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DEAD-box RNA helicases are ubiquitous proteins found in all kingdoms of life and that are associated with all processes involving RNA. Their central roles in biology make these proteins potential targets for therapeutic or prophylactic drugs. The Ded1/DDX3 subfamily of DEAD-box proteins is of particular interest because of their important role(s) in translation. In this paper, we identified and aligned the protein sequences of 28 different DEAD-box proteins from the kinetoplast-protozoan parasite Leishmania infantum, which is the cause of the visceral form of leishmaniasis that is often lethal if left untreated, and compared them with the consensus sequence derived from DEAD-box proteins in general, and from the Ded1/DDX3 subfamily in particular, from a wide variety of other organisms. We identified three potential homologs of the Ded1/DDX3 subfamily and the equivalent proteins from the related protozoan parasite Trypanosoma brucei, which is the causative agent of sleeping sickness. We subsequently tested these proteins for their ability to complement a yeast strain deleted for the essential DED1 gene. We found that the DEAD-box proteins from Trypanosomatids are highly divergent from other eukaryotes, and consequently they are suitable targets for protein-specific drugs. [ABSTRACT FROM AUTHOR]

Background: Endoscopic retrograde cholangiopancreatography (ERCP) has become the gold standard management for patients who present with common bile duct stone (CBDS). Although laparoscopic cholecystectomy is generally recommended for patients who have CBDS clearance, there is still a significant proportion of patients who are managed expectantly. Our study aimed to evaluate the outcomes of expectant management (EM) versus prophylactic cholecystectomy after initial endoscopic removal of CBDS., Method: We performed a retrospective review of all patients who underwent ERCP for choledocholithiasis from 1st January 2017 to 31st December 2019. Patients were further classified into young or elderly group using age 60 years as the cut-off. Primary outcomes measured biliary-related complications in each interventional group whereas secondary outcomes measured all-cause mortality., Results: 136 patients (51.3%) had EM whereas 129 patients (48.7%) were initially planned for LC. There was 20.6% of recurrence of biliary events in EM group as compared to 3.9% in LC group. The median time from first ERCP to recurrence of biliary events in the EM group was 14 months. Overall complications of LC group was low (5.4%) with nil operative-related mortality. However, there was a significant higher proportion of elderly patients in EM group in comparison to LC group (88.2% vs 31%) and 51.4% of EM group died during follow-up period with only one biliary-related death., Conclusion: Prophylactic cholecystectomy should be recommended for patients who have undergone ERCP clearance of CBDS. A watch-and-wait approach may be justified for elderly populations who are not ideal surgical candidates and a follow-up duration of up to 2 years is recommended., Competing Interests: Declarations. Disclosures: Miss Cindy Wong, Mr Naren Kumaran, Dr Arya Krishnan and Miss Nicola Tanner declared no conflicts of interest/disclosure that are relevant to the content of this article. Ethical approval: This study is registered with the local clinical audit team and does not require formal ethical approval., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A thorough literature search is a key feature of scoping reviews. We investigated the search practices used by social science researchers as reported in their scoping reviews. We collected scoping reviews published between 2015 and 2021 from Social Science Citation Index. In the 2484 included studies, we observed a 58% average annual increase in published reviews, primarily from clinical and applied social science disciplines. Bibliographic databases comprised most of the information sources in the primary search strategy (n = 9565, 75%), although reporting practices varied. Most scoping reviews (n = 1805, 73%) included at least one supplementary search strategy. A minority of studies (n = 713, 29%) acknowledged an LIS professional and few listed one as a co-author (n = 194, 8%). We conclude that to improve reporting and strengthen the impact of the scoping review method in the social sciences, researchers should consider (1) adhering to PRISMA-S reporting guidelines, (2) employing more supplementary search strategies, and (3) collaborating with LIS professionals., (© 2024 The Author(s). Research Synthesis Methods published by John Wiley & Sons Ltd.)

Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a 5-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths. Significance: Lung cancer screening has poor adoption. Our study describes the development and validation of a novel blood-based lung cancer screening test utilizing a highly affordable, low-coverage genome-wide sequencing platform to analyze cell-free DNA fragmentation patterns. The test could improve lung cancer screening rates leading to substantial public health benefits. See related commentary by Haber and Skates, p. 2025., (©2024 The Authors; Published by the American Association for Cancer Research.)

This intriguing case report explores an interesting complication following percutaneous cholecystostomy for the management of acute cholecystitis in an elderly female with multiple comorbidities. Despite initial improvement, she later presented with recurrent symptoms, due to a collection of gallstones, that had migrated through the cholecystostomy tract, requiring exploration, stone retrieval and abscess drainage. While percutaneous cholecystostomy remains an effective treatment for managing acute cholecystitis in high-risk surgical candidates, this case highlights the rare yet critical risk of extrahepatic gallstones and abscess formation. It emphasises the necessity for vigilance in detecting and managing complications associated with percutaneous transhepatic cholecystostomy, ensuring timely diagnosis and effective treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Particle trapping and enrichment into confined volumes can be useful in particle processing and analysis. This review is an evaluation of the methods used to trap and enrich particles into constrained volumes in microfluidic and nanofluidic systems. These methods include physical, optical, electrical, magnetic, acoustic, and some hybrid techniques, all capable of locally enhancing nano- and microparticle concentrations on a microscale. Some key qualitative and quantitative comparison points are also explored, illustrating the specific applicability and challenges of each method. A few applications of these types of particle trapping are also discussed, including enhancing biological and chemical sensors, particle washing techniques, and fluid medium exchange systems.

Oncogenic intercellular signaling is regulated by extracellular vesicles (EVs), but the underlying mechanisms remain mostly unclear. Since TCTP (translationally controlled tumor protein) is an EV component, we investigated whether it has a role in genotoxic stress signaling and malignant transformation. By generating a Tctp-inducible knockout mouse model (Tctp -/f- ), we report that Tctp is required for genotoxic stress-induced apoptosis signaling via small EVs (sEVs). Human breast cancer cells knocked-down for TCTP show impaired spontaneous EV secretion, thereby reducing sEV-dependent malignant growth. Since Trp53 -/- mice are prone to tumor formation, we derived tumor cells from Trp53 -/- ;Tctp -/f- double mutant mice and describe a drastic decrease in tumori-genicity with concomitant decrease in sEV secretion and content. Remarkably, Trp53 -/- ;Tctp -/f- mice show highly prolonged survival. Treatment of Trp53 -/- mice with sertraline, which inhibits TCTP function, increases their survival. Mechanistically, TCTP binds DDX3, recruiting RNAs, including miRNAs, to sEVs. Our findings establish TCTP as an essential protagonist in the regulation of sEV-signaling in the context of apoptosis and tumorigenicity., (© 2024. The Author(s).)

Mpox is a neglected zoonotic disease endemic in West and Central Africa. The Mpox outbreak with more than 90,000 cases worldwide since 2022 generated great concern about future outbreaks and highlighted the need for a simple and rapid diagnostic test. The Mpox virus, MPV, is a member of the Orthopoxvirus (OPV) genus that also contains other pathogenic viruses including variola virus, vaccinia virus, camelpox virus, and cowpox virus. Phylogenomic analysis of 200 OPV genomes identified 10 distinct phylogroups with the New World OPVs placed on a very long branch distant from the Old World OPVs. Isolates derived from infected humans were found to be distributed across multiple phylogroups interspersed with isolates from animal sources, indicating the zoonotic potential of these viruses. In this study, we developed a simple and sensitive colorimetric LAMP assay for generic detection of Old World OPVs. We also developed an MPV-specific probe that differentiates MPV from other OPVs in the N1R LAMP assay. In addition, we described an extraction-free protocol for use directly with swab eluates in LAMP assays, thereby eliminating the time and resources needed to extract DNA from the sample. Our direct LAMP assays are well-suited for low-resource settings and provide a valuable tool for rapid and scalable diagnosis and surveillance of OPVs and MPV., (© 2023. The Author(s).)

Objectives: Explore sleep disturbance in postoperative orthopedic trauma patients and determine the impact of melatonin supplementation on postoperative sleep, pain, and quality of life., Materials and Methods: In this prospective, randomized controlled trial at a Level I trauma center, 84 adult orthopedic trauma patients with operative fracture management were randomized 2-weeks postoperatively to either the melatonin or placebo group. Patients randomized to the melatonin group (42 subjects, mean age 41.8 ± 15.5 years) received 5 mg melatonin supplements. Patients in the placebo group (42 subjects, mean age 41.3 ± 14.0 years) received identical glucose tablets. Both groups were instructed to take the tablets 30 minutes before bed for 4 weeks and received sleep hygiene education and access to the Cognitive Behavioral Therapy for Insomnia (CBT-I) Coach app., Main Outcome Measures: Our primary outcome was sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes were pain measured by the Visual Analog Scale (VAS), quality of life measured by the 36-Item Short Form Survey (SF-36), and opioid use., Results: Patients in both groups had significant sleep disturbance (PSQI ≥ 5) at 2-weeks (83%) and 6-weeks (67%) postoperatively. PSQI improved by 3.3 points (p<0.001) at follow-up, but there was no significant difference between groups (melatonin PSQI = 5.6, placebo PSQI = 6.1, P = 0.615). Compared to placebo, melatonin did not affect VAS, SF-36, or opioid use significantly., Conclusion: Sleep disturbance is prevalent in orthopedic trauma patients. Melatonin treatment did not significantly improve subjective sleep quality, pain, quality of life or opioid use., Level of Evidence: Therapeutic Level I., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: We developed Teachable Moment to Opt-Out of Tobacco (TeaM OUT) as a tobacco treatment intervention based on a foundation of a theoretical model of teachable moments, "naturally occurring life transitions or health events thought to motivate individuals to spontaneously adopt risk-reducing health behaviors". The TeaM OUT intervention combines a teachable moment for patients with newly detected incidental pulmonary nodules with a proactive interactive voice response (IVR) system to increase connections to evidence-based tobacco treatment interventions., Methods: We will perform a convergent, nested observational mixed-methods study utilizing both randomized trial and observational methods to test the effectiveness and generalizability of the TeaM OUT intervention through three aims. AIM 1: Among patients recently diagnosed with a pulmonary nodule, we will utilize a pragmatic, stepped wedge randomized controlled design to evaluate the effectiveness of a proactive, teachable moment-based, tobacco treatment outreach intervention (TeaM OUT) on increasing engagement with tobacco treatment resources compared to Enhanced Usual Care. AIM 2: Using a longitudinal observational design, we will evaluate the association of receipt of the TeaM OUT intervention with seven-day point abstinence prevalence and quit motivation compared to Enhanced Usual Care. AIM 3: Qualitatively elicit perspectives from key stakeholders to inform acceptability and utility, implementation barriers and facilitators, and scalability of the TeaM OUT intervention., Discussion: We are hopeful that implementation of TeaM OUT will increase the number of patients who quit using cigarettes with subsequent improvements in their health., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest with the work presented in this manuscript., (Published by Elsevier Inc.)

Background: Behavioral pain treatments may improve postsurgical analgesia and recovery; however, effective and scalable options are not widely available. This study tested a digital perioperative behavioral medicine intervention in orthopedic trauma surgery patients for feasibility and efficacy for reducing pain intensity, pain catastrophizing, and opioid cessation up to 3 months after surgery., Methods: A randomized controlled clinical trial was conducted at an orthopedic trauma surgery unit at a major academic hospital to compare a digital behavioral pain management intervention ("My Surgical Success" [MSS]) to a digital general health education (HE) intervention (HE; no pain management skills). The enrolled sample included 133 patients; 84 patients were randomized (MSS, n = 37; HE, n = 47) and completed study procedures. Most patients received their assigned intervention within 3 days of surgery (85%). The sample was predominantly male (61.5%), White (61.9%), and partnered (65.5%), with at least a bachelor's degree (69.0%). Outcomes were collected at 1-3 months after intervention through self-report e-surveys and electronic medical record review; an intention-to-treat analytic framework was applied. Feasibility was dually determined by the proportion of patients engaging in their assigned treatment and an application of an 80% threshold for patient-reported acceptability. We hypothesized that MSS would result in greater reductions in pain intensity and pain catastrophizing after surgery and earlier opioid cessation compared to the digital HE control group., Results: The engagement rate with assigned interventions was 63% and exceeded commonly reported rates for fully automated Internet-based e-health interventions. Feasibility was demonstrated for the MSS engagers, with >80% reporting treatment acceptability. Overall, both groups improved in the postsurgical months across all study variables. A significant interaction effect was found for treatment group over time on pain intensity, such that the MSS group evidenced greater absolute reductions in pain intensity after surgery and up to 3 months later (treatment × time fixed effects; F [215] = 5.23; P = .024). No statistically significant between-group differences were observed for time to opioid cessation or for reductions in pain catastrophizing ( F [215] = 0.20; P = .653), although the study sample notably had subclinical baseline pain catastrophizing scores (M = 14.10; 95% confidence interval, 11.70-16.49)., Conclusions: Study findings revealed that a fully automated behavioral pain management skills intervention (MSS) may be useful for motivated orthopedic trauma surgery patients and reduce postsurgical pain up to 3 months. MSS was not associated with reduced time to opioid cessation compared to the HE control intervention., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

The type III secretion system (T3SS) is an appendage used by many bacterial pathogens, such as pathogenic Yersinia, to subvert host defenses. However, because the T3SS is energetically costly and immunogenic, it must be tightly regulated in response to environmental cues to enable survival in the host. Here we show that expression of the Yersinia Ysc T3SS master regulator, LcrF, is orchestrated by the opposing activities of the repressive H-NS/YmoA histone-like protein complex and induction by the iron and oxygen-regulated IscR transcription factor. While deletion of iscR or ymoA has been shown to decrease and increase LcrF expression and type III secretion, respectively, the role of H-NS in this system has not been definitively established because hns is an essential gene in Yersinia. Using CRISPRi knockdown of hns, we show that hns depletion causes derepression of lcrF. Furthermore, we find that while YmoA is dispensable for H-NS binding to the lcrF promoter, YmoA binding to H-NS is important for H-NS repressive activity. We bioinformatically identified three H-NS binding regions within the lcrF promoter and demonstrate binding of H-NS to these sites in vivo using chromatin immunoprecipitation. Using promoter truncation and binding site mutation analysis, we show that two of these H-NS binding regions are important for H-NS/YmoA-mediated repression of the lcrF promoter. Surprisingly, we find that IscR is dispensable for lcrF transcription in the absence of H-NS/YmoA. Indeed, IscR-dependent regulation of LcrF and type III secretion in response to changes in oxygen, such as those Yersinia is predicted to experience during host infection, only occurs in the presence of an H-NS/YmoA complex. These data suggest that, in the presence of host tissue cues that drive sufficient IscR expression, IscR can act as a roadblock to H-NS/YmoA-dependent repression of RNA polymerase at the lcrF promoter to turn on T3SS expression., Competing Interests: The authors have declared that no competing interests exist.

The relationship between childhood asthma and gastro-oesophageal reflux (GOR) is contentious. Recent studies in adult asthmatics suggest that GOR is associated with worse control and differences in sputum proteomics related to epithelial integrity, systemic inflammation and host defence. We assessed 127 children with severe asthma undergoing bronchoscopy and pH study. There were no differences in asthma control or measures of airway inflammation or remodelling when those with acid GOR were compared with those without. These results suggest that acid GOR is not an important comorbidity in paediatric severe asthma., Competing Interests: Competing interests: LF is an Asthma UK Senior Clinical Fellow and PI in the Asthma UK Centre for Applied Research. AB is an Emeritus NIHR Senior Investigator and PI in the Asthma UK Centre for Applied Research. SS was an NIHR Career Development Fellow., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Cephalomedullary nail (CMN) length for intertrochanteric femur fractures without subtrochanteric extension has been an ongoing debate. The authors hypothesize that increasing nail length would result in increasing surgical time, greater incidence of acute kidney injury (AKI), postoperative anemia, and blood loss requiring transfusion due to increased intramedullary reaming and pressurization of the canal with nail insertion., Methods: A retrospective chart review of patients aged 65 years or older who underwent CMN for low-energy intertrochanteric femur fractures from 2010 to 2018 was undertaken. Patient demographic data, comorbidities, case duration, postoperative hospital length of stay (LOS), and laboratory data, including serum creatinine, hemoglobin, and hematocrit, were collected for analysis. The following outcome measures were compared: postoperative pneumonia, cardiac complications, sepsis, reintubation/intensive care unit stay, pulmonary embolism, stroke, postoperative AKI, 30-day hospital readmission, 30-day return to operating room, 30-day mortality, 1-year mortality, postoperative anemia (hemoglobin <7 g/dL), and blood transfusion., Results: A total of 247 patients were analyzed (short = 48, intermediate = 39, and long = 160). No notable difference was observed in postoperative pneumonia, cardiac complications, sepsis, reintubation/intensive care unit stay, pulmonary embolism, stroke, mean total hospital LOS, mean postoperative hospital LOS, rate of postoperative AKI, 30-day readmission, 30-day return to operating room, 30-day mortality, or 1-year mortality. Patients receiving long nails had significantly higher rates of postoperative anemia (P = 0.0491), blood transfusion (P = 0.0126), and mean procedure length (P = 0.0044) compared with the two other groups., Discussion: Patients receiving long nails had markedly higher rates of postoperative anemia and blood loss requiring blood transfusion with markedly longer mean procedure length than patients receiving short and intermediate CMNs. Long nails did not result in an increase in other complications evaluated., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

According to legislation, unifloral honeys are characterized by their organoleptic, physicochemical, and microscopic properties. Melissopalynology is the established method for identifying the pollen taken up with the floral nectar by forager bees and is used for authentication of the nectar sources in honey. For cornflower honey ( Centaurea cyanus ), the pollen input does not correlate with the nectar input, because the nectar is produced both in floral and in extrafloral nectaries. The well-known cornflower marker lumichrome has now also been detected in the extrafloral nectar. Therefore, lumichrome is a suitable marker substance for cornflower honey. Four different methods for the sole analysis of lumichrome in honey were validated and compared. Studies over nine years have shown that unifloral cornflower honey should contain approximately 35 mg/kg lumichrome. For a further differentiated cornflower honey specific verification, other nonvolatile compounds like 7-carboxylumichrome and volatiles, such as 3,4-dihydro-3-oxoedulan I and 3,4-dihydro-3-oxoedulan II, should be analyzed. This enables a more specific accuracy for the classification of unifloral cornflower honey.