Dual Copper Photoredox C-H Alkynylation with Arylacetylenes.

In the realm of organic synthesis, direct C-H alkynylation with arylacetylenes has remained a daunting challenge due to competing annulations or alkenylation. Addressing this long-standing issue, herein we demonstrate the merging of copper and photocatalysis to achieve the elusive C-H alkynylation of benzamides using arylacetylenes or arylpropiolic acids. Unlike conventional copper-mediated C-H activations, our protocol circumvents the need for high temperatures and stoichiometric amounts of copper salts or metal/non-metal oxidants. The versatility of the developed dual copper photoredox system is underscored by performing other diverse C-H functionalizations such as amination, selenylation, arylation, sulfonylation, and nitration under slightly modified conditions.

Increasing venture capital investment in spinal surgery: an analysis of investments from 2000 to 2023.

BACKGROUND CONTEXT: Venture capital (VC) plays a vital role in advancing spinal surgery technologies, driven by the growing burden of spinal disorders and high healthcare costs. Despite increasing interest, trends in VC funding for spinal surgery remain understudied. PURPOSE: This study aimed to examine temporal and thematic trends in VC investments in spinal surgery companies from 2000 to 2023. STUDY DESIGN/SETTING: A retrospective cross-sectional study analyzing VC investment trends in privately held US-based spinal surgery companies. METHODS: Using the PitchBook database, we analyzed 1001 VC investments in 227 spinal surgery companies between 2000 and 2023. Investments were categorized into surgical devices, noninvasive devices, biotechnology, surgical software, and clinical services. Total and annual investments were quantified in USD. RESULTS: From 2000 to 2023, $5.37 billion was invested in spine surgery, with nonsurgical devices receiving the largest share (42.6%), followed by surgical devices (26.3%) and biotechnology (22.2%). Annual investment increased by 1782%, with a decline in 2023 likely due to macroeconomic factors. CONCLUSIONS: VC funding in spinal surgery has grown significantly, especially in noninvasive technologies. Further research is needed to assess the long-term impact of these investments and explore alternative financing models.

Cross-Coupling of Gaseous Alkanes with (Hetero)Aryl Bromides via Dual Nickel/Photoredox Catalysis.

Gaseous alkanes represent the most abundant carbon-based chemical feedstocks in our planet. However, the intrinsic inertness of their C-H bonds has rendered the use of these alkanes very difficult for purposes beyond aerobic combustion and energy intensive processes. Thus, clean and energy-efficient transformations for their use in synthetic organic chemistry are still rare. Here we report a catalytic methodology for the direct cross-coupling of gaseous alkanes with (hetero)aryl bromides through the combination of metallaphotoredox-mediated hydrogen atom transfer and nickel catalysis. This protocol provides an efficient platform for the addition of short alkyl groups into diverse (hetero) aromatic rings, providing a wide range of high-value alkyl(hetero)arenes, and bypassing the longstanding need of using preactivated alkylating agents in C(sp2)-C(sp3) cross-couplings. The method features high chemoselectivity, regioselectivity and a remarkable functional group tolerance, operates under mild conditions, and exhibits operational simplicity.

An AI based, open access screening tool for early diagnosis of Burkitt lymphoma.

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.

Expedient radical phosphonylations via ligand to metal charge transfer on bismuth.

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.

A highly diastereoselective one-pot Ugi/radical spirocyclization/aza-Michael addition sequence.

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.

Opportunity cost determines free-operant action initiation latency and predicts apathy.

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.

A visible light mediated alkyl sulfonylative cascade using Hantzsch esters via SO2 insertion.

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.

Cataract surgical training among residents in India: Results from a survey.

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.

Diphenyl Ditelluride: An Unconventional Reducing Agent in the Sulfonylative Cascade of Alkynyl Cyclohexadienones.

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.

Ru(II)-Catalyzed [4 + 2]-Annulation and Arylation of 1,4-Naphthoquinones.

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.

Pd(ii)-catalyzed ß- and γ-C-(sp3)-H dienylation with allenyl acetates.

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.

A fungal epidemic amidst a viral pandemic: Risk factors for development of COVID-19 associated rhino-orbital-cerebral mucormycosis in India.

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.

Assessment of a high-fidelity, virtual reality-based, manual small-incision cataract surgery simulator: A face and content validity study.

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.

Embracing technology in cataract surgical training - The way forward.

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.

A novel, versatile cannula for vitreoretinal surgery: Bapaye aspiration scraper - Initial experience.

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.