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ObjectiveAsian Indians are among the fastest growing United States (US) ethnic subgroups. We characterized mortality trends for leading causes of death among foreign-born and US-born Asian Indians in the US between 2005-2017.Study design and settingUsing US standardized death certificate data, we examined leading causes of death in 73,470 Asian Indians and 20,496,189 non-Hispanic whites (NHWs) across age, gender, and nativity. For each cause, we report age-standardized mortality rates (AMR), longitudinal trends, and absolute percent change (APC).ResultsWe found that Asian Indians' leading causes of death were heart disease (28% mortality males; 24% females) and cancer (18% males; 22% females). Foreign-born Asian Indians had higher all-cause AMR compared to US-born (AMR 271 foreign-born, CI 263-280; 175.8 US-born, CI 140-221; pConclusionsForeign-born Asian Indians were 2.2 times more likely to die of heart disease and 1.6 times more likely to die of cancer. Asian Indian male AMR was 49% greater than female on average, although AMR was consistently lower for Asian Indians when compared to NHWs.

We recently discovered that a rope-pulley system that mechanically coupling the arms, legs and treadmill during walking can assist with forward propulsion in healthy subjects, leading to significant reductions in metabolic cost. However, walking balance may have been compromised, which could hinder the potential use of this device for gait rehabilitation. We performed a secondary analysis by quantifying average step width, step length, and step time, and used their variability to reflect simple metrics of walking balance (n = 8). We predicted an increased variability in at least one of these metrics when using the device, which would indicate disruptions to walking balance. When walking with the device, subjects increased their average step width (p < 0.05), but variability in step width and step length remained similar (p's > 0.05). However, the effect size for step length variability when compared to that of mechanical perturbation experiments suggest a minimal to moderate disruption in balance (Rosenthal ES = 0.385). The most notable decrement in walking balance was an increase in step time variability (p < 0.05; Cohen's d = 1.286). Its effect size reveals a moderate disruption when compared to the effect sizes observed in those with balance deficits (effect sizes ranged between 0.486 to 1.509). Overall, we conclude that healthy subjects experienced minimal to moderate disruptions in walking balance when using with this device. These data indicate that in future clinical experiments, it will be important to not only consider the mechanical and metabolic effects of using such a device but also its potential to disrupt walking balance, which may be exacerbated in patients with poor balance control.

Radiation therapy for cancer patients works by ionizing damage to nuclear DNA, primarily by creating double-strand breaks (DSB). A major shortcoming of traditional radiation therapy is the set of side effect associated with its long-range interaction with nearby tissues. Low-energy Auger electrons have the advantage of an extremely short effective range, minimizing damage to healthy tissue. Consequently, the isotope ⁹⁹mTc, an Auger electron source, is currently being studied for its beneficial potential in cancer treatment. We examined the dose effect of a pyrene derivative ⁹⁹mTc complex on plasmid DNA by using gel electrophoresis in both aqueous and methanol solutions. In aqueous solutions, the average yield per decay for double-strand breaks is 0.011±0.005 at low dose range, decreasing to 0.0005±0.0003 in the presence of 1 M dimethyl sulfoxide (DMSO). The apparent yield per decay for single-strand breaks (SSB) is 0.04±0.02, decreasing to approximately a fifth with 1 M DMSO. In methanol, the average yield per decay of DSB is 0.54±0.06 and drops to undetectable levels in 2 M DMSO. The SSB yield per decay is 7.2±0.2, changing to 0.4±0.2 in the presence of 2 M DMSO. The 95% decrease in the yield of DSB in DMSO indicates that the main mechanism for DSB formation is through indirect effect, possibly by cooperative binding or clustering of intercalators. In the presence of non-radioactive ligands at a near saturation concentration, where radioactive Tc compounds do not form large clusters, the yield of SSB stays the same while the yield of DSB decreases to the value in DMSO. DSBs generated by ⁹⁹mTc conjugated to intercalators are primarily caused by indirect effects through clustering.

Prion strains (or variants) are structurally distinct amyloid conformations arising from a single polypeptide sequence. The existence of prion strains has been well documented in mammalian prion diseases. In many cases, prion strains manifest as variation in disease progression and pathology, and in some cases, these prion strains also show distinct biochemical properties. Yet, the underlying basis of prion propagation and the extent of conformational possibilities available to amyloidogenic proteins remain largely undefined. Prion proteins in yeast that are also capable of maintaining multiple self-propagating structures have provided much insight into prion biology. Here, we explore the vast structural diversity of the yeast prion [RNQ+] in Saccharomyces cerevisiae. We screened for the formation of [RNQ+] in vivo, allowing us to calculate the rate of spontaneous formation as ~2.96x10(-6), and successfully isolate several different [RNQ+] variants. Through a comprehensive set of biochemical and biological analyses, we show that these prion variants are indeed novel. No individual property or set of properties, including aggregate stability and size, was sufficient to explain the physical basis and range of prion variants and their resulting cellular phenotypes. Furthermore, all of the [RNQ+] variants that we isolated were able to facilitate the de novo formation of the yeast prion [PSI+], an epigenetic determinant of translation termination. This supports the hypothesis that [RNQ+] acts as a functional amyloid in regulating the formation of [PSI+] to produce phenotypic diversity within a yeast population and promote adaptation. Collectively, this work shows the broad spectrum of available amyloid conformations, and thereby expands the foundation for studying the complex factors that interact to regulate the propagation of distinct aggregate structures.

Hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide, is most commonly caused by chronic hepatitis B virus (HBV) infection. However, whether HBV plays any direct role in carcinogenesis, other than indirectly causing chronic liver injury by inciting the host immune response, remains unclear. We have established two independent transgenic mouse lines expressing the complete genome of a mutant HBV ("preS2 mutant") that is found at much higher frequencies in people with HCC than those without. The transgenic mice show evidence of stress in the endoplasmic reticulum (ER) and overexpression of cyclin D1 in hepatocytes. These mice do not show any evidence of chronic liver injury, but by 2 years of age a majority of the male mice develop hepatocellular neoplasms, including HCC. Unexpectedly, we also found a significant increase in hepatocarcinogenesis independent of necroinflammation in a transgenic line expressing the entire wildtype HBV. As in the mutant HBV mice, HCC was found only in aged--2-year-old--mice of the wildtype HBV line. The karyotype in all the three transgenic lines appears normal and none of the integration sites of the HBV transgene in the mice is near an oncogene or tumor suppressor gene. The significant increase of HCC incidence in all the three transgenic lines--expressing either mutant or wildtype HBV--therefore argues strongly that in absence of chronic necroinflammation, HBV can contribute directly to the development of HCC.

BackgroundDisaggregated data is a cornerstone of precision health. Vietnamese Americans (VietAms) are the fourth-largest Asian subgroup in the United States (US), and demonstrate a unique burden of disease and mortality. However, most prior studies have aggregated VietAms under the broader Asian American category for analytic purposes. This study examined the leading causes of death among VietAms compared to aggregated Asian Americans and non-Hispanic Whites (NHWs) during the period 2005-2020.MethodsDecedent data, including underlying cause of death, were obtained from the National Center for Health Statistics national mortality file from 2005 to 2020. Population denominator estimates were obtained from the American Community Survey one-year population estimates. Outcome measures included proportional mortality, age-adjusted mortality rates per 100,000 (AMR), and annual percent change (APC) in mortality over time. Data were stratified by sex and nativity status. Due to large differences in age structure, we report native- and foreign-born VietAms separately.FindingsWe identified 74,524 VietAm decedents over the study period (71,305 foreign-born, 3,219 native-born). Among foreign-born VietAms, the three leading causes of death were cancer (26.6%), heart disease (18.0%), and cerebrovascular disease (9.0%). Among native-born VietAms the three leading causes were accidents (19.0%), self-harm (12.0%), and cancer (10.4%). For every leading cause of death, VietAms exhibited lower mortality compared to both aggregated Asians and NHWs. Over the course of the study period, VietAms witnessed an increase in mortality in every leading cause. This effect was mostly driven by foreign-born, male VietAms.Conclusions and relevanceWhile VietAms have lower overall mortality from leading causes of death compared to aggregated Asians and NHWs, these advantages have eroded markedly between 2005 and 2020. These data emphasize the importance of racial disaggregation in the reporting of public health measures.

BackgroundSolid organ transplant (SOT) recipients are predicted to have worse COVID-19 outcomes due to their compromised immunity. However, this association remains uncertain because published studies have had small sample sizes and variability in chronic comorbidity adjustment.MethodsIn this retrospective cohort study conducted at a multihospital health system, we compared COVID-19 outcomes and survival up to 60 days following hospital admission in SOT recipients taking baseline immunosuppressants versus hospitalized control patients.ResultsThe study included 4,562 patients who were hospitalized with COVID-19 (108 SOT recipients and 4,454 controls) from 03/2020 to 08/2020. Mortality at 60 days was higher for SOT recipients (17% SOT vs 10% control; unadjusted odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.04-2.91, P = 0.04). We then conducted a 1:5 propensity matched cohort analysis (100 SOT recipients; 500 controls) using age, sex, race, body mass index, hypertension, diabetes, chronic kidney disease, liver disease, admission month, and area deprivation index. Within 28 days of admission, SOT recipients had fewer hospital-free days (median; 17 SOT vs 21 control; OR = 0.64, 95%CI 0.46-0.90, P = 0.01) but had similar ICU-free days (OR = 1.20, 95%CI 0.72-2.00, P = 0.49) and ventilator-free days (OR = 0.91, 95%CI 0.53-1.57, P = 0.75). There was no statistically significant difference in 28-day mortality (9% SOT vs 12% control; OR = 0.76, 95%CI 0.36-1.57, P = 0.46) or 60-day mortality (16% SOT vs 14% control; OR = 1.15, 95%CI 0.64-2.08, P = 0.64).ConclusionsHospitalized SOT recipients appear to need additional days of hospital care but can achieve short-term mortality outcomes from COVID-19 that are similar to non-SOT recipients in a propensity matched cohort study.

BACKGROUND:Over a third of menopausal hormone therapy (HT) prescriptions in the US are written for women over age 60. Use of HT more than 5 years is associated with increased risk for cardiovascular disease; breast, ovarian, and endometrial cancers; thromboembolic stroke; gallbladder disease; dementia; and incontinence. OBJECTIVES:To explore older women's perceptions of the benefits and risks of long-term HT and examine factors influencing their decisions to use HT > 5 years despite medical risks. METHODS:A qualitative approach was selected to broadly explore thought processes and social phenomena underlying long-term users' decisions not to discontinue HT. Interviews were conducted with 30 women over age 60 reporting use of systemic HT more than 5 years recruited from an urban area in California and a small city in the Rocky Mountain region. Transcripts of interviews were analyzed using conventional grounded theory methods. RESULTS:Women reported using HT to preserve youthful physical and mental function and prevent disease. Gynecologists had reassured participants regarding risk, about which all 30 expressed little concern. Participants, rather than providers, were the principal drivers of long-term use. CONCLUSIONS:Participants perceived estrogen to have anti-aging efficacy, and using HT imparted a sense of control over various aspects of aging. Maintaining this sense of control was prioritized over potential risk from prolonged use. Our findings provide an additional perspective on previous work suggesting the pharmaceutical industry has leveraged older women's self-esteem, vanity, and fear of aging to sell hormones through marketing practices designed to shape the beliefs of both clinicians and patients. Efforts are needed to: 1) address misconceptions among patients and providers about medically supported uses and risks of prolonged HT, and 2) examine commercial influences, such as medical ghostwriting, that may lead to distorted views of HT efficacy and risk.

BACKGROUND:Anti-inflammatory drug development efforts for lung disease have been hampered in part by the lack of noninvasive inflammation biomarkers and the limited ability of animal models to predict efficacy in humans. We used 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in a human model of lung inflammation to assess whether pioglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, and zileuton, a 5-lipoxygenase inhibitor, reduce lung inflammation. METHODS:For this single center, single-blind, placebo-controlled cohort study, we enrolled healthy volunteers sequentially into the following treatment cohorts (N = 6 per cohort): pioglitazone plus placebo, zileuton plus placebo, or dual placebo prior to bronchoscopic endotoxin instillation. 18F-FDG uptake pre- and post-endotoxin was quantified as the Patlak graphical analysis-determined Ki (primary outcome measure). Secondary outcome measures included the mean standard uptake value (SUVmean), post-endotoxin bronchoalveolar lavage (BAL) cell counts and differentials and blood adiponectin and urinary leukotriene E4 (LTE4) levels, determined by enzyme-linked immunosorbent assay, to verify treatment compliance. One- or two-way analysis of variance assessed for differences among cohorts in the outcome measures (expressed as mean ± standard deviation). RESULTS:Ten females and eight males (29±6 years of age) completed all study procedures except for one volunteer who did not complete the post-endotoxin BAL. Ki and SUVmean increased in all cohorts after endotoxin instillation (Ki increased by 0.0021±0.0019, 0.0023±0.0017, and 0.0024±0.0020 and SUVmean by 0.47±0.14, 0.55±0.15, and 0.54±0.38 in placebo, pioglitazone, and zileuton cohorts, respectively, p

This study aimed to investigate the effects of anti-tumor necrosis factor (TNF)-α antibody (Ab) on alteration of penile structure in the hyperprolactinemia (hyperPRL) rat model. HyperPRL was induced in 8-week-old male Sprague-Dawley rats by allografting anterior pituitary (AP) glands under the renal capsule (+AP rats). Rats implanted with cerebral cortex (CX) were used as sham control (+CX rats). At 6 weeks post implantation, rats received either a single intra-testicular dose of TNF-α Ab (12.5 μg/kg) or testosterone replacement (2 doses of testosterone enanthate [TE], 3 mg/kg), and they were sacrificed 1 week later. Blood and penile tissue was collected for analysis. Compared to +CX rats, the +AP group had lower serum testosterone concentration and neuronal nitric oxide synthase (nNOS) expression, but exhibited a higher ratio of collagen III/I in the corpus cavernosum. Smooth muscle content exhibited no significant changes. At 1 week post TNF-α Ab injection, the collagen III/I ratio in the +AP group was decreased, and the smooth muscle content and nNOS expression increased significantly. These findings were comparable to those observed in +AP rats receiving TE. Testicular TNF-α suppresses testosterone release, which in turn results in the erectile dysfunction (ED) seen in hyperPRL. Intra-testicular TNF-α Ab treatment is as effective as testosterone supplementation on penile structure normalization in the hyperPRL model.

The Affordable Care Act (ACA) has expanded access to health insurance for millions of Americans, but the impact of Medicaid expansion on healthcare delivery and utilization remains uncertain.To determine the early impact of the Medicaid expansion component of ACA on hospital and ED utilization in California, a state that implemented the Medicaid expansion component of ACA and Florida, a state that did not.Analyze all ED encounters and hospitalizations in California and Florida from 2009 to 2014 and evaluate trends by payer and diagnostic category. Data were collected from State Inpatient Databases, State Emergency Department Databases and the California Office of Statewide Health Planning and Development.Hospital and ED encounters.Population-based study of California and Florida state residents.Implementation of Medicaid expansion component of ACA in California in 2014.Changes in ED visits and hospitalizations by payer, percentage of patients hospitalized after an ED encounter, top diagnostic categories for ED and hospital encounters.In California, Medicaid ED visits increased 33% after Medicaid expansion implementation and self-pay visits decreased by 25% compared with a 5.7% increase in the rate of Medicaid patient ED visits and a 5.1% decrease in rate of self-pay patient visits in Florida. In addition, California experienced a 15.4% increase in Medicaid inpatient stays and a 25% decrease in self pay stays. Trends in the percentage of patients admitted to the hospital from the ED were notable; a 5.4% decrease in hospital admissions originating from the ED in California, and a 2.1% decrease in Florida from 2013 to 2014.We observed a significant shift in payer for ED visits and hospitalizations after Medicaid expansion in California without a significant change in top diagnoses or overall rate of these ED visits and hospitalizations. There appears to be a shift in reimbursement burden from patients and hospitals to the government without a dramatic shift in patterns of ED or hospital utilization.

Patients undergoing radical prostatectomy (RP) are at high risk for erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis.We previously showed that corpora cavernosum smooth muscle cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN) rats.Sprague-Dawley rats underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM).Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia-inducible factor-1α and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle α-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats.CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury-induced ED.

A broad range of anti-cancer agents, including glucocorticoids (GCs) and tyrosine kinase inhibitors (TKIs), kill cells by upregulating the pro-apoptotic BCL2 family member, BIM. A common germline deletion in the BIM gene was recently shown to favor the production of non-apoptotic BIM isoforms, and to predict inferior responses in TKI-treated chronic myeloid leukemia (CML) and EGFR-driven lung cancer patients. Given that both in vitro and in vivo GC resistance are predictive of adverse outcomes in acute lymphoblastic leukemia (ALL), we hypothesized that this polymorphism would mediate GC resistance, and serve as a biomarker of poor response in ALL. Accordingly, we used zinc finger nucleases to generate ALL cell lines with the BIM deletion, and confirmed the ability of the deletion to mediate GC resistance in vitro. In contrast to CML and lung cancer, the BIM deletion did not predict for poorer clinical outcome in a retrospective analysis of 411 pediatric ALL patients who were uniformly treated with GCs and chemotherapy. Underlying the lack of prognostic significance, we found that the chemotherapy agents used in our cohort (vincristine, L-asparaginase, and methotrexate) were each able to induce ALL cell death in a BIM-independent fashion, and resensitize BIM deletion-containing cells to GCs. Together, our work demonstrates how effective therapy can overcome intrinsic resistance in ALL patients, and suggests the potential of using combinations of drugs that work via divergent mechanisms of cell killing to surmount BIM deletion-mediated drug resistance in other cancers.

A subset of patients with Ewing's sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies. Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway that could also be suppressed by small interfering (si) RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing's sarcoma. The growth of two Ewing's sarcoma cell lines (TC-32 and TC-71) was inhibited by the fully human anti-IGF-1R antibody, R1507 (clonogenic and MTT assays). TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573 Ewing's cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71 cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalization/degradation, an effect which was associated with a decrease in p-IGF-1R, p-IRS-1, and p-Akt. EWS/FLI-1 siRNA also decreased p-Akt, due to its ability to increase IGF-BP3 levels and subsequently decrease IGF-1 and IGF-2 levels, thus inhibiting signaling through p-IGF-1R. This inhibition correlated with growth suppression and apoptosis. The attenuation of Akt activation was confirmed in TC-71 and HEK-293 (human embryonic kidney) cells by transfecting them with IGF-1R siRNA. We conclude that antibodies and siRNA to IGF-1R, as well as siRNA to EWS/FLI-1, act via intersecting IGF/IGF-1R signals that suppress a common point in this pathway, namely the phosphorylation of Akt.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.

Understanding how stability and/or maneuverability affects motor control strategies can provide insight on moving about safely in an unpredictable world. Stability in human movement has been well-studied while maneuverability has not. Further, a tradeoff between stability and maneuverability during movement seems apparent, yet has not been quantified. We proposed that greater maneuverability, the ability to rapidly and purposefully change movement direction and speed, is beneficial in uncertain environments. We also hypothesized that gaining maneuverability comes at the expense of stability and perhaps also corresponds with decreased muscle coactivation.We used a goal-directed forward lean movement task that integrated both stability and maneuverability. Subjects (n = 11) used their center of pressure to control a cursor on a computer monitor to reach a target. We added task uncertainty by shifting the target anterior-posterior position mid-movement. We used a balance board with a narrow beam that reduced the base of support in the medio-lateral direction and defined stability as the probability that subjects could keep the balance board level during the task.During the uncertainty condition, subjects were able to change direction of their anterior-posterior center of pressure more rapidly, indicating that subjects were more maneuverable. Furthermore, medio-lateral center of pressure excursions also approached the edges of the beam and reduced stability margins, implying that subjects were less stable (i.e. less able to keep the board level). On the narrow beam board, subjects increased muscle coactivation of lateral muscle pairs and had greater muscle activity in the left leg. However, there were no statistically significant differences in muscle activity amplitudes or coactivation with uncertainty.These results demonstrate that there is a tradeoff between stability and maneuverability during a goal-directed whole-body movement. Tasks with added uncertainty could help individuals learn to be more maneuverable yet sufficiently stable.

Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective "early" and "late" colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations.

Colonization of the infant gut by microorganisms over the first year of life is crucial for development of a balanced immune response. Early alterations in the gastrointestinal microbiota of neonates has been linked with subsequent development of asthma and atopy in older children. Here we describe high-resolution culture-independent analysis of stool samples from 6-month old infants fed daily supplements of Lactobacillus casei subsp. Rhamnosus (LGG) or placebo in a double-blind, randomized Trial of Infant Probiotic Supplementation (TIPS). Bacterial community composition was examined using a high-density microarray, the 16S rRNA PhyloChip, and the microbial assemblages of infants with either high or low LGG abundance were compared. Communities with high abundance of LGG exhibited promotion of phylogenetically clustered taxa including a number of other known probiotic species, and were significantly more even in their distribution of community members. Ecologically, these aspects are characteristic of communities that are more resistant to perturbation and outgrowth of pathogens. PhyloChip analysis also permitted identification of taxa negatively correlated with LGG abundance that have previously been associated with atopy, as well as those positively correlated that may prove useful alternative targets for investigation as alternative probiotic species. From these findings we hypothesize that a key mechanism for the protective effect of LGG supplementation on subsequent development of allergic disease is through promotion of a stable, even, and functionally redundant infant gastrointestinal community.

BACKGROUND: The initial prodromal state of psychosis (IPS) is defined as an early disease stage prior to the onset of overt psychosis characterized by sub-threshold or more unspecific psychiatric symptoms. Little is known regarding the biochemical changes during this period. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the metabolic/proteomic profiles of cerebrospinal fluid (CSF) of first-onset drug naïve paranoid schizophrenia patients (n = 54) and individuals presenting with initial prodromal symptoms (n = 24), alongside healthy volunteers (n = 70) using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy and surface enhanced laser desorption ionization (SELDI) mass spectrometry, respectively. Partial least square discriminant analysis (PLS-DA) showed that 36%/29% of IPS patients displayed proteomic/metabolic profiles characteristic of first-onset, drug naïve schizophrenia, i.e., changes in levels of glucose and lactate as well as changes in a VGF-derived peptide (VGF23-62) and transthyretin protein concentrations. However, only 29% (n = 7) of the investigated IPS patients (who to date have been followed up for up to three years) have so far received a diagnosis of schizophrenia. The presence of biochemical alterations in the IPS group did not correlate with the risk to develop schizophrenia. CONCLUSIONS/SIGNIFICANCE: Our results imply that schizophrenia-related biochemical disease processes can be traced in CSF of prodromal patients. However, the biochemical disturbances identified in IPS patients, at least when measured at a single time point, may not be sufficient to predict clinical outcome.

Purpose: To understand changes in purchasing behaviors and use of tobacco products such as e-cigarettes and cigarettes among different tobacco user groups during the COVID-19 pandemic using a mixed methods approach., Methods: A quantitative online survey was conducted in October-November 2020 using a national probability sample of US adults (N = 1,460) comprising exclusive cigarette smokers (n = 1,080), dual users of both cigarettes and e-cigarettes (n = 143), and exclusive e-cigarette users (n = 237). Simultaneously, ten online focus groups were conducted with 61 adults in the Atlanta, GA area including exclusive smokers (n = 16), current E-cigarette users (n = 22), and transitioning (recently quit or currently quitting) smokers and/or E-cigarette users (n = 23)., Results: From the survey, dual users vs. exclusive smokers had higher odds of buying cheaper cigarette brands (adjusted odds ratio (aOR) 2.50, 95% confidence interval (CI) = 1.49, 4.20), buying cigarettes online (aOR = 2.79; 95% CI = 1.02, 7.69), buying from Indian Reservations (aOR = 3.99; 95% CI = 2.07, 7.69), buying fewer cigarettes than normal (aOR = 4.01; 95% CI = 2.42, 6.65) and buying other tobacco products (aOR = 4.44; 95% CI = 2.24, 8.79). From the focus groups, participants perceived reduced accessibility, fear of contracting COVID-19, rising prices, and convenience to influence their purchasing behaviors and tobacco use., Conclusions: Exclusive and dual users differed in their tobacco purchasing behaviors during the COVID-19 pandemic, such that dual users were more likely to change their purchasing behaviors (e.g., buying other tobacco products) than exclusive users. Educational campaigns and public health workers may promote interventions targeting dual users either to switch to reduced-risk products or quit smoking, particularly during stressful societal situations such as the COVID-19 pandemic., Implications: The findings inform public health educators and policymakers to develop policies and interventions carefully tailored for tobacco user groups targeting the perceived factors influencing purchasing behaviors during challenging situations affecting tobacco product availability., Competing Interests: We have read the journal’s policy, and the authors of this manuscript have the following competing interests: D.L.A. has received funds for work done at the World Health Organization Tobacco Free Initiative, as a Special Government Employee of the U.S. Food and Drug Administration, as a consultant for Pfizer, as an employee of Cherokee National Operational Systems and as an independent contractor for McKing Consulting. Other authors declare no conflicts of interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Kute et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Osteoarthritis (OA) is a degenerative joint disease prevalent in the elderly. Currently, the relationship between the senescence inhibitor Klotho and OA remains unclear. This study investigated the relationship between serum soluble Klotho (S-Klotho) and OA., Methods: This cross-sectional study was based on the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Three multifactorial logistic regression models were constructed to assess the association between serum Klotho and OA. Restricted cubic spline (RCS) curves were further used to assess whether there was a nonlinear relationship between serum Klotho and OA. Finally, stratified analyses and interaction tests were used to evaluate the association's stability. To further investigate the relationship between serum Klotho and OA, we recruited 107 patients for analysis at the First Affiliated Hospital of Guangxi Medical University., Results: The final 8,918 participants included in this study comprised 50.55% females and 49.45% males, with 18.10% of participants suffering from OA and a mean S-Klotho level of 846.41 (5.61) pg/ml. All three logistic regression models observed a negative association between continuous S-Klotho and OA risk. When S-Klotho was categorized into tertiles, the fully adjusted model showed that participants in the third tertile had a 17% lower risk of OA than those in the first tertile (OR = 0.83, 95% CI: 0.70, 0.99, P = 0.035). The RCS curves showed a linear negative association between S-Klotho and the incidence of OA (P for overall = 0.025; P for non-linearity = 0.667). Further subgroup analyses and interaction tests suggested that the negative association between S-Klotho and OA remained stable in different conditions. Research conducted in China has shown that the negative correlation between serum Klotho levels and the prevalence of OA remains evident among Chinese individuals (OR: 0.77, 95% CI: 0.66, 0.90, P<0.001)., Conclusion: Our study suggests that elevated levels of the senescence inhibitor S-Klotho may be a potential protective factor for OA, which may provide new insights into the diagnosis and treatment of OA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Qiu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study compared field-of-view (FOV) optimized and constrained undistorted single-shot diffusion-weighted imaging (FOCUS DWI) with deep-learning-based reconstruction (DLR) to conventional DWI for breast imaging., Methods: This study prospectively enrolled 49 female patients suspected of breast cancer from July to December 2023. The patients underwent conventional and FOCUS breast DWI and data were reconstructed with and without DLR. Two radiologists independently evaluated three images per patient using a 5-point Likert scale. Objective evaluations, including signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC), were conducted using manual region of interest-based analysis. The subjective and objective evaluations were compared using the Friedman test., Results: The scores for the overall image quality, anatomical details, lesion conspicuity, artifacts, and distortion in FOCUS-DLR DWI were higher than in conventional DWI (all P < 0.001). The SNR of FOCUS-DLR DWI was higher than that of conventional and FOCUS DWI (both P < 0.001), while FOCUS and conventional DWI were similar (P = 0.096). Conventional, FOCUS, and FOCUS-DLR DWI had similar CNR and ADC values., Conclusion: Our findings indicate that images produced by FOCUS-DLR DWI were superior to conventional DWI, supporting the applicability of this technique in clinical practice. DLR provides a new approach to optimize breast DWI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ming et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Several scoring systems have been proposed to predict the risk of death due to severe fever with thrombocytopenia syndrome (STFS), but they have limitations. We developed a new prognostic nomogram for STFS-related death and compared its performance with previous scoring systems and the Acute Physiology and Chronic Health Evaluation score (APACHE II Score)., Methods: A total of 292 STFS patients were retrospectively enrolled between January 2016 and March 2023. Boruta's algorithm and backward stepwise regression were used to select variables for constructing the nomogram. Time-dependent receiver operating characteristic (ROC) curves and clinical decision curves were generated to compare the strengths of the nomogram with others., Results: Age, Sequential Organ Failure Assessment Score (SOFA score), state of consciousness, continuous renal replacement therapy (CRRT), and D-dimer were significantly correlated with mortality in both univariate and multivariate analyses (P<0.05). We developed a nomogram using these variables to predict mortality risk, which outperformed the SFTS and APACHE II scores (Training ROC: 0.929 vs. 0.848 vs. 0.792; Validation ROC: 0.938 vs. 0.839 vs. 0.851; P<0.001). In the validation set, the SFTS model achieved an accuracy of 76.14%, a sensitivity of 95.31%, a specificity of 25.00%, a precision of 77.22%, and an F1 score of 85.32%. The nomogram showed a superior performance with an accuracy of 86.36%, a precision of 88.24%, a recall of 93.75%, and an F1 score of 90.91%., Conclusion: Age, consciousness, SOFA Score, CRRT, and D-Dimer are independent risk factors for STFS-related death. The nomogram based on these factors has an excellent performance in predicting STFS-related death and is recommended for clinical practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fuzzy front-end is the research frontier of manufacturing industry. This study investigates the relationship between market-oriented FFE activities and manufacturing startup growth performance by adopting an open innovative ancient Chinese Taoism Yin-Yang approach under this post-pandemic circumstance. This study also examines the moderating behavioral effect of Chinese Zen-originated CEO mindfulness between market-oriented FFE activities and manufacturing startup growth performance. Data for this study were gathered from 343 Chinese manufacturing startups' CEOs across different manufacturing industries, including both high-tech and conventional manufacturing industries. The collected data were analyzed by using structural equation modeling and Bootstrap method. The quantitative analysis results show that most market-oriented FFE activities have positive effects on manufacturing startup growth performance and the Chinese Zen-originated CEO mindfulness positively moderates the relationship between most FFE activities and startup growth performance., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: the authors have declared that no competing interests exist., (Copyright: © 2024 Huang, Hu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The swimming pool reactor (SPR) is an innovative and environmentally friendly heating source. An SPR building was selected as the research subject, and a 3D dynamic interaction model incorporating the liquid sloshing effect was created using ANSYS software and the secondary development characteristics of user-programmable features (UPFs). Energy dissipation from scattered waves was accounted for using viscous-spring boundary elements, while the dynamic hydraulic effect was modeled via the Housner equivalent mechanical model. Considering soil-structure interaction (SSI) effects, this study examines the impact of isolation measures on the structure's seismic mitigation performance. It investigates how varying foundation conditions affect the seismic resistance of the isolated structure. Results indicate that seismic isolation ratios for acceleration, floor response spectra, displacement, and base shear diminish as site stiffness decreases. However, regarding sloshing wave height, seismic isolation amplified the height under all conditions but remained within safe limits. These findings offer valuable insights for seismic design across different SPRs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To prospectively observe the self-correction of congenital auricular deformity (CAD) and explore the potential factors affecting the self-correction., Methods: This study was a multi-center prospective observational study. Newborns aged 0-3 days from 12 Maternal and Child Health Hospitals or Maternity Hospitals were chosen as the participants and prospectively followed up until week 6 after birth. The primary and secondary outcome was the score of deformity, and the secondary outcome was the improvement rate, respectively., Results: A total of 135 newborns diagnosed with CAD (237 ears) were recruited. Boys and girls accounted for 50.37% (117 ears) and 49.63% (120 ears). The top morphological type was the constricted ear (107 ears, 45.15%). The score of deformity at baseline, week 3, and week 6 after enrollment was 4.00, 3.00, and 2.00, decreasing over time (P < 0.05). The higher the severity of deformity, the worse the self-correcting effect (P < 0.05). The scores of deformity of Stahl's ear were lower than those of others after follow-up (P < 0.05). No significant differences among the scores of deformity in different genders (P >0.05). The total improvement rate at week 3 and week 6 was 29.96% (71/237 ears) and 37.13% (88/237), respectively. The improvement rate of the Stahl's ear at week 3 and week 6 after enrollment was higher than that of four other morphological types (P < 0.05)., Conclusions: Some CAD tends to self-correction, but for most CADs, there is still a need for early correction. Morphological types and severity of deformity are the main influencing factors on self-correcting effect, whereas sex was not., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sarmentosin (SA) and Quercetin (QC) are two active components of Sedum Sarmentosum Bunge, which is a traditional Chinese herbal medicine. This study aimed to investigate the role and regulatory mechanism of SA and QC in fatty liver of Genetic Improvement of Farmed Tilapia (GIFT) tilapia. GIFT tilapia were randomly divided into two groups with three replicates per treatment (30 fish in each replicate): normal diet group (average weight 3.51±0.31 g) and high-fat diet group (average weight 3.44±0.09 g). After 8 weeks feeding trial, growth index, lipid deposition, and biochemical indexes were measured. Lipid deposition, and lipid and inflammation-related gene expression were detected in a primary hepatocyte model of fatty liver of GIFT tilapia treated with SA or QC. Our results showed that high-fat diet caused lipid deposition and peroxidative damage in the liver of GIFT tilapia. The cell counting kit-8 assay results indicated that 10 μM SA and 10 μM of QC both had the least effect on hepatocyte proliferation. Moreover, both 10 μM of SA and 10 μM of QC showed lipolytic effects and inhibited the expression of lipid-related genes (FAS, Leptin, SREBP-1c, and SREBP2) in fatty liver cells. Interestingly, QC induced autophagosome-like subcellular structure and increased the expression of IL-8 in fatty liver cells. In conclusion, this study confirmed that SA and QC improved fatty liver caused by high-fat diet, providing a novel therapeutic approach for fatty liver of GIFT tilapia., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Sarcopenia is considered to be an important predictor of adverse outcomes following spinal surgery, but the specific relationship between the two is not clear. The purpose of this meta-analysis is to systematically review all relevant studies to evaluate the impact of sarcopenia on spinal surgery outcomes., Methods: We systematically searched PubMed, Embase and the Cochrane Library for relevant articles published on or before January 9, 2023. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated in a random effects meta-analysis. The main outcome was the risk of adverse outcomes after spinal surgery, including adverse events and mortality. This systematic review and meta-analysis was conducted following the PRISMA guidelines to evaluate the impact of sarcopenia on spinal surgery outcomes. In addition, we also conducted a subgroup analysis and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results., Results: Twenty-four cohort studies, with a total of 243,453 participants, met the inclusion criteria. The meta-analysis showed that sarcopenia was significantly associated with adverse events (OR 1.63, 95% CI 1.17-2.27, P < 0.001) but was no significantly associated with mortality (OR 1.17, 95% CI 0.93-1.46, P = 0.180), infection (OR 2.24, 95% CI 0.95-5.26, P < 0.001), 30-day reoperation (OR 1.47, 95% CI 0.92-2.36, P = 0.413), deep vein thrombosis (OR 1.78, 95% CI 0.69-4.61, P = 0.234), postoperative home discharge (OR 0.60, 95% CI 0.26-1.37, P = 0.002) and blood transfusion (OR 3.28, 95% CI 0.74-14.64, P = 0.015)., Conclusion: The current meta-analysis showed that patients with sarcopenia have an increased risk of adverse events and mortality after spinal surgery. However, these results must be carefully interpreted because the number of studies included is small and the studies are significantly different. These findings may help to increase the clinicians' awareness of the risks concerning patients with sarcopenia to improve their prognosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study investigates the impact of maternal health on infant development by developing a mathematical model that delineates the relationship between maternal health indicators and infant behavioral characteristics and sleep quality. The main contributions of this study are as follows: (1) The use of Spearman's correlation coefficient to conduct correlation analysis and explore the main factors that influence infant behavioral characteristics based on maternal indicators. (2) The development of a combined model using machine learning techniques, including random forest (RF) and multilayer perceptron (MLP) to establish the relationship between maternal health (physical and psychological health) and infant behavioral characteristics. The model is trained and validated by the real data respectively. (3) The use of the Fuzzy C-means (FCM) dynamic clustering model to classify infant sleep quality. An RF regression model is constructed to predict infant sleep quality using maternal indicators. This study is significant in gaining a deeper understanding of the relationship between maternal health indicators and infant development, and provides a basis for future intervention measures., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To examine the impact of pre-harvest fungicide applications on the postharvest storage performance of tomato fruits, we measured the lycopene content, hardness, soluble solids content, rotting rate, and weight loss rate of the fruits, as well as conducted a sensory assessment. Protective and systematic fungicides were sprayed on tomatoes 20 days before harvest in order to prevent rotting and weight loss during storage. Our findings showed that, the fungicide-treated tomatoes had a significantly lower rotting rate of 16.00% and a weight loss rate of 3.96%. However the control group experienced 65.33% rotting rate and 6.90% weight loss rate on 12th days of storage. Out of the pre-harvest applications, 'Zineb' a protective fungicide significantly delayed the loss of hardness and soluble solids accumulation in tomato fruits during storage, but it had no significant effect on lycopene content. On the other hand, when comparing to the examined treatment, the systemic fungicides did not have any significant effect on the postharvest storage performance of tomato fruits. Sensory evaluation results indicated that systemic fungicides improved the aroma of the fruits, while protective fungicides had a greater impact on the appearance and juiciness of the fruits. This study offers a potential novel solution for preserving fruits and vegetables which have been frequently infected by phytopathogens during storage, and consequently mitigate/reduce postharvest losses., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Lan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fluctuations in the financial market are influenced by various driving forces and numerous factors. Traditional financial research aims to identify the factors influencing stock prices, and existing works construct a common neural network learning framework that learns temporal dependency using a fixed time window of historical information, such as RNN and LSTM models. However, these models only consider the short-term and point-to-point relationships within stock series. The financial market is a complex and dynamic system with many unobservable temporal patterns. Therefore, we propose an adaptive period-aggregation model called the Latent Period-Aggregated Stock Transformer (LPAST). The model integrates a variational autoencoder (VAE) with a period-to-period attention mechanism for multistep prediction in the financial time series. Additionally, we introduce a self-correlation learning method and routing mechanism to handle complex multi-period aggregations and information distribution. Main contributions include proposing a novel period-aggregation representation scheme, introducing a new attention mechanism, and validating the model's superiority in long-horizon prediction tasks. The LPAST model demonstrates its potential and effectiveness in financial market prediction, highlighting its relevance in financial research and predictive analytics., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Tang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Nowadays, federated learning is one of the most prominent choices for making decisions. A significant benefit of federated learning is that, unlike deep learning, it is not necessary to share data samples with the model owner. The weight of the global model in traditional federated learning is created by averaging the weights of all clients or sites. In the proposed work, a novel method has been discussed to generate an optimized base model without hampering its performance, which is based on a genetic algorithm. Chromosome representation, crossover, and mutation-all the intermediate operations of the genetic algorithm have been illustrated with useful examples. After applying the genetic algorithm, there is a significant improvement in inference time and a huge reduction in storage space. Therefore, the model can be easily deployed on resource-constrained devices. For the experimental work, sports data has been used in balanced and unbalanced scenarios with various numbers of clients in a federated learning environment. In addition, we have used four famous deep learning architectures, such as AlexNet, VGG19, ResNet50, and EfficientNetB3, as the base model. We have achieved 92.34% accuracy with 9 clients in the balanced data set by using EfficientNetB3 as the base model using a GA-based approach. Moreover, after applying the genetic algorithm to optimize EfficientNetB3, there is an improvement in inference time and storage space by 20% and 2.35%, respectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Friedman's standards, developed almost 50 years ago, may no longer align with the needs of today's obstetric population and current pregnancy management practices. This study aims to analyze contemporary labor patterns and estimate labor duration in China, focusing on first-stage labor data from Chinese parturients with a spontaneous onset of labor., Methods: This retrospective observational study utilized data from electronic medical records of a tertiary hospital in Changsha, Hunan. Out of a total of 2,689 parturients, exclusions were made for multiple gestations, preterm, post-term, or stillbirth, cesarean delivery, non-vertex presentation, and neonatal intensive care unit admission. Average labor curves were constructed by parity using repeated-measure analysis, and labor duration was estimated through interval-censored regression, stratified by cervical dilation at admission. We performed an analysis to assess the impact of oxytocin augmentation and amniotomy on labor progression and conducted a sensitivity analysis using women with complicated outcomes., Results: Nulliparous women take over 180 minutes for cervical dilation from 3 to 4 cm, and the duration from 5 to 6 cm exceeds 145 minutes. Multiparous women experience shorter labor durations than nulliparous. Labor acceleration is observed after 5 cm in nulliparous, but no distinct inflection point is evident in the average labor curve. In the second stage of labor, the 95th percentile for nulliparous, with and without epidural analgesia, is 142 minutes and 127 minutes, respectively., Conclusions: These findings provide valuable insights for the reassessment of labor and delivery processes in contemporary obstetric populations, including current Chinese obstetric practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Due to the competitive nature of the construction industry, the efficiency of requirement analysis is important in enhancing client satisfaction and a company's reputation. For example, determining the optimal configuration of panels (generally called panelization) that form the structure of a building is one aspect of cost estimation. However, existing methods typically rely on rule-based approaches that may lead to suboptimal material usage, particularly in complex designs featuring angled walls and openings. Such inefficiency can increase costs and environmental impact due to unnecessary material waste. To address these challenges, this research proposes a Panelization Algorithm for Architectural Designs, referred to as PAAD, which utilizes a genetic evolutionary strategy built on the 2D bin packing problem. This method is designed to balance between strict adherence to manufacturing constraints and the objective of optimizing material usage. PAAD starts with multiple potential solutions within the predefined problem space, facilitating dynamic exploration of panel configurations. It approaches structural rules as flexible constraints, making necessary corrections in post-processing, and through iterative developments, the algorithm refines panel sets to minimize material use. The methodology is validated through an analysis against an industry implementation and expert-derived solutions, highlighting PAAD's ability to surpass existing results and reduce the need for manual corrections. Additionally, to motivate future research, a synthetic data generator, the architectural drawing encodings used, and a preliminary interface are also introduced. This not only highlights the algorithm's practical applicability but also encourages its use in real-world scenarios., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fisher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Media information plays an essential role in the stock market. Recent financial research has verified that media information could shock stock price by influencing investors' expectation. Now, a new type of interactive media, called Digital Interactive Media (DIM), is popular in Chinese stock market and becomes the main channel for investors to understand listed companies. Unlike general news media or investor forums, DIM enables direct interaction between listed companies and investors. In the modern society where digital economy is booming, media information would largely affect investors' decisions. Therefore, it is urgent to use natural language processing (NLP) technology to deconstruct the massive questions and answers (Q&A) interactive information in DIM and extract valuable factors that affect stock prices and stock performances to explore the influence mechanism of digital interactive information on stock performances. This paper firstly uses web crawling technology to obtain approximately 110000 Q&A text information from the digital interactive platform ('Panoramic Network') from 2015 to 2021. Then we use big data text analysis technology and emotional quantification technology to extract valuable influencing factors from the massive text. A Multiple Linear Regression (MLR) model was created to explore specific influence mechanism of digital interactive information on stock price performance. The empirical results show that the emotions implicit in investors' questions do not significantly impact stock performance. However, the emotions and attitudes of the answers by listed companies can significantly affect corresponding stock prices, which indirectly confirms the Proximate Cause Effect of behavioral finance. This effect is particularly evident in the stock prices on the current trading day and the next trading day. In the Robustness Test, this paper replaces dependent variable and adds relevant control variables, and the conclusion remains valid. In the Endogeneity Test, this paper selects sample data before the launch of Panorama Network in 2014 as a comparison, and uses a Difference-in-Difference (DID) model to prove the significant impact of the launch of Panorama Network on Chinese stock market. In the Heterogeneity Test, the paper classifies the market value, region, and industry of listed companies and regressed the sub samples, once again confirming the reliability of the empirical conclusions. The results of Robustness Test, Endogeneity Test, and Heterogeneity Test conducted in this paper all support empirical conclusions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

With the increasing frequencies of extreme weather events caused by climate change, the risk of forest damage from insect attacks grows. Storms and droughts can damage and weaken trees, reduce tree vigour and defence capacity and thus provide host trees that can be successfully attacked by damaging insects, as often observed in Norway spruce stands attacked by the Eurasian spruce bark beetle Ips typographus. Following storms, partially uprooted trees with grounded crowns suffer reduced water uptake and carbon assimilation, which may lower their vigour and decrease their ability to defend against insect attack. We conducted in situ measurements on windthrown and standing control trees to determine the concentrations of non-structural carbohydrates (NSCs), of phenolic defences and volatile monoterpene emissions. These are the main storage and defence compounds responsible for beetle´s pioneer success and host tree selection. Our results show that while sugar and phenolic concentrations of standing trees remained rather constant over a 4-month period, windthrown trees experienced a decrease of 78% and 37% of sugar and phenolic concentrations, respectively. This strong decline was especially pronounced for fructose (-83%) and glucose (-85%) and for taxifolin (-50.1%). Windthrown trees emitted 25 times greater monoterpene concentrations than standing trees, in particular alpha-pinene (23 times greater), beta-pinene (27 times greater) and 3-carene (90 times greater). We conclude that windthrown trees exhibited reduced resources of anti-herbivore and anti-pathogen defence compounds needed for the response to herbivore attack. The enhanced emission rates of volatile terpenes from windthrown trees may provide olfactory cues during bark beetle early swarming related to altered tree defences. Our results contribute to the knowledge of fallen trees vigour and their defence capacity during the first months after the wind-throw disturbance. Yet, the influence of different emission rates and profiles on bark beetle behaviour and host selection requires further investigation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lehmanski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The relationship between physical activity and hyperuricemia (HUA) remains inconsistent, and the dose-response association between moderate-to- vigorous physical activity (MVPA) level and HUA still unclear. In this study, we aimed to investigate the dose-response association of MVPA with HUA, and to explore an appropriate range of MVPA level for preventing HUA., Methods: Data from the US National Health and Nutrition Examination Survey (NHANES) 2007-2018 were used, including 28740 non-gout adult Americans. MVPA level was self-reported using the Global Physical Activity Questionnaire and serum uric acid was measured using timed endpoint method. The dose-response relationship between MVPA level and HUA was modeled with restricted cubic spline analysis. Logistic regression analysis were applied to estimate odd ratios (ORs) and 95% confidence intervals (CIs) of the relationships between MVPA level and HUA., Results: A total of 28740 adults were included in the study (weighted mean age, 47.3 years; 46.5% men), with a prevalence rate of HUA was 17.6%. The restricted cubic spline functions depicted a general U-shaped relationship between MVPA level and HUA. The MVPA level of 933 and 3423 metabolic equivalent (MET) -min/wk were the cut-off discriminating for the risk of HUA. Participants with MVPA levels in the range of 933-3423 MET-min/wk had lower risk of HUA and they had the lowest risk when MVPA levels at around 1556 MET-min/wk. Compared with the moderate-activity group (600-2999 Met-min/wk), the low-activity group (< 600 Met-min/wk) had a greater risk of HUA (OR, 1.13 [95%CI, 1.02-1.26]) after fully adjusting for potential confounders., Conclusions: Compared with the moderate MVPA level, the low MVPA level was associated with the higher risk of HUA. And there may be a U-shaped dose-response relationship between MVPA level and HUA. When MVPA level was approximately 933-3423 MET-min/wk, the risk of HUA may at a lower level and the risk reached the lowest when MVPA level at around 1556 MET-min/wk., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)