bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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 &lt; 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

Abstract
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

AbstractBackgroundAn 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.MethodsSPECTRA 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.ResultsOne 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.ConclusionsIn 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

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

Abstract

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 &lt;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 &lt;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

AbstractAimsThe 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 resultsThe 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 &gt;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).ConclusionAfter 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

AbstractBackgroundParoxetine (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.MethodsIn 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.ResultsIn 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.ConclusionThe 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

Abstract

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

Abstract
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 &lt; 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 &lt; 0.05). Color difference had a significant effect on response time of broilers (P &lt; 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.