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Cancer therapy is a dynamically evolving field, witnessing the emergence of innovative approaches that offer a promising outlook for patients grappling with persistent disease. Within the realm of therapeutic exploration, chimeric antigen receptor (CAR) T cells as well as CAR NK cells, have surfaced as novel approaches, each possessing unique attributes and transformative potential. Immune cells engineered to express CARs recognizing tumour‐specific antigens, have shown remarkable promise in treating terminal cancers by combining the precision of antibody specificity with the potent cytotoxic function of T cells. However, their application in solid tumours is still in its nascent stages, presenting unique major challenges. On the same note, CAR NK cells offer a distinct immunotherapeutic approach, utilizing CARs on NK cells, providing advantages in safety, manufacturing simplicity, and a broader scope for cancer treatment. Extracellular vesicles (EVs) have emerged as promising therapeutic agents due to their ability to carry crucial biomarkers and biologically active molecules, serving as vital messengers in the intercellular communication network. In the context of cancer, the therapeutic potential of EVs lies in delivering tumour‐suppressing proteins, nucleic acid components, or targeting drugs with precision, thereby redefining the paradigm of precision medicine. The fusion of CAR technology with the capabilities of EVs has given rise to a new therapeutic frontier. CAR T EVs and CAR NK EVs, leveraging the power of EVs, have the potential to alleviate challenges associated with live‐cell therapies. EVs are suggested to reduce the side effects linked to CAR T cell therapy and hold the potential to revolutionize the penetrance in solid tumours. EVs act as carriers of pro‐apoptotic molecules and RNA components, enhancing immune responses and thereby expanding their therapeutic potential. In this review article, we navigate dynamic landscapes, with our objective being to evaluate comparative efficacy, safety profiles, manufacturing complexities, and clinical applicability. [ABSTRACT FROM AUTHOR]

Objective: To assess the capacity of fetal pancreatic size, before standard blood glucose testing for screening and diagnosis, to predict maternal gestational diabetes mellitus (GDM). Methods: This was a retrospective cohort study of low‐risk pregnant women recruited during routine second‐trimester fetal anatomical screening at 20–25 weeks' gestation at two ultrasound units in Israel between 2017 and 2020. The predictive performance of fetal pancreatic circumference ≥ 80th and ≥ 90th centiles and glucose challenge test (GCT) was examined for the outcome of GDM. The independent‐samples t‐test was used to compare mean pancreatic circumference centile between pregnancies with GDM and those without GDM. Diagnostic performance was evaluated with 2 × 2 contingency tables and receiver‐operating‐characteristics (ROC) curves. Results: Overall, 195 women were selected for statistical analysis. Twenty‐four (12.3%) women were diagnosed subsequently with GDM. The mean ± SD fetal pancreatic circumference centile was significantly higher in the GDM group compared with the non‐GDM group (82.4 ± 14.6 vs 62.8 ± 27.6; P < 0.001). The pancreatic circumference centile was correlated positively with the estimated fetal weight centile (Pearson's coefficient, 0.243; P = 0.001). The 80th centile cut‐off for pancreatic circumference had the highest sensitivity (70.8%) and positive predictive value (23.3%) for future maternal GDM, with the best trade‐off between sensitivity and specificity achieved at the 75th centile cut‐off (sensitivity, 79%; specificity, 60%). The GCT had better specificity (90.2%) and negative predictive value (97.9%) compared with both cut‐offs in pancreatic circumference. The area under the ROC curve was higher for pancreatic circumference compared with GCT (0.71 vs 0.64) and only the former was statistically significant (P = 0.001). Conclusions: Fetal pancreatic circumference has a higher positive predictive capacity compared with GCT. Measuring pancreatic circumference can identify pregnancies at high risk for maternal GDM, thereby promoting earlier diagnosis and treatment, decreasing the time period during which the fetus is exposed to high maternal glucose levels and improving infant outcome. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess radiographic marginal bone changes 22 months post extraction, which is 1 year after implant loading in alveolar ridge preservation (ARP) sites grafted with a combination of collagen‐embedded xenogenic bone substitute (DBBM‐C) and collagen matrix (CMX), comparing them with implants placed in naturally healed sites. Methods: This randomized controlled clinical trial was conducted over 22 months. Patients who needed a single tooth extraction and subsequent implant placement in nonmolar areas were enrolled. The test group received deproteinized bovine bone mineral with 10% collagen covered by a procaine collagen membrane, while the control group allowed spontaneous healing. Radiographic bone level changes were documented using periapical radiographs at implant placement and follow‐up visits (6, 10, and 22 months postextraction). Early implant soft tissue exposure, clinical parameters, and patient‐reported outcomes were recorded. Results: Twenty‐two out of 28 participants completed a 22‐month follow‐up, 9 in the test group and 13 in the control group. At 10‐month postextraction follow‐up, the mean MBL was 1.01 ± 1.04 mm in the treatment group and 0.81 ± 0.93 mm in the control group (p = 0.804). At 22 months, the mean MBL was 2.09 ± 1.03 mm in the treatment group and 1.58 ± 0.73 mm in the control group (p = 0.339). No statistically significant differences in probing depth (PD) and bleeding on probing (BOP) were found at the 22 ‐month follow‐up as well. Soft tissue mean recession was observed in the control group (0.36 ± 0.84 mm), while no recession was found in the test group (p = 0.2). Early implant soft tissue exposure occurred in 33% of test group participants, while none was observed in the control group (p = 0.047). Conclusion: One year after implant loading, no significant differences in marginal bone resorption were found between implants placed in ARP‐treated and naturally healed sites. However, ARP‐treated sites exhibited early implant soft‐tissue exposure, suggesting a possible impairment in soft tissue healing. [ABSTRACT FROM AUTHOR]

It is well known that medication adherence is critical to patient outcomes and can decrease patient mortality. The Pharmacy Quality Alliance (PQA) has recognized and identified medication adherence as an important indicator of medication‐use quality. Hence, there is a need to use the right methods to assess medication adherence. The PQA has endorsed the proportion of days covered (PDC) as the primary method of measuring adherence. Although easy to calculate, the PDC has however several drawbacks as a method of measuring adherence. PDC is a deterministic approach that cannot capture the complexity of a dynamic phenomenon. Group‐based trajectory modeling (GBTM) is increasingly proposed as an alternative to capture heterogeneity in medication adherence. The main goal of this paper is to demonstrate, through a simulation study, the ability of GBTM to capture treatment adherence when compared to its deterministic PDC analogue and to the nonparametric longitudinal K‐means. A time‐varying treatment was generated as a quadratic function of time, baseline, and time‐varying covariates. Three trajectory models are considered combining a cat's cradle effect, and a rainbow effect. The performance of GBTM was compared to the PDC and longitudinal K‐means using the absolute bias, the variance, the c‐statistics, the relative bias, and the relative variance. For all explored scenarios, we find that GBTM performed better in capturing different patterns of medication adherence with lower relative bias and variance even under model misspecification than PDC and longitudinal K‐means. [ABSTRACT FROM AUTHOR]

Silicon (Si) content in plant tissues is considered a functional trait that can provide multiple morpho‐physiological benefits to plant individuals. However, it is still unclear whether and how these individual benefits extend to plant community processes and ecosystem functioning. Here we investigated how plant Si content is associated with plant community properties and the ecosystem structure of herbaceous communities in Israel. We sampled 15 sites across the Mediterranean and desert ecosystems and built models to evaluate how plant silicon content (community‐weighted mean and standard variation) is associated with variables such as species richness, biomass production, plant cover, and functional diversity. Finally, we used model selection techniques to test whether models depicting plant Si content perform better than models using data on soil Si instead. Sites with lower susceptibility to drought had significantly more Si‐accumulating grass species and higher soils Si content. Models with plant Si content instead of soil Si, always performed better, although those considering Si content variation had overall stronger associations with community properties than only mean Si content. For instance, up to 51% of plant Si content variation was explained by climate, biomass production, and species richness, combined. Still, mean plant Si content and plant cover combined explained up to 42% of plant functional diversity. Our results suggest the that plant Si content serves as a proxy for understanding the ecological properties and functioning of arid and Mediterranean ecosystems. Nevertheless, the significance of Si has not been fully explored in other ecosystem types, where its influence may be less pronounced compared with the ecosystems examined in this study. In light of various global change scenarios, enhancing our understanding of Si as a plant functional trait could help bridge existing knowledge gaps and improve ecological modeling, thus enabling more accurate forecasts of changes in plant distributions. [ABSTRACT FROM AUTHOR]

Let g$g$ be a random matrix distributed according to uniform probability measure on the finite general linear group GLn(Fq)$\mathrm{GL}_n(\mathbb {F}_q)$. We show that Tr(gk)$\mathrm{Tr}(g^k)$ equidistributes on Fq$\mathbb {F}_q$ as n→∞$n \rightarrow \infty$ as long as logk=o(n2)$\log k=o(n^2)$ and that this range is sharp. We also show that nontrivial linear combinations of Tr(g1),...,Tr(gk)$\mathrm{Tr}(g^1),\ldots, \mathrm{Tr}(g^k)$ equidistribute as long as logk=o(n)$\log k =o(n)$ and this range is sharp as well. Previously equidistribution of either a single trace or a linear combination of traces was only known for k⩽cqn$k \leqslant c_q n$, where cq$c_q$ depends on q$q$, due to work of the first author and Rodgers. We reduce the problem to exhibiting cancellation in certain short character sums in function fields. For the equidistribution of Tr(gk)$\mathrm{Tr}(g^k)$, we end up showing that certain explicit character sums modulo Tk+1$T^{k+1}$ exhibit cancellation when averaged over monic polynomials of degree n$n$ in Fq[T]$\mathbb {F}_q[T]$ as long as logk=o(n2)$\log k = o(n^2)$. This goes far beyond the classical range logk=o(n)$\log k =o(n)$ due to Montgomery and Vaughan. To study these sums, we build on the argument of Montgomery and Vaughan but exploit additional symmetry present in the considered sums. [ABSTRACT FROM AUTHOR]

Clinical trials in public health—particularly those conducted in low‐ and middle‐income countries—often involve communicable and non‐communicable diseases with high disease burden and unmet needs. Trials conducted in these regions often are faced with resource limitations, so improving the efficiencies of these trials is critical. Adaptive trial designs have the potential to save trial time and resources and reduce the number of patients receiving ineffective interventions. In this paper, we provide a detailed account of the implementation of vaccine and cluster randomized trials within the framework of Bayesian adaptive trials, with emphasis on computational efficiency and flexibility with regard to stopping rules and allocation ratios. We offer an educated approach to selecting prior distributions and a data‐driven empirical Bayes method for plug‐in estimates for nuisance parameters. [ABSTRACT FROM AUTHOR]

BACKGROUND: Natural products present an environmentally attractive alternative to synthetic pesticides which have been implicated in the off‐target effect. Currently, the assessment of pesticide toxicity on soil microorganisms relies on the OECD 216 N transformation assay (OECD stands for the Organisation Economic Co‐operation and Development, which is a key international standard‐setting organisation). We tested the hypotheses that (i) the OECD 216 assay fails to identify unacceptable effects of pesticides on soil microbiota compared to more advanced molecular and standardized tests, and (ii) the natural products tested (dihydrochalcone, isoflavone, aliphatic phenol, and spinosad) are less toxic to soil microbiota compared to a synthetic pesticide compound (3,5‐dichloraniline). We determined the following in three different soils: (i) ammonium (NH4+) and nitrate (NO3−) soil concentrations, as dictated by the OECD 216 test, and (ii) the abundance of phylogenetically (bacteria and fungi) and functionally distinct microbial groups [ammonia‐oxidizing archaea (AOA) and bacteria (AOB)] using quantitative polymerase chain reaction (q‐PCR). RESULTS: All pesticides tested exhibited limited persistence, with spinosad demonstrating the highest persistence. None of the pesticides tested showed clear dose‐dependent effects on NH4+ and NO3− levels and the observed effects were <25% of the control, suggesting no unacceptable impacts on soil microorganisms. In contrast, q‐PCR measurements revealed (i) distinct negative effects on the abundance of total bacteria and fungi, which were though limited to one of the studied soils, and (ii) a significant reduction in the abundance of both AOA and AOB across soils. This reduction was attributed to both natural products and 3,5‐dichloraniline. CONCLUSION: Our findings strongly advocate for a revision of the current regulatory framework regarding the toxicity of pesticides to soil microbiota, which should integrate advanced and well‐standardized tools. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Clinical misdiagnosis between cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) poses treatment challenges and carries risks of recurrence, metastases and increased morbidity and mortality. We aimed to identify discriminant proteins markers for cSCC and BCC using a minimally invasive proteome sampling method called e‐biopsy, employing electroporation for non‐thermal cell permeabilization and machine learning. E‐biopsy facilitated ex vivo proteome extraction from 21 cSCC and 21 BCC pathologically validated human cancers. LC/MS/MS profiling of 126 proteomes was followed by machine learning analysis to identify proteins distinguishing cSCC from BCC. For identified panel validation, we used proteomes sampled by e‐biopsy from unrelated 20 cSCC and 46 BCC human cancers, and differential expression analysis of published transcriptomics. Cornulin, the most commonly chosen discriminative biomarker by machine learning models, was also validated using fluorescent immunohistochemistry. One hundred and ninety‐two proteomes sampled from one hundred eight patients were analysed. Machine learning‐based approaches resulted in a set of 11 potential biomarker proteins that can be used to construct a patient classification model with 95.2% average cross‐validation accuracy, BCC precision of 93.6 ± 14.5%, cSCC precision of 98.4 ± 7.2%, specificity of 97.7 ± 11.8% and sensitivity 92.7 ± 15.3%. Protein–protein interaction analysis revealed a novel interaction network connecting 10 of the 11 resulted proteins. Histological and transcriptomic validation confirmed cornulin as a discriminant marker significantly lower in cSCC than in BCC. E‐biopsy combined with machine learning provides a novel approach to molecular sampling from skin for biomarker detection and differential expression analysis between cSCC and BCC. [ABSTRACT FROM AUTHOR]

Background: The incidence rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) skin cancers are rising, while the current diagnostic process is time‐consuming. We describe the development of a novel approach to high‐throughput sampling of tissue lipids using electroporation‐based biopsy, termed e‐biopsy. We report on the ability of the e‐biopsy technique to harvest large amounts of lipids from human skin samples. Materials and Methods: Here, 168 lipids were reliably identified from 12 patients providing a total of 13 samples. The extracted lipids were profiled with ultra‐performance liquid chromatography and tandem mass spectrometry (UPLC‐MS‐MS) providing cSCC, BCC, and healthy skin lipidomic profiles. Results: Comparative analysis identified 27 differentially expressed lipids (p < 0.05). The general profile trend is low diglycerides in both cSCC and BCC, high phospholipids in BCC, and high lyso‐phospholipids in cSCC compared to healthy skin tissue samples. Conclusion: The results contribute to the growing body of knowledge that can potentially lead to novel insights into these skin cancers and demonstrate the potential of the e‐biopsy technique for the analysis of lipidomic profiles of human skin tissues. [ABSTRACT FROM AUTHOR]

Background: Regional metastases are considered the most important prognostic factor in OSCC patients. We aimed to investigate the impact of regional disease among different age groups with OSCC. Methods: A retrospective comparison between patients 40 years old or younger, 41–69 years old, and 70 years or older treated for OSCC between 2000 and 2020 in a tertiary‐care center. Results: 279 patients were included. The mean age was 65 ± 17.7 and 133 were male (47.7%). Thirty‐six (12.9%) were 40 years old or younger, 101 (36.2%) were 41–69 years and 142 (50.9%) were 70 years or older. Five‐year overall survival and disease‐specific survival (DSS) were significantly better among patients younger than 40 compared to the mid‐age group and patients 70 years or older (76.7% vs. 69.4% vs.48.2%, Log‐rank p < 0.001, and 76.7% vs. 75.3% vs. 46.5%, Log‐rank p < 0.001, respectively). While an association between regional spread and overall survival and DSS was demonstrated among all age groups, the odds ratio (OR) for death of any cause and death of disease regarding cervical metastasis was much higher among patients younger than 40 compared with the 41–69 and 70+ age groups (death of any cause‐OR = 23, p‐value = 0.008, OR = 2.6, p‐value = 0.026, OR = 2.4, p‐value = 0.13, respectively. Death of disease‐OR = 23, p‐value = 0.008, OR = 2.3, p‐value = 0.082, OR = 4.1, p‐value = 0.001, respectively). In univariate analysis, regional metastasis was associated with disease‐free survival only among patients younger than 40 (p‐value = 0.04). Conclusions: Regional metastases correspond with worse prognosis in young patients compared to older patients. These patients may benefit from a comprehensive treatment approach with close post‐treatment follow‐up. Level of Evidence: 3 Laryngoscope, 134:2212–2220, 2024 [ABSTRACT FROM AUTHOR]

Biological membranes have a stunning ability to adapt their composition in response to physiological stress and metabolic challenges. Little is known how such perturbations affect individual organelles in eukaryotic cells. Pioneering work has provided insights into the subcellular distribution of lipids in the yeast Saccharomyces cerevisiae, but the composition of the endoplasmic reticulum (ER) membrane, which also crucially regulates lipid metabolism and the unfolded protein response, remains insufficiently characterized. Here, we describe a method for purifying organelle membranes from yeast, MemPrep. We demonstrate the purity of our ER membrane preparations by proteomics, and document the general utility of MemPrep by isolating vacuolar membranes. Quantitative lipidomics establishes the lipid composition of the ER and the vacuolar membrane. Our findings provide a baseline for studying membrane protein biogenesis and have important implications for understanding the role of lipids in regulating the unfolded protein response (UPR). The combined preparative and analytical MemPrep approach uncovers dynamic remodeling of ER membranes in stressed cells and establishes distinct molecular fingerprints of lipid bilayer stress. Synopsis: This study describes a new technology for isolating organelle membranes from yeast, MemPrep. Combined with quantitative lipidomics, MemPrep establishes molecular fingerprints of membrane-based forms of endoplasmic reticulum (ER) stress. MemPrep provides quantitative insight into the compositions of the yeast vacuole and ER membrane. The ER membrane composition is significantly distinct from the whole cell lipidome. Lipid metabolic perturbation causes dramatic changes of the ER membrane composition, which sometimes trigger ER stress. Inositol depletion and prolonged proteotoxic stress lead to distinct lipid fingerprints and membrane proteomes. Increased membrane thickness and low levels of anionic lipids are common denominators of lipid bilayer stress. Combined with proteomics and quantitative lipidomics, this method for purification of specific yeast membranes establishes molecular fingerprints of membrane-based forms of endoplasmic reticulum (ER) stress. [ABSTRACT FROM AUTHOR]

There is ongoing debate over the usefulness of and need for attention checks in online experiments. This paper investigates the value of these tests in decisions‐from‐experience (i.e., multi‐trial repeated choice) tasks. In five studies (Ntotal = 1519), we comprehensively compared the behavior of attentive and inattentive participants (i.e., those who passed or failed a simple attention check) among online participants; and also compared those results to the results of lab studies reported elsewhere. We found meaningful differences between the behavior of attentive and inattentive participants even at the first trial. Overall, attentive participants were more likely to notice less‐obvious average values of the different alternatives, while inattentive participants exhibited higher sensitivity to typical outcomes. The findings show that even one simple attention test is sufficient to differentiate between attentive and inattentive participants in repetitive tasks. Importantly, our results fully replicated three previously run lab studies among attentive participants, but not inattentive ones. This finding highlights the importance of using attention tests to avoid spurious conclusions. [ABSTRACT FROM AUTHOR]

Cellulose modification often employs chemical processes to tailor its properties and functionalities to fit the demands of a wide range of applications, maximizing its potential as a versatile and sustainable material. From both synthetic and environmental standpoints, one of the ultimate goals is to achieve significant modifications to enhance the end properties of the cellulose while minimizing the number of modified building blocks. The current study demonstrates that a synthetic glucose derivative, 6‐deoxy‐6‐fluoro‐glucose (6F‐Glc), fed into the fertilized cotton ovules, resulted in the accumulation of fluorine inside the cotton fibers with no apparent alteration to their morphology or development. These fibers exhibited a degree of substitution of 0.006, which is 170 times lower than that reported for chemical methods for cellulose modification. However, the physical characterization of the modified fibers showed a surprisingly large impact of this low‐level modification on the cellulose structure (e.g., hydrogen bonding network rearrangement) and a modest increase in the mechanical properties of the fibers. The obtained results exemplify the use of biological systems to introduce low quantities of new functionalities while maximizing the impact on fiber properties. [ABSTRACT FROM AUTHOR]

Objective: To explore the efficacy and safety of semaglutide 2.4 mg in people with overweight/obesity who were also being treated with antidepressants (ADs). Methods: Across the Semaglutide Treatment Effect for People with obesity (STEP) 1–3 and 5 trials, adults with overweight/obesity and type 2 diabetes (STEP 2 only) were enrolled. People with severe major depressive disorder within 2 years prior to screening or with a patient health questionnaire‐9 score ≥15 at screening were excluded. Participants were categorized into subgroups according to baseline AD status (on/off ADs) in this post hoc exploratory analysis of the STEP trials. Results: Of 3683 participants randomized, 539 were on ADs at baseline. Mean body weight change from baseline to week 68 was greater for semaglutide versus placebo, regardless of baseline AD use. In STEP 1, for participants on ADs at baseline, mean change from baseline was −15.7% with semaglutide versus −0.2% with placebo and −14.7% versus −2.8% for those not on ADs at baseline. Similar patterns were seen in STEP 2, 3, and 5. The prevalence of adverse events (AEs) was generally similar between semaglutide and placebo in participants on ADs at baseline. Conclusions: In adults with overweight/obesity, semaglutide provided clinically meaningful weight loss regardless of baseline AD use, with an AE profile consistent with previous studies. [ABSTRACT FROM AUTHOR]

Objectives: Hematological malignancy (HM) patients treated with anti‐CD20 monoclonal antibodies are at higher risk for severe COVID‐19. A previous single‐center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort. Methods: We included HM patients from 15 centers, from five countries treated with anti‐CD20, comparing those treated with obinutuzumab (O‐G) to rituximab (R‐G) between December 2021 and June 2022, when Omicron lineage was dominant. Results: We collected data on 1048 patients. Within the R‐G (n = 762, 73%), 191 (25%) contracted COVID‐19 compared to 103 (36%) in the O‐G. COVID‐19 patients in the O‐G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID‐19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe‐critical COVID‐19 occurred in 31.1% of patients in the O‐G and 22.5% in the R‐G. In multivariable analysis, O‐G had a 2.08‐fold increased risk for severe‐critical COVID‐19 compared to R‐G (95% CI 1.13–3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T‐C) prophylaxis. Further analysis comparing O‐G to R‐G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID‐19‐related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293). Conclusions: Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID‐19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk–benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks. [ABSTRACT FROM AUTHOR]

Objectives: Postoperative antibiotic therapy is a common practice following septoplasty with intra‐septal splints placement (ISS), even though there is a lack of evidence to support it. We sought to investigate the role of antibiotic therapy in septal surgeries with the placement of ISS. Design: A retrospective comparative study was conducted using the electronic charts of adult patients who underwent septoplasty with the placement of ISS with or without turbinate reduction. Nasal cultures were taken routinely during surgery as part of the department's protocol for monitoring infectious diseases. The ISS were also routinely examined for the presence of bacteria after their removal on the eighth day following surgery. Setting: A large otolaryngology department in a tertiary medical center. Participants: Adult patients who underwent septoplasty in our institution. Main outcome measures: We analyzed all post‐operative infections to search for risk factors in the cohort. Results: Post‐operative infection rates following septoplasty with ISS were low at 6%, which is consistent with previously published rates. Infection rates were significantly higher in patients who were not treated with antibiotics (OR = 8.2, 95%CI: 1.63–41.1; p =.01, φ = 0.04). Diabetes was associated with an increased risk of postoperative infection regardless of prophylactic antibiotic therapy (OR = 5.2, 95%CI: 1.15–23.5; p =.032, φ =.04). The detection of Klebsiella pneumonia before surgery was associated with an increased rate of postoperative infection (OR = 16.6, 95%CI: 3.02–91.54; p =.001, φ = 0.12). Conclusions: Patients undergoing septoplasty with the placement of ISS are at increased risk of gram‐negative bacterial colonisation, and development of postoperative nasal infection. A single preoperative dose of IV antibiotic therapy should be considered a potential prophylactic option for septoplasty with ISS. [ABSTRACT FROM AUTHOR]

Background: Elderly patients account for nearly 70% of all primary central nervous system lymphoma (PCNSL) cases. They cannot tolerate aggressive treatment and have poor prognosis with a median overall survival (OS) of less than 2 years and progression‐free survival (PFS) of 6–16 months. Ibrutinib penetrates the blood–brain barrier and has shown activity in PCNSL. Methods: This prospective study investigated whether ibrutinib maintenance is feasible, and whether it can benefit elderly PCNSL patients in terms of expected 2‐year PFS. It is an open label, phase 2 study in newly diagnosed PCNSL patients 60–85 years old who responded to first‐line high‐dose methotrexate (HDMTX)‐based treatment with partial or complete response. Ibrutinib maintenance (560 mg/d) was continued until disease progression or intolerable toxicity. Results: Twenty patients were enrolled, with a median age of 72 years (range, 61–80). Median time on ibrutinib maintenance was 12.5 (range, 2–46) months. Twelve patients stopped treatment: five due to central nervous system relapse and seven due to adverse events that were mainly grade 2. Five patients died (25%) all due to relapse. The 1‐ and 2‐year PFS are 90% and 72.6%, respectively, and the 2‐year OS is 89%. Conclusions: The study reached its primary end points and also showed that ibrutinib maintenance is tolerated reasonably well by the elderly. Therefore, this study supports the concept that ibrutinib maintenance should be further evaluated as an optional consolidation measure in the elderly. Ibrutinib maintenance following first‐line high dose methotrexate‐based chemotherapy in elderly patients with primary central nervous system lymphoma is feasible and probably also effective. [ABSTRACT FROM AUTHOR]

Decision‐makers in emergency settings need to employ the breadth of evidence available so as to inform critical judgments, yet the acute time pressure suggests that in some cases only partial information could be employed. Investigating this tension, the current study focuses on the usefulness of extraneous information that arrives from outside the organization and supplements the information that is available through local information systems. Namely, we explore the extent to which the use of Health Information Exchanges (HIEs)—a network that integrates patients' clinical information across medical organizations and points of care—facilitates diagnosis decisions in hospitals' emergency departments (EDs). Adopting the lens of cognitive decision‐making theory, we advance hypotheses regarding the moderating effects of the tasks' cognitive requirements (diagnosis complexity) and clinicians' time availability (ED crowdedness) on the relation between the use of extraneous information (in the form of HIE data) and decision quality (ED revisit rate). Our empirical investigation employs complete field data collected from a network of hospitals, capturing over half‐a‐million patient ED encounters. The results reveal that, in general, ED clinicians' use of the HIE improves decision quality, as reflected in reduced patient revisits to the ED. However, when diagnosis complexity is low, this effect is reversed, such that HIE use is associated with increased ED revisit rates. Our discussion highlights the conditions under which extraneous information contributes to better decision‐making and calls for a mindful use of interorganizational information exchanges in emergency settings. [ABSTRACT FROM AUTHOR]

Worldwide habitat loss, land‐use changes, and climate change threaten biodiversity, and we urgently need models that predict the combined impacts of these threats on organisms. Current models, however, overlook microhabitat diversity within landscapes and so do not accurately inform conservation efforts, particularly for ectotherms. Here, we built and field‐parameterized a model to examine the effects of habitat loss and climate change on activity and microhabitat selection by a diurnal desert lizard. Our model predicted that lizards in rock‐free areas would reduce summer activity levels (e.g. foraging, basking) and that future warming will gradually decrease summer activity in rocky areas, as even large rocks become thermally stressful. Warmer winters will enable more activity but will require bushes and small rocks as shade retreats. Hence, microhabitats that may seem unimportant today will become important under climate change. Modelling frameworks should consider the microhabitat requirements of organisms to improve conservation outcomes. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is ubiquitously distributed in the population worldwide and its most frequent clinical presentation is cutaneous warts. Despite various treatment options currently available, many patients experience persistent and refractory disease. We sought to evaluate the clinical effectiveness and safety profile of intralesional HPV 9‐valent vaccine for the treatment of recalcitrant warts. A retrospective study was performed for all cases of cutaneous warts treated with intralesional 9‐valent HPV vaccine between January 2017 and March 2021. Epidemiologic, clinical, and treatment data, including safety and effectiveness scores, were reviewed. Our cohort was composed of 20 patients: 13 adults and seven children. Twelve patients (60%) displayed a complete response whereas 8 patients (40%) showed a partial response. Older age was associated with a better response to treatment, while a history of laser therapy was associated with a worse prognosis. Adverse events were local, transient, and negligible. No systemic adverse effects were reported. Intralesional 9‐valent HPV vaccine may be considered for the treatment of recalcitrant cutaneous warts. Controlled studies are required to confirm these results. [ABSTRACT FROM AUTHOR]

Introduction: Extracorporeal photopheresis (ECP) is considered an effective treatment for patients with chronic graft vs host disease (cGVHD) and demonstrates efficacy in ameliorating GVHD. The mechanism by which ECP acts against cGVHD is not fully understood. Preliminary observations have hinted at the potential involvement of neutrophil extracellular traps (NETs) formation in the pathogenesis of cGVHD. We aimed to assess the influence of ECP on the formation of NETs in patients with cGVHD as a potential mechanism in this setting. Methods: Patients treated with ECP for cGVHD at the Rabin Medical Center were included in this study. Blood samples were obtained at three different time points: before starting an ECP cycle, at the end of the first day of treatment, and 24 h following the initiation of the ECP treatment cycle. Neutrophils were harvested from all blood samples. NET formation was assessed by measurement of NET‐bound specific neutrophil elastase activity and by immunofluorescence staining. Results: Six patients (two females and four males) with cGVHD were included in the study. We observed a significant increase in NET formation among all six patients following ECP. Net‐bound specific neutrophil elastase activity was elevated from a median value of 2.23 mU/mL (interquartile range [IQR] 2.06‐2.47 mU/mL) at baseline to a median value of 13.06 mU/mL (IQR 10.27‐15.97 mU/mL) immediately after the treatment and to a peak median value of 14.73 mU/mL (IQR 9.6‐22.38 mU/mL) 24 h following the initiation of the ECP cycle. A qualitative assessment of NET formation using immunofluorescence staining has demonstrated markedly increased expression of citrullinated histone H3, a marker of NET formation, following ECP treatment. Conclusions: Our preliminary data indicate that ECP induces NET formation among patients with cGVHD. The contribution of increased NET formation to the therapeutic effect of cGVHD should be further investigated. [ABSTRACT FROM AUTHOR]

It is common practice to use hierarchical Bayesian model for the informing of a pediatric randomized controlled trial (RCT) by adult data, using a prespecified borrowing fraction parameter (BFP). This implicitly assumes that the BFP is intuitive and corresponds to the degree of similarity between the populations. Generalizing this model to any K≥1 historical studies, naturally leads to empirical Bayes meta‐analysis. In this paper we calculate the Bayesian BFPs and study the factors that drive them. We prove that simultaneous mean squared error reduction relative to an uninformed model is always achievable through application of this model. Power and sample size calculations for a future RCT, designed to be informed by multiple external RCTs, are also provided. Potential applications include inference on treatment efficacy from independent trials involving either heterogeneous patient populations or different therapies from a common class. [ABSTRACT FROM AUTHOR]

Objectives: Dysregulation of BCL‐2 family members has been reported in acute lymphocytic leukemia (ALL), with various BH3‐dependencies of the leukemic clone. We conducted a multicenter retrospective cohort of patients with relapsed/refractory B or T ALL, with ven‐chemotherapy or ven‐navitoclax combinations, to assess efficacy and safety. Methods: Seventeen patients were included in the analysis, median age was 32 years, with 6 B‐ALL and 11 T‐ALL patients. Nine patients received venetoclax combined with chemotherapy, and 13 patients received venetoclax in combination with navitoclax, vincristine and asparaginase, of which 5 were already exposed to venetoclax in previous lines. Results: ORR was 55% and 46% among the ven‐chemotherapy and the ven‐navitoclax‐chemotherapy, respectively. Most of the responders proceeded to an allogenic bone marrow transplant in both cohorts. The most common adverse effects of the ven‐navitoclax combination were infectious complications and hepatotoxicity. Conclusions: Our data demonstrated the possible efficacy of ven‐chemotherapy and ven‐navitoclax in r/r ALL with moderate toxicity. [ABSTRACT FROM AUTHOR]

The Hula Valley has two key Acheulian sites: Gesher Benot Ya'aqov (GBY), a large flake Acheulian site with hundreds of basalt bifaces and a significant number of flint handaxes, and Ma'ayan Barukh (MB), where more than 3500 flint handaxes were collected. Over the last one million years, the valley was filled by alluvium and basalt flows, devoid of flint sources suitable for handaxe production. We conducted archaeological and geological surveys combined with an inductively coupled plasma mass spectrometry geochemical study to determine the source(s) of flint, comparing elemental compositions of handaxes from GBY and MB with those of different flint sources using a novel statistical method. The results demonstrate that Hula Valley Acheulian flint handaxes were derived from Eocene flint. For GBY, the nearest matching source for its small number of excavated handaxes is a secondary deposit of the Dishon streambed found ~8 km northwest of the site. A more likely source for both GBY and the thousands of MB handaxes is the Dishon flint extraction and reduction complex located 20 km to the west, a possibility also supported by the near absence of production waste flakes at the sites themselves. These findings support direct procurement strategy as early as the Lower Paleolithic. [ABSTRACT FROM AUTHOR]

Objectives: The use of a toothbrush with radio frequency (RF) has shown to be of benefit regarding the reduction of plaque, calculus, and dental staining and improving teeth shade compared to conventional powered and manual toothbrushes. Aim: To evaluate the efficacy of the RF toothbrush in the reduction of calculus accumulation and its effect on periodontal parameters as well as subject satisfaction as compared to an identical sham‐tooth brush. Materials and Methods: Patients who are under a strict maintenance program were included. Patients were allocated to test (RF toothbrush) or control (sham) randomly and were examined at baseline, one and three months. Clinical photos were taken and a consequential calculus assessment via ImageJ software. Clinical assessment included the following: plaque index (PI), bleeding on probing (BOP), probing pocket depth (PPD), and recession (REC). Patient satisfaction was assessed via a questionnaire. Results: Fifty‐eight patients (29 control, 29 test) were included. At baseline mean PPD, BOP, PI, REC, and calculus accumulation were similar between the groups. Mean buccal calculus was lower in the test group at one month 4.0% versus 6.7%, p <.05. Calculus accumulation within the groups was lower in the test group at 1 and 3 months when compared to baseline at the buccal aspect (2.8% vs. 8.9%, p <.05% and 3.8% vs. 8.9%, p <.05) and lingual aspect (6.7% vs. 16.5%, p <.05% and 8.9% vs. 16.5%, p <.05). No statistically significant results were found regarding periodontal parameters PPD, BOP, PI, and REC. No difference was found between groups regarding patient satisfaction. Conclusion: RF seems to have an additive effect on preventing calculus accumulation on the buccal aspect of anterior mandibular teeth at 1 month. Nevertheless, at 3 months, no difference between the toothbrushes is seen regarding calculus formation and maintaining periodontal health (ClinicalTrials.gov, Identifier NCT04640857). [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T‐cells (CAR‐T) are widely used for the treatment of relapsed/refractory diffuse large B cell lymphoma (DLBCL). The data for CAR‐T cell therapy in patients with extra‐nodal (EN) lymphoma is restricted. We included 126 consecutive patients with DLBCL treated with commercially available CAR‐T cells (tisagenlecleucel, n = 100, 79.4% and axicabtagene ciloleucel, n = 26, 20.6%). At lymphodepletion, 72 of 126 (57%) patients had EN disease, 42 of 126 (33%) patients had nodal disease (ND)‐only and 12 of 126 (10%) showed no disease assessed by PET‐CT. There were no significant differences in CAR‐T related toxicities and in the median Progression free survival (PFS) between EN patients and ND (10.76 [95% CI: 7.8–13.6] vs. 14.1 [95% CI: 10–18.1] months, p =.126). Similarly, median overall survival (OS) was not significantly different (15.36 [95% CI 12.5–18.2] vs. 18.4 [95% CI 14.8–22.1] months, p =.100). Subgroup analysis according to the number of EN involved sites showed that median PFS and OS were significantly higher in patients with <3 EN sites (12.3 months [95% CI 9–15.5] vs. 4.28 months [95% CI 0.6–7.9], p =.010) compared to patients with >2 EN sites, respectively (16.5 months [95% CI 13.4–19.6] vs. 8.7 months [95% CI 4.6–12.8], p =.05). In multivariate cox regression analysis, increased number sites of EN disease and high lactate dehydrogenase (LDH) at lymphodepletion negatively impacted PFS (p =.021 and <.001, respectively), while sex, type of product administered, age and performance status did not predict PFS and OS. Of note, all the patients with involvement of gastrointestinal tract (n = 9), urinary tract (n = 9), or pharynx (n = 3) at lymphodepletion, progressed or had an early relapse. In conclusions, patients with >2 EN sites at lymphodepletion have significantly worse clinical outcomes compared to patients with <3 EN sites. Patients with specific sites of EN disease may demonstrate grim prognosis. [ABSTRACT FROM AUTHOR]

Proactive inhibition is a critical ability for smokers who seek to moderate or quit smoking. It allows them to pre‐emptively refrain from seeking and using nicotine products, especially when facing salient smoking cues in daily life. Nevertheless, there is limited knowledge on the impact of salient cues on behavioural and neural aspects of proactive inhibition, especially in smokers with nicotine withdrawal. Here, we seek to bridge this gap. To this end, we recruited 26 smokers to complete a stop‐signal anticipant task (SSAT) in two separate sessions: once in the neutral cue condition and once in the smoking cue condition. We used graph‐based modularity analysis to identify the modular structures of proactive inhibition‐related network during the SSAT and further investigated how the interactions within and between these modules could be modulated by different proactive inhibition demands and salient smoking cues. Findings pointed to three stable brain modules involved in the dynamical processes of proactive inhibition: the sensorimotor network (SMN), cognitive control network (CCN) and default‐mode network (DMN). With the increase in demands, functional connectivity increased within the SMN, CCN and between SMN‐CCN and decreased within the DMN and between SMN‐DMN and CCN‐DMN. Salient smoking cues disturbed the effective dynamic interactions of brain modules. The profiles for those functional interactions successfully predicted the behavioural performance of proactive inhibition in abstinent smokers. These findings advance our understanding of the neural mechanisms of proactive inhibition from a large‐scale network perspective. They can shed light on developing specific interventions for abstinent smokers. [ABSTRACT FROM AUTHOR]

Background: The Middle East has a significant influence on the global aesthetic market. Within the United States and globally, patients with Middle Eastern heritage have a wide range of ethnic and cultural backgrounds that affect their perceptions of beauty and motivations to seek cosmetic treatment. Aims: The aim of this roundtable was to discuss similarities and differences in anatomy and treatment preferences of Middle Eastern patients and explore how these differences may influence aesthetic practices. Patients/Methods: In support of clinicians who wish to serve a diverse patient population, a 6‐part international roundtable series focused on diversity in aesthetics was conducted from August 24, 2021, to May 16, 2022. Results: The results of the fourth roundtable in the series, the Middle Eastern Patient, are described here. A discussion of treatment preferences is included, and specific procedural information is provided for commonly treated areas in this population (forehead, infraorbital area, and jawline). Conclusions: Middle Eastern patients have a variety of aesthetic preferences, which are influenced by a wide range of cultural backgrounds, making it difficult to develop general statements about this demographic. There is an unmet need for research into this diverse group of patients to help physicians understand and incorporate their unique needs and desires into clinical practice. [ABSTRACT FROM AUTHOR]

A core challenge in global change biology is to predict how species will respond to future environmental change and to manage these responses. To make such predictions and management actions robust to novel futures, we need to accurately characterize how organisms experience their environments and the biological mechanisms by which they respond. All organisms are thermodynamically connected to their environments through the exchange of heat and water at fine spatial and temporal scales and this exchange can be captured with biophysical models. Although mechanistic models based on biophysical ecology have a long history of development and application, their use in global change biology remains limited despite their enormous promise and increasingly accessible software. We contend that greater understanding and training in the theory and methods of biophysical ecology is vital to expand their application. Our review shows how biophysical models can be implemented to understand and predict climate change impacts on species' behavior, phenology, survival, distribution, and abundance. It also illustrates the types of outputs that can be generated, and the data inputs required for different implementations. Examples range from simple calculations of body temperature at a particular site and time, to more complex analyses of species' distribution limits based on projected energy and water balances, accounting for behavior and phenology. We outline challenges that currently limit the widespread application of biophysical models relating to data availability, training, and the lack of common software ecosystems. We also discuss progress and future developments that could allow these models to be applied to many species across large spatial extents and timeframes. Finally, we highlight how biophysical models are uniquely suited to solve global change biology problems that involve predicting and interpreting responses to environmental variability and extremes, multiple or shifting constraints, and novel abiotic or biotic environments. [ABSTRACT FROM AUTHOR]

Understanding the impact of variation in lesion topography on the expression of functional impairments following stroke is important, as it may pave the way to modeling structure–function relations in statistical terms while pointing to constraints for adaptive remapping and functional recovery. Multi‐perturbation Shapley‐value analysis (MSA) is a relatively novel game‐theoretical approach for multivariate lesion‐symptom mapping. In this methodological paper, we provide a comprehensive explanation of MSA. We use synthetic data to assess the method's accuracy and perform parameter optimization. We then demonstrate its application using a cohort of 107 first‐event subacute stroke patients, assessed for upper limb (UL) motor impairment (Fugl‐Meyer Assessment scale). Under the conditions tested, MSA could correctly detect simulated ground‐truth lesion‐symptom relationships with a sensitivity of 75% and specificity of ~90%. For real behavioral data, MSA disclosed a strong hemispheric effect in the relative contribution of specific regions‐of‐interest (ROIs): poststroke UL motor function was mostly contributed by damage to ROIs associated with movement planning (supplementary motor cortex and superior frontal gyrus) following left‐hemispheric damage (LHD) and by ROIs associated with movement execution (primary motor and somatosensory cortices and the ventral brainstem) following right‐hemispheric damage (RHD). Residual UL motor ability following LHD was found to depend on a wider array of brain structures compared to the residual motor ability of RHD patients. The results demonstrate that MSA can provide a unique insight into the relative importance of different hubs in neural networks, which is difficult to obtain using standard univariate methods. [ABSTRACT FROM AUTHOR]

Successful management of lake ecosystems and the ecosystem services they provide necessitates ecosystem‐based management. The application of ecosystem‐based management can assist in achieving sustainable management of the ecosystem to ensure continued and sustainable supply of ecosystem services such as fisheries. One concept for defining sustainable fishing is the Safe Operating Space (SOS). In our study, we apply the Ecopath with Ecosim suite of models to predict the SOS required for the management of a commercial fishery. We use the Lake Kinneret (Israel) ecosystem as a case study to illustrate the approach by developing an Ecospace model of the lake and incorporating the spatio‐temporal framework and varying environmental conditions. We test, and demonstrate, the methodology for developing a SOS for a commercial fish population that can be implemented by lake managers elsewhere and illustrate it's use by defining example target values of biomass (e.g., 200 and 250 tons) and catch (e.g., 125 tons/year). Our results show that the SOS for a given target can be defined by a range of fishing efforts and vegetation cover in the lake as a function of lake level. The complexity in defining the actual values highlight the benefit of the approach we present here. [ABSTRACT FROM AUTHOR]

Effect modification (EM) may cause bias in network meta‐analysis (NMA). Existing population adjustment NMA methods use individual patient data to adjust for EM but disregard available subgroup information from aggregated data in the evidence network. Additionally, these methods often rely on the shared effect modification (SEM) assumption. In this paper, we propose Network Meta‐Interpolation (NMI): a method using subgroup analyses to adjust for EM that does not assume SEM. NMI balances effect modifiers across studies by turning treatment effect (TE) estimates at the subgroup‐ and study level into TE and standard errors at EM values common to all studies. In an extensive simulation study, we simulate two evidence networks consisting of four treatments, and assess the impact of departure from the SEM assumption, variable EM correlation across trials, trial sample size and network size. NMI was compared to standard NMA, network meta‐regression (NMR) and Multilevel NMR (ML‐NMR) in terms of estimation accuracy and credible interval (CrI) coverage. In the base case non‐SEM dataset, NMI achieved the highest estimation accuracy with root mean squared error (RMSE) of 0.228, followed by standard NMA (0.241), ML‐NMR (0.447) and NMR (0.541). In the SEM dataset, NMI was again the most accurate method with RMSE of 0.222, followed by ML‐NMR (0.255). CrI coverage followed a similar pattern. NMI's dominance in terms of estimation accuracy and CrI coverage appeared to be consistent across all scenarios. NMI represents an effective option for NMA in the presence of study imbalance and available subgroup data. [ABSTRACT FROM AUTHOR]

A common assumption in prior research on social networking sites (SNS) has been that users' orientations toward SNS use are positioned somewhere along a bipolar, univalent continuum, stretching from negative to positive orientation. However, considering recent findings unfolding the intricacy and variety of SNS use patterns, such a linear conceptualization of users' orientations is too simplistic with limited ability to explain the intricate patterns of SNS use. To alleviate this deficiency in this paper, we draw on the ambivalence literature and explain that users can simultaneously experience both positive and negative orientations toward SNS use based on the positive and negative aspects of their SNS use experience. Focusing on post‐ adoptive SNS use context, we theorise archetypes of SNS users' attitudinal responses to ambivalence, and their associated behavioural outcomes in terms of SNS use patterns. We first follow a typological perspective and develop typologies of attitudinal and behavioural responses to ambivalence toward SNS use. Then, we offer six hypotheses that explain the relations between the archetypes of attitudinal responses to ambivalence toward SNS use and users' SNS use patterns. Lastly, we empirically test our hypotheses using latent profile analysis and ANCOVA applied to two‐wave data collected from 370 ambivalent SNS users. The findings support the hypotheses and validate our typologies. The findings ultimately point to likely choices from a range of post‐adoption SNS use patterns as plausible outcomes of SNS users' attitudinal responses to ambivalence. [ABSTRACT FROM AUTHOR]

Aims: To prospectively evaluate the incidence of myocardial injury after the administration of the fourth dose BNT162b2 mRNA vaccine (Pfizer‐BioNTech) against COVID‐19. Methods and results: Health care workers who received the BNT162b2 vaccine during the fourth dose campaign had blood samples collected for high‐sensitivity cardiac troponin (hs‐cTn) during vaccine administration and 2–4 days afterward. Vaccine‐related myocardial injury was defined as hs‐cTn elevation above the 99th percentile upper reference limit and >50% increase from baseline measurement. Participants with evidence of myocardial injury underwent assessment for possible myocarditis. Of 324 participants, 192 (59.2%) were female and the mean age was 51.8 ± 15.0 years. Twenty‐one (6.5%) participants had prior COVID‐19 infection, the mean number of prior vaccine doses was 2.9 ± 0.4, and the median time from the last dose was 147 (142–157) days. Reported vaccine‐related adverse reactions included local pain at injection site in 57 (17.59%), fatigue in 39 (12.04%), myalgia in 32 (9.88%), sore throat in 21 (6.48%), headache in 18 (5.5%), fever ≥38°C in 16 (4.94%), chest pain in 12 (3.7%), palpitations in 7 (2.16%), and shortness of breath in one (0.3%) participant. Vaccine‐related myocardial injury was demonstrated in two (0.62%) participants, one had mild symptoms and one was asymptomatic; both had a normal electrocardiogram and echocardiography. Conclusion: In a prospective investigation, an increase in serum troponin levels was documented among 0.62% of healthy health care workers receiving the fourth dose BNT162b2 vaccine. The two cases had mild or no symptoms and no clinical sequela. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT05308680. [ABSTRACT FROM AUTHOR]

Speciesism prioritizes humans over animals and pets. Nevertheless, pet owners have a strong attachment bond with their pets, which makes their hierarchical view of pets less clear. Aiming to examine this issue, we present a dilemma involving animals and humans that allowed us to investigate whether animal type, social distance, and pet ownership status can affect moral decision‐making related to pets. Save‐willingness results showed that in the moral dilemmas of pets versus livestock versus wild animals (Studies 1a and 2a) and their own pets versus strangers (Studies 1b and 2b), pet owners prioritize pets whereas non‐owners prioritize pets (Studies 1a and 2a) and strangers (Studies 1b and 2b). Pet owners prefer to save pets more than do non‐owners (Study 1a), and this effect was only observed in females (Study 2a). Save‐decision results showed that in the moral dilemmas of pets versus livestock versus wild animals (Study 2a), pet owners prioritize pets whereas in the dilemmas of pets versus strangers (Study 2b), pet owners prioritize strangers. The same result was found in non‐owners. Pet owners prefer more than do non‐owners to save pets (Study 2). Overall, the separation of save‐willingness and save‐decision results revealed that pet owners show special speciesism (i.e., pettism). [ABSTRACT FROM AUTHOR]

Gram‐negative bacteria form spherical blebs on their cell periphery, which later dissociate from the bacterial cell wall to form extracellular vesicles. These nano scale structures, known as outer membrane vesicles (OMVs), have been shown to promote infection and disease and can induce typical immune outputs in both mammal and plant hosts. To better understand the broad transcriptional change plants undergo following exposure to OMVs, we treated Arabidopsis thaliana (Arabidopsis) seedlings with OMVs purified from the Gram‐negative plant pathogenic bacterium Xanthomonas campestris pv. campestris and performed RNA‐seq analysis on OMV‐ and mock‐treated plants at 2, 6 and 24 h post challenge. The most pronounced transcriptional shift occurred at the first two time points tested, as reflected by the number of differentially expressed genes and the average fold change. OMVs induce a major transcriptional shift towards immune system activation, upregulating a multitude of immune‐related pathways including a variety of immune receptors. Comparing the response of Arabidopsis to OMVs and to purified elicitors, revealed that OMVs induce a similar suite of genes and pathways as single elicitors, however, pathways activated by OMVs and not by other elicitors were detected. Pretreating Arabidopsis plants with OMVs and subsequently infecting with a bacterial pathogen led to a significant reduction in pathogen growth. Mutations in the plant elongation factor receptor (EFR), flagellin receptor (FLS2), or the brassinosteroid‐insensitive 1–associated kinase (BAK1) co‐receptor, did not significantly affect the immune priming effect of OMVs. All together these results show that OMVs induce a broad transcriptional shift in Arabidopsis leading to upregulation of multiple immune pathways, and that this transcriptional change may facilitate resistance to bacterial infection. [ABSTRACT FROM AUTHOR]

Sweet basil, Ocimum basilicum L., is an important culinary herb grown worldwide. Although basil is green, many landraces, breeding lines, and exotic cultivars have purple stems and flowers. This anthocyanin pigmentation is unacceptable in traditional Italian basil used for Pesto sauce production. In the current study, we aimed to resolve the genetics that underlines the different colors. We used the recently published sweet basil genome to map quantitative trait loci (QTL) for flower and stem color in a bi‐parental F2 population. It was found that the pigmentation is governed by a single QTL, harboring an anthocyanidin synthase (ANS) gene (EC 1.14.20.4). Further analysis revealed that the basil genome harbors two homeologous ANS genes, each carrying a loss‐of‐function mutation. ObANS1 carries a single base pair insertion resulting in a frameshift, and ObANS2 carries a missense mutation within the active site. In the purple‐flower parent, ANS1 is functional, and ANS2 carries a nonsense mutation. The functionality of the ObANS1 active allele was validated by complementation assay in an Arabidopsis ANS mutant. Moreover, we have restored the functionality of the missense‐mutated ObANS2 using site‐directed activation. We found that the non‐functional alleles were expressed to similar levels as the functional allele, suggesting polyploids invest futile effort in expressing non‐functional genes, offsetting their advantageous redundancy. This work demonstrated the usefulness of the genomics and genetics of basil to understand the basic mechanism of metabolic traits and raise fundamental questions in polyploid plant biology. [ABSTRACT FROM AUTHOR]

Controlling nerve cells to form pre‐designed 3D neural networks that recapitulate the intricate neural interconnectivity in the brain is essential for developing neuronal interfaces and new regeneration approaches. Here, nerve cells within 3D biomaterials are dynamically localized using nano‐based magnetic manipulations. Nerve cells are transformed into magnetic units and their organizational layout is manipulated using external magnetic field gradients. Iron oxide nanoparticles are incorporated into both Pheochromocytoma cell‐line 12 (PC12) cells and primary mice cortical neurons and the magnetized cells are subjected to multiple magnetic fields using pre‐designed magnetic arrays. Their movement is controlled inside multi‐layered 3D collagen scaffolds, which simulate the innate properties of in‐vivo tissue structures. Via these magnetic manipulations, functional 3D microarchitectures of neural networks are created. In light of the clustered and layered structure of the mammalian central nervous system, this strategy paves the way to creating customized 3D tissue architectures for bioengineering applications, enabling a broad range of advanced implementations and providing efficient models for investigating cellular and tissue behavior. [ABSTRACT FROM AUTHOR]