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Background: Chronic respiratory failure is a common cause of ventilator dependence in the intensive care unit (ICU). The causes of chronic respiratory failure include primary disease or complications, such as ICU-acquired weakness. Traditional practice requires patients to remain immobile and bedridden; however, recent evidence suggests that early adequate exercise promotes recovery without increasing risks. In this study, we explored the efficacy of planned progressive abdominal sandbag training in promoting the successful withdrawal of patients with chronic respiratory failure from mechanical ventilation., Methods: This study was conducted between April 2019 and November 2020. Patients were recruited and divided into two groups: abdominal sandbag training group and control group (no training). The training group participated in a 3-month daily pulmonary rehabilitation program, which involved a 30-min session of progressive sandbag loading on the upper abdomen as a form of diaphragmatic resistant exercise. The pressure support level of the ventilator was adjusted to maintain a tidal volume of 8 mL/kg. To investigate the effect of abdominal sandbag training on patients with chronic respiratory failure, we compared tidal volume, shallow breathing index, maximum respiratory pressure, and diaphragm characteristics between the training and control groups., Results: This study included 31 patients; of them, 17 (54.8 %) received abdominal sandbag training and 14 (45.2 %) did not. No significant between-group difference was found in baseline characteristics. Compared with the control group, the training group exhibited considerable improvements in ventilation-related parameters (p < 0.001): the tidal volume markedly increased (p = 0.012), rapid shallow breathing index declined (p = 0.016), and maximum respiratory pressure increased (p < 0.001) in the training group. The diaphragm motion value (p = 0.048) and diaphragm thickness (p = 0.041) were greater in the training group than in the control group. Nine patients (52.9 %) in the training group were removed from the ventilator compared with 1 (7.1 %) in the control group (p = 0.008)., Conclusion: Abdominal sandbag training may be beneficial for patients dependent on a ventilator. The training improves the function of the diaphragm muscle, thereby increasing tidal volume and reducing the respiratory rate and rapid shallow breathing index, thus facilitating withdrawal from ventilation. This training approach may also improve the thickness and motion of the diaphragm and the rate of ventilator detachment., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Efficient hydrogen (H 2 ) production through photocatalytic water splitting was achieved by using an amino-functionalized azolate/cobalt-based metal-organic framework (MOF). While previous reports highlighted the amino group's role only as a substituent group for enabling light absorption of MOFs in the visible region, our present study revealed its dual role. The amino substituent not only acts as an electron donor to increase the electron availability at the active Co sites but also provides hydrogen-hopping sites within the pore channel, facilitating proton (H + ) diffusion along the framework. This dual functionality significantly boosts the performance of this Co-MOF as a hydrogen evolution cocatalyst. When combined with fluorescein and triethylamine as the photosensitizer and sacrificial agent, respectively, the Co-MOF achieved a remarkable H 2 production rate of 27 mmol g -1 over 4 h. Notably, this performance surpasses those of benchmark platinum (Pt) and titanium dioxide (TiO 2 ) cocatalysts.

not applicable., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: The evolution of artificial intelligence has introduced new ways to disseminate health information, including natural language processing models like ChatGPT. However, the quality and readability of such digitally-generated information remains understudied. This study is the first to compare the quality and readability of digitally-generated health information against leaflets produced by professionals., Methodology: Patient information leaflets for five ENT UK leaflets and their corresponding ChatGPT responses were extracted from the Internet. Assessors with various degree of medical knowledge evaluated the content using the Ensuring Quality Information for Patients (EQIP) tool and readability tools including the Flesch-Kincaid Grade Level (FKGL). Statistical analysis was performed to identify differences between leaflets, assessors, and sources of information., Results: ENT UK leaflets were of moderate quality, scoring a median EQIP of 23. Statistically significant differences in overall EQIP score were identified between ENT UK leaflets but ChatGPT responses were of uniform quality. Non-specialist doctors rated the highest EQIP scores while medical students scored the lowest. The mean readability of ENT UK leaflets was higher than ChatGPT responses. The information metrics of ENT UK leaflets were moderate and varied between topics. Equivalent ChatGPT information provided comparable content quality, but with reduced readability., Conclusions: ChatGPT patient information and professionally-produced leaflets had comparable content, but LLM content were required a higher reading age. With the increasing use of online health resources, this study highlights the need for a balanced approach that considers optimises both the quality and readability of patient education materials., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Angiosarcoma is a rare endothelial-derived malignancy that is extremely diverse in anatomy, aetiology, molecular and immune characteristics. While novel therapeutic approaches incorporating targeted agents and immunotherapy have yielded significant improvements in patient outcomes across several cancers, their impact on angiosarcoma remains modest. Contributed by its heterogeneous nature, there is currently a lack of novel drug targets in this disease entity and no reliable biomarkers that predict response to conventional treatment. This review aims to examine the molecular and immune landscape of angiosarcoma in association with its aetiology, anatomical sites, prognosis and therapeutic options. We summarise current efforts to characterise angiosarcoma subtypes based on molecular and immune profiling. Finally, we highlight promising technologies such as single-cell spatial "omics" that may further our understanding of angiosarcoma and propose strategies that can be similarly applied for the study of other rare cancers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Foreign body (FB) inhalation, ingestion, and insertion account for 11% of emergency admissions for ear, nose, and throat conditions. Children are disproportionately affected, and urgent intervention may be needed to maintain airway patency and prevent blood vessel occlusion. High-quality, readable online information could help reduce poor outcomes from FBs., Objective: We aim to evaluate the quality and readability of available online health information relating to FBs., Methods: In total, 6 search phrases were queried using the Google search engine. For each search term, the first 30 results were captured. Websites in the English language and displaying health information were included. The provider and country of origin were recorded. The modified 36-item Ensuring Quality Information for Patients tool was used to assess information quality. Readability was assessed using a combination of tools: Flesch Reading Ease score, Flesch-Kincaid Grade Level, Gunning-Fog Index, and Simple Measure of Gobbledygook., Results: After the removal of duplicates, 73 websites were assessed, with the majority originating from the United States (n=46, 63%). Overall, the quality of the content was of moderate quality, with a median Ensuring Quality Information for Patients score of 21 (IQR 18-25, maximum 29) out of a maximum possible score of 36. Precautionary measures were not mentioned on 41% (n=30) of websites and 30% (n=22) did not identify disk batteries as a risky FB. Red flags necessitating urgent care were identified on 95% (n=69) of websites, with 89% (n=65) advising patients to seek medical attention and 38% (n=28) advising on safe FB removal. Readability scores (Flesch Reading Ease score=12.4, Flesch-Kincaid Grade Level=6.2, Gunning-Fog Index=6.5, and Simple Measure of Gobbledygook=5.9 years) showed most websites (56%) were below the recommended sixth-grade level., Conclusions: The current quality and readability of information regarding FBs is inadequate. More than half of the websites were above the recommended sixth-grade reading level, and important information regarding high-risk FBs such as disk batteries and magnets was frequently excluded. Strategies should be developed to improve access to high-quality information that informs patients and parents about risks and when to seek medical help. Strategies to promote high-quality websites in search results also have the potential to improve outcomes., (©Tsz Ki Ko, Denise Jia Yun Tan, Ka Siu Fan. Originally published in JMIR Formative Research (https://formative.jmir.org), 15.08.2024.)

This article discusses the psychological effects of facial palsy (FP) in adults. FP is the abnormal functioning of facial muscles resulting from temporary or permanent damage of the facial nerves. Following facial paralysis, patients can develop motor and psychosocial functioning issues impacting quality of life. In addition, real or perceived judgment in social settings of those with FP increases the risk of low self-esteem, anxiety, and depression. Currently, most available research focuses on surgical patients and suggests a lack of psychological support throughout the affliction. A multidisciplinary approach when treating patients with FP can help improve the patient's quality of life., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Extramammary Paget's disease (EMPD) is a rare cancer that occurs within the epithelium of the skin, arising predominantly in areas with high apocrine gland concentration such as the vulva, scrotum, penis and perianal regions. Here, we aim to integrate clinicopathological data with genomic analysis of aggressive, rapidly-progressing de novo metastatic EMPD responding to HER2-directed treatment in combination with other agents, to attain a more comprehensive understanding of the disease landscape., Methods: Immunohistochemical staining on the scrotal wall tumor and bone marrow metastasis demonstrated HER2 overexpression. Whole genome sequencing of the tumor and matched blood was performed., Results: Notable copy number gains (log 2 FC > 0.9) on chromosomes 7 and 8 were detected (n = 81), with 92.6% of these unique genes specifically located on chromosome 8. Prominent cancer-associated genes include ZNF703, HOOK3, DDHD2, LSM1, NSD3, ADAM9, BRF2, KAT6A and FGFR1. Interestingly, ERBB2 gene did not exhibit high copy number gain (log 2 FC = 0.4) although 90% of tumor cells stained HER2-positive. Enrichment in pathways associated with transforming growth factor-beta (TGFβ) (FDR = 0.0376, Enrichment Ratio = 8.12) and fibroblast growth factor receptor (FGFR1) signaling (FDR = 0.0082, Enrichment Ratio = 2.3) was detected. Amplicon structure analysis revealed that this was a simple-linear amplification event., Conclusion: Whole genome sequencing revealed the underlying copy number variation landscape in HER2-positive metastatic EMPD. The presence of alternative signalling pathways and genetic variants suggests potential interactions with HER2 signalling, which possibly contributed to the HER2 overexpression and observed response to HER2-directed therapy combined with other agents in a comprehensive treatment regimen., (© 2024. The Author(s).)

Abstract: Idiopathic multicentric Castleman disease (iMCD) is a rare cytokine-driven disorder characterized by systemic inflammation, generalized lymphadenopathy, and organ dysfunction. Here, we present an unusual occurrence of iMCD in identical twins and examined the immune milieu within the affected lymphoid organs and the host circulation using multiomic high-dimensional profiling. Using spatial enhanced resolution omics sequencing (Stereo-seq) transcriptomic profiling, we performed unsupervised spatially constrained clustering to identify different anatomic structures, mapping the follicles and interfollicular regions. After a cell segmentation approach, interleukin 6 (IL-6) pathway genes significantly colocalized with endothelial cells and fibroblastic reticular cells, confirming observations using a single-cell sequencing approach (10× Chromium). Furthermore, single-cell sequencing of peripheral blood mononuclear cells revealed an "inflammatory" peripheral monocytosis enriched for the expression of S100A family genes in both twins. In summary, we provided evidence of the putative cell-of-origin of IL-6 signals in iMCD and described a distinct monocytic host immune response phenotype through a unique identical twin model., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Recent studies have described several molecular subtypes and deregulation of immuno-oncologic signaling pathways in angiosarcoma. Interestingly, mast cells were enriched in subsets of angiosarcoma, although their significance remains unknown. In this study, we aim to verify this observation using immunohistochemistry (H scores) and NanoString transcriptomic profiling and explore the association between mast cells with clinical and biological features. In the study cohort (N = 60), H scores showed a significant moderate correlation with NanoString mast cell scores (r = 0.525; P < .001). Both H score and NanoString mast cell scores showed a significant positive correlation (P < .05) with head and neck location, nonepithelioid morphology, and lower tumor grade. Mast cell enrichment significantly correlated with higher NanoString regulatory T-cell scores (H score, r = 0.32; P = .01; NanoString mast cell score, r = 0.27; P = .04). NanoString mast cell scores positively correlated with signaling pathways relating to antigen presentation (r = 0.264; P = .0414) and negatively correlated with apoptosis (r = -0.366; P = .0040), DNA damage repair (r = -0.348; P = .0064), and cell proliferation (r = -0.542; P < .001). Interestingly, in the metastatic setting, patients with mast cell-enriched angiosarcoma showed poorer progression-free survival (median, 0.2 vs 0.4 years; hazard ratio = 3.05; P = .0489) along with a trend toward worse overall survival (median, 0.2 vs 0.6 years; hazard ratio, 2.86; P = .0574) compared with patients with mast cell-poor angiosarcoma. In conclusion, we demonstrated the presence of mast cells in human angiosarcoma and provided initial evidence of their potential clinical and biological significance. Future research will be required to elucidate their specific roles and mechanisms, which may uncover novel avenues for therapeutic intervention., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: The internet is an increasingly favorable source of information regarding health-related issues. The aim of this study is to apply appropriate evaluation tools to assess the evidence available online about inferior vena cava (IVC) filters with a focus on quality and readability., Methods: A search was performed during December 2022 using three popular search engines, namely Google, Yahoo, and Bing. Websites were categorized into academic, physician, commercial, and unspecified websites according to their content. Information quality was determined using Journal of the American Medical Association (JAMA) criteria, the DISCERN scoring tool, and whether a Health On the Net Foundation certification (HONcode) seal was present. Readability was established using the Flesch Reading Ease Score (FRES) and Flesch-Kincaid Grade Level (FKGL). Statistical significance was accepted as P < .05., Results: In total, 110 websites were included in our study. The majority of websites were categorized as commercial (25%), followed by hospital (24%), academic (21%), unspecified (16%), and physician (14%). Average scores for all websites using JAMA and DISCERN were 1.93 ± 1.19 (median, 1.5; range, 0-4) and 45.20 ± 12.58 (median, 45.5; range, 21-75), respectively. The highest JAMA mean score of 3.07 ± 1.16 was allocated to physician websites, and the highest DISCERN mean score of 52.85 ± 12.66 was allocated to hospital websites. The HONcode seal appeared on two of the selected websites. Physician, hospital, and unspecified websites had a significantly higher mean JAMA score than academic and commercial websites (all with P < .001). Hospital websites had a significantly higher mean DISCERN score than academic (P = .007), commercial (P < .001), and unspecified websites (P = .017). Readability evaluation generated a mean FRES score of 51.57 ±12.04, which represented a 10th to 12th grade reading level and a mean FKGL score of 8.20 ± 1.70, which represented an 8th to 10th grade reading level. Only 12 sources were found to meet the ≤6th grade target reading level. No significant correlation was found between overall DISCERN score and overall FRES score., Conclusions: The study results demonstrate that the quality of online information about IVC filters is suboptimal, and academic and commercial websites, in particular, must enhance their content quality regarding the use of IVC filters. Considering the discontinuation of the HONcode as a standardized quality assessment marker, it is recommended that a similar certification tool be developed and implemented for the accreditation of patient information online., Competing Interests: Disclosures None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.

Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma harboring NAB2-STAT6 gene fusions. Mechanistic studies and therapeutic development on SFT/HPC are impeded by scarcity and lack of system models. In this study, we established and characterized a novel SFT/HPC patient-derived cell line (PDC), SFT-S1, and screened for potential drug candidates that could be repurposed for the treatment of SFT/HPC. Immunohistochemistry profiles of the PDC was consistent with the patient's tumor sample (CD99+/CD34+/desmin-). RNA sequencing, followed by Sanger sequencing confirmed the pathognomonic NAB2exon3-STAT6exon18 fusion in both the PDC and the original tumor. Transcriptomic data showed strong enrichment for oncogenic pathways (epithelial-mesenchymal transition, FGF, EGR1 and TGFβ signaling pathways) in the tumor. Whole genome sequencing identified potentially pathogenic somatic variants such as MAGEA10 and ABCA2. Among a panel of 14 targeted agents screened, dasatinib was identified to be the most potent small molecule inhibitor against the PDC (IC 50 , 473 nM), followed by osimertinib (IC 50 , 730 nM) and sunitinib (IC 50 , 1765 nM). Methylation profiling of the tumor suggests that this specific variant of SFT/HPC could lead to genome-wide hypomethylation. In conclusion, we established a novel PDC model of SFT/HPC with comprehensive characterization of its genomic, epigenomic and transcriptomic landscape, which can facilitate future preclinical studies of SFT/HPC, such as in vitro drug screening and in vivo drug testing., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Background: Nasopharyngeal carcinoma (NPC) is a rare disease that is strongly associated with exposure to the Epstein-Barr virus and is characterized by the formation of malignant cells in nasopharynx tissues. Early diagnosis of NPC is often difficult owing to the location of initial tumor sites and the nonspecificity of initial symptoms, resulting in a higher frequency of advanced-stage diagnoses and a poorer prognosis. Access to high-quality, readable information could improve the early detection of the disease and provide support to patients during disease management., Objective: This study aims to assess the quality and readability of publicly available web-based information in the English language about NPC, using the most popular search engines., Methods: Key terms relevant to NPC were searched across 3 of the most popular internet search engines: Google, Yahoo, and Bing. The top 25 results from each search engine were included in the analysis. Websites that contained text written in languages other than English, required paywall access, targeted medical professionals, or included nontext content were excluded. Readability for each website was assessed using the Flesch Reading Ease score and the Flesch-Kincaid grade level. Website quality was assessed using the Journal of the American Medical Association (JAMA) and DISCERN tools as well as the presence of a Health on the Net Foundation seal., Results: Overall, 57 suitable websites were included in this study; 26% (15/57) of the websites were academic. The mean JAMA and DISCERN scores of all websites were 2.80 (IQR 3) and 57.60 (IQR 19), respectively, with a median of 3 (IQR 2-4) and 61 (IQR 49-68), respectively. Health care industry websites (n=3) had the highest mean JAMA score of 4 (SD 0). Academic websites (15/57, 26%) had the highest mean DISCERN score of 77.5. The Health on the Net Foundation seal was present on only 1 website, which also achieved a JAMA score of 3 and a DISCERN score of 50. Significant differences were observed between the JAMA score of hospital websites and the scores of industry websites (P=.04), news service websites (P<.048), charity and nongovernmental organization websites (P=.03). Despite being a vital source for patients, general practitioner websites were found to have significantly lower JAMA scores compared with charity websites (P=.05). The overall mean readability scores reflected an average reading age of 14.3 (SD 1.1) years., Conclusions: The results of this study suggest an inconsistent and suboptimal quality of information related to NPC on the internet. On average, websites presented readability challenges, as written information about NPC was above the recommended reading level of sixth grade. As such, web-based information requires improvement in both quality and accessibility, and healthcare providers should be selective about information recommended to patients, ensuring they are reliable and readable., (©Denise Jia Yun Tan, Tsz Ki Ko, Ka Siu Fan. Originally published in JMIR Formative Research (https://formative.jmir.org), 27.11.2023.)

Background: Modern technological advancements have led to increase in the development of surgical robots in dentistry, resulting in excellent clinical treatment outcomes., Purpose: This study aimed to determine the accuracy of automatic robotic implant site preparation for different implant sizes by correlating planned and posttreatment positions, and to compare the performance of robotic and human freehand drilling., Method: Seventy-six drilling sites on partially edentulous models were used, with three different implant sizes (Ø = 3.5 × 10 mm, 4.0 × 10 mm, 5.0 × 10 mm). The robotic procedure was performed using software for calibration and step-by-step drilling processes. After robotic drilling, deviations in the implant position from the planned position were determined. The angulation, depth, and coronal and apical diameters on the sagittal plane of sockets created by human and robotic drilling were measured., Results: The deviation of the robotic system was 3.78° ± 1.97° (angulation), 0.58 ± 0.36 mm (entry point), and 0.99 ± 0.56 mm (apical point). Comparison of implant groups showed the largest deviation from the planned position for 5 mm implants. On the sagittal plane, there were no significant differences between robotic and human surgery except for the 5-mm implant angulation, indicating similar quality between human and robotic drilling. Based on standard implant measurements, robotic drilling exhibited comparable performance to freehand human drilling., Conclusions: A robotic surgical system can provide the greatest accuracy and reliability regarding the preoperative plan for small implant diameters. In addition, the accuracy of robotic drilling for anterior implant surgery can also be comparable to that of human drilling., (© 2023 Wiley Periodicals LLC.)

Background/purpose: The simulated color of restorations plays an important role in improving patient satisfaction. The aim of this study was to test a new intelligent colorimetric solution using the Advanced Reflectionless Technology (ART) monitor and compare them using commercially available shade systems., Materials and Methods: Six participants' right maxillary central incisors were tested with three devices, including the AUO Display Plus (Group A), a Canon single-lens reflex camera with eLAB's polar eyes filter (Group E), and the VITA Easyshade V (Group V). Each porcelain tooth was divided into three areas, and was assigned a CIELAB L∗a∗b∗ value by using the VITA Easyshade V. The original data were compared with the CIELAB L∗a∗b∗ obtained using the VITA Easyshade V. A prosthodontist compared the color of the porcelain veneers by eyes and gave the scores from 1 to 3., Results: For the ΔE, the three areas of Group A had the smallest differences between the color of the fabricated teeth and that of the original teeth. Colorimetric analysis indicated that Groups A and V did not differ much in the color of the three areas of the tooth. Groups E and A exhibited significant differences between the cervical third and middle third of the tooth, and Groups E and V exhibited significant differences between the middle third and incisal third of the tooth., Conclusion: Compared with traditional monitors, ART is closer to real images in terms of color, contrast, and detail grayscale. Technicians are able to produce realistic and pleasing colors., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Objective: Bibliometrics analysis is a widely used approach that enables influential research within specific fields to be identifiedTo identify the 100 most-cited articles in breast radiology and analyse the trend in breast imaging research., Methods and Materials: A systematic search was conducted using the Thomson Rheuters Web of Science database. The results were ranked according to citation count and screened to create a single database. Data including first author, year of publication, journal, country of origin, primary institution, number of citations and average number of citations per year were extracted, as well as the impact factor and the 5-year impact factor of journals publishing the articles., Results: The systematic search yielded a total of 114,426 articles, after filters were applied to include papers that were available in English only. Citations for the 100 most-cited articles ranged from 515 to 3660. Half of the articles on the list were published between 2001 and 2010. Radiology has the most number of publications ( n = 17), followed by JAMA-Journal of The American Medical Association ( n = 9). CA-A Cancer Journal For Clinicians had the highest impact factor of 286.13. Mammogram ( n = 49) was the most commonly studied modality, followed by Magnetic Resonance ( n = 26). The most common topic of publication was diagnosis ( n = 83)., Conclusion: This research serves as a guide to the most influential articles on the topic of breast radiology., Competing Interests: Competing interests: The authors declare that they have no competing interests, (© 2023 The Authors. Published by the British Institute of Radiology.)

Southeast (SE) Asia is a highly biodiverse region, yet it is also estimated to cumulatively contribute a third of the total global marine plastic pollution. This threat is known to have adverse impacts on marine megafauna, however, understanding of its impacts has recently been highlighted as a priority for research in the region. To address this knowledge gap, a structured literature review was conducted for species of cartilaginous fishes, marine mammals, marine reptiles, and seabirds present in SE Asia, collating cases on a global scale to allow for comparison, coupled with a regional expert elicitation to gather additional published and grey literature cases which would have been omitted during the structured literature review. Of the 380 marine megafauna species present in SE Asia, but also studied elsewhere, we found that 9.1 % and 4.5 % of all publications documenting plastic entanglement (n = 55) and ingestion (n = 291) were conducted in SE Asian countries. At the species level, published cases of entanglement from SE Asian countries were available for 10 % or less of species within each taxonomic group. Additionally, published ingestion cases were available primarily for marine mammals and were lacking entirely for seabirds in the region. The regional expert elicitation led to entanglement and ingestion cases from SE Asian countries being documented in 10 and 15 additional species respectively, highlighting the utility of a broader approach to data synthesis. While the scale of the plastic pollution in SE Asia is of particular concern for marine ecosystems, knowledge of its interactions and impacts on marine megafauna lags behind other areas of the world, even after the inclusion of a regional expert elicitation. Additional funding to help collate baseline data are critically needed to inform policy and solutions towards limiting the interactions of marine megafauna and plastic pollution in SE Asia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Angiosarcomas are rare malignant tumors of the endothelium, arising commonly from the head and neck region (AS-HN) and recently associated with ultraviolet (UV) exposure and human herpesvirus-7 infection. We examined 81 cases of angiosarcomas, including 47 cases of AS-HN, integrating information from whole genome sequencing, gene expression profiling and spatial transcriptomics (10X Visium). In the AS-HN cohort, we observed recurrent somatic mutations in CSMD3 (18%), LRP1B (18%), MUC16 (18%), POT1 (16%) and TP53 (16%). UV-positive AS-HN harbored significantly higher tumor mutation burden than UV-negative cases (p = 0.0294). NanoString profiling identified three clusters with distinct tumor inflammation signature scores (p < 0.001). Spatial transcriptomics revealed topological profiles of the tumor microenvironment, identifying dominant but tumor-excluded inflammatory signals in immune-hot cases and immune foci even in otherwise immune-cold cases. In conclusion, spatial transcriptomics reveal the tumor immune landscape of angiosarcoma, and in combination with multi-omic information, may improve implementation of treatment strategies., (© 2023. The Author(s).)

NiFe layered double hydroxides (LDHs) intercalated with dioctyl sulfosuccinate with varied Fe 3+ /(Ni 2+ + Fe 3+ ) ratios (0.04-0.25) were prepared by constant-pH co-precipitation from an aqueous solution of Ni and Fe perchlorates at room temperature. The interlayer dioctyl sulfosuccinate was exchanged with carbonate by the reaction of the product with an aqueous solution of sodium carbonate. The basal spacing of the NiFe-LDHs containing carbonate varied (0.80-0.90 nm) depending on the Fe 3+ /(Ni 2+ + Fe 3+ ) ratio; larger basal spacing was attained from the LDH with smaller Fe 3+ /(Ni 2+ + Fe 3+ ) due to the weaker attractive force between the LDH layer and the interlayer anion, proving that the Fe 3+ /(Ni 2+ + Fe 3+ ) ratios were associated with the layer charge density of NiFe-LDHs.

Whilst the pathophysiology at a cellular level has been defined, the cause of Parkinson's disease (PD) remains poorly understood. This neurodegenerative disorder is associated with impaired dopamine transmission in the substantia nigra, and protein accumulations known as Lewy bodies are visible in affected neurons. Cell culture models of PD have indicated impaired mitochondrial function, so the focus of this paper is on the quality control processes involved in and around mitochondria. Mitochondrial autophagy (mitophagy) is the process through which defective mitochondria are removed from the cell by internalisation into autophagosomes which fuse with a lysosome. This process involves many proteins, notably including PINK1 and parkin, both of which are known to be coded on genes associated with PD. Normally in healthy individuals, PINK1 associates with the outer mitochondrial membrane, which then recruits parkin, activating it to attach ubiquitin proteins to the mitochondrial membrane. PINK1, parkin, and ubiquitin cooperate to form a positive feedback system which accelerates the deposition of ubiquitin on dysfunctional mitochondria, resulting in mitophagy. However, in hereditary PD, the genes encoding PINK1 and parkin are mutated, resulting in proteins that are less efficient at removing poorly performing mitochondria, leaving cells more vulnerable to oxidative stress and ubiquitinated inclusion bodies, such as Lewy bodies. Current research that looks into the connection between mitophagy and PD is promising, already yielding potentially therapeutic compounds; until now, pharmacological support for the mitophagy process has not been part of the therapeutic arsenal. Continued research in this area is warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ko et al.)

Introduction During the coronavirus disease 2019 (COVID-19) pandemic, private hospitals in Mandalay started to manage COVID-19 infections according to national treatment guidelines since February 2021. Variations of clinical characteristics and their outcomes in different surges could be evaluated in the private hospital. This study aimed to assess the clinical profile and outcomes of COVID-19 patients admitted at a private hospital during three surges in Mandalay. Methods This study is a retrospective record review of the case series of COVID-19 patients admitted at City Hospital, Mandalay. The study was conducted from January to December 2022. All of the hospital records of COVID-19 patients admitted during the second wave from February 2020 to 26 May 2021, the third wave from 27 May 2021 to 27 January 2022, and the fourth wave from 28 January to April 2022 were included in the study. Results A total of 1606 admitted cases were included in the study. The mean with standard deviation (SD) of age was 55.7±18.5, and males were 778 (48.4%). The mean duration of hospital stay in days was 10.8±5.94, 10.6±6.11, and 7.3±2.88 in second, third, and fourth waves, respectively. The mean duration of hospital stay was shortened in the fourth wave. Comorbid conditions with hypertension and/or diabetes diseases were mostly observed in three waves of COVID-19 infection. Fever was the most presented symptom in three waves. Cough, sore throat, and rhinorrhea were observed more in the fourth wave compared with previous waves. Complication with pneumonia (71.3%), liver dysfunction (21.0%), acute respiratory distress syndrome (10.0%), thrombocytopenia (6.2%), acute kidney injury (5.5%), bleeding (3.9%), and pulmonary embolism (2.9%) were investigated. Antiviral treatment such as remdesivir or molnupiravir was used more in the patients of third and fourth waves than those of the second wave. Oxygen therapy (59.9%), prone position (35.5%), non-invasive ventilation (9.5%), invasive ventilation (0.5%), inotropes (4.6%), and renal replacement therapy (1.1%) were recorded in serious cases. Only 7.9% and 9.4% died in the hospital in second and third waves. No mortality was observed in the fourth wave. Conclusions The study recommended that COVID-19 patients with comorbid conditions of hypertension or diabetes and ages 65 and older should be taken with intensive care support at the hospital. This study also concluded that a private hospital in Mandalay could tackle with COVID-19 severe cases in line with national treatment guidelines since the second wave and could provide better management in the fourth wave. Antiviral treatment should be used in severe COVID-19 cases for further emergency management. In conclusion, private hospital involvement in the COVID-19 pandemic is supportive of the healthcare provision in Myanmar in an emergency situation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kyu et al.)

Parkinson's disease (PD) is an increasing threat to first-world nations as their population ages, with around one in 100 suffering from it by age 60. Incurable, with treatments that do little to delay disease progression, PD induces severe disability and even death in those afflicted. The search for preventative measures has revealed the widely used psychoactive stimulant caffeine, which competitively inhibits adenosine receptors to induce a wide variety of effects. The inhibition of inflammation and microglial cell activation to reduce reactive oxygen species (ROS)-induced cellular damage and the resultant mitochondrial dysfunction of the dopaminergic neurons appears to be the main pathway, inducing neuronal loss via the activation of the intrinsic pathway to apoptosis. Mouse models and human data reinforce that caffeine delays the onset of PD in a dose-dependent manner. Evidence suggests it is more beneficial in men than women and is not beneficial at all in women undergoing hormone replacement therapy (HRT). Additionally, some studies suggest that although caffeinated drinks such as cola and tea are beneficial, there may be other products in coffee that prevent the effect, though this requires further research. Although there is strong evidence that caffeine is neuroprotective, there is less evidence that it delays the onset of PD. Given the association with cardiovascular disease, it may be disadvantageous overall to the majority of the population to supplement caffeine, though still a beneficial preventative technique for individuals with a genetic predisposition to PD that may otherwise suffer early onset., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ko et al.)

The aim of the study was to characterise the most frequently cited articles on the topic of hearing implants. A systematic search was carried out using the Thomson Reuters Web of Science Core Collection database. Eligibility criteria restricted the results to primary studies and reviews published from 1970 to 2022 in English dealing primarily with hearing implants. Data including the authors, year of publication, journal, country of origin, number of citations and average number of citations per year were extracted, as well as the impact factors and five-year impact factor of journals publishing the articles. The top 100 papers were published across 23 journals and were cited 23,139 times. The most-cited and influential article describes the first use of the continuous interleaved sampling (CIS) strategy utilised in all modern cochlear implants. More than half of the studies on the list were produced by authors from the United States, and the Ear and Hearing journal had both the greatest number of articles and the greatest number of total citations. To conclude, this research serves as a guide to the most influential articles on the topic of hearing implants, although bibliometric analyses mainly focus on citations. The most-cited article was an influential description of CIS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ko et al.)

Bismuth oxyhalides and layered alkali titanates are promising components to design high-performance hybrid photocatalysts. In this work, a hybrid photocatalyst composed of lepidocrocite-type layered cesium titanate (Cs 0.7 Ti 1.77 Li 0.23 O 4 , CsTLO) and bismuth oxyiodide (BiOI) was designed rationally based on lattice matching. BiOI formed on the layered titanate by ion exchange of CsTLO with Bi cations and subsequent growth of BiOI nanodisks (6 nm in the thickness and 125 nm in the lateral size) in an aqueous solution of cesium iodide, resulting in the hybrid where BiOI nanodisks were lying flat on the layered titanate and exposed the (001) facet predominantly. The present hybrid exhibited efficient photodegradation of methylene blue (4, 10, and 14 times higher than that of CsTLO, Bi-TLO, and BiOI, respectively), which was ascribed to the efficient charge transfer in the bulk and at the interface assisted by the built-in internal electric fields and the high activity of (001) BiOI for direct oxidation of the pollutant.

Purpose: Delivering high-quality cancer care to patients through a multidisciplinary team (MDT) care approach remains a challenge, particularly in low- and middle-income countries characterized by fragmented health systems and limited human resources for cancer care. City Cancer Challenge (C/Can) is supporting cities in low- and middle-income countries as they work to improve access to equitable quality cancer care. C/Can has developed an innovative methodology to address the MDT gap, piloted in four cities-Asunciòn, Cali, Kumasi, and Yangon., Methods: Collaborating with a network of partners, C/Can and ASCO have developed a package of technical cooperation support focusing on two priority areas that have emerged as core needs: first developing consensus-based, city-wide patient management guidelines for the most common cancers and second, building capacity for the implementation of MDTs in institutions providing cancer care in the city., Results: The real-time application of C/Can's MDT approach in Cali and Asuncion underlined the importance of engaging the right stakeholders early on and embedding MDT guidelines in local and national regulatory frameworks to achieve their sustainable uptake. The results in Cali and Asuncion were essential for informing the process in Yangon, asserting the clear benefits of city-to-city knowledge exchange. Finally, the global COVID-19 pandemic prompted a rapid adaptation of the methodology from an in-person to virtual format; the unexpected success of the virtual program in Kumasi has led to its application in subsequent C/Can cities., Conclusion: The application of C/Can's methodology in this first set of cities has reinforced not only the importance of both resource appropriate guidelines and a highly trained health workforce but also the need for commitment to work across institutions and disciplines.

The field of immuno-oncology is now at the forefront of cancer care and is rapidly evolving. The immune checkpoint blockade has been demonstrated to restore antitumor responses in several cancer types. However, durable responses can be observed only in a subset of patients, highlighting the importance of investigating the tumor microenvironment (TME) and cellular heterogeneity to define the phenotypes that contribute to resistance as opposed to those that confer susceptibility to immune surveillance and immunotherapy. In this review, we summarize how some of the most widely used conventional technologies and biomarkers may be useful for the purpose of predicting immunotherapy outcomes in patients, and discuss their shortcomings. We also provide an overview of how emerging single-cell spatial omics may be applied to further advance our understanding of the interactions within the TME, and how these technologies help to deliver important new insights into biomarker discovery to improve the prediction of patient response.

Liquid biopsy circulating tumor DNA (ctDNA)-based approaches may represent a non-invasive means for molecular interrogation of gastrointestinal stromal tumors (GISTs). We deployed a customized 29-gene Archer ® LiquidPlex™ targeted panel on 64 plasma samples from 46 patients. The majority were known to harbor KIT mutations ( n = 41, 89.1%), while 3 were PDGFRA exon 18 D842V mutants and the rest ( n = 2) were wild type for KIT and PDGFRA . In terms of disease stage, 14 (30.4%) were localized GISTs that had undergone complete surgical resection while the rest ( n = 32) were metastatic. Among ten patients, including 7 on tyrosine kinase inhibitors, with evidence of disease progression at study inclusion, mutations in ctDNA were detected in 7 cases (70%). Known somatic mutations in KIT ( n = 5) or PDGFRA ( n = 1) in ctDNA were identified only among 6 of the 10 patients. These KIT mutants included duplication, indels, and single-nucleotide variants. The median mutant AF in ctDNA was 11.0% (range, 0.38%-45.0%). In patients with metastatic progressive KIT -mutant GIST, tumor burden was higher with detectable KIT ctDNA mutation than in those without (median, 5.97 cm vs. 2.40 cm, p = 0.0195). None of the known tumor mutations were detected in ctDNA for localized cases ( n = 14) or metastatic cases without evidence of disease progression ( n = 22). In patients with serial samples along progression of disease, secondary acquired mutations, including a potentially actionable PIK3CA exon 9 c.1633G>A mutation, were detected. ctDNA mutations were not detectable when patients responded to a switch in TKI therapy. In conclusion, detection of GIST-related mutations in ctDNA using a customized targeted NGS panel represents an attractive non-invasive means to obtain clinically tractable information at the time of disease progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ko, Lee, Ng, Yang, Farid, Teh, Chan and Somasundaram.)

The biodegradation and biosorption efficiency of an indigenous siderophores-producing bacterial community on azo dyes with immobilization in chitosan beads was evaluated in this study. 13 bacterial strains were isolated from textile wastewater streams. The bacterial strains were tested for the production of siderophores as well as their ability to decolorize toxic azo dyes in aqueous solution. Both qualitatively and quantitatively, all of the strains displayed high siderophores productivity. Furthermore, they displayed remarkable decolorization efficiency for azo dyes (Acid Black 1 and Reactive Black 5) in both free and immobilized form. The immobilization process was found not only to enhance the decolorization but also the degradation of azo dyes by the bacterial isolates. In a SEM micrograph, bacterial strains were immobilized, and the pores in chitosan bead to be trapped and adsorbed for dyes from synthetic wastewater. The extent of dye compounds degradation were examined using UV-visible and FTIR spectrophotometers on treated water samples and dye absorbed beads. After 72 h of incubation, the UV-visible analysis revealed that the bacterial community could significantly reduce both azo dyes in wastewater by 90% at 300 mgL -1 dyes initial concentration. FTIR study confirmed the bonds of these dyes were broken to form less toxic chemicals via the bacterial community immobilized in chitosan beads. The immobilized bacterial community thus demonstrated effective approach of azo dye biosorption and biodegradation., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Primary care is crucial to the health of individuals and communities, but it faces numerous structural and systemic challenges. Our study assessed the state of primary care in Virginia to prepare for Medicaid expansion. It also provides insight into the frontline of health care prior to an unprecedented global COVID-19 pandemic., Methods: We surveyed 1622 primary care practices to understand organizational characteristics, scope of care, capacity, and organizational stress., Results: Practices (484) varied in type, ownership, location, and care for medically underserved and diverse patient populations. Most practices accepted uninsured and Medicaid patients. Practices reported a broad scope of care, including offering behavioral health and medication-assisted therapy for opioid addiction. Over half addressed social needs like transportation and unstable housing. One in three practices experienced a significant stress in 2019, prepandemic, and only 18.8% of practices anticipated a stress in 2020., Conclusions: Primary care serves as the foundation of our health care system and is an essential service, but it is severely stressed, under-resourced, and overburdened in the best of times. Primary care needs strategic workforce planning, adequate access to resources, and financial investment to sustain its value and innovation., Competing Interests: Conflict of interest: The authors of this manuscript have no conflicts of interest to disclose, beyond being primary care clinicians and researchers., (© Copyright 2021 by the American Board of Family Medicine.)

All-inorganic iodide perovskites were prepared by a mechanochemical reaction between a layered cesium titanate and bismuth (or antimony) triiodide under ambient conditions. The layered cesium titanate was a sacrificial template and also acted as a milling media for the formation of the perovskite nanoparticles with the size of a few nanometres.

Background: Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death., Methods: Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy's Cancer Centre and King's College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality., Results: Three hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died <7 days. Male sex [hazard ratio (HR): 1.97 (95% confidence interval (CI): 1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer [2.03 (1.16-3.56)] and a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients (<7 days from diagnosis)., Conclusions: Findings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients., (© 2021. The Author(s).)

In the USA, Black women are at disproportionately higher risk for HIV compared to women of other races/ethnicities, which can be explained by the Substance Abuse, Violence and AIDS (SAVA) syndemic. Disparities in HIV, substance use and violence are driven by multiple influences, including structural factors (e.g. housing and poverty), which exacerbate social- and individual-level factors leading to more sex partners, engaging in unprotected sex, having sex for money, experiencing forced sex from an intimate partner or increased substance use, all of which increase HIV risk. Pre-exposure prophylaxis (PrEP), a pill that can prevent HIV, is a discreet and underutilised method that Black women experiencing syndemics can use to decrease their risk. This study explored Black women's interest in, and barriers to adopting PrEP over 6 months. Thirty Black women (age M  = 32.2) who experienced multiple substance use, violence and HIV-related syndemic factors were interviewed four times over a 6-month period. Results demonstrated that experiencing intimate partner violence, substance use, community violence and other structural factors (poor access to social services, transport and childcare) all acted as barriers to PrEP adoption. Future research should consider multi-level interventions that include methods such as media campaigns, providing PrEP or referrals where women who experience syndemic and structural factors seek help, and implement a PrEP adherence programmes and interventions in support group settings.

Adipocyte browning appears to be a potential therapeutic strategy to combat obesity and related metabolic disorders. Recent studies have shown that apelin, an adipokine, stimulates adipocyte browning and has negative cross-talk with angiotensin II receptor type 1 (AT 1 receptor) signaling. Here, we report that losartan, a selective AT 1 receptor antagonist, induces browning, as evidenced by an increase in browning marker expression, mitochondrial biogenesis, and oxygen consumption in murine adipocytes. In parallel, losartan up-regulated apelin expression, concomitant with increased phosphorylation of protein kinase B and AMP-activated protein kinase. However, the siRNA-mediated knockdown of apelin expression attenuated losartan-induced browning. Angiotensin II cotreatment also inhibited losartan-induced browning, suggesting that AT 1 receptor antagonism-induced activation of apelin signaling may be responsible for adipocyte browning induced by losartan. The in vivo browning effects of losartan were confirmed using both C57BL/6J and ob/ob mice. Furthermore, in vivo apelin knockdown by adeno-associated virus carrying-apelin shRNA significantly inhibited losartan-induced adipocyte browning. In summary, these data suggested that AT 1 receptor antagonism by losartan promotes the browning of white adipocytes via the induction of apelin expression. Therefore, apelin modulation may be an effective strategy for the treatment of obesity and its related metabolic disorders., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Kim et al.)

Myanmar has introduced routine viral load (VL) testing for people living with HIV (PLHIV) starting first-line antiretroviral therapy (ART). The first VL test was initially scheduled at 12-months and one year later this changed to 6-months. Using routinely collected secondary data, we assessed program performance of routine VL testing at 12-months and 6-months in PLHIV starting ART in the Integrated HIV-Care Program, Myanmar, from January 2016 to December 2017. There were 7153 PLHIV scheduled for VL testing at 12-months and 1976 scheduled for VL testing at 6-months. Among those eligible for testing, the first VL test was performed in 3476 (51%) of the 12-month cohort and 952 (50%) of the 6-month cohort. In the 12-month cohort, 10% had VL > 1000 copies/mL, 79% had repeat VL tests, 42% had repeat VL > 1000 copies/mL (virologic failure) and 85% were switched to second-line ART. In the 6-month cohort, 11% had VL > 1000 copies/mL, 83% had repeat VL tests, 26% had repeat VL > 1000 copies/mL (virologic failure) and 39% were switched to second-line ART. In conclusion, half of PLHIV initiated on ART had VL testing as scheduled at 12-months or 6-months, but fewer PLHIV in the 6-month cohort were diagnosed with virologic failure and switched to second-line ART. Programmatic implications are discussed.

In₂O₃/SnO₂ composite nanoparticles (NPs) were synthesized by a hydrothermal method. Fringes and spotty patterns were observed in high-resolution TEM images and corresponding selected area electron diffraction pattern, respectively, suggesting the nanoparticles were single crystals. X-ray diffraction results revealed that the In₂O₃/SnO₂ composite NP sensor consisted of three phases: In₂O₃, SnO₂ and In₂Sn₂O 7-x (indium tin oxide: ITO). Energy-dispersive X-ray spectrum of the 9:1 In₂O₃/SnO₂ composite NPs showed the atomic ratio of In₂O₃ to SnO₂ was close to 9:1. The response of the chemiresistive sensor to CO was 9.2, which is within the highest 15% among the response values reported for the past 10 years. The ITO NP-based gas sensor is selective toward CO against other reducing gases such as toluene, acetone and benzene. The enhanced response of the 9:1 In₂O₃/SnO₂ composite NP sensor to CO compared to the pure In₂O₃ NP sensor can be explained mainly by the stronger resistance modulation at the In₂O₃/SnO₂ junctions.

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

There are considerable challenges in analyzing large-scale compositional data. In this paper, we introduce the Spike-and-Slab Lasso linear regression in the presence of compositional covariates for parameter estimation and variable selection. We consider the well-known isometric log-ratio (ilr) coordinates to avoid misleading statistical inference. The separable and non-separable (adaptative) Spike-and-Slab Lasso penalties are compared to verify the advantages of each approach. The proposed method is illustrated on simulated and on real Brazilian child malnutrition data.

Ion exchange of layered alkali titanates (Na 2 Ti 3 O 7 , K 2 Ti 4 O 9 , and Cs 2 Ti 5 O 11 ) with several alkali metal halides surprisingly proceeded in the solid-state at room temperature. The reaction was governed by thermodynamic parameters and was completed within a shorter time when the titanates with a smaller particle size were employed. On the other hand, the required time for the ion exchange was shorter in the cases of Cs 2 Ti 5 O 11 than those of K 2 Ti 4 O 9 irrespective of the particle size of the titanates, suggesting faster diffusion of the interlayer cation in the titanate with lower layer charge density.

Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) harboring BIM deletion polymorphism (BIM deletion) have poor responses to EGFR TKI. Mechanistically, the BIM deletion induces preferential splicing of the non-functional exon 3-containing isoform over the functional exon 4-containing isoform, impairing TKI-induced, BIM-dependent apoptosis. Histone deacetylase inhibitor, vorinostat, resensitizes BIM deletion-containing NSCLC cells to EGFR-TKI. In the present study, we determined the safety of vorinostat-gefitinib combination and evaluated pharmacodynamic biomarkers of vorinostat activity. Patients with EGFR-mutated NSCLC with the BIM deletion, pretreated with EGFR-TKI and chemotherapy, were recruited. Vorinostat (200, 300, 400 mg) was given daily on days 1-7, and gefitinib 250 mg was given daily on days 1-14. Vorinostat doses were escalated based on a conventional 3 + 3 design. Pharmacodynamic markers were measured using PBMC collected at baseline and 4 hours after vorinostat dose on day 2 in cycle 1. No dose-limiting toxicities (DLT) were observed in 12 patients. We determined 400 mg vorinostat as the recommended phase II dose (RP2D). Median progression-free survival was 5.2 months (95% CI: 1.4-15.7). Disease control rate at 6 weeks was 83.3% (10/12). Vorinostat preferentially induced BIM mRNA-containing exon 4 over mRNA-containing exon 3, acetylated histone H3 protein, and proapoptotic BIM EL protein in 11/11, 10/11, and 5/11 patients, respectively. These data indicate that RP2D was 400 mg vorinostat combined with gefitinib in BIM deletion/EGFR mutation double-positive NSCLC. BIM mRNA exon 3/exon 4 ratio in PBMC may be a useful pharmacodynamic marker for treatment., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

In 2 O 3 nanoparticle (NP)-decorated WO 3 nanorods (NRs) were prepared using sol-gel and hydrothermal methods. The In 2 O 3 NRs and WO 3 NPs were crystalline. WO 3 NP-decorated In 2 O 3 NRs were also prepared using thermal evaporation and hydrothermal methods. The NO 2 sensing performance of the In 2 O 3 NP-decorated WO 3 NR sensor toward NO 2 was compared to that of the WO 3 NP-decorated In 2 O 3 NR sensor. The former showed a high response to NO 2 due to a significant reduction of the conduction channel width upon exposure to NO 2 . In contrast, the latter showed a far less pronounced response due to limited reduction of the conduction channel width upon exposure to NO 2 . When the sensors were exposed to a reducing gas instead of an oxidizing gas (NO 2 ), the situation was reversed, i.e., the WO 3 NP-decorated In 2 O 3 NR exhibited a stronger response to the reducing gas than the In 2 O 3 NP-decorated WO 3 NR sensor. Thus, a semiconducting metal oxide (SMO) with a smaller work function must be used as the decorating material in decorated heterostructured SMO sensors for detection of oxidizing gases. The In 2 O 3 NP-decorated WO 3 NR sensor showed higher selectivity for NO 2 compared to other gases, including reducing gases and other oxidizing gases, as well as showed high sensitivity to NO 2 .

Background: A series of interventions are required to prevent mother to child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) starting from HIV testing of pregnant women, initiating antiretroviral therapy (ART) or antiretroviral prophylaxis to HIV-positive pregnant women to providing HIV prophylaxis to newborn babies. Gaps in each step can significantly affect the effectiveness of PMTCT interventions. We aimed to determine the gap in initiation of ART/antiretroviral prophylaxis for pregnant women living with HIV, delay in initiation of ART/antiretroviral prophylaxis and factors associated with the delay., Methods: This is a cross sectional study using routinely collected programme data from five health facilities providing PMTCT services located at Township Health Departments (THD) of Mandalay, Myanmar., Results: There were 363 pregnant women living with HIV enrolled between January 2012 and December 2017. Sixty (16%) women were excluded from the study due to missing data on dates of HIV diagnosis. Of 303 (84%) women included in the study, 89/303 (29%) and 214/303 (71%) were diagnosed with HIV before and during current pregnancy respectively. Among 214 women, 180 (84%) women were started on ART by the censor date (31st March 2018). Among those who started ART, 109 (61%) women had a delay of starting ART > 2 weeks from diagnosis. Women residing in township 4 had a significantly higher risk of delay in initiation of ART/antiretroviral prophylaxis compared to women residing in township 1 [adjusted prevalence ratio 4.2 (95% confidence interval 1.2-14.8]., Conclusions: We found that one in four women living with HIV knew their HIV status before current pregnancy. Although the rate of ART/antiretroviral prophylaxis initiation was high among pregnant women living with HIV, there was a delay. Early initiation of ART/antiretroviral prophylaxis among newly HIV diagnosed pregnant women needs to be strengthened.

[This corrects the article DOI: 10.1093/ofid/ofy355.].

Background: There is limited empirical evidence on the relationship between hyperglycemia, tuberculosis (TB) comorbidity, and mortality in the context of HIV. We assessed whether hyperglycemia at enrollment in HIV care was associated with increased risk of all-cause mortality and whether this relationship was different among patients with and without TB disease., Methods: We conducted a retrospective analysis of adult (≥15 years) HIV-positive patients enrolled into HIV care between 2011 and 2016 who had random blood glucose (RBG) measurements at enrollment. We used hazards regression to estimate associations between RBG and rate of all-cause mortality., Results: Of 25 851 patients, 43% were female, and the median age was 36 years. At registration, the median CD4 count (interquartile range [IQR]) was 162 (68-310) cell/mm 3 , the median RBG level (IQR) was 88 (75-106) mg/dL, and 6.2% (95% confidence interval [CI], 6.0%-6.5%) had hyperglycemia (RBG ≥140 mg/dL). Overall 29% of patients had TB disease, and 15% died during the study period. The adjusted hazard of death among patients with hyperglycemia was significantly higher (adjusted hazard ratio [aHR], 1.2; 95% CI, 1.1-1.4) than among those with normoglycemia without TB disease, but not among patients with TB disease (aHR, 1.0; 95% CI, 0.8-1.2). Using 4 categories of RBG and restricted cubic spline regression, aHRs for death were significantly increased in patients with RBG of 110-140 mg/dL (categorical model: aHR, 1.3; 95% CI, 1.2-1.4; restricted spline: aHR, 1.1; 95% CI, 1.0-1.1) compared with those with RBG <110 mg/dL., Conclusions: Our findings highlight an urgent need to evaluate hyperglycemia screening and diagnostic algorithms and to ultimately establish glycemic targets for PLHIV with and without TB disease.

Background: Early initiation and longer duration of anti-retroviral therapy either as prophylaxis (pARV) or lifelong treatment (ART) in HIV-positive pregnant women prior to delivery has a huge impact in reducing mother to child transmission (MTCT) of HIV, maternal morbidity, mortality and increasing retention in care. In this study, we aimed to determine the following in a 'prevention of mother-to-child transmission' (PMTCT) programme in Central Women Hospital, Mandalay, Myanmar: i) uptake of ART and factors associated with the uptake ii) duration of ART/ pARV received by HIV-positive pregnant women prior to delivery, iii) factors associated with ART/ pARV initiation after delivery and iv) factors associated with shorter duration of ART/ pARV (≤ 8 weeks prior to delivery)., Method: This was a retrospective cohort study using routinely collected data from PMTCT programme. We used multivariable Cox proportional Hazard model or log binomial models to assess the association between socio-demographic and clinical factors with a) uptake of ART/pARV, b) initiation of ART/pARV after delivery, c) shorter (≤8 weeks) duration of ART/PARV prior to delivery., Results: Of the 670 ART naïve HIV-positive women enrolled to PMTCT programme between March 2011 and December 2016, 588 (88%) were initiated on ART/pARV. In adjusted analysis, only pregnancy stage at enrolment was significantly associated with initiation of ART/pARV. Of 585 who had delivered babies on or before the censor date, 522 (89%) were on ART/pARV. Women who lived outside Mandalay were more likely to be initiated on ART after delivery (i.e., delayed ART initiation in those on ART). Among women who were initiated on ART/pARV before delivery (n = 468), only 59% got ART/pARV for > 8 weeks before delivery. Women whose spouses' HIV status was not recorded had 40% higher risk of short duration of ART/pARV., Conclusions: This study shows high uptake of ART/pARV among those enrolled into the PMTCT programme. However, about one in eight pregnant women did not receive ART before delivery. Among those initiated on ART/pARV before delivery, nearly half of them received ART/pARV for less than 8 weeks prior to delivery. These aspects need to be improved in order to eliminate mother-to-child transmission of HIV.

Given that the computed tomography (CT) reconstruction algorithm based on compressed sensing (CS) results in blurred edges, we propose a modified Canny operator that assists the CS algorithm to accurately capture an object's edge, to preserve and further enhance the contrasts in the reconstructed image, thereby improving image quality. We modified two procedures of the traditional Canny operator, namely non-maximum suppression and edge tracking by hysteresis according to the characteristics of low-dose CT reconstruction, and proposed two major modifications: double-response edge detection and directional edge tracking. The newly modified Canny operator was combined with the CS reconstruction algorithm to become an edge-enhanced CS (EECS). Both a 2D Shepp-Logan phantom and a 3D dental phantom were used to conduct reconstruction testing. Root-mean-square error, peak signal-to-noise ratio, and universal quality index were employed to verify the reconstruction results. Qualitative and quantitative results of EECS reconstruction showed its superiority over conventional CS or CS combined with different edge detection techniques, such as Laplacian, Prewitt, Sobel operators, etc. The experiments verified that the proposed modified Canny operator is able to effectively detect the edge location of an object during low-dose reconstruction, enabling EECS to reconstruct images with better quality than those produced by other algorithms.