bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the impact of pre-slaughter management factors on meat quality outcomes in cattle raised for beef: A scoping review
Authors: Sullivan Paxton , Davis Melissa , Bretón Jimena , Edwards-Callaway Lily
Published: December 2022

Introduction

The pre-slaughter management period is a critical juncture in the beef supply chain, having implications not only for animal welfare and product quality, but also for profitability. During this period, cattle are exposed to many stressors in a short time, many of which have been shown to impact meat quality. Understanding how cattle management during this terminal step in the production chain affects meat quality and economic outcomes is crucial.

Methods

The objective of this study was to investigate, synthesize, and report on research evaluating the impact of management factors during the pre-slaughter period on beef meat quality. A systematic approach was used to search for peer-reviewed and primary studies published in English in CAB Abstracts, PubMed, and Web of Science. A total of 3,217 non-duplicate records were screened for eligibility; articles were deemed eligible for inclusion if they included beef cattle in the pre-slaughter period and reported at least one meat quality outcome. After three screening rounds, 85 articles met all inclusion criteria. Data pertinent to the scoping review’s aims were extracted, including study location, population characteristics, pre-slaughter factors reported, and outcomes of interest.

Results

Europe (35, 41%) and South America (21, 25%) represented approximately two-thirds of the studies. Bulls (37, 43.5%) and steers (34, 40.0%) were the most reported sex classes, with the most frequent breed types reported as predominantly British or Continental and Bos indicus breeds (24, 28.2%; 24, 28.2%, respectively). Transportation (n=46), lairage (n=36), and handling (n=35) practices were the most reported pre-slaughter factors. Overall, 59 studies reported pH as an outcome of interest – almost double that of the next highest outcome, bruising (n=35). Muscle pH was most assessed with predictors at the abattoir (n=37); conversely, the effects of transportation were most evaluated on bruising (n=23).

Discussion

A trend across all the categories was that there were relatively few studies evaluating the impact of pre-transport factors on meat quality. Charting the relevant literature is a critical step towards understanding the relationship between pre-slaughter management and end-product quality; doing so will help industry stakeholders in the beef production chain optimize management practices that improve meat quality and enhance profitability.
Evaluating cell viability, capillary perfusion, and collateral tortuosity in an ex vivo mouse intestine fluidics model
Authors: Willi Caroline E. , Abdelazim Hanaa , Chappell John C.
Published: December 2022

Numerous disease conditions involve the sudden or progressive loss of blood flow. Perfusion restoration is vital for returning affected organs to full health. While a range of clinical interventions can successfully restore flow to downstream tissues, the microvascular responses after a loss-of-flow event can vary over time and may involve substantial microvessel instability. Increased insight into perfusion-mediated capillary stability and access-to-flow is therefore essential for advancing therapeutic reperfusion strategies and improving patient outcomes. To that end, we developed a tissue-based microvascular fluidics model to better understand (i) microvascular stability and access-to-flow over an acute time course post-ischemia, and (ii) collateral flow in vessels neighboring an occlusion site. We utilized murine intestinal tissue regions by catheterizing a feeder artery and introducing perfusate at physiologically comparable flow-rates. The cannulated vessel as well as a portion of the downstream vessels and associated intestinal tissue were cultured while constant perfusion conditions were maintained. An occlusion was introduced in a selected arterial segment, and changes in perfusion within areas receiving varying degrees of collateral flow were observed over time. To observe the microvascular response to perfusion changes, we incorporated (i) tissues harboring cell-reporter constructs, specifically Ng2-DsRed labeling of intestinal pericytes, and (ii) different types of fluorescent perfusates to quantify capillary access-to-flow at discrete time points. In our model, we found that perfusion tracers could enter capillaries within regions downstream of an occlusion upon the initial introduction of perfusion, but at 24 h tissue perfusion was severely decreased. However, live/dead cell discrimination revealed that the tissue overall did not experience significant cell death, including that of microvascular pericytes, even after 48 h. Our findings suggest that altered flow conditions may rapidly initiate cellular responses that reduce capillary access-to-flow, even in the absence of cellular deterioration or hypoxia. Overall, this ex vivo tissue-based microfluidics model may serve as a platform upon which a variety of follow-on studies may be conducted. It will thus enhance our understanding of microvessel stability and access-to-flow during an occlusive event and the role of collateral flow during normal and disrupted perfusion.
Potential application of nanotechnology in the treatment, diagnosis, and prevention of schistosomiasis
Authors: Qadeer Abdul , Ullah Hanif , Sohail Muhammad , Safi Sher Zaman , Rahim Abdur , Saleh Tawfik A , Arbab Safia , Slama Petr , Horky Pavel
Published: December 2022

Schistosomiasis is one of the neglected tropical diseases that affect millions of people worldwide. Globally, it affects economically poor countries, typically due to a lack of proper sanitation systems, and poor hygiene conditions. Currently, no vaccine is available against schistosomiasis, and the preferred treatment is chemotherapy with the use of praziquantel. It is a common anti-schistosomal drug used against all known species ofSchistosoma. To date, current treatment primarily the drug praziquantel has not been effective in treatingSchistosomaspecies in their early stages. The drug of choice offers low bioavailability, water solubility, and fast metabolism. Globally drug resistance has been documented due to overuse of praziquantel, Parasite mutations, poor treatment compliance, co-infection with other strains of parasites, and overall parasitic load. The existing diagnostic methods have very little acceptability and are not readily applied for quick diagnosis. This review aims to summarize the use of nanotechnology in the treatment, diagnosis, and prevention. It also explored safe and effective substitute approaches against parasitosis. At this stage, various nanomaterials are being used in drug delivery systems, diagnostic kits, and vaccine production. Nanotechnology is one of the modern and innovative methods to treat and diagnose several human diseases, particularly those caused by parasite infections. Herein we highlight the current advancement and application of nanotechnological approaches regarding the treatment, diagnosis, and prevention of schistosomiasis.
Biomechanical comparison of pedicle screw fixation strength among three different screw trajectories using single vertebrae and one-level functional spinal unit
Authors: Tai Ching-Lung , Chen Weng-Pin , Liu Mu-Yi , Li Yun-Da , Tsai Tsung-Ting , Lai Po-Liang , Hsieh Ming-Kai
Published: December 2022

Three key factors are responsible for the biomechanical performance of pedicle screw fixation: screw mechanical characteristics, bone quality and insertion techniques. To the best of the authors’ knowledge, no study has directly compared the biomechanical performance among three trajectories, i.e., the traditional trajectory (TT), modified trajectory (MT) and cortical bone trajectory (CBT), in a porcine model. This study compared the pullout strength and insertion torque of three trajectory methods in single vertebrae, the pullout strength and fixation stiffness including flexion, extension, and lateral bending in a one-level instrumented functional spinal unit (FSU) that mimics the in vivo configuration were clarified. A total of 18 single vertebrae and 18 FSUs were randomly assigned into three screw insertion methods (n = 6 in each trajectory group). In the TT group, the screw converged from its entry point, passed completely inside the pedicle, was parallel to the superior endplate, was located in the superior third of the vertebral body and reached to at least the anterior third of the vertebral body. In the MT group, the convergent angle was similar to that of the TT method but directed caudally to the anterior inferior margin of the vertebral body. The results of insertion torque and pullout strength in single vertebrae were analyzed; in addition, the stiffness and pullout strength in the one-level FSU were also investigated. This study demonstrated that, in single vertebrae, the insertion torque was significantly higher in CBT groups than in TT and MT groups (p < 0.05). The maximal pullout strength was significantly higher in MT groups than in TT and CBT groups (p < 0.05). There was no significant difference in stiffness in the three motions among all groups. The maximal pullout strength in FSUs of MT and CBT groups were significantly higher than the TT groups (p < 0.05). We concluded that either MT or CBT provides better biomechanical performance than TT in single vertebrae or FSUs. The lack of significance of stiffness in FSUs among three methods suggested that MT or CBT could be a reasonable alternative to TT if the traditional trajectory was not feasible.
Chemical signaling in the developing avian retina: Focus on cyclic AMP and AKT-dependent pathways
Authors: Duarte-Silva A. T. , Ximenes L. G. R. , Guimarães-Souza M. , Domith I. , Paes-de-Carvalho R.
Published: December 2022

Communication between developing progenitor cells as well as differentiated neurons and glial cells in the nervous system is made through direct cell contacts and chemical signaling mediated by different molecules. Several of these substances are synthesized and released by developing cells and play roles since early stages of Central Nervous System development. The chicken retina is a very suitable model for neurochemical studies, including the study of regulation of signaling pathways during development. Among advantages of the model are its very well-known histogenesis, the presence of most neurotransmitter systems found in the brain and the possibility to make cultures of neurons and/or glial cells where many neurochemical functions develop in a similar way than in the intact embryonic tissue. In the chicken retina, some neurotransmitters or neuromodulators as dopamine, adenosine, and others are coupled to cyclic AMP production or adenylyl cyclase inhibition since early stages of development. Other substances as vitamin C and nitric oxide are linked to the major neurotransmitter glutamate and AKT metabolism. All these different systems regulate signaling pathways, including PKA, PKG, SRC, AKT and ERK, and the activation of the transcription factor CREB. Dopamine and adenosine stimulate cAMP accumulation in the chick embryo retina through activation of D1 and A2a receptors, respectively, but the onset of dopamine stimulation is much earlier than that of adenosine. However, adenosine can inhibit adenylyl cyclase and modulate dopamine-dependent cAMP increase since early developmental stages through A1 receptors. Dopamine stimulates different PKA as well as EPAC downstream pathways both in intact tissue and in culture as the CSK-SRC pathway modulating glutamate NMDA receptors as well as vitamin C release and CREB phosphorylation. By the other hand, glutamate modulates nitric oxide production and AKT activation in cultured retinal cells and this pathway controls neuronal survival in retina. Glutamate and adenosine stimulate the release of vitamin C and this vitamin regulates the transport of glutamate, activation of NMDA receptors and AKT phosphorylation in cultured retinal cells. In the present review we will focus on these reciprocal interactions between neurotransmitters or neuromodulators and different signaling pathways during retinal development.
Regulation, targets and functions of CHK
Authors: Zhu Shudong , Sun Rong , Guo Xialing , Bao Yuanwu , Zhang Dianzheng
Published: December 2022

Src family kinases (SFKs) play pivotal roles in multiple signaling pathways (Yeatman, 2004). SFK activity is inhibited by phosphorylation at its C-terminal tyrosine, by CSK (C-terminal Src kinase) and CHK (CSK-homologous kinase). CHK expression is restricted to normal hematopoietic cells, brain, and colon tissues. Downregulation of CHK in brain and colon tumors contributes to tumorigenicity in these tissues. CHK does not phosphorylate Src efficiently, however, in contrast to CSK, CHK inhibits Src kinase activity allosterically. Although the functions of CHK are still largely unknown, potential substrates of CHK including β-synuclein, α-tubulin, α-spectrin, 14-3-3, and Hsp90 have been identified. CHK is regulated epigenetically via promoter methylation. As the unknown roles of CHK are beginning to be revealed, current knowledge of regulation, molecular targets and functions of CHK is summarized, and important topics for future CHK research are discussed.
Reduced macula microvascular densities may be an early indicator for diabetic peripheral neuropathy
Authors: Deng Xiaoyu , Wang Shiqi , Yang Yan , Chen Aizhen , Lu Jinger , Hao Jinkui , Wu Yufei , Lu Qinkang
Published: December 2022

Purpose: To assess the alteration in the macular microvascular in type 2 diabetic patients with peripheral neuropathy (DPN) and without peripheral neuropathy (NDPN) by optical coherence tomography angiography (OCTA) and explore the correlation between retinal microvascular abnormalities and DPN disease.

Methods: Twenty-seven healthy controls (42 eyes), 36 NDPN patients (62 eyes), and 27 DPN patients (40 eyes) were included. OCTA was used to image the macula in the superficial vascular complex (SVC) and deep vascular complex (DVC). In addition, a state-of-the-art deep learning method was employed to quantify the microvasculature of the two capillary plexuses in all participants using vascular length density (VLD).

Results: Compared with the healthy control group, the average VLD values of patients with DPN in SVC (p = 0.010) and DVC (p = 0.011) were significantly lower. Compared with NDPN, DPN patients showed significantly reduced VLD values in the SVC (p = 0.006) and DVC (p = 0.001). Also, DPN patients showed lower VLD values (p < 0.05) in the nasal, superior, temporal and inferior sectors of the inner ring of the SVC when compared with controls; VLD values in NDPN patients were lower in the nasal section of the inner ring of SVC (p < 0.05) compared with healthy controls. VLD values in the DVC (AUC = 0.736, p < 0.001) of the DPN group showed a higher ability to discriminate microvascular damage when compared with NDPN.

Conclusion: OCTA based on deep learning could be potentially used in clinical practice as a new indicator in the early diagnosis of DM with and without DPN.
Molecular recognition at interfaces. Adhesion, wetting and bond scrambling
Authors: Ciferri Alberto
Published: December 2022

The quantitative description of the supramolecular interaction occurring at the adhesion surfaces of different polymers has enabled elaborate dissections of contributions to cohesive and surface energies. An alternative analysis is proposed here based on solubility parameters and binding constants that traditionally describe the weakest and relatively larger association energies in polymer blends. The article emphasizes a feature of supramolecular polymers that has not received adequate consideration: The dynamic bond scrambling that allows a most efficient molecular recognition over significant areas of synthetic and biological surfaces.
A comprehensive description of the TolC effect on the antimicrobial susceptibility profile in Enterobacter bugandensis
Authors: Li Bingyu , Zhang Ji , Li Xiaodong
Published: December 2022

Background

Enterobacter bugandensis is an emerging human pathogen in which multidrug resistant strains have been continuously isolated from various environments. Thus, this organism possesses the potential to pose challenges in human healthcare. However, the mechanisms, especially the efflux pumps, responsible for the multidrug resistance in E. bugandensis remain to be well elucidated.

Methods

The Enterobacter strain CMCC(B) 45301 was specifically identified using whole genome sequencing. The specific CMCC(B) 45301 homologues of the TolC dependent efflux-pump genes characterized in Escherichia coli were identified. The tolC deletion mutant in CMCC(B) 45301 was constructed and subjected to susceptibility tests using 26 different antimicrobial agents, along with the wild type strain. The synergistic effects combining the Bacillus crude extract (BCE) and several other TolC-affected compounds against CMCC(B) 45301 were assayed.

Results

We reclassified the Enterobacter CMCC(B) 45301 strain from species cloacae to bugandensis, on the basis of its whole genome sequence. We found that the CMCC(B) 45301 TolC, AcrAB, AcrD, AcrEF, MdtABC, EmrAB, and MacAB exhibit high similarity with their respective homologues in E. coli and Enterobacter cloacae. Our results for the susceptibility tests revealed that lacking tolC causes 4- to 256-fold decrease in the minimal inhibitory concentrations of piperacillin, gentamicin, kanamycin, tetracycline, norfloxacin, ciprofloxacin, chloramphenicol, and erythromycin against CMCC(B) 45301. In addition, the inhibition zones formed by cefuroxime, cefoperazone, amikacin, streptomycin, minocycline, doxycycline, levofloxacin, florfenicol, trimethoprim-sulfamethoxazole, azithromycin, lincomycin, and clindamycin for the tolC mutant were larger or more obvious than that for the parent. Our data suggested the important role played by TolC in CMCC(B) 45301 susceptibility to common antibiotic families covering ß-lactam, aminoglycoside, tetracycline, fluoroquinolone, phenicol, folate pathway antagonist, macrolide, and lincosamide. Deletion for tolC also increased the susceptibility of CMCC(B) 45301 to berberine hydrochloride and BCE, two natural product-based agents. Finally, we found that erythromycin, norfloxacin, and ciprofloxacin can potentiate the antibacterial activity of BCE against CMCC(B) 45301.

Discussion

The present study elaborated the comprehensive TolC effect on the antimicrobial susceptibility profile in E. bugandensis, which might contribute to the development of more therapeutic options against this nosocomial pathogen.
Advances in machine learning applications for cardiovascular 4D flow MRI
Authors: Peper Eva S. , van Ooij Pim , Jung Bernd , Huber Adrian , Gräni Christoph , Bastiaansen Jessica A. M.
Published: December 2022

Four-dimensional flow magnetic resonance imaging (MRI) has evolved as a non-invasive imaging technique to visualize and quantify blood flow in the heart and vessels. Hemodynamic parameters derived from 4D flow MRI, such as net flow and peak velocities, but also kinetic energy, turbulent kinetic energy, viscous energy loss, and wall shear stress have shown to be of diagnostic relevance for cardiovascular diseases. 4D flow MRI, however, has several limitations. Its long acquisition times and its limited spatio-temporal resolutions lead to inaccuracies in velocity measurements in small and low-flow vessels and near the vessel wall. Additionally, 4D flow MRI requires long post-processing times, since inaccuracies due to the measurement process need to be corrected for and parameter quantification requires 2D and 3D contour drawing. Several machine learning (ML) techniques have been proposed to overcome these limitations. Existing scan acceleration methods have been extended using ML for image reconstruction and ML based super-resolution methods have been used to assimilate high-resolution computational fluid dynamic simulations and 4D flow MRI, which leads to more realistic velocity results. ML efforts have also focused on the automation of other post-processing steps, by learning phase corrections and anti-aliasing. To automate contour drawing and 3D segmentation, networks such as the U-Net have been widely applied. This review summarizes the latest ML advances in 4D flow MRI with a focus on technical aspects and applications. It is divided into the current status of fast and accurate 4D flow MRI data generation, ML based post-processing tools for phase correction and vessel delineation and the statistical evaluation of blood flow.
Surgical treatment of chronic thromboembolic pulmonary hypertension in combination with a left anterior descending artery myocardial bridge: A case report
Authors: Zugurov Ilkhom K. , Osadchii Aleksei M. , Simakova Maria A. , Moiseeva Olga M. , Gordeev Mikhail L.
Published: December 2022

Pulmonary thromboendarterectomy is a potentially curative option for most patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, a special group of patients with CTEPH requires simultaneous cardiac procedures. We report a rare case of successful surgical treatment of a CTEPH patient with a left anterior descending artery myocardial bridge. Despite the complexity of performing pulmonary thromboendarterectomy (PTE), the issue concerning the method of revascularization of the artery in the case of the left anterior descending artery myocardial bridge is controversial. PTE and supracoronary myotomy were performed. In our case, the optimal surgery method for the left anterior descending artery myocardial bridge was chosen intraoperatively based on the depth and length of the myocardial bridge. The patient's significant functional improvement after surgery and hemodynamic normalization were confirmed at the follow-up assessment. This case demonstrates rare but potentially dangerous pathologies that can be treated with minimal adverse effects.
Case report: Rescue treatment with add-on selexipag in a preterm infant with suprasystemic pulmonary hypertension, pulmonary capillary hemangiomatosis, and isolated pulmonary vein stenosis
Authors: Hasan Hosan , Hysko Klea , Jack Thomas , Dingemann Jens , Wetzke Martin , Hansmann Georg
Published: December 2022

An extremely dystrophic, premature female infant, born at 25 3/7 weeks of gestational age (birth weight: 430 g) with severe pulmonary hypertension (PH), was admitted to our neonatal intensive care unit (ICU) requiring cardiorespiratory support, including mechanical ventilation and pulmonary vasodilators such as inhaled nitric oxide (iNO) and continuous intravenous sildenafil infusions. The diagnosis of bronchopulmonary dysplasia (BPD) was made. A hemodynamically relevant, persistent ductus arteriosus (PDA) was surgically ligated after failed pharmacologic PDA closure using indomethacin and ibuprofen. The patient was discharged with an estimated 2/3 systemic pulmonary artery pressure. One month after hospital discharge, on low-flow oxygen supplementation (0.5 L/min FiO2 100%), at the corrected age of 16 weeks, she was readmitted to our emergency department with signs of respiratory distress and circulatory decompensation. Echocardiography demonstrated suprasystemic PH. Severe PH persisted despite initiated invasive mechanical ventilation, triple vasodilating therapy [iNO, macitentan, and continuous intravenous (IV) sildenafil], as well as levosimendan, milrinone, and norepinephrine for recompensation from cardiac shock. Thus, we started off-label oral selexipag therapy (oral IP receptor agonist) in the smallest patient reported so far (4 kg body weight). Subsequently, RV systolic pressure decreased to half-systemic, allowing successful weaning of iNO, norepinephrine, and milrinone, and extubation of the patient over 4 days. The infant was discharged 4 weeks after pediatric intensive care unit (PICU) admission in stable cardiorespiratory condition, with an oral, specific, triple antihypertensive PAH-targeted therapy using selexipag, macitentan, and sildenafil as well as oxygen therapy at low-flow (0.5 l/min) and spironolactone. The first cardiac catheterization at the age of 9 months under aforementioned triple PAH-targeted therapy revealed mild PH with 35% systemic PA pressure (mPAP/mSAP = 0.35) and isolated pulmonary vein stenosis. A transthoracic biopsy at the age of 12 months confirmed the diagnosis of BPD and further showed pulmonary interstitial glycogenosis and severe pulmonary capillary hemangiomatosis, without involvement of the pulmonary venules (chILD A2, A3, and B4 according to the Deutsch-Classification). The patient is currently in stable cardiorespiratory condition undergoing triple PH-targeted therapy including selexipag. This report highlights the potential benefits of the oral prostacyclin mimetic selexipag as an early add-on PH-targeted drug in chronic PH of infancy (cPHi).
A new platform for post-marketing surveillance and real-world evidence data collection for substance-based medical devices
Authors: Cioeta Roberto , Cossu Andrea , Giovagnoni Emiliano , Rigoni Marta , Muti Paola
Published: December 2022

The recent passage of European Union (EU) Regulation 2017/745 on medical devices (MDs) has improved the classification of MDs and revised their approval process and the post-marketing evaluation of their safety and effectiveness, promoting transparency and post-marketing oversight in Europe. This new regulation can better ensure patient safety and provide new opportunities for therapeutic innovation. In addition, the new regulations include and define MDs made of substances or of combinations of substances (substance-based MDs: SBMDs). The impressive growth of the MD, including SBMDs, that have been marketed over the recent years has likely been a relevant factor fueling this change. MD regulation requires a major effort from both industry and regulatory bodies to comply with its provisions. Manufacturers should produce sufficient clinical evidence that an MD, under normal conditions of use, provides adequate performance and that the foreseeable risks and frequency of adverse events (AEs) have an acceptable minimum rate, taking into account the benefits provided. We describe how we implemented the post-marketing surveillance (PMS) system of SBMDs to properly deal with post-market monitoring and confirmation of safety and performance, including AEs and the benefit–risk evaluation, as required by the 2017/745 Regulation. The two pillars of this novel system are: 1) passive vigilance, i.e., spontaneous reporting and 2) active post-marketing clinical follow-up (PMCF) activities, which systematically gather, record, and analyze real-world data (RWD) on performance, quality, function, use, tolerability, and safety of an MD, collected through a dedicated, structured web platform. Active PMCF is achieved through a process of generation, validation, and administration of digital questionnaires to all stakeholders, i.e., patients, physicians, both general practitioners and specialists, and pharmacists. The technology, potential use, advantages, and limitations of this large source of RWD are also discussed.
Large-scale structures in the Earth’s interior: Top-down hemispherical dynamics constrained by geochemical and geophysical approaches
Authors: Iwamori Hikaru , Yoshida Masaki , Nakamura Hitomi
Published: December 2022

Geochemical and geophysical observations for large-scale structures in the Earth’s interior, particularly horizontal variations of long wavelengths such as degree-1 and degree-2 structures, are reviewed with special attention to the cause of hemispherical mantle structure. Seismic velocity, electrical conductivity, and basalt geochemistry are used for mapping the large-scale structures to discuss thermal and compositional heterogeneities and their relations to dynamics of the Earth’s interior. Seismic velocity structure is the major source of information on the Earth’s interior and provides the best spatial resolution, while electrical conductivity is sensitive to water/hydrogen contents. The composition of young basalts reflects the mantle composition, and the formation age of large-scale structures can be inferred based on the radiogenic isotopes. Thus, these different research disciplines and methods complement each other and can be combined to more concretely constrain the structures and their origins. This paper aims to integrate observations from these different approaches to obtain a better understanding of geodynamics. Together with numerical modeling results of convection in the mantle and the core, “top-down hemispherical dynamics” model of the crust-mantle-core system is examined. The results suggest that a top-down link between the supercontinents, mantle geochemical hemisphere, and inner core seismic velocity hemisphere played an essential role in formation of the large-scale structures and dynamics of the Earth’s interior.
A visualized dynamic prediction model for survival of patients with geriatric thyroid cancer: A population-based study
Authors: Zhang Ting-ting , Zeng Jing , Yang Yan , Wang Jin-jing , Kang Yao-jie , Zhang Dong-he , Liu Xiao-zhu , Chen Kang , Wang Xuan , Fang Yi
Published: December 2022

Objective

Thyroid cancer (TC) is a common malignancy with a poor prognosis with aging. However, no accurate predictive survival model exists for patients with geriatric TC.We aimed to establish prediction models of prognosis in elderly TC.

Methods

We retrospectively reviewed the clinicopathology characteristics of patients with geriatric TC in the Surveillance, Epidemiology, and End Results database (SEER) from 2004 to 2018. The risk predictors used to build the nomograms were derived from the Cox proportional risk regression. These nomograms were used to predict 1-, 3-, and 5-year overall survival and cancer-specific survival in elderly patients with TC. The accuracy and discriminability of the new model were evaluated by the consistency index (C-index) and calibration curve. The clinical applicability value of the model was assessed using the decision curve analysis.

Results

We used the SEER database to include 16475 patients with geriatric TC diagnosed from 2004 to 2018. The patients from 2004 to 2015 were randomly sorted out on a scale of 7:3. They were classified into a training group (n = 8623) and a validation group (n = 3669). Patients with TC diagnosed in 2016–2018 were classified into external validation groups (n = 4183). The overall survival nomogram consisted of 10 variables (age, gender, marital status, histologic type, grade, TNM stage, surgery status, and tumor size). A cancer-specific survival nomogram consisted of eight factors (age, tumor size, grade, histologic type, surgery, and TNM stage). The C-index values for the training, validation, and external validation groups were 0.775 (95% confidence interval [CI] 0.785–0.765), 0.776 (95% CI 0.792–0.760), and 0.895(95% CI 0.873–0.917), respectively. The overall survival was consistent with a nomogram based on the calibration curve. Besides, the decision curve analysis showed excellent clinical application value of the nomogram. Additionally, we found that surgery could improve the prognosis of patients with geriatric at high-risk (P < 0.001) but not those at low-risk (P = 0.069).

Conclusion

This was the first study to construct predictive survival nomograms for patients with geriatric TC. The well-established nomograms and the actual results could guide follow-up management strategies.
Semaglutide ameliorates metabolism and hepatic outcomes in an NAFLD mouse model
Authors: Niu Shu , Chen Shuchun , Chen Xing , Ren Qingjuan , Yue Lin , Pan Xiaoyu , Zhao Huiying , Li Zelin , Chen Xiaoyi
Published: December 2022

Purpose

The aim of this study was to evaluate changes in body weight, liver weight, blood glucose, liver injury markers, pro-inflammatory factors and oxidative stress marker levels in obese mice with HFD induced NAFLD after semaglutide use.

Patients and methods

The 24 C57BL6J mice were randomly divided into three groups (NCD, HFD and Sema) for the assessment of metabolic status, inflammatory factor and oxidative stress marker levels, liver histopathology in mice. Liver metabolomics was determined by liquid chromatography/mass spectrometry (LC-MS) method.

Results

The mice body weight, liver weight, blood glucose, TG, TCHO, LDL and pro-inflammatory factors were significantly reduced after semaglutide. Meanwhile, semaglutide increased the SOD level. Semaglutide treatment significantly improved the pathological changes such as hepatocyte steatosis, balloon degeneration and lymphoid foci by HE. It also significantly reduced lipid droplet by Oil Red O. The mitochondria were swollen, the volume increased, the cristae were partially broken and reduced, the intramembrane matrix was partially dissolved, and the mitophagy structure was visible in the visual field. There were 6 metabolites down-regulated and 2 metabolites significantly up-regulated after semaglutide treatment.

Conclusions

Semaglutide can reduce blood glucose level and liver fat accumulation and play an anti-inflammatory role in advanced NAFLD that due to the effects of HFD.
No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization
Authors: Xu Jiawen , Ma Jun , Chen Jialei , Zhang Shaoyun , Zheng Che , Si Haibo , Wu Yuangang , Liu Yuan , Li Mingyang , Wu Limin , Shen Bin
Published: December 2022

Objective

To explore the genetic causal association between osteoporosis (OP) and iron status through Mendelian randomization (MR).

Methods

Publicly available genome-wide association study (GWAS) summary data were used for MR analysis with four iron status-related indicators (ferritin, iron, total iron binding capacity, and transferrin saturation) as exposures and three different types of OP (OP, OP with pathological fracture, and postmenopausal OP with pathological fracture) as outcomes. The inverse-variance weighted (IVW) method was used to analyze the genetic causal association between the four indicators of iron status and OP. The heterogeneity of MR results was determined using IVW and MR–Egger methods. The pleiotropy of MR results was determined using MR–Egger regression. A leave-one-SNP-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism (SNP). The weighted median method was conducted to further validate our results.

Results

Based on IVW, MR–Egger and weighted median models, we found no causal association between iron status (ferritin, iron, total iron binding capacity, or transferrin saturation) and OP (Pbeta > 0.05 in all models). IVW and MR–Egger analysis of OP with pathological fracture and iron status indicators showed no potential genetic causal association (Pbeta> 0.05 in the two analyses). The results of the weighted median were consistent with those of IVW (Pbeta> 0.05 in all analyses). There was no potential genetic causal association between iron status and postmenopausal OP with pathological fracture based on serum iron (Pbeta>0.05 in all models). No heterogeneity or horizontal pleiotropy was found in any of the analyses. None of the leave-one-out tests in the analyses found any SNP that could affect the results of MR.

Conclusion

Our results demonstrate that there is no genetic causal association between OP and iron status, but the effects of other factors were not excluded.
A study of the nonlinear dynamic interrelationship between CO2 emissions and logistics sector output growth
Authors: Wu Jinshun
Published: December 2022

Using provincial panel data spanning from 1995 to 2020, this paper examines the nonlinear interrelationship between logistics carbon dioxide emissions and output growth. For this purpose, we conduct a nonlinear co-integration test in heterogeneous panels; our results suggests a long-run relationship between these two variables. In contrast, adjustment to the equilibrium is inherently nonlinear. Furthermore, we estimate a panel smooth transition vector error correction model. Our major contributions, as we know, are the first study confirming the existence of a dynamic mechanism between logistics carbon dioxide emissions and regional output growth and the Environmental Kuznets Curve in China. Last, the interaction between logistics carbon dioxide emissions and regional output growth varies over the output growth in Chinese provinces and autonomous regions. Our results highlight the importance of considering possible nonlinearities in analyzing output-carbon dioxide emissions causality nexus and designing energy policies.
Analysis of infiltrated immune cells in left atriums from patients with atrial fibrillation and identification of circRNA biomarkers for postoperative atrial fibrillation
Authors: Chen Yubin , Ouyang Tianyu , Yin Yue , Fang Cheng , Tang Can-E , Luo Jingmin , Luo Fanyan
Published: December 2022

Background: Atrial fibrillation (AF) increases the risk of stroke and heart failure. Postoperative AF (POAF) increases the risk of mortality after cardiac surgery. This study aims to explore mechanisms underlying AF, analyze infiltration of immune cells in left atrium (LA) from patients with AF, and identify potential circular RNA (circRNA) biomarkers for POAF.

Methods: Raw data of GSE797689, GSE115574, and GSE97455 were downloaded and processed. AF-related gene co-expression network was constructed using weighted gene correlation network analysis and enrichment analysis of genes in relevant module was conducted. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were applied to investigate pathways significantly enriched in AF group. Infiltration of immune cells was analyzed using single-sample GSEA. Differentially expressed genes (DEGs) between patients with or without AF were identified and competing endogenous RNA (ceRNA) networks of DEGs were constructed. To screen biomarkers for POAF, differentially expressed circRNAs (DEcircRNAs) between patients with or without POAF were identified. Intersection between DEcircRNAs and circRNAs in ceRNA networks of DEGs were extracted and circRNAs in the intersection were further screened using support vector machine, random forest, and neural network to identify biomarkers for POAF.

Results: Three modules were found to be relevant with AF and enrichment analysis indicated that genes in these modules were enriched in synthesis of extracellular matrix and inflammatory response. The results of GSEA and GSVA suggested that inflammatory response-related pathways were significantly enriched in AF group. Immune cells like macrophages, mast cells, and neutrophils were significantly infiltrated in LA tissues from patients with AF. The expression levels of immune genes such as CHGB, HLA-DRA, LYZ, IGKV1-17 and TYROBP were significantly upregulated in patients with AF, which were correlated with infiltration of immune cells. ceRNA networks of DEGs were constructed and has_circ_0006314 and hsa_circ_0055387 were found to have potential predictive values for POAF.

Conclusion: Synthesis of extracellular matrix and inflammatory response were main processes involved in development and progression of AF. Infiltration of immune cells was significantly different between patients with or without AF. Has_circ_0006314 and hsa_circ_0055387 were found to have potential predictive values for POAF.
Pan-cancer and single-cell analysis reveals FAM83D expression as a cancer prognostic biomarker
Authors: Yu Haiyang , Chen Qinhao , Wang Ziming , Qian Xiaojun , Pan Yueyin
Published: December 2022

Background: The family with sequence similarity 83 member D (FAM83D) protein is known to play a significant role in many human diseases. However, its role in cancer remains ambiguous. This study aimed to investigate the function of FAM83D in a pan-cancer analysis, with a special focus on breast cancer.

Methods: Samples were collected from The Cancer Genome Atlas (TCGA) and used for bioinformatic analysis. Datasets from the Gene Expression Omnibus (GEO) and Genotype-Tissue Expression (GTEx) databases were also analyzed for verification. The potential value of FAM83D as a prognostic and diagnostic biomarker was visualized through R software. The “survival” and “GSVA” package were used for univariate, multivariate and pathway enrichment analyseis. We further analyzed the CancerSEA databases and TISIDB websites for single-cell and immune-related profiling. Lastly, we validated those data in vitro using quantitative reverse transcriptase-polymerase chain reaction (RT‒qPCR), cell counting kit-8 (CCK-8), transwell, flow cytometry, and tumorigenicity assays in a murine cell line model.

Results: The expression of FAM83D in tumor samples was significantly higher than in normal tissues for most cancer types in the datasets. We confirmed this finding using RT‒qPCR in a breast cancer cell line. Analysis of multiple datasets suggests that overall survival (OS) was extremely poor for breast cancer patients with high FAM83D expression. The CCK-8 assay demonstrated that MCF-7 cell proliferation was inhibited after genetic silencing of FAM83D. Transwell assay showed that knockdown of FAM83D significantly inhibited the invasion and migration ability of MCF-7 cells compared to the control. The results of flow cytometry showed that silencing FAM83D could block the G1 phase of MCF-7 cells compared with negative groups. The tumorigenicity assay in nude mice indicated that the tumorigenic ability to silence FAM83D decreased compared.

Conclusion: Results suggest that FAM83D expression can serve as a valuable biomarker and core gene across cancer types. Furthermore, FAM83D expression is significantly associated with MCF-7 cell proliferation and thus may be a prospective prognostic biomarker especially for breast cancer.
Trends in forced displacement due to conflict from 2009 to 2021: A decade forecast for effective humanitarian emergency response system in Nigeria
Authors: Izuakor Chidubem Fidelis
Published: December 2022

Internal displacement figures in conflicted affected regions of Nigeria is a significant problem that poses a risk of humanitarian crises accounted for by poor and a neglected emergency response system. The present study analyzed annual conflict/violence-induced internal displacement trends in Nigeria from 2009 to 2021 and predicted the annual figures for the next 10 years. Using the R software, the Autoregressive Integrated Moving Average (ARIMA) was adopted for analysis, while model (0, 0, 1) was chosen as the best fitting model with the minimum AIC coefficient. From the ARIMA forecast, 2022 showed a 4% decrease in displacement figures, further decreasing by 7% in 2023. The figures remained constant for the rest of the forecasted years, showing neither increases nor decreases from 2024 to 2031. Close observation revealed the overlapping trends between increased annual internal displacements and pre-election periods in Nigeria. This study will help inform humanitarian bodies on the significance of early detection and preparation for future displacement crises while considering the cycle of ethno-religious-related electoral violence. Furthermore, future studies should compare the accuracy of ARIMA with other models to ensure its validity using a similar sample.
Residual tumor model in esophageal squamous cell carcinoma after neoadjuvant immunochemotherapy: Frequently involves the mucosa and/or submucosa
Authors: Gao Lei , Hong Zhi-Nuan , Wu Long , Yang Yinghong , Kang Mingqiang
Published: December 2022

Objectives

The efficacy and safety of neoadjuvant immunochemotherapy (nICT) are widely explored in locally advanced esophageal squamous cell carcinoma (ESCC). Whether the “wait-and-see” strategy is applicable in ESCC after nICT is still lacking a theoretical basis. This study aimed to preliminarily explore the distribution of residual tumors and the regression pattern of ESCC after nICT.

Methods

Patients undergoing radical esophagectomy after nICT in Fujian Medical University Union Hospital between January 2020 and March 2022 were identified. The resection specimens were re-evaluated by one experienced pathologist. The pathological response was assessed by tumor regression grade (TRG) (modified Ryan scheme). The TRG grade was divided into grades 0 (pathological complete response), 1, 2, and 3. The pathological stage was evaluated in the Eighth Edition AJCC. In the non-pCR group, the residual model was divided into four types: Type I, regression towards the lumen; type II, regression towards the invasive front; type III, concentric regression; and type IV, scattered regression.

Results

A total of 95 consecutive patients were included for analysis. Seventy-six (80.0%) of 95 patients were in non-pCR (pathological complete response), and nine patients (9/76, 11.84%) had isolated residual tumors in lymph nodes. There was no significant difference in baseline characteristics between the pCR group and the non-pCR group (p > 0.05). The overall distribution of TRG for all esophageal wall layers was TRG 0 = 28 (28/95, 29.5%), TRG 1 = 17 (17/95, 17.9%), TRG 2 = 18 (18.9%, 18/95), and TRG 3 = 32 (32/95, 33.7%). In 67 patients with residual tumors in the esophageal wall (TRG ≧1), 63 (63/67, 94.0%) had residual tumor cells in the mucosa and/or submucosa, and four had isolated residual tumors in the muscle layer (4/67, 6.0%). Further analysis showed eight (8/67, 11.9%) patients with submucosal involvement but without mucosal involvement. The distribution of regression patterns was type I (n = 35, 52.2%), type II (n = 3, 4.5%), type III (n = 8, 11.9%), and type IV (n = 21, 31.3%).

Conclusions

The mucosa and/or submucosa are frequently involved in residual malignancy, and the frequent regression models are regression toward the lumen and random regression. There is an opportunity to carefully test the residual tumors in a subgroup of the population with ESCC following nICT. However, some patients had residual tumors only in the muscle layer or lymph nodes. The clinical application of the wait-and-see strategy in ESCC after nICT should be explored using an appropriate evaluation protocol.
Longitudinal serum proteomics analyses identify unique and overlapping host response pathways in Lyme disease and West Nile virus infection
Authors: Boada Patrick , Fatou Benoit , Belperron Alexia A. , Sigdel Tara K. , Smolen Kinga K. , Wurie Zainab , Levy Ofer , Ronca Shannon E. , Murray Kristy O. , Liberto Juliane M. , Rashmi Priyanka , Kerwin Maggie , Montgomery Ruth R. , Bockenstedt Linda K. , Steen Hanno , Sarwal Minnie M.
Published: December 2022

Advancement in proteomics methods for interrogating biological samples has helped identify disease biomarkers for early diagnostics and unravel underlying molecular mechanisms of disease. Herein, we examined the serum proteomes of 23 study participants presenting with one of two common arthropod-borne infections: Lyme disease (LD), an extracellular bacterial infection or West Nile virus infection (WNV), an intracellular viral infection. The LC/MS based serum proteomes of samples collected at the time of diagnosis and during convalescence were assessed using a depletion-based high-throughput shotgun proteomics (dHSP) pipeline as well as a non-depleting blotting-based low-throughput platform (MStern). The LC/MS integrated analyses identified host proteome responses in the acute and recovery phases shared by LD and WNV infections, as well as differentially abundant proteins that were unique to each infection. Notably, we also detected proteins that distinguished localized from disseminated LD and asymptomatic from symptomatic WNV infection. The proteins detected in both diseases with the dHSP pipeline identified unique and overlapping proteins detected with the non-depleting MStern platform, supporting the utility of both detection methods. Machine learning confirmed the use of the serum proteome to distinguish the infection from healthy control sera but could not develop discriminatory models between LD and WNV at current sample numbers. Our study is the first to compare the serum proteomes in two arthropod-borne infections and highlights the similarities in host responses even though the pathogens and the vectors themselves are different.