deepGraphh: AI-driven web service for graph-based quantitative structure-activity relationship analysis.

Artificial intelligence (AI)-based computational techniques allow rapid exploration of the chemical space. However, representation of the compounds into computational-compatible and detailed features is one of the crucial steps for quantitative structure-activity relationship (QSAR) analysis. Recently, graph-based methods are emerging as a powerful alternative to chemistry-restricted fingerprints or descriptors for modeling. Although graph-based modeling offers multiple advantages, its implementation demands in-depth domain knowledge and programming skills. Here we introduce deepGraphh, an end-to-end web service featuring a conglomerate of established graph-based methods for model generation for classification or regression tasks. The graphical user interface of deepGraphh supports highly configurable parameter support for model parameter tuning, model generation, cross-validation and testing of the user-supplied query molecules. deepGraphh supports four widely adopted methods for QSAR analysis, namely, graph convolution network, graph attention network, directed acyclic graph and Attentive FP. Comparative analysis revealed that deepGraphh supported methods are comparable to the descriptors-based machine learning techniques. Finally, we used deepGraphh models to predict the blood-brain barrier permeability of human and microbiome-generated metabolites. In summary, deepGraphh offers a one-stop web service for graph-based methods for chemoinformatics.

An Outcome Analysis of Fibrin Sealant versus Staples for Fixation of Split-Thickness Skin Grafts.

Background Skin grafting plays a vital role in post-burn and post-traumatic wound management. Split-thickness skin grafts (STSG) are traditionally fixed using staples or sutures, which have tedious application and their removal necessitates painkillers, medical equipment, and human intervention. As an alternative, fibrin sealant is a biological tissue adhesive, composed of thrombin, calcium, and fibrinogen. Fibrin sealant promotes hemostasis and acts as a biological adherent. Objective The aim of this study was to evaluate the outcomes (graft take, wound healing and complications) of fibrin sealant and staples for STSG fixation. Methods It is a randomized controlled trial on 40 patients with wounds of minimum 400 cm 2 . Wound area was divided into equal halves and randomly allocated to the study group or control group. In the study group, 4 mL per 200 cm 2 of fibrin sealant was sprayed followed by STSG application. In the control group, STSG was fixed with only skin staples. Evaluation was done on postoperative days 3, 5, 15, and 30 for graft take, hematoma/seroma, infection, and complete wound healing. Results The mean graft take was significantly higher ( p -value < 0.05) in the study group than in the control group (91 vs. 89%). No seroma or hematoma formation was seen in either group. Complete wound healing was seen in more patients in the study group, but the difference was statistically insignificant. Conclusion Fibrin sealant is an excellent alternative to staples for skin grafting, with the advantage of better graft take and being free of pain that is incurred during staple removal.

Factors affecting biofilm formation by bacteria on fabrics.

Fabrics act as fomites for microorganisms, thereby playing a significant role in infection transmission, especially in the healthcare and hospitality sectors. This study aimed to examine the biofilm formation ability of four nosocomial infection-causing bacteria (Acinetobacter calcoaceticus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) on cotton, polyester, polyester-cotton blend, silk, wool, viscose, and nylon, used frequently in the healthcare sector, by qualitative and quantitative methods. The impact of temperature, pH, and relative humidity (RH) on biofilm formation was also assessed. P. aeruginosa and S. aureus were strong biofilm producers, while E. coli produced weak biofilm. Wool (maximum roughness) showed the highest bacterial load, while silk (lowest roughness) showed the least. P. aeruginosa exhibited a higher load on all fabrics, than other test bacteria. Extracellular polymeric substances were characterized by infrared spectroscopy. Roughness of biofilms was assessed by atomic force microscopy. For biofilm formation, optimum temperature, pH, and RH were 30 °C, 7.0, and 62%, respectively. MgCl2 and CaCl2 were the most effective in removing bacterial biofilm. In conclusion, biofilm formation was observed to be influenced by the type of fabric, bacteria, and environmental conditions. Implementing recommended guidelines for the effective disinfection of fabrics is crucial to curb the risk of nosocomial infections. In addition, designing modified healthcare fabrics that inhibit pathogen load could be an effective method to mitigate the transmission of infections.

Textiles as fomites in the healthcare system.

Nosocomial infections or healthcare-associated infections (HAIs) are acquired under medical care in healthcare facilities. In hospital environments, the transmission of infectious diseases through textiles such as white coats, bed linen, curtains, and towels are well documented. Textile hygiene and infection control measures have become more important in recent years due to the growing concerns about textiles as fomites in healthcare settings. However, systematic research in this area is lacking; the factors contributing to the transmission of infections through textiles needs to be better understood. The review aims to critically explore textiles as contaminants in healthcare systems, and to identify potential risks they may pose to patients and healthcare workers. It delineates different factors affecting bacterial adherence on fabrics, such as surface properties of bacteria and fabrics, and environmental factors. It also identifies areas that require further research to reduce the risk of HAIs and improve textile hygiene practices. Finally, the review elaborates on the strategies currently employed, and those that can be employed to limit the spread of nosocomial infections through fabrics. Implementing textile hygiene practices effectively in healthcare facilities requires a thorough analysis of factors affecting fabric-microbiome interactions, followed by designing newer fabrics that discourage pathogen load. KEY POINTS: • Healthcare textiles act as a potential reservoir of nosocomial pathogens • Survival of pathogens is affected by surface properties of fabric and bacteria • Guidelines required for fabrics that discourage microbial load, for hospital use.

Clinical characteristics of infantile hemangiomas with aggressive, persistent, and destructive ulceration.

BACKGROUND/OBJECTIVES: Ulceration is a common complication of infantile hemangioma (IH). Severe, persistent ulceration occurs in a minority of patients. This study aims to characterize the clinical features of IH with aggressive ulceration (AU). METHODS: Multicenter retrospective study of clinical features of IH with AU. RESULTS: Thirty-five patients with AU were identified and included in the study. The majority of AU occurred in segmental IH (23/35, 65%). Segmental IH with AU were large (≥10 cm2 ; 16/23, 69%, p < .001) with a thin (<3 mm) superficial component (16/23, 69%, p < .001). Localized IH with AU had a thick (>3 mm) superficial component (11/12, 92%, p < .001). All diaper area IH with AU (9/35) were segmental with thin superficial component (100%, p = .02). IH with AU in the head/neck (10/35) were more commonly localized (67%) and mixed (62.5%), while segmental, thick superficial morphology was more common on trunk (9/35) and upper extremities (7/35). CONCLUSIONS: IH resulting in AU differ in clinical features by anatomic site. Those in the diaper area are nearly always segmental with thin superficial component, whereas other sites tend to be localized, mixed, with thick superficial component. These distinct phenotypes may prove useful in the clinical setting for physicians to identify patterns of IH ulceration with increased risk of aggressive, persistent ulceration.

Temporal variation in bacterial community profile on patients' bedsheets in a primary healthcare unit.

Fabrics serve as fomites in spreading nosocomial infections. As a patient is in close contact with bedsheets, it is important to assess the seasonal variation in bacterial diversity on these in healthcare units. The study was conducted to characterise the bacterial diversity on patients' bedsheets across 7 months in a primary healthcare unit. Polyester-cotton blend fabric was stitched on bedsheets, and temporal dynamics of bacterial communities was assessed from May to November 2019. qPCR and amplicon sequencing of 16S rRNA gene was performed for profiling of bacterial community. Results revealed the dominance of Bacillota followed by Pseudomonadota, and Actinomycetota. A seasonal variation was observed in the bacterial load, with maximum values in June. This indicates the impact of environmental conditions on bacterial abundance and composition on fabrics in healthcare unit. The presence of priority pathogens on the patient bedsheets is a human health concern reiterating the need for season-specific laundering protocol.

PDBe: improved findability of macromolecular structure data in the PDB.

The Protein Data Bank in Europe (PDBe), a founding member of the Worldwide Protein Data Bank (wwPDB), actively participates in the deposition, curation, validation, archiving and dissemination of macromolecular structure data. PDBe supports diverse research communities in their use of macromolecular structures by enriching the PDB data and by providing advanced tools and services for effective data access, visualization and analysis. This paper details the enrichment of data at PDBe, including mapping of RNA structures to Rfam, and identification of molecules that act as cofactors. PDBe has developed an advanced search facility with ∼100 data categories and sequence searches. New features have been included in the LiteMol viewer at PDBe, with updated visualization of carbohydrates and nucleic acids. Small molecules are now mapped more extensively to external databases and their visual representation has been enhanced. These advances help users to more easily find and interpret macromolecular structure data in order to solve scientific problems.

Surveillance of bacterial load and multi-drug resistant bacteria on bedsheets in a primary health care unit.

A patient is in close proximity to different types of textiles in hospital environment, which contribute to the transfer of drug-resistant bacteria in healthcare settings. This study was undertaken to estimate the temporal variations in bacterial load on bedsheets in a primary healthcare unit in Delhi. Data were collected for a period of 7 months. Antibiotic susceptibility testing of isolates was performed. The mean count of Acinetobacter spp. was highest (2.10 × 102 CFU/cm2), and Klebsiella spp. showed the least mean count (7.5 × 101 CFU/cm2). The mean bacterial count over the period showed maximum bacterial load for most microbial groups in June, and minimum in November. Enterococcus faecalis and Streptococcus spp. were highly resistant to different antibiotics, while Acinetobacter spp. and Group A Streptococcus showed the least resistance toward the antibiotics tested. Bacterial counts on bedsheets were found to vary with the time of the year, indicating that environmental factors affect bacterial load.

Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: A multicenter study.

BACKGROUND: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. OBJECTIVE: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. METHODS: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. RESULTS: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris-like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. CONCLUSIONS: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.

Limited utility of repeated vital sign monitoring during initiation of oral propranolol for complicated infantile hemangioma.

BACKGROUND: Initial propranolol recommendations for infantile hemangioma published in 2013 were intended as provisional best practices to be updated as evidence-based data emerged. METHODS: A retrospective multicenter study was performed to evaluate utility of prolonged monitoring after first propranolol dose and escalation(s). Inclusion criteria included diagnosis of hemangioma requiring propranolol of greater than or equal to 0.3 mg/kg per dose, younger than 2 years, and heart rate monitoring for greater than or equal to 1 hour. Data collected included demographics, dose, vital signs, and adverse events. RESULTS: A total of 783 subjects met inclusion criteria; median age at initiation was 112 days. None of the 1148 episodes of prolonged monitoring warranted immediate intervention or drug discontinuation. No symptomatic bradycardia or hypotension occurred during monitoring. Mean heart rate change from baseline to 1 hour was -8.19/min (±15.54/min) and baseline to 2 hours was -9.24/min (±15.84/min). Three preterm subjects had dose adjustments because of prescriber concerns about asymptomatic vital sign changes. No significant difference existed in pretreatment heart rate or in heart rate change between individuals with later adverse events during treatment and those without. CONCLUSION: Prolonged monitoring for initiation and escalation of oral propranolol rarely changed management and did not predict future adverse events. Few serious adverse events occurred during therapy; none were cardiovascular.

Evidence on article 5.3 of FCTC (tobacco industry interference in tobacco control activities) in India- a qualitative scoping study.

BACKGROUND: The Tobacco Industry (henceforth TI) yearns to portray itself as being "socially responsible" and fights for the decision-making positions; that are it used to deter, delay or dilute tobacco control measures. There is little documented evidence of Tobacco Industry Interference (henceforth TII) from India, the scope of their interference and challenges faced by the experts for effective tobacco control. This research study seeks to cover this significant gap in the literature on the TI of India. METHODS: A cross-sectional qualitative research design, based upon in-depth interviews (N = 26), was used to explore the key stakeholders' opinions regarding TII in India. The interviews used a set of questions to collect information about the participant's roles and responsibilities in tobacco control, the nature of TII faced by the participants, means of influence by TI, barriers and challenges to tobacco control efforts. RESULTS: Most of the respondents were engaged in tobacco control, training, advocacy and awareness generation activities for 5-10 years or more. The respondents defined the TI and its scope as per their experience with the help of the power ranking methodology. Most of them perceived TI as 'manufacturers' while others consider them as 'advertisers', 'public relation companies', 'wholesalers', 'vendors', and 'Government firms with TI stocks. The research team identified six significant domains: influencing the policy and administrative decisions, Interference in the implementation of tobacco control laws and activities, false propaganda and hiding the truth, manipulating front action groups (FAG), rampant tobacco advertising and promotion activities and others under which TII activities were classified. Most respondents believed that TI players were interfering in the policy decisions, implementing the tobacco control laws and activities and manipulating the FAG. A detailed taxonomic classification of the TII strategies that emerged from our analysis was linked to article 5.3 of FCTC. CONCLUSIONS: The study documented a significant level of TII in different domains, with stakeholders acting at various hierarchical levels. Thus providing insight into the tactics of the TI in order to enable stakeholders to anticipate and pre-empt the kinds of alliances the TI may attempt to build; stimulating academicians and researchers to undertake in-depth analysis into various strategies and therefore underscoring the need to ensuring transparency in official interaction with the TI and its representatives.

Diversity in pediatric dermatology: A report from the Pediatric Dermatology Research Alliance and a call to action.

BACKGROUND/OBJECTIVES: The Pediatric Dermatology Research Alliance (PeDRA) connects pediatric dermatologists, trainees, basic scientists, allied health professionals, and patient advocates to improve the lives of children with skin disease through research. As a training pipeline for future pediatric dermatologists and steward of research in the field, PeDRA has a responsibility to examine its history and take actionable steps to diversify its membership, grant recipients, study leads, research priorities, and leadership. METHODS: In 2020, PeDRA formed an Equity, Diversity, and Inclusion Task Force to address this need. In an effort to assess PeDRA's past and plan for PeDRA's future, a review of PeDRA's membership, leadership, grant awardees, and research topics was conducted. RESULTS/CONCLUSIONS: Results demonstrated gaps in PeDRA's current operational efforts to diversify the pediatric dermatology workforce and identified areas for improvement. Recommendations are proposed as a call to action for the community.

Cutaneous reactions to pediatric cancer treatment part II: Targeted therapy.

Cancer remains a leading cause of morbidity and mortality among children. Targeted therapies may improve survivorship; however, unique side-effect profiles have also emerged with these novel therapies. Changes in hair, skin, and nails-termed dermatologic adverse events (AEs)-are among the most common sequelae and may result in interruption or discontinuation of therapy. Though dermatologic AEs have been detailed in adults, these findings are not well described in the pediatric population. We reviewed the literature to characterize dermatologic AEs to anticancer targeted therapies available as of July 2020 and summarized the spectrum of clinical findings as well as treatment recommendations for children. Dermatologic AEs are among the most common AEs reported in pediatric patients receiving targeted therapy, but morphologic and histologic descriptions are often lacking in current publications. Pediatric dermatologists are uniquely poised to recognize specific morphology of dermatologic AEs and make recommendations for prevention and treatment that may improve quality of life and enable ongoing cancer therapy.

Factors Affecting Bacterial Adhesion on Selected Textile Fibres.

In sectors like healthcare and hospitality, it has been realized that fabrics play a pivotal role in transfer of nosocomial infections. However, there is a major gap in drawing correlation between different fibre types and their interaction with microorganisms. Such information is important to formulate guidelines for textile materials for use in these sectors. In the current study, the adherence of four important bacteria, Staphylococcus aureus, Acinetobacter calcoaceticus, Escherichia coli, and Pseudomonas aeruginosa was studied on six different fibre types namely polyester, wool, polypropylene, viscose, silk and cotton. Among these fibres, viscose showed maximum adherence while silk fibres showed the least attachment of bacterial strains. Bacterial adhesion was correlated with the surface characteristics (surface charge, hydrophobicity etc.) of bacteria, and nanoroughness of fibres. Adhesion of these bacteria was tested on five hydrocarbons of different hydrophobicities. E. coli, the weakest biofilm producer, and with the highest surface energy and lowest hydrophobicity amongst the bacteria compared in the study, had the lowest load on all fibres. Scanning electron microscopy revealed non-uniform binding of gram-negative and gram-positive bacteria. Nanoroughness of fibres favored bacterial adhesion. The study showed correlation between surface properties and adherence of bacteria on fibres, with the results being of direct significance to medical and hospitality sectors.

Activating variants in PDGFRB result in a spectrum of disorders responsive to imatinib monotherapy.

More than 50 individuals with activating variants in the receptor tyrosine kinase PDGFRB have been reported, separated based on clinical features into solitary myofibromas, infantile myofibromatosis, Penttinen syndrome with premature aging and osteopenia, Kosaki overgrowth syndrome, and fusiform aneurysms. Despite their descriptions as distinct clinical entities, review of previous reports demonstrates substantial phenotypic overlap. We present a case series of 12 patients with activating variants in PDGFRB and review of the literature. We describe five patients with PDGFRB activating variants whose clinical features overlap multiple diagnostic entities. Seven additional patients from a large family had variable expressivity and late-onset disease, including adult onset features and two individuals with sudden death. Three patients were treated with imatinib and had robust and rapid response, including the first two reported infants with multicentric myofibromas treated with imatinib monotherapy and one with a recurrent p.Val665Ala (Penttinen) variant. Along with previously reported individuals, our cohort suggests infants and young children had few abnormal features, while older individuals had multiple additional features, several of which appeared to worsen with advancing age. Our analysis supports a diagnostic entity of a spectrum disorders due to activating variants in PDGFRB. Differences in reported phenotypes can be dramatic and correlate with advancing age, genotype, and to mosaicism in some individuals.

A retrospective multicenter study of fatal pediatric melanoma.

BACKGROUND: Pediatric melanoma is rare and diagnostically challenging. OBJECTIVE: To characterize clinical and histopathologic features of fatal pediatric melanomas. METHODS: Multicenter retrospective study of fatal melanoma cases in patients younger than 20 years diagnosed between 1994 and 2017. RESULTS: Of 38 cases of fatal pediatric melanoma identified, 57% presented in white patients and 19% in Hispanic patients. The average age at diagnosis was 12.7 years (range, 0.0-19.9 y), and the average age at death was 15.6 years (range, 1.2-26.2 y). Among cases with known identifiable subtypes, 50% were nodular (8/16), 31% were superficial spreading (5/16), and 19% were spitzoid melanoma (3/16). One fourth (10/38) of melanomas arose in association with congenital melanocytic nevi. LIMITATIONS: Retrospective nature, cohort size, and potential referral bias. CONCLUSIONS: Pediatric melanoma can be fatal in diverse clinical presentations, including a striking prevalence of Hispanic patients compared to adult disease, and with a range of clinical subtypes, although no fatal cases of spitzoid melanoma were diagnosed during childhood.

PDBe: towards reusable data delivery infrastructure at protein data bank in Europe.

The Protein Data Bank in Europe (PDBe, pdbe.org) is actively engaged in the deposition, annotation, remediation, enrichment and dissemination of macromolecular structure data. This paper describes new developments and improvements at PDBe addressing three challenging areas: data enrichment, data dissemination and functional reusability. New features of the PDBe Web site are discussed, including a context dependent menu providing links to raw experimental data and improved presentation of structures solved by hybrid methods. The paper also summarizes the features of the LiteMol suite, which is a set of services enabling fast and interactive 3D visualization of structures, with associated experimental maps, annotations and quality assessment information. We introduce a library of Web components which can be easily reused to port data and functionality available at PDBe to other services. We also introduce updates to the SIFTS resource which maps PDB data to other bioinformatics resources, and the PDBe REST API.

Management of infantile hemangiomas during the COVID pandemic.

The COVID-19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long-term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA-approved monitoring guidelines, clinical practice guidelines, and relevant, up-to-date publications regarding initiation and monitoring of beta-blocker therapy were used to inform the recommendations. Clinical decision-making guidelines about when telehealth is an appropriate alternative to in-office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided.

Structural and functional analysis of Dickkopf 4 (Dkk4): New insights into Dkk evolution and regulation of Wnt signaling by Dkk and Kremen proteins.

Dickkopf (Dkk) family proteins are important regulators of Wnt signaling pathways, which play key roles in many essential biological processes. Here, we report the first detailed structural and dynamics study of a full-length mature Dkk protein (Dkk4, residues 19-224), including determination of the first atomic-resolution structure for the N-terminal cysteine-rich domain (CRD1) conserved among Dkk proteins. We discovered that CRD1 has significant structural homology to the Dkk C-terminal cysteine-rich domain (CRD2), pointing to multiple gene duplication events during Dkk family evolution. We also show that Dkk4 consists of two independent folded domains (CRD1 and CRD2) joined by a highly flexible, nonstructured linker. Similarly, the N-terminal region preceding CRD1 and containing a highly conserved NXI(R/K) sequence motif was shown to be dynamic and highly flexible. We demonstrate that Dkk4 CRD2 mediates high-affinity binding to both the E1E2 region of low-density lipoprotein receptor-related protein 6 (LRP6 E1E2) and the Kremen1 (Krm1) extracellular domain. In contrast, the N-terminal region alone bound with only moderate affinity to LRP6 E1E2, consistent with binding via the conserved NXI(R/K) motif, but did not interact with Krm proteins. We also confirmed that Dkk and Krm family proteins function synergistically to inhibit Wnt signaling. Insights provided by our integrated structural, dynamics, interaction, and functional studies have allowed us to refine the model of synergistic regulation of Wnt signaling by Dkk proteins. Our results indicate the potential for the formation of a diverse range of ternary complexes comprising Dkk, Krm, and LRP5/6 proteins, allowing fine-tuning of Wnt-dependent signaling.

The Mfge8-α8ß1-PTEN pathway regulates airway smooth muscle contraction in allergic inflammation.

Asthma affects ∼300 million people worldwide. Despite multiple treatment options, asthma treatment remains unsatisfactory in a subset of patients. Airway obstruction is a hallmark of allergic asthma and is largely due to airway smooth muscle hypercontractility induced by airway inflammation. Identification of molecular pathways that regulate airway smooth muscle hypercontractility is of considerable therapeutic interest. We previously identified roles for milk fat globule epidermal growth factor-like 8 (Mfge8) in opposing the effects of allergic inflammation on increasing airway smooth muscle contractile force. In this study, we delineate the signaling pathway by which Mfge8 mediates these effects. By using genetic and pharmacologic approaches, we show that the α8ß1 integrin and the phosphatase and tensin homolog (PTEN) mediate the effects of Mfge8 on preventing IL-13-induced increases in airway contractility. Tracheal rings from mice with smooth muscle-specific deletion of α8ß1 or PTEN have enhanced contraction in response to treatment with IL-13. Enhanced IL-13-induced tracheal ring contraction in Mfge8-/- mice was abolished by treatment with the PI3K inhibitor. Mechanistically, IL-13 induces ubiquitination and degradation of PTEN protein. Our findings identify a role for the Mfge8-α8ß1-PTEN pathway in regulating the force of airway smooth muscle contraction in the setting of allergic inflammation.-Khalifeh-Soltani, A., Gupta, D., Ha, A., Podolsky, M. J., Datta, R., Atabai, K. The Mfge8-α8ß1-PTEN pathway regulates airway smooth muscle contraction in allergic inflammation.