bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preprint Highlight: A synthetic signaling network imitating the action of immune cells in response to bacterial metabolism
Authors: De Lora Jacqueline A. 
Published: February 2023

Synthetic cells, built using approaches from bottom-up synthetic biology, aim to mimic biological functions of their natural counterparts. However, engineering multilevel coordination of signaling networks remains challenging. This study demonstrates a minimalist synthetic signaling network mimicking netosis, an innate immune system response that traps and elicits an antimicrobial response against pathogens. Modular DNA particles were activated by the pH shift induced by E. coli metabolism, generating a sticky DNA-cholesterol network that evolved over time to trap the bacteria. Then, giant unilamellar vesicles containing an antibiotic were permeabilized by the DNA particles, reducing the growth of E. coli. The development of this synthetic signaling cascade has implications for artificial cells in therapeutics, biofilm research, biomaterials, and bioremediation. This preprint has been assigned the following badges: New Materials, New Methods. Read the preprint on bioRxiv ( Walczak et al., 2023 ): https://doi.org/10.1101/2023.02.02.526524 .
Functionally redundant multimodal predator cues elicit changes in prey foraging behavior
Authors: Shogren Fiona G , Hebets Eileen A , DeLong John P 
Published: February 2023

Abstract
Many prey species can assess the risk of predation from information acquired through different sensory systems. For many animals, this information is detected with sensory organs specialized for visual (sight) or chemical (smell or taste) stimuli. It is unclear; however, whether information acquired through multiple sensory systems is functionally redundant or interchangeable, especially if the message is the same. Here, we assess prey response to unimodal visual and chemical cues as well as multimodal (visual + chemical) cues. We specifically test if a foraging individual shows a stronger behavioral response to risk when they can perceive that risk through multimodal versus unimodal cues. To do this, we measured the functional response (prey abundance–foraging rate relationship) of Tibellus oblongus spiders foraging on midges while exposing them to visual stimuli, chemical stimuli, or a combination of both visual and chemical stimuli from potential predators. We then determined if the spider’s functional response for the multimodal treatment differed more strongly from a control treatment than from either unimodal treatment. We found that under any simulated predation risk (multimodal and both unimodal), T. oblongus spiders showed longer handling times than in control groups without risk. However, we saw no elevated anti-predator response in the multimodal treatment, suggesting that information from visual and chemical modalities is interchangeable and sufficient to indicate reliably predation risk.
Relatedness modulates reproductive competition among queens in ant societies with multiple queens
Authors: Helanterä Heikki , Ozan Martina , Sundström Liselotte 
Published: February 2023

AbstractReproductive sharing in animal groups with multiple breeders, insects and vertebrates alike, contains elements of both conflict and cooperation, and depends on both relatedness between co-breeders, as well as their internal and external conditions. We studied how queens of the ant Formica fusca adjust their reproductive efforts in response to experimental manipulations of the kin competition regime in their nest. Queens respond to the presence of competitors by increasing their egg laying efforts, but only if the competitors are highly fecund and distantly related. Such a mechanism is likely to decrease harmful competition among close relatives. We demonstrate that queens of Formica fusca fine-tune their cooperative breeding behaviors in response to kinship and fecundity of others in a remarkably precise and flexible manner.
Experimentally advancing morning emergence time does not increase extra-pair siring success in blue tit males
Authors: Santema Peter , Kempenaers Bart 
Published: February 2023

Abstract
Extra-pair paternity occurs frequently in socially monogamous birds, but there is substantial variation in extra-pair siring success among males. Several studies have shown that siring success relates to the timing of morning activity, with the earliest active males being more successful, suggesting that early activity is important for acquiring extra-pair copulations. However, these studies are correlational, and it, therefore, remains unclear whether the relationship between timing and extra-pair siring success is causal. An alternative explanation is that successful extra-pair sires tend to be active earlier (e.g., because they are of high quality or in good condition), but that early activity in itself does not increase siring success. We experimentally advanced the emergence time of male blue tits by exposing them to light about half an hour before their natural emergence time. Although males that were exposed to the light treatment emerged from their roost substantially earlier than males that were exposed to a control treatment, light-treated males were not more likely to sire extra-pair offspring. Furthermore, whereas control males showed the expected relation between emergence time and siring success (although not statistically significant), there was no relation between emergence time and extra-pair siring success among light-treated males. Our results suggest that the timing of emergence from the roost is not an important factor underlying extra-pair siring success.
The HPV16 E6, E7/miR-23b-3p/ICAT signaling axis promotes proliferation, migration, invasion and EMT of cervical cancer cells
Authors: Hu Jing , Liao Deyu , Sun Zijiu , Ren Wei , Zhao Ling , Fang Yuting , Hu Kai , Yu Huomei , Liu Shiyan , Zhou Lan , He Tongchuan , Zhang Yan 
Published: February 2023

Abstract
Cervical cancer (CC) remains one of the most common female malignancies, with higher incidence and mortality rates. more than 99% of CCs are associated with persistent infection with high-risk human papillomavirus. In view of the growing evidence that HPV 16 E6 and E7, two key oncoproteins encoded by HPV 16, regulate the expression of many other multifunctional genes and downstream effectors that contribute to the development of CC. Herein, we undertook a comprehensive effort into how HPV16 E6, E7 oncogenes affect the progression of CC cells. Previous studies have shown that ICAT expression was significantly increased in CC and had a pro-cancer effect. We observed that knockdown of HPV16 E6, E7 expression in SiHa and CasKi cells resulted in significant inhibition of ICAT expression and upregulation of miR-23b-3p expression. Besides, dual luciferase assays confirmed that ICAT was a target gene of miR-23b-3p, and negatively modulated by miR-23b-3p. Functional experiments showed that the overexpression of miR-23b-3p suppressed malignant behaviors of CC cells, such as migration, invasion and EMT. The overexpression of ICAT counteracted the suppressive effect of miR-23b-3p on HPV16-positive CC cells. Furthermore, after the knockdown of HPV16 E6 and E7, the inhibition of miR-23b-3p could increase the ICAT expression and rescue the siRNA HPV16 E6, E7-mediated suppressive impact on the aggressiveness of SiHa and CaSki cells. Collectively, our findings uncover that HPV16 E6, E7/miR-23b-3p/ ICAT axis plays an important role in HPV16-positive CC pathogenesis, which may serve as a promising therapeutic target for HPV16-associated CC.
Mercaptopurine for the Treatment of Ulcerative Colitis: A Randomized Placebo-Controlled Trial
Authors: Löwenberg Mark , Volkers Adriaan , van Gennep Sara , Mookhoek Aart , Montazeri Nahid , Clasquin Esmé , Duijvestein Marjolijn , van Bodegraven Adriaan , Rietdijk Svend , Jansen Jeroen , van Asseldonk Dirk , van der Zanden Esmerij , Dijkgraaf Marcel , West Rachel , de Boer Nanne , D’Haens Geert 
Published: February 2023

Abstract

Background and Aims
Scepticism about the efficacy of thiopurines for ulcerative colitis [UC] is rising. This study aimed to evaluate mercaptopurine treatment for UC.

Methods
In this prospective, randomized, double-blind, placebo-controlled trial, patients with active UC, despite treatment with 5-aminosalicylates [5-ASA], were randomized for therapeutic drug monitoring [TDM]-guided mercaptopurine treatment or placebo for 52 weeks. Corticosteroids were given in the first 8 weeks and 5-ASA was continued. Proactive metabolite-based mercaptopurine and placebo dose adjustments were applied from week 6 onwards by unblinded clinicians. The primary endpoint was corticosteroid-free clinical remission and endoscopic improvement [total Mayo score ≤2 points and no item &gt;1] at week 52 in an intention-to-treat analysis.

Results
Between December 2016 and April 2021, 70 patients were screened and 59 were randomized at six centres. In the mercaptopurine group, 16/29 [55.2%] patients completed the 52-week study, compared to 13/30 [43.3%] on placebo. The primary endpoint was achieved by 14/29 [48.3%] patients on mercaptopurine and 3/30 [10%] receiving placebo (Δ = 38.3%, 95% confidence interval [CI] 17.1–59.4, p = 0.002). Adverse events occurred more frequently with mercaptopurine [808.8 per 100 patient-years] compared to placebo [501.4 per 100 patient-years]. Five serious adverse events occurred, four on mercaptopurine and one on placebo. TDM-based dose adjustments were executed in 22/29 [75.9%] patients, leading to lower mercaptopurine doses at week 52 compared to baseline.

Conclusions
Optimized mercaptopurine treatment was superior to placebo in achieving clinical, endoscopic and histological outcomes at 1 year following corticosteroid induction treatment in UC patients. More adverse events occurred in the mercaptopurine group.
Universal probe with oriented antibody to improve the immunochromatographic assay of lead ions inProcambarus clarkii
Authors: Li Yangyang , Zhu Zhengwei , Qu Wenli , Yang Qing , Liu Yan , Wang Qiao , Duan Shuo , Wu Jine , Gong Zhiyong , Xu Lin 
Published: February 2023

AbstractObjectivesBased on the information from the random inspection of foods by the China Food and Drug Administration in 2022, the contamination levels of lead ions are high in many edible products. Traditional methods of detecting lead ions cannot meet the requirements of on-site analysis of food due to the need for large equipment. The immunochromatographic assay (ICA) is an effective, rapid, on-site analytical technique for determining lead ions in foods. However, the performance of ICA based on the traditional probe (AuNP-mAb) is limited by ignoring the influence of the antibody orientation.Materials and MethodsIn this study, we developed an efficient technology for constructing a universal probe (AuNP-PrA-mAb) based on the oriented immobilization of antibody. The performance of ICA was largely improved due to specific binding of the Fc region of the antibody with recombinant protein A (PrA) on the surface of a gold nanoparticle (AuNP). The ICA based on a universal probe was applied for the qualitative and quantitative detection of lead ions in Procambarus clarkii within 30 min. Meanwhile, a simple and fast pretreatment method based on dilute acid extraction was developed for pretreating the P. clarkii containing lead ions.ResultsThe visual limit of detection and the scanning limit of quantization of the developed ICA strip for lead ions were 0.5 ng/mL and 0.28 ng/mL, respectively. The sensitivity of ICA based on universal probe was 10-fold higher than that of the ICA using traditional probe. Furthermore, the detection results had no obvious difference between the ICA and ICP-MS with t-test statistical method.ConclusionsThe developed ICA based on a universal probe presented broad application prospects in detecting contaminants in foods.
Refinement of an Emergency Department-Based, Advance Care Planning Intervention for Patients With Cognitive Impairment and Their Caregivers
Authors: Ouchi Kei , Joshi Christopher , Kaithamattam Jenson , Gale Seth A , Marshall Gad A , Pietras Alison , Wang Wei , Boyer Edward W , Tulsky James A , Block Susan D , Rentz Dorene , Schonberg Mara A 
Published: February 2023

Abstract

Background and Objectives
Advance care planning (ACP) conversations are important to provide goal-concordant care (i.e., the care that matches the patient’s previously stated goals) near end of life. While 31% of older adults presenting to the emergency department (ED) have dementia, only 39% have previously had ACP conversations. We refined and piloted an ED-based, motivational interview designed to stimulate ACP conversations (ED GOAL) for patients living with cognitive impairment and their caregivers.

Research Design and Methods
We systematically refined ED GOAL and then conducted an acceptability study in an urban, academic medical center. We prospectively enrolled adults aged 50+ with cognitive impairment and their caregivers. Trained clinicians conducted the intervention. We measured acceptability after the intervention and participants’ ACP engagement at baseline and 1-month follow-up.

Results
Specific statements to address both the patient and caregiver were added to the ED GOAL script. Of 60 eligible patient/caregiver dyads approached, 26 participated, and 20 (77%) completed follow-up assessments. Patient mean age was 79 years (SD 8.5); 65% were female, 92.3% were White, 96.2% were non-Hispanic, and 69% had moderate dementia. Most patients/caregivers reported feeling completely heard and understood by the study clinician about their future medical care preferences (58%, 15/26). They also reported that the study clinician was very respectful (96%, 25/26) when eliciting those preferences.

Discussion and Implications
Patients living with cognitive impairment and their caregivers found our refined ED GOAL acceptable and respectful. Future studies need to examine the effect of ED GOAL on ACP engagement among these dyads in the ED.
Pharmacodynamic and immunological interactions of amphotericin B formulations and voriconazole with human neutrophils against matureScedosporium apiospermumandFusariumspp. biofilms
Authors: Vikelouda Katerina , Simitsopoulou Maria , Antachopoulos Charalampos , Skoura Lemonia , Roilides Emmanuel 
Published: February 2023

AbstractBackgroundMould infections caused by Scedosporium apiospermum and Fusarium solani species complex (FSSC) biofilms are rising among immunocompromised and immunocompetent patients. Little is known about the immunomodulatory effects of antifungal agents against these moulds. We examined the effects of deoxycholate and liposomal amphotericin B (DAmB, LAmB) and voriconazole on antifungal activities and immune responses of neutrophils (PMNs) against mature biofilms compared with their planktonic counterparts.MethodsAntifungal activity of human PMNs exposed to mature biofilms and planktonic cells for 24 h was determined at effector-to-target ratios of 2:1 and 5:1, alone or combined with DAmB, LAmB and voriconazole, assessed as fungal damage by XTT assay. Cytokine production was evaluated by multiplex ELISA, following PMN stimulation with biofilms in the presence/absence of each drug.ResultsAll drugs showed additive or synergistic effects with PMNs against S. apiospermum at 0.03–32 mg/L. They showed antagonism primarily against FSSC at 0.06–64 mg/L. Increased IL-8 was produced by PMNs exposed to S. apiospermum biofilms plus DAmB or voriconazole compared with PMNs exposed to biofilms alone (P &lt; 0.01). During combined exposure, IL-1β was increased, an effect only counteracted by increased levels of IL-10 caused by DAmB (P &lt; 0.01). LAmB and voriconazole caused similar IL-10 levels with those released by biofilm-exposed PMNs.ConclusionsThe synergistic, additive or antagonistic effects of DAmB, LAmB or voriconazole on biofilm-exposed PMNs are organism-specific, with FSSC exhibiting greater resilience than S. apiospermum to antifungals. Biofilms of both moulds caused dampened immune responses. The drug-mediated immunomodulating effect on PMNs, evidenced by IL-1β, enhanced host protective functions.
Extended Detection Window for Gamma-Hydroxybutyrate in the Urine of an Elderly Woman
Authors: Berg J A , Rajendiran R , Serkland T T , Methlie C B , Hallin E I , Stokes C L 
Published: February 2023

Abstract
Gamma-hydroxybutyrate (GHB) is a central nervous system depressant that has gained popularity as an illicit recreational drug. We describe a case of an elderly woman who was found unconscious in her home. The paramedics initially suspected an intracranial incident. A head computed tomography was negative, as was the initial urinary drug screening. The diagnosis of GHB intoxication was made with the detection of GHB in a urine sample obtained 28–29 hours after the assumed time of intake. Our case underscores the importance of considering drug testing in a broad range of patients and shows that elderly patients may have an extended detection window of GHB.
Knowledge of and willingness for dispensing oral anticancer drug therapy among community pharmacists: a cross-sectional study from Jordan
Authors: Ayoub Nehad M , Alhamdan Yazan R , Jaradat Sara K , Jibreel Malak 
Published: February 2023

Abstract

Objectives
This study aimed to assess the knowledge of and willingness for dispensing oral anticancer drugs (OADs) among community pharmacists in Jordan.

Methods
A cross-sectional survey was conducted among pharmacists in community pharmacies.

Key findings
Five hundred pharmacists completed the questionnaire. The mean age of respondents was 30.4 ± 6.2 years (range 21–61). Most pharmacists had a bachelor’s degree in pharmacy (80.8%) and were staff pharmacists (61.6%). Two hundred and ten (42.0%) pharmacists indicated not receiving adequate education on OADs at the undergraduate level. The majority of respondents (79.8%) did not attend continuing education events in oncology in the past 2 years. Further, 44.6% of pharmacists never dispensed OADs in their pharmacies. The mean score of knowledge of OADs was 1.7 ± 1.9 out of 12 points (range 0–9). The vast majority of pharmacists surveyed (97.6%) had poor knowledge of OADs. Almost half of the pharmacists (49.8%) agreed or strongly agreed to be comfortable answering questions regarding cancer treatments. More than half of respondents (52.2%) feel comfortable providing patient education on OADs. Half of the respondents (49.6%) disagreed that their current pharmacy settings are equipped with the necessary tools to handle OADs.

Conclusions
A large number of community pharmacists in Jordan lack the foundational knowledge regarding OADs. A substantial proportion of pharmacists never dispensed OADs and were not satisfied with the level of undergraduate education received regarding oncology and oral cancer therapies. Nevertheless, most pharmacists were willing to handle OADs and were positive about receiving further training/education on dispensing OADs. Collectively, efforts are needed to improve pharmacy education on oral chemotherapy and cancer care along with continuous training for pharmacists in their community settings.
Arcuate line hernia: a case report
Authors: Cohen Koral , Kolwitz Christine , Petrone Patrizio , Halpern David 
Published: February 2023

AbstractArcuate line hernias are a rare type of hernia with limited publications regarding their successful repair. The arcuate line is the inferior limit of the posterior leaf of the rectus sheath. An arcuate line hernia is a type of intraparietal hernia, meaning it is not a truly complete fascial defect of the abdominal and, therefore, may present with atypical symptoms. Although published data on arcuate line hernia repairs are limited to a handful of case reports and one literature review, reports regarding robotic repair are exceptionally rare. This case report is the second documented robotic approach to arcuate line hernias known to these authors.
Nitrogen supply alleviates cold stress by increasing photosynthesis and nitrogen assimilation in maize seedlings
Authors: Soualiou Soualihou , Duan Fengying , Li Xia , Zhou Wenbin 
Published: February 2023

Abstract
Cold stress inhibits the early growth of maize, leading to reduced productivity. Nitrogen (N) is an essential nutrient that stimulates maize growth and productivity, but the relationship between N availability and cold tolerance is poorly characterized. Therefore, we studied the acclimation of maize under combined cold stress and N treatments. Exposure to cold stress caused a decline in growth and N assimilation, but increased abscisic acid (ABA) and carbohydrate accumulation. The application of different N concentrations from the priming stage to the recovery period resulted in the following observations: (i) high N supply alleviated cold stress-dependent growth inhibition, as shown by increased biomass, chlorophyll and Rubisco content and PSII efficiency; (ii) cold stress-induced ABA accumulation was repressed under high N, presumably due to enhanced stomatal conductance; (iii) the mitigating effects of high N on cold stress could be due to the increased activities of N assimilation enzymes and improved redox homeostasis. After cold stress, the ability of maize seedlings to recover increased under high N treatment, indicating the potential role of high N in the cold stress tolerance of maize seedlings.
A Deeper Dive Into Combat Medic Training
Authors: Suresh Mithun R , Staudt Amanda M , Trevino Jennifer D , Papalski Wayne N , Greydanus Dominique J , Valdez-Delgado Krystal K , Mann-Salinas Elizabeth A , VanFosson Christopher A 
Published: February 2023

ABSTRACT
The recent article by Knisely et al. provides a comprehensive review and summary of recent literature describing simulation techniques, training strategies, and technologies to teach medics combat casualty care skills. Some of the results reported by Knisely et al. align with the findings of our team’s work, and these findings may be helpful to military leadership with their ongoing efforts to maintain medical readiness. Accordingly, we provide some additional contextual understanding to the results of Knisely et al. in this commentary. Our team recently published two papers describing the results of a large survey that examined Army medic pre-deployment training. Combining the findings of Knisely et al. along with some of the contextual information from our work, we provide some recommendations for improving and optimizing the pre-deployment training paradigm for medics.
The Thousand-Pulsar-Array programme on MeerKAT – XI. Application of the rotating vector model
Authors: Johnston S , Kramer M , Karastergiou A , Keith M J , Oswald L S , Parthasarathy A , Weltevrede P 
Published: February 2023

ABSTRACTIn spite of the rich phenomenology of the polarization properties of radio pulsars, the rotating vector model (RVM) created 50 years ago remains the best method to determine the beam geometry of a pulsar. We apply the RVM to a sample of 854 radio pulsars observed with the MeerKAT telescope in order to draw conclusions about the population of pulsars as a whole. The main results are that (i) the geometrical interpretation of the position angle (PA) traverse is valid in the majority of the population, (ii) the pulsars for which the RVM fails tend to have a high fraction of circular polarization compared to linear polarization, (iii) emission heights obtained through both geometrical and relativistic methods show that the majority of pulsars must have emission heights less than 1000 km independent of the spin period, (iv) orthogonal mode jumps are seen in the PA traverse in about one third of the population. All these results are weakly dependent on the pulsar spin-down energy.