Nevin Manimala

JAMA Netw Open. 2026 May 1;9(5):e2612042. doi: 10.1001/jamanetworkopen.2026.12042.

ABSTRACT

IMPORTANCE: Trends in the incidence of de novo stage IV breast cancer in the general population and in the percentage with stage IV disease remain underreported.

OBJECTIVES: To evaluate the incidence, percentage, and survival of people with de novo stage IV breast cancer diagnosed from 2010 through 2021.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used data from the Surveillance, Epidemiology, and End Results program to identify all individuals diagnosed with de novo invasive breast cancer between January 1, 2010, and December 31, 2021. No exclusion criteria were applied. Data analyses were conducted from January 2024 to June 2025.

MAIN OUTCOMES AND MEASURES: Age-adjusted incidence rates of breast cancer and annual percentage changes (APC) from 2010 through 2021 were calculated. Among the diagnosed breast cancers, the yearly percentage of stage IV disease was also calculated. Changes in overall survival (OS) were evaluated for patients with stage IV breast cancer using multivariable Cox proportional hazards regression models stratified by tumor subtype.

RESULTS: Of 761 471 breast cancer diagnoses (median [IQR] age at diagnosis, 60 [50-70] years; 99.2% female), 43 934 (5.8%) were stage IV. Stage IV incidence increased from 9.5 (95% CI, 9.2-9.9) cases per 100 000 females in 2010 to 11.2 (95% CI, 10.9-11.6) cases per 100 000 females in 2021, an APC of 1.2% (95% CI, 0.8%-1.6%). The incidence of stages I to III disease also increased, from 163.0 (95% CI, 161.6-164.4) cases per 100 000 females in 2010 to 177.4 (95% CI, 176.1-178.8) cases per 100 000 females in 2021. Stage IV incidence increased across all tumor subtypes, with an APC of 2.0% (95% CI, 1.5%-2.6%) for hormone receptor (HR)-positive/ERBB2-negative, 1.6% (95% CI, 0.2%-2.9%) for HR-positive/ERBB2-positive, 1.3% (95% CI, -0.1%-2.7%) for HR-negative/ERBB2-positive, and 2.7% (95% CI, 1.4%-4%) for triple-negative disease. Stage IV incidence increased statistically significantly across all age groups and numerically across all racial groups. Among males, there was a statistically significant increase in stage IV incidence, with an APC of 3.7% (95% CI, 1.0%-6.5%). The percentage of stage IV diagnoses increased statistically significantly from 2010 through 2021 in each tumor subtype: 4.4% to 95.4% for HR-positive/ERBB2-negative, 8.1% to 91.6% for HR-positive/ERBB2-positive, 10.4% to 89.4% for HR-negative/ERBB2-positive disease, and 6.7% to 92.9% for triple-negative breast cancer. For each successive year, OS among patients diagnosed with stage IV improved, with adjusted hazard ratios of 0.99 (95% CI, 0.98-0.99) for HR-positive/ERBB2-negative, 0.97 (95% CI, 0.95-0.99) for HR-positive/ERBB2-positive, and 0.97 (95% CI, 0.94-0.99) for HR-negative/ERBB2-positive; changes for triple-negative breast cancer were not statistically significant (AHR, 0.99 [95% CI, 0.97-1.01]; P = .33).

CONCLUSIONS AND RELEVANCE: In this cohort study of individuals with stage IV breast cancer, incidence increased significantly overall, across ages, and for both sexes from 2010 through 2021. The percentage of individuals with stage IV vs stages I to III diagnoses also increased. Although OS improved, research is warranted to determine factors contributing to increased incidence, including potential changes in natural history of breast cancer, disease screening, and incidence and mortality of other conditions.

PMID:42118535 | DOI:10.1001/jamanetworkopen.2026.12042

JAMA Netw Open. 2026 May 1;9(5):e2612051. doi: 10.1001/jamanetworkopen.2026.12051.

ABSTRACT

IMPORTANCE: Azithromycin is commonly used during pregnancy to treat bacterial infections, but its effects on neurodevelopmental disorders (NDDs) remain inconclusive.

OBJECTIVE: To evaluate the risk of NDDs in children prenatally exposed to azithromycin compared with those exposed to other antibiotics or with no antibiotic exposure during gestation.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from an administrative health claims database (January 1, 2012, to October 31, 2024). The study evaluated a mother-infant cohort of mothers aged 12 to 55 years with a live birth between December 1, 2012, and December 31, 2023, who filled at least 1 prescription for an antibiotic or were unexposed to antibiotics during pregnancy. Mothers with antibiotic exposure within 90 days before pregnancy were excluded.

EXPOSURES: Propensity scores were used to match children exposed to azithromycin with those exposed to other antibiotics or no antibiotics during the entire, early, and late pregnancy periods.

MAIN OUTCOMES AND MEASURES: Cox proportional hazards regression models were applied to assess the incidence of NDDs, including attention-deficit/hyperactivity disorder, autism spectrum disorder, speech and language disorder (SLD), developmental coordination disorder, and behavioral disorders, during follow-up, in the azithromycin cohort compared with those exposed to other antibiotic classes or those with no antibiotic exposure.

RESULTS: Among 15 527 mother-infant dyads (mean [SD] maternal age, 32.4 [4.1] years) included in this study, 742 (4.8%) were exposed to azithromycin, 3079 (19.8%) were exposed to other antibiotics, and 11 706 (75.4%) remained unexposed to antibiotics during pregnancy. After a mean (SD) follow-up of 5.5 (3.0) years, late pregnancy azithromycin exposure was associated with a lower risk of SLD compared with those unexposed (adjusted hazard ratio [AHR], 0.61; 95% CI, 0.39-0.94) as well as a lower risk of overall NDDs (AHR, 0.69; 95% CI, 0.49-0.98) and SLD (AHR, 0.59; 95% CI, 0.39-0.91) compared with those exposed to other antibiotics.

CONCLUSIONS AND RELEVANCE: In this cohort study, late pregnancy azithromycin exposure was associated with a lower risk of NDDs, particularly SLDs. However, azithromycin prescribing during pregnancy should remain guided by clinical necessity and existing safety recommendations; further studies using larger and more diverse populations are warranted to confirm these findings.

PMID:42118534 | DOI:10.1001/jamanetworkopen.2026.12051

JAMA Netw Open. 2026 May 1;9(5):e2612183. doi: 10.1001/jamanetworkopen.2026.12183.

ABSTRACT

IMPORTANCE: The growth of the US criminal legal system has broad implications for individual and societal economic and social well-being. Although this system primarily targets adults, children may experience adverse consequences from the criminal legal contacts (CLCs) of their parents and other family members.

OBJECTIVE: To examine the prevalence of children’s family member CLCs within the past year and past 5 years and how prevalence varied across relationship type, child age, and cohort period.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study created 2 samples (a courts sample and an incarceration sample) using secure criminal legal system records from 24 states and US Census Bureau surveys and administrative data between January 1, 2000, and December 31, 2021. Children were linked to parents and other family members using birth records and household surveys, and then family members were linked to criminal legal system records. Data were analyzed between July 15, 2023, and March 1, 2025.

EXPOSURE: Family CLCs.

MAIN OUTCOMES AND MEASURES: Mean prevalence rates of family CLCs were estimated for 4 types of recent (prior year and prior 5 years) family CLCs, including charges, convictions, felony convictions, and postadjudication incarceration, across family relationship (parent vs overall), child age (0-17 years), and cohort period (2000-2021).

RESULTS: The final courts sample included 371 100 000 observations for family charges and convictions linked to 43 490 000 unique children (56.7% aged 0-9 years and 43.2% aged 10-17 years; 50.7% boys), and the incarceration sample included 784 200 000 observations linked to 76 610 000 unique children (58.0% aged 0-9 years and 41.9% aged 10-17 years; 50.7% boys). Between 2000 and 2021, 15.0% of children had a family member charged within the past 5 years. In addition, 11.6% of children experienced a family member’s conviction, 3.6% a family member’s felony conviction, and 1.4% a family member’s incarceration within the past 5 years. Parent CLCs constituted a substantial proportion of children’s family CLCs (73.0%-78.7%) across 5-year exposures, with 11.8% of children experiencing a parent’s CLC within the past 5 years. Overall prevalence varied little by age, although parent CLCs were somewhat higher in early childhood. Prevalence of family CLCs among children increased substantially between 2000 and 2019 from 6.6% to 19.6% for past-5-year family criminal charges.

CONCLUSIONS AND RELEVANCE: This cross-sectional study found pervasive and increasing rates of children experiencing family CLCs. Given the adverse consequences of family CLCs for children, these findings have profound implications for child and adolescent well-being and the professionals who work with them.

PMID:42118533 | DOI:10.1001/jamanetworkopen.2026.12183

JAMA Netw Open. 2026 May 1;9(5):e2612191. doi: 10.1001/jamanetworkopen.2026.12191.

ABSTRACT

IMPORTANCE: Children who live in households with firearms are several times more likely to die by suicide and unintentional firearm injury, compared with those in homes without guns. This risk can be mitigated by locking and unloading all household firearms.

OBJECTIVE: To describe firearm storage practices in homes with children overall and by the age of the youngest child in the household, and to estimate the number of children living in homes with firearms that are loaded and unlocked.

DESIGN, SETTING, AND PARTICIPANTS: A probability-based national survey study was conducted between December 18 and December 25, 2024, in the US. Eligible participants were firearm owners living with children younger than 18 years. Survey weights were incorporated to account for nonresponse and to produce nationally representative estimates.

EXPOSURE: Whether a child younger than 13 years lives in the household.

MAIN OUTCOMES AND MEASURES: The outcome of interest was firearm storage practices in the child’s home, categorized as (1) at least 1 gun loaded and unlocked; (2) no guns loaded and unlocked, but at least 1 loaded and locked or unloaded and unlocked; and (3) all guns unloaded and locked.

RESULTS: A total of 879 respondents personally owned a gun, lived in a household with 1 or more children younger than 18 years, and provided full information about storage. Among these gun owners, 65.3% were aged 18 to 44 years, 63.8% were male, and 70.2% lived with children aged 0 to 12 years. An estimated 21.1% (95% CI, 18.3%-24.3%) reported at least 1 gun loaded and unlocked; 34.8% (95% CI, 31.4%-38.3%) that all firearms were unloaded and locked; and the remainder otherwise (ie, neither any guns loaded and unlocked, nor all locked and unloaded). Among gun-owning adults whose children were all aged 13 to 17 years, an estimated 26.1% (95% CI, 20.2%-33.0%) stored at least 1 firearm loaded and unlocked, compared with 17.1% (95% CI, 12.9%-22.2%) of those whose children were all younger than 13 years and 17.4% (95% CI, 11.6%-25.2%) of those with both adolescents and younger children. Extrapolating to the 2024 US population, an estimated 32.3 million children younger than 18 years lived in a household with firearms, of whom 6.7 million (95% CI, 5.7-7.5 million) lived in a household with at least 1 loaded and unlocked gun.

CONCLUSIONS AND RELEVANCE: In this survey study of adult firearm owners who lived in households with children younger than 18 years, more than 1 in 5 reported that at least 1 firearm in their household was both loaded and unlocked, a practice more common when all children in the household were teenagers. More effective approaches to motivating parents to make their firearms inaccessible to both their teenagers and their younger children are needed.

PMID:42118532 | DOI:10.1001/jamanetworkopen.2026.12191

Menopause. 2026 May 12. doi: 10.1097/GME.0000000000002788. Online ahead of print.

ABSTRACT

OBJECTIVE: To explore any association between risk-reducing bilateral salpingooophorectomy (RRSO) and bone mineral density (BMD) and fracture risk among women with a germline likely pathogenic or pathogenic variant in genes causing hereditary breast and ovarian cancer.

METHODS: Longitudinal prospective observational study. Clinical, biochemical, and BMD assessments were performed at study entry (V0) and after 18 months (V1). Four groups were compared: RRSO (RRSO in premenopause without hormone therapy [HT]), RRSO+HT (RRSO followed by HT), MEN (natural menopause with/without RRSO), and FERT (regular menstrual cycles not undergoing RRSO).

RESULTS: One hundred four women were enrolled (52 BRCA1 germline likely pathogenic or pathogenic variant, 49 BRCA2, 3 other genes): 30 RRSO, 10 RRSO+HT, 29 MEN, 35 FERT. The V0 evaluation was performed at 2.85 ± 2.03 years from RRSO. At V0, no difference in lumbar spine (LS) and femoral neck BMD was detected comparing RRSO to RRSO+HT, MEN, and FERT. At V1 RRSO was associated with higher femoral neck BMD than MEN (P = 0.016), together with worse LS BMD than FERT (P = 0.045). The temporal decline of LS BMD in RRSO was more pronounced than MEN (P = 0.019). Calculated risk of fracture (Fracture Risk Assessment Tool [FRAX]) at V0 was lower in RRSO than MEN (P < 0.001), similar to RRSO+HT and FERT; at V1, FRAX was higher in RRSO than FERT (P = 0.014).

CONCLUSIONS: RRSO was associated with greater and prolonged bone health decline in women ovariectomized at premenopausal age, not receiving HT. This high-risk population deserves long-term BMD monitoring, and HT mitigating effect might be considered.

PMID:42118531 | DOI:10.1097/GME.0000000000002788

Anal Sci. 2026 May 12. doi: 10.1007/s44211-026-00902-4. Online ahead of print.

ABSTRACT

A portable microfluidic titration system using a smartphone camera was developed as a detector for onsite quantitative analysis. Two types of cross-shaped microfluidic devices with different channel geometries were designed and evaluated to improve the visual detectability of the equivalence point under limited spatial resolution. An expanding-channel device was found to promote molecular diffusion downstream, resulting in enhanced visibility of the equivalence point compared to a constant-width device. Using the optimized device, a strong acid-strong base system was subjected to acid-base titration using bromothymol blue as the indicator. The color images captured by the smartphone camera were analyzed by extracting the red channel intensity profiles and used to determine the distance corresponding to the equivalence point. A linear relationship was obtained between the measured distance and hydrochloric acid concentration in the range of 25-150 mM. The applicability of the proposed system was demonstrated by analyzing a real hot-spring water sample. The determined acid concentration was in good agreement with that obtained by conventional volumetric titration, with no statistically significant difference at the 95% confidence level. These results indicate that the proposed portable microfluidic titration system enables reliable quantitative analysis without the use of microscopes or specialized optical instruments, highlighting its potential for onsite analytical applications.

PMID:42118521 | DOI:10.1007/s44211-026-00902-4

Phys Eng Sci Med. 2026 May 12. doi: 10.1007/s13246-026-01739-x. Online ahead of print.

ABSTRACT

The early diagnosis of Parkinson’s disease (PD) using SPECT imaging continues to be challenging due to the subtle dopaminergic deficits present in the early stages of the disease. This study proposes a novel hybrid approach combining conventional and deep learning features to improve PD classification, and applies it to reclassify scans without evidence of dopaminergic deficit (SWEDD) cases. We used SPECT images from early PD patients and healthy controls (HC) and extracted SBR metrics, morphometric, and deep learning features. Our multi-stage feature selection pipeline employed near-zero variance filtering, ANOVA F-test analysis, correlation-based feature elimination, and Random Forest importance scoring. We evaluated multiple machine learning algorithms and selected Linear Discriminant Analysis as the optimal classifier, then applied this model to reclassify 79 SWEDD cases. Feature selection reduced 79 significant features to 15 optimal features: 1 SBR metric (6.7%), 7 morphometric (46.7%), and 7 deep features (46.7%). The hybrid Linear Discriminant model achieved the best performance, outperforming individual feature approaches with 97.40% test accuracy, 96.25% sensitivity, 98.65% specificity, and 99.59% AUC. Statistical analysis revealed morphometric features had the highest mean importance (0.0699 ± 0.0539), followed by deep (0.0400 ± 0.0570) and SBR features (0.0206 ± 0.019). SWEDD reclassification identified 5 cases (6.3%) with imaging patterns consistent with early PD, while 74 cases (93.7%) maintained HC characteristics. This study presents a proof-of-concept demonstration of the effectiveness of integrating conventional measures with deep learning techniques for improving the early diagnosis of PD, while offering new insights into SWEDD case reclassification.

PMID:42118513 | DOI:10.1007/s13246-026-01739-x

Saudi Dent J. 2026 May 12;38(5):65. doi: 10.1007/s44445-026-00178-4.

ABSTRACT

Periodontal wound dressings have advanced from passive protectants to bioactive agents. This study compared the efficacy of Blue®m gel and a hyaluronic acid (HA) gel in promoting wound healing and controlling postoperative pain after functional crown lengthening surgery. A prospective, randomized, patient and outcome assessor-blinded study was conducted on 40 systemically healthy patients (aged 20-60 years) requiring crown lengthening of posterior teeth. Participants were divided into two groups: Blue®m gel (Group A) and custom-formulated HA gel (Group B). Both gels were applied to the surgical site immediately after suturing and then three times daily for 1 week. Wound healing was assessed at 1, 2, and 3 weeks using the Early Wound Healing Index (EHS, including CSR for closure, CSH for hemostasis and CSI for inflammation) and the Landry Wound Healing Index. Postoperative pain was evaluated via a Numeric Pain Rating Scale (NPRS) on Days 1, 2, and 3. Outcome comparisons between groups were performed with Chi-square tests for categorical healing indices and Mann-Whitney test for ordinal data. Both interventions yielded excellent clinical outcomes with comparable healing patterns. By Week 1, 100% of sites in both groups had complete incision closure (merged margins). Approximately 20% of patients in each group showed slight fibrin presence and mild redness at Week 1, which resolved entirely by Week 2. Consequently, EHS scores were high in both groups (most cases scoring 9-10 at Week 1 and 10 by Week 2) with no significant intergroup difference (p > 0.05). The Landry index reflected progressive improvement from predominantly red tissue at Week 1 to fully pink, healthy tissue by Week 3 in both groups (p > 0.05). Postoperative pain was mild and diminished rapidly: On Day 1, pain scores ranged from 0 to 4 in Group A and 1 to 2 in Group B, dropping significantly by Day 3 with no difference between the two groups (p > 0.05). No adverse effects were observed with either gel. Blue®m gel and HA gel demonstrated favorable clinical outcomes in soft tissue wound healing and early postoperative pain control, with no statistically significant differences observed between groups. Both agents can be safely recommended as effective periodontal dressings in this context, with the choice between them potentially guided by practical considerations such as cost and availability.

PMID:42118509 | DOI:10.1007/s44445-026-00178-4

Drug Saf. 2026 May 12. doi: 10.1007/s40264-026-01677-3. Online ahead of print.

ABSTRACT

Spontaneous reporting databases play a central role in pharmacovigilance for monitoring the safety of drugs and vaccines. Conventional statistical signal detection has relied primarily on disproportionality analyses based on reporting frequencies, whereas information on the timing of adverse event onset has not been fully exploited. Time to onset (TTO), defined as the interval between the initiation of drug administration and the occurrence of an adverse event, provides complementary information that captures temporal patterns of event manifestation beyond simple occurrence counts. This review summarizes the definition, calculation, characteristics, and limitations of TTO analyses in spontaneous reporting databases and provides an overview of statistical signal detection methods incorporating TTO information. In particular, nonparametric distribution-comparison approaches, such as the Kolmogorov-Smirnov and Anderson-Darling tests, are well suited to spontaneous reporting data, in which the underlying population and exposure size are unknown. These methods enable the detection of abnormalities in the temporal structure of adverse event onset that may not be identifiable through frequency-based analyses alone. Furthermore, disproportionality analysis and TTO-based approaches are not competing methods but complementary strategies that capture different dimensions of safety signals-reporting frequency and temporal patterns-and their combined use may improve both sensitivity and interpretability of signal detection. The review also discusses survival analysis-based methods and Weibull modeling for TTO data, outlining their theoretical background and applications while emphasizing their inherent limitations when applied to spontaneous reporting systems. Because of reporting bias, incomplete time information, and the absence of non-event cases, such methods should not be used to estimate population-level risks or to infer causality. In conclusion, TTO analyses using spontaneous reporting databases should be positioned as exploratory tools for characterizing onset patterns, generating hypotheses, and informing the design of subsequent epidemiological and safety studies, rather than as a direct basis for clinical or regulatory decision making.

PMID:42118500 | DOI:10.1007/s40264-026-01677-3

Discov Nano. 2026 May 12;21(1):185. doi: 10.1186/s11671-026-04610-w.

ABSTRACT

In industries like chemical processing, energy systems, metallurgy, filtration, and electronics cooling, activation energy in magneto-nanofluid flow with variant viscosity is essential for regulating reaction rates, maximizing heat and mass transfer, enhancing energy efficiency, and guaranteeing safe operation. This work is important because it advances our knowledge of heat and mass transmission in magnetized nanofluid flows, where the fluid viscosity varies nonlinearly with temperature or other physical parameters. The study’s primary goal is to create a numerical model capable of precisely analyzing the intricate relationship between magnetic forces, nonlinear viscosity, porous media, and nanoparticle transport. To get the perfect predictions, the governing model employed the efficacy of artificial neural networks with Levenberg Marquardt structure back propagation (ANN-LMSB), which is designed to investigate energy activation with exponential viscosity variant with temperature on magneto-hydrodynamic nanofluid flow past porous plate (MHD-NFPP). To articulate mathematical modeling, the Reynolds exponential model is used. By employing the model of Darcy-Brinkman-Forchheimer, the momentum equation is additionally formulated. Thermophoresis force and Brownian diffusion have been inspected by implementing Buongiorno model. Along with magnetic body force, mass conservation, nanoparticle concentration, momentum, and energy equations are expressed. Initially, the flow of fluid is denoted by the scheme of PDEs, which are transformed into the structure of ODEs. By employing Adams numerical method, a data set for suggested ANN-LMSB is produced for diverse scenarios by alteration of stretching parameter, the Hartmann number, the thermal and concentration Grashof numbers, the thermophoresis, the Brownian motion, Prandtl number, the chemical reaction constant, Schmidt number, and relative temperature parametric number. By training, testing, and validation procedures of ANN-LMSB, estimated solution of distinct cases is verified, and for the perfection of the suggested model, the comparison for verification is carried out. Afterwards, execution of suggested ANN-LMSB was validated by regression evaluation, mean square error, and histogram studies. Correctness level in range from 10^-9 to 10^-11 approves distinction of suggested methodology established on the closeness of the recommended and reference results.

PMID:42118499 | DOI:10.1186/s11671-026-04610-w