bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with knowledge about malaria prevention among women of reproductive age, Tete Province, Mozambique, 2019–2020
Authors: Afai Gerson , Rossetto Erika Valeska , Baltazar Cynthia Semá , Candrinho Baltazar , Saifodine Abuchahama , Zulliger Rose
Published: March 2022

Background

Mozambique is a malaria endemic country with an estimated prevalence of malaria in children 6–59 months old that is twice as high in rural areas (46.0%) as in urban areas (18.0%). However, only 46.0% of women aged 15–49 years had complete knowledge about malaria in 2018. This study aimed to identify the factors associated with malaria knowledge among women of reproductive age in a high malaria burden district.

Methods

Data from a cross-sectional study, using a population-based malaria research study in Mágoe District, 2019, were analysed. This analysis included women aged 15–49 years. A multivariate logistic regression model was developed to determine factors associated with complete knowledge of malaria that calculated adjusted odds ratio (aOR) and 95% confidence interval (CI) at a p < 0.05 significance level. Complete malaria knowledge was defined as when a woman correctly identified: fever as a malaria symptom, mosquito bites as the means of malaria transmission, mosquito nets as a tool for malaria prevention, malaria as curable, and were able to name an anti-malarial.

Results

A total of 1899 women were included in this analysis. There was complete malaria knowledge among 49% of the respondents. Seventy one percent mentioned fever as one of malaria symptoms, 92% mentioned mosquito bite as the cause of malaria infection, 94% identified that mosquito nets prevent malaria, 92% agreed that malaria has cure, and 76% were able to name at least one anti-malarial medicine. In the multivariate analysis, the following characteristics were associated with significantly higher odds of having complete malaria knowledge: having a secondary school or above education level (adjusted Odds Ratio, aOR = 2.5 CI [1.3–4.6] p = 0.005), being from the middle socioeconomic status group (aOR = 1.5 CI [1.1–2.1] p = 0.005), being from older age group of 35–39 (aOR = 1.9; CI [1.1–3.1] p < 0.001), having 1–2 children (aOR = 1.8; CI [1.2–2.6] p = 0.003), and having interviews completed in Portuguese or Cinyungwe (aOR = 2.3; CI [1.3–4.1] p = 0.004 and aOR = 2.1; CI [1.5–2.8] p < 0.001, respectively).

Conclusion

Most women in this study had some malaria knowledge, but gaps in complete knowledge remained. In order to broaden knowledge, educational messages about malaria prevention should be more effectively targeted to reach younger, less-educated women and in non-dominant languages.
Multi-functional self-assembly nanoparticles originating from small molecule natural product for oral insulin delivery through modulating tight junctions
Authors: Jia Xiaohui , Yuan Zhihua , Yang Yuqin , Huang Xuemei , Han Nana , Liu Xiaojing , Lin Xiaoyu , Ma Tao , Xu Bing , Wang Penglong , Lei Haimin
Published: March 2022

Background

Oral administration of insulin (INS) could be absorbed into systemic circulation only if the carrier protected it from the hostile gastrointestinal conditions. However, traditional macromolecular carriers have not totally overcome challenges in addressing these biological barriers.

Result

In this study, inspired by small molecule natural products (SMNPs), we demonstrate the multi-functional self-assembly nanoparticles (BA-Al NPs) originating from baicalin (BA) and AlCl3 through coordination bonds and hydrogen bonds. As a novel carrier for oral insulin delivery (INS@BA-Al NPs), it displayed effective capacity in pH stimuli-responsive insulin release, intestinal mucoadhesion and transepithelial absorption enhance. Meanwhile, BA improved the paracellular permeability for insulin absorption, because of its downregulation at both mRNA and protein level on internal tight junction proteins. In vivo experiments exhibited remarkable bioavailability of INS and an ideal glucose homeostasis in the type I diabetic rat model.

Conclusion

This study offers a novel frontier of multi-functional carriers based on SMNPs with self-assembly character and bioactivity, which could be a promising strategy for diabetes therapy.

Graphical Abstract
Lipid based nanoparticles as a novel treatment modality for hepatocellular carcinoma: a comprehensive review on targeting and recent advances
Authors: Mahmoud Khaled , Swidan Shady , El-Nabarawi Mohamed , Teaima Mahmoud
Published: March 2022

Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles—specifically lipid based nanoparticles—are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, phytosomes, lipid coated nanoparticles, and nanoassemblies. Multiple approaches are used to enhance the tumor uptake as well tumor specificity such as intratumoral injection, passive targeting, active targeting, and stimuli responsive nanoparticles. In this review, the effect of utilizing lipidic nanoparticles is being discussed as well as the different tumor uptake enhancement techniques used.

Graphical Abstract
Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA
Authors: Chen Xutao , Wan Zhuo , Yang Liu , Song Shuang , Fu Zhaoyue , Tang Kang , Chen Lihua , Song Yingliang
Published: March 2022

Background

Periodontitis is characterized by progressive inflammation and alveolar bone loss resulting in tooth loss finally. Macrophages including pro-inflammatory M1-like macrophages and reparative M2-like macrophages play a vital role in inflammation and tissue homeostasis in periodontitis. Among them, reparative M2-like macrophages have been shown to promote tissue repair and prevent bone loss. However, the mechanism of reparative M2 macrophages-induced osteoprotective effect remains elusive.

Results

Exosomes from reparative M2-like macrophages (M2-Exos) were isolated and identified successfully. M2-Exos could promote bone marrow stromal cells (BMSCs) osteogenic differentiation while suppressing bone marrow derived macrophage (BMDM) osteoclast formation, and prohibit pathological alveolar bone resorption because of the intercellular communication via exosomes. High expression level of IL-10 mRNA was detected not only in reparative M2-like macrophages but also in M2-Exos. Meanwhile, IL-10 expression level in BMSCs or BMDM was also upregulated significantly after co-culturing with M2-Exos in a concentration-dependent manner. In vitro, recombinant IL-10 proteins had the ability to selectively promote osteogenic differentiation of BMSCs and hinder osteoclast differentiation of BMDM. Moreover, after treatment with M2-Exos and IL-10R antibody together, the capacity of promoting osteogenesis and suppressing osteoclastogenesis of M2-Exos was significantly reversed. In vivo experiments further showed that M2-Exos reduced alveolar bone resorption in mice with periodontitis via IL-10/IL-10R pathway.

Conclusion

In conclusion, our results demonstrate that the reparative M2-like macrophages could promote osteogenesis while inhibiting osteoclastogenesis in vitro as well as protect alveolar bone against resorption in vivo significantly. M2-Exos could upregulate the IL-10 cytokines expression of BMSCs and BMDM via delivering exosomal IL-10 mRNA to cells directly, leading to activation of the cellular IL-10/IL-10R pathway to regulate cells differentiation and bone metabolism. These results might partly account for the mechanism of osteoprotective effect of reparative M2-like macrophages and provide a novel perspective and a potential therapeutic approach on improving alveolar resorption by M2-Exos.

Graphical Abstract
Self-esteem in patients with venous thromboembolism predicts time trade-off values for own health
Authors: Stalmeier Peep F. M. , Volmeijer Eva E.
Published: March 2022

Background

The time trade-off (TTO) is a commonly used preference based method to assess health related values used in health economic analyses. Surprisingly little is known about the factors influencing the TTO. Since self-esteem is a predictor for health status measurements, and health status affects the TTO, we studied the relation between self-esteem and TTO values.

Methods

Data of 128 patients treated with vitamin K antagonists for venous thromboembolism on Short Form-36 (SF-36), Rosenberg self-esteem and patient characteristics were collected. TTO values were obtained for ‘current health’ and three chronic health states related to thrombosis, in face-to-face interviews with patients. Regression analyses were performed with the TTO as dependent variable. Analyses were performed in two groups; the complete sample, and traders only. Selected predictors were entered in four blocks: socio-demographic factors, medical-clinical factors, health status, and self-esteem.

Results

In the complete sample (N = 128), bivariate regression analysis showed that self-esteem explained 14% of the variance in TTO values for current health (p < .000, N = 117). In traders, multivariate regression analysis showed a significant relationship between self-esteem and TTO values for current health. Self-esteem increased the variance explained (R2) by 8.8%, from 28.1 to 36.9%, (p = 0.01; N = 57). For hypothetical health states, the effect of self-esteem was weaker and mostly absent after controlling for selected variables.

Conclusions

In patients willing to trade-off time, higher self-esteem was associated with higher TTO values for own current health. Self-esteem explained an appreciable proportion of the variance in TTO values in traders. For hypothetical health states such associations were weak or absent.
Coagulation dysfunction events associated with tigecycline: a real-world study from FDA adverse event reporting system (FAERS) database
Authors: Guo Mingxing , Liang Jinwei , Li Dandan , Zhao Ying , Xu Wanyi , Wang Lei , Cui Xiangli
Published: March 2022

Background

Tigecycline has broad-spectrum anti-bacterial activity and often used for critically ill patients with complicated infections. Only a few clinical studies have reported the coagulation disorder induced by tigecycline. The aim of this study was to investigate the association between tigecycline and coagulation dysfunction using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Method

Data from January 2005 to December 2020 in FAERS were retrieved. We investigated the clinical characteristics of the coagulation dysfunction events and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare tigecycline with the full database and other antibiotics.

Results

The total number of reports of coagulation dysfunction related to tigecycline as the primary suspect drug was 223. The median time to event of the coagulation dysfunction events was 10 (interquartile range [IQR] 6.75–13) days. 80.72% coagulation-related adverse events appeared within the first 14 days since the initiation of tigecycline administration. The overall ROR (95% CI) for coagulation-related adverse events was 3.55 (3.08, 4.09). The RORs (95% CI) for thrombocytopenia, hypofibrinogenaemia, coagulopathy, activated partial thromboplastin time prolonged, international normalized ratio increased, prothrombin time prolonged were 8.21 (6.34, 10.62), 705.41 (526.81, 944.54), 30.67 (21.92, 42.92), 42.98 (24.85, 74.31), 4.67 (2.51, 8.71), and 27.99 (15.01, 52.19), respectively. In analyses stratified on comparing tigecycline to vancomycin and daptomycin, significant coagulation dysfunction signals were found with the RORs (95% CI) 2.74 (2.34, 3.22) and 3.08 (2.57, 3.70).

Conclusions

We found a strong signal of high frequency of reporting coagulation dysfunction in tigecycline. Health professionals should be aware of the potential coagulation disorders risk and monitor coagulation parameters during anti-bacterial therapy with tigecycline, particularly the need to monitor fibrinogen levels.
Association between inflammatory cytokines and anti-SARS-CoV-2 antibodies in hospitalized patients with COVID-19
Authors: Jing Xixi , Xu Min , Song Deye , Yue Tingting , Wang Yali , Zhang Pan , Zhong Yanjun , Zhang Min , Lam Tommy Tsan-Yuk , Faria Nuno Rodrigues , De Clercq Erik , Li Guangdi
Published: March 2022

Background

COVID-19 patients may experience “cytokine storm” when human immune system produces excessive cytokines/chemokines. However, it remains unclear whether early responses of inflammatory cytokines would lead to high or low titers of anti-SARS-CoV-2 antibodies.

Methods

This retrospective study enrolled a cohort of 272 hospitalized patients with laboratory-confirmed SARS-CoV-2. Laboratory assessments of serum cytokines (IL-2R, IL-6, IL-8, IL-10, TNF-α), anti-SARS-CoV-2 IgG/IgM antibodies, and peripheral blood biomarkers were conducted during hospitalization.

Results

At hospital admission, 36.4% patients were severely ill, 51.5% patients were ≥ 65 years, and 60.3% patients had comorbidities. Higher levels of IL-2R and IL-6 were observed in older patients (≥65 years). Significant differences of IL-2R (week 2 to week ≥5 from symptom onset), IL-6 (week 1 to week ≥5), IL-8 (week 2 to week ≥5), and IL-10 (week 1 to week 3) were observed between moderately-ill and severely ill patients. Anti-SARS-CoV-2 IgG titers were significantly higher in severely ill patients than in moderately ill patients, but such difference was not observed for IgM. High titers of early-stage IL-6, IL-8, and TNF-α (≤2 weeks after symptom onset) were positively correlated with high titers of late-stage IgG (≥5 weeks after symptom onset). Deaths were mostly observed in severely ill older patients (45.9%). Survival analyses revealed risk factors of patient age, baseline COVID-19 severity, and baseline IL-6 that affected survival time, especially in severely ill older patients.

Conclusion

Early responses of elevated cytokines such as IL-6 reflect the active immune responses, leading to high titers of IgG antibodies against COVID-19.
A survey of few-shot learning in smart agriculture: developments, applications, and challenges
Authors: Yang Jiachen , Guo Xiaolan , Li Yang , Marinello Francesco , Ercisli Sezai , Zhang Zhuo
Published: March 2022

With the rise of artificial intelligence, deep learning is gradually applied to the field of agriculture and plant science. However, the excellent performance of deep learning needs to be established on massive numbers of samples. In the field of plant science and biology, it is not easy to obtain a large amount of labeled data. The emergence of few-shot learning solves this problem. It imitates the ability of humans’ rapid learning and can learn a new task with only a small number of labeled samples, which greatly reduces the time cost and financial resources. At present, the advanced few-shot learning methods are mainly divided into four categories based on: data augmentation, metric learning, external memory, and parameter optimization, solving the over-fitting problem from different viewpoints. This review comprehensively expounds on few-shot learning in smart agriculture, introduces the definition of few-shot learning, four kinds of learning methods, the publicly available datasets for few-shot learning, various applications in smart agriculture, and the challenges in smart agriculture in future development.
Concerns among people who use opioids during the COVID-19 pandemic: a natural language processing analysis of social media posts
Authors: Sarker Abeed , Nataraj Nisha , Siu Wesley , Li Sabrina , Jones Christopher M. , Sumner Steven A.
Published: March 2022

Background

Timely data from official sources regarding the impact of the COVID-19 pandemic on people who use prescription and illegal opioids is lacking. We conducted a large-scale, natural language processing (NLP) analysis of conversations on opioid-related drug forums to better understand concerns among people who use opioids.

Methods

In this retrospective observational study, we analyzed posts from 14 opioid-related forums on the social network Reddit. We applied NLP to identify frequently mentioned substances and phrases, and grouped the phrases manually based on their contents into three broad key themes: (i) prescription and/or illegal opioid use; (ii) substance use disorder treatment access and care; and (iii) withdrawal. Phrases that were unmappable to any particular theme were discarded. We computed the frequencies of substance and theme mentions, and quantified their volumes over time. We compared changes in post volumes by key themes and substances between pre-COVID-19 (1/1/2019—2/29/2020) and COVID-19 (3/1/2020—11/30/2020) periods.

Results

Seventy-seven thousand six hundred fifty-two and 119,168 posts were collected for the pre-COVID-19 and COVID-19 periods, respectively. By theme, posts about treatment and access to care increased by 300%, from 0.631 to 2.526 per 1000 posts between the pre-COVID-19 and COVID-19 periods. Conversations about withdrawal increased by 812% between the same periods (0.026 to 0.235 per 1,000 posts). Posts about drug use did not increase (0.219 to 0.218 per 1,000 posts). By substance, among medications for opioid use disorder, methadone had the largest increase in conversations (20.751 to 56.313 per 1,000 posts; 171.4% increase). Among other medications, posts about diphenhydramine exhibited the largest increase (0.341 to 0.927 per 1,000 posts; 171.8% increase).

Conclusions

Conversations on opioid-related forums among people who use opioids revealed increased concerns about treatment and access to care along with withdrawal following the emergence of COVID-19. Greater attention to social media data may help inform timely responses to the needs of people who use opioids during COVID-19.
Self-perceived preparedness and training needs of healthcare personnel on humanitarian mission: a pre- and post-deployment survey
Authors: Haverkamp Frederike J. C. , van Leest Tristan A. J. , Muhrbeck Måns , Hoencamp Rigo , Wladis Andreas , Tan Edward C. T. H.
Published: March 2022

Background

Humanitarian healthcare workers are indispensable for treating weapon-wounded patients in armed conflict, and the international humanitarian community should ensure adequate preparedness for this task. This study aims to assess deployed humanitarian healthcare workers’ self-perceived preparedness, training requirements and mental support needs.

Methods

Medical professionals deployed with the International Committee of the Red Cross (ICRC) between October 2018 and June 2020 were invited to participate in this longitudinal questionnaire. Two separate questionnaires were conducted pre- and post-deployment to assess respondents’ self-perceived preparedness, preparation efforts, deployment experiences and deployment influence on personal and professional development.

Results

Response rates for the pre- and post-deployment questionnaires were 52.5% (114/217) and 26.7% (58/217), respectively. Eighty-five respondents (85/114; 74.6%) reported feeling sufficiently prepared to treat adult trauma patients, reflected by predeployment ratings of 3 or higher on a scale from 1 (low) to 5 (high). Significantly lower ratings were found among nurses compared to physicians. Work experience in a high-volume trauma centre before deployment was associated with a greater feeling of preparedness (mean rank 46.98 vs. 36.89; p = 0.045). Topics most frequently requested to be included in future training were neurosurgery, maxillofacial surgery, reconstructive surgery, ultrasound, tropical diseases, triage, burns and newborn noncommunicable disease management. Moreover, 51.7% (30/58) of the respondents regarded the availability of a mental health professional during deployment as helpful to deal with stress.

Conclusion

Overall, deployed ICRC medical personnel felt sufficiently prepared for their missions, although nurses reported lower preparedness levels than physicians. Recommendations were made concerning topics to be covered in future training and additional preparation strategies to gain relevant clinical experience. Future preparatory efforts should focus on all medical professions, and their training needs should be continuously monitored to ensure the alignment of preparation strategies with preparation needs.
Early results of fixed-bearing unicompartmental knee replacement designed for the lateral compartment
Authors: Asadollahi Saeed , Wilson Hannah A. , Thomson Fraser R. , Vaz Kenneth , Middleton Rob , Jenkins Cathy , Alvand Abtin , Bottomley Nicholas , Dodd Chris A. , Price Andrew J. , Murray David W. , Jackson William F.
Published: March 2022

Background

Isolated lateral compartment knee arthritis is less prevalent than medial. While the reported results of medial unicompartmental knee replacement (UKR) have been good and comparable to total knee replacement, the results of lateral UKR have been mixed. We present the short-term results and survivorship of a fixed-bearing UKR designed specifically for the lateral compartment.

Methods

We report the result of 130 primary fixed-bearing lateral Oxford (FLO) UKRs (123 patients) performed between 2015 and 2019 with a minimum follow-up of 1 year. The indications for lateral UKR were: isolated lateral osteoarthritis (n = 122), post-trauma (n = 5) and osteonecrosis (n = 3). The mean age was 69.1 (± 11.6), mean BMI 28.4 (± 4.9), 66.9% female, 60% right-sided, and mean follow-up 3 (range 1–4.8 years, standard deviation ± 1) years. The primary outcome measure was the Oxford knee score (OKS). Survival analysis was performed with “revision for any reason”, “reoperation”, and “implant failure” as the endpoints.

Results

Six patients died from unrelated reasons. None of the implants failed. One required the addition of a medial UKR for medial arthritis. There were no other reoperations. At 4 years, the survival for implant failure was 100% and for both revision and all reoperations was 99.5% (95% CI 96.7–99.9%). At the last review, at a mean of 3 years, the mean Oxford knee score was 41.

Conclusion

The good survivorship and outcome scores suggest that UKR designed for the lateral compartment is an excellent alternative to total knee replacement in selected patients with isolated lateral tibiofemoral arthritis at short-term follow-up.
Heterotopic ossification after total hip arthroplasty: When is development completed?
Authors: Willburger Roland E. , Brinkhoff Friederike , Nottenkämper Jan , Krapp Jan , Oberberg Stella
Published: March 2022

Background

Heterotopic ossifications (HO) are a common complication after total hip arthroplasty (THA). Nonsteroidal anti-inflammatory drugs have proven to reduce the occurrence of HO. It is still unclear when the formation of HO is finished. Aim of our study was to answer this question.

Methods

In a prospective study, the occurrence of periarticular HO was checked during the follow-up (FU) examinations. In total, 75 consecutive patients who underwent THA were included. To ensure a high follow-up rate, only patients with a life expectancy of at least 10 years were included. A medical ossification prophylaxis with mostly etoricoxib (90 mg once daily) was administered. Follow-up examinations were performed at 3 months, 1 year, 3, 5, and 10 years postoperatively. Each time, a clinical and radiological examination was carried out. The HO was graded according to Brooker’s method.

Results

Low-grade HO classified by Brooker grade I and II occurred significantly more frequent than HO grade III. In patients with present HO, a possible increase in Brooker stage could further be observed within 3 years postoperatively. After 3 years, the formation of HO was completed in all patients.

Conclusion

Three years after THA, the formation of HO is complete. After more than 3 years postoperatively, if HO occurs or increases, other triggering causes such as new trauma, periarticular infection, or implant loosening should be considered.
3D surface reconstruction of the femur and tibia from parallel 2D contours
Authors: Lin Bigui , Jin Dadi , Socorro Borges Miguel Angel
Published: March 2022

Background

Segmented structures, such as bones, are typically stored as 2D contours contained on evenly spaced images (slices). Contour interpolation algorithms to turn 2D contours into a 3D surface may differ in their results, causing discrepancies in analysis. This study aimed to create an accurate and consistent algorithm for the interpolation of femur and tibial contours that can be used in computer-assisted surgical navigation systems.

Methods

The implemented algorithm performs contour interpolation in a step-by-step manner, determining an optimal surface between each pair of consecutive contours. Determining such a surface is reduced to the problem of finding certain minimum-cost cycles in a directed toroidal graph. The algorithm assumes that the contours are ordered. The first step in the algorithm is the determination of branching patterns, followed by the removal of keyholes from contours, optimization of a target function based on the surface area, and mesh triangulation based on the optimization results and mesh seal.

Results

The algorithm was tested on contours segmented on computed tomography images from femoral and tibial specimens; it was able to generate qualitatively good 3D meshes from the set of 2D contours for all the tested examples.

Conclusion

The contour interpolation algorithm proved to be quite effective using optimization based on minimizing the area of the triangles that form the 3D surface. The algorithm can be used for the 3D reconstruction of other types of 2D cuts, but special attention must be paid with the branches, since the proposed algorithm is not designed for complex branching structures.
The application of mass spectrometry imaging in traditional Chinese medicine: a review
Authors: Huang Lieyan , Nie Lixing , Dai Zhong , Dong Jing , Jia Xiaofei , Yang Xuexin , Yao Lingwen , Ma Shuang-cheng
Published: March 2022

Mass spectrometry imaging is a frontier technique which connects classical mass spectrometry with ion imaging. Various types of chemicals could be visualized in their native tissues using mass spectrometry imaging. Up to now, the most commonly applied mass spectrometry imaging techniques are matrix assisted laser desorption ionization mass spectrometry imaging, desorption electrospray ionization mass spectrometry imaging and secondary ion mass spectrometry imaging. This review gives an introduction to the principles, development and applications of commonly applied mass spectrometry imaging techniques, and then illustrates the application of mass spectrometry imaging in the investigation of traditional Chinese medicine. Recently, mass spectrometry imaging has been adopted to explore the spatial distribution of endogenous metabolites in traditional Chinese medicine. Data collected from mass spectrometry imaging can be further utilized to search for marker components of traditional Chinese medicine, discover new compounds from traditional herbs, and differentiate between medicinal plants that are similar in botanical features. Moreover, mass spectrometry imaging also plays a role in revealing the pharmacological and toxicological mechanisms of traditional Chinese medicine.
Prevalence of human papilloma virus (HPV) genotypes between outpatients males and females referred to seven laboratories in Tehran, Iran
Authors: Rezaee Azhar Iman , Yaghoobi Mahmood , Mossalaeie Mir Majid , Kollaee Darabi Abolghasem , Nejadeh Amir Houshang , Jamshidi Mahbobeh , Ahani Ali , Karkhane Mahmoodi Masoud , Ghalichi Leila , Shabanzadeh Ayda , Ataei-Pirkooh Angila , Marjani Arezoo , Khamseh Azam , Shafiei Motahareh , Hosseini Parastoo , Soltani Saber , Zandi Milad , Ghafari Parsa , Aboofazeli Amir , Ghaziasadi Azam , Jazayeri Seyed Mohammad
Published: March 2022

Background

Human papilloma virus (HPV) causes the most common sexually-transmitted infection especially among sexually-active individuals. The aim of study was to characterize the molecular characterization of HPV genotypes between 5176 female and male patients.

Methods

HPV DNA was extracted from genital swabs of the study participants and amplified by Real Time Polymerase Chain Reaction (PCR). Genotyping was performed for 2525 cases using REALQUALITY RQ-Multi HPV Detection Kit for the identification of 14 high risk (HR) and 2 low risk (LR) HPV genotypes. Demographic figures were analyzed in correlation with virological data statistically.

Results

Out of 5176 cases from 7 laboratories, 2727 (53%) were positive for HPV, of which. 2372(87%) women and 355 (13%) men were HPV positive. However, in an intra-gender analysis, positive rate was higher in men (355/637, 55.7%) than in women (2372/4539, 52%; P value 0.007). HPV positive patients were younger than negative individuals. Positive rate was higher among age categories 20–40. Genotyping was performed for 2525 cases. Out of 1219 (48%) patients who contained single genotypes, 566 (22%) and 653 (26%) harboured HR and LR genotypes, respectively. In females and males, 1189 (54%) and 117 (37%) contained multiple genotypes. No substantial associations were found between different age categories and HR/LR and multiple genotypes distribution.

Conclusion

The prevalence of HPV infection in both genders was high. However, men had a higher rate of infection. These observations highlighted the necessity for a plan for targeted education to younger population in the society as well as application of infection control measures against HPV infection, especially in terms of general population mass HPV vaccination.
Klinefelter syndrome mosaicism in boys with neurodevelopmental disorders: a cohort study and an extension of the hypothesis
Authors: Vorsanova Svetlana G. , Demidova Irina A. , Kolotii Alexey D. , Kurinnaia Oksana S. , Kravets Victor S. , Soloviev Ilya V. , Yurov Yuri B. , Iourov Ivan Y.
Published: March 2022

Background

Klinefelter syndrome is a common chromosomal (aneuploidy) disorder associated with an extra X chromosome in males. Regardless of numerous studies dedicated to somatic gonosomal mosaicism, Klinefelter syndrome mosaicism (KSM) has not been systematically addressed in clinical cohorts. Here, we report on the evaluation of KSM in a large cohort of boys with neurodevelopmental disorders. Furthermore, these data have been used for an extension of the hypothesis, which we have recently proposed in a report on Turner’s syndrome mosaicism in girls with neurodevelopmental disorders.

Results

Klinefelter syndrome-associated karyotypes were revealed in 49 (1.1%) of 4535 boys. Twenty one boys (0.5%) were non-mosaic 47,XXY individuals. KSM was found in 28 cases (0.6%) and manifested as mosaic aneuploidy (50,XXXXXY; 49,XXXXY; 48,XXXY; 48,XXYY; 47,XXY; and 45,X were detected in addition to 47,XXY/46,XY) and mosaic supernumerary marker chromosomes derived from chromosome X (ring chromosomes X and rearranged chromosomes X). It is noteworthy that KSM was concomitant with Rett-syndrome-like phenotypes caused by MECP2 mutations in 5 boys (0.1%).

Conclusion

Our study provides data on the occurrence of KSM in neurodevelopmental disorders among males. Accordingly, it is proposed that KSM may be a possible element of pathogenic cascades in psychiatric and neurodegenerative diseases. These observations allowed us to extend the hypothesis proposed in our previous report on the contribution of somatic gonosomal mosaicism (Turner’s syndrome mosaicism) to the etiology of neurodevelopmental disorders. Thus, it seems to be important to monitor KSM (a possible risk factor or a biomarker for adult-onset multifactorial brain diseases) and analysis of neuromarkers for aging in individuals with Klinefelter syndrome. Cases of two or more supernumerary chromosomes X were all associated with KSM. Finally, Rett syndrome-like phenotypes associated with KSM appear to be more common in males with neurodevelopmental disorders than previously recognized.
Acute inhibition of OGA sex-dependently alters the networks associated with bioenergetics, autophagy, and neurodegeneration
Authors: Huynh Van N. , Benavides Gloria A. , Johnson Michelle S. , Ouyang Xiaosen , Chacko Balu K. , Osuma Edie , Mueller Toni , Chatham John , Darley-Usmar Victor M. , Zhang Jianhua
Published: March 2022

The accumulation of neurotoxic proteins characteristic of age-related neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases is associated with the perturbation of metabolism, bioenergetics, and mitochondrial quality control. One approach to exploit these interactions therapeutically is to target the pathways that regulate metabolism. In this respect, the nutrient-sensing hexosamine biosynthesis pathway is of particular interest since it introduces a protein post-translational modification known as O-GlcNAcylation, which modifies different proteins in control versus neurodegenerative disease postmortem brains. A potent inhibitor of the O-GlcNAcase enzyme that removes the modification from proteins, Thiamet G (TG), has been proposed to have potential benefits in Alzheimer’s disease. We tested whether key factors in the O-GlcNAcylation are correlated with mitochondrial electron transport and proteins related to the autophagy/lysosomal pathways in the cortex of male and female mice with and without exposure to TG (10 mg/kg i.p.). Mitochondrial complex activities were measured in the protein homogenates, and a panel of metabolic, autophagy/lysosomal proteins and O-GlcNAcylation enzymes were assessed by either enzyme activity assay or by western blot analysis. We found that the networks associated with O-GlcNAcylation enzymes and activities with mitochondrial parameters, autophagy-related proteins as well as neurodegenerative disease-related proteins exhibited sex and TG dependent differences. Taken together, these studies provide a framework of interconnectivity for multiple O-GlcNAc-dependent pathways in mouse brain of relevance to aging and sex/age-dependent neurodegenerative pathogenesis and response to potential therapies.
Do entrapment, injuries, outcomes and potential for self-extrication vary with age? A pre-specified analysis of the UK trauma registry (TARN)
Authors: Nutbeam Tim , Kehoe Anthony , Fenwick Rob , Smith Jason , Bouamra Omar , Wallis Lee , Stassen Willem
Published: March 2022

Background

Motor vehicle collisions (MVCs), particularly those associated with entrapment, are a common cause of major trauma. Current extrication methods are focused on spinal movement minimisation and mitigation, but for many patients self-extrication may be an appropriate alternative. Older drivers and passengers are increasingly injured in MVCs and may be at an increased risk of entrapment and its deleterious effects. The aim of this study is to describe the injuries, trapped status, outcomes, and potential for self-extrication for patients following an MVC across a range of age groups.

Methods

This is a retrospective study using the Trauma Audit and Research Network (TARN) database. Patients were included if they were admitted to an English hospital following an MVC from 2012 to 2019. Patients were excluded when their outcomes were not known or if they were secondary transfers. Simple descriptive analysis was used across the age groups: 16–59, 60–69, 70–79 and 80+  years. Logistic regression was performed to develop a model with known confounders, considering the odds of death by age group, and examining any interaction between age and trapped status with mortality.

Results

70,027 patients met the inclusion criteria. Older patients were more likely to be trapped and to die following an MVC (p < 0.0001). Head, abdominal and limb injuries were more common in the young with thoracic and spinal injuries being more common in older patients (all p < 0.0001). No statistical difference was found between the age groups in relation to ability to self-extricate. After adjustment for confounders, the 80 + age group were more likely to die if they were trapped; adjusted OR trapped 30.2 (19.8–46), not trapped 24.2 (20.1–29.2).

Conclusions

Patients over the age of 80 are more likely to die when trapped following an MVC. Self-extrication should be considered the primary route of egress for patients of all ages unless it is clearly impracticable or unachievable. For those patients who cannot self-extricate, a minimally invasive extrication approach should be employed to minimise entrapment time.
Manifesto of the pediatricians of Emilia-Romagna region, Italy, in favor of vaccination against COVID in children 5–11 years old
Authors: Esposito Susanna ,   the Pediatricians of Emilia-Romagna Region, Italy
Published: March 2022

Background

Following the authorization by the regulatory authorities of vaccination against COVID for children aged between 5 and 11, in Emilia-Romagna Region, Italy, the pediatricians of the Italian Society of Pediatrics (SIP), the Italian Society of Neonatology (SIN), the Cultural Association of Pediatrics, the Italian Federation of Pediatricians (FIMP) and the Italian Union of Family Pediatricians (SIMPeF), who work in the hospital and in the territorial setting, have made a univocal and convinced appeal in favor of vaccination also in this age group.

Main findings

In order to contribute to a conscious choice, on the part of parents, based on exhaustive and correct information, a 24-point manifesto was developed. The manifesto showed that vaccines against COVID are the most effective and safest tool we have to counter the spread of SARS-CoV-2 and vaccination against COVID is a right of children just as it is for adults. Children between 5 and 11 years are not protected from the virus and a large part of the newly infected is this age. Although SARS-CoV-2 infection is certainly more benign in children, in some cases it can cause a serious pathology and long COVID. The stress caused by the pandemic, the prolonged closure of schools and the interruption of sports and recreational activities have had a devastating effect on the mental health of children and on the development of their personality. Vaccinating children against COVID serves to protect them from severe forms of disease and long COVID, allowing them to attend school face-to-face and lead a normal social life. The safety of vaccinatin is very high and vaccines against COVID have no influence on fertility nor can they cause developmental or growth side effects.

Conclusions

The manifesto highlighted that the vaccine against COVID for children aged between 5 and 11 is effective and safe and represents an extraordinary gift for safeguarding health of the younger ones. The invitation, therefore, to parents is to have their children vaccinated against COVID as early as possible.
Effects of transcranial direct current stimulation on patients with post-stroke fatigue: a study protocol for a double-blind randomized controlled trial
Authors: Sun Xing , Dong Xiangli , Yuan Qin , Yu Guohua , Shuai Lang , Ma Chaolin , Sun Weiming
Published: March 2022

Introduction

Post-stroke fatigue (PSF) is an abnormal, persistent, and unexplained physical and psychological tiredness in patients after stroke. It is a common symptom of stroke patients with poor quality of life and bleak prognosis, and the incidence rate is up to 39% to 72%. It has been widely reported that medicine treatments achieved a lot of progress, there still needs to develop more powerful new strategies to more powerful effect. The transcranial direct-current stimulation (tDCS) shows great potential for the treatment of PSF. This study proposes to apply a double-blind randomized controlled clinical trial to explore the effect and safety of tDCS combined with routine rehabilitation for PSF.

Methods and analysis

One hundred patients with PSF will be randomly divided into two groups. One of the groups will receive conventional rehabilitation therapy and active tDCS, whereas another group will receive conventional rehabilitation treatment and sham tDCS. Both groups will receive the intervention for 4 weeks, during which time they will undergo either active or sham tDCS 20 min a day, 6 days a week. Primary outcome: Fatigue Severity Scale (FSS) will be measured at baseline every weekend during the intervention period. Secondary results: Fatigue Impact Scale (FIS), Functional Assessment Chronic Illness Therapy (Fatigue) (FACIT-F), and Specialized Quality of Life Scale in Stroke (SS-QOL) will be measured at baseline and at the end of the intervention time of 4 weeks. Throughout the study, adverse events and adverse reactions will be measured during every treatment. The research study “Effects of transcranial direct current stimulation on patients with post-stroke fatigue” has been approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University: Clinical Medicine Ethics Review [2015]043 in Nov 2015.

Discussion

This study will provide insight into the efficacy of transcranial direct-current stimulation for post-stroke fatigue. This is a double-blind randomized controlled trial whose aim is to assess the effects of tDCS on PSF. This study can provide more information about the treatment of PSF. This study has a period of follow-up, which allows for greater accuracy. It is a single-center trial, and this may be a limitation. The other limitation of this study is the relatively small number of participants; thus, the influence of chance on experimental results cannot be completely ruled out.

Trial registration

Chinese Clinical Trial Registry ChiCTR2000031120. Registered on March 22, 2020. This protocol version number is V1.1.
Simultaneous manipulation of multiple genes within a same regulatory stage for iterative evolution of Trichoderma reesei
Authors: Sun Xianhua , Liang Yazhe , Wang Yuan , Zhang Honglian , Zhao Tong , Yao Bin , Luo Huiying , Huang Huoqing , Su Xiaoyun
Published: March 2022

Background

While there is growing interest in developing non-canonical filamentous fungi as hosts for producing secretory proteins, genetic engineering of filamentous fungi for improved expression often relies heavily on the understanding of regulatory mechanisms.

Results

In this study, using the cellulase-producing filamentous fungus Trichoderma reesei as a model system, we designed a semi-rational strategy by arbitrarily dividing the regulation of cellulase production into three main stages-transcription, secretion, and cell metabolism. Selected regulatory or functional genes that had been experimentally verified or predicted to enhance cellulase production were overexpressed using strong inducible or constitutive promoters, while those that would inhibit cellulase production were repressed via RNAi-mediated gene silencing. A T. reesei strain expressing the surface-displayed DsRed fluorescent protein was used as the recipient strain. After three consecutive rounds of engineering, the cellulase activity increased to up to 4.35-fold and the protein concentration increased to up to 2.97-fold in the genetically modified strain.

Conclusions

We demonstrated that, as a proof-of-concept, selected regulatory or functional genes within an arbitrarily defined stage could be pooled to stimulate secretory cellulase production, and moreover, this method could be iteratively used for further improvement. This method is semi-rational and can essentially be used in filamentous fungi with little regulatory information.
Echinococcus spp. and genotypes infecting humans in Tibet Autonomous Region of China: a molecular investigation with near-complete/complete mitochondrial sequences
Authors: Zhao Yanping , Gesang Dunzhu , Wan Li , Li Jiandong , Qiangba Gezhen , Danzeng Wangmu , Basang Zhuoga , Renzhen Nibu , Yin Jiefang , Gongsang Quzhen , Cai Huimin , Pang Huasheng , Wang Daxi , Asan  , Zhang Qingda , Li Junhua , Chen Weijun
Published: March 2022

Background

Molecular markers are essential to identify Echinococcus species and genotypes in areas with multiple Echinococcus species to understand their epidemiology and pathology. Tibet Autonomous Region (TAR) is one of the areas worst hit by echinococcosis. However, molecular epidemiology is still missing among echinococcosis patients in TAR. This research explored the Echinococcus species and genotypes infecting humans in TAR and the population diversity and the possible origin of G1 in TAR.

Methods

Cyst samples were collected in one echinococcosis-designated hospital in TAR. Echinococcus species and genotypes were identified through a maximum-likelihood approach with near-complete/complete mtDNA using IQ-TREE. Phylogenetic networks were built with PopART, and the phylogeographical diffusion pattern was identified using a Bayesian discrete phylogeographic method.

Results

Using phylogenetic trees made with near-complete/complete mtDNA obtained from 92 cysts from TAR patients, the Echinococcus species and genotypes infecting humans in TAR were identified as Echinococcus granulosus (s.s.) G1 (81, 88.04%), accounting for the majority, followed by G6 of the E. canadensis cluster (6, 6.52%), E. granulosus (s.s.) G3 (3, 3.26%), and E. multilocularis (2, 2.17%). An expansion trend and a possible recent bottleneck event were confirmed among the G1 samples in TAR. Adding the other near-complete mtDNA of G1 samples globally from the literature, we identified the possible phylogeographic origin of the G1 samples in TAR as Turkey.

Conclusions

Using near-complete/complete mtDNA sequences of Echinococcus spp. obtained from echinococcosis patients, a variety of Echinococcus species and genotypes infecting humans throughout TAR were identified. As far as we know, this is the first comprehensive molecular investigation of Echinococcus species and genotypes infecting humans throughout TAR. We identified, for the first time to our knowledge, the possible origin of the G1 in TAR. We also enriched the long mtDNA database of Echinococcus spp. and added two complete E. multilocularis mtDNA sequences from human patients. These findings will improve our knowledge of echinococcosis, help to refine the targeted echinococcosis control measures, and serve as a valuable baseline for monitoring the Echinococcus species and genotypes mutations and trends of the Echinococcus spp. population in TAR.

Graphical Abstract
Phylogenetic relationship between the endosymbiont “Candidatus Riesia pediculicola” and its human louse host
Authors: Hammoud Alissa , Louni Meriem , Missé Dorothée , Cortaredona Sébastien , Fenollar Florence , Mediannikov Oleg
Published: March 2022

Background

The human louse (Pediculus humanus) is a haematophagous ectoparasite that is intimately related to its host. It has been of great public health concern throughout human history. This louse has been classified into six divergent mitochondrial clades (A, D, B, F, C and E). As with all haematophagous lice, P. humanus directly depends on the presence of a bacterial symbiont, known as “Candidatus Riesia pediculicola”, to complement their unbalanced diet. In this study, we evaluated the codivergence of human lice around the world and their endosymbiotic bacteria. Using molecular approaches, we targeted lice mitochondrial genes from the six diverged clades and Candidatus Riesia pediculicola housekeeping genes.

Methods

The mitochondrial cytochrome b gene (cytb) of lice was selected for molecular analysis, with the aim to identify louse clade. In parallel, we developed four PCR primer pairs targeting three housekeeping genes of Candidatus Riesia pediculicola: ftsZ, groEL and two regions of the rpoB gene (rpoB-1 and rpoB-2).

Results

The endosymbiont phylogeny perfectly mirrored the host insect phylogeny using the ftsZ and rpoB-2 genes, in addition to showing a significant co-phylogenetic congruence, suggesting a strict vertical transmission and a host–symbiont co-speciation following the evolutionary course of the human louse.

Conclusion

Our results unequivocally indicate that louse endosymbionts have experienced a similar co-evolutionary history and that the human louse clade can be determined by their endosymbiotic bacteria.

Graphical Abstract