Lesliehagan8112

Screening for diabetic retinopathy is recommended for children with type 1 diabetes (T1D) and type 2 diabetes (T2D), yet screening rates remain low. Point-of-care diabetic retinopathy screening using autonomous artificial intelligence (AI) has become available, providing immediate results in the clinic setting, but the cost-effectiveness of this strategy compared with standard examination is unknown.

To assess the cost-effectiveness of detecting and treating diabetic retinopathy and its sequelae among children with T1D and T2D using AI diabetic retinopathy screening vs standard screening by an eye care professional (ECP).

In this economic evaluation, parameter estimates were obtained from the literature from 1994 to 2019 and assessed from March 2019 to January 2020. Parameters included out-of-pocket cost for autonomous AI screening, ophthalmology visits, and treating diabetic retinopathy; probability of undergoing standard retinal examination; relative odds of undergoing screening; and sensitivity, specutonomous AI systems is effective and cost saving for children with diabetes and their caregivers at recommended adherence rates.

These results suggest that point-of-care diabetic retinopathy screening using autonomous AI systems is effective and cost saving for children with diabetes and their caregivers at recommended adherence rates.

Recent studies have demonstrated the successful application of artificial intelligence (AI) for automated retinal disease diagnostics but have not addressed a fundamental challenge for deep learning systems the current need for large, criterion standard-annotated retinal data sets for training. Low-shot learning algorithms, aiming to learn from a relatively low number of training data, may be beneficial for clinical situations involving rare retinal diseases or when addressing potential bias resulting from data that may not adequately represent certain groups for training, such as individuals older than 85 years.

To evaluate whether low-shot deep learning methods are beneficial when using small training data sets for automated retinal diagnostics.

This cross-sectional study, conducted from July 1, 2019, to June 21, 2020, compared different diabetic retinopathy classification algorithms, traditional and low-shot, for 2-class designations (diabetic retinopathy warranting referral vs not warranting referraod using self-supervision with an AUC of 0.7467 (95% CI, 0.7239-0.7695). At very low shots (n = 10), the traditional approach had performance close to chance, with an AUC of 0.5178 (95% CI, 0.4909-0.5447) compared with the best low-shot method (AUC, 0.5778 [95% CI, 0.5512-0.6044]).

These findings suggest the potential benefits of using low-shot methods for AI retinal diagnostics when a limited number of annotated training retinal images are available (eg, with rare ophthalmic diseases or when addressing potential AI bias).

These findings suggest the potential benefits of using low-shot methods for AI retinal diagnostics when a limited number of annotated training retinal images are available (eg, with rare ophthalmic diseases or when addressing potential AI bias).

Prior studies have shown that only a small proportion of patients with hormone receptor (HR)-positive metastatic breast cancer (MBC) experience benefit from programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors given as monotherapy. There are data suggesting that activity may be greater with combination strategies.

To compare the efficacy of eribulin plus pembrolizumab vs eribulin alone in patients with HR-positive, ERBB2 (formerly HER2)-negative MBC.

Multicenter phase 2 randomized clinical trial of patients with HR-positive, ERBB2-negative MBC who had received 2 or more lines of hormonal therapy and 0 to 2 lines of chemotherapy.

Patients were randomized 11 to eribulin, 1.4 mg/m2 intravenously, on days 1 and 8 plus pembrolizumab, 200 mg/m2 intravenously, on day 1 of a 21-day cycle or eribulin alone. At time of progression, patients in the eribulin monotherapy arm could cross over and receive pembrolizumab monotherapy.

The primary end point was progression-free survival (PF both drugs. The PD-L1 22C3 assay was performed on archival tumor samples in 65 patients 24 (37%) had PD-L1-positive tumors. Analysis indicated that PD-L1 status, TILs, TMB, and genomic alterations were not associated with PFS.

In this randomized clinical trial of patients with HR-positive, ERBB2-negative MBC, the addition of pembrolizumab to eribulin did not improve PFS, ORR, or OS compared with eribulin alone in either the intention-to-treat or PD-L1-positive populations. Further efforts to explore the benefits of adding checkpoint inhibition to chemotherapy among less heavily pretreated patients are needed.

ClinicalTrials.gov Identifier NCT03051659.

ClinicalTrials.gov Identifier NCT03051659.

Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need.

To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater.

The phase 3 KEYNOTE-062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1 CPS of 1 or greater from 200 centers in 29 countries between September 18, 2015, and May 26, 2017.

Patients were randomized 111 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin 80 mg/m2/d on day 1 plus fluorouracil 800 mg/m2/d on days 1 to 5 or capecitabine 1000 mg/m2 twice daily), or chemotherapy plus placebo, every 3 weeks.

Primary end points were overall survival (OS) and progression-free survival (PFS) in patients with PD3 vs 10.8 months; HR, 0.85; 95% CI, 0.62-1.17; P = .16) or for PFS in patients with CPS of 1 or greater (6.9 vs 6.4 months; HR, 0.84; 95% CI, 0.70-1.02; P = .04). Grade 3 to 5 treatment-related adverse event rates for pembrolizumab, pembrolizumab plus chemotherapy, and chemotherapy were 17%, 73%, and 69%, respectively.

This phase 3 randomized clinical trial found that among patients with untreated, advanced G/GEJ cancer, pembrolizumab was noninferior to chemotherapy, with fewer adverse events observed. Pembrolizumab or pembrolizumab plus chemotherapy was not superior to chemotherapy for the OS and PFS end points tested.

ClinicalTrials.gov Identifier NCT02494583.

ClinicalTrials.gov Identifier NCT02494583.

Leucine-rich repeat and fibronectin type 2 gene (LRFN2) variant rs2494938 has recently been found associated with esophageal cancer in a genome-wide association study in an Asian population. However, this association has not been replicated in any Indian population despite high incidence of the disease.

In the present case-control study, 166 cases and 459 controls were included. Phospho(enol)pyruvicacidmonopotassium Taqman assay technique using real-time PCR was employed to investigate the association of the variant with esophageal cancer in the population of Jammu and Kashmir (J&K). The Hardy-Weinberg equilibrium for rs2494938 was assessed using the Chi-square test. The allele- and genotype-specific risk was estimated by odds ratio (OR) with 95% confidence interval (CI).

Variant rs2494938 was observed to be significantly associated with esophageal cancer with an allelic OR of 1.59 (1.23-2.04 at 95% CI, P = 0.0003).

The study highlights LRFN2 as a candidate gene for esophageal cancer susceptibility in the population of J&K and calls for a detailed study with a large sample size and involving more ethnic groups of India.

The study highlights LRFN2 as a candidate gene for esophageal cancer susceptibility in the population of J&K and calls for a detailed study with a large sample size and involving more ethnic groups of India.The molybdenum cofactor (Moco) is the prosthetic group of all molybdenum-dependent enzymes except for nitrogenase. The multistep biosynthesis pathway of Moco and its function in molybdenum-dependent enzymes are already well understood. The mechanisms of Moco transfer, storage and insertion, on the other hand, are not. In the cell, Moco is usually not found in its free form and remains bound to proteins because of its sensitivity to oxidation. The green alga Chlamydomonas reinhardtii harbors a Moco carrier protein (MCP) that binds and protects Moco but is devoid of enzymatic function. It has been speculated that this MCP acts as a means of Moco storage and transport. Here, the search for potential MCPs has been extended to the prokaryotes, and many MCPs were found in cyanobacteria. A putative MCP from Rippkaea orientalis (RoMCP) was selected for recombinant production, crystallization and structure determination. RoMCP has a Rossmann-fold topology that is characteristic of nucleotide-binding proteins and a homotetrameric quaternary structure similar to that of the MCP from C. reinhardtii. In each protomer, a positively charged crevice was identified that accommodates up to three chloride ions, hinting at a potential Moco-binding site. Computational docking experiments supported this notion and gave an impression of the RoMCP-Moco complex.Native cytochrome c6 was purified from an extract of strain BP-1 of the thermophilic cyanobacterium Thermosynechococcus elongatus. The protein was crystallized, and with only slight modifications of the buffer and vapour-diffusion conditions two different space groups were observed, namely H3 and C2. Both crystal structures were solved; they contained three and six molecules per asymmetric unit and were refined to 1.7 and 2.25 Å resolution, respectively. To date, the structure of native cytochrome c6 from T. elongatus has only been reported as a monomer using NMR spectroscopy, i.e. without addressing putative oligomerization, and related structures have only previously been solved using X-ray crystallography after recombinant gene overexpression in Escherichia coli. The reported space groups of related cyanobacterial cytochrome c6 structures differ from those reported here. Interestingly, the protein-protein interfaces that were observed utilizing X-ray crystallography could also explain homo-oligomerization in solution; specifically, trimerization is indicated by infra-red dynamic light scattering and blue native gel electrophoresis in solution. Trimers were also detected by mass spectrometry. Furthermore, there is an indication of post-translational methylation in the crystal structure. Additionally, the possibility of modifying the crystal size and the redox activity in the context of photosynthesis is shaping the investigated cytochrome as a highly suitable model protein for advanced serial crystallography at highly brilliant X-ray free-electron laser sources.The PII-like protein SbtB has been identified as a regulator of SbtA, which is one of the key bicarbonate transporters in cyanobacteria. While SbtB from Synechocystis sp. PCC 6803 has previously been shown to be a trimer, a new crystal form is reported here which crystallizes in what is thought to be a non-native tetramer in the crystal, with the C-terminus in an extended conformation. The crystal structure shows the formation of an intermolecular disulfide bond at Cys94 between SbtB monomers, which may stabilize this conformation in the crystal. This motivates the need for future studies to investigate the potential role that the oxidation and reduction of these cysteines may play in the activation and/or function of SbtB.