bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of Depression in Adults
Authors: Simon Gregory E. , Moise Nathalie , Mohr David C. 
Published: June 2024

ImportanceApproximately 9% of US adults experience major depression each year, with a lifetime prevalence of approximately 17% for men and 30% for women.ObservationsMajor depression is defined by depressed mood, loss of interest in activities, and associated psychological and somatic symptoms lasting at least 2 weeks. Evaluation should include structured assessment of severity as well as risk of self-harm, suspected bipolar disorder, psychotic symptoms, substance use, and co-occurring anxiety disorder. First-line treatments include specific psychotherapies and antidepressant medications. A network meta-analysis of randomized clinical trials reported cognitive therapy, behavioral activation, problem-solving therapy, interpersonal therapy, brief psychodynamic therapy, and mindfulness-based psychotherapy all had at least medium-sized effects in symptom improvement over usual care without psychotherapy (standardized mean difference [SMD] ranging from 0.50 [95% CI, 0.20-0.81] to 0.73 [95% CI, 0.52-0.95]). A network meta-analysis of randomized clinical trials reported 21 antidepressant medications all had small- to medium-sized effects in symptom improvement over placebo (SMD ranging from 0.23 [95% CI, 0.19-0.28] for fluoxetine to 0.48 [95% CI, 0.41-0.55] for amitriptyline). Psychotherapy combined with antidepressant medication may be preferred, especially for more severe or chronic depression. A network meta-analysis of randomized clinical trials reported greater symptom improvement with combined treatment than with psychotherapy alone (SMD, 0.30 [95% CI, 0.14-0.45]) or medication alone (SMD, 0.33 [95% CI, 0.20-0.47]). When initial antidepressant medication is not effective, second-line medication treatment includes changing antidepressant medication, adding a second antidepressant, or augmenting with a nonantidepressant medication, which have approximately equal likelihood of success based on a network meta-analysis. Collaborative care programs, including systematic follow-up and outcome assessment, improve treatment effectiveness, with 1 meta-analysis reporting significantly greater symptom improvement compared with usual care (SMD, 0.42 [95% CI, 0.23-0.61]).Conclusions and RelevanceEffective first-line depression treatments include specific forms of psychotherapy and more than 20 antidepressant medications. Close monitoring significantly improves the likelihood of treatment success.
Acetaminophen and Ibuprofen in Pediatric Central Nervous System Malaria
Authors: Birbeck Gretchen L. , Seydel Karl B. , Mwanza Suzanna , Tembo Derby , Chilombe Moses , Watts Arthur , Ume-Ezeoke Ifunanya , Mathews Manoj , Patel Archana A. , Mwenechanya Musaku , Pensulo Paul , McDermott Michael P. 
Published: June 2024

ImportanceA third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae.ObjectiveTo compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.5 °C or higher.Design, Setting, and ParticipantsThis randomized clinical trial was conducted at inpatient pediatric services of 1 tertiary care and 1 district hospital in Zambia and a tertiary care center in Malawi. Included were children aged 2 to 11 years with CNS malaria (excluding those with creatinine &amp;gt;1.2 mg/dL), who were enrolled from 2019 to 2022. Data analysis took place from December 2022 to April 2023.InterventionThe aggressive antipyretic group received acetaminophen (30 mg/kg load, then 15 mg/kg) plus ibuprofen, 10 mg/kg, every 6 hours, regardless of clinical temperature for 72 hours. The usual care group received 15 mg/kg of acetaminophen as needed every 6 hours for a temperature of 38.5 °C or higher.Main Outcomes and MeasuresThe primary outcome variable was Tmax over 72 hours, the total duration of follow-up. Secondary outcomes included seizures and parasite clearance.ResultsFive hundred fifty-three patients were screened, 226 (40.9%) were ineligible, and 57 (10.3%) declined. A total 256 participants (n = 128/group) had a mean (SD) age of 4.3 (2.1) years; 115 (45%) were female, and 141 (55%) were male. The aggressive antipyretic group had a lower Tmax, 38.6 vs 39.2 °C (difference, −0.62 °C; 95% CI, −0.82 to −0.42; P &amp;lt; .001) and lower odds of experiencing multiple or prolonged seizures, 10 (8%) vs 34 children (27%) in the usual care group (odds ratio [OR], 0.26; 95% CI, 0.12 to 0.56). No group difference in parasite clearance time was detected. Severe adverse events occurred in 40 children (15%), 25 (20%) in the usual care group and 15 (12%) in the aggressive antipyretic group, including 13 deaths (10 [8%] and 3 [2%], respectively). Increased creatinine resulted in study drug discontinuation in 8 children (6%) in the usual care group and 13 children (10%) in the aggressive antipyretic group (OR, 1.74; 95% CI, 0.63 to 5.07).Conclusions and RelevanceThis study found that aggressive antipyretic therapy reduced mean Tmax to temperature levels comparable with the Tmax among children without neurological impairments in prior observational studies and improved acute seizure outcomes with no prolongation of parasitemia.Trial RegistrationClinicalTrials.gov Identifier: NCT03399318
The Glasgow Microenvironment Score: an exemplar of contemporary biomarker evolution in colorectal cancer
Authors: Knight Katrina , Bigley Christopher , Pennel Kathryn , Hay Jennifer , Maka Noori , McMillan Donald , Park James , Roxburgh Campbell , Edwards Joanne 
Published: June 2024

AbstractColorectal cancer remains a leading cause of mortality worldwide. Significant variation in response to treatment and survival is evident among patients with similar stage disease. Molecular profiling has highlighted the heterogeneity of colorectal cancer but has had limited impact in daily clinical practice. Biomarkers with robust prognostic and therapeutic relevance are urgently required. Ideally, biomarkers would be derived from H&E sections used for routine pathological staging, have reliable sensitivity and specificity, and require minimal additional training. The biomarker targets would capture key pathological features with proven additive prognostic and clinical utility, such as the local inflammatory response and tumour microenvironment. The Glasgow Microenvironment Score (GMS), first described in 2014, combines assessment of peritumoural inflammation at the invasive margin with quantification of tumour stromal content. Using H&E sections, the Klintrup–Mäkinen (KM) grade is determined by qualitative morphological assessment of the peritumoural lymphocytic infiltrate at the invasive margin and tumour stroma percentage (TSP) calculated in a semi‐quantitative manner as a percentage of stroma within the visible field. The resulting three prognostic categories have direct clinical relevance: GMS 0 denotes a tumour with a dense inflammatory infiltrate/high KM grade at the invasive margin and improved survival; GMS 1 represents weak inflammatory response and low TSP associated with intermediate survival; and GMS 2 tumours are typified by a weak inflammatory response, high TSP, and inferior survival. The prognostic capacity of the GMS has been widely validated while its potential to guide chemotherapy has been demonstrated in a large phase 3 trial cohort. Here, we detail its journey from conception through validation to clinical translation and outline the future for this promising and practical biomarker.
Natural colonisation rates in a UK upland landscape under different conservation management approaches following sheep removal
Authors: Porton G. , Wrigley R. , Scott C. E. , Spracklen D. V. 
Published: June 2024

Abstract

Natural colonisation could provide a cost‐effective means to increase woodland coverage across the UK uplands. However, there is a shortage of evidence of which factors affect the success of natural colonisation, including grazing management. The species of grazer, grazing intensity and the stage of regeneration may alter the impact of grazing on the ability of trees to colonise an area.

In this study, we quantify the effect of removing sheep from an area in the Yorkshire Dales National Park, England, and explore whether cattle or ungrazed management alters tree colonisation rates. We also tested other environmental factors such as distance from woodland, elevation and soil geology to understand the other constraints on natural colonisation. Naturally colonised trees were recorded within 60 plots at Ingleborough National Nature Reserve and surrounding Yorkshire Wildlife Trust reserves. A series of generalised linear models, with a negative binomial distribution, were created to understand the effects that years since removal of sheep, current management, elevation, distance from woodland and soil geology had on the number of naturally colonising trees.

The number of naturally colonising trees per hectare was 16% higher each year after sheep removal, with both cattle and ungrazed management being equally effective in promoting natural colonisation. Natural colonisation decreased by 25% for every additional 100 m from the nearest woodland and naturally colonising trees were much more frequent on limestone soil.

Practical implication. This study shows that sheep grazing is a key limiting factor of natural colonisation in the UK uplands. Significant natural colonisation was possible on both cattle grazed and ungrazed sites and developed at a similar rate, highlighting a change in grazing animal can be as important as grazing cessation. Tree planting will still be required to restore tree cover to areas away from seed sources and improve diversity of future woodlands.
Modifiable factors associated with Huntington's disease progression in presymptomatic participants
Authors: Gil‐Salcedo Andres , Massart Renaud , de Langavant Laurent Cleret , Bachoud‐Levi Anne‐Catherine 
Published: June 2024

AbstractObjectiveHuntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor, cognitive, and psychiatric symptoms. Our aim here was to identify factors that can be modified to slow disease progression even before the first symptoms appear.MethodsWe included 2636 presymptomatic individuals (comparison with family controls) drawn from the prospective observational cohort Enroll‐HD, with more than 35 CAG repeats and at least two assessments of disease progression measured with the composite Huntington's disease rating Scale (cUHDRS). The association between sociodemographic factors, health behaviors, health history, and cUHDRS trajectory was assessed with a mixed‐effects random forest using partial dependence plots and Shapley additive explanation method.ResultsParticipants were followed by an average of 3.4 (SD = 1.97) years. We confirmed the negative impact of age and a high number of CAG repeats. We found that a high level of education, a body mass index (BMI) <23 kg/m2 before the age of 40 and >23 kg/m2 thereafter, alcohol consumption of <15 units per week, current coffee consumption and no smoking were linked to slow disease progression, as did no previous exposure to antidepressants or anxiolytic, no psychiatric history or comorbidities, and being female. Other comorbidities or marital status showed no major association with HD evolution.InterpretationReducing modifiable risk factors for HD is one way to support the presymptomatic population. A high level of education, low‐to‐moderate alcohol consumption, no smoking, and BMI control are likely to slow disease progression in this population.
Functionalized Annealed Microgels for Spatial Control of Osteogenic and Chondrogenic Differentiation
Authors: Lowen Jeremy M. , Wheeler Erika E. , Shimamoto Nathan K. , Ramos‐Rodriguez David H. , Griffin Katherine H. , Bond Gabriella C. , Leach J. Kent 
Published: June 2024

AbstractThe biophysical heterogeneity of the bone–cartilage interface requires complex materials to mimic differences in bone density, extracellular matrix composition, and mineralization. Biomaterial approaches to repair osteochondral tissue typically use multilayer scaffolds, which require multistep fabrication and may undergo delamination at the construct interface. This work describes the development of functionalized microgels for the repair of osteochondral tissues using an N‐cadherin peptide, bone morphogenetic protein‐2 (BMP‐2) peptide, and changes in stiffness to create pro‐osteogenic and prochondrogenic microgels. Microgels, when annealed into a scaffold, outperforms bulk hydrogel controls evidenced by upregulation of osteogenic and chondrogenic markers in mesenchymal stromal cells (MSCs). The macroporous void space present in microgel anneals scaffolds enabled robust cell proliferation and extracellular matrix (ECM) deposition throughout the entire scaffold. A bilayer functionalized annealed microgel scaffold is then created and the ability to spatially control the differentiation of MSCs is assessed. Osteochondral bilayer scaffolds exhibit distinct regions of osteogenic and chondrogenic protein expression as a function of microgel population upon immunostaining for osteocalcin and aggrecan, respectively. Spatial transcriptomics confirm osteogenic and chondrogenic genes are upregulated in their respective microgel regions. These studies highlight the tunable and functionalizable nature of microgels and the importance of macroporous void space.
Dual‐Wing Ligand Constructed Metal–Organic Framework Membranes with Finely Tuned Apertures for Natural Gas Separation
Authors: Shi Yapeng , Liu Yang , Wang Zhenggong , Lai Weikang , Liao Yining , Lu Kuan , Niu Zheng , Jin Jian 
Published: June 2024

AbstractMetal–organic framework (MOF) membranes with apparent molecular sieving effects have great potential for gas separation. However, their application in light‐gas separation (e.g., CO2/CH4 and H2/CH4) remains challenging due to their enlarged pore structures under transmembrane pressure. In this work, a series of MOF membranes constructed from dual‐wing (DW) ligands including 2‐chloromethylbenzimidazole, 2‐methylbenzimidazole, 2‐ethylbenzimidazole, and 2‐phenylbenzimidazole are reported, to finely tune apertures and enhance molecule sieving property for small‐size gases. These DW‐ligands provide steric resistance in two directions perpendicular to the coordination bond, leading to a much finer pore structure. The introduction of the DW‐ligands endows the DW/ZIF‐8 membranes with an adjustable bottleneck door for regulating gas diffusion, blocking the transport of large‐sized CH4 while allowing small‐sized H2 and CO2 to permeate. The membranes show significantly improved molecular sieving property with a CO2/CH4 mixed‐gas selectivity of 58.6 in the case of 2‐chloromethylbenzimidazole23/ZIF‐8, which represents the highest value among the reported ZIF membranes. This membrane also exhibits exceptional separation performance for H2/CH4 and H2/C3H8 with separation factors of 430 and 34341, which are the highest values among the reported MOF membranes. This study presents a facile and efficient strategy for regulating MOF aperture and constructing high‐performance membranes for natural gas separation.
A Cu‐Based Single‐Atom Nanozyme Platform with Multi‐Enzyme Simulated Activities for Immunotherapy of Prostate Cancer by Regulating Cholesterol Metabolism and Triggering Pyroptosis
Authors: Xu Bo , Niu Rui , Deng Ruiping , Tang Ying , Wang Chunxi , Wang Yinghui 
Published: June 2024

AbstractImmunotherapy, one of the most promising antitumor strategies, is used to treat prostate cancer (PCa). However, owing to the immunosuppressive tumor microenvironment (TME), the therapeutic effect of the antitumor immune response is greatly weakened. Therefore, there is an urgent need to explore new methods to enhance antitumor immune responses. In this study, a single‐atom nanozyme platform (Cu SA‐DOX@COD) that can trigger pyroptosis is developed to activate antitumor immune responses via a gasdermin E (GSDME)‐dependent pathway. It triggered pyroptosis by catalyzing the production of reactive oxygen species (ROS) and depleting reduced glutathione through intrinsic multi‐enzyme simulated activities and providing an oxygen source for cholesterol (CHOL) oxidation. Meanwhile, the loaded CHOL oxidase not only reduces the CHOL content of tumor cells to increase cell membrane permeability and inhibit tumor cell proliferation and invasion but also oxidizes CHOL and increases the level of H2O2 in tumor cells to enhance pyroptosis. In addition, the loaded doxorubicin activated caspase‐3 to cleave GSDME and further augment pyroptosis. Consequently, Cu SA‐DOX@COD enhances tumor cell immunocompetence and reshapes the immunosuppressive TME by triggering pyroptosis caused by a ROS storm, chemotherapy, and depleting CHOL, thereby activating systemic antitumor immunity to treat PCa.
Low Environmental Impact Magnetic Chitosan and Chitin Cryogels for PFAS Remediation
Authors: García‐Castrillo Marta , Barandika Gotzone , Lizundia Erlantz 
Published: June 2024

AbstractPolymers derived from renewable carbon feedstock are destined to play a pivotal role in the transition to a sustainable circular economy, displacing conventional fossil‐carbon materials. Chitin (CT) and chitosan (CS) are well‐suited to develop multifunctional materials that are mechanically resilient and easy to process. Their abundance of hydroxyl and amine groups facilitates hydrogen bonding and electrostatic interactions, making them suitable for persistent pollutant removal from drinking water. Therefore, porous CS cryogels are fabricated by dissolution in acetic acid, coagulation, and subsequent freeze‐drying. To enhance durability in harsh environments, CT cryogels are obtained through acetylation. Furthermore, Fe3O4 nanoparticles are incorporated to enable removal by external magnetic fields. The rapid removal of per‐ and polyfluoroalkyl substances (PFASs) with capacities reaching 451 mg g−1 offers competitive performance against state‐of‐the‐art materials. The shear‐thinning properties of CS enable rapid additive manufacturing in predetermined free‐standing shapes, useful for accessing sites with complex geometries. Life cycle assessment (LCA) confirms the suitability of chitosan and CT cryogels for low environmental impact water remediation applications. Furthermore, the cryogels can be recycled, closing the material loops back into the economic cycle. Altogether, this work demonstrates the potential of chitosan and CT as competitive alternatives to fossil‐carbon derived systems for sustainable environmental remediation.
Nickel Nanoplates Enclosed by (111) Facets as Durable Oxygen Evolution Catalysts in Anion Exchange Membrane Water Electrolyzers
Authors: Kabiraz Mrinal Kanti , Kim Jeonghyeon , Lee Hye Jin , Park Saehyun , Lee Young Wook , Choi Sang‐Il 
Published: June 2024

AbstractThe long‐term stability of Ni‐based catalysts, employed in the anode of anion exchange membrane water electrolyzers (AEMWE), has been a persisting concern. In this work, through a simple and powerful electrochemical anodization process, vertically aligned β‐NiOOH atomic sheets (vertical‐β‐NiOOH) grown on Fe‐doped Ni nanoplates (FeNi nanoplates) as a solution are offered. This innovative electrocatalyst demonstrates sustained stability of constant current density for over 120 d during the oxygen evolution reaction.The zero‐gap AEMWE cell harnessing the anodized FeNi nanoplates achieves a remarkable current density of 2.26 A cm−2 at 1.80 V with an energetic efficiency of 85.1%. It is anticipated that the electrochemically produced highly active, stable Ni‐based nanostructures demonstrate the potential in pushing the boundaries of AEMWE technology.
Photoexcited Polaron Relaxation as a Structurally Sensitive Reporter of Charge Trapping in a Conducting Polymer
Authors: Umar Abdul Rashid , Dorris Austin L. , Grieco Christopher 
Published: June 2024

AbstractConjugated polymers (CPs) play a central role in electronic applications due to their easily tuned electronic and ionic conductivities via chemical or electrochemical doping. Although doping improves charge conduction by introducing high densities of carriers into the CP, the accompanying structural changes and their impact on carrier mobility remain elusive. Methods capable of probing carrier distributions and their dependence on polymer morphology are needed to better understand how to improve conductivity. Here, a transient absorption (TA) spectroscopy approach is demonstrated, capable of directly probing mobile and trapped carriers in doped CPs and that is also sensitive to polymer nanostructure by using a model polythiophene system with tuned crystallinity. Exciting polarons in the polymer films produces distinct photoinduced absorption signals in the near‐infrared spectrum that decay during the picosecond timescale in the form of biphasic, stretched exponential kinetics, which reflect a distribution of mobile (free) and trapped polarons. The kinetic analysis provides evidence for mobile polarons irrespective of polymer film crystallinity, whereas polarons located in impure amorphous phases with reduced chain ordering exist within a deeper distribution of trap states. Altogether, these observations suggest a stronger correlation of carrier trapping with local chain ordering (planarity or aggregation) rather than polymer crystallinity.
Bio‐Inspired Micro‐ and Nano‐Scale Surface Features Produced by Femtosecond Laser‐Texturing Enhance TiZr‐Implant Osseointegration
Authors: Lackington William Arthur , Bellon Benjamin , Guimond Stefanie , Schweizer Peter , Cancellieri Claudia , Ambeza Antoine , Chopard‐Lallier Anne‐Lise , Pippenger Benjamin , Armutlulu Andac , Maeder Xavier , Schmutz Patrik , Rottmar Markus 
Published: June 2024

AbstractSurface design plays a critical role in determining the integration of dental implants with bone tissue. Femtosecond laser‐texturing has emerged as a breakthrough technology offering excellent uniformity and reproducibility in implant surface features. However, when compared to state‐of‐the‐art sandblasted and acid‐etched surfaces, laser‐textured surface designs typically underperform in terms of osseointegration. This study investigates the capacity of a bio‐inspired femtosecond laser‐textured surface design to enhance osseointegration compared to state‐of‐the‐art sandblasted & acid‐etched surfaces. Laser‐texturing facilitates the production of an organized trabeculae‐like microarchitecture with superimposed nano‐scale laser‐induced periodic surface structures on both 2D and 3D samples of titanium‐zirconium‐alloy. Following a boiling treatment to modify the surface chemistry, improving wettability to a contact angle of 10°, laser‐textured surfaces enhance fibrin network formation when in contact with human whole blood, comparable to state‐of‐the‐art surfaces. In vitro experiments demonstrate that laser‐textured surfaces significantly outperform state‐of‐the‐art surfaces with a 2.5‐fold higher level of mineralization by bone progenitor cells after 28 days of culture. Furthermore, in vivo evaluations reveal superior biomechanical integration of laser‐textured surfaces after 28 days of implantation. Notably, during abiological pull‐out tests, laser‐textured surfaces exhibit comparable performance, suggesting that the observed enhanced osseointegration is primarily driven by the biological response to the surface.