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Abstract Background The modified pancreatitis activity scoring system (mPASS) was proposed to assess the activity of acute pancreatitis (AP) while it doesn’t include indicators that directly reflect pathophysiology processes and imaging characteristics. Objectives To determine the threshold of admission mPASS and investigate radiomics and laboratory parameters to construct a model to predict the activity of AP. Methods AP inpatients at institution 1 were randomly divided into training and validation groups based on a 5:5 ratio. AP inpatients at Institution 2 were served as test group. The cutoff value of admission mPASS scores in predicting severe AP was selected to divide patients into high and low level of disease activity group. LASSO was used in screening features. Multivariable logistic regression was used to develop radiomics model. Meaningful laboratory parameters were used to construct combined model. Results There were 234 (48 years ± 10, 155 men) and 101 (48 years ± 11, 69 men) patients in two institutions. The threshold of admission mPASS score was 112.5 in severe AP prediction. The AUC of the radiomics model was 0.79, 0.72, and 0.76 and that of the combined model incorporating rad-score and white blood cell were 0.84, 0.77, and 0.80 in three groups for activity prediction. The AUC of the combined model in predicting disease without remission was 0.74. Conclusions The threshold of admission mPASS was 112.5 in predicting severe AP. The model based on CECT radiomics has the ability to predict AP activity. Its ability to predict disease without remission is comparable to mPASS. Critical relevance statement This work is the first attempt to assess the activity of acute pancreatitis using contrast-enhanced CT radiomics and laboratory parameters. The model provides a new method to predict the activity and prognosis of AP, which could contribute to further management. Key Points Radiomics features and laboratory parameters are associated with the activity of acute pancreatitis. The combined model provides a new method to predict the activity and prognosis of AP. The ability of the combined model is comparable to the modified Pancreatitis Activity Scoring System. Graphical Abstract

Yamamoto's integral was the integral associated with 2-posets, which was first introduced by Yamamoto. In this paper, we obtained the values of infinite series involving harmonic numbers and reciprocal of binomial coefficients by using some techniques of Yamamoto's integral. We determine the value of infinite series of the form: $ \sum\limits_{m_1,\ldots,m_n,\ell_1,\ldots,\ell_k\geq 1}\frac{H_{m_1}^{(a_1)}\cdots H_{m_n}^{(a_n)}} {m_1^{b_1}\cdots m_n^{b_n}\ell_1^{c_1}\cdots\ell_k^{c_k} \binom{m_1+\cdots+m_n+\ell_1+\cdots+\ell_k}{\ell_k}}, $ in terms of a finite sum of multiple zeta values, for positive integers $ a_1, \ldots, a_n, b_1, \ldots, b_n, c_1, \ldots, c_k $.

Abstract To assess cardiometabolic profiles and proteomics to identify biomarkers associated with the metabolically healthy and unhealthy obesity. Young adults (N = 156) enrolled were classified as not having obesity, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) based on NCEP ATP-III criteria. Plasma proteomics at study entry were measured using Olink Cardiometabolic Explore panel. Linear regression was used to assess associations between proteomics and obesity groups as well as cardiometabolic traits of glucose, insulin, and lipid profiles at baseline and follow-up visits. Enriched biological pathways were further identified based on the significant proteomic features. Among the baseline 95 (61%) and 61 (39%) participants classified as not having obesity and having obesity (8 MHO and 53 MUHO), respectively. Eighty of the participants were followed-up with an average 4.6 years. Forty-one proteins were associated with obesity (FDR

Abstract Bird sex chromosomes play a unique role in sex-determination, and affect the sexual morphology and behavior of bird species. Core waterbirds, a major clade of birds, share the common characteristics of being sexually monomorphic and having lower levels of inter-sexual conflict, yet their sex chromosome evolution remains poorly understood. Here, by we analyse of a chromosome-level assembly of a female crested ibis (Nipponia nippon), a typical core waterbird. We identify neo-sex chromosomes resulting from fusion of microchromosomes with ancient sex chromosomes. These fusion events likely occurred following the divergence of Threskiornithidae and Ardeidae. The neo-W chromosome of the crested ibis exhibits the characteristics of slow degradation, which is reflected in its retention of abundant gametologous genes. Neo-W chromosome genes display an apparent ovary-biased gene expression, which is largely driven by genes that are retained on the crested ibis W chromosome but lost in other bird species. These results provide new insights into the evolutionary history and expression patterns for the sex chromosomes of bird species.

Abstract Background Due to cardiotoxicity concerns, the concurrent use of epirubicin and trastuzumab has not been fully studied. This study aimed to examine the cardiotoxicity and pathological complete response (pCR) rate associated with the concurrent regimens in patients with human epidermal growth factor receptor 2 (HER2)‐positive early breast cancer (EBC). Methods We conducted a systematic search for relevant literature in the NCBI/PubMed, the Cochrane database, and international conference abstracts for phase II or III randomized controlled trials between January 1, 2000, and February 28, 2021, focusing on the concurrent regimens in patients with HER2‐positive EBC. To compare the risk of cardiotoxicity and the odds of the pCR rate, we performed linear meta‐regression analyses to investigate the effects of multiple covariates. Results We analyzed 7 neoadjuvant trials involving the concurrent use of epirubicin and trastuzumab with 1797 patients. The median cumulative dose of epirubicin used was 300 mg/m2, with a total of 96 reported adverse cardiac events. The concurrent regimens did not result in a significant increase in cardiotoxicity compared to nonconcurrent regimens (risk ratio [RR] = 1.18, 95% confidence interval [CI] = 0.68–2.05). Compared with nonconcurrent or non‐anthracycline‐containing regimens, concurrent regimens were associated with a significant increase in the pCR rate (odds ratio = 1.48, 95% CI = 1.04–2.12). The linear fixed‐effects meta‐regression analysis indicated that in trials including more patients with hormone receptor‐positive EBC, the RR of cardiotoxicity significantly increased with concurrent regimens, and the pCR rate became less significant. Conclusions The combination of trastuzumab and a low dose of epirubicin positively impacted the pCR rate without a significant increase in cardiotoxicity. We recommend exploring concurrent regimens for HR‐negative, HER2‐positive tumors to enhance pCR rates, with caution advised for HR‐positive tumors due to potential cardiotoxicity.

Introduction Patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) and concomitant multivessel coronary artery disease (CAD) are considered patients with extremely high-risk atherosclerotic cardiovascular disease (ASCVD), and current guidelines specify a lower low-density lipoprotein cholesterol (LDL-C) target for this population. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to effectively reduce LDL-C levels on a statin background. Additionally, several studies have confirmed the role of PCSK9 inhibitors in plaque regression and reducing residual cardiovascular risk in patients with ACS. However, those studies included coronary lesions with a degree of stenosis

The application of green prevention and control techniques (GCTs) is a vital measure for improving the quality of agricultural products and enhancing the safety of the ecological environment and agricultural production. However, realistically, limited by the small-scale, part-time and decentralized business model, the adoption of GCTs by family farms in China faces practical problems such as insufficient internal transformation force and ability, as well as low external supervision efficiency. To reveal the directions of promoting family farms' GCTs adoption behavior, we establish a comprehensive theoretical model through the application of a novel integrated approach combining two dominant psychological theories of behavior change: the Theory of Planned Behavior (TPB) and the Norm Activation Model (NAM). We apply this framework to targeted research of vegetable growers in Henan Province in China using survey data (sample n = 653) analyzed through structural equation modeling (SEM). The integrated TPB-NAM model provides insight into both internal motivation and external environmental conditions for farmers' predicted adoption of GCTs. First, internal motivation, value cognition and personal norms are all driving factors affecting the GCTs behavioral intention of vegetable family farms. When GCTs are driven by the dual motivations of “self-interest” (personal norms) and “others-interest” (value cognition), personal norms can be activated by two factors: awareness of consequences and responsibility attribution. Furthermore, social norms, capital endowment and government regulation are the pressure and obstacle factors affecting the GCTs application of vegetable family farms. Social norms can indirectly affect the application of GCTs by forming personal norms. In addition, there are differences between the influencing factors and mechanism of GCTs adoption behavior intention of family farms of different sizes. Based on this, we propose some specific policy suggestions from three aspects: enhance value cognition, improve environmental awareness and responsibility perception, fill in the shortcomings of capital endowment, and implement differentiated incentive and restraint policies.

ObjectiveTo develop a CT-based nomogram to predict the response of advanced esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemotherapy plus immunotherapy.MethodsIn this retrospective study, 158 consecutive patients with advanced ESCC receiving contrast-enhanced CT before neoadjuvant chemotherapy plus immunotherapy were randomized to a training cohort (TC, n = 121) and a validation cohort (VC, n = 37). Response to treatment was assessed with response evaluation criteria in solid tumors. Patients in the TC were divided into the responder (n = 69) and non-responder (n = 52) groups. For the TC, univariate analyses were performed to confirm factors associated with response prediction, and binary analyses were performed to identify independent variables to develop a nomogram. In both the TC and VC, the nomogram performance was assessed by area under the receiver operating characteristic curve (AUC), calibration slope, and decision curve analysis (DCA).ResultsIn the TC, univariate analysis showed that cT stage, cN stage, gross tumor volume, gross volume of all enlarged lymph nodes, and tumor length were associated with the response (all P < 0.05). Binary analysis demonstrated that cT stage, cN stage, and tumor length were independent predictors. The independent factors were imported into the R software to construct a nomogram, showing the discriminatory ability with an AUC of 0.813 (95% confidence interval: 0.735–0.890), and the calibration curve and DCA showed that the predictive ability of the nomogram was in good agreement with the actual observation.ConclusionThis study provides an accurate nomogram to predict the response of advanced ESCC to neoadjuvant chemotherapy plus immunotherapy.

African swine fever virus (ASFV) infection poses enormous threats and challenges to the global pig industry; however, no effective vaccine is available against ASFV, attributing to the huge viral genome (approximately189 kb) and numerous encoding products (>150 genes) due to the limited understanding on the molecular mechanisms of viral pathogenesis. Elucidating the host-factor/viral-protein interaction network will reveal new targets for developing novel antiviral therapies. Using proteomic analysis, we identified 255 cellular proteins that interact with the ASFV-encoded pE301R protein when transiently expressed in HEK293T cells. Gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) database enrichment, and protein-protein interaction (PPI) network analyses revealed that pE301R-interacting host proteins are potentially involved in various biological processes, including protein translation and folding, response to stimulation, and mitochondrial transmembrane transport. The interactions of two putative cellular proteins (apoptosis inducing factor mitochondria associated 1 (AIFM1) and vimentin (VIM)) with pE301R-apoptosis inducing factor have been verified by co-immunoprecipitation. Our study revealed the inhibitory role of pE301R in interferon (IFN) induction that involves VIM sequestration by pE301R, identified interactions between ASFV pE301R and cellular proteins, and predicted the potential function of pE301R and its associated biological processes, providing valuable information to enhance our understanding of viral protein function, pathogenesis, and potential candidates for the prevention and control of ASFV infection.

Environmental pollution is widespread and poses significant risks to both human populations and diverse animal species. As part of conservation initiatives, many endangered animals are housed in zoos and breeding centers close to human activities, potentially exposing them to health threats arising from environmental contamination, such as mercury (Hg). By analyzing non-invasive fecal samples from 13 Chinese zoos, we assessed total mercury (THg) and methylmercury (MeHg) exposure in two non-human primate species: the endangered species golden snub-nosed monkey (Rhinopithecus roxellana), and the most widely distributed rhesus macaque (Macaca mulatta). The concentration of THg in golden snub-nosed monkeys (mean ± s.d.: 76.7 ± 35.6 ng/g; median: 71.8 ng/g, range: 11.2–200.0 ng/g, n = 71) was significantly higher than that in rhesus macaques (mean ± s.d.: 32.3 ± 54.7 ng/g; median: 17.5 ng/g, range: 7.4–409.0 ng/g, n = 98). No significant differences were observed in both MeHg and MeHg % between these two species. Age and sex did not predict fecal Hg. Among adults, approximately 85 % of sampled individuals exhibited hazard quotient (HQ) values exceeding 1, indicating mercury poses a health risk to captive primate populations. The average HQ for golden snub-nosed monkeys was 2.98 ± 1.68 (range: 0.46–8.21, n = 43), while for rhesus macaques was 1.84 ± 1.64 (range: 0.61–12.49, n = 71). Our findings suggest that conservation efforts for captive primates may be compromised by Hg pollution, particularly in golden snub-nosed monkeys. Further investigation and ongoing biomonitoring from an ecotoxicological perspective, are crucial to ensuring the health of captive primate populations.

Due to the potential applications in biomedical engineering, it becomes more and more important to understand the process of engulfment and internalization of nanoparticles (NPs) by cell membranes. Despite the fact that the interaction between cell membranes and passive particles has been widely studied, the interaction between cell membranes and self-propelled nonspherical NPs remains to be elucidated. Here, we present a theoretical model to systematically investigate the influence of the active force, aspect ratio of NPs, particle size, and membrane properties (adhesion energy density and membrane tension) on the cellular uptake of a nonspherical nanoparticle. It is found that the active force generated by an NP can trigger a type of first-order wrapping transition from a small partial wrapping state to a large one. In addition, the phase diagram in the force-aspect ratio (particle size, adhesion energy density, and membrane tension) space displays more complex behaviors compared with that for the passive wrapping mediated merely by adhesion. These results may provide useful guidance to the study of activity-driven cellular entry of active particles into cells. [ABSTRACT FROM AUTHOR]

Background: Mandibular third molar impaction in adult patients is one of the most common problems in dental practice. However, limited data are available on the association between mandibular third molar impaction and craniofacial skeletal problems. Aim: This study aimed to establish a prediction model to evaluate the risk factors for mandibular third molar impaction. Methods: Panoramic and lateral cephalometric radiographs of orthodontic patients aged ≥20 years were obtained from the Tri-Service General Hospital. The radiographs were analyzed by a single examiner. Panoramic radiographs were used to evaluate the mandibular third molar impaction. Lateral cephalometric radiographs were used to evaluate five linear and six angular measurements to define the facial pattern of the participants. The association between cephalometric measurements and mandibular third molar impaction was determined using one-way analysis of variance and logistic regression analysis. Results: This study included 60 participants. The incidence of mandibular third molar impaction was associated with the mandibular plane angle (MPA) and mandibular length (Co-Gn) (P < 0.001). The presence of mandibular third molar impaction was found to gradually increase with increasing MPA and decreasing mandibular length. Conclusion: Individuals with a greater MPA and lesser mandibular length had a higher incidence of mandibular third molar impaction.

The study of catalytic reaction mechanism is a critical and extremely challenging project. Online monitoring of reactants, intermediates and products during catalytic reactions can provide key evidence for the in-depth study of complex catalytic reaction networks, reaction pathways and reaction kinetics. As an online mass spectrometry based on soft ionization technique, vacuum ultraviolet photoionization mass spectrometry (VUV-PIMS) has proven itself as a versatile and powerful analytical technique for online and real-time process monitoring, which has gradually become a highly concerned characterization technique for catalytic reaction processes due to its advantages of high molecular ion yield, simple spectrum interpretation and high sensitivity. Compared with other commonly used synchrotron radiation and laser-based VUV light sources, the low pressure discharge lamps filled with various rare gases are compact, easy to operate, and low cost, such as krypton discharge lamps. However, the relatively low photon intensity of these lamps limits their applications. The efforts have been taken to develop stronger VUV light sources or lamp-based efficient combined ion sources to solve this issue. In this paper, the development of VUV-PIMS technology, especially the research progress of photoionization ion sources based on the VUV lamp, were reviewed, such as high-pressure photoionization (HPPI) source, single photon ionization-photoelectron ionization (SPI-PEI) combined ion source, and single photon ionization-chemical ionization (SPI-CI) combined ion source. By combining capillary sampling technology or molecular beam sampling technology, the applications of VUV-PIMS for real-time and online monitoring of stable products and active intermediates in catalytic processes were introduced, such as ammonia synthesis, methane/ethane catalytic conversion, methanol to olefins. The applications in online monitoring of these catalytic reaction processes exhibited an excellent performance and wide potential applications of VUV-PIMS in process monitoring and reaction mechanism research. Finally, the future development trend of VUV-PIMS was prospected for the application requirements of accurate characterization of catalytic reaction process.

Abstract Background Esophagectomy is the main treatment for esophageal squamous cell carcinoma (ESCC), and patients with histopathologically negative margins still have a relatively higher recurrence rate. Contrast-enhanced CT (CECT) radiomics might noninvasively obtain potential information about the internal heterogeneity of ESCC and its adjacent tissues. This study aimed to develop CECT radiomics models to preoperatively identify the differences between tumor and proximal tumor-adjacent and tumor-distant tissues in ESCC to potentially reduce tumor recurrence. Methods A total of 529 consecutive patients with ESCC from Centers A (n = 447) and B (n = 82) undergoing preoperative CECT were retrospectively enrolled in this study. Radiomics features of the tumor, proximal tumor-adjacent (PTA) and proximal tumor-distant (PTD) tissues were individually extracted by delineating the corresponding region of interest (ROI) on CECT and applying the 3D-Slicer radiomics module. Patients with pairwise tissues (ESCC vs. PTA, ESCC vs. PTD, and PTA vs. PTD) from Center A were randomly assigned to the training cohort (TC, n = 313) and internal validation cohort (IVC, n = 134). Univariate analysis and the least absolute shrinkage and selection operator were used to select the core radiomics features, and logistic regression was performed to develop radiomics models to differentiate individual pairwise tissues in TC, validated in IVC and the external validation cohort (EVC) from Center B. Diagnostic performance was assessed using area under the receiver operating characteristics curve (AUC) and accuracy. Results With the chosen 20, 19 and 5 core radiomics features in TC, 3 individual radiomics models were developed, which exhibited excellent ability to differentiate the tumor from PTA tissue (AUC: 0.965; accuracy: 0.965), the tumor from PTD tissue (AUC: 0.991; accuracy: 0.958), and PTA from PTD tissue (AUC: 0.870; accuracy: 0.848), respectively. In IVC and EVC, the models also showed good performance in differentiating the tumor from PTA tissue (AUCs: 0.956 and 0.962; accuracy: 0.956 and 0.937), the tumor from PTD tissue (AUCs: 0.990 and 0.974; accuracy: 0.952 and 0.970), and PTA from PTD tissue (AUCs: 0.806 and 0.786; accuracy: 0.760 and 0.786), respectively. Conclusion CECT radiomics models could differentiate the tumor from PTA tissue, the tumor from PTD tissue, and PTA from PTD tissue in ESCC.

Objective The present study is to analyze the effects of the coronavirus disease 2019 (COVID 2019) outbreak and the subsequent lockdown on the outcomes of spinal metastasis patients. Methods The study was a retrospective analysis of data from a prospective cohort study. All patients underwent surgical intervention for spinal metastases between January 2019 and December 2021 and had at least 3 months of postoperative follow-up. The primary outcome was overall mortality during the 4 different stages (pre-COVID-19 era, COVID-19 pandemic except in Taiwan, national lockdown, lifting of the lockdown). The secondary outcomes were the oncological severity scores, medical/surgical accessibility, and patient functional outcome during the 4 periods as well as survival/mortality. Results A total of 233 patients were included. The overall mortality rate was 41.20%. During the Taiwan lockdown, more patients received palliative surgery than other surgical methods, and no total en bloc spondylectomy was performed. The time from surgeon visit to operation was approximately doubled after the COVID-19 outbreak in Taiwan (75.97, 86.63, 168.79, and 166.91 hours in the 4 periods, respectively). The estimated survival probability was highest after the national lockdown was lifted and lowest during the lockdown. In the multivariate analysis, increased risk of mortality was observed with delay of surgery, with emergency surgery having a higher risk with delays above 33 hours, urgent surgery (below 59 and above 111 hours), and elective surgery (above 332 hours). Conclusion The COVID-19 pandemic and related policies have altered daily clinical practice and negatively impacted the survival of patients with spinal metastases.

Abstract Background Disinfectants are important in the food industry to prevent the transmission of pathogens. Excessive use of disinfectants may increase the probability of bacteria experiencing long-term exposure and consequently resistance and cross-resistance to antibiotics. This study aims to investigate the cross-resistance of multidrug-resistant, drug-resistant, and drug-susceptible isolates of Salmonella enterica serovar Typhimurium (S. Typhimurium) with different sequence types (STs) to a group of antibiotics after exposure to different food-grade disinfectants. Methods A panel of 27 S. Typhimurium strains with different antibiograms and STs were exposed to increasing concentrations of five food-grade disinfectants, including hydrogen peroxide (H2O2), benzalkonium chloride (BAC), chlorine dioxide (ClO2), sodium hypochlorite (NaClO), and ethanol. Recovered evolved strains were analyzed using genomic tools and phenotypic tests. Genetic mutations were screened using breseq pipeline and changes in resistance to antibiotics and to the same disinfectant were determined. The relative fitness of evolved strains was also determined. Results Following exposure to disinfectants, 22 out of 135 evolved strains increased their resistance to antibiotics from a group of 14 clinically important antibiotics. The results also showed that 9 out of 135 evolved strains had decreased resistance to some antibiotics. Genetic mutations were found in evolved strains. A total of 77.78% of ST34, 58.33% of ST19, and 66.67% of the other STs strains exhibited changes in antibiotic resistance. BAC was the disinfectant that induced the highest number of strains to cross-resistance to antibiotics. Besides, H2O2 induced the highest number of strains with decreased resistance to antibiotics. Conclusions These findings provide a basis for understanding the effect of disinfectants on the antibiotic resistance of S. Typhimurium. This work highlights the link between long-term exposure to disinfectants and the evolution of resistance to antibiotics and provides evidence to promote the regulated use of disinfectants.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

Background: Although food-grade disinfectants are extensively used worldwide, it has been reported that the long-term exposure of bacteria to these compounds may represent a selective force inducing evolution including the emergence of antibiotic resistance. However, the mechanism underlying this correlation has not been elucidated. This study aims to investigate the genomic evolution caused by long-term disinfectant exposure in terms of antibiotic resistance in Salmonella enterica Typhimurium. Methods: S. Typhimurium isolates were exposed to increasing concentrations of benzalkonium chloride (BAC) and variations of their antibiotic susceptibilities were monitored. Strains that survived BAC exposure were analyzed at whole genome perspective using comparative genomics, and Sanger sequencing-confirmed mutations in ramR gene were identified. Next, the efflux activity in ramR-mutated strains shown as bisbenzimide accumulation and expression of genes involved in AcrAB-TolC efflux pump using quantitative reverse transcriptase PCR were determined. Results: Mutation rates of evolved strains varied from 5.82 × 10−9 to 5.56 × 10-8, with fold increase from 18.55 to 1.20 when compared with strains evolved without BAC. Mutations in ramR gene were found in evolved strains. Upregulated expression and increased activity of AcrAB-TolC was observed in evolved strains, which may contribute to their increased resistance to clinically relevant antibiotics. In addition, several indels and point mutations in ramR were identified, including L158P, A37V, G42E, F45L, and R46H which have not yet been linked to antimicrobial resistance. Resistance and mutations were stable after seven consecutive cultivations without BAC exposure. These results suggest that strains with sequence type (ST) ST34 were the most prone to mutations in ramR among the three STs tested (ST34, ST19, ST36). Conclusions: This work demonstrated that disinfectants, specifically BAC forces S. Typhimurium to enter a specific evolutionary trajectory towards antibiotic resistance illustrating the side effects of long-term exposure to BAC and probably also to other disinfectants. Most significantly, this study provides new insights in understanding the emergence of antibiotic resistance in modern society.