bluuebunny/crossref_metadata_2025 huggingface dataset:
Calculus of archimedean Rankin–Selberg integrals with recurrence relations
Authors: Ishii Taku , Miyazaki Tadashi
Published: July 2022

Let

n
n

and

n
′

n’

be positive integers such that

n
−

n
′

∈
{
0
,
1
}

n-n’\in \{0,1\}

. Let

F
F

be either

R

\mathbb {R}

or

C

\mathbb {C}

. Let

K
n

K_n

and

K

n
′

K_{n’}

be maximal compact subgroups of

G
L

(
n
,
F
)

\mathrm {GL}(n,F)

and

G
L

(

n
′

,
F
)

\mathrm {GL}(n’,F)

, respectively. We give the explicit descriptions of archimedean Rankin–Selberg integrals at the minimal

K
n

K_n

- and

K

n
′

K_{n’}

-types for pairs of principal series representations of

G
L

(
n
,
F
)

\mathrm {GL}(n,F)

and

G
L

(

n
′

,
F
)

\mathrm {GL}(n’,F)

, using their recurrence relations. Our results for

F
=

C

F=\mathbb {C}

can be applied to the arithmetic study of critical values of automorphic

L
L

-functions.
Using Machine Learning Techniques and National Tuberculosis Surveillance Data to Predict Excess Growth in Genotyped Tuberculosis Clusters
Authors: Althomsons Sandy P , Winglee Kathryn , Heilig Charles M , Talarico Sarah , Silk Benjamin , Wortham Jonathan , Hill Andrew N , Navin Thomas R
Published: July 2022

The early identification of clusters of persons with tuberculosis (TB) that will grow to become outbreaks creates an opportunity for intervention in preventing future TB cases. We used surveillance data (2009–2018) from the United States, statistically derived definitions of unexpected growth, and machine-learning techniques to predict which clusters of genotype-matched TB cases are most likely to continue accumulating cases above expected growth within a 1-year follow-up period. We developed a model to predict which clusters are likely to grow on a training and testing data set that was generalizable to a validation data set. Our model showed that characteristics of clusters were more important than the social, demographic, and clinical characteristics of the patients in those clusters. For instance, the time between cases before unexpected growth was identified as the most important of our predictors. A faster accumulation of cases increased the probability of excess growth being predicted during the follow-up period. We have demonstrated that combining the characteristics of clusters and cases with machine learning can add to existing tools to help prioritize which clusters may benefit most from public health interventions. For example, consideration of an entire cluster, not only an individual patient, may assist in interrupting ongoing transmission.
AT2 Receptor Stimulation Inhibits Vascular Smooth Muscle Cell Senescence Induced by Angiotensin II and Hyperglycemia
Authors: Bai Hui-Yu , Li Hui , Zhou Xiang , Gu Hai-Bo , Shan Bao-Shuai
Published: July 2022

BACKGROUND

Hyperglycemia has been widely reported to induce vascular senescence. We have previously demonstrated that angiotensin II (Ang II) could promote brain vascular smooth muscle cell (VSMC) senescence, and its type 2 (AT2) receptor deletion could enhance VSMC senescence. Therefore, we examined the possible cross-talk between Ang II and hyperglycemia on VSMC senescence, and the roles of AT2 receptor agonist, compound 21 (C21) on it.

METHODS

Aortic VSMCs were prepared from adult male mice and stimulated with Ang II and/or high glucose (Glu) and/or C21 and/or an autophagy inhibitor, 3-methyladenine (3-MA), and/or an autophagy agonist, rapamycin (RAP) for the indicated times. Cellular senescence, oxidative stress, and protein expressions were evaluated.

RESULTS

Combination treatment with Ang II and Glu synergistically increased the proportion of VSMC senescent area compared with control group and each treatment alone, which was almost completely attenuated by C21 treatment. Moreover, combination treatment induced significant changes in the levels of superoxide anion, the expressions of p21 and pRb, and the ratio of LC3B II/I expression, which were also significantly attenuated by C21 treatment. The proportion of VSMC senescent area and the levels of superoxide anion by combination treatment were increased after 3-MA treatment, and the proportion of senescent area and the expressions of p21 and pRb were decreased after RAP treatment, both of which were further attenuated by C21 treatment.

CONCLUSIONS

Ang II and hyperglycemia synergistically promoted VSMC senescence, at least partly through the participation by autophagy, oxidative stress, and p21-pRb pathway, which could be inhibited by C21.
Lie Detection: A Strategic Analysis of the Verifiability Approach
Authors: Ioannidis Konstantinos , Offerman Theo , Sloof Randolph
Published: July 2022

The Verifiability Approach is a lie detection method based on the insight that truth-tellers provide precise details whereas liars sometimes remain vague to avoid being exposed. We provide a game-theoretic foundation for the strategic effect that underlies this approach. We consider a speaker who wants to be acquitted and an investigator who prefers to find out the truth. The investigator can verify the speaker’s statement at some cost; verification gets more reliable the more details are provided. If, after a falsified statement, the investigator convicts, an additional penalty is imposed. Constructing precise but false statements is assumed to be cognitively costly. We derive all equilibria and thereby the conditions under which the investigator can infer valuable information from the speaker’s statement at face value. If cognitive costs are not prohibitively high, these require that liars are deterred from making false precise statements if always verified. Strategic information revelation by the speaker and verification by the investigator then necessarily work in tandem in a partially pooling equilibrium. Improvements in reliability result in more valuable information via the statements per se, whereas larger lying costs or a harsher penalty do not once the deterrence condition for the existence of this equilibrium is met.
Adaptation and Validation of Addenbrooke’s Cognitive Examination-III in Bengali for Screening MCI and Dementia
Authors: Bhattacharyya Bidisha , Mukherjee Ruchira , Mukherjee Adreesh , Das Gautam , Dogra Atanu Kumar , Das Sujata , Biswas Atanu
Published: July 2022

Objective

Bengali, the 6th most spoken language globally with 268 million speakers, demands a culturally appropriate tool for screening any cognitive compromise in this population. Addenbrooke Cognitive Examination-III (ACE-III) is a standardized tool used for screening and/or diagnostic purpose worldwide. The aim of the present study was to adapt and validate ACE-III into Bengali language.

Methods

The ACE-III UK Version A (2012) was adapted with linguistically and culturally appropriate items and validated on Bengali speakers. The participants consisted of 40 dementia and 22 Mild Cognitive Impairment (MCI) patients and 120 healthy-controls. Reliability and validity were examined. Discriminant function analysis was done. Sensitivity and specificity were evaluated and optimum cut-offs were established for MCI and dementia.

Results

Both sensitivity and specificity of ACE-III-Bengali of identifying dementia was 1; sensitivity for MCI ranged from 0.83 to 1, specificity from 0.76 to 1. Discriminant function analysis showed a significant difference in all domains of ACE-III-Bengali between healthy individuals and persons with neurocognitive impairment. Separate optimum ACE-III-Bengali cut-off scores were established according to level of education. For low education (<Class 10) cut-off was 83 for dementia and 86 for MCI, whereas, for high education (≥Class 10) it was 85 and 88 for dementia and MCI, respectively. The area under curve for distinguishing dementia and MCI ranged from 0.949 to 0.955.

Conclusion

The ACE-III-Bengali is found to have high diagnostic accuracy in identifying dementia and MCI in the Bengali population.
A Validity Measure for the Automated Neuropsychological Assessment Metrics
Authors: Meyers John E , Miller Ronald Mellado , Vincent Andrea S
Published: July 2022

The Automated Neuropsychological Assessment Metrics (ANAM) is one of the most widely used and validated neuropsychological instruments for assessing cognition. The ANAM Test System includes a reporting tool, the ANAM Validity Indicator Report that generates scores for the embedded effort measure, the ANAM Performance Validity Index (APVI). The current study seeks to develop a proxy for the APVI, using raw subtest summary test scores. This would be useful for situations where the APVI score is unavailable (e.g., validity report not generated at the time of the assessment) or when the item level data needed to generate this score are inaccessible. ANAM scores from a large data set of 1,000,000+ observations were used for this retrospective analysis. Results of linear regression analysis suggest that the APVI can be reasonably estimated from the raw subtest summary test scores that are presented on the ANAM Performance Report. Clinically, this means that an important step in the interpretation process, checking the validity of test data, can still be performed even when the APVI is not available.
LmTag: functional-enrichment and imputation-aware tag SNP selection for population-specific genotyping arrays
Authors: Thanh Nguyen Dat , Hoang Nguyen Quan , Thuy Duong Nguyen , Vo Nam S
Published: July 2022

Despite the rapid development of sequencing technology, single-nucleotide polymorphism (SNP) arrays are still the most cost-effective genotyping solutions for large-scale genomic research and applications. Recent years have witnessed the rapid development of numerous genotyping platforms of different sizes and designs, but population-specific platforms are still lacking, especially for those in developing countries. SNP arrays designed for these countries should be cost-effective (small size), yet incorporate key information needed to associate genotypes with traits. A key design principle for most current platforms is to improve genome-wide imputation so that more SNPs not included in the array (imputed SNPs) can be predicted. However, current tag SNP selection methods mostly focus on imputation accuracy and coverage, but not the functional content of the array. It is those functional SNPs that are most likely associated with traits. Here, we propose LmTag, a novel method for tag SNP selection that not only improves imputation performance but also prioritizes highly functional SNP markers. We apply LmTag on a wide range of populations using both public and in-house whole-genome sequencing databases. Our results show that LmTag improved both functional marker prioritization and genome-wide imputation accuracy compared to existing methods. This novel approach could contribute to the next generation genotyping arrays that provide excellent imputation capability as well as facilitate array-based functional genetic studies. Such arrays are particularly suitable for under-represented populations in developing countries or non-model species, where little genomics data are available while investment in genome sequencing or high-density SNP arrays is limited. $\textrm{LmTag}$ is available at: https://github.com/datngu/LmTag.
MorbidGCN: prediction of multimorbidity with a graph convolutional network based on integration of population phenotypes and disease network
Authors: Dong Guiying , Zhang Zi-Chao , Feng Jianfeng , Zhao Xing-Ming
Published: July 2022

Exploring multimorbidity relationships among diseases is of great importance for understanding their shared mechanisms, precise diagnosis and treatment. However, the landscape of multimorbidities is still far from complete due to the complex nature of multimorbidity. Although various types of biological data, such as biomolecules and clinical symptoms, have been used to identify multimorbidities, the population phenotype information (e.g. physical activity and diet) remains less explored for multimorbidity. Here, we present a graph convolutional network (GCN) model, named MorbidGCN, for multimorbidity prediction by integrating population phenotypes and disease network. Specifically, MorbidGCN treats the multimorbidity prediction as a missing link prediction problem in the disease network, where a novel feature selection method is embedded to select important phenotypes. Benchmarking results on two large-scale multimorbidity data sets, i.e. the UK Biobank (UKB) and Human Disease Network (HuDiNe) data sets, demonstrate that MorbidGCN outperforms other competitive methods. With MorbidGCN, 9742 and 14 010 novel multimorbidities are identified in the UKB and HuDiNe data sets, respectively. Moreover, we notice that the selected phenotypes that are generally differentially distributed between multimorbidity patients and single-disease patients can help interpret multimorbidities and show potential for prognosis of multimorbidities.
Doubly robust evaluation of high-dimensional surrogate markers
Authors: Agniel Denis , Hejblum Boris P , Thiébaut Rodolphe , Parast Layla
Published: July 2022

When evaluating the effectiveness of a treatment, policy, or intervention, the desired measure of efficacy may be expensive to collect, not routinely available, or may take a long time to occur. In these cases, it is sometimes possible to identify a surrogate outcome that can more easily, quickly, or cheaply capture the effect of interest. Theory and methods for evaluating the strength of surrogate markers have been well studied in the context of a single surrogate marker measured in the course of a randomized clinical study. However, methods are lacking for quantifying the utility of surrogate markers when the dimension of the surrogate grows. We propose a robust and efficient method for evaluating a set of surrogate markers that may be high-dimensional. Our method does not require treatment to be randomized and may be used in observational studies. Our approach draws on a connection between quantifying the utility of a surrogate marker and the most fundamental tools of causal inference—namely, methods for robust estimation of the average treatment effect. This connection facilitates the use of modern methods for estimating treatment effects, using machine learning to estimate nuisance functions and relaxing the dependence on model specification. We demonstrate that our proposed approach performs well, demonstrate connections between our approach and certain mediation effects, and illustrate it by evaluating whether gene expression can be used as a surrogate for immune activation in an Ebola study.
Constrained groupwise additive index models
Authors: Masselot Pierre , Chebana Fateh , Campagna Céline , Lavigne Éric , Ouarda Taha B M J , Gosselin Pierre
Published: July 2022

In environmental epidemiology, there is wide interest in creating and using comprehensive indices that can summarize information from different environmental exposures while retaining strong predictive power on a target health outcome. In this context, the present article proposes a model called the constrained groupwise additive index model (CGAIM) to create easy-to-interpret indices predictive of a response variable, from a potentially large list of variables. The CGAIM considers groups of predictors that naturally belong together to yield meaningful indices. It also allows the addition of linear constraints on both the index weights and the form of their relationship with the response variable to represent prior assumptions or operational requirements. We propose an efficient algorithm to estimate the CGAIM, along with index selection and inference procedures. A simulation study shows that the proposed algorithm has good estimation performances, with low bias and variance and is applicable in complex situations with many correlated predictors. It also demonstrates important sensitivity and specificity in index selection, but non-negligible coverage error on constructed confidence intervals. The CGAIM is then illustrated in the construction of heat indices in a health warning system context. We believe the CGAIM could become useful in a wide variety of situations, such as warning systems establishment, and multipollutant or exposome studies.
Fast and functionally specific cortical thickness changes induced by visual stimulation
Authors: Zaretskaya Natalia , Fink Erik , Arsenovic Ana , Ischebeck Anja
Published: July 2022

Structural characteristics of the human brain serve as important markers of brain development, aging, disease progression, and neural plasticity. They are considered stable properties, changing slowly over time. Multiple recent studies reported that structural brain changes measured with magnetic resonance imaging (MRI) may occur much faster than previously thought, within hours or even minutes. The mechanisms behind such fast changes remain unclear, with hemodynamics as one possible explanation. Here we investigated the functional specificity of cortical thickness changes induced by a flickering checkerboard and compared them to blood oxygenation level-dependent (BOLD) functional MRI activity. We found that checkerboard stimulation led to a significant thickness increase, which was driven by an expansion at the gray–white matter boundary, functionally specific to V1, confined to the retinotopic representation of the checkerboard stimulus, and amounted to 1.3% or 0.022 mm. Although functional specificity and the effect size of these changes were comparable to those of the BOLD signal in V1, thickness effects were substantially weaker in V3. Furthermore, a comparison of predicted and measured thickness changes for different stimulus timings suggested a slow increase of thickness over time, speaking against a hemodynamic explanation. Altogether, our findings suggest that visual stimulation can induce structural gray matter enlargement measurable with MRI.
Inferior temporal cortex leads prefrontal cortex in response to a violation of a learned sequence
Authors: Esmailpour Hamideh , Raman Rajani , Vogels Rufin
Published: July 2022

Primates learn statistical regularities that are embedded in visual sequences, a form of statistical learning. Single-unit recordings in macaques showed that inferior temporal (IT) neurons are sensitive to statistical regularities in visual sequences. Here, we asked whether ventrolateral prefrontal cortex (VLPFC), which is connected to IT, is also sensitive to the transition probabilities in visual sequences and whether the statistical learning signal in IT originates in VLPFC. We recorded simultaneously multiunit activity (MUA) and local field potentials (LFPs) in IT and VLPFC after monkeys were exposed to triplets of images with a fixed presentation order. In both areas, the MUA was stronger to images that violated the learned sequence (deviants) compared to the same images presented in the learned triplets. The high-gamma and beta LFP power showed an enhanced and suppressed response, respectively, to the deviants in both areas. The enhanced response was present also for the image following the deviant, suggesting a sensitivity for temporal adjacent dependencies in IT and VLPFC. The increased response to the deviant occurred later in VLPFC than in IT, suggesting that the deviant response in IT was not inherited from VLPFC. These data support predictive coding theories that propose a feedforward flow of prediction errors.
Estimated Number of People Who Inject Drugs in the United States
Authors: Bradley Heather , Hall Eric W , Asher Alice , Furukawa Nathan W , Jones Christopher M , Shealey Jalissa , Buchacz Kate , Handanagic Senad , Crepaz Nicole , Rosenberg Eli S
Published: July 2022

Background

Public health data signal increases in the number of people who inject drugs (PWID) in the United States during the past decade. An updated PWID population size estimate is critical for informing interventions and policies aiming to reduce injection-associated infections and overdose, as well as to provide a baseline for assessments of pandemic-related changes in injection drug use.

Methods

We used a modified multiplier approach to estimate the number of adults who injected drugs in the United States in 2018. We deduced the estimated number of nonfatal overdose events among PWID from 2 of our previously published estimates: the number of injection-involved overdose deaths and the meta-analyzed ratio of nonfatal to fatal overdose. The number of nonfatal overdose events was divided by prevalence of nonfatal overdose among current PWID for a population size estimate.

Results

There were an estimated 3 694 500 (95% confidence interval [CI], 1 872 700–7 273 300) PWID in the United States in 2018, representing 1.46% (95% CI, .74–2.87) of the adult population. The estimated prevalence of injection drug use was highest among males (2.1%; 95% CI, 1.1–4.2), non-Hispanic Whites (1.8%; 95% CI, .9–3.6), and adults aged 18–39 years (1.8%; 95% CI, .9–3.6).

Conclusions

Using transparent, replicable methods and largely publicly available data, we provide the first update to the number of people who inject drugs in the United States in nearly 10 years. Findings suggest the population size of PWID has substantially grown in the past decade and that prevention services for PWID should be proportionally increased.
Semantic-Based Hybrid Query Reformulation for Biomedical Information Retrieval
Authors: Selmi Wided , Kammoun Hager , Amous Ikram
Published: July 2022

Query reformulation is a well-known technique intended to improve the performance of Information Retrieval Systems. Among the several available techniques, Query Expansion (QE) reformulates the initial query by adding similar terms, drawn from several sources (corpus, knowledge resources), to the query terms in order to retrieve more relevant documents. Most QE methods are based on the relationships between the original query term and candidate terms (new terms) in order to select the most similar expansion terms. In this paper, we suggested a new hybrid query reformulation through QE and term re-weighting techniques. The suggested approach aimed to demonstrate the effectiveness of QE with a semantic selection of candidate terms according to the specificity of original query terms in the improvement of retrieval performance. To this end, we exploited both relationships defined by knowledge resources and the distributed semantics, recently revealed by neural network analysis. For term re-weighting, we proposed a new semantic method based on semantic similarity measure that assigns a weight to each term of the expanded query. The conducted experiments on OHSUMED and TREC 2014 CDS test collections, including long and short queries, yielded significant results that outperformed the baseline and state-of-the-art approaches.
Modified Multi-Key Fully Homomorphic Encryption Scheme in the Plain Model
Authors: Xu Wenju , Wang Baocang , Qu Quanbo , Zhou Tanping , Duan Pu
Published: July 2022

Multi-key fully homomorphic encryption (MFHE) supports arbitrary meaningful computations on encrypted data under different public keys even without access to the secret key, which is well tailored for the secure multiparty computation scenarios. Based on the Gentry–Sahai–Waters scheme (a single-key FHE in Crypto 2013) with the underlying learning with errors problem, MW16 scheme (Eurocrypt 2016) utilizes the method of ‘linear combination procedure’ (LCP) as a subroutine to construct the auxiliary information for the expanded ciphertexts of MFHE scheme. However, every party shares a common random string (CRS) to be distributed by a trusted setup, which is unpractical. Meanwhile, the noise in the auxiliary information is too much compared with the one in fresh ciphertexts. In this paper, we propose a modified MFHE scheme in the plain model, i.e. without CRS, to enhance the practicability of MFHE. Specifically, every involved party generates his own public key independent on a CRS. Then a potential improvement on the LCP is developed to provide auxiliary information, which largely reduces the noise and leads to a smaller modulus for our MFHE. Furthermore, the feasibility of our proposal is also proved by theoretical performance comparisons.
Prediction of Li-Ion Battery Discharge Patterns in IoT Devices Under Random Use Via Machine Learning Algorithms
Authors: Gökçen Ahmet , Gökçen Alkım , Şahin Savaş
Published: July 2022

This study presents foreseeing of the Lithium-ion battery discharge models for the Internet of Things (IoT) devices under randomized use patterns. IoT systems run in harmony with the human–machine interface, communication protocols and sharing data so long as uninterrupted data communication is exploited for their devices. Hence, forecasting the battery discharge duration is a very important issue for the regularization of IoT device performances. The well-known discharge duration is generally about the age-related electrochemical phenomena of an electrochemistry for Lithium-ion battery. The discharge changes of the battery were obtained from the input–output dynamics of the random battery use obtained from the randomized battery usage dataset in the NASA Ames prognostics data repository. They were investigated by machine learning methods and their results were estimated for life expectancy regularization of the IoT devices. In order to find the appropriate models of battery usage under randomized patterns, artificial neural network (ANN), Gaussian process and nonlinear regression models are evaluated in terms of battery capacity and internal resistance change as a function of discharged energy. The ${R}^2$, Adjusted ${R}^2$, root-mean-square-error (RMSE) and normalized-mean-square-error (NMSE) criteria were used to compare the performances of the obtained models for different settings. According to the results, ANN model, with settings of radial basis function activation function within single hidden-layer, and 20 hidden-layer neurons, shows the best performance in terms of ${R}^2=1.0000$ and $\mathrm{NMSE}={\mathrm{1.7384.10}}^{-4}$ metrics. $\mathrm{RMSE}={\mathrm{0.9896.10}}^{-4}$ is achieved by the ANN model with the settings of single hidden-layer with 10 neurons and hyperbolic-tangent activation function.
The Self-Determination Inventory: Student Report American Sign Language Translation
Authors: Garberoglio Carrie Lou , Gerasimova Daria , Shogren Karrie A , Palmer Jeffrey Levi , Johnson Paige M , Ryan Claire , Pace Jesse R , Hicks Tyler , Millen Kaitlyn , Higgins Jennifer , Cawthon Stephanie W
Published: July 2022

Research literature and community narratives both emphasize the importance of self-determination in the lives of deaf youth. This paper describes the development, initial validation, and potential applications of a translated measure of self-determination for deaf youth, the SDI:SR ASL Translation (SDI:SR ASL). A sample of 3,309 young people who completed the SDI:SR, of whom 392 were deaf, was used in this validation study. Results provide preliminary support for the use of SDI:SR ASL with deaf youth. Findings also indicate that deaf youth who take the SDI:SR ASL score more similarly to youth without disabilities taking the SDI:SR than youth with disabilities. The SDI:SR ASL can be an important tool for researchers and practitioners to better understand self-determination among deaf youth and facilitate continued development of self-determination skills.
Histologic response to steroids in eosinophilic esophagitis is dependent on delivery compound
Authors: Schupack Daniel A , Johnson Kimberly , Akambase Joseph A , Geno Debra , Lavey Crystal , Lennon Ryan J , Ravi Karthik , Snyder Diana L , Katzka David A , Alexander Jeffrey A
Published: July 2022

Topical steroids are commonly used in treatment of eosinophilic esophagitis (EoE), but currently there is lack of data to clarify most effective regimen. We aimed to study the achievement of histologic remission using the same dose of budesonide in two different delivery formulations. Patients with established EoE treated with pharmacy compounded budesonide capsule or budesonide Rincinol gel (both 3 mg twice daily) were studied retrospectively. Those with pre-treatment and post-treatment histologic assessment were included with main endpoint being histologic remission. 103 patients (62 gel, 41 capsule) were included, with higher rate of histologic remission with gel (84 vs. 59%, P=0.004). A subset of patients in both groups had lack of steroid response (<50% drop in eosinophils) (15% for gel, 32% for capsule). Formulation/delivery vehicle of steroid treatments to esophageal mucosa in EoE appears important for treatment efficacy, with budesonide gel having higher likelihood of histologic remission compared to budesonide capsules in our population. A truly steroid refractory group appears likely in our population. Larger, prospective studies may help clarify best regimen of topical steroids in EoE and may work to identify patients likely to benefit from alternative therapies.
Symptoms classically attributed to laryngopharyngeal reflux correlate poorly with pharyngeal reflux events on multichannel intraluminal impedance testing
Authors: Salgado Sanjay , Borges Lawrence F , Cai Jennifer X , Lo Wai-Kit , Carroll Thomas L , Chan Walter W
Published: July 2022

Laryngopharyngeal reflux (LPR) is thought to be a common etiology of throat and airway symptoms. Diagnosis of LPR is challenging, given the variable symptomatology and response to therapy. Identifying symptoms that better correlate with LPR may inform management strategies. We aimed to examine the association between patient-reported symptoms and objectively identified LPR on ambulatory reflux monitoring. This was a retrospective cohort study of consecutive adults with suspected LPR undergoing combined hypopharyngeal–esophageal multichannel intraluminal impedance–pH testing (HEMII-pH) at a tertiary center. All patients completed standardized symptom surveys for presenting symptoms, reflux symptom index (RSI), and voice handicap index (VHI). LPR was defined as >1 full-column pharyngeal reflux event on HEMII-pH over 24 hours. Univariate and multivariable analyses were performed. A total of 133 patients were included (mean age = 55.9 years, 69.9% female). Of this 83 (62.4%) reported concomitant esophageal symptoms. RSI and VHI did not correlate with proximal esophageal or pharyngeal reflux events (Kendall’s tau correlations P > 0.05), although the mean RSI was higher in the LPR group (21.1 ± 18.9 vs. 17.1 ± 8.3, P = 0.044). Cough, but not other laryngeal symptoms, was more common among patients with esophageal symptoms (58% vs. 36%, P = 0.014). Neither laryngeal symptoms nor esophageal symptoms of reflux predicted LPR on univariate or multivariable analyses (all P > 0.05). Neither laryngeal symptoms classically attributed to LPR nor typical esophageal symptoms correlated with pharyngeal reflux events on HEMII-pH. Clinical symptoms alone are not sufficient to make an LPR diagnosis. Broad evaluation for competing differential diagnoses and objective reflux monitoring should be considered in patients with suspected LPR symptoms.
Blood biomarkers as predictors of pathological lymph node metastasis in clinical stage T1N0 esophageal squamous cell carcinoma
Authors: Ohsawa Manato , Hamai Yoichi , Emi Manabu , Ibuki Yuta , Kurokawa Tomoaki , Yoshikawa Toru , Hirohata Ryosuke , Kitasaki Nao , Okada Morihito
Published: July 2022

Accurate preoperative evaluation of lymph node (LN) metastasis is important for determining the treatment strategy for superficial esophageal cancer. Blood biomarkers, such as the neutrophil–lymphocyte, platelet–lymphocyte, and lymphocyte–monocyte ratios (NLR, PLR, and LMR, respectively), have clinical applications as predictors of LN metastasis for different cancers. Here, we investigated the use of these ratios as predictors of pathological LN metastasis and prognosis in patients with clinical stage T1N0M0 esophageal squamous cell carcinoma (ESCC). Patients (n = 185) with cT1N0M0 ESCC who underwent esophagectomy with R0 resection between April 2003 and August 2021 were enrolled. We investigated the ability of pretreatment NLR, PLR, and LMR to predict pathological LN metastasis. The optimal cutoff values of NLR, PLR, and LMR to predict pathological LN metastasis were 2.1, 122, and 4.8, respectively. Univariate and multivariate analyses revealed that the primary tumor length, depth of invasion, and NLR were significant predictors of LN metastasis. Furthermore, similar to the 5-year overall survival, the 5-year relapse-free survival was significantly better in the low NLR group than in the high NLR group. The NLR was the most useful predictor of pathological LN metastasis. Patients diagnosed with clinical stage I ESCC and with a high NLR require adequate LN dissection and may be good candidates for preoperative adjuvant therapy.
PU.1-driven Th9 Cells Promote Colorectal Cancer in Experimental Colitis Models Through Il-6 Effects in Intestinal Epithelial Cells
Authors: Gerlach Katharina , Popp Vanessa , Wirtz Stefan , Al-Saifi Ragheed , Gonzalez Acera Miguel , Atreya Raja , Dregelies Theresa , Vieth Michael , Fichtner-Feigl Stefan , McKenzie Andrew N J , Rosenbauer Frank , Weigmann Benno , Neurath Markus F
Published: July 2022

Background and Aims

Colorectal cancer [CRC] is one of the most frequent malignancies, but the molecular mechanisms driving cancer growth are incompletely understood. We characterised the roles of the cytokine IL-9 and Th9 cells in regulating CRC development.

Methods

CRC patient samples and samples from AOM/DSS treated mice were analysed for expression of IL-9, CD3, and PU.1 by FACS analysis and immunohistochemistry. IL-9 citrine reporter mice, IL-9 knockout mice, and PU.1 and GATA3 CD4-Cre conditional knockout mice were studied in the AOM/DSS model. DNA minicircles or hyper-IL-6 were used for overexpression of cytokines in vivo. Effects of IL-6 and IL-9 were determined in organoid and T cell cultures. Claudin2/3 expression was studied by western blotting and bacterial translocation by FISH.

Results

We uncovered a significant expansion of IL-9- and PU.1-expressing mucosal Th9 cells in CRC patients, with particularly high levels in patients with colitis-associated neoplasias. PU.1+ Th9 cells accumulated in experimental colorectal neoplasias. Deficiency of IL-9 or inactivation of PU.1 in T cells led to impaired tumour growth in vivo, suggesting a protumoral role of Th9 cells. In contrast, GATA3 inactivation did not affect Th9-mediated tumour growth. Mechanistically, IL-9 controls claudin2/3 expression and T cell-derived IL-6 production in colorectal tumours. IL-6 abrogated the anti-proliferative effects of IL-9 in epithelial organoids in vivo. IL-9-producing Th9 cells expand in CRC and control IL-6 production by T cells.

Conclusions

IL-9 is a crucial regulator of tumour growth in colitis-associated neoplasias and emerges as potential target for therapy.
The Long-Run Effects of Peers on Mental Health
Authors: Kiessling Lukas , Norris Jonathan
Published: July 2022

This paper studies how peers in school affect students’ mental health. Guided by a theoretical framework, we find that increasing students’ relative ranks in their cohorts by one standard deviation improves their mental health by 6% of a standard deviation conditional on own ability. These effects are more pronounced for low-ability students, persistent for at least 14 years and carry over to economic long-run outcomes. Moreover, we document a pronounced asymmetry: Students who receive negative rather than positive shocks react more strongly. Our findings therefore provide evidence on how the school environment can have long-lasting consequences for individuals’ well-being.
Assessing heat stress tolerance in Castanea sativa
Authors: Dorado F Javier , Solla Alejandro , Alcaide Francisco , Martín M Ángela
Published: July 2022

Increasing temperatures and heat waves decimate the productivity and survival of valuable trees like the European chestnut (Castanea sativa Miller). The main objectives of this study were to assess variation in heat stress tolerance within and between chestnut populations, select molecular markers associated with heat stress tolerance, and to use the selected markers to explore the adaptive potential of C. sativa to tolerate heat stress. Forty-eight trees from three Spanish wild chestnut populations of contrasting climate characteristics were used. Seven out of 20 expressed sequence tag- simple sequence repeat (EST-SSR) markers were selected. To validate the markers, progenies of the 48 trees were subjected to heat stress for 7 days and their heat tolerance was assessed through morphological and physiological changes. Leaf proline content induced by heat was highest in the least thermophilic population. Genetic structure analysis of populations revealed a cluster that included 81 per cent of the seedlings of the most thermophilic population. Signatures of positive selection for heat stress tolerance were detected using VIT099 and POR016 markers, associated with the antioxidant response of plants to heat damage. These markers should be included as candidates for their use in early selection of individuals tolerant to heat stress in C. sativa. Molecular and physiological findings converged in this study to better understand chestnut adaptation to global warming.
Induction and inhibition of Drosophila X chromosome gene expression are both impeded by the dosage compensation complex
Authors: Meisel Richard P , Asgari Danial , Schlamp Florencia , Unckless Robert L
Published: July 2022

Sex chromosomes frequently differ from the autosomes in the frequencies of genes with sexually dimorphic or tissue-specific expression. Multiple hypotheses have been put forth to explain the unique gene content of the X chromosome, including selection against male-beneficial X-linked alleles, expression limits imposed by the haploid dosage of the X in males, and interference by the dosage compensation complex on expression in males. Here, we investigate these hypotheses by examining differential gene expression in Drosophila melanogaster following several treatments that have widespread transcriptomic effects: bacterial infection, viral infection, and abiotic stress. We found that genes that are induced (upregulated) by these biotic and abiotic treatments are frequently under-represented on the X chromosome, but so are those that are repressed (downregulated) following treatment. We further show that whether a gene is bound by the dosage compensation complex in males can largely explain the paucity of both up- and downregulated genes on the X chromosome. Specifically, genes that are bound by the dosage compensation complex, or close to a dosage compensation complex high-affinity site, are unlikely to be up- or downregulated after treatment. This relationship, however, could partially be explained by a correlation between differential expression and breadth of expression across tissues. Nonetheless, our results suggest that dosage compensation complex binding, or the associated chromatin modifications, inhibit both up- and downregulation of X chromosome gene expression within specific contexts, including tissue-specific expression. We propose multiple possible mechanisms of action for the effect, including a role of Males absent on the first, a component of the dosage compensation complex, as a dampener of gene expression variance in both males and females. This effect could explain why the Drosophila X chromosome is depauperate in genes with tissue-specific or induced expression, while the mammalian X has an excess of genes with tissue-specific expression.
Apomixis: genetic basis and controlling genes
Authors: Xu Yuantao , Jia Huihui , Tan Chunming , Wu Xiaomeng , Deng Xiuxin , Xu Qiang
Published: July 2022

Apomixis is the phenomenon of clonal reproduction by seed. As apomixis can produce clonal progeny with exactly the same genotype as the maternal plant, it has an important application in genotype fixation and accelerating agricultural breeding strategies. The introduction of apomixis to major crops would bring many benefits to agriculture, including permanent fixation of superior genotypes and simplifying the procedures of hybrid seed production, as well as purification and rejuvenation of crops propagated vegetatively. Although apomixis naturally occurs in more than 400 plant species, it is rare among the major crops. Currently, with better understanding of apomixis, some achievements have been made in synthetic apomixis. However, due to prevailing limitations, there is still a long way to go to achieve large-scale application of apomixis to crop breeding. Here, we compare the developmental features of apomixis and sexual plant reproduction and review the recent identification of apomixis genes, transposons, epigenetic regulation, and genetic events leading to apomixis. We also summarize the possible strategies and potential genes for engineering apomixis into crop plants.
Vitamin D Supplementation and Antibiotic Use in Older Australian Adults: An Analysis of Data From the D-Health Trial
Authors: Pham Hai , Waterhouse Mary , Baxter Catherine , Duarte Romero Briony , McLeod Donald S A , Armstrong Bruce K , Ebeling Peter R , English Dallas R , Hartel Gunter , Kimlin Michael G , O’Connell Rachel L , van der Pols Jolieke C , Venn Alison J , Webb Penelope M , Whiteman David C , Neale Rachel E
Published: July 2022

Background

Vitamin D supplementation may reduce the risk or severity of infection, but this has been investigated in few large population-based trials. We analyzed data from the D-Health Trial, using prescription of antibiotics as a surrogate for infection.

Methods

The D-Health Trial is a randomized, double-blind, placebo-controlled trial in which 21 315 Australians aged 60–84 years were randomized to 60 000 IU of supplementary vitamin D3 or placebo monthly for 5 years. For this analysis, the primary outcome was the number of antibiotic prescription episodes; secondary outcomes were total number of prescriptions, repeat prescription episodes, and antibiotics for urinary tract infection. We estimated incidence rate ratios (IRRs) using negative binomial regression, and odds ratios using logistic regression.

Results

Vitamin D supplementation slightly reduced the number of prescription episodes (IRR, 0.98; 95% confidence interval [CI], .95–1.01), total prescriptions (IRR, 0.97; 95% CI, .93–1.00), and repeat prescription episodes (IRR, 0.96; 95% CI, .93–1.00). There was stronger evidence of benefit in people predicted to have insufficient vitamin D at baseline (prescription episodes IRR, 0.93; 95% CI, .87–.99).

Conclusions

Vitamin D may reduce the number of antibiotic prescriptions, particularly in people with low vitamin D status. This supports the hypothesis that vitamin D has a clinically relevant effect on the immune system.

Clinical Trials Registration

Australian New Zealand Clinical Trials Registry: ACTRN12613000743763. https://www.anzctr.org.au/.
Biomarkers of mitochondrial origin: a futuristic cancer diagnostic
Authors: Gayan Sukanya , Joshi Gargee , Dey Tuli
Published: July 2022

Cancer is a highly fatal disease without effective early-stage diagnosis and proper treatment. Along with the oncoproteins and oncometabolites, several organelles from cancerous cells are also emerging as potential biomarkers. Mitochondria isolated from cancer cells are one such biomarker candidates. Cancerous mitochondria exhibit different profiles compared with normal ones in morphology, genomic, transcriptomic, proteomic and metabolic landscape. Here, the possibilities of exploring such characteristics as potential biomarkers through single-cell omics and Artificial Intelligence (AI) are discussed. Furthermore, the prospects of exploiting the biomarker-based diagnosis and its futuristic utilization through circulatory tumor cell technology are analyzed. A successful alliance of circulatory tumor cell isolation protocols and a single-cell omics platform can emerge as a next-generation diagnosis and personalized treatment procedure.
Early biomolecular changes in brain microvascular endothelial cells under Epstein–Barr virus influence: a Raman microspectroscopic investigation
Authors: Indari Omkar , Tiwari Deeksha , Tanwar Manushree , Kumar Rajesh , Jha Hem Chandra
Published: July 2022

The brain microvascular endothelial cells (ECs) play an important role in protecting the brain from hazardous pathogens. However, some viral pathogens can smartly modulate the endothelial pathways to gain entry inside the brain. Further, these viruses can cause endothelial dysfunction which could develop serious neurological ailments. Epstein–Barr virus (EBV), an oncogenic virus, has also been linked to various neurological disorders. The virus primarily infects epithelial and B cells, however, it also has a tendency to infect ECs and cause endothelial activation. However, the impact of EBV influence on ECs is still underexplored. Studying the early events of virus-mediated cellular modulation could help in understanding the virus’ infection strategy or aftermath. Raman microspectroscopy has been widely utilized in biomedical sciences to decipher cellular changes. To understand the EBV-influenced EC modulation by studying intracellular biomolecular changes at early time points, we utilized the Raman microspectroscopy tool. We treated the ECs with EBV and acquired the Raman spectra at different time points (2, 4, 6, 12, 24 and 36 h) and different sites (nucleus and periphery) to check changes in Raman intensities associated with specific biomolecules. In the EBV-treated cells, the status of various biomolecules in terms of Raman intensities was observed to be altered compared with uninfected cells. Specifically, the cholesterol, polysaccharide, nucleotides, nucleic acid and proline moieties were altered at different time points. We also investigated the possible correlation between these molecules using molecular network analysis and observed various associated factors. These factors could be influenced by EBV to alter the associated biomolecular levels. Our study paves the pathway to study EBV infection in human brain microvascular ECs and highlights specific biomolecular alterations, which can be focused for further mechanistic investigations.
Liver cirrhosis and immune dysfunction
Authors: Hasa Elda , Hartmann Phillipp , Schnabl Bernd
Published: July 2022

Cirrhosis is end-stage liver disease resulting from various etiologies and is a common cause of death worldwide. The progression from compensated to decompensated cirrhosis to acute-on-chronic liver failure (ACLF) is due to multiple factors, including continuation of alcohol use or continued exposure to other toxins, an imbalance of the gut microbiota (dysbiosis), increased gut permeability and a disrupted immune response. This disrupted immune response is also named cirrhosis-associated immune dysfunction, which is characterized by worsening systemic inflammation with concomitant immune paralysis, as liver disease deteriorates. This review highlights central immunologic events during the exacerbation of cirrhosis and characterizes the different immune cell populations involved therein.
An Outsider’s Perspective on Why We Climb Mountains and Why Projects Like the i5k Matter
Authors: Molik David C
Published: July 2022

Initiatives like the i5k are creating evermore genome assemblies. These initiatives are resource heavy, and their justifications and economics deserve attention. Scientifically, these initiatives are important, paving the way for cross-species analysis, requiring the building of new computational analysis and tools, and creating other new resources. However, an open question remains of how we quantitively measure the impact of genomes, and by extension these initiatives. This forum article discusses one such method which is to look at the publications about a species over time, however, this method does not show any signal from a published genome, leaving an open question of how to measure impact.