Electron beam profile measurement using enhanced dual-techniques in high heat flux test facility at Institute for Plasma Research.

During operation of an ITER-like plasma fusion device, Plasma Facing Components (PFCs) of a divertor are subjected to steady-state and transient heat loads of up to 20 MW/m2. At High Heat Flux Test Facility (HHFTF) at Institute for Plasma Research, PFCs are subjected to such heat flux scenarios using 200 kW electron beam (EB). A heat flux distribution on PFCs is significantly influenced by the EB profile and scanning technique. A novel dual-technique approach is used to measure EB cross-sectional profiles in HHFTF. A single setup is designed, fabricated, and installed in HHFTF consisting of (1) the knife-edge technique involving graphite and tungsten rectangular tiles bonded on a copper block adjacent to each other to form a sharp edge and (2) the wire scanner technique wherein tungsten wires are placed at equal distances. Current collected by the setup is measured as EB is rastered across the wire and tile boundaries. Current measured as a function of EB position is used to calculate the EB profile using a customized LabVIEW software application. Experiments are conducted by varying EB power from 28 to 200 kW and correspondingly the full width at half maximum of the EB profile grows from 5.30 to 16.04 mm, as observed by both these techniques. The COMSOL Multiphysics simulation of the wire scanner technique is performed to verify the experimental results. X-ray and infra-red imaging diagnostics of HHFTF are also used to measure the EB profile in a unique and first-of-its-kind way, and they are found to agree well with the dual-technique measurements.

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In the ongoing, randomised, double-blind phase 3 TOPAZ-1 study, durvalumab, a PD-L1 inhibitor, plus gemcitabine and cisplatin was associated with significant improvements in overall survival compared with placebo, gemcitabine, and cisplatin in people with advanced biliary tract cancer at the pre-planned intermin analysis. In this paper, we present patient-reported outcomes from TOPAZ-1. METHODS: In TOPAZ-1 (NCT03875235), participants aged 18 years or older with previously untreated, unresectable, locally advanced, or metastatic biliary tract cancer with an Eastern Cooperative Oncology Group performance status of 0 or 1 and one or more measurable lesions per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) were randomly assigned (1:1) to the durvalumab group or the placebo group using a computer-generated randomisation scheme. Participants received 1500 mg durvalumab or matched placebo intravenously every 3 weeks (on day 1 of the cycle) for up to eight cycles in combination with 1000 mg/m2 gemcitabine and 25 mg/m2 cisplatin intravenously on days 1 and 8 every 3 weeks for up to eight cycles. Thereafter, participants received either durvalumab (1500 mg) or placebo monotherapy intravenously every 4 weeks until disease progression or other discontinuation criteria were met. Randomisation was stratified by disease status (initially unresectable vs recurrent) and primary tumour location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer). Patient-reported outcomes were assessed as a secondary outcome in all participants who completed the European Organisation for Research and Treatment of Cancer's 30-item Quality of Life of Cancer Patients questionnaire (QLQ-C30) and the 21-item Cholangiocarcinoma and Gallbladder Cancer Quality of Life Module (QLQ-BIL21). We calculated time to deterioration-ie, time from randomisation to an absolute decrease of at least 10 points in a patient-reported outcome that was confirmed at a subsequent visit or the date of death (by any cause) in the absence of deterioration-and adjusted mean change from baseline in patient-reported outcomes. FINDINGS: Between April 16, 2019, and Dec 11, 2020, 685 participants were enrolled and randomly assigned, 341 to the durvalumab group and 344 to the placebo group. Overall, 345 (50%) of participants were male and 340 (50%) were female. Data for the QLQ-C30 were available for 318 participants in the durvalumab group and 328 in the placebo group (median follow-up 9·9 months [IQR 6·7 to 14·1]). Data for the QLQ-BIL21 were available for 305 participants in the durvalumab group and 322 in the placebo group (median follow-up 10·2 months [IQR 6·7 to 14·3]). The proportions of participants in both groups who completed questionnaires were high and baseline scores were mostly similar across treatment groups. For global health status or quality of life, functioning, and symptoms, we noted no difference in time to deterioration or adjusted mean changes from baseline were observed between groups. Median time to deterioration of global health status or quality of life was 7·4 months (95% CI 5·6 to 8·9) in the durvalumab group and 6·7 months (5·6 to 7·9) in the placebo group (hazard ratio 0·87 [95% CI 0·69 to 1·12]). The adjusted mean change from baseline was 1·23 (95% CI -0·71 to 3·16) in the durvalumab group and 0·35 (-1·63 to 2·32) in the placebo group. INTERPRETATION: The addition of durvalumab to gemcitabine and cisplatin did not have a detrimental effect on patient-reported outcomes. These results suggest that durvalumab, gemcitabine, and cisplatin is a tolerable treatment regimen in patients with advanced biliary tract cancer. FUNDING: AstraZeneca.

Patient-Reported Outcomes From the Phase III HIMALAYA Study of Tremelimumab Plus Durvalumab in Unresectable Hepatocellular Carcinoma.

PURPOSE: In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here. METHODS: Participants were randomly assigned to receive STRIDE, durvalumab, or sorafenib. PROs were assessed (preplanned secondary outcome) using the European Organization for Research and Treatment of Cancer 30-item Quality of Life Questionnaire and the 18-item HCC module. Time to deterioration (TTD), change from baseline and improvement rate in global health status/quality of life (GHS/QoL), functioning, and disease-related symptoms were analyzed. RESULTS: In total, 1,171 participants were randomly assigned to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389) and were evaluable for PRO assessments. Across treatment arms, compliance rates for PROs were >77% at baseline and >70% overall. Baseline scores were comparable across treatment arms. TTD in GHS/QoL, physical functioning, fatigue, appetite loss, and abdominal pain was numerically longer for both STRIDE and durvalumab versus sorafenib. Clinically meaningful deterioration in PROs was not observed in any treatment arm. However, TTD in nausea and abdominal swelling was numerically longer for STRIDE versus sorafenib, and the likelihood of clinically meaningful improvement in GHS/QoL, role, emotional and social functioning, and disease-related symptoms was greater with STRIDE and durvalumab versus sorafenib. PROs with STRIDE and durvalumab were generally similar. CONCLUSION: Compared with sorafenib, STRIDE and durvalumab were associated with clinically meaningful, patient-centered GHS/QoL, functioning, and symptom benefits in people with uHCC. These findings support the benefits of the STRIDE regimen compared with sorafenib for a diverse population reflective of the global uHCC population.

From black to green: Quantifying the impact of economic growth, resource management, and green technologies on CO2 emissions.

In an exploration of environmental concerns, this groundbreaking research delves into the relationship between GDP per capita, coal rents, forest rents, mineral rents, oil rents, natural gas rents, fossil fuels, renewables, environmental tax and environment-related technologies on CO2 emissions in 30 highly emitting countries from 1995 to 2021 using instrumental-variables regression Two-Stage least squares (IV-2SLS) regression and two-step system generalized method of moments (GMM) estimates. Our results indicate a significant positive relationship between economic growth and CO2 emissions across all quantiles, showcasing an EKC with diminishing marginal effects. Coal rents exhibit a statistically significant negative relationship with emissions, particularly in higher quantiles, and mineral rents show a negative association with CO2 emissions in lower and middle quantiles, reinforcing the idea of resource management in emissions reduction. Fossil fuels exert a considerable adverse impact on emissions, with a rising effect in progressive quantiles. Conversely, renewable energy significantly curtails CO2 emissions, with higher impacts in lower quantiles. Environmental tax also mitigates CO2 emissions. Environment-related technologies play a pivotal role in emission reduction, particularly in lower and middle quantiles, emphasizing the need for innovative solutions. These findings provide valuable insights for policymakers, highlighting the importance of tailoring interventions to different emission levels and leveraging diverse strategies for sustainable development.

Impact of Skin Pigmentation on Cerebral Regional Saturation of Oxygen Using Near-Infrared Spectroscopy: A Systematic Review.

OBJECTIVES: Near-infrared spectroscopy (NIRS) is used in critical care settings to measure regional cerebral tissue oxygenation (rSo2). However, the accuracy of such measurements has been questioned in darker-skinned individuals due to the confounding effects of light absorption by melanin. In this systematic review, we aim to synthesize the available evidence on the effect of skin pigmentation on rSo2 readings. DATA SOURCES: We systematically searched MEDLINE, Cochrane Database of Systematic Reviews, Embase, and Google Scholar from inception to July 1, 2023. STUDY SELECTION: In compliance with our PROSPERO registration (CRD42022347548), we selected articles comparing rSo2 measurements in adults either between racial groups or at different levels of skin pigmentation. Two independent reviewers conducted full-text reviews of all potentially relevant articles. DATA EXTRACTION: We extracted data on self-reported race or level of skin pigmentation and mean rSo2 values. DATA SYNTHESIS: Of the 11,495 unique records screened, two studies (n = 7,549) met our inclusion criteria for systematic review. Sun et al (2015) yielded significantly lower rSo2 values for African Americans compared with Caucasians, whereas Stannard et al (2021) found little difference between self-reported racial groups. This discrepancy is likely because Stannard et al (2021) used a NIRS platform which specifically purports to control for the effects of melanin. Several other studies that did not meet our inclusion criteria corroborated the notion that skin pigmentation results in lower rSo2 readings. CONCLUSIONS: Skin pigmentation likely results in attenuated rSo2 readings. However, the magnitude of this effect may depend on the specific NIRS platform used.

Dealing With Pericylindrical Melts in Keratoprosthesis: Tenon Patch Graft to the Rescue.

PURPOSE: The aim of this study was to describe the outcomes of autologous Tenon patch graft in the management of Auro keratoprosthesis-related pericylindrical corneal melt. METHODS: We report 3 cases of sterile pericylindrical corneal melt in patients with Auro keratoprosthesis implantation after a mean duration of 5 years (1.5-8 years). Case 1 was a patient with severe graft-versus-host disease. Cases 2 and 3 were cases of chemical injury.All these cases of sterile pericylindrical corneal melt (4-6 mm) underwent autologous Tenon patch graft. The technique included freshening of the edges around the melt, followed by measuring the size of the defect. A Tenon graft harvested from the patient's own eye was used to seal the defect and act as a scaffold. The Tenon patch graft was spread over the melt and held in place by the application of fibrin glue and/or interrupted 10-0 nylon sutures. A bandage contact lens was then placed on the eye. RESULTS: Tenon patch graft was well taken in all patients. The mean duration of epithelial healing was 1 month. Globe integrity was well maintained with no postoperative complications at a mean follow-up duration of 12 months (6-18 months). CONCLUSIONS: Corneal melt is one of the most dreaded complications of KPro because its occurrence could threaten visual prognosis and globe integrity. Autologous Tenon patch is a simple yet innovative and effective option to steer such eyes away from potentially dreadful complications.

'AJ's Orbicularis Oris Stitch: A Novel and Simple Technique of Reconstructing Central Arch Mandibular Defects in Resource-Constrained Set Up'.

Lip and oral cavity SCC account for 2nd highest incidence of cancers and 3rd most common cause of mortality from cancer in India. Reconstruction of defects of central arch invading cancers results in poor cosmetic and functional outcomes if free flaps are not used. 30 patients with Oral SCC in the age group 20-75 years requiring central arch segmental mandibulectomy were included. Reconstruction was done with pedicled bipaddled PMMC flap with 'AJ's orbicularis oris stitch' using Fiber wire. Patients were divided into 4 groups according to extent of lip and skin loss post excision of primary tumour. Patients were evaluated with subjective scores for drooling, oral competence and cosmesis. There were 4, 12, 9 and 5 patients in Group A, B, C and D respectively. Mean subjective scores using our technique for drooling, oral competence and cosmesis were 3.75/4,3.75/4 and 3.5/4 for group A, 3.45/4, 3.36/4 and 3.09/4 for group B, 2.8/4, 2.6/4 and 2.3/4 for group C defects and 2.5/4, 3/4 and 2.5/4 for group D defects respectively. Over all scores for all patients were 3.2/4, 3.14/4 and 2.84/4 for drooling, oral competence and cosmesis. This simple, quick and inexpensive technique of reconstruction of central mandibular arch defects can drastically improve cosmetic and functional outcomes in a resource restrained set up. However, long term results and comparison studies are required for standardisation of the technique.

Comprehensive Phytochemical Analysis and Bioactivity Evaluation of Padina boergesenii: Unveiling Its Prospects as a Promising Cosmetic Component.

Marine macroalgae, such as Padina boergesenii, are gaining recognition in the cosmetics industry as valuable sources of natural bioactive compounds. This study aimed to investigate the biochemical profile of P. boergesenii and evaluate its potential as a cosmetic ingredient. Fourier-transform infrared (FTIR), gas chromatography-mass spectrometry (GCMS), and high-resolution liquid chromatography-mass spectrometry quadrupole time-of-flight (HRLCMS QTOF) analyses were employed to assess the functional groups, phycocompounds, and beneficial compounds present in P. boergesenii. Pigment estimation, total phenol and protein content determination, DPPH antioxidant analysis, and tyrosinase inhibition assay were conducted to evaluate the extracts' ability to counteract oxidative stress and address hyperpigmentation concerns. Elemental composition and amino acid quantification were determined using inductively coupled plasma atomic emission spectrometry (ICP-AES) and HRLCMS, respectively. FTIR spectroscopy confirmed diverse functional groups, including halo compounds, alcohols, esters, amines, and acids. GCMS analysis identified moisturizing, conditioning, and anti-aging compounds such as long-chain fatty alcohols, fatty esters, fatty acids, and hydrocarbon derivatives. HRLCMS QTOF analysis revealed phenolic compounds, fatty acid derivatives, peptides, terpenoids, and amino acids with antioxidant, anti-inflammatory, and skin-nourishing properties. Elemental analysis indicated varying concentrations of elements, with silicon (Si) being the most abundant and copper (Cu) being the least abundant. The total phenol content was 86.50 µg/mL, suggesting the presence of antioxidants. The total protein content was 113.72 µg/mL, indicating nourishing and rejuvenating effects. The ethanolic extract exhibited an IC50 value of 36.75 µg/mL in the DPPH assay, indicating significant antioxidant activity. The methanolic extract showed an IC50 value of 42.784 µg/mL. Furthermore, P. boergesenii extracts demonstrated 62.14% inhibition of tyrosinase activity. This comprehensive analysis underscores the potential of P. boergesenii as an effective cosmetic ingredient for enhancing skin health. Given the increasing use of seaweed-based bioactive components in cosmetics, further exploration of P. boergesenii's potential in the cosmetics industry is warranted to leverage its valuable properties.

Three Consecutive Cases of Ocular Polyhexamethylene Biguanide (PHMB) Toxicity Due to Compounding Error.

Acanthamoeba keratitis is treated with long-term biguanide therapy, and the treatment itself can lead to ocular side effects. Knowledge of possible toxic complications can help in the better titration of the treatment regimen. Here, we describe the toxic side effects of polyhexamethylene biguanide (PHMB), which occurred in three consecutive patients treated with in-house compounded PHMB. There was an error in compounding the solution, with the resultant concentration of PHMB being around 0.2%. Patients developed ocular toxicity like conjunctival inflammation, persistent epithelial defect, and large pigment clumps on endothelium within six weeks of initiation of therapy. All of them developed rapidly progressive cataract and mydriatic pupil within three months. PHMB has the potential to cause irreversible damage to ocular structures, and the toxicity is time and concentration-dependent.

From Meaningful Outcomes to Meaningful Change Thresholds: A Path to Progress for Establishing Digital Endpoints.

This paper examines the use of digital endpoints (DEs) derived from digital health technologies (DHTs), focusing primarily on the specific considerations regarding the determination of meaningful change thresholds (MCT). Using DHTs in drug development is becoming more commonplace. There is general acceptance of the value of DHTs supporting patient-centric trial design, capturing data outside the traditional clinical trial setting, and generating DEs with the potential to be more sensitive to change than conventional assessments. However, the transition from exploratory endpoints to primary and secondary endpoints capable of supporting labeling claims requires these endpoints to be substantive with reproducible population-specific values. Meaningful change represents the amount of change in an endpoint measure perceived as important to patients and should be determined for each digital endpoint and given population under consideration. This paper examines existing approaches to determine meaningful change thresholds and explores examples of these methodologies and their use as part of DE development: emphasizing the importance of determining what aspects of health are important to patients and ensuring the DE captures these concepts of interest and aligns with the overarching endpoint strategy. Examples are drawn from published DE qualification documentation and responses to qualification submissions under review by the various regulatory authorities. It is the hope that these insights will inform and strengthen the development and validation of DEs as drug development tools, particularly for those new to the approaches to determine MCTs.

Preferred practice patterns and review on rosacea.

Rosacea is a chronic, inflammatory facial dermatosis commonly found in fair skin tone population. Recent studies have shown the increasing prevalence in the dark skin tone population as well. Ocular involvement is very common and can occur without cutaneous features. Common ocular features are chronic blepharoconjunctivitis with eyelid margin inflammation and meibomian gland dysfunction. Corneal complications include corneal vascularization, ulceration, scarring, and rarely, perforation. Diagnosis is largely based on clinical signs, although it is often delayed in the absence of cutaneous changes, particularly in children. The management ranges from local therapy to systemic treatment, depending on the severity of the disease. There is a positive association between demodicosis and rosacea; however, causality is always argued. In this review, we describe the epidemiology, clinical features, and treatment of rosacea and ocular rosacea.

Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

External ventricular drainage in the management of pediatric patients with posterior fossa tumors and hydrocephalus: a retrospective cohort study.

PURPOSE: To determine whether intraoperative adjunctive EVD placement in patients with a posterior fossa tumor (PFT) led to improved surgical, radiographic, and clinical outcomes compared to those who did not receive an EVD. METHODS: Patients were grouped as those who underwent routine intraoperative adjunctive EVD insertion and those who did not at time of PFT resection. Patients who pre-operatively required a clinically indicated EVD insertion were excluded. Comparative analyses between both groups were conducted to evaluate clinical, radiological, and pathological outcomes. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were computed for post-operative outcomes. RESULTS: Fifty-five selected patients were included, 15 who had an EVD placed at the time of PFT resection surgery, and 40 who did not. Children without an EVD did not experience a higher rate of complications or poorer post-operative outcomes compared to those with an EVD placed during resection surgery. There was no significant difference in the degree of gross total resection (p = 0.129), post-operative CSF leak (p = 1.000), and post-operative hemorrhage (p = 0.554) between those with an EVD and those without. The frequency of new cranial nerve deficits post-operatively was higher in those with an EVD (40%) compared to those without (3%, p = 0.001). There was a trend towards more frequently observed post-operative hydrocephalus in the EVD group (p = 0.057). CONCLUSION: The routine use of EVD as an intraoperative adjunct in clinically stable pediatric patients with posterior fossa tumors and hydrocephalus may not be associated with improved radiological or clinical outcomes.

Advancing Digital Health Innovation in Oncology: Priorities for High-Value Digital Transformation in Cancer Care.

Although health care delivery is becoming increasingly digitized, driven by the pursuit of improved access, equity, efficiency, and effectiveness, progress does not appear to be equally distributed across therapeutic areas. Oncology is renowned for leading innovation in research and in care; digital pathology, digital radiology, real-world data, next-generation sequencing, patient-reported outcomes, and precision approaches driven by complex data and biomarkers are hallmarks of the field. However, remote patient monitoring, decentralized approaches to care and research, "hospital at home," and machine learning techniques have yet to be broadly deployed to improve cancer care. In response, the Digital Medicine Society and Moffitt Cancer Center convened a multistakeholder roundtable discussion to bring together leading experts in cancer care and digital innovation. This viewpoint highlights the findings from these discussions, in which experts agreed that digital innovation is lagging in oncology relative to other therapeutic areas. It reports that this lag is most likely attributed to poor articulation of the challenges in cancer care and research best suited to digital solutions, lack of incentives and support, and missing standardized infrastructure to implement digital innovations. It concludes with suggestions for actions needed to bring the promise of digitization to cancer care to improve lives.

A Novel Pulsed Stimulation Pattern in Spinal Cord Stimulation: Clinical Results and Postulated Mechanisms of Action in the Treatment of Chronic Low Back and Leg Pain.

OBJECTIVES: The aim of this article is to discuss the possible mechanisms of action (MOAs) and results of a pilot study of a novel, anatomically placed, and paresthesia-independent, neurostimulation waveform for the management of chronic intractable pain. MATERIALS AND METHODS: A novel, multilayered pulsed stimulation pattern (PSP) that comprises three temporal layers, a Pulse Pattern layer, Train layer, and Dosage layer, was developed for the treatment of chronic intractable pain. During preliminary development, the utility was evaluated of anatomical PSP (aPSP) in human subjects with chronic intractable pain of the leg(s) and/or low back, compared with that of traditional spinal cord stimulation (T-SCS) and physiological PSP. The scientific theory and testing presented in this article provide the preliminary justification for the potential MOAs by which PSP may operate. RESULTS: During the pilot study, aPSP (n = 31) yielded a greater decrease in both back and leg pain than did T-SCS (back: -60% vs -46%; legs: -63% vs -43%). In addition, aPSP yielded higher responder rates for both back and leg pain than did T-SCS (61% vs 48% and 78% vs 50%, respectively). DISCUSSION: The novel, multilayered approach of PSP may provide multimechanistic therapeutic relief through preferential fiber activation in the dorsal column, optimization of the neural onset response, and use of both the medial and lateral pathway through the thalamic nuclei. The results of the pilot study presented here suggest a robust responder rate, with several subjects (five subjects with back pain and three subjects with leg pain) achieving complete relief from PSP during the acute follow-up period. These clinical findings suggest PSP may provide a multimechanistic, anatomical, and clinically effective management for intractable chronic pain. Because of the limited sample size of clinical data, further testing and long-term clinical assessments are warranted to confirm these preliminary findings.

Limited Effects of Ultra-low Oxygen Concentration during Extended Embryo Culture on In vitro Fertilisation Outcomes in Indian Women: A Retrospective Cross-sectional Study.

Background: Amongst various other factors, oxygen (O2) concentration in embryo culture plays an important role in determining pregnancy outcomes in women undergoing in vitro fertilisation. Some studies have reported that lowering O2 levels in embryo culture provides better results. Aims: To explore the effects of low- and ultra-low- O2 concentrations (5% and 2%, respectively) in extended embryo culture on various outcome parameters of pregnancy. Settings and Design: This was a retrospective cross-sectional study. Materials and Methods: In this study 382 participants had their embryos cultured in varying O2 concentrations (5% or 2%), followed by either a fresh embryo transfer (ET) or frozen embryo transfer (FET). Outcomes such as pregnancy rate, implantation rate, abortion rate, twinning rate, and live birth rate were compared between the groups. Statistical Analysis Used: Chi square test was applied to compare the primary and secondary outcomes between different groups. Results: No significant differences were observed in pregnancy rate and implantation rate between 5% and 2% O2 groups, irrespective of their mode of ET. The abortion rate was significantly higher in 5% O2 group than in 2% group during FET (24.71% vs. 11.49%, P = 0.02). While the proportion of good-quality embryos was higher in 5% O2 group, these did not translate to better pregnancy outcomes. Additionally, embryos cultured in 2% O2 concentration had a significantly better implantation rate when they were transferred fresh rather than frozen (71.34% vs. 61.46%, P = 0.04). There were no other differences observed. Conclusion: Only marginal benefits were observed in switching human embryos to ultra-low O2 concentration after the initial days of culture.

Health-Related Quality of Life of Patients with Metastatic Pancreatic Cancer: A Systematic Literature Review.

Background: Metastatic pancreatic cancer (mPaC) has a poor prognosis and available treatments provide only moderate improvements in survival. Preserving or improving health-related quality of life (HRQoL) is therefore an important treatment outcome for patients with mPaC. This systematic review identified HRQoL data in patients with mPaC before and after treatment, compared these with data from the general population, and reported the effects of different mPaC treatments on HRQoL. Methods: Searches were performed in Embase, PubMed, and the Cochrane Library from January 2008 to May 2021, and the articles identified were screened for HRQoL data in patients with mPaC. Abstracts from relevant congresses were also manually searched. Publications included were randomized controlled trials and observational studies written in English that reported HRQoL data for adult patients with non-resectable mPaC who were on or off treatment. Results: Thirty relevant publications were identified and HRQoL scores were collected. Overall, baseline mean scores from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), 5-dimension EuroQol questionnaire (EQ-5D), and Functional Assessment of Cancer Therapy-General (FACT-G) for newly diagnosed and previously treated patients with mPaC were worse than those of the general population. Baseline scores were generally better for previously treated patients than for newly diagnosed patients, indicating that mPaC treatments preserve or improve HRQoL. Identified publications also reported changes in HRQoL following first- or subsequent-line chemotherapy. When reported, 10 studies found improvements in overall HRQoL compared with baseline scores, four reported no changes in overall HRQoL after treatment, and six found deteriorations in overall HRQoL. Conclusion: Patients with mPaC had worse HRQoL than the general population. Available anti-cancer therapies can improve or preserve HRQoL.

Trends in diversity, equity and inclusion publications in neurological journals: 2015-2020.

BACKGROUND: Contemporary information on health equity related efforts by scientific neurological journals, as measured by publications related to diversity, equity and inclusion (DEI) and health disparities related to social determinants of health (SDH) are lacking. OBJECTIVE: To assess the yearly rates of DEI and SDH related publications in the highest cited general neurology and neurological sub-specialty journals and compare them to the highest cited medical journals over a 6-year period. METHODS: We included publications from 15 general neurology and neurological subspecialty journals between January 1st 2015 to December 31st 2020. For comparison we included the 15 most cited medical journals as measured by H-Index. We performed a PubMed search in each of the listed journals using key MeSH terms. Two-proportions Z-test and chi-square trend analyses were used to compare differences between journal types. RESULTS: Total yearly proportion of DEI and SDH related publications in neurological journals was 3.9% compared to 6.2% in the highest cited medical journals for years 2015 to 2020 (p=0.001). There was no change in overall trend in publications related to DEI and SDH topics in neurological (ρ = -0.082, p=0.45) or highest cited medical journals between 2015 and 2020 (ρ = -0.065, p=0.54). CONCLUSION: Neurological journals had a significantly lower yearly proportion of DEI and SDH related publications compared to top-cited medical journals. Despite heightened awareness of racial/ethnic health disparities and inequities driven by SDH there was no change in related publications in neurological journals between 2015-2020.

Marine Alga Ulva fasciata-Derived Molecules for the Potential Treatment of SARS-CoV-2: An In Silico Approach.

SARS-CoV-2 is the causative agent of the COVID-19 pandemic. This in silico study aimed to elucidate therapeutic efficacies against SARS-CoV-2 of phyco-compounds from the seaweed, Ulva fasciata. Twelve phyco-compounds were isolated and toxicity was analyzed by VEGA QSAR. Five compounds were found to be nonmutagenic, noncarcinogenic and nontoxic. Moreover, antiviral activity was evaluated by PASS. Binding affinities of five of these therapeutic compounds were predicted to possess probable biological activity. Fifteen SARS-CoV-2 target proteins were analyzed by the AutoDock Vina program for molecular docking binding energy analysis and the 6Y84 protein was determined to possess optimal binding affinities. The Desmond program from Schrödinger's suite was used to study high performance molecular dynamic simulation properties for 3,7,11,15-Tetramethyl-2-hexadecen-1-ol-6Y84 for better drug evaluation. The ligand with 6Y84 had stronger binding affinities (-5.9 kcal/mol) over two standard drugs, Chloroquine (-5.6 kcal/mol) and Interferon α-2b (-3.8 kcal/mol). Swiss ADME calculated physicochemical/lipophilicity/water solubility/pharmacokinetic properties for 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, showing that this therapeutic agent may be effective against SARS-CoV-2.

Natural Language Processing for Automated Classification of Qualitative Data From Interviews of Patients With Cancer.

OBJECTIVES: This study sought to explore the use of novel natural language processing (NLP) methods for classifying unstructured, qualitative textual data from interviews of patients with cancer to identify patient-reported symptoms and impacts on quality of life. METHODS: We tested the ability of 4 NLP models to accurately classify text from interview transcripts as "symptom," "quality of life impact," and "other." Interview data sets from patients with hepatocellular carcinoma (HCC) (n = 25), biliary tract cancer (BTC) (n = 23), and gastric cancer (n = 24) were used. Models were cross-validated with transcript subsets designated for training, validation, and testing. Multiclass classification performance of the 4 models was evaluated at paragraph and sentence level using the HCC testing data set and analyzed by the one-versus-rest technique quantified by the receiver operating characteristic area under the curve (ROC AUC) score. RESULTS: NLP models accurately classified multiclass text from patient interviews. The Bidirectional Encoder Representations from Transformers model generally outperformed all other models at paragraph and sentence level. The highest predictive performance of the Bidirectional Encoder Representations from Transformers model was observed using the HCC data set to train and BTC data set to test (mean ROC AUC, 0.940 [SD 0.028]), with similarly high predictive performance using balanced and imbalanced training data sets from BTC and gastric cancer populations. CONCLUSIONS: NLP models were accurate in predicting multiclass classification of text from interviews of patients with cancer, with most surpassing 0.9 ROC AUC at paragraph level. NLP may be a useful tool for scaling up processing of patient interviews in clinical studies and, thus, could serve to facilitate patient input into drug development and improving patient care.