bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis induction
Authors: Ryczkowska Małgorzata , Maciejewska Natalia , Olszewski Mateusz , Witkowska Milena , Makowiec Sławomir 
Published: November 2022

AbstractThe anticancer properties of quinolones is a topic of interest among researchers in the scientific world. Because these compounds do not cause side effects, unlike the commonly used cytostatics, they are considered a promising source of new anticancer drugs. In this work, we designed a brief synthetic pathway and obtained a series of novel 8-phenyltetrahydroquinolinone derivatives functionalized with benzyl-type moieties at position 3. The compounds were synthesized via classical reactions such as nucleophilic substitution, solvent lysis, and condensation. Biological evaluation revealed that 3-(1-naphthylmethyl)-4-phenyl-5,6,7,8-tetrahydro-1H-quinolin-2-one (4a) exhibited potent cytotoxicity toward colon (HTC-116) and lung (A549) cancer cell lines. Analysis of the mechanism of action of compounds showed that compound 4a induced cell cycle arrest at the G2/M phase, leading to apoptotic cell death via intrinsic and extrinsic pathways. Taken together, the findings of the study suggest that tetrahydroquinolinone derivatives bearing a carbonyl group at position 2 could be potential lead compounds to develop anticancer agents for the treatment of lung cancers.
Females exhibit higher GluA2 levels and outperform males in active place avoidance despite increased amyloid plaques in TgF344-Alzheimer’s rats
Authors: Chaudry Osama , Ndukwe Kelechi , Xie Lei , Figueiredo-Pereira Maria , Serrano Peter , Rockwell Patricia 
Published: November 2022

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disease that is most prevalent in females. While estrogen provides neuroprotection in females, sex mediated differences in the development of AD pathology are not fully elucidated. Therefore, comparing events between sexes in early-stage AD pathology may reveal more effective therapeutic targets of intervention. To address sex differences, we analyzed early-stage 9-month male and female TgF344-AD (Tg-AD) rats, an AD model carrying the APPswe and Presenilin 1 (PS1ΔE9) mutations that develops progressive age-dependent AD pathology similar to humans. Tg-AD females significantly outperformed Tg-AD males in the active place avoidance (aPAT) test that assesses hippocampal-dependent spatial learning and memory. However, comparisons between Tg-AD male or female rats and their WT counterparts showed significant deficits for female but not male rats. Nevertheless, Tg-AD females experienced significantly less hippocampal neuronal loss with higher GluA2 subunit levels than Tg-AD males. Unexpectedly, Tg-AD females displayed higher levels of hippocampal amyloid plaques than Tg-AD males. Thus, we propose that GluA2 may provide a neuroprotective function for Tg-AD females in our rat model by mitigating cognitive impairment independently of amyloid plaques. Elucidating this protective mechanism in AD could lead to new targets for early intervention.
Pinning potential in highly performant CaKFe4As4 superconductor from DC magnetic relaxation and AC multi-frequency susceptibility studies
Authors: Ionescu A. M. , Ivan I. , Crisan D. N. , Galluzzi A. , Polichetti M. , Ishida S. , Iyo A. , Eisaki H. , Crisan A. 
Published: November 2022

AbstractWe have investigated the pinning potential of high-quality single crystals of superconducting material CaKFe4As4 having high critical current density and very high upper critical field using both magnetization relaxation measurements and frequency-dependent AC susceptibility. Preliminary studies of the superconducting transition and of the isothermal magnetization loops confirmed the high quality of the samples, while temperature dependence of the AC susceptibility in high magnetic fields show absolutely no dependence on the cooling conditions, hence, no magnetic history. From magnetization relaxation measurements were extracted the values of the normalized pinning potential U*, which reveals a clear crossover between elastic creep and plastic creep. The extremely high values of U*, up to 1200 K around the temperature of 20 K lead to a nearly zero value of the probability of thermally-activated flux jumps at temperatures of interest for high-field applications. The values of the creep exponents in the two creep regimes resulted from the analysis of the magnetization relaxation data are in complete agreement with theoretical models. Pinning potentials were also estimated, near the critical temperature, from AC susceptibility measurements, their values being close to those resulted (at the same temperature and DC field) from the magnetization relaxation data.
Linoleic acid binds to SARS-CoV-2 RdRp and represses replication of seasonal human coronavirus OC43
Authors: Goc Anna , Sumera Waldemar , Rath Matthias , Niedzwiecki Aleksandra 
Published: November 2022

AbstractFatty acids belong to a group of compounds already acknowledged for their broad antiviral efficacy. However, little is yet known about their effect on replication of human coronaviruses. To shed light on this subject, we first screened 15 fatty acids, three lipid-soluble vitamins, and cholesterol, on SARS-CoV-2 RdRp, and identified the four fatty acids with the highest RdRp inhibitory potential. Among them, linoleic acid was found to have the greatest interaction with SARS-CoV-2 RdRp, with its direct binding to the cavity formed by the RNA double helix and protein. Linoleic acid forms hydrophobic interactions with multiple residues, and at the same time forms electrostatic interactions including the hydrogen bond with Lys593 and Asp865. In line with these results, a dose-dependent inhibition of HCoV-OC43 replication in vitro was observed, additionally strengthened by data from in vivo study, which also confirmed anti-inflammatory potential of linoleic acid. Based on these results, we concluded that our study provides a new understanding of the antiviral properties of fatty acids against human coronaviruses including the SARS-CoV-2 strain. Particularly, they lays down a new prospect for linoleic acid’s RdRp-inhibitory activity, as a candidate for further studies, which are warranted to corroborate the results presented here.
Hyperfibrinolysis and fibrinolysis shutdown in patients with traumatic brain injury
Authors: Nakae Ryuta , Murai Yasuo , Wada Takeshi , Fujiki Yu , Kanaya Takahiro , Takayama Yasuhiro , Suzuki Go , Naoe Yasutaka , Yokota Hiroyuki , Yokobori Shoji 
Published: November 2022

AbstractTraumatic brain injury (TBI) is associated with coagulation/fibrinolysis disorders. We retrospectively evaluated 61 TBI cases transported to hospital within 1 h post-injury. Levels of thrombin-antithrombin III complex (TAT), D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were measured on arrival and 3 h, 6 h, 12 h, 1 day, 3 days and 7 days after injury. Multivariate logistic regression analysis was performed to identify prognostic factors for coagulation and fibrinolysis. Plasma TAT levels peaked at admission and decreased until 1 day after injury. Plasma D-dimer levels increased, peaking up to 3 h after injury, and decreasing up to 3 days after injury. Plasma PAI-1 levels increased up to 3 h after injury, the upward trend continuing until 6 h after injury, followed by a decrease until 3 days after injury. TAT, D-dimer, and PAI-1 were elevated in the acute phase of TBI in cases with poor outcome. Multivariate logistic regression analysis showed that D-dimer elevation from admission to 3 h after injury and PAI-1 elevation from 6 h to 1 day after injury were significant negative prognostic indicators. Post-TBI hypercoagulation, fibrinolysis, and fibrinolysis shutdown were activated consecutively. Hyperfibrinolysis immediately after injury and subsequent fibrinolysis shutdown were associated with poor outcome.
How phosphorylation impacts intrinsically disordered proteins and their function
Authors: Newcombe Estella A. , Delaforge Elise , Hartmann-Petersen Rasmus , Skriver Karen , Kragelund Birthe B. 
Published: November 2022

Abstract
Phosphorylation is the most common post-translational modification (PTM) in eukaryotes, occurring particularly frequently in intrinsically disordered proteins (IDPs). These proteins are highly flexible and dynamic by nature. Thus, it is intriguing that the addition of a single phosphoryl group to a disordered chain can impact its function so dramatically. Furthermore, as many IDPs carry multiple phosphorylation sites, the number of possible states increases, enabling larger complexities and novel mechanisms. Although a chemically simple and well-understood process, the impact of phosphorylation on the conformational ensemble and molecular function of IDPs, not to mention biological output, is highly complex and diverse. Since the discovery of the first phosphorylation site in proteins 75 years ago, we have come to a much better understanding of how this PTM works, but with the diversity of IDPs and their capacity for carrying multiple phosphoryl groups, the complexity grows. In this Essay, we highlight some of the basic effects of IDP phosphorylation, allowing it to serve as starting point when embarking on studies into this topic. We further describe how recent complex cases of multisite phosphorylation of IDPs have been instrumental in widening our view on the effect of protein phosphorylation. Finally, we put forward perspectives on the phosphorylation of IDPs, both in relation to disease and in context of other PTMs; areas where deep insight remains to be uncovered.
The chameleonic behavior of p53 in health and disease: the transition from a client to an aberrant condensate scaffold in cancer
Authors: Marques Mayra A. , de Oliveira Guilherme A.P. , Silva Jerson L. 
Published: November 2022

Abstract
In 1972, the Weber statement, “The multiplicity of interactions and the variety of effects that follow from them show that multimer proteins are unlikely to be limited to a minimal number of allowed conformations,” first addressed the dynamic nature of proteins. This idea serves as a foundation for understanding why several macromolecules, such as p53, exhibit the properties of a molecular chameleon. Functionally competent states comprise a myriad of p53 three-dimensional arrangements depending on the stimuli. For instance, the interaction of p53 with nuclear components could induce liquid–liquid phase separation (LLPS) and the formation of membraneless organelles. The functional or deleterious role of p53 in liquid droplets is still unclear. Functional aspects display p53 interconverting between droplets and tetramer with its functional abilities maintained. In contrast, the aberrant phase separation is likely to fuel the aggregation path, usually associated with the onset and progression of age-related neurodegenerative diseases and cancer. Here, we gathered the most relevant aspects that lead p53 to phase separation and the resulting structural effects, attempting to understand p53’s functional and disease-relevant processes. Aberrant phase separation and aggregation of mutant p53 have become important therapeutic targets against cancer.
Astrocyte strategies in the energy-efficient brain
Authors: Fernández-González Irene , Galea Elena 
Published: November 2022

AbstractAstrocytes generate ATP through glycolysis and mitochondrion respiration, using glucose, lactate, fatty acids, amino acids, and ketone bodies as metabolic fuels. Astrocytic mitochondria also participate in neuronal redox homeostasis and neurotransmitter recycling. In this essay, we aim to integrate the multifaceted evidence about astrocyte bioenergetics at the cellular and systems levels, with a focus on mitochondrial oxidation. At the cellular level, the use of fatty acid β-oxidation and the existence of molecular switches for the selection of metabolic mode and fuels are examined. At the systems level, we discuss energy audits of astrocytes and how astrocytic Ca2+ signaling might contribute to the higher performance and lower energy consumption of the brain as compared to engineered circuits. We finish by examining the neural-circuit dysregulation and behavior impairment associated with alterations of astrocytic mitochondria. We conclude that astrocytes may contribute to brain energy efficiency by coupling energy, redox, and computational homeostasis in neural circuits.
The Effect of Vocal Hygiene Education Programs on Voice Quality in Professional Voice Users: A Systematic Review
Authors: Vermeulen Rouxjeanne , du Toit Maria , van Lierde Kristiane , van der Linde Jeannie 
Published: November 2022

Purpose:
This study aimed to critically appraise recent peer-reviewed scientific evidence on the effect of vocal hygiene education on voice quality and function directly and indirectly measured by auditory-perceptual, acoustic, and self-report measures in professional voice users.

Method:
A systematic review was conducted utilizing the Preferred Reporting Items for Systematic review and Meta-Analyses Protocols (PRISMA-P) guidelines. Five databases were searched using the keywords “vocal hygiene,” “vocal hygiene education,” “vocal health,” “vocal quality,” and “voice quality” with Boolean phrases “AND” and “OR.” Twenty-three studies that met the eligibility criteria were included. Scoring was based on the American Speech-Language-Hearing Association's levels of evidence and quality indicators, as well as the Newcastle–Ottawa Scale for assessing the risk of bias.

Results:

Four studies (17%) linked low awareness of vocal hygiene or insufficient vocal hygiene education to self-reported acute and chronic voice symptoms, as well as a greater perception of voice handicap among professional voice users. Numerous studies (
n
= 10; 43%) showed that adequate voice training or vocal hygiene education was linked to positive voice outcomes. Six studies (6.26%), however, demonstrated that vocal hygiene education is more effective when combined with direct voice therapy. When vocal hygiene education is presented in isolation, the superiority of a direct voice therapy approach, with or without vocal hygiene education, is seen over a vocal hygiene education program alone (indirect treatment).

Conclusions:
Recent literature demonstrates mixed results obtained through auditory-perceptual, acoustic, and self-rating measures on the effects of vocal hygiene instruction on vocal quality and function in professional voice users. However, the compelling positive outcomes presented do warrant implementation of vocal hygiene education programs in combination with direct voice therapy for professional voice users.
A Descriptive Study of Speech Breathing in Children With Cerebral Palsy During Two Types of Connected Speech Tasks
Authors: Kovacs Sydney , Darling-White Meghan 
Published: November 2022

Purpose:
This study examined speech breathing during two connected speech tasks in children with cerebral palsy (CP) and typically developing (TD) peers. Understanding how the respiratory system supports speech production during various speech tasks can help researchers construct appropriate models of speech production and clinicians remediate speech disorders effectively.

Method:
Four children with CP and four age- and sex-matched TD peers completed two speech tasks, reading and extemporaneous speech. Respiratory kinematic and acoustic data were collected. Dependent variables included utterance length, speech rate, sound pressure level, and lung volume variables.

Results:
Based on descriptive results, children with CP and speech motor involvement demonstrated reduced utterance length and speech rate, equivalent intensity levels, and changes in lung volume variables indicative of respiratory physiological impairment as compared to their TD peers. However, children with CP and no speech motor involvement exhibited speech production and speech breathing variables in the more typical range. In relation to task effects, the majority of children (CP and TD) produced shorter utterances, slower speech rates, equivalent intensity levels, higher lung volume initiation, termination, excursion, higher percent vital capacity per syllable, and longer inspiratory duration during extemporaneous speech as compared to reading.

Conclusions:
Two major themes emerged from the data: (a) Children with CP, particularly those with concomitant speech motor involvement, demonstrate different speech production and speech breathing patterns than their TD peers. (b) Speech task impacts speech production and speech breathing variables in both children with CP and their TD peers, but the extemporaneous speech task did not seem to exaggerate group differences.
Serological diagnosis of toxoplasmosis: evaluation of the commercial test recomLine Toxoplasma IgG immunoblot (Mikrogen) based on recombinant antigens
Authors: Jean-Pierre Vincent , Miozzo Julien , Fricker-Hidalgo Hélène , Garnaud Cécile , Robert Marie Gladys , Pelloux Hervé , Brenier-Pinchart Marie-Pierre 
Published: November 2022

Background: IgG detection to determine immune status to Toxoplasma gondii infection and seroconversion mainly relies on ELISA techniques and, if necessary, on a confirmatory test, Western blot. This study evaluated the performance of the recomLine Toxoplasma IgG immunoblot (IB-recomLine) (Mikrogen) as a confirmatory test on a large number of sera. A total of 171 sera were selected (113 patients) and had previously been analyzed by two ELISA tests, ARCHITECT (Abbott) and VIDAS (bioMérieux) ± LDBIO-Toxo II IgG Western blot (WB-LDBIO) (LDBio). The sera were classified into three groups: group 1 included 50 sera without difficulty in interpreting the IgG results (patients with documented past infection or uninfected); group 2 included 47 sera with difficulty in interpreting the ELISA results; and group 3 included 74 sequential sera from 25 pregnant women with seroconversion. Results: In group 1, overall IgG agreements were 94% and 90% with ARCHITECT and VIDAS, respectively. In group 2, low agreement was observed between IB-recomLine and WB-LDBIO, with eight false-positive and 13 false-negative results. In group 3, 4/13 seroconversions were detected earlier with IB-recomLine compared to other tests. Conclusions: IB-recomLine allowed for earlier diagnosis of toxoplasmic seroconversion compared to both ELISA tests and WB-LDBIO but led to insufficient performance to confirm the immune status when ELISA results were discordant or equivocal.
Neue Aspekte zur Therapie des Dravet-Syndroms
Authors: Schubert-Bast Susanne , Strzelczyk Adam 
Published: November 2022

ZUSAMMENFASSUNGDas Dravet-Syndrom ist gekennzeichnet durch eine schwer behandelbare Epilepsie und assoziierte Komorbiditäten. Nun stehen neben Stiripentol mit Cannabidiol und Fenfluramin zwei neue und spezifische Therapieoptionen zur Verfügung. In diesem Beitrag erfolgt ein Überblick über die gebräuchlichsten und neuen Antikonvulsiva, deren Wirkung, Sicherheitsprofil sowie die potenziellen Interaktionen.
Genetische Aspekte kindlicher Epilepsiesyndrome
Authors: Syrbe Steffen 
Published: November 2022

ZUSAMMENFASSUNGKindliche Epilepsiesyndrome sind Erkrankungen mit früh beginnenden epileptischen Anfällen und assoziierten Störungen der motorischen und kognitiven Entwicklung. Die Klassifikation der Epilepsiesyndrome nach elektroklinischen Kriterien bildet die Grundlage für die Therapie und die prognostische Einschätzung. Zunehmend kann eine steigende Zahl monogenen Ursachen zugeordnet werden. Die Kenntnis des genetischen Hintergrundes erlaubt so eine Einteilung nach pathophysiologischen zellulären Ursachen, kann den diagnostischen Prozess erleichtern und die Therapieentscheidung zukünftig unterstützen.
Kognition bei Epilepsien im Kindes- und Jugendalter
Authors: Borggraefe Ingo , Sorg Anna Lisa , Cornell Sonia 
Published: November 2022

ZUSAMMENFASSUNGKognitive Einschränkungen sind bei etwa jedem fünften Kind mit einer Epilepsie vorhanden. Ein besonders hohes Risiko besteht bei früher Epilepsiemanifestation. Die Ursache der Epilepsie beeinflusst neben anderen Faktoren das Ausmaß der kognitiven Einschränkungen am stärksten. Die Erkennung von kognitiven Einschränkungen bei Kindern mit Epilepsie kann Auswirkungen auf entsprechende Förderkonzepte und Lebenswege für die betroffenen Kinder haben. Ferner muss erkannt werden, ob die medikamentöse Behandlung der Anfälle zu einer eingeschränkten kognitiven Leistungsfähigkeit beiträgt. In einigen Fällen können frühzeitige epilepsiechirurgische Eingriffe, sofern der Patient dafür infrage kommt, einen kognitiven Abbau aufhalten.
Severe Maternal Morbidity in Twins
Authors: Binstock Anna , Bodnar Lisa M. , Himes Katherine P. 
Published: November 2022

Objective While twin gestations are at increased risk of severe maternal morbidity (SMM), there is limited information about timing and causes of SMM in twins. Furthermore, existing data rely on screening definitions of SMM because a gold standard approach requires chart review. We sought to determine the timing and cause of SMM in twins using a gold standard definition outlined by the American College of Obstetricians and Gynecologists (ACOG).
Study Design We used a perinatal database to identify all twin deliveries from 1998 to 2013 at a single academic medical center (n = 2,367). Deliveries were classified as screen positive for SMM if they met any of the following criteria: (1) one of the Centers for Disease Control and Prevention (CDC) International Classification of Diseases Ninth Revision diagnosis and procedure codes for SMM; (2) a prolonged postpartum length of stay (>3 standard deviations beyond mean length of stay by mode of delivery); or (3) maternal intensive care unit admission. We identified true cases of SMM through medical record review of all screen-positive deliveries using the definition of SMM outlined in the ACOG Obstetric Care Consensus. We also determined cause and timing of SMM.
Results A total of 165 (7%) of twin deliveries screened positive for SMM. After chart review of all screen-positive cases, 2.4% (n = 56) were classified as a true case of SMM using the ACOG definition for a positive predictive value of 34%. The majority of SMM occurred postpartum (65%). Hemorrhage was the most common cause of SMM, followed by hypertensive and pulmonary etiologies.
Conclusion Commonly used approaches to screen for SMM perform poorly in twins. This has important implications for quality initiatives and epidemiologic studies that rely on screening definitions of maternal morbidity. Our study demonstrates that the immediate postpartum period is a critical time for maternal health among women with twin pregnancies.
Key Points
Understanding the Factors that Determine a Fellow's Choice in Neonatal–Perinatal Medicine and How They Establish Their Rank List
Authors: Kane Sara K. , Palmer Megan M. , Slaven James E. , Niehaus Jason Z. 
Published: November 2022

Objective Little is known about why neonatology fellows pick the fellowship program they do. Understanding why fellows choose neonatology and rank their programs would be of benefit to program leadership and to other applicants.
Study Design This was a survey study sent to current neonatology fellows in the United States between September 2020 and October 2020, and were asked to rank their choices on a Likert scale. Respondents were also able to give free text responses to open-ended questions.
Results The most important factor fellows state for choosing their program was location, with multiple reasons given. There were significant differences in how certain subgroups ranked programs.
Conclusion Location of the fellowship program is the most important factor for fellows. There are differences within subgroups of fellows on how they rank their fellowship program. Fellowship directors can use this information to better inform selections on who to interview and how to rank fellows.
Key Points