bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of embryo injected with ochratoxins A on hatching quality and jejunum antioxidant capacity of ducks at hatching
Authors: Liu Jinhui , Jiang Xiayu , Peng Xin , Yuan Yihan , Shen Yu , Li Yongxia , Yan Zixing , Yuan Xi , Yang Ye , Zhai Shuangshuang
Published: August 2022

Numerous studies have shown that ochratoxins A (OTA) exerts diverse toxicological effects, namely, hepatotoxicity, nephrotoxicity, genotoxicity, enterotoxicity, and immunotoxicity. The main objective of this study was to investigate the influence of embryonic exposure to OTA by different injection times and OTA doses on hatching quality and jejunal antioxidant capacity of ducks at hatching. In total, 480 fertilized eggs were weighed and randomly assigned into a 4 × 4 factorial design including four OTA doses (0, 2, 4, and 8 ng/g egg) on 8, 13, 18, and 23 of embryonic development (E8, E13, E18, and E23). Each treatment included 6 repeats with 5 eggs per repeat. The results showed that the injection time affected the hatching weight (P < 0.0001). The relative length of the jejunum and ileum on E18 and E23 was lower than on E8 and E13 (P < 0.05). Injection time, doses, and their interaction had no effect on jejunum morphology, namely, villous height (Vh), crypt depth (Cd), and villous height/crypt depth ratio Vh/Cd (P > 0.05). The injection time affected the activities of Superoxide dismutase (SOD) (P < 0.0001), total antioxidant capacity (T-AOC) (P < 0.05) and the malondialdehyde (MDA) content (P < 0.0001). The activity of SOD and T-AOC activities in the jejunum of ducklings injected with OTA at the E8 and E13 was lower than that injected at the E18 (P < 0.05). The highest MDA content was observed in ducklings injected with OTA at the E13 (P < 0.05). The injection time (P < 0.0001), OTA doses and their interaction affected the contents of IL-1β (P < 0.05), which significantly increased especially on E13. In conclusion, the embryo injected with ochratoxins A affected the hatching weight, the relative length of jejunum and ileum, decreased the antioxidant capacity and increased the content of proinflammatory cytokine IL-1β of the jejunum.
Genetic features of bovine viral diarrhea virus subgenotype 1c in newborn calves at nucleotide and synonymous codon usages
Authors: Wang Huihui , Wang Mengzhu , Feng Xili , Li Yicong , Zhang Derong , Cheng Yan , Liu Junlin , Wang Xiezhong , Zhang Licheng , La Hua , You Xiaoqian , Ma Zhongren , Zhou Jianhua
Published: August 2022

Bovine viral diarrhea virus (BVDV), serving as an important pathogen for newborn calves, poses threat to reproductive and economic losses in the cattle industry. To survey the infection rate and genetic diversity of BVDV in newborn calves in northern China, a total of 676 sera samples of newborn calves were collected from four provinces between 2021 and 2022. All sera samples were individually detected for BVDV infection by RT-PCR and ELISA. Our results showed that the overall serological rate was 9.76% (66/676) and the average positive rate of BVDV RNA was 8.14% (55/676) in the newborn calves. Eight BVDV strains were successfully isolated from RT-PCR positive sera samples, and four isolates displayed the cytopathic effect (CPE). Based on phylogenetic tree at the genome level, the eight strains were classified into subgenotype 1c. Moreover, the BVDV isolates had a close genetic relationship with the GSTZ strain at either nucleotide or codon usage level. Interestingly, in comparison of synonymous codon usage patterns between the BVDV isolates with CPE and ones without CPE, there were four synonymous codons (UCG, CCC, GCA, and AAC) which displayed the significant differences (p < 0.05) at codon usage pattern, suggesting that synonymous codon usage bias might play a role in BVDV-1c biotypes. In addition, the usage of synonymous codons containing CpG dinucleotides was suppressed by the BVDV-1c isolates, reflecting one of strategies of immune evasion of BVDV to its host. Taken together, our study provided data for monitoring and vaccination strategies of BVDV for newborn calves in northern China.
Conservation of Resources, Psychological Distress, and Resilience During the COVID-19 Pandemic
Authors: Egozi Farkash Hadas , Lahad Mooli , Hobfoll Stevan E. , Leykin Dima , Aharonson-Daniel Limor
Published: August 2022

Objectives: The Conservation of Resources (COR) theory suggests that stress results from threatened or actual loss of resources following significant life events. This study used COR theory as the framework to explore the reflection of loss of resources during the COVID-19 pandemic on psychological distress and resilience, in an adult Jewish Israeli population.

Methods: We examined the association between background variables, stress, loneliness, concern, COVID-19-related post traumatic symptoms (PTS), resilience factors and COR via an online survey among 2,000 adults during April 2020.

Results: Positive relationships were identified between resource loss and PTS (r = 0.66, p < 0.01), and between resource gain and resilience (r = 0.30, p < 0.01). Psychological variables were significantly associated with PTS and explained 62.7% of the variance, F (20, 1,413) = 118.58, p < 0.001.

Conclusion: Loss of resources, stress, loneliness and concern were found to be risk factors for distress and PTS, whereas resilience factors played a protective role. We thus recommend using the COR theory to explore COVID-19 effects elsewhere.
From Public Health Policy to Impact for COVID-19: A Multi-Country Case Study in Switzerland, Spain, Iran and Pakistan
Authors: Tavakkoli Maryam , Karim Aliya , Fischer Fabienne Beatrice , Monzon Llamas Laura , Raoofi Azam , Zafar Shamsa , Sant Fruchtman Carmen , de Savigny Don , Takian Amirhossein , Antillon Marina , Cobos Muñoz Daniel
Published: August 2022

Objectives: With the application of a systems thinking lens, we aimed to assess the national COVID-19 response across health systems components in Switzerland, Spain, Iran, and Pakistan.

Methods: We conducted four case studies on the policy response of national health systems to the early phase of the COVID-19 pandemic. Selected countries include different health system typologies. We collected data prospectively for the period of January–July 2020 on 17 measures of the COVID-19 response recommended by the WHO that encompassed all health systems domains (governance, financing, health workforce, information, medicine and technology and service delivery). We further monitored contextual factors influencing their adoption or deployment.

Results: The policies enacted coincided with a decrease in the COVID-19 transmission. However, there was inadequate communication and a perception that the measures were adverse to the economy, weakening political support for their continuation and leading to a rapid resurgence in transmission.

Conclusion: Social pressure, religious beliefs, governance structure and level of administrative decentralization or global economic sanctions played a major role in how countries’ health systems could respond to the pandemic.
The Impact of Listening to, Reciting, or Memorizing the Quran on Physical and Mental Health of Muslims: Evidence From Systematic Review
Authors: Che Wan Mohd Rozali Wan Nor Atikah , Ishak Ismarulyusda , Mat Ludin Arimi Fitri , Ibrahim Farah Wahida , Abd Warif Nor Malia , Che Roos Nur Aishah
Published: August 2022

Objectives: Listening to or memorizing the Quran has been suggested to affect the psychosocial health and well-being of Muslims. Muslims who memorized Quran have a higher quality of life (QoL) and lower anxiety and stress. Hence, this systematic review was conducted to evaluate the studies that assessed the effect of listening to, reciting, or memorizing the Quran on physical and mental health.

Methods: This review was performed on articles published from the inception and April 2021. Databases including ProQuest, PubMed and Web of Science were searched on 19 April 2021. Keywords such as “Quran”, “al- Quran,” “al- Kareem,” “Holy Quran,” “memori,” “Tahfiz,” “Huffaz,” “listening” and “reciting” were used for databases searching. The risk of bias was assessed using Cochrane risk of bias tool and Joanna Briggs Institute (JBI). Only 20 articles were included in data synthesis out of a total of 230.

Results: The findings revealed that listening to, reciting or memorizing the Quran had a favorable effect on depression, anxiety, physiologic parameters, quality of life, quality of sleep and intelligence quotient.

Conclusion: The current evidence suggests that, listening to, reciting or memorizing the Quran may be useful as an intervention to improve physical and mental health.
On the Aeroelasticity of the Active Span and Passive Pitching Polymorphing Wing: A Parametric Study
Authors: Haider Zawar , Ajaj Rafic M. , Seneviratne Lakmal
Published: August 2022

This paper presents an aeroelastic analysis of a polymorphing wing capable of active span extension and passive pitch variation. The wing is split into two segments: an inboard segment responsible for span extension/retraction and an outboard segment capable of pitch variation. The two segments are connected through an overlapping spar and a torsional spring. A finite element aeroelastic model is developed where the wing structure is discretized into Euler–Bernoulli beam elements and the aerodynamic loads are calculated using Theodorsen’s unsteady model. A comprehensive parametric analysis is carried out with and without span extension to analyze the effect of varying critical design parameters, such as elastic axis position of outboard section and torsional spring rigidity, and conditions for aeroelastic phenomena of flutter and divergence are studied. A gust load analysis is carried out to quantify the capability of the outboard wing passive twist mechanism to alleviate loads. Finally, a nonlinear analysis is carried out by replacing the linear torsional spring with a nonlinear cubic spring to study the effects of cubic hardening and softening on the aeroelasticity of the polymorphing wing.
Regional and Seasonal Dependence of the Potential Contrail Cover and the Potential Contrail Cirrus Cover over Europe
Authors: Dischl Rebecca , Kaufmann Stefan , Voigt Christiane
Published: August 2022

Ambient weather conditions strongly impact contrail formation and persistence. The implementation of contrail avoidance and mitigation strategies, therefore, requires regional and altitude-dependent information on the frequency of contrail occurrence. To this end, we have developed a method to quantify the potential contrail cover based on 10 years of high-resolution reanalysis of climatology and weather data from the European Center for Medium-Range Weather Forecast (ECMWF). We use the Schmidt–Appleman threshold temperature for contrail formation and additionally select thresholds for the relative humidity to evaluate the occurrence of persistent contrails and assess their regional and seasonal variation. We find a potential contrail cirrus cover of 10% to 20% above Europe at higher altitudes of 200 and 250 hPa in the 10-year climatology and a weak seasonal variation. At lower altitudes, near 300 hPa, a steep onset and a high potential contrail cirrus cover of 20% is found in late fall and in winter, decreasing to 2% potential contrail cirrus cover in summer. In comparison to ECMWF data, evaluations using data from the National Centers for Environmental Prediction (NCEP) show a significantly lower potential contrail cirrus cover. Our results help to investigate the seasonal and altitude dependence of contrail mitigation strategies, in particular for warming nighttime contrails that contribute strongly to the total climate impact from aviation.
Development of a Swine Production Cost Calculation Model
Authors: Alves Laya Kannan Silva , Gameiro Augusto Hauber , Schinckel Allan Paul , Garbossa Cesar Augusto Pospissil
Published: August 2022

This paper aims to present a tool that offers pig producers a standard method to calculate and control their production costs and, consequently, provides the necessary information to guide strategic decision-making. Following these premises, a mathematical model to estimate swine production costs were developed using Microsoft Excel® software (version 2207). Case studies were used to assist in the characterization and construction of the model. Through the panel method, the tool was validated by professionals in the sector. Costs were considered according to the Neoclassical Economic Theory of Costs and allocated in the order of variable costs, fixed operating costs, and opportunity costs of capital and land. These costs together create the total cost. The model provides the total cost per batch, per market pig, per arroba, and per kilogram, which facilitates the interpretation of the results and economic evaluations of the system. The model is adaptable to different types of swine farming, as well as the consideration of all costs involved in the production system, whether explicit or implicit. The model developed has the potential to be used as a management tool in commercial swine production systems, assisting the producer in the decision-making process through the management and control of production costs.
Prostacyclin Synthesis and Prostacyclin Receptor Expression in the Porcine Myometrium: Prostacyclin Potential to Regulate Fatty Acid Transporters, Cytokines and Contractility-Related Factors
Authors: Blitek Agnieszka , Luba Mateusz , Szymanska Magdalena
Published: August 2022

Although prostacyclin (PGI2) has been well described as a regulator of smooth muscle activity, limited data are available concerning its role in the myometrium of pigs. The present research aimed to examine profiles of PGI2 synthase (PTGIS) and PGI2 receptor (PTGIR) expression and 6-keto PGF1α (a PGI2 metabolite) concentrations in the myometrium of gilts throughout the estrous cycle and during early pregnancy using qPCR, Western blot, and/or ELISA methods. Furthermore, myometrial explants were exposed to iloprost (a stable PGI2 analog) to investigate the effect of PGI2 on the mRNA expression of factors engaged in smooth muscle contraction, nutrient transport, prostaglandin synthesis and action, and inflammatory response. PTGIS mRNA expression was greater in cyclic than in pregnant gilts on days 11–12 after estrus and was accompanied by greater concentrations of 6-keto PGF1α detected in cyclic than in pregnant animals on days 11–20. Iloprost stimulated fatty acid transporters and contractility-related calponin 1 and caldesmon 1 mRNA expression and decreased interleukin 1β and tumor necrosis factor transcript abundance. The obtained results indicate a physiologically relevant role of PGI2 during the estrous cycle in the porcine myometrium with its importance for regulating the expression of contractility-, nutrient transport- and inflammatory response-related factors.
Plethora of Antibiotics Usage and Evaluation of Carbapenem Prescribing Pattern in Intensive Care Units: A Single-Center Experience of Malaysian Academic Hospital
Authors: Lau Chee Lan , Periyasamy Petrick , Saud Muhd Nordin , Robert Sarah Anne , Gan Lay Yen , Chin Suet Yin , Pau Kiew Bing , Kong Shue Hong , Tajurudin Farah Waheeda , Yin Mei Kuen , Ghan Sheah Lin , Azman Nur Jannah , Chua Xin Yun , Lye Poy Kei , Tan Stephanie Wai Yee , Dort Dexter Van , Ramli Ramliza , Tan Toh Leong , Mohamad Yusof Aliza , Cheah Saw Kian , Wan Mat Wan Rahiza , Naina-Mohamed Isa
Published: August 2022

Excessive antibiotic consumption is still common among critically ill patients admitted to intensive care units (ICU), especially during the coronavirus disease 2019 (COVID-19) period. Moreover, information regarding antimicrobial consumption among ICUs in South-East Asia remains scarce and limited. This study aims to determine antibiotics utilization in ICUs by measuring antibiotics consumption over the past six years (2016–2021) and specifically evaluating carbapenems prescribed in a COVID-19 ICU and a general intensive care unit (GICU) during the second year of the COVID-19 pandemic. (2) Methods: This is a retrospective cross-sectional observational analysis of antibiotics consumption and carbapenems prescriptions. Antibiotic utilization data were estimated using the WHO Defined Daily Doses (DDD). Carbapenems prescription information was extracted from the audits conducted by ward pharmacists. Patients who were prescribed carbapenems during their admission to COVID-19 ICU and GICU were included. Patients who passed away before being reviewed by the pharmacists were excluded. (3) Results: In general, antibiotics consumption increased markedly in the year 2021 when compared to previous years. Majority of carbapenems were prescribed empirically (86.8%). Comparing COVID-19 ICU and GICU, the reasons for empirical carbapenems therapy in COVID-19 ICU was predominantly for therapy escalation (64.7% COVID-19 ICU vs. 34% GICU, p < 0.001), whereas empirical prescription in GICU was for coverage of extended-spectrum beta-lactamases (ESBL) gram-negative bacteria (GNB) (45.3% GICU vs. 22.4% COVID-19 ICU, p = 0.005). Despite microbiological evidence, the empirical carbapenems were continued for a median (interquartile range (IQR)) of seven (5–8) days. This implies the need for a rapid diagnostic assay on direct specimens, together with comprehensive antimicrobial stewardship (AMS) discourse with intensivists to address this issue.
Serum Proteomic and Oxidative Modification Profiling in Mice Exposed to Total Body X-Irradiation
Authors: Yamaguchi Masaru , Tatara Yota , Nugraha Eka Djatnika , Sato Yoshiaki , Miura Tomisato , Hosoda Masahiro , Syaifudin Mukh , Tokonami Shinji , Kashiwakura Ikuo
Published: August 2022

The details of the dose-dependent response of serum proteins exposed to ionizing radiation, especially the oxidative modification response in amino acid sequences of albumin, the most abundant protein, are unknown. Thus, a proteomic analysis of the serum components from mice exposed to total body X-irradiation (TBI) ranging from 0.5 Gy to 3.0 Gy was conducted using LC-MS/MS. The analysis of oxidative modification sequences of albumin (mOMSA) in TBI mouse serum revealed significant moderate or strong correlations between the X-irradiation exposure dose and modification of 11 mOMSAs (especially the 97th, 267th and 499th lysine residues, 159th methionine residue and 287th tyrosine residues). In the case of X-irradiation of serum alone, significant correlations were also found in the 14 mOMSAs. In addition, a dose-dependent variation in six proteins (Angiotensinogen, Odorant-binding protein 1a, Serine protease inhibitor A3K, Serum paraoxonase/arylesterase 1, Prothrombin and Epidermal growth factor receptor) was detected in the serum of mice exposed to TBI. These findings suggest the possibility that the protein variation and serum albumin oxidative modification responses found in exposed individuals are important indicators for considering the effects of radiation on living organisms, along with DNA damage, and suggests their possible application as biomarkers of radiation dose estimation.
Phytochemical Screening, Antioxidant, and Enzyme Inhibitory Properties of Three Prangos Species (P. heyniae, P. meliocarpoides var. meliocarpoides, and P. uechtritzii) Depicted by Comprehensive LC-MS and Multivariate Data Analysis
Authors: Dall’Acqua Stefano , Sut Stefania , Zengin Gokhan , Peron Gregorio , Elbasan Fevzi , Yildiztugay Evren , Bibi Sadeer Nabeelah , Mahomoodally Mohamad Fawzi
Published: August 2022

The aim of the present study was to identify/quantify bioactive compounds and determine the antioxidant activity and enzyme inhibitory effects of various solvent extracts (n-hexane, ethyl acetate, methanol, and water) of Prangos heyniae H. Duman and M.F. Watson, Prangos meliocarpoides var. meliocarpoides, and Prangos uechtritzii Boiss. and Hausskn. This is the first time such a report has been designed to validate the phytochemical composition and bioactivity (especially enzyme inhibitory properties) of these plants. A combined approach of liquid chromatography (LC) with mass spectrometry (HR-MS and MSn) allowed to identify that P. heyniae contains condensed tannins; P. meliocarpoides is rich in hydrolysable tannins; and P. uechtritzii possesses coumarins, flavonoids, and hydroxycinnamic acids. Different extracts were tested for antioxidant activities using a battery of assays, such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC), total antioxidant capacity (TAC) (phosphomolybdenum), and metal chelating. Enzyme inhibitory effects were investigated using acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, α-amylase, and α-glucosidase as target enzymes. The obtained results depended on the extraction solvents used for each Prangos species. The methanol extract of P. meliocarpoides var. meliocarpoides exhibited significant radical scavenging activity (DPPH: 52.27 mg Trolox equivalent (TE)/g; ABTS: 92.84 mg TE/g), the most potent-reducing potential (CUPRAC: 154.04 mg TE/g; FRAP: 104.34 mg TE/g), and high TAC (2.52 mmol TE/g). Moreover, the strongest BChE (7.97 mg galantamine equivalent/g), α-amylase (0.46 mmol acarbose equivalent/g), and tyrosinase (81.15 mg kojic acid equivalent/g) inhibitory effects were observed for the hexane extract of P. meliocarpoides var. meliocarpoides. Correlation analysis showed a significant positive correlation between hydrolysable tannins and antioxidant activities. The same trend was also observed between the same class of compounds and the inhibitory effects on enzymatic activities. These results suggest a principal role of hydrolysable tannins in the observed bioactivities of Prangos. Our results suggested that the tested Prangos species could be valuable as sources of natural agents in the development of health-promoting applications.
Climate Change and Respiratory Diseases: Relationship between SARS and Climatic Parameters and Impact of Climate Change on the Geographical Distribution of SARS in Iran
Authors: Bahrami Giti , Rafiey Hassan , Shakiba Alireza , Noroozi Mehdi , Sajjadi Homeira , Seddighi Hamed
Published: August 2022

Climate change affects human health, and severe acute respiratory syndrome (SARS) incidence is one of the health impacts of climate change. This study is a retrospective cohort study. Data have been collected from the Iranian Ministry of Health and Medical Education between 17 February 2016 and17 February 2018. The Neural Network Model has been used to predict SARS infection. Based on the results of the multivariate Poisson regression and the analysis of the coexistence of the variables, the minimum daily temperature was positively associated with the risk of SARS in men and women. The risk of SARS has increased in women and men with increasing daily rainfall. According to the result, by changes in bioclimatic parameters, the number of SARS patients will be increased in cities of Iran. Our study has shown a significant relationship between SARS and the climatic variables by the type of climate and gender. The estimates suggest that hospital admissions for climate-related respiratory diseases in Iran will increase by 36% from 2020 to 2050. This study demonstrates one of the health impacts of climate change. Policymakers can control the risks of climate change by mitigation and adaptation strategists.
Seasonal Variation Characteristics of VOCs and Their Influences on Secondary Pollutants in Yibin, Southwest China
Authors: Kong Lan , Luo Tianzhi , Jiang Xia , Zhou Shuhua , Huang Gang , Chen Dongyang , Lan Yuting , Yang Fumo
Published: August 2022

Volatile organic compounds (VOCs) have a crucial impact on the formation of ozone and secondary organic aerosols in the near-surface atmosphere. Understanding the composition characteristics and sources of VOCs is necessary for determining effective control policies to mitigate VOCs and related secondary pollutions. We performed on-line measurements of VOC species in typical months of each season in Yibin, a fast-growing city in Sichuan Basin in China, to identify VOC seasonal characteristics, sources, and the potential for secondary pollution formation. The average mixing ratio of VOCs in Yibin was 22.3 ppbv. Five major emission sources were identified through the positive matrix factorization model, namely, gasoline vehicle, diesel vehicle, industrial manufacturing, solvent utilization, regional background, and secondary formation. Aromatics and alkenes played leading roles in the secondary formation of ozone and secondary organic aerosols. Furthermore, m/p-xylene, ethylene, and toluene were identified to be the major reactive species. Future management should consider targeting these compounds when evaluating ozone and aerosol reduction strategies. Vehicle and solvent utilization emission mitigation would be the primary and effective ways to improve air quality in the fast-developing city in this region.
Study of Quaternary Ammonium Additives towards High-Rate Zinc Deposition and Dissolution Cycling for Application in Zinc-Based Rechargeable Batteries
Authors: Qiu Kaipei , Trudgeon David , Li Xiaohong , Yufit Vladimir , Chakrabarti Barun , Brandon Nigel , Shah Akeel
Published: August 2022

Aqueous zinc-based rechargeable batteries, such as Zn-Ni and Zn-Air, have been increasingly re-investigated over the last decade due to the abundant and inexpensive nature of zinc, the high solubility of zinc ions, and rapid kinetics and most negative standard potential of the Zn(II)/Zn redox couple in aqueous media. However, the overwhelming challenge that has prevented the implementation of next-generation Zn batteries lies in their poor rechargeability—flowing electrolytes have proven to be of benefit to zinc deposition and dissolution cycling, but the rapid zinc deposition–dissolution at practical current densities of 100 mA cm2 or over is still questionable. Herein, we demonstrated that applying an optimal concentration of quaternary ammonium electrolyte additives with carefully selected cations’ alkyl groups can effectively improve the high-rate zinc cycling performance at 100 mA cm2/20 mAh cm2. The resultant additives significantly reduced the initial coulombic efficiency loss to only 1.11% with coulombic efficiency decay rate of 0.79% per cycle, which is less than a quarter of the benchmark of 6.25% and 3.75% per cycle for no additives.
Exploring the Epiphytic Microbial Community Structure of Forage Crops: Their Adaptation and Contribution to the Fermentation Quality of Forage Sorghum during Ensiling
Authors: Nazar Mudasir , Ullah Muhammad Wajid , Wang Siran , Zhao Jie , Dong Zhihao , Li Junfeng , Kaka Niaz Ali , Shao Tao
Published: August 2022

In this study, the effects of epiphytic microbiota from different forages on the fermentation characteristics and microbial community structure of forage sorghum silage were investigated. The gamma irradiated sterilized forage sorghum was treated through sterile water, epiphytic microbiota of forage sorghum (FSm), Sudan grass (SDm), Napier grass (NPm), and maize (MZm). NPm and SDm inoculated silages showed similar pH value and lactic acid (LA) and acetic acid (AA) contents at day 3 and 60 of ensiling. The final silage of FSm and MZm showed lower (p < 0.05) pH and AA content and a higher LA content compared to the NPm and SDm silages. Bacterial species from the Weisella genus were predominantly present in FSm, NPm, and SDm, while Lactococcus dominated the MZm silage during early ensiling. Lactobacillus was predominant in all inoculated terminal silages. Overall, the four inoculated microbiota decreased the pH value of silage and were dominated by lactic acid bacteria (LAB); however, the NPm and SDm treatments resulted in comparatively higher AA contents which could have an inhibitory effect on the secondary fermentation developed by the yeast and enhanced the aerobic stability of forage sorghum silage.
Relationship between Joint Stiffness, Limb Stiffness and Whole–Body Center of Mass Mechanical Work across Running Speeds
Authors: Jin Li , Hahn Michael E.
Published: August 2022

The lower–extremity system acts like a spring in the running stance phase. Vertical stiffness (Kvert) and leg stiffness (Kleg) reflect the whole–body center of mass (COM) and leg–spring system loading and response in running, while joint stiffness (Kjoint) represents joint–level dynamic loading and response. This study aimed to investigate whether Kjoint is associated with Kvert and Kleg across different running speeds. Twenty healthy subjects were recruited into a treadmill running study (1.8 to 3.8 m/s, with 0.4 m/s intervals). We found that Kjoint accounted for 38.4% of the variance in Kvert (p = 0.046) and 42.4% of the variance in Kleg (p = 0.028) at 1.8 m/s; Kjoint also accounted for 49.8% of the variance in Kvert (p = 0.014) and 79.3% of the variance in Kleg (p < 0.0001) at 2.2 m/s. Kknee had the strongest unique association with Kvert and Kleg at 1.8 and 2.2 m/s. Kjoint was associated with Kleg at a wider range of speeds. These findings built a connection between joint stiffness and limb stiffness within a certain range of running speeds. Kknee may need to be considered as an important factor in future limb stiffness optimization and general running performance enhancement.
Clinical Application of Pharmacokinetics to Appraise Adherence to Levetiracetam in Portuguese Epileptic Patients
Authors: Silva Rui , Bicker Joana , Almeida Anabela , Carona Andreia , Silva Ana , Sales Francisco , Santana Isabel , Falcão Amílcar , Fortuna Ana
Published: August 2022

Adherence to antiseizure drug treatment determines its effectiveness and safety, and consequently affects patients’ quality of life. Herein, we assessed adherence to levetiracetam in Portuguese patients with refractory epilepsy (n = 115), with resort to a pharmacokinetic drug monitoring approach. The pharmacokinetic parameters of levetiracetam in each patient were determined in steady-state while admitted to the hospital. Then, adherence was assessed by comparing the plasma concentration of the drug observed on the first day of hospitalization with the predicted plasma concentration, considering previously determined pharmacokinetic parameters. The rate of adherence was assessed according to gender, age, diagnosis, and antiseizure drug regimen. Among 115 enrolled patients, 49 (42.6%) were identified as non-adherent, 30 (26.1%) classified as under-consumers, and 19 (16.5%) as over-consumers. A relationship between adherence, daily dose and plasma concentrations was herein reported for the first time. Adherent patients received higher daily doses of levetiracetam [2500 (2000–3000) mg] than non-adherent over-consumers [1500 (1000–2000) mg] and non-adherent under-consumers [2000 (1500–3000) mg]. Higher average steady-state plasma concentrations of levetiracetam were found in non-adherent under-consumers [27.28 (15.33–36.36) mg/L], followed by adherent patients [22.05 (16.62–29.81) mg/L] and non-adherent over-consumers [17.50 (10.69–24.37) mg/L]. This study demonstrates that adherence (or lack thereof) influences the plasma concentrations of levetiracetam in steady-state and its pharmacological effects. Moreover, it emphasizes the importance of educating patients to encourage adherence to therapy. Otherwise, the risk of developing toxic and subtherapeutic concentrations is undeniable, compromising the therapeutic effect and safety of treatment.
Blood Eosinophils and Exhaled Nitric Oxide: Surrogate Biomarkers of Airway Eosinophilia in Stable COPD and Exacerbation
Authors: Antus Balazs , Barta Imre
Published: August 2022

In recent years, tremendous efforts have been devoted to characterizing the inflammatory processes in chronic obstructive pulmonary disease (COPD) in order to provide more personalized treatment for COPD patients. While it has proved difficult to identify COPD-specific inflammatory pathways, the distinction between eosinophilic and non-eosinophilic airway inflammation has gained clinical relevance. Evidence has shown that sputum eosinophil counts are increased in a subset of COPD patients and that these patients are more responsive to oral or inhaled corticosteroid therapy. Due to feasibility issues associated with sputum cell profiling in daily clinical practice, peripheral blood eosinophil counts and fractional exhaled nitric oxide levels have been evaluated as surrogate biomarkers for assessing the extent of airway eosinophilia in COPD patients, both in stable disease and acute exacerbations. The diagnostic value of these markers is not equivalent and depends heavily on the patient’s condition at the time of sample collection. Additionally, the sensitivity and specificity of these tests may be influenced by the patient’s maintenance treatment. Overall, eosinophilic COPD may represent a distinct disease phenotype that needs to be further investigated in terms of prognosis and treatment outcomes.
A Cross-Sectional Comparative Study of Sleep Disturbances in Children with ADHD and Matched Controls
Authors: Joseph Angela Ann , Gupta Anupama , Hazari Nandita , Kalaivani Mani , Pandey Ravindra Mohan , Sagar Rajesh , Mehta Manju , Shukla Garima
Published: August 2022

Background: Systematic reviews conducted on sleep disturbances in attention deficit hyperactivity disorder (ADHD) have found inconsistent results due to the presence of several moderating variables which were not controlled for in previous studies. The aim of this study was to examine sleep disturbances in children with ADHD compared to their typically developing peers after controlling for moderating variables (age, sex, medication status, body mass index, and psychiatric and medical comorbidities). Methods: ADHD was diagnosed using DSM-IV-TR criteria (Diagnostic and Statistical Manual of Mental Disorders) and Conners’ Parent Rating Scales. Children recruited (aged 6–12 years) for the ADHD group (n = 40) met the following criteria: IQ > 80, unmedicated, and no psychiatric or medical comorbidities. The control group consisted of age- and sex-matched typically developing peers (n = 40). Sleep was assessed subjectively (through parent reported questionnaires and sleep logs) and objectively (using video polysomnography). Results: 65% of children with ADHD had a sleep disorder, as compared to 17% of controls. The ADHD group reported more sleep disturbances and disorders, both on subjective measures and objective measures. Conclusions: Sleep disturbances and primary sleep disorders in children with ADHD exist independent of moderating variables and differences in sleep assessment methods, thereby bolstering support for previously documented literature on the ADHD and sleep connection.
Prevalence and Risk Factors for Enlarged Perivascular Spaces in Young Adults from a Neurology Clinic-Based Cohort
Authors: Zou Qiaoqiao , Wang Mingliang , Wei Xiaoer , Li Wenbin
Published: August 2022

(1) Background: This study aimed to investigate the prevalence and risk factors for enlarged perivascular spaces (EPVS) in young adults from a neurology clinic-based cohort (≤45 years old) via unenhanced brain MRI. (2) Methods: A total of 931 young adults from a neurology clinic-based cohort who underwent unenhanced brain MRI between 1 January 2021 and 30 June 2021 were retrospectively included in this study. The EPVS were rated in the centrum semiovale (CSO-EPVS), basal ganglia (BG-EPVS), and midbrain (MB-EPVS) using a visual rating scale. The degrees of the CSO-EPVS, BG-EPVS, and MB-EPVS were all divided by a cutoff value of 1. Demographic factors, vascular risk factors, and symptoms were analyzed using the chi-square test and logistic regression to determine the risk factors of EPVS. (3) Results: The overall prevalence of EPVS was 99.8% (929/931). The CSO-EPVS, BG-EPVS, and MB-EPVS were predominantly scored as 1 (52.1%, 79.1%, and 58.3%, respectively). Logistic regression analysis identified age and hypertension as factors affecting the degrees of CSO-EPVS and BG-EPVS (p < 0.05). Hypertension (p < 0.001) and diabetes (p = 0.014) were revealed to be factors affecting the degree of BG-EPVS. Furthermore, patients with headache (OR = 1.807; p = 0.001) and dizziness (OR = 1.574; p = 0.025) were associated with MB-EPVS. (4) Conclusions: EPVS were frequently found in young adults and could be related to the symptoms. Age, hypertension, and diabetes were the risk factors for the severity of EPVS in the corresponding brain regions.
Immune Checkpoint Inhibitors for Gastrointestinal Malignancies: An Update
Authors: DeCarli Kathryn , Strosberg Jonathan , Almhanna Khaldoun
Published: August 2022

Gastrointestinal (GI) malignancies are a heterogenous group of cancers with varying epidemiology, histology, disease course, prognosis and treatment options. Immune checkpoint inhibitors (ICIs) have changed the landscape of modern cancer treatment, though they have demonstrated survival benefit in other solid tumors more readily than in GI malignancies. This review article presents an overview of the landscape of ICI use in GI malignancies and highlights recent updates in this rapidly evolving field.
The Effects of a Mediterranean Diet Intervention on Cancer-Related Fatigue for Patients Undergoing Chemotherapy: A Pilot Randomized Controlled Trial
Authors: Kleckner Amber S. , Reschke Jennifer E. , Kleckner Ian R. , Magnuson Allison , Amitrano Andrea M. , Culakova Eva , Shayne Michelle , Netherby-Winslow Colleen S. , Czap Susan , Janelsins Michelle C. , Mustian Karen M. , Peppone Luke J.
Published: August 2022

Cancer-related fatigue is a common, burdensome symptom of cancer and a side-effect of chemotherapy. While a Mediterranean Diet (MedDiet) promotes energy metabolism and overall health, its effects on cancer-related fatigue remain unknown. In a randomized controlled trial, we evaluated a rigorous MedDiet intervention for feasibility and safety as well as preliminary effects on cancer-related fatigue and metabolism compared to usual care. Participants had stage I–III cancer and at least six weeks of chemotherapy scheduled. After baseline assessments, randomization occurred 2:1, MedDiet:usual care. Measures were collected at baseline, week 4, and week 8 including MedDiet adherence (score 0–14), dietary intake, and blood-based metabolic measures. Mitochondrial respiration from freshly isolated T cells was measured at baseline and four weeks. Participants (n = 33) were 51.0 ± 14.6 years old, 94% were female, and 91% were being treated for breast cancer. The study was feasible, with 100% completing the study and >70% increasing their MedDiet adherence at four and eight weeks compared to baseline. Overall, the MedDiet intervention vs. usual care had a small-moderate effect on change in fatigue at weeks 4 and 8 (ES = 0.31, 0.25, respectively). For those with a baseline MedDiet score <5 (n = 21), the MedDiet intervention had a moderate-large effect of 0.67 and 0.48 at weeks 4 and 8, respectively. The MedDiet did not affect blood-based lipids, though it had a beneficial effect on fructosamine (ES = −0.55). Fatigue was associated with mitochondrial dysfunction including lower basal respiration, maximal respiration, and spare capacity (p < 0.05 for FACIT-F fatigue subscale and BFI, usual fatigue). In conclusion, the MedDiet was feasible and attenuated cancer-related fatigue among patients undergoing chemotherapy, especially those with lower MedDiet scores at baseline.
Single-Chain Fragment Variable: Recent Progress in Cancer Diagnosis and Therapy
Authors: Muñoz-López Paola , Ribas-Aparicio Rosa María , Becerra-Báez Elayne Irene , Fraga-Pérez Karla , Flores-Martínez Luis Fernando , Mateos-Chávez Armando Alfredo , Luria-Pérez Rosendo
Published: August 2022

Cancer remains a public health problem worldwide. Although conventional therapies have led to some excellent outcomes, some patients fail to respond to treatment, they have few therapeutic alternatives and a poor survival prognosis. Several strategies have been proposed to overcome this issue. The most recent approach is immunotherapy, particularly the use of recombinant antibodies and their derivatives, such as the single-chain fragment variable (scFv) containing the complete antigen-binding domains of a whole antibody that successfully targets tumor cells. This review describes the recent progress made with scFvs as a cancer diagnostic and therapeutic tool, with an emphasis on preclinical approaches and their potential use in clinical trials.
Clinical Strategies Targeting the Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma
Authors: Skorupan Nebojsa , Palestino Dominguez Mayrel , Ricci Samuel L. , Alewine Christine
Published: August 2022

Pancreatic cancer has a complex tumor microenvironment which engages in extensive crosstalk between cancer cells, cancer-associated fibroblasts, and immune cells. Many of these interactions contribute to tumor resistance to anti-cancer therapies. Here, new therapeutic strategies designed to modulate the cancer-associated fibroblast and immune compartments of pancreatic ductal adenocarcinomas are described and clinical trials of novel therapeutics are discussed. Continued advances in our understanding of the pancreatic cancer tumor microenvironment are generating stromal and immune-modulating therapeutics that may improve patient responses to anti-tumor treatment.
Genomic Landscape Alterations in Primary Tumor and Matched Lymph Node Metastasis in Hormone-Naïve Prostate Cancer Patients
Authors: Russo Giorgio Ivan , Bonacci Paolo , Bivona Dalida , Privitera Grete Francesca , Broggi Giuseppe , Caltabiano Rosario , Vella Jessica , Lo Giudice Arturo , Asmundo Maria Giovanna , Cimino Sebastiano , Morgia Giuseppe , Stefani Stefania , Musso Nicolò
Published: August 2022

Background: Prostate cancer (PCa) is a disease with a wide range of clinical manifestations. Up to the present date, the genetic understanding of patients with favorable or unfavorable prognosis is gaining interest for giving the appropriate tailored treatment. We aimed to investigate genetic changes associated with lymph node metastasis in a cohort of hormone-naïve Pca patients. Methods: We retrospectively analyzed data from 470 patients who underwent surgery for PCa between 2010 and 2020 at the Department of Urology, University of Catania. Inclusion criteria were patients with lymph node metastasis and patients with PCa with extra capsular extension (pT3) and negative lymph node metastasis. The final cohort consisted of 17 different patients (11 PCa with lymph node metastasis and 6 PCa without lymph node metastasis). Through the cBioPortal online tool, we analyzed gene alterations and their correlations with clinical factors. Results: A total of 688 intronic, synonym and nonsynonym mutations were sequenced. The gene with the most sequenced mutations was ERBB4 (83 mutations, 12% of 688 total), while the ones with the lower percentage of mutations were AKT1, FGFR2 and MLH1 (1 mutation alone, 0.14%). Conclusion: In the present study we found mostly concordance concerning the ERBB4 mutation between both primary PCa samples and matched lymph node metastasis, underlining that the identification of alterations in the primary tumor is extremely important for cancer prognosis prediction.
Breast Cancer in Asia: Incidence, Mortality, Early Detection, Mammography Programs, and Risk-Based Screening Initiatives
Authors: Lim Yu Xian , Lim Zi Lin , Ho Peh Joo , Li Jingmei
Published: August 2022

Close to half (45.4%) of the 2.3 million breast cancers (BC) diagnosed in 2020 were from Asia. While the burden of breast cancer has been examined at the level of broad geographic regions, literature on more in-depth coverage of the individual countries and subregions of the Asian continent is lacking. This narrative review examines the breast cancer burden in 47 Asian countries. Breast cancer screening guidelines and risk-based screening initiatives are discussed.
Development and Characterization of a Luciferase Labeled, Syngeneic Murine Model of Ovarian Cancer
Authors: Russell Shonagh , Lim Felicia , Peters Pamela N. , Wardell Suzanne E. , Whitaker Regina , Chang Ching-Yi , Previs Rebecca A. , McDonnell Donald P.
Published: August 2022

Despite advances in surgery and targeted therapies, the prognosis for women with high-grade serous ovarian cancer remains poor. Moreover, unlike other cancers, immunotherapy has minimally impacted outcomes in patients with ovarian cancer. Progress in this regard has been hindered by the lack of relevant syngeneic ovarian cancer models to study tumor immunity and evaluate immunotherapies. To address this problem, we developed a luciferase labeled murine model of high-grade serous ovarian cancer, STOSE.M1 luc. We defined its growth characteristics, immune cell repertoire, and response to anti PD-L1 immunotherapy. As with human ovarian cancer, we demonstrated that this model is poorly sensitive to immune checkpoint modulators. By developing the STOSE.M1 luc model, it will be possible to probe the mechanisms underlying resistance to immunotherapies and evaluate new therapeutic approaches to treat ovarian cancer.
Recombinant Attenuated Salmonella enterica as a Delivery System of Heterologous Molecules in Cancer Therapy
Authors: Becerra-Báez Elayne Irene , Meza-Toledo Sergio Enrique , Muñoz-López Paola , Flores-Martínez Luis Fernando , Fraga-Pérez Karla , Magaño-Bocanegra Kevin Jorge , Juárez-Hernández Uriel , Mateos-Chávez Armando Alfredo , Luria-Pérez Rosendo
Published: August 2022

Over a century ago, bacterial extracts were found to be useful in cancer therapy, but this treatment modality was obviated for decades. Currently, in spite of the development and advances in chemotherapies and radiotherapy, failure of these conventional treatments still represents a major issue in the complete eradication of tumor cells and has led to renewed approaches with bacteria-based tumor therapy as an alternative treatment. In this context, live-attenuated bacteria, particularly Salmonella enterica, have demonstrated tumor selectivity, intrinsic oncolytic activity, and the ability to induce innate or specific antitumor immune responses. Moreover, Salmonella enterica also has strong potential as a delivery system of tumor-associated antigens, cytotoxic molecules, immunomodulatory molecules, pro-apoptotic proteins, and nucleic acids into eukaryotic cells, in a process known as bactofection and antitumor nanoparticles. In this review, we present the state of the art of current preclinical and clinical research on the use of Salmonella enterica as a potential therapeutic ally in the war against cancer.
Safety and Efficacy of Allogeneic Natural Killer Cells in Combination with Pembrolizumab in Patients with Chemotherapy-Refractory Biliary Tract Cancer: A Multicenter Open-Label Phase 1/2a Trial
Authors: Leem Galam , Jang Sung-Ill , Cho Jae-Hee , Jo Jung Hyun , Lee Hee Seung , Chung Moon Jae , Park Jeong Youp , Bang Seungmin , Yoo Da-Kyung , Cheon Hyo-Cheon , Kim Jae-Eun , Lim Kyeong-Pill , Jung In-Hye , Im Jung-Min , Chung Yong-Yoon , Park Seung Woo
Published: August 2022

Background and Aim: This study investigated the administration of combination therapy, allogeneic natural killer (NK) cells and pembrolizumab in the treatment of advanced biliary tract cancer to determine the safety and tolerability (phase 1) and the efficacy and safety (phase 2a). Methods: Forty patients (phase 1, n = 6; phase 2a, n = 34) were enrolled between December 2019 and June 2021. The patients received highly activated allogeneic NK cells (“SMT-NK”) on weeks 1 and 2 and pembrolizumab on week 1. This 3-week schedule (one cycle) was repeated until confirmed disease progression, intolerable adverse events (AEs), patient withdrawal, or finishing the maximum treatment schedule. The tumor response was evaluated after every three cycles. Results: In phase 1, four patients (66.7%) experienced seven AEs, but no severe AE was observed. In phase 2a, 126 AEs occurred in 29 patients (85.3%). Severe AEs (≥grade 3) were reported in 16 patients (47.1%). The overall response rate (ORR) was 17.4% in the full analysis set and 50.0% in the per-protocol set. Conclusions: SMT-NKs plus pembrolizumab resulted in no severe AEs directly related to the drug combination. The combination therapy also exerted antitumor activity with improved efficacy compared to the recent monotherapy with pembrolizumab in patients with advanced biliary tract cancer.