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38095470

Compared with pure forest, mixed forest alters microbial diversity and increases the complexity of interdomain networks in arid areas.

The results provide a comparative study of the response of soil microbial ecology to the afforestation of different tree species and deepen the understanding of the factors controlling soil microbial community structure.

38095471

Metagenomic next-generation sequencing of cell-free DNA for the identification of viruses causing central nervous system infections.

This study provides significant new data on the application of metagenomic next-generation sequencing (mNGS) to clinical diagnostics of central nervous system (CNS) viral infections, which can have high mortality rates and severe sequelae. Conventional diagnostic procedures for identifying viruses can be inefficient and rely on preconceived assumptions about the pathogen, making mNGS an appealing alternative. However, the effectiveness of mNGS is affected by the presence of human DNA contamination, which can be minimized by using cell-free DNA (cfDNA) instead of whole-cell DNA (wcDNA). This multi-center retrospective study of patients with suspected viral CNS infection found that mNGS using cfDNA had a significantly lower proportion of human DNA and higher sensitivity for detecting viruses than mNGS using wcDNA. Herpesviruses, particularly VZV, were found to be the most common DNA viruses in these patients. Overall, mNGS using cfDNA is a promising complementary diagnostic method for detecting CNS viral infections.

38095472

Orange-spotted grouper nervous necrosis virus-encoded protein A induces interferon expression via RIG-I/MDA5-MAVS-TBK1-IRF3 signaling in fish cells.

As a major pathogen, nervous necrosis virus (NNV) infects more than 120 fish species worldwide and is virulent to larvae and juvenile fish, hampering the development of the fish fry industry. Understanding virus-host interaction and underlying mechanisms is an important but largely unknown issue in fish virus studies. Here, using channel catfish ovary and fathead minnow cells as models for the study of innate immunity signaling, we found that NNV-encoded ProA activated interferon signaling via the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) pathway which was still suppressed by the infection of wild-type NNV. This finding has important implications for the comprehension of NNV protein function and the immune response from different cells. First, RIG-I is the key node for anti-NNV innate immunity. Second, the response intensity of RLR signaling determines the degree of NNV proliferation. This study expands our knowledge regarding the overview of signal pathways affected by NNV-encoded protein and also highlights potential directions for the control of aquatic viruses.

38095474

Hierarchic regulation of a metabolic pathway: H-NS, CRP, and SsrB control <i>myo</i>-inositol utilization by <i>Salmonella enterica</i>.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">The capacity to utilize myo-inositol (MI) as sole carbon and energy source is widespread among bacteria, among them the intestinal pathogen <i>S</i>. Typhimurium. This study elucidates the complex and hierarchical regulation that underlies the utilization of MI by <i>S</i>. Typhimurium under substrate limitation. A total of seven regulatory factors have been identified so far, allowing the pathogen an environment-dependent, efficient, and fine-tuned regulation of a metabolic property that provides growth advantages in different environments.

38095475

Rapid expansion of lymphogranuloma venereum infections with fast diversification and spread of <i>Chlamydia trachomatis</i> L genovariants.

Numerous international organizations, including the World Health Organization, have been drawing attention to the global increase in sexually transmitted infections. Twenty years ago, lymphogranuloma venereum (LGV) was mainly considered a tropical disease; in recent decades, however, LGV has been increasingly present in high-income countries. This increase has been linked to men who have sex with men who participate in highly interconnected sexual networks, leading to a rapid spread of LGV. This study focuses on the spread of LGV, presenting the largest time series of LGV prevalence in Spain, which includes more than a thousand diagnosed cases in one large city. The number of LGV cases diagnosed was analyzed over time, and a selection of strains was subjected to molecular genotyping. The results indicate that the LGV epidemic is gradually evolving toward an increasingly complex diversification due to the selection of successful genovariants that have emerged by mutation and recombination events, suggesting that we are moving toward an unpredictable scenario.

38095476

Expanding the microbiologist toolbox <i>via</i> new far-red-emitting dyes suitable for bacterial imaging.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">By harnessing the versatility of fluorescence microscopy and super-resolution imaging, bacteriologists explore critical aspects of bacterial physiology and resolve bacterial structures sized beyond the light diffraction limit. These techniques are based on fluorophores with profitable photochemical and tagging properties. The paucity of available far-red (FR)-emitting dyes for bacterial imaging strongly limits the multicolor choice of bacteriologists, hindering the possibility of labeling multiple structures in a single experiment. The set of FR fluorophores characterized in this study expands the palette of dyes useful for microbiologists, as they can be used for bacterial LIVE/DEAD staining and for tagging the membranes of viable <i>Escherichia coli</i> and <i>Bacillus subtilis</i> cells. The absence of toxicity makes these dyes suitable for live-cell imaging and allows monitoring of bacterial membrane biogenesis. Moreover, a newly synthesized FR-fluorophore can be employed for imaging bacterial membranes with stimulated emission depletion microscopy, a super-resolution technique capable of increasing the resolving power of conventional microscopes.

38095473

High prevalence and genetic diversity of <i>Treponema paraluisleporidarum</i> isolates in European lagomorphs.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">Syphilis is an ancient disease of humans and lagomorphs caused by two distinct but genetically closely related bacteria (&gt;98% sequence identity based on the whole genome) of the genus <i>Treponema</i>. While human syphilis is well studied, little is known about the disease in the lagomorph host. Yet, comparative studies are needed to understand mechanisms in host-pathogen coevolution in treponematoses. Importantly, <i>Treponema paraluisleporidarum</i>-infected hare populations provide ample opportunity to study the syphilis-causing pathogen in a naturally infected model population without antibiotic treatment, data that cannot be obtained from syphilis infection in humans. We provide data on genetic diversity and are able to highlight various types of repetitions in one of the two hypervariable regions at the <i>tp0548</i> locus that have not been described in the human syphilis-causing sister bacterium <i>Treponema pallidum</i> subsp. <i>pallidum</i>.

38095477

The effect of double (S238F/W159H) mutations on the structure and dynamics of PET degrading enzyme.

Polyethylene terephthalate (PET) is one of the highly produced synthetic polymers worldwide and had acquired attention due to its impact resistance, high clarity, and light weight. PET has become the first choice in making disposable bottles, leading to massive scales of production resulting in very high utilization across various facets of our daily life. Unfortunately, PET accumulates as waste and is highly resistant to biodegradation, thus presenting a serious threat to the ecosystem. Degradation of PET by enzymatic hydrolysis is a promising strategy to depolymerize the PET into its monomers. In recent studies, a plastic-degrading enzyme known as PETase (<i>Is</i>PETase) from the <i>Ideonella sakaiensis</i> has been identified to hydrolyze PET. The wild-type enzyme from <i>Ideonella</i> sp., has been engineered to improve the catalytic activity. While the <i>Is</i>PETase and its variants have been the subject of extensive structural and biochemical studies, the corresponding computational studies to support the improved activity of the mutant enzyme is not fully understood. In this work, we employed all-atom classical molecular dynamics simulations of the wild-type and double mutant <i>Is</i>PETase enzymes to investigate the underlying reason for the improved catalytic activity in the double mutant by means of structure-dynamics-function relationship. Our results show that the engineered mutations reshape the active site structure, volume, and dynamics of the protein loops which is crucial for substrate binding. We also demonstrate that addition of aromatic and hydrogen bond-forming residues near catalytic site improves binding affinity. This work will enable the rational design of mutants for enhanced PET degrading activity.Communicated by Ramaswamy H. Sarma.

38095478

Complete genome sequence of PETase type IIa-harboring <i>Marinobacter nanhaiticus</i> D15-8W, isolated from a South China Sea sediment.

<i>Marinobacter nanhaiticus</i> D15-8W is known for its ability to metabolize polycyclic aromatic hydrocarbons. Here, we report the complete circular genome sequence of this strain to be 5,336,660 bp (G + C content, 58.6%; 4,869 protein-coding sequences) with one plasmid (69,655 bp).

38095479

Photothermal Ferrotherapy - Induced Immunogenic Cell Death via Iron-Based Ternary Chalcogenide Nanoparticles Against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is highly malignant and prone to recurrence and metastasis. Patients with TNBC have limited therapeutic options, often resulting in poor prognosis. Some new treatments for TNBC have been considered in the past decade, such as immunotherapy, photothermal therapy (PTT), and ferroptosis therapy, that allow the rapid and minimally invasive ablation of cancer. However, a multifunctional nanodrug system with more potent efficacy for TNBC is still needed. The use of iron-based ternary chalcogenide nanoparticles (NPs), namely AgFeS₂ , is reported, which synergistically combines photothermal therapy, ferrotherapy, and immunotherapy in one system for the treatment of TNBC. AgFeS₂ possesses excellent photothermal conversion performance for tumor near-infrared (NIR) phototherapy. Upon photoirradiation, these NPs generate heat, accelerate the release of iron ions, and effectively catalyze the Fenton reaction, resulting in cell apoptosis and ferroptosis. Additionally, AgFeS₂ promotes the release of tumor-specific antigens and triggers an immune response via immunogenic cell death (ICD), thereby providing unique synergistic mechanisms for cancer therapy. The present study demonstrates the great potential of iron-based ternary chalcogenide as a new therapeutic platform for a combination of photothermal therapy, ferrotherapy, and immunotherapy for the suppression of TNBC.

38095480

Bempedoic acid: a new player for statin-intolerant patients and beyond.

Low-density lipoproteins (LDL) cause atherosclerotic cardiovascular disease, a condition associated with significant morbidity and mortality. Statins represent the cornerstone for preventing cardiovascular events in patients with elevated LDL-cholesterol (LDL-C) levels, however, they are associated with frequent musculoskeletal adverse effects, which lead to drug discontinuation or limit their use to low (and less effective) doses. Bempedoic acid (BA) is a newly approved, safe, cholesterol-lowering agent that inhibits ATP-citrate lyase, an enzyme upstream to 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, the target of statins. Unlike statins, BA is not associated with musculoskeletal side effects, representing a promising drug for statin-intolerant patients. This review aims to summarize the current evidence on the efficacy, safety, and impact on clinical outcomes of BA, to review current indications for its use, and to highlight the ongoing clinical trials that will help deepen our knowledge of this promising compound.

38095481

Comparison of the efficacy of intranasal atomised dexmedetomidine versus intranasal atomised ketamine as a premedication for sedation and anxiolysis in children undergoing spinal dysraphism surgery: A randomized controlled trial.

Preoperative anxiety leads to adverse clinical outcomes and long-term maladaptive behavioural changes. The role of intranasal atomised dexmedetomidine and atomised ketamine as premedication to produce sedation and anxiolysis in paediatric neurosurgical patients has not been extensively studied.

38095482

The analgesic efficacy of pectoral nerve block for breast augmentation: a meta-analysis of randomized controlled studies.

Many patients suffered from serious pain after breast augmentation, but the analgesic efficacy of pectoral nerve block for these patients was not well established. Thus, this meta-analysis was intended to study the analgesic efficacy of pectoral nerve block for breast augmentation.

38095483

Onconephrology: mitigation of renal injury in chemotherapy administration.

Onconephrology was first coined as a name for the intersection of cancer medicine and nephrology in the early 2010s. It was recognized then that beyond and understanding of kidney physiology, a new generation of nephrologists skilled in both molecular biology and precision medicine were needed to deal with the challenges of emerging cancer therapies. Stem cell transplants, biologic agents, adjuvants blocking basic cellular signaling pathways, immunotherapy were found to promote novel anticancer outcomes, but also to pose new risks to the kidneys. The field rapidly overlapped with emerging expertise in vascular glomerular disease, glomerular disease, and the same biologic agents now applied to auto immune systemic and kidney diseases.

38095484

Fermionic Reduced Density Low-Rank Matrix Completion, Noise Filtering, and Measurement Reduction in Quantum Simulations.

Fermionic reduced density matrices summarize the key observables in Fermionic systems. In electronic systems, the two-particle reduced density matrix (2-RDM) is sufficient to determine the energy and most physical observables of interest. Here, we consider the possibility of using matrix completion to reconstruct the two-particle reduced density matrix to chemical accuracy from partial information. We consider the case of noiseless matrix completion, where the partial information corresponds to a subset of the 2-RDM elements, as well as noisy completion, where the partial information corresponds to both a subset of elements and statistical noise in their values. Through experiments on a set of 24 molecular systems, we find that 2-RDM can be efficiently reconstructed from a reduced amount of information. In the case of noisy completion, this results in a multiple orders of magnitude reduction in the number of measurements needed to determine the 2-RDM with chemical accuracy. These techniques can be readily applied to both classical and quantum algorithms for quantum simulations.

38095485

Bismuth-Based Electrocatalysts for Identical Value-Added Formic Acid Through Coupling CO₂ Reduction and Methanol Oxidation.

It is an effective way to reduce atmospheric CO₂ via electrochemical CO₂ reduction reaction (CO₂ RR), while the slow oxygen evolution reaction (OER) occurs at the anode with huge energy consumption. Herein, methanol oxidation reaction (MOR) is used to replace OER, coupling CO₂ RR to achieve co-production of formate. Through enhancing OCHO* adsorption by oxygen vacancies engineering and synergistic effect by heteroatom doping, Bi/Bi₂ O₃ and Ni&#9472;Bi(OH)₃ are synthesized for efficient production of formate via simultaneous CO₂ RR and methanol oxidation reaction (MOR), achieving that the coupling of CO₂ RR//MOR only required 7.26&#160;kWh&#160;g_formate ^-1 power input, much lower than that of CO₂ RR//OER (13.67&#160;kWh&#160;g_formate ^-1 ). Bi/Bi₂ O₃ exhibits excellent electrocatalytic CO₂ RR performance, achieving FE_formate &gt;80% in a wide potential range from -0.7 to -1.2&#160;V (vs RHE). For MOR, Ni&#9472;Bi(OH)₃ exhibits efficient MOR catalytic performance with the FE_formate &gt;98% in the potential range of 1.35-1.6&#160;V (vs RHE). Not only demonstrates the two-electrode systems exceptional stability, working continuously for over 250&#160;h under a cell voltage of 3.0&#160;V, but the cathode and anode can maintain a FE of over 80%. DFT calculation results reveal that the oxygen vacancies of Bi/Bi₂ O₃ enhance the adsorption of OCHO* intermediate, and Ni&#9472;Bi(OH)₃ reduce the energy barrier for the rate determining step, leading to high catalytic activity.

38095486

New Data on the Increased hip Fracture Risk in Type 2 Diabetes and Its Reduction in Those With High Physical Activity.

38095487

Strategies for Synthesizing Supramolecular Block Copolymers.

Over the past decade, controlled supramolecular polymerization has been extensively studied and gradually shifted to supramolecular block copolymerization. Supramolecular block copolymers (BCPs) are considered the holy grail for developing supramolecular materials with new functionalities due to their fascinating structures and ability to introduce diverse functions. From a thermodynamic view to kinetic aspects, great progress has been made in the synthetic strategies of BCPs in the past few years. This Concept summarizes various strategies to realize supramolecular block copolymerization. The focus is on providing researchers with a methodological basis for achieving heterogeneous nucleation-elongation.

38095488

Engineering Interfacial Pt─O─Ti Site at Atomic Step Defect for Efficient Hydrogen Evolution Catalysis.

The hydrogen evolution reaction (HER) activity of defect-stabilized low-Pt-loading catalysts is closely related with defect type in support materials, while the knowledge about the effect of higher-dimensional defects on the property and activity of trapped Pt atomic species is scarce. Herein, small size (5-10&#160;nm) TiO₂ nanoparticles with abundant surface step defects (one kind of line defect) are used to direct the uniform anchoring of Pt atomic clusters (Pt-ACs) via Pt&#9472;O&#9472;Ti linkage. The as-made low-Pt catalysts (Pt-ACs/S-TiO₂ -NP) exhibit exceptional HER intrinsic activity due to the unique step-site Pi-O-Ti species, in which the mass activity and turnover frequency are as high as 21.46&#160;A&#160;mg&#160;_Pt ^-1 and 21.69&#160;s^-1 at the overpotential of 50&#160;mV, both far beyond those of benchmark Pt/C catalysts and other Pt-ACs/TiO₂ samples with less step sites. Spectroscopic measurements and theoretical calculations reveal that the step-defect-located Pt&#9472;O&#9472;Ti sites can simultaneously induce the charge transfer from TiO₂ substrate to the trapped Pt-ACs and the downshift of d-band center, which helps the proton reduction to H* intermediates and the following hydrogen desorption process, thus improving the HER. The work provides a deep insight on the interactions between high-dimensional defect and well-dispersed atomic metal motifs for superior HER catalysis.

38095489

A comparison of the continuous supraclavicular brachial plexus block using the proximal longitudinal oblique approach and the interscalene brachial plexus block for arthroscopic shoulder surgery: A randomised, controlled, double-blind trial.

Continuous interscalene brachial plexus block (ISB) is widely used for arthroscopic shoulder surgery, but the incidence of hemidiaphragmatic paresis (HDP) has been reported to reach 100%. Several methods, including injections distal to the C5-C6 nerve roots, have been attempted to reduce the HDP incidence. However, catheter placement distal to the C5-C6 nerve roots interferes with the surgical site.

38095490

Peri-weaning cholera toxin consumption suppresses chemically-induced carcinogenesis in mice.

Gastrointestinal bacteria are known to have an impact on local and systemic immunity, and consequently either promote or suppress cancer development. Following the notion that perinatal bacterial exposure might confer immune system competency for life, we investigated whether early-life administration of cholera-toxin (CT), a protein exotoxin of the small intestine pathogenic bacterium Vibrio cholerae, may shape local and systemic immunity to impart a protective effect against tumor development in epithelia distantly located from the gut. For that, newborn mice were orally treated with low non-pathogenic doses of CT and later challenged with the carcinogen 7,12-dimethylbenzanthracene (DMBA), known to cause mainly mammary, but also skin, lung and stomach cancer. Our results revealed that CT suppressed the overall incidence and multiplicity of tumors, with varying efficiencies among cancer types, and promoted survival. Harvesting mouse tissues at an earlier time-point (105 instead of 294 days), showed that CT does not prevent preneoplastic lesions per se but it rather hinders their evolution into tumors. CT pretreatment universally increased apoptosis in the cancer-prone mammary, lung and nonglandular stomach, and altered the expression of several cancer-related molecules. Moreover, CT had a long-term effect on immune system cells and factors, the most prominent being the systemic neutrophil decrease. Finally, CT treatment significantly affected gut bacterial flora composition, leading among others to a major shift from Clostridia to Bacilli class abundance. Overall, these results support the notion that early-life CT consumption is able to affect host's immune, microbiome and gene expression profiles toward the prevention of cancer.

38095491

An estimation of physiochemical properties of bladder cancer drugs via degree-based chemical bonding topological descriptors.

The use of topological descriptors remains a significant approach due to numerous advances in the field of drug design. Descriptors provide numerical representations of a molecule's chemical characteristics when used with QSPR models. The QSPR analysis for bladder medications is the main focus of this study. Linear regression model is developed for the computed indices values, the physicochemical properties of the bladder medications are examined.Communicated by Ramaswamy H. Sarma.

38095492

Fundamental Aspects and Relevance of Components in Antihistamine Eye Drops.

Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non-IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.

38095493

The Importance of Preventing and Managing Tear Dysfunction Syndrome in Allergic Conjunctivitis and How to Tackle This Problem.

Tear dysfunction syndrome, also known as dry eye disease (DED), is a multifactorial disease of the ocular surface characterized by the loss of tear film homeostasis. DED shows a significant clinical overlap with ocular allergy (OA), which alters tear film homeostasis, thus predisposing the patient to DED. Both conditions constitute the most common ocular surface disorders and have a potentially severe impact on patients' quality of life. Clinical practice guidelines recommend topical therapies as first-line treatment for OA. However, eye drop formulations may contain additional substances that can contribute to ocular surface damage and the development of DED. Therefore, physicians treating ocular allergy should be aware of problems affecting the tear film, the role of tear film disruption in OA, and topical treatment to prevent or minimize DED. The aim of this review is to present an updated overview of the topic.

38095494

Very Rapid Improvement in Extended Nitric Oxide Parameters Is Associated With Clinical and Functional Improvement in Patients With Chronic Rhinosinusitis With Nasal Polyps Treated With Dupilumab.

Dupilumab, an anti-IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP.

38095495

Anaphylaxis Management in the GALAXIA 2022 Update.

38095496

Olfactory Function and Biologic Treatments: Comment on Available Real-Life Studies.

38095497

Reply to "Olfactory Function and Biologic Treatments: A Comment on Available Real-life Studies".

38095499

Kounis Syndrome After Lidocaine Injection.

38095498

Kounis Syndrome Induced by Lidocaine.

38095500

Immunoglobulin E Deficiency and Autoimmune Disease.

38095501

In Reply to "Immunoglobulin E Deficiency and Autoimmune Disease".

38095502

Strain on Scarce Intensive Care Beds Drives Reduced Patient Volumes, Patient Selection, and Worse Outcome: A National Cohort Study.

Strain on ICUs during the COVID-19 pandemic required stringent triage at the ICU to distribute resources appropriately. This could have resulted in reduced patient volumes, patient selection, and worse outcome of non-COVID-19 patients, especially during the pandemic peaks when the strain on ICUs was extreme. We analyzed this potential impact on the non-COVID-19 patients.

38095504

Exploring the role of hyperinsulinemia in obesity-associated tumor development.

Although there has been a long-standing connection between hyperinsulinemia and cancer development, there is a lack of understanding of the role of the insulin receptor on cells that can become cancerous. In a recent issue of Cell Metabolism, Zhang and colleagues, using a diet-induced obesity mouse model, identified a direct function of insulin receptors on pancreatic acinar cells expressing a KRASG12D mutation in promoting obesity-associated pancreatic cancer. Furthermore, insulin receptor signaling from hyperinsulinemia promoted the secretion of digestive enzymes that contributed to acinar to ductal metaplasia. These findings highlight an important connection between obesity, diabetes, and pancreatic tumor development and suggest potential strategies for obesity-associated cancer prevention targeting the insulin receptor signaling pathways.

38095503

Fatty acid binding protein 4 (FABP4) induces chondrocyte degeneration via activation of the NF-κb signaling pathway.

The pathogenesis of osteoarthritis (OA) is still unclear. Fatty acid binding protein 4 (FABP4), a novel adipokine, has been found to play a role in OA. This study aimed to explore the role of NF-κB in FABP4-induced OA. In the in vivo study, four pairs of 12-week-old male FABP4 knockout (KO) and wild-type (WT) mice were included. The activation of NF-κB was assessed. In parallel, 24 6-week-old male C57/Bl6 mice were fed a high-fat diet (HFD) and randomly allocated to four groups: daily oral gavage with (1) PBS solution; (2) QNZ (NF-κB-specific inhibitor, 1 mg/kg/d); (3) BMS309403 (FABP4-specific inhibitor, 30 mg/kg/d); and (4) BMS309403 (30 mg/kg/d) + QNZ (1 mg/kg/d). The diet and treatment were sustained for 4 months. The knee joints were obtained to assess cartilage degradation, NF-κB activation, and subchondral bone sclerosis. In the in vitro study, a mouse chondrogenic cell line (ATDC5) was cultured. FABP4 was supplemented to stimulate chondrocytes, and the activation of NF-κB was investigated. In parallel, QNZ and NF-κB-specific siRNA were used to inhibit NF-κB. In vivo, the FABP4 WT mice had more significant NF-κB activation than the KO mice. Dual inhibition of FABP4 and NF-κB alleviated knee OA in mice. FABP4 has no significant effect on the activation of the JNK signaling pathway. In vitro, FABP4 directly activated NF-κB in chondrocytes. The use of QNZ and NF-κB-siRNA significantly alleviated the expression of catabolic markers of chondrocytes induced by FABP4. FABP4 induces chondrocyte degeneration by activating the NF-κB pathway.

38095505

Hyper-crosslinked Isoporous Block Copolymer Membranes with Robust Solvent Resistance and Customized Pore Sizes for Precise Separation.

Isoporous block copolymer membranes are viewed as the next-generation separation membranes for their unique structures and urgent application in precise separation. However, an obvious weakness for such membranes is their poor solvent-resistance which limits their applications to aqueous solution, and isoporous membranes with superior solvent-resistance and tunable pore size have been rarely prepared before. Herein, self-supporting isoporous membranes with excellent solvent resistance are prepared by the facile yet robust hyper-crosslinking approach which is able to create a rigid network in whole membranes. The hyper-crosslinking is found to be a novel and non-destructive approach that does not change pore size and isoporous structure during the reaction, and the resulting hyper-crosslinked isoporous membranes display superior structural and separation stability to a broad range of solvents with varied polarities for months to years. More importantly, hyper-crosslinking has proved to be a universal strategy that is applicable to isoporous membranes with varied pore size and pore chemistry, offering an important opportunity to prepare solvent-resistant isoporous membranes with customizable pore size and pore functionality that are important to realize their accurate separations in organic solvents. This concept is demonstrated finally by precise and on-demand separation of nanoparticles with the prepared membranes.

38095506

Deep Learning-Based Localization and Detection of Malpositioned Endotracheal Tube on Portable Supine Chest Radiographs in Intensive and Emergency Medicine: A Multicenter Retrospective Study.

We aimed to develop a computer-aided detection (CAD) system to localize and detect the malposition of endotracheal tubes (ETTs) on portable supine chest radiographs (CXRs).

38095507

Global health economics: The Equitable Impact Sensitive Tool (EQUIST) - development, validation, implementation and evaluation of impact (2011 to 2022).

The Equitable Impact Sensitive Tool (EQUIST) was developed to address the limitations of the traditional cost-effectiveness analysis (CEA) in global health, which often overlooked equity considerations. Its primary aim was to create more effective and efficient health systems by explicitly incorporating equity as a key driver in health policy decisions. This was done in response to the recognition that, while CEA helped reduce mortality rates through interventions like childhood vaccinations, it was insufficient in addressing growing inequalities in health, especially in low-and-middle-income countries (LMICs).

38095509

Medical demography in Lebanon: Balancing demand and supply amidst crisis.

38095510

Mycobiomes of two distinct clades of ambrosia gall midges (Diptera: Cecidomyiidae) are species-specific in larvae but similar in nutritive mycelia.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">Ambrosia gall midges are endophagous insect herbivores whose larvae live enclosed within a single gall for their entire development period. They may exhibit phytomycetophagy, a remarkable feeding mode that involves the consumption of plant biomass and mycelia of their cultivated gall symbionts. Thus, AGMs are ideal model organisms for studying the role of microorganisms in the evolution of host specificity in insects. However, compared to other fungus-farming insects, insect-fungus mutualism in AGMs has been neglected. Our study is the first to use DNA metabarcoding to characterize the complete mycobiome of the entire system of the gall-forming insects as we profiled gall surfaces, nutritive mycelia, and larvae. Interestingly, larval mycobiomes were significantly different from their nutritive mycelia, although <i>Botryosphaeria dothidea</i> dominated the nutritive mycelia, regardless of the evolutionary separation of the tribes studied. Therefore, we confirmed a long-time hypothesized paradigm for the important evolutionary association of this fungus with AGMs.

38095512

Hydro-Photo-Thermo-Responsive Multicolor Luminescence Switching of a Ternary MOF Hybrid for Advanced Information Anticounterfeiting.

Developing smart materials capable of solid-state multicolor photoluminescence (PL) switching in response to multistimuli is highly desirable for advanced anticounterfeiting. Here, a ternary MOF hybrid showing hydro-photo-thermo-responsive multicolor PL switching in the solid state is presented. This hybrid is constructed by co-immobilizing Eu³⁺ and methyl viologen (MV) cations within an anionic MOF via the cation-exchange approach. The confined guest cations are well arranged in the framework channels, facilitating the synergistic realization of stimuli-responsive multiple PL color-switching through intermolecular coupling. The hybrid undergoes a rapid and reversible PL color-switching from red to blue upon water simulation, which is achieved by activating the blue emission of the framework linker while simultaneously quenching the Eu³⁺ emission. Furthermore, the hybrid displays photo-thermo-responsive PL switching from red to dark. UV-light irradiation or heating triggers the chromic conversion of MV to its colored radical form, which exhibits perfect spectral overlap with Eu³⁺ , thus activating F&#246;rster resonance energy transfer (FRET) from Eu³⁺ to MV radicals and quenching the Eu³⁺ emission. Inspired by these results, PL morse patterns are designed and fabricated using a novel triple-level encryption strategy, showcasing the exciting potential of this hybrid in advanced anticounterfeiting applications.

38095511

Copper-Catalyzed C-H (Phenylsulfonyl)difluoromethylation of Acrylamides: Scope, Mechanism, and Critical Role of Additives.

Herein, we report the Cu-complex catalyzed, native functional group-assisted, and TFA/NMF additives promoted (phenylsulfonyl)difluoromethylation of vinylic C(sp² )-H bond of acrylamides. Using our in-home designed reagent, this reaction enables the construction of the C(sp² )-CF₂ SO₂ Ph bond from simple C-H bond activation by copper catalysis under mild reaction conditions with total Z-selectivity. The versatility of utilized fluorinated group was illustrated by its conversion into value-added CF₂ moieties as well as the remarkable =CHF residue. The performed experimental and computational mechanistic studies enabled to identify the true nature of active catalyst and substrate, as well as establish critical roles of TFA and NMF additives. In this reaction, the TFA acts as a promoter of the much-needed Cu^II /Cu^II &#8594;Cu^III /Cu^I disproportionation, while the NMF facilitates the following ligand exchange and C-C coupling processes. We ruled out the generation of radical intermediates and established the C-H activation to be irreversible and the rate-determining step of the entire process.

38095508

Data-Driven Compound Identification in Atmospheric Mass Spectrometry.

Aerosol particles found in the atmosphere affect the climate and worsen air quality. To mitigate these adverse impacts, aerosol particle formation and aerosol chemistry in the atmosphere need to be better mapped out and understood. Currently, mass spectrometry is the single most important analytical technique in atmospheric chemistry and is used to track and identify compounds and processes. Large amounts of data are collected in each measurement of current time-of-flight and orbitrap mass spectrometers using modern rapid data acquisition practices. However, compound identification remains a major bottleneck during data analysis due to lacking reference libraries and analysis tools. Data-driven compound identification approaches could alleviate the problem, yet remain rare to non-existent in atmospheric science. In this perspective, the authors review the current state of data-driven compound identification with mass spectrometry in atmospheric science and discuss current challenges and possible future steps toward a digital era for atmospheric mass spectrometry.

38095514

Harnessing p53 to improve immunotherapy for lung cancer treatment.

Immunotherapy, especially immune checkpoint blockade (ICB), has become a critical therapy for lung cancer treatment in recent years. Tumor mutational burden (TMB) is one of the decisive biomarkers for predicting immune checkpoint blockade effect. Writing in Cancer Cell, Zhu and colleagues use autochthonous and syngeneic mouse models to show that p53 mutation and tumor heterogeneity may be responsible for resistance in lung cancer patients. Pole-induced high-TMB shows enhanced immunogenicity in KrasG12D mice, however, loss of p53 in KrasG12D PoleP286/+ mice can lead to an immune suppressive profile of lung tumors which diminishes immune response to ICB. Moreover, high TMB causes high shared mutations which helps promote immune protection and immune memory. Heterogeneity can drive immune escape to tumor cells causing resistance to ICB. Decreased cGAS/STING signaling may explain possible resistance to ICB. Based on the new model found by Zhu and colleagues for lung cancer, combined ICB with STING agonists or p53 inducers may be new therapeutic options to improve the efficacy of ICB for lung cancer patients with high TMB.

38095513

A Lysosome-Targeted Magnetic Nanotorquer Mechanically Triggers Ferroptosis for Breast Cancer Treatment.

Targeting ferroptosis has attracted exponential attention to eradicate cancer cells with high iron-dependent growth. Increasing the level of intracellular labile iron pool via small molecules and iron-containing nanomaterials is an effective approach to induce ferroptosis but often faces insufficient efficacy due to the fast drug metabolism and toxicity issues on normal tissues. Therefore, developing a long-acting and selective approach to regulate ferroptosis is highly demanded in cancer treatment. Herein, a lysosome-targeted magnetic nanotorquer (T7-MNT) is proposed as the mechanical tool to dynamically induce the endogenous Fe²⁺ pool outbreak for ferroptosis of breast cancer. T7-MNTs target lysosomes via the transferrin receptor-mediated endocytosis in breast cancer cells. Under the programmed rotating magnetic field, T7-MNTs generate torques to trigger endogenous Fe²⁺ release by disrupting the lysosomal membrane. This magneto-mechanical manipulation can induce oxidative damage and antioxidant defense imbalance to boost frequency- and time-dependent lipid peroxidization. Importantly, in vivo studies show that T7-MNTs can efficiently trigger ferroptosis under the magnetic field and play as a long-acting physical inducer to boost ferrotherapy efficacy in combination with RSL3. It is anticipated that this dynamic targeted strategy can be coupled with current ferroptosis inducers to achieve enhanced efficacy and inspire the design of mechanical-based ferroptosis inducers for cancer treatment.

38095516

Brain uptake pharmacokinetics of albiglutide, dulaglutide, tirzepatide, and DA5-CH in the search for new treatments of Alzheimer's and Parkinson's diseases.

A number of peptide incretin receptor agonists (IRAs) show promise as therapeutics for Alzheimer's disease (AD) and Parkinson's disease (PD). Transport across the blood-brain barrier (BBB) is one way for IRAs to act directly within the brain. To determine which IRAs are high priority candidates for treating these disorders, we have studied their brain uptake pharmacokinetics.

38095515

Diagnostic Efficacy of Photostimulated Chemiluminescence Assay for Detecting Anti-HIV Antibodies: A Retrospective Study.

The transmission of human immunodeficiency virus (HIV) through blood poses a slightly increased risk. As a result, patients requiring blood transfusions should be screened for HIV antibodies. This study examined the diagnostic effectiveness of the photostimulated chemiluminescence assay in detecting anti-HIV antibodies and determined the cut-off value for this method. The performance of the fully automated photostimulated chemiluminescence assay system was validated according to CNAS-GL038:2019 (2020) and CNAS-GL037:2019 (2019) guidelines. A retrospective study was conducted at the Department of Medical Laboratory, Nanjing Tongren Hospital, affiliated with Southeast University, from January 2020 to December 2022. A total of 77,386 cases were tested for anti-HIV antibodies using the photostimulated chemiluminescence assay, with 79 cases initially testing positive. The method's performance in detecting anti-HIV antibodies was evaluated using the Receiver Operating Characteristic (ROC) curve and the average Coefficient of Variation (CV) value of 3-year in-house quality control. The precision, detection limit, coincidence rate, and critical value of the performance verification results met the requirements. Using Western blotting (WB) as the reference method, positive cases were initially screened using the light-induced chemiluminescence method to determine the cut-off index (COI) value and draw the ROC curve. The maximum area under the ROC curve using the chemiluminescence method was 0.997, with a cutoff value of < 28.56, sensitivity of 98%, specificity of 100%, Jordan index of 0.98, and an average CV value of 3.55%. In conclusion, the photostimulated chemiluminescence assay has good diagnostic efficacy in detecting anti-HIV antibodies and is suitable for rapid screening before blood transfusion and surgery.

38095517

Outcomes After Respiratory Extracorporeal Life Support in Teens and Young Adults: An Extracorporeal Life Support Organization Registry Analysis.

A recent study from Germany found that survival after respiratory extracorporeal life support (ECLS) was lower among patients 10-20 years old than 20-30 years old. The objective of this study was to compare survival between teenage and young adult patients who receive respiratory ECLS.

38095518

Sex-Based Differences in Receipt of ICU Care: Nuances in Understanding "Less Is Better?"

38095519

Outcomes in Young Patients After Respiratory Extracorporeal Membrane Oxygenation-Youth Is Not Always Protective.

38095520

Testing the Age Limits of Extracorporeal Cardiopulmonary Resuscitation: How Old Is Too Old?

38095522

Weaning From Venovenous Extracorporeal Membrane Oxygenation-The Regensburg Way?

38095521

Critical Care Is a Concept, Not a Location.

38095523

Mechanical Power and Safer Lung Ventilation: Not Ready for Prime Time.

38095524

One Limb or Two? Does It Make a Difference in Femoral Venoarterial Extracorporeal Membrane Oxygenation?

38095525

Globalize the Definition, Localize the Treatment: Increasing Equity and Embracing Heterogeneity on the Road to Precision Medicine for Acute Respiratory Distress Syndrome.

38095526

Changes in Cancer Therapy After ICU Admission: The Long Arm of Delirium.

38095527

Procalcitonin As Diagnostic Tool for CNS Infections-Overall, Not Good Enough (Yet?).

38095528

Is Respiratory System Compliance Calculation During Assisted Mechanical Ventilation Reliable?

38095530

The Value of a Biomarker Should be Judged on What it Adds to the Clinical Assessment: Not the Area Under the Curve.

38095529

The authors reply.

38095531

The authors reply.

38095532

Diselenophene-Dithioalkylthiophene Based Quinoidal Small Molecules for Ambipolar Organic Field Effect Transistors.

This work presents a series of novel quinoidal organic semiconductors based on diselenophene-dithioalkylthiophene (DSpDST) conjugated cores with various side-chain lengths (-thiohexyl, -thiodecyl, and -thiotetradecyl, designated DSpDSTQ-6, DSpDSTQ-10, and DSpDSTQ-14, respectively). The purpose of this research is to develop solution-processable organic semiconductors using dicyanomethylene end-capped organic small molecules for organic field effect transistors (OFETs) application. The physical, electrochemical, and electrical properties of these new DSpDSTQs are systematically studied, along with their performance in OFETs and thin film morphologies. Additionally, the molecular structures of DSpDSTQ are determined through density functional theory (DFT) calculations and single-crystal X-ray diffraction analysis. The results reveal the presence of intramolecular S (alkyl)&#183;&#183;&#183;Se (selenophene) interactions, which result in a planar SR-containing DSpDSTQ core, thereby promoting extended &#960;-orbital interactions and efficient charge transport in the OFETs. Moreover, the influence of thioalkyl side chain length on surface morphologies and microstructures is investigated. Remarkably, the compound with the shortest thioalkyl chain, DSpDSTQ-6, demonstrates ambipolar carrier transport with the highest electron and hole mobilities of 0.334 and 0.463 cm² V^-1 s^-1 , respectively. These findings highlight the excellence of ambipolar characteristics of solution-processable OFETs based on DSpDSTQs even under ambient conditions.

38095533

Rapid screening and evaluation of natural antioxidants from leaf, stem, and root of Artemisia argyi by online liquid microextraction combined with HPLC-based antioxidant assay system coupled with calibration quantitative analysis.

To reveal the utilization value of leaf, stem, and root of Artemisia argyi, a rapid online liquid microextraction combined with a high-performance liquid chromatography coupled with 2,2-nitrogen-di (3-ethyl-benzothiazole-6-sulfonic acid) diammonium salt antioxidant assay system was established for analysis of antioxidants in the leaf, stem, and root of A. argyi, and a calibration quantitative method of antioxidant activity with equivalent chlorogenic acid was proposed. Thirty-three positive peaks were identified; among them, 12 compounds were found that possess good antioxidant activity including eleven organic acids (components 2-4, 8, 11-14, 17, 19, and 21) and one flavonoids (component 22). The proposed calibration quantitative method avoided the influence of content of compound and compared the extent of radical scavenging capacity of five antioxidant compounds, which were ranked as follow: 3,5-dicaffeoylquinic acid > 3,4-dicaffeoylquinic acid ≈ 4,5-dicaffeoylquinic acid > 1,4-dicaffeoylquinic acid > chlorogenic acid. In conclusion, this study provided composition and biological potential for the future development of the leaf, stem, and root of A. argyi. It is believed that the online liquid microextraction combined with high-performance liquid chromatography based antioxidant assay system can be widely used for the rapid screening of natural antioxidant components in the different parts of natural products.

38095534

Machine learning-based delta check method for detecting misidentification errors in tumor marker tests.

Misidentification errors in tumor marker tests can lead to serious diagnostic and treatment errors. This study aims to develop a method for detecting these errors using a machine learning (ML)-based delta check approach, overcoming limitations of conventional methods.

38095536

Osimertinib covalently binds to CD34 and eliminates myeloid leukemia stem/progenitor cells.

Osimertinib is a third-generation covalent epidermal growth factor receptor (EGFR) inhibitor that is used in treating non-small cell lung cancer. First-generation EGFR inhibitors were found to elicit pro-differentiation effect on acute myeloid leukemia (AML) cells in preclinical studies, but clinical trials yielded mostly negative results. Here, we report that osimertinib selectively induced apoptosis of CD34+ leukemia stem/progenitor cells but not CD34- cells in EGFR-negative acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Covalent binding of osimertinib to CD34 at cysteines 199 and 177 and suppression of Src family kinases (SFK) and downstream STAT3 activation contributed to osimertinib-induced cell death. SFK and STAT3 inhibition induced synthetic lethality with osimertinib in primary CD34+ cells. CD34 expression was elevated in AML cells compared to their normal counterparts. Genomic, transcriptomic, and proteomic profiling identified mutation and gene expression signatures of AML patients with high CD34 expression, and univariate and multivariate analyses indicated the adverse prognostic significance of high expression of CD34. Osimertinib treatment induced responses in AML patient-derived xenograft models that correlated with CD34 expression while sparing normal CD34+ cells. Clinical responses were observed in two CD34high AML patients who were treated with osimertinib on a compassionate-use basis. These findings reveal the therapeutic potential of osimertinib for treating CD34high AML and CML and describe an EGFR-independent mechanism of osimertinib-induced cell death in myeloid leukemia.

38095537

Swelling of Ti₃ C₂ T_x MXene in Water and Methanol at Extreme Pressure Conditions.

Pressure-induced swelling has been reported earlier for several hydrophilic layered materials. MXene Ti3C2Tx is also a hydrophilic layered material composed by 2D sheets but so far pressure-induced swelling is reported for this material only under conditions of shear stress at MPa pressures. Here, high-pressure experiments are performed with MXenes prepared by two methods known to provide "clay-like" materials. MXene synthesized by etching MAX phase with HCl+LiF demonstrates the effect of pressure-induced swelling at 0.2 GPa with the insertion of additional water layer. The transition is incomplete with two swollen phases (ambient with d(001) = 16.7Å and pressure-induced with d(001) = 19.2Å at 0.2 GPa) co-existing up to the pressure point of water solidification. Therefore, the swelling transition corresponds to change from two-layer water intercalation (2L-phase) to a never previously observed three-layer water intercalation (3L-phase) of MXene. Experiments with MXene prepared by LiCl+HF etching have not revealed pressure-induced swelling in liquid water. Both MXenes also show no anomalous compressibility in liquid methanol. The presence of pressure-induced swelling only in one of the MXenes indicates that the HCl+LiF synthesis method is likely to result in higher abundance of hydrophilic functional groups terminating 2D titanium carbide.

38095535

In-Induced Electronic Structure Modulations of Bi─O Active Sites for Selective Carbon Dioxide Electroreduction to Liquid Fuel in Strong Acid.

The formation of carbonate in neutral/alkaline solutions leads to carbonate crossover, severely reducing carbon dioxide (CO₂ ) single pass conversion efficiency (SPCE). Thus, CO₂ electrolysis is a prospective route to achieve high CO₂ utilization under acidic environment. Bimetallic Bi-based catalysts obtained utilizing metal doping strategies exhibit enhanced CO₂ -to-formic acid (HCOOH) selectivity in alkaline/neutral media. However, achieving high HCOOH selectivity remains challenging in acidic media. To this end, Indium (In) doped Bi2O2CO3 via hydrothermal method is prepared for in-situ electroreduction to In-Bi/BiOx nanosheets for acidic CO2 reduction reaction (CO2RR). In doping strategy regulates the electronic structure of Bi, promoting the fast derivatization of Bi2O2CO3 into Bi-O active sites to enhance CO2RR catalytic activity. The optimized Bi₂ O₂ CO₃ -derived catalyst achieves the maximum HCOOH faradaic efficiency (FE) of 96% at 200 mA cm^-2 . The SPCE for HCOOH production in acid is up to 36.6%, 2.2-fold higher than the best reported catalysts in alkaline environment. Furthermore, in situ Raman and X-ray photoelectron spectroscopy demonstrate that In-induced electronic structure modulation promotes a rapid structural evolution from nanobulks to Bi/BiO_x nanosheets with more active species under acidic CO₂ RR, which is a major factor in performance improvement.

38095538

Editorial 2024.

38095539

Fimepinostat impairs NF-κB and PI3K/AKT signaling and enhances gemcitabine efficacy in H3K27M-mutated diffuse intrinsic pontine glioma.

Diffuse intrinsic pontine glioma (DIPG) is the most aggressive pediatric brain tumor, and the oncohistone H3.3K27M mutation is associated with significantly worse clinical outcomes. Despite extensive research efforts, effective approaches for treating DIPG are lacking. Through drug screening, we identified the combination of gemcitabine and fimepinostat as a potent therapeutic intervention for H3.3K27M DIPG. H3.3K27M facilitated gemcitabine-induced apoptosis in DIPG, and gemcitabine stabilized and activated p53, including increasing chromatin accessibility for p53 at apoptosis-related loci. Gemcitabine simultaneously induced a pro-survival program in DIPG through activation of RELB-mediated NF-κB signaling. Specifically, gemcitabine induced the transcription of long terminal repeat elements, activated cGAS-STING signaling, and stimulated non-canonical NF-κB signaling. A drug screen in gemcitabine-treated DIPG cells revealed that fimepinostat, a dual inhibitor of HDAC and PI3K, effectively suppressed the gemcitabine-induced NF-κB signaling in addition to blocking PI3K/AKT activation. Combination therapy comprising gemcitabine and fimepinostat elicited synergistic anti-tumor effects in vitro and in orthotopic H3.3K27M DIPG xenograft models. Collectively, p53 activation using gemcitabine and suppression of RELB-mediated NF-κB activation and PI3K/AKT signaling using fimepinostat is a potential therapeutic strategy for treating H3.3K27M DIPG.

38095540

Efficient and precise fabrication of Wolter type-I x-ray mirrors via nickel electroforming replication using quartz glass mandrels.

This study presents an approach for fabricating Wolter type-I mirrors for x-ray telescopes using a nickel electroforming replication process with quartz glass mandrels. The proposed method addresses the challenges encountered in conventional fabrication techniques, which involve using electroless nickel-coated aluminum mandrels that are susceptible to corrosion and thermal deformation. Quartz glass mandrels offer excellent chemical, thermal, and mechanical stability, enabling the efficient production of high-performance mirrors. Wolter type-I mirrors for telescopes possess a large aperture that collects x-ray photons from the universe. However, previous nickel electroforming replication processes using quartz glass mandrels have challenges in fabricating large mirrors, particularly due to bubble pit formation during nickel shell development. In this study, we introduced an efficient pitting inhibition technique via vacuum degassing. This technique facilitates the precise replication of pit-free Wolter type-I mirrors for telescopes using quartz glass mandrels. We demonstrated the fabrication process on a Wolter type-I mirror proposed for FOXSI-4 [(FOXSI) Focusing Optics X-ray Solar Imager], resulting in three mirrors obtained from the same mandrel without repolishing or repairing. The figure error of the mirror was within 1 µm over most areas in both longitudinal and circumferential directions. The ray-tracing simulation indicated that the performance of the mirror was ∼12 arcsec in half-power diameter, comparable to the performance achieved by previous high-resolution x-ray missions.

38095541

Passive shimming for the 9.4 T whole-body MRI superconducting magnet.

A superconducting magnet with a warm-bore size of 800 mm and a center magnetic field of 9.4 T for the whole-body magnetic resonance imaging (MRI) system was developed in IEECAS, China. To achieve a highly homogeneous magnetic field over the 400 mm diameter of spherical volume (DSV), both active shimming and passive shimming techniques were employed. This paper mainly focuses on the implementation of passive shimming for the 9.4 T MRI magnet system. After four iterations, we were able to achieve peak-to-peak and root mean square field homogeneities over the DSV at 3.05 and 0.94 ppm, respectively. In addition, this paper analyzes the electromagnetic forces and system errors of passive shimming for ultra-high fields, providing valuable insights into MRI magnet engineering.

38095542

Chemoproteomics, A Broad Avenue to Target Deconvolution.

As a vital project of forward chemical genetic research, target deconvolution aims to identify the molecular targets of an active hit compound. Chemoproteomics, either with chemical probe-facilitated target enrichment or probe-free, provides a straightforward and effective approach to profile the target landscape and unravel the mechanisms of action. Canonical methods rely on chemical probes to enable target engagement, enrichment, and identification, whereas click chemistry and photoaffinity labeling techniques improve the efficiency, sensitivity, and spatial accuracy of target recognition. In comparison, recently developed probe-free methods detect protein-ligand interactions without the need to modify the ligand molecule. This review provides a comprehensive overview of different approaches and recent advancements for target identification and highlights the significance of chemoproteomics in investigating biological processes and advancing drug discovery processes.

38095544

The Clinical and Pathological Characteristics of Patients with Oxalate Nephropathy.

Oxalate nephropathy (ON) is characterized by deposition of calcium oxalate crystals in the kidney and is commonly underrecognized. Causes of ON include primary hyperoxaluria, enteric hyperoxaluria and ingestion of excess oxalate or its precursors.

38095545

Transcatheter mitral paravalvular closure: a single centre experience with techniques and outcomes.

In patients with symptomatic mitral PVL, successful transcatheter reduction of the PVL to less than mild is associated with significant improvement in short- and midterm survival.

38095546

Managing mental health in chronic care in general practice: a feasibility study of the Healthy Mind intervention.

Mental health issues are common among patients with chronic physical conditions. This study aims to evaluate the feasibility of the Healthy Mind intervention, a general practice-based programme that provides problem-solving therapy (PST) to patients with poor mental well-being and type 2 diabetes (T2D) and/or ischaemic heart disease (IHD).

38095543

Noninvasive Nonlinear Optical Computational Histology.

Cancer remains a global health challenge, demanding early detection and accurate diagnosis for improved patient outcomes. An intelligent paradigm is introduced that elevates label-free nonlinear optical imaging with contrastive patch-wise learning, yielding stain-free nonlinear optical computational histology (NOCH). NOCH enables swift, precise diagnostic analysis of fresh tissues, reducing patient anxiety and healthcare costs. Nonlinear modalities are evaluated, including stimulated Raman scattering and multiphoton imaging, for their ability to enhance tumor microenvironment sensitivity, pathological analysis, and cancer examination. Quantitative analysis confirmed that NOCH images accurately reproduce nuclear morphometric features across different cancer stages. Key diagnostic features, such as nuclear morphology, size, and nuclear-cytoplasmic contrast, are well preserved. NOCH models also demonstrate promising generalization when applied to other pathological tissues. The study unites label-free nonlinear optical imaging with histopathology using contrastive learning to establish stain-free computational histology. NOCH provides a rapid, non-invasive, and precise approach to surgical pathology, holding immense potential for revolutionizing cancer diagnosis and surgical interventions.

38095547

Prolonged cough and dyspnea following a single episode of intense silica exposure.

Long term exposure to silica at worksites can cause silicosis. This typically has two radiographic forms, simple silicosis and complicated or conglomerate silicosis. Patients with acute silicosis have rapid progression of disease with fulminant respiratory failure over months rather than years. The patient described in this case report had a one-time 4 to 5-h exposure to silica and sand dust at work when his mask malfunctioned. He developed cough and shortness of breath. During his initial clinic visit he had significant cough. His chest examination was clear without crackles or wheezes. His pulmonary function tests were within normal limits. His chest x-ray was clear. Both symptoms, especially the cough, persisted over the next 6+ months even after treatment with oral corticosteroids and inhaled corticosteroids and long-acting beta agonists. Consequently, this patient developed severe cough following a one-time exposure to silica particulates. Laboratory studies have demonstrated that silica exposure can cause reactive oxygen species which potentially could have activated transient receptor potential vanilloid 1 channels in the afferent sensory nerves in his bronchial epithelium. This could cause sustained cough for more than 6 months. His symptoms improved but did not resolve with corticosteroid treatment. Therefore, this case demonstrates that acute silica exposure can cause sustained airway symptoms in healthy workers.

38095548

Development and validation of a risk prediction model for postoperative gastrointestinal complications in patients undergoing aortic arch surgery.

Postoperative gastrointestinal complications (GICs) were potentially fatal to patients who underwent aortic arch surgery. The aim of this study was to construct a prediction model of GICs.

38095549

Copper management strategies in obligate bacterial symbionts: balancing cost and benefit.

Bacteria employ diverse mechanisms to manage toxic copper in their environments, and these evolutionary strategies can be divided into two main categories: accumulation and rationalization of metabolic pathways. The strategies employed depend on the bacteria's lifestyle and environmental context, optimizing the metabolic cost-benefit ratio. Environmental and opportunistically pathogenic bacteria often possess an extensive range of copper regulation systems in order to respond to variations in copper concentrations and environmental conditions, investing in diversity and/or redundancy as a safeguard against uncertainty. In contrast, obligate symbiotic bacteria, such as Neisseria gonorrhoeae and Bordetella pertussis, tend to have specialized and more parsimonious copper regulation systems designed to function in the relatively stable host environment. These evolutionary strategies maintain copper homeostasis even in challenging conditions like encounters within phagocytic cells. These examples highlight the adaptability of bacterial copper management systems, tailored to their specific lifestyles and environmental requirements, in the context of an evolutionary the trade-off between benefits and energy costs.

38095550

Considerations when asking about "disability" in disability inclusive research.

There are several ways to include "disability" in research studies, which can be confusing or overwhelming for researchers, community members, and students. The aim of this paper is to share conceptualizations of disability and how to ask about "disability" in research studies. The paper provides a general introduction and brief analysis of the methodological approaches which can be used.

38095551

Unexpected giant coronary aneurysm.

38095552

Pd@Bi₂Ru₂O₇/BiVO₄ Z-Scheme Heterojunction Nanocomposite Photocatalyst for the Degradation of Trichloroethylene.

Photocatalytic degradation of chlorinated persistent organic pollutants is a very challenging process due to the high redox potential of the C-Cl bond that requires wide band gap catalysts that are activated under UV light. Designing a Z-scheme heterojunction between visible light-activated metal oxides with compatible band gaps enables these redox potentials. Herein, we report the design of a pyrochlore/Aurivillius Z-scheme heterojunction to enhance the photocatalytic activity of BiVO₄ for the degradation of trichloroethylene. We prepared Bi₂Ru₂O₇/BiVO₄ heterostructured photocatalysts by a controlled hydrothermal approach. Upon optimizing the Bi₂Ru₂O₇ ratio to 1.0 wt %, the heterostructured photocatalyst demonstrated enhanced activity in the degradation of trichloroethylene (TCE) under simulated sunlight irradiation compared to bare BiVO₄ and Bi₂Ru₂O₇, respectively. Decorating the surface of the catalyst with palladium nanodomains to create the Pd@Bi₂Ru₂O₇/BiVO₄ nanocomposite showed a substantial increase in the photocatalytic degradation of TCE. The material characterization indicated that the architecture of the material provides a synergy of enhancing the redox potential of the photocatalyst and improving the charge carrier dynamics. Furthermore, the photoelectrochemical characterization confirmed that the dual heterojunctions in the Pd@Bi₂Ru₂O₇/BiVO₄ nanocomposite resulted in improved interfacial charge carrier transfer and enhanced the electron/hole separation efficiency compared to the nonpalladized catalysts. This work provides a promising approach for band gap engineering of visible light photocatalysts for the degradation of halogenated persistent organic pollutants.

38095553

Identification and characterisation of a novel EhOrc1/Cdc6 from the human pathogen <i>Entamoeba histolytica</i>: an <i>in silico</i> approach.

The onset of a pre-replication complex on origin commences DNA replication. The Origin recognition complex (Orc), Cell division cycle protein 6 (Cdc6), and the minichromosome maintenance (Mcm) replicative helicase, along with Chromatin licensing and DNA replication factor 1 (Cdt1), make up the pre-replication complex in eukaryotes. Eukaryotic Orc is made up of six subunits, designated Orc1-6 while monomeric Cdc6 has sequence similarity with Orc1. However, Orc has remained unexplored in the protozoan parasite <i>Entamoeba histolytica</i>. Here we report a single functional Orc1/Cdc6 protein in <i>E. histolytica</i>. Its structural and functional aspects have been highlighted by a detailed <i>in silico</i> analysis that reflects physicochemical characteristics, predictive 3D structure modelling, protein-protein interaction studies, molecular docking and simulation. This <i>in silico</i> study provides insight into EhOrc1/Cdc6 and points out that <i>E. histolytica</i> carries pre-replication machinery that is less complex than higher eukaryotes and closer to archaea. Additionally, it lays the groundwork for future investigations into the methods of origin recognition, and anomalies of cell cycle observed in this enigmatic parasite.Communicated by Ramaswamy H. Sarma.

38095555

Packing up the genome.

Nucleotide and force-dependent mechanisms control how the viral genome of lambda bacteriophage is inserted into capsids.

38095554

Haematopoietic development and HSC formation in vitro: promise and limitations of gastruloid models.

Haematopoietic stem cells (HSCs) are the most extensively studied adult stem cells. Yet, six decades after their first description, reproducible and translatable generation of HSC in vitro remains an unmet challenge. HSC production in vitro is confounded by the multi-stage nature of blood production during development. Specification of HSC is a late event in embryonic blood production and depends on physical and chemical cues which remain incompletely characterised. The precise molecular composition of the HSC themselves is incompletely understood, limiting approaches to track their origin in situ in the appropriate cellular, chemical and mechanical context. Embryonic material at the point of HSC emergence is limiting, highlighting the need for an in vitro model of embryonic haematopoietic development in which current knowledge gaps can be addressed and exploited to enable HSC production. Gastruloids are pluripotent stem cell-derived 3-dimensional (3D) cellular aggregates which recapitulate developmental events in gastrulation and early organogenesis with spatial and temporal precision. Gastruloids self-organise multi-tissue structures upon minimal and controlled external cues, and are amenable to live imaging, screening, scaling and physicochemical manipulation to understand and translate tissue formation. In this review, we consider the haematopoietic potential of gastruloids and review early strategies to enhance blood progenitor and HSC production. We highlight possible strategies to achieve HSC production from gastruloids, and discuss the potential of gastruloid systems in illuminating current knowledge gaps in HSC specification.

38095556

An unusual cause of severe tricuspid regurgitation: migration of left renal vein stent in nutcracker syndrome.

38095557

The association of <i>Sort1</i> expression with LDL subfraction and inflammation in patients with coronary artery disease.

Controversial effect of sortilin on lipoprotein metabolism in the development of atherosclerosis reveals the need for more extensive research.

38095558

Integrating machine learning and high throughput screening for the discovery of allosteric AKT1 inhibitors.

Evidence from clinical and experimental investigations reveals the role of AKT in oral cancer, which has led to the development of therapeutic and pharmacological medications for inhibiting AKT protein. Despite prodigious effort, researchers are searching for new allosteric inhibitors as orthosteric inhibitors are non-selective and exert off-target effects. In the current study, we proposed an integrated computational workflow for identifying allosteric AKT1 inhibitors as this isoform is highly correlated with poor prognosis and survival. To achieve this objective, 84 classification QSAR models with six different machine learning algorithms were developed. The models created with RDKit_RF and RDKit_kstar outperformed internal and test set validation with an ROC of 0.98. The outperformed models were then used to screen Chembl, which contains over a million compounds, for AKT1 inhibitors. The Tanimoto similarity search approach identified the compounds structurally resembling AKT allosteric inhibitors. The filtered compounds were further subjected to docking phases, molecular dynamic simulation and mmpbsa to verify the binding mode of selected ones. All these analyses suggested hit 5 (CHEMBL3948083) as the potential allosteric inhibitor of AKT1 as the stability parameters, favourable binding affinity (-107.78 ± 11.56 KJ/mol) and ligand interaction were better in comparison to other compounds and reference compound. The residual analysis demonstrated that allosteric and isoform-specific residues such as Trp80 and Val270 contributed the larger energy for ligand binding. The proposed integrated approach in this study might achieve a futuristic outcome when employed in a pharmaceutical scheme different from the conventional method.Communicated by Ramaswamy H. Sarma.

38095559

Synthesis, molecular modelling and pharmacological evaluation of novel indole-thiazolidinedione based hybrid analogues as potential pancreatic lipase inhibitors.

A series of novel indole-thiazolidinedione hybrid analogues (<b>7a</b> to <b>7&#8201;u</b>) were synthesised, characterised and evaluated for their potential Pancreatic Lipase (PL) inhibition. Amongst the screened analogues, <b>7r</b> was found to be the most active PL inhibitor with an IC₅₀ of 2.67&#8201;&#181;M. Furthermore, enzyme inhibition kinetics study revealed a competitive mode of inhibition by the analogues. This fact was confirmed <i>via</i> fluorescence spectroscopy which further suggested the presence of one binding site for the synthesized analogues. Molecular docking was performed using human PL (PDB ID: 1LPB) and were in agreement with the <i>in&#160;vitro</i> results (Pearson's <i>r</i>&#8201;=&#8201;0.8355, <i>p</i>&#8201;&lt;&#8201;0.05). A molecular dynamics study (100&#8201;ns) indicated that <b>7r</b> was stable in a dynamic environment. The analogue <b>7r</b> exhibited potential antioxidant activity and was devoid of cytotoxic effect on RAW 264.7 cells. Based on the <i>in-vitro</i> profiles, <b>7r</b> was selected for the <i>in-vivo</i> pharmacological evaluation. Oral triglyceride tolerance test highlighted effect of <b>7r</b> on the inhibition of triglyceride absorption. A four-week treatment of <b>7r</b> in the HFD feed mice provided information regarding its anti-obesity effect with respect to parameters such as body weight, triglycerides, total cholesterol and high-density lipids. Quantification of the faecal triglyceride contents inveterates the potential role of <b>7r</b> in the PL inhibition. Overall, the synthesized analogue <b>7r</b> exerted an anti-obesity effect comparable to orlistat. All these results demonstrated the potential role of the newly synthesised indole-thiazolidinedione hybrid analogues in PL inhibition and may be studied further to find potential drug candidates for treating obesity.Communicated by Ramaswamy H. Sarma.

38095561

Uncovering Distinct Peptide Charging Behaviors in Electrospray Ionization Mass Spectrometry Using a Large-Scale Dataset.

Electrospray ionization is a powerful and prevalent technique used to ionize analytes in mass spectrometry. The distribution of charges that an analyte receives (charge state distribution, CSD) is an important consideration for interpreting mass spectra. However, due to an incomplete understanding of the ionization mechanism, the analyte properties that influence CSDs are not fully understood. Here, we employ a machine learning-based approach and analyze CSDs of hundreds of thousands of peptides. Interestingly, half of the peptides exhibit charges that differ from what one would naively expect (the number of basic sites). We find that these peptides can be classified into two regimes (undercharging and overcharging) and that these two regimes display markedly different charging characteristics. Notably, peptides in the overcharging regime show minimal dependence on basic site count, and more generally, the two regimes exhibit distinct sequence determinants. These findings highlight the rich ionization behavior of peptides and the potential of CSDs for enhancing peptide identification.

38095563

Eating behaviours and personality characteristics of clinicians and researchers working in eating disorders.

Disturbances in eating behaviours and differences in personality characteristics, such as perfectionism, cognitive flexibility, and obsessive-compulsive behaviours, are commonly reported in individuals with eating disorders (ED) and can influence the development and maintenance of EDs. The presence of these characteristics in ED professionals may also have an influence on their patients. The aim of this study was to gain a better understanding of the presence of these behaviours and characteristics in ED clinicians/researchers (EDCR). This study examined whether these constructs differed amongst 83 EDCR and 47 general mental health clinicians/researchers (MHCR), who completed an online survey, measuring eating disorder symptomology, orthorexia nervosa, perfectionism, cognitive flexibility, and obsessive-compulsive traits. Significantly less dietary restraint, eating concerns and orthorexia nervosa behaviours, but significantly poorer ability to seek out alternative solutions (i.e. a component of cognitive flexibility) were found in the EDCR group compared with the MHCR group. Moderation analysis found no effect of ED history on the relationship between eating behaviours and group. These results suggest that working in the ED field may be a protective factor against developing certain disordered eating behaviours. However, poorer cognitive flexibility may adversely impact EDCRs, and should be considered when carrying out their clinical and/or research duties.

38095562

Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement.

Aging is a dynamic, time-dependent process that is characterized by a gradual accumulation of cell damage. Continual functional decline in the intrinsic ability of living organisms to accurately regulate homeostasis leads to increased susceptibility and vulnerability to diseases. Many efforts have been put forth to understand and prevent the effects of aging. Thus, the major cellular and molecular hallmarks of aging have been identified, and their relationships to age-related diseases and malfunctions have been explored. Here, we use data from the CAS Content Collection to analyze the publication landscape of recent aging-related research. We review the advances in knowledge and delineate trends in research advancements on aging factors and attributes across time and geography. We also review the current concepts related to the major aging hallmarks on the molecular, cellular, and organismic level, age-associated diseases, with attention to brain aging and brain health, as well as the major biochemical processes associated with aging. Major age-related diseases have been outlined, and their correlations with the major aging features and attributes are explored. We hope this review will be helpful for apprehending the current knowledge in the field of aging mechanisms and progression, in an effort to further solve the remaining challenges and fulfill its potential.

38095564

"Skip" corpectomy technique in multilevel cervical spondylotic myelopathy and ossified posterior longitudinal ligament: Outcomes with over 10-years follow-up.

Skip corpectomy is a surgical technique that includes C4 and C6 corpectomies and fusion via autografts and a cervical plate and is frequently performed in patients with CSM and OPLL. This study presents long-term clinical and radiological outcomes of 48 patients who underwent skip corpectomy with 10-year follow-up.

38095566

Queuine as a potential multi-target drug for alzheimer's disease: insights from protein dynamics.

Alzheimer's disease (AD) is a neurodegenerative disorder with a complex pathogenesis. One promising approach to treating AD is simultaneously targeting multiple aspects of the disease using a multi-target drug (MTD). In this study, multi-target drug (MTD) potential of the nutraceutical molecule Queuine was explored using molecular docking and molecular dynamics (MD) simulations with five different protein targets engaged in AD: AChE, beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1), N-methyl-D-aspartate receptor (NMDAR), monoamine oxidase A (MAO-A), and Synapsin III. Queuine revealed significant binding affinities, the docking scores being -10.1, -5.97, -5.63, -8.40, and -10.56 kcal/mol for AChE, BACE-1, NMDAR, MAO-A, and Synapsin III, respectively. MD simulations showed that Queuine formed stable complexes and preserved its stability throughout the simulation, the backbone fluctuations remaining within 2.5 Å specifically in the case of the BACE-1. Elastic network model simulations and principal component analysis were carried out to illustrate the dynamics of the protein systems. Significant hinge-bending and twisting-type motions that may be relevant to function were observed around the dimerization interfaces or binding sites. Structural clustering based on PCA analysis and cross-correlation maps demonstrated that Queuine binding altered the protein dynamics more drastically in the case of highly mobile proteins NMDAR and MAO-A. We propose that the neuroprotective effect of Queuine may stem from its prominent inhibitory action on enzymes BACE-1 and AChE. Our results suggest that Queuine may serve as a promising MTD candidate for the treatment of AD.Communicated by Ramaswamy H. Sarma.

38095567

The usefulness of traction-assisted endoscopic papillectomy for ampullary early tumors(with video).

<b>Objective</b> Endoscopic papillectomy(EP) is a minimally invasive treatment for early ampullary tumors. However, the optimal method is unclear. The aim of this study is to explore the efficacy and safety of traction-assisted EP treatments for ampullary early tumors.<b>Methods</b> We retrospective analyzed the patients with ampullary adenoma or early adenocarcinoma underwent endoscopic papillectomy between January 2010 and August 2023, including patient characteristics, lesion size, papilla type, pathological diagnosis and lesion surrounding conditions, en-bloc resection rate, complete resection rate, procedure time, complications, recurrences.<b>Results</b> During the study period, a total of 106 patients with ampullary adenoma or early adenocarcinoma underwent EP. The number of patients in traction group (clip combined with dental floss traction, CDT-EP) and non-traction group (hot snare papillectomy, HSP or endoscopic mucosal resection, EMR) were 45 and 61 respectively. The traction group has a higher en-bloc resection rate and complete resection rate than the non-traction group (92.86% <i>vs.</i> 68.85%, <i>p</i>&#8201;=&#8201;0.003; 90.48% <i>vs.</i> 60.66%, <i>p</i>&#8201;=&#8201;0.001), and the procedure time is slightly shorter[(1.57&#8201;&#177;&#8201;1.93)min <i>vs.</i> (1.98&#8201;&#177;&#8201;1.76)min, <i>p</i>&#8201;=&#8201;0.039]. The complications and recurrence in the traction group were lower than those in the non-traction group (7.14% <i>vs.</i> 19.72%, <i>p</i>&#8201;=&#8201;0.076; 7.14% <i>vs.</i> 11.78%, <i>p</i>&#8201;=&#8201;0.466), and all complications were successfully treated by endoscopy or conservative medical treatment. There was no statistical difference between the two groups in terms of patient characteristics, papilla type, pathological diagnosis and lesion surrounding conditions (<i>p</i>&#8201;&gt;&#8201;0.050), but there were differences in lesion size[(13&#8201;&#177;&#8201;1.09)mm <i>vs.</i> (11&#8201;&#177;&#8201;1.65)mm, <i>p</i>&#8201;=&#8201;0.002]. The recurrence rate of the traction group is lower than that of the non-traction group, but the difference is not significant(7.14% <i>vs.</i> 13.11%, <i>p</i>&#8201;=&#8201;0.335), and the non-traction group mainly has early recurrence. Further analysis shows that the size of the lesion, whether en-bloc resection or not, and the method of resection as independent risk factors for incomplete resection (OR = 1.732, <i>p</i>&#8201;=&#8201;0.031; OR = 3.716, <i>p</i>&#8201;=&#8201;0.049; OR = 2.120, <i>p</i>&#8201;=&#8201;0.027).<b>Conclusions</b> CDT- EP, HSP and EMR are all suitable methods for the treatment of ampullary adenoma or early adenocarcinoma. Assisted traction technology can reduce the operation difficulty of large and difficult to expose lesions, thereby improving the efficacy and safety of EP.

38095565

Do letters matter? The influence of spelling on acoustic duration.

The present article describes a modified and extended replication of a corpus study by Brewer (2008. <i>Phonetic reflexes of orthographic characteristics in lexical representation</i>. Tucson, AZ: University of Arizona PhD thesis) which reports differences in the acoustic duration of homophonous but heterographic sounds. The original findings point to a quantity effect of spelling on acoustic duration, i.e.,&#160;the more letters are used to spell a sound, the longer the sound's duration. Such a finding would have extensive theoretical implications and necessitate more research on how exactly spelling would come to influence speech production. However, the effects found by Brewer (2008) did not consistently reach statistical significance and the analysis did not include many of the covariates which are known by now to influence segment duration, rendering the robustness of the results at least questionable. Employing a more nuanced operationalization of graphemic units and a more advanced statistical analysis, the current replication fails to find the reported effect of letter quantity. Instead, we find an effect of graphemic complexity. Speakers realize consonants that do not have a visible graphemic correlate with shorter durations: the /s/ in <i>tux</i> is shorter that the /s/ in <i>fuss</i>. The effect presumably resembles orthographic visibility effects found in perception. In addition, our results highlight the need for a more rigorous approach to replicability in linguistics.

38095568

"Returning to the core tasks": a qualitative interview study about how general practitioners in home health care solved problems during the COVID-19 pandemic.

Optimizing care at home, or home health care (HHC), is necessary as the population of care-dependent older people receiving care at home steadily increases. The COVID-19 pandemic tested Swedish primary care professionals as they provided HHC for a population of very frail older homebound people, but a better understanding of what healthcare workers did to manage the crisis may be useful for the further development of HHC. In this study, we aimed to understand how HHC physicians solved the problems of providing home healthcare during the pandemic to learn lessons on how to improve future HHC.

38095569

Neutralizing monoclonal antibodies for the prevention of severe COVID-19: a retrospective study during Omicron BA.1 variant surge.

Among treatment options for Coronavirus disease 2019 (COVID-19), monoclonal antibodies (mAbs) showed to be effective in preventing disease progression, but real-world data during the Omicron variant surge are still lacking. Multicentre retrospective study evaluating the effectiveness of sotrovimab and casirivimab-imdevimab in fragile patients with mild SARS-CoV-2 infection between November 2021 and March 2022. Unfavourable outcome was defined as increased need for oxygen supplementation and/or death. Of 268 study-participants, 12 (4.48%) previously needed supplemental oxygen, while 6 (2.24%) had active solid neoplasia (2.24%); 186 (69%) have previously received SARS-CoV-2 vaccination. Overall, 22 (8%) had unfavourable outcomes (42% versus 6% of patients with and without previous oxygen need and 50% versus 7% of patients with and without active solid neoplasia). Both supplemental oxygen therapy before SARS-CoV-2 infection and solid malignant tumour have shown to be risk factors for treatment failure. Log-rank test did not identify differences between sotrovimab and casirivimab-imdevimab treatment. Despite diffusion of Omicron variant, the rate of unfavourable outcome was higher than expected. The presence of underlying risk factors, including solid cancer and previous oxygen therapy are independently associated with risk of COVID-19 progression, suggesting the need for antiviral treatments not limited to mAbs and implementation of vaccine campaign.

38095570

The role of postoperative piriformis fossa and greater trochanter tubercle distance to predict cutout failure after cephalomedullary nail fixation.

This study investigated the association between postoperative piriformis fossa and greater trochanter tubercle distance (PG) and cutout failure after cephalomedullary nail (CMN) osteosynthesis for intertrochanter fracture (ITF). A rotating femur model was designed to analyze PG variation during femur rotation.