bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive risk-aware sharable and individual subspace learning for cancer survival analysis with multi-modality data
Authors: Zhao Zhangxin , Feng Qianjin , Zhang Yu , Ning Zhenyuan
Published: November 2022

Biomedical multi-modality data (also named multi-omics data) refer to data that span different types and derive from multiple sources in clinical practices (e.g. gene sequences, proteomics and histopathological images), which can provide comprehensive perspectives for cancers and generally improve the performance of survival models. However, the performance improvement of multi-modality survival models may be hindered by two key issues as follows: (1) how to learn and fuse modality-sharable and modality-individual representations from multi-modality data; (2) how to explore the potential risk-aware characteristics in each risk subgroup, which is beneficial to risk stratification and prognosis evaluation. Additionally, learning-based survival models generally refer to numerous hyper-parameters, which requires time-consuming parameter setting and might result in a suboptimal solution. In this paper, we propose an adaptive risk-aware sharable and individual subspace learning method for cancer survival analysis. The proposed method jointly learns sharable and individual subspaces from multi-modality data, whereas two auxiliary terms (i.e. intra-modality complementarity and inter-modality incoherence) are developed to preserve the complementary and distinctive properties of each modality. Moreover, it equips with a grouping co-expression constraint for obtaining risk-aware representation and preserving local consistency. Furthermore, an adaptive-weighted strategy is employed to efficiently estimate crucial parameters during the training stage. Experimental results on three public datasets demonstrate the superiority of our proposed model.
The role of neurofilament light in genetic frontotemporal lobar degeneration
Authors: Zetterberg Henrik , Teunissen Charlotte , van Swieten John , Kuhle Jens , Boxer Adam , Rohrer Jonathan D , Mitic Laura , Nicholson Alexandra M , Pearlman Rodney , McCaughey Stella Mayo , Tatton Nadine
Published: November 2022

Genetic frontotemporal lobar degeneration caused by autosomal dominant gene mutations provides an opportunity for targeted drug development in a highly complex and clinically heterogeneous dementia. These neurodegenerative disorders can affect adults in their middle years, progress quickly relative to other dementias, are uniformly fatal and have no approved disease-modifying treatments. Frontotemporal dementia, caused by mutations in the GRN gene which encodes the protein progranulin, is an active area of interventional drug trials that are testing multiple strategies to restore progranulin protein deficiency. These and other trials are also examining neurofilament light as a potential biomarker of disease activity and disease progression and as a therapeutic endpoint based on the assumption that cerebrospinal fluid and blood neurofilament light levels are a surrogate for neuroaxonal damage. Reports from genetic frontotemporal dementia longitudinal studies indicate that elevated concentrations of blood neurofilament light reflect disease severity and are associated with faster brain atrophy. To better inform patient stratification and treatment response in current and upcoming clinical trials, a more nuanced interpretation of neurofilament light as a biomarker of neurodegeneration is now required, one that takes into account its relationship to other pathophysiological and topographic biomarkers of disease progression from early presymptomatic to later clinically symptomatic stages.
Interictal epileptiform discharges as a predictive biomarker for recurrence of poststroke epilepsy
Authors: Abe Soichiro , Tanaka Tomotaka , Fukuma Kazuki , Matsubara Soichiro , Motoyama Rie , Mizobuchi Masahiro , Yoshimura Hajime , Matsuki Takayuki , Manabe Yasuhiro , Suzuki Junichiro , Ishiyama Hiroyuki , Tojima Maya , Kobayashi Katsuya , Shimotake Akihiro , Nishimura Kunihiro , Koga Masatoshi , Toyoda Kazunori , Murayama Shigeo , Matsumoto Riki , Takahashi Ryosuke , Ikeda Akio , Ihara Masafumi ,   PROPOSE Study Investigators, Nagatsuka Kazuyuki , Nakamura Fumiaki , Tomari Shinya , Yamaguchi Yoshitaka , Nakamura Takashi , Makita Naoki , Nakamura Yuki , Okuno Yoshiaki , Hosoki Satoshi , Fujii Ryo , Arimizu Takuro
Published: November 2022

Poststroke epilepsy is a major ischaemic/haemorrhagic stroke complication. Seizure recurrence risk estimation and early therapeutic intervention are critical, given the association of poststroke epilepsy with worse functional outcomes, quality of life and greater mortality. Several studies have reported risk factors for seizure recurrence; however, in poststroke epilepsy, the role of EEG in predicting the risk of seizures remains unclear. This multicentre observational study aimed to clarify whether EEG findings constitute a risk factor for seizure recurrence in patients with poststroke epilepsy. Patients with poststroke epilepsy were recruited from the PROgnosis of POst-Stroke Epilepsy study, an observational multicentre cohort study. The enrolled patients with poststroke epilepsy were those admitted at selected hospitals between November 2014 and June 2017. All patients underwent EEG during the interictal period during admission to each hospital and were monitored for seizure recurrence over 1 year. Board-certified neurologists or epileptologists evaluated all EEG findings. We investigated the relationship between EEG findings and seizure recurrence. Among 187 patients with poststroke epilepsy (65 were women with a median age of 75 years) admitted to the lead hospital, 48 (25.7%) had interictal epileptiform discharges on EEG. During the follow-up period (median, 397 days; interquartile range, 337–450 days), interictal epileptiform discharges were positively correlated with seizure recurrence (hazard ratio, 3.82; 95% confidence interval, 2.09–6.97; P < 0.01). The correlation remained significant even after adjusting for age, sex, severity of stroke, type of stroke and generation of antiseizure medications. We detected periodic discharges in 39 patients (20.9%), and spiky/sharp periodic discharges were marginally associated with seizure recurrence (hazard ratio, 1.85; 95% confidence interval, 0.93–3.69; P = 0.08). Analysis of a validation cohort comprising 187 patients with poststroke epilepsy from seven other hospitals corroborated the association between interictal epileptiform discharges and seizure recurrence. We verified that interictal epileptiform discharges are a risk factor for seizure recurrence in patients with poststroke epilepsy. Routine EEG may facilitate the estimation of seizure recurrence risk and the development of therapeutic regimens for poststroke epilepsy.
Genetics of congenital olfactory dysfunction: a systematic review of the literature
Authors: Deller Matthias , Gellrich Janine , Lohrer Elisabeth C , Schriever Valentin A
Published: November 2022

Olfaction, as one of our 5 senses, plays an important role in our daily lives. It is connected to proper nutrition, social interaction, and protection mechanisms. Disorders affecting this sense consequently also affect the patients’ general quality of life. Because the underlying genetics of congenital olfactory disorders (COD) have not been thoroughly investigated yet, this systematic review aimed at providing information on genes that have previously been reported to be mutated in patients suffering from COD. This was achieved by systematically reviewing existing literature on 3 databases, namely PubMed, Ovid Medline, and ISI Web of Science. Genes and the type of disorder, that is, isolated and/or syndromic COD were included in this study, as were the patients’ associated abnormal features, which were categorized according to the affected organ(-system). Our research yielded 82 candidate genes/chromosome loci for isolated and/or syndromic COD. Our results revealed that the majority of these are implicated in syndromic COD, a few accounted for syndromic and isolated COD, and the least underly isolated COD. Most commonly, structures of the central nervous system displayed abnormalities. This study is meant to assist clinicians in determining the type of COD and detecting potentially abnormal features in patients with confirmed genetic variations. Future research will hopefully expand this list and thereby further improve our understanding of COD.
Impact of Vaccination With the SCB-2019 Coronavirus Disease 2019 Vaccine on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Household Contact Study in the Philippines
Authors: Tadesse Birkneh Tilahun , Bravo Lulu , Marks Florian , Aziz Asma Binte , You Young Ae , Sugimoto Jonathan , Li Ping , Garcia Joyce , Rockhold Frank , Clemens Ralf ,   for the Household Contact Study Group, Roa Camilo , Borja-Tabora Charissa , Carlos Josefina , Montellano May Emmeline B , Reyes Mari Rose A de Los , Alberto Edison R , Salvani-Bautista Milagros , Kim Deok Ryun , Kim Hwa Young , Hong Sye Lim , Kang Sophie S Y , Njau Irene
Published: November 2022

Background

An exploratory household transmission study was nested in SPECTRA, the phase 2/3 efficacy study of the adjuvanted recombinant protein-based COVID-19 vaccine SCB-2019. We compared the occurrence of confirmed COVID-19 infections between households and household contacts of infected SPECTRA placebo or SCB-2019 recipients.

Methods

SPECTRA participants at 8 study sites in the Philippines who developed real-time reverse transcriptase–polymerase chain reaction (rRT-PCR)–confirmed COVID-19 were contacted by a study team blinded to assignment of index cases to vaccine or placebo groups to enroll in this household transmission study. Enrolled households and household contacts were monitored for 3 weeks using rRT-PCR and anti–SARS-CoV-2 N-antigen IgG/IgM testing to detect new COVID-19 infections.

Results

One hundred fifty-four eligible COVID-19 index cases (51 vaccinees, 103 placebo) were included. The secondary attack rate per household for symptomatic COVID-19 infection was 0.76% (90% CI: .15–3.90%) if the index case was an SCB-2019 vaccinee compared with 5.88% (90% CI: 3.20–10.8%) for placebo index cases, a relative risk reduction (RRR) of 79% (90% CI: −28% to 97%). The RRR of symptomatic COVID-19 per household member was similar: 84% (90% CI: 28–97%). The impact on attack rates in household members if index cases were symptomatic (n = 130; RRR = 80%; 90% CI: 7–96%) or asymptomatic (n = 24; RRR = 100%; 90% CI: −76% to 100%) was measurable but the low numbers undermine the clinical significance.

Conclusions

In this prospective household contact study vaccination with SCB-2019 reduced SARS-CoV-2 transmission compared with placebo in households and in household members independently of whether or not index cases were symptomatic.
Type 2 diabetes mellitus and higher rate of complete atrioventricular block: a Danish Nationwide Registry
Authors: Haxha Saranda , Halili Andrim , Malmborg Morten , Pedersen-Bjergaard Ulrik , Philbert Berit T , Lindhardt Tommi B , Hoejberg Soeren , Schjerning Anne-Marie , Ruwald Martin H , Gislason Gunnar H , Torp-Pedersen Christian , Bang Casper N
Published: November 2022

Aims

The present study aimed to determine the association between Type 2 diabetes mellitus (T2DM) and third-degree (complete) atrioventricular block.

Methods and results

This nationwide nested case–control study included patients older than 18 years, diagnosed with third-degree atrioventricular block between 1 July 1995 and 31 December 2018. Data on medication, comorbidity, and outcomes were collected from Danish registries. Five controls, from the risk set of each case of third-degree atrioventricular block, were matched on age and sex to fit a Cox regression model with time-dependent exposure and time-dependent covariates. Subgroup analysis was conducted with Cox regression models for each subgroup. We located 25 995 cases with third-degree atrioventricular block that were matched with 130 004 controls. The mean age was 76 years and 62% were male. Cases had more T2DM (21% vs. 11%), hypertension (69% vs. 50%), atrial fibrillation (25% vs. 10%), heart failure (20% vs. 6.3%), and myocardial infarction (19% vs. 9.2%), compared with the control group. In Cox regression analysis, adjusting for comorbidities and atrioventricular nodal blocking agents, T2DM was significantly associated with third-degree atrioventricular block (hazard ratio: 1.63, 95% confidence interval: 1.57–1.69). The association remained in several subgroup analyses of diseases also suspected to be associated with third-degree atrioventricular block. There was a significant interaction with comorbidities of interest including hypertension, atrial fibrillation, heart failure, and myocardial infarction.

Conclusion

In this nationwide study, T2DM was associated with a higher rate of third-degree atrioventricular block compared with matched controls. The association remained independent of atrioventricular nodal blocking agents and other comorbidities known to be associated with third-degree atrioventricular block.
Long-term mortality, cardiovascular events, and bleeding in stable patients 1 year after myocardial infarction: a Danish nationwide study
Authors: Christensen Daniel Mølager , Schjerning Anne-Marie , Smedegaard Lærke , Charlot Mette Gitz , Ravn Pauline B , Ruwald Anne Christine , Fosbøl Emil , Køber Lars , Torp-Pedersen Christian , Schou Morten , Gerds Thomas , Gislason Gunnar , Sehested Thomas S G
Published: November 2022

Aims

Outcomes after myocardial infarction (MI) improved during recent decades alongside better risk factor management and implementation of guideline-recommended treatments. However, it is unknown whether this applies to stable patients who are event-free 1 year after MI.

Methods and results

Using nationwide Danish registries, we included all patients with first-time MI during 2000–17 who survived 1 year free from bleeding and cardiovascular events (n = 82 108, median age 64 years, 68.2% male). Follow-up started 1 year after MI and continued through January 2022. Crude risks of mortality, cardiovascular events, and bleeding were estimated in consecutive 3-year periods. Standardized risks were calculated with respect to the distribution of age, sex, comorbidities, and treatments in the latter period. Guideline-recommended treatment use increased during the study period: e.g. statins (68.6–92.5%) and percutaneous coronary intervention (23.9–68.2%). The crude 5-year risks of outcomes decreased (all P-trend <0.001): Mortality, 18.6% (95% confidence interval [CI]: 17.9–19.2) to 12.5% (CI: 11.9–13.1); Recurrent MI, 7.5% (CI: 7.1–8.0) to 5.5% (CI: 5.1–6.0); Bleeding, 3.9% (CI: 3.6–4.3) to 2.7% (CI: 2.4–3.0). Crude 5-year risk of mortality in 2015–17 was as low as 2.6% for patients aged <60 years. Use of guideline-recommended treatments was associated with improved outcomes: After standardization for changes in treatments, 5-year risk of mortality in 2000–02 was 15.5% (CI: 14.9–16.2).

Conclusions

For patients who were event-free 1 year after MI, the long-term risks of mortality, cardiovascular events, and bleeding decreased significantly, along with an improved use of guideline-recommended treatments between 2000 and 2017. In the most recent period, 1 year after MI, the risk of additional events was lower than previously reported.
Sex-related characteristics and short-term outcomes of patients undergoing transcatheter tricuspid valve intervention for tricuspid regurgitation
Authors: Scotti Andrea , Coisne Augustin , Taramasso Maurizio , Granada Juan F , Ludwig Sebastian , Rodés-Cabau Josep , Lurz Philipp , Hausleiter Jörg , Fam Neil , Kodali Susheel K , Rosiene Joel , Feinberg Ari , Pozzoli Alberto , Alessandrini Hannes , Biasco Luigi , Brochet Eric , Denti Paolo , Estévez-Loureiro Rodrigo , Frerker Christian , Ho Edwin C , Monivas Vanessa , Nickenig Georg , Praz Fabien , Puri Rishi , Sievert Horst , Tang Gilbert H L , Andreas Martin , Von Bardeleben Ralph Stephan , Rommel Karl-Philipp , Muntané-Carol Guillem , Gavazzoni Mara , Braun Daniel , Koell Benedikt , Kalbacher Daniel , Connelly Kim A , Juliard Jean-Michel , Harr Claudia , Pedrazzini Giovanni , Russo Giulio , Philippon François , Schofer Joachim , Thiele Holger , Unterhuber Matthias , Himbert Dominique , Alcázar Marina Ureña , Wild Mirjam G , Windecker Stephan , Jorde Ulrich , Maisano Francesco , Leon Martin B , Hahn Rebecca T , Latib Azeem
Published: November 2022

Aims

The impact of sexuality in patients with significant tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI) is unknown. The aim of this study was to investigate sex-specific outcomes in patients with significant TR treated with TTVI vs. medical therapy alone.

Methods and results

The Transcatheter Tricuspid Valve Therapies (TriValve) registry collected data on patients with significant TR from 24 centres who underwent TTVI from 2016 to 2021. A control cohort was formed by medically managed patients with ≥severe isolated TR diagnosed in 2015–18. The primary endpoint was freedom from all-cause mortality. Secondary endpoints were heart failure (HF) hospitalization, New York Heart Association (NYHA) functional status, and TR severity. One-year outcomes were assessed for the TriValve cohort and compared with the control cohort with the inverse probability of treatment weighting (IPTW). A total of 556 and 2072 patients were included from the TriValve and control groups, respectively. After TTVI, there was no difference between women and men in 1-year freedom from all-cause mortality 80.9% vs. 77.9%, P = 0.56, nor in HF hospitalization (P = 0.36), NYHA Functional Classes III and IV (P = 0.17), and TR severity >2+ at last follow-up (P = 0.42). Multivariable Cox-regression weighted by IPTW showed improved 1-year survival after TTVI compared with medical therapy alone in both women (adjusted hazard ratio 0.45, 95% confidence interval 0.23–0.83, P = 0.01) and men (adjusted hazard ratio 0.42, 95% confidence interval 0.18–0.89, P = 0.03).

Conclusion

After TTVI in high-risk patients, there were no sex-related differences in terms of survival, HF hospitalization, functional status, and TR reduction up to 1 year. The IPTW analysis shows a survival benefit of TTVI over medical therapy alone in both women and men.
Antidepressant and Neuroprotective Effects of 3-Hydroxy Paroxetine, an Analog of Paroxetine in Rats
Authors: Hernández-Arrambide Pedro Efraín , Carrasco-Carballo Alan , Parra Irving , Chamorro-Arenas Delfino , Martínez Isabel , Luna Félix , Sartillo-Piscil Fernando , Tizabi Yousef , Mendieta Liliana
Published: November 2022

Background

Paroxetine (PX) is a widely used antidepressant with side effects such as weakness, dizziness, and trouble sleeping. In search of novel compounds with better efficacy and fewer side effects, we synthesized 3HPX, a hydroxylated analog of PX, and compared the 2 in silico for their pharmacokinetic and binding properties and in vivo for their antidepressant and potential neuroprotective effects.

Methods

In silico studies compared pharmacological properties as well as interactions of PX and 3HPX with the serotonin transporter. In vivo studies utilized an animal model of comorbid depression-Parkinson disease. Adult male Wistar rats were injected (sterotaxically) with lipopolysaccharide in the striatum (unilaterally), followed by 14 days of once-daily injections (i.p.) of 10 mg/kg PX or 3HPX. Animals were tested for motor asymmetry and locomotor activity as well as indices of anhedonia and helplessness using sucrose preference and forced swim tests, respectively. Brains of these animals were collected after the last test, and tyrosine hydroxylase–positive neurons in substantia nigra pars compacta and Iba-1–positive stained microglia in ipsilateral striatum were measured.

Results

In silico findings indicated that 3HPX could bind stronger to serotonin transporter and also have a better clearance and hence less toxicity compared with PX. In vivo results revealed a more effective reversal of immobility in the swim test, substantial increase in tyrosine hydroxylase–positive cells in the substantia nigra pars compacta, and more ramified Iba-1+ cells by 3HPX compared with PX.

Conclusion

The findings suggest superior effectiveness of 3HPX as an antidepressant and neuroprotectant compared with PX and hence potential utility in Parkinson disease depression co-morbidity.
Comparison of ultrafiltration and microdialysis for ceftriaxone protein-binding determination
Authors: Sanz-Codina Maria , Wicha Sebastian G , Wulkersdorfer Beatrix , Al Jalali Valentin , Van Os Wisse , Vossen Matthias G , Bauer Martin , Lackner Edith , Dorn Christoph , Zeitlinger Markus
Published: November 2022

Background

High protein binding (PB) of antibiotics has an impact on their antimicrobial activity. It has been questioned whether in vitro PB determination can capture the dynamic and concentration-dependent PB of highly bound antibiotics.

Objectives

This clinical study compared in vitro ultrafiltration (UF) and in vivo IV microdialysis (MD) methods to determine ceftriaxone PB.

Methods

Six healthy male volunteers received a single IV 2 g dose of ceftriaxone. Unbound ceftriaxone plasma concentrations were measured with MD and venous plasma sampling with subsequent UF. Pharmacokinetic parameters were determined using non-compartmental pharmacokinetic analysis. Non-linear mixed-effects modelling was used to quantify the PB. The PTA was estimated.

Results

The Cmax of ceftriaxone total plasma concentration (297.42 ± 21.0 mg/L) was approximately 5.5-fold higher than for free concentrations obtained with UF (52.83 ± 5.07 mg/L), and only 3.5-fold higher than for free concentrations obtained with MD (81.37 ± 26.93 mg/L). Non-linear, saturable PB binding was confirmed for both UF and MD. Significantly different dissociation constants (Kd) for the albumin/ceftriaxone complex were quantified: in UF it was 23.7 mg/L (95% CI 21.3–26.2) versus 15.9 mg/L (95% CI 13.6–18.6) in MD. Moreover, the estimated number of binding sites (95% CI) per albumin molecule was 0.916 (0.86–0.97) in UF versus 0.548 in MD (0.51–0.59). The PTA obtained with MD was at most 27% higher than with UF.

Conclusions

In vitro UF versus in vivo intravasal MD revealed significantly different PB, especially during the distribution phase. The method of PB determination could have an impact on the breakpoint determination and dose optimisation of antibiotics.
Effects of light color and intensity on discrimination of red objects in broilers
Authors: Pan Chenghao , Wang Shouyi , He Pengguang , Hayat Khawar , Jin Hao , Bai Leshang , Hu Yuchen , Pan Jinming
Published: November 2022

Poultry are sensitive to red objects, such as comb and blood on the body surface, likely inducing injurious pecking in flocks. Light is an important factor that affects the pecking behavior of poultry. A wooden box was built to investigate the effects of Light Emitting Diode (LED) light color (warm white and cold white) and intensity (5 and 50 lux) of background light on the discrimination of red objects in broilers. A piece of red photographic paper (Paper 1) was used to simulate a red object and paired with another piece of paper (Paper 2 to 8) with a different color. Bigger number of the paired paper indicated greater color difference. The experiment consisted of three phases: adaptation, training, and test. In the adaptation phase, birds were selected for the adaptation to reduce the stress from the box. In the training phase, birds were trained to discriminate and peck at Paper 1 when paired with Paper 8 under one type of background light. Twenty-three birds were tested when the paired paper was changed from Paper 7 to 2. Each pair of paper included 12 trials for every bird, and response time to peck and proportion of choices of Paper 1 in the last 10 trials were collected. The results showed that broilers tested under 5 lux light had longer response times than broilers tested under 50 lux light (P < 0.05). When Paper 1 was paired with paper 7, broilers tested under warm white light had lower proportion of choices of Paper 1 than those tested under cold white light (P < 0.05). Color difference had a significant effect on response time of broilers (P < 0.05). Moreover, the proportion of choices of Paper 1 decreased to 50% (chance-level performance) when color of the paired paper was gradually similar to Paper 1. Conclusively, rearing broilers in warm white rather than cold white light with appropriate light intensity should be recommended to reduce damaging pecking behavior in broiler production.
Real-time unmanned aerial vehicle flight path prediction using a bi-directional long short-term memory network with error compensation
Authors: Chen Sifan , Chen Baihe , Shu Peng , Wang Zhensheng , Chen Chengbin
Published: November 2022

In recent years, unmanned aerial vehicle (UAV) autonomous flight technology has been applied in many fields. However, in the process of autonomous operation, the UAV may deviate from the set flight path due to various disturbance factors, which results in mission failure. In order to find the abnormal situation in time and take corresponding measures, it is necessary to monitor the operation state of the UAV. Predicting the UAV flight path is the main monitoring method at present; however, the accuracy and real-time of the existing prediction methods are limited. Therefore, this paper proposes an error compensation Bessel bidirectional long short-term memory real-time path prediction model deployed in ground stations. First, because of inconsistency of the units in all directions of the original positioning information provided by global positioning system, the Bessel geodetic coordinate transformation is introduced to unify the units of three-dimensional coordinate data, so as to improve the prediction accuracy. Second, considering the problems of poor data quality and data missing in the operation process, the least square fitting method is used to supplement and correct the positioning coordinate data to obtain more reliable and accurate path observation values as the model input. Finally, a deep learning path prediction model based on bi-directional long short-term memory (BiLSTM) network is constructed, and the appropriate network parameters are determined with the prediction accuracy and time as evaluation indicators. In order to further improve the prediction accuracy, a compensator based on proportional integral differential error control theory is designed according to the output characteristics of the BiLSTM network, which is used for providing compensation values for the prediction results of the model. The training and testing results using the actual flight data of UAV operation show that, under the experimental environment built, the model proposed in this paper can complete the UAV flight path prediction with root mean square error < 1 meter within 0.1 second, and has better performance and higher prediction accuracy than other neural network models.
Body mass index and molecular subtypes of colorectal cancer
Authors: Murphy Neil , Newton Christina C , Song Mingyang , Papadimitriou Nikos , Hoffmeister Michael , Phipps Amanda I , Harrison Tabitha A , Newcomb Polly A , Aglago Elom K , Berndt Sonja I , Brenner Hermann , Buchanan Daniel D , Cao Yin , Chan Andrew T , Chen Xuechen , Cheng Iona , Chang-Claude Jenny , Dimou Niki , Drew David , Farris Alton B , French Amy J , Gallinger Steven , Georgeson Peter , Giannakis Marios , Giles Graham G , Gruber Stephen B , Harlid Sophia , Hsu Li , Huang Wen-Yi , Jenkins Mark A , Laskar Ruhina S , Le Marchand Loic , Limburg Paul , Lin Yi , Mandic Marko , Nowak Johnathan A , Obón-Santacana Mereia , Ogino Shuji , Qu Conghui , Sakoda Lori C , Schoen Robert E , Southey Melissa C , Stadler Zsofia K , Steinfelder Robert S , Sun Wei , Thibodeau Stephen N , Toland Amanda E , Trinh Quang M , Tsilidis Kostas K , Ugai Tomotaka , Van Guelpen Bethany , Wang Xiaoliang , Woods Michael O , Zaidi Syed H , Gunter Marc J , Peters Ulrike , Campbell Peter T
Published: November 2022

Background

Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease.

Methods

We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables.

Results

Higher BMI was associated with increased CRC risk (OR per 5 kg/m2 = 1.18, 95% CI = 1.15 to 1.22). The positive association was stronger for men than women but similar across tumor subtypes defined by individual molecular markers. In analyses by Jass type, higher BMI was associated with elevated CRC risk for types 1-4 cases but not for type 5 CRC cases (considered familial-like/Lynch syndrome microsatellite instability-H, CpG island methylator phenotype-low or negative, BRAF-wild type, KRAS-wild type, OR = 1.04, 95% CI = 0.90 to 1.20). This pattern of associations for BMI and Jass types was consistent by sex and design of contributing studies (cohort or case-control).

Conclusions

In contrast to previous reports with fewer study participants, we found limited evidence of heterogeneity for the association between BMI and CRC risk according to molecular subtype, suggesting that obesity influences nearly all major pathways involved in colorectal carcinogenesis. The null association observed for the Jass type 5 suggests that BMI is not a risk factor for the development of CRC for individuals with Lynch syndrome.
A novel genome sequence ofJasminum sambachelps uncover the molecular mechanism underlying the accumulation of jasmonates
Authors: Xu Min , Gao Qiang , Jiang Mengwei , Wang Wenling , Hu Juan , Chang Xiaojun , Liu Dinggao , Liang Yuwei , Jiang Yifan , Chen Fei , Li Chuhao , Huang Haoran , Chen Feng , Li Fan , Trigiano Robert N , Wang Jihua , Jiao Chen , Zhou Xiaofan , Zhang Liangsheng
Published: November 2022

Jasminum sambac is a well-known plant for its attractive and exceptional fragrance, the flowers of which are used to produce scented tea. Jasmonate (JA), an important plant hormone was first identified in Jasminum species. Jasmine plants contain abundant JA naturally, of which the molecular mechanisms of synthesis and accumulation are not clearly understood. Here, we report a telomere-to-telomere consensus assembly of a double-petal J. sambac genome along with two haplotype-resolved genomes. We found that gain-and-loss, positive selection, and allelic specific expression of aromatic volatile-related genes contributed to the stronger flower fragrance in double-petal J. sambac compared with single- and multi-petal jasmines. Through comprehensive comparative genomic, transcriptomic, and metabolomic analyses of double-petal J. sambac, we revealed the genetic basis of the production of aromatic volatiles and salicylic acid (SA), and the accumulation of JA under non-stress conditions. We identified several key genes associated with JA biosynthesis, and their non-stress related activities lead to extraordinarily high concentrations of JA in tissues. High JA synthesis coupled with low degradation in J. sambac results in accumulation of high JA under typical environmental conditions, similar to the accumulation mechanism of SA. This study offers important insights into the biology of J. sambac, and provides valuable genomic resources for further utilization of natural products.
Hyperbaric Oxygen Therapy for Veterans With Treatment-resistant PTSD: A Longitudinal Follow-up Study
Authors: Doenyas-Barak Keren , Kutz Ilan , Levi Gabriela , Lang Erez , Beberashvili Ilia , Efrati Shai
Published: November 2022

Introduction

PTSD is common among veteran combatants. PTSD is characterized by brain changes, for which available treatments have shown limited effect. In a short-term study, we showed that hyperbaric oxygen therapy (HBOT) induced neuroplasticity and improved clinical symptoms of veterans with treatment-resistant PTSD. Here, we evaluated the long-term clinical symptoms of the participants of that study.

Materials and Methods

Veterans from our short-term study were recruited 1 or more years after completing HBOT. The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and self-reported questionnaires were administered at a single site visit. Changes in clinical scores between long-term, short-term, and pretreatment evaluations were analyzed.

Results

Of the 28 participants who received HBOT during or following the short-term study, 22 agreed to participate in the current study. At a mean of 704 ± 230 days after completing the HBOT course, the mean CAPS-5 score (26.6 ± 14.4) was significantly better (lower) than at the pre-HBOT evaluation (47.5 ± 13.1, P < .001) and not statistically different from the short-term evaluation (28.6 ± 16.7, P = .745). However, for the CAPS-5 subcategory D (cognition and mood symptoms), the mean score was significantly better (lower) at long-term than at short-term evaluation (7.6 ± 5.1 vs. 10.0 ± 6.0, P < .001). At the long-term compared to the pretreatment evaluation, higher proportions of the participants were living with life partners (10 (46%) vs. 17 (77%), P = .011) and were working (9 (41%) vs. 16 (73%), P = .033). Decreases were observed between pretreatment and the long-term follow-up, in the number of benzodiazepine users (from 10 (46%) to 4 (18%), P = .07) and in the median (range) cannabis daily dose (from 40.0 g (0-50) to 22.5 g (0-30), P = .046).

Conclusions

The beneficial clinical effects of HBOT are persistent and were not attenuated at long-term follow-up of about 2 years after completion of HBOT. Additional long-term effects of the treatment were observed in social function and in decreased medication use.
Incidence and survival of primary central nervous system tumors diagnosed in 4 Canadian provinces from 2010 to 2015
Authors: Walker Emily V , Davis Faith G , Yasmin Farzana , Smith Trenton R , Yuan Yan
Published: November 2022

Background

The Brain Tumor Registry of Canada was established in 2016 to enhance infrastructure for surveillance and clinical research on Central Nervous System (CNS) tumors. We present information on primary CNS tumors diagnosed among residents of Canada from 2010 to 2015.

Methods

Data from 4 provincial cancer registries were analyzed representing approximately 67% of the Canadian population. Age-standardized incidence rates (ASIR) and 95% confidence intervals (CI) were calculated using the 2011 Canadian population age distribution. Net survival was estimated using the Pohar-Perme method.

Results

A total of 31 644 primary tumors were identified for an ASIR of 22.8 per 100 000 person-years. Nonmalignant tumors made up 47.1% of all classified tumors, with mixed behaviors present in over half of histology groupings. Unclassified were 19.5% of all tumors. The most common histological subtypes are meningiomas (ASIR = 5.5 per 100 000 person-years); followed by glioblastomas (ASIR 4.0 per 100 000 person-years). The overall 5-year net survival rate for CNS tumors was 65.5%; females 70.2% and males 60.4%. GBMs continue to be the most lethal CNS tumors for all sex and age groups.

Conclusions

The low annual frequency of most CNS tumor subtypes emphasizes the value of population-based data on all primary CNS tumors diagnosed among Canadians. The large number of histological categories including mixed behaviors and the proportion of unclassified tumors emphasizes the need for complete reporting. Variation in incidence and survival across histological groups by sex and age highlights the need for comprehensive and histology-specific reporting. These data can be used to better inform research and health system planning.
NPOmix: A machine learning classifier to connect mass spectrometry fragmentation data to biosynthetic gene clusters
Authors: Leão Tiago F , Wang Mingxun , da Silva Ricardo , Gurevich Alexey , Bauermeister Anelize , Gomes Paulo Wender P , Brejnrod Asker , Glukhov Evgenia , Aron Allegra T , Louwen Joris J R , Kim Hyun Woo , Reher Raphael , Fiore Marli F , van der Hooft Justin J J , Gerwick Lena , Gerwick William H , Bandeira Nuno , Dorrestein Pieter C
Published: November 2022

Microbial specialized metabolites are an important source of and inspiration for many pharmaceuticals, biotechnological products and play key roles in ecological processes. Untargeted metabolomics using liquid chromatography coupled with tandem mass spectrometry is an efficient technique to access metabolites from fractions and even environmental crude extracts. Nevertheless, metabolomics is limited in predicting structures or bioactivities for cryptic metabolites. Efficiently linking the biosynthetic potential inferred from (meta)genomics to the specialized metabolome would accelerate drug discovery programs by allowing metabolomics to make use of genetic predictions. Here, we present a k-nearest neighbor classifier to systematically connect mass spectrometry fragmentation spectra to their corresponding biosynthetic gene clusters (independent of their chemical class). Our new pattern-based genome mining pipeline links biosynthetic genes to metabolites that they encode for, as detected via mass spectrometry from bacterial cultures or environmental microbiomes. Using paired datasets that include validated genes-mass spectral links from the Paired Omics Data Platform, we demonstrate this approach by automatically linking 18 previously known mass spectra (17 for which the biosynthesis gene clusters can be found at the MIBiG database plus palmyramide A) to their corresponding previously experimentally validated biosynthetic genes (e.g., via nuclear magnetic resonance or genetic engineering). We illustrated a computational example of how to use our Natural Products Mixed Omics (NPOmix) tool for siderophore mining that can be reproduced by the users. We conclude that NPOmix minimizes the need for culturing (it worked well on microbiomes) and facilitates specialized metabolite prioritization based on integrative omics mining.
Obesity in children with narcolepsy: metabolic and endocrine comorbidities
Authors: Arvis Laura , Doye Emilie , Perge Kevin , Zhang Min , Thieux Marine , Guyon Aurore , Franco Patricia , Villanueva Carine
Published: November 2022

Study Objectives

Narcolepsy with cataplexy is associated with obesity in children. We proposed to assess whether metabolic complications were linked to narcolepsy regardless of obesity. The second aim of the study was to compare endocrine comorbidities in obese children with narcolepsy and control patients.

Methods

We performed a case-control study in Pediatric Sleep Unit and Pediatric Endocrinology Unit of Woman Mother Child Hospital (Lyon, France) comparing 22 children with narcolepsy with 22 sex-, pubertal stage-, and BMI-matched non-syndromic obese patients. Clinical examination, biological measurements including an oral glucose tolerance test, and abdominal ultrasound were performed.

Results

No difference regarding glucidic, lipid profile, hepatic, respiratory, and cardiovascular parameters were found between narcoleptic and control participants. Insulin sensitivity did not differ between the two groups. Control patients had more first-degree family history of overweight or obesity than children with narcolepsy (83% vs. 50%, p = .05). Prevalence of precocious puberty in children with narcolepsy was not higher than in control participants, but all the cases of advanced puberty involved children with narcolepsy who were diagnosed before 11 years old. All cases of central hypothyroidism belong to the narcoleptic group, who presented lower thyroid-stimulating hormone and fTA values compared to control children (respectively p = .03 and p = .001).

Conclusions

No difference regarding metabolic complications was found between children with narcolepsy and control participants. Thus, metabolic disorders may be related to weight gain rather than a narcolepsy-specific risk. The presence of hypothyroidism and advanced puberty suggests a global involvement of hypothalamic structures in children with narcolepsy.
SARS-CoV-2 intra-host single-nucleotide variants associated with disease severity
Authors: Zhang Yi , Jiang Ning , Qi Weiqiang , Li Tao , Zhang Yumeng , Wu Jing , Zhang Haocheng , Zhou Mingzhe , Cui Peng , Yu Tong , Fu Zhangfan , Zhou Yang , Lin Ke , Wang Hongyu , Wei Tongqing , Zhu Zhaoqin , Ai Jingwen , Qiu Chao , Zhang Wenhong
Published: November 2022

Variants of severe acute respiratory syndrome coronavirus 2 frequently arise within infected individuals. Here, we explored the level and pattern of intra-host viral diversity in association with disease severity. Then, we analyzed information underlying these nucleotide changes to infer the impetus including mutational signatures and immune selection from neutralizing antibody or T-cell recognition. From 23 January to 31 March 2020, a set of cross-sectional samples were collected from individuals with homogeneous founder virus regardless of disease severity. Intra-host single-nucleotide variants (iSNVs) were enumerated using deep sequencing. Human leukocyte antigen (HLA) alleles were genotyped by Sanger sequencing. Medical records were collected and reviewed by attending physicians. A total of 836 iSNVs (3–106 per sample) were identified and distributed in a highly individualized pattern. The number of iSNVs paced with infection duration peaked within days and declined thereafter. These iSNVs did not stochastically arise due to a strong bias toward C > U/G > A and U > C/A > G substitutions in reciprocal proportion with escalating disease severity. Eight nonsynonymous iSNVs in the receptor-binding domain could escape from neutralization, and eighteen iSNVs were significantly associated with specific HLA alleles. The level and pattern of iSNVs reflect the in vivo viral–host interaction and the disease pathogenesis.
Translocation of Fungicides and Their Efficacy in ControllingPhellinus noxius, the Cause of Brown Root Rot Disease
Authors: Liao Ting-Zhi , Chen Yu-Hsuan , Tsai Jyh-Nong , Chao Chieh , Huang Tzu-Pi , Hong Cheng-Fang , Wu Zong-Chi , Tsai Isheng Jason , Lee Hsin-Han , Klopfenstein Ned B. , Kim Mee-Sook , Stewart Jane E. , Atibalentja Ndeme , Brooks Fred E. , Cannon Philip G. , Farid A. Mohd , Hattori Tsutomu , Kwan Hoi-Shan , Ching Lam Regent Yau , Ota Yuko , Sahashi Norio , Schlub Robert L. , Shuey Louise S. , Tang Alvin M. C. , Chung Chia-Lin
Published: November 2022

Brown root rot disease (BRRD), caused by Phellinus noxius, is an important tree disease in tropical and subtropical areas. To improve chemical control of BRRD and deter emergence of fungicide resistance in P. noxius, this study investigated control efficacies and systemic activities of fungicides with different modes of action. Fourteen fungicides with 11 different modes of action were tested for inhibitory effects in vitro on 39 P. noxius isolates from Taiwan, Hong Kong, Malaysia, Australia, and Pacific Islands. Cyproconazole, epoxiconazole, and tebuconazole (Fungicide Resistance Action Committee [FRAC] 3, target-site G1) inhibited colony growth of P. noxius by 99.9 to 100% at 10 ppm and 97.7 to 99.8% at 1 ppm. The other effective fungicide was cyprodinil + fludioxonil (FRAC 9 + 12, target-site D1 + E2), which showed growth inhibition of 96.9% at 10 ppm and 88.6% at 1 ppm. Acropetal translocation of six selected fungicides was evaluated in bishop wood (Bischofia javanica) seedlings by immersion of the root tips in each fungicide at 100 ppm, followed by liquid or gas chromatography tandem mass spectrometry analyses of consecutive segments of root, stem, and leaf tissues at 7 and 21 days posttreatment. Bidirectional translocation of the fungicides was also evaluated by stem injection of fungicide stock solutions. Cyproconazole and tebuconazole were the most readily absorbed by roots and efficiently transported acropetally. Greenhouse experiments suggested that cyproconazole, tebuconazole, and epoxiconazole have a slightly higher potential for controlling BRRD than mepronil, prochloraz, and cyprodinil + fludioxonil. Because all tested fungicides lacked basipetal translocation, soil drenching should be considered instead of trunk injection for their use in BRRD control.
Complete Genome Sequence Data of Novel Streptomyces angustmyceticus Strain CQUSa03, a Potential Biological Control Agent for Potato Oomycete and Fungal Diseases
Authors: Luo Xiumei , Qu Jingtao , Ren Maozhi
Published: November 2022

Streptomyces angustmyceticus CQUSa03 was recently isolated from the rhizosphere soil of a potato resistant variety, which showed strong biocontrol activity against potato late blight and other fungal diseases. To elucidate the biocontrol mechanism, the whole genome of CQUSa03 was sequenced using second-generation Illumina and third-generation Nanopore sequencing technologies. The assembled genome of CQUSa03 was 8,107,672 bp, containing one chromosome and three plasmids, with an average GC content of 72.29%, 6,914 protein-coding genes, 21 rRNA, and 68 tRNA. In addition, 29 important secondary metabolite biosynthetic gene clusters were identified in the CQUSa03 genome. The related genes of β-1,3-glucanase and chitinase, which can degrade the cell wall of fungal pathogens, were also found. CQUSa03 is predicted to have great potential in agriculture by producing a variety of antagonistic active compounds, cell wall hydrolases, and bacteriostatic peptides to control diseases. The genome sequence provided a theoretical basis for analyzing the biocontrol mechanism of S. angustmyceticus CQUSa03 and laid a foundation for the development and industrialization of biocontrol agents.
In Vitro Fungicide Sensitivity and Effect of Organic Matter Concentration on Fungicide Bioavailability in Take-All Root Rot Pathogens Isolated from North Carolina
Authors: Stephens Cameron M. , Gannon Travis W. , Thiessen Lindsey D. , Cubeta Marc A. , Kerns James P.
Published: November 2022

Take-all root rot (TARR) of ultradwarf bermudagrass is caused by Gaeumannomyces graminis (Gg), Gaeumannomyces graminicola (Ggram), Candidacolonium cynodontis (Cc), and Magnaporthiopsis cynodontis (Mc). Multiple pathogens have recently been associated with this disease, and biological parameters such as fungicide sensitivity have not been explored in ultradwarf bermudagrass. Although fungicides are commonly used to mitigate disease development, high organic matter present in the turfgrass system could limit the bioavailability of fungicides. Fungicide bioavailability can be influenced by organic matter concentration, and the physicochemical properties of fungicides could provide insight into their binding affinity. However, the influence of organic matter content on fungicide bioavailability has not been investigated. Therefore, the in vitro sensitivity of Gg, Ggram, Cc, and Mc to 14 different fungicides across three chemical classes was determined. An in vitro bioavailability assay was developed using three fungicides and three organic matter concentrations. Generally, demethylation inhibitor and quinone outside inhibitor fungicides provided the greatest reduction in mycelial growth, whereas succinate dehydrogenase inhibitors did not reduce mycelial growth. These data can serve as a foundation for TARR pathogen sensitivity to inform in vitro fungicide sensitivity studies and field efficacy trials. Pyraclostrobin and propiconazole have a high affinity to bind to organic matter, which was evident as more fungicide was required to inhibit Gg growth as organic matter concentration increased. This was not observed when evaluating azoxystrobin, which has a lower binding affinity. Understanding how TARR pathogens respond to fungicide in vitro and how organic matter concentration affects in vitro sensitivity will improve fungicide selection for management of TARR.