bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biorelevant In Vitro Skin Permeation Testing and In Vivo Pharmacokinetic Characterization of Lidocaine from a Nonaqueous Drug-in-Matrix Topical System
Authors: Greuber Emileigh , Vought Kip , Patel Kalpana , Suzuki Hiroaki , Usuda Kazuhiro , Shiramizu Akira , Koplowitz Luana Pesco , Koplowitz Barry , Maibach Howard I. , Lissin Dmitri 
Published: August 2021

AbstractRecently, lidocaine topical systems utilizing nonaqueous matrices have been developed and provide efficient lidocaine delivery through the skin, such that lower concentrations of drug provide equivalent or greater drug delivery than drug-in-matrix hydrogel lidocaine patches. This study characterizes drug delivery from a nonaqueous lidocaine topical system with increasing drug load both in vitro and in vivo. Topical systems formulated with either 1.8% or 5.4% lidocaine were applied to healthy volunteers’ backs (n = 15) for 12 h in a single-center, open-label, four-treatment, four-period crossover pharmacokinetic study. Subjects were dosed with either three 1.8% systems or one, two, or three 5.4% systems in each period. Blood was collected for up to 48 h, and plasma lidocaine levels were measured with a validated HPLC method. In parallel, human and mouse skin models characterized the in vitro skin permeation profile. The pharmacokinetic profile was linear between one, two, and three lidocaine 5.4% applications. Application of three lidocaine 1.8% systems (108 mg lidocaine) was bioequivalent to one lidocaine 5.4% system (108 mg lidocaine). Both topical systems remained well adhered to the skin and irritation was mild. The 5.4% system had approximately threefold higher skin permeability than the 1.8% system in the mouse and human skin models. The results indicate increasing the drug load by three times results in triple the drug delivery both in vivo and in vitro. The relationship between the in vitro permeation and in vivo absorption correlates and is nonlinear.
GATA3 is essential for separating patterning domains during facial morphogenesis
Authors: Abe Makoto , Cox Timothy C. , Firulli Anthony B. , Kanai Stanley M. , Dahlka Jacob , Lim Kim-Chew , Engel James Douglas , Clouthier David E. 
Published: August 2021

ABSTRACT
Neural crest cells (NCCs) within the mandibular and maxillary prominences of the first pharyngeal arch are initially competent to respond to signals from either region. However, mechanisms that are only partially understood establish developmental tissue boundaries to ensure spatially correct patterning. In the ‘hinge and caps’ model of facial development, signals from both ventral prominences (the caps) pattern the adjacent tissues whereas the intervening region, referred to as the maxillomandibular junction (the hinge), maintains separation of the mandibular and maxillary domains. One cap signal is GATA3, a member of the GATA family of zinc-finger transcription factors with a distinct expression pattern in the ventral-most part of the mandibular and maxillary portions of the first arch. Here, we show that disruption of Gata3 in mouse embryos leads to craniofacial microsomia and syngnathia (bony fusion of the upper and lower jaws) that results from changes in BMP4 and FGF8 gene regulatory networks within NCCs near the maxillomandibular junction. GATA3 is thus a crucial component in establishing the network of factors that functionally separate the upper and lower jaws during development.
Molecular and physiological responses predict acclimation limits in juvenile brook trout (Salvelinus fontinalis)
Authors: Mackey Theresa E. , Hasler Caleb T. , Durhack Travis , Jeffrey Jennifer D. , Macnaughton Camille J. , Ta Kimberly , Enders Eva C. , Jeffries Ken M. 
Published: August 2021

ABSTRACTUnderstanding the resilience of ectotherms to high temperatures is essential because of the influence of climate change on aquatic ecosystems. The ability of species to acclimate to high temperatures may determine whether populations can persist in their native ranges. We examined physiological and molecular responses of juvenile brook trout (Salvelinus fontinalis) to six acclimation temperatures (5, 10, 15, 20, 23 and 25°C) that span the thermal distribution of the species to predict acclimation limits. Brook trout exhibited an upregulation of stress-related mRNA transcripts (heat shock protein 90-beta, heat shock cognate 71 kDa protein, glutathione peroxidase 1) and downregulation of transcription factors and osmoregulation-related transcripts (nuclear protein 1, Na+/K+/2Cl− co-transporter-1-a) at temperatures ≥20°C. We then examined the effects of acclimation temperature on metabolic rate (MR) and physiological parameters in fish exposed to an acute exhaustive exercise and air exposure stress. Fish acclimated to temperatures ≥20°C exhibited elevated plasma cortisol and glucose, and muscle lactate after exposure to the acute stress. Fish exhibited longer MR recovery times at 15 and 20°C compared with the 5 and 10°C groups; however, cortisol levels remained elevated at temperatures ≥20°C after 24 h. Oxygen consumption in fish acclimated to 23°C recovered quickest after exposure to acute stress. Standard MR was highest and factorial aerobic scope was lowest for fish held at temperatures ≥20°C. Our findings demonstrate how molecular and physiological responses predict acclimation limits in a freshwater fish as the brook trout in the present study had a limited ability to acclimate to temperatures beyond 20°C.
Prevalence of substance abuse and its associated factors among medical students: a cross-sectional study
Authors: Karn Mitesh , Kandel Dipendra , Subedi Nuwadatta 
Published: August 2021

Background: Substance abuse by medical students poses a significant risk not only on their personal life but also on their professional life by putting their patients at risk. Our study aims to find out the prevalence of substance abuse and factors associated with it among medical students. Methods: A descriptive, online-questionnaire based, cross-sectional study was carried out at Gandaki Medical College, a medical school in Gandaki Province of Nepal. Whole sampling technique was used. SPSS-25.0 software was used for statistical analysis. Descriptive statistics were used for analyzing demographic and substance abuse related variables. Chi square and Fishers exact test was used to find out if any differences existed in substance abuse by demographic characteristics. Results: Among 420 eligible participants, 219 participated in the survey (response rate: 52.2%). Alcohol was the most commonly used substance with overall lifetime prevalence of 58% followed by cigarette smoking and illegal drug abuse at 21.9% and 13.7%, respectively. The abuse of substances was significantly higher (p<0.05) in males, who were offered substances by friends, and amongst study participants who worked with an intoxicated colleague. The most common reason for substance abuse was “For pleasure, curiosity or to go along with friends” (23%, n=18). Major and minor dysfunction due to alcohol abuse was reported by 8(3.7%) and 33(15.1%) participants, while the same dysfunctions due to drug abuse were reported by 1(0.5%) and 14(6.4%) participants, respectively. Conclusions: The prevalence of substance abuse was high among medical students and was found to be associated with male gender, if offer of substances were made by friends, and amongst those who worked with an intoxicated colleague. This problem of substance abuse among medical students should be addressed timely as failing to do so might have serious consequences on the healthcare system of the country.
Young infant clinical signs study­­, Pakistan: a data note
Authors: Shahid Shahira , Tikmani Shiyam Sunder , Brown Nick , Zaidi Anita K.M. , Jehan Fyezah , Nisar Muhammad Imran 
Published: August 2021

Neonatal sepsis is the leading cause of child death globally with most of these deaths occurring in the first week of life. It is of utmost public health importance that clinical signs predictive of severe illness and need for referral are identified early in the course of illness. From 2002-2005, a multi country trial called the Young Infant Clinical Signs Study (YICSS) was conducted in seven sites across three South-Asian (Bangladesh, India, and Pakistan), two African (Ghana, and South Africa), and one South American (Bolivia) country. The study aimed to develop a simplified algorithm to be used by primary healthcare workers for the identification of sick young infants needing prompt referral and treatment. The main study enrolled 8,889 young infants between the ages of 0-59 days old. This dataset contains observations on 2950 young infants aged 0-59 days from the Pakistan site. The data was collected between 2003-2004 with information on the most prevalent signs and symptoms. The data from this study was used to update the Integrated Management of Childhood Illness guidelines. The World Health Organisation (WHO) seven-sign algorithm has been used in other major community-based trials to study possible serious bacterial infection and its treatment regimens.
Affordable and effective optokinetic response methods to assess visual acuity and contrast sensitivity in larval to juvenile zebrafish
Authors: Gómez Sánchez Alicia , Álvarez Yolanda , Colligris Basilio , Kennedy Breandán N. 
Published: August 2021

The optokinetic response (OKR) is an effective behavioural assay to investigate functional vision in zebrafish. The rapid and widespread use of gene editing, drug screening and environmental modulation technologies has resulted in a broader need for visual neuroscience researchers to access affordable and more sensitive OKR, contrast sensitivity (CS) and visual acuity (VA) assays. Here, we demonstrate how 2D- and 3D-printed, striped patterns or drums coupled with a motorised base and microscope provide a simple, cost-effective but efficient means to assay OKR, CS and VA in larval-juvenile zebrafish. In wild-type, five days post-fertilisation (dpf) zebrafish, the 2D or 3D drums printed with the standard OKR stimulus of 0.02 cycles per degree (cpd), 100% black-white contrast evoked equivalent responses of 24.2 or 21.8 saccades per minute, respectively. Furthermore, although the OKR number was significantly reduced compared to the 0.02 cpd drum (p<0.0001), the 2D and 3D drums evoked equivalent responses with the 0.06 and 0.2 cpd drums. Notably, standard OKRs varied with time of day; peak responses of 29.8 saccades per minute occurred in the early afternoon with significantly reduced responses occurring in the early morning or late afternoon (18.5 and 18.4 saccades per minute, respectively). A customised series of 2D printed drums enabled analysis of VA and CS in 5-21 dpf zebrafish. The saccadic frequency in VA and CS assays was inversely proportional to age, spatial frequency and contrast of the stimulus. OKR, VA and CS of zebrafish larvae can be efficiently measured using 2D- or 3D-printed striped drums. For data consistency the luminance of the OKR light source, the time of day when the analysis is performed, and the order of presentation of VA and CS drums must be considered. These simple methods allow effective and more sensitive analysis of functional vision in zebrafish.
Recurrent cervical stitch sinus arising from the deep neck space after thyroidectomy: case study and review
Authors: Chen Hsing-Fu , Papadakis Marios , Jeng Seng-Feng 
Published: August 2021

Objective: We describe a one-stage surgical technique for the management of recurrent cervical stitch sinus after thyroidectomy. Method: A retrospective, single-centre study of all patients who were operated on because of cervical neck sinus after thyroidectomy. We provide a detailed description of our surgical approach, based on guided sinus removal after prior tract staining with methylene blue and subsequent obliteration using local strap muscle flap. Results: A total of seven patients with a mean age of 46 years were included in the study. All patients had a past history of thyroidectomy because of goitre (n=5) or thyroid cancer (n=2) which had previously been unsuccessfully debrided two or three times. Surgical sinus removal was successful in all cases and no recurrence was observed during the follow-up time. Conclusions: We conclude that a comprehensive en bloc resection down to the suture granuloma is essential in order to provide surgical cure and prevent recurrence.
Effect of interface pressure and skin surface temperature on pressure injury incidence: a turning schedule pilot study
Authors: Tarigan Sumiati , Yusuf Saldy , Syam Yuliana 
Published: August 2021

Objective: This study aimed to evaluate the interface pressure and skin surface temperature in relation to the incidence of pressure injury (PI) using three different turning schedules. Method: This was a pilot study with a three-armed randomised clinical trial design. Participants at risk of PI and treated in the high dependency care unit in a regional hospital in Makassar, Indonesia participated in this study. Patients were repositioned at three different turning schedules (two-, three- and four-hourly intervals). Interface pressure measurement and skin surface temperature were measured between 14:00 and 18:00 every three days. The incidence of PI was assessed during the two-week observation period. Results: A total of 44 participants took part in the study. A one-way ANOVA test revealed no difference in interface pressure among the three different turning schedule groups within two weeks of observations: day zero, p=0.56; day four, p=0.95; day seven, p=0.56; day 10, p=0.63; and day 14, p=0.92. Although the average periumbilical temperature and skin surface temperature were not significant (p>0.05), comparison between these observation sites was significant on all observation days (p<0.05). Regarding the incidence of PI, the proportional hazard test for the development of PI in the three groups was considered not different (hazard ratio: 1.46, 95% confidence interval: 0.43–4.87, p=0.54). Conclusion: No difference in interface pressure and incidence of PI on the three turning schedules was observed; however, there was a potential increase in skin surface temperature in comparison with periumbilical temperature for all three turning schedules.
Testing the association between the early parent–child relationship and teacher reported socio-emotional difficulties at 11 years: a quantile mediation analysis
Authors: Rush Robert , Westrupp Elizabeth , Law James 
Published: August 2021

The importance of the relationship between socio-emotional difficulties in childhood and adult mental health are well recognised but how such difficulties emerge is less well recognised. Specifically this paper explores the extent of the relationship between parenting beliefs in the first year of the child’s life, parenting skills reported when the child was three years and different quantiles of socio-emotional development recorded by teachers at 11 years. In addition, it explores the extent to which language development at school entry has the potential to mediate these relationships.
This paper draws on data from the UK’s Millennium Cohort Study (MCS) to investigate the relation between parenting attitudes when the child was ten months old and parent–child relationship when the child was three years of age to child socio-emotional development measured using the Strengths and Difficulties Questionnaire at 11 years, and the mediating role of naming vocabulary measured on the British Abilities Scales (BAS) at school entry (five years).
Unadjusted associations were found for both parental factors on child mental health problems, but this did not hold for parent beliefs once the models were adjusted. The relationships varied in the quantile analysis suggesting that this approach adds to our understanding of these relationships. Vocabulary at school entry mediated the relation to socio-emotional difficulties especially for children with higher levels of mental health problems. Results are discussed in relation to the mechanisms in any intervention to improve mental health outcomes at the end of primary school.
Smart Cooperative Distance Learning: Ein multiagentenbasierter Ansatz zur Unterstützung des kooperativen Lernens im Distanzunterricht
Authors: Gösling Henning , Dreesbach Tobias , Schulte to Brinke Jan , Thomas Oliver 
Published: August 2021

ZusammenfassungLehrkräfte können auf eine Vielzahl von etablierten Unterrichtsmethoden zurückgreifen, um kooperatives Lernen in den Präsenzunterricht zu integrieren. Im Distanzunterricht während der Corona-Pandemie werden diese Methoden jedoch häufig nicht eingesetzt. Dadurch gehen das gemeinschaftliche, strukturierte Lernen und die damit einhergehenden positiven Effekte auf die Schülerinnen und Schüler verloren. Eine State-of-the-Art-Analyse zeigt, dass kaum technische Lösungen existieren, die methodenbasiertes, kooperatives Lernen in einem Distanzunterricht unterstützen – und falls doch, handelt es sich um sehr spezielle Lösungen für die Umsetzung einer konkreten Unterrichtsmethode. Wir schlagen daher das Konzept eines Smart Cooperative Distance Learning Systems vor. Dabei handelt es sich um ein Multiagentensystem in einer Cloud, welches insbesondere die methodenbasierte, kooperative Ausführung von Lerneinheiten unterstützt. Ein Szenario dient zur Veranschaulichung des Smart Cooperative Distance Learning Systems.
Spatiotemporal distribution and sociodemographic and socioeconomic factors associated with primary and secondary syphilis in Guangdong, China, 2005–2017
Authors: Tang Shangqing , Shi Lishuo , Chen Wen , Zhao Peizhen , Zheng Heping , Yang Bin , Wang Cheng , Ling Li 
Published: August 2021

Background
Previous studies exploring the factors associated with the incidence of syphilis have mostly focused on individual-level factors. However, recent evidence has indicated that social-level factors, such as sociodemographic and socioeconomic factors, also affect the incidence of syphilis. Studies on the sociodemographic and socioeconomic factors associated with syphilis incidence are scarce, and they have rarely controlled for spatial effects, even though syphilis shows spatial autocorrelation.

Methodology/Principal findings
Syphilis data from 21 cities in Guangdong province between 2005 and 2017 were provided by the National Notifiable Infectious Disease Reporting Information System. The incidence time series, incidence map, and space-time scanning data were used to visualize the spatiotemporal distribution. The spatial panel data model was then applied to explore the relationship between sociodemographic factors (population density, net migration rate, male:female ratio, and the number of health institutions per 1,000 residents), socioeconomic factors (gross domestic product per capita, the proportion of secondary/tertiary industry), and the incidence of primary and secondary syphilis after controlling for spatial effects. The incidence of syphilis increased slowly from 2005 (11.91 per 100,000) to 2011 (13.42 per 100,000) and then began to decrease, reaching 6.55 per 100,000 in 2017. High-risk clusters of syphilis tended to shift from developed areas to underdeveloped areas. An inverted U-shaped relationship was found between syphilis incidence and gross domestic product per capita. Moreover, syphilis incidence was significantly associated with population density (β = 2.844, P = 0.006), the number of health institutions per 1,000 residents (β = -0.095, P = 0.007), and the net migration rate (β = -0.219, P = 0.002).

Conclusions/Significance
Our findings suggest that the incidence of primary and secondary syphilis first increase before decreasing as economic development increases further. These results emphasize the necessity to prevent syphilis in regions at the early stages of economic growth.
Community burden of hypertension and treatment patterns: An in-depth age predictor analysis: (The Rural Community Risk of Non-Communicable Disease Study - Nyive Phase I)
Authors: Osei-Yeboah James , Owusu-Dabo Ellis , Owiredu William K. B. A. , Lokpo Sylvester Yao , Agode Francis Delali , Johnson Beatrice Bella 
Published: August 2021

Background
This study aimed to describe the burden, treatment patterns and, age threshold for predicting hypertension among rural adults in Nyive in the Ho Municipality of the Volta Region, Ghana.

Methods
A population-based cross-sectional study design was employed. A total of 417 adults aged 20 years and above were randomly selected from households within the Nyive community. The WHO STEPwise approach for non-communicable diseases risk factor surveillance (STEPS) instrument was used to obtain socio-demographic and clinical information including age, gender, educational background, marital status, and occupation as well as hypertension treatment information. Blood pressure was measured using standard methods. The risk of hypertension and the critical age at risk of hypertension was determined using binary logistic regression model and the receiver-operator characteristics (ROC) analysis.

Results
The direct and indirect age-standardized hypertension prevalence was higher in males (562.58/487.34 per 1000 residents) compared to the females (489.42/402.36 per 1000 residents). The risk of hypertension among the study population increased by 4.4% (2.9%-5.9% at 95% CI) for one year increase in age while the critical age at risk of hypertension was >39 years among females and >35 years among males. About 64(46.72%) of the hypertensive participants were not on treatment whereas only 42(30.66%) had their blood pressure controlled.

Conclusion
Rural hypertension is high among adults in Nyive. The critical age at risk of hypertension was lower among males. The estimated annual increase of risk of hypertension was 4.7% for females and 3.1% for males. High levels of undiagnosed and non-treatment of hypertension and low levels of blood pressure control exist among the rural folks.
Eosinophilic meningitis in New Caledonia: The role of Angiostrongylus cantonensis?
Authors: Melot Bénédicte , Delvallez Gauthier , Gourinat Ann-Claire , Molko Nicolas , Goarant Cyrille , Ducrot Yves-Marie , Huguon Emilie , Cazorla Cécile , Chauvet Martine , Biron Antoine , Colot Julien 
Published: August 2021

IntroductionEosinophilic meningitis is a rare form of meningitis with sequelae or death occurring in approximately 2–3% of cases. The most frequent etiological agent is the parasiteAngiostrongylus cantonensis. The aim of this study was to characterize New Caledonian cases and to assess the extent to which ofA.cantonensiswas involved.Material and methodsWe performed a retrospective study of all cases of eosinophilic meningitis (EM) admitted to the Territorial Hospital of New Caledonia, from 2004 to 2019. We performed a descriptive and a multivariate analysis to identify association of variables with severe and fatal cases (or cases with sequelae).ConclusionAngiostrongyliasis was confirmed as being responsible for 17 of the 92 reported EM cases in New Caledonia from 2004 to 2019 with most being young adults and non-walking infants, and with two peaks of incidence one during the dry season and one during the rainy season. Considering the high incidence and regularity of cases, the potential reservoirs should be identified to target prevention campaigns.