bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual Course-Based Undergraduate Research Experience (CURE) During the COVID-19 Pandemic
Authors: Hernandez-Ruiz Eugenia , Dvorak Abbey L , Alderete Celeste
Published: June 2022

Translation of research to practice is essential for competent practitioners but requires skills and experience in reading and understanding research. Course-based undergraduate research experiences (CUREs) may be a means of developing research skills for all students in a course. For successful CUREs, faculty evaluate students’ research skill development and decide on a project that appropriately promotes student learning. In this case, we chose an open-ended project. We then evaluated the experiences of music students (music therapy, music performance, and music digital media) as they participated in a virtual CURE during the COVID-19 pandemic. Results of a sequential explanatory mixed-methods design with two surveys and open-ended responses of the whole group (n = 22) and a focus group with a volunteer subsample of students (n = 7) indicated important gains in understanding research articles, writing a scholarly paper, understanding the relevance of research to their coursework, and developing communication and teamwork skills. Student suggestions for improvement included clarification of the expectations and timelines, particularly in a virtual setting, and better distribution of effort during the semester. Overall, a virtual CURE may support student research skill development and help them become more effective research consumers.
Beyond Antifeminist Discourses: Analyzing How Material and Social Factors Shape Online Resistance to Feminist Politics
Authors: Holm Malin
Published: June 2022

Online platforms present new challenges to feminist politics since they provide antifeminist groups with additional possibilities to come together and advocate their claims towards wider publics. This article argues that new analytical perspectives are needed to understand how antifeminist discourses are successfully produced and promulgated online. In particular, it suggests that in addition to analyzing the content of antifeminist discourses we need to pay attention to how the design and governance of online platforms, as well as the resources among antifeminist activists, shape online resistance to feminist politics. Two analytical dimensions are introduced that help to specify how the design and governance of online platforms, as well as the social composition of antifeminist groups, enable these to come together online and influence mainstream publics. To demonstrate the usefulness of this analytical approach, a study of an influential antifeminist blogosphere in the Swedish context is used as an illustrative case.
Prevalence and Distribution of Phony Peach Disease (Caused byXylella fastidiosa) in the United States
Authors: Johnson Kendall A. , Bock Clive H. , Vinson Edgar L. , Brannen Phillip M.
Published: June 2022

Peach is an important specialty fruit crop in the United States, and phony peach disease (PPD), caused by Xylella fastidiosa subsp. multiplex, has been a major cause of yield loss since it was first observed in 1885. Under a federal eradication program, surveys of PPD were conducted from 1929 to 1972, when the program was terminated. No surveys have been conducted in approximately 50 years; therefore, the current prevalence of PPD in the United States is unknown, especially in the Southeast, where damage was previously most severe. To ascertain the status of PPD, we surveyed orchards in Alabama, Florida, Georgia, and South Carolina from June to August 2020 and, except for South Carolina and northern Georgia, PPD was prevalent. Trees in 17 orchards were subjected to confirmation of X. fastidiosa using the AmplifyRP XRT+ for X. fastidiosa to corroborate our visual assessments; based on these tests, PPD incidence in the orchards ranged from 0 to 30.5%. Ancillary written surveys of relative PPD presence and prevalence were sent to fruit pathologists from universities in 20 states where PPD was historically reported. Only 35.0% of respondents reported that PPD either currently or recently occurred in their state and, of these, three reported PPD to be of significant concern. The results of the physical and written surveys indicate that PPD remains prevalent mainly in the southeastern region of the United States but, in other states where previously reported, it is either not present or has very low prevalence when compared with historical accounts of the disease.
The Comparative Effectiveness of Vasoactive Treatments for Hepatorenal Syndrome: A Systematic Review and Network Meta-Analysis*
Authors: Pitre Tyler , Kiflen Michel , Helmeczi Wryan , Dionne Joanna C. , Rewa Oleksa , Bagshaw Sean M. , Needham-Nethercott Natalie , Alhazzani Waleed , Zeraatkar Dena , Rochwerg Bram
Published: June 2022

OBJECTIVE:

Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the comparative effectiveness of inpatient treatments for HRS by performing a network meta-analysis of randomized clinical trials (RCTs).

DATA SOURCES:

We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process & Other Non-Indexed Citations, Scopus, and Web of Science from inception.

STUDY SELECTION AND DATA EXTRACTION:

Pairs of reviewers independently identified eligible RCTs that enrolled patients with type 1 or 2 HRS. Pairs of reviewers independently extracted data.

DATA SYNTHESIS:

We assessed risk of bias using the Cochrane tool for RCTs and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. Our main outcomes are all-cause mortality, HRS reversal, and serious adverse events. Of 3,079 citations, we included 26 RCTs examining 1,736 patients. Based on pooled analysis, terlipressin increases HRS reversal compared with placebo (142 reversals per 1,000 [95% CI, >87.7 to >210.9]; high certainty). Norepinephrine (112.7 reversals per 1,000 [95% CI, 52.6 to >192.3]) may increase HRS reversal compared with placebo (low certainty). The effect of midodrine+octreotide (67.8 reversals per 1,000 [95% CI, <2.8 to >177.4]; very low) on HRS reversal is uncertain. Terlipressin may reduce mortality compared with placebo (93.7 fewer deaths [95% CI, 168.7 to <12.5]; low certainty). Terlipressin probably increases the risk of serious adverse events compared with placebo (20.4 more events per 1,000 [95% CI, <5.1 to >51]; moderate certainty).

CONCLUSIONS:

Terlipressin increases HRS reversal compared with placebo. Terlipressin may reduce mortality. Until access to terlipressin improves, initial norepinephrine administration may be more appropriate than initial trial with midodrine+octreotide. Our review has the potential to inform future guideline and practice in the treatment of HRS.
Molecular mechanism of vitiligo treatment by bailing tablet based on network pharmacology and molecular docking
Authors: Li Jinming , Yang Meng , Song Yeqiang
Published: June 2022

Background:

Bailing tablet, a patent Chinese medicine, is widely used to treat vitiligo in China. However, the underlying mechanism of this combined drug in treating vitiligo still remains unclear.

Objective:

This study aimed to investigate the pharmacological mechanism of bailing tablet in the prevention and treatment of vitiligo using network pharmacology and molecular docking.

Methods:

Genetic data of vitiligo and normal people were obtained by gene expression omnibus (GEO) DataSets database and GEO difference analysis was conducted to obtain differential genes. The main active compounds and corresponding target genes of bailing tablet were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Combined with the results of GEO difference analysis, the main compounds and corresponding target genes of bailing tablet in the treatment of vitiligo were screened. The network diagram of “traditional Chinese medicine compound target” was constructed by Cytoscape software. According to the differential genes, the core targets with potential therapeutic effect were searched, the protein–protein interaction network was constructed, and the key proteins were explored by topological analysis (CytoNCA). Meanwhile, the core targets were analyzed by biological process (gene ontology) and signal pathway (Kyoto encyclopedia of genes and genomes) function enrichment. Molecular docking technology was adopted to verify the combination of main components and core targets.

Results:

A total of 170 active compounds and 1777 prediction targets were screened from 11 traditional Chinese medicines of bailing tablet, of which 65 active components and 68 related prediction targets were closely related to vitiligo. A total of 320 key proteins were obtained by analyzing the topological characteristics of the protein–protein interaction network, mainly including neurotrophic receptor tyrosine kinase 1, tumor protein P53, cullin 3, estrogen receptor 1, etc. The main biological processes involve oxidative stress response, cell response to reactive oxygen species, and reactive oxygen species metabolism. Bailing tablet treats vitiligo mainly by regulating immune inflammation, apoptosis, and autophagy, which involves phosphatidylinositol-4,5-bisphosphate 3-kinase Akt signal pathway, mitogen-activated protein kinase signal pathway, Janus kinase signal transducer and activator of transcription signal pathway, melanin production, and helper T cell (Th)1, Th2, and Th17 differentiation pathway, etc. Molecular docking results showed that the main components could bind to the target protein well.

Conclusions:

Based on network pharmacology and molecular docking, the mechanism of bailing tablet in the treatment of vitiligo through multicomponent, multitarget, and multichannel was deeply explored.
Efficacy of subcutaneous Levothyroxine in a case of refractory hypothyroidism: A case report
Authors: Naman Annabelle , Delemer Brigitte , Marot Didier , Michelet Elise , Decoudier Bénédicte , Barraud Sara
Published: June 2022

Rationale:

Daily oral synthetic levothyroxine (LT4) is the main treatment for hypothyroidism, which, in most cases, allows the regression of symptoms and the normalization of the thyroid function. However, rarely, despite a high dose of oral LT4, hypothyroidism persists and is called refractory hypothyroidism. Intravenous or intramuscular treatment is then often necessary. We report the case of a patient with refractory hypothyroidism successfully treated with subcutaneous LT4.

Interventions and outcomes:

After 4 weeks of weekly intravenous injections of 200 µg LT4 in complement to the oral treatment, thyroid balance was improved (TSH: 21.8 mIU/L). We tested the replacement of intravenous with subcutaneous injections of LT4 and gradually increased injection frequency from 1 to 3 injections per week (600 µg/week). Simultaneously, oral treatment was gradually tapered off, and within a few months, thyroid function tests were normalized. Two years later, hormone levels remained normal without symptoms of hypothyroidism. The only side effect was a local reaction in the first few weeks of injections, which spontaneously resolved.

Lessons:

In this case of unexplained oral LT4 malabsorption, subcutaneous injection allowed a self-administrated physiological dose of LT4 3 times weekly. Considering the efficacy of subcutaneous injection of LT4, this treatment could be a safe and easy alternative for patients with malabsorption.
Intramedullary spinal cord abscess associated with right-to-left shunt via right superior vena cava draining into left atrium: A case report
Authors: Hirose Satoshi , Sudo Naohiro , Okada Masahiro , Natori Naotoshi , Akimoto Takayoshi , Hara Makoto , Nakajima Hideto
Published: June 2022

Rationale:

Intramedullary spinal cord abscess (ISCA) is a rare but treatable bacterial infection of the central nervous system, and the etiology in no less than 40% of the cases is cryptogenic. Although a few cases of ISCA in individuals with a right-to-left shunt (RL shunt) have been reported, only few arguments focused on the association between RL shunt and ISCA have been provoked. The right superior vena cava (RSVC) draining into the left atrium (LA) is an uncommon systemic venous anomaly that results in an RL shunt, and this anomaly causes several types of neurological complication such as stroke or brain abscess. We report the first case of ISCA associated with RSVC-LA RL shunt.

Patient concerns:

A 36-year-old man developed progressive paraparesis, dysuria, and spontaneous pain in the lumbar region and lower extremities. Spinal magnetic resonance imaging revealed an intramedullary lesion extended from Th12 to L2 with ring-shaped gadolinium enhancement. Cerebrospinal fluid (CSF) study exhibited a marked pleocytosis, and CSF culture grew Streptococcus intermedius. Cardiovascular computed tomography angiography identified RSVC-LA RL shunt, which caused transient acute cardiac syndrome due to air embolus.

Diagnoses:

The patient was diagnosed with ISCA associated with an RSVC-LA RL shunt.

Interventions:

The patient was treated with a combination of intravenous administration of meropenem and vancomycin in a daily dose of 6 and 2.5 g, respectively, followed by intravenous administration of ampicillin in a daily dose of 750 mg. The intravenous antibiotic therapy was continued for 37 days.

Outcomes:

A favorable neurological outcome was obtained by the intravenous antibiotic therapy, and recurrence of infection was prevented by continuous oral antibiotic therapy for 18 months.

Lessons:

With a literature review of ISCA associated with RL shunt, we insist that screening for RSVC-LA is beneficial to patients who are diagnosed with cryptogenic ISCA as its identification leads to appropriate preventive therapy.
Age : pleural fluid ADA ratio and other indicators for differentiating between tubercular and malignant pleural effusions
Authors: Zhou Jiupeng , Yang Yuanli , Zhang Yongfeng , Liu Heng , Dou Quanli
Published: June 2022

Most of pleural effusions are caused by tuberculosis and malignant tumor. Difficult sampling and bacterial sparing nature of these diseases challenge doctors’ diagnosis in China.

This study aimed to develop a new convenient and effective method for the differentiation of tuberculous and malignant pleural effusion.

A prospective cohort study of patients hospitalized with malignant (n = 90) and tuberculous (n = 130) pleural effusions from September 2018 to October 2020 was performed. The diagnostic performance of the age to pleural fluid ADA ratio (age/ADA) and other indicators to distinguish tuberculous and malignant pleural effusions was evaluated by receiver operating characteristic (ROC) curve analysis.

The areas under the curve (AUC) of age/ADA and pleural fluid ADA were largest. Age/ADA showed sensitivity and specificity of 81.5% (95%CI 73.8%–87.8%) and 97.8% (95%CI 92.2%–99.7%) respectively. The sensitivity and specificity of pleural fluid ADA were 83.1% (95%CI 75.5%–89.1%) and 93.3% (95%CI 86.1%–97.5%) respectively. The positive likelihood [36.69 (95%CI 9.3–144.8)] of age/ADA was significantly higher than that of pleural fluid ADA [12.46 (95%CI 5.7–27.1)]. The AUCs for Cancer Ratio and Cancer Ratio plus were lower and showed a sensitivity of 80.0% (95%CI 72.1%–86.5%), 80.0% (95%CI 70.2%–87.7%) and a specificity of 81.5% (95%CI 73.8%–87.8%), 80.0% (95%CI 70.2%–87.7%) respectively.

Age/ADA has a higher diagnostic accuracy than ADA. Age/ADA is a promising diagnostic index for tuberculous and malignant pleural effusion with high sensitivity and specificity, especially the high positive likelihood ratio. The diagnostic accuracy of Cancer Ratio and Cancer Ratio plus are inferior to those of age/ADA and ADA.
Advanced parental age is an independent risk factor for term low birth weight and macrosomia
Authors: Chung Yoo Hyun , Hwang In Sun , Jung Gyul , Ko Hyun Sun
Published: June 2022

We aimed to investigate association between parental age and the risks of term low birth weight and macrosomia.

This was a retrospective cohort study using a national database including 2,245,785 term singleton live births with complete parental age data. Old parental age was defined as 35 years or older. Odd ratios (OR) for term low birth weight and macrosomia were analyzed using univariate and multivariate logistic regression analysis.

Neonatal sex, maternal occupation, parity, nationality, age, and paternal age were significant factors of term low birth weight and macrosomia, in univariate analysis. In multivariate analysis, old maternal age (≥35 years old) showed increased odds of term low birth weight and macrosomia (aOR = 1.122, 95% CI: 1.083 –1.162; and aOR = 1.166, 95% CI: 1.143 – 1.189, respectively). Similarly, old paternal age (≥35 years old) showed increased odds of term low birth weight and macrosomia (aOR = 1.090, 95% CI: 1.058 –1.122; and aOR = 1.101, 95% CI: 1.083 – 1.119, respectively). Maternal education that lasted more than 12 years had reduced odds of term low birth weight and macrosomia (OR = 0.817, 95% CI: 0.792 –0.842; and OR = 0.894, 95% CI: 0.879 – 0.91, respectively). Paternal education that lasted more than 12 years also had reduced odds of term low birth weight and macrosomia (OR = 0.865, 95% CI: 0.84 –0.892; and OR = 0.897, 95% CI: 0.881 – 0.913, respectively).

This study suggests that not only maternal age but also paternal age are significantly associated with term low birth weight and macrosomia. In addition, parental education levels are also associated with term low birth weight and macrosomia.
HIV Testing Services Outcomes in CDC-Funded Health Departments During COVID-19
Authors: Patel Deesha , Williams Weston O. , Wright Carolyn , Taylor-Aidoo Nicole , Song Wei , Marandet Angele , DiNenno Elizabeth A.
Published: June 2022

Background:

Organizations offering HIV prevention services have reported interruptions during the COVID-19 pandemic. The national extent of these interruptions and their public health impact remain largely unexplored.

Methods:

Using data from 60 state and local health departments, we compared HIV testing services outcomes in calendar years 2019 and 2020, including the number of Centers for Disease Control and Prevention (CDC)-funded HIV tests conducted, the percentage of persons with newly diagnosed HIV infection (ie, HIV positivity), and the percentage linked to HIV medical care within 30 days after new diagnoses (ie, linkage to care) using χ2 and robust Poisson models. We also assessed the independent associations between the pandemic period (ie, March—December 2020) and the number of COVID-19 cases with monthly HIV testing services outcomes using multivariable robust Poisson models.

Results:

There was a 46.0% (P < 0.001) reduction in the number of CDC-funded HIV tests conducted in 2020 (n = 1,255,895) compared with 2019 (n = 2,324,421). Although there were fewer persons with newly diagnosed HIV in 2020 (n = 5581 vs. n = 7739 in 2019), HIV positivity was greater in 2020 (0.4% vs. 0.3% in 2019; adjusted prevalence ratio [aPR] = 1.33, 95% confidence interval [CI]: 1.05 to 1.69). When adjusting for the monthly number of COVID-19 cases, the pandemic period was associated with a 56% reduction in the number of monthly CDC-funded HIV tests (adjusted rate ratio = 0.44, 95% CI: 0.37 to 0.52) but 28% higher monthly HIV positivity (aPR = 1.28 95% CI: 1.16 to 1.41) and 10% higher linkage to care (aPR = 1.10, 95% CI: 1.02 to 1.18).

Discussion:

Despite increased HIV positivity, a drastic reduction in the number of CDC-funded HIV tests was observed in 2020, affecting the ability to identify persons with newly diagnosed HIV. CDC and health departments will need to expand testing strategies to cover tests not conducted in 2020 while adapting to the continuing pandemic.

A visual abstract is available for this article at: http://links.lww.com/QAI/B941
Inhibitory effects of GT0918 on acute lung injury and the molecular mechanisms of anti-inflammatory response
Authors: Hou Xiaodan , Yan Honghua , Wang Ao , Liu Cong , Zhou Qianxiang , Ma Liandong , Chen Jie , Ren Zhihua , Tong Youzhi
Published: June 2022

Coronavirus disease 2019 (COVID-19) has caused the public health crisis in the whole world. Anti-androgens block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and protect against severe clinical COVID-19 outcomes. GT0918, a novel androgen receptor antagonist, accelerated viral clearance and increased recovery rate in outpatients by blocking SARS-CoV-2 infection though down-regulating ACE2 and TMPRSS2 expression. Further clinical study showed that GT0918 reduced mortality rate and shortened hospital stay in hospitalized COVID-19 patients. GT0918 also exhibits protective efficacy in severe COVID-19 patient in critical care. However, the mechanism of GT0918 treatment for severe COVID-19 disease is unknown. Here, we found GT0918 decreased the expression and secretion of proinflammatory cytokines through NF-κB signaling pathway. The acute lung injury induced by LPS or Poly(I:C) was also attenuated in GT0918-treated mice, compared with vehicle control group. Moreover, GT0918 elevated the NRF2 protein level but not mRNA transcription activity. GT0918 induced proinflammatory cytokines downregulation was partially dependent on NRF2. In conclusion, our data demonstrate that GT0918 reduced cytokine release and suppressed inflammatory responses through inhibiting NF-κB signaling and activating NRF2. GT0918 is not only effective for treatment of mild to moderate COVID-19 patients, but also a potential therapeutic drug for severe COVID-19 patients by reducing the risk of cytokine storm and acute respiratory distress syndrome.
On the growth of the wallpaper groups
Authors: Grigorchuk Rostislav , Kravaris Cosmas
Published: June 2022

Coordination sequences (also called growth functions) appear in various areas of chemistry and crystallography, such as ice crystals and zeolites, and various areas of mathematics, such as lattice theory and geometric group theory. Cannon's method of cone types is modified for finding the coordination sequence of the Cayley graph of a group. This method is then applied to compute the growth functions and the growth series of the Cayley graphs of the wallpaper groups (the 2D crystallographic groups). The paper has several tables and colored figures summarizing and illustrating the results.
Postoperative radiation therapy improves prognoses in extramammary Paget's disease presenting with multiple lymph node metastases
Authors: Okumura Mao , Ogata Dai , Namikawa Kenjiro , Tsutsui Keita , Takahashi Akira , Okuma Kae , Kashihara Tairo , Igaki Hiroshi , Akiyama Masashi , Yamazaki Naoya
Published: June 2022

Invasive extramammary Paget's disease may cause lymph node and distant metastases. Complete lymph node dissection is generally performed for extramammary Paget's disease presenting with lymph node metastases. Patients with extramammary Paget's disease and multiple lymph node metastases typically have poor prognoses, and there is no effective postoperative treatment to prevent recurrence or further metastases in such patients to date. This study aimed to evaluate the efficacy of postoperative radiotherapy in patients with extramammary Paget's disease and multiple lymph node metastases. We enrolled 26 patients with extramammary Paget's disease with ≥3 lymph node metastases who were treated at the National Cancer Center Hospital in Japan between January 2000 and June 2021. The patients were divided into those who underwent complete lymph node dissection only or with postoperative radiotherapy. We evaluated recurrence‐free survival, distant metastasis‐free survival, and overall survival outcomes with Kaplan–Meier curves. Among the 26 enrolled patients, 16 underwent complete lymph node dissection only and 10 underwent complete lymph node dissection with postoperative radiotherapy. The median follow‐up period was 16 months. The 5‐year recurrence‐free, distant metastasis‐free, and overall survival values were 47.3%, 63.0%, and 90% in those with complete lymph node dissection and postoperative radiotherapy, while these outcomes were all 0% (p = 0.001, 0.004, and 0.009, respectively) in those with only complete lymph node dissection. Thus, survival was significantly prolonged with postoperative radiotherapy. Additional postoperative radiotherapy may substantially improve the prognoses of patients with extramammary Paget's disease and ≥3 lymph node metastases, and undergoing curative surgery.
Assessing time processing ability and daily time management in persons with dementia: Psychometric properties of three instruments
Authors: Persson Ann‐Christine , Möller Marika C. , Dahlberg Lena , Löfgren Monika , Janeslätt Gunnel
Published: June 2022

Introduction

Persons with dementia experience time‐related problems, but there is a lack of instruments evaluating their time processing ability and daily time management. This study aimed to evaluate the psychometric properties of the instruments KaTid®‐Senior measuring time processing ability, and Time‐S© Senior and Time‐Proxy© measuring daily time management for persons with dementia.

Methods

Persons with dementia (n = 53) and their significant others (n = 49) participated in the study. Rasch analyses were used to evaluate the instruments' rating scale functioning; internal scale validity; person‐response validity; unidimensionality; person‐separation reliability; and internal consistency. Versions excluding items with poor fit to the Rasch model were also evaluated.

Results

Overall, the Rasch analyses showed acceptable psychometric properties. All instruments met the criteria for unidimensionality and the reliability was good. More challenging items should be added in KaTid‐Senior for better targeting of persons with mild dementia. Person‐response validity issues in Time‐S Senior need to be addressed.

Conclusion

The instruments can validly and reliably be used to assess time processing ability and daily time management in persons with dementia in clinical research and healthcare settings. In turn, this can contribute to the development of methods to compensate for impaired time processing ability and daily time management. The assessments can also increase the possibility of early detection of impaired time processing ability and daily time management, thereby facilitating adequate timing of interventions and enhanced occupational performance.
Functional bioplastics from food residual: Potentiality and safety issues
Authors: Boccalon Elisa , Gorrasi Giuliana
Published: June 2022

Plastic pollution and food waste are two global issues with much in common. Plastic containers were introduced as a practical and easy remedy to improve food preservation and reduce the risk of creating waste, but ironically, to address one problem, another has been made worse. The spread of single‐use containers has dramatically increased the amount of plastic that has to be discarded, and the most urgent task is now to find a solution to what has become part of the problem. An innovative way around it consists of promoting the valorization of food residues by turning them into novel materials for packaging. Although the results are promising, the aim of completely replacing plastics with biodegradable materials still seems far from being achieved. This review illustrates the main strategies adopted thus far to produce new bioplastic materials and composites from waste resources and focuses on the pros and cons of the food recovery process to look for the aspects that represent an obstacle to the development of the circular food economy on an industrial scale.
Integrity of hypothalamic–pituitary‐testicular axis in exceptional longevity
Authors: Aleksic Sandra , Desai Dimpi , Ye Kenny , Duran Sally , Gao Tina , Crandall Jill , Atzmon Gil , Barzilai Nir , Milman Sofiya
Published: June 2022

Hypothalamic integrity increasingly is being recognized as a marker of healthy longevity in rodent models. Insight into hypothalamic function in humans with exceptional longevity can be gained via investigation of the hypothalamic–pituitary‐testicular (HPT) axis in men with exceptional longevity. This study aimed to characterize the HPT axis function, defined by levels of testosterone (T) and luteinizing hormone (LH), in 84 Ashkenazi Jewish men aged 90–106 years. We found that 94% of men exhibited preserved hypothalamic–pituitary function, as evidenced by either normal testosterone and LH levels (25%) or an appropriate rise in LH in response to aging‐related primary testicular dysfunction (69%), a hormone pattern mirroring female menopause. Total T level was not associated with metabolic parameters or survival. These results demonstrate a high prevalence of testicular dysfunction with preserved hypothalamic–pituitary function in men with exceptional longevity. Thus, the role of hypothalamic integrity and HPT axis in healthy aging warrants further investigation.
Documentation and diagnosis of delirium in Parkinson's disease
Authors: Cullinan Rachel J. , Richardson Sarah J. , Yarnall Alison J. , Burn David J. , Allan Louise M. , Lawson Rachael A.
Published: June 2022

Objective

To assess the accuracy of documentation of the symptoms and diagnosis of delirium in medical notes of inpatients with Parkinson's disease (PD).

Methods

The DETERMINE‐PD pilot study assessed PD inpatients over 4‐months. Delirium prevalence was classified prospectively using a standardized assessment at a single visit on the basis of Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM‐5) criteria. Incident delirium was diagnosed retrospectively using detailed clinical vignettes and validated consensus method. Inpatient medical notes and discharge summaries of those with delirium were reviewed for documentation of symptoms, diagnosis and follow‐up.

Results

Forty‐four PD patients consented to take part in the study, accounting for 53 admissions. We identified 30 cases (56.6%) of delirium during the participants' stay in hospital. Of those with delirium identified by the research team, delirium symptoms were documented in the clinical notes of 72.3%; 37.9% had a delirium diagnosis documented. Older patients were more likely to have delirium (p = 0.027) and have this diagnosis documented (p = 0.034). Time from documentation of symptoms to diagnosis ranged from <24 h to 7 days (mean 1.6 ± 4.4 days). Hypoactive delirium was significantly less likely to have been identified and formally diagnosed (63% of not documented were hypoactive vs. 37% hyperactive, mixed or unclear, p = 0.016). Only 11.5% of discharge summaries included diagnosis of delirium.

Conclusion

Delirium in PD is common. Documentation of symptoms of delirium was common; however, fails to lead to a documentation of diagnosis in over half of admissions with delirium and was even less commonly communicated in the Primary Care discharge summaries. This highlights the need for increased education about delirium symptomatology and diagnosis in PD.
Downregulation of GPR160 inhibits the progression of glioma through suppressing epithelial to mesenchymal transition (EMT) biomarkers
Authors: Abbas Azar , Jun Peng , Yuan Jiang Yuan , Sun Li , Jiang Jinwei , Yuan Shengtao
Published: June 2022

Background

Glioma is one of the most fatal types of malignant tumours, the cause of which is mostly unknown. Orphan GPCRs (GPRs) have been previously implicated in tumour growth and metastasis. Therefore, these GPRs could prove to be alternative and promising therapeutic targets for cancer treatment.

Objective

The role of GPR160 in glioma has not yet been assessed. This study aims to explore the association of GPR160 with glioma progression and investigate its role in epithelial‐to‐mesenchymal transition (EMT) and metastasis.

Methods

Changes in protein expression were assessed using western blot analysis and immunofluorescent staining assays, while mRNA expression changes were evaluated using qRT‐PCR. To detect the changes in progression and metastasis, MTT, EdU proliferation, wound healing, transwell migration, and flow cytometry assays were carried out in vitro. An epithelial to mesenchymal phenotypic analysis was performed to detect EMT.

Results

We demonstrated that knockdown of GPR160 inhibited proliferation, colony formation, and cell viability and promoted apoptosis. Pro‐apoptotic biomarkers were upregulated, while anti‐apoptotic biomarkers were downregulated. Cell lines with GPR160 knockdown (GPR160 KD) showed a slowed migration rate and decreased invasion ability. EMT mesenchymal biomarkers were downregulated in GPR160 KD cell lines, while epithelial biomarkers were upregulated.

Conclusion

This study provides evidence that GPR160 is a potential therapeutic target in glioma for the first time. These findings can be used to discover in detail the molecular mechanism and pathways through which GPR160 promotes glioma progression.
Systematic review and network meta‐analysis comparing ofatumumab with other disease‐modifying therapies available in Japan for the treatment of patients with relapsing multiple sclerosis
Authors: Drudge Christopher , Zhao Melody , Tanaka Satoru , Tanaka Nozomu , Otaka Hiromichi , Kawachi Izumi , Häring Dieter A. , Brennan Róisín , Adlard Nicholas , Samjoo Imtiaz A.
Published: June 2022

Objective

No head‐to‐head clinical trials have compared ofatumumab with other disease‐modifying therapies (DMTs) available in Japan for patients with relapsing multiple sclerosis (RMS). In this study, a network meta‐analysis (NMA) was conducted to compare the efficacy of ofatumumab to other DMTs currently available in Japan for the treatment of patients with RMS.

Methods

Systematic searches were conducted in biomedical databases from inception to June 2020 to identify randomized controlled trials. Only English‐ and Japanese‐language publications describing studies conducted in Japan were included. Trials with sufficiently similar study and patient characteristics were included in a Bayesian NMA. A sensitivity analysis was conducted to explore the impact of potential sources of uncertainty.

Results

Four trials, each comparing a DMT with placebo in a ≥50% Japanese population, were sufficiently similar that comparative efficacy could be assessed for annualized relapse rate (ARR). Ofatumumab numerically reduced ARR compared with fingolimod (rate ratio [RR]: 0.84, 95% credible interval [CrI]: 0.20–3.39), dimethyl fumarate (RR: 0.61, 95% CrI: 0.16–2.30), and placebo (RR: 0.41, 95% CrI: 0.12–1.39), but not natalizumab (RR: 1.33, 95% CrI: 0.33–5.45). In a subgroup analysis of Japanese patients only, ofatumumab reduced relapses compared with all other treatments including natalizumab. These results were limited by the lack of studies reporting direct comparisons between included treatments and by heterogenous reporting of outcome data.

Conclusion

These findings, although limited by the paucity of evidence for Japanese patients, suggest that monoclonal antibody therapies (ie, natalizumab and ofatumumab) may provide improved efficacy compared with other DMTs available in Japan for patients with RMS.
Beyond inappropriate fire regimes: A synthesis of fire‐driven declines of threatened mammals in Australia
Authors: Santos Julianna L. , Hradsky Bronwyn A. , Keith David A. , Rowe Kevin C. , Senior Katharine L. , Sitters Holly , Kelly Luke T.
Published: June 2022

Fire can promote biodiversity, but changing patterns of fire threaten species worldwide. While scientific literature often describes ‘‘inappropriate fire regimes’’ as a significant threat to biodiversity, less attention has been paid to the characteristics that make a fire regime inappropriate. We go beyond this generic description and synthesize how inappropriate fire regimes contribute to declines of animal populations using threatened mammals as a case study. We developed a demographic framework for classifying mechanisms by which fire regimes cause population decline and applied the framework in a systematic review to identify fire characteristics and interacting threats associated with population declines in Australian threatened land mammals (n = 99). Inappropriate fire regimes threaten 88% of Australian threatened land mammals. Our review indicates that intense, large, and frequent fires are the primary cause of fire‐related population declines, particularly through their influence on survival rates. However, several species are threatened by a lack of fire, and there is considerable uncertainty in the evidence base for fire‐related declines. Climate change and predation are documented or predicted to interact with fire to exacerbate mammalian declines. This demographic framework will help target conservation actions globally and will be enhanced by empirical studies of animal survival, movement, and reproduction.
The effect of neuropsychiatric medication on pediatric nonalcoholic fatty liver disease
Authors: Ryan Jamie L. , Sherman Ashley K. , Heble Daniel E. , Friesen Craig A. , Daniel James F. , Fischer Ryan T. , Slowik Voytek
Published: June 2022

Obese and overweight children are at risk of developing nonalcoholic fatty liver disease (NAFLD), which can lead to steatohepatitis, cirrhosis, and liver transplantation. Neuropsychiatric conditions affect an increasing proportion of children and often require neuropsychiatric medications (NPMs) that are associated with weight gain and/or drug‐induced liver injury. We sought to evaluate the role that the extended use of NPMs play in pediatric NAFLD. Medical chart review was conducted for 260 patients with NAFLD (NPM = 77, non‐NPM = 183) seen in the Liver Care Center at Children’s Mercy Hospital between 2000 and 2016. Outcome measures included body mass index (BMI) percentile, BMI z‐score, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and gamma glutamyltransferase, and were collected at diagnosis, 6–18 month follow‐up, and 18–36 months. Controlling for race and metformin, there was a significant increase over time in BMI z‐score (p < 0.01) and total bilirubin (p = 0.03), with only initial decreases in ALT (p < 0.01) and AST (p < 0.01). Except for higher total bilirubin in the non‐NPM group, no main effect of group or interaction effect was found. Similar patterns remained when subjects were analyzed by NPM drug class. Further study is needed to confirm these findings and to evaluate the effects of NPM dose and duration of exposure, by drug class, on pediatric NAFLD outcomes.
Contrast‐enhanced ultrasound for the evaluation of symptomatic and asymptomatic carotid plaques: A systematic review and meta‐analysis
Authors: Sultan Salahaden R. , Bashmail Fatima T. , Alzahrani Nouf A. , Alharbi Shahd I. , Anbar Rayan , Alkharaiji Mohammed
Published: June 2022

Background

Contrast‐enhanced ultrasound (CEUS) is a promising imaging modality for the assessment of plaque vulnerability. We aimed to systematically review and meta‐analyze the ability of CEUS parameters to differentiate between symptomatic and asymptomatic carotid plaques and to assess its reproducibility.

Methods

PubMed, EMBASE, and Cochrane Library databases were searched for studies that potentially evaluated carotid plaques using CEUS. From the initial 2870 searches, 11 relevant publications comprising a total of 821 carotid plaques were reviewed. Data on CEUS parameters including quantitative and semi‐quantitative parameters were extracted and analyzed.

Results

The overall analysis showed significantly higher CEUS parameters in symptomatic carotid plaques compared to asymptomatic carotid plaques (standardised mean difference (SMD) .95, 95% confidence interval (CI) .56–1.27, p < .01). Intra and inter‐observer reproducibility of quantitative CEUS parameters were excellent (intra‐observer, r = .95, 95% CI .87–1; inter‐observer, r = .93, 95% CI .80–.1). Semi‐quantitative CEUS parameters showed good intra‐observer reliability and moderate inter‐observer reliability (intra‐observer, r = .77, 95% CI .64–.89; inter‐observer, r = .75, 95% CI .61–.89). Heterogeneity among studies compared CEUS parameters in symptomatic and asymptomatic plaques and studies assessed inter‐observer reproducibility, and significant biases in studies assessing CEUS reproducibility were present.

Conclusion

CEUS is a useful vascular imaging method to differentiate between symptomatic and asymptomatic carotid plaques with moderate to excellent reproducibility. Quantitative CEUS analysis appeared to be more sensitive and reliable in assessing carotid plaques than semi‐quantitative parameters. Further longitudinal prospective trials evaluating carotid plaque in asymptomatic population using CEUS to determine plaque characteristics that can become symptomatic are required.
Emergence of current European thinking and policies on doctoral education
Authors: Kovačević Melita , Bitušíková Alexandra , Dagen Tamara
Published: June 2022

In today's age of knowledge and technology, societies are changing fast, on both macro and micro levels. Hardly anyone could have predicted several years ago such an acceleration of change and its impact on society, and in particular, on higher education. In Europe as well as globally, higher education has been undergoing many changes for more than two decades. In many countries, the number of higher education institutions has increased, mass education has replaced more elite systems, universities have adopted different agenda, and research has become more competitive. In this new context, doctoral education has also needed to be redefined in order to better respond to societal and academic challenges. Doctoral education—a crucial segment of higher education and the main link between the European Higher Education Area and the European Research Area—has been receiving continuous attention for more than 15 years. This paper provides an overall view on changes in doctoral education in Europe, the background of this change process, and the context that led to these major changes. The main analysis will be presented from a European academic context perspective, but it will also reflect a global perspective. It will provide an analysis of all the milestones and consider the relevant policies and recommendations on the supranational level and their reflection on the national level. While taking the reader on a 15‐year journey of the doctoral education system in Europe, a brief look to the future of doctoral education will be sketched as well.
Disturbance and nutrients synchronise kelp forests across scales through interacting Moran effects
Authors: Castorani Max C. N. , Bell Tom W. , Walter Jonathan A. , Reuman Daniel C. , Cavanaugh Kyle C. , Sheppard Lawrence W.
Published: June 2022

Spatial synchrony is a ubiquitous and important feature of population dynamics, but many aspects of this phenomenon are not well understood. In particular, it is largely unknown how multiple environmental drivers interact to determine synchrony via Moran effects, and how these impacts vary across spatial and temporal scales. Using new wavelet statistical techniques, we characterised synchrony in populations of giant kelp Macrocystis pyrifera, a widely distributed marine foundation species, and related synchrony to variation in oceanographic conditions across 33 years (1987–2019) and >900 km of coastline in California, USA. We discovered that disturbance (storm‐driven waves) and resources (seawater nutrients)—underpinned by climatic variability—act individually and interactively to produce synchrony in giant kelp across geography and timescales. Our findings demonstrate that understanding and predicting synchrony, and thus the regional stability of populations, relies on resolving the synergistic and antagonistic Moran effects of multiple environmental drivers acting on different timescales.
Control of fungi isolated from cereals: variations in the susceptibility of fungal species to essential oils, ozone, and UV‐C
Authors: Levinskaitė Loreta , Vaičekauskytė Viktorija
Published: June 2022

The application of synthetic chemicals for food protection is a cause for public concern and raises the demand for more environment‐friendly approaches. In the present study, we investigated the inhibitory efficacy of alternative measures, namely, fumigation with essential oils (EOs), ozone treatment, and ultraviolet‐C (UV‐C) irradiation against fungi associated with wheat and oat cereals. Oregano oil exhibited the strongest antifungal properties when compared to clove and cinnamon oils. Ozone fumigation induced a significant inhibition of fungal survival after 1 h of treatment. Aspergillus niger was the most sensitive to gaseous and aqueous ozone. UV‐C irradiation for 15 min had a substantial effect on Aspergillus flavus and Penicillium cyclopium, whereas 60–90 min were needed to achieve a similar effect in other tested fungi. The current findings indicated that the susceptibility of fungi differed based on the applied antifungal measures.
Inulin fructans – food applications and alternative plant sources: a review
Authors: Mudannayake Deshani C. , Jayasena Dinesh D. , Wimalasiri Kuruppu M. S. , Ranadheera C. Senaka , Ajlouni Said
Published: June 2022

Fructans are water soluble, non‐digestible fructose polymers found as storage polysaccharides in certain plants. They are classified as inulin‐type, graminan‐type and branched‐type, while the former being the most extensively researched fructan type. Inulin fructans vary in different plants, with respect to the chain length, degree of polymerisation and molecular weight. Being one of the most versatile functional food ingredients, inulin fructans are well known for their unique bifidogenic and prebiotic properties as well as techno‐functional properties including fibre enhancing, fat and sugar replacing and viscosity and texture modifying attributes in food systems. Therefore, incorporation of inulin fructans into more frequently consumed dairy and non‐dairy products has become an emerging trend in the food industry. Despite the commercial manufacture of inulin fructans from chicory, a growing interest has emerged to extract this functional ingredient from inulin‐rich alternative plant sources including jerusalem artichoke, globe artichoke, yacon, burdock, asparagus species, garlic, agave and dandelion, which can potentially be good sources of inulin for food and nutraceutical applications in future. This review provides an in‐depth insight of inulin fructans including the chemistry, food applications and health benefits, and also giving special reference to alternative plant sources.
Impact of protein oxidation induced by different cooking methods in channel fish (Ietalurus punetaus) on structure and in vitro digestion of protein
Authors: Jiang Qixing , Zhang Zhiyun , Yang Fang , Gao Pei , Yu Dawei , Xu Yanshun , Xia Wenshui
Published: June 2022

This study was designed to evaluate the effect of different cooking methods on the protein digestion characteristics of channel fish (Ietalurus punetaus). The channel fish muscles were subjected to different cooking methods, namely boiling, steaming and roasting and were subjected to in vitro gastrointestinal digestion simulation using raw fish as a control. All the cooking methods increased the protein digestibility (1.60–8.28%) and decreased the protein particle size at the end of the gastrointestinal digestion. The highest protein digestibility (66.78%) and the smallest protein particle size values (600.7 nm) were observed for the steamed group. Samples which were steam cooked showed lowest β‐sheet content (9.63 ± 0.81%) and were accompanied with moderate protein oxidation. As the core temperature increased from 40°C to 90°C, protein oxidation increased significantly (P < 0.05) with the increase of carbonyl groups and Schiff bases and decrease of sulfhydryl groups in all cooked groups. Based on the results, steaming was recommended as the best methods of cooking channel fish for improved protein digestibility.