bluuebunny/crossref_metadata_2025_split huggingface dataset:
Referral patterns to primary mental health services in Western Sydney (Australia): an analysis of routinely collected data (2005–2018)
Authors: Munasinghe Sithum , Page Andrew , Mannan Haider , Ferdousi Shahana , Peek Brendan 
Published: May 2020

Abstract
Background
Regionally-specific approaches to primary mental health service provision through Primary Health Networks (PHNs) have been a feature of recent national mental health reforms. No previous studies have been conducted to investigate local patterns of primary mental health care (PMHC) services in Western Sydney. This study is designed to (i) understand the socio-demographic and economic profiles (ii) examine the inequalities of service access, and (iii) investigate the service utilisation patterns, among those referred to PMHC services in Western Sydney, Australia.

Methods
This study used routinely collected PMHC data (2005–2018), population-level general practice and Medicare rebates data (2013–2018) related to mental health conditions, for the population catchment of the Western Sydney PHN. Sex- and age-specific PMHC referrals were examined by socio-demographic, diagnostic, referral- and service-level factors, and age-specific referrals to PMHC services as a percentage of total mental health encounters were investigated.

Results
There were 27,897 referrals received for 20,507 clients, of which, 79.19% referrals resulted in follow-up services with 138,154 sessions. Overall, 60.09% clients were female, and median age was 31 years with interquartile ranged 16–46 years. Anxiety and depression were the predominant mental health condition, and 9.88% referred for suicidal risk. Over two-thirds of referrals started treatments during the first month of the referral and 95.1% of the total sessions were delivered by face to face. The younger age group (0–24) had greater referral opportunities as a percentage of total visits to a general practitioner and Medicare rebates, however demonstrating poor attendance rates with reduced average sessions per referral compared with older adults.

Conclusion
Children and young adults were more likely to be referred to PMHC services than older adults, but were less likely to attend services. Further research is needed to identify the strategies to address these differences in access to PMHC services to optimise the effectiveness of services.
Emerging agents that target signaling pathways in cancer stem cells
Authors: Yang Yue , Li Xiaoman , Wang Ting , Guo Qianqian , Xi Tao , Zheng Lufeng 
Published: May 2020

AbstractCancer stem cells (CSCs) contribute to the initiation, recurrence, and metastasis of cancer; however, there are still no drugs targeting CSCs in clinical application. There are several signaling pathways playing critical roles in CSC progression, such as the Wnt, Hedgehog, Notch, Hippo, and autophagy signaling pathways. Additionally, targeting the ferroptosis signaling pathway was recently shown to specifically kill CSCs. Therefore, targeting these pathways may suppress CSC progression. The structure of small-molecule drugs shows a good spatial dispersion, and its chemical properties determine its good druggability and pharmacokinetic properties. These characteristics make small-molecule drugs show a great advantage in drug development, which is increasingly popular in the market. Thus, in this review, we will summarize the current researches on the small-molecule compounds suppressing CSC progression, including inhibitors of Wnt, Notch, Hedgehog, and autophagy pathways, and activators of Hippo and ferroptosis pathways. These small-molecule compounds emphasize CSC importance in tumor progression and propose a new strategy to treat cancer in clinic via targeting CSCs.
Managing acute pain in HIV+/AIDS patients: knowledge and practice trends among emergency physicians of major tertiary care centers of a developing country
Authors: Ahmed Aliya , Afshan Gauhar , Irshad Khan Robyna , Afzal Badar , Jamali Seemin , Farooq Nighat , Saleem Sarosh , Naeem Rubaba , Khan Uzma 
Published: May 2020

Abstract
Objective
To assess knowledge and practice trends in managing acute pain in patients infected with human immunodeficiency virus (HIV+) or having acquired immunodeficiency syndrome (AIDS) among emergency physicians of four tertiary care hospitals. Acute pain management in such patients is complex because of multiple concomitant painful conditions related to their disease. After obtaining ethical approval and written informed consent, emergency physicians were requested to fill out a questionnaire.

Results
Out of 84 physicians who participated, 49 had managed HIV+/AIDS patients during the preceding year. Out of the 49, 30 (61.2%) physicians stated that they used a combination of analgesics for acute pain in these patients. Forty-two (50%) out of the 84 participants believed that routine doses of opioids were adequate for pain relief, while 42 (50%) agreed that pain management was more complex in these patients mainly due to presence of multiple coexisting problems and psychological issues. Only 26 (31%) respondents considered that pain was under-reported and under-treated in these patients, mainly because physicians were more focused on patients’ other disease related complications and issues. Formulation of guidelines are recommended for effective acute pain management in these patients encompassing associated issues, including concomitant painful conditions, opioid dependence, psychiatric problems, etc.
Efflux pump activity, biofilm formation and antibiotic resistance profile of Klebsiella spp. isolated from clinical samples at Lagos University Teaching Hospital
Authors: Akinpelu Sharon , Ajayi Abraham , Smith Stella I. , Adeleye Adeyemi I. 
Published: May 2020

AbstractObjectiveNosocomial and community acquired multidrug resistantKlebsiellainfections are wide spread resulting in high morbidity and mortality due to limited number of antibiotics treatment options. This study investigated efflux pump activity, biofilm forming potential and antibiotic susceptibility profile ofKlebsiellaspp. isolated from clinical samples in a tertiary hospital in Lagos Nigeria. Eighteen clinicalKlebsiellaspp. isolated from urine, blood and sputum were subjected to antibiotic susceptibility testing using the disc diffusion method. Efflux pump activity was evaluated by the ethidium bromide cartwheel method and biofilm forming ability was determined by the tissue culture plate technique.ResultsAll 18 (100%)Klebsiellaisolates were resistant to cefuroxime, cefixime, amoxicillin − clavulanate, ampicillin + cloxacillin, cefotaxime, and imipenem. Seventeen (94.4%) were resistant to ofloxacin while sixteen (88.9%) were resistance to nalidixic acid, Gentamicin and levofloxacin. AllKlebsiellaisolates possessed active efflux pump with the ability to form biofilm. However, their biofilm forming capabilities varied as 4 (22.2%) were strong, 3 (16.7%) were moderate and 11 (61.1%) were weak biofilm formers. Findings in this study reveal multiple factors at play in mediating the high level of antibiotic resistance observed inKlebsiellaisolates. Hence a multifaceted approach is advocated in managing the infections caused by the pathogen.
Partial reduction of amyloid β production by β-secretase inhibitors does not decrease synaptic transmission
Authors: Satir Tugce Munise , Agholme Lotta , Karlsson Anna , Karlsson Mattias , Karila Paul , Illes Sebastian , Bergström Petra , Zetterberg Henrik 
Published: May 2020

Abstract
Background
Alzheimer’s disease (AD) is the most common form of age-related neurodegenerative diseases. Cerebral deposition of Aβ peptides, especially Aβ42, is considered the major neuropathological hallmark of AD and the putative cause of AD-related neurotoxicity. Aβ peptides are produced by sequential proteolytic processing of APP, with β-secretase (BACE) being the initiating enzyme. Therefore, BACE has been considered an attractive therapeutic target in AD research and several BACE inhibitors have been tested in clinical trials, but so far, all have had negative outcomes or even led to worsening of cognitive function. AD can be triggered by Aβ years before the first symptoms appear and one reason for the failures could be that the clinical trials were initiated too late in the disease process. Another possible explanation could be that BACE inhibition alters physiological APP processing in a manner that impairs synaptic function, causing cognitive deterioration.

Methods
The aim of this study was to investigate if partial BACE inhibition, mimicking the putative protective effect of the Icelandic mutation in the APP gene, could reduce Aβ generation without affecting synaptic transmission. To investigate this, we used an optical electrophysiology platform, in which effects of compounds on synaptic transmission in cultured neurons can be monitored. We employed this method on primary cortical rat neuronal cultures treated with three different BACE inhibitors (BACE inhibitor IV, LY2886721, and lanabecestat) and monitored Aβ secretion into the cell media.

Results
We found that all three BACE inhibitors tested decreased synaptic transmission at concentrations leading to significantly reduced Aβ secretion. However, low-dose BACE inhibition, resulting in less than a 50% decrease in Aβ secretion, did not affect synaptic transmission for any of the inhibitors tested.

Conclusion
Our results indicate that Aβ production can be reduced by up to 50%, a level of reduction of relevance to the protective effect of the Icelandic mutation, without causing synaptic dysfunction. We therefore suggest that future clinical trials aimed at prevention of Aβ build-up in the brain should aim for a moderate CNS exposure of BACE inhibitors to avoid side effects on synaptic function.
Treatment of rickets and dyslipidemia in twins with progressive familial intrahepatic cholestasis type 2
Authors: Sura Sunitha R. , Germain-Lee Emily L. 
Published: May 2020

Abstract
Background
Progressive Familial Intrahepatic Cholestasis Type 2 (PFIC2) is a rare congenital cholestatic liver disease that progresses to end stage liver disease. It is associated with fat soluble vitamin D deficiency rickets and severe dyslipidemia; however, treatment of these secondary effects remains a challenge.

Case presentation
One year old twin males born to a mother with intrahepatic cholestasis during pregnancy presented with jaundice, pruritus and failure to thrive. Lab evaluation revealed significant transaminitis, direct hyperbilirubinemia and normal gamma glutamyl transferase (GGT). Genetic studies confirmed PFIC2. Further evaluation for fat soluble vitamin deficiencies revealed severe vitamin D deficiency rickets. High dose vitamin D replacement therapy using Ergocalciferol (Vitamin D2) 50,000 IU three times a week over 10 weeks led to the improvement of Vitamin D, 25-Hydroxy (25-OH) serum levels and resolution of rickets. Dyslipidemia with very low high density lipoprotein-cholesterol (HDL-C) and high triglycerides was more profound in our patients compared to what has been described in the literature thus far. The dyslipidemia improved 2 months after internal biliary diversion.

Conclusions
Higher doses of Vitamin D therapy are needed for treatment of rickets secondary to cholestasis. Extremely low HDL-C levels are characteristic of PFIC and improve with treatment of underlying cholestasis. Maternal intrahepatic cholestasis during pregnancy can be an early warning sign.
Clinical examination factors that predict delayed recovery in individuals with concussion
Authors: Martinez Corina , Christopherson Zachary , Lake Ashley , Myers Heather , Bytomski Jeffrey R. , Butler Robert J. , Cook Chad E. 
Published: May 2020

Abstract
Background
Risk factors for prolonged recovery after concussion have been well researched, but specific objective clinical examination findings have not. This study examined whether clinical examination results could predict delayed recovery (DR) in individuals with concussion diagnosis. A secondary aim explored the influence of early examination on individual prognosis.

Methods
The study was a retrospective, observational cohort design that included 163 individuals seen at a concussion clinic who were followed longitudinally until cleared for sports activity. Cognitive, visual, balance, vestibular, and cervical clinical testing and symptom assessment were performed at initial evaluation. DR was calculated by taking the median value associated with time to clearance for activity. Bivariate logistic regression analysis was calculated to determine odds ratios (and 95% confidence intervals) for the odds of DR with presence or absence of each clinical finding. Multivariate analyses were used to define the best predictors of DR.

Results
80 of 163 individuals were considered delayed in their clearance to activity. Cognitive impairments (OR = 2.72; 95%CI = 1.40, 5.28), visual exam findings (OR = 2.98; 95%CI = 1.31, 6.80), and vestibular exam findings (OR = 4.28; 95%CI = 2.18, 8.43) all increased the odds of a DR. Multivariate modeling retained cognitive symptoms and clinical examination-vestibular testing as predictors of delayed recovery. Time to examination after injury was a mediator for DR.

Conclusions
The clinical examination provides value in identifying individuals who are likely to exhibit a delayed clearance. In particular, vestibular impairments identified clinically at initial evaluation and cognitive symptoms were associated with increased odds of a DR to return to activity. Our data support that early implementation of a standardized clinical examination can help to identify individuals who may be more at risk of prolonged recovery from concussion.
Can emotional design really evoke emotion in multimedia learning?
Authors: Li Jiansheng , Luo Chuanlan , Zhang Qi , Shadiev Rustam 
Published: May 2020

AbstractThe aim of this study was to investigate the effects of emotional design on learners’ performance and emotions. If emotional design has any effects on learners’ performance and emotions, then we attempted to explore dimensions that are accounted for such effects. 316 Chinese university students participated in this study. The students were divided into two groups: NED group - students in this group learned material based on neutral design, and PED group - students in this group learned material based on positive design. We explored the differences between two groups in student learning performance as well as emotion. Prior knowledge, retention, and transfer tests were also carried out and outcomes were compared across two groups. In addition, student emotion was measured using a positive affect scale and biofeedback instruments. The results showed that PED group outperformed NED group on retention and transfer tests. However, insignificant difference was found between two groups on student emotion. Our results suggest that, although the effect of emotional design was insignificant on student emotion, it was significant on student learning performance (i.e. on retention and transfer tests). Based on our results, several implications were drawn and suggestions were made for educators and researchers.
Extended-spectrum ß-lactamase-producing Escherichia coli among humans, chickens and poultry environments in Abuja, Nigeria
Authors: Aworh Mabel Kamweli , Kwaga Jacob , Okolocha Emmanuel , Harden Lyndy , Hull Dawn , Hendriksen Rene S. , Thakur Siddhartha 
Published: May 2020

Abstract
Background
Globally, chicken is known to be a reservoir for the spread of antimicrobial resistance genes to humans. In Nigeria, antimicrobial drugs are readily accessible for use in poultry production, either for preventive or therapeutic purposes. Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) are transmissible to humans because of their zoonotic potentials. People working very closely with chickens either on farms or markets are at greater risk. The aim of this study was to investigate the prevalence and zoonotic transmission of ESBL-EC among poultry-workers, chickens, and poultry environments in Abuja, Nigeria.

Methods
We conducted a cross-sectional study among workers, chickens and poultry environment in selected farms/chicken markets in Abuja. Stool, faecal, and environmental samples were collected from apparently healthy workers, chickens, and farm/market environments from December 2018 to April 2019. Data were collected electronically using an open data kit (ODK) installed on a Smartphone. Antimicrobial resistance was determined using broth micro-dilution methods against a panel of 14 antimicrobial agents. We carried out the phenotypic and genotypic characterization of the isolates. Data were analyzed by computing frequencies, proportions and spearman’s correlation (ρ).

Results
Of 429 samples, 26.8% (n = 115) were positive for Escherichia coli (E. coli). Of the 115 E. coli isolates, 32.2% (n = 37) were confirmed ESBL producers by phenotypic characterization. Prevalence of ESBL-EC was highest among both poultry-workers (37.8%; n = 14) and chickens (37.8%; n = 14) followed by the environment (24.3%; n = 9). Both human and chicken isolates showed similar patterns of multidrug resistance to tested antimicrobials with a positive correlation (ρ = 0.91). Among ESBL producers, we observed the dissemination of blaCTX-M (10.8%; n = 4) genes. The coexistence of blaCTX-M-15 and blaTEM-1 genes was observed in 8.1% (n = 3) of the isolates, out of which (66.7%; n = 2) were chicken isolates from the farm, while a single human isolate was from the chicken market.

Conclusions
ESBL-EC isolates were prevalent amongst apparently healthy individuals, chickens and the poultry farm/market environment in Abuja. It is important to educate healthcare workers that people in proximity with poultry are a high-risk group for faecal carriage of ESBL-EC, hence pose a higher risk to the general population for the spread of antimicrobial resistance.
The pyruvate dehydrogenase kinase 2 (PDK2) is associated with conidiation, mycelial growth, and pathogenicity in Fusarium graminearum
Authors: Gao Tao , He Dan , Liu Xin , Ji Fang , Xu Jianhong , Shi Jianrong 
Published: May 2020

Abstract
Pyruvate dehydrogenase kinase (PDK) is a mitochondrial enzyme in a variety of eukaryotes, including the plant pathogen Fusarium graminearum. This enzyme can reduce the oxidation of glucose to acetyl-coA by phosphorylation and selectively inhibits the activity of pyruvate dehydrogenase (PDH), which is a kind of pyruvate dehydrogenase complex (PDC). In this study, we investigated the F. graminearum pyruvate dehydrogenase kinase encoded by FgPDK2, which is a homologue of Neurospora crassa PDK2. The disruption of the FgPDK2 gene led to several phenotypic defects including effects on mycelial growth, conidiation, pigmentation, and pathogenicity. The mutants also showed decreased resistance to osmotic stress and cell membrane/wall-damaging agents. The FgPDK2 deletion mutant exhibited reduced virulence. All of these defects were restored by genetic complementation of the mutant with the complete FgPDK2 gene. Overall, the results demonstrated that FgPDK2 is crucial for the growth of F. graminearum and can be exploited as a potential molecular target for novel fungicides to control Fusarium head blight caused by F. graminearum.

Graphical abstract
Primary squamous cell carcinoma of the liver: an unexpected pathological finding
Authors: Tuminello Fabio , Castiglione Davide , Broggi Giuseppe , Vecchio Giada Maria , Basile Antonio , Puleo Stefano , Pesce Antonio 
Published: May 2020

Abstract
Background
Primary squamous cell carcinoma of the liver is a very rare cancer requiring a complete diagnostic investigation, as it presents some differences from other primary hepatic malignancies. We describe the case of an elderly patient with primitive squamous cell carcinoma of the liver treated by percutaneous microwave ablation and transarterial chemoembolization.

Case presentation
Although the pathogenesis remains uncertain, a possible transformation of the biliary epithelium caused by chronic inflammation or metaplasia and subsequent malignant transformation of preexisting benign hepatic cysts has been suggested. A critical review of the existing literature was performed by focusing on the pathogenesis, clinical presentation, and the suggested therapeutic strategies.

Conclusion
A multidisciplinary approach is needed to face rare hepatic malignancies where there are no clear guidelines.
Plasma Homocysteine and Cardiovascular Organ Damage in a Population with a High Prevalence of Risk Factors
Authors: Kozakova Michaela , Morizzo Carmela , Penno Giuseppe , Shore Angela C , Nilsson Jan , Palombo Carlo 
Published: May 2020

Abstract

Purpose
It is unclear whether plasma homocysteine (Hcy) has a direct noxious impact on the cardiovascular (CV) system or whether its association with cardiovascular events (CVEs) is mediated by established risk factors. To explore the role of Hcy in CV impairment, the study evaluated cross-sectional relationships between plasma Hcy and indices of CV organ damage together with the associations of these indices with the history of CVEs.

Methods
In 269 patients with a high prevalence of diabetes, dyslipidemia, and hypertension, the carotid intima-media thickness, ankle–brachial index (ABI), reactive hyperemic index, carotid–femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, and cardiac index were measured.

Results
132 patients had carotid plaque, 31 ABI &lt; 0.90, 126 endothelial dysfunction, 66 increased cfPWV, 125 LV hypertrophy (LVH), 153 decreased cardiac index, and 115 a history of CVEs. Plasma Hcy levels were related to LV mass and ABI, after adjustment for covariates and creatinine. Significantly higher Hcy levels were found in patients with LVH (8.5 [4.4] vs 7.6 [2.8] μmol/L; adjusted P = .001) and ABI &lt; 0.9 (10.4 [3.8] vs 7.9 [3.4] μmol/L; adjusted P = .001) than in those with LV mass and ABI within limits. Hcy levels were comparable between patients with and without carotid plaques, increased arterial stiffness, impaired endothelial, and LV pump function. Within markers of CV organ damage, only LVH was associated with a history of CVEs.

Conclusion
This study demonstrated an independent association between Hcy and LV mass as well as between LVH and a history of CVEs and suggests that LVH may represent 1 of the pathophysiologic links between Hcy and CV risk.