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Social anxiety disorder (SAD) is often complicated by anticipatory anxiety, hyperarousal, and variability in response to first-line treatments such as cognitive behavioral therapy (CBT) and pharmacotherapy. These limitations highlight the need for adjunctive modalities capable of enhancing the magnitude and durability of treatment response. This case report explores outcomes following spectral EEG-guided personalized repetitive transcranial magnetic stimulation (PrTMS) in a patient with SAD, performance-only subtype. Weekly psychometric assessments revealed reductions in social anxiety intensity, avoidance behaviors, and negative self-appraisal, along with improvements in mood and daily function. Symptom changes were quantified using the Liebowitz Social Anxiety Scale (LSAS), Social Phobia Inventory (SPIN), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-Item Scale (GAD-7), and Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Clinical improvements were accompanied by increased alpha band power, decreased delta band power, and an increased alpha-delta ratio on serial spectral resting-state EEGs. Our findings suggest that PrTMS may warrant further investigation as a potential adjunctive treatment for SAD. Further large-scale, blinded, and randomized studies are warranted to validate our observations on the feasibility of PrTMS for SAD.

Chronic axial spinal pain is a major contributor to disability and healthcare expenditures, with facet joints recognized as one of the established sources of pain. To provide evidence-based guidance in performing diagnostic and therapeutic facet joint interventions. A multidisciplinary panel of experts from various medical and pharmaceutical disciplines, convened by the American Society of Interventional Pain Physicians (ASIPP), reviewed the available evidence, considered patient perspectives, and formulated recommendations for facet joint interventions in the management of chronic pain.The methodology included the development of key questions with evidence-based statements and recommendations. Grading of the evidence and recommendations followed a modified approach described by ASIPP, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and the Agency for Healthcare Research and Quality (AHRQ) methods for grading strength of recommendations. The evidence review included existing guidelines, systematic reviews, comprehensive reviews, randomized controlled trials (RCTs), and observational studies evaluating the effectiveness and safety of facet joint interventions in chronic pain management.In the development of consensus statements and guidelines, a modified Delphi technique was utilized to minimize bias related to group interactions. Panelists without a primary conflict of interest voted on approval of specific guideline statements. Each panelist was permitted to suggest revisions to guideline wording and provide additional qualifying remarks or comments regarding implementation of the guidelines in clinical practice. To achieve consensus and inclusion in the final guidelines, each guideline statement required at least 80% agreement among eligible panel members without a primary conflict of interest. A total of 48 authors participated in the development of these guidelines, of whom 39 participated in the voting process. A total of 37 recommendations were developed, with 100% acceptance for all items. The Summary of Recommendations is presented separately. These recommendations addressed diagnostic, therapeutic, and special considerations related to facet joint interventions. For diagnostic and therapeutic interventions, the level of evidence ranged from II to III, with moderate to strong recommendations. For special considerations and safety assessments, the level of evidence ranged from II to V. The evidence provided recommendations regarding diagnosis, treatment, sedation, concurrent antithrombotic therapy, and precautions required in special clinical circumstances. The limitations of these guidelines include a paucity of high-quality studies in some aspects of diagnosis and therapy. These guidelines for facet joint interventions were developed through a comprehensive review of the literature, including methodologic quality assessment and determination of the level of evidence and strength of recommendations. These guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

To evaluate the evidence supporting preventive pelvic floor muscle therapy (PFMT) in reducing pregnancy associated pelvic floor dysfunction (PFD) and assess the alignment of insurance coverage, clinical guidelines, and legislative initiatives with current evidence in the United States (U.S.). Despite growing evidence supporting PFMT, U.S. insurers restrict coverage to treatment of dysfunction rather than its prevention. We review the pathophysiologic mechanisms linking childbirth to PFD, summarize the evidence supporting preventive PFMT, and evaluate U.S. insurance coverage practices, PFMT implementation guidelines, and relevant legislation. International approaches to pelvic floor health promotion are also examined. Vaginal birth places significant mechanical strain on the pelvic floor, frequently injuring the structures responsible for maintaining continence and preventing pelvic organ prolapse (POP). Evidence from a 2020 Cochrane review, RCTs, and other meta-analyses demonstrates that antenatal PFMT significantly reduces the risk of urinary incontinence (UI) during pregnancy and postpartum. The preventive efficacy of postpartum PFMT remains less clearly defined, as many studies evaluate mixed populations of continent and incontinent patients vs strictly continent. U.S. insurance does not cover preventive PFMT, resulting in significant out-of-pocket costs. Clinical and public health guidelines inconsistently address preventive PFMT, and legislative efforts remain limited. Preventive PFMT represents an evidence-based strategy for reducing pregnancy associated PFD. Aligning clinical guidelines, insurance coverage, and legislative initiatives with current evidence may improve access to preventive pelvic floor care and strengthen maternal health outcomes.

Typhus (FBT), caused by Rickettsia typhi, rarely causes neurological disease. Herein, we describe neurological involvement in two cases of FBT. In the first case, an adult presented with persistent fever which deteriorated into status epilepticus. He was successfully treated with doxycycline and made a complete recovery. In the second case, a patient suffered an ischemic stroke and had a protracted clinical course but ultimately made a near complete recovery. In addition to these cases, we conducted a comprehensive narrative review of 43 cases of neurologic involvement in FBT reported from 1989 to 2025. Cases were excluded if there were pathologic discrepancies with typical cases of FBT. Presentations ranged from cranial nerve palsies to meningitis and fulminant encephalitis. This review highlights the spectrum of CNS complications associated with FBT and underscores the importance of early recognition and treatment with doxycycline to improve outcomes. Given the potential severity of neurologic involvement, clinicians in endemic areas should maintain a high index of suspicion for FBT in patients presenting with a febrile illness and neurologic symptoms.

Mitral valve prolapse (MVP) is associated with an increased risk of infective endocarditis (IE), particularly in patients with mitral regurgitation and leaflet thickening. Historically, a subset of patients with mitral valve prolapse were considered for antibiotic prophylaxis before dental procedures. Conversely, current recommendations limit prophylaxis to the highest-risk cardiac conditions, such as congenital heart defects, mechanical valves, heart transplant with valvular issues, and a history of IE. We present a case of a 59-year-old man with a history of MVP with mildly thickened posterior leaflet, hypertension, hyperlipidemia, and prior tobacco use who presented to the hospital with nausea and vomiting four weeks after a tooth extraction. Initial laboratory evaluation was notable for elevated inflammatory markers, elevated transaminases, hyperbilirubinemia, and elevated troponin levels. Blood cultures grew methicillin-sensitive Staphylococcus aureus (MSSA). Transthoracic echocardiography demonstrated MVP with new moderate mitral regurgitation. Brain MRI showed multifocal embolic infarcts and a small subarachnoid hemorrhage. Transesophageal echocardiography (TEE) revealed vegetations involving both mitral valve leaflets, extension into the mitral annulus and left atrial wall, and annular abscess formation. The patient's hospital course was complicated by septic shock, respiratory failure, intermittent ventricular tachycardia, transient complete heart block, acute tubular necrosis, postoperative atrial fibrillation, and new-onset cardiomyopathy. He ultimately required urgent mitral valve replacement with extensive debridement of the mitral annulus and left atrial wall, followed by prolonged intravenous antibiotic therapy. Follow-up imaging showed a well-seated prosthetic valve without recurrent vegetation. This case highlights the severe complications of IE in patients with MVP and mildly thickened leaflets following dental procedures. Current guidelines do not recommend routine prophylaxis in this population. This case raises important questions regarding whether selected moderate-risk MVP patients with leaflet thickening and mitral regurgitation may benefit from individualized prophylactic strategies.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality, driven by invasive behavior and frequent resistance to systemic therapies. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) benefit patients with EGFR-mutant NSCLC, but their efficacy is often limited by tumor-intrinsic and environmental resistance mechanisms. Benzo[a]pyrene (BaP), a ubiquitous polycyclic aromatic hydrocarbon from tobacco smoke, combustion, and dietary sources, is a known carcinogen; however, its role in modulating therapeutic responses is poorly understood. Studies, including ours, implicate the platelet-activating factor-receptor (PAFR) pathway in mediating environmental pollutant and therapy-induced effects on tumor growth and microvesicle particle (MVP) release. We hypothesized that PAFR activation mediates BaP-induced NSCLC progression and influences EGFR-TKI responses. We assessed the effects of BaP, PAFR agonist CPAF, EGFR-TKIs, and their combinations on cell viability, proliferation, migration, anchorage-independent growth, and MVP secretion. BaP did not alter cell survival but significantly increased migration, growth, colony formation, and MVP release, similar to CPAF, and these effects were blocked by a PAFR antagonist or acid sphingomyelinase inhibitor. Notably, BaP did not significantly reduce EGFR-TKI efficacy at tested concentrations. These results show that environmental carcinogens modulate NSCLC behavior through PAFR signaling without compromising EGFR-TKI responsiveness, highlighting PAFR as a potential therapeutic target.

Rapid wetland assessments are designed to require minimal field effort (e.g. half-day site visit), but still provide critical information on wetland ecological condition and functioning. Many wetland functions occur within or are supported by the soil, yet soil condition is seldom-or only minimally-included in most state rapid assessments. We focus on the Ohio Rapid Assessment Method for wetlands (ORAM) and evaluate soil bulk density as an indicator of wetland soil condition that can be incorporated into rapid wetland assessments. Soil bulk density ([Formula: see text]) is relatively easy to measure and requires only basic instrumentation. It also correlates well with more intensive metrics of soil condition (e.g. carbon content, aggregation). We sampled 45 wetlands in west-central Ohio, that exhibited a range of wetland type and ecological condition. From each wetland, we collected five soil cores (to 15-cm depth) and then analyzed the soil samples for [Formula: see text], carbon content, and water-stable aggregates. These three measurements were used to develop a four-bin [Formula: see text] metric of soil condition. Incorporating this metric into the current ORAM improved relationships with [Formula: see text] (r = 0.48 to r = 0.58) and soil condition (r = -0.53 to r = -0.64). Additional gains could be achieved with higher weighting of the [Formula: see text] metric. Alternatively, the current scoring system could be left intact, but protection of wetlands with high quality soils ensured by providing special status when [Formula: see text] is less than 0.40 g cm[Formula: see text] (highest quality) or less than 0.73 g cm[Formula: see text] (high quality). The online version contains supplementary material available at 10.1007/s13157-026-02044-9.

Prior to mass deforestation of uplands and drainage efforts in lowlands, floodplain wetlands were abundant in river valleys. Deforestation of steep slopes and the associated accumulation of alluvial sediment in valley bottoms have left floodplains much drier and largely disconnected from their adjacent rivers, restricting the ecosystem and societal benefits floodplains can provide. By exporting alluvial sediments from floodplains, long buried wetlands can be restored with improved connectivity to stream networks. Such floodplain wetland restoration efforts can provide benefits at orders-of-magnitude lower costs than conventional stormwater control measures (SCMs) by minimizing pipes and other hardened infrastructure. Particularly in urban and suburban watersheds, floodplains are often one of the last open areas to locate SCMs that have the potential to intercept large volumes of runoff. They can also be coupled with recreational opportunities or urban canopy restoration programs, expanding the societal benefits of and opportunities to fund floodplain wetland restoration. This paper presents insights from planning, design, modeling, and construction of eight floodplain wetland restoration projects. The eight projects were compared using success criteria that spanned two themes: 1) maximizing the benefits that the floodplain wetland can provide and 2) maximizing the economic efficiency and durability of the project. As a part of the comparison, we note characteristics for identifying good sites for floodplain wetlands, design optimization strategies for various project goals (e.g., nutrient reductions vs. offloading excessively erosive streamflow vs. flood reduction), and construction sequencing approaches for efficiency and cost minimization. Removing alluvium from floodplains can provide expanded flood storage and lowered flood elevations, restored off-channel habitat for fish/birds, improved water quality, reduced erosion/biotic disturbance for mussels/macroinvertebrates, and, in some cases, the economic benefits of an abundant source of high-quality topsoil for farmers, landscapers, and developers.

To record the history of the adoption and utilization of the surgical technique of buccal mucosal grafts for urologic procedures. Academic and historic medical articles available on PubMed and open search engines were reviewed for information linked to physicians who have utilized buccal mucosal grafts from 1894 to 2021. In the late 19th and early 20th centuries, oral grafts were primarily used by ophthalmologists. Dr. Kirill Sapezhko was the pioneering urologist who applied this surgical technique for urethral stricture disease, publishing his case series in 1894. Almost 50 years later in 1941, Dr. Graham Humby in London published a case report on the use of oral mucosa for treatment of hypospadias in an 8-year-old patient. There was then a large gap in reports for several decades. Articles commonly recognized as milestone publications do not appear until 1992 from Dr. R. A. Bürger in Germany and Dr. Antonio Dessanti in Italy. Literature involving buccal mucosal grafts then expanded exponentially and it has become the gold standard for anterior urethral stricture repair. The literature inconsistently recognizes Dr. Sapezhko's innovation of oral mucosal grafts in urethral stricture repair. The history of oral mucosal grafts highlights how knowledge can be lost for periods of time, which can cause lack of widespread acknowledgement of the origin of surgical techniques.

Firearm-related injury is the leading cause of death in children in the United States. Safe storage counseling with gun lock distribution is an evidence-based practice to reduce firearm injury; however, it is infrequently employed in the pediatric intensive care unit (PICU), creating a missed opportunity for injury prevention. We assessed caregiver perceptions after implementing safe storage counseling in our PICU, hypothesizing that caregivers would find this practice acceptable and increase intent to safely secure firearms. With multidisciplinary PICU clinicians and family advisory board input, we created a workflow for universal safe storage counseling and lock distribution. We identified patients with planned discharge or transfer daily and approached those with a caregiver at bedside to provide safe storage counseling, a free cable gun lock, and a postcounseling survey. 350 (86%) of 407 caregivers, predominantly mothers, completed the postcounseling survey. This was the first time receiving counseling from a health care clinician for 87% of caregivers; 97% found the PICU an acceptable location. The majority (78%) reported an increased likelihood of asking about safe storage of firearms in other homes where their children spend time, 87% reported they intended to share information received. 30% planned to use the lock provided, and 56% would give the lock to someone else. Others planned to remove a firearm (3%) and/or change their firearm storage practices (17%). We demonstrated high acceptability and potential impact of a universal approach to safe storage counseling and gun lock distribution in the PICU.

Ataxia telangiectasia and Rad3-related (ATR) initiates cell cycle checkpoints to maintain genome integrity in the presence of replication stress or various forms of DNA damage. However, how ATR is activated for checkpoint initiation remains incompletely understood. The canonical model suggests that binding of an ATR-activator protein relieves the autoinhibitory PIKK regulatory domain (PRD) within the kinase domain, thereby activating ATR by granting substrate access to the catalytic centre. To better understand the checkpoint initiation mechanism, we conducted a genetic screen in fission yeast that identified a charge-reversal mutation, E1369K, in the conserved FRAP-ATM-TRRAP (FAT) domain of Rad3, the ortholog of ATR. In vitro kinase assays show that the mutation converts Rad3 into a constitutively active form. This allows rescue of the Rad3 kinase signaling defect in cells lacking the phosphorylation of the Rad9-Rad1-Hus1 (9-1-1) complex specifically in the DNA replication checkpoint, not the damage checkpoint pathway. Since the mutation is not in the kinase domain and is away from the PRD, these findings show that, in addition to the canonical mechanism, Rad3 may also be activated allosterically via the FAT domain, a mechanism likely conserved in higher eukaryotes.

Bioaerosols comprise an array of airborne particles that can be benign, contain irritants (i.e., allergens), or disseminate pathogens. Current fieldable devices are incapable of discriminating between benign bioaerosols and pathogenic bioaerosols. Thus, rapid on-site detection and identification at the point of exposure of the components comprising bioaerosols is critical to assess health risks; elimination of both false positives and false negatives is essential to ensure that the correct countermeasures are deployed. The sandwich enzyme-linked immunosorbent assay (sandwich ELISA) remains a gold standard technique for accurate, sensitive detection of proteins, bacteria, and viruses. ELISAs require recognition of the target by two biorecognition elements (BREs) and thus effectively eliminate false positives. The sandwich ELISA, however, suffers from laborious manual processes, which severely impacts its utility in point-of-care (POC). Centrifugal microfluidics offers an automated solution to execute multi-step ELISAs. Here, we introduce a centrifugal microfluidic device that operates based on passive capillary and siphon valving networks to detect human serum albumin (HSA) concentrations in collected bioaerosol samples. We investigate key aspects for minimizing the assay operation time by investigating siphon valve mechanisms, co-incubation time for HSA with a capture antibody and detection antibody conjugated with streptavidin-horse radish peroxidase (strep-HRP), and incubation time for tetramethylbenzidine with strep-HRP for electrochemical amperometric detection. The fully integrated device quantifies HSA concentrations in 15 minutes based on a small sample volume of 12.5 μL. Using the device, we successfully quantify HSA concentrations in bioaerosol samples and obtain results similar to standard 96 well plate-based ELISA.

SARS-CoV-2 typically utilises host receptor angiotensin-converting enzyme 2 (ACE2) for viral entry. Despite low ACE2 expression, monocyte-derived macrophages, the predominant lung macrophage during severe COVID-19, are often found with SARS-CoV-2 in infected lungs. As macrophage inflammation and cytokine storm are key immunopathological events that drive severe COVID-19, insights into mechanisms underlying viral entry into macrophages are critical to devise novel COVID-19 therapies. Mounting evidence supports that COVID-19 pathogenesis is associated with apoptosis, a type of programmed cell death which releases large extracellular vesicles called apoptotic bodies (ApoBDs). Here, we show that ApoBDs from SARS-CoV-2-infected cells carried infectious virions. Macrophages efferocytose these ApoBDs, enabling SARS-CoV-2 entry and pro-inflammatory responses including inflammasome and NF-κB signalling. To demonstrate targetability of this ApoBD efferocytosis-mediated viral entry, we screen for inhibitors of SARS-CoV-2-induced ApoBD formation and identified T-type voltage-gated calcium channel (T-channel) blockers. Mechanistically, T-channel blockers impair the extracellular calcium influxes required for ApoBD biogenesis. Importantly, blockade of ApoBD formation by T-channel blockers is able to limit cell-to-cell viral transmission, macrophage inflammation and lung immunopathology. Our discovery reveals a novel route for SARS-CoV-2 infection and cytokine storm induction, expanding our understanding of COVID-19 pathogenesis and demonstrating a therapeutic target for infectious diseases.

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Background/Objectives: Children of families facing unmet social needs experience higher rates of adverse outcomes compared to those not experiencing unmet social needs. This study aimed to identify factors associated with families' unmet social needs as reported by parents or guardians at their children's primary care visits. Methods: This cross-sectional study recruited English-speaking primary caregivers of children less than 18 years of age from the Southwestern Ohio Ambulatory Research Network (SOAR-Net) who were surveyed between January 2023 and August 2024. Surveys included the Maternal Social Support Index, Social Capital Scale, RAND Depression Screener, Children with Special Health Care Needs Screener, Medical Expenses of Children Survey, a 10-item social needs screener, and demographics. Data were analyzed with chi-square or Fisher's exact tests, adjusted logistic regression, and ANOVA. Results: Among 1167 respondents (78% response rate), 1114 provided complete data. Primary caregivers were predominantly mothers (79.9%) or fathers (13.6%), White (72.0%) or Black (16.0%), and had an associate's degree or less (65.1%). The mean (SD) index child's age was 6.4 (5.3) years, and 52.4% were female. Underinsurance, positive depression screens, and poor child health were positively associated with unmet social needs. Higher scores for social support and social capital were associated with fewer social needs. Multinomial logistic regression revealed significant relationships with reporting two or more unmet social needs with the following variables: childhood underinsurance, household annual income < $50,000, positive depression screens, raising a child with a chronic health condition, and Black race/ethnicity. Conclusions: Several significant social factors were independently associated with a greater number of unmet social needs. These findings highlight the complex interplay among social factors in children's healthcare. Future research should explore the putative longitudinal stability of these relationships.

Bridging therapy is commonly administered prior to B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR)-T cell therapy in relapsed/refractory multiple myeloma (RRMM) to maintain disease control during the manufacturing period. However, the optimal choice and intensity of bridging therapy remain unclear, and it is debated whether outcomes are primarily influenced by bridging strategy or underlying disease biology. We aimed to evaluate the impact of different bridging strategies on outcomes after BCMA-directed CAR-T cell therapy in RRMM, while accounting for disease biology, response prior to infusion, and baseline hematopoietic reserve. This retrospective multicenter real-world study included 90 consecutive patients with RRMM treated with BCMA-directed CAR-T cells (idecabtagene vicleucel or ciltacabtagene autoleucel) in Austria between January 2024 and July 2025. Bridging approaches were categorized as polychemotherapy (PCHT), talquetamab-based regimens (Tal), or other strategies. Survival outcomes were estimated using the Kaplan-Meier method, and factors associated with progression-free survival (PFS) were analyzed using univariable and multivariable Cox proportional hazards models. Logistic regression models were applied to assess associations with early toxicity. After a median follow-up of 9.9 months, estimated median PFS was 17.1 months. In unadjusted analyses, PCHT was associated with inferior PFS compared with other bridging approaches. However, this association was not retained after adjustment for extramedullary disease/plasma cell leukemia (EMD/PCL) and IMWG high-risk status. CAR-T product type and number of prior lines of therapy showed no effect on PFS. EMD/PCL emerged as the strongest independent predictor of inferior PFS in multivariable analysis (adjusted hazard ratio 4.85), whereas IMWG high-risk status was not independently prognostic. In a secondary model, achieving at least a very good partial response prior to CAR-T infusion was associated with a trend toward improved PFS but did not reach statistical significance. Talquetamab-based bridging was associated with numerically favorable PFS without increased toxicity. The CAR-HEMATOTOX score independently predicted inferior PFS. Importantly, PCHT was not associated with higher CAR-HEMATOTOX scores, prolonged cytopenia, increased infectious complications, or lower ALC levels as a surrogate for CAR-T expansion. In this nationwide real-world analysis, disease biology - particularly the presence of EMD/PCL - was the dominant determinant of outcome after CAR-T cell therapy, outweighing the impact of bridging strategy. These findings suggest that inferior outcomes observed after intensive bridging are largely driven by adverse baseline disease characteristics rather than treatment-related effects, supporting a biology-adapted approach to bridging and emphasizing the importance of achieving optimal disease control prior to CAR-T infusion.

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We report an unusual case of juvenile myelomonocytic leukemia (JMML) in a 4-year-old male who had persistent monocytosis and intermittent anemia and thrombocytopenia beginning at 1&#x2009;year of age. Given a history of recurrent skin infections, the patient initially received an evaluation for a primary immune disorder, but workup was inconclusive. Bone marrow examination was performed to further evaluate persistent and progressive cytopenias. The findings fulfilled the criteria for JMML with peripheral blood monocytosis &#x2265; 1&#xd7;109/L, blast/promonocyte percentage of <20% in peripheral blood and bone marrow, clinical evidence of organ infiltration with hepatosplenomegaly, and absent BCR::ABL1 fusion and KMT2A gene rearrangements. Additionally, next generation sequencing (NGS) studies performed on the bone marrow aspirate revealed multiple acquired somatic mutations, including a KRAS G12D mutation, meeting criteria for the diagnosis of JMML in the context of this case. A novel ETV6 R369W mutation in the setting of JMML was also detected, which may explain the striking megakaryocytic dysplasia in the bone marrow beyond what is typically seen in JMML. This case showed interesting features overlapping with Ras-associated autoimmune leukoproliferative disorder (RALD), including monocytosis and recurrent infections. Furthermore, this case demonstrated a need for more definitive criteria for distinguishing JMML from RALD.