bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness analysis of atezolizumab plus bevacizumab versus sorafenib in first line treatment for Chinese subpopulation with unresectable hepatocellular carcinoma
Authors: Tseng Chien-Yu , Tsai Yi-Wen , Shiu Ming-Neng
Published: November 2023

Objective

We aimed to evaluate the cost-effectiveness of atezolizumab plus bevacizumab (atezo-bev) versus sorafenib treatment in Taiwan.

Methods

Using sorafenib as the comparator, we developed a partitioned survival model to evaluate the costs and quality-adjusted life year (QALY) of the atezo-bev treatment. The time horizon of the study was 15 years, and the annual discount rate was 3%. We analyzed the incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB) from the treatment effects (determined from the progression-free and overall survival outcomes of the IMbrave150 study), direct medical costs (collected and estimated from the National Health Insurance Research Database, Taiwan), and utility parameters (referred to the NICE technology appraisal guidance), as well as the deterministic sensitivity and probabilistic sensitivity.

Results

Compared with sorafenib, the incremental effectiveness of atezo-bev treatment was 1.7 QALY, with an incremental cost of USD 127,607. The ICER was USD 75,192 per QALY, which was less than the predefined willingness to pay in Taiwan.

Conclusion

The combined treatment of atezo-bev is cost-effective when compared with sorafenib, which is currently the first-line treatment option for unresectable HCC in Taiwan.
Multi-omics analysis reveals CLIC1 as a therapeutic vulnerability of gliomas
Authors: Wang Chengcheng , He Zheng
Published: November 2023

Introduction: Despite advances in comprehending cancer biology, malignant gliomas remain incurable. The present work conducted a multi-omics analysis for investigating the significance of chloride intracellular channel 1 (CLIC1) in gliomas.

Methods: Multi-omics data of glioma covering transcriptomics, genomics, DNA methylation and single-cell transcriptomics from multiple public cohorts were enrolled for analyzing CLIC1. In vitro experiments were conducted to measure apoptosis and cell mobility in U251 and U373 glioma cells following transfection of CLIC1 siRNAs.

Results: Elevated CLIC1 expression was proven to stably and independently estimate worse survival outcomes. CLIC1 expression was higher in more advanced stage, wild-type IDH and unmethylated MGMT samples. Tumorigenic and anticancer immunity pathways were remarkably enriched in CLIC1-up-regulated tumors. Additionally, CLIC1 was positively linked with cancer-immunity cycle, stromal activation, DNA damage repair and cell cycle. Suppressing CLIC1 resulted in apoptosis and attenuated cell motility of glioma cells. More frequent genomic alterations were found in CLIC1-up-regulated tumors. CLIC1 expression presented a remarkably negative connection to DNA methylation. High CLIC1 expression samples were more sensitive to camptothecin, cisplatin, doxorubicin, erlotinib, paclitaxel, rapamycin, clofarabine, tanespimycin, methotrexate, everolimus, TAK-733, trametinib and AZD8330. Tumors with upregulated CLIC1 presented abundant immune cell infiltration, higher expression of immune-checkpoints and -modulators and similar transcriptome profiling, indicative of well response to immune-checkpoint blockade (ICB). Nevertheless, due to elevated TIDE score, tumors with CLIC1 upregulation appeared to be resistant to ICB. Single-cell analysis unveiled that CLIC1 was expressed ubiquitously in tumor cells and tumor microenvironment.

Conclusions: Overall, CLIC1 was a promising treatment vulnerability in glioma.
A novel Glycyrrhiza glabra extract liquiritin targeting NFATc1 activity and ROS levels to counteract ovariectomy-induced osteoporosis and bone loss in murine model
Authors: Hong Guoju , Zhou Lin , Zheng Guanqiang , Zheng Xiaoxia , Chen Zhenqiu , He Wei , Wei Qiushi
Published: November 2023

Osteoporosis, a prevalent osteolytic condition worldwide, necessitates effective strategies to inhibit excessive bone resorption by curbing osteoclast hyperactivation. Liquiritin (LIQ), an flavanone derivative employed in acute lung injury and rheumatoid arthritis treatment, possesses an unclear role in addressing excessive bone resorption. In this investigation, we found that LIQ demonstrates the ability to inhibit osteoclast formation and the bone-resorbing activity induced by RANKL. At a specific concentration, LIQ significantly attenuated NF-κB-Luc activity induced by RANKL and curtailed NF-κB activation in RANKL-stimulated RAW264.7 cells, resulting in reduced IκB-α breakdown and diminished nuclear NF-κB levels. Furthermore, LIQ markedly inhibited RANKL-induced NFATc1 activation, as evidenced by diminished NFATc1 luciferase activity, reduced NFATc1 mRNA levels, and decreased nuclear NFATc1 protein levels. Subsequent experiments demonstrated that LIQ effectively restrained the RANKL-induced elevation of intracellular calcium as well as reactive oxygen species. Additionally, LIQ exhibited a downregulating effect on the expression of osteoclast-specific genes, which include Acp5, Cathepsin K, Atp6v0d2, Nfatc1, c-Fos, and Mmp9. Notably, our findings revealed the potential of LIQ to counteract decreased bone density in mice that underwent ovariectomy. Collectively, the data indicate that LIQ impedes osteoclast formation triggered by RANKL and the subsequent reduction in bone mass by mitigating ROS levels and suppressing the Ca2+/MAPK-NFATc1 signaling pathway, suggesting its promising candidacy as a therapeutic agent for RANKL-mediated osteoporosis.
Potential antioxidative and anti-hyperuricemic components in Rodgersia podophylla A. Gray revealed by bio-affinity ultrafiltration with SOD and XOD
Authors: Liang Can , Xu Yongbing , Fan Minxia , Muema Felix Wambua , Chen Guilin , Guo Mingquan , Hu Guangwan
Published: November 2023

Rodgersia podophylla A. Gray (R. podophylla) is a traditional Chinese medicine with various pharmacological effects. However, its antioxidant and anti-hyperuricemia components and mechanisms of action have not been explored yet. In this study, we first assessed the antioxidant potential of R. podophylla with 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) assays. The results suggested that the ethyl acetate (EA) fraction of R. podophylla not only exhibited the strongest DPPH, ABTS radical scavenging and ferric-reducing activities, but also possessed the highest total phenolic and total flavonoid contents among the five fractions. After that, the potential superoxide dismutase (SOD) and xanthine oxidase (XOD) ligands from the EA fraction were quickly screened and identified through the bio-affinity ultrafiltration liquid chromatography-mass spectrometry (UF-LC-MS). Accordingly, norbergenin, catechin, procyanidin B2, 4-O-galloylbergenin, 11-O-galloylbergenin, and gallic acid were considered to be potential SOD ligands, while gallic acid, 11-O-galloylbergenin, catechin, bergenin, and procyanidin B2 were recognized as potential XOD ligands, respectively. Moreover, these six ligands effectively interacted with SOD in molecular docking simulation, with binding energies (BEs) ranging from −6.85 to −4.67 kcal/mol, and the inhibition constants (Ki) from 9.51 to 379.44 μM, which were better than the positive controls. Particularly, catechin exhibited a robust binding affinity towards XOD, with a BE value of −8.54 kcal/mol and Ki value of 0.55 μM, which surpassed the positive controls. In conclusion, our study revealed that R. podophylla possessed remarkable antioxidant and anti-hyperuricemia activities and that the UF-LC-MS method is suitable for screening potential ligands for SOD and XOD from medicinal plants.
Across the stages: a multiscale extension of the generalized stochastic microdosimetric model (MS-GSM2) to include the ultra-high dose rate
Authors: Battestini Marco , Missiaggia Marta , Attili Andrea , Tommasino Francesco , La Tessa Chiara , Cordoni Francesco G. , Scifoni Emanuele
Published: November 2023

Ultra-high dose rate (UHDR) irradiations with different types of radiation have shown a larger sparing of normal tissue and unchanged tumor control with respect to conventional delivery. In recent years, there has been an accumulation of experimental evidence related to the so-called FLASH effect. However, the underpinning mechanism remains, to date, extremely debated and largely unexplained, while the involvement of multiple scales of radiation damage has been suggested. Since it is believed that the chemical environment plays a crucial role in the FLASH effect, this work aims to develop a multi-stage tool, the multiscale generalized stochastic microdosimetric model (MS-GSM2), that can capture several possible effects on DNA damage at the UHDR regime, such as reduction of DNA damage yield due to organic radical recombination, damage fixation due to oxygenation, and spatial and temporal dose deposition effects, allowing us to explore most of the candidate mechanisms for explaining the FLASH effect. The generalized stochastic microdosimetric model (GSM2) is a probabilistic model that describes the time evolution of DNA damage in a cell nucleus using microdosimetric principles, accounting for different levels of spatio-temporal stochasticity. In particular, the GSM2 describes radiation-induced DNA damage formation and kinetic repair in the case of protracted irradiation without considering the Poissonian assumption to treat the number of radiation-induced DNA damage. In this work, we extend the GSM2, coupling the evolution of DNA damage to fast chemical reaction kinetics, described by a system of ordinary differential equations, accounting for an additional level of stochasticity, i.e., in chemistry. We simulate energy deposition by particles in a microscopic volume, which mimics the cell nucleus, in order to examine the combined effects of several chemical species and the time evolution of DNA damage. We assume that UHDR modifies the time evolution of the peroxyl radical concentration, with a consequent reduction in the yield of the indirect DNA damage. This damage reduction emerges only at UHDR and is more pronounced at high doses. Moreover, the indirect damage yield reduction depends on the radiation quality. We show that the MS-GSM2 can describe the empirical trend of dose- and dose rate-dependent cell sensitivity over a broad range, particularly the larger sparing of healthy tissue occurring at the FLASH regime. The complete generality of the MS-GSM2 also allows us to study the impact of different dose delivery time structures and radiation qualities, including high LET beams.
Not all kidney cysts are created equal: a distinct renal cystogenic mechanism in tuberous sclerosis complex (TSC)
Authors: Soleimani Manoocher
Published: November 2023

Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disease caused by mutations in either TSC1 or TSC2 genes. Approximately, two million individuals suffer from this disorder worldwide. TSC1 and TSC2 code for the proteins harmartin and tuberin, respectively, which form a complex that regulates the mechanistic target of rapamycin complex 1 (mTORC1) and prevents uncontrollable cell growth. In the kidney, TSC presents with the enlargement of benign tumors (angiomyolipomas) and cysts whose presence eventually causes kidney failure. The factors promoting cyst formation and tumor growth in TSC are poorly understood. Recent studies on kidney cysts in various mouse models of TSC, including mice with principal cell- or pericyte-specific inactivation of TSC1 or TSC2, have identified a unique cystogenic mechanism. These studies demonstrate the development of numerous cortical cysts that are predominantly comprised of hyperproliferating A-intercalated (A-IC) cells that express both TSC1 and TSC2. An analogous cellular phenotype in cystic epithelium is observed in both humans with TSC and in TSC2+/− mice, confirming a similar kidney cystogenesis mechanism in TSC. This cellular phenotype profoundly contrasts with kidney cysts found in Autosomal Dominant Polycystic Kidney Disease (ADPKD), which do not show any notable evidence of A-IC cells participating in the cyst lining or expansion. RNA sequencing (RNA-Seq) and confirmatory expression studies demonstrate robust expression of Forkhead Box I1 (FOXI1) transcription factor and its downstream targets, including apical H+-ATPase and cytoplasmic carbonic anhydrase 2 (CAII), in the cyst epithelia of Tsc1 (or Tsc2) knockout (KO) mice, but not in Polycystic Kidney Disease (Pkd1) mutant mice. Deletion of FOXI1, which is vital to H+-ATPase expression and intercalated (IC) cell viability, completely inhibited mTORC1 activation and abrogated the cyst burden in the kidneys of Tsc1 KO mice. These results unequivocally demonstrate the critical role that FOXI1 and A-IC cells, along with H+-ATPase, play in TSC kidney cystogenesis. This review article will discuss the latest research into the causes of kidney cystogenesis in TSC with a focus on possible therapeutic options for this devastating disease.
Impact of the COVID-19 pandemic on community-based brain injury associations across Canada: a cross-sectional survey study
Authors: Salazar Ana Paula , Bottari Carolina , Lecours Sophie , McDonald Michelle , Gignac Monique A. M. , Swaine Bonnie , Schmidt Julia , Lemsky Carolyn , Brosda Ashley , Engel Lisa
Published: November 2023

Background

The COVID-19 pandemic created new difficulties for people living with brain injury, their families, and caregivers while amplifying the challenges of community-based associations that support them. We aimed to understand the effects of the pandemic on clients who live with brain injury, as well as on the provision of community brain injury services/programs in Canada.

Methods

Online cross-sectional survey conducted in January 2022. Representatives of brain injury associations across Canada completed the 31 open- and closed-ended questions about meeting clients’ needs, addressing public health guidelines, and sustaining the association. Data were analyzed using descriptive statistics (close-ended questions) and qualitative content analysis (open-ended questions).

Results

Of the 45 key representatives from associations in Pacific/Western (40%), Central (56%), and Atlantic Canada (4%), the majority were paid executive directors (67%). Participants reported that the most frequent psychosocial challenges experienced by their clients during the pandemic were social isolation (98%), loneliness (96%), and anxiety (93%). To alleviate these challenges, associations implemented wellness checks and psychosocial support. Most respondents (91%) affirmed that clients faced multiple technological barriers, such as a lack of technological knowledge and financial resources for devices and/or internet. In the open-ended questions, twenty-nine (64%) associations reported providing clients with devices, technology training, and assistance. Regarding public health measures, thirty (67%) respondents reported that clients had challenges understanding and/or following public health guidelines. Forty-two associations (93%) provided tailored information to help clients understand and comply with public health measures. Although associations (67%) received pandemic-related funding from the Canadian government they still struggled with the association’s sustainability. Thirty-four (76%) lost funding or financial resources that prevented them from delivering programs or required the use of reserve funds to continue to do so. Only 56% reported receiving sufficient funding to address additional COVID-19-related expenses.

Conclusion

Although the pandemic added further challenges to the sustainability of brain injury associations across Canada, they quickly adapted services/programs to respond to the increasing and varied needs of clients, while complying with protective measures. To ensure community associations’ survival it is essential to aptly recognize the vital role played by these associations within the brain injury care continuum.
An analysis of actors participating in the design and implementation of workplace breastfeeding interventions in Mexico using the NetMap analysis approach
Authors: Litwan Kathrin , Lara-Mejía Vania , Chahine Teresa , Hernández-Cordero Sonia , Vilar-Compte Mireya , Pérez-Escamilla Rafael
Published: November 2023

Introduction

While breastfeeding is recognized as providing optimal nutrition for infants and toddlers, maternal employment is a commonly mentioned barrier to breastfeeding. The goal was to (a) identify key actors participating in the design and implementation of workplace breastfeeding interventions in Mexico, (b) understand the complexity of interactions between the actors, and (c) map the connections and influence between the actors when looking into networks of Advice, Command, Funding, and Information.

Method

Following the NetMap methodology, a total of 11 semi-structured interviews with 12 interview partners from 10 organizations were conducted. Interview data were analyzed, and networks were analyzed and visualized, using a social network mapping software.

Results

A total of 83 actors from five different actor groups were identified. Four networks were constructed along the four types of connections: Advice, Command, Funding, and Information. The actors were connected by 580 connections with 446 unique links. Based on various network statistics, the Mexican Institute of Social Security, the Mexican Secretary of Labor and Social Welfare, UNICEF, and the Mexican Secretary of Health were identified to be key actors.

Conclusion

To increase the likelihood of success of workplace breastfeeding interventions, the role of the actors “Employers” and “Women” needs to expand. They should be actively involved in the decision-making process, together with the identified key actors. It is further recommended to re-introduce a national breastfeeding strategy for Mexico that includes policies for workplace breastfeeding interventions.
Barriers to COVID-19 vaccine uptake: classification and the role of Health Literacy and Media Literacy
Authors: Ranjbaran Soheila , Chollou Khalil Maleki , Pourrazavi Sara , Babazadeh Towhid
Published: November 2023

Background

Vaccination is one of the most influential and cost-effective health interventions for preventing and reducing COVID-19 diseases. Unfortunately, the majority of the world's population is deprived of vaccination. Health Literacy (HL) and Media Literacy (ML) are essential to the COVID-19 vaccination. The present study investigates the barriers to COVID-19 vaccine uptake, focusing on classification and the roles of HL and ML.

Methods

A cross-sectional study was conducted among people 18–65 years old in Sarab City, located in East Azerbaijan, Iran, between September to October 2020. Multistage cluster sampling was employed to recruit 298 people from Health Care Services Centers (HCCs).

Results

The results of this research demonstrated that about 32.6% of participants reported that they have fully injected COVID-19 vaccines. Also, HL was positively associated with ML (r = 0.214, p < 0.05). Barriers of COVID-19 vaccine uptake were classified into personal, interpersonal, group and organizational, society and decision-making factors. Besides, barriers to the COVID-19 vaccine were significantly correlated with HL (r = −0.298, p < 0.05) and ML (r = 0.266, p < 0.05). Additionally, in the hierarchical regression model, demographic characteristics accounted for 8.2% of the variation in barriers to the COVID-19 vaccine (F = 4.34; p = 0.001), that monthly income (ß = −0.237; p < 0.05) and marriage statues (ß = 0.131; p < 0.05) were statistically associated with low barriers. HL as predictor variables explained an additional 14.4% of variation in barriers of COVID-19 vaccine (F = 53.84; p < 0.001) and ML explained an extra 9.2% of the variation (F = 38.83; p < 0.001). In total, demographic characteristics, HL dimensions and ML were able to explain 31.8% of the variation in barriers to COVID-19 vaccine.

Conclusions

According to the findings, various strategies are needed to increase the COVID-19 vaccination uptake. This is due to the fact that barriers to COVID-19 vaccination uptake are multifactorial. These facts can help health policymakers and healthcare providers design media-based interventions to reduce barriers to COVID-19 vaccination uptake among adults. Enhancing vaccine HL and ML for adults and improving vaccine confidence are of high priority.
Monkeypox as a potential emerging pandemic: a discussion on future risks and preparedness in Saudi Arabia
Authors: Shoaib Haneen Mohammad
Published: November 2023

Monkeypox, a zoonotic disease caused by the Monkeypox virus, has emerged as a potential threat with pandemic potential in various regions. While it is challenging to predict specific outbreaks, understanding the factors contributing to Monkeypox’s pandemic potential is important. This discussion paper explores the future risks and preparedness measures concerning Monkeypox in Saudi Arabia. The study reviews the past and current knowledge on the Monkeypox outbreak, including its clinical presentation, transmission dynamics (animals-to-humans and humans-to-human), epidemiology, and diagnostic methods. Furthermore, it explores the potential risk factors for the spread of Monkeypox within the Gulf Cooperation Council (GCC) countries, mainly in the Saudi Arabian context, considering factors such as urbanization and travel and trade patterns. The paper emphasizes the importance of early virus detection, surveillance systems, and laboratory capacity in vaccinating and responding to Monkeypox cases. Additionally, it highlights the future risks and preparedness in Saudi Arabia and the usage of social media during the pandemic seeking support and awareness about Monkeypox, and it also highlights the need for effective communication strategies of leaders through social media channels to disseminate accurate information to the public, healthcare providers, and policymakers. The discussion concludes by calling for collaborative efforts among health authorities, researchers, and international medical partners to enhance surveillance, develop outbreak response plans, and ensure the availability of vaccines and treatment options. This research serves as a foundation for guiding future preventive measures and strengthening the overall preparedness of Saudi Arabia in facing the potential emergence of Monkeypox as a future pandemic.
Broad Brush Surveys: a rapid qualitative assessment approach for water and sanitation infrastructure in urban sub-Saharan cities
Authors: Nel Melissa , Simuyaba Melvin , Muchelenje Justina , Chirwa Taonga , Simwinga Musonda , Speight Vanessa , Mhlanga Zenzile , Jacobs Heinz , Nel Nicole , Seeley Janet , Mwanaumo Erastus , Viljoen Lario , Hoddinott Graeme , Bond Virginia
Published: November 2023

Introduction

Broad Brush Surveys (BBS) are a rapid, qualitative assessment approach using four meta-indicators -physical features, social organization, social networks and community narratives - to gauge how local context interfaces with service/intervention options, implementation and uptake.

Methods

In 2021, responding to rapid urbanization and the accompanying need for water and sanitation services, BBS was innovatively applied by social scientists and engineers to assess water and sanitation infrastructure, both formal and informal, in two African cities - Lusaka and Cape Town. In four urban communities, identified with local stakeholders, BBS data collection included: four mapping group discussions with local stakeholders (participants = 24); eight transect walks/drives; 60 structured observations of water and sanitation options, transport depots, health facilities, weekends, nights, rainy days; seven mixed gender focus group discussions (FGDs) with older and young residents (participants = 86); 21 key-informant interviews (KII, participants = 21).

Results

Findings were rapidly summarized into community profiles, including narrative reports, maps and posters, and first discussed with community stakeholders, then at national/provincial levels. The meta-indicator framework and set sequence of qualitative activities allowed the detail on water and sanitation to gradually emerge. For example, the mapping discussion identified water sources considered a risk for waterborne infections, further observed in the transect walks and then structured observations, which compared their relative condition and social interactions and what local residents narrated about them. FGDs and KIIs elaborated on the control of these sources, with nuanced detail, including hidden sources and the use of different water sources for different activities also emerging.

Discussion

We demonstrated that despite some limitations, BBS provided useful insight to systems and social processes surrounding formal and informal water and sanitation infrastructure in and across designated urban areas. Furthermore, BBS had the potential to galvanize local action to improve infrastructure, and illuminated the value of informal options in service delivery.
Milk β-hydroxybutyrate metrics and its consequences for surveillance of hyperketonaemia on commercial dairy farms
Authors: De Jong Elise , Rijpert-Duvivier Angelique , Veldman Hendrik , Steeneveld Wilma , Jorritsma Ruurd
Published: November 2023

Dairy cows that are unable to adapt to a change in their metabolic status are at risk for hyperketonaemia (HK). Reported HK herd level prevalences range a lot and we hypothesized that this is partly due to differences in used tests and monitoring protocols. Insights in milk β-hydroxybutyrate (BHB) metrics can potentially explain why the reported incidences or prevalences vary between test strategies. Automated collection and repeated analyses of individual milk samples with the DeLaval Herd Navigator™ (HN) provides real-time data on milk BHB concentrations. We aimed to use that information to gain insight in BHB metrics measured in milk from 3 to 60 days in milk (DIM). Using different cut-offs (0.08, 0.10 and 0.15 mmol/L), 5 BHB metrics were determined. Furthermore, the impact of 4 arbitrary test protocols on the detected incidence of HK was assessed. We used HN data of 3,133 cows from 35 herds. The cumulative incidence of HK between 3 and 60 DIM varied between 30.5 and 76.7% for different cut-off values. We found a higher HK incidence for higher parity cows. The first elevated BHB concentrations were roughly found between one and two weeks after calving. For higher parity cows the maximum BHB concentrations were higher, the onset of HK was earlier after calving, and the number of episodes of HK was higher. It appeared that the sensitivity of a HK test protocol can be increased by increasing the testing frequency from once to twice a week. Also extending the number of days of the test window from 4–14 to 4–21 days enhances the chance to find cows experiencing HK. In conclusion, HN data provided useful insights in milk BHB metrics. The chosen cut-off value had a large effect on the reported metrics which explains why earlier reported incidences or prevalences vary such a lot. Differences in test period and sample selection also had a large impact on the observed HK incidence. We suggest to take this in consideration while evaluating whether HK is an issue on farm level and use a uniform protocol for benchmarking of HK between farms.
Big Tech, Competition Policy, and Strategic Management: An Alternative Perspective to Teece
Authors: Arend Richard J.
Published: November 2023

Teece asserts that competition policy is so outdated that it now significantly degrades the ability of Big Tech firms to bring socially beneficial innovations to market. He suggests that strategic management research is essential in the struggle to update such policies. We counter that none of these assertions are accurate, let alone backed by evidence. While the larger goal of improving laws and policies through scientific research is a worthy one, the specific focus on doing so to aid a set of powerful firms that have allegedly caused—directly or indirectly—great societal damage is quite unappealing. To balance his pro-Big Tech perspective, we provide logical and theory-based arguments and evidence that indicates Big Tech has often been bad for innovation and society while their regulation has been good, and that more oversight—specifically tailored to digital platforms—would be better. We then offer three alternative paths for us, as management scholars, to take that leverage our distinctive skills and that fulfill our ethical and professional mandates, in the pursuit of improving the strategic decisions and actions that policymakers and firms take.
Long-Term Effects of Whole-Body Vibration on Hind Limb Muscles, Gait and Pain in Lame Dogs with Borderline-to-Severe Hip Dysplasia—A Pilot Study
Authors: Gomes Mayara Viana Freire , Rahal Sheila Canevese , Santos Ivan Felismino Charas dos , Dadalto Carmel Rezende , Mamprim Maria Jaqueline , Negrão Roberta Rocha , Hormaza Joel Mesa , Tsunemi Miriam Harumi , Gómez Álvarez Constanza B.
Published: November 2023

This pilot study aimed to evaluate the long-term effects of Whole-Body Vibration (WBV) on hind limb muscles, gait and pain in lame dogs with borderline-to-severe hip dysplasia. Ten lame client-owned dogs with borderline-to-severe hip dysplasia, aged from 1.5 to 9.0 years and weighing 14.5 to 53.0 kg, were enrolled. The WBV training program consisted of 15 min sessions three times weekly for 16 weeks. Muscles of the hind limbs were evaluated using measurements of thigh circumference, the cross-sectional thickness of selected hind limb muscles by ultrasound assessment, and vastus lateralis muscle activity determined by surface electromyography (EMG). Lameness and clinical signs of pain were assessed by visual lameness scoring, orthopedic examination and an owner-based questionnaire. Kinetic analysis was performed by using a pressure-sensitive walkway. Manual thigh circumference measurements of both hind limbs showed significant increases over the trial period with a greater degree of change observed after week 8. Ultrasound measurements of the left gluteal muscles and the quadriceps femoris muscles of both hind limbs showed significant increases in the cross-section thickness post WBV. Owner’s perception of pain also showed a decrease in signs of pain at week 12 and week 16 compared to baseline. Based on graphs of the EMG activity patterns of the vastus lateralis muscle, 65% of the hind limbs had an improvement after 48 WBV sessions when compared to pre-session patterns. However, no significant differences were observed in visual lameness evaluation and kinetic analysis. Therefore, further studies will help to better clarify the role of WBV in canine rehabilitation protocols.
Growth Performance, Rumen Fermentation, In Vivo Digestibility, and Meat Quality of Pelibuey Lambs Fed a Diet with Ensiled Coffee Pulp
Authors: Munguía-Ameca Graciela , Ortega-Cerrilla María Esther , Herrera-Haro José Guadalupe , Bárcena-Gama Ricardo , Nava-Cuéllar Cuauhtémoc , Zetina-Córdoba Pedro
Published: November 2023

Coffee pulp has been included in ruminant diets; but until now, little has been known about how the addition of ensiled coffee pulp (ECP) affects the growth performance of lambs. This study explores the diet’s antioxidant capacity, tannins, and caffeine concentration and its effect on water intake, growth performance, rumen variables, in vivo digestibility, nitrogen balance, and carcass and meat characteristics of lambs fed ECP. Thirty-six male Pelibuey lambs were distributed randomly to one of three treatments (n = 12): without ECP0; diet with 10% ECP10, and diet with 20% ECP20. The diets’ antioxidant capacity, tannins, and caffeine concentration were similar (p > 0.05) for all treatments. The diets’ antioxidant compounds and the blood serum’s antioxidant capacity were affected (p < 0.05). Dry matter and water intake, body-weight gain, and feed conversion were not significant (p > 0.05). No differences (p > 0.05) were found in the rumen variables or the nitrogen balance. However, the in vivo digestibility of crude protein was affected (p < 0.05). Carcass and meat quality were not affected (p > 0.05) by the inclusion of ECP, except temperature and redness (a*) at seven days of storage, respectively. Including up to 20% of ECP in the diet of lambs did not affect the growth performance, rumen variables, or nitrogen balance; however, the antioxidant compounds of the diets, the antioxidant capacity in blood serum, and the in vivo digestibility of crude protein were different. There was an increase in the redness (a*) and lower temperature in the Longissimus dorsi muscle, keeping lightness (L*), yellowness (b*), water-holding capacity, and texture at seven storage days.
Diagnostic and Prognostic Value of Clinical Scoring and Lung Ultrasonography to Assess Pulmonary Lesions in Veal Calves
Authors: Hoffelner Julia , Peinhopf-Petz Walter , Wittek Thomas
Published: November 2023

This study on veal calf respiratory disease assessed the association between an on-farm clinical scoring system and lung ultrasonography with the postmortem inspection of the lungs. The comparisons allowed the calculation of predictive values of the diagnostic methods. In total, 600 calves on an Austrian veal calf farm were examined at the beginning and the end of the fattening period. Overall, the area under the curve (AUC) for ultrasonographic scores was 0.90 (rsp = 0.78) with a sensitivity (Se) of 0.86. The specificity (Sp) was 0.78, and the positive predictive value (PPV) was 0.74. The AUC for the physical examination was 0.76 (rsp = 0.55) with a Se of 0.64, an Sp of 0.81, and a PPV of 0.69. For the combination of ultrasonography and physical examination, an AUC curve of 0.85 (rsp = 0.69) was calculated. A Se of 0.65 and a Sp of 0.88 with a PPV of 0.73 was calculated. This study concluded that both physical and ultrasonographic examination scoring are reliable examination methods for the detection of lung diseases in veal calves.
Study of the Sea Temperature Backgrounds to Tropical Cyclones Affecting Hainan Province in the Dry Season
Authors: Zhu Jingjing , Zhao Xiaoping , Wu Hui , Wu Shengan , Hu Deqiang , Xing Caiying
Published: November 2023

Using the best path data set of tropical cyclones from the China Meteorological Administration, NCEP/NCAR (National Centers for Environmental Prediction–National Center for Atmospheric Research) reanalysis data, JMA (Japan Meteorological Agency) SST (surface sea temperature) data and NCEP subsurface sea temperature data, the sea temperature background of tropical cyclones affecting Hainan Province in the dry season was analyzed using typical cases from November to December. The results show that there was a significant positive correlation between the number of tropical cyclones affecting Hainan Province and the sea surface temperature in the South China Sea and the Western Pacific. The high SST in the South China Sea and Northwest Pacific were favorable for the occurrence and development of tropical cyclones. The circulation situation also had a significant impact on tropical cyclones during the concurrent period. The wind field convergence was conducive to the occurrence and development of tropical cyclones. The high subsurface sea temperature in the Western Pacific at the depth of 5–50 m was conducive to the strengthening of convection in the Pacific warm pool and the occurrence of the tropical cyclones. The typical cases of 1993 and 2017 have effectively verified the impact of the sea surface temperature background and circulation situation on tropical cyclones affecting the Hainan Province from November to December.
Application of FY Satellite Data in Precipitation of Eastward-Moving Southwest China Vortex: A Case Study of Precipitation in Zhejiang Province
Authors: Mao Chengyan , Qing Yiyu , Qian Zhitong , Zhang Chao , Gu Zhenhai , Gong Liqing , Liao Junyu , Li Haowen
Published: November 2023

Based on the high-resolution data from April to October (the warm season) during the 2010 to 2020 timeframe provided by the FY-2F geostationary meteorological satellite, the classification and application evaluation of the eastward-moving southwest vortex cloud system affecting Zhejiang Province was conducted using cloud classification (CLC) and black body temperature (TBB) products. The results show that: (1) when the intensity of the eastward-moving southwest vortex is strong, the formed precipitation is predominantly regional convective precipitation. The cloud system in the center and southeast quadrant of the southwest vortex is dominated by cumulonimbus and dense cirrus clouds with convective precipitation, while the other quadrants are mainly composed of stratiform clouds, resulting in stable precipitation; (2) The original text is modified as follows: By using the TBB threshold method to identify stratiform and mixed cloud rainfall, we observed a deviation of one order of magnitude. This deviation is advantageous for moderate rain. However, the precipitation results from mixed clouds identified by the TBB threshold method are being overestimated; By means of the application of stratiform and mixed cloud rainfall identified by the TBB threshold method, an order of magnitude deviation was identified (3) The TBB can be consulted to estimate the precipitation, above which there is a large error. Moreover, the dispersion of precipitation produced by deep convective clouds is the largest, while the dispersion of precipitation produced by stratiform clouds is the smallest and has better predictability. Compared to CLC products, cloud type results based on TBB identification are better for convective cloud precipitation application.
Sequential Recovery of Critical Metals from Leached Liquor of Processed Spent Lithium-Ion Batteries
Authors: Ajiboye Ayorinde Emmanuel , Dzwiniel Trevor L.
Published: November 2023

The processing and extraction of critical metals from black mass is important to battery recycling. Separation and recovery of critical metals (Co, Ni, Li, and Mn) from other metal impurities must yield purified metal salts, while avoiding substantial losses of critical metals. Solvent extraction in batch experiments were conducted using mixed metal sulphates obtained from the leach liquor obtained from spent and shredded lithium-ion batteries. Selective extraction of Mn2+, Fe3+, Al3+ and Cu2+ from simulated and real leached mixed metals solution was carried out using di-2-ethylhexylphophoric acid (D2EPHA) and Cyanex-272 at varying pH. Further experiments with the preferred extractant (D2EPHA) were performed under different conditions: changing the concentration of extractant, organic to aqueous ratio, and varying the diluents. At optimum conditions (40% v/v D2EPHA in kerosene, pH 2.5, O:A = 1:1, 25 °C, and 20 min), 85% Mn2+, 98% Al3+, 100% Fe3+, and 43% Cu2+ were extracted with losses of only trace amounts (<5.0%) of Co2+, Ni2+, and Li+. The order of extraction efficiency for the diluents was found to be kerosene > Exxal-10 >>> dichloromethane (CH2Cl2) > toluene. Four stages of stripping of metals loaded on D2EPHA were performed as co-extracted metal impurities were selectively stripped, and a purified MnSO4 solution was produced. Spent extractant was regenerated after Fe3+ and Al3+ were completely stripped using 1.0 M oxalic acid (C2H2O4).
Prospection of Peptide Inhibitors of Thrombin from Diverse Origins Using a Machine Learning Pipeline
Authors: Balakrishnan Nivedha , Katkar Rahul , Pham Peter V. , Downey Taylor , Kashyap Prarthna , Anastasiu David C. , Ramasubramanian Anand K.
Published: November 2023

Thrombin is a key enzyme involved in the development and progression of many cardiovascular diseases. Direct thrombin inhibitors (DTIs), with their minimum off-target effects and immediacy of action, have greatly improved the treatment of these diseases. However, the risk of bleeding, pharmacokinetic issues, and thrombotic complications remain major concerns. In an effort to increase the effectiveness of the DTI discovery pipeline, we developed a two-stage machine learning pipeline to identify and rank peptide sequences based on their effective thrombin inhibitory potential. The positive dataset for our model consisted of thrombin inhibitor peptides and their binding affinities (KI) curated from published literature, and the negative dataset consisted of peptides with no known thrombin inhibitory or related activity. The first stage of the model identified thrombin inhibitory sequences with Matthew’s Correlation Coefficient (MCC) of 83.6%. The second stage of the model, which covers an eight-order of magnitude range in KI values, predicted the binding affinity of new sequences with a log room mean square error (RMSE) of 1.114. These models also revealed physicochemical and structural characteristics that are hidden but unique to thrombin inhibitor peptides. Using the model, we classified more than 10 million peptides from diverse sources and identified unique short peptide sequences (<15 aa) of interest, based on their predicted KI. Based on the binding energies of the interaction of the peptide with thrombin, we identified a promising set of putative DTI candidates. The prediction pipeline is available on a web server.
Targeting Autophagy, Apoptosis, and Oxidative Perturbations with Dapagliflozin Mitigates Cadmium-Induced Cognitive Dysfunction in Rats
Authors: Arab Hany H. , Eid Ahmed H. , Alsufyani Shuruq E. , Ashour Ahmed M. , El-Sheikh Azza A. K. , Darwish Hany W. , Sabry Fatma M.
Published: November 2023

Cognitive decline and Alzheimer-like neuropathology are common manifestations of cadmium toxicity. Thanks to its antioxidant/anti-apoptotic features, dapagliflozin has demonstrated promising neuroprotective actions. However, its effect on cadmium-induced neurotoxicity is lacking. The present work aimed to examine whether dapagliflozin could protect rats from cadmium-evoked cognitive decline. In this study, the behavioral disturbances and hippocampal biomolecular alterations were studied after receiving dapagliflozin. Herein, cadmium-induced memory/learning decline was rescued in the Morris water maze, novel object recognition task, and Y-shaped maze by dapagliflozin. Meanwhile, the hippocampal histopathological abnormalities were mitigated. The molecular mechanisms revealed that dapagliflozin lowered hippocampal expression of p-tau and Aβ42 neurotoxic proteins while augmenting acetylcholine. The cognitive enhancement was triggered by hippocampal autophagy stimulation, as indicated by decreased SQSTM-1/p62 and Beclin 1 upregulation. Meanwhile, a decrease in p-mTOR/total mTOR and an increase in p-AMPK/total AMPK ratio were observed in response to dapagliflozin, reflecting AMPK/mTOR cascade stimulation. Dapagliflozin, on the other hand, dampened the pro-apoptotic processes in the hippocampus by downregulating Bax, upregulating Bcl-2, and inactivating GSK-3β. The hippocampal oxidative insult was mitigated by dapagliflozin as seen by lipid peroxide lowering, antioxidants augmentation, and SIRT1/Nrf2/HO-1 pathway activation. In conclusion, dapagliflozin’s promising neuroprotection was triggered by its pro-autophagic, anti-apoptotic, and antioxidant properties.
From Living in Saltwater to a Scarcity of Salt and Water, and Then an Overabundance of Salt—The Biological Roller Coaster to Which the Renin–Angiotensin System Has Had to Adapt: An Editorial
Authors: Nádasy György L. , Balla András , Szekeres Mária
Published: November 2023

Angiotensin II (Ang II) is a hormone with much more complex actions than is typical for other agonists with heterotrimeric G protein-coupled receptors (GPCRs) [...]
MicroRNAs as Molecular Biomarkers for the Characterization of Basal-like Breast Tumor Subtype
Authors: Tariq Muhammad , Richard Vinitha , Kerin Michael J.
Published: November 2023

Breast cancer is a heterogeneous disease highlighted by the presence of multiple tumor variants and the basal-like breast cancer (BLBC) is considered to be the most aggressive variant with limited therapeutics and a poor prognosis. Though the absence of detectable protein and hormonal receptors as biomarkers hinders early detection, the integration of genomic and transcriptomic profiling led to the identification of additional variants in BLBC. The high-throughput analysis of tissue-specific micro-ribonucleic acids (microRNAs/miRNAs) that are deemed to have a significant role in the development of breast cancer also displayed distinct expression profiles in each subtype of breast cancer and thus emerged to be a robust approach for the precise characterization of the BLBC subtypes. The classification schematic of breast cancer is still a fluid entity that continues to evolve alongside technological advancement, and the transcriptomic profiling of tissue-specific microRNAs is projected to aid in the substratification and diagnosis of the BLBC tumor subtype. In this review, we summarize the current knowledge on breast tumor classification, aim to collect comprehensive evidence based on the microRNA expression profiles, and explore their potential as prospective biomarkers of BLBC.
Nerve Growth Factor, Antimicrobial Peptides and Chemotherapy: Glioblastoma Combination Therapy to Improve Their Efficacy
Authors: Chernov Alexandr , Kudryavtsev Igor , Komlev Aleksei , Alaverdian Diana , Tsapieva Anna , Galimova Elvira , Shamova Olga
Published: November 2023

Glioblastoma (GBM) is an aggressive and lethal malignancy of the central nervous system with a median survival rate of 15 months. We investigated the combined anticancer effects of nerve growth factor (NGF), cathelicidin (LL-37), and protegrin-1 (PG-1) with chemotherapy (temozolomide, doxorubicin, carboplatin, cisplatin, and etoposide) in the glioblastoma U251 cell line to overcome the limitations of conventional chemotherapy and to guarantee specific treatments to succeed. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to study cell viability and to determine the cytotoxic effects of NGF, LL-37, and PG-1 and their combination with chemotherapy in U251 cells. Synergism or antagonism was determined using the combination index (CI) method. Caspase-3 activity was evaluated spectrophotometrically using a caspase-3 activity assay kit. Apoptosis was analyzed with flow cytometry using propidium iodide (PI) and YO-PRO-1. NGF and the peptides showed a strong cytotoxic effect on U251 glioma cells in the MTT test (IC50 0.0214, 3.1, and 26.1 μM, respectively) compared to chemotherapy. The combination of PG-1 + etoposide had a synergistic effect on apoptosis of U251 glioma cells. It should be noted that the cells were in the early and late stages of apoptosis, respectively, compared with the control cells. The caspase-3 activation analysis revealed that the caspase-3 level was not significantly (p > 0.05) increased in U251 cells following PG-1 with etoposide treatment compared with that in the untreated cells, suggesting that the combination of PG-1 and etoposide may induce caspase-independent apoptosis in U251 cells. NGF, LL-37, and PG-1 represent promising drug candidates as the treatment regimen for GBM. Furthermore, the synergistic efficacy of the combined protocol using PG-1 and etoposide may overcome some of the typical limitations of the conventional therapeutic protocols, thus representing a promising approach for GBM therapy.