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Abstract Objective Effective management of hypertension requires not only medical intervention but also significant patient self-management. The challenge, however, lies in the diversity of patients' personal barriers to managing their condition. The objective of this research is to identify and categorize personalized barriers to hypertension self-management using the TASKS framework (Task, Affect, Skills, Knowledge, Stress). This study aims to enhance patient-centered strategies by aligning support with each patient's specific needs, recognizing the diversity in their unique circumstances, beliefs, emotional states, knowledge levels, and access to resources. This research is based on observations from a single study focused on eight patients, which may have been a part of a larger project. Results The analysis of transcripts from eight patients and the Global Hypertension Practice Guidelines revealed 69 personalized barriers. These barriers were distributed as follows: emotional barriers (49%), knowledge barriers (24%), logical barriers (17%), and resource barriers (10%). The findings highlight the significant impact of emotional and knowledge-related challenges on hypertension self-management, including difficulties in home blood pressure monitoring and the use of monitoring tools. This study emphasizes the need for tailored interventions to address these prevalent barriers and improve hypertension management outcomes.

Abstract Moyamoya disease (MMD) is a rare stenoocclusive cerebral vasculopathy often treated by neurosurgical revascularization using extracranial-intracranial bypasses to prevent ischemic or hemorrhagic events. Little is known about the vascular risk profile of adult MMD patients compared to the general population. We therefore analyzed 133 adult MMD patients and compared them with data from more than 22,000 patients from the German Health Update database. Patients with MMD showed an age- and sex-adjusted increased prevalence of arterial hypertension, especially in women between 30 and 44 years and in patients of both sexes between 45 and 64 years. Diabetes mellitus was diagnosed significantly more frequently in MMD patients with increasing age, whereas the vascular risk profile in terms of obesity, nicotine and alcohol consumption was similar to that of the general population. Antihypertensive medication was changed one year after surgical revascularization in 67.5% of patients with a tendency towards dose reduction in 43.2% of all patients. After revascularization, physicians need to be aware of a high likelihood of changes in arterial hypertension and should adjust all other modifiable systemic vascular risk factors to achieve the best treatment possible.

Abstract Background Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes. Methods The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases. Results In front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p

Purpose: Current guidelines recommend debriefing following medical resuscitations to improve patient outcomes. The goal of this study was to describe national trends in postresuscitation debriefing practices among pediatric critical care medicine (PCCM) fellows to identify potential gaps in fellow education. Methods: A 13-item survey was distributed to fellows in all 76 ACGME-accredited PCCM programs in the United States in the spring of 2021. The online survey addressed frequency and timing of debriefings following medical resuscitations, whether formal training is provided, which medical professionals are present, and providers’ comfort level leading a debriefing. Results were analyzed using descriptive statistics. Results: A total of 102 responses (out of a possible N of 536) were gathered from current PCCM fellows. All fellows (100%) reported participation in a medical resuscitation. Only 21% stated that debriefings occurred after every resuscitation event, and 44% did not follow a structured protocol for debriefing. While 66% reported feeling very or somewhat comfortable leading the debriefing, 19% felt either somewhat uncomfortable or very uncomfortable. A vast majority (92%) of participating fellows believed that debriefing would be helpful in improving team member performance during future resuscitations, and 92% expressed interest in learning more about debriefing. Conclusions: The majority of PCCM fellows do not receive formal training on how to lead a debriefing. Given that 74% of fellows in our study did not feel very comfortable leading a debriefing but almost universally expressed that this practice is useful for provider well-being and performance, there is a clear need for increased incorporation of debriefing training into PCCM curricula across the United States.

Before revascularization, moyamoya patients require hemodynamic evaluation. In this study, we evaluated the scoring system Prior Infarcts, Reactivity and Angiography in Moyamoya Disease (PIRAMID). We also devised a new scoring system, MRI-Based Assessment of Risk for Stroke in Moyamoya Angiopathy (MARS-MMA), and compared the scoring systems with respect to the capability to predict impaired [15O]water PET cerebral perfusion reserve capacity (CPR). We evaluated 69 MRI, 69 DSA and 38 [15O]water PET data sets. The PIRAMID system was validated by ROC curve analysis with neurological symptomatology as a dependent variable. The components of the MARS-MMA system and their weightings were determined by binary logistic regression analysis. The comparison of PIRAMID and MARS-MMA was performed by ROC curve analysis. The PIRAMID score correlated well with the symptomatology (AUC = 0.784). The MARS-MMA system, including impaired breath-hold-fMRI, the presence of the Ivy sign and arterial wall contrast enhancement, correlated slightly better with CPR impairment than the PIRAMID system (AUC = 0.859 vs. 0.827, Akaike information criterion 140 vs. 146). For simplified clinical use, we determined three MARS-MMA grades without loss of diagnostic performance (AUC = 0.855). The entirely MRI-based MARS-MMA scoring system might be a promising tool to predict the risk of stroke.

Optimization techniques can be used to find the optimal combination of inputs and parameters and help identify the most efficient solution. Aggregation operators (AOs) play a prominent role in discernment between two circulations of prospect and pull out anxieties from that insight. The most fundamental objective of this research is to extend the interaction AOs to the interval-valued Pythagorean fuzzy hypersoft set (IVPFHSS), the comprehensive system of the interval-valued Pythagorean fuzzy soft set (IVPFSS). The IVPFHSS adroitly contracts with defective and ambagious facts compared to the prevalent Pythagorean fuzzy soft set and interval-valued intuitionistic fuzzy hypersoft set (IVIFHSS). It is the dominant technique for enlarging imprecise information in decision-making (DM). The most important intention of this exploration is to intend interactional operational laws for IVPFHSNs. We extend the AOs to interaction AOs under IVPFHSS setting such as interval-valued Pythagorean fuzzy hypersoft interactive weighted average (IVPFHSIWA) and interval-valued Pythagorean fuzzy hypersoft interactive weighted geometric (IVPFHSIWG) operators. Also, we study the significant properties of the proposed operators, such as Idempotency, Boundedness, and Homogeneity. Still, the prevalent multi-criteria group decision-making (MCGDM) approaches consistently carry irreconcilable consequences. Meanwhile, our proposed MCGDM model is deliberate to accommodate these shortcomings. By utilizing a developed mathematical model and optimization technique, Industry 5.0 can achieve digital green innovation, enabling the development of sustainable processes that significantly decrease environmental impact. The impacts show that the intentional model is more operative and consistent in conducting inaccurate data based on IVPFHSS.

The widespread use of English around the world has changed its status from being a language spoken by some powerful countries to language used by a large number of non-native speakers around the world (Llurda, 2004). In recent years, the total number of non-native English language teachers is greater than the English language teachers whose native language is English. Therefore, to study English as an International Language (EIL) from the perspective of government school English teachers, whose native language is not English, is essential. This research paper investigates the attitudes and perceptions of government school English teachers in Pakistan regarding pronunciation in English as an international language (EIL). A quantitative research design was employed, with data collected from 28 government school teachers through online questionnaires. Data obtained through online questionnaires from high school English teachers revealed that English has always been considered the correct standard for English Language Teaching (ELT). The findings suggest that participants perceive English as an international language as a language easily understood by everyone and are using it for various communicative purposes. They are open to and embrace all varieties of English and demonstrate adaptability and flexibility in their behavior and speech when interacting with individuals from diverse cultural backgrounds. Findings revealed insights into teachers' attitudes, beliefs, and experiences related to pronunciation teaching

Background: There is no consensus on the most effective treatments of pulmonary arterial hypertension (PAH). Our objective was to compare effects of medications for PAH. Methods: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov from inception to December 2021. We performed a frequentist random-effects network meta-analysis on all included trials. We rated the certainty of the evidence using the Grades of Recommendation, Assessment, Development, and Evaluation approach. Results: We included 53 randomised controlled trials with 10 670 patients. Combination therapy with endothelin receptor antagonist (ERA) plus phosphodiesterase-5 inhibitors (PDE5i) reduced clinical worsening (120.7 fewer events per 1000, 95% CI 136.8–93.4 fewer; high certainty) and was superior to either ERA or PDE5i alone, both of which reduced clinical worsening, as did riociguat monotherapy (all high certainty). PDE5i (24.9 fewer deaths per 1000, 95% CI 35.2 fewer to 2.1 more); intravenous/subcutaneous prostanoids (18.3 fewer deaths per 1000, 95% CI 28.6 fewer deaths to 0) and riociguat (29.1 fewer deaths per 1000, 95% CI 38.6 fewer to 8.7 more) probably reduce mortality as compared to placebo (all moderate certainty). Combination therapy with ERA+PDE5i (49.9 m, 95% CI 25.9–73.8 m) and riociguat (49.5 m, 95% CI 17.3–81.7 m) probably increase 6-min walk distance as compared to placebo (moderate certainty). Conclusion: Current PAH treatments improve clinically important outcomes, although the degree and certainty of benefit vary between treatments.

Plain English summary Australian women from non-English speaking migrant and refugee communities face reduced access to sexual and reproductive healthcare and many then go on to experience poor health outcomes as a result. There is an urgent need for new approach to improve access to healthcare for underserved communities, one that centres these women in the process of finding, developing and disseminating the solutions themselves. Human-centred design can be a more ethical and effective methodology in working with communities to develop these health solutions. This study aimed to evaluate how well Shifra, a small Australian-based not-for-profit focused on improving access to healthcare for refugees and new migrants, undertook human-centred design approach when developing a Smartphone app that delivers local, safe and culturally relevant health information to non-English speaking Australians. The authors interviewed refugees, health and social sector experts and computer programmers involved in creating Shifra to evaluate how well they used human-centred design to achieve its goals. This evaluation found that Shifra’s approach was successful whilst also highlighting several important recommendations for improving collaborative efforts with refugee communities. These findings could help other projects also seeking to undertake an authentic community co-design process.

The current research work focuses on the extraction and optimization of the hydrogel (AVM) from the seeds of Artemisia vulgaris using Box–Behnken design-response surface methodology (BBD-RSM). The AVM was obtained through a hot water extraction process. The influence of different factors, including pH (U = 4 to 10), temperature (V = 25 to 110 °C), seed/water ratio, i.e., S/W ratio (W = 1/10 to 1/70 w/v), and seed/water contact time, i.e., S/W time (X = 1 to 12 h) on the yield of AVM was evaluated. The p-value for the analysis of variance (ANOVA) was found to be w/v, and S/W time of 8.73 h according to Design-Expert Software. The study of the pH-responsive behavior of AVM in tablet form (formulation AVT3) revealed that AVM is a pH-responsive material with significantly high swelling at pH 7.4. However, less swelling was witnessed at pH 1.2. Moreover, AVM was found to be a sustained release material for esomeprazole at pH 7.4 for 12 h. The drug release from AVT3 was according to the super case-II transport mechanism and zero-order kinetics.

Abstract Ibrutinib inhibits Bruton tyrosine kinase while venetoclax is a specific inhibitor of the anti-apoptotic protein BCL2. Both drugs are highly effective as monotherapy against chronic lymphocytic leukemia (CLL), and clinical trials using the combination therapy have produced remarkable results in terms of rate of complete remission and frequency of undetectable minimal residual disease. However, the laboratory rationale behind the success of the drug combination is still lacking. A better understanding of how these two drugs synergize would eventually help develop other rational combination strategies. Using an ex vivo model that promotes CLL proliferation, we show that modeled ibrutinib proliferative responses, but not viability responses, correlate well with patients’ actual clinical responses. Importantly, we demonstrate for the first time that ibrutinib and venetoclax act on distinct CLL subpopulations that have different proliferative capacities. While the dividing subpopulation of CLL responds to ibrutinib, the resting subpopulation preferentially responds to venetoclax. The combination of these targeted therapies effectively reduced both the resting and dividing subpopulations in most cases. Our laboratory findings help explain several clinical observations and contribute to the understanding of tumor dynamics. Additionally, our proliferation model may be used to identify novel drug combinations with the potential of eradicating residual disease.

This study was undertaken to estimate the antioxidant activity and total tannin content of Moringa olifera Lam. (Moringa) leaves and find a suitable extraction condition for maximum yield. Two types of solvent and three different extraction times and temperatures were experimented for extraction. Moringa leaves were oven-dried and powdered to determine the antioxidant activity in terms of total phenolic content (TPC), ferric reducing antioxidant power (FRAP), and DPPH radical scavenging activity and total tannin content. The maximum TPC value noted in methanol extract, and it ranges from 6.46 ± 0.34 g to 3.91±0.19 g gallic acid equivalent (GAE)/100g dry sample (DM). The FRAP values varied from 211.6 ± 3.75 to 344.13 ± 3.26 mg ascorbic acid equivalent (AAE)/100g DM and 166.67 ± 2.90 to 224.93 ± 1.94 mg AAE/100g DM, for methanol and ethanol extract, respectively. The DPPH radical scavenging activity ranged from 46.32 ± 1.07 to 58.09 ± 0.92% for methanol extract and 56.76 ± 1.48% to 69.72 ± 1.15% for ethanol extract. The total tannin content varied from 6.84 ± 0.05 to 10.22 ± 1.11 mg GAE/100 g dry sample and 6.77 ± 0.08 to 9.23 ± 0.51 mg GAE/ 100g DMfor methanol and ethanol extract, respectively. The highest antioxidant yield for methanol and ethanol extract of Moringa leaves differed for various conditions. Overall, Moringa leaves showed excellent antioxidant properties that can be commercially and domestically used.

BackgroundHypoglycemia prognostic models contingent on prospective, self-reported survey data offer a powerful avenue for determining real-world event susceptibility and interventional targets. ObjectiveThis protocol describes the design and implementation of the 1-year iNPHORM (Investigating Novel Predictions of Hypoglycemia Occurrence Using Real-world Models) study, which aims to measure real-world self-reported severe and nonsevere hypoglycemia incidence (daytime and nocturnal) in American adults with type 1 or 2 diabetes mellitus prescribed insulin and/or secretagogues, and develop and internally validate prognostic models for severe, nonsevere daytime, and nonsevere nocturnal hypoglycemia. As a secondary objective, iNPHORM aims to quantify the effects of different antihyperglycemics on hypoglycemia rates. MethodsiNPHORM is a prospective, 12-wave internet-based panel survey that was conducted across the United States. Americans (aged 18-90 years) with self-reported type 1 or 2 diabetes mellitus prescribed insulin and/or secretagogues were conveniently sampled via the web from a pre-existing, closed, probability-based internet panel (sample frame). A sample size of 521 baseline responders was calculated for this study. Prospective data on hypoglycemia and potential prognostic factors were self-assessed across 14 closed, fully automated questionnaires (screening, baseline, and 12 monthly follow-ups) that were piloted using semistructured interviews (n=3) before fielding; no face-to-face contact was required as part of the data collection. Participant responses will be analyzed using multivariable count regression and machine learning techniques to develop and internally validate prognostic models for 1-year severe and 30-day nonsevere daytime and nocturnal hypoglycemia. The causal effects of different antihyperglycemics on hypoglycemia rates will also be investigated. ResultsRecruitment and data collection occurred between February 2020 and March 2021 (ethics approval was obtained on December 17, 2019). A total of 1694 participants completed the baseline questionnaire, of whom 1206 (71.19%) were followed up for 12 months. Most follow-up waves (10,470/14,472, 72.35%) were completed, translating to a participation rate of 179% relative to our target sample size. Over 70.98% (856/1206) completed wave 12. Analyses of sample characteristics, quality metrics, and hypoglycemia incidence and prognostication are currently underway with published results anticipated by fall 2022. ConclusionsiNPHORM is the first hypoglycemia prognostic study in the United States to leverage prospective, longitudinal self-reports. The results will contribute to improved real-world hypoglycemia risk estimation and potentially safer, more effective clinical diabetes management. Trial RegistrationClinicalTrials.gov NCT04219514; https://clinicaltrials.gov/ct2/show/NCT04219514 International Registered Report Identifier (IRRID)DERR1-10.2196/33726

Background: The negative impact of continued school closures during the height of the COVID-19 pandemic warrants the establishment of cost-effective strategies for surveillance and screening to safely reopen and monitor for potential in-school transmission. Here, we present a novel approach to increase the availability of repetitive and routine COVID-19 testing that may ultimately reduce the overall viral burden in the community. Methods: We implemented a testing program using the SalivaClear࣪ pooled surveillance method that included students, faculty and staff from K-12 schools (student age range 5–18 years) and universities (student age range >18 years) across the country (Mirimus Clinical Labs, Brooklyn, NY). The data analysis was performed using descriptive statistics, kappa agreement, and outlier detection analysis. Findings: From August 27, 2020 until January 13, 2021, 253,406 saliva specimens were self-collected from students, faculty and staff from 93 K-12 schools and 18 universities. Pool sizes of up to 24 samples were tested over a 20-week period. Pooled testing did not significantly alter the sensitivity of the molecular assay in terms of both qualitative (100% detection rate on both pooled and individual samples) and quantitative (comparable cycle threshold (Ct) values between pooled and individual samples) measures. The detection of SARS-CoV-2 in saliva was comparable to the nasopharyngeal swab. Pooling samples substantially reduced the costs associated with PCR testing and allowed schools to rapidly assess transmission and adjust prevention protocols as necessary. In one instance, in-school transmission of the virus was determined within the main office and led to review and revision of heating, ventilating and air-conditioning systems. Interpretation: By establishing low-cost, weekly testing of students and faculty, pooled saliva analysis for the presence of SARS-CoV-2 enabled schools to determine whether transmission had occurred, make data-driven decisions, and adjust safety protocols. We provide strong evidence that pooled testing may be a fundamental component to the reopening of schools by minimizing the risk of in-school transmission among students and faculty. Funding: Skoll Foundation generously provided funding to Mobilizing Foundation and Mirimus for these studies.

South Asians (SAs), originating from the Indian subcontinent (India, Pakistan, Sri Lanka, Bangladesh, Nepal, and Bhutan), represent one quarter of the global population and are the largest visible minority in Canada. SAs experience the highest rates of coronary artery disease in Canada. Although conventional cardiovascular risk factors remain predictive in SA, the excess risk is not fully explained by these risk factors alone. Abdominal obesity, metabolic syndrome, and insulin resistance likely contribute a greater risk in SAs than in other populations. The South Asian Heart Alliance has been recently formed to investigate and recommend the best strategies for the prevention of cardiometabolic disease in SAs in Canada. This topic review represents a comprehensive overview of the magnitude of cardiovascular disease in SAs in Canada, with a review of conventional and novel risk markers in the SA population. Both primary and secondary prevention strategies are suggested and when possible, adapted specifically for the SA population. The need for SAs and their healthcare professionals to be more aware of the problem and potential solutions, along with the need for population-specific research, is highlighted. Résumé: Les Asiatiques du sud originaires du sous-continent indien (Inde, Pakistan, Sri Lanka, Bangladesh, Népal et Bhoutan) représentent le quart de la population mondiale et constituent la plus importante minorité visible au Canada. C’est aussi au sein de cette population qu’on observe les taux de coronaropathie les plus élevés au Canada. Bien que les facteurs de risque cardiovasculaire classiques conservent leur valeur prédictive chez les Asiatiques du sud, ils n’expliquent pas à eux seuls le risque excédentaire observé. L’obésité abdominale, le syndrome métabolique et l’insulinorésistance constituent vraisemblablement des facteurs de risque plus importants chez les Asiatiques du sud que dans les autres populations. La South Asian Heart Alliance a récemment été mise sur pied afin d’explorer les stratégies exemplaires pour la prévention des maladies cardiométaboliques chez les Asiatiques du sud au Canada et de formuler des recommandations à cet égard. Cette revue thématique présente un aperçu de l’importance des maladies cardiovasculaires au sein de la population des Asiatiques du sud du Canada, ainsi qu’un résumé des marqueurs de risque classiques et nouveaux dans cette population. Les auteurs proposent des stratégies de prévention primaire et secondaire adaptées, dans la mesure du possible, à la population des Asiatiques du sud. Ils font également ressortir l’importance de sensibiliser davantage les Asiatiques du sud et les professionnels de la santé aux risques et aux solutions possibles, ainsi que la nécessité de mener des recherches axées sur cette population particulière.

Coal-Water Slurry (CWS) is an attractive alternative fuel with lower cost and reliable in terms of transportation and handling. The efficiency of CWS gasification depends on the preparation of CWS to ensure the higher carbon contents and low viscosity which will enhance the heating rates along with the atomization of CWS. In this paper, the rheology of CWS was studiedwith coal loading 30 to 60% and the rheological behavior was discussed with the help of Power-law, Casson and Herschel Buckley models which shows that CWS exhibits pseudo-plastic (shear thinning) behavior. The CWS was prepared by using Poly-Vinyl Alcohol (PVA) and Triethanol Amine (TEA) as dispersants and Xanthan gum as a stabilizer. The experimental results showed that for a constant coal loading viscosity decreases as the shear rate increases and out of these rheological models, power-law fits best on the experimental data with the highest R2 of 0.99

Objective To determine the prevalence of physician burnout during the pandemic and differences by gender, ethnicity or sexual orientation.Design, setting and participants We conducted a cross-sectional survey (August–October in 2020) of internal medicine physicians at two academic hospitals in Vancouver, Canada.Primary and secondary outcomes Physician burnout and its components, emotional exhaustion, depersonalisation and personal accomplishment were measured using the Maslach Burnout Inventory.Results The response rate was 38% (n=302/803 respondents, 49% women,). The prevalence of burnout was 68% (emotional exhaustion 63%, depersonalisation 39%) and feeling low personal accomplishment 22%. In addition, 21% reported that they were considering quitting the profession or had quit a position. Women were more likely to report emotional exhaustion (OR 2.00, 95% CI: 1.07 to 3.73, p=0.03) and feeling low personal accomplishment (OR 2.26, 95% CI: 1.09 to 4.70, p=0.03) than men. Visible ethnic minority physicians were more likely to report feeling lower personal accomplishment than white physicians (OR 1.81, 95% CI: 1.28 to 2.55, p=0.001). There was no difference in emotional exhaustion or depersonalisation by ethnicity or sexual orientation. Physicians who reported that COVID-19 affected their burnout were more likely to report any burnout (OR: 3.74, 95% CI: 1.99 to 7.01, p

Objective: To evaluate the clinical value of early post-operative computed tomographic angiography (CTA) after direct extracranial-intracranial (EC-IC) bypass surgery in moyamoya patients.Methods: A retrospective analysis of all adult moyamoya patients treated at our center from 2013 to 2019 with a direct EC-IC bypass was performed. Early post-operative CTA (within 24 h after surgery) was compared with conventional digital subtraction angiography (DSA) 6–12 months after surgery. If available, magnetic resonance time-of-flight angiography (MR-TOF) was evaluated 3 months and 6–12 months post-operatively as well. Imaging results were analyzed and compared with CTA, MR-TOF and DSA, whereat DSA was used as the final and definite modality to decide on bypass patency.Results: A total of 103 direct EC-IC bypasses in 63 moyamoya patients were analyzed. All inclusion criteria were met in 32 patients (53 direct bypasses). In 84.9% the bypass appeared definitively, in 5.7% uncertainly and in 9.4% not patent according to early post-operative CTA. MR-TOF suggested definitive bypass patency in 86.8% 3 months after surgery and in 93.5% 6–12 months after surgery. DSA 6–12 months post-operatively showed a patency in 98.1% of all bypasses. The positive predictive value (to correctly detect an occluded bypass) on post-operative CTA was 12.5%, the negative predictive value (to correctly detect a patent bypass) was 100% with a sensitivity of 100% and a specificity of 86.5%.Conclusion: Early post-operative CTA has a high predictive value to confirm the patency of a bypass. On the other hand, a high false positive rate of (according to CTA) occluded bypasses after direct EC-IC bypass surgery can be seen. This must be considered critically when initiating possible therapeutic measures.

Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P

The growing concerns about climate changes and environmental pollution have galvanized considerable research efforts in recent years to develop effective and innovative remediation technologies for contaminated soils and water caused by industrial and domestic activities. In this context, the establishment of effective treatment methods for wastewater has been critically important and urgent, since water pollution can take place on a very large scale (e.g., oceanic oil spills) and have massive impacts on ecosystems and human lives. Functional materials play a central role in the advancement of these technologies due to their highly tunable properties and functions. This article focuses on reviewing the recent progress in the application of various functional materials for wastewater treatment. Our literature survey is first concentrated on new modification methods and outcomes for a range of functional materials which have been actively investigated in recent years, including biofilm carriers, sand filters, biomass, biopolymers, and functional inorganic materials. Apart from the development of modified functional materials, our literature survey also covers the technological applications of superhydrophilic/superhydrophobic meshes, hybrid membranes, and reusable sponges in oil–water separation. These devices have gained significantly enhanced performance by using new functional materials as the key components (e.g., coating materials), and are therefore highly useful for treatment of oily wastewater, such as contaminated water collected from an oil spill site or oil–water emulsions resulting from industrial pollution. Based on our state-of-the-art literature review, future directions in the development and application of functional materials for wastewater treatment are suggested.

We conducted a phase I/II multicenter trial using 6 cycles of brentuximab vedotin (BV) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for treatment of patients with CD30-positive (+) B-cell lymphomas. Thirty-one patients were evaluable for toxicity and 29 for efficacy including 22 with primary mediastinal B-cell lymphoma (PMBCL), 5 with diffuse large B-cell lymphoma (DLBCL), and 2 with gray zone lymphoma (GZL). There were no treatment-related deaths; 32% of patients had non-hematological grade 3/4 toxicities. The overall response rate was 100% (95% CI: 88-100) with 86% (95% CI: 68-96) of patients achieving complete response at the end of systemic treatment. Consolidative radiation following end of treatment response assessment was permissible and used in 52% of all patients including 59% of patients with PMBCL. With a median follow-up of 30 months, the 2-year progression-free survival (PFS) and overall survival (OS) were 85% (95% CI: 66-94) and 100%, respectively. In the PMBCL cohort, 2-year PFS was 86% (95% CI: 62-95). In summary, BV-R-CHP with or without consolidative radiation is a feasible and active frontline regimen for CD30+ B-cell lymphomas (NCT01994850).

Abstract: Attempts to improve upon the activity of ibrutinib in chronic lymphocytic leukemia (CLL) include the addition of targeted therapies. The combination of lenalidomide and rituximab demonstrated an overall response rate (ORR) of 66% with a complete response (CR) of 12% in the relapsed/refractory setting. Based on these data, we conducted a phase 1 study of rituximab (R), lenalidomide (L), and ibrutinib (I) in relapsed/refractory CLL. Patients received R 375 mg/m2 cycles 1 to 6 day 1, L on cycles 1 to 12 days 1 to 21, and I until disease progression. Dose escalation used a standard 3+3 design from a dose level (DL) of L 5 mg (DL1) and increasing to 15 mg (DL3) for a total of 3 dose levels. Twelve patients were enrolled; there were 2 dose-limiting toxicities of grade 4 neutropenia at DL3; thus, DL2 was the recommended phase 2 dose. A high incidence of sustained grade 4 neutropenia occurred at all dose levels, prompting study withdrawal in 5 patients, despite growth factor support. The ORR was 67%; ORR at the RP2D was 100% (1 CR). The 12-month progression-free survival at the RP2D was 83%. Preliminary efficacy data with the triplet did not appear superior to prior reports of the rituximab-lenalidomide doublet or single-agent ibrutinib. Given these findings and the sustained neutropenia, this regimen was not pursued. The study was registered at www.clinicaltrials.gov as #NCT02200848.

Complex neurological conditions can give rise to large scale transcriptomic changes that drive disease progression. It is likely that alterations in one or a few transcription factors or cofactors underlie these transcriptomic alterations. Identifying the driving transcription factors/cofactors is a non-trivial problem and a limiting step in the understanding of neurological disorders. Epilepsy has a prevalence of 1% and is the fourth most common neurological disorder. While a number of anti-seizure drugs exist to treat seizures symptomatically, none is curative or preventive. This reflects a lack of understanding of disease progression. We used a novel systems approach to mine transcriptome profiles of rodent and human epileptic brain samples to identify regulators of transcriptional networks in the epileptic brain. We find that Enhancer of Zeste Homolog 2 (EZH2) regulates differentially expressed genes in epilepsy across multiple rodent models of acquired epilepsy. EZH2 undergoes a prolonged upregulation in the epileptic brain. A transient inhibition of EZH2 immediately after status epilepticus (SE) robustly increases spontaneous seizure burden weeks later. This suggests that EZH2 upregulation is a protective. These findings are the first to characterize a role for EZH2 in opposing epileptogenesis and debut a bioinformatic approach to identify nuclear drivers of complex transcriptional changes in disease.

Background and purpose: Patients with Moyamoya Disease (MMD) need hemodynamic evaluation of vascular territories at risk of stroke. Today's investigative standards include H215O PET/CT with pharmacological challenges with acetazolamide (ACZ). Recent developments suggest that CO2-triggered blood‑oxygen-level-dependent (BOLD) functional MRI might provide comparable results to current standard methods for evaluation of territorial hemodynamics, while being a more widely available and easily implementable method. This study examines results of a newly developed quantifiable analysis algorithm for CO2-triggered BOLD MRI in Moyamoya patients and correlates the results with H215O PET/CT with ACZ challenge to assess comparability between both modalities. Methods: CO2-triggered BOLD MRI was performed and compared to H215O PET/CT with ACZ challenge in patients with angiographically proven MMD. Images of both modalities were analyzed retrospectively in a blinded, standardized fashion by visual inspection, as well as with a semi-quantitative analysis using stimuli-induced approximated regional perfusion-weighted data and BOLD-signal changes with reference to cerebellum. Results: 20 consecutive patients fulfilled the inclusion criteria, a total of 160 vascular territories were analyzed retrospectively. Visual analysis (4-step visual rating system) of standardized, color-coded cerebrovascular reserve/reactivity maps showed a very strong correlation (Spearman's rho = 0.9, P

Waste Electronic and Electrical Equipment (WEEE) is one of the fastest growing waste streams worldwide, with significant economic value due to the precious metals contained within. Currently, only a small share of the total globally produced quantity produced is treated effectively and a large amount of valuable non-renewable resources are being wasted. Moreover, the methods currently applied in industry on a large scale are not always environmentally friendly. Thus, an economically viable and environmentally friendly method that would achieve high recovery of certain elements is sought. The objective of this paper is to assess four different organic halides as leaching agents for gold recovery from WEEE. Two of them have been previously tested (namely N-bromosuccinimide, NBS, and N-chlorosuccinimide, NCS) and have shown promising results, whereas the other two are novel and were selected due to their lower toxicity levels (trichloroisocyanuric acid, TCICA, and tribromoisocyanuric acid, TBICA). Both commercially supplied pure gold powder and WEEE dust from a recycling company were used as the gold source. Results show that from a technical standpoint, the NBS is a superior solution with both substrates, reaching 61% and 99% extraction efficiency from WEEE dust and pure gold, respectively. The other three methods recorded lower recovery efficiency (with the highest value reaching 36% for NCS, 53% for TCICA and 29% for TBICA). However, taking into account the price of gold and the expenses of the extraction process, only three of the lixiviants tested (NBS, NCS and TCICA) could be potentially profitable and viable on a larger scale.

Lipid transfer protein (LTP) is a kind of small molecular protein, which is named for its ability to transfer lipid between cell membranes. It has been proved that the protein is involved in the responding to abiotic stresses. In this study, TaLTP-s, a genomic sequence of TaLTP was isolated from A genome of wheat (Triticum aestivum L). Sequencing analysis exhibited that there was no diversity in the coding region of TaLTP-s, but seven single nucleotide polymorphisms (SNPs) and 1 bp insertion/deletion (InDel) were detected in the promoter regions of different wheat accessions. Nucleotide diversity (π) in the region was 0.00033, and linkage disequilibrium (LD) extended over almost the entire TaLTP-s region in wheat. The dCAPS markers based on sequence variations in the promoter regions (SNP-207 and SNP-1696) were developed, and three haplotypes were identified based on those markers. Association analysis between the haplotypes and agronomic traits of natural population consisted of 262 accessions showed that three haplotypes of TaLTP-s were significantly associated with plant height (PH). Among the three haplotypes, HapIII is considered as the superior haplotype for increasing plant height in the drought stress environments. The G variance at the position of 207 bp could be a superior allele that significantly increased number of spikes per plant (NSP). The functional marker of TaLTP-s provide a tool for marker-assisted selection regarding to plant height and number of spikelet per plant in wheat.

Myelodysplastic syndrome (MDS) is a clonal stem-cell disorder characterized by dyshematopoiesis. We report a patient who presented with cytopenias and microangiopathic hemolytic anemia. Chromosome microarray analysis (CMA), using single nucleotide polymorphism arrays, on peripheral blood revealed genomic imbalances indicative of MDS, which was confirmed by bone marrow examination. This report highlights the importance of suspecting MDS in patients with cytopenias and microangiopathic hemolytic anemia. CMA of peripheral blood may assist in the preliminary diagnosis of MDS, representing a comparatively less invasive diagnostic procedure and may aid bone marrow evaluation when an aspirate sample is insufficient for conventional cytogenetic analysis.