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Objective The primary objective is to compare miscarriage rates in frozen-thawed embryo transfer (FET) cycles, according to the endometrial preparation used either artificial through the administration of exogenous estrogen and progesterone or natural without any treatment, during a spontaneous ovulatory cycle. The secondary objective is to compare the live birth rates between the two endometrial preparations. Study design This is a retrospective study done at KK Women’s and Children’s Hospital Singapore. We included women who underwent FET cycles either with hormone replacement treatment (HRT) or no treatment (natural) for the endometrial preparation, regardless of their cycle number, from 1 January 2011 till 31 December 2015. Results A total of 2,752 FET cycles were included in our analysis. The natural cycle followed by vaginal progesterone support was used in 1,221 cycles and the HRT cycle with estrogen and vaginal progesterone was used in 1,531 cycles. There is a significantly higher miscarriage rate in the HRT group (38.4%) compared with the natural group (22.3%). The live birth rate is significantly higher in the natural group (22.8%) compared with the HRT group (17.3%). The multivariate analysis further shows that the HRT therapy is independently associated with an increased risk of miscarriage (adjusted odds ratio 2.05; 95% confidence interval 1.45–2.90; p

The present analysis of more than 180,000 sentences from movie plots across the period from 1940 to 2019 emphasizes how gender stereotypes are expressed through the cultural products of society. By applying a network analysis to the word co-occurrence networks of movie plots and using a novel method of identifying story tropes, we demonstrate that gender stereotypes exist in Hollywood movies. An analysis of specific paths in the network and the words reflecting various domains show the dynamic changes in some of these stereotypical associations. Our results suggest that gender stereotypes are complex and dynamic in nature. Specifically, whereas male characters appear to be associated with a diversity of themes in movies, female characters seem predominantly associated with the theme of romance. Although associations of female characters to physical beauty and marriage are declining over time, associations of female characters to sexual relationships and weddings are increasing. Our results demonstrate how the application of cognitive network science methods can enable a more nuanced investigation of gender stereotypes in textual data.

Abstract Background Patients with prolonged length of hospital stay (LOS) not only increase their risks of nosocomial infections but also deny other patients access to inpatient care. Hepatobiliary (HPB) malignancies have some of highest incidences in East and Southeast Asia and the management of patients undergoing HPB surgeries have yet to be standardized. With improved neurosurgery techniques for intracranial aneurysms and tumors, neurosurgeries (NS) can be expected to increase. Elective surgeries account for far more operations than emergencies surgeries. Thus, with potentially increased numbers of elective HPB and NS, this study seeks to explore perioperative factors associated with prolonged LOS for these patients to improve safety and quality of practice. Methods A retrospective cross-sectional medical record review study from January 2014 to January 2015 was conducted at a 1250-bed tertiary academic hospital in Singapore. All elective HPB and NS patients over 18 years old were included in the study except day and emergency surgeries, resulting in 150 and 166 patients respectively. Prolonged LOS was defined as above median LOS based on the complexity of the surgical procedure. The predictor variables were preoperative, intraoperative, and postoperative factors. Student’s t-test and stepwise logistic regression analyses were conducted to determine which factors were associated with prolonged LOS. Results Factors associated with prolonged LOS for the HPB sample were age and admission after 5 pm but for the NS sample, they were functional status, referral to occupational therapy, and the number of hospital-acquired infections. Conclusion Our findings indicate that preoperative factors had the greatest association with prolonged LOS for HPB and NS elective surgeries even after adjusting for surgical complexity, suggesting that patient safety and quality of care may be improved with better pre-surgery patient preparation and admission practices.

Guided-mode resonances have been exploited to filter the normal-incidence transmission of mid-infrared wavelengths through a photonic crystal slab. A two-dimensionally periodic structure has been integrated with a quantum dot infrared photodetector to narrow its mid-wavelength infrared photoresponse spectrum. Finite-difference time-domain simulations were employed to extract the filter transmittance, which is dominated by a peak near 6µm. The simulated resonance is linearly tunable with the air-hole radius but it is insensitive to small changes in the incidence angle. To realize this filter, a patterned Ge slab was fabricated on a CaF2 cladding layer, on the InGaAs/GaAs photodetector. Filters fabricated on a plain GaAs substrate were also characterized by Fourier-transform infrared spectroscopy. This transmittance was consistent with the corresponding simulation, however the resonance peak was degraded in comparison to the filtered photodetector and its associated simulations. [ABSTRACT FROM AUTHOR]

We have studied the influence of SiO2and TiO2dielectric layers on the atomic intermixing of InxGa1?xAs/InP quantum well structures using the impurity-free vacancy disordering technique. Photoluminescence results revealed that an enhancement of interdiffusion was obtained when the samples were capped with SiO2. Although TiO2layers were able to suppress the interdiffusion in the InGaAs/InP system, the suppression was not significant compared to the AlGaAs/GaAs system. Based on a fitting procedure that was deconvoluted from the photoluminescence spectra as well as a theoretical modeling, the electron-heavy hole and electron-light hole transitions were identified, and a ratio of the group V to the group III diffusion coefficients (k) was obtained. The kratio of the InGaAs/InP samples capped with SiO2is relatively larger than that of samples capped with TiO2layers. [ABSTRACT FROM AUTHOR]

We compare the characteristics of phase-pure MOCVD grown ZB and WZ InAs nanowire transistors in several atmospheres: air, dry pure N2 and O2, and N2 bubbled through liquid H2O and alcohols to identify whether phase-related structural/surface differences affect their response. Both WZ and ZB give poor gate characteristics in dry state. Adsorption of polar species reduces off-current by 2–3 orders of magnitude, increases on–off ratio and significantly reduces sub-threshold slope. The key difference is the greater sensitivity of WZ to low adsorbate level. We attribute this to facet structure and its influence on the separation between conduction electrons and surface adsorption sites. We highlight the important role adsorbed species play in nanowire device characterisation. WZ is commonly thought superior to ZB in InAs nanowire transistors. We show this is an artefact of the moderate humidity found in ambient laboratory conditions: WZ and ZB perform equally poorly in the dry gas limit yet equally well in the wet gas limit. We also highlight the vital role density-lowering disorder has in improving gate characteristics, be it stacking faults in mixed-phase WZ or surface adsorbates in pure-phase nanowires. [ABSTRACT FROM AUTHOR]

In this work, proton and arsenic ion implantation induced intermixing in AlInGaAs/InGaAs quantum wells (QWs) has been studied and compared with InGaAsP/InGaAs QWs. The different interdiffusion results obtained from the two QW structures are compared and discussed based on thermal annealing studies, different implantation ion species, dynamic annealing effects of barrier layers, as well as interdiffusion mechanisms. [ABSTRACT FROM AUTHOR]

The effects of growth temperature and V/III ratio on the morphology and crystallographic phases of InP nanowires that are grown by metal organic chemical vapour deposition have been studied. We show that higher growth temperatures or higher V/III ratios promote the formation of wurtzite nanowires while zinc-blende nanowires are favourable at lower growth temperatures and lower V/III ratios. A schematic map of distribution of zinc-blende and wurtzite structures has been developed in the range of growth temperatures (400-510 degC) and V/III ratios (44 to 700) investigated in this study. [ABSTRACT FROM AUTHOR]

Modern technology is heavily reliant on silicon dioxide and silicon nitride thin films. These films have many electronic and optical applications, and in some cases silicon oxynitride films of intermediate composition are desirable. We have systematically deposited several SiOxNy films by magnetron sputter deposition and thoroughly investigated their composition with Rutherford backscattering spectrometry and optical measurements. The as-deposited stress in these thin films was also measured and all were found to be compressive.Temperature-dependent stress measurements up to 450 degC were then used to extract the biaxial modulus and coefficient of thermal expansion for each SiOxNy. The SiO2-like films exhibit negative thermal expansion, which is consistent with a strong but porous structure. Increasing the nitrogen content results in the thermal expansion coefficient increasing towards values reported elsewhere for Si3N4. [ABSTRACT FROM AUTHOR]

This paper presents a study on the emission wavelength extension of InAsSb nanostructures using InGaAsSb sandwich layers. Due to the reduced lattice mismatch between InAsSb nanostructure layer and buffer/capping layer, the introduction of InGaAsSb sandwich layers leads to larger island size, reduced compressive strain and lower confinement barrier for InAsSb nanostructures, thus resulting in a longer emission wavelength. For InGaAsSb sandwich layers with nominal Sb concentration higher than 10%, type II band alignment is observed for the InAsSb/InGaAsSb heterostructure, which also contributes to the extension of emission wavelength. The InGaAsSb sandwich layers provide an effective approach to extend the emission wavelength of InAsSb nanostructures well beyond 2 um, which is very useful for device applications in the mid-infrared region. [ABSTRACT FROM AUTHOR]

Straight, vertically aligned GaAs nanowires were grown on Si(111) substrates coated with thin GaAs buffer layers. We find that the V/III precursor ratio and growth temperature are crucial factors influencing the morphology and quality of buffer layers. A double layer structure, consisting of a thin initial layer grown at low V/III ratio and low temperature followed by a layer grown at high V/III ratio and high temperature, is crucial for achieving straight, vertically aligned GaAs nanowires on Si(111) substrates. An in situ annealing step at high temperature after buffer layer growth improves the surface and structural properties of the buffer layer, which further improves the morphology of the GaAs nanowire growth. Through such optimizations we show that vertically aligned GaAs nanowires can be fabricated on Si(111) substrates and achieve the same structural and optical properties as GaAs nanowires grown directly on GaAs(111)B substrates. [ABSTRACT FROM AUTHOR]

InP nanowires were grown on (111)B InP substrates by metal-organic chemical vapour deposition in the presence of colloidal gold particles as catalysts. Transmission electron microscopy and photoluminescence measurements were carried out to investigate the effects of V/III ratio and nanowire diameter on structural and optical properties. Results show that InP nanowires grow preferably in the wurtzite crystal structure than the zinc blende crystal structure with increasing V/III ratio or decreasing diameter. Additionally, time-resolved photoluminescence (TRPL) studies have revealed that wurtzite nanowires show longer recombination lifetimes of [?]2500 ps with notably higher quantum efficiencies. [ABSTRACT FROM AUTHOR]

We report on a detailed analysis of the dark currents of a quantum dot infrared photodetector annealed at various temperatures from 700 to 850 °C. Annealing induced intermixing of the quantum dot and barrier material and therefore a reduction of the quantum dot confining potential, which caused a shift in the spectral response from 7 to 9.3 µm for an 850 °C anneal. An analysis of the dark currents reveals that the dark current mechanisms are similar for the annealed and as-grown devices, indicating that annealing up to 850 °C may not have an adverse effect on the semiconductor material quality. [ABSTRACT FROM AUTHOR]

In-plane bandgap energy control of InAs quantum dots (QDs) grown on GaAs substrates is demonstrated using selective-area epitaxy. Transmission electron microscopy and cathodoluminescence are used for characterization of the selectively grown dots. A single-step growth of a thin InAs quantum well and InAs QDs emitting at 1010 and 1100 nm (at 77 K) on the same wafer is demonstrated. Non-uniform growth profile is reported for the selectively grown QDs in the mask openings. Surface migration of adatoms from higher order facets to (1 0 0) facets results in enhanced deposition rates closer to the edge of the openings and vapour phase diffusion of adatoms results in density variations across the openings over length scales greater than the surface migration length of the adatoms. [ABSTRACT FROM AUTHOR]

The growth of epitaxial Ge nanowires is investigated on (100), (111) B and (110) GaAs substrates in the growth temperature range from 300 to 380 °C. Unlike epitaxial Ge nanowires on Ge or Si substrates, Ge nanowires on GaAs substrates grow predominantly along the \langle 110\rangle direction. Using this unique property, vertical \langle 110\rangle Ge nanowires epitaxially grown on GaAs(110) surface are realized. In addition, these Ge nanowires exhibit minimal tapering and uniform diameters, regardless of growth temperatures, which is an advantageous property for device applications. Ge nanowires growing along the \langle 110\rangle directions are particularly attractive candidates for forming nanobridge devices on conventional (100) surfaces. [ABSTRACT FROM AUTHOR]

We report and compare proton and phosphorous ion implantation-induced intermixing of InAs/InP quantum dots (QDs). After ion implantation at 20-300 degC, the QDs are rapid thermally annealed at 850 degC for 30 s. Proton implantation induces less energy shift than P ion implantation for a given concentration of atomic displacements due to the more efficient dynamic annealing of the defects created by protons. The implantation-induced energy shift reaches a maximum value of about 260 meV for a dose of 5 x 1012 ions cm[?]2 in the P ion implanted QDs, which also show narrower PL linewidths compared to the proton implanted QDs. We also report the effects of an InGaAs top cap layer on the ion implantation-induced QD intermixing and show that defect production and annihilation processes evolve differently in InGaAs and InP layers and vary with the implantation temperature. When the implantation is performed at higher temperatures, the energy shift of the P ion implanted QDs capped with an InP layer increases due to the reduction in larger defect cluster formation at higher temperatures, while the energy shift of the proton implanted QDs decreases due to increased dynamic annealing irrespective of their cap layers. [ABSTRACT FROM AUTHOR]

The domestication of ducks represents a pivotal evolutionary shift from the unguided propagation of wild species to deliberate human-mediated selection, culminating in distinct behavioural, morphological, and physiological traits that differentiate domesticated ducks from their wild counterparts. This transition has yielded breeds with traits fine-tuned to specific economic roles, such as egg production, meat yield, or dual-purpose functionality. Duck domestication plays a significant role in poultry production globally, meeting the growing demand for eggs and meat in various regions. Here, we focus on the Jinding Duck (JDD), a breed renowned for its prolific egg-laying traits. Employing whole-genome resequencing data from 325 individuals across five Chinese indigenous duck breeds, we aimed to dissect the unique population structure and assess the genetic diversity within the JDD cohort. The findings reveal the distinct genetic heritage of JDD, diverged from other domesticated breeds, and show a relative paucity of genetic diversity. A salient discovery was a 200 kb genomic interval containing three genes (NCF2, SMG7, and ARPC5) with almost exclusive haplotypes, which were inherited from Anas platyrhynchos or Anas zonorhyncha, impacting the morphological attributes of JDD. The study highlights a c.28G>A non-synonymous mutation in the first exon of the LAMC1 gene, which is potentially influencing feather morphology in JDD. Our findings suggest that unique blue eggshell colouration in JDD is likely attributable to variations within the promoter element of the ABCG2 gene, distinguishing it from other breeds. Moreover, the MAP7 and FHL1 genes emerge as significant factors in the laying performance of JDD. These genetic insights are not only crucial for improving the JDD breed but also provide valuable information that could be applied to duck breeding programmes worldwide, helping enhance productivity and meet international demands for high-efficiency poultry breeds., (Copyright © 2024. Published by Elsevier B.V.)

Background: Klebsiella pneumoniae (KP) is an opportunistic pathogen causing severe pneumonia and sepsis. Carbapenem-resistant KP (CRKP) has become a major pathogen in many centres., Aim: To investigate the association between carbapenem resistance and the mortality rate, length of stay, and hospital cost in patients with Klebsiella pneumoniae infection., Methods: The retrospective cohort study was conducted in the intensive care units of a large teaching tertiary hospital in southwest China between January 1 st , 2020 and December 31 st , 2022. To examine the impact of carbapenem resistance on mortality rates and economic burden, multivariate Cox regression and generalized linear models were constructed., Findings: The study included 282 adult patients with KP infection (135 CSKP; 147 CRKP). CRKP-infected patients demonstrated higher mortality risk (unadjusted hazard ratio (aHR): 1.980; 95% confidence interval (CI): 1.206-3.248; P = 0.007; aHR: 1.767; 95% CI: 1.038-3.005; P = 0.036) compared to CSKP-infected patients. Stratified analysis, according to type of KP infection, revealed that patients with healthcare-associated CRKP infection had a significantly higher mortality risk compared to those with CSKP infection (log-rank P = 0.015). Patients with CRKP infection had longer hospital stays than those infected with CSKP (adjusted mean: 38.74 vs 29.71 days; P = 0.003), and hospital-related expenses were notably higher among CRKP patients than CSKP patients (adjusted cost: £40,126.73 vs 25,713.74; P < 0.001)., Conclusion: CRKP infections increase mortality rates, prolong hospital stays, and raise healthcare costs. Healthcare facilities should adopt targeted strategies, including curtailing pre-infection hospitalization periods and managing medications more judiciously., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objective: Total thyroidectomy can be used as a definitive treatment modality for thyrotoxicosis. This study assessed the outcomes of patients treated with surgery at a single secondary care site., Method: A retrospective cohort study was conducted analysing consecutive patients who underwent thyroid surgery for thyrotoxicosis between 24 November 2000 and 26 April 2019 ( n = 595)., Results: Total thyroidectomy was performed in 95.4 per cent of patients. Two-thirds of patients had Graves' disease histology. Of patients, 22.8 per cent became transiently hypothyroid whilst on levothyroxine (thyroid hormone replacement therapy). Transient and persistent hypocalcaemia was present in 23.3 per cent and 2.8 per cent of patients respectively. Recurrent laryngeal nerve palsy was transient and persistent in 3.6 per cent and 0.3 per cent respectively. Of patients, 2.5 per cent developed post-operative haematomas that required surgical evacuation in the operating theatre., Conclusion: The overall complication rate for thyroid surgery is higher in thyrotoxic than in euthyroid patients. Compared to other treatment modalities, total thyroidectomy appears to be the most effective, definitive means of managing Graves' disease.

Background: The transition from hedonic to compulsive use in Substance Use Disorders (SUD) is a critical point in SUD progression and hence relevant for assessment and treatment. To measure the habitual patterns of substance consumption, the Craving Automated Scales (CAS) for alcohol (CAS-A), substances (CAS-S) and cigarette smoking (CAS-CS) were developed and introduced to different countries. In this study, we aimed to investigate the structural stability of CAS across substances and cultures., Methods: This study analyzed the CAS-scores of a sample of 370 participants in Germany, China and the UK, including 262 opioid-users, 65 smokers and 43 alcohol-users. We performed stability analyses to check the stability (i. e. factorial invariance) of factor solutions. Based on confirmed stability of the general factor (gfactor) solution and the calculations rule obtained in the previous validation of CAS-alcohol (CAS-A), the factor structures of CAS-A, CAS-S and CAS-CS were compared., Results: The gfactor solutions based on calculations rule shows good stability, with the mean stability coefficients of 0.990 and 0.977 for CAS-S and CAS-CS respectively. The gfactor patterns were similar for CAS-A, CAS-S and CAS-CS, as well as across samples (Germany, China and the UK), with most factor-loadings larger than 0.7. Based on these findings, CAS-S and CAS-CS were also associated with established clinical measures of SUD., Conclusions: Our findings suggest the two-gfactor solution based on a proposed calculation rule has a high stability across substances and cultures. This could be in line with common neurobiological mechanisms underlying habitual substance use. Moreover, comparing CAS with established clinical tools suggests that CAS might assess the automated behavior in substance consumption in a more sophisticated way.

The naturally occurring cannabis plant has played an established role in pain management throughout recorded history. However, in recent years, both natural and synthetic cannabis-based products for medicinal use (CBPM) have gained increasing worldwide attention due to growing evidence supporting their use in alleviating chronic inflammatory and neuropathic pain associated with an array of conditions. In view of these products' growing popularity in both the medical and commercial fields, we carried out a systematic review to ascertain the effects of cannabis and its synthetically derived products on orofacial pain and inflammation. The application of topical dermal cannabidiol formulation has shown positive findings such as reducing pain and improving muscle function in patients suffering from myofascial pain. Conversely, two orally-administered synthetic cannabinoid receptor agonists (AZD1940 and GW842166) failed to demonstrate significant analgesic effects following surgical third molar removal. There is a paucity of literature pertaining to the effects of cannabis-based products in the orofacial region; however, there is a wealth of high-quality evidence supporting their use for treating chronic nociceptive and neuropathic pain conditions in other areas. Further research is warranted to explore and substantiate the therapeutic role of CBPMs in the context of orofacial pain and inflammation. As evidence supporting their use expands, healthcare professionals should pay close attention to outcomes and changes to legislation that may impact and potentially benefit their patients., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Gamma oscillations comprise a loosely defined, heterogeneous group of functionally different activities between 30 and 100 Hz in the cortical and subcortical local field potential (LFP) of the motor network. Two distinct patterns seem to emerge which are easily conflated: Finely-tuned gamma (FTG) oscillations - a narrowband activity with peaks between 60 and 90 Hz - have been observed in multiple movement disorders and are induced by dopaminergic medication or deep brain stimulation (DBS). FTG has been linked with levodopa or DBS-induced dyskinesias, which makes it a putative biomarker for adaptive DBS. On the other hand, gamma activity can also present as a broad phenomenon (30-100 Hz) in the context of motor activation and dynamic processing. Here, we contrast FTG, either levodopa-induced or DBS-induced, from movement-related broadband gamma synchronisation and further elaborate on the functional role of FTG and its potential implications for adaptive DBS. Given the unclear distinction of FTG and broad gamma in literature, we appeal for more careful separation of the two. To better characterise cortical and subcortical FTG as biomarkers for dyskinesia, their sensitivity and specificity need to be investigated in a large clinical trial., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This paper systematically reviewed and assessed all retrievable pharmacoeconomic studies on denosumab for the treatment of osteoporosis. Denosumab was more cost-effective in patients with older age, prior fracture experience, lower BMD T-scores, and more risk factors. ESCEO-IOF guidelines were more applicable to improve the quality of pharmacoeconomic studies in osteoporosis., Introduction: There are many pharmacoeconomic studies on denosumab for osteoporosis. However, the corresponding reviews are outdated or incomplete and need to be updated and refined. This article aims to systematically review and evaluate all retrievable pharmacoeconomic studies of denosumab for osteoporosis., Methods: A systematic literature search was performed utilizing PubMed, EMBASE(Ovid), Proquest(EconLit), Chongqing VIP, WanFang Database, and Chinese National Knowledge Infrastructure to identify full-text articles published before September 2021. The quality of full-text articles was evaluated by the Consolidated Health Economic Evaluation Reporting Standards(CHEERS) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases International Osteoporosis Foundation guideline(ESCEO-IOF)., Results: In total, 21 full-text articles were eligible for inclusion. Denosumab for postmenopausal osteoporosis was not dominant compared to zoledronate and teriparatide. However, denosumab was dominant compared with strontium ranelate, raloxifene, and ibandronate in patients over 65 years. The probabilities of denosumab being cost-effective or dominant were more than 85% compared with no treatment and risedronate in patients aged over 70 years. Compared to alendronate, the highest rate of denosumab dominance occurred in patients aged 65 to 75 years, at about 65%. Most of the articles had higher CHEERS scores than ESCEO-IOF scores (converted into percentages)., Conclusions: The cost-effectiveness of denosumab for the treatment of osteoporosis was influenced by multiple factors. Generally, denosumab was more cost-effective in patients with older age, prior fracture experience, lower BMD T-scores, and more risk factors. ESCEO-IOF guidelines were more applicable to improve the transparency, generalization, and quality of pharmacoeconomic studies in osteoporosis., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Synopsis: Archerfishes (Toxotidae) are variously found in the fresh- and brackish-water environments of Asia Pacific and are well known for their ability to shoot water at terrestrial prey. These shots of water are intended to strike their prey and cause it to fall into the water for capture and consumption. While this behavior is well known, there are competing hypotheses (blowpipe vs. pressure tank hypothesis) of how archerfishes shoot and which oral structures are involved. Current understanding of archerfish shooting structures is largely based on two species, Toxotes chatareus and T. jaculatrix . We do not know if all archerfishes possess the same oral structures to shoot water, if anatomical variation is present within these oral structures, or how these features have evolved. Additionally, there is little information on the evolution of the Toxotidae as a whole, with all previous systematic works focusing on the interrelationships of the family. We first investigate the limits of archerfish species using new and previously published genetic data. Our analyses highlight that the current taxonomy of archerfishes does not conform to the relationships we recover. Toxotes mekongensis and T. siamensis are placed in the synonymy of T. chatareus , Toxotes carpentariensis is recognized as a species and removed from the synonymy of T. chatareus , and the genus Protoxotes is recognized for T. lorentzi based on the results of our analyses. We then take an integrative approach, using a combined analysis of discrete hard- and soft-tissue morphological characters with genetic data, to construct a phylogeny of the Toxotidae. Using the resulting phylogenetic hypothesis, we then characterize the evolutionary history and anatomical variation within the archerfishes. We discuss variation in the oral structures and the evolution of the mechanism with respect to the interrelationships of archerfishes, and find that the oral structures of archerfishes support the blowpipe hypothesis but soft-tissue oral structures may also play a role in shooting. Finally, by comparing the morphology of archerfishes to their sister group, we find that the Leptobramidae has relevant shooting features in the oral cavity, suggesting that some components of the archerfish shooting mechanism are examples of co-opted or exapted traits., Sinopsis Malay: Pelbagai jenis Ikan Sumpit (Toxotidae) dapat dijumpai di persekitaran air tawar dan payau di Asia Pasifik dan mereka terkenal dengan kebolehan mereka menembak air ke arah mangsa di darat. Tembakan air ini bertujuan untuk menyerang mangsa mereka dan menyebabkan mereka jatuh ke dalam air untuk ditangkap dan dimakan. Walaupun tingkah laku ini diketahui umum, terdapat hipotesis yang bersaing (hipotesis sumpitan vs. tangki tekanan) tentang cara ikan sumpit menembak dan struktur mulut yang terlibat. Pemahaman semasa tentang struktur menembak ikan sumpit adalah sebahagian besarnya berdasarkan dua spesies, Toxotes chatareus dan T. jaculatrix . Kami tidak pasti sama ada semua ikan sumpit mempunyai struktur mulut yang sama untuk menembak air, jika variasi anatomi terdapat dalam struktur mulut ini, atau bagaimana ciri-ciri ini telah berkembang. Tambahan pula, terdapat sedikit maklumat tentang evolusi Toxotidae secara keseluruhan, dengan semua penyelidikan sistematik sebelum ini memfokuskan pada hubungan saling keluarga. Kami pada mulanya mengkaji had spesies ikan sumpit ini menggunakan data genetik baharu dan yang diterbitkan sebelum ini. Analisis kami menunjukkan bahawa taksonomi semasa ikan sumpit tidak mematuhi hubungan yang kami perolehi. Toxotes mekongensis dan T. siamensis diletakkan bersama kesinoniman T. chatareus , Toxotes carpentariensis yang diiktiraf sebagai satu spesies dan dikeluarkan daripada kesinoniman T. chatareus , dan genus Protoxotes yang diiktiraf untuk T. lorentzi adalah berdasarkan hasil analisis kami. Kemudian kami mengambil pendekatan integratif, menggunakan analisis gabungan karakter morfologi tisu keras dan lembut diskret dengan data genetik, untuk membina filogeni Toxotidae. Menggunakan hipotesis filogenetik yang terhasil, kami kemudian mencirikan sejarah evolusi dan variasi anatomi dalam ikan sumpit. Kami membincangkan variasi dalam struktur mulut dan evolusi mekanisme berkenaan yang berkaitan dengan ikan sumpit, dan mendapati bahawa struktur mulut ikan sumpit menyokong hipotesis sumpitan tetapi struktur mulut tisu lembut juga mungkin memainkan peranan dalam cara menembak. Akhir sekali, dengan membandingkan morfologi ikan sumpit kepada kumpulan saudara mereka, kami mendapati bahawa Leptobramidae mempunyai ciri penangkapan yang relevan dalam rongga mulut mereka, menunjukkan bahawa beberapa komponen mekanisme penangkapan ikan sumpit merupakan contoh ciri-ciri yang diikut-sertakan atau diguna semula., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Background: Osteosarcoma is the most frequent malignant bone malignancy and the current treatments are ineffective. Ivermectin, an anti-protozoal drug, has been shown to have anti-cancer activity. This work investigated the potential of repurposing ivermectin to augment chemotherapy's efficacy in osteosarcoma., Methods: Proliferation, migration and apoptosis assays were performed in ivermectin-treated osteosarcoma cells. Combination studies were performed. Osteosarcoma xenograft mouse model was established to investigate the in vivo efficacy of ivermectin. Intracellular reactive oxygen species (ROS) and mitochondrial superoxide, membrane potential, ATP, 8-OHdG level, protein carbonylation and lipid peroxidation were determined after ivermectin treatment., Results: Ivermectin was effective and acted synergistically with doxorubicin in osteosarcoma cells regardless of cellular origin and genetic profiling. This was achieved through suppressing inhibiting growth and migration, and inducing caspase-dependent apoptosis. Ivermectin also significantly inhibited osteosarcoma growth in vivo and its combination with doxorubicin resulted in much greater efficacy than doxorubicin alone. Importantly, the effective dose of ivermectin was clinically feasible and did not cause significant toxicity in mice. Mechanistical analysis showed that ivermectin induced oxidative stress and damage, and mitochondrial dysfunction., Conclusions: Our findings indicate that ivermectin has utility in treating patients with osteosarcoma, especially those resistant to chemotherapy.

Finely-tuned gamma (FTG) oscillations can be recorded from cortex or the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) on dopaminergic medication, and have been associated with dyskinesias. When recorded during deep brain stimulation (DBS) on medication the FTG is entrained to half the stimulation frequency. We investigated whether these characteristics are shared off medication by recording local field potentials (LFP) from the STN from externalised DBS leads in 14 PD patients after overnight withdrawal of medication. FTG was induced de-novo by DBS in the absence of dyskinesias in a third of our cohort. The FTG could outlast stimulation or arise only after DBS ceased. FTG frequencies decreased during and across consecutive DBS blocks, but did not shift with changing stimulation frequency off medication. Together with the sustained after-effects this argues against simple entrainment by DBS in the off medication state. We also found significant coherence between STN-LFP and electroencephalogram (EEG) signals at FTG frequencies. We conclude that FTG is a network phenomenon that behaves differently in the off medication state, when it is neither associated with dyskinesias nor susceptible to entrainment., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Local field potentials (LFPs) may afford insight into the mechanisms of action of deep brain stimulation (DBS) and potential feedback signals for adaptive DBS. In Parkinson's disease (PD) DBS of the subthalamic nucleus (STN) suppresses spontaneous activity in the beta band and drives evoked resonant neural activity (ERNA). Here, we investigate how STN LFP activities change over time following the onset and offset of DBS. To this end we recorded LFPs from the STN in 14 PD patients during long (mean: 181.2 s) and short (14.2 s) blocks of continuous stimulation at 130 Hz. LFP activities were evaluated in the temporal and spectral domains. During long stimulation blocks, the frequency and amplitude of the ERNA decreased before reaching a steady state after ~70 s. Maximal ERNA amplitudes diminished over repeated stimulation blocks. Upon DBS cessation, the ERNA was revealed as an under-damped oscillation, and was more marked and lasted longer after short duration stimulation blocks. In contrast, activity in the beta band suppressed within 0.5 s of continuous DBS onset and drifted less over time. Spontaneous activity was also suppressed in the low gamma band, suggesting that the effects of high frequency stimulation on spontaneous oscillations may not be selective for pathological beta activity. High frequency oscillations were present in only six STN recordings before stimulation onset and their frequency was depressed by stimulation. The different dynamics of the ERNA and beta activity with stimulation imply different DBS mechanisms and may impact how these activities may be used in adaptive feedback., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Threatened miscarriage is a common complication of pregnancy. Results of randomised controlled trials on the efficacy of progestogen in the treatment of threatened miscarriage remain inconsistent., Objective: To investigate whether the use of progestogen is associated with improved event rate of live birth and other benefits in women with threatened miscarriage., Search Strategy: Ovid MEDLINE, Ovid Embase and Cochrane CENTRAL Register of Controlled Trials from their inception until 8 July 2019., Selection Criteria: Randomised controlled trials comparing progestogen with a placebo or no treatment for pregnancy outcomes in women with threatened miscarriage., Data Collection and Analysis: Two authors independently conducted data extraction and assessed study quality. We calculated risk ratios (RR) and 95% confidence intervals using the Mantel-Haenszel approach for dichotomous outcomes., Main Results: Ten trials with a total of 5056 participants were eligible for analysis. The use of progesterone increased the incidence of live birth (RR 1.07, 95% CI 1.00-1.15; P = 0.04; I 2  = 18%), with benefit only seen with the use of oral progestogen (RR 1.17, 95% CI 1.04-1.31; P = 0.008; I 2  = 0%) and not with vaginal progesterone (RR 1.04, 95% CI 1.00-1.08; P = 0.07; I 2  = 0%). Similarly, progestogen reduced the risk of miscarriage (RR 0.73, 95% CI 0.59-0.92), with benefit only seen with oral progestogen and not with vaginal progesterone., Conclusion: Progestogens may have benefits on live birth rate and miscarriage rate for women with threatened miscarriage. These benefits appear to be confined to the use of oral progestogen, and no statistically significant improvements were seen with vaginal progesterone., Tweetable Abstract: A meta-analysis of 10 trials found that progestogens increased live birth rates and reduced miscarriage rates for women with threatened miscarriage., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Aims: We aimed to explore a new Methylobacterium isolate to produce polyhydroxybutyrate (PHB) by using methanol as a sole carbon resource and improve PHB production., Methods and Results: A new PHB-producing isolate (Methylobacterium sp. 1805) was obtained from oil fields by using methanol as a sole carbon source. The fermentation situation of PHB production was further optimized by using Box-Behnken response surface methodology (RSM). Before optimization, the cell biomass was 0·6 g l -1 after 3-day culture and 0·3 g l -1 PHB was produced after 5-day methanol-inducing stage. The RSM growth medium was optimized as 15 g l -1 glycerol, 10 g l -1 beef extract and 0·65 g l -1 MgSO 4 ·7H 2 O. The RSM methanol-inducing medium was optimized as 0·65 g l -1 MgSO 4 (metal ions), 20 mmol l -1 PBS pH 6·5 and final 2% methanol (v/v). The biomass and PHB production reached 1·0 and 0·55 g l -1 after 3-day culture, respectively. The PHB yield increased by about 80% when compared with before optimization., Conclusions: The optimization of a two-stage fermentation process improved PHB production from methanol by using Methylobacterium sp. 1805., Significance and Impact of the Study: A new Methylobacterium isolate was isolated and produced high-level PHB by using methanol as a sole carbon resource. The bacteria will provide a potential tool for C1 resource in producing PHB., (© 2019 The Society for Applied Microbiology.)

Objective: To elucidate the biological function of microRNA-300 (miRNA-300) in influencing the progression of non-small cell lung cancer (NSCLC)., Patients and Methods: The relative level of miRNA-300 in NSCLC tissues and cells was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The influences of miRNA-300 on the proliferative, migratory, and invasive potentials of A549 cells were assessed. The binding relationship between miRNA-300 and ETS1 was verified by the Dual-Luciferase Reporter Gene Assay. Finally, the regulatory effect of the interactive miRNA-300 and ETS1 on the progression of NSCLC was identified., Results: MiRNA-300 was downregulated in NSCLC tissues and cells. The overexpression of miRNA-300 suppressed A549 cells to proliferate, migrate, and invade. MiRNA-300 could bind to ETS1 3'UTR and suppress its level in A549 cells. Notably, the knockdown of miRNA-300 could reverse the regulatory role of ETS1 in the cellular behaviors of NSCLC., Conclusions: MiRNA-300 suppresses NSCLC to proliferate, migrate, and invade by targeting ETS1.

Objective: To establish optimum stimulus frequency and location of bone conducted vibration provoking a skull vibration induced nystagmus (SVIN) in superior semi-circular canal dehiscences., Methods: SVIN 3D components in 40 patients with semi-circular canal dehiscence (27 unilateral and 13 bilateral) were compared with a group of 18 patients with severe unilateral vestibular loss and a control group of 11 volunteers., Results: In unilateral semi-circular canal dehiscences, SVIN torsional and horizontal components observed on vertex location in 88% beat toward the lesion side in 95%, and can be obtained up to 800Hz (around 500Hz being optimal). SVIN slow-phase-velocity was significantly higher on vertex stimulation at 100 and 300Hz (P=0.04) than on mastoids. SVIN vertical component is more often upbeating than downbeating. A SVIN was significantly more often observed in unilateral than bilateral semi-circular-canal dehiscences (P=0.009) and with a higher slow phase velocity (P=0.008). In severe unilateral vestibular lesions the optimal frequency was 100Hz and SVIN beat toward the intact side. The mastoid stimulation was significantly more efficient than vertex stimulation at 60 and 100Hz (P<0.01)., Conclusion: SVIN reveals instantaneously in unilateral semi-circular canal dehiscences a characteristic nystagmus beating, for the torsional and horizontal components, toward the lesion side and with a greater sensitivity toward high frequencies on vertex stimulation. SVIN three components analysis suggests a stimulation of both superior semi-circular canal and utricle. SVIN acts as a vestibular Weber test, assessing a vestibular asymmetrical function and is a useful indicator for unilateral semi-circular canal dehiscence., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Pruritus is a leading cause of reduced health-related quality of life (QoL) in atopic dermatitis (AD). Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. In identical Phase 3 studies (NCT02118766, NCT02118792), crisaborole reduced disease and pruritus severity versus vehicle., Objective: Quantify the relationship between pruritus and QoL using data from these studies., Methods: Patients aged ≥2 years were randomly assigned 2 : 1 to receive crisaborole:vehicle twice daily for 28 days. QoL was measured at baseline and day 29 using the Dermatology Life Quality Index (DLQI; patients aged ≥16 years), the Children's Dermatology Life Quality Index (CDLQI; patients aged 2-15 years) and the Dermatitis Family Impact (DFI; caregivers of patients aged 2-17 years). Pruritus was measured using the Severity of Pruritus Scale (SPS), a 4-point scale from 0 ('no itching') to 3 ('bothersome itching/scratching that disturbs sleep'), and captured morning and evening via electronic diary. Data from crisaborole and vehicle arms were pooled for this analysis. A repeated-measures longitudinal model was used to estimate relationships between pruritus (SPS) and QoL (DLQI, CDLQI and DFI in separate analyses)., Results: One thousand five hundred and twenty two patients received crisaborole or vehicle. A linearity assumption for the relationship between SPS and DLQI (n = 294), CDLQI (n = 1200), and DFI (n = 1293) was appropriate. For DLQI, SPS score of 0 was associated with 'no negative effect on patient QoL'; SPS score of 1 was associated with 'small effect on patient QoL'; SPS score of 2 was associated with 'moderate effect on patient QoL'; and SPS score of 3 was associated with 'very large effect on patient QoL'. The pattern of relationships between SPS and CDLQI and DFI was similar., Conclusions: The relationships between SPS and DLQI, CDLQI and DFI substantiate the significant link between pruritus and patient/caregiver QoL in AD., (© 2019 European Academy of Dermatology and Venereology.)

Background: Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate-to-severe chronic plaque psoriasis., Objectives: To consider the benefits and risks of tofacitinib in patients with moderate-to-severe psoriasis., Methods: Data were pooled from one phase II, four phase III and one long-term extension study comprising 5204 patient-years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of 'clear' or 'almost clear', ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure., Results: Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients' quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID., Conclusions: Tofacitinib has a benefit-risk profile in moderate-to-severe psoriasis consistent with that of other systemic treatments., (© 2018 British Association of Dermatologists.)

Biopolymers are increasingly employed for neuroscience applications as scaffolds to drive and promote neural regrowth, thanks to their ability to mediate the upload and subsequent release of active molecules and drugs. Synthetic degradable polymers are characterized by different responses ranging from tunable distension or shrinkage to total dissolution, depending on the function they are designed for. In this paper we present a biocompatible microfabricated poly-ε-caprolactone (PCL) scaffold for primary neuron growth and maturation that has been optimized for the in vitro controlled release of brain-derived neurotrophic factor (BDNF). We demonstrate that the designed morphology confers to these devices an enhanced drug delivery capability with respect to monolithic unstructured supports. After incubation with BDNF, micropillared PCL devices progressively release the neurotrophin over 21 days in vitro. Moreover, the bioactivity of released BDNF is confirmed using primary neuronal cultures, where it mediates a consistent activation of BDNF signaling cascades, increased synaptic density, and neuronal survival. These results provide the proof-of-principle on the fabrication process of micropatterned PCL devices, which represent a promising therapeutic option to enhance neuronal regeneration after lesion and for neural tissue engineering and prosthetics.

Background: Tofacitinib is an oral Janus kinase inhibitor. Final safety and efficacy data from an open-label extension study of tofacitinib in psoriasis are reported., Objectives: To evaluate the long-term safety and durability of efficacy of tofacitinib in adults with moderate-to-severe chronic plaque psoriasis., Methods: Eligible patients who completed qualifying phase II/III tofacitinib studies received tofacitinib 10 mg twice daily (q12h) until month 3; subsequently, the dose could be adjusted by investigators to either 5 or 10 mg q12h. Adverse events (AEs) are reported up to month 66 and laboratory data up to month 54. Efficacy end points up to month 54 included Physician's Global Assessment of 'clear' or 'almost clear' (PGA response) and 75% improvement in Psoriasis Area and Severity Index (PASI 75)., Results: Overall, 2867 patients received tofacitinib, with a median treatment duration of 35·6 months. Adverse events (AEs) and serious AEs were reported in 82·5% and 13·7% of patients, respectively; 13·9% of patients discontinued owing to AEs; and 29 patients died. Incidence rates (patients with event/100 patient-years) were 1·16 for serious infections, 0·67 for malignancies and 0·26 for major adverse cardiovascular events. After initial changes in qualifying studies, most laboratory parameters were generally stable over 54 months. PGA response was achieved by 52-62% of patients and PASI 75 by 56-74% of patients at each study visit through month 54., Conclusions: In patients with psoriasis, the safety profile of tofacitinib over 66 months was similar to previous reports in phase III studies and efficacy was sustained through 54 months (NCT01163253)., (© 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: KRAS mutations are prevalent in non-small cell lung cancer (NSCLC) but its clinical implications remain to be determined. Continual profiling of KRAS mutations in patients is challenging, and the study aims to determine the potential use of urinary DNA in disease predictions., Methods: A total of 150 patients were recruited. To ascertain the clinical relevance of urinary DNA, matched tumor profiles were analyzed. Serial measurements were taken to gauge the reliability of the assay. These results were correlated to overall survival using the Kaplan-Meier estimate., Results: A good overall concordance of 93% (consolidated results from serial measurements) was achieved between tumor tissue and urinary DNA profiling. Of the discordant KRAS cases, we observed subsequent positive detection during monitoring and very low concentrations of mutant DNA. In addition, we noted that KRAS-positive patients detected using urinary DNA have good prognostic utility. Interestingly, we also observed that the trend is highly correlative of the rate of change in KRAS mutant DNA concentrations and the period of monitoring., Conclusions: Urinary DNA offered a non-invasive approach to probe NSCLC dynamics, and in our study we showed that it had predictive capabilities for KRAS-positive patients. Serial monitoring of urinary samples showed that it had a predictive role in identifying patients with worse outcome.

Background: Transmission of microbes in the hospital environment occurs frequently through human interactions with high-touch surfaces such as patient beds and over-bed tables. Although stringent cleaning routines are implemented as a preventive measure to minimize transmission of microbes, it is desirable to have high-touch surfaces made of antimicrobial materials. Physical texturing of solid surfaces offers a non-bactericidal approach to control the colonization of such surfaces by microbes., Aim: To investigate the efficacy of micro-textured polycarbonate films in reducing bacterial load on over-bed tables in a hospital ward., Methods: Two different micro-patterns were fabricated on polycarbonate film via a thermal imprinting method. Micro-textured films were then mounted on patient over-bed tables in a general hospital ward and the bacterial load monitored over 24 h. Total colony counts, which represented on-specific bacterial loading, and meticillin-resistant Staphylococcus aureus counts were monitored at each time-point., Findings: Over a period of 24 h, both micro-textured surfaces showed consistently lower bacterial load as compared to the unpatterned polycarbonate and the bare over-bed table laminate. This study supports the findings of earlier laboratory-scale studies that microscale physical texturing can reduce bacterial colonization on a solid surface., Conclusion: Results of the current study suggest that micro-textured surfaces could provide a viable method for reducing microbial contamination of high-touch surfaces in hospitals., (Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Aggregate data model-based meta-analysis is a regression approach to compare the dose-response and/or time-course across different treatments using summary level data from the literature. Literature search and systematic review following the Cochrane approach yielded 912 sources for investigational and approved treatments for psoriasis. In addition, data for tofacitinib were obtained from an internal database. Tofacitinib is an oral Janus kinase inhibitor. Two mathematical models were developed for Psoriasis Area and Severity Index (PASI) response in moderate to severe psoriasis patients to quantify the time to maximum effect for PASI75 and to evaluate the dose-response relationship for PASI responders (PASI50, PASI75, PASI90, PASI100) at Week 12. Body weight exhibited an inverse effect on the placebo component of both models, suggesting that body weight affects the overall PASI response regardless of drug. This analysis provides a quantitative framework for efficacy comparisons across psoriasis treatments., (© 2017, The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)