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Young adulthood (18-30 years old) is a crucial period due to its developmental tasks such as career establishment and financial independence. However, young adults' relative lack of resources makes them vulnerable to employment disruptions (job loss and income loss), which may have both immediate and long-term effects on their financial wellbeing and mental health. The economic impact of COVID-19 restrictions resulted in an increase in unemployment and a decrease in income worldwide, especially for young adults. This study examined to what extent and how job loss and income loss due to the pandemic influenced young adults' perception of their present financial wellbeing, future financial wellbeing, and psychological wellbeing by using cross-sectional survey data collected from six countries (China, Italy, Lithuania, Portugal, Slovenia, and the United States). Results showed that the impact of income loss and job loss on all three types of wellbeing were mediated by young adults' negative perception of the COVID-19 lockdown restriction (i.e., perceived as a misfortune). Cross-country differences existed in the key variables. The association between employment disruptions, young adults' perception of the COVID-19 lockdown restriction, and wellbeing were equivalent across countries except China. Implications for policy and practice are discussed., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial interests to disclose., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Despite being bio-epidemiological phenomena, the causes and effects of pandemics are culturally influenced in ways that go beyond national boundaries. However, they are often studied in isolated pockets, and this fact makes it difficult to parse the unique influence of specific cultural psychologies. To help fill in this gap, the present study applies existing cultural theories via linear mixed modeling to test the influence of unique cultural factors in a multi-national sample (that moves beyond Western nations) on the effects of age, biological sex, and political beliefs on pandemic outcomes that include adverse financial impacts, adverse resource impacts, adverse psychological impacts, and the health impacts of COVID. Our study spanned 19 nations (participant N = 14,133) and involved translations into 9 languages. Linear mixed models revealed similarities across cultures, with both young persons and women reporting worse outcomes from COVID across the multi-national sample. However, these effects were generally qualified by culture-specific variance, and overall more evidence emerged for effects unique to each culture than effects similar across cultures. Follow-up analyses suggested this cultural variability was consistent with models of pre-existing inequalities and socioecological stressors exacerbating the effects of the pandemic. Collectively, this evidence highlights the importance of developing culturally flexible models for understanding the cross-cultural nature of pandemic psychology beyond typical WEIRD approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Conway, Woodard, Zubrod, Tiburcio, Martínez-Vélez, Sorgente, Lanz, Serido, Vosylis, Fonseca, Lep, Li, Zupančič, Crespo, Relvas, Papageorgiou, Gianniou, Truhan, Mojtahedi, Hull, Lilley, Canning, Ulukök, Akın, Massaccesi, Chiappini, Paracampo, Korb, Szaflarski, Touré, Camara, Magassouba, Doumbouya, Mutlu, Bozkurt, Grotkowski, Przepiórka, Corral-Frías, Watson, Corona Espinosa, Lucas, Paleari, Tchalova, Gregory, Azrieli, Bartz, Farmer, Goldberg, Rosenkranz, Pickett, Mackelprang, Graves, Orr and Balmores-Paulino.)

Mechanisms by which specific histone modifications regulate distinct gene networks remain little understood. We investigated how H3K79me2, a modification catalyzed by DOT1L and previously considered a general transcriptional activation mark, regulates gene expression during cardiogenesis. Embryonic cardiomyocyte ablation of Dot1l revealed that H3K79me2 does not act as a general transcriptional activator, but rather regulates highly specific transcriptional networks at two critical cardiogenic junctures: embryonic cardiogenesis, where it was particularly important for left ventricle-specific genes, and postnatal cardiomyocyte cell cycle withdrawal, with Dot1L mutants having more mononuclear cardiomyocytes and prolonged cardiomyocyte cell cycle activity. Mechanistic analyses revealed that H3K79me2 in two distinct domains, gene bodies and regulatory elements, synergized to promote expression of genes activated by DOT1L. Surprisingly, H3K79me2 in specific regulatory elements also contributed to silencing genes usually not expressed in cardiomyocytes. These results reveal mechanisms by which DOT1L successively regulates left ventricle specification and cardiomyocyte cell cycle withdrawal., (© 2022. The Author(s).)

Cefepime (CEF) is a cephalosporin and can be administered in secondary peritonitis together with metronidazole to treat sepsis. This study aimed to develop and validate an LC-ESI-QTOF-MS method for the quantification of cefepime in the plasma and peritoneal microdialysate of healthy Wistar rats. Chromatographic separation was performed using a CLC-ODS C 18 column (250 × 4.6 mm), a C 18 pre-column (4 mm, 5 μm) and isocratic elution. Gallic acid was used as the internal standard. The mobile phase consisted of (A) ultrapure water (pH adjusted to 3.5) and (B) acetonitrile (80:20, v/v) at 0.8 ml/min. Quantification was performed using a mass spectrometer with electrospray ionization in positive mode to monitor ions with m/z 481.1322 (CEF) and m/z 171.0288 (IS). The method was validated for selectivity, precision, accuracy, linearity, stability, lower limit of quantification, carryover, recovery and matrix effect. Calibration was done in the ranges 1-40 and 1-100 μg/ml for the peritoneal microdialysate and plasma, respectively. Plasma extraction recovery ranged from 93.9 to 99.9%. The technique was validated and successfully applied in a pilot pharmacokinetic study for estimating the free concentration of CEF in the peritoneal microdialysate of rats for the first time., (© 2022 John Wiley & Sons Ltd.)

Introduction: The various rectal endoluminal radiation techniques all have steep, but different, dose gradients. In rectal contact brachytherapy (CXB) doses are typically prescribed and reported to the applicator surface and not to the gross tumor volume (GTV), clinical target volume (CTV) or organs at risk (OAR), which is crucial to understand tumor response and toxicity rates. To quantify the above-described problem, we performed a dose modeling study using a fixed prescription dose at the surface of the applicator and varied tumor response scenarios., Methods: Endorectal ultrasound-based 3D-volume-models of rectal tumors and the rectal wall were used to simulate the delivered dose to GTV, CTV and the rectal wall layers, assuming treatment with Maastro HDR contact applicator for rectal cancer with a fixed prescription dose to the applicator surface (equivalent to 3 × 30 Gy CXB) and various response scenarios., Results: An identical prescribed dose to the surface of the applicator resulted in a broad range of doses delivered to the GTV, CTV and the uninvolved intestinal wall. For example, the equieffective dose in 2 Gy per fraction (EQD2) D90% of the GTV varied between 63 and 231 Gy, whereas the EQD2 D2cc of the rectal wall varied between 97 and 165 Gy., Conclusion: Doses prescribed at the surface are not representative of the dose received by the tumor and the bowel wall. This stresses the relevance of dose reporting and prescription to GTV and CTV volumes and OAR in order to gain insight between delivered dose, local control and toxicity and to optimize treatment protocols., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Although emerging adults (i.e., individuals aged 18-29 years old) may be at a lesser risk of COVID-19 severe illness and mortality, studies have found that the negative impact of COVID-19 on mental health and well-being is higher among emerging adults when compared to other age groups. The current study aimed to identify profile(s) based on resilience resources, which could help emerging adults in managing the disruptions to their lives following the pandemic. A cross-national sample of 1,768 emerging adults from China, Italy, Lithuania, Portugal, Slovenia, and the US was utilized to identify profiles based on different resilience dimensions (ego-resiliency, positivity, religiosity, socioeconomic status, family support, peer support). Results of the Latent Profile Analysis suggest the presence of four different profiles: no resources, only peer, only family, and well-equipped. The association of these profiles with demographic variables, adulthood markers, self-perceived COVID-19 impact, present well-being, and future life perception was investigated. Implications for resilience theory as well as for future interventions are discussed., Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03658-y., Competing Interests: Competing interestsThe Authors declare that there is no conflict of interest., (© The Author(s) 2022.)

Objective: The growing prevalence and impact of cancer on the family system calls for a palliative care approach with the family as the unit of care. This study aimed at providing an overview of the intervention programs that have been developed to offer support to the family caregivers of oncologic patients receiving palliative care., Method: Sixteen articles were included in the final review, encompassing (i) studies focused on intervention programs with family caregivers of cancer patients in palliative care, (ii) studies including a pre- and post-test evaluation of the intervention program, (iii) and studies whose cancer patients were at least 18 years old., Results: A great heterogeneity was verified with respect to care settings, number of sessions, outcome measures, or timing of assessment within the reviewed programs. These findings mirrored the complexity of the palliative care approach, which is difficult to standardize. Nonetheless, some interventions with different features accomplished good and sometimes similar results. The studies' main outcomes were clustered in five categories: psychological symptomatology, general quality of life, caregiving role, family relational variables, and bereavement/grief. Moreover, 44% of the main outcomes were psychological symptomatology of family caregivers, with an emphasis toward anxiety and depression. Also shown was a growing emergence of technology use among these interventions., Significance of Results: Results revealed a scarcity of family-oriented programs and lack of certified mental health professionals as interventionists. Future studies and interventions should focus on the positive outcomes of the caregiving experience and must acknowledge the cultural differences when trying to replicate programs. Considering that there is no precise formula for dealing with terminal illness and grief, we submit that family-centered and systemic lenses are excellent approaches for support during this adjustment process. In conclusion, the present study advocates for increased investment in the field, underscoring the importance of family caregivers' mental health.

Background and Objective: Circular RNAs (circRNAs) are endogenous molecules of non-coding RNA that form a covalently closed loop at the 3' and 5' ends. Recently, the role of these molecules in the regulation of gene expression and their involvement in several human pathologies has gained notoriety. The identification of circRNAs is highly dependent on computational methods for analyzing RNA sequencing data. However, bioinformatics software is known to be problematic in terms of usability. Evidence points out that tools for identifying circRNAs can have such problems, negatively impacting researchers in this field. Here we present a heuristic-based framework for evaluating the usability of command-line circRNA identification software., Methods: We used heuristics evaluation to comprehensively identify the usability issues in a sample of circRNA identification tools., Results: We identified 46 usability issues presented individually in four tools. Most of the issues had cosmetic or minor severity. These are unlikely to challenge experienced users but may cause inconvenience for novice users. We also identified severe issues with the potential to harm users regardless of their experience. The areas most affected were the documentation and the installability of the tools., Conclusions: With the proposed framework, we formally describe, for the first time, the usability problems that can affect users in this area of circRNA research. We hope that our framework can help researchers evaluate their software's usability during development., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Foodborne pathogens represent a significant cause of negative impacts on human health and the economy worldwide. Unfortunately, information about epidemiological insights in Latin American countries is scarce. The consumption of ready-to-eat street food in Ecuador is extensive, and information about the presence of foodborne pathogens, their virulence factors, and antimicrobial resistance is negligible. This data includes the occurrence, phenotypic antibiotic resistance profiles, and antibiotic resistance genes of Enterobacterales isolated from ready-to-eat street food in Ambato, central Ecuador during 2020 and 2021. The most common genera detected were Escherichia coli , Klebsiella spp. , and Cronobacter spp . Agar disk diffusion assays were performed to determine their phenotypic resistance. The presence of antibiotic resistance genes conferring resistance against colistin, β-Lactams, aminoglycosides, tetracyclines, sulfonamides, fluoroquinolones, and amphenicols was detected via polymerase chain reaction (PCR) amplification., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Tubón J et al.)

Patients with relapsed/refractory multiple myeloma (RRMM) need proven subsequent therapies after early-line lenalidomide treatment failure. The phase 2 MM-014 trial (NCT01946477) investigated pomalidomide, dexamethasone, and daratumumab after 1 to 2 prior treatment lines (62.5%, 1 prior line) in patients with RRMM and prior lenalidomide (75.0%, lenalidomide refractory). With a median follow-up of 28.4 months, overall response rate was 77.7% (52.7% achieved very good partial response or better) and median progression-free survival was 30.8 months. For patients with lenalidomide-refractory disease, these outcomes were 76.2%, 47.6%, and 23.7 months, respectively. No new safety signals were observed; 64.3% experienced grade 3/4 neutropenia. Health-related quality of life was preserved or trended toward improvement through 12 treatment cycles. Pomalidomide, dexamethasone, and daratumumab given immediately after early-line lenalidomide-based treatment continues to demonstrate safety and efficacy, supporting pomalidomide-dexamethasone as a foundation of combination therapy in RRMM and providing evidence that the immunomodulatory agent class delivers benefit after lenalidomide treatment failure.

Background: Liver transplantation in an animal model is challenging due to hemodynamics and intraoperative anesthetic care. Several models are described in the literature employing different techniques such as venovenous bypass or aortic cross-clamping to maintain hemodynamic stability, although few groups keep the animal alive in the postoperative period. This study aims to evaluate a liver transplantation clinical model in pigs without venovenous bypass or aortic cross-clamping., Methods: Male pigs weighing 20 to 35 kg underwent liver transplantation surgery without using venovenous bypass or aorta cross-clamping. Protocols were approved by the Animal Care and Use Committee of the University of São Paulo, Brazil., Results: Ten LTs were performed. Cold ischemia and warm ischemia were 119 ± 33.28 minutes and 26 ± 9.6 minutes, respectively. Hemodynamic changes were significantly higher after the postrevasculazation phase: heart rate (P < .001), medium arterial pressure (P < .001), and cardiac output (P = .03). Hypotension was treated with intravenous fluids and, in some cases, with vasoactive drugs especially during the post-reperfusion period. No animals died during the procedure and almost survival until the first postoperative day. Serum aspartate aminotransferase and lactate increased their values in the post-reperfusion phase., Conclusions: Practice-based on laboratory animals improves surgical skills and the development of experimental models aimed at new advances in this field. Perfecting our technique on the swine model, we could move forward to create a small-for-size model, test new therapeutic strategies, and define the boundaries for safely performing an enlarged liver resection or a partial liver graft transplant., (Copyright © 2022. Published by Elsevier Inc.)

This article describes the occurrence, antibiograms, and detection of antibiotic resistance genes of Enterobacterales isolated from fresh vegetables commercialized in Riobamba, Ecuador. Escherichia coli isolates were screened to detect diarrheagenic pathotypes via PCR. Agar diffusion assay was performed to determine the phenotypic antibiotic resistance of the Enterobacterales strains. The presence of antibiotic resistance genes conferring resistance against beta-lactams, mobile colistin resistance, carbapenems, quinolones, tetracyclines, and sulphonamides was detected via PCR amplification., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Inc.)

Phosphoinositide 3-kinase-δ (PI3Kδ) inhibitors are active in lymphoid malignancies, although associated toxicities can limit their use. Umbralisib is a dual inhibitor of PI3Kδ and casein kinase-1ε (CK1ε). This study analyzed integrated comprehensive toxicity data from 4 open-label, phase 1 and 2 studies that included 371 adult patients (median age, 67 years) with relapsed/refractory non-Hodgkin lymphoma (follicular lymphoma [n = 147]; marginal zone lymphoma [n = 82]; diffuse large B-cell lymphoma/mantle cell lymphoma [n = 74]; chronic lymphocytic leukemia [n = 43]; and other tumor types [n = 25]) who were treated with the recommended phase 2 dose of umbralisib 800 mg or higher once daily. At data cutoff, median duration of umbralisib treatment was 5.9 months (range, 0.1-75.1 months), and 107 patients (28.8%) received umbralisib for ≥12 months. Any-grade treatment-emergent adverse events (AEs) occurred in 366 (98.7%) of 371 patients, with the most frequent being diarrhea (52.3%), nausea (41.5%), and fatigue (31.8%). Grade 3 or higher treatment-emergent AEs occurred in 189 (50.9%) of 371 patients and included neutropenia (11.3%), diarrhea (7.3%), and increased aminotransferase levels (5.7%). Treatment-emergent serious AEs occurred in 95 (25.6%) of 371 patients. AEs of special interest were limited and included pneumonia (29 of 371 [7.8%]), noninfectious colitis (9 of 371 [2.4%]), and pneumonitis (4 of 371 [1.1%]). AEs led to discontinuation of umbralisib in 51 patients (13.7%). Four patients (1.1%) died of AEs, none of which was deemed related to umbralisib. No cumulative toxicities were reported. The favorable long-term tolerability profile and low rates of immune-mediated toxicities support the potential use of umbralisib for the benefit of a broad population of patients with lymphoid malignancies., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The relative mRNA abundance of 10 genes associated with folliculogenesis was compared between late preantral (secondary) and early antral (tertiary) ovarian follicles in goats. In total, 100 follicles in each category were mechanically isolated. The relative transcript abundance of the mRNAs were determined by qPCR. Data were analyzed using unpaired Student's t-test. Of the 10 tested genes, ABLIM mRNA was not detected in either follicle category, six genes (SLIT3, TYMS, GTPBP1, AKR1C4, PIK3R6, and MAOB) were upregulated in secondary follicles compared with tertiary follicles, and three genes (ARHGEF12, CLEC6A, and CYTL1) showed similar mRNA abundances in both secondary and tertiary follicles. In conclusion, SLIT3, GTPBP1, AKR1C4, and PIK3R6 mRNA abundance was upregulated in secondary follicles (preantral phase) compared with in tertiary follicles (antral phase) in goats.

Toxocariasis is still a neglected parasitic disease worldwide and much about its biology and diagnosis has yet to be understood. The migration of third stage larvae via bloodstream suggests a potential use of molecular tools in diagnosis as well to deepen the knowledge about its migration behaviors. Conventional PCR was applied in serum and tissue samples from BALB/c mice infected with 5 and 500 embryonated eggs. Blood samples were collected at 15, 30, 60, 90 and 120 days post-infection. Organs were excised at 170 days post infection. There was no DNA amplification in serum samples in any group or day post-infection; contrarily, tissue samples showed DNA amplification. These results also support a continuous larval migration after and/or simultaneously with the neurotropic-myotropic phase. Thus, molecular tools might be useful as a differential diagnosis method, but do not replace immunodiagnostics techniques., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Despite global demand, the large-scale effects of social-emotional learning (SEL) programming in developing countries remain underexplored. Using a randomized control trial, this study examined the effectiveness of a school-wide SEL intervention-Programa Compasso (PC)-among 3,018 sociodemographically diverse, Portuguese-speaking children (M age  = 9.85 years) attending 90 public primary schools across Rio de Janeiro, Brazil in 2017. Average impacts of PC on children's executive function, emotion knowledge, and behavior problems after one school year were null. Moderation analyses did, however, reveal evidence for positive impacts of PC on children's labeling of emotional expressions and inhibitory control within low-homicide communities (d = 0.15 SDs), and null effects on these same outcomes in high-violence areas. Implementation and cultural considerations are discussed., (© 2021 The Authors. Child Development © 2021 Society for Research in Child Development.)

Macroeconomic crises occur cyclically, entailing devastating social consequences for individuals and families. Previous research addressing families' responses to socioeconomic upheavals has been mainly conducted with couples with young or adolescent children. Less research attention has been given to middle-aged couples with emerging adult children who might be struggling to support their offspring's transition to adulthood emotionally and financially. The present study examines the impact of economic stressors on family and individual functioning reported by couples with emerging adult children in Portugal. Using a sample of 317 heterosexual middle-aged couples, structural equation models were built to assess the links between economic hardship, economic pressure, and family functioning and psychological well-being. Following an actor-partner interdependence model (APIM) approach, both actor and partner effects were tested. The results showed that greater economic hardship was indirectly linked with (a) poor family functioning as reported by men and women, via the economic pressure felt by men, revealing an actor and a partner effect and (b) poor psychological well-being via each partner's own feeling of economic pressure, revealing only actor effects. Findings also indicated that economic stress processes may operate differently across socioeconomic status (SES) groups, with men from low/medium-low SES reporting a more pronounced association between economic pressure and family functioning. This study added support to previous literature on the adverse impact of economic stressors on family and individual functioning, extending family economic stress research to the Portuguese cultural setting and to an understudied stage of the family life cycle. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objectives: To evaluate the effect of Miofascial Release (MFR) on knee extensors strength, at different duration times of application., Method: 51 healthy individuals were randomly assigned to one of three groups (3min, 5min or placebo) in this randomized clinical trial. The knee extensors strength was assessed in two conditions: pre and post-intervention, using an isokinetic dynamometer, at speeds of 60° and 120°/s. MFR was applied on the anterior surface of the thigh for 3min or 5 min, according to the experimental groups. The placebo group underwent through the application of a non-therapeutic gel, associated with 3min of a light touch on the skin. Peak torque, total work and mean power were the isokinetic variables analyzed through a multivariate analysis of variance (MANOVA) with p ≤ 0.05., Results: Our findings suggest a main effect and interaction between moments (pre and post-intervention) and speeds (60° and 120°/s) for total work and mean power (p < 0.01). Likewise, main effect and interaction of speed were observed for peak torque (p < 0.01). There were no significant differences for the other analyzed variables., Conclusion: No significant main effect of MFR were detected in any of the proposed application time on peak torque, total work and mean power, in the knee extensors, compared to the placebo group., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. This research did not receive any type of funding., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To validate the collapsed cone (CC) algorithm against Monte Carlo (MC) simulations for model-based dose calculations in high-dose-rate (HDR) liver brachytherapy., Methods and Materials: Doses for liver brachytherapy treatment plans of 10 cases were retrospectively recalculated with a model-based approach using Monte Carlo n-Particle Code (MCNP) 6 (Dm,m-MC) and Oncentra Brachy ACE (Dm,m-ACE). Tissue segmentation consisted of assigning uniform compositions and mass densities to predefined Hounsfield Unit (HU) thresholds. Resulting doses were compared according to dose volume histogram parameters typical for clinical routine. These included the percentage liver volume receiving 5 Gy (V5Gy) or 10 Gy (V10Gy), the maximum dose to one cubic centimeter (D1cc) of organs at risk, the clinical target volume (CTV) fractions receiving 150% (V150), 100% (V100), 95% (V95) and 90% (V90) of the prescribed dose and the absolute doses to 95% (D95) and 90% (D90) of the CTV volumes., Results: Doses from Oncentra Brachy ACE agreed well with MC simulations. Differences were seen far from the source, in low-density regions and bone structures. Median percentage deviations were 1.1% for the liver V5Gy and 0.4% for the liver V10Gy, with deviations of largest magnitude amounting to 2.2% and 1.0%, respectively. Organs at risk had median deviations ranging from 0.3% to 1.5% for D1cc, with outliers ranging up to 4.6%. CTV volume parameter deviations ranged between -1.5% and 0.5%, dose parameter deviations ranged mostly between -2% and 1%, with two outliers at -4.0% and -3.4% for a small CTV., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

The traditional sediment quality triad generally uses three lines of evidence (LOE) in the assessment, integrating environmental chemistry, ecology and ecotoxicology. However the assessment is performed without considering the multivariate structure within LOE. In order to improve the sediment quality assessment, the M-Triad is proposed. Instead of averaging the values within a LOE, the new approach is based on the Euclidean distance between each sampling station and the reference station (s) for each LOE. These distances are then plotted in a radar-chart to obtain the area of the triangle and the quality assessment is subsequently obtained from the difference between the triangle areas of the impacted and the reference station. Three studies were selected to test the applicability of the M-Triad. In two cases, the M-Triad returned a more realistic ranking of the stations as observed in the principal component analysis (PCA) from each LOE By including the Euclidean distance, the use of M-Triad is advantageous when multiple variables with negative or uncorrelated patterns within a LOE are analyzed simultaneously. The combination of the M-Triad and the results of the PCA allows one to identify multiple contamination gradients and how biota and bioassays respond to each of these gradients. In comparison to the traditional method, the M-Triad reduces the uncertainty of the final analysis, permitting a more comprehensive ecological assessment., Competing Interests: Declaration of competing interest On behalf of the co-authors, whose names are listed immediately below, I certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Phosphatidylinositol-3-kinase (PI3K) inhibitors have shown activity in relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). PI3K inhibitors have been hampered by poor long-term tolerability and toxicity, which interfere with continuous use. Umbralisib, a dual inhibitor of PI3Kδ/casein kinase-1ε, exhibits improved selectivity for PI3Kδ compared with other PI3K inhibitors. This phase IIb trial was designed to evaluate the efficacy and safety of umbralisib in patients with R/R iNHL., Patients and Methods: In this multicohort, open-label, phase IIb study, 208 patients with R/R marginal zone, follicular, or small lymphocytic lymphoma (MZL, FL, or SLL) unresponsive to prior treatments (≥ 1 MZL; ≥ 2 FL/SLL), including ≥ 1 anti-CD20-based therapy, were administered umbralisib 800 mg orally once daily until disease progression, unacceptable toxicity, or study withdrawal. Primary end point is overall response rate; secondary end points include time to response, duration of response, progression-free survival, and safety., Results: The median follow-up is 27.7 months (efficacy) and 21.4 months (safety). The overall response rate was 47.1%, and tumor reduction occurred in 86.4% of patients. The median time to response was 2.7-4.6 months. The median duration of response was not reached for MZL, 11.1 months for FL, and 18.3 months for SLL. Median progression-free survival was not reached for MZL, 10.6 months for FL, and 20.9 months for SLL. At least one grade ≥ 3 treatment-emergent adverse event (TEAE) was reported in 53.4% of patients. TEAEs led to umbralisib discontinuation in 32 patients (15.4%). A total of 31 patients (14.9%) discontinued because of a treatment-related adverse event. Grade ≥ 3 TEAEs reported in ≥ 10% of patients: neutropenia (11.5%) and diarrhea (10.1%). Increased ALT/AST (grade ≥ 3) occurred in 6.7%/7.2% of patients., Conclusion: Umbralisib achieved meaningful clinical activity in heavily pretreated patients with iNHL. The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and adverse event-related discontinuations., Competing Interests: Nathan H. FowlerEmployment: BostongeneConsulting or Advisory Role: Roche/Genentech, TG Therapeutics, Verastem, Bayer, Celgene, NovartisResearch Funding: Roche, Celgene, Gilead Sciences, TG Therapeutics, Novartis, AbbVie, BeiGene Felipe SamaniegoConsulting or Advisory Role: Astex Pharmaceuticals, ADC Therapeutics, Imbrium Therapeutics Wojciech JurczakResearch Funding: TG Therapeutics Nilanjan GhoshConsulting or Advisory Role: Seattle Genetics, TG Therapeutics, AstraZeneca, Verastem, Pharmacyclics/Janssen, Karyopharm Therapeutics, Genmab, Bristol-Myers Squibb, Gilead Sciences, Adaptive Biotechnologies, Beigene, AbbVie, IncyteSpeakers' Bureau: AbbVie, Janssen Oncology, Kite/Gilead Sciences, Seattle Genetics, AstraZeneca, Bristol-Myers Squibb, Celgene, Pharmacyclics/Janssen, EpizymeResearch Funding: Pharmacyclics, TG Therapeutics, Genentech/Roche, Seattle Genetics, Bristol-Myers Squibb/Celgene, Gilead Sciences Enrico DerenziniConsulting or Advisory Role: AstraZenecaResearch Funding: TG-Therapeutics, ADC Therapeutics James A. ReevesResearch Funding: Sarah Cannon Research Institute, Eli Lilly, Tesaro, TG Therapeutics, Genentech, Celgene, Merck, Bristol-Myers Squibb, Boston Biomedical Inc, AstraZeneca, NovoCure, Calithera Biosciences, Novartis, Guardant Health, Acerta Pharma, Rhizen Pharmaceuticals, Takeda, Onconova Therapeutics, Sanofi, CTI Biopharma, Eisai, Janssen Chan Y. CheahHonoraria: Roche/Genentech, Janssen-Cilag, TG Therapeutics, Loxo/Lilly, AstraZeneca, Bristol-Myers Squibb, Gilead Sciences, Ascentage Pharma, MDSConsulting or Advisory Role: Janssen-Cilag, Roche/Genentech, TG Therapeutics, Loxo/Lilly, Gilead Sciences, AstraZeneca, Bristol-Myers Squibb, Ascentage Pharma, MDSSpeakers' Bureau: Janssen-CilagResearch Funding: Roche, Celgene, AbbVieTravel, Accommodations, Expenses: Roche Tycel PhillipsHonoraria: Seattle Genetics, Incyte, Pharmacyclics, Bayer, Gilead Sciences, GenentechConsulting or Advisory Role: Seattle Genetics, Pharmacyclics, Incyte, Genentech, Bayer, Gilead Sciences, Curis, Kite/Gilead, Celgene, GenmabResearch Funding: AbbVie, Pharmacyclics/Janssen, Bayer Ewa Lech-MarandaConsulting or Advisory Role: Roche, Amgen, AbbVie, Astellas Pharma, Novartis, Janssen-Cilag, Sanofi/Aventis, Takeda, Gilead Sciences Bruce D. ChesonConsulting or Advisory Role: TG Therapeutics, AbbVie, Pharmacyclics/Janssen, Morphosys, Celgene, Karyopharm Therapeutics, Epizyme, Gilead Sciences, SymBio Pharmaceuticals, Parexel, Merck, Glaxo Smith Kline, Beigene, Kite, Reddy Biosimilar, Bayer, CelgeneResearch Funding: TG Therapeutics, Trillium Therapeutics, Seattle Genetics, Bristol-Myers Squibb, Gilead Sciences, Pharmacyclics, AbbVie, AstraZenecaTravel, Accommodations, Expenses: SymBio Pharmaceuticals Paolo F. CaimiConsulting or Advisory Role: Genentech, Seattle Genetics, TG Therapeutics, Kite Pharma, ADC Therapeutics, Bayer, Amgen, Verastem, EpizymeSpeakers' Bureau: CelgeneResearch Funding: Genentech, ADC Therapeutics Lori A. LeslieConsulting or Advisory Role: Kite/Gilead, TG Therapeutics, Celgene/BMS, Seattle Genetics, AbbVie, PCYC/Janssen, ADC Therapeutics, BeiGene, AstraZenecaSpeakers' Bureau: Kite Pharma, Celgene/BMS, Seattle Genetics, AbbVie, PCYC/Janssen, ADC Therapeutics, BeiGene, AstraZeneca, Epizyme, Karyopharm Julio C. ChavezConsulting or Advisory Role: Kite/Gilead, Novartis, Karyopharm Therapeutics, MorphoSys, TeneoBio, AbbVie, JanssenSpeakers' Bureau: AstraZeneca, BeiGene, MorphoSys, EpizymeResearch Funding: Merck Gustavo FonsecaHonoraria: Amgen, CelgeneConsulting or Advisory Role: Amgen, Celgene, Bayer, Abvie/Pharmacyclics, Dava Oncology, KaryopharmSpeakers' Bureau: Amgen, CelgeneResearch Funding: Celgene, Amgen, TG Therapeutics, Verastem OncologyTravel, Accommodations, Expenses: Amgen, Celgene Sunil BabuStock and Other Ownership Interests: Fort Wayne Medical Oncology & Hematology, Lutheran HospitalHonoraria: Bristol-Myers Squibb, Alexion Pharmaceuticals, Lilly, Bayer, AstraZenecaConsulting or Advisory Role: Bristol-Myers Squibb, Alexion Pharmaceuticals, AstraZeneca, argenx, Boehringer Ingelheim, Bayer, Kite Pharma, Janssen OncologySpeakers' Bureau: Alexion PharmaceuticalsResearch Funding: Bristol-Myers Squibb, Novartis, Genentech/Roche, AstraZeneca/MedImmune, Janssen Oncology, Amgen, TG Therapeutics, AbbVie, Lilly, Alexion Pharmaceuticals, Merck, Novartis, Syndax, Nektar, Sanofi, argenxTravel, Accommodations, Expenses: Bristol-Myers Squibb, Alexion Pharmaceuticals, Lilly, Janssen Oncology, Genentech/Roche Daniel J. HodsonResearch Funding: Gilead Sciences John M. BurkeConsulting or Advisory Role: Genentech/Roche, AbbVie, Seattle Genetics, Bayer, AstraZeneca, Adaptive Biotechnologies, Verastem, MorphoSys, Kura Oncology, Epizyme, BeiGene, Kymera, NovartisSpeakers' Bureau: Seattle Genetics, Beigene Jeff P. SharmanLeadership: US OncologyConsulting or Advisory Role: Pharmacyclics, Celgene, TG Therapeutics, Genentech, AbbVie, Acerta Pharma/AstraZeneca, Beigene, PfizerResearch Funding: Pharmacyclics, Genentech, Celgene, Acerta Pharma, Gilead Sciences, Seattle Genetics, TG Therapeutics, Merck, Takeda John M. PagelConsulting or Advisory Role: Gilead Sciences, AstraZeneca, Actinium Pharmaceuticals, BeiGene, Loxo Hari P. MiskinEmployment: TG TherapeuticsLeadership: TG TherapeuticsStock and Other Ownership Interests: TG TherapeuticsTravel, Accommodations, Expenses: TG Therapeutics Peter SportelliEmployment: TG TherapeuticsLeadership: TG TherapeuticsStock and Other Ownership Interests: TG TherapeuticsTravel, Accommodations, Expenses: TG Therapeutics Owen A. O'ConnorEmployment: TG TherapeuticsLeadership: TG TherapeuticsBoard Appointments, Stock, and Other Ownership Interests: TG Therapeutics, Kymera, Myeloid Therapeutics, NomoCan PharmaceuticalsHonoraria: MundipharmaConsulting or Advisory Role: Mundipharma Research, Astex PharmaceuticalsResearch Funding: Merck, Celgene/Bristol-Myers Squibb, Seagen, Mundipharma, Astex Pharmaceuticals, ADC Therapeutics Michael S. WeissEmployment: TG TherapeuticsLeadership: TG TherapeuticsStock and Other Ownership Interests: TG TherapeuticsTravel, Accommodations, Expenses: TG Therapeutics Pier Luigi ZinzaniConsulting or Advisory Role: Sanofi, Verastem, Celltrion, Gilead Sciences, Janssen-Cilag, Bristol-Myers Squibb, SERVIER, Sandoz, MSD, Immune Design, Celgene, Portola Pharmaceuticals, Roche, EUSA Pharma, Kyowa Hakko Kirin, TG Therapeutics, TakedaSpeakers' Bureau: Verastem, Celltrion, Gilead Sciences, Janssen-Cilag, Bristol-Myers Squibb, SERVIER, Sandoz, MSD, Immune Design, Celgene, Portola Pharmaceuticals, Roche, EUSA Pharma, Kyowa Hakko KirinNo other potential conflicts of interest were reported.

This is a review of the published contributions made by Brazilian researchers between 2010 and 2020 on the natural history of human toxocariasis and the effects of human toxocariasis on nonhuman paratenic hosts., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Chieffi et al.)

Brachytherapy has an excellent clinical outcome for different treatment sites. However, in vivo treatment verification is not performed in the majority of hospitals due to the lack of proper monitoring systems. This study investigates the use of an imaging panel (IP) and the photons emitted by a high dose rate (HDR) 192 Ir source to track source motion and obtain some information related to the patient anatomy. The feasibility of this approach was studied by monitoring the treatment delivery to a 3D printed phantom that mimicks a prostate patient. A 3D printed phantom was designed with a template for needle insertion, a cavity ('rectum') to insert an ultrasound probe, and lateral cavities used to place tissue-equivalent materials. CT images were acquired to create HDR 192 Ir treatment plans with a range of dwell times, interdwell distances and needle arrangements. Treatment delivery was verified with an IP placed at several positions around the phantom using radiopaque markers on the outer surface to register acquired IP images with the planning CT. All dwell positions were identified using acquisition times ≤0.11 s (frame rates ≥ 9 fps). Interdwell distances and dwell positions (in relation to the IP) were verified with accuracy better than 0.1 cm. Radiopaque markers were visible in the acquired images and could be used for registration with CT images. Uncertainties for image registration (IP and planning CT) between 0.1 and 0.4 cm. The IP is sensitive to tissue-mimicking insert composition and showed phantom boundaries that could be used to improve treatment verification. The IP provided sufficient time and spatial resolution for real-time source tracking and allows for the registration of the planning CT and IP images. The results obtained in this study indicate that several treatment errors could be detected including swapped catheters, incorrect dwell times and dwell positions., (Creative Commons Attribution license.)

The training set of atomic configurations is key to the performance of any Machine Learning Force Field (MLFF) and, as such, the training set selection determines the applicability of the MLFF model for predictive molecular simulations. However, most atomistic reference datasets are inhomogeneously distributed across configurational space (CS), and thus, choosing the training set randomly or according to the probability distribution of the data leads to models whose accuracy is mainly defined by the most common close-to-equilibrium configurations in the reference data. In this work, we combine unsupervised and supervised ML methods to bypass the inherent bias of the data for common configurations, effectively widening the applicability range of the MLFF to the fullest capabilities of the dataset. To achieve this goal, we first cluster the CS into subregions similar in terms of geometry and energetics. We iteratively test a given MLFF performance on each subregion and fill the training set of the model with the representatives of the most inaccurate parts of the CS. The proposed approach has been applied to a set of small organic molecules and alanine tetrapeptide, demonstrating an up to twofold decrease in the root mean squared errors for force predictions on non-equilibrium geometries of these molecules. Furthermore, our ML models demonstrate superior stability over the default training approaches, allowing reliable study of processes involving highly out-of-equilibrium molecular configurations. These results hold for both kernel-based methods (sGDML and GAP/SOAP models) and deep neural networks (SchNet model).

Introduction: Functional mobility (FM) is a concept that incorporates the capacity of a person to move independently and safely to accomplish tasks. It has been proposed as a Parkinson's disease (PD) functional and global health outcome. In this study, we aimed to identify which kinematic and clinical outcomes changes better predict FM changes when PD patients are submitted to a specialized multidisciplinary program. Methods: PD patients engaged in a pre-defined specialized multidisciplinary program were assessed at admission and discharge. Change from baseline was calculated for all kinematic and clinical outcomes, and Timed Up and Go (TUG) was defined as the primary outcome for FM. A stepwise multivariate linear regression was performed to identify which outcome measures better predict TUG changes. Results: Twenty-four patients were included in the study. The changes in TUG Cognitive test, supervised step length, and free-living (FL) step time asymmetry were identified as the best predictors of TUG changes. The supervised step length and FL step time asymmetry were able to detect a small to moderate effect of the intervention ( d values ranging from -0.26 to 0.42). Conclusions: Our results support the use of kinematic outcome measures to evaluate the efficacy of multidisciplinary interventions on PD FM. The TUG Cognitive, step length, and FL step time asymmetry were identified as having the ability to predict TUG changes. More studies are needed to identify the minimal clinically important difference for step length and FL step time asymmetry in response to a multidisciplinary intervention for PD FM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bouça-Machado, Branco, Fonseca, Fernandes, Abreu, Guerreiro, Ferreira and The CNS Physiotherapy Study Group.)

Dynamics of flexible molecules are often determined by an interplay between local chemical bond fluctuations and conformational changes driven by long-range electrostatics and van der Waals interactions. This interplay between interactions yields complex potential-energy surfaces (PESs) with multiple minima and transition paths between them. In this work, we assess the performance of the state-of-the-art Machine Learning (ML) models, namely, sGDML, SchNet, Gaussian Approximation Potentials/Smooth Overlap of Atomic Positions (GAPs/SOAPs), and Behler-Parrinello neural networks, for reproducing such PESs, while using limited amounts of reference data. As a benchmark, we use the cis to trans thermal relaxation in an azobenzene molecule, where at least three different transition mechanisms should be considered. Although GAP/SOAP, SchNet, and sGDML models can globally achieve a chemical accuracy of 1 kcal mol -1 with fewer than 1000 training points, predictions greatly depend on the ML method used and on the local region of the PES being sampled. Within a given ML method, large differences can be found between predictions of close-to-equilibrium and transition regions, as well as for different transition mechanisms. We identify key challenges that the ML models face mainly due to the intrinsic limitations of commonly used atom-based descriptors. All in all, our results suggest switching from learning the entire PES within a single model to using multiple local models with optimized descriptors, training sets, and architectures for different parts of the complex PES.

We tested the hypothesis that the ubiquity of marine meiofaunal nematodes and their indiscriminate passive dispersal create assemblages that are less limited by its environment; whereas the relatively smaller population sizes of macrofauna, associated with their ability to track environmental conditions before settlement, renders their distribution more environmentally-restricted. We compared the empirical distribution of macrofauna and nematode species with that of communities simulated under different assumptions of selection (e.g. environmental filtering) and non-selection (e.g. dispersal limitation) processes. Selection processes were the prime driver of both meio- and macrofauna assemblages, with rare species strongly contributing to this component. The total number of species explained by non-selection processes was 27% higher in nematodes than in macrofauna. Our results underline the importance of a species-level approach to determine the contribution of selection and non-selection assembly processes. Moreover, they highlight the important yet overlooked role of dispersal and stochastic processes in determining species dynamics., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Patients with multiple myeloma who have relapsed after or become refractory to lenalidomide in early treatment lines represent a clinically important population in need of effective therapies. The safety and efficacy of pomalidomide, low-dose dexamethasone, and daratumumab was evaluated in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM) after one to two prior treatment lines in the phase 2 MM-014 study. Patients received pomalidomide 4 mg daily from days 1-21 and dexamethasone 40 mg weekly (28-day cycles). Daratumumab 16 mg/kg was administered per label. Primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS) and safety. Per protocol, all patients (N = 112) had received lenalidomide in their most recent prior regimen (75.0% lenalidomide refractory). ORR was 77.7% (76.2% in lenalidomide-refractory patients); median follow-up was 17.2 months. Median PFS was not reached (1-year PFS rate 75.1%). The most common hematologic grade 3/4 treatment-emergent adverse event was neutropenia (62.5%). Grade 3/4 infections were reported in 31.3% of patients, including 13.4% with grade 3/4 pneumonia. These results demonstrate the safety and efficacy of pomalidomide-based therapy as early as second line in patients with RRMM, even immediately after lenalidomide failure, indicating that switching from the immunomodulatory agent class is not necessary.

Cancer is a disease that impacts not only the patient but also affects the entire family. Family members experience high levels of distress. Therefore, screening for cancer-specific distress among family members of people with cancer is important but relatively unexplored. This cross-sectional study aims to analyze the psychometric properties of a screening tool for family members of people with cancer. We examined the usefulness of the emotional thermometers burden version (ET-BV) in detecting caregiver emotional distress. The ET-BV is a simple multidomain visual analogue scale distributed in two major domains: "emotional upset" and "impact." A total of 364 cancer patients' family members completed the ET-BV and Brief Symptom Inventory. Analyses were aimed to examine the diagnostic accuracy (receiver operating characteristic) of the ET-BV. A fair to good diagnostic accuracy was achieved for ET-BV. For emotional upset thermometers, a cutoff of ≥5 was determined and for impact thermometers, a cutoff of ≥4 was established. ET-BV seems to be a useful, quick, and simple tool for distress screening in family members of people with cancer. A revision of a specific thermometer is discussed in order to increase ET screening performance and clinical utility.

Background: Laparoscopic liver resections (LLR) have been increasingly performed in recent years. Most of the available evidence, however, comes from specialized centers in Asia, Europe and USA. Data from South America are limited and based on single-center experiences. To date, no multicenter studies evaluated the results of LLR in South America. The aim of this study was to evaluate the experience and results with LLR in South American centers., Methods: From February to November 2019, a survey about LLR was conducted in 61 hepatobiliary centers in South America, composed by 20 questions concerning demographic characteristics, surgical data, and perioperative results., Results: Fifty-one (83.6%) centers from seven different countries answered the survey. A total of 2887 LLR were performed, as follows: Argentina (928), Brazil (1326), Chile (322), Colombia (210), Paraguay (9), Peru (75), and Uruguay (8). The first program began in 1997; however, the majority (60.7%) started after 2010. The percentage of LLR over open resections was 28.4% (4.4-84%). Of the total, 76.5% were minor hepatectomies and 23.5% major, including 266 right hepatectomies and 343 left hepatectomies. The conversion rate was 9.7%, overall morbidity 13%, and mortality 0.7%., Conclusions: This is the largest study assessing the dissemination and results of LLR in South America. It showed an increasing number of centers performing LLR with the promising perioperative results, aligned with other worldwide excellence centers.

This study proposes an index for food labeling in order to promote sustainable consumption. The index is calculated by ranking multiple features from the environmental, health and nutritional dimensions of the target product in relation to a pre-set reference value; the obtained scores from each dimension are plotted in a radar chart resulting in a triangular area. An increase in area represents a greater impact. As examples, tuna and the potato-based foods at three different processing levels (in natura or minimally processed, processed and ultra-processed) were analyzed. For both cases, the index increases according to the processing grades and has proved to be capable of expressing in numbers and graphically a wide range of environmental, nutritional and health issues., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Species responses to stress are expected to be dependent on their life-history strategy. In this study, we compare the responses of two free-living marine nematodes, Litoditis marina and Diplolaimella dievengatensis, both considered opportunistic, fast-growing, and stress-tolerant species, to the exposure to sublethal concentrations of sodium dodecyl sulfate (SDS) surfactant. Specifically, we evaluated the growth and reproduction rates, as well as the survival of individuals exposed from eggs and/or juveniles (J1) onwards. Exposure to SDS significantly affected the growth and reproduction rates of both species. However, whereas growth and reproduction rates of D. dievengatensis were significantly enhanced at low and intermediate concentrations of SDS (0.001% and 0.003%), for L. marina both parameters were significantly reduced by all SDS concentrations tested (0.001%, 0.003% and 0.006%). Exposure to SDS did not affect the survival of adult nematodes of D. dievengatensis, while for L. marina, survival of males exposed to 0.006% SDS was significantly reduced compared to the control. Responses of the life-history traits growth, fecundity and survival did not exhibit clear trade-offs. The contrasting responses of D. dievengatensis and L. marina indicate that biologically and ecologically similar species can have remarkably distinct tolerances to stress, and that, in agreement with recent studies, rhabditid nematodes cannot a priori be considered very stress tolerant. Consequently, single species traits and phylogenetic relatedness are poor predictors of nematode responses to toxic stress posed by anthropogenic activities., (Copyright © 2020 Elsevier B.V. All rights reserved.)

External beam radiotherapy with photon beams is a highly accurate treatment modality, but requires extensive quality assurance programs to confirm that radiation therapy will be or was administered appropriately. In vivo dosimetry (IVD) is an essential element of modern radiation therapy because it provides the ability to catch treatment delivery errors, assist in treatment adaptation, and record the actual dose delivered to the patient. However, for various reasons, its clinical implementation has been slow and limited. The purpose of this report is to stimulate the wider use of IVD for external beam radiotherapy, and in particular of systems using electronic portal imaging devices (EPIDs). After documenting the current IVD methods, this report provides detailed software, hardware and system requirements for in vivo EPID dosimetry systems in order to help in bridging the current vendor-user gap. The report also outlines directions for further development and research. In vivo EPID dosimetry vendors, in collaboration with users across multiple institutions, are requested to improve the understanding and reduce the uncertainties of the system and to help in the determination of optimal action limits for error detection. Finally, the report recommends that automation of all aspects of IVD is needed to help facilitate clinical adoption, including automation of image acquisition, analysis, result interpretation, and reporting/documentation. With the guidance of this report, it is hoped that widespread clinical use of IVD will be significantly accelerated., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: I Olaciregui-Ruiz and B Mijnheer declare that their department licensed portal dosimetry software to Elekta Oncology Systems Ltd. for the development of the iViewDose product. This product is currently not commercially available. P Greer declares research collaborations with Varian Medical Systems. B McCurdy declares funded research collaborations on EPID dosimetry with Varian Medical Systems. N. Jornet declares that she is member of the European scientific advisory board of Sun Nuclear. F Verhaegen declares research collaborations and a patent on in vivo dosimetry with Varian Medical Systems., (© 2020 The Authors.)

Background: Red blood cell (RBC) alloimmunization is an important transfusion complication which is prevalent among sickle cell disease (SCD) patients. Autoimmune diseases are a known risk factor for RBC alloimmunization, suggesting that autoimmunity and post-transfusion alloantibody development occur through similar physiopathological pathways. Polymorphisms in the FcγR2B gene have already been associated with several autoimmune disorders and hypothetically could be associated with RBC alloimmunization. Our goal was to evaluate if important polymorphisms of FcγR2B have an impact on the risk of RBC alloimmunization among SCD patients., Study Design and Methods: This was a case-control study in which alloimmunized and non-alloimmunized SCD patients were compared in terms of the genotype frequency of the FcγR2B polymorphisms -386G/C, -120 T/A, and 695C/T, genotyped through direct Sanger sequencing., Results: A total of 237 patients met the eligibility criteria, 120 cases (alloimmunized) and 117 controls (non-alloimmunized). RBC alloimmunization was associated with female sex (p < 0.001), lifetime number of RBC units transfused (p = 0.002) and 120 T/A FcγR2B genotype (p = 0.031). The FcγR2B promoter region haplotype 2B.4 (386C120A) was positively associated with RBC alloimunization (p = 0.045). The logistic regression (LR) model identified female sex (OR 10.03, CI 95% 5.16-19.49; p < 0.001) and FcγR2B 2B.4 haplotype (OR 4.55, CI95% 1.1118.65; p = 0.035) as independent predictors of RBC alloimmunization in SCD patients., Conclusion: SCD patients with the FcγR2B 2B.4 haplotype had over a fourfold higher risk for RBC alloimmunization. This highlights the role played by FcγR2B on RBC alloimmunization and may be helpful in identifying the immune responders., (© 2020 AABB.)

Background: Cross-transmission is a major concern in dental offices. Various disinfection methods have been frequently used to reduce its incidence. Standard procedures include decontamination and sterilization. Traditional decontamination methods include: Alcohol 70 % and chlorhexidine digluconate, however, antimicrobial photodynamic therapy (aPDT) could be added as an option. The objective was to evaluate the effectiveness of aPDT on decontamination of high-speed handpieces, contaminated by Staphylococcus aureus (SA) and Escherichia coli (EC), and compare it to autoclave sterilized and to conventional chemical decontamination methods., Methods: Sterilized, SA and EC contaminated high-speed handpieces were divided in 7 groups: G1- sterilized in an autoclave. G2- contaminated untreated control. G3- contaminated and decontaminated using Alcohol 70 %. G4- contaminated and decontaminated using chlorhexidine digluconate 2%. G5- contaminated and laser treated. G6- contaminated and photosensitizer treated. G7- contaminated and photodynamic therapy., Results: The groups G3, G4, G7 did not show bacterial growth, G5 and G6 showed bacterial growth similar to G2. The study did not find SA or EC sensible to laser irradiation only, differently from some authors and did not consider biofilm in our experiments., Conclusion: Our experiment showed that, laser and photosensitizer isolated were not effective to inhibit Staphylococcus aureus (SA) and Escherichia coli (EC) growth, but when associated in aPDT technique, can be compared to chemical disinfection agents that are traditionally used and effective against this pathogen., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Invasive lobular carcinoma is often challenging to diagnose due to the lack of physical examination findings and macrocalcifications on mammography. The cells of invasive lobular carcinoma form a distinct single file pattern that can be identified on histology slides. Often, when patients present, there is metastasis to the bones, lymph nodes, and gastrointestinal tract. Tumor markers are a valuable tool in identification, especially the loss of E-cadherin protein. However, if E-cadherin protein is not available, epidermal membrane antigen, which inhibits E-cadherin, can prove to be a significant diagnostic tool. Epidermal membrane antigen was the key tumor marker in our patient case. Other tumor markers and histology stains can drive treatment plans and help predict prognosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Klumpp et al.)

In this study, new polyurethanes (PUs) were prepared by using inulin and polycaprolactone as polyols. Their structure and morphology were determined by Fourier transform infrared spectroscopy (FTIR), Raman dispersive spectroscopy, Nuclear magnetic resonance spectroscopy ( 1 H NMR and 13 C NMR), and scanning electron microscopy (SEM), whereas their mechanical properties were evaluated by a universal testing machine. Additionally, their water uptake, swelling behavior, and degradation were evaluated to be used as drug delivery carriers. Therefore, an anti-cancer drug was loaded to these PUs with 25% of loading efficiency and its release behavior was studied using different theoretical models to unveil its mechanism. Finally, the ability of the new PUs to be used as a clip marker in breast biopsy was evaluated. The results clearly demonstrate that these PUs are safe and can be used as intelligent drug release matrices for targeted drug delivery and exhibits positive results to be used for clip marker and in general for breast cancer applications.

Objective: In selected rectal cancer patients with residual local disease following neoadjuvant chemoradiation (CRT) and the preference of an organ preservation pathway, additional treatment with dose escalation by endoluminal radiotherapy (RT) may ultimately result in a clinical complete response. To date, the widespread introduction of selective endoluminal radiation techniques is hampered by a lack of evidence-based guidelines that describe the radiation treatment volume in relation to the residual tumor mass. In order to convert an incomplete response into a complete one with additional treatment such as dose-escalation with endoluminal RT from a theoretical perspective, it seems important to treat all remaining microscopic tumor cells after CRT. In this setting, residual tumor extension beneath normal appearing mucosa (microscopic intramural spread - MIS) becomes relevant for accurate tumor volume and margin estimation. With the goal of providing evidence-based guidelines that define an appropriate treatment volume and patient selection, we present results from a meta-analysis based on individual patient data of studies that have assessed the extent or range of MIS of rectal cancers after neoadjuvant CRT. This meta-analysis should provide an estimate of the residual tumor volume/extension that needs to be targeted by any additional radiation therapy boost in order to achieve complete tumor eradication after initial incomplete or near-complete response following standard CRT., Methods and Materials: A PubMed search was performed. Additional articles were selected based on identification from reference lists. Papers were eligible when reporting MIS in patients who were treated by total mesorectal excision or local excision/transanal endoscopic microsurgery (TEM) after neo-adjuvant long-course CRT. The mean MIS was calculated for the entire group along with the 70th until 95th percentiles. Additional exploratory subgroup analyses were performed., Results: Individual patient data from 349 patients with residual disease from five studies were analyzed. 80% of tumors showed no MIS. In order to appropriately treat MIS in 95% of rectal cancer patients after CRT, a margin of 5.5 mm around the macroscopic tumor would suffice. An exploratory subgroup analysis showed that T-stage after CRT (ypT) and time interval between neoadjuvant CRT and surgery are significant factors predicting the extent of MIS (p < 0.001.) The group of ypT1 had the smallest MIS, followed by the ypT3-4 group, while the ypT2 group had the largest MIS (p < 0.001). Regarding time interval between CRT and surgery, a statistically significant difference was seen when comparing the three time-interval groups (less than 8 weeks, 8-12 weeks, and more than 12 weeks), where waiting more than 12 weeks after CRT resulted in the largest MIS (p < 0.0001)., Conclusion: Based on this meta-analysis, in order to treat the MIS for 95% of rectal cancer patients after CRT, a Clinical Target Volume (CTV) margin of 5.5 mm from the lateral most edge of the macroscopic tumor would suffice. 80% of tumors showed no MIS and would not require an extra CTV margin for treatment. These findings support the feasibility of localized radiotherapy boosts for dose-escalation to improve response among patients with incomplete response after standard CRT and can also be applied in the surgical setting., Competing Interests: Declaration of Competing Interest Authors E.J. Van Limbergen, M. Berbee, A. Verrijssen, F. Verhaegen and J. Melenhorst report a research grant from Varian Medical Systems on “Phase-II trial on endoluminal boosting in rectal cancer using the MAASTRO applicator”. In addition, authors E.J. Van Limbergen, M. Berbee, F. Verhaegen, M. Bellezzo and G. Paiva Fonseca have a patent EP16204735, rectal brachytherapy applicator with royalties paid to Maastro Clinic/University Maastricht., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: The definition of sarcopenia based on appendicular lean mass/height (2) (ALM/height (2) ) is often used, although it can underestimate the prevalence of sarcopenia in overweight/obese patients with heart failure. Therefore, new methods have been proposed to overcome this limitation. We aimed to evaluate the prevalence of sarcopenia by three methods and compare body composition in this population., Methods and Results: We enrolled 168 male patients with heart failure (left ventricular ejection fraction <40%). Sixty-six patients (39.3%) were identified with sarcopenia by at least one method. The lower 20th percentile defined as the cut-off point for sarcopenia was 7.03 kg/m 2 , -2.32 and 0.76 for Baumgartner's (20.8%), Newman's (21.4%), and Studenski's methods (21.4%), respectively. Patients with body mass index (BMI) <25 kg/m 2 were more likely to be identified by Baumgartner's than Studenski's method (P < 0.001). However, in patients with BMI ≥ 25 kg/m 2 , Studenski's and Newman's methods were more likely to detect sarcopenia than Baumgartner's method (both P < 0.005). Patients were further divided into three subgroups: (i) patients classified in all indexes (n = 8), (ii) patients classified in Baumgartner's (sarcopenic; n = 27), and (iii) patients classified in both Newman's and Studenski's methods (sarcopenic obesity; n = 31). Comparing body composition among groups, all sarcopenic groups presented lower total lean mass compared with non-sarcopenic patients, whereas sarcopenic obese patients had higher total lean mass than lean sarcopenic patients., Conclusions: Our results demonstrate that the prevalence of sarcopenia in overweight/obese patients is similar to lean sarcopenic patients when other methods are considered. In patients with higher BMI, Studenski's method seems to be more feasible to detect sarcopenia., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Objective: The aims of this study were to assess the reliability, reproducibility and validity of mesiodistal and buccolingual measurements comparing these measurements collected using an electronic hand-held digital calliper, on dry dentitions and on dental casts, with measurements obtained from 3D digital models created using a portable intra-oral scanner., Design: The mesiodistal and buccolingual diameter of the crown of 1304 teeth were measured on dry dentitions and on dental casts, and secondly on 3D digital models created using an intra-oral 3D scanner. Reliability, reproducibility and validity were evaluated using the intraclass correlation coefficient (ICC) and the Bland-Altman graphic method., Results: The results of the intraclass correlation coefficient expressed an excellent degree of agreement in the intra- and inter-observer error analysis, as well as in the comparison of the mesiodistal and buccolingual dimensions taken with the calliper and those taken in digital 3D models. The results of the Bland-Altman method showed that the greatest differences were found in the mesiodistal diameter of the molars and in the buccolingual diameter of the upper premolars., Conclusions: Mesiodistal and buccolingual measurements obtained from digital 3D models are suitable for recording dentitions for forensic purposes., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Predictions of the effects of global change on ecological communities are largely based on single habitats. Yet in nature, habitats are interconnected through the exchange of energy and organisms, and the responses of local communities may not extend to emerging community networks (i.e., metacommunities). Using large mesocosms and meiofauna communities as a model system, we investigated the interactive effects of ocean warming and acidification on the structure of marine metacommunities from three shallow-water habitats: sandy soft-bottoms, marine vegetation, and rocky reef substrates. Primary producers and detritus-key food sources for meiofauna-increased in biomass under the combined effect of temperature and acidification. The enhanced bottom-up forcing boosted nematode densities but impoverished the functional and trophic diversity of nematode metacommunities. The combined climate stressors further homogenized meiofauna communities across habitats. Under present-day conditions metacommunities were structured by habitat type, but under future conditions they showed an unstructured random pattern with fast-growing generalist species dominating the communities of all habitats. Homogenization was likely driven by local species extinctions, reducing interspecific competition that otherwise could have prevented single species from dominating multiple niches. Our findings reveal that climate change may simplify metacommunity structure and prompt biodiversity loss, which may affect the biological organization and resilience of marine communities., (© 2019 John Wiley & Sons Ltd.)

Cerebral cavernous malformations (CCMs) are dilated capillaries causing epilepsy and stroke. Inheritance of a heterozygous mutation in CCM3/PDCD10 is responsible for the most aggressive familial form of the disease. Here we studied the differences and commonalities between the transcriptomes of microdissected lesional neurovascular units (NVUs) from acute and chronic in vivo Ccm3/Pdcd10 ECKO mice, and cultured brain microvascular endothelial cells (BMECs) Ccm3/Pdcd10 ECKO .We identified 2409 differentially expressed genes (DEGs) in acute and 2962 in chronic in vivo NVUs compared to microdissected brain capillaries, as well as 121 in in vitro BMECs with and without Ccm3/Pdcd10 loss (fold change ≥ |2.0|; p < 0.05, false discovery rate corrected). A functional clustered dendrogram generated using the Euclidean distance showed that the DEGs identified only in acute in vivo NVUs were clustered in cellular proliferation gene ontology functions. The DEGs only identified in chronic in vivo NVUs were clustered in inflammation and immune response, permeability, and adhesion functions. In addition, 1225 DEGs were only identified in the in vivo NVUs but not in vitro BMECs, and these clustered within neuronal and glial functions. One miRNA mmu-miR-3472a was differentially expressed (FC = - 5.98; p = 0.07, FDR corrected) in the serum of Ccm3/Pdcd10 +/- when compared to wild type mice, and this was functionally related as a putative target to Cand2 (cullin associated and neddylation dissociated 2), a DEG in acute and chronic lesional NVUs and in vitro BMECs. Our results suggest that the acute model is characterized by cell proliferation, while the chronic model showed inflammatory, adhesion and permeability processes. In addition, we highlight the importance of extra-endothelial structures in CCM disease, and potential role of circulating miRNAs as biomarkers of disease, interacting with DEGs. The extensive DEGs library of each model will serve as a validation tool for potential mechanistic, biomarker, and therapeutic targets.

The purpose of this framework is to identify the relative importance of selection and dispersion processes in structuring ecological communities. Using a "pattern-oriented modelling" approach, it consists of five steps: (a) aggregate information from the empirical community and its environment, (b) simulate communities under different degrees of dispersal and selection, (c) select the best set of simulations into a composite model using the environmental boundary (EB) and niche breadth (NB) of each observed species, (d) validate the composite model by comparing expected and observed results from three additional community patterns and (e) classify each observed species along the selection/non-selection continuum. A free-living marine nematodes data set from a coastal bay was used as empirical example. A total of 20 parameterizations were applied varying selection and dispersion levels. In the absence of selection, species from high-dispersal parameter sets showed maximum EBs and NBs, whilst selection parameter sets generated species with narrower EB and NB values. EB and NB values declined with decreasing dispersal. The composite model encompassed 96% of the 194 nematode species and predicted all the three patterns evaluated without further calibration, i.e., they are independent: (1) abundance-rank distribution, the assemblage structures along both the (2) spatial and (3) environmental gradients. Non-selection and selection parameter sets accounted for 34% and 85% of the observed species, respectively. The main advantage of this approach is that empirical niche measurements are placed in the context of model-generated expectations, enabling a deeper understanding of community assembly processes and how they vary from species to species.

Objective: The issues surrounding a patient's terminal phase of cancer and the imminent death of the individual represent a major family crisis affecting all its members. The goal of this study was to assess the prevalence of psychological morbidity in family caregivers of persons with terminal cancer in terms of psychological distress, depression, anxiety, somatization, and complicated anticipatory grief, and to determine which factors may influence these responses., Method: One hundred and twelve family caregivers of individuals with terminal cancer completed an assessment protocol comprising the Brief Symptom Inventory (depression, anxiety, somatization, and a computed score for global distress), the Marwit-Meuser Caregiver Grief Inventory - Short Form (anticipatory grief), the Family Inventory of Needs (importance and satisfaction of needs), and the Systemic Clinical Outcome Routine Evaluation -15 (family functioning). Prevalence of psychological morbidity was determined through descriptive and frequency statistics. Predictors of psychological morbidity were ascertained through structural equation modelling methods.ResultRegarding the prevalence of psychological morbidity in family caregivers, 66.1% reported high levels of distress, 68.8% showed high risk of depression, 72.3% showed high risk of anxiety, 50.9% reported high levels of somatization, and 25.9% showed high risk of complicated anticipatory grief. It was found that the predictors of age, gender, relationship to the family member with terminal cancer, the caregiving role played (i.e., primary vs. nonprimary), the satisfaction of needs by healthcare professionals, and family functioning play an important role in terms of one's risk of developing psychological morbidity.Significance of resultsThis study revealed an alarming prevalence of psychological morbidity in family caregivers of individuals living with terminal cancer, making it crucial to move forward from a patient-centered approach to a family-centrad approach to reduce the risk of family maladjustment when facing the imminent death of a family member and to prevent postdeath unadjusted responses.

Chromadoridae is a widespread family of mostly free-living marine nematodes. This systematic review provides for each genus: a historical background, an updated diagnosis and a list of species. Our review recognizes 37 valid genera, 395 valid species, 57 descriptions without enough morphological information for accurate identification (species inquirenda) and 10 species incerta sedis. We also recognize 21 species as nomena nuda. Additionally, polytomous keys were constructed for the subfamilies and for the genera of the three major subfamilies (Chromadorinae, Euchromadorinae and Hypodontolaiminae) using the most important diagnostic characters. A phylogenetic analysis based on rDNA sequences of species available in the GenBank was also conducted. Phylogenetic trees based on the 18S and 28S rDNA confirmed the classification into three subfamilies (Spilipherinae, Hypodontolaiminae and Chromadorinae), despite the absence of defined synapomorphies. Phylogenetic relationships at lower taxonomic level are problematic given the large number of sequences not identified to species level.

The purpose of this study was to determine important genes, functions, and networks contributing to the pathobiology of cerebral cavernous malformation (CCM) from transcriptomic analyses across 3 species and 2 disease genotypes. Sequencing of RNA from laser microdissected neurovascular units of 5 human surgically resected CCM lesions, mouse brain microvascular endothelial cells, Caenorhabditis elegans with induced Ccm gene loss, and their respective controls provided differentially expressed genes (DEGs). DEGs from mouse and C. elegans were annotated into human homologous genes. Cross-comparisons of DEGs between species and genotypes, as well as network and gene ontology (GO) enrichment analyses, were performed. Among hundreds of DEGs identified in each model, common genes and 1 GO term (GO:0051656, establishment of organelle localization) were commonly identified across the different species and genotypes. In addition, 24 GO functions were present in 4 of 5 models and were related to cell-to-cell adhesion, neutrophil-mediated immunity, ion transmembrane transporter activity, and responses to oxidative stress. We have provided a comprehensive transcriptome library of CCM disease across species and for the first time to our knowledge in Ccm1/Krit1 versus Ccm3/Pdcd10 genotypes. We have provided examples of how results can be used in hypothesis generation or mechanistic confirmatory studies.

Marine meiofauna comprises up to 22 phyla. Its morphological identification requires time and taxonomists' expertise, and molecular tools can make this task faster. We aim to disentangle meiofaunal diversity patterns at Araçá Bay by applying a model selection approach and estimating the effectiveness of metabarcoding (18S rDNA) and morphological methods for estimating the response of meiofauna diversity in small-scale interactions with environmental variables. A rarefaction curve indicated that ten samples were sufficient for estimating the total number of meiofauna OTUs in a tidal flat. In both approaches, richness was predicted by mean sand percentage, sediment sorting, and bacteria concentration. Nematode genera composition differed significantly between approaches, the result of taxonomic mismatch in the genetic database. The similarity between the model selected for diversity descriptors, the richness of nematode genera and meiofauna composition emphasized the utility of predictive models for metabarcoding estimates to detect small-scale interactions of these organisms., (Copyright © 2018 Elsevier Ltd. All rights reserved.)