Age-related Variation in Sleep-dependent Obstruction in Surgically Naive Children.

OBJECTIVE: Little is known about age-related variations in sites and grade of sleep-dependent airway obstruction in children with obstructive sleep apnea (OSA) or obstructive sleep-disordered breathing (oSDB). The objective was to compare sites and grade of obstruction on drug-induced sleep endoscopy (DISE) across different age groups of surgically naïve children with OSA or oSDB. METHODS: A retrospective chart review was performed for surgically naïve children aged 0-18 years with OSA/oSDB who underwent DISE from July 2021 to August 2023. Participants were categorized into: infants (aged 0-1 years), younger toddlers (aged 1-2 years), older toddlers (aged 2-3 years), preschool (aged 3-5 years), younger school-aged (aged 5-10 years), and older school-aged (aged 10-18 years). On DISE, obstruction was rated 0 = none/mild, 1 = moderate, 2 = severe for inferior turbinates, adenoid, velum, palatine tonsils/lateral pharyngeal wall, lingual tonsils, tongue base, epiglottis, and supra-arytenoid tissue. A series of multiple regression analyses were used to identify age differences in the grade of obstruction across all sites combined and at each individual site separately. RESULTS: The sample consisted of 252 children aged 1 month to 17 years with 57.9% males. Older patients had greater total obstruction scores (B = 0.42, SE = 0.10, p < 0.01) and greater number of sites that were severely obstructed (B = 0.11, SE = 0.05, p = 0.03). Older age groups had more obstruction at inferior turbinates (p = 0.02), adenoid (p < 0.01), palatine tonsils/lateral pharyngeal wall (p < 0.01), lingual tonsil (p < 0.01), and base of tongue (p < 0.01). Younger age groups had more obstruction at the supra-arytenoid tissue (p < 0.01). CONCLUSION: Varying patterns of sleep-dependent airway obstruction should be expected across different age groups in children with OSA or oSDB. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Rapid Production Nasal Osteotomy Simulators With Multi-Modality Manufacturing: 3D Printing, Casting, and Molding.

OBJECTIVE: To expand and improve upon previously described nasal osteotomy models with the goals of decreasing cost and production time while ensuring model fidelity. To assess change in participant confidence in their understanding of and ability to perform nasal osteotomies following completion of the simulation course. STUDY DESIGN: Prospective study. SETTING: Simulation training course for otolaryngology residents at West Virginia University. METHODS: A combined methodology of 3D printing, silicone molding, and resin casting was used to design a nasal osteotomy model to address material issues such as print delamination. Multiple models were then used in a simulation lab on performing nasal osteotomies. Model utility and impact on participant confidence was assessed at baseline, postlecture, and postsimulation lab. RESULTS: Using a combined manufacturing methodology, we achieved a production time reduction of 97.71% and a cost reduction of 82.02% for this polyurethane resin nasal osteotomy model relative to a previously described osteotomy model. Participants in the simulation course were noted to have a significant improvement in confidence in their understanding of and ability to perform nasal osteotomies from baseline and postlecture and also from postlecture and postsimulation lab (P < .05 for all). CONCLUSION: By incorporating multiple manufacturing modalities (molding and casting) in addition to 3D printing, this study achieved a large reduction in both production time and cost in fabrication of a nasal osteotomy simulator and addressed material limitations imposed by fused deposition modeling printers. This design methodology serves as an example on how these barriers may be addressed in unrelated simulation projects. Model fidelity was improved with addition of a silicone soft tissue midface. Improvement in participant confidence was noted following completion of the simulation lab.

The Effect of Aromatherapy on Anxiety and Pain in Patients Undergoing Oculoplastic Surgery.

PURPOSE: To determine the effect of aromatherapy on postoperative anxiety and pain in patients undergoing oculoplastic surgery. METHODS: A randomized controlled study of 60 patients who underwent monitored anesthesia care sedation for oculoplastic procedures from August 2018 to November 2020. Patients were randomized to an aromatherapy (n = 32) or placebo (n = 28) condition. Anxiety was measured with State-Trait Anxiety Inventory and visual analog scale for anxiety. Pain was measured with a visual analog scale for pain. RESULTS: Compared with control patients, aromatherapy patients had significantly lower postoperative State-Trait Anxiety Inventory state anxiety (24.1 vs. 29.1; p = 0.05) and visual analog scale pain scores (1.9 vs. 3.2; p = 0.05). Aromatherapy patients also had shorter stays in the postanesthesia care unit than control patients (57.7 vs. 79.4 minutes; p = 0.03). CONCLUSIONS: Patients who received aromatherapy reported lower postoperative anxiety and pain. Aromatherapy may be a useful adjuvant analgesic and/or anxiolytic for patients undergoing oculoplastic procedures with monitored anesthesia care sedation.

Human papillomavirus circulating tumor DNA: a diagnostic tool in squamous cell carcinoma of unknown primary-a pilot study.

Introduction: Neck mass is the most common presentation of human papillomavirus-related (HPV-related) oropharyngeal squamous cell carcinoma (OPSCC). Recently, circulating tumor HPV-DNA (ctHPVDNA) assays have been developed to detect active OPSCC. This pilot study investigates the diagnostic accuracy of ctHPVDNA in establishing HPV status for known vs. unknown OPSCC presenting as a neck mass. Methods: A single-institution pilot study was conducted on all patients with OPSCC presenting as a neck mass between 2021 and 2022. The diagnostic accuracy of ctHPVDNA was compared to that of standard diagnostic procedures used to obtain HPV status according to the American Society of Clinical Oncology (ASCO) guideline for squamous cell carcinoma of unknown primary (SCCUP). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ctHPVDNA were calculated. Results: A total of 27 patients were included; 70.4% were current or former smokers, 48.1% (N = 13) had identifiable primaries, and 51.9% (N = 14) had SCCUP. Four patients with known primaries required operative direct laryngoscopy with biopsy (DLB) to establish HPV status. Two patients with SCCUP underwent diagnostic transoral robotic surgery (TORS) to establish HPV status and localize the primary. Twelve patients underwent therapeutic TORS and neck dissection. The gold standard for HPV status was based on final histopathologic p16 or HPV in situ hybridization (ISH) staining during workup/treatment. ctHPVDNA had 95.8% sensitivity, 100% specificity, 100% PPV, and 75% NPV in predicting HPV-positive OPSCC in the whole sample. Binary logistic regression model using ctHPVDNA results to predict HPV-positive OPSCC was significant (-2 log likelihood = 5.55, χ2 = 8.70, p <.01, Nagelkerke's R squared = .67). Among patients with identifiable primaries, all patients had HPV-positive tumors on final pathology, and ctHPVDNA was positive in 100%. In the unknown primary patients, ctHPVDNA had 90.9% sensitivity, 100% specificity, 100% PPV, and 75% NPV. Discussion: ctHPVDNA demonstrated good diagnostic accuracy for both known and unknown primaries. Incorporation of ctHPVDNA into the diagnostic algorithm for SCCUP may reduce the need for multiple procedures to establish HPV status.

Predictors of Success of Adenoidectomy in the Treatment of Pediatric Chronic Rhinosinusitis.

Objectives: There is consensus for adenoidectomy as treatment of chronic rhinosinusitis (CRS) in children younger than 6 years but less consensus for those aged 6 years and older. The present clinical research study investigated predictors of adenoidectomy success for pediatric CRS. Methods: A retrospective chart review was conducted for 107 children who presented to an otolaryngology clinic and had an adenoidectomy for CRS after failure of maximal medical therapy. Results: The majority of sample was male (N = 63; 58.9%) with mean age of 4.88 (SD = 2.54) and mean Lund-Mackay score of 7.76 (SD = 3.87). Patients who had success with adenoidectomy were older on average [mean (M) = 5.46; SD = 2.83] than patients who failed the procedure (M = 4.36; SD = 2.40; F = 4.06, P = .047). This equated to 67.9% of children aged 6 years and older and 39.2% of children younger than 6 years succeeding with the surgery. Conclusions: Adenoidectomy is a good first-line surgery for children aged 12 years and younger, especially in the 6 to 12 years group which had a high rate of success with 68% experiencing remission of symptoms after surgery.

GhLCYε-3 characterized as a lycopene cyclase gene responding to drought stress in cotton.

Drought stress significantly affects crop productivity. Carotenoids are essential photosynthetic pigment for plants, bacteria, and algae, with signaling and antioxidant functions. Lutein is a crucial branch product in the carotenoid synthesis pathway, which effectively improves the stress tolerance of higher plants. lycopene cyclase, a central enzyme for lutein synthesis, holds great significance in regulating lutein production. This research establishes a correlation between lutein content and stress resistance by measuring the drought resistance and lutein content of various cotton materials. To identify which crucial genes are associated with lutein, the lycopene cyclase family (LCYs) was analyzed. The research found that LCYs form a highly conserved family divided into two subfamilies, LCY-ε (lycopene ε-cyclase) and LCY-ß (lycopene ß-cyclase). Most members of the LCY family contain photoresponsive elements and abscisic acid elements. qRT-PCR demonstrates showed that most genes responded positively to drought stress, and GhLCYε-3 was expressed significantly differently under drought stress. Virus-induced gene silencing (VIGS) assay showed that the content of GhLCYε-3 was significantly increased with MDA and PRO, and the contents of chlorophyll and lutein were significantly decreased in pYL156 plants. The decrease in GhLCYε-3 expression is speculated to lead to reduced lutein content in vivo, resulting in the accumulation of reactive oxygen species (ROS) and decreased drought tolerance. This research enriched the understanding of LCY gene family and lutein function, and provided a new reference for cotton planting in arid areas. Synopsis: Lycopene cyclase plays an important role in enhancing the ability of scavenging ROS and drought resistance of plants.

Risk Factors associated with Recurrent Acute Rhinosinusitis.

KEY POINTS: Few studies have evaluated the association of recurrent acute rhinosinusitis (RARS) with other comorbidities. Allergic rhinitis, asthma, primary antibody deficiency, and autoimmune disorders are associated with RARS. Evaluation for these comorbidities should be considered when treating patients with RARS.

Role of Acute Rhinosinusitis in Periorbital Infections in Children.

OBJECTIVE: Periorbital cellulitis in children are commonly caused by acute rhinosinusitis (ARS). This study investigated the association of ARS and the severity of periorbital cellulitis in children. STUDY DESIGN: Retrospective case-control study of children with periorbital cellulitis with ARS versus periorbital cellulitis without ARS. SETTING: Patients were seen at West Virginia University Children's Hospitals between August 2011 to August 2022. METHODS: Patients were divided into cases and controls based on presence or absence of ARS. ARS was defined based on clinical symptoms with objective presence of disease on CT scan. Patients' characteristics, treatment, hospital length of stay, and readmission were collected. RESULTS: The sample consisted of 118 pediatric patients with orbital cellulitis. Patients with ARS were younger than patients without ARS (6.3 vs 8.5, p = 0.025), however there were no sex differences between two groups (p = 0.540). The ARS group had higher incidence of postseptal cellulitis (51.5% vs 9.6%, p < 0.001). As compared to patients without ARS, patients with ARS were more likely to be admitted (p < 0.001), have a longer length of stay (median of 3.5 days vs 0.5 days, p < 0.001), require IV antibiotics (95.3% vs 54.9%, p < 0.001), and require surgical intervention (23.1% vs 5.8%, p < 0.001). Readmission rate was similar between the two groups. CONCLUSION: Children presenting with acute periorbital cellulitis who have ARS tend to have more severe infection requiring higher level of care. ARS should be assessed and incorporated into the plan of care of pediatric patients with periorbital infections.

Impact of recurrent acute rhinosinusitis on quality of life.

KEY POINTS: Quality of life (QoL) in patients with recurrent acute rhinosinusitis (RARS) is understudied. QoL for RARS patients is similar to chronic rhinosinusitis patients, although objective disease severity is lower. QoL of RARS patients is similarly affected during active and inactive infection.

Association of autoimmune disorders with chronic rhinosinusitis in adults.

INTRODUCTION: Increasing evidence suggests that autoimmune disorders and their immunomodulating medications may increase the risk of rhinosinusitis compared to rhinitis. GOAL: To investigate the association between autoimmune disorders and rhinosinusitis. METHODS: We performed a case-control study of patients referred to West Virginia University from August 2020 to October 2022 for rhinologic complaints. Rhinosinusitis patients were diagnosed with either chronic rhinosinusitis (CRS) or recurrent acute rhinosinusitis (RARS). These patients were compared to non-rhinosinusitis patients. Patients' characteristics, comorbidities, and type of treatment of autoimmune disorders were reviewed. RESULTS: The sample consisted of 527 rhinosinusitis [184 CRS without nasal polyps (CRSsNP), 263 CRS with nasal polyps (CRSwNP) and 80 RARS patients] patients and 564 non-rhinosinusitis patients. Patients with rhinosinusitis were more likely to be older, males, have asthma, and have current and past smoking history (all with p-value < 0.05). Autoimmune disorders, primary antibody deficiency, and immunomodulator agents were more common in rhinosinusitis patients (16.5 % vs 9.4 %, OR = 1.9, p < 0.001; 5.1 % vs 0.5 %, OR = 10.1, p < 0.001; and 3.8 % vs 1.1 %, OR = 3.7, p = 0.003 respectively). Multivariate logistic regression adjusting for confounders showed that autoimmune disorders were strongly associated with rhinosinusitis [OR = 1.6, 95 % CI = 1.10-2.48], whereas the immunomodulators did not reach statistical significance [OR = 2.4, 95 % CI = 0.87-6.47]. Subgroup analysis showed the autoimmune disorders did not significantly differ between CRS and RARS groups [OR = 1.0, 95 % CI = 0.5-2.1], or between the CRSsNP and CRSwNP groups [OR = 0.9, 95 % CI = 0.5-1.7]. CONCLUSION: Autoimmune disorders are associated with rhinosinusitis, both CRS and RARS, independently of other risk factors.

Case Series on Autosomal Recessive Non-Syndromic Retinitis Pigmentosa Caused by POMGNT1 Mutations with a Report of a New Variant.

Recessive Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) mutations can cause early onset muscle-eye-brain disease but have also more recently been associated with non-syndromic Retinitis Pigmentosa. In this case series, we describe three sisters affected by non-syndromic autosomal recessive POMGNT1 retinopathy with a report of a new variant. The three patients received care at West Virginia University Eye Institute, including full ophthalmic examination with additional fundus imaging, optical coherence tomography (OCT), electroretinogram (ERG), and visual field testing. Diagnostic panel testing of 330 genes was also obtained. The proband was seen for cataract evaluation at age 42, and her fundus examination was suggestive of retinitis pigmentosa. Her oldest sister had been treated for acute anterior uveitis with retinal vasculitis. Another sister was diagnosed with multiple sclerosis (MS) and peripheral retinal degeneration. Posterior subcapsular cataracts were diagnosed between age 42 and 55 in all three sisters, each with constricted fields with preserved central vision. We identified one pathogenic POMGNT1 variant (c.751 + 1G > A) and one likely pathogenic variant (c.1010T > C p.Ile337Thr) in all three sisters. A thorough family history and examination of the siblings with genotyping might have led to an earlier diagnosis of retinal inherited disease and avoidance of immunomodulatory treatment in the oldest sibling.

Analysis of the histidine kinase gene family and the role of GhHK8 in response to drought tolerance in cotton.

As an important member of the two-component system (TCS), histidine kinases (HKs) play important roles in various plant developmental processes and signal transduction in response to a wide range of biotic and abiotic stresses. So far, the HK gene family has not been investigated in Gossypium. In this study, a total of 177 HK gene family members were identified in cotton. They were further divided into seven groups, and the protein characteristics, genetic relationship, gene structure, chromosome location, collinearity, and cis-elements identification were comprehensively analyzed. Whole genome duplication (WGD) / segmental duplication may be the reason why the number of HK genes doubled in tetraploid Gossypium species. Expression analysis revealed that most cotton HK genes were mainly expressed in the reproductive organs and the fiber at initial stage. Gene expression analysis revealed that HK family genes are involved in cotton abiotic stress, especially drought stress and salt stress. In addition, gene interaction networks showed that HKs were involved in the regulation of cotton abiotic stress, especially drought stress. VIGS experiments have shown that GhHK8 is a negative regulatory factor in response to drought stress. Our systematic analysis provided insights into the characteristics of the HK genes in cotton and laid a foundation for further exploring their potential in drought stress resistance in cotton.

GhIMP10D, an inositol monophosphates family gene, enhances ascorbic acid and antioxidant enzyme activities to confer alkaline tolerance in Gossypium hirsutum L.

BACKGROUND: Inositol monophosphates (IMP) are key enzymes in the ascorbic acid (AsA) synthesis pathways, which play vital roles in regulating plant growth and development and stresses tolerance. To date, no comprehensive analysis of the expression profile of IMP genes and their functions under abiotic stress in cotton has been reported. RESULTS: In this study, the genetic characteristics, phylogenetic evolution, cis-acting elements and expression patterns of IMP gene family in cotton were systematically analyzed. A total of 28, 27, 13 and 13 IMP genes were identified in Gossypium hirsutum (G. hirsutum), Gossypium barbadense (G. barbadense), Gossypium arboreum (G. arboreum), and Gossypium raimondii (G. raimondii), respectively. Phylogenetic analysis showed that IMP family genes could cluster into 3 clades. Structure analysis of genes showed that GhIMP genes from the same subgroup had similar genetic structure and exon number. And most GhIMP family members contained hormone-related elements (abscisic acid response element, MeJA response element, gibberellin response element) and stress-related elements (low temperature response element, defense and stress response element, wound response element). After exogenous application of abscisic acid (ABA), some GhIMP genes containing ABA response elements positively responded to alkaline stress, indicating that ABA response elements played an important role in response to alkaline stress. qRT-PCR showed that most of GhIMP genes responded positively to alkaline stress, and GhIMP10D significantly upregulated under alkaline stress, with the highest up-regulated expression level. Virus-induced gene silencing (VIGS) experiment showed that compared with 156 plants, MDA content of pYL156:GhIMP10D plants increased significantly, while POD, SOD, chlorophyII and AsA content decreased significantly. CONCLUSIONS: This study provides a thorough overview of the IMP gene family and presents a new perspective on the evolution of this gene family. In particular, some IMP genes may be involved in alkaline stress tolerance regulation, and GhIMP10D showed high expression levels in leaves, stems and roots under alkaline stress, and preliminary functional verification of GhIMP10D gene suggested that it may regulate tolerance to alkaline stress by regulating the activity of antioxidant enzymes and the content of AsA. This study contributes to the subsequent broader discussion of the structure and alkaline resistance of IMP genes in cotton.

GhCYS2 governs the tolerance against cadmium stress by regulating cell viability and photosynthesis in cotton.

Cysteine, an early sulfur-containing compound in plants, is of significant importance in sulfur metabolism. CYS encodes cysteine synthetase that further catalyzes cysteine synthesis. In this investigation, CYS genes, identified from genome-wide analysis of Gossypium hirsutum bioinformatically, led to the discovery of GhCYS2 as the pivotal gene responsible for Cd2+ response. The silencing of GhCYS2 through virus-induced gene silencing (VIGS) rendered plants highly susceptible to Cd2+ stress. Silencing GhCYS2 in plants resulted in diminished levels of cysteine and glutathione while leading to the accumulation of MDA and ROS within cells, thereby impeding the regular process of photosynthesis. Consequently, the stomatal aperture of leaves decreased, epidermal cells underwent distortion and deformation, intercellular connections are dramatically disrupted, and fissures manifested between cells. Ultimately, these detrimental effected culminating in plant wilting and a substantial reduction in biomass. The association established between Cd2+ and cysteine in this investigation offered a valuable reference point for further inquiry into the functional and regulatory mechanisms of cysteine synthesis genes.

Development of a model to predict antidepressant treatment response for depression among Veterans.

BACKGROUND: Only a limited number of patients with major depressive disorder (MDD) respond to a first course of antidepressant medication (ADM). We investigated the feasibility of creating a baseline model to determine which of these would be among patients beginning ADM treatment in the US Veterans Health Administration (VHA). METHODS: A 2018-2020 national sample of n = 660 VHA patients receiving ADM treatment for MDD completed an extensive baseline self-report assessment near the beginning of treatment and a 3-month self-report follow-up assessment. Using baseline self-report data along with administrative and geospatial data, an ensemble machine learning method was used to develop a model for 3-month treatment response defined by the Quick Inventory of Depression Symptomatology Self-Report and a modified Sheehan Disability Scale. The model was developed in a 70% training sample and tested in the remaining 30% test sample. RESULTS: In total, 35.7% of patients responded to treatment. The prediction model had an area under the ROC curve (s.e.) of 0.66 (0.04) in the test sample. A strong gradient in probability (s.e.) of treatment response was found across three subsamples of the test sample using training sample thresholds for high [45.6% (5.5)], intermediate [34.5% (7.6)], and low [11.1% (4.9)] probabilities of response. Baseline symptom severity, comorbidity, treatment characteristics (expectations, history, and aspects of current treatment), and protective/resilience factors were the most important predictors. CONCLUSIONS: Although these results are promising, parallel models to predict response to alternative treatments based on data collected before initiating treatment would be needed for such models to help guide treatment selection.

Changes in terpene biosynthesis and submergence tolerance in cotton.

BACKGROUND: Flooding is among the most severe abiotic stresses in plant growth and development. The mechanism of submergence tolerance of cotton in response to submergence stress is unknown. RESULTS: The transcriptome results showed that a total of 6,893 differentially expressed genes (DEGs) were discovered under submergence stress. Gene Ontology (GO) enrichment analysis showed that DEGs were involved in various stress or stimulus responses. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that DEGs related to plant hormone signal transduction, starch and sucrose metabolism, glycolysis and the biosynthesis of secondary metabolites were regulated by submergence stress. Eight DEGs related to ethylene signaling and 3 ethylene synthesis genes were identified in the hormone signal transduction. For respiratory metabolism, alcohol dehydrogenase (ADH, GH_A02G0728) and pyruvate decarboxylase (PDC, GH_D09G1778) were significantly upregulated but 6-phosphofructokinase (PFK, GH_D05G0280), phosphoglycerate kinase (PGK, GH_A01G0945 and GH_D01G0967) and sucrose synthase genes (SUS, GH_A06G0873 and GH_D06G0851) were significantly downregulated in the submergence treatment. Terpene biosynthetic pathway-related genes in the secondary metabolites were regulated in submergence stress. CONCLUSIONS: Regulation of terpene biosynthesis by respiratory metabolism may play a role in enhancing the tolerance of cotton to submergence under flooding. Our findings showed that the mevalonate pathway, which occurs in the cytoplasm of the terpenoid backbone biosynthesis pathway (ko00900), may be the main response to submergence stress.

Characterization and gene expression patterns analysis implies BSK family genes respond to salinity stress in cotton.

Identification, evolution, and expression patterns of BSK (BR signaling kinase) family genes revealed that BSKs participated in the response of cotton to abiotic stress and maintained the growth of cotton in extreme environment. The steroidal hormone brassinosteroids (BR) play important roles in different plant biological processes. This study focused on BSK which were downstream regulatory element of BR, in order to help to decipher the functions of BSKs genes from cotton on growth development and responses to abiotic stresses and lean the evolutionary relationship of cotton BSKs. BSKs are a class of plant-specific receptor-like cytoplasmic kinases involved in BR signal transduction. In this study, bioinformatics methods were used to identify the cotton BSKs gene family at the cotton genome level, and the gene structure, promoter elements, protein structure and properties, gene expression patterns and candidate interacting proteins were analyzed. In the present study, a total of 152 BSKs were identified by a genome-wide search in four cotton species and other 11 plant species, and phylogenetic analysis revealed three evolutionary clades. It was identified that BSKs contain typical PKc and TPR domains, the N-terminus is composed of extended chains and helical structures. Cotton BSKs genes show different expression patterns in different tissues and organs. The gene promoter contains numerous cis-acting elements induced by hormones and abiotic stress, the hormone ABA and Cold-inducing related elements have the highest count, indicating that cotton BSK genes may be regulated by various hormones at different growth stages and involved in the response regulation of cotton to various stresses. The expression analysis of BSKs in cotton showed that the expression levels of GhBSK06, GhBSK10, GhBSK21 and GhBSK24 were significantly increased with salt-inducing. This study is helpful to analyze the function of cotton BSKs genes in growth and development and in response to stress.

Combined transcriptomic and metabolomic analyses elucidate key salt-responsive biomarkers to regulate salt tolerance in cotton.

BACKGROUND: Cotton is an important industrial crop and a pioneer crop for saline-alkali land restoration. However, the molecular mechanism underlying the cotton response to salt is not completely understood. METHODS: Here, we used metabolome data and transcriptome data to analyze the salt tolerance regulatory network of cotton and metabolic biomarkers. RESULTS: In this study, cotton was stressed at 400 m M NaCl for 0 h, 3 h, 24 h and 48 h. NaCl interfered with cotton gene expression, altered metabolite contents and affected plant growth. Metabolome analysis showed that NaCl stress increased the contents of amino acids, sugars and ABA, decreased the amount of vitamin and terpenoids. K-means cluster analysis of differentially expressed genes showed that the continuously up-regulated genes were mainly enriched in metabolic pathways such as flavonoid biosynthesis and amino acid biosynthesis. CONCLUSION: The four metabolites of cysteine (Cys), ABA(Abscisic acid), turanose, and isopentenyladenine-7-N-glucoside (IP7G) were consistently up-regulated under salt stress, which may indicate that they are potential candidates for cotton under salt stress biomarkers. Combined transcriptome and metabolome analysis revealed accumulation of cysteine, ABA, isopentenyladenine-7-N-glucoside and turanose were important for salt tolerance in cotton mechanism. These results will provide some metabolic insights and key metabolite biomarkers for salt stress tolerance, which may help to understanding of the metabolite response to salt stress in cotton and develop a foundation for cotton to grow better in saline soil.

Systematic analysis and expression of Gossypium 2ODD superfamily highlight the roles of GhLDOXs responding to alkali and other abiotic stress in cotton.

BACKGROUND: 2-oxoglutarate-dependent dioxygenase (2ODD) is the second largest family of oxidases involved in various oxygenation/hydroxylation reactions in plants. Many members in the family regulate gene transcription, nucleic acid modification/repair and secondary metabolic synthesis. The 2ODD family genes also function in the formation of abundant flavonoids during anthocyanin synthesis, thereby modulating plant development and response to diverse stresses. RESULTS: Totally, 379, 336, 205, and 204 2ODD genes were identified in G. barbadense (Gb), G. hirsutum (Gh), G. arboreum (Ga), and G. raimondii (Gb), respectively. The 336 2ODDs in G. hirsutum were divided into 15 subfamilies according to their putative functions. The structural features and functions of the 2ODD members in the same subfamily were similar and evolutionarily conserved. Tandem duplications and segmental duplications served essential roles in the large-scale expansion of the cotton 2ODD family. Ka/Ks values for most of the gene pairs were less than 1, indicating that 2ODD genes undergo strong purifying selection during evolution. Gh2ODDs might act in cotton responses to different abiotic stresses. GhLDOX3 and GhLDOX7, two members of the GhLDOX subfamily from Gh2ODDs, were significantly down-regulated in transcription under alkaline stress. Moreover, the expression of GhLDOX3 in leaves was significantly higher than that in other tissues. These results will provide valuable information for further understanding the evolution mechanisms and functions of the cotton 2ODD genes in the future. CONCLUSIONS: Genome-wide identification, structure, and evolution and expression analysis of 2ODD genes in Gossypium were carried out. The 2ODDs were highly conserved during evolutionary. Most Gh2ODDs were involved in the regulation of cotton responses to multiple abiotic stresses including salt, drought, hot, cold and alkali.

Development of a model to predict combined antidepressant medication and psychotherapy treatment response for depression among veterans.

BACKGROUND: Although research shows that more depressed patients respond to combined antidepressants (ADM) and psychotherapy than either alone, many patients do not respond even to combined treatment. A reliable prediction model for this could help treatment decision-making. We attempted to create such a model using machine learning methods among patients in the US Veterans Health Administration (VHA). METHODS: A 2018-2020 national sample of VHA patients beginning combined depression treatment completed self-report assessments at baseline and 3 months (n = 658). A learning model was developed using baseline self-report, administrative, and geospatial data to predict 3-month treatment response defined by reductions in the Quick Inventory of Depression Symptomatology Self-Report and/or in the Sheehan Disability Scale. The model was developed in a 70 % training sample and tested in the remaining 30 % test sample. RESULTS: 30.0 % of patients responded to treatment. The prediction model had a test sample AUC-ROC of 0.657. A strong gradient was found in probability of treatment response from 52.7 % in the highest predicted quintile to 14.4 % in the lowest predicted quintile. The most important predictors were episode characteristics (symptoms, comorbidities, history), personality/psychological resilience, recent stressors, and treatment characteristics. LIMITATIONS: Restrictions in sample definition, a low recruitment rate, and reliance on patient self-report rather than clinician assessments to determine treatment response limited the generalizability of results. CONCLUSIONS: A machine learning model could help depressed patients and providers predict likely response to combined ADM-psychotherapy. Parallel information about potential harms and costs of alternative treatments would be needed, though, to inform optimal treatment selection.