Multidisciplinary approach in resection of stage IIIA lung cancer with severe aortic stenosis: A case report.

Thoracic surgery in the context of complex multimorbidity and clinical deterioration presents a unique set of challenges when balancing risk and benefit. Advances in anaesthesia, surgical technique, and imaging, have allowed for operative options for patients that were once deemed too high-risk. An effective proactive multi-disciplinary approach is essential for successful outcomes. We report the case of a 65-year-old patient with a background of severe aortic stenosis who underwent lung resection for stage IIIA lung cancer, where pivotal multi-disciplinary team input from the anaesthetic, surgery, critical care and radiology teams, clarified the cause of his clinical deterioration, contributed to decisions over his management and ensured a good clinical outcome.

Machine Learning for Biological Design.

We briefly present machine learning approaches for designing better biological experiments. These approaches build on machine learning predictors and provide additional tools to guide scientific discovery. There are two different kinds of objectives when designing better experiments: to improve the predictive model or to improve the experimental outcome. We survey five different approaches for adaptive experimental design that iteratively search the space of possible experiments while adapting to measured data. The approaches are Bayesian optimization, bandits, reinforcement learning, optimal experimental design, and active learning. These machine learning approaches have shown promise in various areas of biology, and we provide broad guidelines to the practitioner and links to further resources.

The Villain Who Saved the Day: The Paradoxical Value of Amiodarone in Managing Recurrent Ventricular Tachycardia Secondary to Amiodarone-Induced Thyroiditis.

Thyroiditis is a rare and serious complication for patients taking amiodarone. It can manifest with symptoms of hyperthyroidism and serious life-threatening arrhythmias. We present a case of a patient with amiodarone-induced thyrotoxicosis presenting with an electrical storm in which rhythm control was achieved with the utilization of amiodarone.

Porphyria cutanea tarda: an under-recognised manifestation of haemochromatosis.

We present a case of a woman who presented with a photosensitive skin rash and blisters on her extremities which did not improve with steroids. These were associated with polyarthralgia and a deranged liver function test on her admission. Further workup revealed that the patient has an undiagnosed porphyria cutanea tarda (PCT) and hereditary haemochromatosis. The patient later underwent regular venesections which improved her condition. This case report not only illustrates the challenge in diagnosing PCT but also aims to highlight the association between PCT and hereditary haemochromatosis.

Middle Ear Neuroendocrine Tumor Mimicking As Chronic Otitis Media.

Neuroendocrine neoplasms (NEN) of the head and neck are a rare and diverse group of tumors. Here, we report a case of a 40-year-old man presenting with symptoms resembling chronic left otitis media, including left ear otorrhea, otalgia, and reduced hearing. Otoscopic examination revealed a whitish mass located behind the tympanic membrane. The patient underwent examination under anesthesia and left cortical mastoidectomy, and a histopathological examination of the middle ear biopsy indicated the presence of an epithelial tumor with neuroendocrine differentiation, suggestive of middle ear adenoma. A staging CT scan performed three months after the mastoidectomy showed a hypodensity in the middle ear cavity, with no significant bony erosion, which could potentially indicate a residual or recurrent tumor. Consequently, a radical mastoidectomy was performed. The histopathological examination confirmed the presence of middle ear adenoma with neuroendocrine differentiation.

Case report of culture-negative endocarditis in lupus nephritis.

Background: Cardiovascular involvement is frequent in systemic lupus erythematosus (SLE). Valvular abnormalities are increasingly being recognized with the advent of echocardiography. Case summary: We present a case of a 46-year-old lady who presented to the emergency department with upper limb ischaemia. On examination, she had poor dentition and a short systolic murmur on auscultation. A blood workup revealed a diagnosis of SLE. Further investigations showed vegetations on the mitral valve. Initially, an infective endocarditis (IE) diagnosis was made, which was treated with antibiotics. High-dose steroids and immunosuppressants were initiated due to her clinical deterioration and biopsy-proven lupus nephritis. She improved clinically before being discharged home. Discussion: It can be difficult to distinguish between IE and Libman-Sacks endocarditis (LSE), especially in the setting of risk factors for both. Antibiotics and immunosuppressants might be started simultaneously in these cases. A multidisciplinary team is required to manage challenging cases of culture-negative endocarditis. Procalcitonin may have a role in differentiating bacterial endocarditis and LSE.

Overstimulation of the ergoreflex-A possible mechanism to explain symptoms in long COVID.

Long COVID refers to a multitude of symptoms that persist long after SARS-CoV-2 infection. Fatigue and breathlessness are the most common symptoms of long COVID across a range of studies. They are also cardinal symptoms of chronic heart failure (CHF). In this review, we propose that fatigue and breathlessness in patients with long COVID may be explained by skeletal muscle abnormalities, in a manner similar to patients with CHF. The ergoreflex is a cardiorespiratory reflex activated by exercise, which couples ventilation and cardiovascular function to exercise intensity. At least part of the symptomatology of CHF is related to abnormal skeletal muscle and an enhanced ergoreflex, resulting in heightened sympathetic, vasoconstrictor and ventilator drives. Similarly, SARS-CoV-2 infection results in a hyperinflammatory and hypercatabolic state. This leads to reduction in skeletal muscle mass and altered function. We postulate that the ergoreflex is chronically overstimulated, resulting in fatigue and breathlessness. Exercise training preserves muscle mass and function as well as reduces ergoreflex activation; therefore may have a role in improving symptoms associated with long COVID. Should the ergoreflex be proven to be an important pathophysiological mechanism of long COVID, tailored exercise interventions should be trialed with the aim of improving both symptoms and perhaps outcomes in patients with long COVID.

Machine Learning Guided Batched Design of a Bacterial Ribosome Binding Site.

Optimization of gene expression levels is an essential part of the organism design process. Fine control of this process can be achieved by engineering transcription and translation control elements, including the ribosome binding site (RBS). Unfortunately, the design of specific genetic parts remains challenging because of the lack of reliable design methods. To address this problem, we have created a machine learning guided Design-Build-Test-Learn (DBTL) cycle for the experimental design of bacterial RBSs to demonstrate how small genetic parts can be reliably designed using relatively small, high-quality data sets. We used Gaussian Process Regression for the Learn phase of the cycle and the Upper Confidence Bound multiarmed bandit algorithm for the Design of genetic variants to be tested in vivo. We have integrated these machine learning algorithms with laboratory automation and high-throughput processes for reliable data generation. Notably, by Testing a total of 450 RBS variants in four DBTL cycles, we have experimentally validated RBSs with high translation initiation rates equaling or exceeding our benchmark RBS by up to 34%. Overall, our results show that machine learning is a powerful tool for designing RBSs, and they pave the way toward more complicated genetic devices.

A Novel Use of Modified Tracheostomy Tubes in Preventing External Auditory Canal Stenosis.

BACKGROUND: Postoperative or post-traumatic canal restenosis in patients with external auditory canal (EAC) stenosis is a troublesome complication faced by many ear surgeons following canalplasty or meatoplasty. Many ear prostheses and surgical methods have been introduced to prevent the occurrence of such complication. Our aim in this study is to explore the feasibility of using modified non-fenestrated uncuffed tracheostomy tubes (TT) as postoperative stents after ear canal surgery. METHODS: Canalplasty or meatoplasty was performed under general anesthesia via the posterior auricular transcanal approach. The EAC diameter and length were measured and a non-fenestrated uncuffed TT of suitable size was fitted into the ear canal. The TT was then modified during fitting, to fit onto the concha. Patients were advised on the importance of compliance. The adequacy of the size of the EAC after the surgery was assessed during follow-ups. RESULTS: A total of 3 patients (4 ears) were included in our study. Various sizes of TTs were fitted into their EAC following canalplasty or meatoplasty. All of them showed excellent postoperative outcome on follow up 2 years after the surgery, with no evidence of postoperative EAC stenosis. CONCLUSION: Modified TT stent after canalplasty or meatoplasty is proposed as an excellent alternative in preventing restenosis of EAC in centers with limited resources.

eQTLHap: a tool for comprehensive eQTL analysis considering haplotypic and genotypic effects.

MOTIVATION: The high accuracy of recent haplotype phasing tools is enabling the integration of haplotype (or phase) information more widely in genetic investigations. One such possibility is phase-aware expression quantitative trait loci (eQTL) analysis, where haplotype-based analysis has the potential to detect associations that may otherwise be missed by standard SNP-based approaches. RESULTS: We present eQTLHap, a novel method to investigate associations between gene expression and genetic variants, considering their haplotypic and genotypic effect. Using multiple simulations based on real data, we demonstrate that phase-aware eQTL analysis significantly outperforms typical SNP-based methods when the causal genetic architecture involves multiple SNPs. We show that phase-aware eQTL analysis is robust to phasing errors, showing only a minor impact ($<4\%$) on sensitivity. Applying eQTLHap to real GEUVADIS and GTEx datasets detects numerous novel eQTLs undetected by a single-SNP approach, with 22 eQTLs replicating across studies or tissue types, highlighting the utility of phase-aware eQTL analysis. AVAILABILITY AND IMPLEMENTATION: https://github.com/ziadbkh/eQTLHap. CONTACT: ziad.albkhetan@gmail.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Briefings in Bioinformatics online.

Enhancing quality of life in progressive multiple sclerosis with powered robotic exoskeleton.

Wearable powered robotic exoskeleton can provide high repetitions and high-intensity gait training. It can promote a sense of well-being when the user is in upright posture to walk around different environment. We present a case of a lady with progressive multiple sclerosis who received 15 sessions of robotic exoskeleton training. Post training, she demonstrated improvement in lower limb strength, sense of well-being and self-esteem that led to improved transfer ability, increased social outings and better quality of life (QOL). Previously, she was depressed and reluctant to go out for social activities. This case suggests the potential of robotic exoskeleton to enhance QOL in people with mobility challenges.

Can bone wax cause cholesterol granuloma in the petrous apex? A case report.

BACKGROUND: Cholesterol granuloma (CG) is a rare entity but is the commonest lesion in the petrous apex. They are associated with chronic ear disease and previous temporal bone surgery. While bone wax has been known to cause foreign body reaction due to its non-resorbable property in the mastoid, it has not been documented to cause CG formation. CASE PRESENTATION: We described a 43 years old male who presented with a right mastoid swelling, nine years after a right retro-sigmoid craniotomy and excision for a cerebellopontine angle meningioma. He also had multiple cranial neuropathies involving trigeminal, facial and vestibulocochlear nerves. Temporal bone CT and MRI showed features suggestive of cholesterol granuloma with extensive bony erosions. He was treated with surgical excision and drainage where bone wax residues were found intraoperatively. Histopathological analysis of the lesion confirmed the diagnosis of cholesterol granuloma. Post-operatively, the mastoid swelling resolved and his recovery was uneventful. CONCLUSION: Our case showed that CG could manifest as a complication of bone wax usage in a neurosurgical procedure. Even though further study is needed to draw a definitive conclusion on this theory, we believe this paper will contribute to the current literature as it is the only reported case of cholesterol granuloma with bone wax as the possible causative agent. This is important so that surgeons are aware of this potential complication and use this haemostatic agent more judiciously.

Machine Learning Techniques for Classifying the Mutagenic Origins of Point Mutations.

There is increasing interest in developing diagnostics that discriminate individual mutagenic mechanisms in a range of applications that include identifying population-specific mutagenesis and resolving distinct mutation signatures in cancer samples. Analyses for these applications assume that mutagenic mechanisms have a distinct relationship with neighboring bases that allows them to be distinguished. Direct support for this assumption is limited to a small number of simple cases, e.g., CpG hypermutability. We have evaluated whether the mechanistic origin of a point mutation can be resolved using only sequence context for a more complicated case. We contrasted single nucleotide variants originating from the multitude of mutagenic processes that normally operate in the mouse germline with those induced by the potent mutagen N-ethyl-N-nitrosourea (ENU). The considerable overlap in the mutation spectra of these two samples make this a challenging problem. Employing a new, robust log-linear modeling method, we demonstrate that neighboring bases contain information regarding point mutation direction that differs between the ENU-induced and spontaneous mutation variant classes. A logistic regression classifier exhibited strong performance at discriminating between the different mutation classes. Concordance between the feature set of the best classifier and information content analyses suggest our results can be generalized to other mutation classification problems. We conclude that machine learning can be used to build a practical classification tool to identify the mutation mechanism for individual genetic variants. Software implementing our approach is freely available under an open-source license.

Inferring structural variant cancer cell fraction.

We present SVclone, a computational method for inferring the cancer cell fraction of structural variant (SV) breakpoints from whole-genome sequencing data. SVclone accurately determines the variant allele frequencies of both SV breakends, then simultaneously estimates the cancer cell fraction and SV copy number. We assess performance using in silico mixtures of real samples, at known proportions, created from two clonal metastases from the same patient. We find that SVclone's performance is comparable to single-nucleotide variant-based methods, despite having an order of magnitude fewer data points. As part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) consortium, which aggregated whole-genome sequencing data from 2658 cancers across 38 tumour types, we use SVclone to reveal a subset of liver, ovarian and pancreatic cancers with subclonally enriched copy-number neutral rearrangements that show decreased overall survival. SVclone enables improved characterisation of SV intra-tumour heterogeneity.

Sensory properties of yellow pea and macadamia honeys from conventional and flow hive extraction methods.

BACKGROUND: The process of harvesting honey is time consuming and labor intensive. A new system, the Flow Frame, has drastically simplified the harvesting process, enabling honey to be extracted directly from the hive with minimal processing. The sensory profile of honey is influenced, first, by botanical origin and subsequently by processing and storage parameters. A reduction in harvest processing may thus influence the sensory profile of honey harvested from FFs compared to that of honey produced from conventional processing. To test this hypothesis, two monofloral honeys (macadamia and yellow pea) were harvested from FFs, or by conventional honey extraction. Sensory profiling using conventional descriptive analysis was carried out for each floral source with an experienced trained panel. RESULTS: The two monofloral honeys harvested using the FF system had significantly (p < 0.05) higher floral and cleaner aftertaste sensory scores than the honey extracted using commercial (C) methods that involve the use of heat and centrifugation. CONCLUSION: The flow system retains honey's natural sensory properties compared to harvesting methods that require heat and centrifugation. © 2019 Society of Chemical Industry.

Solitary Extramedullary Plasmacytoma of the Sphenoid Sinus: A Case Report.

Solitary extramedullary plasmacytomas are rare, discrete mass of neoplastic monoclonal plasma cells in the soft tissue with no evidence of multiple myeloma. They constitute 3 % of all plasma cell tumors and less than 1 % of head and neck malignancies. A 43 year old lady presented to our clinic with complains of diplopia and headache for 4 weeks. Computed Tomography scan showed a mass lesion in the sphenoid sinus eroding the sinus floor, right wall, basisphenoid and parasellar area. A biopsy of the mass reported as plasmacytoma. Systemic examination revealed no evidence of dissemination of the disease confirming the diagnosis of a solitary extramedullary plasmacytoma. The patient was subjected to 25 fractions of radiotherapy. Here, we report a rare case of solitary extramedullary plasmacytoma of the sphenoid sinus.

Effects of Electrolyte Anions on the Reduction of Carbon Dioxide to Ethylene and Ethanol on Copper (100) and (111) Surfaces.

The CO2 electroreduction reaction has been investigated on Cu(100) and Cu(111) surfaces in 0.1 m aqueous solutions of KClO4 , KCl, KBr, and KI electrolyte. The formation of ethylene and ethanol on these surfaces generally increased as the electrolyte anion was changed from ClO4- →Cl- →Br- →I- . For example, on Cu(100) at -1.23 V versus RHE, as the electrolyte anion changed from ClO4- to I- , the faradaic efficiency (FE) of ethylene formation increased from 31 to 50 %, FEethanol increased from 7 to 16 %, and the associated current densities increased five- and sevenfold, respectively. A remarkable total FE of up to 74 % for C2 and C3 products was obtained in the presence of KI. Despite surface roughening in the presence of the electrolytes, the Cu(100) electrode still enhanced the formation of C2 compounds better than Cu(111). The favorable reduction of CO2 to C2 products in KI electrolyte was correlated with a higher *CO population on the surface, as shown using linear sweep voltammetry. In situ Raman spectroscopy indicated that the coordination environment of *CO was altered by the used electrolyte anion. Thus, apart from affecting the morphology of the electrode and local pH value, we propose that the anion plays a critical role in enhancing the formation of C2 products by tuning the coordination environment of adsorbed *CO, which gives rise to more efficient C-C coupling.