Impact of COVID infection on lung function test and quality of life.

Post-COVID-19 pulmonary sequalae are well-recognized early in the pandemic. Survivorship clinics are crucial for managing at-risk patients. However, it is unclear who requires pulmonary function test (PFT) and when PFTs should be performed. We aim to investigate for whom and how these interval PFTs should be performed. We performed a single-centre, prospective cohort study on COVID-19 survivors between 1st May 2020 and 31st April 2022. These patients were followed up at 6, 9 and 12 months with interval PFT and Short Form-36 (SF-36) Health Survey. Those with PFT defects were offered a computed tomography scan of the thorax. Of the 46 patients recruited, 17 (37%) had severe/critical illness. Compared to those with mild/moderate disease, these patients were more likely to experience DLCO defects (59% versus 17%, p = 0.005) and had lower SF-36 scores (mean physical component summary score of 45 ± 12 versus 52 ± 8, p = 0.046). These differences were most notable at 6 months, compared to the 9- and 12-months intervals. DLCO defects were also associated with older age, raised inflammatory markers and extensive CXR infiltrates. Besides interstitial-like abnormalities, obesity and undiagnosed lung conditions accounted for 39% of the PFT abnormalities. Interval PFTs can be performed earliest 6 months post-COVID-19. Patients with normal tests were unlikely to develop new abnormalities and would not require repeat PFTs. Abnormal PFTs can be followed-up with repeat PFTs 6 monthly until resolution. Non-COVID-19 differentials should be considered for persistent PFT abnormalities.

Vertically Aligned One-Dimensional Crystal-Structured Sb2Se3 for High-Efficiency Flexible Solar Cells via Regulating Selenization Kinetics.

Recently, antimony selenide (Sb2Se3) has exhibited an exciting potential for flexible photoelectric applications due to its unique one-dimensional (1D) chain-type crystal structure, low-cost constituents, and superior optoelectronic properties. The 1D structure endows Sb2Se3 with a strong anisotropy in carrier transport and a lasting mechanical deformation tolerance. The control of the crystalline orientation of the Sb2Se3 film is an essential requirement for its device performance optimization. However, the current state-of-the-art Sb2Se3 devices suffer from unsatisfactory orientation control, especially for the (001) orientation, in which the chains stand vertically. Herein, we achieved an unprecedented control of the (001) orientation for the growth of the Sb2Se3 film on a flexible Mo-coated mica substrate by balancing the collision rate and kinetic energy of Se vapor particles with the surface of Sb film by regulating the selenization kinetics. Based on this (001)-oriented Sb2Se3 film, a high efficiency of 8.42% with a record open-circuit voltage (VOC) of 0.47 V is obtained for flexible Sb2Se3 solar cells. The vertical van der Waals gaps in the (001) orientation provide favorable diffusion paths for Se atoms, which results in a Se-rich state at the bottom of the Sb2Se3 film and promotes the in situ formation of the MoSe2 interlayer between Mo and Sb2Se3. These phenomena contribute to a back-surface field enhanced absorber layer and a quasi-Ohmic back contact, improving the device's VOC and the collection of carriers. This method provides an effective strategy for the orientation control of 1D materials for efficient photoelectric devices.

Global Epidemiology and Genetics of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading cancers worldwide. Classically, HCC develops in genetically susceptible individuals who are exposed to risk factors, especially in the presence of liver cirrhosis. Significant temporal and geographic variations exist for HCC and its etiologies. Over time, the burden of HCC has shifted from the low-moderate to the high sociodemographic index regions, reflecting the transition from viral to nonviral causes. Geographically, the hepatitis viruses predominate as the causes of HCC in Asia and Africa. Although there are genetic conditions that confer increased risk for HCC, these diagnoses are rarely recognized outside North America and Europe. In this review, we will evaluate the epidemiologic trends and risk factors of HCC, and discuss the genetics of HCC, including monogenic diseases, single-nucleotide polymorphisms, gut microbiome, and somatic mutations.

Liquid-Phase van der Waals Epitaxy of a Few-Layer and Unit-Cell Thick Ruddlesden-Popper Halide Perovskite.

2D Ruddlesden-Popper (RP) halide perovskites with natural multiple quantum well structures are an ideal platform to integrate into vertical heterostructures, which may introduce plentiful intriguing optoelectronic properties that are not accessible in a single bulk crystal. Here, we report liquid-phase van der Waals epitaxy of a 2D RP hybrid perovskite (4,4-DFPD)2PbI4 (4,4-DFPD is 4,4-difluoropiperidinium) on muscovite mica and fabricate a series of perovskite-perovskite vertical heterostructures by integrating it with a second 2D RP perovskite R-NPB [NPB = 1-(1-naphthyl)ethylammonium lead bromide] sheets. The grown (4,4-DFPD)2PbI4 nanobelt array can be multiple layers to unit-cell thin and are crystallographically aligned on the mica substrate. An interlayer photo emission in this R-NPB/(4,4-DFPD)2PbI4 heterostructure with a lifetime of about 25 ns at 120 K has been revealed. Our demonstration of epitaxial (4,4-DFPD)2PbI4 array grown on mica via liquid-phase van der Waals epitaxy provides a paradigm to prepare orderly distributed 2D RP hybrid perovskites for further integration into multiple heterostructures. The discovery of a new interlayer emission in the R-NPB/(4,4-DFPD)2PbI4 heterostructure enriches the basic understanding of interlayer charge transition in halide perovskite systems.

Giant pyroelectricity in nanomembranes.

Pyroelectricity describes the generation of electricity by temporal temperature change in polar materials1-3. When free-standing pyroelectric materials approach the 2D crystalline limit, how pyroelectricity behaves remained largely unknown. Here, using three model pyroelectric materials whose bonding characters along the out-of-plane direction vary from van der Waals (In2Se3), quasi-van der Waals (CsBiNb2O7) to ionic/covalent (ZnO), we experimentally show the dimensionality effect on pyroelectricity and the relation between lattice dynamics and pyroelectricity. We find that, for all three materials, when the thickness of free-standing sheets becomes small, their pyroelectric coefficients increase rapidly. We show that the material with chemical bonds along the out-of-plane direction exhibits the greatest dimensionality effect. Experimental observations evidence the possible influence of changed phonon dynamics in crystals with reduced thickness on their pyroelectricity. Our findings should stimulate fundamental study on pyroelectricity in ultra-thin materials and inspire technological development for potential pyroelectric applications in thermal imaging and energy harvesting.

A High-Yield Streptomyces Transcription-Translation Toolkit for Synthetic Biology and Natural Product Applications.

Streptomyces spp. are a major source of clinical antibiotics and industrial chemicals. Streptomyces venezuelae ATCC 10712 is a fast-growing strain and a natural producer of chloramphenicol, jadomycin, and pikromycin, which makes it an attractive candidate as a next-generation synthetic biology chassis. Therefore, genetic tools that accelerate the development of S. venezuelae ATCC 10712, as well as other Streptomyces spp. models, are highly desirable for natural product engineering and discovery. To this end, a dedicated S. venezuelae ATCC 10712 cell-free system is provided in this protocol to enable high-yield heterologous expression of high G+C (%) genes. This protocol is suitable for small-scale (10-100 µL) batch reactions in either 96-well or 384-well plate format, while reactions are potentially scalable. The cell-free system is robust and can achieve high yields (~5-10 µM) for a range of recombinant proteins in a minimal setup. This work also incorporates a broad plasmid toolset for real-time measurement of mRNA and protein synthesis, as well as in-gel fluorescence staining of tagged proteins. This protocol can also be integrated with high-throughput gene expression characterization workflows or the study of enzyme pathways from high G+C (%) genes present in Actinomycetes genomes.

Orientation-Controlled Large-Area Epitaxial PbI2 Thin Films with Tunable Optical Properties.

Lead iodide (PbI2) as a layered material has emerged as an excellent candidate for optoelectronics in the visible and ultraviolet regime. Micrometer-sized flakes synthesized by mechanical exfoliation from bulk crystals or by physical vapor deposition have shown a plethora of applications from low-threshold lasing at room temperature to high-performance photodetectors with large responsivity and faster response. However, large-area centimeter-sized growth of epitaxial thin films of PbI2 with well-controlled orientation has been challenging. Additionally, the nature of grain boundaries in epitaxial thin films of PbI2 remains elusive. Here, we use mica as a model substrate to unravel the growth mechanism of large-area epitaxial PbI2 thin films. The partial growth leading to uncoalesced domains reveals the existence of inversion domain boundaries in epitaxial PbI2 thin films on mica. Combining the experimental results with first-principles calculations, we also develop an understanding of the thermodynamic and kinetic factors that govern the growth mechanism, which paves the way for the synthesis of high-quality large-area PbI2 on other substrates and heterostructures of PbI2 on single-crystalline graphene. The ability to reproducibly synthesize high-quality large-area thin films with precise control over orientation and tunable optical properties could open up unique and hitherto unavailable opportunities for the use of PbI2 and its heterostructures in optoelectronics, twistronics, substrate engineering, and strain engineering.

A Rare Case of Dengue Encephalitis with Raised Procalcitonin.

BACKGROUND Dengue virus is a common arbovirus with uncertain neurotropism. Dengue encephalitis is a rare but fatal manifestation of severe dengue. Diagnosis requires high clinical suspicion. It should be routinely considered in patients with encephalopathy, especially in countries where dengue virus is endemic. Unlike other forms of severe dengue, the typical warning signs and biochemical derangements are not reliable markers for dengue encephalitis. Alternative biochemical markers of dengue encephalitis are needed. CASE REPORT We present a case of dengue encephalitis with distinctly raised procalcitonin (13.2 µg/L), in the absence of the typical warning signs and biochemical derangements of severe dengue. The patient was a 65-year-old man with fever and sudden loss of consciousness in the absence of other localizing signs/symptoms. Inflammatory markers were raised, with findings of leptomeningeal enhancement on brain computed tomography suggestive of meningoencephalitis. Septic workup was unremarkable (normal renal and liver functions, negative blood and urine cultures). The typical neurotropic microorganisms were not detected in the cerebrospinal fluid. On day 4 of admission, the patient reported abdominal pain and hematuria with a new onset of bicytopenia. Subsequent investigations for dengue infection were positive for serum dengue NS1 antigen and dengue RNA (type 2 strain) in cerebrospinal fluid, confirming the diagnosis of dengue encephalitis. The patient was managed supportively and experienced full clinical recovery. CONCLUSIONS Dengue encephalitis is a rare condition with nonspecific biochemical and imaging abnormalities. We demonstrated that a raised procalcitonin level can occur in the setting of dengue encephalitis. In endemic countries, this finding may prompt further investigations for dengue encephalitis in patients with meningoencephalitis.

A Streptomyces venezuelae Cell-Free Toolkit for Synthetic Biology.

Prokaryotic cell-free coupled transcription-translation (TX-TL) systems are emerging as a powerful tool to examine natural product biosynthetic pathways in a test tube. The key advantages of this approach are the reduced experimental time scales and controlled reaction conditions. To realize this potential, it is essential to develop specialized cell-free systems in organisms enriched for biosynthetic gene clusters. This requires strong protein production and well-characterized synthetic biology tools. The Streptomyces genus is a major source of natural products. To study enzymes and pathways from Streptomyces, we originally developed a homologous Streptomyces cell-free system to provide a native protein folding environment, a high G+C (%) tRNA pool, and an active background metabolism. However, our initial yields were low (36 µg/mL) and showed a high level of batch-to-batch variation. Here, we present an updated high-yield and robust Streptomyces TX-TL protocol, reaching up to yields of 266 µg/mL of expressed recombinant protein. To complement this, we rapidly characterize a range of DNA parts with different reporters, express high G+C (%) biosynthetic genes, and demonstrate an initial proof of concept for combined transcription, translation, and biosynthesis of Streptomyces metabolic pathways in a single "one-pot" reaction.

Computed tomography venography versus intravascular ultrasound in the diagnosis of iliofemoral vein stenosis.

Background: Iliofemoral vein stenosis can cause debilitating chronic venous disease. Diagnostic tools include both computed tomography venography (CTV) and intravascular ultrasonography (IVUS). We aim to compare the diagnostic performance of CTV and IVUS. Patients and methods: We performed a retrospective study of patients with chronic venous disease presenting with iliac vein compression or post-thrombotic limb symptoms, excluding those with acute deep vein thrombosis, high anaesthesia risk, or who had contrast allergy. All patients received CTV before IVUS, as part of the diagnostic work-up and intervention. The cross-sectional area (CSA) of iliofemoral vein segments obtained from both studies were compared against reference CSAs to derive percentage stenosis. A 50% reduction in CSA was considered significant. Results: We studied 50 patients between May 2018 and April 2019. 58% of patients had severe disease CEAP C5-6. 48% of patients had at least one vein segment with significant stenosis. The left proximal common iliac vein was the most commonly stenosed vein segment (n = 12, 24% on IVUS). CSA measurements from CTV were greater than those of IVUS, with a correlation coefficient of 0.57 (p < 0.005). Conversely, percentage stenosis measured on CTV was lower than on IVUS, with approximately one-third of significant stenosis missed on CTV (58 veins from CTV vs. 78 from IVUS, p < 0.005). With IVUS as the gold standard, CTV has low sensitivity (37.2%, 95% CI 26.5-48.9) and high specificity (92.5%, 95% CI 89.3-94.9) in detecting significant stenosis. Conclusions: CTV has limited diagnostic performance in identifying iliofemoral vein stenosis. Patients with normal CTV findings should proceed with IVUS imaging if the clinical features are supportive of iliofemoral vein stenosis.

Endovascular Deep Vein Stenting of Symptomatic Post-Thrombotic and Non-Thrombotic Iliac Vein Stenotic Lesions: A Multicentre Cohort Experience from Singapore.

INTRODUCTION: This paper presents our experience with deep venous stenting in a multi-ethnic Asian cohort of patients with symptomatic Non-Thrombotic Iliac Vein Lesions (NIVL) and Post-Thrombotic Syndrome (PTS). MATERIALS AND METHODS: This was a multicentre retrospective cohort study of patients who had symptomatic deep venous disease. Stent patency rate was evaluated using Duplex ultrasonography immediately post-intervention and at 3, 6 and 12 months. Clinical outcomes were evaluated using the revised Venous Clinical Severity Score (rVCSS) and Visual Analogue Scale (VAS) pain score at baseline and 3 months post-procedure. RESULTS: 87 patients (males = 47/87 (54.0%)); median age = 62 years (IQR 55 - 70)) and 115 limbs were analysed (left = 76/115 (66.1%)). Median follow-up time was 175 (IQR 57 - 257) days. 97/115 (84.3%) had NIVLs and 55/115 (47.8%) had May-Thurner-Syndrome. 43/115 (37.4%) had Clinical, Etiology, Anatomy and Pathophysiology (CEAP) 6 disease. Primary stent patency rates were 98.2% (112/114), 97.9% (93/95), 95.7% (89/93) and 92.8% (64/69) immediately post-intervention, 3, 6 and 12 months, respectively. The 6-month secondary patency rate was 99.1% (114/115). Mean rVCSS and VAS improved from 11.52 (±3.54) to 5.77 (±2.36) (P < 0.01) and 6.62 (±1.93) to 2.92 (±1.50) (P < 0.01) respectively, at 3 months. 41/43 (95.3%) venous ulcers healed over a median time of 169 days (IQR 120 - 253). CONCLUSIONS: Short term primary patency rates following deep venous stenting are excellent, with few re-interventions. Patients presented with NIVLs rather than PTS. There was excellent clinical improvement at 3 months, with a high and expedient venous ulcer healing rate.

Multiple neoplasia in a patient with Gitelman syndrome harboring germline monoallelic MUTYH mutation.

Gitelman syndrome is a rare, recessively inherited disease characterized by chronic hypokalemia and hypomagnesemia as a result of defective electrolyte co-transport at the level of the distal convoluted tubule of the kidney. Here, we present the first report of a patient with Gitelman syndrome who developed multiple neoplasia including colorectal polyposis, synchronous colorectal cancers, recurrent breast fibroadenomata and a desmoid tumor. Whole-exome sequencing confirmed germline compound heterozygous mutations of c.179C > T and c.1326C > G in SLC12A3, and in addition, identified a monoallelic germline c.934-2A > G splice site mutation in MUTYH. In vitro, magnesium deficiency potentiated oxidative DNA damage in lymphoblastoid cell lines derived from the same patient. We postulate that monoallelic MUTYH mutations may manifest in the presence of cooperative non-genetic mechanisms, in this case possibly magnesium deficiency from Gitelman syndrome.

Growth front smoothing effects in extremely high pressure vapor deposition.

Recent experimental chemical vapor depositions of silicon at extreme pressures of ~ 50 MPa (~ 500 atm) have been observed to generate remarkably smooth surfaces not predicted by low-pressure deposition models. In this paper, we propose an anti-shadowing mechanism where the collision of particles within the valleys of the surface growth front leads to smoothening. We conduct Monte Carlo simulations to simulate the evolution of film roughness at pressures between 1 and 50 MPa. We observe that surface roughness approaches an asymptotic invariant value that follows power law behavior as a function of pressure. The film thickness at which invariance begins is shown to have a similar power law behavior with respect to pressure. Our simulated results compare favorably with recent experimental observations and provide insight into the fundamental mechanisms underlying film evolution at pressures between one and hundreds of atmospheres.

High-Crystallinity Epitaxial Sb2Se3 Thin Films on Mica for Flexible Near-Infrared Photodetectors.

The V-VI binary chalcogenide, Sb2Se3, has attracted considerable attention for its applications in thin film optoelectronic devices because of its unique 1D structure and remarkable optoelectronic properties. Herein, we report an Sb2Se3 thin film epitaxially grown on a flexible mica substrate through a relatively weak (van der Waals) interaction by vapor transport deposition. The epitaxial Sb2Se3 thin films exhibit a single (120) out-of-plane orientation and a 0.25° full width at half-maximum of (120) rocking curve in X-ray diffraction, confirming the high crystallinity of the epitaxial films. The Sb2Se3(120) plane is epitaxially aligned on mica(001) surface with the in-plane relationship of Sb2Se3[2̅10]//mica[010] and Sb2Se3[001]//mica[100]. Compared to the photodetector made of a nonepitaxial Sb2Se3 film, the photocurrent of the epitaxial Sb2Se3 film photodetector is almost doubled. Furthermore, because of the flexibility and high sensitivity of the epitaxial Sb2Se3 film photodetector on mica, it has been successfully employed to detect the heart rate of a person. These encouraging results will facilitate the development of epitaxial Sb2Se3 film-based devices and potential applications in wearable electronics.

Review of imaging and endovascular intervention of iliocaval venous compression syndrome.

Iliocaval venous compression syndrome (ICS) is the extrinsic compression of the common iliac vein by the overlying iliac artery against the vertebra. Chronic compression can lead to venous stenosis and stasis, which manifests as chronic venous disease and treatment resistance. Therefore, early recognition of ICS and prompt treatment are essential. Clinical presentations of ICS can be ambiguous and diagnosis requires a high index of suspicion with the relevant imaging studies. The initial imaging test is typically a Duplex ultrasound for vessel assessment and pelvic ultrasound to exclude a compressive mass, which is followed by computed tomography (CT) or magnetic resonance (MR) venography. CT and MRI can identify the anatomical causes for venous compression. In patients with high clinical suspicion for ICS, negative findings on CT and MR venography would still warrant further investigations. Definitive diagnosis can be established using catheter-based venography complemented with intravascular ultrasonography but the nature of their invasiveness limits its utility as a routine imaging modality. In this review paper, we will discuss the evidence, utility and limitations of the existing imaging modalities and endovascular intervention used in the management of ICS.

A chiral switchable photovoltaic ferroelectric 1D perovskite.

Spin and valley degrees of freedom in materials without inversion symmetry promise previously unknown device functionalities, such as spin-valleytronics. Control of material symmetry with electric fields (ferroelectricity), while breaking additional symmetries, including mirror symmetry, could yield phenomena where chirality, spin, valley, and crystal potential are strongly coupled. Here we report the synthesis of a halide perovskite semiconductor that is simultaneously photoferroelectricity switchable and chiral. Spectroscopic and structural analysis, and first-principles calculations, determine the material to be a previously unknown low-dimensional hybrid perovskite (R)-(-)-1-cyclohexylethylammonium/(S)-(+)-1 cyclohexylethylammonium) PbI3. Optical and electrical measurements characterize its semiconducting, ferroelectric, switchable pyroelectricity and switchable photoferroelectric properties. Temperature dependent structural, dielectric and transport measurements reveal a ferroelectric-paraelectric phase transition. Circular dichroism spectroscopy confirms its chirality. The development of a material with such a combination of these properties will facilitate the exploration of phenomena such as electric field and chiral enantiomer-dependent Rashba-Dresselhaus splitting and circular photogalvanic effects.

Missense PALB2 germline variant disrupts nuclear localization of PALB2 in a patient with breast cancer.

The PALB2 protein is essential to RAD51-mediated homologous recombination (HR) repair. Germline monoallelic PALB2 pathogenic variants confer significant risks for breast cancer. However, the majority of PALB2 variants remain classified as variants of unknown significance (VUS). We aim to functionally and mechanistically evaluate three novel PALB2 VUS. Patient-derived lymphoblastoid cell lines containing the VUS were analyzed for nuclear localization and foci formation of RAD51 as a measure of HR efficiency. To understand the mechanism underlying the HR deficiency, PALB2 nuclear localization was assessed using immunofluorescence studies. Among these VUS, c.3251C>T (p.Ser1084Leu) occurred in a patient with metastatic breast cancer while c.1054G>C (p.Glu352Gln) and c.1057A>G (p.Lys353Glu) were seen in patients with squamous cell carcinoma of skin and renal cell carcinoma respectively. Variant c.3251C>T was located within the WD40 domain which normally masked the nuclear export signal sequence responsible for nuclear delocalization of PALB2. Correspondingly, c.3251C>T displayed aberrant cytoplasmic localization of PALB2 which led to an impaired RAD51 nuclear localization and foci formation. On the other hand, both c.1054G>C and c.1057A>G showed intact HR functions and nuclear localization of PALB2, consistent with their locations within domains of no known function. Additionally, the prevalence of c.1054G>C was similar among healthy controls and patients with breast cancer (as seen in other studies), suggestive of its non-pathogenicity. In conclusion, our studies provided the functional evidence showing the deleterious effect of c.3251C>T, and non-deleterious effects of c.1054G>C and c.1057A>G. Using the ClinGen Pathogenicity calculator, c.3251C>T remains a VUS while c.1054G>C and c.1057A>G may be classified as likely benign variants.