bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacteria associated with Parthenium hysterophorus root exudate influence olfactory oviposition responses of Anopheles gambiae
Authors: Milugo Trizah K. , Torto Baldwyn , Tchouassi David P. 
Published: March 2024

IntroductionPreviously, we documented that the malaria vector Anopheles gambiae responds to volatile emissions from the root exudate water of the invasive plant, Parthenium hysterophorus. However, the origin of the volatiles remains to be investigated. Here, we isolated bacteria from the root exudate water of the plant, test the influence of their volatiles in gravid An. gambiae oviposition, and examined relationships between volatile profiles and oviposition.MethodsBacteria from root exudate water of P. hysterophorus were isolated using culture on Luria Bertani medium and identified by sequencing the 16S rRNA gene. Cultures of individual isolates were evaluated for egg laying response by gravid An. gambiae and number of eggs laid compared using generalized linear models relative to those in crude bacteria-mixture. Headspace volatile emissions of the bacterial isolates were analyzed by gas chromatography coupled to mass spectrometry (GC-MS) and relationships between volatile organic compound (VOC) profiles and gravid mosquito oviposition examined using Random Forest Analysis. Proximate analysis was performed to assess the difference in volatile chemistry among the different isolates.ResultsThree isolates were identified as Gram-negative bacteria belonging to two families: Enterobacteriaceae (Enterobacter sp. and Enterobacter mori) and Alcaligenaceae (Alcaligens aquatilis). An. gambiae laid 3-fold more eggs in cultures of A. aquatilis than in those of Enterobacter sp. In turn, approx. 4-fold more eggs were laid in cultures of E. mori than A. aquatilis. Overall, 16 VOCs were identified in the headspace of the isolates belonging to the chemical classes benzenoids, pyrazines, aldehydes, terpenes, alcohols, alkanes, and indoles. Random Forest Analysis identified 10 compounds contributing the most to the attraction of odors of the bacteria isolates to oviposition. Specifically, dodecane and indole were emitted in higher amounts in odors of Enterobacter sp than the other two species. Proximate analysis revealed differential attraction of the isolates on the gravid mosquito to be associated with their volatile profiles.ConclusionOur results provide first report of E. mori or A. aquatilis mediating attractive oviposition responses in An. gambiae in support of the important role microbes play in insect oviposition. The potential use of the microbes and associated volatiles in malaria vector management needs further investigation.
Associations of anxiety and depression with restless leg syndrome: a systematic review and meta-analysis
Authors: An Tianyang , Sun Haiyang , Yuan Lu , Wu Xiuling , Lu Baoquan 
Published: March 2024

BackgroundThe levels of anxiety and depression among patients with restless leg syndrome (RLS) are controversial. The aim of this systematic review and meta-analysis was to compare the levels of depression and anxiety among individuals with RLS with those of healthy controls.MethodsWe conducted an extensive electronic search of the PubMed, Web of Science, EMBASE, and Cochrane Library databases from their inception dates to 20 June 2023. Studies presenting data on depression and anxiety in individuals with RLS were included, and a comprehensive meta-analysis was performed.ResultsTwenty-one studies matched the inclusion criteria. Significantly more depressive symptoms were present in the individuals with RLS than in those without RLS, as measured by the Beck Depression Inventory [mean difference (MD) = 6.58, 95% confidence interval (CI) = 5.54–7.62, p &lt; 0.01; heterogeneity I2 = 0%, p = 0.99]. Similarly, the results from the Beck Anxiety Inventory indicated that there were significantly more pronounced anxiety symptoms in the individuals with RLS than in those without RLS (MD = 9.30, 95%CI = 7.65–10.94, p &lt; 0.01; heterogeneity I2 = 0%, p = 0.92). The other anxiety and depression scales also yielded statistically significant results. Significant heterogeneity was observed in the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, with the primary contributing factor probably being the scoring criteria of the scales.ConclusionThis meta-analysis found that the levels of depression and anxiety symptoms were significantly higher in individuals with RLS than in their healthy counterparts.Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023410364, (identifier CRD42023410364).
Grasping affordance judgments depend on the object emotional value
Authors: Felippin Matheus Ribeiro , Azevedo Ivo Lopes , Saunier Ghislain , Keniston Les , Nogueira-Campos Anaelli Aparecida 
Published: March 2024

IntroductionThe concept of affordance refers to the opportunities for action provided by the environment, often conveyed through visual information. It has been applied to explain visuomotor processing and movement planning. As emotion modulates both visual perception and the motor system, it is reasonable to ask whether emotion can influence affordance judgments. If present, this relationship can have important ontological implications for affordances. Thus, we investigated whether the emotional value of manipulable objects affected the judgment of the appropriate grasping that could be used to interact with them (i.e., their affordance).MethodsVolunteers were instructed to use a numerical scale to report their judgment on how an observed object should be grasped. We compared these judgments across emotional categories of objects (pleasant, unpleasant and neutral), while also considering the expected effect of object size.ResultsWe found that unpleasant objects were rated as more appropriately graspable by a precision grip than pleasant and neutral objects. Simultaneously, smaller object size also favored this judgment. This effect was seen in all emotional categories examined in equal magnitude.DiscussionOur findings suggest that the emotional value of objects modulates affordance judgments in a way that favors careful manipulation and minimal physical contact with aversive stimuli. Finally, we discuss how this affective aspect of our experience of objects overlaps with what affordances are conceptualized to be, calling for further reexamination of the relationship between affordances and emotions.
Proportional sway-based electrotactile feedback improves lateral standing balance
Authors: Raghav Hari Krishna V. S. , Kim Jeonghee , Chang Shuo-Hsiu , Choe Yoonsuck , Park Hangue 
Published: March 2024

IntroductionPlantar cutaneous augmentation is a promising approach in balance rehabilitation by enhancing motion-dependent sensory feedback. The effect of plantar cutaneous augmentation on balance has been mainly investigated in its passive form (e.g., textured insole) or on lower-limb amputees. In this study, we tested the effect of plantar cutaneous augmentation on balance in its active form (i.e., electrical stimulation) for individuals with intact limbs.MethodsTen healthy subjects participated in the study and were instructed to maintain their balance as long as possible on the balance board, with or without electrotactile feedback evoked on the medial side of the heel, synched with the lateral board sway. Electrotactile feedback was given in two different modes: 1) Discrete-mode E-stim as the stimulation on/off by a predefined threshold of lateral board sway and 2) Proportional-mode E-stim as the stimulation frequency proportional to the amount of lateral board sway. All subjects were distracted from the balancing task by the n-back counting task, to test subjects’ balancing capability with minimal cognitive involvement.ResultsProportional-mode E-stim, along with the n-back counting task, increased the balance time from 1.86 ± 0.03 s to 1.98 ± 0.04 s (p = 0.010). However, discrete-mode E-stim did not change the balance time (p = 0.669). Proportional-mode E-stim also increased the time duration per each swayed state (p = 0.035) while discrete-mode E-stim did not (p = 0.053).DiscussionThese results suggest that proportional-mode E-stim is more effective than discrete-mode E-stim on improving standing balance. It is perhaps because the proportional electrotactile feedback better mimics the natural tactile sensation of foot pressure than its discrete counterpart.
Integrating multi-omics data to reveal the effect of genetic variant rs6430538 on Alzheimer's disease risk
Authors: Qiu Shizheng , Sun Meili , Xu Yanwei , Hu Yang 
Published: March 2024

IntroductionGrowing evidence highlights a potential genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD); however, the role of the PD risk variant rs6430538 in AD remains unclear.MethodsIn Stage 1, we investigated the risk associated with the rs6430538 C allele in seven large-scale AD genome-wide association study (GWAS) cohorts. In Stage 2, we performed expression quantitative trait loci (eQTL) analysis to calculate the cis-regulated effect of rs6430538 on TMEM163 in both AD and neuropathologically normal samples. Stage 3 involved evaluating the differential expression of TMEM163 in 4 brain tissues from AD cases and controls. Finally, in Stage 4, we conducted a transcriptome-wide association study (TWAS) to identify any association between TMEM163 expression and AD.ResultsThe results showed that genetic variant rs6430538 C allele might increase the risk of AD. eQTL analysis revealed that rs6430538 up-regulated TMEM163 expression in AD brain tissue, but down-regulated its expression in normal samples. Interestingly, TMEM163 showed differential expression in entorhinal cortex (EC) and temporal cortex (TCX). Furthermore, the TWAS analysis indicated strong associations between TMEM163 and AD in various tissues.DiscussionIn summary, our findings suggest that rs6430538 may influence AD by regulating TMEM163 expression. These discoveries may open up new opportunities for therapeutic strategies targeting AD.
Sound-localization-related activation and functional connectivity of dorsal auditory pathway in relation to demographic, cognitive, and behavioral characteristics in age-related hearing loss
Authors: Wu Junzhi , Nie Shuai , Li Chunlin , Wang Xing , Peng Ye , Shang Jiaqi , Diao Linan , Ding Hongping , Si Qian , Wang Songjian , Tong Renjie , Li Yutang , Sun Liwei , Zhang Juan 
Published: March 2024

BackgroundPatients with age-related hearing loss (ARHL) often struggle with tracking and locating sound sources, but the neural signature associated with these impairments remains unclear.Materials and methodsUsing a passive listening task with stimuli from five different horizontal directions in functional magnetic resonance imaging, we defined functional regions of interest (ROIs) of the auditory “where” pathway based on the data of previous literatures and young normal hearing listeners (n = 20). Then, we investigated associations of the demographic, cognitive, and behavioral features of sound localization with task-based activation and connectivity of the ROIs in ARHL patients (n = 22).ResultsWe found that the increased high-level region activation, such as the premotor cortex and inferior parietal lobule, was associated with increased localization accuracy and cognitive function. Moreover, increased connectivity between the left planum temporale and left superior frontal gyrus was associated with increased localization accuracy in ARHL. Increased connectivity between right primary auditory cortex and right middle temporal gyrus, right premotor cortex and left anterior cingulate cortex, and right planum temporale and left lingual gyrus in ARHL was associated with decreased localization accuracy. Among the ARHL patients, the task-dependent brain activation and connectivity of certain ROIs were associated with education, hearing loss duration, and cognitive function.ConclusionConsistent with the sensory deprivation hypothesis, in ARHL, sound source identification, which requires advanced processing in the high-level cortex, is impaired, whereas the right–left discrimination, which relies on the primary sensory cortex, is compensated with a tendency to recruit more resources concerning cognition and attention to the auditory sensory cortex. Overall, this study expanded our understanding of the neural mechanisms contributing to sound localization deficits associated with ARHL and may serve as a potential imaging biomarker for investigating and predicting anomalous sound localization.
Managing infectious diarrhea among young children in community pharmacies in Saudi Arabia and the implications for AMR
Authors: Alnezary Faris S. , Alamri Amira R. , Alrehaili Rafa D. , Alnizari Dina S. , Alzahrani Fahad , Mahmoud Mansour , Almutairi Masaad S. , Kurdi Amanj , Godman Brian 
Published: March 2024

IntroductionDiarrhea remains a major global health issue for children under five, contributing substantially to morbidity and mortality. Community pharmacists play a pivotal role in the management of these children; however, their competence in managing childhood diarrhea in Saudi Arabia is under-researched. This is important to ensure optimal patient care.MethodSimulated patients (SPs) presenting with three pediatric diarrhea scenarios were used to evaluate pharmacists’ practice in terms of their counselling, history taking, over-the-counter (OTC) prescribing, medication instructions, diet/fluid advice, and/or information provision. Pharmacists’ practice was categorized into adequate, less adequate, and poor.Results182 community pharmacists, primarily male and non-Saudi, participated in the study, of which 60% were in chain pharmacies. Only 5% showed adequate practice in currently managing pediatric diarrhea. Of the 182 simulated patient visits, 62% received medication in all three scenarios and 20% were referred to physicians, with 16% of pharmacists failing to provide any form of intervention. The main medications recommended were kaolin (34%), pectin (34%) and metronidazole (11%). While most pharmacists (86%) asked about the patient's identity and age, 15% provided incorrect management information, 16% failed to provide guidance on the prescribed medicines, and 18% dispensed antimicrobials without a valid prescription.ConclusionA high level of inadequate management of pediatric diarrhea in Saudi Arabia was observed. This highlights the need for extensive training to improve community pharmacists’ practice in service delivery including providing counselling and advice on the appropriate management of childhood diarrhea. The latter is particularly important to reduce antimicrobial resistance.
The change of psychosocial stress factors in families with infants and toddlers during the COVID-19 pandemic. A longitudinal perspective on the CoronabaBY study from Germany
Authors: Buechel Catherine , Friedmann Anna , Eber Stefan , Behrends Uta , Mall Volker , Nehring Ina 
Published: March 2024

BackgroundOver nearly three years, the COVID-19 pandemic has had a lasting impact on people's lives and mental health worldwide with its far-reaching restrictions and concerns about infections and other personal consequences. Families were particularly affected and showed increased stress and psychological problems. Long-term effects cannot be ruled out. So far, data on young families are sparse. The present longitudinal analysis (n = 932) of the CoronabaBY study investigated the development of parenting stress, parental affective symptoms, and child's mental health in young families with children aged 0–3 years in Germany as well as potential influencing factors.MethodsThe observational study includes two measurement points over the course of the pandemic (baseline and follow-up). Data was collected by app using standardized questionnaires.ResultsN = 932 participants, mainly mothers (94.7%) born in Germany (93.1%) with higher education (61.3% with at least high school diploma) and a comfortable financial situation participated in the longitudinal study. Children were on average 14.7 months old at baseline (SD: 12, range: 1–39 months). While the proportion of parents who perceived the pandemic as stressful decreased significantly from baseline (60%) to follow-up (52.3%), the proportion with parenting stress increased significantly (from 40.1% to 45.4%). Both parental and child mental health problems remained constant over time, with infants crying/feeding/sleeping problems ranging above pre-pandemic comparative data. Most predictive for high parenting stress at follow-up was high parenting stress at baseline. This was also true for parental affective symptoms (depression/anxiety) and child mental health problems.ConclusionsDespite faded pandemic restrictions, parents remained burdened. Support services do not appear to have been sufficient to help families out of their stressful situation. Our results indicate a need for action regarding low-threshold services that effectively reach affected families.Trial registrationThe study was pre-registered in OSF (https://osf.io/search/?q=tksh5&amp;page=1).
Assessment of the implementation of accelerated drug marketing registration procedures for antineoplastic and immunomodulating agents in China: based on 2016–2022 review data
Authors: Lan Yipeng , Lin Xiaofeng , Yu Jialin , Wang Li , Sun Lihua , Huang Zhe 
Published: March 2024

Objective:Since 2016, China has successively implemented Accelerated Drug Marketing Registration Procedures (ADMRPs) for drugs, including Breakthrough Therapy Drug (BTD), Conditional Approval (CA), and Priority Review and Approval (PRA), which have played an important role in promoting the development and review of clinically urgently needed drugs. In this study, we focused on the antineoplastic and immunomodulating agents approved for marketing through ADMRPs, to provide a reference for promoting the formation of a stable and mature regulatory system for the review and approval of antineoplastic drugs and immunomodulating agents in China.Methods:Reviewed the National Medical Products Administration (NMPA) drug review reports for the years 2016–2022 and screened the antineoplastic and immunomodulating agents approved through ADMRPs. Then, with the help of the NMPA website and the Yaozhi Database, two researchers independently queried and entered the detailed information of the selected drugs, and checked with each other. The attribute classification and main characteristics of the drugs were then analyzed with descriptive statistics to obtain the trend of drug types, drug review and approval status, and timeliness.Results:A total of 206 antineoplastic and immunomodulating agents were approved for marketing through five accelerated marketing registration procedures (or procedure combinations), with the average review time shortened by about 81 days. Among them, imported drugs accounted for a larger proportion, the most drugs for treating non-small cell lung cancer and lymphoma, and the largest number of PD-1/PDL-1 inhibitors, but pediatric drugs and rare disease drugs accounted for a smaller proportion.Conclusion:ADMRPs can promote the accessibility of antineoplastic and immunomodulating agents in China and safeguard the life and health rights of more patients. Nevertheless, it is necessary to pay attention to the expansion of the types of indications for medicines and to increase the development of drugs that are urgently needed by a small number of patients.
The application of Phase 0 and microtracer approaches in early clinical development: past, present, and future
Authors: Roffel A. F. , Hoogdalem E.-J. van 
Published: March 2024

Phase 0 microdosing studies were introduced to the drug development community approximately 20 years ago. A microdose is defined as less than 1/100th of the dose calculated based on animal data to yield a pharmacological effect in humans, with a maximum of 100 μg, or 30 nmoles for protein products. In our experience, Phase 0 microdose studies have not been fully embraced by the pharmaceutical industry. This notion is based on the number of Phase 0 studies that we have been involved in. Thus, we conducted at least 17 Phase 0 microdose studies in the Zero’s (on average, two per year), but in the years beyond this, it was only 15 studies (1.4 per year); in these latter years, we did conduct a total of 23 studies which employed an intravenous (i.v.) microdose for absolute bioavailability (ABA) assessments (two per year on average), which are the most used and potentially informative type of clinical study using a microdose, albeit they are formally not microdose studies. In the current review, we summarize the past use of and experience with Phase 0 microdose designs in early clinical development, including intravenous 14C microdose ABA studies, and assess what is needed to increase the adoption of useful applications of Phase 0/microdose studies in the near future.
Analysis of volatile organic compounds in Korean-bred strawberries: insights for improving fruit flavor
Authors: Jee Eungu , Do Eunsu , Gil Chan Saem , Kim Seolah , Lee Sun Yi , Lee Seonghee , Ku Kang-Mo 
Published: March 2024

IntroductionThe strawberry industry in South Korea has witnessed a significant 65% growth over the past decade, surpassing other fruits and vegetables in production value. While sweetness and acidity are well-recognized flavor determinants, the role of volatile organic compounds (VOCs) in defining the desirable flavor profiles of strawberries is also crucial. However, existing research has predominantly concentrated on a limited range of commercial cultivars, neglecting the broader spectrum of strawberry varieties.MethodsThis study embarked on developing a comprehensive VOC database for a diverse array of strawberry cultivars sourced both domestically and internationally. A total of 61 different strawberry cultivars from Korea (45), the USA (7), Japan (8), and France (1) were analyzed for their VOC content using Tenax TA Thermo Desorption tubes and Gas Chromatography-Mass Spectrometry (GC-MS). In addition to VOC profiling, heritability was assessed using one-way ANOVA to compare means among multiple groups, providing insights into the genetic basis of flavor differences.Results and discussionThe analysis identified 122 compounds categorized into esters, alcohols, terpenes, and lactones, with esters constituting the majority (46.5%) of total VOCs in Korean cultivars. ‘Arihyang’, ‘Sunnyberry’, and ‘Kingsberry’ exhibited the highest diversity of VOCs detected (97 types), whereas ‘Seolhong’ showed the highest overall concentration (57.5mg·kg-1 FW). Compared to the USA cultivars, which were abundant in γ-decalactone (a peach-like fruity aroma), most domestic cultivars lacked this compound. Notably, ‘Misohyang’ displayed a high γ-decalactone content, highlighting its potential as breeding germplasm to improve flavor in Korean strawberries. The findings underscore the importance of a comprehensive VOC analysis across different strawberry cultivars to understand flavor composition. The significant variation in VOC content among the cultivars examined opens avenues for targeted breeding strategies. By leveraging the distinct VOC profiles, particularly the presence of γ-decalactone, breeders can develop new strawberry varieties with enhanced flavor profiles, catering to consumer preferences for both domestic and international markets.