Search

Auditory distractions are recognized to considerably challenge the quality of information encoding during speech comprehension. This study explores electroencephalography (EEG) microstate dynamics in ecologically valid, noisy settings, aiming to uncover how these auditory distractions influence the process of information encoding during speech comprehension. We examined three listening scenarios: (1) speech perception with background noise (LA), (2) focused attention on the background noise (BA), and (3) intentional disregard of the background noise (BUA). Our findings showed that microstate complexity and unpredictability increased when attention was directed towards speech compared with tasks without speech (LA > BA & BUA). Notably, the time elapsed between the recurrence of microstates increased significantly in LA compared with both BA and BUA. This suggests that coping with background noise during speech comprehension demands more sustained cognitive effort. Additionally, a two-stage time course for both microstate complexity and alpha-to-theta power ratio was observed. Specifically, in the early epochs, a lower level was observed, which gradually increased and eventually reached a steady level in the later epochs. The findings suggest that the initial stage is primarily driven by sensory processes and information gathering, while the second stage involves higher level cognitive engagement, including mnemonic binding and memory encoding., (© 2023 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Cryosurgery is a common destructive treatment method for intraepidermal carcinoma (IEC) above the knee. Curettage alone is a simple, non-aggressive and inexpensive treatment method commonly used on benign skin lesions. However, only one study has assessed curettage for treatment of IEC., Objective: We aimed to (1) compare the effectiveness of cryosurgery (standard method) to curettage (experimental method) for treatment of IEC in regard to overall clearance rates at 1-year follow-up, and (2) investigate whether wound healing times differed between the treatment groups., Methods: In this randomized and controlled, non-inferiority trial, adult patients with one or more IEC with a diameter of 5-20 mm, located above the knee and suitable for destructive treatment were recruited from Sahlgrenska University Hospital (Gothenburg, Sweden). Lesions were randomized to treatment with either cryosurgery or curettage. Wound healing was assessed by a nurse after 4-6 weeks and through self-report forms. Overall clearance was assessed by a dermatologist after 1 year., Results: In total, 183 lesions in 147 patients were included, with 93 lesions randomized to cryosurgery and 90 to curettage. Eighty-eight (94.6%) of the lesions in the cryosurgery group and 71 (78.9%) in the curettage group showed an overall clearance at the 1-year follow-up visit (p = 0.002). The non-inferiority analysis was inconclusive. Curettage resulted in both shorter self-reported wound healing times (mean time 3.1 vs. 4.8 weeks, p < 0.001) and a larger proportion of healed wounds after 4-6 weeks (p < 0.001)., Conclusions: Cryosurgery and curettage both result in high clearance rates for treatment of IEC, but cryosurgery is significantly more effective. On the other hand, curettage may result in shorter wound healing times., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Purpose of Review: Insomnia and obstructive sleep apnea have previously been viewed as completely independent conditions. However, there is now increasing recognition that insomnia and sleep apnea frequently co-occur. Co-morbid insomnia and sleep apnea (COMISA) is a highly prevalent condition that is associated with impairment of sleep, daytime function, mental health and physical health outcomes, and mortality risk. This review aims to provide an update on COMISA prevalence, consequences, treatment approaches, and future research directions., Recent Findings: People with COMISA experience worse sleep, mental health, physical health, quality of life and longevity compared to people with neither condition, and often compared to those with insomnia alone and sleep apnea alone. Emerging evidence suggests that cognitive behavioral therapy for insomnia is an effective treatment in the presence of treated and untreated sleep apnea, that may also improve manifestations and subsequent management of sleep apnea. Future research is required to understand the etiology of COMISA, and to develop and implement tailored treatment approaches., Summary: It is important for sleep and respiratory technicians, researchers and clinicians to be aware of the high co-morbidity rates, consequences, and treatment requirements of patients with co-morbid insomnia and sleep apnea., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Acclimation is a multigenic trait by which plants adjust photosynthesis and metabolism to cope with a changing environment. Here, natural variations of photosynthetic efficiency and acclimation of the central carbohydrate metabolism were analyzed in response to low and elevated temperatures. For this, 18 natural accessions of Arabidopsis thaliana, originating from Cape Verde Islands and Europe, were grown at 22°C before being exposed to 4°C and 34°C for cold and heat acclimation, respectively. Absolute amounts of carbohydrates were quantified together with their subcellular distribution across plastids, cytosol and vacuole. Linear electron transport rates (ETRs) were determined together with the maximum quantum efficiency of photosystem II (Fv/Fm) for all growth conditions and under temperature fluctuation. Under elevated temperature, ETR residuals under increasing photosynthetic photon flux densities significantly correlated with the degree of temperature fluctuation at the original habitat of accessions, indicating a geographical east/west gradient of photosynthetic acclimation capacities. Plastidial sucrose concentrations positively correlated with maximal ETRs under fluctuating temperature, indicating a stabilizing role within the chloroplast. Our findings revealed specific subcellular carbohydrate distributions that contribute differentially to the photosynthetic efficiency of natural Arabidopsis thaliana accessions across a longitudinal gradient. This sheds light on the relevance of subcellular metabolic regulation for photosynthetic performance in a fluctuating environment and supports the physiological interpretation of naturally occurring genetic variation of temperature tolerance and acclimation., (© 2023 The Authors. Physiologia Plantarum published by John Wiley & Sons Ltd on behalf of Scandinavian Plant Physiology Society.)

When bacterial communities mix, immigration history can fundamentally affect the community composition as a result of priority effects. Priority effects arise when an early immigrant exhausts resources and/or alters habitat conditions, thereby influencing the establishment success of the late arriver. The strength of priority effects is context-dependent and expected to be stronger if environmental conditions favour the growth of the first arriver. In this study, we conducted a two-factorial experiment testing the importance of nutrient availability and grazing on the strength of priority effects in complex aquatic bacterial communities. We did so by mixing two dissimilar communities, simultaneously, and with a 38 h time-delay. Priority effects were measured as the invasion resistance of the first community to the invading second community. We found stronger priority effects in treatments with high nutrient availability and absence of grazing, but in general, the arrival timing was less important than the selection by nutrients and grazing. At the population level, the results were complex, but priority effects may have been driven by bacteria belonging to for example, the genera Rhodoferax and Herbaspirillum. Our study highlights the importance of arrival timing in complex bacterial communities, especially if environmental conditions favour rapid community growth., (© 2023 The Authors. Environmental Microbiology published by Applied Microbiology International and John Wiley & Sons Ltd.)

A comprehensive model for routine multi-disciplinary health assessment for children in out-of-home care was piloted in a Norwegian region. This paper reports on identified service needs and mental disorders among 196 children (0-17 years) receiving the assessment. Cross-sectional data was extracted from assessment reports. Results show needs across a range of services, with a mean of 2.8 recommended services for children aged 0-6 and 3.3 for children aged 7-17. Mental disorders were identified in 50% of younger children, and 70% of older children. For all children, overall service need was associated with mental disorders, in addition to male gender among younger children. Need for specialized mental health services was associated with mental disorders among younger children and increasing age among older children. The high frequency of service needs and mental disorders illustrate the importance of offering comprehensive health assessments routinely to this high-risk child population and necessitates coordinated service delivery., (© 2023. The Author(s).)

Background: Gel dosimeters are a potential tool for measuring the complex dose distributions that characterize modern radiotherapy. A prototype tabletop solid-tank fan-beam optical CT scanner for readout of gel dosimeters was recently developed. This scanner does not have a straight raypath from source to detector, thus images cannot be reconstructed using filtered backprojection (FBP) and iterative techniques are required. Iterative image reconstruction requires a system matrix that describes the geometry of the imaging system. Stored system matrices can become immensely large, making them impractical for storage on a typical desktop computer., Purpose: Here we develop a method to reduce the storage size of optical CT system matrices through use of polar coordinate discretization while accounting for the refraction in optical CT systems., Methods: A ray tracing simulator was developed to track the path of light rays as they traverse the different mediums of the optical CT scanner. Cartesian coordinate discretized system matrices (CCDSMs) and polar coordinate discretized system matrices (PCDSMs) were generated by discretizing the reconstruction area of the optical CT scanner into a Cartesian pixel grid and a polar coordinate pixel grid, respectively. The length of each ray through each pixel was calculated and used to populate the system matrices. To ensure equal weighting during iterative reconstruction, the radial rings of PCDSMs were asymmetrically spaced such that the area of each polar pixel was constant. Two clinical phantoms and several synthetic phantoms were produced and used to evaluate the reconstruction techniques under known conditions. Reconstructed images were analyzed in terms of spatial resolution, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), signal nonuniformity (SNU), and Gamma map pass percentage., Results: A storage size reduction of 99.72% was found when comparing a PCDSM to a CCDSM with the same total number of pixels. Images reconstructed with a PCDSM were found to have superior SNR, CNR, SNU, and Gamma (1 mm, 1%) pass percentage compared to those reconstructed with a CCDSM. Increasing spatial resolution in the radial direction with increasing radial distance was found in both PCDSM and CCDSM reconstructions due to the outer regions refracting light more severely. Images reconstructed with a PCDSM showed a decrease in spatial resolution in the azimuthal directions as radial distance increases, due to the widening of the polar pixels. However, this can be mitigated with only a slight increase in storage size by increasing the number of projections. A loss of spatial resolution in the radial direction within 5 mm radially from center was found when reconstructing with a PCDSM, due to the large innermost pixels. However, this was remedied by increasing the number of radial rings within the PCDSM, yielding radial spatial resolution on par with images reconstructed with a CCDSM and a storage size reduction of 99.26%., Conclusions: Discretizing the image pixel elements in polar coordinates achieved a system matrix storage size reduction of 99.26% with only minimal reduction in the image quality., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

The latest evidence suggested that the onset of dilated cardiomyopathy (DCM) is closely associated with immune microenvironment disturbance. Since N 6 -methyladenosine (m6A) RNA methylation impacts on immunocyte function and antitumor immunity, it is predictable that m6A RNA methylation may result in immune microenvironment disorder. Here, we attempted to verify this hypothesis. We used single-sample gene set enrichment analysis (ssGSEA) to investigate the infiltration abundance of immunocytes, single-cell RNA-Seq to identify key m6A regulator, and a doxorubicin (Dox)-induced DCM mouse model to confirm our findings. ssGSEA revealed a higher infiltration abundance of CD8 + T lymphocytes, NK cells, monocytes, and B + lymphocytes in DCM myocardium tissue. Single-cell RNA-Seq indicated a critical role of IGFBP2 in DCM. Cross-checking analysis hinted an interaction between IGFBP2 and NSUN5, ALYREF, RRP8, and ALKBH3. Mechanically, IGFBP2-mediated RNA methylation deteriorated the immune microenvironment and thus increased the risk of DCM by enhancing CD8 + T lymphocyte, NK cell, monocyte, B + lymphocyte infiltration and activating check-point, MHC-I, and T cell co-stimulation signaling pathways. In the DCM mouse model, echocardiography indicated a significant reduction in ejection fraction (EF) and fractional shortening (FS) and an increase in left ventricular internal dimensions at systole (LVIDs) and diastole (LVIDd). MASSON staining indicated an increased fibrosis in myocardium tissue. qPCR and immunofluorescence staining indicated a significant increase in mRNA and protein levels of IGFBP2. The present study indicated that IGFBP2-mediated RNA methylation remodeled the immune microenvironment and increased the risk of DCM. IGFBP2 may serve as potential therapeutic target for DCM., (© 2023 Wiley Periodicals LLC.)

NASH is one of the leading causes of chronic liver disease with the potential of evolving towards end-stage liver disease and HCC, even in the absence of cirrhosis. Apart from becoming an increasingly prevalent indication for liver transplantation in cirrhotic and HCC patients, its burden on the healthcare system is also exerted by the increased number of noncirrhotic NASH patients. Intermittent fasting has recently gained more interest in the scientific community as a possible treatment approach for different components of metabolic syndrome. Basic science and clinical studies have shown that apart from inducing body weight loss, improving cardiometabolic parameters, namely blood pressure, cholesterol, and triglyceride levels; insulin and glucose metabolism; intermittent fasting can reduce inflammatory markers, endoplasmic reticulum stress, oxidative stress, autophagy, and endothelial dysfunction, as well as modulate gut microbiota. This review aims to further explore the main NASH pathogenetic metabolic drivers on which intermittent fasting can act upon and improve the prognosis of the disease, and summarize the current clinical evidence., (Copyright © 2023 American Association for the Study of Liver Diseases.)

International guidelines exclude from surgery patients with peritoneal carcinosis of colorectal origin and a peritoneal cancer index (PCI) ≥ 16. This study aims to analyze the outcomes of patients with colorectal peritoneal carcinosis and PCI greater or equal to 16 treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) (CRS + HIPEC). We retrospectively performed a multicenter observational study involving three Italian institutions, namely the IRCCS Policlinico San Matteo in Pavia, the M. Bufalini Hospital in Cesena, and the ASST Papa Giovanni XXIII Hospital in Bergamo. The study included all patients undergoing CRS + HIPEC for peritoneal carcinosis from colorectal origin from November 2011 to June 2022. The study included 71 patients: 56 with PCI < 16 and 15 with PCI ≥ 16. Patients with higher PCI had longer operative times and a statistically significant higher rate of not complete cytoreduction, with a Completeness of Cytoreduction score (CC) 1 (microscopical disease) of 30.8% (p = 0.004). The 2-year OS was 81% for PCI < 16 and 37% for PCI ≥ 16 (p < 0.001). The 2-years DFS was 29% for PCI < 16 and 0% for PCI ≥ 16 (p < 0.001). The 2-year peritoneal DFS for patients with PCI < 16 was 48%, and for patients with PCI ≥ 16 was 57% (p = 0.783). CRS and HIPEC provide reasonable local disease control for patients with carcinosis of colorectal origin and PCI ≥ 16. Such results form the basis for new studies to reassess the exclusion of these patients, as set out in the current guidelines, from CRS and HIPEC. This therapy, combined with new therapeutical strategies, i.e., pressurized intraperitoneal aerosol chemotherapy (PIPAC), could offer reasonable local control of the disease, preventing local complications. As a result, it increases the patient's chances of receiving chemotherapy to improve the systemic control of the disease., (© 2023. Italian Society of Surgery (SIC).)

Objective: This study investigated the moderating role of baseline depressive symptoms on the association between baseline pain severity and time to recovery in individuals with acute grade I-II whiplash-associated disorders., Design: This is a secondary analysis of a randomized controlled trial investigating the effectiveness of a government-regulated rehabilitation guideline for the management of grade I-II whiplash-associated disorders. Participants who completed baseline questionnaires for neck pain intensity and depressive symptoms and follow-up questionnaire on self-reported recovery were included in the analysis. Cox proportional hazards models were built, and hazard rate ratios were reported to describe the association between baseline neck pain intensity and time to self-reported recovery and to assess the effect modification of baseline depressive symptoms., Results: Three hundred three participants provided data for this study. Despite baseline level of depressive symptoms and neck pain intensity being independently associated with delayed recovery, the association between baseline neck pain intensity and time to recovery was not stronger for individuals with significant postcollision depressive symptoms (hazard rate ratio = 0.91; 95% confidence interval = 0.79-1.04) than for those without depressive symptoms (hazard rate ratio = 0.92; 95% confidence interval = 0.83-1.02)., Conclusions: Baseline depressive symptoms are not an effect modifier of the association between baseline neck pain intensity and time to self-reported recovery in acute whiplash-associated disorders., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

NAFLD is the most common chronic liver disease worldwide, characterized by lipid accumulation in the liver, and usually evolves from steatohepatitis to fibrosis, cirrhosis, or even HCC. Its incidence is rapidly rising in parallel with the increasing prevalence of obesity and metabolic syndrome. Current therapies are limited to lifestyle changes including dietary intervention and exercise, in which dietary modification exerts an important part in losing weight and preventing NAFLD. In this review, we briefly discuss the roles and mechanisms of dietary components including fructose, non-nutritive sweeteners, fat, proteins, and vitamins in the progression or prevention of NAFLD. We also summarize several popular dietary patterns such as calorie-restricted diets, intermittent fasting, ketogenic diets, Mediterranean diets, and dietary approach to stop hypertension diets and compare the effects of low-fat and low-carbohydrate diets in preventing the development of NAFLD. Moreover, we summarize the potential drugs targeting metabolic-related targets in NAFLD., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Music listening often entails spontaneous perception and body movement to a periodic pulse-like meter. There is increasing evidence that this cross-cultural ability relates to neural processes that selectively enhance metric periodicities, even when these periodicities are not prominent in the acoustic stimulus. However, whether these neural processes emerge early in development remains largely unknown. Here, we recorded the electroencephalogram (EEG) of 20 healthy 5- to 6-month-old infants, while they were exposed to two rhythms known to induce the perception of meter consistently across Western adults. One rhythm contained prominent acoustic periodicities corresponding to the meter, whereas the other rhythm did not. Infants showed significantly enhanced representations of meter periodicities in their EEG responses to both rhythms. This effect is unlikely to reflect the tracking of salient acoustic features in the stimulus, as it was observed irrespective of the prominence of meter periodicities in the audio signals. Moreover, as previously observed in adults, the neural enhancement of meter was greater when the rhythm was delivered by low-pitched sounds. Together, these findings indicate that the endogenous enhancement of metric periodicities beyond low-level acoustic features is a neural property that is already present soon after birth. These high-level neural processes could set the stage for internal representations of musical meter that are critical for human movement coordination during rhythmic musical behavior. RESEARCH HIGHLIGHTS: 5- to 6-month-old infants were presented with auditory rhythms that induce the perception of a periodic pulse-like meter in adults. Infants showed selective enhancement of EEG activity at meter-related frequencies irrespective of the prominence of these frequencies in the stimulus. Responses at meter-related frequencies were boosted when the rhythm was conveyed by bass sounds. High-level neural processes that transform rhythmic auditory stimuli into internal meter templates emerge early after birth., (© 2022 The Authors. Developmental Science published by John Wiley & Sons Ltd.)

Tropical and subtropical dry woodlands are rich in biodiversity and carbon. Yet, many of these woodlands are under high deforestation pressure and remain weakly protected. Here, we assessed how deforestation dynamics relate to areas of woodland protection and to conservation priorities across the world's tropical dry woodlands. Specifically, we characterized different types of deforestation frontier from 2000 to 2020 and compared them to protected areas (PAs), Indigenous Peoples' lands and conservation areas for biodiversity, carbon and water. We found that global conservation priorities were always overrepresented in tropical dry woodlands compared to the rest of the globe (between 4% and 96% more than expected, depending on the type of conservation priority). Moreover, about 41% of all dry woodlands were characterized as deforestation frontiers, and these frontiers have been falling disproportionately in areas with important regional (i.e. tropical dry woodland) conservation assets. While deforestation frontiers were identified within all tropical dry woodland classes of woodland protection, they were lower than the average within protected areas coinciding with Indigenous Peoples' lands (23%), and within other PAs (28%). However, within PAs, deforestation frontiers have also been disproportionately affecting regional conservation assets. Many emerging deforestation frontiers were identified outside but close to PAs, highlighting a growing threat that the conserved areas of dry woodland will become isolated. Understanding how deforestation frontiers coincide with major types of current woodland protection can help target context-specific conservation policies and interventions to tropical dry woodland conservation assets (e.g. PAs in which deforestation is rampant require stronger enforcement, inactive deforestation frontiers could benefit from restoration). Our analyses also identify recurring patterns that can be used to test the transferability of governance approaches and promote learning across social-ecological contexts., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Papillary muscle rupture is a fatal complication with a high operative mortality. Most patients experience cardiogenic shock and hypoxia due to pulmonary edema caused by severe mitral regurgitation. Although preoperative stabilization using a mechanical assist device potentially improves surgical outcomes, an appropriate strategy has not yet been established. ECPELLA, combining venoarterial extracorporeal membrane oxygenation and Impella, has the potential to stabilize preoperative status and improve outcome in patients with refractory cardiogenic shock due to papillary muscle rupture. Herein, we present 3 cases involving the efficacy of ECPELLA and our tips of surgical and ECPELLA management in patients with papillary muscle rupture., (© 2022. The Japanese Society for Artificial Organs.)

Background: Glenoid baseplate malpositioning during reverse total shoulder arthroplasty can contribute to perimeter impingement, dislocation, and loosening. Despite advances in preoperative planning, conventional instrumentation may lead to considerable inaccuracy in implant positioning unless patient-specific guides are used. Optical navigation has the potential to improve accuracy and precision when implanting a reverse shoulder arthroplasty baseplate. This systematic review aimed to analyze the most recent evidence on the accuracy and precision of glenoid baseplate positioning using intraoperative navigation and its potential impact on component selection and surgical time., Methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. The PubMed, Scopus, and EMBASE databases were queried in July 2022 to identify all studies that compared navigation vs. conventional instrumentation for reverse shoulder arthroplasty. Data of deviation from the planned baseplate version and inclination, the use of standard or augmented glenoid components, and surgical time were extracted. Quantitative analysis from the included publications was performed using the inverse-variance approach and Mantel-Haenszel method., Results: Of the 2,048 records identified in the initial query, only 10 articles met the inclusion and exclusion criteria, comprising 667 shoulders that underwent reverse total shoulder arthroplasty. The pooled mean difference (MD) of the deviation from the planned baseplate position for the clinical studies was -0.44 (95% confidence interval [CI], -3.26; p = 0.76; I2 = 36%) for version and -8.75 (95% CI, -16.83 to -0.68; p = 0.02; I2 = 83%) for inclination, both in favor of navigation. The odds ratio of selecting an augmented glenoid component after preoperative planning and navigation-assisted surgery was 8.09 (95% CI, 3.82-17.14; p < 0.00001; I2 = 60%). The average surgical time was 12 minutes longer in the navigation group (MD 12.46, 95% CI, 5.20-19.72; p = 0.0008; I2 = 71%)., Conclusions: Preoperative planning integrated with computer-assisted navigation surgery seems to increase the accuracy and precision of glenoid baseplate inclination compared with the preoperatively planned placement during reverse total shoulder arthroplasty. The surgical time and proportion of augmented glenoid components significantly increase when using navigation. However, the clinical impact of these findings on improving prosthesis longevity, complications, and patient functional outcomes is still unknown., Level of Evidence: Level III, systematic review and meta-analysis. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/A991)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Conventional forest inventories are labour-intensive. This limits the spatial extent and temporal frequency at which woody vegetation is usually monitored. Remote sensing provides cost-effective solutions that enable extensive spatial coverage and high sampling frequency. Recent studies indicate that convolutional neural networks (CNNs) can classify woody forests, plantations, and urban vegetation at the species level using consumer-grade unmanned aerial vehicle (UAV) imagery. However, whether such an approach is feasible in species-rich savanna ecosystems remains unclear. Here, we tested whether small data sets of high-resolution RGB orthomosaics suffice to train U-Net, FC-DenseNet, and DeepLabv3 + in semantic segmentation of savanna tree species. We trained these models on an 18-ha training area and explored whether models could be transferred across space and time. These models could recognise trees in adjacent (mean F1-Score = 0.68) and distant areas (mean F1-Score = 0.61) alike. Over time, a change in plant morphology resulted in a decrease of model accuracy. Our results show that CNN-based tree mapping using consumer-grade UAV imagery is possible in savanna ecosystems. Still, larger and more heterogeneous data sets can further improve model robustness to capture variation in plant morphology across time and space., (© 2023. Springer Nature Limited.)

Lumpy skin disease virus (LSDV), camelpox virus (CPV), and orf virus (ORFV) are members of the family Poxviridae. These viruses are usually isolated or produced in embryonated eggs or primary cells because continuous cell lines are less sensitive to infection. Disadvantages of the use of eggs or primary cells include limited availability, potential endogenous contaminants, and a limited ability to perform multiple passages. In this study, we developed a diploid cell culture from sheep embryonic hearts (EHs) and demonstrated its high proliferative and long-term storage capacities. In addition, we demonstrated its sensitivity to representatives of three genera of the family Poxviridae: Capripoxvirus (LSDV), Orthopoxvirus (CPV), and Parapoxvirus (ORFV). The cell culture had a doubling time of 24 h and reached 40 passages with satisfactory yield. This is comparable to that observed in primary lamb testis (LT) cells at passage 5 (P5). After infection, each poxvirus titer was 7.0-7.6 log TCID 50 /mL for up to five passages and approximately 6.8, 6.4, and 5.6 for the three viruses at P6-P25, P30, and P40, respectively. The sensitivity of sheep EH cells to poxvirus infection did not decrease after long-term storage in liquid nitrogen and was higher than that of primary LT cells, which are used for capripoxvirus and parapoxvirus detection and growth, and Vero cells, which are used for orthopoxvirus detection and growth. Thus, EH diploid cells are useful for poxvirus isolation and production without embryonated eggs or primary cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Controlled mRNA storage and stability is essential for oocyte meiosis and early embryonic development. However, how to regulate mRNA storage and stability in mammalian oogenesis remains elusive. Here we showed that LSM14B, a component of membraneless compartments including P-body-like granules and mitochondria-associated ribonucleoprotein domain (MARDO) in germ cell, is indispensable for female fertility. To reveal loss of LSM14B disrupted primordial follicle assembly and caused mRNA reduction in non-growing oocytes, which was concomitant with the impaired assembly of P-body-like granules. 10× Genomics single-cell RNA-sequencing and immunostaining were performed. Meanwhile, we conducted RNA-seq analysis of GV-stage oocytes and found that Lsm14b deficiency not only impaired the maternal mRNA accumulation but also disrupted the translation in fully grown oocytes, which was closely associated with dissolution of MARDO components. Moreover, Lsm14b-deficient oocytes reassembled a pronucleus containing decondensed chromatin after extrusion of the first polar body, through compromising the activation of maturation promoting factor, while the defects were restored via WEE1/2 inhibitor. Together, our findings reveal that Lsm14b plays a pivotal role in mammalian oogenesis by specifically controlling of oocyte mRNA storage and stability., (© 2023. The Author(s).)

The rapidly increasing availability of sequence information for tumor patients, combined with expanding treatment options, motivates efforts to monitor the course of disease for individual patients by analyzing patient-specific mutations in liquid biopsies, as highly specific markers of the malignancy. We discuss the suitability of established molecular methods to monitor patients with malignancies, in particular leukemias, comparing these to the recently developed super rolling circle amplification technique for highly sensitive, parallel measurements of mutant sequences using readily available instruments. The very high sensitivity for tumor-specific mutations-in combination with low cost and ready access at clinics-promises to allow routine monitoring of increasing numbers of tumor patients, in order to initiate improved treatments at the earliest timepoint possible, when necessary. A method with high-enough accuracy to enable monitoring in peripheral blood rather than bone marrow samples would present a great practical advantage, not least from the patient perspective. We describe scenarios in which sufficiently sensitive, inexpensive methods for mutational analysis can provide valuable guidance for the clinician in choosing among therapeutic options and adjusting ongoing treatment and help to promptly identify recurrences of disease in treated patients., (© 2023 The Association for the Publication of the Journal of Internal Medicine.)

Objective: The purpose of this systematic review with meta-analysis was to examine the effectiveness of exercise with behavior change techniques (BCTs) on core outcome sets in people with knee osteoarthritis., Literature Survey: We searched randomized controlled trials (RCTs) in eight databases (MEDLINE, Embase, CENTRAL, CINAHL, PsycINFO, PEDro, ICTRP, and ClinicalTrials.gov) up to November 4, 2021., Methodology: Eligible participants were people with knee osteoarthritis. The intervention was exercise with BCTs. Primary outcomes included physical function, quality of life (QOL) 6 to 12 months after intervention, and adverse events. Secondary outcomes were knee pain, exercise adherence, mobility, and self-efficacy 3 months or more after intervention. The bias risk was assessed using the Risk of Bias 2 tool. The random-effects model was used for the meta-analysis., Synthesis: We found 16 individual BCTs, and 37.7% of trials used a single BCT. For meta-analysis, we included 21 RCTs (n = 1623). Most outcomes had a very low certainty of evidence, and the risk of bias was the consistent reason for downgrading evidence levels. The standardized mean difference (SMD) with 95% confidence interval (95% CI) was 0.00 (-0.24, 0.24) in physical function, 0.33 (-0.51, 1.17) in exercise adherence, and 0.04 (-0.39, 0.47) in self-efficacy. The risk ratio (95% CI) of adverse events was 3.6 (0.79, 16.45). QOL was not pooled due to insufficient data (very low certainty of evidence). In contrast, the SMD (95% CI) for knee pain reduction and mobility improvement was -0.33 (-0.53, -0.13) and 0.21 (-0.05, 0.47) with moderate and low certainty of evidence, respectively., Conclusion: The evidence is inconclusive regarding the effectiveness of BCTs with exercises on core outcome sets. Further research should explore the effectiveness of BCTs with valid design., Protocol Registration: PROSPERO (CRD42020212904)., (© 2022 American Academy of Physical Medicine and Rehabilitation.)

Background: Post-acute myocardial infarction papillary muscle rupture (post-AMI PMR) may present variable clinical scenarios and degree of emergency due to result of cardiogenic shock. Veno-arterial extracorporeal life support (V-A ECLS) has been proposed to improve extremely poor pre- or postoperative conditions. Information in this respect is scarce., Methods: From the CAUTION (meChanical complicAtion of acUte myocardial infarcTion: an InternatiOnal multiceNter cohort study) database (16 different Centers, data from 2001 to 2018), we extracted adult patients who were surgically treated for post-AMI PMR and underwent pre- or/and postoperative V-A ECLS support. The end-points of this study were in-hospital survival and ECLS complications., Results: From a total of 214 post-AMI PMR patients submitted to surgery, V-A ECLS was instituted in 23 (11%) patients. The median age was 61.7 years (range 46-81 years). Preoperatively, ECLS was commenced in 10 patients (43.5%), whereas intra/postoperative in the remaining 13. The most common V-A ECLS indication was post-cardiotomy shock, followed by preoperative cardiogenic shock and cardiac arrest. The median duration of V-A ECLS was 4 days. V-A ECLS complications occurred in more than half of the patients. Overall, in-hospital mortality was 39.2% (9/23), compared to 22% (42/219) for the non-ECLS group., Conclusions: In post-AMI PMR patients, V-A ECLS was used in almost 10% of the patients either to promote bridge to surgery or as postoperative support. Further investigations are required to better evaluate a potential for increased use and its effects of V-A ECLS in such a context based on the still high perioperative mortality., (© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Astrocytes constitute the parenchymal border of the blood-brain barrier (BBB), modulate the exchange of soluble and cellular elements, and are essential for neuronal metabolic support. Thus, astrocytes critically influence neuronal network integrity. In hypoxia, astrocytes upregulate a transcriptional program that has been shown to boost neuroprotection in several models of neurological diseases. We investigated transgenic mice with astrocyte-specific activation of the hypoxia-response program by deleting the oxygen sensors, HIF prolyl-hydroxylase domains 2 and 3 (Phd2/3). We induced astrocytic Phd2/3 deletion after onset of clinical signs in experimental autoimmune encephalomyelitis (EAE) that led to an exacerbation of the disease mediated by massive immune cell infiltration. We found that Phd2/3-ko astrocytes, though expressing a neuroprotective signature, exhibited a gradual loss of gap-junctional Connexin-43 (Cx43), which was induced by vascular endothelial growth factor-alpha (Vegf-a) expression. These results provide mechanistic insights into astrocyte biology, their critical role in hypoxic states, and in chronic inflammatory CNS diseases., (© 2023 The Authors. GLIA published by Wiley Periodicals LLC.)

Background: Insights into the burden, needs and treatment of migraine from internet-based surveys in diverse real-world migraine populations are needed, especially at a time when novel preventive migraine medications are becoming part of the therapeutic armamentarium. The objectives of this analysis are to describe traditional preventive (orals and onabotulinum toxin A) treatment patterns in the OVERCOME (EU) study migraine cohort, as well as treatment patterns and patient satisfaction with current treatment in a subgroup of respondents eligible for migraine preventive medication., Methods: The cross-sectional non-interventional OVERCOME (EU) study was conducted (October 2020-February 2021) via an online survey among adults (aged ≥ 18 years) resident in Germany or Spain. Participants, registered in existing online panels, who were willing to provide consent were considered. The migraine cohort included participants reporting headache/migraine in the past year, identified based on a validated migraine diagnostic questionnaire and/or self-reported physician diagnosis. A subgroup of survey respondents defined as eligible for migraine preventive medication at the point in time the cross-sectional survey was taken was also analysed. Variables assessed included sociodemographic and migraine-related clinical characteristics, preventive (traditional and calcitonin gene-related peptide monoclonal antibodies) treatment patterns and patient satisfaction with current treatment. Results are descriptive only., Results: Of the 20,756 participants in the migraine cohort, 78.5% sought professional medical care, 50.8% received a migraine diagnosis and only 17.7% had ever used preventive medication. Half (53.3%) of participants currently using preventives took their most recent medication for six months or less. Most patients (73.9%) classified as eligible for preventive medication (based on headache frequency and/or at least moderate disability due to migraine) reported not using traditional preventives and many of those who did (66.8%) were not satisfied with their current standard of care., Conclusions: Our findings highlight the low proportion of people diagnosed with migraine despite a higher rate of consultation and suggest the need for better access to treatment for people with migraine and new preventive therapies with improved efficacy and safety profiles to improve adherence and patient satisfaction., (© 2023. The Author(s).)

This paper reports on a superhydrophilic to superhydrophobic transformation of TiO 2 nanoparticles doped zinc phosphate coating systems when a hydrophobic agent is applied. The objective of the reported research was to demonstrate the feasibility of a neutron imaging technique for evaluating the performance of the proposed nano-coating system and reveal the differences in water ingress mechanisms which are specific to plain, superhydrophilic, overhydrophobic, and superhydrophobic specimens. The engineered nano-coatings were designed to improve hydrophobic response with inducing the required roughness pattern and introducing the photocatalytic performance. The effectiveness of the coatings was assessed using high-resolution neutron imaging (HR-NI), SEM, CLSM, and XRD techniques. High-resolution neutron imaging revealed that the superhydrophobic coating effectively prevents water ingress into the porous ceramic substrate, whereas water imbibition was observed for superhydrophilic coating during the test duration. The moisture transport kinetics was modeled based on the Richards equation for plain ceramic and superhydrophilic specimens using obtained penetration depth values from HR-NI. SEM, CLSM, and XRD studies confirm the desired TiO 2 -doped zinc phosphate coatings with increased surface roughness, photocatalytic reactivity, and chemical bonding. The research results demonstrated that a two-layer superhydrophobic system is capable of creating effective water barriers on the surface with contact angles of 153°, which remained effective even after surface damage., (© 2023. The Author(s).)

Anthropogenic eutrophication is a global environmental problem threatening the ecological functions of many inland freshwaters and diminishing their abilities to meet their designated uses. Water authorities worldwide are being pressed to improve their abilities to monitor, predict, and manage the incidence of harmful algal blooms (HABs). While most water quality management decisions are still based on conventional monitoring programs that lack the needed spatio-temporal resolution for effective lake/reservoir management, recent advances in remote sensing are providing new opportunities towards better understanding water quality variability in these important freshwater systems. This study assessed the potential of using the Sentinel 2 Multispectral Instrument to predict and assess the spatio-temporal variability in the water quality of the Qaraoun Reservoir, a poorly monitored Mediterranean hypereutrophic monomictic reservoir that is subject to extensive periods of HABs. The work first evaluated the ability to transfer and recalibrate previously developed reservoir-specific Landsat 7 and 8 water quality models when used with Sentinel 2 data. The results showed poor transferability between Landsat and Sentinel 2, with most models experiencing a significant drop in their predictive skill even after recalibration. Sentinel 2 models were then developed for the reservoir based on 153 water quality samples collected over 2 years. The models explored different functional forms, including multiple linear regressions (MLR), multivariate adaptive regression splines (MARS), random forests (RF), and support vector regressions (SVR). The results showed that the RF models outperformed their MLR, MARS, and SVR counterparts with regard to predicting chlorophyll-a, total suspended solids, Secchi disk depth, and phycocyanin. The coefficient of determination (R 2 ) for the RF models varied between 85% for TSS up to 95% for SDD. Moreover, the study explored the potential of quantifying cyanotoxin concentrations indirectly from the Sentinel 2 MSI imagery by benefiting from the strong relationship between cyanotoxin levels and chlorophyll-a concentrations., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Cyanobacterial harmful algal blooms (CHABs) are a global environmental concern that encompasses public health issues, water availability, and water quality owing to the production of various secondary metabolites (SMs), including cyanotoxins in freshwater, brackish water, and marine ecosystems. The frequency, extent, magnitude, and duration of CHABs are increasing globally. Cyanobacterial species traits and changing environmental conditions, including anthropogenic pressure, eutrophication, and global climate change, together allow cyanobacteria to thrive. The cyanotoxins include a diverse range of low molecular weight compounds with varying biochemical properties and modes of action. With the application of modern molecular biology techniques, many important aspects of cyanobacteria are being elucidated, including aspects of their diversity, gene-environment interactions, and genes that express cyanotoxins. The toxicological, environmental, and economic impacts of CHABs strongly advocate the need for continuing, extensive efforts to monitor cyanobacterial growth and to understand the mechanisms regulating species composition and cyanotoxin biosynthesis. In this review, we critically examined the genomic organization of some cyanobacterial species that lead to the production of cyanotoxins and their characteristic properties discovered to date., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Neurodegenerative syndromes present as proteinopathies - does ribosomal infidelity contribute to the protein toxicity that is the driving force for neuronal cell loss? Intracellular and extracellular protein aggregates overwhelm the clearance capacity of cells and tissues. Proteins aggregate when hydrophobic residues are exposed. Hydrophobic residues become exposed when proteins are misfolded. Protein misfolding can originate from translational errors at the ribosome. Indeed, the most error-prone process in gene expression is translation at the ribosome. Recent evidence indicates that manipulating the ribosomal accuracy impacts on the lifespan of model organisms and a reduced translational accuracy is accompanied by neurodegeneration. The first hit in aging-associated neurodegenerative disease may be the well-documented decline of cellular buffering capacity by aging. A second hit that impacts on the quality of protein synthesis could be the driving force for the observed loss of proteostasis in neurodegeneration. This hypothesis provides an explanation for the late onset of most neurodegenerative diseases., (© 2023 The Authors. BioEssays published by Wiley Periodicals LLC.)

Cruciferous plants are frequently used for ecologically benign weed control in agricultural production. Most effective Broccoli varieties were screened using the entropy method-based topsis model at first. Result showed that varieties of Lvwawa and Lvbaoshiwere most effective in allelopathic suppression on radishes. Column and thin-layer chromatography were used to extract the allelopathic compounds from broccoli residues, which contained various herbicidal active substances; among them, purified single-molecule indole-3-acetonitrile has a stronger inhibitory effect than pendimethalin (commercial herbicide). The weed inhibition rate increased with increasing broccoli residue dosage, with a 40 g/m 2 broccoli residue dose yielding the highest suppression rate. Its effect was similar to that of indole-3-acetic acid. Too much of this substance leads to the plant's death. Moreover, broccoli residues had effective control effect on weeds in natural soils in greenhouse and field trials. The results demonstrated that broccoli residue could be used for weed management in field for abundant allopathic suppression molecules to weeds, and that Indole-3-acetonitrile is one of the most important allopathic molecule., (© 2023 The Authors. Chemistry & Biodiversity published by Wiley-VHCA AG, Zurich, Switzerland.)

The eutrophication of river-type urban landscape (RTUL) lakes is different from that of natural lakes. In this study, Xiaofu Lake, a typical RTUL lake with high anthropogenic interference, was used as the study area. Monitoring data from 2018 to 2020 were used to analyze the temporal and spatial distribution characteristics of chlorophyll a (Chl-a) concentrations with meteorological, hydrodynamic, and nutrient factors. Correlation and regression analyses were used to identify the relationship between the factors influencing eutrophication and the Chl-a. The MIKE21 model is used to simulate changes in water quality indicators. The study determined the relationship between river water quality and environmental factors and explored the causes of eutrophication in the water bodies of Xiaofu Lake. The results showed that from 2018 to 2020, the water quality showed seasonal variation and differences in spatial distribution. Except for total nitrogen, which remained at a high level (average 8.23 mg/L), other water qualities remained between classes II and IV. The proportions of mild, moderate, and severe eutrophication in the study area were 25%, 69%, and 6%, respectively. Indicators that were highly correlated with water eutrophication were turbidity, water temperature, total phosphorus, and permanganate index. The contribution of water temperature, ammonia nitrogen, and permanganate index to eutrophication was 30.5%, 22.6%, and 20.9%, respectively. The high proportion of sewage in the source of recharge water is one of the reasons for the deterioration of water quality. In addition, the change in water eutrophication was closely related to the gate operation in the region. PRACTITIONER POINTS: There are differences between river-type urban landscape (RTUL) lakes and natural lakes, and the conditions that cause eutrophication are different. RTUL are subject to strong human interference and rely on water transfer and gate scheduling to maintain water quantity. The high proportion of sewage treatment plant tailwater in upstream water is the main reason for the long-term pollution of RTUL. The indicators highly correlated with water eutrophication are turbidity, water temperature, total phosphorus, and permanganate index., (© 2023 Water Environment Federation.)

Papillary muscle rupture (PMR) is a rare complication of acute myocardial infarction (AMI) associated with high mortality and morbidity. Surgery is the gold-standard treatment for these patients, but it is burdened by a high perioperative risk due to hemodynamic instability. Mitral transcatheter edge-to-edge repair (M-TEER) was reported to be safe and effective in unstable patients with significant mitral regurgitation. However, data in patients with post-AMI PMR are limited to a few case reports. In this review, we summarized all data available regarding percutaneous treatment of post-AMI PMR. These results show that M-TEER is safe and effective in this setting with low in-hospital mortality and complications and high rate of significant mitral regurgitation reduction., (© 2023 Wiley Periodicals LLC.)

The progression of disease for an individual can be described mathematically as a stochastic process. The individual experiences a failure event when the disease path first reaches or crosses a critical disease level. This happening defines a failure event and a first hitting time or time-to-event, both of which are important in medical contexts. When the context involves explanatory variables then there is usually an interest in incorporating regression structures into the analysis and the methodology known as threshold regression comes into play. To date, most applications of threshold regression have been based on parametric families of stochastic processes. This paper presents a semiparametric form of threshold regression that requires the stochastic process to have only one key property, namely, stationary independent increments. As this property is frequently encountered in real applications, this model has potential for use in many fields. The mathematical underpinnings of this semiparametric approach for estimation and prediction are described. The basic data element required by the model is a pair of readings representing the observed change in time and the observed change in disease level, arising from either a failure event or survival of the individual to the end of the data record. An extension is presented for applications where the underlying disease process is unobservable but component covariate processes are available to construct a surrogate disease process. Threshold regression, used in combination with a data technique called Markov decomposition, allows the methods to handle longitudinal time-to-event data by uncoupling a longitudinal record into a sequence of single records. Computational aspects of the methods are straightforward. An array of simulation experiments that verify computational feasibility and statistical inference are reported in an online supplement. Case applications based on longitudinal observational data from The Osteoarthritis Initiative (OAI) study are presented to demonstrate the methodology and its practical use., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The Migraine Disability Assessment Scale (MIDAS) is one of the tools for measuring and understanding disability caused by migraine. The purpose of this study was to validate a Kiswahili translation of the MIDAS (MIDAS-K) among patients suffering from migraines in Dar es Salaam, Tanzania., Methods: A psychometric validation study of MIDAS was conducted after translation to Kiswahili. A total of 70 people with migraine were recruited by systematic random sampling and they completed the MIDAS-K questionnaire twice, 10-14 days apart. Internal consistency, split-half reliability, and test-retest reliability, convergent and divergent validity were examined., Results: 70 patients (F:M; 59:11) with median (25th, 75th) headache days of 4.0 (2.0, 7.0) were recruited. Twenty-eight out of 70 (40%) of the population had severe disability on MIDAS-K. The overall test-retest reliability of MIDAS-K was high (ICC = 0.86; 95% CI = 0.78-0.92 p < 0.001). Factor analysis showed a two-factor structure; the number of days missed and reduced efficiency. MIDAS-K had a good internal consistency of 0.78, good split-half reliability of 0.80 and acceptable test-retest reliability for all items as well as total MIDAS-K scores., Conclusion: The Kiswahili version of the MIDAS questionnaire (MIDAS-K) is a valid, responsive, and reliable tool to measure migraine-related disability among Tanzanians and other Swahili-speaking populations. Quantification of migraine disability in the region will guide policies directed at care allotment, improvement in the provision of interventions for migraine, as well as enhancement of health-related quality of life for patients with migraine in our region., (© 2023 American Headache Society.)

Low dimensional materials have attracted great research interest from both theoretical and experimental point of views. These materials exhibit novel physical and chemical properties due to the confinement effect in low dimensions. The experimental observations of graphene open a new platform to study the physical properties of materials restricted to two dimensions. This featured article provides a review on the novel properties of quasi one-dimensional (1D) material known as graphene nanoribbon. Graphene nanoribbons can be obtained by unzipping carbon nanotubes (CNT) or cutting the graphene sheet. Alternatively, it is also called the finite termination of graphene edges. It gives rise to different edge geometries, namely zigzag and armchair, among others. There are various physical and chemical techniques to realize these materials. Depending on the edge type termination, these are called the zigzag and armchair graphene nanoribbons (ZGNR and AGNR). These edges play an important role in controlling the properties of graphene nanoribbons. The present review article provides an overview of the electronic, transport, optical, and magnetic properties of graphene nanoribbons. However, there are different ways to tune these properties for device applications. Here, some of them, such as external perturbations and chemical modifications, are highlighted. Few applications of graphene nanoribbon have also been briefly discussed., (© 2022 John Wiley & Sons Ltd.)

The use of continuous subcutaneous insulin infusion (CSII) via insulin pumps is today considered standard of care for type 1 diabetes (T1D). Closed-loop systems combining continuous glucose monitoring with automated algorithm-driven insulin delivery have been shown to be safe and efficacious in randomized controlled trials and real-life studies in both paediatric and adult participants with T1D. Implementation of hybrid closed-loop (HCL) systems has shown incremental effectiveness, with further reduction of hypoglycaemia and hyperglycaemia. Although less extensively studied in type 2 diabetes (T2D), insulin pumps have demonstrated their effectiveness in glucose control, along with a reduction in need for insulin and a neutral effect on weight. Recent studies have also shown promising results with the use of HCL systems in T2D. Cost-effectiveness studies in both T1D and T2D have shown that pump use is cost-effective in several countries, leading to improvements in quality-adjusted life-years. Insulin pumps are currently reimbursed for T1D in many European countries, but in only a few for individuals with T2D. HCL systems are to be evaluated in future trials performed in T2D to compare their incremental efficacy and cost-effectiveness in comparison with available intensification tools which include multiple daily insulin injections, metformin, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. There is a need for updated guidelines for the use of CSII and HCL in individuals living with T2D based on the emerging evidence, with identification of and recommendations for the people who would benefit the most, which would eventually form a basis for reimbursement and health policies., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

CD30 is a transmembrane protein from the tumour necrosis factor receptor superfamily. It is expressed on a small subset of activated T and B lymphocytes, and various lymphoid neoplasms. CD30 is a particularly interesting treatment target because its levels are high in tumours but low in healthy tissues. Several therapeutic strategies targeting CD30 have been developed, including monoclonal antibodies, conjugated antibodies (combination of brentuximab vedotin with chemotherapy or immunotherapy), bispecific antibodies and cell and gene therapies, such as anti-CD30 CAR-T cells in particular. We briefly review the biology of CD30 which makes it a good therapeutic target, and we describe all of the anti-CD30 therapies that have emerged to date., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The 6p25 deletion syndrome is a rare genetic disorder characterized by a wide spectrum of congenital anomalies. Ophthalmic abnormalities appear to be highly associated with the syndrome, although this relationship has not been well characterized to date. We conducted a systematic literature review to highlight the ocular features in patients with this deletion syndrome and describe a 7-month-old female who has a 6.07 MB 6p25.1p25.3 deletion and a 4.25 MB 17q25.3 duplication. Our patient presented with multiple congenital anomalies, including macrocephaly, frontal bossing, low set ears, tent-shaped mouth, saddle nose, flat midface, and hearing impairment. Her ophthalmic features included proptosis, down-slanting palpebral fissures, hypertelorism, nystagmus, bilateral posterior embryotoxon, and decentered and abnormally shaped pupils. A systematic review of the published cases with sufficient clinical eye descriptions included 63 cases with a confirmed 6p25 deletion. The most common eye findings observed were posterior embryotoxon, iris hypoplasia, corectopia, cornea opacity, and glaucoma., (© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Herein we report the structure-activity relationship (SAR) studies and optimization of new highly potent and selective CRTH2 receptor antagonists as potential follow-ups of our previous reported clinical candidate setipiprant (ACT-129968) for the treatment of respiratory diseases. Structural modification of the amide part of setipiprant (ACT-129968) led to the identification of the tetrahydrocarbazole derivative (S)-B-1 (ACT-453859) ((S)-2-(3-((5-chloropyrimidin-2-yl)(methyl)amino)-6-fluoro-1,2,3,4-tetrahydro-9H-carbazol-9-yl)acetic acid). This compound which displayed a substantial improvement in potency in the presence of plasma versus setipiprant (ACT-129968) has exhibited an excellent overall pharmacokinetic profile. Further lead optimization to overcome a safety issue as observed in non-clinical studies with (S)-B-1 (ACT-453859), led to the discovery of the 4-azaindole derivative (S)-72 (ACT-774312) ((S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid) which was selected as a potential follow-up of setipiprant (ACT-129968)., (© 2023 Wiley-VCH GmbH.)

Arcobacter spp. has gained clinical significance as an emerging diarrheagenic pathogen associated with water reservoirs in recent years. The complete clinical significance of Arcobacter remains rather speculative due to the virulence and antibiotic susceptibility of individual strains. This study aimed to assess the prevalence of Arcobacter spp. in fish, water, and shellfish. A total of 150 samples were collected from the Adana, Kayseri and Kahramanmaras provinces in Turkey. Arcobacter spp. was isolated from 32 (21%) of the 150 samples. The most prevalent species was A. cryaerophilus, 17 (56%), A. butzleri 13 (37%) and A. lacus 2 (6%). As a result, the ratios of the mviN, irgA, pldA, tlyA and hecA target genes were found as 17 (51%), 1 (3%), 7 (23%), 7 (23%), 1 (3%), respectively. While bla OXA-61, tetO and tetW were positive in all isolates, were found as mcr1/2/6, mcr3/7, and mcr5, genes %37.5, %25, and %34.3, respectively. Although in A. butzleri was found 10 (58%), 1 (3%), 3 (43%), 2 (28%) (mviN, irgA, pldA, and tlyA, respectively) virulence genes 7 (42%), 4 (57%), 5 (72%), 1 (3%) was found (mviN, irgA, tlyA, and hecA, respectively) virulence genes in A. cryoaerophilus. Moreover, was found for the mcr 1/2/6 7 (58%) genes, for the mcr 3/7 genes 3 (38%) in A. butzleri. In A. cryoaerophilus was found for the mcr 1/2/6 genes 5 (42%), for the mcr 3/7 genes 5 (62%), and for the mcr 5 gene 10 (100%). Thus, the current study indicated that the existence of Arcobacter spp. isolated from fish and mussel samples may pose a potential risk to public health., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Horizontal transfer of transposable elements (TEs) is an important mechanism contributing to genetic diversity and innovation. Bats (order Chiroptera) have repeatedly been shown to experience horizontal transfer of TEs at what appears to be a high rate compared with other mammals. We investigated the occurrence of horizontally transferred (HT) DNA transposons involving bats. We found over 200 putative HT elements within bats; 16 transposons were shared across distantly related mammalian clades, and 2 other elements were shared with a fish and two lizard species. Our results indicate that bats are a hotspot for horizontal transfer of DNA transposons. These events broadly coincide with the diversification of several bat clades, supporting the hypothesis that DNA transposon invasions have contributed to genetic diversification of bats., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Non-gene-editing microbiome engineering (NgeME) is the rational design and control of natural microbial consortia to perform desired functions. Traditional NgeME approaches use selected environmental variables to force natural microbial consortia to perform the desired functions. Spontaneous food fermentation, the oldest kind of traditional NgeME, transforms foods into various fermented products using natural microbial networks. In traditional NgeME, spontaneous food fermentation microbiotas (SFFMs) are typically formed and controlled manually by the establishment of limiting factors in small batches with little mechanization. However, limitation control generally leads to trade-offs between efficiency and the quality of fermentation. Modern NgeME approaches based on synthetic microbial ecology have been developed using designed microbial communities to explore assembly mechanisms and target functional enhancement of SFFMs. This has greatly improved our understanding of microbiota control, but such approaches still have shortcomings compared to traditional NgeME. Here, we comprehensively describe research on mechanisms and control strategies for SFFMs based on traditional and modern NgeME. We discuss the ecological and engineering principles of the two approaches to enhance the understanding of how best to control SFFM. We also review recent applied and theoretical research on modern NgeME and propose an integrated in vitro synthetic microbiota model to bridge gaps between limitation control and design control for SFFM., (© 2023 Institute of Food Technologists®.)

Previous work showed that FABP5 inhibitors suppressed the malignant progression of prostate cancer cells, and this suppression might be achieved partially by promoting apoptosis. But the mechanisms involved were not known. Here, we investigated the effect of inhibitors on apoptosis and studied the relevant mechanisms. WtrFABP5 significantly reduced apoptotic cells in 22Rv1 and PC3 by 18% and 42%, respectively. In contrast, the chemical inhibitor SB-FI-26 produced significant increases in percentages of apoptotic cells in 22Rv1 and PC3 by 18.8% (±4.1) and 4.6% (±1.1), respectively. The bio- inhibitor dmrFABP5 also did so by 23.1% (±2.4) and 15.8% (±3.0), respectively, in these cell lines. Both FABP5 inhibitors significantly reduced the levels of the phosphorylated nuclear fatty acid receptor PPARγ, indicating that these inhibitors promoted apoptosis-induction sensitivity of the cancer cells by suppressing the biological activity of PPARγ. Thus, the phosphorylated PPARγ levels were reduced by FABP5 inhibitors, the levels of the phosphorylated AKT and activated nuclear factor kapper B (NFκB) were coordinately altered by additions of the inhibitors. These changes eventually led to the increased levels of cleaved caspase-9 and cleaved caspase-3; and thus, increase in the percentage of cells undergoing apoptosis. In untreated prostate cancer cells, increased FABP5 suppressed the apoptosis by increasing the biological activity of PPARγ, which, in turn, led to a reduced apoptosis by interfering with the AKT or NFκB signaling pathway. Our results suggested that the FABP5 inhibitors enhanced the apoptosis-induction of prostate cancer cells by reversing the biological effect of FABP5 and its related pathway., (© 2023 The Authors. Cell Biology International published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.)

Key Message: Positive selection genes are related to metabolism, while differentially expressed genes are related to photosynthesis, suggesting that genetic adaptation and expression regulation may play independent roles in different gene classes. Genome-wide investigation of the molecular mechanisms for high-altitude adaptation is an intriguing topic in evolutionary biology. The Qinghai-Tibet Plateau (QTP) with its extremely variable environments is an ideal site for studying high-altitude adaptation. Here, we used transcriptome data of 100 individuals from 20 populations collected from various altitudes on the QTP to investigate the adaptive mechanisms of the aquatic plant Batrachium bungei at both the genetic and transcriptional level. To explore genes and biological pathways that may contribute to QTP adaptation, we employed a two-step approach, in which we identified positively selected genes and differentially expressed genes using the landscape genomic and differential expression approaches. The positive selection analysis showed that genes involved in metabolic regulation played a crucial role in B. bungei adaptation to the extreme environments of the QTP, especially intense ultraviolet radiation. Altitude-based differential expression analysis suggested that B. bungei could increase the rate of energy dissipation or reduce the efficiency of light energy absorption by down regulating the expression of photosynthesis-related genes to adapt to the strong ultraviolet radiation. Weighted gene co-expression network analysis identified ribosomal genes as hubs of altitude adaptation in B. bungei. Only a small part of genes (about 10%) overlapped between positively selected genes and differentially expressed genes in B. bungei, suggesting that genetic adaptation and gene expression regulation might play relatively independent roles in different categories of functional genes. Taken together, this study enriches our understanding of the high-altitude adaptation mechanism of B. bungei on the QTP., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Real-time motion monitoring (RTMM) is necessary for accurate motion management of intrafraction motions during radiation therapy (RT)., Purpose: Building upon a previous study, this work develops and tests an improved RTMM technique based on real-time orthogonal cine magnetic resonance imaging (MRI) acquired during magnetic resonance-guided adaptive RT (MRgART) for abdominal tumors on MR-Linac., Methods: A motion monitoring research package (MMRP) was developed and tested for RTMM based on template rigid registration between beam-on real-time orthogonal cine MRI and pre-beam daily reference 3D-MRI (baseline). The MRI data acquired under free-breathing during the routine MRgART on a 1.5T MR-Linac for 18 patients with abdominal malignancies of 8 liver, 4 adrenal glands (renal fossa), and 6 pancreas cases were used to evaluate the MMRP package. For each patient, a 3D mid-position image derived from an in-house daily 4D-MRI was used to define a target mask or a surrogate sub-region encompassing the target. Additionally, an exploratory case reviewed for an MRI dataset of a healthy volunteer acquired under both free-breathing and deep inspiration breath-hold (DIBH) was used to test how effectively the RTMM using the MMRP can address through-plane motion (TPM). For all cases, the 2D T2/T1-weighted cine MRIs were captured with a temporal resolution of 200 ms interleaved between coronal and sagittal orientations. Manually delineated contours on the cine frames were used as the ground-truth motion. Common visible vessels and segments of target boundaries in proximity to the target were used as anatomical landmarks for reproducible delineations on both the 3D and the cine MRI images. Standard deviation of the error (SDE) between the ground-truth and the measured target motion from the MMRP package were analyzed to evaluate the RTMM accuracy. The maximum target motion (MTM) was measured on the 4D-MRI for all cases during free-breathing., Results: The mean (range) centroid motions for the 13 abdominal tumor cases were 7.69 (4.71-11.15), 1.73 (0.81-3.05), and 2.71 (1.45-3.93) mm with an overall accuracy of <2 mm in the superior-inferior (SI), the left-right (LR), and the anterior-posterior (AP) directions, respectively. The mean (range) of the MTM from the 4D-MRI was 7.38 (2-11) mm in the SI direction, smaller than the monitored motion of centroid, demonstrating the importance of the real-time motion capture. For the remaining patient cases, the ground-truth delineation was challenging under free-breathing due to the target deformation and the large TPM in the AP direction, the implant-induced image artifacts, and/or the suboptimal image plane selection. These cases were evaluated based on visual assessment. For the healthy volunteer, the TPM of the target was significant under free-breathing which degraded the RTMM accuracy. RTMM accuracy of <2 mm was achieved under DIBH, indicating DIBH is an effective method to address large TPM., Conclusions: We have successfully developed and tested the use of a template-based registration method for an accurate RTMM of abdominal targets during MRgART on a 1.5T MR-Linac without using injected contrast agents or radio-opaque implants. DIBH may be used to effectively reduce or eliminate TPM of abdominal targets during RTMM., (© 2023 American Association of Physicists in Medicine.)

The literature on the presence of microplastics (MPs) and their potential impact on terrestrial ecosystems is still scarce. Interestingly, soil MPs are detected as organic carbon (SOC) using traditional quantification methods (e.g., loss on ignition [LOI]), although its dynamics in the environment will be different. The objective of this study was to quantify the carbon (C) contribution of MPs to the SOC in superficial soil samples from a coastal urban wetland (Avellaneda, Buenos Aires, Argentina) with the features of a humid subtropical forest and compare with hydrocarbon contribution. Soil samples were split for analysis of moisture content; texture (sieve and pipet method); organic matter as a LOI (8 h at 450 °C); total hydrocarbons (THCs; gravimetry of solvent extractable matter); n-alkanes (solvent extraction and gas chromatography-flame ionization detection analysis); and extraction of MPs (floatation in NaCl aq , filtration, H 2 O 2 digestion, and visual sorting under a stereomicroscope). The superficial soil was a sandy clay loam with a large organic matter content (19%-30%). The THC averaged 2.5 ± 1.9 g kg and the marked predominance of odd-numbered carbon n-alkanes maximizing at C29 and C31 show the contribution of the terrestrial plant waxes. The average number of MPs was 587 ± 277 items kg of dry soil, predominantly fibers. Taking account of the C content, THCs and MPs add to the soil 1.23 ± 1.10 ton C ha and 0.10-0.97 ton C ha, respectively. Therefore, in this system with humid forest characteristics, the MPs represent between 0.12% and 1.25% of soil estimated carbon, in a magnitude similar to the C contribution of THCs (0.6%-4.2%). This preliminary study shows the relevance of discriminating MPs from other carbon sources and presents a description of their impact on soils to advance future research or tools for decision-makers. Integr Environ Assess Manag 2023;19:698-705. © 2022 SETAC., (© 2022 SETAC.)

Objective: The Accelerating Innovation for Mothers project established a new database of candidate medicines under development between 2000 and 2021 for five pregnancy-related conditions, including fetal growth restriction. The objective was to assess medicines for fetal growth restriction and their potential for clinical use globally., Design: Landscape analysis., Setting: Global (focus on low- and middle-income countries, LMICs)., Sample: Drugs, dietary supplements and biologics under investigation for prevention or treatment of fetal growth restriction., Methods: A research pipeline database of medicines was created through searching AdisInsight, PubMed and various grant and clinical trial databases. Analysis of clinical and preclinical candidates were descriptive., Main Outcomes Measures: Fetal growth restriction candidates in clinical development were identified and ranked as high, medium or low potential based on prespecified criteria, including efficacy, safety and accessibility., Results: Of the 444 unique candidates in the database across all five pregnancy-related conditions, 63 were for fetal growth restriction. Of these, 31 were in clinical development (phases I, II or III) and 32 were in preclinical development. Three candidates, aspirin, l-arginine and vitamin D, were ranked as having high potential as preventive agents. There were no high-potential candidates for treating fetal growth restriction, although five candidates were ranked as having medium potential: allylestrenol, dalteparin, omega-3 fatty acids, tadalafil, and United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP)., Conclusions: l-Arginine, aspirin and vitamin D are promising, high-potential preventative agents for fetal growth restriction. Based on the medicines pipeline, new pharmacological agents for fetal growth restriction are unlikely to emerge in the near future., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Signal peptide peptidase (SPP) and SPP-like (SPPL) aspartyl intramembrane proteases are known to contribute to sequential processing of type II-oriented membrane proteins referred to as regulated intramembrane proteolysis. The ER-resident family members SPP and SPPL2c were shown to also cleave tail-anchored proteins, including selected SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins facilitating membrane fusion events. Here, we analysed whether the related SPPL2a and SPPL2b proteases, which localise to the endocytic or late secretory pathway, are also able to process SNARE proteins. Therefore, we screened 18 SNARE proteins for cleavage by SPPL2a and SPPL2b based on cellular co-expression assays, of which the proteins VAMP1, VAMP2, VAMP3 and VAMP4 were processed by SPPL2a/b demonstrating the capability of these two proteases to proteolyse tail-anchored proteins. Cleavage of the four SNARE proteins was scrutinised at the endogenous level upon SPPL2a/b inhibition in different cell lines as well as by analysing VAMP1-4 levels in tissues and primary cells of SPPL2a/b double-deficient (dKO) mice. Loss of SPPL2a/b activity resulted in an accumulation of VAMP1-4 in a cell type- and tissue-dependent manner, identifying these proteins as SPPL2a/b substrates validated in vivo. Therefore, we propose that SPPL2a/b control cellular levels of VAMP1-4 by initiating the degradation of these proteins, which might impact cellular trafficking., (© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)