A Computed Tomography-Based Fracture Prediction Model With Images of Vertebral Bones and Muscles by Employing Deep Learning: Development and Validation Study.

BACKGROUND: With the progressive increase in aging populations, the use of opportunistic computed tomography (CT) scanning is increasing, which could be a valuable method for acquiring information on both muscles and bones of aging populations. OBJECTIVE: The aim of this study was to develop and externally validate opportunistic CT-based fracture prediction models by using images of vertebral bones and paravertebral muscles. METHODS: The models were developed based on a retrospective longitudinal cohort study of 1214 patients with abdominal CT images between 2010 and 2019. The models were externally validated in 495 patients. The primary outcome of this study was defined as the predictive accuracy for identifying vertebral fracture events within a 5-year follow-up. The image models were developed using an attention convolutional neural network-recurrent neural network model from images of the vertebral bone and paravertebral muscles. RESULTS: The mean ages of the patients in the development and validation sets were 73 years and 68 years, and 69.1% (839/1214) and 78.8% (390/495) of them were females, respectively. The areas under the receiver operator curve (AUROCs) for predicting vertebral fractures were superior in images of the vertebral bone and paravertebral muscles than those in the bone-only images in the external validation cohort (0.827, 95% CI 0.821-0.833 vs 0.815, 95% CI 0.806-0.824, respectively; P<.001). The AUROCs of these image models were higher than those of the fracture risk assessment models (0.810 for major osteoporotic risk, 0.780 for hip fracture risk). For the clinical model using age, sex, BMI, use of steroids, smoking, possible secondary osteoporosis, type 2 diabetes mellitus, HIV, hepatitis C, and renal failure, the AUROC value in the external validation cohort was 0.749 (95% CI 0.736-0.762), which was lower than that of the image model using vertebral bones and muscles (P<.001). CONCLUSIONS: The model using the images of the vertebral bone and paravertebral muscle showed better performance than that using the images of the bone-only or clinical variables. Opportunistic CT screening may contribute to identifying patients with a high fracture risk in the future.

User-Centered Framework for Implementation of Technology (UFIT): Development of an Integrated Framework for Designing Clinical Decision Support Tools Packaged With Tailored Implementation Strategies.

BACKGROUND: Electronic health record-based clinical decision support (CDS) tools can facilitate the adoption of evidence into practice. Yet, the impact of CDS beyond single-site implementation is often limited by dissemination and implementation barriers related to site- and user-specific variation in workflows and behaviors. The translation of evidence-based CDS from initial development to implementation in heterogeneous environments requires a framework that assures careful balancing of fidelity to core functional elements with adaptations to ensure compatibility with new contexts. OBJECTIVE: This study aims to develop and apply a framework to guide tailoring and implementing CDS across diverse clinical settings. METHODS: In preparation for a multisite trial implementing CDS for pediatric overweight or obesity in primary care, we developed the User-Centered Framework for Implementation of Technology (UFIT), a framework that integrates principles from user-centered design (UCD), human factors/ergonomics theories, and implementation science to guide both CDS adaptation and tailoring of related implementation strategies. Our transdisciplinary study team conducted semistructured interviews with pediatric primary care clinicians and a diverse group of stakeholders from 3 health systems in the northeastern, midwestern, and southeastern United States to inform and apply the framework for our formative evaluation. RESULTS: We conducted 41 qualitative interviews with primary care clinicians (n=21) and other stakeholders (n=20). Our workflow analysis found 3 primary ways in which clinicians interact with the electronic health record during primary care well-child visits identifying opportunities for decision support. Additionally, we identified differences in practice patterns across contexts necessitating a multiprong design approach to support a variety of workflows, user needs, preferences, and implementation strategies. CONCLUSIONS: UFIT integrates theories and guidance from UCD, human factors/ergonomics, and implementation science to promote fit with local contexts for optimal outcomes. The components of UFIT were used to guide the development of Improving Pediatric Obesity Practice Using Prompts, an integrated package comprising CDS for obesity or overweight treatment with tailored implementation strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT05627011; https://clinicaltrials.gov/study/NCT05627011.

Construction of an assessment scale for thirst severity in critically ill patients and its reliability and validity.

OBJECTIVE: Developing a severity assessment scale for critically ill patients' thirst and conducting reliability and validity tests, aiming to provide healthcare professionals with a scientific and objective tool for assessing the level of thirst. METHODS: Based on literature review and qualitative interviews, a pool of items was generated, and a preliminary scale was formed through two rounds of Delphi expert consultation. Convenience sampling was employed to select 178 ICU patients in a top-three hospital from May 2023 to October 2023 as the study subjects to examine the reliability and validity of the severity assessment scale for critically ill patients' thirst. RESULTS: The developed severity assessment scale for critically ill patients' thirst consists of 8 evaluation items and 26 evaluation indicators. The agreement coefficients for two rounds of expert consultation were 100% and 92.6% for the positive coefficient, and the authority coefficients were .900 and .906. Kendall's concordance coefficients were .101 and .120 (all p < .001). The overall Cronbach's α coefficient for the scale was .827. The inter-rater reliability coefficient was .910. The Item-Content Validity Index (I-CVI) ranged from .800 to 1.000, and the Scale-Content Validity Index/Average (S-CVI/Ave) was .950. CONCLUSION: The critically ill patients' thirst assessment scale is reliable and valid and can be widely used in clinical practice. PATIENT OR PUBLIC CONTRIBUTION: The AiMi Academic Services (www.aimieditor.com) for English language editing and review services. IMPLICATIONS FOR CLINICAL PRACTICE: The scale developed in this study is a simple and ICU-specific scale that can be used to assess the severity of thirst in critically ill patients. As such, the severity of thirst in critically ill patients can be evaluated quickly so that targeted interventions can be implemented according to the patient's specific disease and treatment conditions. Therefore, patient comfort can be improved, and thirst-related health problems can be prevented.

Novel Allelic Gene Variations in CmCLAVATA3 (CmCLV3) Were Identified in a Genetic Population of Melon (Cucumis melo L.).

Carpel number (CN) is an important trait affecting the fruit size and shape of melon, which plays a crucial role in determining the overall appearance and market value. A unique non-synonymous single nucleotide polymorphism (SNP) in CmCLAVATA3 (CmCLV3) is responsible for the variation of CN in C. melo ssp. agrestis (hereafter agrestis), but it has been unclear in C. melo ssp. melo (hereafter melo). In this study, one major locus controlling the polymorphism of 5-CN (multi-CN) and 3-CN (normal-CN) in melo was identified using bulked segregant analysis (BSA-seq). This locus was then fine-mapped to an interval of 1.8 Mb on chromosome 12 using a segregating population containing 1451 progeny. CmCLV3 is still present in the candidate region. A new allele of CmCLV3, which contains five other nucleotide polymorphisms, including a non-synonymous SNP in coding sequence (CDS), except the SNP reported in agrestis, was identified in melo. A cis-trans test confirmed that the candidate gene, CmCLV3, contributes to the variation of CNs in melo. The qRT-PCR results indicate that there is no significant difference in the expression level of CmCLV3 in the apical stem between the multi-CN plants and the normal-CN plants. Overall, this study provides a genetic resource for melon fruit development research and molecular breeding. Additionally, it suggests that melo has undergone similar genetic selection but evolved into an independent allele.

Toward Inclusive Approaches in the Design, Development, and Implementation of eHealth in the Intellectual Disability Sector: Scoping Review.

BACKGROUND: The use of eHealth is more challenging for people with intellectual disabilities (IDs) than for the general population because the technologies often do not fit the complex needs and living circumstances of people with IDs. A translational gap exists between the developed technology and users' needs and capabilities. User involvement approaches have been developed to overcome this mismatch during the design, development, and implementation processes of the technology. The effectiveness and use of eHealth have received much scholarly attention, but little is known about user involvement approaches. OBJECTIVE: In this scoping review, we aimed to identify the inclusive approaches currently used for the design, development, and implementation of eHealth for people with IDs. We reviewed how and in what phases people with IDs and other stakeholders were included in these processes. We used 9 domains identified from the Centre for eHealth Research and Disease management road map and the Nonadoption, Abandonment, and challenges to the Scale-up, Spread, and Sustainability framework to gain insight into these processes. METHODS: We identified both scientific and gray literature through systematic searches in PubMed, Embase, PsycINFO, CINAHL, Cochrane, Web of Science, Google Scholar, and (websites of) relevant intermediate (health care) organizations. We included studies published since 1995 that showed the design, development, or implementation processes of eHealth for people with IDs. Data were analyzed along 9 domains: participatory development, iterative process, value specification, value proposition, technological development and design, organization, external context, implementation, and evaluation. RESULTS: The search strategy resulted in 10,639 studies, of which 17 (0.16%) met the inclusion criteria. Various approaches were used to guide user involvement (eg, human or user-centered design and participatory development), most of which applied an iterative process mainly during technological development. The involvement of stakeholders other than end users was described in less detail. The literature focused on the application of eHealth at an individual level and did not consider the organizational context. Inclusive approaches in the design and development phases were well described; however, the implementation phase remained underexposed. CONCLUSIONS: The participatory development, iterative process, and technological development and design domains showed inclusive approaches applied at the start of and during the development, whereas only a few approaches involved end users and iterative processes at the end of the process and during implementation. The literature focused primarily on the individual use of the technology, and the external, organizational, and financial contextual preconditions received less attention. However, members of this target group rely on their (social) environment for care and support. More attention is needed for these underrepresented domains, and key stakeholders should be included further on in the process to reduce the translational gap that exists between the developed technologies and user needs, capabilities, and context.

Internet Tool to Support Self-Assessment and Self-Swabbing of Sore Throat: Development and Feasibility Study.

BACKGROUND: Sore throat is a common problem and a common reason for the overuse of antibiotics. A web-based tool that helps people assess their sore throat, through the use of clinical prediction rules, taking throat swabs or saliva samples, and taking throat photographs, has the potential to improve self-management and help identify those who are the most and least likely to benefit from antibiotics. OBJECTIVE: We aimed to develop a web-based tool to help patients and parents or carers self-assess sore throat symptoms and take throat photographs, swabs, and saliva samples for diagnostic testing. We then explored the acceptability and feasibility of using the tool in adults and children with sore throats. METHODS: We used the Person-Based Approach to develop a web-based tool and then recruited adults and children with sore throats who participated in this study by attending general practices or through social media advertising. Participants self-assessed the presence of FeverPAIN and Centor score criteria and attempted to photograph their throat and take throat swabs and saliva tests. Study processes were observed via video call, and participants were interviewed about their views on using the web-based tool. Self-assessed throat inflammation and pus were compared to clinician evaluation of patients' throat photographs. RESULTS: A total of 45 participants (33 adults and 12 children) were recruited. Of these, 35 (78%) and 32 (71%) participants completed all scoring elements for FeverPAIN and Centor scores, respectively, and most (30/45, 67%) of them reported finding self-assessment relatively easy. No valid response was provided for swollen lymph nodes, throat inflammation, and pus on the throat by 11 (24%), 9 (20%), and 13 (29%) participants respectively. A total of 18 (40%) participants provided a throat photograph of adequate quality for clinical assessment. Patient assessment of inflammation had a sensitivity of 100% (3/3) and specificity of 47% (7/15) compared with the clinician-assessed photographs. For pus on the throat, the sensitivity was 100% (3/3) and the specificity was 71% (10/14). A total of 89% (40/45), 93% (42/45), 89% (40/45), and 80% (30/45) of participants provided analyzable bacterial swabs, viral swabs, saliva sponges, and saliva drool samples, respectively. Participants were generally happy and confident in providing samples, with saliva samples rated as slightly more acceptable than swab samples. CONCLUSIONS: Most adult and parent participants were able to use a web-based intervention to assess the clinical features of throat infections and generate scores using clinical prediction rules. However, some had difficulties assessing clinical signs, such as lymph nodes, throat pus, and inflammation, and scores were assessed as sensitive but not specific. Many participants had problems taking photographs of adequate quality, but most were able to take throat swabs and saliva samples.

Effect of environmental level of methomyl on hatching, morphology, immunity and development related genes expression in zebrafish (Danio rerio) embryo.

The extensive use of carbamate pesticides has led to a range of environmental and health problems, such as surface and groundwater contamination, and endocrine disorders in organisms. In this study, we focused on examining the effects of toxic exposure to the carbamate pesticide methomyl on the hatching, morphology, immunity and developmental gene expression levels in zebrafish embryos. Four concentrations of methomyl (0, 2, 20, and 200 µg/L) were administered to zebrafish embryos for a period of 96 h. The study found that exposure to methomyl accelerated the hatching process of zebrafish embryos, with the strongest effect recorded at the concentration of 2 µg/L. Methomyl exposure also trigged significantly reductions in heart rate and caused abnormalities in larvae morphology, and it also stimulated the synthesis and release of several inflammatory factors such as IL-1ß, IL-6, TNF-α and INF-α, lowered the IgM contents, ultimately enhancing inflammatory response and interfering with immune function. All of these showed the significant effects on exposure time, concentration and their interaction (Time × Concentration). Furthermore, the body length of zebrafish exposed to methomyl for 96 h was significantly shorter, particularly at higher concentrations (200 µg/L). Methomyl also affected the expression levels of genes associated with development (down-regulated igf1, bmp2b, vasa, dazl and piwi genes), demonstrating strong developmental toxicity and disruption of the endocrine system, with the most observed at the concentration of 200 µg/L and 96 h exposure to methomyl. The results of this study provide valuable reference information on the potential damage of methomyl concentrations in the environment on fish embryo development, while also supplementing present research on the immunotoxicity of methomyl.

Autosomal dominant neurodevelopmental disorders associated with KIF1A gene variants in 6 pediatric patients. / å ­ä¾‹KIF1AåŸºå› å˜å¼‚ç›¸å ³å¸¸æŸ“è‰²ä½“æ˜¾æ€§é—ä¼ ç¥žç»å‘è‚²éšœç¢æ‚£å„¿ä¸´åºŠå’Œé—ä¼ å­¦åˆ†æž.

OBJECTIVES: To analyze the clinical and genetic characteristics of children with autosomal dominant neurodevelopmental disorders caused by kinesin family member 1A (KIF1A) gene variation. METHODS: Clinical and genetic testing data of 6 children with KIF1A gene de novo heterozygous variation diagnosed in Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from the year 2018 to 2020 were retrospectively analyzed. Pathogenic variants were identified based on whole exome sequencing, and verified by Sanger sequencing. Moreover, the effect of variants on three-dimensional structure and stability of protein was analyzed by bioinformatics. RESULTS: Among 6 patients there were 4 males and 2 females, and the age of consultation varied from 7 months to 18 years. All cases had varying degrees of motor developmental delay since childhood, and 4 of them had gait abnormalities or fell easily. In addition, 2 children were accompanied by delayed mental development, epilepsy and abnormal eye development. Genetic tests showed that all 6 cases had heterozygous de novo variations of KIF1A gene, including 4 missense mutations c.296C>T (p.T99M), c.761G>A (p.R254Q), c.326G>T (p.G109V), c.745C>G (p.L249V) and one splicing mutation c.798+1G>A, among which the last three variants have not been previously reported. Bioinformatics analysis showed that G109V and L249V may impair their interaction with the neighboring amino acid residues, thereby impacting protein function and reducing protein stability, and were assessed as "likely pathogenic". Meanwhile, c.798+1G>A may damage an alpha helix in the motor domain of the KIF1A protein, and was assessed as "likely pathogenic". CONCLUSIONS: KIF1A-associated neurological diseases are clinically heterogeneous, with motor developmental delay and abnormal gait often being the most common clinical features. The clinical symptoms in T99M carriers are more severe, while those in R254Q carriers are relatively mild.

Time to develop severe acute malnutrition and its predictors among children living with HIV in the era of test and treat strategies at South Gondar hospitals, northwest, Ethiopia, 2021: a multicentre retrospective cohort study.

BACKGROUND: Although severe acute malnutrition is a major public issue among HIV infected children, there is no prior evidence in Ethiopia. Hence, this study aims to assess the time to develop severe acute malnutrition and its predictors among children living with human immunodeficiency virus in Ethiopia, 2012. METHODS: An institution based retrospective cohort study was conducted in South Gondar hospitals among 363 HIV infected children from February 10, 2014, to January 7, 2021. Epi-data version 3.1 was used to enter data, which was then exported to STATA version 14 for analysis. Besides, WHO (World Health Organization) Anthro Plus software was used to assess the nutritional status of the children. A standardized data extraction tool was used to collect the data. The Kaplan Meier survival curve was used to estimate the median survival time. The Cox-proportional hazard model assumption was checked via the Schoenfeld residual ph test and a stph plot. Bivariable and multivariable Cox proportional hazard models were employed at 95% confidence intervals (CI). A variable having a p-value < 0.05 was considered a statistically significant predictor of severe acute malnutrition. RESULTS: A total of 363 children living with HIV, 97 (26.72%) developed severe acute malnutrition during the follow-up period. The overall incidence rate was 5.4 (95% CI: 4.7-5.9) person per year with a total of 21, 492 months or 1791 years of observation. Moreover, the median survival time was 126 months. Treatment failure [AHR =3.4 (95% CI: 2.05-5.75)], CD4 count below threshold [AHR =2.5 (95% CI: 1.64-3.95)], and WHO stage III & IV [AHR =2.9 (95% CI: 1.74-4.73)] were all significant predictors of severe acute malnutrition. CONCLUSION: The time to develop severe acute malnutrition was found to be very low. Treatment failure, CD4 count below threshold, and WHO stage III were all significant predictors of severe acute malnutrition. Hence, emphasizing those predictor variables is essential for preventing and controlling the occurrence of severe acute malnutrition among HIV infected children.

Gastric Adenoma: A High Incidence Rate of Developing Carcinoma and Risk of Metachronous Gastric Cancer according to Long-Term Follow-Up.

INTRODUCTION: Gastric adenomas are histologically defined as benign epithelial tumors. While some of them remain adenomas for a long time, others progress to carcinomas. However, long-term outcomes of such cases are not entirely clear. Here, we explored the risk factors and incidence of developing carcinoma from gastric adenoma as well as metachronous gastric cancer. METHODS: This study was conducted at a facility that adopted a follow-up strategy for gastric adenoma. Lesions histologically diagnosed as gastric intestinal-type adenomas between January 2004 and December 2016 were analyzed. Clinicopathological data were collected from patients' medical records, and histological changes from adenoma to carcinoma during endoscopic follow-up and risk factors of cancer development were evaluated. RESULTS: This study involved 409 lesions from 376 patients. The analysis of the development of gastric cancer from adenoma and metachronous gastric cancer was ultimately performed for 282 lesions from 258 patients and 269 lesions from 246 patients, respectively, due to different follow-up periods. The 5-year rate of carcinoma development was 34.0%. Risk factors for carcinoma development upon multivariate analysis were lesion size ≥15 mm and morphological depression. All cases with both factors developed gastric carcinoma, and 50.5% of those with either factor developed carcinoma within 5 years. Gastric adenoma was accompanied by metachronous gastric cancer in 1.5% of the patients annually. The only risk factor for metachronous gastric carcinoma was primary adenoma progressing to carcinoma during the follow-up period. DISCUSSION/CONCLUSION: Given the high rate of carcinoma development in patients with risk factors, resection of gastric adenoma should be considered during the initial examination. Careful observation and follow-up should also be conducted to detect not only changes in the primary adenoma but also the occurrence of metachronous carcinoma, especially in cases of adenoma progressing to carcinoma.

Overexpression of MaTPD1A impairs fruit and pollen development by modulating some regulators in Musa itinerans.

BACKGROUND: Pollen formation and development is important for crop fertility and is a key factor for hybrid development. Previous reports have indicated that Arabidopsis thaliana TAPETUM DETERMINANT1 (AtTPD1) and its rice (Oryza sativa) homolog, OsTPD1-like (OsTDL1A), are required for cell specialization and greatly affect pollen formation and development. Little is known about the role of the TPD1 homolog in banana pollen development. RESULTS: Here, we report the identification and characterization of TPD1 homologs in diploid banana (Musa itinerans) and examine their role in pollen development by overexpressing the closest homolog, MaTPD1A. MaTPD1A exhibits high expression in stamen and localizes in the plasma membrane. MaTPD1A-overexpressing plants produce no pollen grains and smaller and seedless fruit compared to wild-type plants. Transcriptome analysis showed that in plant hormone, starch and sucrose metabolism, and linolenic acid metabolism-related pathways were affected by overexpression of MaTPD1A, and the expression of several key regulators, such as PTC1 and MYB80, which are known to affect anther development, is affected in MaTPD1A-overexpressing lines. CONCLUSIONS: Our results indicate that MaTPD1A plays an important role in pollen formation and fruit development in diploid banana, possibly by affecting the expression of some key regulators of pollen development.

Late Adiposity Rebound and the Probability of Developing and Reversing Childhood Obesity.

OBJECTIVE: To evaluate the associations between late adiposity rebound (at or after 7.0 years of age) and the probability of developing and reversing obesity during elementary school years. STUDY DESIGN: Using nationally representative cohorts from Early Childhood Longitudinal Studies, Kindergarten Class of 1998-1999 and 2010-2011, weighted extended Cox hazard models were used to assess the probability of developing and reversing obesity (cut-offs for extended models were 6 and 12 months after kindergarten entry, respectively). Measurements used in the study were collected 6 times between kindergarten and fifth grade (Early Childhood Longitudinal Studies, Kindergarten Class of 1998-1999) and 8 times between kindergarten through fourth grade (Early Childhood Longitudinal Studies, Kindergarten Class of 2010-2011). RESULTS: Among children with obesity at kindergarten entry, within 6 months, the risk of developing obesity was 73% and 76% lower for boys with late adiposity rebound than their classmates without late adiposity rebound (hazard ratio 0.27 and 0.24). Six months after entering kindergarten, similar association was observed for both boys and girls. Among children without obesity at kindergarten entry, within 12 months, the probability of reversing obesity was 52% and 54% higher for boys with late adiposity rebound than their peers without late adiposity rebound (hazard ratio 1.52 and 1.54). Twelve months after entering kindergarten, the probability of reversing obesity among both sexes with late adiposity rebound was 6-8 times that among children without late adiposity rebound. CONCLUSIONS: Late adiposity rebound was significantly associated with a decreased risk of developing obesity and an increased probability of reversing obesity among kindergarteners.

Needs assessment for a curriculum for difficult conversations -a survey from 5 Chinese accredited neurology residency training programs.

BACKGROUND: Communication skill is a core competency in neurology residency training. Specific training in this area at the residency level is often lacking, especially regarding difficult conversations. The aim of this study is to evaluate the current state in teaching residents about difficult conversations in 5 Chinese accredited neurology residency training programs and determine whether there is a perceived need for a formalized curriculum in this field. METHODS: An anonymous, 27-question, cross-sectional online survey addressing difficult conversations for neurological residents were distributed to five grade-A, class-3 hospitals selected from the affiliated teaching hospitals of medical schools qualified to provide neurology residency training in China. RESULTS: A total of 182 residents responded to the survey, and the response rate was 67.16% (182/271). Of the participants, 84.6% were female and the average age was 26.8 years. The majority of respondent residents (n = 168; 92.31%) reported being exposed to at least one difficult conversation in their medical careers. Only 43 (23.63%) participants reported having previously received formal communication skills training. In comparison with residents without previous training, those with previous training indicated significantly more confidence (P = 0.003) and were under lower pressure (P = 0.037) in managing difficult conversations. Only 97 (53.3%) residents indicated interest in receiving formal training. Time, lack of enthusiasm, lack of educational materials and faculty expertise were commonly cited barriers to formalized training. CONCLUSION: This survey provides a preliminary assessment of the current status of education on the topic of difficult conversations in five accredited Chinese neurology residency training programs. Our results suggest that there is an unmet need to further develop and implement educational activities by teaching residents to lead difficult conversations. Future efforts should be made to establish and promote a standard and targeted communication curriculum in difficult conversation for Chinese neurological residents.

Transcriptomic insights into citrus segment membrane's cell wall components relating to fruit sensory texture.

BACKGROUND: During fresh fruit consumption, sensory texture is one factor that affects the organoleptic qualities. Chemical components of plant cell walls, including pectin, cellulose, hemicellulose and lignin, play central roles in determining the textural qualities. To explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture, we performed mRNA-seq analyses of the segment membranes of two citrus cultivars, Shiranui and Kiyomi, with different organoleptic textures. RESULTS: Segment membranes were sampled at two developmental stages of citrus fruit, the beginning and end of the expansion period. More than 3000 differentially expressed genes were identified. The gene ontology analysis revealed that more categories were significantly enriched in 'Shiranui' than in 'Kiyomi' at both developmental stages. In total, 108 significantly enriched pathways were obtained, with most belonging to metabolism. A detailed transcriptomic analysis revealed potential critical genes involved in the metabolism of cell wall structures, for example, GAUT4 in pectin synthesis, CESA1, 3 and 6, and SUS4 in cellulose synthesis, CSLC5, XXT1 and XXT2 in hemicellulose synthesis, and CSE in lignin synthesis. Low levels, or no expression, of genes involved in cellulose and hemicellulose, such as CESA4, CESA7, CESA8, IRX9 and IRX14, confirmed that secondary cell walls were negligible or absent in citrus segment membranes. A chemical component analysis of the segment membranes from mature fruit revealed that the pectin, cellulose and lignin contents, and the segment membrane's weight (% of segment) were greater in 'Kiyomi'. CONCLUSION: Organoleptic quality of citrus is easily overlooked. It is mainly determined by sensory texture perceived in citrus segment membrane properties. We performed mRNA-seq analyses of citrus segment membranes to explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture. Transcriptomic data showed high repeatability between two independent biological replicates. The expression levels of genes involved in cell wall structure metabolism, including pectin, cellulose, hemicellulose and lignin, were investigated. Meanwhile, chemical component contents of the segment membranes from mature fruit were analyzed. This study provided detailed transcriptional regulatory profiles of different organoleptic citrus qualities and integrated insights into the mechanisms affecting citrus' sensory texture.

Infliximab Is Not Associated With Increased Risk of Malignancy or Hemophagocytic Lymphohistiocytosis in Pediatric Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Immunosuppressive therapy for inflammatory bowel disease (IBD) in pediatric patients is thought to increase the risk of malignancy and lymphoproliferative disorders, including hemophagocytic lymphohistiocytosis (HLH). We compared unadjusted incidence rates of malignancy and HLH in pediatric patients with IBD exposed to infliximab (IFX) with patients not exposed to biologics and calculated standardized incidence ratios (SIRs). METHODS: We collected and analyzed data from 5766 participants in a prospective study of long-term outcomes of pediatric patients with IBD (NCT00606346), from May 31, 2007 through June 30, 2016. Patients were 17 years old or younger and had Crohn's disease, ulcerative colitis, or IBD-unclassified with 24,543.0 patient-years of follow-up. We estimated incidence rates for malignancy and HLH as events/1000 patient-years of follow-up. We calculated age-, sex-, and race-adjusted SIRs, with 95% confidence intervals (CIs), using the Surveillance, Epidemiology, and End Results Program (SEER) database. RESULTS: Thirteen of the 15 patients who developed a malignancy and all 5 of the patients who developed HLH had been exposed to thiopurines; 10 patients with malignancy had also been exposed to a biologic agent. Unadjusted incidence rates showed no increased risk of malignancy (0.46/1000 patient-years) or HLH (0.0/1000 patient-years) in patients exposed to IFX as the only biologic vs those unexposed to biologics (malignancy: 1.12/1000 patient-years; HLH: 0.56/1000 patient-years). SIRs did not demonstrate an increased risk of malignancy among patients exposed to IFX (SIR, 1.69; 95% CI, 0.46-4.32) vs patients not exposed to a biologic agent (SIR, 2.17; 95% CI, 0.59-5.56), even when patients were stratified by thiopurine exposure. CONCLUSIONS: In determination of age-, sex-, and race-adjusted SIRs using data from a large clinical study and the SEER database, we found that IFX exposure did not associate with increased risk of malignancy or HLH in pediatric patients with IBD. Thiopurine exposure is an important precedent event for the development of malignancy or HLH in pediatric patients with IBD.

Yield enhancement strategies of rare pharmaceutical metabolites from endophytes.

Endophytes are barely untapped as vital sources in the medicine. They are microorganisms which mostly exist in plants. As they are exploited, it is accepted that endophytes can produce active metabolites that possess same function as their hosts such as taxol, podophyllotoxin, hypericin, and azadirachtin. These metabolites have been promising potential usefulness in safety and human health concerns. We are supposed to adopt measures to raise production for the low yield of metabolites. This paper summarizes the latest advances in various bioprocess optimization strategies. These techniques can overcome the limitations associated with rare pharmaceutical metabolite-producing endophytic fungi. These strategies include strain improvement, genome shuffling, medium optimization, fermentation conditions optimization, addition of specific factor, addition of solid sorbent, and co-culturing. It will enable endophytes to produce high and sustainable production of rare pharmaceutical metabolites.

Developing an OBL: Key Considerations Before Spending a Dime Or Too Much Time.

The office-based laboratory (OBL) industry has proliferated over the past decade as surgical cases have increasingly migrated from inpatient to outpatient surgical settings, including OBLs, ambulatory surgery centers and infusion centers. Although many physicians and patients prefer to provide and receive care in an OBL setting because it provides a high quality, lower cost and convenient alternative to receiving care in a hospital, the OBL industry is nonetheless under attack on a variety of fronts. Governmental and commercial payor reimbursement for OBL procedures has declined substantially over time, and there have been lawsuits, governmental investigations and news articles that have been critical of care provided in OBLs. These issues have generated headwinds for this young but growing industry. It is therefore important for physicians and investors alike interested in developing an OBL to be aware of the complex landscape of laws and regulations that apply to OBLs. This article provides an overview of key legal, corporate, tax, financial and structural considerations for operators to be aware of before opening an OBL.

[Forty-three Years of Dedicated Efforts in Advancing Pharmacist Expertise: Aspiring to Become a Pharmacist and Cultivate Pharmacists Proficient in Recommending Prescription Medicines to Doctors].

When I graduated from university, my aim was to become a pharmacist capable of recommending prescription medicines to doctors and teaching others to do the same. To achieve this goal, I developed comprehensive curricula incorporating progressive educational tools such as problem-based learning and small group discussions. Subsequently, the effectiveness of these tools and curricula was evaluated, and the findings of these assessments were published in various peer-reviewed journal articles. Consequently, a body of evidence on the most effective ways to recommend prescription medicines to doctors was gradually established. This paper aims to summarize this comprehensive body of research spanning over 43 years, with the objective of highlighting the valuable insights gained thus far, identifying the best practice techniques, and exploring potential avenues for future research.

Cross-Modal Sensory Boosting to Improve High-Frequency Hearing Loss: Device Development and Validation.

Background: High-frequency hearing loss is one of the most common problems in the aging population and with those who have a history of exposure to loud noises. This type of hearing loss can be frustrating and disabling, making it difficult to understand speech communication and interact effectively with the world. Objective: This study aimed to examine the impact of spatially unique haptic vibrations representing high-frequency phonemes on the self-perceived ability to understand conversations in everyday situations. Methods: To address high-frequency hearing loss, a multi-motor wristband was developed that uses machine learning to listen for specific high-frequency phonemes. The wristband vibrates in spatially unique locations to represent which phoneme was present in real time. A total of 16 participants with high-frequency hearing loss were recruited and asked to wear the wristband for 6 weeks. The degree of disability associated with hearing loss was measured weekly using the Abbreviated Profile of Hearing Aid Benefit (APHAB). Results: By the end of the 6-week study, the average APHAB benefit score across all participants reached 12.39 points, from a baseline of 40.32 to a final score of 27.93 (SD 13.11; N=16; P=.002, 2-tailed dependent t test). Those without hearing aids showed a 10.78-point larger improvement in average APHAB benefit score at 6 weeks than those with hearing aids (t14=2.14; P=.10, 2-tailed independent t test). The average benefit score across all participants for ease of communication was 15.44 (SD 13.88; N=16; P<.001, 2-tailed dependent t test). The average benefit score across all participants for background noise was 10.88 (SD 17.54; N=16; P=.03, 2-tailed dependent t test). The average benefit score across all participants for reverberation was 10.84 (SD 16.95; N=16; P=.02, 2-tailed dependent t test). Conclusions: These findings show that vibrotactile sensory substitution delivered by a wristband that produces spatially distinguishable vibrations in correspondence with high-frequency phonemes helps individuals with high-frequency hearing loss improve their perceived understanding of verbal communication. Vibrotactile feedback provides benefits whether or not a person wears hearing aids, albeit in slightly different ways. Finally, individuals with the greatest perceived difficulty understanding speech experienced the greatest amount of perceived benefit from vibrotactile feedback.

Development of a Real-Time Dashboard for Overdose Touchpoints: User-Centered Design Approach.

BACKGROUND: Overdose Fatality Review (OFR) is an important public health tool for shaping overdose prevention strategies in communities. However, OFR teams review only a few cases at a time, which typically represent a small fraction of the total fatalities in their jurisdiction. Such limited review could result in a partial understanding of local overdose patterns, leading to policy recommendations that do not fully address the broader community needs. OBJECTIVE: This study explored the potential to enhance conventional OFRs with a data dashboard, incorporating visualizations of touchpoints-events that precede overdoses-to highlight prevention opportunities. METHODS: We conducted 2 focus groups and a survey of OFR experts to characterize their information needs and design a real-time dashboard that tracks and measures decedents' past interactions with services in Indiana. Experts (N=27) were engaged, yielding insights on essential data features to incorporate and providing feedback to guide the development of visualizations. RESULTS: The findings highlighted the importance of showing decedents' interactions with health services (emergency medical services) and the justice system (incarcerations). Emphasis was also placed on maintaining decedent anonymity, particularly in small communities, and the need for training OFR members in data interpretation. The developed dashboard summarizes key touchpoint metrics, including prevalence, interaction frequency, and time intervals between touchpoints and overdoses, with data viewable at the county and state levels. In an initial evaluation, the dashboard was well received for its comprehensive data coverage and its potential for enhancing OFR recommendations and case selection. CONCLUSIONS: The Indiana touchpoints dashboard is the first to display real-time visualizations that link administrative and overdose mortality data across the state. This resource equips local health officials and OFRs with timely, quantitative, and spatiotemporal insights into overdose risk factors in their communities, facilitating data-driven interventions and policy changes. However, fully integrating the dashboard into OFR practices will likely require training teams in data interpretation and decision-making.