bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 and Health Systems Functioning in Sub-Saharan Africa Using the “WHO Building Blocks”: The Challenges and Responses
Authors: Amu Hubert , Dowou Robert Kokou , Saah Farrukh Ishaque , Efunwole John Adebayo , Bain Luchuo Engelbert , Tarkang Elvis Enowbeyang
Published: April 2022

Sub-Saharan Africa (SSA) has made major progress in improving access to health care over the past three decades. Despite efforts made toward achieving universal health coverage, the health systems of countries in the sub-region are inundated by a myriad of challenges that have become more virulent amid the COVID-19 pandemic. This paper discusses the health systems challenges and responses in SSA amidst the COVID-19 using the World Health Organization's (WHO) building blocks of health systems functioning. Long-lasting abysmal health system financing and insufficient government investment in SSA pose major challenges to the effective health systems functioning amid the COVID-19 pandemic. This situation also makes it difficult for the health system to meet the demands of the COVID-19 pandemic and at the same time, cater for other essential health services. Countries in SSA must prioritize the reformation of their health systems through effective health system policy development and implementation, human resources development, training, service delivery, governance and regulation, and sustainable health financing.
Reconceptualizing the Curriculum for Malaysian Advanced Nursing Education: An Outlook on Mechanical Ventilation Weaning Pedagogy
Authors: Alias Norlidah , AwangHarun Sakinah , Jamaludin Khairul Azhar
Published: April 2022

Although Advanced Nursing Education (ANE) in Malaysia is still in its early stages, the demand for skilled nurses, particularly those who can perform weaning processes from mechanical ventilation (WPMV), is increasing. These nurses, especially in the Cardiothoracic Intensive Care Unit (CICU) need to be equipped with critical thinking skills in order to make decisions on WPMV. However, the Malaysian ANE is still struggling to achieve this. Therefore, this paper is aimed at reconceptualizing the Malaysian ANE with a specific focus on the development of a Mechanical Ventilation Weaning Pedagogy framework. Building upon previous studies, relevant theories, and WPMV best practices outside Malaysia, this study proposed the development of a pedagogy based on four fundamentals: the Fundamental Pattern of Knowing, Curriculum Planning model, an ideal learning content for WPMV skills development, and local experts' opinions. The findings of this study can serve as a reference for stakeholders, nursing education providers, and relevant parties in improving the current ANE.
Dual-Energy CT in the Acute Setting: Bowel Trauma
Authors: Wang Tanche Jimmy , Barrett Sarah , Ali Ismail , Khosa Faisal , Nicolaou Savvas , Murray Nicolas
Published: April 2022

Traumatic bowel and mesenteric injuries (TBMI) have significant morbidity and mortality. The physical examination is often limited and sometimes not feasible in the trauma patient. Multidetector CT (MDCT) detection of TBMI is challenging and can be life-saving. Dual-energy CT (DECT) utilizes iodine overlay, monoenergetic imaging, and metal artifact reduction to enhance the conspicuity of TBMI. DECT may improve the conspicuity of TBMI leading to increased diagnostic accuracy and confidence. The aim of the article is to review the state of the art and applications of DECT in bowel trauma.
Lessons From the Commercial Failure of Project Loon for 6G Research Roadmap Design
Authors: Zhang Liang , Zhang Chuanting , Dang Shuping , Shihada Basem
Published: April 2022

Currently, the sixth-generation (6G) communication research roadmap is being frequently discussed and designed, in which, undoubtedly, aerial telecommunication infrastructures play crucial roles for boosting transmission capacity, enlarging coverage, and democratizing the benefits of information and communications technology (ICT) over the globe. However, the sudden news released in January 2021 that Alphabet is shutting down Project Loon, one of the most important projects enabling communications over aerial infrastructures, surprises the academia of communications science. There is no question that the failure of Project Loon will yield profound impacts on and even shift the current 6G research roadmap design. The latent mismatch between academia and industry in communication science should also raise adequate attention. Therefore, in this article, we analyze the commercial failure of Project Loon by public information from reliable sources and summarize a series of important lessons for the 6G research roadmap design.
Expect Nothing: The (Lack of) Influence of Subjective Life Expectancy on Valuation of Child Health States
Authors: Lipman Stefan A.
Published: April 2022

Objective

Earlier research has shown that individuals' subjective life expectancy (SLE) affects health state valuation with time trade-off (TTO). Individuals with longer expected life durations are less willing to trade-off life duration, which yields higher utilities. In this article, the influence of SLE is explored in the valuation of EQ-5D-Y-3L with a proxy perspective, i.e., adults' valuation of health states considering the life of a 10-year-old child. As SLE for children is likely higher, this might explain earlier findings suggesting that individuals are less willing to trade-off years of life for children than for adults.

Methods

A total of 197 respondents were recruited to take part in digital TTO interviews, facilitated by trained interviewers. TTO interviews were implemented in accordance with the recommended protocol for the valuation of EQ-5D-Y-3L. Respondents valued 10 EQ-5D-Y-3L health states for a 10-year-old child, after which they were asked to report how old they themselves expected to become and also how old they expected a 10-year-old child to become.

Results

Generally, adult respondents reported higher SLE for children than for themselves. Neither SLE was systematically associated with the willingness to trade lifetime or the number of life years traded off in TTO tasks. This null-result was substantiated by regression analyses per health state.

Conclusion

The results of this study suggest that individuals' expectations about longevity are not associated with EQ-5D-Y-3L valuation. This lack of association is in contrast to earlier work and might be explained by the psychological distance introduced with proxy perspective valuation, or by the methodological differences with earlier work.
Social Drone Sharing to Increase UAV Patrolling Autonomy in Pre- and Post-Emergency Scenarios
Authors: Bisio Isabella-Sole , Morando Luca , Recchiuto Carmine Tommaso , Sgorbissa Antonio
Published: April 2022

Multirotor drones are becoming increasingly popular in a number of application fields, with a unique appeal to the scientific community and the general public. Applications include security, monitoring and surveillance, environmental mapping, and emergency scenario management: in all these areas, two of the main issues to address are the availability of appropriate software architectures to coordinate teams of drones and solutions to cope with the short-term battery life. This article proposes the novel concepts of Social Drone Sharing (SDS) and Social Charging Station (SCS), which provide the basis to address these problems. Specifically, the article focuses on teams of drones in pre- and post-event monitoring and assessment. Using multirotor drones in these situations can be difficult due to the limited flight autonomy when multiple targets need to be inspected. The idea behind the SDS concept is that citizens can volunteer to recharge a drone or replace its batteries if it lands on their property. The computation of paths to inspect multiple targets will then take into account the availability of SCSs to find solutions compatible with the required inspection and flight times. The main contribution of this article is the development of a cloud-based software architecture for SDS mission management, which includes a multi-drone path-optimization algorithm taking the SDS and SCS concepts into account. Experiments in simulation and a lab environment are discussed, paving the path to a larger trial in a real scenario.
Varicoceles in Men With Non-obstructive Azoospermia: The Dilemma to Operate or Not
Authors: Kaltsas Aris , Markou Eleftheria , Zachariou Athanasios , Dimitriadis Fotios , Mamoulakis Charalampos , Andreadakis Sotirios , Giannakis Ioannis , Tsounapi Panagiota , Takenaka Atsushi , Sofikitis Nikolaos
Published: April 2022

The knowledge on male reproduction is constantly expanding, especially in treating infertility due to non-obstructive azoospermia (NOA). Varicocele is occasionally diagnosed in a subpopulation of males with NOA. Varicocele repair in NOA-men may contribute to the reappearance of spermatozoa in semen. However, spontaneous pregnancies are observed in only a small percentage of NOA-men post-varicocelectomy. Additionally, it has been reported that the repair of varicocele in NOA-men (before the performance of sperm retrieval techniques) may increase the testicular sperm recovery rate. In addition, it increases the pregnancy rate in intracytoplasmic sperm injection (ICSI) programs in NOA-men without spermatozoa in the semen post-varicocelectomy. In addition, to the improvement in Sertoli cellular secretory function, varicocelectomy may increase the secretory function of Leydig cells, which subsequently results in improved androgen production, raising the probability to negate the need for testosterone replacement therapy in cases of late-onset hypogonadism. On the other hand, the benefit of varicocelectomy in patients with NOA is still debatable. The current review study aims to provide a critical and extensive review of varicocele repair in males with NOA. This study additionally focuses on the impact of varicocele repair on sperm retrieval rates and its influence on the ICSI outcomes for those couples who remain negative for spermatozoa in their semen samples post-varicocelectomy.
The Effectiveness of Simulation in Education 4.0: Application in a Transesophageal Echocardiography Training Program in Malaysia
Authors: AwangHarun Sakinah , Md Hashim Noorjahan Haneem , Kadiman Suhaini
Published: April 2022

Introduction

A Malaysian Higher Education Provider has applied technology as part of its pedagogical approach, in alignment with Education 4. 0. The use of simulation, which aligns with the principles of Education 4.0, employs digital technologies and supports learning by bridging the classroom and the clinical areas. We reported the effectiveness of learning in our program that utilizes multimodal pedagogy, including interactive lectures, pre-recorded video lectures, simulation, and hands-on supervised clinical sessions, using the program's cumulative assessment data.

Methodology

This program evaluation was based on Kirkpatrick's framework. End-points for learning (Kirkpatrick level 2) were analyzed based on improved overall post-test theoretical and clinical assessment performance. Quantitative data analysis of theoretical pre-test, theoretical post-test, clinical assessment, and post-test scores was performed to compare cohorts.

Results

The performance of 19 trainees, over six cohorts from 2012 to 2019, were analyzed. All our trainees had equal opportunities to learn using the multimodal pedagogy, including a simulator. The analysis of pre- and post-theoretical test scores showed a significant improvement in the mean scores (pre-test 48.7% (± SD 9), post-test 64.1% (± SD11.5); p ≤ 0.001). Overall, 19 out of 21 trainees completed the clinical assessment and case presentation satisfactorily

Conclusion

The Kirkpatrick framework served as a useful framework to perform the evaluation of the TEE program. The significant improvement in post-test scores, when compared with pre-test scores, suggested that the program is effective with regard to learning. As part of a multimodal pedagogy, simulation has proven to be an added value to our training program, and this was reflected by the improvement in the clinical assessment scores when compared to the pre-test scores. This result aligned with the concept of technology-enhanced learning in Education 4.0, where simulation in TEE training is applicable in the Malaysian context.
Effect of Dietary Paeoniae Radix Alba Extract on the Growth Performance, Nutrient Digestibility and Metabolism, Serum Biochemistry, and Small Intestine Histomorphology of Raccoon Dog During the Growing Period
Authors: Wang Jing , Li Guangyu , Zhong Wei , Zhang Haihua , Yang Qianlong , Chen Lihong , Wang Jinming , Yang Xuewen
Published: April 2022

Paeoniae radix alba extract (PRA extract) has the functions of regulating immunity, resisting inflammation, and has antioxidant properties. However, current recommendations of dietary PRA extract levels for raccoon dogs were inadequate. The purpose of this experimental study was to gain information allowing for better estimating the effects of PRA extract on raccoon dogs, and their PRA requirements. Fifty healthy male raccoon dogs of (120 ± 5) days old were randomly divided into 5 groups (group PRA0, PRA1, PRA2, PRA4, PRA8) with 10 animals in each group and 1 in each replicate. Five kinds of experimental diets were prepared with five levels of Paeoniae radix alba extract (0, 1, 2, 4, 8 g/kg) in the basic diet. The prefeeding period was 7 days and the experimental period was 40 days. The results showed that the average daily feed intake in group PRA1 and PRA2 was significantly higher than that in other groups (P< 0.01). The dry matter excretion in group PRA8 was significantly higher than that in other groups (P< 0.01), while the dry matter digestibility and protein digestibility in group PRA8 were significantly lower than those in other groups (P< 0.01). Nitrogen retention in group PRA1 and PRA2 was significantly higher than that in group PRA8 (P< 0.05). With the increase of the content of Paeoniae radix alba extract in diet, the activity of alkaline phosphatase in group PRA2 was significantly higher than that in group PRA0 (P< 0.05); The activity of serum SOD in group PRA4 was significantly higher than that in other groups (P< 0.01). The content of serum IgA in group PRA2 was significantly higher than that in other groups (P< 0.05). The content of TNF-α in intestinal mucosa in group PRA1 and group PRA2 was significantly lower than that in group PRA0 (P< 0.05). In conclusion, we found that dietary Paeoniae radix alba extract intake significantly improved the feed intake and nitrogen deposition of Ussuri raccoon dog, increased the content of serum IgA and reduced the content of TNF-α in the small intestinal mucosa. We suggest that an estimated dietary Paeoniae radix alba extract level of 1 to 2 g/kg could be used as a guide to achieve the optimal performance of raccoon dogs.
Putting Access to Veterinary Care on the Map: A Veterinary Care Accessibility Index
Authors: Neal Sue M. , Greenberg Mike J.
Published: April 2022

Access to veterinary care is a complex problem that sits at the intersection of a number of societal factors including income inequality, access to transportation, language and cultural differences as well as the spatial distribution of veterinary care providers. This research aims to create an index evaluating accessibility of veterinary care across the contiguous United States and thus fill an important gap in the literature. The location and number of employees of veterinary clinics were aggregated at the county level. Projected pet population and household counts were used to normalize the number of employees to provide a relative assessment of the distribution of care access. Existing US Census data was used as percentile rankings to identify counties which may experience additional, non-spatial, barriers to care. By combining the percentile rankings of each of the variables, an overall index was created, evaluating the relative accessibility of veterinary care in each of the counties of the contiguous US. This work can be used by organizations looking to improve access to care or by policymakers considering legislation that impacts this issue. It may also be of use to individuals in human health care as they consider the intersection of human wellness and companion animal wellness.
Aging in Cats: Owner Observations and Clinical Finding in 206 Mature Cats at Enrolment to the Cat Prospective Aging and Welfare Study
Authors: Dowgray Nathalie , Pinchbeck Gina , Eyre Kelly , Biourge Vincent , Comerford Eithne , German Alexander J.
Published: April 2022

Two hundred and six cats, aged between 7 and 10 years, from the North-west of the UK, were enrolled in a cat aging and welfare study to determine the frequency of age-related conditions and associations with husbandry, owner observations of physical appearance, activity and behavior. This is the largest study to date of mature cats that includes data from an owner questionnaire and clinical examinations. At enrolment, owners frequently reported physical changes (53%), behavioral changes (47%), changes to eating patterns (41%), and activity changes (40%) in their mature cats. On physical examination, 45% cats were in overweight condition and 12% were obese. A heart murmur was detected in 29% cats, whilst indirect systolic blood pressure (SBP) was >160 mmHg in 5% cats. Dental disease was present in 54% cats and was associated with a matted hair coat (P = 0.01), increased sleeping (P = 0.02), absence of gray hairs (P = 0.03), and increased irritability to other pets (P = 0.04). Abnormalities were evident in 58% of cats that allowed an orthopedic examination (OE) to be performed. These cats were older than cats with a normal OE (P = 0.01), and abnormal OE findings were associated with a matted coat (P = 0.03) and increased grooming (P = 0.04). Aazotaemia was present in 10% cats, and this was associated with cats being observed to “sniff their food and then walk away” (P = 0.04). Hyperthyroidism was diagnosed in 3% cats, who were older (P = 0.02), had a leaner BCS (P = 0.02) and lesser blood creatinine concentrations (P = 0.01). Hyperthyroid cats were also more likely to have increased liver enzyme activity and increased SBP (P = <0.001) compared with non-hyperthyroid cats. Of the 176 cats where all clinical assessments were conducted, only 12% had no evidence of any disease. Clinical abnormalities are commonly identified when thorough, clinical assessments are performed in mature pet cats visiting primary care practice.
Fermentation Quality and Microbial Community of Corn Stover or Rice Straw Silage Mixed with Soybean Curd Residue
Authors: Wang Xiaolin , Song Jiamei , Liu Zihan , Zhang Guangning , Zhang Yonggen
Published: April 2022

The objective of this study was to investigate the fermentation quality and microbial community of corn stover (CS) or rice straw (RS) silage mixed with soybean curd residue (SCR). In this study, SCR and CS or RS were mixed at ratios of 75:25, 70:30, and 65:35, respectively, and measured for nutrient content, fermentation indices, and bacterial diversity after 30 days of ensiling. The results showed an increase in lactic acid (LA) concentration (p < 0.01) and crude protein (CP) content (p < 0.0001), a decrease in pH value (p < 0.01), the content of NDF (p < 0.01) and ADF (p < 0.01), and ammonia nitrogen (AN) concentration (p < 0.01) as the proportion of SCR in raw materials (CS or RS) increased. The addition of SCR to silage led to a decrease in bacterial diversity and contributed to an increased relative abundance of beneficial microorganisms, such as Lactobacillus, and a corresponding decrease in the relative abundance of undesirable microorganisms, such as Clostridium and Enterobacter. Collectively, the mixed silage of soybean curd residue with corn stover or rice straw preserved more nutrients and helped improve fermentation quality.
Targeted Mop up and Robust Response Tools Can Achieve and Maintain Possum Freedom on the Mainland
Authors: Cook Briar , Mulgan Nick
Published: April 2022

Unfenced sites on mainland New Zealand have long been considered impossible to defend from reinvasion by possums, and are thus unsuitable for eradication. In July 2019, we began eliminating possums from 11,642 ha (including approximately 8700 ha of suitable possum habitat) in South Westland, using alpine rivers and high alpine ranges to minimise reinvasion. Two aerial 1080 (sodium fluoroacetate) applications, each with two pre-feeds, were used. Here, we detail the effort to mop up existing possums and subsequent invaders in the 13 months following the aerial operation. Possums were detected and caught using a motion-activated camera network, traps equipped with automated reporting and a possum search dog. The last probable survivor was eliminated on 29 June 2020, 11 months after the initial removal operation. Subsequently, possums entered the site at a rate of 4 per year. These were detected and removed using the same methods. The initial elimination cost NZD 163.75/ha and ongoing detection and response NZD 15.70/ha annually. We compare costs with possum eradications on islands and ongoing suppression on the mainland.
Polyphenolic Compounds from Lespedeza bicolor Protect Neuronal Cells from Oxidative Stress
Authors: Tarbeeva Darya V. , Pislyagin Evgeny A. , Menchinskaya Ekaterina S. , Berdyshev Dmitrii V. , Kalinovskiy Anatoliy I. , Grigorchuk Valeria P. , Mishchenko Natalia P. , Aminin Dmitry L. , Fedoreyev Sergey A.
Published: April 2022

Pterocarpans and related polyphenolics are known as promising neuroprotective agents. We used models of rotenone-, paraquat-, and 6-hydroxydopamine-induced neurotoxicity to study the neuroprotective activity of polyphenolic compounds from Lespedeza bicolor and their effects on mitochondrial membrane potential. We isolated 11 polyphenolic compounds: a novel coumestan lespebicoumestan A (10) and a novel stilbenoid 5’-isoprenylbicoloketon (11) as well as three previously known pterocarpans, two pterocarpens, one coumestan, one stilbenoid, and a dimeric flavonoid. Pterocarpans 3 and 6, stilbenoid 5, and dimeric flavonoid 8 significantly increased the percentage of living cells after treatment with paraquat (PQ), but only pterocarpan 6 slightly decreased the ROS level in PQ-treated cells. Pterocarpan 3 and stilbenoid 5 were shown to effectively increase mitochondrial membrane potential in PQ-treated cells. We showed that pterocarpans 2 and 3, containing a 3’-methyl-3’-isohexenylpyran ring; pterocarpens 4 and 9, with a double bond between C-6a and C-11a; and coumestan 10 significantly increased the percentage of living cells by decreasing ROS levels in 6-OHDA-treated cells, which is in accordance with their rather high activity in DPPH• and FRAP tests. Compounds 9 and 10 effectively increased the percentage of living cells after treatment with rotenone but did not significantly decrease ROS levels.
Clinical-Pathological Study on Expressions β-APP, GFAP, NFL, Spectrin II, CD68 to Verify Diffuse Axonal Injury Diagnosis, Grade and Survival Interval
Authors: Hunea Iuliana , Riscanu Laura , Girlescu Nona , Diac Madalina , Knieling Anton , David Sofia , Furnica Cristina , Lucasevici Codrin , Dragomir Irina Catrinel , Iliescu Diana Bulgaru , Ciocoiu Manuela
Published: April 2022

Traumatic brain injury (TBI) is one of the leading causes of death worldwide, particularly in young people. Diffuse axonal injuries (DAI) are the result of strong rotational and translational forces on the brain parenchyma, leading to cerebral oedema and neuronal death. DAI is typically characterized by coma without focal lesions at presentation and is defined by localized axonal damage in multiple regions of the brain parenchyma, often causing impairment of cognitive and neuro-vegetative function. Following TBI, axonal degeneration has been identified as a progressive process that begins with the disruption of axonal transport, leading subsequently to axonal swelling, axonal ballooning, axonal retraction bulges, secondary disconnection and Wallerian degeneration. The objective of this paper is to report on a series of patients who have suffered fatal traumatic brain injury, in order to verify neurological outcomes in dynamics, relative to the time of injury, using antibodies for neurofilament (NFL), spectrin II, beta-amyloid (β-APP), glial fibrillary acidic protein (GFAP) and cluster of differentiation 68 (CD68). From the studied cases, a total of 50 cases were chosen, which formed two study groups. The first study group comprises 30 cases divided according to survival interval. The control group comprises 20 cases with no history of traumatic brain injury. Cardiovascular disease and history of stroke, cases suffering from loss of vital functions, a post-traumatic survival time of less than 15 min, autolysis and putrefaction were established as criteria for exclusion. Based on their expression, we tested for diagnosis and degree of DAI as a strong predictor of mortality. Immunoreactivity was significantly increased in the DAI group compared to the control group. The earliest changes were recorded for GFAP and CD68 immunolabeling, followed by β-APP, spectrin II and NFM. The most intense changes in immunostaining were recorded for spectrin II. Comparative analysis of brain apoptosis, reactive astrocytosis and inflammatory reaction using specific immunohistochemical markers can provide important information on diagnosis of DAI and prognosis, and may elucidate the timing of the traumatic event in traumatic brain injury.
Middle Latitude Geomagnetic Disturbances Caused by Hall and Pedersen Current Circuits Driven by Prompt Penetration Electric Fields
Authors: Kikuchi Takashi , Hashimoto Kumiko K. , Tanaka Takashi , Nishimura Yukitoshi , Nagatsuma Tsutomu
Published: April 2022

The prompt penetration electric field (PPEF) drives the DP2 currents composed of the two-cell Hall current vortices surrounding the Region-1 field-aligned currents (R1FACs), and the zonal equatorial electrojet (EEJ, Cowling current) at the dayside equator, which is connected to the R1FACs by the Pedersen currents at middle latitudes. The midlatitude H- and D-components of the disturbance magnetic field are caused by the DP2 currents, as well as by the magnetospheric currents, such as magnetopause currents, FACs, ring currents, and so on. If the DP2 current is the major source for the midlatitude geomagnetic disturbances, H and D are supposed to be caused by the Hall and Pedersen currents, respectively. The H-D correlation would be negative in both morning and afternoon sectors, and H/D-EEJ correlation would be negative/positive in the morning and positive/negative in the afternoon. We picked out 39 DP2 events in the morning and 34 events in the afternoon from magnetometer data at Paratunka, Russia (PTK, 45.58° N geomagnetic latitude (GML)), which are characterized by negative H–D correlation with correlation coefficient (cc) < −0.8. We show that the midlatitude H/D is highly correlated with EEJ at Yap, Micronesia (0.38° S GML) in the same local time zone, meeting the Pedersen–Cowling current circuit between midlatitude and equator in the DP2 current system. Using the global simulation, we confirmed that the ionospheric currents with north–south direction at midlatitude is the Pedersen currents developing concurrently with the Cowling current. We suggest that the negative H-D correlation provides a clue to detect the PPEF when magnetometers are available at middle latitudes.
Process- and Product-Related Foulants in Virus Filtration
Authors: Isu Solomon , Qian Xianghong , Zydney Andrew L. , Wickramasinghe S. Ranil
Published: April 2022

Regulatory authorities place stringent guidelines on the removal of contaminants during the manufacture of biopharmaceutical products. Monoclonal antibodies, Fc-fusion proteins, and other mammalian cell-derived biotherapeutics are heterogeneous molecules that are validated based on the production process and not on molecular homogeneity. Validation of clearance of potential contamination by viruses is a major challenge during the downstream purification of these therapeutics. Virus filtration is a single-use, size-based separation process in which the contaminating virus particles are retained while the therapeutic molecules pass through the membrane pores. Virus filtration is routinely used as part of the overall virus clearance strategy. Compromised performance of virus filters due to membrane fouling, low throughput and reduced viral clearance, is of considerable industrial significance and is frequently a major challenge. This review shows how components generated during cell culture, contaminants, and product variants can affect virus filtration of mammalian cell-derived biologics. Cell culture-derived foulants include host cell proteins, proteases, and endotoxins. We also provide mitigation measures for each potential foulant.
The Expression of Signaling Genes in Breast Cancer Cells
Authors: Rzymowska Jolanta , Wilkołaski Andrzej , Szatkowska Lidia , Grzybowska Ludmiła
Published: April 2022

The aim of the study was to investigate the effect of paclitaxel on the expression of genes encoding signaling factors in breast cancer cells in in vitro conditions after incubation with the said chemotherapeutic. The tested cells were harvested from the mammary glands of 36 patients with early breast cancer. The microarray technology was employed for the identification of gene expression. For this purpose, mRNA isolated from tumor cells was used. A significant effect of paclitaxel on the genome of breast cancer cells was confirmed. Paclitaxel changed the functions of cancer cells by increasing the expression of most genes encoding signaling proteins and receptors. The analysis of the results suggested that this cytostatic agent produces a beneficial therapeutic effect at a lower dose (60 ng/mL). In contrast, a high dose of paclitaxel (300 ng/mL) was associated with a high cytotoxicity.
Impact of SARS-CoV-2 Infection on the Course of Inflammatory Bowel Disease in Patients Treated with Biological Therapeutic Agents: A Case-Control Study
Authors: Papa Alfredo , Scaldaferri Franco , Covino Marcello , Tursi Antonio , Furfaro Federica , Mocci Giammarco , Lopetuso Loris Riccardo , Maconi Giovanni , Bibbò Stefano , Fiorani Marcello , Laterza Lucrezia , Mignini Irene , Napolitano Daniele , Parisio Laura , Pizzoferrato Marco , Privitera Giuseppe , Pugliese Daniela , Schepis Tommaso , Schiavoni Elisa , Settanni Carlo Romano , Vetrone Lorenzo Maria , Armuzzi Alessandro , Danese Silvio , Gasbarrini Antonio
Published: April 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised concerns in patients with inflammatory bowel disease (IBD), not only due to consequences of coronavirus disease 2019 itself but also as a possible cause of IBD relapse. The main objective of this study was to assess the role of SARS-CoV-2 in IBD clinical recurrence in a cohort of patients undergoing biological therapy. Second, we evaluated the difference in C-reactive protein (CRP) levels between the start and end of the follow-up period (ΔCRP) and the rate of biological therapy discontinuation. Patients with IBD positive for SARS-CoV-2 infection were compared with non-infected patients. IBD recurrence was defined as the need for intensification of current therapy. We enrolled 95 IBD patients with SARS-CoV-2 infection and 190 non-infected patients. During follow-up, 11 of 95 (11.6%) SARS-CoV-2-infected patients experienced disease recurrence compared to 21 of 190 (11.3%) in the control group (p = 0.894). Forty-six (48.4%) SARS-CoV-2-infected patients discontinued biological therapy versus seven (3.7%) in the control group (p < 0.01). In the multivariate analysis, biological agent discontinuation (p = 0.033) and ΔCRP (p = 0.017), but not SARS-CoV-2 infection (p = 0.298), were associated with IBD recurrence. SARS-CoV-2 infection was not associated with increased IBD recurrence rates in this cohort of patients treated with biological agents.
Biocompatibility of Surface-Modified Membranes for Chronic Hemodialysis Therapy
Authors: Bonomini Mario , Piscitani Luca , Di Liberato Lorenzo , Sirolli Vittorio
Published: April 2022

Hemodialysis is a life-sustaining therapy for millions of people worldwide. However, despite considerable technical and scientific improvements, results are still not fully satisfactory in terms of morbidity and mortality. The membrane contained in the hemodialyzer is undoubtedly the main determinant of the success and quality of hemodialysis therapy. Membrane properties influence solute removal and the interactions with blood components that define the membrane’s biocompatibility. Bioincompatibility is considered a potential contributor to several uremic complications. Thus, the development of more biocompatible polymers used as hemodialyzer membrane is of utmost importance for improving results and clinical patient outcomes. Many different surface-modified membranes for hemodialysis have been manufactured over recent years by varying approaches in the attempt to minimize blood incompatibility. Their main characteristics and clinical results in hemodialysis patients were reviewed in the present article.
Alteration of Neural Pathways and Its Implications in Alzheimer’s Disease
Authors: Kim Sujin , Nam Yunkwon , Kim Hyeon soo , Jung Haram , Jeon Seong Gak , Hong Sang Bum , Moon Minho
Published: April 2022

Alzheimer’s disease (AD) is a neurodegenerative disease accompanied by cognitive and behavioral symptoms. These AD-related manifestations result from the alteration of neural circuitry by aggregated forms of amyloid-β (Aβ) and hyperphosphorylated tau, which are neurotoxic. From a neuroscience perspective, identifying neural circuits that integrate various inputs and outputs to determine behaviors can provide insight into the principles of behavior. Therefore, it is crucial to understand the alterations in the neural circuits associated with AD-related behavioral and psychological symptoms. Interestingly, it is well known that the alteration of neural circuitry is prominent in the brains of patients with AD. Here, we selected specific regions in the AD brain that are associated with AD-related behavioral and psychological symptoms, and reviewed studies of healthy and altered efferent pathways to the target regions. Moreover, we propose that specific neural circuits that are altered in the AD brain can be potential targets for AD treatment. Furthermore, we provide therapeutic implications for targeting neuronal circuits through various therapeutic approaches and the appropriate timing of treatment for AD.
Endoscopic Applications of Near-Infrared Photoimmunotherapy (NIR-PIT) in Cancers of the Digestive and Respiratory Tracts
Authors: Furumoto Hideyuki , Kato Takuya , Wakiyama Hiroaki , Furusawa Aki , Choyke Peter L. , Kobayashi Hisataka
Published: April 2022

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and promising therapy that specifically destroys target cells by irradiating antibody-photo-absorber conjugates (APCs) with NIR light. APCs bind to target molecules on the cell surface, and when exposed to NIR light, cause disruption of the cell membrane due to the ligand release reaction and dye aggregation. This leads to rapid cell swelling, blebbing, and rupture, which leads to immunogenic cell death (ICD). ICD activates host antitumor immunity, which assists in killing still viable cancer cells in the treated lesion but is also capable of producing responses in untreated lesions. In September 2020, an APC and laser system were conditionally approved for clinical use in unresectable advanced head and neck cancer in Japan, and are now routine in appropriate patients. However, most tumors have been relatively accessible in the oral cavity or neck. Endoscopes offer the opportunity to deliver light deeper within hollow organs of the body. In recent years, the application of endoscopic therapy as an alternative to surgery for the treatment of cancer has expanded, providing significant benefits to inoperable patients. In this review, we will discuss the potential applications of endoscopic NIR-PIT, especially in thoracic and gastrointestinal cancers.
Gut Microbiota–Brain Axis as a Potential Modulator of Psychological Stress after Spinal Cord Injury
Authors: Musleh-Vega Samir , Ojeda Jorge , Vidal Pia M.
Published: April 2022

A growing body of evidence from preclinical and clinical studies has associated alterations of the gut microbiota–brain axis with the progression and development of a number of pathological conditions that also affect cognitive functions. Spinal cord injuries (SCIs) can be produced from traumatic and non-traumatic causes. It has been reported that SCIs are commonly associated with anxiety and depression-like symptoms, showing an incidence range between 11 and 30% after the injury. These psychological stress-related symptoms are associated with worse prognoses in SCIs and have been attributed to psychosocial stressors and losses of independence. Nevertheless, emotional and mental modifications after SCI could be related to changes in the volume of specific brain areas associated with information processing and emotions. Additionally, physiological modifications have been recognized as a predisposing factor for mental health depletion, including the development of gut dysbiosis. This condition of imbalance in microbiota composition has been shown to be associated with depression in clinical and pre-clinical models. Therefore, the understanding of the mechanisms underlying the relationship between SCIs, gut dysbiosis and psychological stress could contribute to the development of novel therapeutic strategies to improve SCI patients’ quality of life.
Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma
Authors: Everix Liesbeth , Nair Shankari , Driver Cathryn H. S. , Goethals Ingeborg , Sathekge Mike M. , Ebenhan Thomas , Vandevoorde Charlot , Bolcaen Julie
Published: April 2022

Despite numerous innovative treatment strategies, the treatment of glioblastoma (GB) remains challenging. With the current state-of-the-art therapy, most GB patients succumb after about a year. In the evolution of personalized medicine, targeted radionuclide therapy (TRT) is gaining momentum, for example, to stratify patients based on specific biomarkers. One of these biomarkers is deficiencies in DNA damage repair (DDR), which give rise to genomic instability and cancer initiation. However, these deficiencies also provide targets to specifically kill cancer cells following the synthetic lethality principle. This led to the increased interest in targeted drugs that inhibit essential DDR kinases (DDRi), of which multiple are undergoing clinical validation. In this review, the current status of DDRi for the treatment of GB is given for selected targets: ATM/ATR, CHK1/2, DNA-PK, and PARP. Furthermore, this review provides a perspective on the use of radiopharmaceuticals targeting these DDR kinases to (1) evaluate the DNA repair phenotype of GB before treatment decisions are made and (2) induce DNA damage via TRT. Finally, by applying in-house selection criteria and analyzing the structural characteristics of the DDRi, four drugs with the potential to become new therapeutic GB radiopharmaceuticals are suggested.
Analysis of Secreted Proteins from Prepubertal Ovarian Tissues Exposed In Vitro to Cisplatin and LH
Authors: Marcozzi Serena , Ciccosanti Fabiola , Fimia Gian Maria , Piacentini Mauro , Caggiano Cinzia , Sette Claudio , De Felici Massimo , Klinger Francesca Gioia
Published: April 2022

It is well known that secreted and exosomal proteins are associated with a broad range of physiological processes involving tissue homeostasis and differentiation. In the present paper, our purpose was to characterize the proteome of the culture medium in which the oocytes within the primordial/primary follicles underwent apoptosis induced by cisplatin (CIS) or were, for the most part, protected by LH against the drug. To this aim, prepubertal ovarian tissues were cultured under control and in the presence of CIS, LH, and CIS + LH. The culture media were harvested after 2, 12, and 24 h from chemotherapeutic drug treatment and analyzed by liquid chromatography–mass spectrometry (LC-MS). We found that apoptotic conditions generated by CIS in the cultured ovarian tissues and/or oocytes are reflected in distinct changes in the extracellular microenvironment in which they were cultured. These changes became evident mainly from 12 h onwards and were characterized by the inhibition or decreased release of a variety of compounds, such as the proteases Htra1 and Prss23, the antioxidants Prdx2 and Hbat1, the metabolic regulators Ldha and Pkm, and regulators of apoptotic pathways such as Tmsb4x. Altogether, these results confirm the biological relevance of the LH action on prepuberal ovaries and provide novel information about the proteins released by the ovarian tissues exposed to CIS and LH in the surrounding microenvironment. These data might represent a valuable resource for future studies aimed to clarify the effects and identify biomarkers of these compounds’ action on the developing ovary.
5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insulinoma β-TC-6 Cells
Authors: Filip Kamila , Lewińska Anna , Adamczyk-Grochala Jagoda , Marino Gammazza Antonella , Cappello Francesco , Lauricella Marianna , Wnuk Maciej
Published: April 2022

5-Azacytidine (5-azaC), a methyltransferase inhibitor and anticancer drug, can promote several cellular stress responses such as apoptosis, autophagy, and senescence. The action of 5-azaC is complex and can be modulated by dose, time of treatment, and co-administration with oxidants. Insulinoma is a rare pancreatic neuroendocrine tumor with limited chemotherapeutic options. In the present study, two cellular models of insulinoma were considered, namely NIT-1 and β-TC-6 mouse cells, to evaluate the effects of 5-azaC post-treatment during hydrogen peroxide-induced oxidative stress. 5-azaC attenuated the development of oxidant-induced senescent phenotype in both cell lines. No pro-apoptotic action of 5-azaC was observed in cells treated with the oxidant. On the contrary, 5-azaC stimulated an autophagic response, as demonstrated by the increase in phosphorylated eIF2α and elevated pools of autophagic marker LC3B in oxidant-treated β-TC-6 cells. Notably, autophagy resulted in increased necrotic cell death in β-TC-6 cells with higher levels of nitric oxide compared to less affected NIT-1 cells. In addition, 5-azaC increased levels of RNA methyltransferase Trdmt1, but lowered 5-mC and m6A levels, suggesting Trdmt1 inhibition. We postulate that the 5-azaC anticancer action may be potentiated during oxidative stress conditions that can be used to sensitize cancer cells, at least insulinoma cells, with limited drug responsiveness.
Comprehensive Analysis of CDK1-Associated ceRNA Network Revealing the Key Pathways LINC00460/LINC00525-Hsa-Mir-338-FAM111/ZWINT as Prognostic Biomarkers in Lung Adenocarcinoma Combined with Experiments
Authors: Li Wen , Feng Shan-Shan , Wu Hao , Deng Jing , Zhou Wang-Yan , Jia Ming-Xi , Shi Yi , Ma Liang , Zeng Xiao-Xi , Zuberi Zavuga , Fu Da , Liu Xiang , Chen Zhu
Published: April 2022

Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide, and effective biomarkers are still lacking for early detection and prognosis prediction. Here, based on gene expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA), 806 long non-coding RNAs (lncRNAs), 122 microRNAs (miRNAs) and 1269 mRNAs associated with CDK1 were identified. The regulatory axis of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT was determined according to the correlation between gene expression and patient prognosis. The abnormal up-regulation of FAM111B/ZWINT in LUAD was related to hypomethylation. Furthermore, immune infiltration analysis suggested FAM111B/ZWINT could affect the development and prognosis of cancer by regulating the LUAD immune microenvironment. EMT feature analysis suggested that FAM111B/ZWINT promoted tumor spread through the EMT process. Functional analysis showed FAM111B/ZWINT was involved in cell cycle events such as DNA replication and chromosome separation. We analyzed the HERB and GSCALite databases to identify potential target medicines that may play a role in the treatment of LUAD. Finally, the expression of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT axis was verified in LUAD cells by RT-qPCR, and these results were consistent with bioinformatics analysis. Overall, we constructed a CDK1-related ceRNA network and revealed the LINC00460/LINC00525-hsa-mir-338-FAM111/ZWINT pathways as potential diagnostic biomarkers or therapeutic targets of LUAD.
Parents’ Communication with Teachers about Food and Nutrition Issues of Primary School Students
Authors: Aydin Gozde , Margerison Claire , Worsley Anthony , Booth Alison
Published: April 2022

Parents and teachers have a major influence in the formation of primary school children’s eating behaviours. Although the cooperation of parents and teachers has frequently been recommended in the promotion of healthy eating habits among primary school children, little is known about the communication between these two groups regarding food- and nutrition-related issues. This paper reports findings from semi-structured interviews with primary school parents (n = 19) and primary teachers (n = 17), as well as findings from a survey of 787 parents in Australia. Audio-recorded interviews were analysed using NVivo and descriptive statistics were calculated for the survey questions. The results indicated that their communications involved various topics, including allergies, lunchbox content, and supervision requests, through diverse communication channels. The risk of offending each other and time scarcity were reported as communication barriers. Parents mainly expected teachers to ensure that their children were given enough time to eat their lunch, teach healthy eating, and be good role models of healthy eating. This study highlights the need to overcome communication barriers between parents and teachers and support teachers in their multifaceted professional roles.
Scaphoid Fracture Detection by Using Convolutional Neural Network
Authors: Yang Tai-Hua , Horng Ming-Huwi , Li Rong-Shiang , Sun Yung-Nien
Published: April 2022

Scaphoid fractures frequently appear in injury radiograph, but approximately 20% are occult. While there are few studies in the fracture detection of X-ray scaphoid images, their effectiveness is insignificant in detecting the scaphoid fractures. Traditional image processing technology had been applied to segment interesting areas of X-ray images, but it always suffered from the requirements of manual intervention and a large amount of computational time. To date, the models of convolutional neural networks have been widely applied to medical image recognition; thus, this study proposed a two-stage convolutional neural network to detect scaphoid fractures. In the first stage, the scaphoid bone is separated from the X-ray image using the Faster R-CNN network. The second stage uses the ResNet model as the backbone for feature extraction, and uses the feature pyramid network and the convolutional block attention module to develop the detection and classification models for scaphoid fractures. Various metrics such as recall, precision, sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC) are used to evaluate our proposed method’s performance. The scaphoid bone detection achieved an accuracy of 99.70%. The results of scaphoid fracture detection with the rotational bounding box revealed a recall of 0.789, precision of 0.894, accuracy of 0.853, sensitivity of 0.789, specificity of 0.90, and AUC of 0.920. The resulting scaphoid fracture classification had the following performances: recall of 0.735, precision of 0.898, accuracy of 0.829, sensitivity of 0.735, specificity of 0.920, and AUC of 0.917. According to the experimental results, we found that the proposed method can provide effective references for measuring scaphoid fractures. It has a high potential to consider the solution of detection of scaphoid fractures. In the future, the integration of images of the anterior–posterior and lateral views of each participant to develop more powerful convolutional neural networks for fracture detection by X-ray radiograph is probably important to research.