bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare copy number variation in autoimmune Addison’s disease
Authors: Artaza Haydee , Eriksson Daniel , Lavrichenko Ksenia , Aranda-Guillén Maribel , Bratland Eirik , Vaudel Marc , Knappskog Per , Husebye Eystein S. , Bensing Sophie , Wolff Anette S. B. , Kämpe Olle , Røyrvik Ellen C. , Johansson Stefan
Published: March 2024

Autoimmune Addison’s disease (AAD) is a rare but life-threatening endocrine disorder caused by an autoimmune destruction of the adrenal cortex. A previous genome-wide association study (GWAS) has shown that common variants near immune-related genes, which mostly encode proteins participating in the immune response, affect the risk of developing this condition. However, little is known about the contribution of copy number variations (CNVs) to AAD susceptibility. We used the genome-wide genotyping data from Norwegian and Swedish individuals (1,182 cases and 3,810 controls) to investigate the putative role of CNVs in the AAD aetiology. Although the frequency of rare CNVs was similar between cases and controls, we observed that larger deletions (>1,000 kb) were more common among patients (OR = 4.23, 95% CI 1.85-9.66, p = 0.0002). Despite this, none of the large case-deletions were conclusively pathogenic, and the clinical presentation and an AAD-polygenic risk score were similar between cases with and without the large CNVs. Among deletions exclusive to individuals with AAD, we highlight two ultra-rare deletions in the genes LRBA and BCL2L11, which we speculate might have contributed to the polygenic risk in these carriers. In conclusion, rare CNVs do not appear to be a major cause of AAD but further studies are needed to ascertain the potential contribution of rare deletions to the polygenic load of AAD susceptibility.
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

Introduction

Previously, 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.

Methods

Bacteria 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.

Results

Three 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.

Conclusion

Our 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.
Deconstructing co-occurring marine heatwave and phytoplankton bloom events in the Arkona Sea in 2018
Authors: Cahill Bronwyn , Chrysagi Evridiki , Vortmeyer-Kley Rahel , Gräwe Ulf
Published: March 2024

Between May and August 2018, two separate marine heatwaves (MHWs) occurred in the Arkona Sea in the western Baltic Sea. These heatwaves bookended an extended period of phytoplankton growth in the region. Data from the Ocean and Land Colour Instrument (OLCI) on board the European Sentinel-3 satellite revealed an eddy-like structure containing high chlorophyll a (Chl-a) concentrations (ca. 25 mg.m-3) persisting for several days at the end of May in the Arkona Sea. Combining ocean colour observations, a coupled bio-optical ocean model and a particle tracking model, we examined the three dimensional relationship between these co-occurring MHW and phytoplankton bloom events. We find that the onset of the MHW in May provided the optimal conditions for phytoplankton growth, i.e. sufficient light and nutrients. Wind-driven surface eddy circulation, geostrophic eddy stirring and transient submesoscale dynamics along the edges of the eddy provided a transport path for nutrient fluxes and carbon export, and helped to sustain the phytoplankton bloom. The bloom may have indirectly had an enhancing effect on the MHW, through the impact of water constituent-induced heating rates on air-sea energy fluxes. The subsurface signature of the MHW plays a critical role in de-coupling surface and subsurface dynamics and terminating the phytoplankton bloom. Subsurface temperature anomalies of up to 8°C between 15 and 20 m depth are found to persist up to 15 days after the surface signature of the MHW has disappeared. The study reveals how surface and subsurface dynamics of MHWs and phytoplankton blooms are connected under different environmental conditions. It extends our knowledge on surface layer processes obtained from satellite data.
Could persistent organic pollutants affect future generations of sea turtles by maternal transfer? First results for Caretta caretta nests along the North-Western coast of Italy
Authors: Ceciarini Ilaria , Capanni Francesca , Minoia Lorenzo , Consales Guia , Amico Carlo , Zuffi Marco Alberto Luca , Terracciano Giuliana , Mancusi Cecilia , Neri Alessandra , Franchi Enrica , Raimondi Giovanni , Prestanti Alessia , Bonucci Francesco , Marchini Daniela , Cancelli Fabrizio , Caruso Chiara , Tonelli Laura , Venturi Lucia , Ventrella Sergio , Caliani Ilaria , Marsili Letizia
Published: March 2024

Since 2013, loggerhead sea turtle (Caretta caretta, Linnaeus 1758) nesting has been observed further north along the Italian coast, reaching the Tuscan coast (NW Mediterranean Sea). The four nesting events that occurred in Tuscany in the summer of 2019 spurred the scientific community to monitor these occurrences more carefully, following them from egg deposition to hatching. This provided an opportunity to collect samples for conducting multidisciplinary investigations, including the toxicological investigations of the biological material collected from the four nests. The aim of this study was to conduct an initial assessment of persistent organic pollutants in the eggs laid in Tuscany, aiming to establish a baseline on this topic for subsequent nesting events that have occurred until today. Organochlorine compounds (OCs), specifically polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and its metabolites, and hexachlorobenzene (HCB), were analyzed and detected in unhatched eggs, embryos, and chorio-allantoic membranes (CAMs). OCs were detected in all samples, with PCBs > DDTs ≫ HCB. A significant spatial variation in pollutant levels and profiles among sea turtle nesting locations was found. Embryos showed higher levels of contamination than egg contents regardless of the developmental stages. Depth of the laying chamber and egg mass were not significant factors in OC bioaccumulation. For the first time in the Mediterranean Sea, this study assessed the role of CAM in the transfer of contaminants to the embryo. Overall, the OC levels found were lower compared to the results from other studies conducted worldwide on loggerhead sea turtle biological material. This was the first assessment of nest biological material for the North-Western coast of Italy.
Into the wild: coupling otolith and archival tag records to test assumptions underpinning otolith chemistry applications in wild fish
Authors: Hüssy Karin , Haase Stefanie , Mion Monica , Hilvarsson Annelie , Radtke Krzysztof , Thomsen Tonny B. , Krüger-Johnsen Maria , Casini Michele , Sturrock Anna M.
Published: March 2024

Chronological records of elemental concentrations in fish otoliths are a widely used tool to infer the environmental conditions experienced by individual fish. To interpret elemental signals within the otolith, it is important to understand how both external and internal factors impact ion uptake, transport and incorporation. In this study, we have combined chronological records from otoliths and archival data storage tags to quantify the influence of internal (sex, size, age, growth) and external (temperature, depth, salinity) conditions on otolith elemental chemistry of cod (Gadus morhua) in natural settings of the Baltic Sea. This study focused on elements primarily under physiological control: Phosphorus (P), magnesium (Mg) and zinc (Zn); and elements under environmental control: Strontium (Sr), barium (Ba) and manganese (Mn). Based on known spatial and temporal patterns in environmental conditions and fish size, growth, and maturity, we posed a series of hypotheses of expected otolith element patterns. Partial effects of internal and external drivers on element concentration were analyzed using a Linear Mixed Model approach with random variables (fish and year). Predicted effects of otolith concentrations of all elements under physiological control (P, Mg, Zn) showed similar trends, with distinct seasonal patterns (lowest concentration in late spring, highest concentrations in winter), and a positive correlation with water temperature, in addition to higher Zn and lower P in spawning individuals. Predicted effects of otolith concentrations of elements expected to be predominantly under environmental control showed the predicted geographic and depth-related trends based on ambient salinity (Ba) and coastal hypoxia (Mn). However, contrary to expectation, Sr was unrelated to salinity. Predicted otolith Ba, Sr and Mn concentrations also exhibited pronounced seasonal patterns that were out of phase with each other but appeared to be partly explained by spawning/feeding migrations. While performing laboratory validation studies for adult fish is typically not possible, these results highlight the importance of assessing local water chemistry and freshwater endmembers in one’s study system before otolith elemental chemistry can be reliably used to reconstruct fish habitat use and environmental histories.
Localization of hyperpolarization-activated cyclic nucleotide-gated channels in the vertebrate retinas across species and their physiological roles
Authors: Kim Daniel , Roh Hyeonhee , Lee Hyung-Min , Kim Sang Jeong , Im Maesoon
Published: March 2024

Transmembrane proteins known as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control the movement of Na+ and K+ ions across cellular membranes. HCN channels are known to be involved in crucial physiological functions in regulating neuronal excitability and rhythmicity, and pacemaker activity in the heart. Although HCN channels have been relatively well investigated in the brain, their distribution and function in the retina have received less attention, remaining their physiological roles to be comprehensively understood. Also, because recent studies reported HCN channels have been somewhat linked with the dysfunction of photoreceptors which are affected by retinal diseases, investigating HCN channels in the retina may offer valuable insights into disease mechanisms and potentially contribute to identifying novel therapeutic targets for retinal degenerative disorders. This paper endeavors to summarize the existing literature on the distribution and function of HCN channels reported in the vertebrate retinas of various species and discuss the potential implications for the treatment of retinal diseases. Then, we recapitulate current knowledge regarding the function and regulation of HCN channels, as well as their relevance to various neurological disorders.
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

Background

The 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.

Methods

We 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.

Results

Twenty-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 < 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 < 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.

Conclusion

This 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

Introduction

The 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).

Methods

Volunteers 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.

Results

We 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.

Discussion

Our 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.
Influencing factors of corticomuscular coherence in stroke patients
Authors: Gao Zhixian , Lv Shiyang , Ran Xiangying , Wang Yuxi , Xia Mengsheng , Wang Junming , Qiu Mengyue , Wei Yinping , Shao Zhenpeng , Zhao Zongya , Zhang Yehong , Zhou Xuezhi , Yu Yi
Published: March 2024

Stroke, also known as cerebrovascular accident, is an acute cerebrovascular disease with a high incidence, disability rate, and mortality. It can disrupt the interaction between the cerebral cortex and external muscles. Corticomuscular coherence (CMC) is a common and useful method for studying how the cerebral cortex controls muscle activity. CMC can expose functional connections between the cortex and muscle, reflecting the information flow in the motor system. Afferent feedback related to CMC can reveal these functional connections. This paper aims to investigate the factors influencing CMC in stroke patients and provide a comprehensive summary and analysis of the current research in this area. This paper begins by discussing the impact of stroke and the significance of CMC in stroke patients. It then proceeds to elaborate on the mechanism of CMC and its defining formula. Next, the impacts of various factors on CMC in stroke patients were discussed individually. Lastly, this paper addresses current challenges and future prospects for CMC.
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

Introduction

Plantar 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.

Methods

Ten 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.

Results

Proportional-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).

Discussion

These 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

Introduction

Growing 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.

Methods

In 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.

Results

The 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.

Discussion

In 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

Background

Patients 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 methods

Using 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).

Results

We 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.

Conclusion

Consistent 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.
Case report: Metastatic ovarian mucinous carcinoma to the breast: diagnostic challenges and pitfalls
Authors: Laokulrath Natthawadee , Lim Siew Kuan , Lim Hwee Yong , Gudi Mihir , Tan Puay Hoon
Published: March 2024

Metastases to the breast from extramammary sources are extremely rare, with the ovary, primarily high-grade serous carcinoma, being the most common origin. We report a case of breast metastases from advanced stage ovarian mucinous carcinoma in a 48-year-old female— a case hitherto unreported in the literature. The case is noteworthy for its atypical presentation marked by an areolar rash, clinically suggestive of Paget disease of the nipple. This unique clinical scenario, coupled with histopathological examination revealing in-situ-like carcinoma component, posed a diagnostic challenge in discerning the tumour origin. We emphasize the need for heightened awareness among pathologists to avoid misdiagnosing metastatic carcinomas as primary breast tumours, a potential pitfall with significant clinical implications.
Case report: Complex left-carina resection: three-year single-center experience
Authors: Tombelli Simone , Viggiano Domenico , Salimbene Ottavia , Trigiani Marco , Voltolini Luca , Gonfiotti Alessandro
Published: March 2024

Carinal and tracheobronchial angle tumors have long been a contraindication for surgical removal; the technique of tracheal sleeve pneumonectomy makes it possible to approach this malignancy but still represents a surgical challenge. Left sleeve pneumonectomy is less common compared with right sleeve pneumonectomy and represents a minority component in the literature’s case series due to the complexity of the anatomy. In addition, there is no standard for treatment strategy, and it must be assessed on a case-by-case basis. From 2020 to 2023, we performed three left tracheal sleeve pneumonectomies and one neocarina reconstruction surgery for benign lesions without lung resections. All cases were performed without cardiovascular support such as cardiopulmonary bypass and via median sternotomy. With a median length of stay of 21.5 days (between 14 days and 40 days), all patients were transferred to a physiotherapeutic rehabilitation facility for functional reactivation, where they received physiotherapeutic respiratory therapy given the slow functional recovery. The recorded 30-day mortality was 0. There is no standardized approach for left-sided sleeve pneumonectomy, and it is still a surgical challenge due to intraoperative and postoperative difficulties.
Case Report: TRPV4 gene mutation causing neuronopathy, distal hereditary motor, type VIII
Authors: Wang Fengge , Jin Xuemei , Zhu Yongning , Jiang Shuli , Zhang Xiaoyan , Wang Yanping , Man Dongmei , Wang Fuling
Published: March 2024

Neuronopathy, distal hereditary motor, type VIII is an exceedingly rare autosomal dominant genetic disorder, also known as congenital non-progressive distal spinal muscular atrophy. It is characterized by progressive weakness in distal motor function and atrophy of muscles, without accompanying sensory impairment. Presently, there is limited literature on this condition, and accurate epidemiological data regarding its incidence remains unavailable. We report a paediatric case of distal hereditary motor, type VIII that is caused by a heterozygous missense mutation in the TRPV4 gene (NM_021625): c.805C>T. The proband is a 7-year-old male child. During pregnancy, his mother had prenatal ultrasound revealing “inward turning of the feet”, a condition persisting after birth. The proband is currently unable to stand independently, exhibiting bilateral clubfoot deformity. Although possessing normal cognitive function, he cannot walk unaided. Computed radiography findings reveal pelvic tilt, bilateral knee joint valgus, and bilateral clubfoot. The patient underwent familial exome sequencing, revealing a mutation in the TRPV4 gene (NM_021625): c.805C>T (p.Arg269Cys). Considering the patient’s medical history, clinical manifestations, imaging studies, and genetic test results, the diagnosis for this individual is Neuronopathy, distal hereditary motor, type VIII. This report documents a case involving the TRPV4 gene mutation associated with Neuronopathy, distal hereditary motor, type VIII, contributing valuable case reference for the early diagnosis of this condition.
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

Introduction

Diarrhea 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.

Method

Simulated 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.

Results

182 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.

Conclusion

A 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

Background

Over 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.

Methods

The observational study includes two measurement points over the course of the pandemic (baseline and follow-up). Data was collected by app using standardized questionnaires.

Results

N = 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.

Conclusions

Despite 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 registration

The study was pre-registered in OSF (https://osf.io/search/?q=tksh5&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.
History and future perspectives of adipose tissue macrophage biology
Authors: Kado Tomonobu , Nishimura Ayumi , Tobe Kazuyuki
Published: March 2024

Macrophages contribute to adipose tissue homeostasis; however, they are also thought to be responsible for insulin resistance in obesity. Macrophages, which were oversimplified in past methodologies, have become rather difficult to understand comprehensively as recent developments in research methodology have revealed their diversity. This review highlights recent studies on adipose tissue macrophages, identifies controversial issues that need to be resolved and proposes a scenario for further development of adipose tissue macrophage biology.
Pathophysiology of human hearing loss associated with variants in myosins
Authors: Miyoshi Takushi , Belyantseva Inna A. , Sajeevadathan Mrudhula , Friedman Thomas B.
Published: March 2024

Deleterious variants of more than one hundred genes are associated with hearing loss including MYO3A, MYO6, MYO7A and MYO15A and two conventional myosins MYH9 and MYH14. Variants of MYO7A also manifest as Usher syndrome associated with dysfunction of the retina and vestibule as well as hearing loss. While the functions of MYH9 and MYH14 in the inner ear are debated, MYO3A, MYO6, MYO7A and MYO15A are expressed in inner ear hair cells along with class-I myosin MYO1C and are essential for developing and maintaining functional stereocilia on the apical surface of hair cells. Stereocilia are large, cylindrical, actin-rich protrusions functioning as biological mechanosensors to detect sound, acceleration and posture. The rigidity of stereocilia is sustained by highly crosslinked unidirectionally-oriented F-actin, which also provides a scaffold for various proteins including unconventional myosins and their cargo. Typical myosin molecules consist of an ATPase head motor domain to transmit forces to F-actin, a neck containing IQ-motifs that bind regulatory light chains and a tail region with motifs recognizing partners. Instead of long coiled-coil domains characterizing conventional myosins, the tails of unconventional myosins have various motifs to anchor or transport proteins and phospholipids along the F-actin core of a stereocilium. For these myosins, decades of studies have elucidated their biochemical properties, interacting partners in hair cells and variants associated with hearing loss. However, less is known about how myosins traffic in a stereocilium using their motor function, and how each variant correlates with a clinical condition including the severity and onset of hearing loss, mode of inheritance and presence of symptoms other than hearing loss. Here, we cover the domain structures and functions of myosins associated with hearing loss together with advances, open questions about trafficking of myosins in stereocilia and correlations between hundreds of variants in myosins annotated in ClinVar and the corresponding deafness phenotypes.
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

Introduction

The 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.

Methods

This 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 discussion

The 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.
The correlations between parental warmth and children’s approaches to learning: a moderated mediation model of self-efficacy and teacher-child closeness
Authors: Liu Yongli , Wang Wei , Wei Sumei , Wang Pengcheng , Chen Kun , Liu Jing , Chen Junjun
Published: March 2024

Researchers have increasingly considered approaches to learning (ATL) a key indicator of school readiness. Our study purposed to examine the impacts of parental warmth on children’s approaches to learning, and the mediating role of self-efficacy, as well as the moderating role of teacher-child closeness in this relationship. Using a whole-group sampling method, 414 Chinese children aged 5–6 years participated this research together with their parents and teachers. Parents of those children were asked to fill out in person questionnaires on parental warmth, children’s approaches to learning, and self-efficacy. Children’s teachers completed the questionnaire regarding teacher-child closeness. Results indicated that children with high parental warmth were more likely to get high approaches to learning and their self-efficacy played a partial mediating role in this link. In addition, teacher-child closeness moderated the correlation between parental warmth and children’s self-efficacy. Specifically, the association between parental warmth and children’s self-efficacy was stronger for children with high teacher-child closeness than those with low teacher-child closeness. The results extend our understanding of how parental warmth affects children’s approaches to learning, revealing that strategies that could enhance self-efficacy would be effective in improving children’s approaches to learning.
Age-related changes in motor planning for prior intentions: a mouse tracking reach-to-click task
Authors: Zhang Shujing , Wilmut Kate , Zhang Kaiyu , Wang Shan
Published: March 2024

When we complete sequential movements with different intentions, we plan our movements and adjust ahead. Such a phenomenon is called anticipatory planning for prior intentions and is known to decline with age. In daily life activities, we often need to consider and plan for multiple demands in one movement sequence. However, previous studies only considered one dimension of prior intentions, either different types of onward actions or different precisions of fit or placement. Therefore, in this study, we investigated anticipatory planning for both extrinsic (movement direction) and intrinsic (fit precision) target-related properties in a computer-based movement task and analyzed the computer cursor movement kinematics of both young and older adults. We found that older people consider and adjust for different properties step-by-step, with movement direction being considered as a prior intention during reach movement and fit precision as a motor constraint during drop movement. The age-related changes in the completion of onward actions are constrained by one’s general cognitive ability, sensorimotor performance and effective motor planning for prior intentions. Age-related decline in motor planning can manifest as counterproductive movement profiles, resulting in suboptimal performance of intended actions.
Enhancing emotional health and engagement in Chinese English language learners: an approach from teachers’ autonomy- supportive behavior, teachers’ harmony, and peer support in a two-sample study
Authors: Yang Liu
Published: March 2024

Background

In the evolving landscape of Chinese education, understanding the factors that influence the emotional health and engagement of English language learners is increasingly vital. Against this backdrop, our study delves into how teachers’ autonomy-supportive behavior, teachers’ harmony, and peer support impact these key educational outcomes.

Aim

This study investigates the roles of teachers’ autonomy-supportive behavior, teachers’ harmony, and peer support in influencing the emotional health and engagement of English language learners in China.

Method

Involving a diverse sample of 68 English Language Teachers and their 389 students from various Chinese universities, the study leverages a convenience sampling method.

Results

Key findings indicate that students’ emotional health is predominantly influenced by peer support, while student engagement is significantly affected by a combination of teachers’ autonomy-supportive behavior, peer support, and teachers’ harmony. These outcomes highlight the importance of both teacher behavior and peer relationships in educational settings, underscoring their crucial roles in enhancing student well-being and engagement. The study’s methodology, incorporating a diverse sample from multiple educational institutions and a comprehensive analytical approach, offers robust insights. However, the limitations of convenience sampling and reliance on self-reported data necessitate a careful interpretation of the findings.

Implications

Implications from this research are vital for educational policy and practice, emphasizing the need for interventions that enhance teacher-student relationships and foster supportive peer environments. This study adds to the body of knowledge on factors influencing emotional health and engagement among English language learners, advocating for a comprehensive approach in educational strategies and interventions.