A validated experimental NMR parameter dataset of organic molecules to assist benchmarking of 3D structure determination methods.

Over 1000 accurately defined and validated experimental long-range proton-carbon () and proton-proton () scalar coupling constants, with assigned H/C chemical shifts and their corresponding 3D structures are reported for fourteen relatively complex organic molecules. The experimental dataset comprises 775 , 300 , 332 H chemical shifts and 336 C chemical shifts, all validated against DFT-calculated values to identify misassignments. A subset of 565 , 205 , 172 H chemical shifts and 202 C chemical shifts from rigid portions of these molecules have been identified which could be particularly valuable for benchmarking computational methods for predicting NMR parameters.

Neoadjuvant Immunotherapy Followed by Surgery Compared with Upfront Surgery Alone in Operable Colon Cancer with Deficient Mismatch Repair: Modeling Oncological Outcomes and Numbers Needed to Treat.

Background: Trials on neoadjuvant immunotherapy in operable colon cancer with deficient mismatch repair (dMMR) reported high pathological response rates in the surgical specimen, but long-term survival is not known. Neoadjuvant immunotherapy as a stand-alone therapy without subsequent radical surgery is currently not investigated in colon cancer.

Objective: The aim of this study was to model outcomes between trial data and real-world patients after surgery.

Patient-derived organoids from pancreatic cancer after pancreatectomy: Feasibility and organoid take rate in treatment-naïve periampullary tumors.

Background/objective: Patient-derived organoids (PDOs) have emerged as essential for ex vivo modelling for pancreatic cancer (PDAC) but reports on efficacy and organoid take rate are scarce. This study aimed to assess the feasibility of establishing PDOs from resected specimens in periampullary tumors.

Methods: Patients undergoing surgery for suspected periampullary cancer were included.

Retrospective analysis on the outcomes of contact lens-associated keratitis in a tertiary centre: an evidence-based management protocol to optimise resource allocation.

Background/aims: Contact lens-associated keratitis (CLAK) is a common sight-threatening complication of contact lens use. Current management protocols in the UK are based on historical practice and necessitate a review for every patient within 48 hours regardless of severity, increasing the treatment burden on a resource-limited healthcare service. Our study aims to identify the different risk factors associated with CLAK, categorise CLAK using a novel grading system and recommend modifications to current management protocols based on the outcomes in the individual subgroups.

Backbone H, C and N resonance assignment of the ubiquitin specific protease 7 catalytic domain (residues 208-554) in complex with a small molecule ligand.

The backbone H, C and N resonance assignment of Ubiquitin Specific Protease 7 catalytic domain (residues 208-554) was performed in its complex with a small molecule ligand and in its apo form as a reference. The amide H-N signal intensities were boosted by an amide hydrogen exchange protocol, where expressed H, C, N-labeled protein was unfolded and re-folded to ensure exchange of amide deuterons to protons. The resonance assignments were used to determine chemical shift perturbations on ligand binding, which are consistent with the binding site observed by crystallography.

The Co-Creation of a Patient Information Leaflet for Patients With the Rare Eye Infection keratitis.

keratitis (AK) is a rare but severe eye disease. A research engagement event, "The Cornea Day," in London, UK in 2013, identified the lack of credible information about AK and a need for practical day to day management strategies. Experiences of 15 AK patients attending The Cornea Day were distilled into a survey that was administered to a wider group of 76 patients, carers, researchers, and clinicians.

Phenotypic plasticity underlies local invasion and distant metastasis in colon cancer.

Phenotypic plasticity represents the most relevant hallmark of the carcinoma cell as it bestows it with the capacity of transiently altering its morphological and functional features while to the metastatic site. However, the study of phenotypic plasticity is hindered by the rarity of these events within primary lesions and by the lack of experimental models. Here, we identified a subpopulation of phenotypic plastic colon cancer cells: EpCAM cells are motile, invasive, chemo-resistant, and highly metastatic.

The Impact of COVID-19 on Acute and Elective Corneal Surgery at Moorfields Eye Hospital London.

Purpose: Moorfields Eye Hospital sits as a major tertiary centre for ophthalmic care in the United Kingdom and became a central hub to provide safe and effective ophthalmic care across London and surrounding regions during the COVID-19 pandemic. We explore the impact on both the acute and elective corneal services during the first wave of this pandemic.

Methods: A retrospective review of the proportion of corneal transplants and anterior segment trauma repairs was performed during the period of March 23rd to July 1st 2020 compared with an identical period in 2019.

Evaluation and management of a spontaneous corneal rupture secondary to pellucid marginal degeneration, using swept-source anterior segment optical coherence tomography.

We describe a case of bilateral spontaneous corneal perforation secondary to pellucid marginal degeneration and present the associated swept-source anterior segment optical coherence tomography (SS-ASOCT) findings and management principles used. A 47-year-old woman presented with ocular pain, redness, foreign body sensation and clear discharge in the right eye in 2017 and with very similar symptoms in 2019 in the left eye. Clinically she had a corneal perforation at the inferior cornea with associated loss of anterior chamber volume.

A template to quantify the location and density of CD3 + and CD8 + tumor-infiltrating lymphocytes in colon cancer by digital pathology on whole slides for an objective, standardized immune score assessment.

Background: In colon cancer, the location and density of tumor-infiltrating lymphocytes (TILs) can classify patients into low and high-risk groups for prognostication. While a commercially available 'Immunoscore' exists, the incurred expenses and copyrights may prevent universal use. The aim of this study was to develop a robust and objective quantification method of TILs in colon cancer.

Prevalence of PD-L1 expression is associated with EMAST, density of peritumoral T-cells and recurrence-free survival in operable non-metastatic colorectal cancer.

Introduction: Microsatellite instability (MSI) predict response to anti-PD1 immunotherapy in colorectal cancer (CRC). CRCs with MSI have higher infiltration of immune cells related to a better survival. Elevated Microsatellite Alterations at Tetranucleotides (EMAST) is a form of MSI but its association with PD-L1 expression and immune-cell infiltration is not known.

Elevated Microsatellite Alterations at Selected Tetranucleotides (EMAST) in Colorectal Cancer is Associated with an Elderly, Frail Phenotype and Improved Recurrence-Free Survival.

Background: Elevated microsatellite alterations at selected tetranucleotides (EMAST) is a poorly investigated form of microsatellite instability (MSI) in colorectal cancer (CRC).

Objective: The aim of this study was to investigate the clinicopathological features of EMAST in CRC and its relation to outcome.

Methods: A population-based, consecutive cohort of surgically treated stage I-III CRC patients investigated for high-frequency MSI (MSI-H) and EMAST.

Elevated Microsatellite Alterations at Selected Tetranucleotides (EMAST) Is Not Attributed to MSH3 Loss in Stage I-III Colon cancer: An Automated, Digitalized Assessment by Immunohistochemistry of Whole Slides and Hot Spots.

Introduction: EMAST is a poorly understood form of microsatellite instability (MSI) in colorectal cancer (CRC) for which loss of MSH3 has been proposed as the underlying mechanism, based on experimental studies. We aimed to evaluate whether MSH3 loss is associated with EMAST in CRC.

Methods: A consecutive cohort of patients with stage I-III CRC.

Patients' experiences of unilateral spatial neglect between stroke onset and discharge from inpatient rehabilitation: a thematic analysis of qualitative interviews.

The purpose of this qualitative study was to explore how stroke patients with unilateral spatial neglect experience; (a) performance in activities of daily living; (b) alterations in bodily perceptions; and (c) personal hopes and expectations, looking at the period between stroke onset and discharge from inpatient rehabilitation. We conducted individual semi-structured interviews with 7 (5 men, 2 women, mean age 69 years) consecutively sampled participants. All interviews were transcribed verbatim and analyzed using thematic analysis.

Correlation of Blood T-Cells to Intratumoural Density and Location of CD3 and CD8 T-Cells in Colorectal Cancer.

Aim: To test the feasibility of conducting parallel analyses of circulating T-cells in blood and intratumoural T-cells in colorectal cancer. A pre-operative 'liquid biopsy' to determine immune status would facilitate clinical decision-making.

Materials And Methods: A total of 18 patients with stage I-III colorectal cancer (CRC) were included.

Assessment of clinically related outcomes and biomarker analysis for translational integration in colorectal cancer (ACROBATICC): study protocol for a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastasis.

Background: More accurate predictive and prognostic biomarkers for patients with colorectal cancer (CRC) primaries or colorectal liver metastasis (CLM) are needed. Outside clinical trials, the translational integration of emerging pathways and novel techniques should facilitate exploration of biomarkers for improved staging and prognosis.

Methods: An observational study exploring predictive and prognostic biomarkers in a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastases.

The prognostic yield of biomarkers harvested in chemotherapy-naive stage II colon cancer: can we separate the wheat from the chaff?

The TNM-system fails to accurately predict disease recurrence in a considerate number of patients. While node-negative (stage II) colon cancer is considered to have an overall good prognosis, the 5-year cancer-specific survival is reported at 81-83% in patients who did not have adjuvant chemotherapy. Thus, reliance on node-status alone has lead to under-treatment in a subgroup of stage II patients with an unfavorable prognosis.

Elevated microsatellite alterations at selected tetranucleotides in early-stage colorectal cancers with and without high-frequency microsatellite instability: same, same but different?

Microsatellite instability (MSI) is associated with better prognosis in colorectal cancer (CRC). Elevated microsatellite alterations at selected tetranucleotides (EMAST) is a less-understood form of MSI. Here, we aim to investigate the role of EMAST in CRC±MSI related to clinical and tumor-specific characteristics.

Feasibility of a randomized controlled trial of functional strength training for people between six months and five years after stroke: FeSTivaLS trial.

Background: Functional Strength Training (FST) could enhance recovery late after stroke. The aim of this study was to evaluate the feasibility of a subsequent fully powered, randomized controlled trial.

Methods: The study was designed as a randomized, observer-blind trial.

Validity and reliability of an alternative method for measuring power output during six-second all-out cycling.

In a laboratory setting where both a mechanically-braked cycling ergometer and a motion analysis (MA) system are available, flywheel angular displacement can be estimated by using MA. The purpose of this investigation was to assess the validity and reliability of a MA method for measuring maximal power output (Pmax) in comparison with a force transducer (FT) method. Eight males and eight females undertook three identical sessions, separated by 4 to 6 days; the first being a familiarization session.

GPR103 antagonists demonstrating anorexigenic activity in vivo: design and development of pyrrolo[2,3-c]pyridines that mimic the C-terminal Arg-Phe motif of QRFP26.

GPR103, a G-protein coupled receptor, has been reported to have orexigenic properties through activation by the endogenous neuropeptide ligands QRFP26 and QRFP43. Recognizing that central administration of QRFP26 and QRFP43 increases high fat food intake in rats, we decided to investigate if antagonists of GPR103 could play a role in managing feeding behaviors. Here we present the development of a new series of pyrrolo[2,3-c]pyridines as GPR103 small molecule antagonists with GPR103 affinity, drug metabolism and pharmacokinetics and safety parameters suitable for drug development.