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Burkitt Lymphoma (BL) is a highly treatable cancer. However, delayed diagnosis of BL contributes to high mortality in BL endemic regions of Africa. Lack of enough pathologists in the region is a major reason for delayed diagnosis. The work described in this paper is a proof-of-concept study to develop a targeted, open access AI tool for screening of histopathology slides in suspected BL cases. Slides were obtained from a total of 90 BL patients. 70 Tonsillectomy samples were used as controls. We fine-tuned 6 pre-trained models and evaluated the performance of all 6 models across different configurations. An ensemble-based consensus approach ensured a balanced and robust classification. The tool applies novel features to BL diagnosis including use of multiple image magnifications, thus enabling use of different magnifications of images based on the microscope/scanner available in remote clinics, composite scoring of multiple models and utilizing MIL with weak labeling and image augmentation, enabling use of relatively low sample size to achieve good performance on the inference set. The open access model allows free access to the AI tool from anywhere with an internet connection. The ultimate aim of this work is making pathology services accessible, efficient and timely in remote clinics in regions where BL is endemic. New generation of low-cost slide scanners/microscopes is expected to make slide images available immediately for the AI tool for screening and thus accelerate diagnosis by pathologists available locally or online.
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Bismuth, in spite of its low cost and low toxicity, has found limited application in organic synthesis. Although the photoactivity of Bi(iii) salts has been well studied, this has not been effectively exploited in photocatalysis. To date, only a single report exists for the Bi-based photocatalysis, wherein carbon centered radicals were generated using ligand to metal charge transfer (LMCT) on bismuth. In this regard, expanding the horizon of bismuth LMCT catalysis for the generation of heteroatom centered radicals, we hereby report an efficient radical phosphonylation using BiCl3 as the LMCT catalyst. Phosphonyl radicals generated via visible-light induced LMCT of BiCl3 were subjected to a variety of transformations like alkylation, amination, alkynylation and cascade cyclizations. The catalytic system tolerated a wide range of substrate classes, delivering excellent yields of the scaffolds. The reactions were scalable and required low catalytic loading of bismuth. Detailed mechanistic studies were carried out to probe the reaction mechanism. Diverse radical phosphonylations leading to the formation of sp3-C-P, sp2-C-P, sp-C-P, and P-N bonds in the current work present the candidacy of bismuth as a versatile photocatalyst for small molecule activation.
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We hereby report a highly diastereoselective synthesis of chalcogenated azaspirotricycles via a one-pot Ugi/spirocyclization/aza-Michael addition sequence. The reaction proceeds via a key visible light mediated spirocyclization step under mild, metal-free and energy efficient conditions. A variety of complex sulfenylated and selenylated azaspirotricycles were obtained in good yields. The reaction was found to be scalable and preliminary mechanistic studies indicated that the spirocyclization step proceeds via radical intermediates.
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BACKGROUND: Apathy, a disabling and poorly understood neuropsychiatric symptom, is characterised by impaired self-initiated behaviour. It has been hypothesised that the opportunity cost of time (OCT) may be a key computational variable linking self-initiated behaviour with motivational status. OCT represents the amount of reward which is foregone per second if no action is taken. Using a novel behavioural task and computational modelling, we investigated the relationship between OCT, self-initiation and apathy. We predicted that higher OCT would engender shorter action latencies, and that individuals with greater sensitivity to OCT would have higher behavioural apathy. METHODS: We modulated the OCT in a novel task called the 'Fisherman Game', Participants freely chose when to self-initiate actions to either collect rewards, or on occasion, to complete non-rewarding actions. We measured the relationship between action latencies, OCT and apathy for each participant across two independent non-clinical studies, one under laboratory conditions (n = 21) and one online (n = 90). 'Average-reward' reinforcement learning was used to model our data. We replicated our findings across both studies. RESULTS: We show that the latency of self-initiation is driven by changes in the OCT. Furthermore, we demonstrate, for the first time, that participants with higher apathy showed greater sensitivity to changes in OCT in younger adults. Our model shows that apathetic individuals experienced greatest change in subjective OCT during our task as a consequence of being more sensitive to rewards. CONCLUSIONS: Our results suggest that OCT is an important variable for determining free-operant action initiation and understanding apathy.
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Apatía , Adulto , Humanos , Cognición , Simulación por Computador , Motivación , Refuerzo en PsicologíaRESUMEN
We hereby report a visible light mediated alkyl sulfonylative cascade cyclization of alkynyl and dialkynyl cyclohexadienones via SO2 insertion. The protocol utilizes alkyl Hantzsch esters as the alkyl source and DABSO as the SO2 source with 4-CzIPN as the organophotocatalyst. A variety of dihydrochromenone derivatives were obtained in good yields under mild energy efficient conditions. Additionally, fluorescence quenching and control studies were carried out to probe the mechanism.
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Purpose: To assess the quantum of cataract surgical training opportunities for trainees enrolled in ophthalmology residency programs in India. Methods: An anonymous online survey was sent across to resident ophthalmologists across India through various social media platforms. The results were tabulated and analyzed. Results: A total of 740 resident ophthalmologists participated in the survey. In all, 40.1% (297/740) were independently performing cataract surgeries. Of those who were not performing independent cataract surgeries, 62.5% (277/443) were in the third year of residency. A significantly higher proportion of trainees who were not operating independent cataract surgeries were enrolled in MD/MS programs as compared with DNB courses (65.6% vs. 43.7%; P < 0.0001). Of those who were operating independent cases; 97.1% had exposure to manual small incision cataract surgery (MSICS), whereas only 14.1% performed phacoemulsification. It was noted that 31.3% of residents reported that on an average a trainee in their training program performed less than 100 independent cataract surgeries throughout the residency. Apart from cataract surgery, the most performed surgeries by residents were pterygium excision (85.3%), followed by enucleation/evisceration (68.1%). When it came to training aids, 47.2% (349/740) of the respondents reported no access to wet lab, animal/cadaver eyes, or surgical simulators for training. Conclusion: The amount of surgical exposure in terms of cataract surgery across residency programs in India is low with most of the ophthalmology residents who participated in this survey not operating cataracts independently; even in their final year of residency. Exposure to phacoemulsification in residency programs is very limited across the country. Although some programs do provide well-rounded surgical exposure to trainees, such centers are scarce; the stark variations in infrastructure, training opportunities, and surgical numbers warrant an overhaul in the structure and curriculum of residency programs in India.
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Extracción de Catarata , Catarata , Animales , Curriculum , Ojo , IndiaRESUMEN
Herein, we report a reductive hydrazo-sulfonylative difunctionalization cascade of alkynyl cyclohexadienones employing PhTeTePh as an uncommon reducing agent. Diphenyl ditelluride is a commercially available solid with a good solubility profile in most organic solvents, and this is the first report illustrating it as a reducing agent. The protocol afforded a variety of difunctionalized dihydrochromenones and dihydrobenzofuranones in good yields under relatively mild conditions. The reactions were scalable, and mechanistic studies were conducted to probe the reaction mechanism. Additionally, photophysical studies of the products were carried out, which revealed that they had significant absorption (400-450 nm) and emission (520-570 nm) in the visible region.
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Recent years have seen the emergence of transition metal catalyzed C-H activation as a powerful synthetic tool in organic chemistry. Allenes have fascinated synthetic chemists due to their unique reactivity. While directing group assisted functionalization of C(sp2)-H bonds with allenes is well documented in the literature, their coupling with more challenging aliphatic C(sp3)-H bonds remains elusive. In this regard, we hereby report a Pd(ii) catalyzed 8-aminoquinoline directed aliphatic C(sp3)-H dienylation protocol using allenyl acetates. A variety of carboxylic acids including fatty acids and amino acids were efficiently functionalized at ß and γ-positions to afford diversely functionalized 1,3-dienes. Preliminary mechanistic studies revealed the crucial role of the base in the success of the transformation. The reaction proceeds via regioselective 2,3-migratory insertion of the allene with the alkylpalladium(ii) species followed by ß-acetoxy elimination.
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Naphthoquinones form the core of a variety of drugs and natural products. As a result, the conjugation of 1,4-naphthoquinones with organic building blocks would offer a facile strategy toward scaffolds of biological interest. In this regard, we hereby report a Ru(II)-catalyzed [4 + 2] annulation of 1,4-naphthoquinones with benzoic acids to afford various naphthoquinone lactones. Additionally, ketone directed arylation of naphthoquinones using acetophenones under Ru(II)-catalysis was also illustrated. The feedstock availability of these precursors allowed access to a large library of naphthoquinone derivatives in good to excellent yields under fairly mild conditions. The practicality of these protocols was justified by carrying out a gram scale synthesis and further functionalizations. Also, preliminary mechanistic studies were carried out to probe the reaction mechanism.
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PURPOSE: To study the risk factors for development of COVID-19 associated rhino-orbital-cerebral mucormycosis (ROCM) during the COVID-19 pandemic in India. METHODS: Multi-centric retrospective case-control study conducted from October 2020 to May 2021. Cases comprised of consecutive patients of COVID-19-associated ROCM (CA-ROCM) presenting at the participating ophthalmic institutes. Controls comprised of COVID-19-positive or COVID-19-recovered patients who did not develop ROCM. Comparative analysis of demographic, COVID-19 infection, treatment parameters and vaccination status between cases and controls performed. Clinical and imaging features of CA-ROCM analyzed. RESULTS: There were 179 cases and 361 controls. Mean age of presentation in cases was 52.06 years (p = .001) with male predominance (69.83%, p = .000011). Active COVID-19 infection at the time of presentation of ROCM (57.54%, p < .0001), moderate to severe COVID-19 (p < .0001), steroid administration (OR 3.63, p < .00001), uncontrolled diabetes (OR 32.83, p < .00001), random blood sugar >178 mg/dl were associated with development of CA-ROCM. Vaccination showed a protective effect (p = .0049). In cases with intracranial or cavernous sinus extension there was history of steroid administration (OR 2.89, p = .024) and orbital apex involvement on imaging (OR 6.202, p = .000037) compared to those with only rhino-orbital disease. CONCLUSION: Male gender, active COVID-19 infection, moderate or severe COVID-19, uncontrolled diabetes, steroid administration during COVID-19 treatment are risk factors for developing rhino-orbital-cerebral mucormycosis. Vaccination is protective. Random blood sugar of >178 mg/dl in COVID-19 positive or recovered patients should warrant close observation and early detection of ROCM. Presence of ophthalmoplegia, blepharoptosis at first clinical presentation and orbital apex involvement on imaging are associated with intracranial extension in ROCM.
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COVID-19 , Oftalmopatías , Mucormicosis , Enfermedades Orbitales , Humanos , Masculino , Persona de Mediana Edad , Femenino , Pandemias , Glucemia , Tratamiento Farmacológico de COVID-19 , Estudios de Casos y Controles , Mucormicosis/epidemiología , Estudios Retrospectivos , COVID-19/epidemiología , Factores de Riesgo , Enfermedades Orbitales/diagnóstico por imagen , Enfermedades Orbitales/epidemiología , India/epidemiología , EsteroidesRESUMEN
Purpose: To establish the face and content validity of the HelpMeSee Eye Surgery Simulator - a virtual reality-based cataract surgery simulator for manual small-incision cataract surgery (MSICS). Methods: The face and content validity were assessed on the sclero-corneal tunnel construction course. A questionnaire with 11 questions focused on the visual realism, with resemblance to real life surgery, and the training value of the simulator was developed. Thirty-five experienced MSICS surgeons participated in the study. Responses were recorded using a seven-point scoring system. Results: Overall, 74.3% (26/35) of the respondents agreed that the overall visual representation of the eye and the instruments in the simulator were realistic. The task of injecting a visco-elastic through the paracentesis was reported to be the most visually realistic task with a mean score of 5.78 (SD: 1.09; range: 2-7). With regard to content validity, 77.1% (27/35) of the subjects felt agreed that the errors and complications represented throughout the entire tunnel construction module were similar to those encountered in real life; the task of entering the anterior chamber with the keratome had a mean score of 5.54 (SD: 0.98; range 1-7), being rated the highest in that aspect. Overall, 94.3% (33/35) of the subjects agreed that the simulator would be useful in developing hand-eye co-ordination. A similar number of 94.3% (33/35) agreed that based on their experience, they would recommend cataract surgical training on this simulator. Conclusion: The results suggest that the HelpMeSee Eye Surgery Simulator appears to have sufficient face and content validity for cataract surgical training.
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Extracción de Catarata , Catarata , Oftalmología , Realidad Virtual , Humanos , Competencia Clínica , Oftalmología/educaciónRESUMEN
While ophthalmology as a surgical branch itself has evolved technologically with newer instruments, techniques and procedures; ophthalmic surgical training appears to have stagnated in terms of how it is delivered and how trainees' learning and performance are assessed. This collaborative editorial attempts to identify the lacunae in ophthalmic residency training and highlight how technological tools such as surgical simulators can be incorporated into ophthalmic training even in limited-resource settings with good results.
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Extracción de Catarata , Catarata , Internado y Residencia , Oftalmología , Humanos , Oftalmología/educación , Educación de Postgrado en Medicina/métodos , Competencia Clínica , Tecnología , Extracción de Catarata/educaciónRESUMEN
The purpose of this article is to form a basic guide for beginning the cadaver dissection training programs focused on oculoplastic surgical procedures. Ours was a collaborative study between the departments of Ophthalmology and Anatomy in a tertiary care teaching institute. We formed a step-wise approach to begin the cadaver dissection focused on the oculoplastic surgical procedures. The basics of cadaver procurement, processing, and preparation for dissections were described. The operative requirements of trainees, surgical handling of cadavers, and basic oculoplastic surgical steps were discussed. The types of embalming (cadaver preservation process) and steps have been described in detail. We have emphasized the preoperative discussion about the proposed dissections using standard teachings and skull models for easier understanding. Additional helping tools like soft embalming and injectable substances for better intra-dissection understanding (intra-arterial, intravenous and orbital injections) have been described. Post-dissection cadaver handing and soft-tissue disposal protocols have also been described. Overall, the cadaver dissections provide holistic surgical learning for the residents, specialty trainees, and practitioners. This article may act as a basic step-wise guide for starting the cadaver-based oculoplastics lab dissection in various institutes and workshops.
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Disección , Embalsamiento , Cadáver , Humanos , AprendizajeRESUMEN
Herein, we developed two distinct pyridine N-oxide directed C-H activation protocols to achieve [4+1] annulation and alkoxylation of benzamide derivatives by merging Co-catalysis with visible-light photoredox catalysis. The protocols deliver the respective products in good yields under facile conditions at room temperature. The use of an inexpensive photocatalyst coupled with molecular oxygen bypassing the need of stoichiometric oxidants forms the chief highlight of the work. The protocols are scalable and the products could be further modified. Additionally, preliminary studies were carried out to probe the reaction mechanism.
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Cobalto , Oxidantes , Benzamidas , Catálisis , Estructura Molecular , OxígenoRESUMEN
The induction of posterior vitreous detachment (PVD) is an important step in the successful outcome of vitreoretinal surgery for various indications. This may pose a significant challenge intraoperatively in cases of strong adhesion between the posterior hyaloid and retina. Various techniques to achieve intraoperative PVD have been described which involve active aspiration as well as non-aspiration techniques to achieve a plane of separation between the posterior hyaloid and retina. Very frequently, combinations of these techniques might be necessary to achieve successful PVD induction. We describe a novel instrument that combines aspiration as well as non-aspiration techniques for PVD induction, Bapaye aspiration scraper. It is also useful in various vitreoretinal interface procedures due to its design and is compatible with small-gauge vitrectomy systems which are commonly used in modern vitreoretinal surgery.
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Cirugía Vitreorretiniana , Desprendimiento del Vítreo , Cánula , Humanos , Retina , Vitrectomía/métodos , Desprendimiento del Vítreo/cirugíaRESUMEN
PURPOSE: To present a literature review on various immunopathologic dysfunctions following COVID-19 infection and their potential implications in development of rhino-orbital-cerebral mucormycosis (ROCM). METHODS: A literature search was performed via Google Scholar and PubMed with subsequent review of the accompanying references. Analogies were drawn between the immune and physiologic deviations caused by COVID-19 and the tendency of the same to predispose to ROCM. RESULTS: Sixty-two articles were reviewed. SARS-CoV-2 virus infection leads to disruption of epithelial integrity in the respiratory passages, which may be a potential entry point for the ubiquitous Mucorales to become invasive. COVID-19 related GRP78 protein upregulation may aid in spore germination and hyphal invasion by Mucorales. COVID-19 causes interference in macrophage functioning by direct infection, a tendency for hyperglycemia, and creation of neutrophil extracellular traps. This affects innate immunity against Mucorales. Thrombocytopenia and reduction in the number of natural killer (NK) cells and infected dendritic cells is seen in COVID-19. This reduces the host immune response to pathogenic invasion by Mucorales. Cytokines released in COVID-19 cause mitochondrial dysfunction and accumulation of reactive oxygen species, which cause oxidative damage to the leucocytes. Hyperferritinemia also occurs in COVID-19 resulting in suppression of the hematopoietic proliferation of B- and T-lymphocytes. CONCLUSIONS: COVID-19 has a role in the occurrence of ROCM due to its effects at the entry point of the fungus in the respiratory mucosa, effects of the innate immune system, creation of an environment of iron overload, propagation of hyperglycemia, and effects on the adaptive immune system.