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Abstract Background Macular corneal dystrophy (MCD) is an inherited, autosomal recessive disorder of defective keratan sulfate (KS) metabolism. It is caused by the mutations in carbohydrate sulfotransferase 6 gene (CHST6) which is essential for the sulfation of KS. Unlike the western world, MCD is the most common corneal stromal dystrophy in India, especially in south Indian population; it could be due to high frequency of consanguineous marriages. Case presentation This study presents the clinical findings of one North Indian MCD family, including 6 patients and 3 unaffected relatives. We used slit lamp examination and in vivo confocal microscopy for assessment. Mutation screening was performed with Sanger sequencing, and corneal structure was analyzed through histochemistry and immunohistochemistry. Our comparative findings revealed that all the patients identified with the deletion of major portion of CHST6 that included the Open Reading Frame (ORF). Although all the patients showed significantly reduced central corneal thickness (CCT-250 μm), a drastic decrease in stromal keratocyte count, and depletion of Bowman’s layer compared to controls. Conclusions This study first time revealed that MCD patients from one family with a deletion of major portion of CHST6 that included ORF leads to severe corneal morphological changes.

Background: Coronary artery disease (CAD) results from the narrowing of coronary arteries that leads to inadequate blood supply to the heart muscles, resulting in Acute Coronary Syndrome (ACS). The coronary collaterals which develop will be an alternative source of blood flow in CAD. Myocardial ischemia stimulates the development of coronary collaterals by releasing various angiogenic growth factors, like the Vascular Endothelial Growth Factor (VEGF). Serum VEGF will serve as an important biomarker in CAD; thus, it can predict coronary collateral development. Aim: To study the factors affecting the development of coronary collaterals in hypertensive and non-hypertensive patients with CAD. Methods: The study includes 100 patients who have done coronary angiography, with an average age of 60±15. Consent was obtained from all patients, and 2 ml of blood was collected. The serum VEGF concentration and cystatin-C were quantified. Coronary Angiograms, along with other reports, were collected and analyzed. CAD was diagnosed for those with ≥ 70% stenosis inany one of the major coronary artery. Coronary collateral gradings was performed as per Rentrop Scoring system. The serum VEGF and cystatin-C levels were correlated with the collateral scores and other cardiovascular risk factors. Results: A significant correlation was found between the collateral scores and serum VEGF level in hypertensive patients only. No significant correlation was found between VEGF level, collateral scores and cardiovascular risk factors. Conclusions: Cardiovascular risk factors in turn increase the serum VEGF level, which results in collateral development. Age and sex did not show show any significant association especially old age and females, with serum VEGF levels.

Background: The term "text neck" can be defined as repetitive strain injury and pain due to excessive viewing and texting on a smartphone for a prolonged duration. Long-term untreated text neck results in inflammation of ligaments and muscles, which can lead to permanent arthritic changes. Many smart phone users experience thumb/wrist pain, but some people who develop pain are smart phone addicts. The present study checks the prevalence and awareness of text neck and thumb text syndrome in young adults. Methods: A cross-sectional study was conducted with 200 volunteers between 18-25 years age who have been using mobile phone in the last 5 years. A structured questionnaire was created, validated, and used for the study. Descriptive statistics was used to assess responses received from participants. The prevalence of text neck syndrome and thumb text syndrome has been established. Results: About 50.3% of the participants were unaware of text neck syndrome and 57.1% of text thumb syndrome. Maximum mobile phone usage included texting and calls. About 45.2% of the participants use their right thumb and index finger to text. 33% of people have a head forward posture when using mobile phones. An analysis of pain, discomfort, and duration during mobile phone use was done and will be presented at a forum. Conclusion: The prevalence of text neck and thumb text syndrome in the young adult population indicates the need to plan future pain management strategies and increase user awareness

The design of high gain converter with photovoltaic (PV) module is carried out in this paper for air conditioning application. The solar based power system gaining large importance due to the renewable nature and increased life time. To understand power and voltage characteristic of PV module, the five parameter single diode model is evolved and analyzed. Due to the varying power characteristic of PV panel to the temperature and irradiance change, perturb and observe maximum power point tracking algorithm is imposed to harvest the maximal potential PV power. Air conditioner require high currents so solar modules are connected in parallel instead of series configuration. Since the output voltage of PV module is low, it requires a DC to DC power electronic converter with large voltage gain to boost the output voltage. Various converters such as conventional boost, buck/boost and Luo converters to provide high voltage gain are analyzed in this work and Luo converter is found to give small ripple in current and voltage as compared to the other two converters for the same voltage gain. Further, in Luo converter, voltage gain can be improved by lifting technique in which self-lift and re-lift techniques are employed. The Re-lift Luo converter has high voltage gains twice that of self-lift Luo and reduced ripple for solar power application. For air conditioning application AC output is obtained using a full bridge single phase voltage source inverter.

Background: Data from three randomised controlled trials supports the use of mitoxantrone, a cytotoxic agent, in active relapsing and secondary progressive multiple sclerosis (MS). The drug has recently been licenced [...]

Introduction: European Society for Clinical Nutrition and Metabolism guidelines recommend that patients with cancer should be screened for malnutrition at diagnosis. The dietetic assessment and intervention in lung cancer study investigated the nutritional status of patients with non-small cell lung cancer (NSCLC) and the need for dietetic intervention., Methods: In this observational cohort pilot study, patients with stage 3b and 4 NSCLC were assessed prior to starting first line systemic anticancer therapy (SACT) with a range of measurements and questionnaires. We report the outcomes related to the Patient Generated Subjective Global Assessment tool (PG-SGA), RESULTS: 96 patients were consented between April 2017 and August 2019. The PG-SGA identified that 78% of patients required specialist nutritional advice; with 52% patients having a critical need for dietetic input and symptom management. Results were dominated by symptom scores. As a screening test, one or more symptoms or recent weight loss history had a sensitivity of 88% (95% CI 78.44% to 94.36%) and specificity of 95.24% (95% CI 76.18% to 99.88%) for need for dietetic intervention., Conclusion: A large proportion of patients with NSCLC have a high symptom burden and are at risk of malnutrition prior to starting SACT and would benefit from dietetic review. It is imperative that oncologists and healthcare professionals discuss weight loss history and symptoms with lung cancer patients to correct nutritional deficiencies and resolve symptoms prior to starting treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Vagus nerve stimulation (VNS) delivered during motor rehabilitation enhances recovery from a wide array of neurological injuries and was recently approved by the U.S. FDA for chronic stroke. The benefits of VNS result from precisely timed engagement of neuromodulatory networks during rehabilitative training, which promotes synaptic plasticity in networks activated by rehabilitation. Previous studies demonstrate that lesions that deplete these neuromodulatory networks block VNS-mediated plasticity and accompanying enhancement of recovery. There is a great deal of interest in determining whether commonly prescribed pharmacological interventions that influence these neuromodulatory networks would similarly impair VNS effects. Here, we sought to directly test the effects of three common pharmaceuticals at clinically relevant doses that target neuromodulatory pathways on VNS-mediated plasticity in rats. To do so, rats were trained on a behavioral task in which jaw movement during chewing was paired with VNS and received daily injections of either oxybutynin, a cholinergic antagonist, prazosin, an adrenergic antagonist, duloxetine, a serotonin-norepinephrine reuptake inhibitor, or saline. After the final behavioral session, intracortical microstimulation (ICMS) was used to evaluate reorganization of motor cortex representations, with area of cortex eliciting jaw movement as the primary outcome. In animals that received control saline injections, VNS paired with training significantly increased the movement representation of the jaw compared to naïve animals, consistent with previous studies. Similarly, none of the drugs tested blocked this VNS-dependent reorganization of motor cortex. The present results provide direct evidence that these common pharmaceuticals, when used at clinically relevant doses, are unlikely to adversely impact the efficacy of VNS therapy., Competing Interests: MK has a financial interest in MicroTransponder, Inc., which is developing VNS for stroke. RR has a financial interest in Xnerve Medical, Inc., which is developing several VNS based therapies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morrison, Abe, Danaphongse, Ezhil, Somaney, Adcock, Rennaker, Kilgard and Hays.)

Vagus nerve stimulation (VNS) paired with motor rehabilitation enhances recovery of function after neurological injury in rats and humans. This effect is ascribed to VNS-dependent facilitation of plasticity in motor networks. Previous studies document an inverted-U relationship between VNS intensity and cortical plasticity, such that moderate intensities increase plasticity, while low or high intensity VNS does not. We tested the interaction of moderate and high intensity VNS trains to probe the mechanisms that may underlie VNS-dependent plasticity. Rats performed a behavioral task where VNS was paired with jaw movement during chewing. For five days, subjects received 100 pairings of moderate intensity VNS (Standard VNS), 100 pairings alternating between moderate and high intensity VNS (Interleaved VNS), or 50 pairings of moderate intensity VNS (Short VNS) approximately every 8 s. After the final behavioral session, intracortical microstimulation (ICMS) was used to evaluate movement representations in motor cortex. 100 pairings of moderate intensity VNS enhanced motor cortex plasticity. Replacing half of moderate intensity stimulation with high intensity VNS blocked this enhancement of plasticity. Removing high intensity stimulation, leaving only 50 pairings of moderate intensity VNS, reinstated plasticity. These results demonstrate that there is a period for at least 8 s after high intensity stimulation in which moderate intensity VNS is not able to engage mechanisms required for synaptic reorganization. More importantly, this study demonstrates that changes in stimulation parameters are a critical determinant of the magnitude of plasticity and likely the efficacy of VNS-enhanced recovery., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose of Review: Systemic therapy for lung cancer is increasing in intensity and duration. European nutrition guidelines suggest screening for weight loss and malnutrition, however acknowledges there is a lack of evidence. We discuss current data round this issue and identify opportunities for further research., Recent Findings: International guidelines now exist to aid the definition of weight loss in cancer, including cachexia, sarcopenia and malnutrition. These allow consistent definition of overlapping, but distinct clinical syndromes. Nutritional status can be assessed in a range of ways including questionnaires, functional assessments, blood markers, physical activity, weight and BMI. Weight loss is commonly associated with a proinflammatory state. Future treatment is likely to be a combination of dietetic support and pharmacological treatment of cachexia., Summary: There is a paucity of data on dietetic intervention. It is potentially quick, inexpensive and patient specific, using a holistic approach to aid patients who are malnourished or at risk of malnutrition. Lung cancer-related weight loss is common, further strategies are needed to effectively assess and intervene. Dietetic intervention has the potential to improve patients' quality of life and outcomes.

Purpose: Prophylactic irradiation to the chest wall after diagnostic or therapeutic procedures in patients with malignant pleural mesothelioma (MPM) has been a widespread practice across Europe, although the efficacy of this treatment is uncertain. In this study, we aimed to determine the efficacy of prophylactic radiotherapy in reducing the incidence of chest wall metastases (CWM) after a procedure in MPM., Methods: After undergoing a chest wall procedure, patients with MPM were randomly assigned to receive prophylactic radiotherapy (within 42 days of the procedure) or no radiotherapy. Open thoracotomies, needle biopsies, and indwelling pleural catheters were excluded. Prophylactic radiotherapy was delivered at a dose of 21 Gy in three fractions over three consecutive working days, using a single electron field adapted to maximize coverage of the tract from skin surface to pleura. The primary outcome was the incidence of CWM within 6 months from random assignment, assessed in the intention-to-treat population. Stratification factors included epithelioid histology and intention to give chemotherapy., Results: Between July 30, 2012, and December 12, 2015, 375 patients were recruited from 54 centers and randomly assigned to receive prophylactic radiotherapy (n = 186) or no prophylactic radiotherapy (n = 189). Participants were well matched at baseline. No significant difference was seen in the incidence of CWM at 6 months between the prophylactic radiotherapy and no radiotherapy groups (no. [%]: 6 [3.2] v 10 [5.3], respectively; odds ratio, 0.60; 95% CI, 0.17 to 1.86; P = .44). Skin toxicity was the most common radiotherapy-related adverse event in the prophylactic radiotherapy group, with 96 patients (51.6%) receiving grade 1; 19 (10.2%), grade 2; and 1 (0.5%) grade 3 radiation dermatitis (Common Terminology Criteria for Adverse Events, version 4.0)., Conclusion: There is no role for the routine use of prophylactic irradiation to chest wall procedure sites in patients with MPM.

Objective: This study tested the hypothesis that shows advanced image analysis can differentiate fit and unfit patients for radical radiotherapy from standard radiotherapy planning imaging, when compared to formal lung function tests, FEV1 (forced expiratory volume in 1 s) and TLCO (transfer factor of carbon monoxide)., Methods: An apical region of interest (ROI) of lung parenchyma was extracted from a standard radiotherapy planning CT scan. Software using a grey level co-occurrence matrix (GLCM) assigned an entropy score to each voxel, based on its similarity to the voxels around it., Results: Density and entropy scores were compared between a cohort of 29 fit patients (defined as FEV1 and TLCO above 50 % predicted value) and 32 unfit patients (FEV1 or TLCO below 50% predicted). Mean and median density and median entropy were significantly different between fit and unfit patients ( p = 0.005, 0.0008 and 0.0418 respectively; two-sided Mann-Whitney test)., Conclusion: Density and entropy assessment can differentiate between fit and unfit patients for radical radiotherapy, using standard CT imaging., Advances in Knowledge: This study shows that a novel assessment can generate further data from standard CT imaging. These data could be combined with existing studies to form a multiorgan patient fitness assessment from a single CT scan., (© 2019 The Authors. Published by the British Institute of Radiology.)

This corrects the article DOI: 10.1038/nature22364.

Lung cancer is the leading cause of cancer mortality worldwide. Treatment pathways include regular cross-sectional imaging, generating large data sets which present intriguing possibilities for exploitation beyond standard visual interpretation. This additional data mining has been termed "radiomics" and includes semantic and agnostic approaches. Textural analysis (TA) is an example of the latter, and uses a range of mathematically derived features to describe an image or region of an image. Often TA is used to describe a suspected or known tumour. TA is an attractive tool as large existing image sets can be submitted to diverse techniques for data processing, presentation, interpretation and hypothesis testing with annotated clinical outcomes. There is a growing anthology of published data using different TA techniques to differentiate between benign and malignant lung nodules, differentiate tissue subtypes of lung cancer, prognosticate and predict outcome and treatment response, as well as predict treatment side effects and potentially aid radiotherapy planning. The aim of this systematic review is to summarize the current published data and understand the potential future role of TA in managing lung cancer.

Several studies have recently reported on the value of CT texture analysis in predicting survival, although the topic remains controversial, with further validation needed in order to consolidate the evidence base. The aim of this study was to investigate the effect of varying the input parameters in the Kaplan-Meier analysis, to determine whether the resulting P-value can be considered to be a robust indicator of the parameter's prognostic potential. A retrospective analysis of the CT-based normalised entropy of 51 patients with lung cancer was performed and overall survival data for these patients were collected. A normalised entropy cut-off was chosen to split the patient cohort into two groups and log-rank testing was performed to assess the survival difference of the two groups. This was repeated for varying normalised entropy cut-offs and varying follow-up periods. Our findings were also compared with previously published results to assess robustness of this parameter in a multi-centre patient cohort. The P-value was found to be highly sensitive to the choice of cut-off value, with small changes in cut-off producing substantial changes in P. The P-value was also sensitive to follow-up period, with particularly noisy results at short follow-up periods. Using matched conditions to previously published results, a P-value of 0.162 was obtained. Survival analysis results can be highly sensitive to the choice in texture cut-off value in dichotomising patients, which should be taken into account when performing such studies to avoid reporting false positive results. Short follow-up periods also produce unstable results and should therefore be avoided to ensure the results produced are reproducible. Previously published findings that indicated the prognostic value of normalised entropy were not replicated here, but further studies with larger patient numbers would be required to determine the cause of the different outcomes.

Background: Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC., Methods: In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival., Results: We observed widespread intratumor heterogeneity for both somatic copy-number alterations and mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always clonal. However, heterogeneous driver alterations that occurred later in evolution were found in more than 75% of the tumors and were common in PIK3CA and NF1 and in genes that are involved in chromatin modification and DNA damage response and repair. Genome doubling and ongoing dynamic chromosomal instability were associated with intratumor heterogeneity and resulted in parallel evolution of driver somatic copy-number alterations, including amplifications in CDK4, FOXA1, and BCL11A. Elevated copy-number heterogeneity was associated with an increased risk of recurrence or death (hazard ratio, 4.9; P=4.4×10 -4 ), which remained significant in multivariate analysis., Conclusions: Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

This paper reports a modelling study of tumour volume dynamics in response to stereotactic ablative radiotherapy (SABR). The main objective was to develop a model that is adequate to describe tumour volume change measured during SABR, and at the same time is not excessively complex as lacking support from clinical data. To this end, various modelling options were explored, and a rigorous statistical method, the Akaike information criterion, was used to help determine a trade-off between model accuracy and complexity. The models were calibrated to the data from 11 non-small cell lung cancer patients treated with SABR. The results showed that it is feasible to model the tumour volume dynamics during SABR, opening up the potential for using such models in a clinical environment in the future.