Direct sputum whole genome sequencing (dsWGS) can revolutionize Mycobacterium tuberculosis (Mtb) diagnosis by enabling rapid detection clinically relevant resistance mutations and strain diversity without the biohazard of culture. We searched PubMed, Web of Science, and Google Scholar, identifying 8 studies meeting inclusion criteria for testing protocols for dsWGS. Utilising meta-regression, we identified factors positively associated with dsWGS success, including higher Mtb bacillary load, mechanical disruption, enzymatic/chemical lysis and sequencing volume. Decontamination with sodium hydroxide (NaOH) was negatively associated with dsWGS success (OR = 0.00032, 95 % CI: 1.33 × 10ˆ-6-0.077; p = 0.004), likely due to its harsh effects on Mtb cells. Mechanical lysis (OR = 6120, 95 % CI: 7.23-5.18 × 10ˆ6; p = 0.011) and enzymatic/chemical lysis (OR = 131, 95 % CI: 1.68-1.03 × 10ˆ4; p = 0.028) were positively associated with sequencing success, as was heat inactivation (OR = 4.66, 95 % CI: 1.24-17.5; p = 0.023). Total sequencing volume was also strongly associated with dsWGS success (OR = 10.35, 95 % CI: 4.43-24.2; p = 6.53 × 10ˆ-8). In addition to these effects, we also observed high variability in pre-processing approaches, highlighting the need for standardized practices and identified pre-processing steps including decontamination and DNA extraction as priorities for further optimization. Considering the strong association between Mtb load and successful dsWGS, protocols for optimal sputum sample collection, handling, and storage could also further enhance the success rate of dsWGS.
Publications by Year: 2026
2026
Intrinsic enteric neurons regulate gut motility, secretion, and absorption, whereas extrinsic dorsal root ganglia sensory neurons are key in colon interoception and visceral pain. A new study raises the question of whether some initial interoceptive signals could originate from enteric neurons.
BACKGROUND: Computed tomographic (CT) lung cancer screening (LCS) reduces lung cancer-specific mortality and improves survival. We reviewed contemporary literature to develop consensus recommendations on perioperative quality standards for LCS programs to optimize outcomes.
METHODS: The Society of Thoracic Surgeons (STS) Task Force on Lung Cancer Screening and STS Workforce on Evidence Based Surgery convened a multidisciplinary panel of thoracic surgeons, radiation oncologists, and interventional pulmonologists. A comprehensive literature review was conducted using the PICO (Population, Intervention, Comparisons, Outcome) framework. Consensus statements were developed through a modified Delphi process addressing: (1) preoperative biopsy and diagnostic surgical procedures, (2) acceptable rates of complications from diagnostic and therapeutic procedures, and (3) timing of intervention after a suspicious LCS finding, and the role of the multidisciplinary team in patient management. Consensus required ≥75% agreement.
RESULTS: The panel developed 23 consensus statements after 3 Delphi rounds; 20 achieved consensus in the first round. Surgery without tissue diagnosis was acceptable for carefully selected patients, favoring minimally invasive, parenchymal-sparing approaches. Pneumonectomy without diagnosis was unanimously rejected. Programs should track benign resection rates. Acceptable complication benchmarks included pneumothorax <5%, hemoptysis <2%, and mortality <1% for bronchoscopic biopsy; and surgical morbidity <10% and 30-day mortality <1%, per STS database standards. Definitive resection should occur within 12 weeks of the inciting imaging study. Multidisciplinary teams should include thoracic surgery, oncology, pulmonology, and radiology. Preoperative pulmonary rehabilitation and smoking cessation were emphasized.
CONCLUSIONS: This STS consensus defines perioperative quality standards for CT LCS programs, supporting shared decision-making, multidisciplinary care, and quality improvement.
BACKGROUND: Respiratory viral infections are common and can trigger asthma exacerbations in children. The roles of the nasal microbiome and phageome (viruses that infect microbes) are not well understood.
OBJECTIVE: We sought to characterize the epidemiology of respiratory viral infections and the interplay between the nasal microbiome, phageome, and viral infections in school-age children with asthma.
METHODS: We performed metagenomic sequencing and quantitative RT-PCR detection of respiratory viruses on 375 nasal samples from 227 school-age children with asthma collected routinely 3 times over a year. Surveys on parent-reported cold and asthma symptoms were administered routinely every 2 months. We evaluated multikingdom changes to the nasal microbiome during infection. A sparse partial least-squares discriminant analysis model identified microbial signatures associated with prospective viral infection risk.
RESULTS: Respiratory viruses were identified in 124 (33%) samples, with rhinovirus being the most prevalent. Cold and asthma symptoms within the previous 14 days had a sensitivity of 79% and 59%, respectively, for quantitative RT-PCR-confirmed infection. Respiratory viral infection increased asthma symptoms and was accompanied by loss of nasal bacterial diversity and a reproducible bloom of pathobionts with no change in the mycobiome or phageome. A baseline bacteriome-dominated profile was protective (adjusted odds ratio, 0.41 [95% CI, 0.25-0.67]; P < .001), whereas phageome profiles increased risk (adjusted odds ratio, 3.74 [95% CI, 1.85-7.55]; P < .001) of viral infection. Specific phages inversely correlated with Staphylococcus epidermidis abundance, the most protective commensal against infection risk.
CONCLUSIONS: The nasal microbiome and phageome exert opposing influences on respiratory viral infection risk, highlighting their potential roles in modulating susceptibility to viral infections.
Broadly neutralizing antibodies (bNAbs) against HIV-1 can suppress viremia in vivo and inform vaccine development. Here we characterized 007, a V3 glycan site bNAb exhibiting high levels of antiviral activity against multiclade pseudovirus panels. 007 targets an N332gp120 glycan-independent V3 epitope, a site of the HIV-1 envelope protein (Env) vulnerability to which only weakly neutralizing antibodies had previously been identified. Functional analyses demonstrated distinct binding and neutralization profiles compared to classical V3 glycan site bNAbs. A 007 Fab-Env cryogenic electron microscopy structure revealed contacts with the V3 324GD/NIR327 motif and interactions with N156gp120 and N301gp120 glycans. In contrast to classical V3 bNAbs, 007 binding to Env does not depend on the N332gp120 glycan, rendering it resistant to common escape mutations. Structures of 007 IgG-Env trimer complexes showed two Env trimers crosslinked by three bivalent IgGs. Bivalent 007 IgG was more potent than monovalent 007 IgG heterodimer, suggesting a role for avidity in potent neutralization. Finally, in HIV-1ADA-infected humanized mice, 007 caused transient decline of viremia and overcame classical V3 escape mutations, highlighting 007's potential for HIV-1 prevention, therapy, functional cure and vaccine design.
BACKGROUND: The mental health impacts of climate change and armed conflict are well-documented separately, yet little is known about their intersection and the compounding effects on vulnerable populations exposed to both crises.
AIMS/OBJECTIVE: This scoping review aims to map the current evidence on the combined effects of climate change and conflict-related hazards on mental health outcomes. Specifically, we categorize the pathways through which climate change and conflict interact to influence psychological well-being.
METHODS: We searched seven databases (PubMed, APA PsycINFO, CINAHL, Embase, Scopus, the Cochrane Library, and Google Scholar) and conducted a comprehensive gray literature search. We included populations directly affected by armed conflict and climate hazards simultaneously. Eligible studies reported mental health outcomes, including but not limited to posttraumatic stress disorder, anxiety, depression, well-being, or resilience.
RESULTS: The initial search yielded 2,865 records, 27 of which met the inclusion criteria after deduplication and screening. Populations studied aligned with the Vulnerable Populations Conceptual Model, which includes women, children, the elderly, and other high-risk groups. Slow-onset climate hazards, particularly drought, were the most frequently examined. Geographically, research was focused primarily on sub-Saharan Africa and parts of Asia. The evidence included a nearly equal distribution of conceptual and empirical studies (13 and 14 respectively), with displacement and lack of resources being the dominant pathways mediating the interaction between climate and conflict on mental health.
CONCLUSION: Despite growing evidence, substantial gaps remain regarding the effects of climate change and conflict on mental health outside Africa and parts of Asia. Mental health initiatives should prioritize populations exposed to both climate and conflict hazards, addressing displacement, vulnerability, and resilience through integrated, context-sensitive interventions.
OBJECTIVES: To determine population values of femoroacetabular translation using dynamic hip ultrasonography (DHUS) in professional ballet dancers.
DESIGN: Cross-sectional cohort.
SETTING: Three ballet companies.
PARTICIPANTS: Ninety professional ballet dancers.
INTERVENTIONS: Dynamic hip ultrasonography was performed (12 images/dancer, 1080 images). Biometrics included Trochanteric Prominence Angle Test and Beighton Score.
MAIN OUTCOME MEASURES: Anterior and posterior DHUS measures were documented, and femoroacetabular translation was calculated.
RESULTS: Anterior exam mean values for female dancers in neutral (N), neutral flexed (NF), and extension external rotation (EER) positions were 4.3 ± 2.05, 9.4 ± 2.61, and 11.4 ± 2.83, respectively, and anterior translation 2.1 ± 2.08; for posterior exam, posterior neutral, posterior flexion adduction internal rotation, and posterior stand positions showed a median value (interquartile range [IQR]) 0 (0-2) and mean values of 11.7 ± 4.89 and 8.8 ± 4.63, respectively, and posterior femoroacetabular translation 10.4 ± 4.62. Ultrasound measures for male dancers' anterior exam showed 5.5 ± 2.86, 10.9 ± 2.82, and 12.9 ± 2.78 and anterior translation 1.9 ± 1.62, and posterior exam measures showed median (IQR) 0 (0-3) and mean 11.3 ± 4.69 and 10.1 ± 5.36 and posterior femoroacetabular translation 9.6 ± 3.82. Differences by sex were found in N and NF positions: male dancers had greater translation versus female dancers in the left (P = 0.03 and P = 0.03, respectively) and right hips (P = 0.02 and P = 0.004, respectively). Males had greater EER in the right hip compared with females (P < 0.001).
CONCLUSIONS: Dynamic hip ultrasonography determined population values in professional ballet dancers. Sex-based differences among dancers were found.
BACKGROUND: Federal rules governing opioid treatment programs (OTPs)-altered during and in the aftermath of the COVID-19 public health emergency-granted OTPs greater flexibility in clinical care (eg, take-home methadone doses, telehealth). Revised rules have not appeared to impact patient safety and were largely welcomed by patients and clinicians. Despite this, OTPs varied in adoption, and some have returned to pre-pandemic practice. In this qualitative study, we examined variation in clinical practices across U.S. Department of Veterans Affairs (VA) OTPs following the opportunity for reform, as well as the beliefs and perspectives of OTP administrators that may shed light on variability in decisions to adopt programmatic changes.
METHODS: We contacted OTP administrators (medical directors, program managers) at all 33 VA OTPs nationally. We conducted semi-structured interviews from September 2023 to June 2024. Data were analyzed using an inductive-deductive analytic approach employing the framework method. Transcripts were coded and charted into a framework matrix that included site characteristics, clinical practices and requirements, and summaries of domains developed during the coding stage, allowing for comparison across sites.
RESULTS: Administrators from 28/33 VA OTPs completed interviews. Participants described diverse clinic policies regarding take-home schedules, frequency and response to toxicology testing, and requirements to attend groups. Telehealth utilization increased in almost all locations. Decisions to adopt more flexible clinical requirements appeared to reflect differential perceptions of patient and community risks and beliefs about the effects of the regulations on the therapeutic environment. While leaders appreciated the opportunity to individualize treatment, they also expressed a need for guidance to ensure consistent, equitable care.
CONCLUSIONS: This study reveals variation in OTP clinical practice across VA in the wake of regulatory reform. To inform decision-making in the new regulatory environment, research examining the effects of OTP clinical practices on patient engagement, retention, and quality of care should be prioritized.