bluuebunny/crossref_metadata_2025 huggingface dataset:
Pigmentary complications after non-medical male circumcision
Authors: Tirana Radwa , Othman Doa , Gad Dalia , Elsadek Menan , Fahmy Mohamed A. Baky
Published: April 2022

Background

A wide spectrum of complications are reported after male circumcision (MC), the non-aesthetic complications are well known, but the pigmentary complications scale are not reported precisely.

Methods

This is a prospective cohort study of 550 circumcised boys; aged from 6 months to 14 years (62% aged 5 years) who were examined and appropriately investigated for the incidence of pigmentary complications after circumcision. Most diagnoses were clinically, but dermoscopy was done for 17 case and a skin biopsy for 14 cases. Patients with personal or family history of vitiligo, or congenital nevi were excluded. Available hospital records details and parents' statements were revised. The main outcome measures are the incidence of different pigmentary complications and circumcision details; data were analyzed by a non-parametric tests including the Mann–Whitney U test.

Results

69 cases had 72 confirmed pigmentary complications discovered at 2–36 months after commencement of circumcision (mean 18). 48 cases had pigmentary complications directly related to MC, 11 cases were probably related and 10 unrelated to MC. The most common lesion is the circular hyperpigmented scar (29 cases); liner hyperpigmented scar in 13, spotted exogenous melanosis in 18 cases, melanocytic nevi (7), hypopigmentation diagnosed in 3 cases, but kissing nevus is the rarest finding (2). Topical corticosteroid was tried in 15 cases, surgical excision of pigmented scar were done for 19 cases, local laser used for 4 resistant cases and reassurance with follow up for the rest.

Conclusion

Pigmentary complications after male circumcision are not rare and its management is challenging.
The development of empathy in the healthcare setting: a qualitative approach
Authors: YU Chou Chuen , TAN Laurence , LE Mai Khanh , TANG Bernard , LIAW Sok Ying , TIERNEY Tanya , HO Yun Ying , LIM Beng Eng Evelyn , LIM Daphne , NG Reuben , CHIA Siew Chin , LOW James Alvin
Published: April 2022

Background

Healthcare professionals’ empathetic behaviors have been known to lead to higher satisfaction levels and produce better health outcomes for patients. However, empathy could decrease over time especially during training and clinical practice. This study explored factors that contributed to the development of empathy in the healthcare setting. Findings could be used to improve the effectiveness and sustainability of empathy training.

Method

A qualitative approach, informed by aspects of grounded theory, was utilized to identify factors that enabled the development of empathy from the perspectives of doctors, nurses, allied healthcare workers and students. Twelve sessions of focus group discussions were conducted with 60 participants from two hospitals, a medical school, and a nursing school. Data was analyzed independently by three investigators who later corroborated to refine the codes, subthemes, and themes. Factors which influence the development of empathy were identified and categorized. This formed the basis of the creation of a tentative theory of empathy development for the healthcare setting.

Results

The authors identified various personal (e.g. inherent characteristics, physiological and mental states, professional identity) and external (e.g. work environment, life experience, situational stressors) factors that affected the development of empathy. These could be further categorized into three groups based on the stability of their impact on the individuals’ empathy state, contributed by high, medium, or low stability factors. Findings suggest empathy is more trait-like and stable in nature but is also susceptible to fluctuation depending on the circumstances faced by healthcare professionals. Interventions targeting medium and low stability factors could potentially promote the development of empathy in the clinical setting.

Conclusions

Understanding factors that impact the development of empathy allows us to develop measures that could be implemented during training or at the workplace leading to improve the quality of care and higher clinical work satisfaction.
Global diversity of policy, coverage, and demand of COVID-19 vaccines: a descriptive study
Authors: Chen Zhiyuan , Zheng Wen , Wu Qianhui , Chen Xinghui , Peng Cheng , Tian Yuyang , Sun Ruijia , Dong Jiayi , Wang Minghan , Zhou Xiaoyu , Zhao Zeyao , Zhong Guangjie , Yan Xuemei , Liu Nuolan , Hao Feiran , Zhao Sihong , Zhuang Tingyu , Yang Juan , Azman Andrew S. , Yu Hongjie
Published: April 2022

Background

Hundreds of millions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, but progress on vaccination varies considerably between countries. We aimed to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines.

Methods

We conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 8 February 2022. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries’ target populations according to their national immunization program policies.

Results

Messenger RNA and adenovirus vectored vaccines were the most commonly used COVID-19 vaccines in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (180 countries). One hundred ninety-two countries have authorized vaccines for the general public, with 40.1% (77/192) targeting individuals over 12 years and 32.3% (62/192) targeting those ≥ 5 years. Forty-eight and 151 countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 162.1 doses administered per 100 individuals in target populations, with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0.1% to more than 95.0% of country target populations, and numbers of doses administered per 100 individuals in target populations ranged from 0.2 to 308.6. Doses administered per 100 individuals in whole populations correlated with healthcare access and quality index (R2 = 0.59), socio-demographic index (R2 = 0.52), and gross domestic product per capita (R2 = 0.61). At least 6.4 billion doses will be required to complete interim vaccination programs—3.3 billion for primary immunization and 3.1 billion for additional/booster programs. Globally, 0.53 and 0.74 doses per individual in target populations are needed for primary immunization and additional/booster dose programs, respectively.

Conclusions

There is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.
TMT-based proteomic analysis reveals integrins involved in the synergistic infection of reticuloendotheliosis virus and avian leukosis virus subgroup J
Authors: Cui Xiyao , Zhang Xinyue , Xue Jingwen , Yao Yongxiu , Zhou Defang , Cheng Ziqiang
Published: April 2022

Background

Co-infection with the avian leukosis virus subgroup J (ALV-J) and the reticuloendotheliosis virus (REV) increases mutual viral replication, causing a more serious pathogenic effect by accelerating the progression of neoplasia and extending the tumor spectrum. However, the molecular mechanism underlying the synergistic replication of ALV-J and REV remains unclear.

Results

Here, we performed this study to compare the differentially expressed proteins among CEF cells infected with ALV-J, REV or both at the optimal synergistic infection time using TMT-based quantitative proteomics. We identified a total of 719 (292 upregulated and 427 downregulated) and 64 (35 upregulated and 29 downregulated) proteins by comparing co-infecting both viruses with monoinfecting ALV-J and REV, respectively. GO annotation and KEGG pathway analysis showed the differentially expressed proteins participated in virus-vector interaction, biological adhesion and immune response pathways in the synergistic actions of ALV-J and REV at the protein levels. Among the differentially expressed proteins, a large number of integrins were inhibited or increased in the co-infection group. Further, eight integrins, including ITGα1, ITGα3, ITGα5, ITGα6, ITGα8, ITGα9, ITGα11 and ITGβ3, were validated in CEF cells by qRT-PCR or western blot.

Conclusions

These findings proved that integrins may be key regulators in the mechanism of synergistic infection of REV and ALV-J, which will provide more insight into the pathogenesis of synergism of REV and ALV-J at protein level.
Axillary masses as clinical manifestations of male sweat gland carcinoma associated with extramammary Paget’s disease and accessory breast carcinoma: two cases report and literature review
Authors: Wu Jing , Chen Hongdan , Dong Juanhui , Cao Yong , Li Wei , Zhang Fan , Zeng Xiaohua
Published: April 2022

Background

Male cases of accessory breast carcinoma and sweat gland carcinoma associated with extramammary Paget’s disease of the axilla are uncommon. In clinical diagnosis and treatment, it is necessary to determine the disease carefully and make a reasonable treatment strategy according to the patient’s situation.

Case presentation

We described two male cases of the special tumor with an axillary mass as the first clinical symptom, one of which was diagnosed as accessory breast cancer and the other as sweat gland cancer associated with extramammary Paget’s disease. We treated the two diseases individually in the hopes of providing a reference for the diagnosis and management of diseases with axillary nodules as the initial symptom.

Conclusions

The reports of these two cases can provide reference and corresponding thinking for clinical differentiation of axillary lymphadenopathy caused by different causes and subsequent treatment. These two cases may further enrich the database of rare cases and provide some ideas for the treatment of axillary lymphadenopathy caused by different causes.
The relationship between self-efficacy and treatment satisfaction among patients with anticoagulant therapy: a cross-sectional study from a developing country
Authors: Al-Jabi Samah W. , Dalu Amal Abu , Koni Amer A. , Khdour Maher R. , Taha Adham Abu , Amer Riad , Zyoud Sa’ed H.
Published: April 2022

Background

Thromboembolic events are a common complicated health problem. Although anticoagulants have several positive effects on these conditions, they also have several characteristics that strongly affect compliance and satisfaction. The purpose of this investigation is to explore the association between treatment satisfaction and self-efficacy in a sample of patients using anticoagulation therapy and determine the influence of sociodemographic and clinical factors on both aspects.

Methods

This was a cross-sectional exploratory study carried out in Palestine. The Arabic version of the Anti-Coagulant Treatment Satisfaction Scale (ACTS) assessed treatment satisfaction. In addition, the Arabic version of the 6-Item Self-Efficacy for Managing Chronic Diseases (SES6C) was used to assess self-efficacy.

Results

A total of 300 patients using anticoagulants (average age 51.95 and SD 17.98) were included. There is a modest correlation between treatment satisfaction and self-efficacy (r = 0.345; p <  0.001). The mean and median self-efficacy scores were 38.41 ± 9.88 and 39.00 (interquartile range: 33.00–46.00), respectively. Overall, patients reported a moderate burden and benefit score. The mean and median of the acting burden were 43.30 ± 10.45, and 43.30 (interquartile range: 36.00 to 51.00), respectively. The results showed that young age, higher education, employment, use of fewer medications, and having fewer diseases were significantly associated with higher self-efficacy behaviors. The results also showed that new oral anti-coagulants (NOACs) had a higher degree of self-efficacy and ACTS benefit scores (41.00 (33.75–47.00), p = 0.002; 13.00 (12.00–15.00), p <  0.001, respectively), than vitamin k antagonists (VKA).

Conclusions

The results demonstrated a significant relationship between treatment satisfaction and self-efficacy, and certain sociodemographic and clinical characteristics influence both. We found that there is a higher degree of self-efficacy and treatment satisfaction among patients who use NOACs than those who use UFH / VKA. Therefore, patients should be motivated to increase their knowledge about anticoagulant therapy. Healthcare providers should play an active role in educating patients, increasing their self-esteem, and awareness about anticoagulant drugs. Importantly, this study was an explanatory one, and it includes a low proportion of patients with venous thromboembolism. This encourages future research on a large scale of patients, considering the indications of anticoagulant therapy.
Changes in leukocytes and CRP in different stages of major depression
Authors: Singh Deepti , Guest Paul C. , Dobrowolny Henrik , Vasilevska Veronika , Meyer-Lotz Gabriela , Bernstein Hans-Gert , Borucki Katrin , Neyazi Alexandra , Bogerts Bernhard , Jacobs Roland , Steiner Johann
Published: April 2022

Background

We recently reported increased levels of neutrophils, monocytes and C-reactive protein (CRP) correlated with symptom severity in acute schizophrenia. Here, we investigated if a similar pattern of innate immune system activation occurs in major depression (MD).

Methods

We assessed differential blood counts, CRP, depression symptoms (HAMD-21) and psychosocial functioning (GAF) in controls (n = 129) and patients with first (FEMD:n = 82) or recurrent (RMD:n = 47) disease episodes of MD at baseline (T0; hospital admission) and after 6-weeks treatment (T6).

Results

Considering smoking, BMI and gender as covariates, neutrophils (FEMD:p = 0.034, RMD:p = 0.034) and CRP (FEMD:p < 0.001, RMD:p = 0.021) were higher, and eosinophils (FEMD:p = 0.005, RMD:p = 0.004) lower in patients versus controls at T0. Baseline lymphocyte counts were elevated in RMD (p = 0.003) but not FEMD. Results were confirmed by analyses of nonsmokers. At follow-up, eosinophils rose significantly in FEMD (p = 0.011) but no significant changes were observed in RMD. Improvement in HAMD-21 correlated with T0–T6 changes of neutrophil counts in FEMD (r = 0.364,p = 0.024). Compared with our previous schizophrenia study, raised baseline neutrophil and reduced eosinophil counts in MD had smaller effect sizes and treatment had a weaker association with T0-T6 changes in neutrophils. In addition, lymphocytes were elevated at T0 in recurrent MD but not in schizophrenia patients.

Conclusions

These findings suggest that innate immunity may be involved in early stages of MD, and adaptive immunity may be involved in chronic disease. Thus, further studies may lead to new disease stage-dependent MD treatment strategies targeting different aspects of immune system activation.
Recruitment of α4β7 monocytes and neutrophils to the brain in experimental colitis is associated with elevated cytokines and anxiety-like behavior
Authors: Cluny Nina L. , Nyuyki Kewir D. , Almishri Wagdi , Griffin Lateece , Lee Benjamin H. , Hirota Simon A. , Pittman Quentin J. , Swain Mark G. , Sharkey Keith A.
Published: April 2022

Background

Behavioral comorbidities, such as anxiety and depression, are a prominent feature of IBD. The signals from the inflamed gut that cause changes in the brain leading to these behavioral comorbidities remain to be fully elucidated. We tested the hypothesis that enhanced leukocyte–cerebral endothelial cell interactions occur in the brain in experimental colitis, mediated by α4β7 integrin, to initiate neuroimmune activation and anxiety-like behavior.

Methods

Female mice treated with dextran sodium sulfate were studied at the peak of acute colitis. Circulating leukocyte populations were determined using flow cytometry. Leukocyte–cerebral endothelial cell interactions were examined using intravital microscopy in mice treated with anti-integrin antibodies. Brain cytokine and chemokines were assessed using a multiplex assay in animals treated with anti-α4β7 integrin. Anxiety-like behavior was assessed using an elevated plus maze in animals after treatment with an intracerebroventricular injection of interleukin 1 receptor antagonist.

Results

The proportion of classical monocytes expressing α4β7 integrin was increased in peripheral blood of mice with colitis. An increase in the number of rolling and adherent leukocytes on cerebral endothelial cells was observed, the majority of which were neutrophils. Treatment with anti-α4β7 integrin significantly reduced the number of rolling leukocytes. After anti-Ly6C treatment to deplete monocytes, the number of rolling and adhering neutrophils was significantly reduced in mice with colitis. Interleukin-1β and CCL2 levels were elevated in the brain and treatment with anti-α4β7 significantly reduced them. Enhanced anxiety-like behavior in mice with colitis was reversed by treatment with interleukin 1 receptor antagonist.

Conclusions

In experimental colitis, α4β7 integrin-expressing monocytes direct the recruitment of neutrophils to the cerebral vasculature, leading to elevated cytokine levels. Increased interleukin-1β mediates anxiety-like behavior.
Gut microbiota is causally associated with poststroke cognitive impairment through lipopolysaccharide and butyrate
Authors: Wang Huidi , Zhang Mingsi , Li Jie , Liang Jianhai , Yang Mengjia , Xia Genghong , Ren Yueran , Zhou Hongwei , Wu Qiheng , He Yan , Yin Jia
Published: April 2022

Background

Poststroke cognitive impairment (PSCI) is prevalent in stroke patients. The etiology of PSCI remains largely unknown. We previously found that stroke induces gut microbiota dysbiosis which affects brain injury. Hereby, we aimed to investigate whether the gut microbiota contributes to the pathogenesis of PSCI.

Methods

83 stroke patients were recruited and their cognitive function were measured by Montreal Cognitive Assessment (MoCA) scores 3 months after stroke onset. The peripheral inflammatory factor levels and gut microbiota compositions of the patients were analyzed. Fecal microbiota transplantation from patients to stroke mice was performed to examine the causal relationship between the gut microbiota and PSCI. The cognitive function of mice was evaluated by Morris water maze test.

Results

34 and 49 stroke patients were classified as PSCI and non-PSCI, respectively. Compared with non-PSCI patients, PSCI patients showed significantly higher levels of gut Enterobacteriaceae, lipopolysaccharide (LPS) and peripheral inflammation markers. Consistently, stroke mice that received microbiota from PSCI patients (PSCI mice) presented a higher level of Enterobacteriaceae, intestinal Toll-like receptor-4 (TLR4) expression, circulating LPS, LPS-binding protein (LBP) and inflammatory cytokines, and a lower level of fecal butyrate, severer intestine destruction and cognitive impairment than mice that received microbiota from nPSCI patients (nPSCI mice). In addition, we observed exacerbations in blood–brain barrier (BBB) integrity, microglial activation, neuronal apoptosis in the CA1 region of the hippocampus, and Aβ deposition in the thalamus of PSCI mice in comparison with nPSCI mice. Intraperitoneal injection of LPS after stroke caused similar pathology to those seen in PSCI mice. Supplementation with sodium butyrate (NaB) via drinking water rescued these detrimental changes in PSCI mice.

Conclusions

Our data indicate a cause–effect relationship between gut microbiota and PSCI for the first time, which is likely mediated by inflammation-regulating metabolites including LPS and butyrate.
Proteomic landscape subtype and clinical prognosis of patients with the cognitive impairment by Japanese encephalitis infection
Authors: Yin Rong , Yang Linpeng , Hao Ying , Yang Zhiqi , Lu Tao , Jin Wanjun , Dan Meiling , Peng Liang , Zhang Yingjie , Wei Yaxuan , Li Rong , Ma Huiping , Shi Yuanyuan , Fan Pengcheng
Published: April 2022

Background

Cognitive impairment is one of the primary sequelae affecting the quality of life of patients with Japanese encephalitis (JE). The clinical treatment is mainly focused on life support, lacking of targeted treatment strategy.

Methods

A cerebrospinal fluid (CSF) proteomic profiling study was performed including 26 patients with JE in Gansu province of China from June 2017 to October 2018 and 33 other concurrent hospitalized patients who were excluded central nervous system (CNS) organic or CNS infection diseases. The clinical and proteomics data of patients with JE were undergoing combined analysis for the first time.

Results

Two subtypes of JE associated with significantly different prognoses were identified. Compared to JE1, the JE2 subtype is associated with lower overall survival rate and a higher risk of cognitive impairment. The percentages of neutrophils (N%), lymphocyte (L%), and monocytes (M%) decreased in JE2 significantly.

Conclusions

The differences in proteomic landscape between JE subgroups have specificity for the prognosis of cognitive impairment. The data also provided some potential target proteins for treatment of cognitive impairments caused by JE.

Trial registrationChiCTR, ChiCTR2000030499. Registered 1st June 2017,http://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=6333
Emotional blunting in patients with depression. Part I: clinical characteristics
Authors: Christensen Michael Cronquist , Ren Hongye , Fagiolini Andrea
Published: April 2022

Background

Emotional blunting—inability to feel positive or negative emotions, detachment, or reduced emotional responsiveness—is common in people with depression. However, there is a paucity of studies comprehensively investigating this symptom and its functional impact. This study investigated the experience of emotional blunting, and its impact on overall functioning and quality of life, in the acute and remission phases of depression from the perspective of patients and healthcare providers. This paper presents data on the clinical presentation of emotional blunting in depression from the patient perspective.

Methods

Cross-sectional, observational study conducted in Brazil, Canada, and Spain between April 15 and May 18, 2021. Data were collected via a self-completed online survey. Respondents were adults with depression (acute or remission phase), who were currently using a prescribed antidepressant, and who reported emotional blunting during the past 6 weeks. Emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ; total score range 26–130, higher scores indicate greater emotional blunting).

Results

In all, 752 patients completed the survey (62% female; mean age, 45 years). Overall, 44% of patients rated their emotional blunting as extremely severe (acute phase [n = 300], 72%; remission phase [n = 452], 25%; difference, p < 0.01). In all, 56% of patients considered their emotional blunting to be caused by their depression (acute phase, 62%; remission phase, 52%). Mean ODQ total score was 94.8 for patients in the acute phase of depression and 85.7 for those in remission (difference, p < 0.01). Mean score for the ODQ ‘antidepressant as cause’ domain (maximum possible score, 30) was 18.0 in patients in the acute phase and 17.6 in those in remission. Overall, 45% of patients believed that their antidepressant medication was blunting their emotions and 39% were considering stopping or had already stopped their antidepressant because of perceived emotion-related side effects.

Conclusions

Almost three-quarters of patients in the acute phase of depression and one-quarter of those in remission reported severe emotional blunting. Approximately 56% of patients considered their emotional blunting to be caused by their depression, while 45% believed that their antidepressant medication was negatively affecting their emotions. Just over one-third of patients were considering stopping or had stopped their antidepressant as a result.
Effects of a postural cueing for head and neck posture on lumbar lordosis angles in healthy young and older adults: a preliminary study
Authors: Zhai Meiling , Huang Yongchao , Zhou Shi , Feng Jiayun , Pei Chaolei , Wen Li
Published: April 2022

Background

Postural rehabilitation plays an important role in the treatment of non-specific low back pain. Although pelvic inclination has been widely used to improve lumbar lordosis, the effect of cervical anterior inclination on lumbar lordosis in young and older adults in sitting and standing posture is still unclear. This preliminary study was designed to examine the influence of changing the cervical anterior angle on the lumbar lordosis angle, through alterations of the head position under the natural sitting and standing conditions, aiming to provide a basis for establishing a new postural rehabilitation strategy.

Methods

Thirty-six young (24.0 ± 2.2 years, 14 females and 22 males) and 38 older (68.4 ± 5.9 years, 36 females and 2 males) healthy adults participated in this study. The four spinal regional angles—cervical anterior angle, thoracic kyphosis angle, lumbar lordosis angle, and pelvic forward inclination angle, were measured in standing and relaxed sitting postures to determine the effects of a postural cueing for the head and neck posture, “inclining head backward and performing chin tuck,” on lumbar lordosis angle.

Results

In the standing posture, the pelvic forward inclination angle in the older adult group was significantly smaller (P < 0.001, by ANOVA) than that in the young adult group and increased significantly (P < 0.001) in response to the postural cueing. In addition, the thoracic kyphosis angle in the standing (P = 0.001) and sitting (P = 0.003) positions was significantly reduced in response to the postural cueing. However, the lumbar lordosis angle in response to the postural cueing increased significantly in both the standing position (P < 0.001) and sitting position (P < 0.001).

Conclusion

The results suggest that increasing the cervical anterior angle can increase the lumbar lordosis angle, and the cervical anterior inclination can be used as an alternative to pelvic forward inclination to improve the lumbar lordosis angle. Furthermore, the change in head and neck posture can reduce the thoracic kyphosis angle, making it possible to establish a new noninvasive body posture rehabilitation strategy.
DIVIS: a semantic DIstance to improve the VISualisation of heterogeneous phenotypic datasets
Authors: Eid Rayan , Landès Claudine , Pernet Alix , Benoît Emmanuel , Santagostini Pierre , Ghaziri Angelina El , Bourbeillon Julie
Published: April 2022

Background

Thanks to the wider spread of high-throughput experimental techniques, biologists are accumulating large amounts of datasets which often mix quantitative and qualitative variables and are not always complete, in particular when they regard phenotypic traits. In order to get a first insight into these datasets and reduce the data matrices size scientists often rely on multivariate analysis techniques. However such approaches are not always easily practicable in particular when faced with mixed datasets. Moreover displaying large numbers of individuals leads to cluttered visualisations which are difficult to interpret.

Results

We introduced a new methodology to overcome these limits. Its main feature is a new semantic distance tailored for both quantitative and qualitative variables which allows for a realistic representation of the relationships between individuals (phenotypic descriptions in our case). This semantic distance is based on ontologies which are engineered to represent real-life knowledge regarding the underlying variables. For easier handling by biologists, we incorporated its use into a complete tool, from raw data file to visualisation. Following the distance calculation, the next steps performed by the tool consist in (i) grouping similar individuals, (ii) representing each group by emblematic individuals we call archetypes and (iii) building sparse visualisations based on these archetypes. Our approach was implemented as a Python pipeline and applied to a rosebush dataset including passport and phenotypic data.

Conclusions

The introduction of our new semantic distance and of the archetype concept allowed us to build a comprehensive representation of an incomplete dataset characterised by a large proportion of qualitative data. The methodology described here could have wider use beyond information characterizing organisms or species and beyond plant science. Indeed we could apply the same approach to any mixed dataset.
Recruitment of young adult cancer survivors into a randomized controlled trial of an mHealth physical activity intervention
Authors: Valle Carmina G. , Camp Lindsey N. , Diamond Molly , Nezami Brooke T. , LaRose Jessica Gokee , Pinto Bernardine M. , Tate Deborah F.
Published: April 2022

Purpose

Few studies have recruited young adult cancer survivors (YACS) from around the USA into remotely-delivered behavioral clinical trials. This study describes recruitment strategies used in the IMproving Physical Activity after Cancer Treatment (IMPACT) study, a 12-month randomized controlled trial of a mobile physical activity intervention for YACS.

Methods

We conducted formative work to guide development of recruitment messages and used a variety of methods and channels to recruit posttreatment YACS (diagnosed ages 18–39, participating in < 150 min/week of moderate-to-vigorous intensity activity). We used targeted social media advertisements, direct mailings, clinical referrals, and phone calls to potentially eligible individuals identified through local tumor registries. We also asked community organizations to share study information and advertized at a national conference for YACS.

Results

The final sample of 280 participants (23% identified as racial/ethnic minority individuals, 18% male, mean 33.4 ± 4.8 years) was recruited over a 14-month period. About 38% of those who completed initial screening online (n = 684) or via telephone (n = 63) were randomized. The top recruitment approach was unpaid social media, primarily via Facebook posts by organizations/friends (45%), while direct mail yielded 40.7% of participants. Other social media (paid advertisements, Twitter), email, clinic referrals, and conference advertisements each yielded 3% or fewer participants. The most cost-effective methods per participant recruited were unpaid social media posts and direct mailings.

Conclusions

The IMPACT trial successfully met enrollment goals using a national strategy to recruit physically inactive YACS. Our approaches can inform recruitment planning for other remotely-delivered intervention trials enrolling YACS.

Trial registration

ClinicalTrials.govNCT03569605. Registered on 26 June 2018.
The use of standardized Brazilian green propolis extract (EPP-AF) as an adjunct treatment for hospitalized COVID-19 patients (BeeCovid2): a structured summary of a study protocol for a randomized controlled trial
Authors: Silveira Marcelo Augusto Duarte , de Souza Sergio Pinto , dos Santos Galvão Erica Batista , Teixeira Maurício Brito , Gomes Marcel Miranda Dantas , Damiani Lucas Petri , Bahiense Bruno Andrade , Cabral Julia Barros , De Oliveira Cicero Wandson Luiz Macedo , Mascarenhas Talita Rocha , Pinheiro Priscila Carvalho Guedes , Alves Milena Souza , de Melo Rodrigo Morel Vieira , Berretta Andresa Aparecida , Leite Flávia Mendes , Nonaka Carolina Kymie Vasques , de Freitas Souza Bruno Solano , Mendes Ana Verena Almeida , da Guarda Suzete Farias , da Hora Passos Rogério
Published: April 2022

Background

The 2019 coronavirus disease (COVID-19) pandemic continues to spread and affects large numbers of people with unprecedented impacts. Experimental evidence has already been obtained for use of the standardized extract of Brazilian green propolis (EPP-AF) against viral targets, and clinical rationality has been demonstrated for testing this extract as an adjunct to treatment in patients affected by COVID-19. The BeeCovid2 study aims to assess whether EPP-AF has an impact on the improvement of patients hospitalized with COVID-19 by reducing the length of hospital stay.

Methods

BeeCovid2 is a randomized, double-blinded, placebo-controlled clinical study being conducted in Brazil to provide further evidence on the effectiveness of standardized green propolis extract as an adjunctive treatment for adults hospitalized with COVID-19. Hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 and up to 14 days of symptoms were included. Patients under mechanical ventilation at randomization, pregnant women, cancer patients, transplanted or using immunosuppression, HIV patients, patients who used propolis in the last 30 days, bacterial or fungal infection at randomization, impossibility of using medication orally or enterally, and advanced chronic diseases (e.g., advanced heart failure, severe liver disease, and end-stage chronic kidney disease). Enrolled patients are randomized at a 1:1 ratio to receive placebo or standardized propolis extract (900 mg/day) for 10 days. The study treatments are administered in a double-blinded manner, and patients are followed for 28 days. The primary outcome is the difference in length of hospital stay in days between groups. Secondary outcomes include the need for mechanical ventilation, the rate of secondary infection, rate of acute kidney injury, the need for renal replacement therapy, the requirement for vasoactive drugs, the use of an intra-aortic balloon pump (IABP), and the use of extracorporeal membrane oxygenation (ECMO).

Discussion

This trial is very useful and will provide more data on the effectiveness of using the standardized Brazilian green propolis extract as an adjunctive treatment in association with standard care in adults hospitalized with moderate to severe acute COVID-19.

Trial registration

ClinicalTrials.gov NCT04800224. Registered on March 16, 2021.
Regulatory effects of a novel cysteine protease inhibitor in Baylisascaris schroederi migratory larvae on mice immune cells
Authors: Xu Jing-Yun , Gu XiaoBin , Xie Yue , He Ran , Xu Jing , Xiong Lang , Peng XueRong , Yang GuangYou
Published: April 2022

Background

The giant panda (Ailuropoda melanoleuca) is a well-known, rare and endangered species. Baylisascaris schroederi is a pathogenic ascarid. Infection with B. schroederi may cause death in giant pandas. At present, the immune evasion mechanism of B. schroederi is little known. Cysteine protease inhibitors (CPI) play important roles in the regulation of host immune responses against certain nematodes. In this study, we focused on the analysis of the regulation of B. schroederi migratory larvae CPI (rBsCPI-1) on mice immune cells.

Methods

First, the pattern recognition receptors on the surface of peripheral blood mononuclear cells (PBMCs) and the signal pathways that transduce extracellular signals into the nucleus activated by rBsCPI-1 were identified. Then, the regulatory effects of rBsCPI-1 on PBMCs physiological activities were detected. Finally, the effects of rBsCPI-1 on TLR signaling pathway activation and NF-κB phosphorylation in mice immunized with recombinant protein were analysed.

Results

The results suggested that rBsCPI-1 secreted by B. schroederi migratory larvae is mainly recognized by TLR2 and TLR4 on PBMCs. Extracellular signals are transduced into the nucleus through the MAPK and NF-κB signaling pathways, enhancing the phagocytosis, migration, and apoptosis of PBMCs; meanwhile, rBsCPI-1 induces high expression of NO. Thus, rBsCPI-1 plays a role in immune regulation. In addition, the high expression of negative regulatory factors also ensured that TLR activation is maintained at the optimal level.

Conclusions

rBsCPI-1 can transduce regulatory signals into immune cells by activating the TLR2/4-NF-κB/MAPK signaling pathway, having a certain regulatory effect on the physiological activities. Meanwhile, rBsCPI-1 can maintain the immune response in a balance by limiting the over-activation of the TLRs signaling pathway and thus contributes to B. schroederi immune evasion.

Graphical Abstract
Clinical implementation of RNA sequencing for Mendelian disease diagnostics
Authors: Yépez Vicente A. , Gusic Mirjana , Kopajtich Robert , Mertes Christian , Smith Nicholas H. , Alston Charlotte L. , Ban Rui , Beblo Skadi , Berutti Riccardo , Blessing Holger , Ciara Elżbieta , Distelmaier Felix , Freisinger Peter , Häberle Johannes , Hayflick Susan J. , Hempel Maja , Itkis Yulia S. , Kishita Yoshihito , Klopstock Thomas , Krylova Tatiana D. , Lamperti Costanza , Lenz Dominic , Makowski Christine , Mosegaard Signe , Müller Michaela F. , Muñoz-Pujol Gerard , Nadel Agnieszka , Ohtake Akira , Okazaki Yasushi , Procopio Elena , Schwarzmayr Thomas , Smet Joél , Staufner Christian , Stenton Sarah L. , Strom Tim M. , Terrile Caterina , Tort Frederic , Van Coster Rudy , Vanlander Arnaud , Wagner Matias , Xu Manting , Fang Fang , Ghezzi Daniele , Mayr Johannes A. , Piekutowska-Abramczuk Dorota , Ribes Antonia , Rötig Agnès , Taylor Robert W. , Wortmann Saskia B. , Murayama Kei , Meitinger Thomas , Gagneur Julien , Prokisch Holger
Published: April 2022

Background

Lack of functional evidence hampers variant interpretation, leaving a large proportion of individuals with a suspected Mendelian disorder without genetic diagnosis after whole genome or whole exome sequencing (WES). Research studies advocate to further sequence transcriptomes to directly and systematically probe gene expression defects. However, collection of additional biopsies and establishment of lab workflows, analytical pipelines, and defined concepts in clinical interpretation of aberrant gene expression are still needed for adopting RNA sequencing (RNA-seq) in routine diagnostics.

Methods

We implemented an automated RNA-seq protocol and a computational workflow with which we analyzed skin fibroblasts of 303 individuals with a suspected mitochondrial disease that previously underwent WES. We also assessed through simulations how aberrant expression and mono-allelic expression tests depend on RNA-seq coverage.

Results

We detected on average 12,500 genes per sample including around 60% of all disease genes—a coverage substantially higher than with whole blood, supporting the use of skin biopsies. We prioritized genes demonstrating aberrant expression, aberrant splicing, or mono-allelic expression. The pipeline required less than 1 week from sample preparation to result reporting and provided a median of eight disease-associated genes per patient for inspection. A genetic diagnosis was established for 16% of the 205 WES-inconclusive cases. Detection of aberrant expression was a major contributor to diagnosis including instances of 50% reduction, which, together with mono-allelic expression, allowed for the diagnosis of dominant disorders caused by haploinsufficiency. Moreover, calling aberrant splicing and variants from RNA-seq data enabled detecting and validating splice-disrupting variants, of which the majority fell outside WES-covered regions.

Conclusion

Together, these results show that streamlined experimental and computational processes can accelerate the implementation of RNA-seq in routine diagnostics.
Functional characterization of goose IRF1 in IFN induction and anti-NDV infection
Authors: Lin Zhenyu , Wang Jie , Zhang Nian , Yi Jianshu , Wang Zhaofei , Ma Jingjiao , Wang Hengan , Yan Yaxian , Qian Kun , Sun Jianhe , Cheng Yuqiang
Published: April 2022

Interferon regulatory factors (IRFs) play a key role in many aspects of immune response, and IRF1, IRF3, and IRF7 are positive regulators of IFN induction in mammals. However, IRF3, as the most critical regulatory factor in mammals, is naturally absent in birds, which attracts us to study the functions of other members of the avian IRF family. In the present study, we cloned goose IRF1 (GoIRF1) and conducted a series of bioinformatics analyses to compare the protein homology of GoIRF1 with that of IRF1 in other species. The overexpression of GoIRF1 in DF-1 cells induced the activation of IFN-β, and this activation is independent of the dosage of the transfected GoIRF1 plasmids. The overexpression of GoIRF1 in goose embryonic fibroblasts (GEFs) induced the expression of IFNs, proinflammatory cytokines, and IFN-stimulated genes (ISGs); it also inhibited the replication of green fluorescent protein (GFP)-tagged Newcastle disease virus (NDV) (NDV-GFP) and GFP-tagged vesicular stomatitis virus (VSV) (VSV-GFP). Our results suggest that GoIRF1 is an important regulator of IFNs, proinflammatory cytokines, and ISGs and plays a role in antiviral innate immunity in geese.
The Irish cattle population structured by enterprise type: overview, trade & trends
Authors: Brock Jonas , Lange Martin , Tratalos Jamie A. , Meunier Natascha , Guelbenzu-Gonzalo Maria , More Simon J. , Thulke Hans-Hermann , Graham David A.
Published: April 2022

Background

The cattle sector is the most important economic production unit of the Irish farming and agri-food sector. Despite its relevance, there has been limited quantitative information about the structure of differing cattle production types and of the connections between them. This paper addresses this gap by providing, for the first time, an overview of the Irish cattle population structured by enterprise type.

Methods & Results

We collected data from the cattle register for the period 2015 to 2019 and assigned registered herds to one of 18 different herd types using a recently published herd type classification approach. This allows, for the first time, to exploring changes in enterprise types and subtypes over time, and describing the movements between these subtypes and from these subtypes to slaughter.

Conclusions

The overview and associated classification presented in this study will form the basis for a number of future comparative studies, including cross-sectoral assessments of profitability, estimation of the extent of animal health losses on Irish cattle farms or structural analysis of Greenhouse Gas (GHG) emissions across production systems.
Mapping evidence on the risk factors associated with pediatric cancers in sub-Saharan Africa: a scoping review
Authors: Ndlovu Sehlisiwe , Hlongwa Mbuzeleni , Ginindza Themba
Published: April 2022

Background

The rarity and heterogeneity of pediatric cancers make it difficult to assess risk factors associated with the development of cancer in this group. This also determines the quantity and quality of evidence for etiological factors linked to pediatric cancers. Evidence on the risk factors associated with pediatric cancers is scarce; however, it has been accumulating slowly over the years. As the disease burden shifts from communicable to non-communicable diseases, most of these low- to middle-income countries (LMICs) find themselves overburdened with changing health care priorities and needs. In sub-Saharan Africa, it is of major importance to pay particular attention to risk factors associated with pediatric cancer.

Objective

To map evidence on risk factors associated with pediatric cancers in sub-Saharan Africa (SSA).

Methods

This review was guided by Arksey and O’Malley’s framework for conducting scoping reviews. Four electronic databases were searched in December 2018, and another manual search was conducted in February 2022 to include newly published eligible articles. The databases searched included PubMed and Health Source: Nursing/Academic Edition. We also searched articles from an academic search engine, Google scholar. This review included articles reporting the relevant outcomes of this study and articles reporting cancers in children in the 0–15 years age range. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews (PRISMA-ScR): checklist and explanation.

Results

We retrieved 7391 articles from the initial database. The final number of studies that were included for data extraction was 15. Evidence from the retrieved studies suggests that most childhood cancers in the SSA region are infection-induced. The type of cancer mostly reported is Burkitt Lymphoma and is diagnosed mostly in the tropical region of SSA. The type of risk factors was divided into three types: infection-induced, genetic, and demographic risk factors. Overall, based on the articles retrieved, there was limited evidence on the risk factors associated with pediatric cancers in SSA.

Conclusion

The limited evidence on the risk factors coupled with the lack of evidence on the true burden of these malignancies in the SSA hampers efforts to set priorities for childhood cancer control. Formulation of effective preventative (where possible) measures and treatment regimens will need proper assessment of risk factors.
On the critical behavior for time-fractional pseudo-parabolic-type equations with combined nonlinearities
Authors: Bin Sultan Areej , Jleli Mohamed , Samet Bessem , Vetro Calogero
Published: April 2022

We are concerned with the existence and nonexistence of global weak solutions for a certain class of time-fractional inhomogeneous pseudo-parabolic-type equations involving a nonlinearity of the form $|u|^{p}+\iota |\nabla u|^{q}$

|
u
|

p

+
ι

|
∇
u
|

q

, where $p,q>1$
p
,
q
>
1
, and $\iota \geq 0$
ι
≥
0
is a constant. The cases $\iota =0$
ι
=
0
and $\iota >0$
ι
>
0
are discussed separately. For each case, the critical exponent in the Fujita sense is obtained. We point out two interesting phenomena. First, the obtained critical exponents are independent of the fractional orders of the time derivative. Secondly, in the case $\iota >0$
ι
>
0
, we show that the gradient term induces a discontinuity phenomenon of the critical exponent.
A hydrotrope pretreatment for stabilized lignin extraction and high titer ethanol production
Authors: Ji Hairui , Wang Le , Tao Furong , Yao Zhipeng , Li Xuezhi , Dong Cuihua , Pang Zhiqiang
Published: April 2022

The biomass pretreatment strategies using organic acids facilitate lignin removal and enhance the enzymatic digestion of cellulose. However, lignin always suffers a severe and irreversible condensation. The newly generated C–C bonds dramatically affect its further upgrading. In this study, we used a recyclable hydrotrope (p-Toluenessulfonic acid, p-TsOH) to dissolve lignin under mild condition and stabilized lignin with a quenching agent (formaldehyde, FA) during extraction, achieving both value-added lignin extraction and efficient enzymatic saccharification of cellulose. Approximately 63.7% of lignin was dissolved by 80% (wt. %) p-TsOH with 1.5% FA addition at 80 °C, 30 min. The obtained lignin was characterized by FTIR spectroscopy, TGA, 2D HSQC NMR spectroscopy, and GPC. The results indicated that the extracted lignin exhibited excellent properties, such as light color, a low molecular weight (Mw, 5371 g/mol), and a narrow polydispersity (Mw/Mn, 1.63). The pretreated substrate was converted to ethanol via a quasi-simultaneous saccharification and fermentation process (Q-SSF). After fermentation of 60 h, the ethanol concentration reached 38.7 ± 3.3 g/L which was equivalent to a theoretical ethanol yield of 82.9 ± 2.2% based on the glucan content, while the residual glucose concentration was only 4.69 ± 1.4 g/L. In short, this pretreatment strategy protected lignin to form new C–C linkages and improved the enzymatic saccharification of glucan for high-titer ethanol production.

Graphical Abstract