bluuebunny/crossref_metadata_2025 huggingface dataset:
Public service media for better democracies: Testing the role of perceptual and structural variables in shaping citizens’ evaluations of public television
Authors: Campos-Rueda Marcela , Goyanes Manuel
Published: July 2022

As PSM change and adapt –with variable outcomes– to a digital and multiplatform environment, their roles and functions are overly under severe scrutiny. The normative expectations of PSM and their performance have been extensively discussed from a theoretical and regulatory approach, but studies from an audience perspective are still rather scarce. If PSM's primary stakeholder is to be considered the citizenship it serves, it is, therefore, vital to understand what is valuable to society and how citizens assess PSM's performance. Drawing upon representative survey data from Spain (N = 1717), this study examines the role played by structural and perceptual variables in accounting for the citizen's assessment of the national public broadcaster (TVE), considering six roles: watchdog, analysis, mobilization, public forum, social empathy, and information. Findings first indicate that perceptions of independence and citizens' evaluation of TVE's journalists are positively associated with all dimensions of TVE evaluations. However, when exploring the role of political knowledge, results indicate a negative association with some of PSM's most critical functions. All in all, our research illustrates that, despite all the changes in the media landscape, when it comes to delivering the news, citizens seem to stick to values traditionally associated with PSM: independent and qualified journalism trained for and committed to the public service of delivering accurate and unbiased information.
Non-therapeutic penile circumcision of minors: current controversies in UK law and medical ethics
Authors: Lempert Antony , Chegwidden James , Steinfeld Rebecca , Earp Brian D.
Published: July 2022

The current legal status and medical ethics of routine or religious penile circumcision of minors is a matter of ongoing controversy in many countries. We focus on the United Kingdom as an illustrative example, giving a detailed analysis of the most recent British Medical Association guidance from 2019. We argue that the guidance paints a confused and conflicting portrait of the law and ethics of the procedure in the UK context, reflecting deeper, unresolved moral and legal tensions surrounding child genital cutting practices more generally. Of particular note is a lack of clarity around how to apply the “best interests” standard—ordinarily associated with time-sensitive proxy decision making regarding therapeutic options for a medically unwell patient—to a parental request for a medically unnecessary surgery to be carried out on the genitalia of a healthy child. Challenges arise in measuring and assigning weights to intended sociocultural or religious/spiritual benefits, and even to health-related prophylactic benefits, and in balancing these against potential physical, functional, and psychosexual risks or harms. Also of concern are apparently inconsistent safeguarding standards being applied to children based on their birth sex categorization or gender of rearing. We identify and discuss recent trends in British and international medical ethics and law, finding gradual movement toward a more unified standard for evaluating the permissibility of surgically modifying healthy children's genitals before they can meaningfully participate in the decision.
Demographics of Common Compressive Neuropathies in the Upper Extremity
Authors: Rocks Madeline C. , Donnelly Megan R. , Li Alexander , Glickel Steven Z. , Catalano Louis W. , Posner Martin , Hacquebord Jacques H.
Published: July 2022

Background:

The purpose of this study was to compare the demographic differences of the most common peripheral nerve compressions in the upper extremity—carpal tunnel syndrome (CTS), ulnar nerve compression (UNC) at the elbow, combined CTS and UNC, radial tunnel syndrome (RTS), and posterior interosseous nerve syndrome (PINS)—as a means to better understand the etiologies of each.

Methods:

A retrospective chart review was performed of all patients over the age of 18 years seen at our institution in the 2018 calendar year. International Classification of Diseases, Tenth Revision codes were used to identify patients with diagnoses of upper extremity peripheral nerve compressions. Demographic details and relevant comorbidities were recorded for each patient and compared with controls, who were seen the same calendar year with no neuropathies. χ2 analyses, independent-samples t tests, and multivariate logistic regressions were performed ( P < .05).

Results:

A total of 7448 patients were identified. Those with CTS were mainly women, former smokers, and diabetic (all P < .001) and with a greater average body mass index (BMI) ( P = .006) than controls. Patients with UNC were more often men and younger when compared with controls (both P < .001). A history of smoking, diabetes, and average BMI were similar between patients with UNC and controls (all P > .05). Those patients with combined CTS/UNC were mainly men, former smokers, and diabetic (all P < .001) when compared with controls. Patients with RTS/PINS were also mostly men ( P = .007), diabetic ( P = .042), and were more often current smokers ( P < .001).

Conclusions:

The demographics of patients with various compressive neuropathies were not homogeneous, suggesting different etiologies.
Pilot Plant-Based Lifestyle Medicine Program in an Urban Public Healthcare System: Evaluating Demand and Implementation
Authors: Albert Stephanie L. , Massar Rachel E. , Kwok Lorraine , Correa Lilian , Polito-Moller Krisann , Joshi Shivam , Shah Sapana , McMacken Michelle
Published: July 2022

Lifestyle interventions that optimize nutrition, physical activity, sleep health, social connections, and stress management, and address substance use, can reduce cardiometabolic risk. Despite substantial evidence that healthful plant-based diets are beneficial for long-term cardiometabolic health and longevity, uncertainty lies in how to implement plant-based lifestyle programs in traditional clinical settings, especially in safety-net contexts with finite resources. In this mixed-methods implementation evaluation of the Plant-Based Lifestyle Medicine Program piloted in a large public healthcare system, we surveyed participants and conducted qualitative interviews and focus groups with stakeholders to assess program demand in the eligible population and feasibility of implementation within the safety-net setting. Program demand was high and exceeded capacity. Participants’ main motivations for joining the program included gaining more control over life, reducing medication, and losing weight. The program team, approach, and resources were successful facilitators. However, the program faced administrative and payor-related challenges within the safety-net setting, and participants reported barriers to access. Stakeholders found the program to be valuable, despite challenges in program delivery and access. Findings provide guidance for replication. Future research should focus on randomized controlled trials to assess clinical outcomes as a result of program participation.
Intrasaccular neck-bridging: A technical note on Nautilus-assisted coiling of wide-necked cerebral aneurysms. Feasibility study, immediate and early angiographic results
Authors: Sirakov A , Bhogal P , Sirakova K , Minkin K , Ninov K , Karakostov V , Sirakov S
Published: July 2022

Purpose

Various adjunctive devices have been reported to be helpful during the endovascular coiling of complex, wide-necked cerebral aneurysms. This study aimed to describe the utilization of a recently introduced intrasaccular neck-bridging implant specifically designed to facilitate coil embolization.

Methods

We retrospectively reviewed eight consecutive patients who underwent treatment for intracranial aneurysms with the Nautilus intrasaccular bridging system between February 2022 to May 2022. We evaluated the angiographic appearances of treated aneurysms at the end of the procedure and early follow-up, the clinical status and complications.

Results

Eight patients with eight cerebral aneurysms (3 men and 5 women, mean age 52.8 years (range 39–66) were analyzed. Five of the treated aneurysms were managed in an acute case scenario. There were no technical difficulties while executing the technique. No other procedural adverse events were documented. Immediate complete occlusion of the aneurysm was seen in 6 patients, neck remnant in 1 and stable aneurysm reperfusion in one case. Early radiological follow-up was available in five patients, and the observed occlusion rates were – RR class I in all radiologically screened aneurysms.

Conclusion

Nautilus-assisted coil embolization represents a rapid and safe solution for complex cerebral aneurysms. In our opinion this device symbolizes a significant step forward in treating intracranial aneurysms. We believe that the technique's actual value consists of the fact that the device is fully compatible with the modern low-profile microcatheter technology and does not involve the need for antiplatelet medications.
Adaptive formation control for autonomous surface vessels with prescribed-time convergence
Authors: Huang Ziyang , Li Jun , Huang Bing
Published: July 2022

This article is dedicated to solving the problem of predefined-time cooperative control for autonomous surface vessels encountering model uncertainties and external perturbations. By virtue of the prescribed-time stable theory, a robust formation controller is constructed, with which the settling time of the cooperative system can be prescribed in advance. The controller is developed under the backstepping framework, where the dynamic surface control is applied to generate the real-time command. Considering the unmodeled autonomous surface vessel dynamics, the neural network-based nonlinear approximator is incorporated with minimum-learning-parameter technique. Under this scenario, the real-time control can be pursed with one parameter being estimated. Finally, comparative simulation examples are provided to exhibit the effectiveness and advantages of designed control strategies.
When words collide: Bayesian meta-analyses of distractor and target properties in the picture–word interference paradigm
Authors: Bürki Audrey , Alario F-Xavier , Vasishth Shravan
Published: July 2022

In the picture–word interference paradigm, participants name pictures while ignoring a written or spoken distractor word. Naming times to the pictures are slowed down by the presence of the distractor word. The present study investigates in detail the impact of distractor and target word properties on picture naming times, building on the seminal study by Miozzo and Caramazza. We report the results of several Bayesian meta-analyses based on 26 datasets. These analyses provide estimates of effect sizes and their precision for several variables and their interactions. They show the reliability of the distractor frequency effect on picture naming latencies (latencies decrease as the frequency of the distractor increases) and demonstrate for the first time the impact of distractor length, with longer naming latencies for trials with longer distractors. Moreover, distractor frequency interacts with target word frequency to predict picture naming latencies. The methodological and theoretical implications of these findings are discussed.
Chemical Compositions and Anti-Mildew Effects of Cinnamomum micranthum Leaf and Twig Essential Oils on Paper
Authors: Hsu Kuang-Ping , Wu Chia-Chen , Wei Liang Yu , Ho Hui-Tung , Yang Mei-Ling , Ho Chen-Lung
Published: July 2022

In this study, we evaluated the anti-mildew effects of paper treated with essential oils of leaves, twigs, and their main constituents from Cinnamomum micranthum. The main ingredients with the greater anti-mildew effects on paper capability were also purified and identified. Fresh leaves and twigs of C. micranthum were hydrodistillated in a Clevenger-type apparatus, and the resulting oil characterized using GC-FID and GC-MS instruments. The leaf essential oil consisted principally of n-decanal (50.1%), ( E)-β-ocimene (7.9%), ( E)-nerolidol (6.5%), and ( E)-β-caryophyllene (3.8%), and the twig oil's main components were τ-cadinol (18.3%), ( E)-β-ocimene (16.4%), α-cadinol (13.6%), n-decanal (10.6%), and β-selinene (5.8%). Comparing the mildew resistance of the oils on paper exhibited that twig oil was the best anti-mildew activity; at 200 μg/cm2, the twig oil completely inhibited the growth of Aspergillus clavatus, Cladosporium cladosporioides, Chaetonium globosum, Myrothecium verrucaria, and Penicillium citrinum. The twig oil was further divided into 8 fractions (TO1-TO8). TO4 fraction had moderate anti-mildew effects; at the concentration of 200 μg/cm2, all fungi strains were totally inhibited, except A niger, and Trichoderma viride, which were 83.5%, and 93.2% inhibited, respectively. The main ingredients of TO4 fraction were τ-cadinol, and α-cadinol, so we isolated and used the for anti-mildew effect tests; τ-cadinol, and α-cadinol showed moderate anti-mildew activities. Since C. micranthum twig essential oil, τ-cadinol, and α-cadinol were exhibited a great anti-mildew effects on paper, they are worth further investigations and utilization.
Return to Play Criteria Following Surgical Management of Osteochondral Defects of the Knee: A Systematic Review
Authors: Swindell Hasani W. , Chen Aaron Z. , Anderson Matthew J. , Tedesco Liana J. , McCormick Kyle L. , Popkin Charles A. , Saltzman Bryan M. , Trofa David P.
Published: July 2022

Objective

The objective of this study was to identify and describe the existing literature on criteria used for return to play (RTP) following surgical management of osteochondral defects of the knee.

Design

A systematic review was performed to evaluate the surgical management of osteochondral defects of the knee in skeletally mature patients with a minimum of 2-year follow-up using Level I to IV studies in PubMed EMBASE from January 1998 to January 2016.

Results

Twelve studies with at least one explicitly stated criterion for RTP were identified from a review of 253 published articles. The majority of included studies were Levels II and IV (33%, respectively). Autologous chondrocyte implantation (ACI) was exclusively evaluated in 33.3% of papers and 16.7% evaluated osteochondral allograft transplantation (OCA). Eight different RTP criteria were used alone or in combination across the reviewed studies and time was the most often utilized criterion (83.3%). Minimum time to RTP ranged from 3 to 18 months.

Conclusions

This systematic review identifies current criteria used in the available literature to dictate RTP. Time from surgery was the most commonly employed criterion across the reviewed studies. Given the complex biological processes inherent to the healing of cartilaginous defects, further research is needed to design more comprehensive guidelines for RTP that are patient-centered and utilize multiple functional and psychological domains relevant to the process of returning to sport.
‘When Cryptococcus strikes and lupus is found’: a unique covert unveiling of systemic lupus erythematosus presenting as subacute meningitis
Authors: Essien Francis , Westbrook Marquise , Wolfley Graey , Patterson Shane , Carrol Matthew
Published: July 2022

Cryptococcal neoformans is a rare fungal pathogen that has been associated with immunocompromised individuals. Due to its rare occurrence, clinicians have a low index of suspicion for diagnosis, which can lead to increased morbidity and mortality. We present an 81-year-old fully functional woman with no known predisposing risk factors or previous immunocompromising conditions who was found to have cryptococcal meningitis on cerebrospinal fluid analysis in the setting of newly diagnosed uncontrolled type 2 diabetes and systemic lupus erythematosus (SLE).
Facing an eating disorder: A case of body dysmorphic disorder and avoidant/restrictive food intake disorder
Authors: Milligan Ty , Middleman Amy B
Published: July 2022

Eating disorders can be notoriously difficult to diagnose and treat. This patient is an 18-year-old female who presents to care severely underweight and notably cachexic. For a number of years, she had experienced depressive symptoms, anxiety, and continued loss of appetite. She denied purposefully restricting foods, recognized that she was thin, and denied a fear of gaining weight. She was admitted to a disordered eating unit for refeeding and during her inpatient stay disclosed that she had a long-standing “hatred of face.” Ultimately, she received the diagnoses of avoidant/restrictive food intake disorder and body dysmorphic disorder. This case highlights the importance of differentiating body dysmorphia, seen in body dysmorphic disorder, and distorted body image, as seen in anorexia nervosa. This differentiation is significant as the treatment approaches to these distinct diagnoses are not the same.
The Effects of Resistant Starch Consumption in Adult Patients With Chronic Kidney Disease: A Systematic Review
Authors: Kingra Kulwant , Curtis Sarah , Mollard Rebecca C. , Shamloo Maryam , Askin Nicole , Tangri Navdeep , MacKay Dylan
Published: July 2022

Background:

Resistant starches (RSs) are not digested by human digestive enzymes and pass through the upper digestive tract to become substrates for colonic bacteria. Resistant starch supplementation has shown promising results in altering the microbiota of animal models of chronic kidney disease (CKD). Resistant starch consumption may influence the production of uremic toxins in CKD.

Objective:

To conduct a systematic review to determine whether the consumption of RS reduces the progression of kidney disease in adult patients with CKD.

Design:

We included randomized controlled trials comparing RS supplementation to placebo, no treatment, or standard care. Cochrane Central, Embase, MEDLINE, Web of Science, and CINAHL databases were searched. There was no limitation on publication date, but only English manuscripts were included. The search was conducted in July 2020.

Patients:

Adult outpatient populations with CKD, using any recognized diagnostic criteria.

Measurements:

The primary outcome was change in glomerular filtration rate (GFR) from baseline through the end of the trial in patients not on dialysis; secondary outcomes included change in uremic toxin concentrations (p-cresol/p-cresyl sulfate [p-CS], indoxyl sulfate [IS]) and inflammatory markers (tumor necrosis factor alpha [TNF-α], C-reactive protein [CRP], interleukin 6 [IL-6]) from baseline through the end of the trial, and changes in self-reported symptom scores.

Methods:

The Cochrane Collaboration Risk of Bias tool was used to assess risk of bias in included studies. The systematic review results are reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.

Results:

We identified 4 unique studies, reported in 9 publications that met our inclusion criteria, including a total of 215 enrolled participants. Results were calculated using data from the longest reported follow-up time. The primary outcome of changes in kidney function markers was only studied in 1 trial; this trial reported an increase in creatinine and a decrease in blood urea nitrogen; no changes in GFR were reported. A review of the secondary outcomes showed an overall decline in IS, TNF-α, and IL-6, in RS groups, but with mixed results in p-CS and CRP/high-sensitivity CRP. Safety data showed that RS was well tolerated with no reports of excessive side effects.

Limitations:

We determined a meta-analysis was not feasible due to clinical heterogeneity between study populations and differences in reported outcomes in the included studies.

Conclusion:

There is limited and inconsistent evidence on the impact of RS in adult patients with CKD. Further research is needed to determine the safety and efficacy of RS supplementation in this population.
The Challenges of Technology Transfer in the Industry 4.0 Era Regarding Anthropotechnological Aspects: A Systematic Review
Authors: Kovaleski Fanny , Picinin Claudia Tania , Kovaleski João Luiz
Published: July 2022

The fast pace of advances within the Industry 4.0 era has had a direct impact on the process of technology transfer, as well as brought forth new and hitherto unknown challenges. This study pursues the goal to delineate the challenges and/or limitations of the I4’s process of technology transfer in terms of anthropotechnological aspects. For this purpose, the combination of two methodologies, PRISMA and Methodi Ordinatio, was carried out. The final portfolio analysis was divided into quantitative and qualitative sections. As a result, the current and recurring challenges of this interaction were reported in an overlap. Moreover, it was demonstrated that most studies have been focusing their attention on what involves a more holistic issue of the whole scenario, be they in the organizational, educational, cultural, governmental, security, human capital, technologies, innovations, or sustainable development issues. Finally, this research can serve as a starting point for further researches, as well as contribute to the understanding of industries during the implementation of the Industry 4.0 and their challenges regarding processes of technology transfer.
Community engagement; the master key to preventing Nigeria’s obvious pandemic fatigue and the next COVID-19 wave
Authors: Ogundijo Oluwaseun Adeolu , Al-Mustapha Ahmad Ibrahim , Abubakar Ahmed Tijani , Imam Abubakar Musa , Bamidele Folashade , Elelu Nusirat
Published: July 2022

The index case of COVID-19 in Nigeria was in February 2020. The pandemic has resulted in severe social, economic, and public health challenge in Nigeria. Nigeria has experienced pandemic fatigue (PF) characterized by its low testing capacity, poor public adherence to COVID-19 preventive measures, and the urge to return to normal. This viewpoint examines Nigeria’s obvious PF amongst Nigerians and believed that community engagement would be a master key to reducing Nigeria’s PF and preventing another wave of the pandemic in Nigeria. Community engagement (CE) is a viable way for monitoring the spread of the SARS-CoV-2. CE is cost-effective, improves the chances of people voluntarily presenting themselves for COVID-19 testing at the grass-root level, and could halt the spread of COVID-19 in Nigeria especially with the detection of the delta and omicron variants in Nigeria.
CEO Characteristics, Family-controlled Firms and Employer-support Volunteerism: Evidence from India
Authors: Oware Kofi Mintah , Appiah Kingsley
Published: July 2022

This article uses stakeholder and legitimacy theories to examine CEO characteristics, family-controlled firms and employer-support volunteerism in India. A sample size of 800 firm-year observations between 2010 and 2019 utilizes multivariant regression for data interpretation. Our results suggest that CEO duality is statistically insignificant to influence employer-support volunteerism. Second, ageing CEOs have a statistically significant and positive effect on influencing employer-support volunteerism in India. Third, male CEOs have a statistically significant and positive effect on influencing employer-support volunteerism in India. Fourth, family firms are insignificant to influence employer-support volunteerism. However, in a moderating study, family-controlled firms reduce the efficiency in CEO duality towards employer-support volunteerism in India. Fifth, the interactive study shows that ageing and male CEOs in family firms positively influence employer-support volunteerism. Regarding the control variables, we found that ﬁrm size and type of industry are sensitive to employer-support volunteerism in India. The study implies that a CEO non-duality can better address support for volunteerism. Similarly, the characteristics of ageing CEOs are associated with experience and the general desire to undertake volunteerism. Likewise is the engagement of male CEOs who pursue community engagement better than female CEOs. The implication from the study to shareholders and any party interest (example: community) seeking a firm to pursue CSR activities through volunteerism must support CEO non-duality, ageing CEOs and male CEOs’ engagements. Also, family or non-family firms still benefit from undertaking volunteerism when the firms engage ageing CEOs and male CEOs. The results of the study are robust after controlling for firm-specific variables.
Cheers to Mead: A Serious In-Person Game Illustrating the Five Forces
Authors: Yoder Michele E.
Published: July 2022

Porter’s five forces model is an important tool in strategic management. Strategy students use the five forces model to conduct industry analysis by evaluating the external conditions that impact firms in a given industry. The five forces model is deceptively simple, yet it encompasses important nuances that students sometimes struggle to fully understand. Cheers to Mead is an experiential exercise designed to illustrate the factors that contribute to the five forces and how the contributing factors affect industry profit potential. The Cheers to Mead game encourages students to grapple with difficult concepts while participating in an engaging activity.
Ecumenism of Blood and Christian Churches in Contemporary Nigeria
Authors: Amaefule Adolphus Ekedimma
Published: July 2022

There has recently been an upsurge in the persecution of Christians in Nigeria, especially in northern Nigeria by the militant Islamic sect Boko Haram, and in the Middle Belt and other areas of the country by Muslim Fulani herdsmen. One of the characteristics of these persecutions is that while they are targeted mainly at Christians, these Christians are never separated along the lines of their denominations. This article highlights the ecumenical implications that the scenario holds for the various Christian churches in Nigeria, churches that before now have been schooled in elements of extreme denominationalism.
Frankincense essential oil nanoemulsion specifically induces lung cancer apoptosis and inhibits survival pathways
Authors: Abd-Rabou Ahmed A. , Edris Amr E.
Published: July 2022

Background

The volatile fraction of frankincense (Boswellia sacra) oleogum was extracted, formulated in nanoemulsion and tested against lung cancer A549 cell line. First, the gum was hydro-distilled to isolate the volatile fraction (essential oil), which was analyzed via gas chromatography to identify its major volatile constituents. Then, the oil was formulated in two water-based nanoemulsions which differ from one another in the presence of propylene glycol (PG), which is used in the formulation step as a co-surfactant. The pure essential oil as well as its major volatile compound (α-pinene), its two nanoemulsions and a reference drug (Doxorubicin) were evaluated against lung cancer A549 cell lines and WI-38 normal lung cells. The evaluation included cytotoxicity (MTT and IC50), apoptosis (flow cytometric analysis) in addition to genetic assessments for some intrinsic and extrinsic genes relevant to apoptosis and survival pathways.

Results

Chromatographic analysis of frankincense essential oil revealed that α-pinene is the major volatile compound which constituent about 60% of that oil. Emulsification of the oil using the low energy technique gave nanoemulsions having major intense particles population (85–90%) with z-average diameter below 20.0 nm. Frankincense oil nanoemulsion fabricated with (PG) showed the best cytotoxic activity toward lung cancer A549 cell compared to PG-free nanoemulsion, α-pinene and the reference drug doxorubicin, along different incubation periods. Flow cytometric analysis also indicated that PG-containing nanoemulsion can induce cancer cells toward apoptosis better than the other formula and the pure oils. The same nanoemulsion was found to upregulate the pro-apoptotic genes [DR5, FAAD, Caspase 8 (Cas8), p53, and Bax] and downregulate the anti-apoptotic and reoccurrence genes (Bcl-2, NF-kB, and STAT-3). Most importantly, the PG-containing nanoemulsion had the least cytotoxic effect on the normal WI-38 lung cells.

Conclusions

These results point out to the potentials of frankincense essential oil (rich in α-pinene) and its PG-nanoemulsion as a promising adjuvant from plant-source to potentiate the activity of the systematic anti-lung cancer drugs.
Performance of the No-U-Turn sampler in multi-trait variance component estimation using genomic data
Authors: Nishio Motohide , Arakawa Aisaku
Published: July 2022

Background

Multi-trait genetic parameter estimation is an important topic for target traits with few records and with a low heritability and when the genetic correlation between target and secondary traits is strong. However, estimating correlations between multiple traits is difficult for both Bayesian and non-Bayesian inferences. We extended a Hamiltonian Monte Carlo approach using the No-U-Turn Sampler (NUTS) to a multi-trait animal model and investigated the performance of estimating (co)variance components and breeding values, compared to those for restricted maximum likelihood and Gibbs sampling with a population size of 2314 and 578 in a simulated and real pig dataset, respectively. For real data, we used publicly available data for three traits from the Pig Improvement Company (PIC). For simulation data, we generated two quantitative traits by using the genotypes of the PIC data. For NUTS, two prior distributions were adopted: Lewandowski-Kurowicka-Joe (LKJ) and inverse-Wishart distributions.

Results

For the two simulated traits with heritabilities of 0.1 and 0.5, most estimates of the genetic and residual variances for NUTS with the LKJ prior were closer to the true values and had smaller root mean square errors and smaller mean absolute errors, compared to NUTS with inverse-Wishart priors, Gibbs sampling and restricted maximum likelihood. The accuracies of estimated breeding values for lowly heritable traits for NUTS with LKJ and inverse-Wishart priors were 14.8% and 11.1% higher than those for Gibbs sampling and restricted maximum likelihood, respectively, with a population size of 578. For the trivariate animal model with real pig data, the estimates of the genetic correlations for Gibbs sampling and restricted maximum likelihood were strongly affected by population size, compared to NUTS. For both the simulated and pig data, the genetic variances and heritabilities for NUTS with an inverse-Wishart prior were overestimated for low-heritability traits when the population size was 578.

Conclusions

The accuracies of variance components and breeding values estimates for a multi-trait animal model using NUTS with the LKJ prior were equal to or higher than those obtained with restricted maximum likelihood or Gibbs sampling. Therefore, when the population size is small, NUTS with an LKJ prior could be an alternative sampling method for multi-trait analysis in animal breeding.
Epidemiology and clinical characteristics of infection/colonization due to carbapenemase-producing Enterobacterales in neonatal patients
Authors: Wang Jiansheng , Lv Yuanpeng , Yang Weiwei , Zhao Peng , Yin Changfu
Published: July 2022

Background

The aim of this study was to elucidate the epidemiological features of carbapenemase-producing Enterobacterales (CPE) in the pediatric and neonatal patients, to describe clinical characteristics of neonatal patients with CPE infections, and to assess risk factors for neonatal rectal colonization with CPE.

Results

A total of 439 carbapenem-resistant Enterobacterales (CRE) isolates recovered from 367 infant patients were characterised, including 397 isolates of Klebsiella pneumoniae (KP) and 42 isolates of Escherichia coli (EC). Carbapenemase gene blaNDM-1 was the most commonly detected, accounting for 86.56% (n = 380), followed by blaKPC-2 (9.11%, 40) and blaIMP-4 (4.33%, 19). MLST analysis showed 17 different STs detected within CPKP isolates, with ST20, ST2068, ST36 and ST17 being the most frequently isolated types. Eleven STs were identified within CPEC isolates, with ST325 being the dominant types. Eight isolates of NDM-1 producing KP, belonging to ST23, were identified as having hypervirulent traits. The main infections caused by CPE were pneumonia (n = 90) and sepsis (n = 16). All infected patients received monotherapy, with meropenem and ciprofloxacin being the most commonly used antibiotics. All pneumonia patients were cured or improved after treatment. Of the 16 patients with sepsis, 9 were cured or improved, 3 died, and 4 abandoned treatment without any clinical improvement. The rectal prevalences of CPE in the 0–3 days old (DO), the 4–28 DO, and the 29 DO-1 year old groups were decreased from 15.31%, 27.37% and 14.29% in the first stool screening period to 11.78%, 19.59% and 4.07% in the second stool screening period, respectively. Multivariate analysis showed that cesarean section, acidosis, respiration failure, gastric lavage and enema were independent risk factors for rectal colonization in the 0–3 DO group, whereas cesarean section, cephalosporins, gastric lavage and residence in rural area were independently associated with rectal colonization in the 4–28 DO group. The implementation of a series of evidence-based control measures eventually contained the CPE transmission.

Conclusions

Continued vigilance, epidemiological studies, and multimodal infection prevention strategies are urgently needed due to frequent importations.
Transcription-associated metabolomic profiling reveals the critical role of frost tolerance in wheat
Authors: Lv Liangjie , Dong Ce , Liu Yuping , Zhao Aiju , Zhang Yelun , Li Hui , Chen Xiyong
Published: July 2022

Background

Low temperature is a crucial stress factor of wheat (Triticum aestivum L.) and adversely impacts on plant growth and grain yield. Multi-million tons of grain production are lost annually because crops lack the resistance to survive in winter. Particularlly, winter wheat yields was severely damaged under extreme cold conditions. However, studies about the transcriptional and metabolic mechanisms underlying cold stresses in wheat are limited so far.

Results

In this study, 14,466 differentially expressed genes (DEGs) were obtained between wild-type and cold-sensitive mutants, of which 5278 DEGs were acquired after cold treatment. 88 differential accumulated metabolites (DAMs) were detected, including P-coumaroyl putrescine of alkaloids, D-proline betaine of mino acids and derivativ, Chlorogenic acid of the Phenolic acids. The comprehensive analysis of metabolomics and transcriptome showed that the cold resistance of wheat was closely related to 13 metabolites and 14 key enzymes in the flavonol biosynthesis pathway. The 7 enhanced energy metabolites and 8 up-regulation key enzymes were also compactly involved in the sucrose and amino acid biosynthesis pathway. Moreover, quantitative real-time PCR (qRT-PCR) revealed that twelve key genes were differentially expressed under cold, indicating that candidate genes POD, Tacr7, UGTs, and GSTU6 which were related to cold resistance of wheat.

Conclusions

In this study, we obtained the differentially expressed genes and differential accumulated metabolites in wheat under cold stress. Using the DEGs and DAMs, we plotted regulatory pathway maps of the flavonol biosynthesis pathway, sucrose and amino acid biosynthesis pathway related to cold resistance of wheat. It was found that candidate genes POD, Tacr7, UGTs and GSTU6 are related to cold resistance of wheat. This study provided valuable molecular information and new genetic engineering clues for the further study on plant resistance to cold stress.
Role of publicly funded health insurance in financial protection of the elderly from hospitalisation expenditure in India-findings from the longitudinal aging study
Authors: Garg Samir , Bebarta Kirtti Kumar , Tripathi Narayan
Published: July 2022

Background

The elderly face a greater burden of illnesses than other age groups and have a more frequent need of healthcare, including in-patient hospitalisations. Catastrophic expenditure on hospitalisation of the elderly poses a significant challenge to India’s aim of achieving Universal Health Coverage (UHC). India has implemented a policy of Publicly Funded Health Insurance (PFHI) to provide free inpatient care by empanelling private and public hospitals. The existing studies have examined the performance of PFHI in financial protection of the elderly.

Methods

This study utilised the Longitudinal Ageing Study in India (LASI) Wave 1, conducted in 2017–18. LASI is a large-scale nationally representative survey collecting data on elderly health including illness burden, healthcare use and out of pocket expenditure (OOPE). It covered a sample 72,250 individuals aged 45 or above. Financial Protection was measured in terms of Catastrophic Health Expenditure (CHE). Multivariate analysis was conducted to find effect of PFHI on OOPE—quantile and logistic models were applied for OOPE and CHE respectively. For robustness, Propensity Score Matching (PSM) model was applied.

Results

Of the hospitalisations, 35% had taken place in public hospitals. The mean OOPE for a hospitalisation in public sector was Indian Rupees (INR) 8276, whereas it was INR 49,700 in private facilities. Incidence of CHE was several times greater for using private hospitals as compared to public hospitals. Multi-variate analyses showed that enrolment under PFHI was not associated with lower OOPE or CHE. PSM model also confirmed that PFHI-enrolment had no effect on OOPE or CHE. Use of private facilities was a key determinant of OOPE, irrespective of enrolment under PFHI.

Conclusions

This was the first study in India to examine the performance of PFHI in the context of catastrophic hospitalisation expenditure faced by the elderly. It found that PFHI was not effective in financial protection of the elderly. The ongoing reliance on a poorly regulated private sector seems to be a key limitation of PFHI policy. Governments need to find more effective ways of protecting the elderly from catastrophic health expenditure if the goal of UHC has to be realized.
Clinical characteristics and antibodies against Echinococcus granulosus recombinant antigen P29 in patients with cystic echinococcosis in China
Authors: Tao Jia , Du Xiancai , Liu Kejun , Wang Chan , Lv Yongxue , Wang Minglei , Yang Zhiqi , Yang Jihui , Li Shasha , Wu Changyou , Li Minghao , Zhao Wei
Published: July 2022

Objectives

Cystic echinococcosis (CE) is a neglected parasitic zoonotic disease caused by the larval stage of the tapewormEchinococcusgranulosus(E. granulosus). This study aimed to understand the clinical characteristics of human CE in Ningxia Hui Autonomous Region (NHAR) located in northwest China and to investigate the antibody profiles against the recombinantE. granulosusantigen P29 (rEg.P29) in plasma of CE patients.

Methods

A total of 37 human CE patients, along with 37 healthy donors enrolled in this study and demographic and clinical data were analyzed, including age, gender, laboratory data, symptoms, and cysts description. Plasma levels of cytokines, total IgG, and total IgE were determined by sandwich ELISA kits. Specific antibodies against rEg.P29 and hydatid cyst fluid (HCF) were assessed by indirect ELISA.

Results

The results revealed that females have a higher percentage of CE patients than males. The incidence of CE reached a peak in the 41–50 years-old group. The liver was the most frequent location, accounting for 91.9%. Based on the CT images, cysts of 34 patients who had liver involvement, were classified as 1 (2.9%) CE1, 12 (35.3%) CE2, 5 (14.7%) CE3a, 1 (2.9%) CE3b, and 15 (44.2%) CE5. Twenty-nine (78.4%) patients had a single cyst and 8 (21.6%) had at least two cysts. The most frequently reported symptom was upper abdominal pain. The plasma level of IL-6 and total IgE were significantly increased in CE patients compared with healthy donors. Additionally, IgG response to rEg.P29 in CE patients was significantly higher than in healthy donors, and the dominant IgG subclass was IgG4. Further analysis of different patient groups revealed that rEg.P29-specific IgG and IgG4 were only elevated in CE patients with CE2 type cysts.

Conclusions

This study systematically investigated the clinical characteristics of patients with CE and may provide a reference basis for the diagnosis and treatment of CE in NHAR. Furthermore, tests of specific IgG and IgG4 against rEg.P29 can be used as an assisted method for imaging techniques to identify cystic activity and determine the best therapeutic approach for CE.
The value of eosinophil count in the diagnosis of preeclampsia among pregnant women attending the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia, 2021
Authors: Gelaw Yemataw , Asrie Fikir , Walle Muluken , Getaneh Zegeye
Published: July 2022

Background

Currently, studies showed that eosinophil count had clinical significance in the diagnosis and prognosis of diseases. But, the clinical significance of eosinophil count in pregnancy specifically in preeclampsia (PE) is not well studied. The main objective of the present study was to assess the diagnosis value of eosinophils counts among pregnant women with PE.

Methods

A comparative cross-sectional study was conducted on a total of 126 pregnant women at the University of Gondar Comprehensive Specialized Hospital, using a convenient sampling technique. Socio-demographic and clinical data were collected by questionnaire and datasheet from patient’s charts, respectively. A total of six ml of blood was collected from each study participant; three ml for complete cell count analysis using Sysmex XS-500i hematology analyzer and three ml for liver function tests using Humastar 200 chemistry analyzer. The data were entered into Epi-data and exported to SPSS 20 for analysis. The independent t-test was used for normally distributed data and, the Mann–Whitney U test was used for non-normally distributed data. Binary logistic regression and receiver operative curve analyses were also done to assess the diagnosis value of eosinophils count.P-value < 0.05 was considered statistically significant.

Results

The eosinophils count of PE pregnant women were significantly lower than the normotensive (NT) pregnant women (median (IQR): 50 (10—200) vs. 120 (60 – 270); (p = 0.002). The eosinophil count ≤ 55 cells/µL had an AUC of 0.66 (95% CI; 0.56—0.75) for diagnosis of PE with a sensitivity of 50.8%, specificity of 77.8%, and positive and negative predictive value of 69.6% and 61.3%, respectively. The abnormal AST and ALT results were significantly higher among PE pregnant women compared to NT pregnant women (AOR: 14.86; 95% CI: 4.97—44.4 and Fischer exact testp-value = 0.001, respectively).

Conclusion

The eosinophil count ≤ 55cells/µl had a reasonable/acceptable AUC which may use in the diagnosis of PE. AST and ALT were also significantly higher in PE pregnant women compared to NT pregnant women. Multicenter longitudinal studies with a large sample size are recommended to verify the role of eosinophil count in the diagnosis of PE.
Discovery of a novel ALK/ROS1/FAK inhibitor, APG-2449, in preclinical non-small cell lung cancer and ovarian cancer models
Authors: Fang Douglas D. , Tao Ran , Wang Guangfeng , Li Yuanbao , Zhang Kaixiang , Xu Chunhua , Zhai Guoqin , Wang Qixin , Wang Jingwen , Tang Chunyang , Min Ping , Xiong Dengkun , Chen Jianyong , Wang Shaomeng , Yang Dajun , Zhai Yifan
Published: July 2022

Background

Tyrosine kinase inhibitors (TKIs) are mainstays of cancer treatment. However, their clinical benefits are often constrained by acquired resistance. To overcome such outcomes, we have rationally engineered APG-2449 as a novel multikinase inhibitor that is highly potent against oncogenic alterations of anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), and focal adhesion kinase (FAK). Here we present the preclinical evaluation of APG-2449, which exhibits antiproliferative activity in cells carrying ALK fusion or secondary mutations.

Methods

KINOMEscan® and LANCE TR-FRET were used to characterize targets and selectivity of APG-2449. Water-soluble tetrazolium salt (WST-8) viability assay and xenograft tumorigenicity were employed to evaluate therapeutic efficacy of monotherapy or drug combination in preclinical models of solid tumors. Western blot, pharmacokinetic, and flow cytometry analyses, as well as RNA sequencing were used to explore pharmacokinetic–pharmacodynamic correlations and the mechanism of actions driving drug combination synergy.

Results

In mice bearing wild-type or ALK/ROS1-mutant non-small-cell lung cancer (NSCLC), APG-2449 demonstrates potent antitumor activity, with correlations between pharmacokinetics and pharmacodynamics in vivo. Through FAK inhibition, APG-2449 sensitizes ovarian xenograft tumors to paclitaxel by reducing CD44+ and aldehyde dehydrogenase 1-positive (ALDH1+) cancer stem cell populations, including ovarian tumors insensitive to carboplatin. In epidermal growth factor receptor (EGFR)-mutated NSCLC xenograft models, APG-2449 enhances EGFR TKI-induced tumor growth inhibition, while the ternary combination of APG-2449 with EGFR (osimertinib) and mitogen-activated extracellular signal-regulated kinase (MEK; trametinib) inhibitors overcomes osimertinib resistance. Mechanistically, phosphorylation of ALK, ROS1, and FAK, as well as their downstream components, is effectively inhibited by APG-2449.

Conclusions

Taken together, our studies demonstrate that APG-2449 exerts potent and durable antitumor activity in human NSCLC and ovarian tumor models when administered alone or in combination with other therapies. A phase 1 clinical trial has been initiated to evaluate the safety and preliminary efficacy of APG-2449 in patients with advanced solid tumors, including ALK+ NSCLC refractory to earlier-generation ALK inhibitors.

Trial registration

Clinicaltrial.gov registration: NCT03917043 (date of first registration, 16/04/2019) and Chinese clinical trial registration: CTR20190468 (date of first registration, 09/04/2019).