Distinct Clinical Physiologic Phenotypes of Patients With Laryngeal Symptoms Referred for Reflux Evaluation.

BACKGROUND & AIMS: Heterogeneous presentations and disease mechanisms among patients with laryngeal symptoms account for misdiagnosis of laryngopharyngeal reflux (LPR), variations in testing, and suboptimal outcomes. We aimed to derive phenotypes of patients with laryngeal symptoms based on clinical and physiologic data and to compare characteristics across phenotypes. METHODS: A total of 302 adult patients with chronic laryngeal symptoms were prospectively enrolled at 3 centers between January 2018 to October 2020 (age 57.2 ± 15.2 years; 30% male; body mass index 27.2 ± 6.0 kg/m2). Discriminant analysis of principal components (DAPC) was applied to 12 clinical and 11 physiologic variables collected in stable condition to derive phenotypic groups. RESULTS: DAPC identified 5 groups, with significant differences across symptoms, hiatal hernia size, and number of reflux events (P < .01). Group A had the greatest hiatal hernia size (3.1 ± 1.0 cm; P < .001) and reflux events (37.5 ± 51; P < .001), with frequent cough, laryngeal symptoms, heartburn, and regurgitation. Group B had the highest body mass index (28.2 ± 4.6 kg/m2; P < .001) and salivary pepsin (150 ± 157 ng/mL; P = .03), with frequent cough, laryngeal symptoms, globus, heartburn, and regurgitation. Group C frequently reported laryngeal symptoms (93%; P < .001), and had fewest esophageal symptoms (9.6%; P < .001) and reflux events (10.7 ± 11.0; P < .001). Group D commonly reported cough (88%; P < .001) and heartburn. Group E (18%) was oldest (62.9 ± 14.3 years; P < .001) and distinguished by highest integrated relaxation pressure. CONCLUSIONS: DAPC identified distinct clinicophysiologic phenotypes of patients with laryngeal symptoms referred for reflux evaluation: group A, LPR and gastroesophageal reflux disease (GERD) with hiatal hernia; group B, mild LPR/GERD; group C, no LPR/No GERD; group D, reflex cough; and group E, mixed/possible obstructive esophagogastric junction. Phenotypic differences may inform targeted clinical trials design and improve outcomes.

Physical and Mental Health Characteristics of 2,962 Adults With Subjective Cognitive Complaints.

We investigated subjective cognitive complaints (SCCs), as well as physical and mental health factors, in adults and older adults. U.S. residents (N = 2,962) were recruited via the Amazon Mechanical Turk platform and completed a 90-item survey. Overall, 493/1930 (25.5%) of younger adults and 278/1032 (26.9%) of older adults endorsed SCCs. Analyses revealed worse physical and mental health characteristics in the SCC+ compared to the SCC- group, with primarily medium (Cohen's d = 0.50) to large (0.80) effect sizes. Age did not moderate relationships between SCCs and physical/mental health. Results suggest that SCCs are associated with a diverse set of negative health characteristics such as poor sleep and high body mass index, and lower levels of positive factors, including happiness and wisdom. Effect sizes of psychological correlates were at least as large as those of physical correlates, indicating that mental health is critical to consider when evaluating SCCs.

Role of autophagy-related protein in the prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgical resection.

BACKGROUND: Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). METHODS: We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. RESULTS: We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7 and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68-26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01-0.34), p = 0.004, and 0.07 (0.01-0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85-922), p = 0.008, and 17.9 (1.05-306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2 and 74.6% in high LC3 expression patients and 0 and 0% in those with low LC3 expression. CONCLUSION: High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

Surgical resection significantly promotes the overall survival of patients with hepatocellular carcinoma: a propensity score matching analysis.

BACKGROUND: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages. METHODS: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. RESULTS: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were (1) SR and cirrhosis; (2) SR, cirrhosis, and Child-Pugh (C-P) class; (3) SR, hepatitis B virus (HBV) infection, and C-P class; and (4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs. non-SR were 44.0% versus 28.7%, 72.2% versus 42.6%, 42.6% versus 36.2, 44.6% versus 23.5%, and 41.4% versus 15.3% (all P values < 0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages. CONCLUSIONS: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.

Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: a propensity score matching analysis.

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. METHODS: We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan-Meier analysis. RESULTS: In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7-61.2], 62.3 months (CI: 42.1-72.9), and 36.2 months (CI: 15.4-56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. CONCLUSION: The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

Long-term Outcomes of Primary Endoscopic Resection vs Surgery for T1 Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: There is controversy over the best therapeutic approach for T1 colorectal cancer. We performed a systematic review and meta-analysis of long-term outcomes of endoscopic resection (ER) vs those of primary or additional surgery. METHODS: We performed a systematic review of the PubMed, Embase, and Cochrane databases through October 2019 for studies that reported outcomes (overall survival, disease-specific survival, recurrence-free survival at 5 years, recurrence, and metastasis) of ER vs surgery in patients with colorectal neoplasms. Hazard ratios (HR) were calculated based on time to events. RESULTS: In total, 17 published studies with 19,979 patients were included. The median follow-up time among the studies was 36 months. The meta-analysis found no significant differences between primary ER and primary surgery in overall survival (79.6% vs 82.1%, HR, 1.10; 95% CI, 0.84-1.45), recurrence-free survival (96.0% vs 96.7%, HR, 1.28; 95% CI, 0.87-1.88), or disease-specific survival (94.8% vs 96.5%; HR, 1.09; 95% CI, 0.67-1.78). Additional surgery and primary surgery did not produce significant differences in recurrence-free survival (HR, 1.27; 95% CI, 0.85-1.89). A significantly lower proportion of patients who underwent primary ER had procedure-related adverse events (2.3%) than patients who underwent primary surgery (10.9%) (P < .001). Lymphovascular invasion and rectal cancer, but not depth of submucosal invasion, were independently associated with recurrence for all T1 colorectal cancers. CONCLUSIONS: In a systematic review and meta-analysis, we found that ER should be considered as the first-line treatment for endoscopically resectable T1 colorectal cancers. In cases of noncurative resection, additional surgery can have comparable outcomes to primary surgery.

Comparison of overall survival on surgical resection versus transarterial chemoembolization with or without radiofrequency ablation in intermediate stage hepatocellular carcinoma: a propensity score matching analysis.

BACKGROUND: Patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) are recommended to undergo transcatheter arterial chemoembolization (TACE). However, TACE in combination with radiofrequency ablation (RFA) is not inferior to surgical resection (SR), and the benefits of surgical resection (SR) for BCLC stage B HCC remain unclear. Hence, this study aims to compare the impact of SR, TACE+RFA, and TACE on analyzing overall survival (OS) in BCLC stage B HCC. METHODS: Overall, 428 HCC patients were included in BCLC stage B, and their clinical data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. RESULTS: One hundred forty (32.7%) patients received SR, 57 (13.3%) received TACE+RFA, and 231 (53.9%) received TACE. The OS was significantly higher in the SR group than that in the TACE+RFA group [hazard ratio (HR): 1.78; 95% confidence incidence (CI): 1.15-2.75, p = 0.009]. The OS was significantly higher in the SR group than that in the TACE group (HR: 3.17; 95% CI: 2.31-4.36, p < 0.0001). Moreover, the OS was significantly higher in the TACE+RFA group than that in the TACE group (HR: 1.82; 95% CI: 1.21-2.74, p = 0.004). The cumulative OS rates at 1, 3 and 5 years in the SR, TACE+RFA, and TACE groups were 89.2, 69.4 and 61.2%, 86.0, 57.9 and 38.2%, and 69.5, 37.0 and 15.2%, respectively. After propensity score matching, the SR group still had a higher OS than those of the TACE+RFA and TACE groups. The TACE+RFA group had a higher OS than that of the TACE group. CONCLUSION: The SR group had higher OS than the TACE+RFA and TACE groups in BCLC stage B HCC. Furthermore, the TACE+RFA group had higher OS than the TACE group.

A pragmatic trial of a group intervention in senior housing communities to increase resilience.

BACKGROUND: Aging is associated with numerous stressors that negatively impact older adults' well-being. Resilience improves ability to cope with stressors and can be enhanced in older adults. Senior housing communities are promising settings to deliver positive psychiatry interventions due to rising resident populations and potential impact of delivering interventions directly in the community. However, few intervention studies have been conducted in these communities. We present a pragmatic stepped-wedge trial of a novel psychological group intervention intended to improve resilience among older adults in senior housing communities. DESIGN: A pragmatic modified stepped-wedge trial design. SETTING: Five senior housing communities in three states in the US. PARTICIPANTS: Eighty-nine adults over age 60 years residing in independent living sector of senior housing communities. INTERVENTION: Raise Your Resilience, a manualized 1-month group intervention that incorporated savoring, gratitude, and engagement in value-based activities, administered by unlicensed residential staff trained by researchers. There was a 1-month control period and a 3-month post-intervention follow-up. MEASUREMENTS: Validated self-report measures of resilience, perceived stress, well-being, and wisdom collected at months 0 (baseline), 1 (pre-intervention), 2 (post-intervention), and 5 (follow-up). RESULTS: Treatment adherence and satisfaction were high. Compared to the control period, perceived stress and wisdom improved from pre-intervention to post-intervention, while resilience improved from pre-intervention to follow-up. Effect sizes were small in this sample, which had relatively high baseline resilience. Physical and mental well-being did not improve significantly, and no significant moderators of change in resilience were identified. CONCLUSION: This study demonstrates feasibility of conducting pragmatic intervention trials in senior housing communities. The intervention resulted in significant improvement in several measures despite ceiling effects. The study included several features that suggest high potential for its implementation and dissemination across similar communities nationally. Future studies are warranted, particularly in samples with lower baseline resilience or in assisted living facilities.

The impact of person-centred care on job productivity, job satisfaction and organisational commitment among employees in long-term care facilities.

AIM AND OBJECTIVES: This study aimed to explore the effects of person-centred care on their job productivity, job satisfaction and organisational commitment among employees in long-term care facilities. BACKGROUND: Person-centred care has been regarded as the best caregiving model for long-term care facilities. Few studies tested the impact of person-centred care on employee performance. DESIGN: A cross-sectional study was employed. METHODS: This study sent 373 samples with self-report questionnaires to the employees of sixteen long-term care facilities in Taiwan. A total of 366 valid samples were collected. A 33-item person-centred care questionnaire with Likert-scale responses was developed to assess the extent of person-centred care. We adopted hierarchical multiple regression analysis to test the impact of person-centred care on employee performance. We adopted the STROBE guidelines. RESULTS: Friendly environment level and personalised care, respectively, scored the highest with a mean of 4.19 among five dimensions of person-centred care. Personalised care, residents' self-realisation and relationships, and organisational support had significant positive correlations with job productivity. Friendly environment level and organisational support had significant correlations with job satisfaction. Friendly environment level, residents' self-realisation and relationships, and organisational support had significant correlations with organisational commitment. CONCLUSION: Person-centred care has beneficial impact on job satisfaction, job productivity and organisational commitment of employees in long-term care facilities. RELEVANCE TO CLINICAL PRACTICE: Person-centred care appears to be a crucial factor of employee performance in long-term care facilities. The five-dimensional person-centred care questionnaire in this study can serve as an important management tool for improving the effectiveness of person-centred care.

Developing and testing the patient-centred innovation questionnaire for hospital nurses.

AIMS: Develop the patient-centred innovation questionnaire for hospital nurses and establish its validity and reliability. BACKGROUND: Patient-centred care has been adopted by health care managers in their efforts to improve health care quality. It is regarded as a core concept for developing innovation. METHODS: A cross-sectional study was employed to collect data from hospital nurses in Taiwan. This study was divided into two stages: pilot study and main study. In the main study, 596 valid responses were collected. This study adopted reliability analysis, exploratory factor analysis, confirmatory factor analysis and selected nurse innovation scale as a criterion to test criterion-related validity. RESULTS: Five-dimension patient-centred innovation questionnaire was proposed: access and practicability, co-ordination and communication, sharing power and responsibility, care continuity, family and person focus. Each dimension demonstrated a reliability of 0.89-0.98. All dimensions had acceptable convergent and discriminate validity. The patient-centred innovation questionnaire and nurse innovation scale exhibited a significantly positive correlation. CONCLUSIONS: Patient-centred innovation questionnaire not only had a good theoretical basis but also had sufficient reliability and construct validity, and criterion-related validity. IMPLICATIONS FOR NURSING MANAGEMENT: Patient-centred innovation questionnaire could give a measure for evaluating the implementation of patient-centred care and could be used as a management tool during the process of nurse innovation.

Executive functioning trajectories and their prospective association with inflammatory biomarkers in schizophrenia and non-psychiatric comparison participants.

BACKGROUND AND HYPOTHESIS: Cognitive change in people with schizophrenia (PwS) is challenging to assess, but important to understand. Previous studies with limited age ranges and follow-up were subject to practice effects. Controlling for practice effects in a well-established cohort, we examined executive functioning trajectories and their association with inflammatory biomarkers, hypothesizing that PwS will have worsening executive functioning over time compared to non-psychiatric comparison participants (NCs), predicted by higher baseline inflammation with a stronger relationship in PwS than NCs. STUDY DESIGN: Executive functioning was assessed in 350 participants (n = 186 PwS, 164 NCs) at 12-16-month intervals (0 to 7 follow-up visits). Inflammatory biomarkers at baseline included high sensitivity C-Reactive Protein (hs-CRP), Interferon-gamma, Tumor Necrosis Factor (TNF)-alpha, and Interleukin(IL)-6, -8, and - 10. Executive functioning trajectories across diagnostic groups were estimated using a linear mixed-effects model controlling for age, sex, race/ethnicity, and education level, with additional models to assess prediction by baseline inflammation. STUDY RESULTS: Over 4.4 years average follow-up, improvements in executive functioning were attenuated in PwS and older participants. Controlling for practice effects negated improvements, revealing declines among highly educated participants regardless of diagnosis. Higher baseline hs-CRP predicted worse executive functioning only among NCs, while TNF-alpha was predictive of change in all participants only after controlling for practice effects. Only the main effect of hs-CRP on executive function was significant after adjusting for multiple comparisons. None of the other inflammatory biomarkers predicted executive functioning or trajectories of performance among study participants. CONCLUSIONS: Systemic inflammation as reflected by baseline inflammatory biomarker levels did not predict longitudinal declines in executive functioning. Additional studies examining the temporal dynamics of inflammation and cognition in PwS will help further clarify their relationship and associated mechanisms.

Longitudinal relationships between BMI and hs-CRP among people with schizophrenia.

In people with schizophrenia (PwS), inflammation and metabolic issues significantly increase morbidity and mortality. However, our ability to understand inflammatory-metabolic mechanisms in this population has been limited to cross-sectional studies. This study involved 169 PwS and 156 non-psychiatric comparisons (NCs), aged 25-65, observed between 2012 and 2022 with 0 to 5 follow-ups post-baseline. High-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, was measured via a particle-enhanced immuno-turbidimetric assay. Body mass index (BMI) was used as a proxy for metabolic function. The measurement intervals for hs-CRP and BMI ranged between 6 and 48 months. Linear mixed models (LMM) results revealed that at all time points, PwS has a higher hs-CRP (t (316) = 4.73, p < .001) and BMI (t (315) = 4.13, p < .001) than NCs; however, for BMI, this difference decreased over time (t (524) = -5.15, p < .001). To study interrelationships between hs-CRP and BMI, continuous time structural equational modeling (CTSEM) was used, accounting for uneven measurement intervals. CTSEM results showed that both hs-CRP predicted future BMI (Est. = 12.91, 95 % CI [7.70; 17.88]) and BMI predicted future hs-CRP (Est. = 1.54, 95 % CI [1.00; 2.04]), indicating a bidirectional relationship between inflammation and metabolic function. Notably, the influence of hs-CRP on future BMI was more robust than the other lagged relationship (p = .015), especially in PwS (Est. = 2.43, 95 % CI [0.39; 0.97]). Our study highlights the important role of inflammation in metabolic function and offers insights into potential interventions targeting inflammation in PwS.

A New Paradigm for High-dimensional Data: Distance-Based Semiparametric Feature Aggregation Framework via Between-Subject Attributes.

This article proposes a distance-based framework incentivized by the paradigm shift towards feature aggregation for high-dimensional data, which does not rely on the sparse-feature assumption or the permutation-based inference. Focusing on distance-based outcomes that preserve information without truncating any features, a class of semiparametric regression has been developed, which encapsulates multiple sources of high-dimensional variables using pairwise outcomes of between-subject attributes. Further, we propose a strategy to address the interlocking correlations among pairs via the U-statistics-based estimating equations (UGEE), which correspond to their unique efficient influence function (EIF). Hence, the resulting semiparametric estimators are robust to distributional misspecification while enjoying root-n consistency and asymptotic optimality to facilitate inference. In essence, the proposed approach not only circumvents information loss due to feature selection but also improves the model's interpretability and computational feasibility. Simulation studies and applications to the human microbiome and wearables data are provided, where the feature dimensions are tens of thousands.

Deciphering the 'gut-brain axis' through microbiome diversity.

Incentivised by breakthroughs and data generated by the high-throughput sequencing technology, this paper proposes a distance-based framework to fulfil the emerging needs in elucidating insights from the high-dimensional microbiome data in psychiatric studies. By shifting focus from traditional methods that focus on the observations from each subject to the between-subject attributes that aggregate two or more subjects' entire feature vectors, the described approach revolutionises the conventional prescription for high-dimensional observations via microbiome diversity. To this end, we enrich the classical generalised linear models to articulate the multivariable regression relationship between distance-based variables. We also discuss a robust and computationally feasible semiparametric inference technique. Benefitting from the latest advances in the semiparametric efficiency theory for such attributes, the proposed estimators enjoy robustness and good asymptotic properties that guarantee sensitivity in detecting signals between clinical outcomes and microbiome diversity. It offers a readily implementable and easily interpretable solution for deciphering the gut-brain axis in mental health research.

Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice.

The gastrointestinal microbiome plays a significant role in modulating numerous host processes, including metabolism. Prior studies show that when mice receive fecal transplants from obese donors on high-fat diets (HFD) (even when recipient mice are fed normal diets after transplantation), they develop obese phenotypes, demonstrating the prominent role that gut microbiota play in determining lean and obese phenotypes. While much of the credit has been given to gut bacteria, the impact of gut viruses on these phenotypes is understudied. To address this shortcoming, we gavaged mice with viromes isolated from donors fed HFD or normal chow over a 4-week study. By characterizing the gut bacterial biota via 16S rRNA amplicon sequencing and measuring mouse weights over time, we demonstrate that transplanted viruses affect the gut bacterial community, as well as weight gain/loss. Notably, mice fed chow but gavaged with HFD-derived viromes gained more weight than their counterparts receiving chow-derived viromes. The converse was also true: mice fed HFD but gavaged with chow-derived viromes gained less weight than their counterparts receiving HFD-derived viromes. Results were replicated in two independent experiments and phenotypic changes were accompanied by significant and identifiable differences in the fecal bacterial biota. Due to methodological limitations, we were unable to identify the specific bacterial strains responsible for respective phenotypic changes. This study confirms that virome-mediated perturbations can alter the fecal microbiome in vivo and indicates that such perturbations are sufficient to drive lean and obese phenotypes in mice.

Fecal virome transplantation is sufficient to alter fecal microbiota and drive lean and obese body phenotypes in mice.

Background: The gastrointestinal microbiome plays a significant role in numerous host processes and has an especially large impact on modulating the host metabolism. Prior studies have shown that when mice receive fecal transplants from obese donors that were fed high-fat diets (HFD) (even when recipient mice are fed normal diets after transplantation), they develop obese phenotypes. These studies demonstrate the prominent role that the gut microbiota play in determining lean and obese phenotypes. While much of the credit has been given to gut bacteria, studies have not measured the impact of gut viruses on these phenotypes. To address this shortcoming, we gavaged mice with viromes isolated from donors fed HFD or normal chow. By characterizing the mice’s gut bacterial biota and weight-gain phenotypes over time, we demonstrate that viruses can shape the gut bacterial community and affect weight gain or loss. Results: We gavaged mice longitudinally over 4 weeks while measuring their body weights and collecting fecal samples for 16S rRNA amplicon sequencing. We evaluated mice that were fed normal chow or high-fat diets, and gavaged each group with either chow-derived fecal viromes, HFD-derived fecal viromes, or phosphate buffered saline controls. We found a significant effect of gavage type, where mice fed chow but gavaged with HFD-derived viromes gained significantly more weight than their counterparts receiving chow-derived viromes. The converse was also true: mice fed HFD but gavaged with chow-derived viromes gained significantly less weight than their counterparts receiving HFD-derived viromes. These results were replicated in two separate experiments and the phenotypic changes were accompanied by significant and identifiable differences in the fecal bacterial biota. Notably, there were differences in Lachnospirales and Clostridia in mice fed chow but gavaged with HFD-derived fecal viromes, and in Peptostreptococcales, Oscillospirales, and Lachnospirales in mice fed HFD but gavaged with chow-derived fecal viromes. Due to methodological limitations, we were unable to identify specific bacterial species or strains that were responsible for respective phenotypic changes. Conclusions: This study confirms that virome-mediated perturbations can alter the fecal microbiome in an in vivo model and indicates that such perturbations are sufficient to drive lean and obese phenotypes in mice.

Associations Between Ambient Air Pollution and Cognitive Abilities from Midlife to Early Old Age: Modification by APOE Genotype.

BACKGROUND: Fine particulate matter (PM2.5) and nitrogen dioxide (NO2) measures of ambient air pollution are associated with accelerated age-related cognitive impairment, and Alzheimer's disease and related dementias (ADRD). OBJECTIVE: We examined associations between air pollution, four cognitive factors, and the moderating role of apolipoprotein E (APOE) genotype in the understudied period of midlife. METHODS: Participants were ∼1,100 men in the Vietnam Era Twin Study of Aging. Baseline cognitive assessments were from 2003 to 2007. Measures included past (1993-1999) and recent (3 years prior to baseline assessment) PM2.5 and NO2 exposure, in-person assessment of episodic memory, executive function, verbal fluency, and processing speed, and APOE genotype. Average baseline age was 56 years with a 12-year follow-up. Analyses adjusted for health and lifestyle covariates. RESULTS: Performance in all cognitive domains declined from age 56 to 68. Higher PM2.5 exposures were associated with worse general verbal fluency. We found significant exposure-by-APOE genotype interactions for specific cognitive domains: PM2.5 with executive function and NO2 with episodic memory. Higher PM2.5 exposure was related to worse executive function in APOE ɛ4 carriers, but not in non-carriers. There were no associations with processing speed. CONCLUSION: These results indicate negative effects of ambient air pollution exposure on fluency alongside intriguing differential modifications of cognitive performance by APOE genotype. APOE ɛ4 carriers appeared more sensitive to environmental differences. The process by which air pollution and its interaction with genetic risk for ADRD affects risk for later life cognitive decline or progression to dementia may begin in midlife.

Partial least squares regression and principal component analysis: similarity and differences between two popular variable reduction approaches.

In many statistical applications, composite variables are constructed to reduce the number of variables and improve the performances of statistical analyses of these variables, especially when some of the variables are highly correlated. Principal component analysis (PCA) and factor analysis (FA) are generally used for such purposes. If the variables are used as explanatory or independent variables in linear regression analysis, partial least squares (PLS) regression is a better alternative. Unlike PCA and FA, PLS creates composite variables by also taking into account the response, or dependent variable, so that they have higher correlations with the response than composites from their PCA and FA counterparts. In this report, we provide an introduction to this useful approach and illustrate it with data from a real study.

Machine Learning Applied to Omics Datasets Predicts Mortality in Patients with Alcoholic Hepatitis.

Alcoholic hepatitis is a major health care burden in the United States due to significant morbidity and mortality. Early identification of patients with alcoholic hepatitis at greatest risk of death is extremely important for proper treatments and interventions to be instituted. In this study, we used gradient boosting, random forest, support vector machine and logistic regression analysis of laboratory parameters, fecal bacterial microbiota, fecal mycobiota, fecal virome, serum metabolome and serum lipidome to predict mortality in patients with alcoholic hepatitis. Gradient boosting achieved the highest AUC of 0.87 for both 30-day mortality prediction using the bacteria and metabolic pathways dataset and 90-day mortality prediction using the fungi dataset, which showed better performance than the currently used model for end-stage liver disease (MELD) score.