Since the coming of Positive Psychology in the field of second language acquisition (SLA), the significance of emotion, especially positive emotion, has been well recognized by researchers. Educational research has indicated that both emotion and engagement play fundamental roles in learning process and psychological wellbeing, but research on their relationship is scant in SLA. The present study contributed to the development of Positive Psychology in SLA by investigating the relationships between achievement emotions, behavioral engagement, and self-reported English achievements. 633 students from four senior high schools in China participated in the study. Data collected through questionnaires revealed: (1) Participants reported a medium to high level of foreign language enjoyment (FLE), foreign language classroom anxiety (FLCA), and behavioral engagement; females had a higher level of FLE and behavioral engagement than males; the participants reported more anxiety and less enjoyment than western samples; (2) significant correlations were found between FLE, FLCA, behavioral engagement, and self-reported achievement; (3) significant mediating effects of behavioral engagement were found between both achievement emotions and self-reported achievement, and the mediating effect of engagement was stronger between FLCA and self-reported achievement. The findings extended the nomological network of achievement emotions, developed our insights into the complex relationships between emotions, learner engagement and language achievement, and revealed the mediating effects of behavioral engagement. Finally, directions for future study and implications for foreign language educators were provided. Neuroscience and cognitive science have revealed the fundamental role of emotion in learning process . AlthougAlthough relevant research is accumulating, the nomological network of emotion is yet to be fully explored . For insGiven the research gaps, the present study aimed to investigate the relationships between emotions, behavioral engagement, and FL achievement, and also the mediating effect held by behavioral engagement in the relationships. Specifically, the goal of the current study was to reveal: (1) the general levels of achievement emotions  and behavioral engagement of Chinese senior high school FL learners, and the relative level of enjoyment and anxiety in the present sample compared with the western sample; the gender differences in enjoyment, anxiety, and behavioral engagement; (2) the correlations between enjoyment, anxiety, behavioral engagement and FL self-reported achievement (SRA); (3) the mediating effects of behavioral engagement between achievement emotions  and FL self-reported achievements. The findings may narrow the research gap in the field by extending the nomological network of achievement emotions in SLA, and providing original insights into the complex relationships between achievement emotion, engagement, and learning outcomes, especially the mediating effects of behavioral engagement between achievement emotion and FL achievement. A better understanding of the relationships could provide implications for a more accurate intervention to improve learners’ engagement, wellbeing and FL learning achievement.Anxiety is the most investigated achievement emotion in SLA . HorwitzInfluenced by PP, especially the so-called second wave of positive psychology  research operationalized behavioral engagement by gauging word counts and turn counts . In L2 lEducational research has indicated that engagement is a strong predictor of academic achievement . For insEngagement is a result of both environmental facilitators such as classroom interpersonal relations, and personal factors such as motivation and emotions. Indeed, Recently, Probably the only quantitative study that directly investigated the relationship between FLE, FLCA, and engagement is In Previous research has indicated that engagement is a potential mechanism by which achievement emotions influence academic achievement. According to the broaden-and-build theory and previous empirical studies e.g., , positivThe present study hence sat out to narrow the research gaps by examining the relationships between FLCA, FLE, behavioral engagement, and EFL self-reported achievement (SRA) in the context of Chinese high school EFL learning. The present study also aimed to examine behavioral engagement as a mediator between achievement emotions  and SRA.The specific research questions that directed the present study were as follows:RQ1: What are the general levels of FLE, FLCA, and behavioral engagement of the participants? Do participants’ levels of FLE and FLCA differ from their western peers? Are there any gender differences in FLE, FLCA, and behavioral engagement?RQ2: What are the relationships between their FLE, FLCA, behavioral engagement, and EFL self-reported achievements?RQ3: Does behavioral engagement mediate the relationships between achievement emotions and EFL self-reported achievements?SD = 1.05). There were 279 males (44.08%) and 354 females (55.92%). Most of them were year one  and year three students , and only 27 were year two students (4.3%). English was one of the major subjects included in the National College Entrance Examination (NCEE). They had one English class per day, an English morning self-study class every 2 days, each English session took 45 mins.The participants of the current study were 633 EFL learners from four Chinese senior high schools in a city in Zhejiang Province, China, with a convenience sampling being adopted. Two of the schools were second-tier high schools, one first-tier high school and the other one a third-tier high school. The four schools were chosen because they represent participants with varied academic levels so that the findings may be more representative and generalizable. All of the participants were Chinese native speakers with their ages ranging from 15 to 20, and the mean was 16.4  to “5” (very favorable). The three sub-scales consisted of the Foreign Language Enjoyment (FLE) scale , Foreignn = 11), and validity. This scale contained 11 items , in which 3 dimensions had been identified, namely FLE-teacher, FLE-private, and FLE-environment. In the present study, the scale also had high reliability . According to 2 (40) = 196.074; RMSEA = 0.079; CFI = 0.96; TLI = 0.945; SRMR = 0.054].Enjoyment was measured through the FLE scale. It was a modified version of the FLE scale in n = 8) as the original one. The scale was recently validated by n = 8). The scale had good CFA model fit .The FLCA scale was a shortened scale extracted by n = 8). Its model fit was good after deleting an item with factor loading lower than 0.40 (“I do other things in the language classroom when I am supposed to be paying attention.”) .Behavioral engagement was measured through the behavioral engagement scale . There wThe final part was a 5-point Likert scale asking participants to report their conceptualizations about their English standings in the classroom. Items include: 1 = bad, 2 = below average, 3 = average, 4 = above average, 5 = good. Self-reported achievement rather than actual scores was elicited for several reasons: first, previous research has confirmed a high concurrent validity between self-reported academic achievement scores and actual scores . Self-reThe questionnaire had good composite reliability (CR) with McDonald’s ω = 0.81. The questionnaire was finished anonymously in a traditional paper-and-pencil way due to the ban on mobile phone use in the school.Since there were already Chinese versions of the FLE and FLCA scale , they weBefore the study, the author got permission from the headmasters of all schools, and consent was obtained from all the participants as well as their parents. The questionnaires were distributed by the headteacher of each class. Participants were briefly informed of the purpose of the study and were told that their personal information will be strictly protected. 15 mins were given to fill out the questionnaires. As soon as they finished, the headteacher collected the questionnaires then handed them over to the author. Finally, 647 students volunteered in the study, and 14 invalid questionnaires were discarded because of incomplete responses, producing a final sample of 633 participants, so the response rate was 97.8%.t-test and a one sample t-test were conducted for RQ 1. A series of Pearson correlation analyses were adopted for RQ 2. The multiple regression analysis and PROCESS v 3.4.1 (Model 4)   mediatiot-test was conducted. Surprisingly, the result revealed that there is no significant difference between FLE and FLCA .As t-tests were performed to check if there were gender differences in the participants. Results revealed a significant gender difference in FLE and behavioral engagement. Female learners felt significantly more enjoyment than their male peers , and their behavioral engagement was also significantly higher than that of their male classmates . However, in the present study no statistically significant gender difference was found in FLCA .Independent samples t-test was conducted to check if there is any statistically significant difference between the present sample and the western sample in 1 = 3.36, SD = 0.65; M2 = 3.9, SD = 0.6; t = −21.1, p < 0.001, Cohen’s d = −0.84), and the FLCA level in the present study was significantly higher than that of the western sample .A one-sample A series of Pearson correlation analyses were conducted to reveal the bivariate correlations among the observed variables. The results were summarized in r = −0.33, p < 0.001), suggesting that learners with higher enjoyment tended to feel less anxiety in the EFL classroom. FLE was positively and significantly correlated with behavioral engagement , indicating that learners with higher enjoyment were also more behaviorally engaged in learning activities. FLCA was found to be negatively related to behavioral engagement , suggesting that more anxious learners tended to be less engaged in learning activities. FLE was significantly and positively correlated with SRA , while FLCA was negatively correlated with their SRA . This suggested that learners with more enjoyment were likely to perceive themselves as having better achievement in English, while students with more anxiety tended to perceive themselves as less proficient in English. Besides, behavioral engagement was also reported to be significantly and positively correlated with SRA , indicating that those more engaged learners tended to be more confident in their learning achievements and perceive themselves as more proficient in English.As shown in To answer the final research question, the mediating effect of behavioral engagement between achievement emotions  and SRA was investigated. In the model 1, FLE was the antecedent variable X, and SRA was proposed to be the consequent variable Y, while behavioral engagement was the mediating variable M. In the model 2, FLCA was the antecedent variable X, while the mediating variable and consequent variable were the same as the first model. SPSS PROCESS v 3.4.1 Model 4;  was usedTo test the first model, linear regression analysis and PROCESS with 5,000 bootstrap samples were conducted, offering corresponding 95% confidence intervals. The results were as follows , 4.p < 0.001); FLE also influenced learner’s behavioral engagement significantly and positively ; when put into the same regression model, engagement influenced learner’s SRA significantly and positively , and FLE’s positive influence on SRA was still significant  though the effect diminished after engagement being entered into the model.As As To test the second model, the same steps as did in model 1 were followed. The regression analyses results were shown in p < 0.001), and it also negatively and significantly influenced behavioral engagement . When put into the same model, FLCA still influenced SRA significantly and negatively , though the effect diminished, and behavioral engagement positively and significantly influenced SRA . The positive effect of FLE on both behavioral engagement (β = 0.57) and SRA (β = 0.39) was found to be stronger than the negative effect of FLCA on behavioral engagement (β = −0.35) and SRA (β = −0.37).As The results of mediation analysis was shown in The first research question concerns the general levels of FLE, FLCA, and behavioral engagement; the gender and international differences in FLE, FLCA, and behavioral engagement, and international differences in FLE and FLCA. Our participants reported a medium to a high level in FLE, FLCA, and behavioral engagement. Interestingly, we found participants’ levels of FLE and FLCA did not differ significantly. This finding is quite different from most previous studies e.g., , and mayThe second research question is about the correlations between FLE, FLCA, behavioral engagement, and SRA. The results indicated a negative correlation between FLE and FLCA, a positive relationship between FLE and behavioral engagement, and a negative relationship between FLCA and behavioral engagement. SRA was found to be positively correlated with FLE and behavioral engagement, and negatively with FLCA. The findings are in accordance with previous studies e.g., .The third research question concerns the mediating effects of behavioral engagement between FLE, FLCA, and SRA. We first found that FLE positively influenced behavioral engagement and SRA, and FLCA negatively affected behavioral engagement and SRA. Our findings indicated that the positive broadening effects of FLE on both behavioral engagement and SRA were stronger than the negative narrowing effects of FLCA on behavioral engagement and SRA, thus dovetailing with previous research . The preMost previous SLA research only investigated the simple and bivariate relationships between achievement emotions and other factors e.g., . The preThe findings of the present study had important implications for Chinese senior high school EFL educators. The present study found that emotions could directly and indirectly affect self-reported learning achievements through learners’ behavioral engagement. As Despite the important implications the present study provided, there were some limitations in the present study that should be acknowledged. First, to ensure the comparability of FL achievements among different schools, the present study used self-reported achievement rather than actual achievement. Although self-reported achievement has been found to be highly related to actual achievement , it cannThe present study was one of the first attempts to investigate the complex relationships between FLE, FLCA, behavioral engagement, and EFL self-reported achievements of Chinese senior high school EFL learners. The results revealed that: (1) participants reported medium to a high level of FLE, FLCA, and behavioral engagement, and no significant difference was found between FLE and FLCA; female participants had higher levels of FLE and behavioral engagement than their male peers, however, the difference was not significant in FLCA; when compared with western students, our participants felt significantly more anxiety and less enjoyment; (2) behavioral engagement was found to be positively correlated with FLE and SRA, while was negatively correlated with FLCA; SRA was negatively correlated with FLCA, and positively correlated with FLE; FLE and FLCA was negatively correlated (3) behavioral engagement partially mediated the influence of FLE and FLCA on SRA, with the mediating effects between FLE and SRA weaker than that between FLCA and SRA.The present study extended the nomological networks of achievement emotions and revealed the mediating role of behavioral engagement between achievement emotions and EFL self-reported achievement, which was not found in previous SLA studies. Our study highlighted the critical role of engagement in understanding learning achievements . The medThe original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.EF contributed to the conceptualization, data analysis, and drafting of the manuscript. GH contributed to the conceptualization, critical revision, and proofreading of the article. Both authors contributed to manuscript revision, read, and approved the submitted version.The author declares that the research was conducted in the absence of any commercial and financial relationships that can be construed as potential conflicts of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


We present a case of Lemierre's syndrome in a young girl and the role of extracorporeal method of blood purification with continuous venous hemodiafiltration with the use of a highly adsorptive membrane (AN69 HeprAN), thus achieving the combined elimination of cytokines and endotoxins. The use of advanced methods, along with an antibiotic and surgical treatment, will certainly help reduce mortality in this syndrome.Lemierre's syndrome refers to the septic thrombophlebitis of the internal jugular vein. The condition typically begins with an oropharyngeal infection and frequently involves inflammation within the wall of the vein, infected thrombus within the lumen, surrounding soft tissue inflammation, persistent bacteremia, and septic emboli. Lemierre's syndrome is a rare disease; it occurs most commonly in otherwise healthy young adults. The most common etiologic agent is Fus Fusobacterium necrophorum. Traditional treatment modalities used are antimicrobial, anticoagulant, and surgical treatment. A beta-lactamase-resistant beta-lactam antibiotic is recommended as an empiric therapy. Antibiotics should be tailored to the culture results and susceptibility data when available. Alternative options include clindamycin or metronidazole for patients with significant clinical allergy to beta-lactams. Morbidity is significant with prolonged hospitalization in the majority of patients. The overall mortality rate is 5% [Lemierre's syndrome is characterized by the thrombosis of the internal jugular vein that develops following an oropharyngeal infection. Sepsis and septic metastases frequently affect the lungs, the musculoskeletal system, and, occasionally, the liver. The most common offending micro-organism is te is 5% . In 1936te is 5% . Lemierrte is 5% . We pres9/L), anemia , and renal failure . The C-reactive protein (CRP) level was also elevated at 190.2 mg/L, as well as other parameters of acute inflammation like interleukin-6 (10700.0 ng/L), ferritin (240.7 μg/L), and procalcitonin (PCT) (3.83 μg/L). On the same day, an emergency surgery was performed: a total exploration of the complete retropharyngeal, parapharyngeal, and retroesopharyngeal space to the depth of the aortic arch was performed. On the second day of hospitalization, due to a persistent increase in the inflammatory parameters, the CVVHDF method was performed with the adsorptive membrane (AN69 HeprAN) for 72 h. Fusobacterium necrophorum was isolated by a microbiological analysis of an intraoperative sample. Four days later, a surgical revision of the operative area of the neck was performed due to additional surgical debridement of the wound under general anesthesia. A follow-up blood test after the start of the CVVHDF method with the appropriate membrane showed decline in the inflammatory parameters with the CRP value of 126 mg/L, interleukin-6 of 0.12 ng/L, and PCT of 0.41 μg/L. On the seventh day of hospitalization, the inflammatory parameters further declined and the follow-up CT showed regression of previously described inflammatory changes. The patient was extubated and showed a stable respiratory rate, breathing through the tracheal cannula. Since the admission of the patient, an empiric antibiotic therapy was started with intravenous meronem, with subsequent introduction of linezolid and metronidazole, as well as the anticoagulant therapy of low-molecular-weight heparin (enoxaparin). Antibiotic therapy was used for a total of up to 6 weeks. After hospital discharge, the anticoagulant therapy was continued with rivaroxaban for another 4 weeks; after a follow-up neck and chest CT confirmed complete recanalization of the right jugular vein, this was excluded from the therapy.A 19-year-old female without a significant past medical history was urgently admitted to hospital in a serious general condition, presenting with multiorgan failure. The infection with SARS-CoV-2 was ruled out upon admission. She was treated with phenoxymethylpenicillin on an outpatient basis for acute tonsillopharyngitis 3 weeks earlier. 2-3 days before admission, she had a fever up to 40°C, with pain in the right shoulder and right side of the chest, felt a shortness of breath on exertion, and had a dry cough. Upon admission to the hospital, she presented with fever and was hypodynamic, pale, hypotensive, and oligoanuric. The vital signs showed a low blood pressure of 80/60 mmHg, and there was a swelling of the right side of the neck and the right arm. The initial chest X-ray showed subcutaneous emphysema of the right shoulder and hemithorax, bilateral inflammatory infiltrates, and pleural effusions. Computed tomography (CT) of the neck, chest, and abdomen showed a right parapharyngeal abscess and right jugular vein thrombosis . Gas incFusobacterium necrophorum infection, which represents 30% of all causes of Lemierre's syndrome. Fusobacterium necrophorum is an obligate anaerobic bacterium and is notoriously difficult to culture, requiring a longer incubation period than the other bacteria [A clear clinical presentation of Lemierre's syndrome after the performed diagnostic tests is in line with the previous research . Our diabacteria . In the bacteria . In thisbacteria . This trbacteria . MoreoveFusobacterium necrophorum. Prolonged antibiotic and anticoagulation therapy is the basis of the treatment. In a critical patient with a septic shock, as part of Lemierre's syndrome, it is an important adjunctive consideration to supplement the definitive source control and antimicrobial therapy. The use of extracorporeal blood purification in this case proved to be extremely important in preventing the consequences, such as multiorganic injury and faster recovery of the patient.Lemierre's syndrome is a rare illness in the modern era of antibiotic therapy which occurs primarily in young, otherwise healthy individuals. It is characterized by the presence of recent oropharyngeal infection, clinical or radiological evidence of venous thrombosis internal jugular vein, and the presence of anaerobic bacteremia caused primarily by


Alzheimer’s disease (AD), a neurodegenerative disease, is one of the most intractable illnesses which affects the elderly. Clinically manifested as various impairments in memory, language, cognition, visuospatial skills, executive function, etc., the symptoms gradually aggravated over time. The drugs currently used clinically can slow down the deterioration of AD and relieve symptoms but cannot completely cure them. The drugs are mainly acetylcholinesterase inhibitors (AChEI) and non-competitive N-methyl-D-aspartate receptor (NDMAR) antagonists. The pathogenesis of AD is inconclusive, but it is often associated with the expression of beta-amyloid. Abnormal deposition of amyloid and hyperphosphorylation of tau protein in the brain have been key targets for past, current, and future drug development for the disease. At present, researchers are paying more and more attention to excavate natural compounds which can be effective against Alzheimer’s disease and other neurodegenerative pathologies. Marine natural products have been demonstrated to be the most prospective candidates of these compounds, and some have presented significant neuroprotection functions. Consequently, we intend to describe the potential effect of bioactive compounds derived from marine organisms, including polysaccharides, carotenoids, polyphenols, sterols and alkaloids as drug candidates, to further discover novel and efficacious drug compounds which are effective against AD. Dementia is an umbrella term for a particular group of symptoms. The characteristic symptoms of dementia are difficulties with memory, language, problem-solving, and other thinking skills that affect a person’s ability to perform everyday activities. Alzheimer’s disease (AD) is the most common cause of dementia, accounting for an estimated 60% to 80% of cases . AD is a’s Association (NIA-AA) guidelines defined three phases of AD: preclinical AD, MCI (symptomatic predementia) and dementia [Over time, symptoms will worsen and can even be life-threatening. The pathological sequence of AD starts in the center temporal lobe firstly, which is responsible for memory, and then progresses to the regions of the frontal, temporal, parietal, motor, sensory, and subcortical areas. The neuropathology of AD is complex and not yet fully understood . The 201dementia . Preclindementia . Even whdementia . In the dementia . Approxidementia , along wdementia . In the AD has become a serious public health issue with high medical costs and no cure. Most cases appear in people over 65 years of age, and the global morbidity is about 6%, with women having a higher morbidity rate than men. The Alzheimer’s Disease Society International’s Association published a report entitled “The Global Impact of Dementia 2013−2050”, which showed that 44 million people are ill with dementia, a 17% raise from 2009, and that the number of people worldwide with dementia is almost doubling every 20 years. By 2030 and 2050, 76 million and 135 million cases of dementia will be found around the world. China has the highest prevalence rate with about 10 million people of dementia in the world and a yearly increase of 30 percent. In China, the prevalence rate is 5% for those over 65 years old and 30% for those over 85 years old. With the fast aging of China’s population, the number of people with dementia in China will exceed 20 million by 2050, 10% of the elderly over 75 years old will have cognitive impairment, and one third of the elderly over 85 years old will have cognitive impairment .In view of the increasing number of patients with AD, researchers have never stopped exploring therapeutic drug development. In recent years, many researchers have found that in the marine environment there are a large number of unique and different structures, including polysaccharides, carotenoids, polyphenols, sterol and alkaloids, which have biological and pharmacological activities . Marine According to the age of onset, Alzheimer’s Disease (AD) can be divided into two types: early onset (EOAD) and late onset (LOAD). EOAD has certain heritability, accounting for a small number of all Alzheimer’s disease. The majority of patients have LOAD. Age is the greatest risk factor for acquiring AD. In adults older than 85, the prevalence of AD is more than one in three ,18,19. AThe first hypothesis is the amyloid cascade. This hypothesis concludes that Aβ aggregation as an early event in neurodegeneration occurs independently prior to tangles formation, followed by microglia and astrocyte activation, neuroinflammatory responses, oxidative stress, and other cellular molecular events . The patAnother hypothesis is the neuroinflammation hypothesis, which is modified from the above-mentioned amyloid hypothesis. Based on this theory, the pathogenesis of AD is mainly related to a series of activities of microglia in the immune system of the central nervous system (CNS) in which that microglia continuously activate pro-inflammatory cells through the transduction of pro-inflammatory signals . At this2+ hypothesis. Ca2+ dysregulation is a common and pervasive pathophysiological phenomenon in AD. Zhong et al. [2+ homeostasis and its deficiency is a causative factor in AD. By examining cellular, molecular and functional changes in adult/senescent GluN3A knockout (KO) mice, they concluded that chronic ‘degenerative excitotoxicity’ can lead to sporadic AD, and GluN3A is the main pathogenic factor, a lifelong moderate but sustained Ca2+ overload is a causal pathogenic mechanism of sporadic AD. Therefore, GluN3A may be an amyloid-independent therapeutic target [The next hypothesis is the Cag et al.  hypothesc target .The tau hypothesis is based on the notion that tau protein’s hyperphosphorylation leads to NFTs, which is one of the chief pathological conditions of AD . ClinicaThe pathogenesis of AD is usually related to the decrease of neurotransmitter levels, such as serotonin, norepinephrine, dopamine, acetylcholine, etc. Acetylcholine (ACh), which is closely associated with the formation and storage of human’s memory ability, is an important neurotransmitter in the human cerebrum. Decreasing the level of Ah can directly lead to cell damage in the basal nucleus, temporal lobe, and parietal lobe, thereby reducing the level of serotonin and intensifying the development of NFT . The theFinally, the glutamate hypothesis is based on the truth that cognitive disability in AD is closely related to synaptic plasticity, and that N-methyl-D-aspartate receptor (NDMAR) plays a key role . ExcitatCurrently, it is reported that about 24 million people worldwide are living with AD. Alzheimer’s disease has become a public health problem, but before June 2021, there were only two types of medicines have been permitted to treat AD patients, including cholinesterase enzyme inhibitors  and NMDAR antagonists . The patA common kind of drugs for curing of mild to moderate AD and related dementias is cholinesterase inhibitors (ChEIs) . TacrineDonepezil is a second-generation reversible AChEI drug that is also used to treat patients with mild to moderate AD . Its mecRivastigmine is a reversible dual inhibitor of AChE and BChE in a slow treatment speed. There are two ways of administration: oral and transdermal. It is approved by FDA that oral dosage form of rivastigmine is used for treating mild to moderate AD. The optimum therapeutic dose is 6–12 mg/day . GastroiGalantamine, as a standard first-line drug, is used for treating mild to moderate AD. GAL is a selective tertiary isoquinoline alkaloid with a dual mechanism of competing with acetylcholine receptor α-subunit to prevent it combine with acetylcholine inhibitors and to activate acetylcholine . AdverseMemantine, which is an antagonist of the NMDAR, is an FDA-approved prescription drug for the treatment of moderate-to-severe Alzheimer’s disease . The druAducanumab, with the structural formula shown in Sodium Oligomanne Capsules (GV-971) is a low molecular acid oligosaccharide compound prepared from the extract of marine brown algae . In non-Alzheimer’s disease is a chronic disease, and patients usually require long-term medication. For patients on long-term medication, therapeutic effects may be limited (in a fixed dose regimen) due to neurobiological adaptation and drug tolerance, promoting the need increase the dose further. Therefore, lowering the drug dose as much as possible while still achieving the therapeutic effect can reduce the possibility of induced toxicity. Combination drug therapy may be a good method . Hafsa ACurrently, there is no specific drug that can treat AD. Therefore, the development of new specific drugs is an urgent problem to be solved. The huge number of marine organisms can produce a large number of natural products with unique structures, some of which have neuroprotective effects and may be used for AD treatment. At the same time, the successful marketing of GV-197, which was made from marine brown algae extracts in China, shows us the bright prospect of marine biological ingredients as the treating drugs of AD.Marine natural products have increasingly allured great scientific interest since they can show significant biological activity 10 times higher than terrestrial organisms . ThroughPolysaccharides are polymeric carbohydrates formed by the combination of sugar chains and glycosidic bonds with at least ten or more monosaccharides with high molecular weight . So far,2+ responses of neurons [2+ may go in front of the wound and put the neurons to death. Studies have indicated that high attention of fucoidan can cause and prevent the dying of dopaminergic neurons in vivo and in vitro models [Fucoidan A is a so neurons . The supo models ,78. Fucoo models ,79. So, o models . The como models .2O2 and FeSO4, and found that chitosan treatment could inhibit the death of NT2 neuron cells induced by oxidative stress. Moreover, the formation of Aβ in NT2 neurons pretreated with chitosan was significantly lower than that in control cells. The results showed that the Aβ level could controlled by treatment with this chitosan, suggesting that chitosan had a certain protective effect on AD. Yoon et al. synthesized COS derivatives with different substituents. Among the three COS derivatives, Diethylamino-ethyl COS (DEAE-COS) has the strongest AChEIs activity [Chitosan B, calledactivity . The resactivity . Numerouactivity ,88. So factivity . TherefoMannan C is a poPolyphenols are a sort of neuroprotective compound that consist of aromatic ring and one or more phenolic rings in natural plants ,93. AlgaCurrently, drugs used to treat AD work mainly by inhibiting acetylcholinesterase, so the discovery that phlorotannins including dieckol, eckol, and 8,8′-bieckol have an inhibitory effect on BACE-1 enzyme may improve medication and treatment for AD patients ,97. Liu Marine sterols are sterol compounds produced by organisms in ocean. They are the commonest natural organic compounds in the ocean . Marine sterols such as fucosterol E have thS. horneri and evaluated for its effect on cognitive impairment in vivo and its ability to inhibit some key enzymes in vitro by Lin et al. [Carotenoids are a kind of significant pigments in natural world, which extensively exist in animals, plants, fungus, and algae  ,105. Then et al. . It was n et al. ,106. Anon et al. ,108. Then et al. . In addin et al. . Lycopenn et al. . In vitrn et al. . The resn et al. . There aPhlegmariurus carinatus [Trichoderma sp. has a potential anti-inflammatory effect [Diterpenes are terpenoids with four isoprene units which broadly exist in terrestrial and marine organisms . Researcarinatus . Harziany effect .Alkaloids are a kind of alkaline compounds containing nitrogen that exist in nature, mainly in plants, animals and algae. In the ocean, marine macrocyclic alkaloids mainly manzamines I, 3-alkyAmino sulfonate compound is a kind of compound matter that takes the place of hydroxyl group in sulfuric acid and belongs to the sulfur containing protein. For example, homotaurine K, obtainA. ostenfeldii) [Marine toxins are naturally toxic chemicals from the ocean environment . Nereistnfeldii) . The toxnfeldii) . The mecnfeldii) . It was nfeldii) . The mainfeldii) . This wanfeldii) . It coulnfeldii) . Anatoxinfeldii) . In vitrnfeldii) . TherefoThe macrolide caniferolide A M is a kiClinicalTrials.gov identifier NCT02221947) with no serious adverse events and positive results [Bryostatin 1 is a macrolide compound with high oxygen structure, isolated from the marine invertebrate Bugula neritina, which can be used as an effective regulator of protein kinase C (PKC) . It can  results . Bryosta results . TherefoIn 2018, the Alzheimer’s Disease International estimated that around 50 million people worldwide have dementia, a figure expected to triple by 2050, with two-thirds living in low-and middle-income countries . AlzheimSargassum fusiforme can only reach 6.36% [The development of MTDLs also provides opportunities for the development of drugs with marine compounds as the main components. It can be seen from ch 6.36% . Translach 6.36% . It is gch 6.36% ,154,155.ch 6.36% ,158,159,ch 6.36% ,161. Bioch 6.36% . The disTherefore, it can be seen that marine resources offer us a huge library of potential research drugs. Marine natural molecules can be used as lead compounds for the development of drug candidates against AD. In order to ensure that drug development has a promising research progress and provide good opportunities and application prospects in the biomedical field, it is necessary to further exploration of molecular mechanisms, toxicity and side reaction of active ingredients, along with the development of in vivo and in vitro researches, are vital to the development of novel drugs for the treatment of AD, and we need describe their health implications . In concThis review examines the pathogenesis of Alzheimer’s disease in brief and emphatically introduced various marine compounds with the potential to treat Alzheimer’s disease. The literature shows that marine compounds are a cost-effective and environmentally friendly resource with high biomedical potential. Sodium oligomanne capsules (GV-971), an acidic oligosaccharide compound prepared from the extract of marine brown algae, was successfully applied in clinical practice, which also indicates the drug value of marine natural compounds. Nevertheless, the development of potential drugs is mostly undertaken by academics or small biotechnology laboratories. So, it requires the joint efforts and cooperation of researchers from all disciplines, the active advocacy of government departments, and the trust and cooperation between doctors and patients to accelerate the progress of marine compounds from laboratory to clinical trials. In addition, in order to search for anti-AD compounds of marine origin with significant neuroprotective activity and better understand the potential advantages of the characteristics of various marine organisms and their compounds for the healthy of people, it is necessary to encourage and stimulate more investment in biotechnology to contribute to the more sustainable development and use of these marine resources in the future.


Studies on extracorporeal membrane oxygenation (ECMO) with and without an intra-aortic balloon pump (IABP) for cardiogenic shock (CS) have been published, but there have been no meta-analyses that compare the efficacy of these two cardiac support methods. This meta-analysis evaluated the outcomes of these two different treatment measures.The PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials databases were searched until March 2022. Studies that were related to ECMO with or without IABP in patients with CS were screened. Quality assessments were evaluated with the methodological index for nonrandomized studies (MINORS). The primary outcome was in-hospital survival, while the secondary outcomes included duration of ECMO, duration of ICU stay, infection/sepsis, and bleeding. Revman 5.3 and STATA software were used for this meta-analysis.P < 0.0001). However, there were no significant differences in the duration of ECMO , duration of ICU stay , incidence of infection/sepsis , or bleeding  between the two groups of patients with CS.In total, nine manuscripts with 2,573 patients were included in the systematic review. CS patients who received ECMO in combination with IABP had significantly improved in-hospital survival compared with ECMO alone (OR = 1.58, 95% CI = 1.26–1.98, ECMO combined with IABP can improve in-hospital survival more effectively than ECMO alone in patients with CS. Low cardiac output and hypoperfusion are highly associated with multiorgan damage and are typical manifestations of cardiogenic shock (CS). Moreover, treating CS is challenging for the attending doctors in the intensive care units (ICUs) . CardiogECMO has been frequently used to treat CS in patients with myocardial infarction, explosive myocarditis, and sudden cardiac arrest –5. DurinPubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials databases were used in the retrieval process. A combination of ECMO, intra-aortic balloon pump, and cardiogenic shock were the medical subject headings (MeSH) keywords that were searched in the English language articles. All literature in the database was searched until March 2022. The search strategy for PubMed and other databases is described in the Literature inclusion criteria: (1) patients diagnosed with CS; (2) patients treated with ECMO alone vs. ECMO plus IABP; and (3) intervention studies. Exclusion criteria: (1) meta-analyses, reviews, comments, and letters; (2) literature without basic data; (3) literature with duplicate data; and (4) articles on animal experiments. This systematic review was performed by two authors who have previously published multiple meta-analyses. Each author independently judged whether the retrieved literature could be included in the study, and an additional judgment by a third author was provided in case of disagreement.The methodological index for nonrandomized studies (MINORS) was applied for an in-depth assessment of the quality of the research . The indWe extracted the baseline information of the studies, including authors, publication year, country, age, sex composition, body mass index (BMI), patients with diabetes, hypertension, chronic obstructive pulmonary disease (COPD), prior PCI, prior myocardial infarction (MI), a priori coronary artery grafting (CABG), and several other items. Data that was not directly extracted was obtained by data transformation.I-square (I2) statistic. A funnel map was established to assess publication bias, and STATA 13.0 software was used for sensitivity analysis. P-value < 0.05 was considered a statistically significant difference.Statistical analysis of the data was performed using RevMan 5.3 software. We used the fixed or random-effects meta-analysis model and a forest plot to present the pooled estimates of the odds ratio (OR) or mean difference (MD) and 95% confidence interval (CI). The heterogeneity was evaluated using the Seven hundred and ninety-eight articles were obtained by searching with the proposed criteria. A total of 491 duplicate articles and 187 review-type articles were then excluded by reading the titles and abstracts. A total of 120 articles were included in the next retrieval step, and 101 articles were eliminated after carefully reading the full texts. Ultimately, a total of 19 articles were carefully investigated, and 10 of them were excluded because they were not intervention studies . The flo2; 9–43% had diabetes; 4–66% had hypertension; 1–14% had COPD (chronic obstructive pulmonary disease), and 8–65% had MI . The indications for ECMO/IABP included myocarditis, dilated heart disease, acute heart failure, and so on  in the patients with CS   . A 10-ye< 0.005) . MultiplThe duration of ECMO and ICU stay were related to the prognosis of CS patients. Omar et al. proved that the duration of ECMO was an independent predictor of intracranial hemorrhage during ECMO support. They believed that the longer the ECMO duration, the higher the probability of intracranial hemorrhage . Data frInfection or sepsis may lead to fever and increase the burden on the circulatory system. Allou et al. found that 17.7% of patients developed cannula-related infections, including Enterobacteriaceae (38%), and Staphylococcus spp. 28.2%), and Pseudomonas aeruginosa (18.3%) . Yun et .2%, and Bleeding and thrombotic complications during ECMO have a significant impact on patient outcomes . OptimalPotential limitations existed in the process of this meta-analysis. First, all the patients had pre-existing conditions, with different diseases and different levels of lactic acid, which may have affected the outcomes of the study. Moreover, there was no particular order in which the IABP and ECMO were placed, which resulted in heterogeneity. Second, the nine articles were authored from different continents like America, Europe, and Asia, which may have affected the outcomes for the CS patients. Different race populations may have different responses to the same treatment. Third, all patients had different causes of CS and various degrees of myocardial injury and elevated blood lactic acid that occurred before treatment with ECMO or IABP. Fourth, the definition of bleeding may vary in different trials. We did not perform a subgroup analysis of bleeding because of insufficient data. Fifth, the nine studies were not randomized controlled trials but were same-period nonrandom control trials, which may have had an impact on the outcomes. Although there were no RCTs in the clinical intervention study of the combination of ECMO and IABP, we believe that it was reasonable to choose additional IABP therapy according to the patient's clinical needs rather than random selection.This study showed that ECMO combined with IABP could be more effective in improving survival in patients with CS than ECMO alone.The original contributions presented in the study are included in the article/This study was designed by JZ and PZ. PZ and CY contributed data to the paper and statistical analysis. Interpretation of data were performed by PZ. All authors were involved in the drafting and revision of the manuscript and the final version to be published.This work was supported by the National Natural Science Foundation of China (82070372 and 82170418) and Hubei Province's Outstanding Medical Academic Leader Program.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Postoperative delirium (POD) is a common and serious adverse event of surgery in older people. Because of its great impact on patients' safety and quality of life, identification of modifiable risk factors could be useful. Although preoperative medication intake is assumed to be an important modifiable risk factor, the impact of anticholinergic drugs on the occurrence of POD seems underestimated in elective surgery. The aim of this study was to investigate the association between preoperative anticholinergic burden and POD. We hypothesized that a high preoperative anticholinergic burden is an independent, potentially modifiable predisposing and precipitating factor of POD in older people.Between November 2017 and April 2019, 1,470 patients of 70 years and older undergoing elective orthopedic, general, cardiac, or vascular surgery were recruited in the randomized, prospective, multicenter PAWEL trial. Anticholinergic burden of a sub-cohort of 899 patients, who did not receive a multimodal intervention for preventing POD, was assessed by two different tools at hospital admission: The established Anticholinergic Risk Scale (ARS) and the recently developed Anticholinergic Burden Score (ABS). POD was detected by confusion assessment method (CAM) and a validated post discharge medical record review. Logistic regression analyses were performed to evaluate the association between anticholinergic burden and POD.POD was observed in 210 of 899 patients (23.4%). Both ARS and ABS were independently associated with POD. The association persisted after adjustment for relevant confounding factors such as age, sex, comorbidities, preoperative cognitive and physical status, number of prescribed drugs, surgery time, type of surgery and anesthesia, usage of heart-lung-machine, and treatment in intensive care unit. If a patient was taking one of the 56 drugs listed in the ABS, risk for POD was 2.7-fold higher  and 1.5-fold higher per additional point on the ARS .Preoperative anticholinergic drug exposure measured by ARS or ABS was independently associated with POD in older patients undergoing elective surgery. Therefore, identification, discontinuation or substitution of anticholinergic medication prior to surgery may be a promising approach to reduce the risk of POD in older patients. Delirium is a neuropsychiatric syndrome defined by acute decline and fluctuation of attention, cognitive function, and disturbance of awareness . EspeciaAssuming that delirium might be precipitated by an imbalance in cerebral neurotransmission specifically including acetylcholine deficiency , drugs wThis study is based on a secondary analysis of data collected from 1,470 patients between November 2017 and April 2019 for the PAWEL-Study . The complete protocol for this randomized, prospective, multicenter study has been described in detail previously . BrieflyDemographic and clinical data were collected at baseline, no more than 3 weeks before the scheduled surgery, including medical history by Charlson Comorbidity Index , cognitiEach patient's medication was analyzed on admission using the medication list and personal medical history. Long-term medications as well as “as-needed” (“PRN”) medication were included in the analysis if they were taken more than 3 days a week. In view of the high proportion of “over-the-counter”-drugs, the use of sleeping pills was explicitly queried. Preoperative anticholinergic burden was calculated for each patient using the Anticholinergic Risk Scale [ARS ]. BrieflPrimary outcome measure was the occurrence of POD after elective surgery. POD was evaluated daily for up to 7 postoperative days by independent and previously trained assessors , 12 usin2 test and for non-normally distributed continuous variables by Mann-Whitney U test. Logistic regression analysis was used to investigate the independent association of preoperative anticholinergic burden and the incidence of POD . First, univariate logistic regression was performed for both, ARS and ABS. In a second step, the model was adjusted for items that were found to be strong confounders in previous studies . Another group of 377 patients (37.5%) received cardiovascular interventions with or without cardiopulmonary bypass. The remaining 88 patients (9.8%) underwent general surgery . Surgeries were mostly performed under general anesthesia .The sociodemographic and clinical characteristics of all 899 patients aged 70 and older are described in p < 0.001), had more comorbidities (p = 0.004), and revealed a lower MoCA level at baseline assessment (p < 0.001). Furthermore, patients with POD had a longer surgery time (p < 0.001), and were admitted to an intensive care unit more often (p < 0.001). POD occurred significantly more often in patients requiring cardiopulmonary bypass (p < 0.001). General anesthesia was performed more frequently in patients with POD (p = 0.023). POD and non-POD groups did not differ statistically in Body Mass Index, educational level, Barthel Index, preoperative depression, anxiety or treatment with benzodiazepines (see POD was observed in 210 (23.4%) patients. Patients diagnosed with POD took significantly more medications (ines see .p = 0.004). Evaluating medication according to ABS criteria, 71 patients (8%) were taking DAPs. Comparing the POD and non-POD groups, the rate of DAPs was significantly higher in patients with POD . The most frequently prescribed DAP in both groups (according the ABS criteria) was amitriptyline (n = 8 in each group) followed in the delirium group by doxepine (n = 4) and solifenacin (n = 3). In patients without POD, trospium (n = 7) and trimipramine (n = 6) were the most commonly used DAPs, in addition to amitriptyline. The top 10 DAPs prescribed are shown in Using the ARS score, 81 patients (9%) were taking at least one anticholinergic drug. Patients with POD had a significantly higher ARS value than patients without POD  was relatively small in our study population, we found significant group differences. This was the case when ARS was used and when ABS criteria were applied. In the subgroup of 71 patients who received one or two ABS drugs, the POD rate was 42.3% (n = 30/71) and thus almost twice as high as in the group without ABS medication where POD occurred in only 21.7%  and corresponding 95% confidence intervals (CI) are provided in One of the confounding variables we included in the adjusted regression analysis  was the Preoperative anticholinergic medication exposure was assessed by two different scales estimating the overall anticholinergic burden, the weighted ARS and the more recent ABS. The findings of this study suggest that anticholinergic medication usage might be an independent risk factor for POD in older population undergoing elective surgery. The reduction or omission of these drugs preoperatively might thus be beneficial for the prevention of POD.n = 651)  . Yet, inn = 651)  to detern = 651) , 44. Rean = 651) . This len = 651) . Therefon = 651) , Australn = 651) , Taiwanen = 651) , palliatn = 651)  and acutn = 651) , 40, makn = 651) . In contn = 651)  and the n = 651) . Pasina n = 651) . HoweverAs mentioned above, to our best knowledge, this is the first study using the ABS to explore the effect of DAPs on delirium. In comparison to the ARS, ORs for occurrence of POD were clearly higher using the ABS than the ARS. Our results suggest a 2.7-fold risk of developing a POD for each drug included in the ABS. Therefore, our findings provide a strong argument for modifiable delirium risk assessment by ABS in older patients scheduled for surgery. The PAWEL study's intervention bundle AKTIVER (Alltags- und Kognitions-Training & Interdisziplinarität verbessert Ergebnis und mindert das Risiko [“everyday skills and cognition training and interdisciplinarity improves outcome and mitigates risk”]) has been shown to reduce delirium by 33% in patients undergoing elective orthopedic and abdominal surgery by daily application of individualized modules on activation, relaxation and diagnostic chaperonage during the hospital stay . In addiThis study has several limitations. First, our approach to measure anticholinergic drug exposure did not include the dosages of DAPs. It is quite conceivable that higher dosages of DAPs have a stronger negative impact on the development of POD. Second, the ARS was developed in 2008 and was not updated since then. This could lead to an underestimation of anticholinergic burden due to an abandonment of newer DAPs. Third, we collected our information from patients' medication lists and verbal information but had little information about adherence to prescriptions prior to hospital admission. Finally, we did not consider delirium severity and duration in this study. The strengths of our study are the prospective multicenter study-design, the large number of patients and the usage of two different tools to measure anticholinergic burden. In addition to the established ARS as a weighted score, we used ABS as a quick and simple instrument to quantify anticholinergic burden in delirium patients for the first time. A further strength is the relatively high number of strong confounders like cognition included in our multivariable regression analysis.This study of 899 older patients undergoing various elective surgical procedures shows that the preoperative anticholinergic burden, assessed by ARS or ABS, is an independent risk factor for POD in older patients. Delirium occurrence was more than 2.7 times higher if a patient took at least one of the 56 drugs listed in the ABS , even afThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study was approved by the Ethics Commission of the Faculty of Medicine of the Eberhard-Karls University and University Hospital Tübingen with number 233/2017BO1 on October 12, 2017 and by the Ethics Commission of the University of Potsdam with number 38/2017 on December 11, 2017. The study was registered on the German Clinical Trials Register (DRKS-ID: DRKS00012797) in July, 2017. The patients/participants provided their written informed consent to participate in this study.MH, CT, and GE designed this secondary analysis of the PAWEL-Study, planned the data collection, performed the statistical analysis, and prepared and revised the manuscript. CB, CM, FK, EM, SW, LC, BF, MR, CA, and MD were involved in data collection and critically revised the manuscript for final approval of the version to be published. All authors contributed to the article and approved the submitted version.This study was funded by the Innovationsfonds , which had no role in the design of the study and had no role either during its execution, analyses of the data, or in the decision to submit any results. We acknowledge support by the Open Access Publication Fund of the University of Freiburg.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study aimed to assess the relationship of serum uric acid with metabolic syndrome and its components in Tibetan adults on the Tibetan plateau.A total of 307 participants were enrolled in this study and biochemical parameters including serum uric acid, fasting plasma glucose, white blood cell, lymphocyte count, mononuclear cells, alanine aminotransferase, aspartate aminotransferase, creatinine, and lipid profile were analyzed using standard methods. The IDF criteria were applied to define metabolic syndrome. The association of serum uric acid with metabolic syndrome and its components was evaluated by multivariable logistic regression models.p >0.05). After adjusting for the confounding factors, hyperuricemia is positively associated with abdominal obesity , elevated blood pressure , and elevated triglycerides.The overall prevalence of metabolic syndrome was 17.3% (53/307) with 19.6% (31/158) in females and 14.8% (22/149) in male participants. The prevalence of hyperuricemia was 40.7% (125/307) with significant differences between the male  and female  groups. In regression analysis, we observed that the risk of MetS was higher in participants in the hyperuricemia group  compared with those in the normouricemia group. After adjusting for all confounding factors, a 9% higher risk of MetS could be shown in participants with SUA increased per 10umol/L . These relationships were not affected by sex or age (In our study, hyperuricemia is significantly associated with the prevalence of metabolic syndrome and part of its components, and these relationships are not affected by sex or age. Given the high prevalence of MetS and hyperuricemia among Tibetan adults, more studies are required to explore the role of SUA in the pathogenesis of MetS. Individorldwide . The preorldwide , and theorldwide . 8.2% ofSerum uric acid (SUA) is the catabolic product of exogenous dietetic compounds and endogenous purines . Recent 2, and self-reported history of severe liver disease. The detailed flow chart about participant recruitment was shown in This study was a cross-sectional design conducted between November 2019 and February 2020 at the Department of Health Management Centre of the Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region. The inclusion criteria were: aged above 18 years, born and living in the Tibetan plateau, free from gouty arthritis and cancers, free from severe chronic illness, and willing to participate. Exclusion criteria were: pregnant women, lactating mothers, subjects with missing or erroneous information on covariates, estimation of glomerular filtration rate(eGFR)<=60 mL/min/1.73m2 (kg/m2). Blood pressure was measured twice using a digital sphygmomanometer according to the standard protocol in a sitting resting position after at least 5 min of rest, and the average is calculated. Waist circumference (WC) was measured using general tape that was placed midway between the lowest border of the ribs and the iliac crest. The smoking status was determined by “Current or former smoker”, and the alcohol consumption was assessed by “Current or former alcohol drinker”.A standard questionnaire was used to collect demographic and lifestyle information from the participants. Individual anthropometric data such as age, sex, weight, and height were recorded in the hospital’s electronic medical record system. Briefly, Anthropometric data were collected during the visit for the physical examination of the participants. Weight and height were measured according to the recommendations of the World Health Organization, with an accuracy to the nearest 0.1 kg and 0.1 cm respectively, with the participants in lightweight clothing without shoes. BMI was calculated as weight/heightBlood samples from participants who underwent overnight fasting were collected in the morning and analyzed within an hour in the hospital. The hepatic parameters include alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, the renal parameters including creatinine (Cr), the lipid parameters including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), Fasting plasma glucose (FPG), and SUA were measured by an automatic biochemical analyzer (HITACHI 7180). The hematological parameters including white cell count (WBC), lymphocyte count (LYMH), and mononuclear cells were detected by automatic flow cytometry. The eGFR is calculated by the following formula :The diagnostic kits for hematological parameters were purchased from Shenzhen Myriad Biomedical Electronics Company and diagnostic kits for biochemical parameters were purchased from Meikang Biotechnology Company for analysis of the above clinical parameters. The measurements were carried out according to the standard manufacturer’s protocols provided within the kit. The precision of the measurements was maintained regularly by method standard calibration.In the present study, hyperuricemia was defined as SUA concentration >420 µmol/L in men or >360 µmol/L in women . MetS wat-test or rank-sum test was applied to assess continuous variables between the two groups, as appropriate. Multivariable logistic regression analyses  were performed to assess the independent association between SUA and MetS prevalence, and between SUA and MetS components. We applied three models in the regression analysis. Multivariable models were adjusted as follows: model1 was not adjusted; model2 was adjusted for age, and sex; model3 was adjusted for age, sex, WBC, albumin, and TC. To verify the stability of our results, we performed a multivariable logistic regression analysis after diagnosing MetS according to the NCEP-ATP III diagnostic criteria  and Free Statistics software version 1.5 , while continuous data were presented as the mean ± standard deviation or median (interquartile range), as appropriate. The differences in categorical variables between the two groups were detected by the Chi-square test or Fisher exact test as appropriate. The student criteria . Subgrousion 1.5 . A two-tp < 0.05) for all cases) between the normouricemia and hyperuricemia groups.In total, 307 consecutive general adults  were enrolled from Tibetans undergoing medical examination at the Health Management Centre. The baseline characteristics of the participants in the normouricemia and hyperuricemia groups are presented in p <0.01 for all cases), but elevated triglyceride and elevated blood pressure were significantly higher in males than in the female subjects. The prevalence of hyperuricemia was 40.7% with significant differences between the male (53.7%) and female (28.5%) groups (p<0.001). In addition to reduced HDL-C, other components of MetS were significantly higher in subjects in the hyperuricemia group compared to the subjects in the normouricemia group .The prevalence of MetS and its components are presented in Multivariable logistic regression was performed to assess the relationship between SUA and MetS. The detailed results are presented in p > 0.05).After diagnosing Mets using the NCEP-ATP III diagnostic criteria , we condIn this retrospective study among the general population who underwent routine physical examination, we discovered that hyperuricemia as well as the increase of SUA level was positively associated with the presence of MetS. Among the components of MetS, hyperuricemia is only positively associated with elevated blood pressure, elevated TG, and abdominal obesity. Although, the association of SUA with MetS has been studied in different disease states and different ethnic groups , 25–29, Our findings indicated that hyperuricemia is positively associated with MetS after adjusting for other covariates, and the association did not differ by sex and age. This finding was consistent with previous studies , 27, 30.The present study further showed that hyperuricemia was signifficantly associated with MetS-related variables such as elevated blood pressure, abdominal obesity, and elevated TG but not elevated fasting glucose and reduced HDL-C, which is slightly different from other studies. Many studies have demonstrated a strong association between SUA and various MetS-related components, but the association could be differed by study objects , 34, 35.The unstandardized overall prevalence of MetS in our study was 17.3%, which was greater than the prior prevalence among farmers and herders in Lhasa 8.2%) and Tibetans on the Qinghai plateau (8.0%) .2% and T. It was The prevalence of components such as abdominal obesity (46.3%) and reduced HDL-C (65.5%) was elevated significantly than elevated blood pressure 22.8%) and elevated fasting glucose (7.5%). These findings were similar to those from Bangladesh , but not% and eleIn the present study, the mean concentration of serum uric acid was 374.8 ± 90.0 umol/L, hyperuricemia was more manifest in male subjects, which is similar to previous studies , 34. TheThe clinical value of this study is as follows: (1) To our best knowledge, the independent association of hyperuricemia with MetS has not been developed in Tibetans on the Tibetan plateau, and our study found that hyperuricemia was significantly associated with MetS; (2) The findings of this study should be helpful for future research on the establishment of diagnostic or predictive models of metabolic syndrome in Tibetan populations.Our study has some strengths: (1) This study is an observational study and therefore susceptible to potential confounding. We used strict statistical adjustment to minimize residual confounders. (2) We handled the target independent variable as both a continuous variable and a categorical variable. Such an approach can reduce the contingency in the data analysis and enhance the robustness of results; (3) Our multi-model adjustments during regression analysis showed that our results were stable; (4) We used another diagnostic criterion (NCEP-ATP III) to define MetS and showed stable results after multi-model adjustments; (5) Our study extends these findings by showing association of hyperuricemia with MetS in Tibetans on the Tibetan plateau.2, self-reported history of severe chronic illness, and pregnant and lactating women, therefore, the findings of this study cannot be used for these people. Third, we adjusted possible confounders to determine the relationship between SUA and MetS, but the influence of other unmeasured confounding factors could not be ruled out. For example, dietary intake can affect SUA levels, and physical activity can affect weight and blood pressure. But we have no information on the precise quantity of dietary intake and physical activity, future studies may consider collecting this information to explore the effects of dietary intake and physical activity on the relationship between hyperuricemia and MetS. Furthermore, these results are from a single center, and the interpretation of the finding of all Tibetans on the Tibetan Plateau may be limited. Finally, as a cross-sectional study design, it has less power to infer the causal relationship between serum uric acid and metabolic syndrome. Thus, additional prospective studies are needed to verify these findings in the future.This study has some limitations. First, although the sample size in the present study was relatively small, however, we performed multiple sensitivity analyses to ensure the robustness of the results. Second, according to our inclusion and exclusion criteria, we exclude Age<18 years, eGFR<60 mL/min/1.73mIn our study, hyperuricemia was significantly associated with the prevalence of MetS, and these relationships were not affected by sex or age. We also found that hyperuricemia was signiffcantly associated with MetS-related variables such as abdominal obesity, elevated blood pressure, and elevated triglycerides but not elevated fasting glucose and reduced HDL-C. Given the high prevalence of MetS and hyperuricemia among Tibetan adults, more studies are required to explore the role of SUA in the pathogenesis of MetS.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by The Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region ethics committee. The patients/participants provided their written informed consent to participate in this study.SY participated in the design of research schemes, collect and sort out data, and wrote the main manuscript text, and YZ, QZ, SB, HF, WG assist in data collection and LX participated in the design of research schemes. All authors contributed to the article and approved the submitted version.This study was supported by the hospital-level research project of the Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region Chengdu, China (grant number:2019-YJ-3).We thank Free Statistics team for providing technical assistance and valuable tools for data analysis and visualization. We thank Dr. Liu Jie  and Dr. Yang Qilin  for helping in review and comments regarding the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Objective To determine the prevalence and possible variables associated with anal intraepithelial neoplasia and anal cancer in immunocompetent women with high-grade cervical intraepithelial neoplasia.Methods A cross-sectional study involving immunocompetent women with a histological diagnosis of high-grade cervical intraepithelial neoplasia and cervical cancer, conducted between January 2016 and September 2020. All women underwent anal cytology and answered a questionnaire on characterization and potential risk factors. Women with altered cytology were submitted to anoscopy and biopsy.Results A total of 69 women were included in the study. Of these, 7 (10.1%) had abnormal anal cytology results: . Of the anoscopies, 3 (42.8%) showed alterations. Of the 2  biopsies performed, only 1 showed low-grade anal intraepithelial neoplasia. The average number of pregnancies, vaginal deliveries, and abortions was associated with abnormal anal cytology. However, the highest mean regarding the cesarean sections was associated with normal cytology.Conclusion The prevalence of anal intraepithelial neoplasia was compatible with data from recent studies, especially those conducted in Brazil. Opportunistic screening for anal intraepithelial neoplasia in this high-risk population should be considered. Anal cytology is suitable for this purpose, due to its low cost and feasibility in public health services. Anal cancer is a rare occurrence in the general population, but its incidence and mortality have been progressing worldwide since 1975, reaching 1 to 2 per 100 thousand individuals. In women, the prevalence is even higher: 2.06 per 100 thousand individuals.There is strong evidence indicating that persistent infection with an oncogenic type of human papillomavirus (HPV) is a necessary condition for the development of cervical cancer, and it is one of the factors associated with the increased incidence of squamous cell carcinoma in other regions of the lower genital tract, particularly the anal canal.Other risk factors for anal cancer include: infection by the human immunodeficiency virus (HIV), being a homosexual man, engaging in receptive anal sex, the number of lifelong sexual partners, smoking, and a history of squamous cervical intraepithelial neoplasia.Guidelines for the screening of premalignant anal lesions have not yet been standardized.Currently, anal cytology is the main screening method for anal cancer.To date, most studies have focused on men who have sex with other men and people with HIV,Patients of the Lower Genital Tract Pathology and Colposcopy Service of the Gynecology Department at Hospital Universitário da Universidade Federal de Juiz de Fora (HU-UFJF) with a histological diagnosis of high-grade cervical intraepithelial neoplasia (glandular or squamous) or cervical cancer between January 2016 and September 2020 were invited to participate in this cross-sectional study.The exclusion criteria were as follows: HIV infection, current pregnancy, previous or current pelvic radiotherapy, previous or current colorectal cancer, presence of anal tumor on digital rectal examination, and use of immunosuppressive drugs.All women underwent anal cytology. They also answered a questionnaire, through a brief interview, about their main sociodemographic characteristics, sexual and reproductive history, and life habits.Anal cytology was performed using an endocervical brush introduced up to 4 cm into the anal canal, with 360° rotation. The material was placed on a glass slide and a liquid alcohol-based fixative was applied to it. The HU-UFJF Pathology Service analyzed all samples using Papanicolaou staining. All cytological specimens were processed on glass slides  and analyzed by the same pathologist.The results followed the nomenclature recommended by the Bethesda System for Reporting Cervical Cytology: low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells –cannot exclude HSIL (ASC-H), squamous cell carcinoma (SCC) or adenocarcinoma in situ (AIS). Unsatisfactory results were repeated according to the patients' agreement.Patients with abnormal anal cytology were subsequently submitted to HRA. Before the HRA, a digital rectal examination (DRE) was performed to identify possible tumors, stenosis or thickening in the anal canal, which would contraindicate the HRA. All examinations were performed by the same experienced professional. In the HRA, the anal canal is visualized with image magnification through a colposcope, a device similar to a binocular microscope, which has a magnifying lens and a light focus, in an attempt to identify anal lesions. A rigid speculum, the anoscope, is introduced in the anus, and a diluted acetic acid solution (at 5%) is applied to observe the transformation zone between the columnar epithelium of the inferior rectum  and the squamous epithelium of the anal canal  and look for lesions, in a manner homologous to gynecological colposcopy. Then, to refine the examination, an iodine-iodide solution (Schiller solution) was also applied. Finally, all suspicious areas were submitted to biopsy at the same time as anoscopy and sent to the laboratory for analysis.Patients with a histological diagnosis of anal lesions were referred for multidisciplinary follow-up at the Proctology Service of the hospital.The present study was approved by the Ethics in Research Committee of HU-UFJF.Descriptive statistics (absolute and relative frequencies) and central tendency  were presented. The measures of prevalence of anal lesions and their association with sociodemographic, clinical, reproductive and lifestyle variables were studied using the Chi-squared test. The agreement between the diagnostic methods of anal cytology and anoscopy was performed through the Kappa analysis.p < 0.05 were considered statistically significant.The statistical analysis was performed using the Statistical Package for the Social Sciences  software, version 21.0, and values ofOf the 82 women who met the inclusion criteria and agreed to participate, 69 were included in the study, as shown inp = 0.01). The mean number of vaginal deliveries was also higher in the altered anal cytology group (2.14 ± 1.95) compared with the group without alteration (0.98 ± 1.24) (p = 0.05), as well as the mean number of spontaneous abortions . In contrast, the highest mean number of cesarean sections was associated with the normal anal cytology group . The association of cytology and anoscopy results is shown inAmong the 69 patients, 7 (10.1%) showed changes in the result of the anal cytology. The most prevalent changes were ASC-US, ASC-H and HSIL . Of the performed anuscopias, 3 (42.8%) showed changes, representing 4.3% of the total of patients. Only two biopsies were performed, since one of the patients was pregnant at the time of the examination, and we decided to postpone the biopsy until after delivery. One biopsy showed normal results, and the other showed low-grade intraepithelial neoplasia. Anal cancer was not found. There was no statistically significant difference between the normal and altered anal cytology groups in relation to sociodemographic variables, lifestyle, presence of itching or anal bleeding, sexual behavior, and age at the first sexual intercourse. There were differences between both groups in relation to all gestational variables. The mean number of pregnancies was higher in the altered anal cytology group (2.57 ± 2.63) than in the normal anal cytology group (1.66 ± 1.44) , a prevalence considerably higher than that reported among American women between 15 and 44 years of age 33.2%)..2%.33HNo association was found regarding abnormal anal cytology and other variables, such as smoking, drinking, use of illicit drugs, use of condoms, number of sexual partners, and presence of pruritus or anal bleeding, which is in line with similar studies.In general, the result of the HRA was normal in 57.1% of the cases of altered cytology. The decrease in agreement between the examinations can be explained by certain factors. In the anal canal, there is an extensive squamous-columnar junction associated with deep crypts that enable cytology to identify lesions that remain imperceptible to HRA, leading to false-negative results.The only case of biopsy-proven anal intraepithelial neoplasia, a low-grade neoplasia, came from a low grade anal cytology, which corroborates the hypothesis that anal cytology is less discriminating regarding high-grade lesions.Although there is no data yet that demonstrates that the identification and treatment of high-grade anal squamous intraepithelial neoplasia leads to a reduced risk of developing anal cancer, a recent reviewOne of the limitations of the present study was that only patients with abnormal anal cytology were submitted to HRA. The literatureThe prevalence of 10,1% of intraepithelial neoplasia found in the present study was compatible with the prevalence found in recent studies. Parity and the numbers of vaginal deliveries and abortions were associated with abnormal anal cytology. The number of cesarean sections was associated with normal cytology. Despite being uncommon findings, they are associated, in Brazil, with income inequality and poor access to health services, reflecting a pattern already known for cervical intraepithelial lesions and cervical cancer. This reinforces the need for greater medical care for this population, that is most vulnerable to the effects of HPV. Opportunistic screening for anal intraepithelial neoplasia in patients with high-grade cervical intraepithelial neoplasia should be considered, especially in immunocompetent women. The study showed that anal cytology proved to be an adequate test for screening, mainly due to its low cost and availability in the public health service. Although the agreement between the diagnostic methods has been shown to be weak, anal cytology at least enables the identification of HPV-induced lesions, facilitating referral to anoscopy and biopsy. It also promotes public awareness and education regarding a problem that was previously ignored.


Bovine viral diarrhea virus (BVDV) causes reproductive inefficiencies and negatively impacts the economy of low- and middle-income countries (LMICs). It is characterized by a combination of syndromes that result in poor production performance and calf morbidity and mortality. BVDV control is possible by introduction of biosecurity measures, test-and-cull, and vaccination programs as accomplished in high-income countries. Knowledge of BVDV epidemiology is limited in many LMICs, which hinders implementation of effective control programs. We carried out a systematic review and meta-analysis to estimate the burden of BVDV, identify risk factors related to its occurrence, and health and economic impacts on production systems.Relevant BVD articles were collated from library databases; 690 abstracts and full texts were found in an initial search followed by filtering of 59 manuscripts. We accounted for quality and risk of bias in the meta-analysis. Prevalence, exposure, and current infection at regional, production, and farming system levels were estimated using logistic random-effects meta-regression models. Finally, we calculated the proportion of studies that addressed risk factors and health and economic impacts across different production systems to inform future preventative strategies in LMICs.Seroprevalence was high and varied between regions. Mean weighted prevalence was 39.5% (95% CI 25–56.1), 45.2% (95% CI 35.9–54.8), 49.9% (95% CI 25.5–74.3), and 21.6% (95% CI 0.5–56) for sub-Saharan Africa, South America, Middle East, and Asia, respectively. Seroprevalence varied across farming systems, with smallholder farming showing the highest values. Herdsize was the most frequently reported risk factor, and the percentage of articles that reported herdsize as a risk factor were 20.6%, 33.3%, and 38.4% for dairy, beef and mixed systems respectively. Abortion (13.7% of articles) was the main reported health impact in dairy systems. Some articles reported milk drop (4.6% of articles), but no article investigated the economic cost of BVDV in farming systems.Animal-level seroprevalence varied across all regions. Most of the studies focused on BVDV seroprevalence. There were some articles that investigated risk factors and health impacts, and there were even less that investigated economic impacts. Future studies should focus on identifying risk factors and quantifying health and economic impacts across systems. Understanding these aspects is crucial to develop management strategies to apply across diverse production systems in LMICs. Bovine viral diarrhea virus (BVDV) causes a pathogenic infection in livestock, mainly cattle and wild ruminants, with a global distribution , 2 resulFlaviviridae family in the genus Pestiviruses and has 2 main types reported, BVDV-1 and BVDV-2. Recently, there has been a BVDV-3 or HoBi-like virus found in several regions  do not produce antibodies and can only be detected by identifying the virus using either antigen ELISAs or molecular tools such as polymerase chain reactions (PCRs) (Transmission of the disease is mainly driven by presence of persistently infected (PI) animals in a herd or contact with them. PI animals are infected  and 125 , such th and 125 . Animals and 125 , 17. Pres (PCRs) , 85. Mans (PCRs) –11, 19. s (PCRs)  and repos (PCRs) , 21–23. The potential impact of BVDV infection is well-recognized in high-income countries where its epidemiology is well-understood and its economic impacts are well-described and quantified. For example, in North American systems, it has been estimated that infection with BVDV can cost up to US$88/animal in beef herds due to calf mortality which leads to considerable financial losses for individual farmers , 24. AcuSystematic reviews are an important tools for collating data from multiple published studies to improve parameter estimates such as prevalence and to identify research gaps , 29 and This systematic review followed the guidelines and checklist of the PRISMA Group  . SearcheThe search strategy for CAB Abstracts, Embase, Medline, and Global health consisted of search terms and subject headings related to BVD in LMICs according to the 2020 World Bank listing of countries that are LMICs . We usedInclusion criteria were defined based on the population, intervention, comparison, outcomes of an article, and study design framework (known as the PICOS framework), but in case of absence of intervention and comparison groups for PICOS, we also followed the PEO  framework . StudiesWe excluded species that were not cattle , because BVD is predominantly a disease of cattle and they are generally considered to be natural hosts . We exclrobvis traffic light system as outlined by McGuinness et al.  assessment . Assessms et al. .tidyverse  software and spatial libraries sp, sf, ggmap, tmap, and rgdal .Statistical analyses, plotting, and mapping were conducted using the R statistic software , 47 in Ridyverse , meta  can be expressed as a linear model as follows:0 is the intercept, U0j is the random effect for the intercept, and Ck is an addition fixed effect to account for potential heterogeneity by continent. The results of the overall meta-analysis were presented as a forest plot.where robvis traffic light plot , while most countries had very few studies , case-control , or cohort ; in one (1.5%) case, the design was not clear from the description. The majority of the studies reported conducting random (n = 25), purposeful (n = 8), or convenience (n = 8) sampling, with only a few studies designing a multi-stage sampling process (n = 6). Some of the studies did not mention their sampling or selection process. The samples used were mainly serum, bulk tank milk, and animal tissue (ear pinnae tissue “earnotch”). BVDV antibodies or antigens were analyzed by ELISA (n = 50), fluorescent antibody tests (FATs) (n = 3), polymerase chain reactions (PCRs) (n = 7), serum neutralization (SN) or virus neutralization (VN) (n = 8) tests, or virus isolation (VI) (n = 1). Majority of the articles had a combination of various diagnostic tests. Vaccination was not a common practice in most of the study sites reported, and only two studies indicated that routine BVD vaccination was performed.The final set of articles included studies from four regions, Asia, SSA, South America, and the Middle East, and covered 23 individual countries. Brazil had the highest number of studies  reported results of analyses of risk factors, 7 (10.9%) reported results of analyses of health impact, and 3 (4.6%) studies reported analyses of economic impacts of BVD. Only 1 study  reportedOur results show the number of studies that looked at BVD and answered the 11 questions set to address ROB  with a wide variation between regions. The country-level weighted mean seroprevalence range is between 8.2 and 66.4% and is mapped in Weighted means are estimated by production system  and farmOnly nine articles reported prevalence of antigen-positive animals , identifying PI or TI animals. The prevalence of antigen was 7.0%  in Asia, 10.0%  in SSA, 6.0%  in South America, and 9%  in the Middle East .Forty-one studies (64%) reported results of risk factor analyses and the summary is presented in Only seven studies (10.9%) reported on health impacts of BVDV , 59–62. Only 3 (4.6%) studies , 63, 64 The objective of this review was to identify the literature reporting the prevalence of BVDV in LMICs and to summarize the risk factors associated with it, and finally its health and economic impacts. It is generally advised to limit a systematic review to a specific study design to avoid heterogeneity of study types . Our incFrom the final 59 articles from which relevant data could be extracted, there were 64 studies . BetweenThe variations in prevalence at the regional level highlights that there is a significant gap in information across vast parts of the global south where livestock are an important part of many household livelihoods. Based on the weighted meta-analysis using a random-effects model and given this large range in individual study seroprevalence, the regional mean seroprevalence did not vary much across South America, SSA, and the Middle East but appeared to be slightly lower in Asia (21.6%). At the country level, Peru had the highest weighted seroprevalence but with only three studies. The variation may reflect to some extent the importance and scale of cattle keeping in these areas compared to Asia and possibly the lower seroprevalence may be down to a lower cattle density in some parts of Asia. These estimates are similar to the others reported in the literature , 13, 66.In addition to serological surveys, antigen studies also showed the presence of the virus in different regions, suggesting that there is ongoing transmission . Due to In this review, we summarized risk factors based on 41 articles that specifically investigated risk factors. From Age was a frequently studied risk factor in beef and dairy systems. Our results show that there was a variation in directionality of age as a risk factor. Most of the studies indicated that being above 6 months increased the risk of exposure except for one study that reported that there was no association with age . Our revBreed was investigated as a risk factor in proportionally more studies conducted on beef systems than those conducted on dairy and mixed systems . It is dFactors associated with biosecurity and hygiene were risk factors in beef and dairy systems. Farm workers, including veterinarians, milkers and other employees, and being a farm that provides milk to industries were associated with BVDV seropositivity. The high seroprevalence in dairy systems  may alsoExploring the motivations for herd biosecurity, cattle movements, and breeding practices would inform the design and feasibility of future control programs in LMIC settings. For example, when a study in Ireland by Graham et al.  found thThere was little information found in studies on health implications of BVD in LMICs. The health impacts of the disease are the main cause of negative economic impacts . Our revThe review identified that the economic impact of BVD was minimally described and the cost implications were not quantified in production systems in LMICs. The review also highlighted the impact on milk yield in three articles, with all the studies indicating that decrease in milk yield was significantly associated with BVDV infection. The cost implications of BVD have been investigated in many high-income settings, but minimal work has been done in LMICS. Considering the importance of livestock production in livelihood incomes in LMICs, exploring whether BVD is associated with low milk production and poor production outcomes needs to be further investigated.One of our study limitations was the inclusion of studies published only in English and Spanish. This was due to availability of speakers of the English and Spanish languages for data extraction. We excluded articles in languages not English or Spanish, as we believe these may lead to bias to studies conducted by researchers speaking other languages. This could also lead to loss of data from relevant articles that were not conducted in English or Spanish. Another limitation might be the inclusion of all study designs. It is generally advised to limit a systematic review to a specific study design to avoid heterogeneity of study types . We inclIt can be concluded that BVDV is present and circulating in the regions of SSA, Asia, Middle East, and South America, and across various farming and production systems found in these regions; however, the prevalence estimates vary across these regions. The variety of risk factors of epidemiological importance is likely to be linked to various production systems within each locality. Standardized methods of estimating prevalence and the varying prevalence in diverse farming and production systems will need to be considered in trying to offer solutions for disease control strategies. The health and economic impacts associated with BVD are mostly related to reproductive performance but are poorly quantified. Future investigations should focus on quantifying the negative effect of BVD on cattle production systems in LMICs to prioritize and inform future approaches to control.The original contributions presented in the study are included in the article/BZ-S, RK, and BB: writing. BZ-S, LGG, and LH-C: data extraction. LH-C, BB, and BZ-S: statistical analysis. RK, BB, EC, and BZ-S: review and editing. RK, BB, and EC: supervisors. All authors contributed to the article and approved the submitted version.BZ-S was supported by an EastBio PhD studentship funded by BBSRC. BB, LH-C, and EC were supported by the Bill & Melinda Gates Foundation and by a UK aid from the UK Foreign, Commonwealth, and Development Office (Grant Agreement OPP1127286) under the auspices of the Centre for Tropical Livestock Genetics and Health established jointly by the University of Edinburgh, Scotland's Rural College, and the ILRI. LGG was supported by the University of Edinburgh through the Principal's Career Development and the Edinburgh Global Scholarships.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.