), an experimental approach for efficient cell lysis of tissue sections, directly applicable to cDNA amplification. Single-cell RNA-seq combined with DRaqL allowed transcriptomic profiling from alcohol-fixed sections with efficiency comparable with that of profiling from freshly dissociated cells, together with effective exon-exon junction profiling. The combination of DRaqL with protease treatment enabled robust and efficient single-cell transcriptome analysis from formalin-fixed tissue sections. Applying this method to mouse ovarian sections, we were able to predict the transcriptome of oocytes by their size and identified an anomaly in the size-transcriptome relationship relevant to growth retardation of oocytes, in addition to detecting oocyte-specific splice isoforms. Furthermore, we identified differentially expressed genes in granulosa cells in association with their proximity to the oocytes, suggesting distinct epigenetic regulations and cell-cycle activities governing the germ-soma relationship. Thus, DRaqL is a versatile, efficient approach for high-quality single-cell RNA-seq from tissue sections, thereby revealing histological heterogeneity in folliculogenic transcriptome.

A bridge between cultures: interpreters' perspectives of consultations with migrant oncology patients.

BACKGROUND: Migration is increasing worldwide. In previous research into people with cancer from culturally and linguistically diverse backgrounds, interpreter accuracy, professionalism and continuity have emerged as key concerns for patients. Little is known about interpreters' perceptions of their role and the challenges they face. This study aimed to obtain their perspective. METHODS: Thirty interpreters (Greek n = 7, Chinese n = 11, and Arabic n = 12) participated in four focus groups which were audio-taped, transcribed and analysed for themes using N-Vivo software. RESULTS: Skills as an interpreter were broadly perceived as conveying information accurately, being confidential and impartial. Three broad dilemmas faced by interpreters emerged: accuracy versus understanding; translating only versus cultural advocacy and sensitivity; and professionalism versus providing support. Some saw themselves as merely an accurate conduit of information, while others saw their role in broader terms, encompassing patient advocacy, cultural brokerage and provision of emotional support. Perceived challenges in their role included lack of continuity, managing their own emotions especially after bad news consultations, and managing diverse patient and family expectations. Training and support needs included medical terminology, communication and counselling skills and debriefing. Interpreters suggested that oncologists check on interpreter/patient's language or dialect compatibility; use lay language and short sentences; and speak in the first person. CONCLUSIONS: Resolving potential conflicts between information provision and advocacy is an important area of cross-cultural communication research. Further training and support is required to enhance interpreters' competence in managing delicate situations from a professional, cultural and psychological perspective; and to assist doctors to collaborate with interpreters to ensure culturally competent communication. Ultimately, this will improve interpreters' well-being and patient care.

A case of refractory systemic lupus erythematosus with monocytosis exhibiting somatic KRAS mutation.

BACKGROUND: Systemic lupus erythematosus (SLE), an autoimmune disorder that damages various organ systems, is caused by a combination of genetic and environmental factors. Although germline mutations of several genes are known to cause juvenile SLE, most of the susceptibility genetic variants of adult SLE are common variants of the population, somatic mutations that cause or exacerbate SLE have not been reported. We hereby report a refractory SLE case with monocytosis accompanying somatic KRAS mutation that have been shown to cause lupus-like symptoms. CASE PRESENTATION: A 60-year-old female patient who had been diagnosed with SLE was admitted to our hospital. Although prednisolone and tacrolimus treatments had kept her thrombocytopenia and anti-DNA Ab level at bay for more than 4 years, a diagnosis of transverse myelitis was made when she became acutely ill with pleocytosis. Elevated cells (predominately monocytes), protein, IgG, and IL-6 levels were also found in the cerebrospinal fluid (CSF) of the patient. Standard pulse treatments of methylprednisolone, high-dose of prednisolone, and intravenous cyclophosphamide in combination with plasma exchange could not alleviate the refractory neural and autoimmune manifestation. Monocytosis of peripheral blood was also noted. Flow cytometric analysis revealed elevated ratio of CD14+CD16+ atypical monocytes, which excluded the possibility of chronic myelomonocytic leukemia. Lupus-like symptoms with monocytosis reminded us of Ras-associated autoimmune leukoproliferative disorder, and Sanger sequencing of KRAS and NRAS genes from the patients' peripheral blood mononuclear cells (PBMC), sorted CD3+ lymphocytes and CD14+ monocytes, and cerebrospinal fluid were performed. An activating KRAS somatic mutation was found in the patients' DNA at the time of encephalomyelitis diagnosis. CONCLUSION: Somatic mutations of some genes including KRAS may cause the refractoriness of SLE.

Daily ambulatory remote monitoring system for drug escalation in chronic heart failure with reduced ejection fraction: pilot phase of DAVID-HF study.

Aims: Underutilization of guideline-directed heart failure with reduced ejection fraction (HFrEF) medications contributes to poor outcomes. Methods and results: A pilot study to evaluate the safety and efficacy of a home-based remote monitoring system for HFrEF management was performed. The system included wearable armband monitors paired with the smartphone application. An HFrEF medication titration algorithm was used to adjust medication daily. The primary endpoint was HFrEF medication utilization at 120 days. Twenty patients (60.5 ± 8.2 years, men: 85%) with HFrEF were recruited. All received angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI) at recruitment; 45% received ≥50% maximal targeted dose (MTD) with % MTD of 44.4 ± 31.7%. At baseline, 90 and 70% received beta-adrenergic blocker and mineralocorticoid receptor antagonist (MRA), 35% received ≥50% MTD beta-adrenergic blocker with % MTD of 34.1 ± 29.6%, and 25% received ≥50% MTD MRA with % MTD of 25.0 ± 19.9%. At 120 days, 70% received ≥50% MTD ACEI/ARB/ARNI (P = 0.110) with % MTD increased to 64.4 ± 33.5% (P = 0.060). The proportion receiving ≥50% MTD ARNI increased from 15 to 55% (P = 0.089) with % MTD ARNI increased from 20.6 ± 30.9 to 53.1 ± 39.5% (P = 0.006*). More patients received ≥50% MTD MRA (65 vs. 25%, P = 0.011*) with % MTD MRA increased from 25.0 ± 19.9 to 46.2 ± 28.8% (P = 0.009*). Ninety-five per cent of patients had reduced NT-proBNP with the percentage reduction of 26.7 ± 19.7%. Conclusion: Heart failure with reduced ejection fraction medication escalation with remote monitoring appeared feasible.

Fatal Pneumonia Associated With a Novel Genotype of Human Coronavirus OC43.

Since its first discovery in 1967, human coronavirus OC43 (HCoV-OC43) has been associated with mild self-limiting upper respiratory infections worldwide. Fatal primary pneumonia due to HCoV-OC43 is not frequently described. This study describes a case of fatal primary pneumonia associated with HCoV-OC43 in a 75-year-old patient with good past health. The viral loads of the respiratory tract specimens (bronchoalveolar lavage and endotracheal aspirate) from diagnosis to death were persistently high (3.49 × 106-1.10 × 1010 copies/ml). HCoV-OC43 at a 6.46 × 103 copies/ml level was also detected from his pleural fluid 2 days before his death. Complete genome sequencing and phylogenetic analysis showed that the present HCoV-OC43 forms a distinct cluster with three other HCoV-OC43 from United States, with a bootstrap value of 100% and sharing 99.9% nucleotide identities. Pairwise genetic distance between this cluster and other HCoV-OC43 genotypes ranged from 0.27 ± 0.02% to 1.25 ± 0.01%. In contrast, the lowest pairwise genetic distance between existing HCoV-OC43 genotypes was 0.26 ± 0.02%, suggesting that this cluster constitutes a novel HCoV-OC43 genotype, which we named genotype I. Unlike genotypes D, E, F, G, and H, no recombination event was observed for this novel genotype. Structural modeling revealed that the loop with the S1/S2 cleavage site was four amino acids longer than other HCoV-OC43, making it more exposed and accessible to protease, which may have resulted in its possible hypervirulence.

The clinical characteristics and predictors of severe digital ischemia in patients with anti-aminoacyl transfer RNA synthetase antibodies.

Severe digital ischemia (SDI), which presents with digital ulcers, necrosis, or gangrene, has been reported to be a rare manifestation of anti-aminoacyl transfer RNA synthetase (ARS) antibody-positive polymyositis/dermatomyositis or anti-synthetase syndrome. A retrospective study was conducted between 2009 and 2020 at our department to investigate the clinical features of anti-ARS antibody-positive patients with SDI and identify their predictors. A total of 46 patients who were positive for anti-ARS antibody were included, four of whom (8.7%) presented with SDI. The characteristics of the patients with SDI were as follows: the median age was 74 years, with 75% being female; anti-Jo-1 antibody, Raynaud's phenomenon, interstitial lung disease, and myositis were observed in two (50%), four (100%), four (100%), and three patients (75%), respectively. Next, we reviewed the literature of anti-ARS antibody-positive patients with SDI and investigated the predictors of SDI by analyzing a total of 51 patients, including the previously reported five patients with SDI. Multivariable analyses revealed that Raynaud's phenomenon and myositis independently predicted the development of SDI in patients with anti-ARS antibody. In conclusion, digital ulcers, necrosis, or gangrene seem to be more common presentations in our study, and Raynaud's phenomenon and myositis can predict the complications of SDI in anti-ARS antibody-positive patients.