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38095370

On the normativity of evidence - Lessons from philosophy of science and the "VALIDATE" project.

"Evidence" is a key term in medicine and health services research, including Health Technology Assessment (HTA). Randomized clinical trials (RCTs) have undoubtedly dominated the scene of generating evidence for a long period of time, becoming the hallmark of evidence-based medicine (EBM). However, due to a number of misunderstandings, the lay audience and some researchers have sometimes placed too much trust in RCTs compared to other methods of investigation. One of the principal misunderstandings is to consider RCTs findings as isolated and self-apparent pieces of information. In other words, what has been essentially lacking was the awareness of the value-context of the evidence and, in particular, the value- and theory-ladenness (normativity) of scientific knowledge. This paper aims to emphasize the normativity that exists in the production of scientific knowledge, and in particular in the conduct of RCTs as well as in the performance of HTA. The work is based on some lessons learned from Philosophy of Science and the European project "VALIDATE" (VALues In Doing Assessments of healthcare TEchnologies"). VALIDATE was a three-year EU Erasmus+ strategic partnerships project (2018-2021), in which training in the field of HTA was further optimized by using insights from political science and ethics (in accordance with the recent definition of HTA). Our analysis may reveal useful insights for addressing some challenges that HTA is going to face in the future.

38095371

Influence of quercetin on amiodarone pharmacokinetics and biodistribution in rats.

Amiodarone (AMD), a drug of choice to treat cardiac arrhythmias, has a narrow therapeutic index (NTI). It inhibits CYP3A4, CYP2C9, and CYP2D6 enzymes. Quercetin (QUE), a pharmacologically important bioflavonoid in vegetables and fruits, is important in treating cardiovascular comorbidities. QUE alters the bioavailability of drugs used concurrently by dual inhibition of P-glycoproteins (P-gp) and cytochrome (CYP) enzyme systems. The current study aimed to investigate the pre-treatment and co-administration effect of QUE on AMD pharmacokinetics in rats.

38095372

Multi-targeted therapeutic effects of Sankudiwan (SKDW) in myocardial ischemia-reperfusion injury: a comprehensive study.

This study aimed to investigate the therapeutic effects and underlying mechanisms of Sankudiwan (SKDW) on myocardial ischemia-reperfusion injury (MIRI) in a rat model.

38095373

Analgesic effect of the flavonoid herbacetin in nociception animal models.

This study aimed to assess the antinociceptive activity of herbacetin using chemically and thermally induced nociception in a mouse model.

38095374

Characterization and molecular identification of lactic acid bacteria isolated from kefir and evaluation of their antibacterial activity against food-borne pathogens in Saudi Arabia.

Pathogenic bacteria are usually present in raw milk. In order to prevent pathogens from growing, milk should be fermented. The present research work aimed to isolate lactic acid bacteria (LAB) from kefir, a fermented milk beverage, and assess their antibacterial activity against chosen pathogenic strains of bacteria.

38095375

Role of OCTA in the prognosis of dry-type AMD.

This study aimed to determine the prognostic value of Optical Coherence Tomography Angiography (OCTA) in dry-type age-related macular degeneration (AMD).

38095376

Triglyceride glucose index: a novel biomarker in the management of patients with psoriasis.

Triglyceride glucose index is a recently described biomarker that has been associated with various systemic disorders such as cardiovascular diseases. Within this study, we evaluated the effect of biological agent treatment on triglyceride glucose index in patients with psoriasis.

38095377

Activation and upregulation of keratinocyte and epidermal transglutaminases are associated with depletion of their substrates in psoriatic lesions.

Psoriasis is a chronic skin disorder caused by abnormal interactions between epidermal and immune cells. Thus, the interplay between the proliferation and differentiation of epidermal components should be tightly regulated to protect against psoriasis. The differentiation process is primarily controlled by transglutaminases (TGs). However, studies on TG enzymes and their molecular alterations in psoriatic skin lesions are limited. Therefore, this study aimed to investigate TG activity and gene and protein expression in human psoriatic and normal skin tissues.

38095378

Analysis of treatment adherence in patients undergoing phototherapy.

Phototherapy is a convenient and effective treatment alternative for a range of skin diseases. However, a major challenge in patient adherence to phototherapy may be the necessity of visiting a phototherapy center regularly over an extended period of time. The aims of this study were (i) to investigate the adherence rate to phototherapy and (ii) to determine factors associated with adherence to narrow-band ultraviolet B phototherapy (nbUVB) treatment.

38095379

Assessment of efficacy of percutaneous epidural neuroplasty for lumbar stenosis and failed back surgery syndrome: effective and safe?

Chronic, refractory low back and lower extremity pain is a common problem. There are many causes for persistent low back pain, including spinal stenosis (SS), disc herniation, facet disease, sacroiliac disease, adjacent segment disease, ligamentous disease, and failed back surgery syndrome (FBSS). FBSS and SS are common and often result in chronic, persistent pain and disability. After the failure of conservative treatments, percutaneous epidural neuroplasty (PEN) is often used in managing low back pain.

38095380

Management of anesthesia in pregnant women with pulmonary hypertension.

Pulmonary hypertension (PH) is a rare heart disease associated with high maternal and fetal mortality. This study aims to discuss anesthesia management and the fetal and maternal outcomes of patients with PH followed-up at our clinic.

38095381

Quadratus lumborum and erector spinae plane blocks are effective for analgesia in laparoscopic hysterectomy: a randomized controlled trial.

Total laparoscopic hysterectomy is the preferred technique for hysterectomy in obstetrics and gynecology clinics. However, patients who undergo these procedures often experience acute pain that may progress to chronic pain over time. Erector spinae plane block (ESPB) and anterior quadratus lumborum block (QLB) under ultrasound guidance are reported to be effective as part of the multi-modal analgesia protocol. Therefore, this study aimed to compare the effectiveness of erector spinae plane block and anterior quadratus lumborum block in reducing postoperative opioid consumption and pain scores in patients undergoing total laparoscopic hysterectomy.

38095382

The therapeutic effect of decitabine combined with HAG in acute myeloid leukemia: a retrospective case-control analysis.

Explore the efficacy of decitabine combined with homoharringtonine + cytarabine + granulocyte colony-stimulating factor (HAG) in the treatment of acute myeloid leukemia (AML).

38095383

Oxytocin mitigates peripheral nerve damage via Nrf2 and irisin pathway.

Peripheral nerve injuries present challenges in achieving full functional restoration, necessitating effective therapeutic strategies. Oxytocin, known for its neuroprotective and anti-inflammatory properties, has shown potential in nerve recovery. This study aims to elucidate the role of oxytocin in nerve recovery via the nuclear factor erythroid 2-related factor 2 (Nrf2) and irisin pathways.

38095384

Sublingual vs. intranasal dexmedetomidine sedation for flexible fiberoptic bronchoscopy procedure: a retrospective comparative study.

Flexible fiberoptic bronchoscopy (FOB) is an often-employed invasive method in diagnosing, staging, and treating lung diseases. Conventional sedative agents facilitate this process. Dexmedetomidine (DM) has low side effects and is easy to administer for trans-mucosal absorption. This study aimed to investigate trans-mucosal DM used with local anesthesia during the FOB procedure.

38095385

The wound area as a parameter guiding the timing of abdominal closure in the management of patients undergoing open abdominal procedures.

Surgical site infections (SSI) are incomparably troublesome and complicated, and some of them require an open abdomen (OA) procedure. While deciding the timing of abdominal closure, wound area calculation method and laboratory parameters can be used to guide the timing of abdominal closure after OA procedures.

38095386

Roxadustat protects rat renal tubular epithelial cells from hypoxia-induced injury through the TGF-β1/Smad3 signaling pathway.

Roxadustat is used to treat renal anemia. The renoprotective effect of roxadustat needs to be further confirmed, and the mechanism of action is unknown. This study aims to evaluate the effect and mechanism of roxadustat in hypoxia-related nephropathy with the renal tubular epithelial cell line NRK-52E.

38095387

Bone marrow-derived mesenchymal stem cells abate CCl4-induced lung damage via their modulatory effects on inflammation, oxidative stress and apoptosis.

The aim of this study was to assess and compare the therapeutic effects of allogenic and xenogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) on a rat model for treating experimental lung inflammation, oxidative stress, and apoptosis.

38095388

Association of thyroid disease and risk of fatty liver disease: an exposure-wide Mendelian randomization study.

Previous studies have often observed a possible association between thyroid and fatty liver diseases. The pathogenesis of both diseases is complex, with many confounding factors and controversies. We used a two-sample Mendelian randomization (MR) analysis to test the causality between thyroid disease and the risk of developing fatty liver disease.

38095389

Clinical characteristics and risk factors of diabetic foot ulcers with PAD.

This study aimed to analyze the clinical characteristics of patients with diabetic foot ulcers combined with peripheral arterial disease (PAD) and the risk factors.

38095390

Control and treatment of type 2 diabetes in private patients in the Egyptian "DIACONTROL study".

This study aims to identify the characteristics of Egyptian patients suffering from type 2 diabetes mellitus (T2DM), determine disease control rates, and gain insights into clinical treatments.

38095391

Influence of various intermittent fasting regimens on body weight and glycemic control in streptozotocin-induced diabetic rats.

This study aims to compare the effects of various intermittent fasting (IF) regimens, i.e., time-restricted fasting (TRF), alternate day fasting (ADF), and periodic fasting (PF) on body weight, glycemic control and associated metabolic parameters in streptozotocin-induced diabetic rats.

38095392

The potential therapeutic effect of metformin in type 2 diabetic patients with severe COVID-19.

Type 2 diabetes mellitus (T2DM) is regarded as a chief risk factor for(coronavirus disease 2019 (COVID-19) owing to dysregulation of the expression of angiotensin-converting enzyme 2 (ACE2) and chronic low-grade inflammatory disorders. Metformin, an insulin-sensitizing agent for managing T2DM, has pleiotropic anti-inflammatory and oxidant potentials, which may lessen the risk of diabetic complications. So, we aimed to reveal the potential role of metformin monotherapy in treating T2DM patients with COVID-19.

38095393

Predictive factors in the differential diagnosis of benign and malignant causes in patients undergoing endoscopic retrograde cholangiopancreatography for extrahepatic cholestasis.

Diagnosing benign vs. malignant extrahepatic cholestasis is challenging despite the currently available advanced imaging and endoscopic techniques. This study aims to determine the predictive accuracy of initial biochemical data and bile duct dilatation findings in transabdominal ultrasound (US) to differentiate between benign and malignant disease in patients with extrahepatic cholestasis.

38095394

The value of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, red cell distribution width, and their combination in predicting acute pancreatitis severity.

Acute pancreatitis is one of the most common causes of acute abdominal pain requiring hospitalization worldwide. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) are novel inflammatory markers that have been investigated in various diseases associated with an inflammatory response, achieving many positive results. Evaluating the NLR, PLR, RDW, and their combination to predict acute pancreatitis severity can help clinicians have an appropriate initial treatment strategy.

38095395

Relationship between uric acid albumin ratio and peripheral artery disease complexity.

Uric acid to albumin ratio (UAR) reflects inflammatory activity and its predictive value has been shown in various diseases. In this study, we sought to evaluate the value of uric acid to albumin ratio in patients with peripheral arterial disease (PAD).

38095396

Novel insights on acute myocarditis in pediatric patients.

Acute myocarditis (AM) is an inflammatory affliction of the heart muscle characterized by recent onset with a broad spectrum of clinical manifestations that globally affect millions of individuals, notably children and young adults. The absence of distinct patterns of onset or predictable progression poses a significant threat to survival, potentially leading to advanced heart failure and malignant arrhythmias. Myocardial fibrosis, a hallmark of myocardial remodeling, is increasingly recognized as a contributor to adverse outcomes in acute myocarditis cases. Advances in molecular and immunological techniques have highlighted the intricate interplay between viral infections, dysregulated immune responses, and genetic susceptibility. Currently, there is no clear consensus for diagnosis or ongoing follow-up in pediatric patients. The conventional diagnostic tool, endomyocardial biopsy (EMB), considered the gold standard, has been complemented by the effectiveness of cardiac magnetic resonance imaging (CMRI) techniques. Given the procedural complexities and associated complications, there is a pressing need to explore non-invasive alternatives. In this context, biomarkers emerge as promising contenders by evaluating both the inflammatory processes and cardiac remodeling, providing valuable observations into disease severity, progression, and treatment response. Therapeutic strategies in these cases, focusing on the specific pathways or immune components associated with the etiologies, have exhibited promise for better outcomes. Acute myocarditis in children remains a multifaceted clinical challenge, necessitating a comprehensive understanding of its pathophysiology, diagnosis, and management. This review aims to delve into novel insights surrounding the pathophysiology, diagnosis, and management of acute myocarditis in pediatric patients.

38095397

8-Iso-prostaglandin F2α as a potential biomarker in patients with unipolar and bipolar depression.

Previous studies have shown that the disturbance of redox homeostasis plays a role in the pathogenesis of mood disorders. It is currently unclear whether oxidative stress parameters can be used as biomarkers (state vs. trait). The aim of the present study was to investigate oxidative stress markers in patients with major depressive disorder (MDD) and bipolar disorder (BP) in acute depressive episodes and remission, and healthy individuals.

38095398

Comparison of kinesiophobia in patients with rheumatoid arthritis and systemic lupus erythematosus.

Patients with rheumatic disease often experience arthritis and chronic joint pain, which can lead them to avoid movement, known as kinesiophobia. This may result in decreased mobility and endurance, as well as social isolation and depression. This study aimed to assess and compare the prevalence of kinesiophobia among patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and its association with disease activity, functional status, fear of falling, and fatigue.

38095399

Development and validation of a nomogram for 30-day readmission after hip fracture surgery in geriatric patients.

30-day readmission after hip fracture surgery in the elderly is common and costly. A predictive tool to identify high-risk patients could significantly improve outcomes. This study aims to develop and validate a risk nomogram for 30-day readmission after hip fracture surgery in geriatric patients.

38095400

PDCA cycle management combined with detailed management of postoperative deep vein thrombosis in patients undergoing hip replacement surgery.

This study aimed to analyze and explore the effect of Plan-Do-Check-Act (PDCA) cycle management combined with detailed management on postoperative deep venous thrombosis in patients undergoing hip replacement surgery.

38095401

The importance of low visfatin values in osteoid osteoma patient: a prospective study.

Visfatin is currently a cytokine that is extensively researched in the field of bone diseases. In this prospective study, we aimed to investigate the potential of serum visfatin levels as a biomarker for the diagnosis of osteoid osteoma.

38095402

Risk avoidance of screw-induced suprascapular nerve injury in arthroscopic Latarjet procedure and reliable anatomical landmark analysis of Latarjet surgery.

Shoulder dislocation represents a prevalent category within joint dislocation, accounting for about 40% of all joint dislocations, and anterior dislocation stands out as the prevailing type. It has been reported that in 1.6% of patients, the Latarjet procedure performed under arthroscopy involves transferring the coracoid process to the anterior-inferior aspect of the glenoid and fixing it with two bicortical screws. The tip of the screws may impinge the suprascapular nerve located behind the scapula, resulting in shoulder pain and weakness. This study was performed to analyze the risk of suprascapular nerve (SSN) injury caused by bicortical screws during arthroscopic Latarjet surgery and to identify reliable anatomical landmarks for Latarjet surgery.

38095403

Perceived complexity of total hip arthroplasty: results of a survey of orthopedic surgeons.

No analysis of the perception of the complexity of total hip arthroplasty (THA) has been performed so far. This study aimed to evaluate the perceived complexity of the disorders faced by orthopedic surgeons in the evaluation process prior to THA.

38095404

Use of chloroprocaine in orthopedic day surgery: a brief report in a cohort of patients undergoing knee arthroscopy.

Spinal anesthesia with local anesthetics is a viable alternative to general anesthesia in orthopedic surgery, and it is currently considered the standard of care for knee arthroscopy. The use of chloroprocaine may offer several potential advantages over other local anesthetics, including, above all, its rapid onset and short duration of action. The aim of the present retrospective study is to evaluate the post-surgical outcomes of patients who underwent knee arthroscopy using spinal anesthesia with chloroprocaine in an outpatient orthopedic setting.

38095405

Molecular docking and network pharmacological analysis of Scutellaria baicalensis against renal cell carcinoma.

This paper employs network pharmacology and molecular docking to analyze the active components, targets, and molecular mechanisms of Scutellaria baicalensis in treating renal cell carcinoma (RCC).

38095406

Evidence from Mendelian randomization: increased risk of miscarriage in patients with asthma.

Several observational studies have revealed a possible association between asthma and miscarriage. However, inferring causal relationships from observational studies may be fraught with problems like bias, reverse causation, and residual confounding. Therefore, to assess the possible causal effect of asthma on miscarriage, we performed a two-sample Mendelian randomization (MR) analysis.

38095407

Causal association between aspirin use and risk of endometrioid carcinoma: a Mendelian randomization study.

The aim of the study was to investigate the causal relationship between aspirin use and the risk of endometrial endometrioid cancer (EEC) using two-sample Mendelian randomization (TSMR) and multivariable Mendelian randomization (MVMR) study.

38095408

Efficacies of different ovarian hyperstimulation protocols in elderly patients with poor ovarian response.

The aim of the study was to explore which controlled ovarian hyperstimulation (COH) protocol is most suitable for elderly patients with poor ovarian response (POR) undergoing assisted reproductive technology (ART).

38095409

A risk model based on the tumor microenvironment to predict survival and immunotherapy efficacy for ovarian cancer.

Based on the interactions between immune components in the tumor microenvironment and ovarian cancer (OC) cells, immunotherapies have been demonstrated to be effective in dramatically increasing survival rates. This study aimed to identify landmark genes, develop a prognostic risk model, and explore its relevance to the efficacy of immunotherapy.

38095410

The association between the serum concentration of CXC subfamily chemokine 13 and post-surgical clinical outcomes in cervical cancer patients.

This study aimed to investigate the relationship between serum levels of CXC subfamily chemokine 13 (CXCL13) and clinical outcomes following radical surgery for cervical cancer.

38095411

Oxygen-ozone autohemotherapy in breast cancer patients suffering from fatigue and musculoskeletal pain upon aromatase inhibitors treatment: a case-series study.

In patients with breast cancer and positive hormone receptors, aromatase inhibitors are effective in reducing the risk of recurrences and are active in progressing the disease in this setting. On the other hand, fatigue and painful musculoskeletal side effects can significantly reduce treatment compliance. With no further treatment options to control these symptoms, non-pharmaceutical interventions, such as oxygen-ozone therapy, may play a role in managing rheumatologic symptomatology inasmuch. We have previously reported evidence on the effectiveness of oxygen-ozone in the treatment of pain and fatigue in chronic fatigue syndrome and fibromyalgia patients and in oncological patients as well.

38095412

The importance of arterial blood gas analysis as a systemic diagnosis approach in assessing and preventing chronic diseases, from emergency medicine to the daily practice.

Blood gas analysis is a diagnostic tool to evaluate the partial pressures of gas in blood and acid-base content. The use of blood gas analysis enables a clear understanding of respiratory, circulatory, and metabolic disorders. The arterial blood gas (ABG) explicitly analyzes blood taken from an artery, assessing the patient's partial pressure of oxygen (PaO2) and carbon dioxide (PaCO2) pH (acid/base). PaO2 indicates the oxygenation status, and PaCO2 indicates the ventilation status (chronic or acute respiratory failure). PaO2 is affected by hyperventilation, characterized by rapid or deep breathing, and hypoventilation, characterized by slow or shallow breathing. The acid-base balance tested by the ABG procedure measures the pH and PaCO2 directly, while the use of the Hasselbach equation gives the serum bicarbonate (HCO3) and base deficit or excess. The measured HCO3 is based on a strong alkali that frees all CO2 in serum, including dissolved CO2, carbamino compounds, and carbonic acid. The calculation uses a standard chemistry analysis, giving the amount of "total CO2"; the difference will amount to around 1.2 mmol/L. Though ABG is frequently ordered in emergency medicine contests for acute conditions, it may also be needed in other clinical settings. The ABG analysis shows to be an exceptional diagnostic tool, including the group of diseases known as acid-base diseases (ABDs), which include a great variety of conditions such as severe sepsis, septic shock, hypovolemic shock, diabetic ketoacidosis, renal tubular acidosis, chronic respiratory failure, chronic heart failure, and diverse metabolic diseases.

38095413

Menstrual changes after COVID-19 vaccine administration: a systematic review.

During the mass vaccination campaign for COVID-19, cases of menstrual cycle changes in women emerged, so it was thought that the COVID-19 vaccine could affect the menstrual cycle. Over time, these observations have become more frequent, which strengthens the idea. This systematic review aims to show changes in the menstrual cycle after COVID-19 vaccination.

38095415

Elucidating granulocytic myeloid-derived suppressor cell heterogeneity during Staphylococcus aureus biofilm infection.

Myeloid-derived suppressor cells (MDSCs) are pathologically activated immature myeloid cells with immunosuppressive activity that expand during chronic inflammation, such as cancer and prosthetic joint infection (PJI). MDSCs can be broadly separated into two populations based on surface marker expression and function, namely monocytic MDSCs (M-MDSCs) and granulocytic MDSCs (G-MDSCs). G-MDSCs are the most abundant leukocyte infiltrate during PJI; however, how this population is maintained in vivo and cellular heterogeneity is currently unknown. In this study, we identified a previously unknown population of Ly6G + Ly6C + F4/80 + MHCII+ MDSCs during PJI that displayed immunosuppressive properties ex vivo. We leveraged F4/80 and MHCII expression by these cells for further characterization using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), which revealed a distinct transcriptomic signature of this population. F4/80 + MHCII+ MDSCs displayed gene signatures resembling G-MDSCs, neutrophils, and monocytes, but had significantly increased expression of pathways involved in cytokine response/production, inflammatory cell death, and mononuclear cell differentiation. To determine whether F4/80 + MHCII+ MDSCs represented an alternate phenotypic state of G-MDSCs, Ly6G + Ly6C + F4/80-MHCII- G-MDSCs from CD45.1 mice were adoptively transferred into CD45.2 recipients using a mouse model of PJI. A small percentage of transferred G-MDSCs acquired F4/80 and MHCII expression in vivo, suggesting some degree of plasticity in this population. Collectively, these results demonstrate a previously unappreciated phenotype of F4/80 + MHCII+ MDSCs during PJI, revealing that a granulocytic-to-monocytic transition can occur during biofilm infection.

38095416

mSphere of Influence: How host genetics impact microbial pathogenesis and treatment of infectious disease.

Emily Rosowski works in the field of host-pathogen interactions, studying how host innate immune mechanisms control pathogens. In this mSphere of Influence article, she reflects on how "Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections" by D. M. Tobin, F. J. Roca, S. F. Oh, R. McFarland, et al. (Cell 148:434-446, 2012, https://doi.org/10.1016/j.cell.2011.12.023) made an impact on her by investigating how differences in host genetics can affect modes of microbial pathogenesis and inform treatments for infectious disease.

38095414

Influence of dengue virus serotypes on the abundance of <i>Aedes aegypti</i> insect-specific viruses (ISVs).

Label="IMPORTANCE" NlmCategory="OBJECTIVE">In this study, we employed a metagenomic approach to characterize the virome of <i>Aedes aegypti</i> mosquitoes, with and without natural DENV infection, in several regions of Colombia. Our findings indicate that the mosquito virome is predominantly composed of insect-specific viruses (ISVs) and that infection with different DENV serotypes (DENV-1 and DENV-2) could lead to alterations in the relative abundance of viral families and species constituting the core virome in <i>Aedes</i> spp. The study also sheds light on the identification of the genome and evolutionary relationships of the <i>Phasi Charoen-like phasivirus</i> in <i>Ae. aegypti</i> in Colombia, a widespread ISV in areas with high DENV incidence.

38095417

Sulbactam-durlobactam susceptibility test method development and quality control ranges for MIC and disk diffusion tests.

Sulbactam-durlobactam is a &#946;-lactam/&#946;-lactamase inhibitor combination developed to treat hospital-acquired and ventilator-associated bacterial pneumonia caused by <i>Acinetobacter baumannii-calcoaceticus</i> complex (ABC). Durlobactam is a diazabicyclooctane &#946;-lactamase inhibitor with potent activity against Ambler classes A, C, and D serine &#946;-lactamases and restores sulbactam activity against multidrug-resistant ABC. Studies were conducted to establish sulbactam-durlobactam antimicrobial susceptibility testing methods for both broth microdilution minimal inhibitory concentration (MIC) and disk diffusion tests as well as quality control (QC) ranges. To establish the MIC test method, combinations of sulbactam and durlobactam were evaluated using a panel of genetically characterized <i>A. baumannii</i> isolates which were categorized as predicted to be susceptible or resistant based on the spectrum of &#946;-lactamase inhibition by durlobactam. MIC testing with doubling dilutions of sulbactam with a fixed concentration of 4 &#181;g/mL of durlobactam resulted in the greatest discrimination of the pre-defined susceptible and resistant strains. Similarly, the sulbactam/durlobactam 10/10 &#181;g disk concentration showed the best discrimination as well as correlation with the MIC test. <i>A. baumannii</i> NCTC 13304 was selected for QC purposes because it assesses the activity of both sulbactam and durlobactam with clear endpoints. Multi-laboratory QC studies were conducted according to CLSI M23 Tier 2 criteria. A sulbactam-durlobactam broth MIC QC range of 0.5/4-2/4 &#181;g/mL and a zone diameter QC range of 24-30 mm were determined for <i>A. baumannii</i> NCTC 13304 and have been approved by CLSI. These studies will enable clinical laboratories to perform susceptibility tests with accurate and reproducible methods.

38095418

Susceptibility of <i>Toxoplasma gondii</i> to autophagy in human cells relies on multiple interacting parasite loci.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">Autophagy is a process used by cells to recycle organelles and macromolecules and to eliminate intracellular pathogens. Previous studies have shown that some stains of <i>Toxoplasma gondii</i> are resistant to autophagy-dependent growth restriction, while others are highly susceptible. Although it is known that autophagy-mediated control requires activation by interferon gamma, the basis for why parasite strains differ in their susceptibility is unknown. Our findings indicate that susceptibility involves at least five unlinked parasite genes on different chromosomes, including several secretory proteins targeted to the parasite-containing vacuole and exposed to the host cell cytosol. Our findings reveal that susceptibility to autophagy-mediated growth restriction relies on differential recognition of parasite proteins exposed at the host-pathogen interface, thus identifying a new mechanism for cell-autonomous control of intracellular pathogens.

38095419

Interrelation between gut microbiota, SCFA, and fatty acid composition in pigs.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">The vital role of the gut microbiota on its host metabolism makes it essential to know how its modulation is mirrored on the fatty acid composition of the host. Our findings suggest <i>Prevotella</i> spp. and <i>Akkermansia</i> spp. as potential biomarkers for the levels of beneficial short-chain fatty acids and the possible influence of <i>Rikenellaceae</i> RC9 gut group in the backfat and muscle fatty acid composition of the pig.

38095420

Effects of Temperature and Humidity on Energy Dissipation between Human Corneocytes and Nanoasperity Sliding Contacts.

Human haptic perception relies on the ability of sensory receptors underneath the skin corneocyte layer to sense external load, where adhesion and friction play an essential role in nanoscale solid-solid contact. Energy dissipation present at the surface interface due to the change of separation distance during sliding contact was uncovered, but the energy dissipation of human finger skin cell-nanoprobe contact under humidity and temperature conditions has not been investigated yet. In this paper, the energy dissipation of skin corneocyte-nanoprobe interface under variation of both humidity, 0.05-80%RH, and temperature ranging from 25 to 40 °C is directly measured by atomic force microscopy (AFM). Analytical models of dissipation energy for this nanomaterial interface mechanism are developed, and the results are compared to the measured values. AFM measurements of dissipation energy reveal that the amount of dissipated energy caused by water meniscus stretching monotonically increases with humidity and temperature, resulting in adhesion and friction decreases. The purposed analytical model represents that dissipation energy trend.

38095421

The Efficacy of Acupressure for Nausea and Vomiting After Laparoscopic Cholecystectomy: A Meta-analysis Study.

This meta-analysis aims to explore the impact of acupressure on nausea and vomiting for patients undergoing laparoscopic cholecystectomy (LC).

38095422

Stanford University School of Medicine: Our Neurosurgical Heritage.

The legacy of Stanford University's Department of Neurosurgery began in 1858, with the establishment of a new medical school on the West Coast. Stanford Neurosurgery instilled an atmosphere of dedication to neurosurgical care, scientific research, education, and innovation. We highlight key historical events leading to the formation of the medical school and neurosurgical department, the individuals who shaped the department's vision and expansion, as well as pioneering advances in research and clinical care. The residency program was started in 1961, establishing the basis of the current education model with a strong emphasis on training future leaders, and the Moyamoya Center, founded in 1991, became the largest Moyamoya referral center in the United States. The opening of Stanford Stroke Center (1992) and seminal clinical trials resulted in a significant impact on cerebrovascular disease by expanding the treatment window of IV thrombolysis and intra-arterial thrombectomy. The invention and implementation of CyberKnife® (1994) marks another important event that revolutionized the field of radiosurgery, and the development of Stanford's innovative Brain Computer Interface program is pushing the boundaries of this specialty. The more recent launch of the Neurosurgery Virtual Reality and Simulation Center (2017) exemplifies how Stanford is continuing to evolve in this ever-changing field. The department also became a model for diversity within the school as well as nationwide. The growth of Stanford Neurosurgery from one of the youngest neurosurgery departments in the country to a prominent comprehensive neurosurgery center mirrors the history of neurosurgery itself: young, innovative, and willing to overcome challenges.

38095423

Theoretical Study of Microgel Functional Groups' Mobility.

Polymer microgels, micrometer-sized cross-linked polymer particles, are considered to be a promising type of advanced materials for a wide range of applications. To enhance the microgels' applicability, it is essential to incorporate various functional groups into a microparticle polymer network. Yet, the availability of functional groups for the interaction with surroundings depends strongly on the properties of the polymer network and has a great impact on further effective usage. In this theoretical study, we address this question and, with the help of coarse-grained molecular dynamics computer simulations, assess the segmental mobility and accessibility of functional groups bound to polymer network depending on microgel architecture and solvent quality. Additionally, we evaluate the minimum number of functional groups needed to facilitate the hopping mechanism between the functional groups (i.e., charge transfer). As an example of practical implementation of the obtained results, we estimate the optimal network topology for redox-active microgels to provide the maximum charge capacity for the dispersion electrolyte in redox-flow batteries.

38095424

Nanocrystalline Composite Layer Realized by Simple Sintering Without Surface Treatment, Reducing Hydrophilicity and Increasing Thermal Conductivity.

The surface treatment for a polymer-ceramic composite is additionally performed in advanced material industries. To prepare the composite without a surface treatment, the simplest way to manufacture an advanced ceramic-particle is devised. The method is the formation of a nanocrystalline composite layer through the simple liquid-phase sintering. Using magnesia (MgO) which shows hydrophilicity, a nanocrystalline surface layer is realized by liquid-phase sintering. The amorphous matrix of nanocrystalline composite layer makes MgO hydrophobic and ensures miscibility with polymers, and the nanocrystalline MgO ensures high thermal conductivity. In addition, the liquid phase removes the open pores and makes the surface morphology smooth MgO with smooth surface (MgO-SM). Thermal interface materials (TIM) prepared with MgO-SM and epoxy show a high thermal conductivity of &#8776;7.5&#160;W&#160;m^-1 K^-1 , which is significantly higher than 4.5&#160;W m^-1 K^-1 of pure MgO TIM. Consequently, the formation process of a nanocrystalline surface layer utilizing simple liquid-phase sintering is proposed as a fabrication method for a next-generation ceramic-filler. In addition, it is fundamentally identified that the thermal conductivity of MgO depends on the Mg deficiency, and therefore a poly-crystal MgO-SM (produced at a low temperature) has a higher thermal conductivity than a single-crystal MgO (produced at a high temperature).

38095425

Multiscale Synergetic Bandgap/Structure Engineering in Semiconductor Nanofibrous Aerogels for Enhanced Solar Evaporation.

Solar-driven interface evaporation has been identified as a sustainable seawater desalination and water purification technology. Nonetheless, the evaporation performance is still restricted by salt deposition and heat loss owing to weak solar spectrum absorption, tortuous channels, and limited plane area of conventional photothermal material. Herein, the semiconductor nanofibrous aerogels with a narrow bandgap, vertically aligned channels, and a conical architecture are constructed by the multiscale synergetic engineering strategy, encompassing bandgap engineering at the atomic scale and structure engineering at the nano-micro scale. As a proof-of-concept demonstration, a Co-doped MoS₂ nanofibrous aerogel is synthesized, which exhibits the entire solar absorption, superhydrophilic, and excellent thermal insulation, achieving a net evaporation rate of 1.62 kg m^-2 h^-1 under 1 sun irradiation, as well as a synergistically efficient dye ion adsorption function. This work opens up new possibilities for the development of solar evaporators for practical applications in clean water production.

38095426

Oteseconazole versus fluconazole for the treatment of severe vulvovaginal candidiasis: a multicenter, randomized, double-blinded, phase 3 trial.

Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of &#8805;7 and positive <i>Candida</i> infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of <i>Candida</i> species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%; <i>P</i> = 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%; <i>P</i> &lt; 0.0001) and clinical cure (71.25% vs 55.97%; <i>P</i> = 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.

38095427

Pulsed dosing and extended daily dosing of oral vancomycin do not facilitate clearance of <i>Clostridioides difficile</i> colonization in mice.

Vancomycin taper and pulse regimens are commonly used to treat recurrent <i>Clostridioides difficile</i> infections, but the mechanism by which these regimens might reduce recurrences is unclear. Here, we used a mouse model to test the hypothesis that pulse dosing of vancomycin after a 10-day treatment course enhances clearance of <i>C. difficile</i> from the intestinal tract. Mice with <i>C. difficile</i> colonization received 10 days of once-daily oral vancomycin followed by 20 days of treatment with saline (controls), daily vancomycin, or pulse dosing of vancomycin every 2 or 3 days. Stool samples were collected to measure the concentration of C. <i>difficile</i> during and after treatment, vancomycin concentrations, and growth of vegetative <i>C. difficile</i> during every 3 days dosing. Pulse dosing of vancomycin was not effective in maintaining suppression of <i>C. difficile</i> (<i>P</i> &gt; 0.05 in comparison to saline controls); growth of vegetative <i>C. difficile</i> occurred between pulse doses when vancomycin decreased to undetectable levels. Daily dosing of vancomycin suppressed <i>C. difficile</i> during treatment, but recurrent colonization occurred after treatment in more than 75% of mice, and by post-treatment day 14, there was no significant difference among the control, pulse dosing, and daily dosing groups (<i>P</i> &gt; 0.05). These findings demonstrate that pulse dosing of vancomycin every 2 or 3 days does not facilitate the clearance of <i>C. difficile</i> spores in mice. Studies are needed to examine the impact of vancomycin taper and pulsed regimens in patients.

38095428

Synthesis and Antiproliferative Evaluation of d-Glucuronamide-Based Nucleosides and (Triazolyl)methyl Amide-Linked Pseudodisaccharide Nucleosides.

The synthesis and antiproliferative evaluation of novel d-glucopyranuronamide-containing nucleosides is described. Based on our previously reported anticancer d-glucuronamide-based nucleosides, new analogues comprising N/O-dodecyl or N-propargyl substituents at the glucuronamide unit and anomerically-N-linked 2-acetamido-6-chloropurine, 6-chloropurine or 4-(6-chloropurinyl)methyl triazole motifs were synthesized in 4-6 steps starting from acetonide-protected glucofuranurono-6,3-lactone. The methodologies were based on the access to N-substituted glycopyranuronamide precursors, namely 1,2-O-acetyl derivatives or glucuronoamidyl azides for further nucleobase N-glycosylation or 1,3-dipolar cycloaddition with N⁹ - and N⁷ -propargyl-6-chloropurines, respectively. N-Propargyl glucuronamide-based N⁹ -purine nucleosides were converted into (triazolyl)methyl amide-6,6-linked pseudodisaccharide nucleosides via cycloaddition with methyl 6-azido-glucopyranoside. A CuI/Amberlyst A-21 catalytic system employed in the cycloaddition reactions also effected conversion into 6-dimethylaminopurine nucleosides. Antiproliferative evaluation in chronic myeloid leukemia (K562) and breast cancer (MCF-7) cells revealed significant effects exhibited by the synthesized monododecylated purine-containing nucleosides. A N-propargyl 3-O-dodecyl glucuronamide derivative comprising a N⁹ -&#946;-linked 6-chloropurine moiety was the most active compound against MCF-7 cells (GI₅₀ =11.9&#8197;&#956;M) while a related &#945;-(purinyl)methyltriazole nucleoside comprising a N⁷ -linked 6-chloropurine moiety exhibited the highest activity against K562 cells (GI₅₀ =8.0&#8197;&#956;M). Flow cytometry and immunoblotting analysis of apoptosis-related proteins in K562 cells treated with the N-propargyl 3-O-dodecyl glucuronamide-based N⁹ -linked 6-chloropurine nucleoside indicated that it acts via apoptosis induction.

38095429

Transmission of antimicrobial resistance in the gut microbiome of gregarious cockroaches: the importance of interaction between antibiotic exposed and non-exposed populations.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">Antimicrobial resistance is a rising threat to human and animal health. The spread of resistance through the transmission of the symbiotic gut microbiome is of concern and has been explored in theoretical modeling studies. In this study, we employ gregarious insect populations to examine the emergence and transmission of antimicrobial resistance <i>in vivo</i> and validate modeling hypotheses. We find that antimicrobial treatment increases the levels of resistance in treated populations. Most importantly, we show that resistance increased in untreated populations after interacting with the treated ones. The level of resistance transmission was affected by the magnitude and frequency of population mixing. Our results highlight the importance of microbial transmission in the spread of antimicrobial resistance.

38095430

Draft genome sequence of multidrug-resistant <i>Vibrio navarrensis</i> strain DA9 isolated from a coastal canal in the Florida Keys (USA).

A presumptive <i>Vibrio</i> isolate with a multidrug resistance profile was isolated from surface seawater collected from a coastal canal in 2014 and identified as <i>Vibrio navarrensis</i>, designated as strain DA9. Here, we report a 5.1-Mb draft genome sequence of strain DA9 with a G + C content of 47.5%.

38095431

Stereotactic radiosurgery for non-functioning pituitary tumor: a multicenter study of new pituitary hormone deficiency.

Stereotactic radiosurgery (SRS) is used to treat recurrent or residual nonfunctioning pituitary neuroendocrine tumors (NFPA). The objective of the study was to assess imaging and development of new pituitary hormone deficiency.

38095432

Xylan-Directed Cell Wall Assembly in Grasses.

Xylan is the most abundant hemicellulosic polysaccharide in the cell walls of grasses and is pivotal for the assembly of distinct cell wall structures that govern various cellular functions. Xylan also plays a crucial role in regulating biomass recalcitrance, ultimately affecting the utilization potential of lignocellulosic materials. Over the past decades, our understanding of the xylan biosynthetic machinery and cell wall organization has substantially improved, due to the innovative application of multiple state-of-the-art techniques. Notably, novel xylan-based nanostructures have been revealed in the cell walls of xylem vessels, promoting a more extensive exploration of the role of xylan in the formation of cell wall structures. This Update summarizes recent achievements in understanding xylan biosynthesis, modification, modeling and compartmentalization in grasses, providing a brief overview of cell wall assembly from the perspective of xylan. We also discuss the potential for tailoring xylan to facilitate the breeding of elite energy and feed crops.

38095433

Erratum for Gebo et al., "Early antibody treatment, inflammation, and risk of post-COVID conditions".

38095434

Dural Arteriovenous Fistulas With Cognitive Impairment: Angiographic Characteristics and Treatment Outcomes.

Anecdotal cases of rapidly progressing dementia in patients with dural arteriovenous fistulas (dAVFs) have been reported in small series. However, large series have not characterized these dAVFs. We conducted an analysis of the largest cohort of dAVFs presenting with cognitive impairment (dAVFs-CI), aiming to provide a detailed characterization of this subset of dAVFs.

38095435

Bio-Responsive Sliver Peroxide-Nanocarrier Serves as Broad-spectrum Metallo-β-lactamase Inhibitor for Combating Severe Pneumonia.

Metallo-&#946;-lactamases (MBLs) represent a prevalent resistance mechanism in Gram-negative bacteria, rendering last-line carbapenem-related antibiotics ineffective. Here, a bio-responsive sliver peroxide (Ag₂ O₂ )-based nanovesicle, named Ag₂ O₂ @BP-MT@MM, was developed as a broad-spectrum MBL inhibitor for combating MBL-producing bacterial pneumonia. Ag₂ O₂ nanoparticle was first orderly modified with bovine serum albumin and polydopamine to co-load meropenem (MER) and [5-(p-fluorophenyl)-2-ureido]-thiophene-3-carboxamide (TPCA-1) and then encapsulated with macrophage membrane (MM) aimed to target inflammatory lung tissue specifically. The resultant Ag₂ O₂ @BP-MT@MM effectively abrogated MBL activity by displacing the Zn²⁺ cofactor with Ag⁺ in MBLs and displayed potent bactericidal and anti-inflammatory properties, specific targeting abilities, and great bio-responsive characteristics. After intravenous injection, the nanoparticles accumulated prominently at infection sites through MM-mediated targeting and acid-responsive drug release. Ag⁺ released from Ag₂ O₂ decomposition at the infection sites effectively inhibited MBL activity and overcame the resistance of MBL-producing bacteria to MER, resulting in synergistic elimination of MBL-producing bacteria in conjunction with MER. In two murine infection models of NDM-1⁺ Klebsiella pneumoniae-induced severe pneumonia and NDM-1⁺ Escherichia coli-induced sepsis-related bacterial pneumonia, the nanoparticles significantly reduced bacterial loading, pro-inflammatory cytokine levels locally and systemically, and the recruitment and activation of neutrophils and macrophages. The modality also protected the lungs from severe injury. This innovative approach presents a promising new strategy for combating infections caused by MBL-producing carbapenem-resistant bacteria. This article is protected by copyright. All rights reserved.

38095436

A H₂ S-Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation.

Photodynamic therapy (PDT) is a promising treatment against bacteria-caused infections. By producing large amounts of reactive oxygen species (ROS), PDT can effectively eliminate pathogenic bacteria, without causing drug resistance. However, excessive ROS may also impose an oxidative stress on surrounding tissues, resulting in local inflammation. To avoid this major drawback and limit pro-inflammation during PDT, this work prepared a supramolecular photosensitizer (TPP-CN/CP5) based on host-guest interactions between a cysteine-responsive cyano-tetraphenylporphyrin (TPP-CN) and a water-soluble carboxylatopillar[5]arene (CP5). TPP-CN/CP5 not only possesses excellent photodynamic antibacterial properties, but also shows good anti-inflammatory and cell protection capabilities. Under 660&#160;nm light irradiation, TPP-CN/CP5 could rapidly produce abundant ROS for sterilization. After the PDT process, the addition of cysteine (Cys) triggers the release of H₂ S from TPP-CN. H₂ S then stops the induced inflammation by inhibiting the production of related inflammatory factors. Both in vitro and in vivo experiments show the excellent antibacterial effects and anti-inflammatory abilities of TPP-CN/CP5. These results will certainly promote the clinical application of PDT in the treatment of bacterial infectious diseases.

38095437

<i>Mucorales</i> fungi suppress nitric oxide production by macrophages.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">In October 2022, <i>Mucorales</i> fungi were listed in the "High Priority Group" on the first-ever list of fungal priority pathogens by the World Health Organization. As the causative agent of mucormycosis, <i>Mucorales</i> have become of great clinical and public health importance with growing mucormycosis numbers, notably with the exponential rise of COVID-19-associated mucormycosis cases. Despite the dire need, there are limited therapeutic options to treat mucormycosis. Our research fills in critical gaps of knowledge about how <i>Mucorales</i> fungi evade the host immune system. Specifically, we offer evidence that <i>Mucorales</i> block nitric oxide production, which is a key mediator and signaling molecule of the mammalian innate immune response to microbial pathogens. Our work offers new insight into immune evasion mechanisms by <i>Mucorales</i> fungi.

38095438

Wastewater-based surveillance as a tool for public health action: SARS-CoV-2 and beyond.

SUMMARYWastewater-based surveillance (WBS) has undergone dramatic advancement in the context of the coronavirus disease 2019 (COVID-19) pandemic. The power and potential of this platform technology were rapidly realized when it became evident that not only did WBS-measured SARS-CoV-2 RNA correlate strongly with COVID-19 clinical disease within monitored populations but also, in fact, it functioned as a leading indicator. Teams from across the globe rapidly innovated novel approaches by which wastewater could be collected from diverse sewersheds ranging from wastewater treatment plants (enabling community-level surveillance) to more granular locations including individual neighborhoods and high-risk buildings such as long-term care facilities (LTCF). Efficient processes enabled SARS-CoV-2 RNA extraction and concentration from the highly dilute wastewater matrix. Molecular and genomic tools to identify, quantify, and characterize SARS-CoV-2 and its various variants were adapted from clinical programs and applied to these mixed environmental systems. Novel data-sharing tools allowed this information to be mobilized and made immediately available to public health and government decision-makers and even the public, enabling evidence-informed decision-making based on local disease dynamics. WBS has since been recognized as a tool of transformative potential, providing near-real-time cost-effective, objective, comprehensive, and inclusive data on the changing prevalence of measured analytes across space and time in populations. However, as a consequence of rapid innovation from hundreds of teams simultaneously, tremendous heterogeneity currently exists in the SARS-CoV-2 WBS literature. This manuscript provides a state-of-the-art review of WBS as established with SARS-CoV-2 and details the current work underway expanding its scope to other infectious disease targets.

38095439

Complete genome sequence of <i>Heyndrickxia</i> (<i>Bacillus</i>) <i>coagulans</i> BC99 isolated from a fecal sample of a healthy infant.

This study reports the complete genome sequence of <i>Heyndrickxia (Bacillus) coagulans</i> BC99, a promising human probiotic strain isolated from the fecal sample of a healthy infant in Hailaer Inner Mongolia. The genome sequence of BC99 contains a 3,655,496-bp circular chromosome with a GC content of 46.23%. Genome annotation predicted 3,273 protein-coding genes.

38095440

The interplay between the muscle and liver in the regulation of glucolipid metabolism.

38095441

The synergy of transcriptional and epigenetic controls promotes fruit ripening in peach.

38095442

A 3D Cross-Linked Metal-Organic Framework (MOF)-Derived Polymer Electrolyte for Dendrite-Free Solid-State Lithium-Ion Batteries.

Lithium metal batteries (LMBs) with high energy density have received widespread attention; however, there are usually issues with lithium dendrite growth and safety. Therefore, there is a demand for solid electrolytes with high mechanical strength, room-temperature ionic conductivity, and good interface performance. Herein, a 3D cross-linked metal-organic framework (MOF)-derived polymer solid electrolyte exhibits good mechanical and ionic conductive properties simultaneously, in which the MOF with optimized pore size and strong imidazole cation sites can restrict the migration of anions, resulting in a uniform Li⁺ flux and a high lithium-ion transference number (0.54). Moreover, the MOF-derived polymer solid electrolytes with the 3D cross-linked network can promote the rapid movement of Li⁺ and inhibit the growth of lithium dendrites. Lithium symmetric batteries assembled with the 3D MOF-derived polymer solid electrolytes are subjected to lithium plating/stripping and cycled over 2000&#160;h at a current density of 0.1&#160;mA cm^-2 and over 800&#160;h at a current density of 0.2&#160;mA cm^-2 . The Li/P-PETEA-MOF/LiFePO₄ batteries exhibit excellent long-cycle stability and cycle reversibility.

38095444

Boosting Reactive Oxygen Species Generation with a Dual-Catalytic Nanomedicine for Enhanced Tumor Nanocatalytic Therapy.

Generating lethal reactive oxygen species (ROS) within tumors by nanocatalytic medicines is an advanced strategy for tumor-specific therapy in recent years. Nevertheless, the low yield of ROS restrains its therapeutic efficiency. Herein, a dual-catalytic nanomedicine based on tumor microenvironment (TME)-responsive liposomal nanosystem co-delivering CuO₂ and dihydroartemisinin (DHA) (LIPSe@CuO₂&amp;DHA) is developed to boost ROS generation against tumor. The liposomal nanosystem can degrade in the ROS-overexpressed TME and liberate CuO₂ and DHA to initiate Cu-based dual-catalytic ROS generation. Serving as generators of H₂O₂ and Cu²⁺, CuO₂ can self-produce plenty of toxic hydroxyl radicals via Fenton-like reaction in the acidic TME. Meanwhile, the released Cu²⁺ can catalyze DHA to generate cytotoxic C-centered radicals. Together, the self-supplied H₂O₂ and Cu-based dual-catalytic reaction greatly increase the intratumoral level of lethal ROS. Importantly, Cu²⁺ can decrease the GSH-mediated scavenging effect on the produced ROS via a redox reaction and undergo a Cu²⁺-to-Cu⁺ conversion to enhance the Fenton-like reaction, further guaranteeing the high efficiency of ROS generation. Resultantly, LIPSe@CuO₂&amp;DHA induces remarkable cancer cell death and tumor growth inhibition, which may present a promising nanocatalytic medicine for cancer therapy.

38095443

Janus Zn-IV-VI: Robust Photocatalysts with Enhanced Built-In Electric Fields and Strain-Regulation Capability for Water Splitting.

The use of 2D materials to produce hydrogen (H₂ ) fuel via photocatalytic water splitting has been intensively studied. However, the simultaneous fulfillment of the three essential requirements-high photon utilization, rapid carrier transfer, and low-barrier redox reactions-for wide-pH-range production of H₂ still poses a significant challenge with no&#160;additional modulation. By employing the first-principles calculations, it has been observed that the Janus ZnXY₂ structures (X = Si/Ge/Sn, Y = S/Se/Te) exhibit significantly enhanced built-in electric fields (0.20-0.36&#160;eV&#160;&#197;^-1 ), which address the limitations intrinsically. Compared to conventional Janus membranes, the ductile ZnSnSe₂ and ZnSnTe₂ monolayers have stronger regulation of electric fields, resulting in improved electron mobility and excitonic nature (E_binding = 0.50/0.35&#160;eV). Both monolayers exhibit lower energy barriers of hydrogen evolution reaction (HER, 0.98/0.86&#160;eV, pH = 7) and resistance to photocorrosion across pH 0-7. Furthermore, the 1% tensile strain can further boost visible light utilization and intermediate absorption. The optimal AC-type bilayer stacking configuration is conducive to enhancing electric fields for photocatalysis. Overall, Janus ZnXY₂ membranes overcome the major challenges faced by conventional 2D photocatalysts via intrinsic polarization and external amelioration, enabling efficient and controllable photocatalysis without the need for doping or heterojunctions.

38095446

Amorphization of Inorganic Solid Electrolyte Interphase Components and Its Impact on Enhancing Their Transport and Mechanical Properties.

The safety and cycle life of lithium-ion batteries (LIBs) are largely determined by the solid electrolyte interphase (SEI) formed on the surface of the anode. However, there is still a lack of understanding regarding the structure and properties of the individual SEI components. Among others, lithium oxide (Li₂O), lithium carbonate (Li₂CO₃), and lithium fluoride (LiF) are known to be the main components of the inorganic SEI layer in conventional LIBs, but their intrinsic protective roles remain controversial. Herein, we present the transformational effects of their amorphous phase on the mechanical and transport characteristics, based on first-principles calculations. Our studies clearly demonstrate that their amorphous phases exhibit significantly improved Li-ion conductivity when compared to the crystalline structures. Additionally, among them, amorphous LiF emerges as a frontrunner for fast Li⁺ ion transportation, reversing the conventionally understood hierarchy. Under ambient conditions, the amorphous phases of LiF, Li₂O, and Li₂CO₃ are thermodynamically unstable and tend to undergo recrystallization. However, this work highlights that exceptionally ductile and resilient amorphous phases can form if SEI formation and growth would involve some admixing of lithiophilic impurities like nitrogen (N) within the host matrices.

38095447

KSHV-encoded LANA bypasses transcriptional block through the stabilization of RNA Pol II in hypoxia.

Hypoxia can induce the reactivation of Kaposi sarcoma-associated virus (KSHV), which necessitates the synthesis of critical structural proteins. Despite the unfavorable energetic conditions of hypoxia, KSHV utilizes mechanisms to prevent the degradation of essential cellular machinery required for successful reactivation. Our study provides new insights on strategies employed by KSHV-infected cells to maintain steady-state transcription by overcoming hypoxia-mediated metabolic stress to enable successful reactivation. Our discovery that the interaction of latency-associated nuclear antigen with HIF1α and NEDD4 inhibits its polyubiquitination activity, which blocks the degradation of RNA Pol II during hypoxia, is a significant contribution to our understanding of KSHV biology. This newfound knowledge provides new leads in the development of novel therapies for KSHV-associated diseases.

38095445

Chimeric Peptide-Engineered Self-Delivery Nanomedicine for Photodynamic-Triggered Breast Cancer Immunotherapy by Macrophage Polarization.

A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6)&#160;and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG₈ -CREKA. ChiP-CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high-mobility group box-1(HMGB1)&#160;and expose calreticulin (CRT). Moreover, ChiP-CeR can also polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP-CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.

38095448

Evaluation of solid-phase extraction sorbents for purification of oligosaccharides and glycans derivatized by positively charged labels followed by capillary electrophoretic analysis.

The sample preparation including labeling and clean-up represents a key analytical step in the analysis of oligosaccharides and glycans by either chromatographic or electrophoretic separation methods. Although the majority of labeling has been performed by neutral and/or negatively charged tags, the introduction of a positive charge into the saccharide molecule can significantly improve the analysis, especially with mass spectrometry detection. In this work, we present the evaluation of five solid-phase extraction sorbents differing in extraction chemistry for the clean-up and concentration of positively labeled maltooligosaccharides from the reaction mixtures. Maltooligosaccharides containing four to seven glucose units were labeled by cationic tags (2-aminoethyl)trimethylammonium chloride and (carboxymethyl)trimethylammonium chloride hydrazide and the extraction conditions were optimized followed by electrophoretic analysis with conductivity detection. The effects of the solid-phase extraction sorbent chemistry, extraction conditions, and sample composition are discussed. All tested sorbents were capable of cleaning up maltooligosaccharides from the reaction mixtures to some extent after optimization of the solid-phase extraction procedure (51.9%-98.9% recovery). The best-rated amide-based sorbent was used to process the sample of N-linked glycans enzymatically released from ribonuclease B.

38095449

Poly-omic risk scores predict inflammatory bowel disease diagnosis.

Complex traits are characterized by many biological and environmental factors, such that multi-omic data sets are well-positioned to help us understand their underlying etiologies. We applied a prediction framework across multiple omics (metagenomics, metatranscriptomics, metabolomics, and viromics) from the gut ecosystem to predict inflammatory bowel disease (IBD) diagnosis. The predicted scores from our models highlighted key features and allowed us to compare the relative utility of each omic data set in single-omic versus multi-omic models. Our results emphasized the importance of metabolomics and viromics over metagenomics and metatranscriptomics for predicting IBD status. The greater predictive capability of metabolomics and viromics is likely because these omics serve as markers of lifestyle factors such as diet. This study provides a modeling framework for multi-omic data, and our results show the utility of combining multiple omic data types to disentangle complex disease etiologies and biological signatures.

38095450

Core-Satellite Nanoassemblies as SPR/SERS Dual-Mode Plasmonic Sensors for Sensitively Detecting Ractopamine in Complex Media.

Highly sensitive and reliable detection of β-adrenergic agonists is especially necessary due to the illegal abuse of growth-promoting feed additives. Here, we develop a novel surface plasmon resonance/surface-enhanced Raman scattering (SPR/SERS) dual-mode plasmonic sensor based on core-satellite nanoassemblies for the highly sensitive and reliable detection of ractopamine (RAC). The addition of RAC results in the decomposition of core-satellite nanoassemblies and consequently changes the Rayleigh scattering color of dark-field microscopy (DFM) images and the Raman scattering intensity of SERS spectra. The excellent sensitivity, specificity, and uniformity of this strategy were confirmed by detecting RAC in various complex media in the farm-to-table chain, and the limit of detection (LOD) was 0.03 ng/mL in an aqueous solution. In particular, the convenient access to livestock sewage not only ensures animal welfare but also provides great convenience for the market regulation of β-agonists. The success of our on-site strategy only with a portable Raman device promises great application prospects for β-agonist detection.

38095451

A Dynamically Stable Sulfide Electrolyte Architecture for High-Performance All-Solid-State Lithium Metal Batteries.

All-solid-state batteries employing sulfide solid electrolyte and Li metal anode are promising because of their high safety and energy densities. However, the interface between Li metal and sulfides suffers from catastrophic instability which stems the practical use. Here, a dynamically stable sulfide electrolyte architecture to construct the hierarchy of interface stability is reported. By rationally designing the multilayer structures of sulfide electrolytes, the dynamic decomposing-alloying process from MS₄ (M = Ge or Sn) unit in sulfide interlayer can significantly prohibit Li dendrite penetration is revealed. The abundance of highly electronic insulating decompositions, such as Li₂ S, at the sulfide interlayer interface helps to well constrain the dynamic decomposition process and preserve the long-term polarization stability is also highlighted. By using Li₆ PS₅ Cl||Li₁₀ SnP₂ S₁₂ ||Li₆ PS₅ Cl electrolyte architecture, Li metal anode shows an unprecedented critical current density over 3&#160;mA&#160;cm^-2 and achieves the steady over-potential for &#8776;900 hours. Based upon the merits, the Li||LiNi_0.8 Co_0.1 Mn_0.1 O₂ battery delivers a remarkable 75.3% retention even after 600 cycles at 1 C (1C-0.95&#160;mA&#160;cm^-2 ) under a low stack pressure of 15&#160;MPa.

38095452

Reduced sleep quality is highly prevalent and associated with physical function and cardiorespiratory fitness in patients with axial spondyloarthritis: a cross-sectional study.

To assess sleep quality, and its associations with physical function, cardiorespiratory fitness, and spinal mobility, in axial spondyloarthritis (axSpA) patients.

38095453

Sniffing Like a Wine Taster: Multiple Overlapping Sniffs (MOSS) Strategy Enhances Electronic Nose Odor Recognition Capability.

As highly promising devices for odor recognition, current electronic noses are still not comparable to human olfaction due to the significant disparity in the number of gas sensors versus human olfactory receptors. Inspired by the sniffing skills of wine tasters to achieve better odor perception, a multiple overlapping sniffs (MOSS) strategy is proposed in this study. The MOSS strategy involves rapid and continuous inhalation of odorants to stimulate the sensor array to generate feature-rich temporal signals. Computational fluid dynamics simulations are performed to reveal the mechanism of complex dynamic flows affecting transient responses. The proposed strategy shows over 95% accuracy in the recognition experiments of three gaseous alkanes and six liquors. Results demonstrate that the MOSS strategy can accurately and easily recognize odors with a limited sensor number. The proposed strategy has potential applications in various odor recognition scenarios, such as medical diagnosis, food quality assessment, and environmental surveillance.

38095455

Optoelectronic Materials and Devices.

38095456

Flagellar interference with plasmid uptake in biofilms: a joint experimental and modeling study.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">Biofilms are the dominant form of microbial life and bacteria living in biofilms are markedly different from their planktonic counterparts, yet the impact of the biofilm lifestyle on horizontal gene transfer (HGT) is still poorly understood. Horizontal gene transfer by conjugative plasmids is a major driver in bacterial evolution and adaptation, as exemplified by the troubling spread of antibiotic resistance. To either limit or promote plasmid prevalence and dissemination, we need a better understanding of plasmid transfer between bacterial cells, especially in biofilms. Here, we identified a new factor impacting the transfer of plasmids, flagella, which are required for many types of bacterial motility. We show that their absence or altered activity can lead to enhanced plasmid uptake in two bacterial species, <i>Xanthomonas retroflexus</i> and <i>Pseudomonas putida</i>. Moreover, we demonstrate the utility of mathematical modeling to eliminate hypothetical mechanisms.

38095457

Late Editor-In-Chief of Indian Journal of Medical Research.

38095454

High-performance liquid chromatography analysis of alkaloids in various parts of lotus extracts with ion mobility spectrometry and mass spectrometry dual detection.

Using high-performance liquid chromatography coupled with electrospray ionization-ion mobility spectrometry and mass spectrometry, we proposed a dual-detection method for the identification and profiling of alkaloids in various lotus parts including leaf, plumule, stem, seed epicarp, and receptacle. The eluent from high-performance liquid chromatography was split and conducted to electrospray ionization-ion mobility spectrometry and time-of-flight mass spectrometry separately to facilitate the compound identification. In total, 23 kinds of alkaloids were identified based on m/z, drift time, and retention time, including alkaloid isomers such as lirinidine, N-nornuciferine, and O-nornuciferine with identical m/z that are difficult to differentiate using mass spectrometry alone. Using this method, we investigated the changing dynamics of alkaloid accumulation in lotus leaves and lotus stems at different harvesting periods. The total alkaloid content showed an increasing trend with the growth and development of leave and stem. Overall, the developed dual detection method has the advantages of high peak capacity and high sensitivity compared with the conventional detection method and facilitates the identification of detected compounds.

38095458

Elaborated pseudoknots that stimulate -1 programmed ribosomal frameshifting or stop codon readthrough in RNA viruses.

Pseudoknots assume various functions including stimulation of -1 programmed ribosomal frameshifting (PRF) or stop codon readthrough (SCR) in RNA viruses. These pseudoknots vary greatly in sizes and structural complexities. Recent biochemical and structural studies confirm the three-stemmed pseudoknots as the -1 PRF stimulators in the severe acute respiratory syndrome coronavirus 2 (SARS<i>-</i>CoV<i>-</i>2) and related coronaviruses. We reexamined previously reported -1 PRF or SCR stimulating pseudoknots, especially those containing a relatively long connecting loop between the two pseudoknot-forming stems, for their ability to form elaborated structures. Many potential elaborated pseudoknots were identified that contain one or more of the following extra structural elements: stem-loop, embedded pseudoknot, kissing hairpins, and additional loop-loop interactions. The elaborated pseudoknots are found in several different virus families that utilize either the -1 PRF or SCR recoding mechanisms. Model-building studies were performed to not only establish the structural feasibility of the elaborated pseudoknots but also reveal potential additional structural features that cannot be readily inferred from the predicted secondary structures. Some of the structures, such as embedded double pseudoknots and compact loop-loop pseudoknots mediated by the previously established common pseudoknot motif-1 (CPK-1), represent the first of its kind in the literatures. By advancing discovery of new functional RNA structures, we significantly expand the repertoire of known elaborated pseudoknots that could potentially play a role in -1 PRF and SCR regulation. These results contribute to a better understanding of RNA structures in general, facilitating the design of engineering RNA molecules with certain desired functions.Communicated by Ramaswamy H. Sarma.

38095459

Dual Interface Compatibility Enabled via Composite Solid Electrolyte with High Transference Number for Long-Life All-Solid-State Lithium Metal Batteries.

The development of solid-state electrolytes (SSEs) effectively solves the safety problem derived from dendrite growth and volume change of lithium during cycling. In the meantime, the SSEs possess non-flammability compared to conventional organic liquid electrolytes. Replacing liquid electrolytes with SSEs to assemble all-solid-state lithium metal batteries (ASSLMBs) has garnered significant attention as a promising energy storage/conversion technology for the future. Herein, a composite solid electrolyte containing two inorganic components (Li_6.25 Al_0.25 La₃ Zr₂ O₁₂ , Al₂ O₃ ) and an organic polyvinylidene difluoride matrix is designed rationally. X-ray photoelectron spectroscopy and density functional theory calculation results demonstrate the synergistic effect among the components, which results in enhanced ionic conductivity, high lithium-ion transference number, extended electrochemical window, and outstanding dual interface compatibility. As a result, Li||Li symmetric battery maintains a stable cycle for over 2500&#160;h. Moreover, all-solid-state lithium metal battery assembled with LiNi_0.6 Co_0.2 Mn_0.2 O₂ cathode delivers a high discharge capacity of 168&#160;mAh&#160;g^-1 after 360 cycles at 0.1&#160;C at 25&#160;&#176;C, and all-solid-state lithium-sulfur battery also exhibits a high initial discharge capacity of 912&#160;mAh&#160;g^-1 at 0.1&#160;C. This work demonstrates a long-life flexible composite solid electrolyte with excellent interface compatibility, providing an innovative way for the rational construction of next-generation high-energy-density ASSLMBs.

38095460

Characterization and quality evaluation of QiXueShuFu Decoction based on fingerprint and ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry.

QiXueShuFu Decoction (QXSFD) modified from the Bazhen Decoction which was originally from the classic Ming Dynasty is a traditional folk formula that boosts the body's immune system. However, its ambiguous chemical components limited its quality control evaluation. In this study, ultra-performance liquid chromatography (UPLC) fingerprint combined with multivariate analysis was used to evaluate the quality of 15 batches of QXSFD, and UPLC quadrupole-orbitrap mass spectrometry was used to further examine the chemical components in QXSFD, after which representative compounds from each disassembled prescription were selected for comparison. Fifteen batches of samples had 33 common peaks in which 11 differential components could be used as a reference for subsequent quality control. One hundred forty-three components were identified from QXSFD. Saponins were mainly derived from the monarch, terpenes from the minister, and polysaccharides and glycosides from the assistant. In addition, quantitative assay revealed that the content of ferulic acid, chlorogenic acid, 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside and 3,6'-disinapoyl sucrose in the whole prescription were higher than the contents of each disassembled prescription. This is the first comprehensive quality report on the chemical components of QXSFD, which is important for pharmacodynamic material basis and quality control.

38095461

Spermine enhances the activity of anti-tuberculosis drugs.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">This is the first study that attempted to demonstrate the mechanisms of reactive oxygen species (ROS) generation by spermine (Spm) in <i>Mycobacterium tuberculosis</i> (M.tb). Furthermore, this is the first study to demonstrate that it is able to enhance the activity of currently available and World Health Organization (WHO)-approved tuberculosis (TB) drugs. Spermine can easily be obtained since it is already found in our diet. Moreover, as opposed to conventional antibiotics, it is less toxic to humans since it is found in millimolar concentrations in the body. Finally, with the difficulty of curing TB with conventional antibiotics, this study suggests that less toxic molecules, such as Spm, could in a long-term perspective be incorporated in a TB regimen to boost the treatment.

38095462

Effects of variation in sample storage conditions and swab order on 16S vaginal microbiome analyses.

The composition of the human vaginal microbiome has been linked to a variety of medical conditions including yeast infection, bacterial vaginosis, and sexually transmitted infection. The vaginal microbiome is becoming increasingly acknowledged as a key factor in personal health, and it is essential to establish methods to collect and process accurate samples with self-collection techniques to allow large, population-based studies. In this study, we investigate if using AssayAssure Genelock, a nucleic acid preservative, introduces microbial biases in self-collected vaginal samples. To our knowledge, we also contribute some of the first evidence regarding the impacts of multiple swabs taken at one time point. Vaginal samples have relatively low biomass, so the ability to collect multiple swabs from a unique participant at a single time would greatly improve the replicability and data available for future studies. This will hopefully lay the groundwork to gain a more complete and accurate understanding of the vaginal microbiome.

38095463

<i>A. castellanii</i> and <i>P. aeruginosa</i> mutually exacerbate damage to corneal cells during coinfection.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">At the National Cheng Kung University Hospital, numerous cases of amoebic keratitis had been identified with concurrent bacterial infections. Among these bacterial coinfections, <i>Pseudomonas aeruginosa</i> accounted for 50% of the reported cases. However, the impact of pathogenic bacteria on amoeba-induced corneal damage remains unclear. In our study, we successfully demonstrated that <i>P. aeruginosa</i> accumulated on the <i>Acanthamoeba castellanii</i> surface and caused more severe corneal damage. We also indicated that the exposure of <i>P. aeruginosa</i> to amoeba-soluble antigens enhanced its adhesion ability, promoted biofilm formation, and led to more severe corneal cell damage. These findings significantly contributed to our understanding of the risk associated with <i>P. aeruginosa</i> coinfection in the progression of amoeba keratitis.

38095465

Evaluation of a minimal array of <i>Treponema pallidum</i> antigens as biomarkers for syphilis diagnosis, infection staging, and response to treatment.

This manuscript explores the host humoral response to selected antigens of the syphilis agent during infection to evaluate their potential use as diagnostic tests and markers for treatment.

38095464

Structure-based virtual screening and <i>in vitro</i> validation of inhibitors of cyclic dinucleotide phosphodiesterases ENPP1 and CdnP.

Label="IMPORTANCE" NlmCategory="OBJECTIVE">In this paper, we describe novel inhibitors of cyclic dinucleotide phosphodiesterase enzymes from <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>) (CdnP) and mammals (ENPP1). The phosphodiesterase enzymes hydrolyze cyclic dinucleotides, such as 2',3'-cyclic GMP-AMP and c-di-AMP, which are stimulator of interferon gene (STING) agonists. By blocking the hydrolysis of STING agonists, the cyclic GMP-AMP synthase (cGAS)-STING-IRF3 pathway is potentiated. There is strong evidence in tuberculosis and in cancer biology that potentiation of the cGAS-STING-IRF3 pathway leads to improved <i>M.tb</i> clearance and also improved antitumor responses in cancer. In addition to the identification of novel inhibitors and their biochemical characterization, we provide proof-of-concept evidence that our E-3 inhibitor potentiates the cGAS-STING-IRF3 pathway in both macrophage cell lines and also in primary human monocyte-derived macrophages.

38095466

Microbiota-accessible fiber activates short-chain fatty acid and bile acid metabolism to improve intestinal mucus barrier in broiler chickens.

The intestinal mucus barrier, located at the interface of the intestinal epithelium and the microbiota, is the first line of defense against pathogenic microorganisms and environmental antigens. Dietary polysaccharides, which act as microbiota-accessible fiber, play a key role in the regulation of intestinal microbial communities. However, the mechanism via which dietary fiber affects the intestinal mucus barrier through targeted regulation of the gut microbiota is not clear. This study provides fundamental evidence for the benefits of dietary fiber supplementation in broiler chickens through improvement in the intestinal mucus barrier by targeted regulation of the gut ecosystem. Our findings suggest that the microbiota-accessible fiber-gut microbiota-short-chain fatty acid/bile acid axis plays a key role in regulating intestinal function.

38095467

Clinical impact of metagenomic next-generation sequencing of peripheral blood for the diagnosis of invasive mucormycosis: a single-center retrospective study.

Given the high fatality rates, prompt and accurate identification of the fungal culprit is crucial, emphasizing the need for invasive mucormycosis. Unfortunately, mucormycosis lacks definitive biomarkers, depending primarily on smears, cultures, or pathology, all necessitating invasive specimen collection from the infection site. However, obtaining valid specimens early in critically ill patients poses substantial risks and challenges. Whether peripheral blood metagenomic next-generation sequencing (mNGS) can enhance early mucormycosis diagnosis, especially when direct specimen collection from the infection site is challenging, is warranted. This is a large-scale clinical study conducted to evaluate the utility and clinical impact of mNGS of peripheral blood for the diagnosis of invasive mucormycosis. We believe our study provided both novelty in translational medicine and a great value for the medical community to understand the strengths and limitations of mNGS of peripheral blood as a new diagnostic tool for the diagnosis and management of invasive mucormycosis.

38095468

Analysis of antiviral drug properties of thymidine kinase of herpes B virus using recombinant herpes simplex virus 1.

Zoonotic infection of humans with herpes B virus (BV) causes severe neurological diseases. Acyclovir (ACV) and ganciclovir (GCV), most frequently used as anti-herpes drugs, are recommended for prophylaxis and therapy in human BV infection. In this study, we examined the property of BV thymidine kinase (TK) against anti-herpes drugs using a recombinant herpes simplex virus type 1 (HSV-1) carrying BV TK gene. We found that HSV-1 carrying BV TK was similarly sensitive to GCV as HSV-1 carrying varicella zoster virus TK. In addition, we demonstrated that BV TK was not mutated in the GCV- and ACV-resistant HSV-1 carrying BV TK, suggesting that ACV- or GCV-resistant BV might be rare during treatment with these antiviral drugs. These data can provide a new insight into the properties of BV TK in terms of the development of drug resistance.

38095469

The epidemiology of pediatric outpatient acute respiratory tract infections in the US: a multi-facility analysis of multiplex PCR testing from 2018 to 2023.

Post-pandemic, it is essential to understand the epidemiology of pediatric acute respiratory tract infections (ARTIs). Our multi-facility study elucidates the outpatient epidemiology of pediatric ARTI using highly multiplexed PCR testing, providing critical insights into the evolving landscape of the etiological agents with a particular focus on the years following the emergence of SARS-CoV-2. Utilizing data from two different multiplex PCR panels, our research provides a comprehensive analysis of respiratory pathogen positivity from 2018 to 2023. Our findings indicate that over half of the annual test results identified at least one pathogen, primarily of viral origin. Intriguingly, despite the surge in testing during the COVID-19 pandemic, pathogen detection rates remain similar to the pre-pandemic era. These data hold significant implications for directing antimicrobial stewardship strategies, curbing unnecessary antibiotic use in pediatric respiratory diseases, and the value of multiplex PCR testing in the outpatient setting among pediatrics.