Testing for t(3;8) in MYC/BCL6-rearranged large B-cell lymphoma identifies a high-risk subgroup with inferior survival.

ABSTRACT: A reciprocal t(3;8) BCL6::MYC fusion is common in large B-cell lymphoma (LBCL) with MYC and BCL6 disruption. These pseudo-double-hit cases are not adverse, whereas t(3;8)-MYC/BCL6 lymphoma has an inferior prognosis relative to other MYC-rearranged LBCL.

Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study.

ABSTRACT: During the COVID-19 pandemic, ibrutinib with or without rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. Because limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib with or without rituximab for untreated MCL were evaluated for treatment toxicity, response, and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 ≥ 30%). A total of 149 patients from 43 participating centers were enrolled: 74.1% male, median age 75 years, 75.2% Eastern Cooperative Oncology Group status of 0 to 1, 36.2% high-risk, and 8.9% autologous transplant candidates. All patients received ≥1 cycle ibrutinib (median, 8 cycles), 39.0% with rituximab. Grade ≥3 toxicity occurred in 20.3%, and 33.8% required dose reductions/delays. At 15.6-month median follow-up, 41.6% discontinued ibrutinib, 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2%, respectively. ORR was 77.3% (low risk) vs 59.0% (high risk) (P = .05) and 78.7% (ibrutinib-rituximab) vs 64.9% (ibrutinib; P = .13). Median progression-free survival (PFS) was 26.0 months (all patients); 13.7 months (high risk) vs not reached (NR) (low risk; hazard ratio [HR], 2.19; P = .004). Median overall survival was NR (all); 14.8 months (high risk) vs NR (low risk; HR, 2.36; P = .005). Median post-ibrutinib survival was 1.4 months, longer in 41.9% patients receiving subsequent treatment (median, 8.6 vs 0.6 months; HR, 0.36; P = .002). Ibrutinib with or without rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.

No ultrasounds detected from fungi when dehydrated.

Many organisms (including certain plant species) can be observed to emit sounds, potentially signifying threat alerts. Sensitivity to such sounds and vibrations may also play an important role in the lives of fungi. In this work, we explore the potential of ultrasound activity in dehydrating fungi, and discover that several species of fungi do not emit sounds (detectable with conventional instrumentation) in the frequency range of 10kHz to 210kHz upon dehydration. Over 5 terabytes of ultrasound recordings were collected and analysed. We conjecture that fungi interact via non-sound means, such as electrical or chemical.

Kombucha electronics: electronic circuits on kombucha mats.

A kombucha is a tea and sugar fermented by over sixty kinds of yeasts and bacteria. This symbiotic community produces kombucha mats, which are cellulose-based hydrogels. The kombucha mats can be used as an alternative to animal leather in industry and fashion once they have been dried and cured. Prior to this study, we demonstrated that living kombucha mats display dynamic electrical activity and distinct stimulating responses. For use in organic textiles, cured mats of kombucha are inert. To make kombucha wearables functional, it is necessary to incorporate electrical circuits. We demonstrate that creating electrical conductors on kombucha mats is possible. After repeated bending and stretching, the circuits maintain their functionality. In addition, the abilities and electronic properties of the proposed kombucha, such as being lighter, less expensive, and more flexible than conventional electronic systems, pave the way for their use in a diverse range of applications.

Propagation of electrical signals by fungi.

Living fungal mycelium networks are proven to have properties of memristors, capacitors and various sensors. To further progress our designs in fungal electronics we need to evaluate how electrical signals can be propagated through mycelium networks. We investigate the ability of mycelium-bound composites to convey electrical signals, thereby enabling the transmission of frequency-modulated information. Mycelium networks were found to reliably transfer signals with a recoverable frequency comparable to the input, in the 100Hz to 10 000Hz frequency range. Mycelial adaptive responses, such as tissue repair, may result in fragile connections, however. While the mean amplitude of output signals was not reproducible among replicate experiments exposed to the same input frequency, the variance across groups was highly consistent. Our work is supported by NARX modelling through which an approximate transfer function was derived. These findings advance the state of the art of using mycelium-bound composites in analogue electronics and unconventional computing.

Electrical response of fungi to changing moisture content.

Mycelium-bound composites are potential alternatives to conventional materials for a variety of applications, including thermal and acoustic building panels and product packaging. If the reactions of live mycelium to environmental conditions and stimuli are taken into account, it is possible to create functioning fungal materials. Thus, active building components, sensory wearables, etc. might be created. This research describes the electrical sensitivity of fungus to changes in the moisture content of a mycelium-bound composite. Trains of electrical spikes initiate spontaneously in fresh mycelium-bound composites with a moisture content between [Formula: see text] 95% and [Formula: see text] 65%, and between [Formula: see text] 15% and [Formula: see text] 5% when partially dried. When the surfaces of mycelium-bound composites were partially or totally encased with an impermeable layer, increased electrical activity was observed. In fresh mycelium-bound composites, electrical spikes were seen both spontaneously and when induced by water droplets on the surface. Also explored is the link between electrical activity and electrode depth. Future designs of smart buildings, wearables, fungi-based sensors, and unconventional computer systems may benefit from fungi configurations and biofabrication flexibility.

Transfer functions of proteinoid microspheres.

Proteinoids, or thermal proteins, are inorganic entities formed by heating amino acids to their melting point and commencing polymerisation to form polymeric chains. Typically, their diameters range from 1µm to 10µm. Some amino acids incorporated into proteinoid chains are more hydrophobic than others, leading proteinoids to cluster together when they are present in aqueous solutions at specific concentrations, allowing them to grow into microspheres. The peculiar structure of proteinoids composed of linked amino acids endows them with unique properties, including action-potential like spiking of electrical potential. These unique properties make ensembles of proteinoid microspheres a promising substrate for designing future artificial brains and unconventional computing devices. To evaluate a potential of proteinoid microspheres for unconventional electronic devices we measure and analyse the data-transfer capacities of proteinoid microspheres. In experimental laboratory conditions we demonstrate that the transfer function of proteinoids microspheres is a nontrivial phenomenon, which might be due to the wide range of proteinoid shapes, sizes, and structures.

Responsive fungal insoles for pressure detection.

Mycelium bound composites are promising materials for a diverse range of applications including wearables and building elements. Their functionality surpasses some of the capabilities of traditionally passive materials, such as synthetic fibres, reconstituted cellulose fibres and natural fibres. Thereby, creating novel propositions including augmented functionality (sensory) and aesthetic (personal fashion). Biomaterials can offer multiple modal sensing capability such as mechanical loading (compressive and tensile) and moisture content. To assess the sensing potential of fungal insoles we undertook laboratory experiments on electrical response of bespoke insoles made from capillary matting colonised with oyster fungi Pleurotus ostreatus to compressive stress which mimics human loading when standing and walking. We have shown changes in electrical activity with compressive loading. The results advance the development of intelligent sensing insoles which are a building block towards more generic reactive fungal wearables. Using FitzHugh-Nagumo model we numerically illustrated how excitation wave-fronts behave in a mycelium network colonising an insole and shown that it may be possible to discern pressure points from the mycelium electrical activity.

The Course of LIRADS 3 and 4 Hepatic Abnormalities as Correlated With Explant Pathology: A Single Center Experience.

Background and aims: The Liver Reporting and Data System (LI-RADS) is the standard classification of imaging findings of hepatic abnormalities for hepatocellular carcinoma (HCC) surveillance. We aimed to study the course of LI-RADS 3 and 4 (LR-3 and LR-4) abnormalities through correlations with explant pathology. Methods: A single center retrospective study of liver transplant recipients between January 2016 and September 2019 with HCC on explant pathology was conducted. Eligible patients were divided into three subgroups based on their LI-RADS classification: LR-3/4, LR-5 only, and combination of LR-3/4/5. Results: There were 116 eligible patients with 99 LR-3/4 observations (60 LR-3 and 39 LR-4); the rest had LR-5 lesions. LR-4 more often than LR-3 observations progressed to LR-5 (36% vs 12%) and with shorter duration during follow-up (median 175 days and 196 days). Mean size growth of LR-3 and LR-4 abnormalities were 2.6 and 3.8 mm; median growth rates were 0.2 and 0.4 mm/month, respectively. Numbers of HCC lesions per explant, largest HCC lesion size, and cumulative size were higher in LR-3/4/5 subgroup than LR-5 subgroup (P = 0.007, 0.007 and 0.006, respectively); 68% of LR-3 and 82% of LR-4 abnormalities were confirmed HCC on explant (P = 0.09). Conclusion: Compared to LR-3, more LR-4 abnormalities progressed to LR-5 (12% and 36%, respectively) in a shorter time and with faster growth rate. A high proportion of LR-3 and LR-4 lesions (68% and 82%, respectively) were confirmed HCC on explant, raising the question of whether excluding HCC based on radiologic criteria alone is adequate in those with LR-3/4 abnormalities.

Cardiac Magnetic Resonance in the Evaluation of COVID-19.

Cardiovascular involvement following COVID-19 is heterogeneous, prevalent and is often missed by echocardiography and serum biomarkers (such as troponin I and brain natriuretic peptide). Cardiac magnetic resonance (CMR) is the gold standard non-invasive imaging modality to phenotype unique populations after COVID-19, such as competitive athletes with a heightened risk of sudden cardiac death, patients with multisystem inflammatory syndrome, and people suspected of having COVID-19 vaccine-induced myocarditis. This review summarises the key attributes of CMR, reviews the literature that has emerged for using CMR for people who may have COVID-19-related complications after COVID-19, and offers expert opinion regarding future avenues of investigation and the importance of reporting findings.

Fungal electronics.

Fungal electronics is a family of living electronic devices made of mycelium bound composites or pure mycelium. Fungal electronic devices are capable of changing their impedance and generating spikes of electrical potential in response to external control parameters. Fungal electronics can be embedded into fungal materials and wearables or used as stand alone sensing and computing devices.

Marimo actuated rover systems.

BACKGROUND: The potential to directly harness photosynthesis to make actuators, biosensors and bioprocessors has been previously demonstrated in the literature. Herein, this capability has been expanded to more advanced systems - Marimo Actuated Rover Systems (MARS) - which are capable of autonomous, solar powered, movement. RESULTS: We demonstrate this ability is both a practical and viable alternative to conventional mobile platforms for exploration and dynamic environmental monitoring. Prototypes have been successfully tested to measure their speed of travel and ability to automatically bypass obstacles. Further, MARS is electromagnetically silent, thus avoiding the background noise generated by conventional electro/mechanical platforms which reduces instrument sensitivity. The cost of MARS is significantly lower than platforms based on conventional technology. CONCLUSIONS: An autonomous, low-cost, lightweight, compact size, photosynthetically powered rover is reported. The potential for further system enhancements are identified and under development.

Risk Factors for Repeat Infection and Mortality After Extraction of Infected Cardiovascular Implantable Electronic Devices.

OBJECTIVES: This study sought to investigate the factors associated with repeat infection following lead extraction procedures. BACKGROUND: Although lead extraction is an essential therapy for patients with cardiovascular implantable electronic device (CIED) infection, repeat infection still occurs in some patients. METHODS: The authors reviewed data for consecutive patients who underwent extraction of infected CIEDs from August 2003 to May 2019. Repeat infection was defined as infective endocarditis, sepsis with no alternative focus, or pocket infection after extraction of infected CIEDs. RESULTS: Extraction of infected CIEDs was performed in 496 patients. The most commonly implicated pathogen was Staphylococcus aureus (n = 188). In 449 patients (90.5%), all leads were completely extracted using only transvenous techniques. Thirty-three patients (6.7%) underwent surgical lead extraction, and 14 (2.8%) had retained leads or lead components. After a median follow-up of 352 [40 to 1,255] days after CIED extraction, 144 patients (29.0%) died. Repeat infection occurred in 47 patients (9.5%) with the median time from the extraction to repeat infection of 103 [45 to 214] days. In multivariable analysis, presence of a left ventricular assist device, younger age at extraction, and S. aureus infection were independent predictors of repeat infection. Additionally, chronic kidney disease, congestive heart failure, presence of septic emboli, S. aureus infection, and occurrence of major complications were independent predictors of increased mortality. CONCLUSIONS: Patients with S. aureus infection have a high risk of repeat infection and poor prognosis after CIED extraction. Repeat infection is also predicted by younger age and the presence of a left ventricular assist device, whereas mortality was predicted by congestive heart failure, chronic kidney disease, and septic emboli.

Health Care Professionals' Confidence and Preferences for Diagnostic Assays for SARS-CoV-2: A Global Study.

Background: The COVID-19 pandemic has led to an urgent requirement for novel diagnostic tests that determine infection with SARS-CoV-2 and the development of an immune response against it. The perspective of end users on the characteristics and clinical use of these assays has not been previously considered. Methods: We surveyed 17,186 health care professions (HCPs) in 29 countries to gauge opinion on the design, use, diagnostic impact and diagnostic accuracy of COVID-19 tests. Results were correlated with national statistics on the burden of disease and testing in individual countries. Results: HCPs overwhelmingly recognized the importance of COVID-19 tests but 37.1% were unsure of the appropriate timing of investigations relative to disease symptoms. Confidence in the diagnostic accuracy of assays varied inversely with COVID-19-related mortality in individual countries but had no relationship with the total number of tests performed. There was global consensus that the most important impact of positive antigen and antibody testing was confidence in returning to work following recovery. Saliva was the preferred sampling fluid for COVID-19 diagnostic tests in all groups surveyed. Conclusions: HCP input can ensure novel assays are fit for purpose in varied global health care settings, but HCPs may require support to effectively use novel diagnostics thus minimizing waste when supplies are limited.

Ibrutinib for mantle cell lymphoma at first relapse: a United Kingdom real-world analysis of outcomes in 211 patients.

Ibrutinib is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL) and clinical trial data supports use at second line compared to later relapse. We aimed to investigate outcomes and tolerability for ibrutinib when given second line in a real-world setting. Our multicentre retrospective analysis included 211 R/R MCL patients, median age 73 years, receiving ibrutinib second-line within the United Kingdom's National Health Service. Overall response to ibrutinib was 69% (complete response 27%). The median progression-free survival (PFS) was 17·8 months (95% CI 13·1-22·2) and median overall survival (OS) 23·9 months (95% CI 15·0-32·8). Drug-related adverse event led to dose reduction in 10% of patients and discontinuation in 5%. In patients with progressive disease, accounting for 100 of 152 patients stopping ibrutinib, 43% received further systemic therapy. Post-ibrutinib rituximab, bendamustine and cytarabine (R-BAC) showed a trend toward improved survival compared to alternative systemic treatments (post-ibrutinib median OS 14·0 months, 95% CI 8·1-19·8, vs. 3·6 months, 95% CI 2·6-4·5, P = 0·06). Our study confirms the clinical benefit and good tolerability of ibrutinib at first relapse in a real-world population. Patients progressing on ibrutinib had limited survival but outcomes with R-BAC in select patients were promising.

Efficacy of R-BAC in relapsed, refractory mantle cell lymphoma post BTK inhibitor therapy.

Patients with mantle cell lymphoma progressing on Bruton's tyrosine kinase inhibitor (BTKi) have very poor prognosis and there is currently no standard of care. In this retrospective cohort study, patients progressing on BTKi received R-BAC (rituximab, bendamustine, cytarabine). Overall response rate was 83% (complete response 60%) and 31% were bridged to allogeneic stem cell transplant (alloSCT). Median progression-free survival was 10.1 months (95% confidence interval (CI) 6·9-13·3) and median overall survival was 12·5 months (95% CI 11·0-14·0). In those consolidated with alloSCT only one patient relapsed. R-BAC demonstrates a high response rate in the post-BTKi setting and in transplant eligible patients is an effective bridge to alloSCT.

Contactless sensing of liquid marbles for detection, characterisation & computing.

Liquid marbles (LMs) are of growing interest in many fields, including microfluidics, microreactors, sensors, and signal carriers. The generation of LMs is generally performed manually, although there has recently been a burst of publications involving 'automatic marble makers'. The characteristics of a LM is dependent on many things, including how it is generated, it is therefore important to be able to characterise LMs once made. Here is presented a novel contactless LM sensor, constructed on a PCB board with a comb-like structure of 36 interlacing electrical traces, 100 µm wide and 100 µm apart. This cheap, scalable, and easy to use sensor exploits the inherent impedance (comprised of the electrical resistance, capacitive reactance and inductive reactance) of different LMs. With it, parameters of a LM can be easily determined, without interfering with the LM. These parameters are (1) particle size of the LM coating, (2) the concentration of a NaCl solution used as the LM core, and (3) the volume of the LM. Additionally, due to the comb-like nature of the sensor, the accurate positioning (down to the inter-trace spacing) of the LM can be ascertained. The new sensor has been shown to work under both static and dynamic (mobile) conditions. The capacitance of a LM was recorded to be 0.10 pF, which compares well with the calculated value of 0.12 pF.