bluuebunny/crossref_metadata_2025 huggingface dataset:
A toddler with an unusually severe polyarticular arthritis and a lung involvement: a case report
Authors: Basile Pietro , Gortani Giulia , Taddio Andrea , Pastore Serena , Corona Federica , Tesser Alessandra , Barbi Egidio , Tommasini Alberto
Published: November 2022

Background

COPA syndrome is a rare hereditary inflammatory disease caused by mutations in the gene encoding the coatomer protein subunit alpha, causing excessive production of type I interferon.

This case is a reminder for the general paediatrician, highlighting the relevance of the association between arthritis and lung involvement in toddlers.

Case presentation

We report the case of a 2-year-old girl with intermittent limping and joint pain. Her family history was relevant for a Still disease with lung involvement in the mother. Physical examination showed moderate wrist swelling. Laboratory findings on admission showed an increase in inflammatory markers, positive rheumatoid factor, antibodies antinuclear antibody (ANA) and cyclic citrullinated peptide (anti-CCP). Wrists’ ultrasound documented synovial thickening, and chest X-rays showed an unexpected severe interstitial pneumopathy. Genetic testing confirmed the diagnosis of a heterozygous mutation of the COPA gene in c.841C > T (p.R281W). Janus kinase treatment was started (baricitinib, 4 mg daily per os) with a remarkable improvement in limping and joint pain after two weeks.

Conclusions

In cases of recurrent arthritis with family history and multiple involvement organs, a genetic disorder should be suspected and genetic testing should be performed. Furthermore, this case suggests that therapy with jak inhibitors may be effective and safe in interferonopathies.
Acute effects of NIV on peripheral muscle function and aerobic performance in patients with chronic obstructive pulmonary disease: a pilot study
Authors: de Medeiros Nogueira Mariana Galvão , Silva Gabriely Azevêdo Gonçalo , Marinho Marcelo Henrique Tavares , de Fátima Costa Brito Ozana , de Brito Vieira Wouber Hérickson , Ururahy Marcela Abbott Galvão , Nogueira Ivan Daniel Bezerra , da Silva Ivanízia Soares , de Miranda Silva Nogueira Patrícia Angélica
Published: November 2022

Background

Non-invasive ventilation (NIV) reduces respiratory load and demands on peripheral muscles.

Methods

This study aims to evaluate the acute effects of bi-level NIV on peripheral muscle function during isokinetic exercise and aerobic performance in chronic obstructive pulmonary disease (COPD) patients. This is a pilot crossover study performed with a non-probabilistic sample of 14 moderate to very severe COPD patients. Procedures carried out in two days. Dyspnea, quality of life, lung function, respiratory muscle strength, functional capacity (6-min walk test—6MWT), and isokinetic assessment of the quadriceps were assessed. Blood samples (lactate, lactate dehydrogenase, and creatine kinase concentration) were also collected. Right after, NIV was performed for 30 min (bi-level or placebo, according to randomization) followed by new blood sample collection, 6MWT, and isokinetic dynamometer tests. Before and after evaluations, the subjective perception of dyspnea and fatigue in the lower limbs was quantified. After a wash-out period of seven days, participants returned, and all assessments were performed again.

Results

NIV showed improvements in perceived exertion and dyspnea after isokinetic exercise (p < 0.02 and p < 0.05, respectively).

Conclusions

NIV improves the perception of dyspnea and fatigue during the isokinetic exercise.
Posterior atlantoaxial internal fixation using Harms technique assisted by 3D-based navigation robot for treatment of atlantoaxial instability
Authors: Lang Zhao , Han Xiaoguang , Fan Mingxing , Liu Yajun , He Da , Tian Wei
Published: November 2022

Background

To evaluate the accuracy of screw placement using the TiRobot surgical robot in the Harms procedure and to assess the clinical outcomes of this technique.

Methods

This retrospective study included 21 patients with atlantoaxial instability treated by posterior atlantoaxial internal fixation (Harms procedure) using the TiRobot surgical robot between March 2016 and June 2021. The precision of screw placement, perioperative parameters and clinical outcomes were recorded. Screw placement was assessed based on intraoperative guiding pin accuracy measurements on intraoperative C-arm cone-beam computed tomography (CT) images using overlay technology and the incidence of screw encroachment identified on CT images.

Results

Among the 21 patients, the mean age was 44.8 years, and the causes of atlantoaxial instability were os odontoideum (n = 11), rheumatoid arthritis (n = 2), unknown pathogenesis (n = 3), and type II odontoid fracture (n = 5). A total of 82 screws were inserted with robotic assistance. From intraoperative guiding pin accuracy measurements, the average translational and angular deviations were 1.52 ± 0.35 mm (range 1.14–2.25 mm) and 2.25° ± 0.45° (range 1.73°–3.20º), respectively. Screw placement was graded as A for 80.5% of screws, B for 15.9%, and C for 3.7%. No complications related to screw misplacement were observed. After the 1-year follow-up, all patients with a neurological deficit experienced neurological improvement based on Nurick Myelopathy Scale scores, and all patients with preoperative neck pain reported improvement based on Visual Analog Scale scores.

Conclusions

Posterior atlantoaxial internal fixation using the Harms technique assisted by a 3D-based navigation robot is safe, accurate, and effective for treating atlantoaxial instability.
Exploring risk factors for cervical lymph node metastasis in papillary thyroid microcarcinoma: construction of a novel population-based predictive model
Authors: Huang Yanling , Mao Yaqian , Xu Lizhen , Wen Junping , Chen Gang
Published: November 2022

Background

Machine learning was a highly effective tool in model construction. We aim to establish a machine learning-based predictive model for predicting the cervical lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC).

Methods

We obtained data on PTMC from the SEER database, including 10 demographic and clinicopathological characteristics. Univariate and multivariate logistic regression (LR) analyses were applied to screen the risk factors for cervical LNM in PTMC. Risk factors with P < 0.05 in multivariate LR analysis were used as modeling variables. Five different machine learning (ML) algorithms including extreme gradient boosting (XGBoost), random forest (RF), adaptive boosting (AdaBoost), gaussian naive bayes (GNB) and multi-layer perceptron (MLP) and traditional regression analysis were used to construct the prediction model. Finally, the area under the receiver operating characteristic (AUROC) curve was used to compare the model performance.

Results

Through univariate and multivariate LR analysis, we screened out 9 independent risk factors most closely associated with cervical LNM in PTMC, including age, sex, race, marital status, region, histology, tumor size, and extrathyroidal extension (ETE) and multifocality. We used these risk factors to build an ML prediction model, in which the AUROC value of the XGBoost algorithm was higher than the other 4 ML algorithms and was the best ML model. We optimized the XGBoost algorithm through 10-fold cross-validation, and its best performance on the training set (AUROC: 0.809, 95%CI 0.800–0.818) was better than traditional LR analysis (AUROC: 0.780, 95%CI 0.772–0.787).

Conclusions

ML algorithms have good predictive performance, especially the XGBoost algorithm. With the continuous development of artificial intelligence, ML algorithms have broad prospects in clinical prognosis prediction.
Pathways to ovarian cancer diagnosis: a qualitative study
Authors: Lawson-Michod Katherine A. , Watt Melissa H. , Grieshober Laurie , Green Sarah E. , Karabegovic Lea , Derzon Samantha , Owens Makelle , McCarty Rachel D. , Doherty Jennifer A. , Barnard Mollie E.
Published: November 2022

Background

Ovarian cancer is often diagnosed at a late stage, when survival is poor. Qualitative narratives of patients’ pathways to ovarian cancer diagnoses may identify opportunities for earlier cancer detection and, consequently, earlier stage at diagnosis.

Methods

We conducted semi-structured interviews of ovarian cancer patients and survivors (n = 14) and healthcare providers (n = 11) between 10/2019 and 10/2021. Interviews focused on the time leading up to an ovarian cancer diagnosis. Thematic analysis was conducted by two independent reviewers using a two-phase deductive and inductive coding approach. Deductive coding used a priori time intervals from the validated Model of Pathways to Treatment (MPT), including self-appraisal and management of symptoms, medical help-seeking, diagnosis, and pre-treatment. Inductive coding identified common themes within each stage of the MPT across patient and provider interviews.

Results

The median age at ovarian cancer diagnosis was 61.5 years (range, 29–78 years), and the majority of participants (11/14) were diagnosed with advanced-stage disease. The median time from first symptom to initiation of treatment was 2.8 months (range, 19 days to 4.7 years). The appraisal and help-seeking intervals contributed the greatest delays in time-to-diagnosis for ovarian cancer. Nonspecific symptoms, perceptions of health and aging, avoidant coping strategies, symptom embarrassment, and concerns about potential judgment from providers prolonged the appraisal and help-seeking intervals. Patients and providers also emphasized access to care, including financial access, as critical to a timely diagnosis.

Conclusion

Interventions are urgently needed to reduce ovarian cancer morbidity and mortality. Population-level screening remains unlikely to improve ovarian cancer survival, but findings from our study suggest that developing interventions to improve self-appraisal of symptoms and reduce barriers to help-seeking could reduce time-to-diagnosis for ovarian cancer. Affordability of care and insurance may be particularly important for ovarian cancer patients diagnosed in the United States.
Effect of vitamin D supplementation on the severity of stress urinary incontinence in premenopausal women with vitamin D insufficiency: a randomized controlled clinical trial
Authors: Shahraki Sedigheh Khodabandeh , Emadi Seyedeh Fatemeh , Salarfard Mahla , Chenari Zahra , Tadayyonfar Faezeh , Alikamali Maryam
Published: November 2022

Background

Urinary incontinence, especially stress urinary incontinence (SUI), is one of the problems experienced by premenopausal women. Given the role of vitamin D in enhancing muscle strength and function, this study explored the effect of vitamin D3 supplementation on SUI in premenopausal women.

Methods

A randomized controlled trial was performed with 60 premenopausal women referring to Kerman gynecological clinic in 2020 and 2021. Eligible women received a 5000-unit vitamin D supplement or placebo weekly for 3 months. The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) was utilized to assess SUI severity before and after the intervention. The t-test, Chi-square test, and repeated measures ANOVA were carried out in SPSS software (version 22) to analyze the data. P-values smaller than 0.05 were considered significant.

Results

Before the intervention, there was no significant difference between the intervention and control groups in SUI severity (P = 0.652) and the impact of SUI severity on premenopausal women’s lives (P = 0.804). In contrast, after 8-12 weeks of vitamin D supplementation, these scores decreased significantly in the intervention group relative to the control group (P <  0.001). In addition, after vitamin D supplementation, the number of SUI and urinary leakage symptoms decreased in the intervention group (P <  0.001).

Conclusion

Vitamin D supplementation improves SUI in premenopausal women.

Trial registration

This trial was registered with the Iranian Registry of Clinical Trials; https://fa.irct.ir/trial/53474 (IRCT20190724044318N2) on 11/02/2021.
Preparing students to deal with the consequences of the workforce shortage among health professionals: a qualitative approach
Authors: Golz Christoph , Oulevey Bachmann Annie , Defilippis Tiziana Sala , Kobleder Andrea , Peter Karin Anne , Schaffert René , Schwarzenbach Xenia , Kampel Thomas , Hahn Sabine
Published: November 2022

Background

Healthcare is facing a shortage of qualified healthcare professionals. The pandemic has brought to light the fragile balance that affects all healthcare systems. Governments have realized that these systems and the professionals working in them need support at different levels to strengthen the retention of the workforce. Health professionals’ education can play an important role in ensuring that new generations of workers have sound personal and professional competencies to successfully face the challenges of professional practice. These challenges are described in the literature, but the extent to which they are considered in health professionals’ education is less clear.

Methods

This qualitative study compares the professional challenges and educational needs described in the literature with the current curricula for health professionals offered in Switzerland. Data were collected nationally through focus group interviews with 65% of Switzerland’s directors of bachelor’s and master’s programs of health professions (nursing, physiotherapy, occupational therapy, midwifery, nutrition and dietetics, osteopathy, radiologic medical imaging technology, health promotion and prevention, and health sciences). The data attained were analyzed using knowledge mapping.

Results

The results reveal a gap among education programs with regard to occupational health promotion and cultural diversity. Both topics are taught with a sole focus on patients, and students are expected to adopt similar strategies for their health promotion and stress management. Physicians are insufficiently involved in interprofessional education. The programs fail to enhance health professionals’ political, economic and digital competencies.

Conclusion

The results of this study offer clear guidance about what topics need to be integrated into curricula to improve health professionals’ well-being at work and their preparedness to face daily professional challenges.
The reimbursement for expensive medicines: stakeholder perspectives on the SMA medicine nusinersen and the Dutch Coverage Lock policy
Authors: Scheijmans Féline E. V. , Zomers Margot L. , Fadaei Sina , Onrust Marthe R. , van der Graaf Rieke , Delden Johannes J. M. van , van der Pol W. Ludo , van Thiel Ghislaine J. M. W.
Published: November 2022

Background

The reimbursement for expensive medicines poses a growing challenge to healthcare worldwide. In order to increase its control over the costs of medicines, the Dutch government introduced the Coverage Lock (CL) policy in 2015. The CL postpones decisions regarding reimbursement of expensive medicines until detailed advice on i.e., cost-effectiveness has been given. The CL has been in place for six years, has raised many questions and concerns, but currently, no evaluation is known to the authors. A better understanding of the effects of the CL on all stakeholders involved may contribute to reflections on the CL process and help find ways to improve it. An evaluation of Dutch policy will also be relevant for other countries that aim to optimize reimbursement procedures for expensive treatments. To perform this evaluation, we focused on the CL procedure for the medicine nusinersen. Nusinersen is the first treatment for spinal muscular atrophy (SMA). Following EMA approval in May 2017, it was placed in the CL. The analysis of cost-effectiveness and added therapeutic value resulted in an advice for reimbursement limited to children younger than 9.5 years at the start of treatment; this was implemented from August 2018 onwards.

Methods

Qualitative stakeholder perspective analysis of the CL procedure focusing on nusinersen with 15 stakeholders.

Results

Stakeholders raised key issues of the CL based on their experience with nusinersen: emotional impact of the CL, duration of the CL procedure, appropriateness of the CL procedure for different types of medicines, transparency of the CL, a wish for patient-centred decision-making and the lack of uniformity of access to expensive treatments.

Discussion

Stakeholders supported measures to control healthcare expenses and to ensure reasonable pricing. They considered the delay in access to therapies and lack of procedural transparency to be the main challenges to the CL. Stakeholders also agreed that the interests of patients deserve more attention in the practical implementation of the reimbursement decision. Stakeholders suggested a number of adjustments to improve the CL, such as a faster start with conditional reimbursement programs to ensure access and intensify European collaboration to speed up the assessment of the medicine.
Systematic evaluation of the pre-eclampsia drugs, dietary supplements and biologicals pipeline using target product profiles
Authors: McDougall Annie R. A. , Hastie Roxanne , Goldstein Maya , Tuttle Andrew , Tong Stephen , Ammerdorffer Anne , Gülmezoglu A. Metin , Vogel Joshua P.
Published: November 2022

Background

The Accelerating Innovation for Mothers (AIM) project established a database of candidate medicines in research and development (R&D) between 2000 and 2021 for five pregnancy-related conditions, including pre-eclampsia. In parallel, we published target product profiles (TPPs) that describe optimal characteristics of medicines for use in preventing/treating pre-eclampsia. The study objective was to use systematic double screening and extraction to identify all candidate medicines being investigated for pre-eclampsia prevention/treatment and rank their potential based on the TPPs.

Methods

Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched (Jan–May 2021). The AIM database was screened for all candidates being investigated for pre-eclampsia. Candidates in clinical development were evaluated against nine prespecified criteria from TPPs identified as key for wide-scale implementation, and classified as high, medium or low potential based on matching to the TPPs. Preclinical candidates were categorised by product type, archetype and medicine subclass.

Results

The AIM database identified 153 candidates for pre-eclampsia. Of the 87 candidates in clinical development, seven were classified as high potential (prevention: esomeprazole, l-arginine, chloroquine, vitamin D and metformin; treatment: sulfasalazine and metformin) and eight as medium potential (prevention: probiotic lactobacilli, dalteparin, selenium and omega-3 fatty acid; treatment: sulforaphane, pravastatin, rosuvastatin and vitamin B3). Sixty-six candidates were in preclinical development, the most common being amino acid/peptides, siRNA-based medicines and polyphenols.

Conclusions

This is a novel, evidence-informed approach to identifying promising candidates for pre-eclampsia prevention and treatment — a vital step in stimulating R&D of new medicines for pre-eclampsia suitable for real-world implementation.
Study protocol of the GLOW study: maximising treatment options for recurrent glioblastoma patients by whole genome sequencing-based diagnostics—a prospective multicenter cohort study
Authors: van Opijnen Mark P. , Broekman Marike L. D. , de Vos Filip Y. F. , Cuppen Edwin , van der Hoeven Jacobus J. M. , van Linde Myra E. , Compter Annette , Beerepoot Laurens V. , van den Bent Martin J. , Vos Maaike J. , Fiebrich Helle-Brit , Koekkoek Johan A. F. , Hoeben Ann , Kho Kuan H. , Driessen Chantal M. L. , Jeltema Hanne-Rinck , Robe Pierre A. J. T. , Maas Sybren L. N.
Published: November 2022

Background

Glioblastoma (GBM), the most common glial primary brain tumour, is without exception lethal. Every year approximately 600 patients are diagnosed with this heterogeneous disease in The Netherlands. Despite neurosurgery, chemo -and radiation therapy, these tumours inevitably recur. Currently, there is no gold standard at time of recurrence and treatment options are limited. Unfortunately, the results of dedicated trials with new drugs have been very disappointing. The goal of the project is to obtain the evidence for changing standard of care (SOC) procedures to include whole genome sequencing (WGS) and consequently adapt care guidelines for this specific patient group with very poor prognosis by offering optimal and timely benefit from novel therapies, even in the absence of traditional registration trials for this small volume cancer indication.

Methods

The GLOW study is a prospective diagnostic cohort study executed through collaboration of the Hartwig Medical Foundation (Hartwig, a non-profit organisation) and twelve Dutch centers that perform neurosurgery and/or treat GBM patients. A total of 200 patients with a first recurrence of a glioblastoma will be included. Dual primary endpoint is the percentage of patients who receive targeted therapy based on the WGS report and overall survival. Secondary endpoints include WGS report success rate and number of targeted treatments available based on WGS reports and number of patients starting a treatment in presence of an actionable variant. At recurrence, study participants will undergo SOC neurosurgical resection. Tumour material will then, together with a blood sample, be sent to Hartwig where it will be analysed by WGS. A diagnostic report with therapy guidance, including potential matching off-label drugs and available clinical trials will then be sent back to the treating physician for discussing of the results in molecular tumour boards and targeted treatment decision making.

Discussion

The GLOW study aims to provide the scientific evidence for changing the SOC diagnostics for patients with a recurrent glioblastoma by investigating complete genome diagnostics to maximize treatment options for this patient group.

Trial registration: ClinicalTrials.gov Identifier: NCT05186064.
Prevalence of malaria and its risk factors in Lake Tana and surrounding areas, northwest Ethiopia
Authors: Adugna Fasil , Wale Melaku , Nibret Endalkachew
Published: November 2022

Background

In Ethiopia, malaria is a major concern to the health, and socio-economic development of the country because of its occurrence at the peak agricultural activities. Factors such as environmental, human host, parasite, and vector determine malaria transmission. Therefore, the present study was conducted to determine the prevalence and associated factors of malaria among febrile patients who visited selected health centres.

Methods

Institutional-based cross-sectional study was conducted between October 2020 to July 2021 in eight selected health centres located in Lake Tana and its surrounding areas. A simple random sampling technique was used to select febrile patients. Thick and thin blood films were prepared and processed according to the WHO guidelines. Socio-demographic and malaria risk factors were collected from study participants who could read and write using a self-administered questionnaire, whereas face-to-face interview was used to collect information from those participants who could not write and read. The strength of association between risk factors and malaria was assessed using univariate and multivariate logistic regression models.

Results

Of the total (531) febrile patients, 75.3% were malaria negative and 24.7% (overall prevalence) were malaria confirmed cases. Most of the infections were caused by Plasmodium falciparum (72.5%) followed by Plasmodium vivax (23.7%) and mixed-species (3.8%). The highest prevalence was recorded in Kidist Hana (51.5%) followed by Robit (34.8%), Gorgora (30.3%), and Wusha Tiris (25%) health centres. In terms of months, the highest prevalence (37.5%) was detected in October whereas the lowest (14%) was in March. Logistic regression analysis revealed that gender (p = 0.023), educational level (p = 0.025), study month (p = 0.036), presence of eave in the house (p = 0.002) and wall openings (p = 0.041), not using bed nets (p = 0.001), sleeping in the same house with cattle (p = 0.031) and the distance between mosquito-breeding site and living house (p = 0.020) were explanatory risk factors significantly associated with malaria among studied participants.

Conclusions

In this study, we confirmed that the occurrence of malaria prevalence was high and continued against the Ethiopian malaria elimination plan of 2021–2025. Therefore, to meet the goals of this plan, the current prevention and control efforts should be stepped up even better in the coming years.
How can health technology assessment support our response to public health emergencies?
Authors: Ananthakrishnan Aparna , Luz Alia Cynthia Gonzales , KC Sarin , Ong Leslie , Oh Cecilia , Isaranuwatchai Wanrudee , Dabak Saudamini Vishwanath , Teerawattananon Yot , Turner Hugo C.
Published: November 2022

Public health emergencies (PHEs), such as the COVID-19 crisis, are threats to global health and public order. We recommend that countries bolster their PHE responses by investing in health technology assessment (HTA), defined as a systematic process of gathering pertinent information on and evaluating health technologies from a medical, economic, social and ethical standpoint. We present examples of how HTA organizations in low- and middle-income countries have adapted to supporting PHE-related decisions during COVID-19 and describe the ways HTA can help the response to a PHE. In turn, we advocate for HTA capacity to be further developed globally and for increased institutional acceptance of these methods as a building block for preparedness and response to future PHEs. Finally, the long-term potential of HTA in strengthening health systems and embedding confidence and transparency into scientific policy should be recognized.
Covert Contraceptive Use amongst the urban poor in Accra, Ghana: experiences of health providers
Authors: Kushitor Mawuli , Henry Elizabeth G. , Obeng-Dwamena Akua Danquah , Agyekum Martin Wiredu , Agula Caesar , Toprah Theophilus , Shah Iqbal , Bawah Ayaga A.
Published: November 2022

Background

An estimated one-third of women in Ghana use contraceptives without the knowledge of their partners, a phenomenon known as Covert Contraceptive Use (CCU). Most research on CCU to date has focused on individual women to the neglect of the role of health system. This study explores CCU in urban poor communities of Accra, Ghana, from the experiences and perspectives of health providers.

Methods

Qualitative in-depth interviews were conducted with health care providers in both the public and private sectors at multiple levels, from the community clinic to the tertiary hospital, to gain insights into the strategies women use and the ways in which the health system supports the practice of CCU.

Results

Five major thematic areas emerged: use of easily concealed-methods, discrete-access-and-information-keeping, time-of-day, non-verbal-communication and use of relationships. The study further revealed that fear, mistrust, shyness, myths, and misperceptions regarding contraceptives explain CCU among women in the communities that the providers serve.

Conclusion

Importantly, disclosure of methods used by providers without women’s consent could potentially lead to violent outcomes for both women and the providers. Our results highlight the pivotal role that providers play in confidentially supporting women’s choices regarding the use of contraceptives.
Lipidomics combined with transcriptomic and mass spectrometry imaging analysis of the Asiatic toad (Bufo gargarizans) during metamorphosis and bufadienolide accumulation
Authors: Sun Bo , Jiang Shan , Li Mingli , Zhang Yan , Zhou Yanyan , Wei Xiaolu , Wang Hongjie , Si Nan , Bian Baolin , Zhao Haiyu
Published: November 2022

Background

To adapt to life on land, Asiatic toads (Bufo gargarizans) must remodel their bodies and refine their chemical defenses in water. The full scope of the mechanisms underlying these processes has yet to be revealed. Bufadienolides (BDs) are chemical defense substances secreted by toads when they are in danger, and they have high medicinal value in treating heart failure, cancer, and hepatitis. However, the artificial breeding of toads to increase BDs has been unsuccessful due to the high mortality of toad larvae during metamorphosis.

Method

Toad larvae at different growth stages were selected to study the changes in the metamorphosis process under the same growth conditions. The differences of tadpoles were explored, including body remodeling, energy metabolism, synthesis and regulation of BDs, through lipidomic technology, transcriptomic technology, and mass spectrometry imaging technology during metamorphosis.

Results

During metamorphosis, tadpoles underwent significant changes in lipid metabolism due to body remodeling to adapt to terrestrial life, which involved ketosis, lipogenesis, cholesterol metabolism, and fatty acid oxidation. The accumulation trend of BDs was observed. “Pentose phosphate pathway” and “Aromatase activity” may be the critical pathway and GO term in BD synthesis, involving 16 genes predominantly expressed in the liver. The involved genes were mainly expressed in the liver, consistent with the synthetic site observed by mass spectrometry imaging.

Conclusion

Together, our findings presented the changes in the toad larvae during metamorphosis and highlighted the accumulation process of BDs as well as the regulatory pathways and synthetic site, providing research and theoretical basis for future development of the toad resources.
Chemometrics integrated with in silico pharmacology to reveal antioxidative and anti-inflammatory markers of dandelion for its quality control
Authors: Liu Feng-Jie , Yang Jiao , Chen Xu-Yan , Yu Ting , Ni Hui , Feng Liang , Li Ping , Li Hui-Jun
Published: November 2022

Background

Dandelion is an herb with high nutritional and medicinal values, which has been listed in Chinese Pharmacopeia, European Pharmacopoeia and British Pharmacopoeia, gaining increasing acceptance around the world. However, the current quality control of dandelion is lagging behind. Only in Chinese Pharmacopeia, cichoric acid is used as a marker compound for its quality evaluation, whereas, it can not comprehensively reflect the bioactivity of dandelion.

Methods

This study developed a strategy by integrating chemometrics with in silico pharmacology to reveal the bioactive markers of dandelion for its quality control. Firstly, the major chemicals in dandelion were characterized using HPLC-DAD-MS/MS, and the corresponding antioxidant and anti-inflammatory activities were evaluated in vitro. Subsequently, the active components were screened by relating the chemicals and bioactivity of dandelion via grey relational assay and partial least squares regression analysis. The potential active components were then subjected to a validation for their activities. Moreover, in silico pharmacology was utilized to evaluate the contribution of active components to efficacy.

Results

A total of 22 phenolic compounds were characterized. Among them, cichoric acid, caffeic acid and luteolin were identified as quality markers owing to their good correlations with the bioactivities of dandelion. These three markers were quantified in frequently-used dandelion species, viz. Taraxacum mongolicum Hand.-Mazz. (TAM) and T. officinale F. H. Wigg. (TAO). TAM, with acceptably higher content of cichoric acid and caffeic acid, showed better antioxidant activity than TAO. While TAO included higher content of luteolin, presenting slightly more effective in anti-inflammation.

Conclusion

An useful strategy for the quality marker discovery was successfully designed. And the results provided more knowledge for the quality evaluation of dandelion.
FIT-based risk-stratification model effectively screens colorectal neoplasia and early-onset colorectal cancer in Chinese population: a nationwide multicenter prospective study
Authors: Zhao Shengbing , Wang Shuling , Pan Peng , Xia Tian , Wang Rundong , Cai Quancai , Chang Xin , Yang Fan , Gu Lun , He Zixuan , Wu Jiayi , Meng Qianqian , Wang Tongchang , Fang Qiwen , Mou Xiaomei , Yu Honggang , Zheng Jinghua , Bai Cheng , Zou Yingbin , Chen Dongfeng , Zou Xiaoping , Ren Xu , Xu Leiming , Yao Ping , Xiong Guangsu , Shu Xu , Dang Tong , Zhang Li , Wang Wen , Kang Shengchao , Cao Hongfei , Gong Aixia , Li Jun , Zhang Heng , Du Yiqi , Li Zhaoshen , Bai Yu ,   Gastrointestinal Early Cancer Prevention & Treatment Alliance of China (GECA)
Published: November 2022

No fully validated risk-stratification strategies have been established in China where colonoscopies resources are limited. We aimed to develop and validate a fecal immunochemical test (FIT)-based risk-stratification model for colorectal neoplasia (CN); 10,164 individuals were recruited from 175 centers nationwide and were randomly allocated to the derivation (n = 6776) or validation cohort (n = 3388). Multivariate logistic analyses were performed to develop the National Colorectal Polyp Care (NCPC) score, which formed the risk-stratification model along with FIT. The NCPC score was developed from eight independent predicting factors and divided into three levels: low risk (LR 0–14), intermediate risk (IR 15–17), and high risk (HR 18–28). Individuals with IR or HR of NCPC score or FIT+ were classified as increased-risk individuals in the risk-stratification model and were recommended for colonoscopy. The IR/HR of NCPC score showed a higher prevalence of CNs (21.8%/32.8% vs. 11.0%, P < 0.001) and ACNs (4.3%/9.2% vs. 2.0%, P < 0.001) than LR, which was also confirmed in the validation cohort. Similar relative risks and predictive performances were demonstrated between non-specific gastrointestinal symptoms (NSGS) and asymptomatic cohort. The risk-stratification model identified 73.5% CN, 82.6% ACN, and 93.6% CRC when guiding 52.7% individuals to receive colonoscopy and identified 55.8% early-onset ACNs and 72.7% early-onset CRCs with only 25.6% young individuals receiving colonoscopy. The risk-stratification model showed a good risk-stratification ability for CN and early-onset CRCs in Chinese population, including individuals with NSGS and young age.
Use of an innovative cuff pressure control and subglottic secretions drainage system in COVID-19 ARDS patients undergoing pronation
Authors: Tanzarella Eloisa Sofia , Lombardi Gianmarco , Baroni Silvia , Sarlo Francesca , Cutuli Salvatore Lucio , Carelli Simone , Cesarano Melania , Gennenzi Veronica , Pintaudi Gabriele , Vargas Joel , Dell’Anna Antonio Maria , Grieco Domenico Luca , Urbani Andrea , Antonelli Massimo , De Pascale Gennaro
Published: November 2022

We conducted a proof of concept study where Anapnoguard endotracheal tubes and its control unit were used in 15 patients with COVID-19 acute respiratory distress syndrome. Anapnoguard system provides suction, venting, rinsing of subglottic space and controls cuff pressure detecting air leakage through the cuff. Alpha-amylase and pepsin levels, as oropharyngeal and gastric microaspiration markers, were assessed from 85 tracheal aspirates in the first 72 h after connection to the system. Oropharyngeal microaspiration occurred in 47 cases (55%). Episodes of gastric microaspiration were not detected. Patient positioning, either prone or supine, did not affect alpha-amylase and pepsin concentration in tracheal secretions. Ventilator-associated pneumonia (VAP) rate was 40%. The use of the AG system provided effective cuff pressure control and subglottic secretions drainage. Despite this, no reduction in the incidence of VAP has been demonstrated, compared to data reported in the current COVID-19 literature. The value of this new technology is worth of being evaluated for the prevention of ventilator-associated respiratory tract infections.
Self-management strategies and multicomponent training to mitigate the effects of the interruption of physical exercise programmes in the pandemic context on functionality, sedentary behaviour, physical capacity, mental health, body composition and quality of life in older adults: a blinded randomized controlled study protocol
Authors: Farche Ana Claudia Silva , Cassemiliano Gabriela , Rossi Paulo Giusti , Carnavale Bianca Ferdin , Lee Stefany , Message Laura Bonome , da Silva Santos Vinícius Ramon , Ansai Juliana Hotta , Ferriolli Eduardo , Pereira Natália Duarte , Oviedo Guillermo Rúben , Guerra-Balic Myriam , Giné-Garriga Maria , Lopes Marina Araújo , de Medeiros Takahashi Anielle Cristhine
Published: November 2022

Background

Considering the confinement recommended by the World Health Organization due to the pandemic caused by COVID-19, many community physical exercise programmes for older adults have had their activities cancelled. In this context, proposing strategies to recover the possible adverse effects of the confinement period is pertinent. The use of self-management strategies associated with regular physical activity reduces sedentary behaviour and improves physical capacity in older adults. Thus, the purpose of this study was to describe a multicomponent training programme combined with a self-management strategy protocol to mitigate the effects of interruptions in physical exercise programmes on functionality, physical capacity, mental health, body composition and quality of life in older adults.

Methods

This will be a blinded, randomized and controlled clinical trial performed in São Carlos, SP, Brazil. Eighty older adults will be divided into two groups: multicomponent training (Multi) and multicomponent training + self-management strategies (Multi+SM). The intervention will be performed over 16 weeks on three alternate days of every week, with 50-min sessions. The assessment of physical capacity will be performed before the interruption of physical exercise programmes (T0: initial assessment, March 2020), preintervention (T1: immediately after the return of the exercise programme) and postintervention (T2). The assessments of physical activity level, quality of life, mental health, functionality and body composition will be performed at T1 and T2.

Discussion

The results from this MC+SM protocol will allow us to contribute clinical support to evaluate the variables analysed and to guide future public health policies with the aim of minimizing the possible deleterious effects arising from the physical exercise interruption periods caused by epidemics and pandemics.

Trial registration

RBR-10zs97gk. Prospectively registered in Brazilian Registry of Clinical Trials (ReBEC) on 17 June 2021. Registry name: Use of self-management strategies combined with multicomponent training to mitigate the effects of social distancing due to COVID-19 on capacity, physical capacity, mental health and quality of life in older adults - A blind, randomized and controlled clinical trial.
Effect of sulfur doping of zinc-imidazole coordination polymer (ZnIm CP) as a novel photocatalyst for degradation of ionic dyes
Authors: Mohsen Mostafa , Baraka Ahmad , Naeem Ibrahim , Tantawy Hesham , Awaad Mohamed , Abuzalat Osama
Published: November 2022

Zinc-Imidazole coordination polymer (ZnImCP) was simply synthesized hydrothermally at relatively low temperature (70 °C) from zinc acetate and imidazole. ZnImCP was treated by sulfide solution to produce sulfur-doped samples (S-ZnImCPs). Structures of the synthesized ZnImCP and S-ZnImCPs were characterized through FTIR, PXRD, and, Raman, SEM/EDX, N2-BET, UV–VIS DRS, and pHpzc analyses. The photocatalytic performances of pristine CP and sulfur modified CPs under visible and ultra-violet irradiations for degrading the cationic methylene blue (MB) and the anionic methyl orange (MO) were investigated considering different initial pH values 4, 7 and 10. Under visible light, the results indicate that these CPs display considerable photocatalytic degradation towards the cationic MB for the initial pH 4 and 7 where degradation increases with sulfur content. While under ultra-violet, results indicate considerable photocatalytic degradation towards both dyes for the initial pH 7 and 10 where degradation increases with sulfur content which indicates the gainful of non-metal dopping. The buffering nature of CPs and the type of radiation considering determined band-gap values effectively influence the degradation mechanisms.
Progress and perspectives of enzymatic preparation of human milk fat substitutes
Authors: Liu Zeqing , Dai Lingmei , Liu Dehua , Du Wei
Published: November 2022

Human milk fat substitutes (HMFS) with triacylglycerol profiles highly similar to those of human milk fat (HMF) play a crucial role in ensuring the supply in infant nutrition. The synthesis of HMFS as the source of lipids in infant formula has been drawing increasing interest in recent years, since the rate of breastfeeding is getting lower. Due to the mild reaction conditions and the exceptionally high selectivity of enzymes, lipase-mediated HMFS preparation is preferred over chemical catalysis especially for the production of lipids with desired nutritional and functional properties. In this article, recent researches regarding enzymatic production of HMFS are reviewed and specific attention is paid to different enzymatic synthetic route, such as one-step strategy, two-step catalysis and multi-step processes. The key factors influencing enzymatic preparation of HMFS including the specificities of lipase, acyl migration as well as solvent and water activity are presented. This review also highlights the challenges and opportunities for further development of HMFS through enzyme-mediated acylation reactions.
The microbial community associated with Parascaris spp. infecting juvenile horses
Authors: Cain Jennifer L. , Norris Jamie K. , Ripley Nichol E. , Suri Parul , Finnerty Constance A. , Gravatte Holli S. , Nielsen Martin K.
Published: November 2022

Background

Parasitic nematodes, including large roundworms colloquially known as ascarids, affect the health and well-being of livestock animals worldwide. The equine ascarids,Parascarisspp., are important parasites of juvenile horses and the first ascarids to develop widespread anthelmintic resistance. The microbiota has been shown to be an important factor in the fitness of many organisms, including parasitic nematodes, where endosymbioticWolbachiahave been exploited for treatment of filariasis in humans.

Methods

This study used short-read 16S rRNA sequences and Illumina sequencing to characterize and compare microbiota of whole worm small intestinal stages and microbiota of male and female intestines and gonads. Diversity metrics including alpha and beta diversity, and the differential abundance analyses DESeq2, ANCOM-BC, corncob, and metagenomeSeq were used for comparisons.

Results

Alpha and beta diversity of whole worm microbiota did not differ significantly between groups, but Simpson alpha diversity was significantly different between female intestine (FI) and male gonad (MG) (P= 0.0018), and Shannon alpha diversity was significantly different between female and male gonads (P = 0.0130), FI and horse jejunum (HJ) (P = 0.0383), and FI and MG (P= 0.0001). Beta diversity (Fig. 2B) was significantly different between female and male gonads (P = 0.0006), male intestine (MI) and FG (P = 0.0093), and MG and FI (P = 0.0041). When comparing organs,Veillonellawas differentially abundant for DESeq2 and ANCOM-BC (p < 0.0001), corncob (P = 0.0008), and metagenomeSeq (P = 0.0118), andSarcinawas differentially abundant across four methods (P < 0.0001). Finally, the microbiota of all individualParascarisspp. specimens were compared to establish shared microbiota between groups.

Conclusions

Overall, this study provided important information regarding theParascarisspp. microbiota and provides a first step towards determining whether the microbiota may be a viable target for future parasite control options.

Graphical abstract
High-grade desmoplastic infantile astrocytoma in a 1-year-old child with Down’s syndrome: a case report
Authors: Habib Muhammad Hamza , Alavi Mehvish Zahra , Goraya Amber , Zaman Samina , Ahmed Alia
Published: November 2022

Background

Down’s syndrome is the most common chromosomal abnormality in humans. It has been associated with central nervous system tumors such as primary acute lymphoblastic leukemia and germinomas, but desmoplastic infantile astrocytoma has not yet been reported with Down’s syndrome. Desmoplastic infantile astrocytoma is a rare intracranial tumor that mostly occurs in the first 2 years of life. It usually presents as a large, aggressive tumor with both solid and cystic components. Genetically, it has been linked to theBRAFV600E mutation. Despite the rapid growth pattern, it usually has a favorable prognosis after neurosurgical excision. The presence of this extremely rare, genetically linked tumor, and its combination with Down’s syndrome, the most common human genetic defect, makes this a very novel clinical presentation. It also raises a very research-worthy question of an undiscovered link between these two genetic disorders.

Case presentation

In this case, we report a 1-year-old Pakistani origin male child with Down’s syndrome, who presented with progressive macrocephaly and developmental regression over the last 2 months. He was unable to sit by himself, and had lost his handgrip bilaterally. Down’s Syndrome was diagnosed soon after birth, based on typical facial features and presence of palmar crease, and later confirmed karyotypically for Trisomy 21. Upon presentation, initial blood tests did not show any abnormality. Magnetic resonance imaging of the brain was done, and showed a mixed intensity cystic mass with solid dural component posteriorly in the right parieto temporo occipital region. Craniotomy was performed, and about 85% of the tumor mass was excised. Histological examination and immunochemistry confirmed the suspected radiological diagnosis of desmoplastic infantile astrocytoma. After surgical excision, our patient gradually reacquired his previously regressed developmental milestones. Unfortunately, the remaining mass, which could not be excised due to its attachment to the highly vascular dura mater, showed regrowth on repeat brain magnetic resonance imaging. As his parents did not consent to further surgery, chemotherapy was offered as the next treatment option to prevent tumor regrowth.

Conclusions

This case report highlights the need for more case data and research to understand desmoplastic infantile astrocytoma, and their genetic correlation with Down’s syndrome. From a clinical standpoint, since desmoplastic infantile astrocytoma has a good postresection prognosis in a majority of early-diagnosed clinical cases, pediatricians, radiologists, and pathologists should consider desmoplastic infantile astrocytoma in their initial differential diagnosis in Down’s syndrome patients with macrocephaly and developmental regression during the first 2 years of life.
Oral–visceral iatrogenic Kaposi sarcoma following treatment for acute lymphoblastic leukemia: a case report and review of the literature
Authors: Nyeko Richard , Geriga Fadhil , Angom Racheal , Kambugu Joyce Balagadde
Published: November 2022

Background

There have hardly been any reported cases of children presenting with Kaposi sarcoma as a second malignancy following treatment for acute lymphoblastic leukemia outside a transplant setting.

Case presentation

We report a case of a 5-year-old boy of Bantu origin, which, to our knowledge, could be only the second reported case of oral–visceral Kaposi sarcoma after acute lymphoblastic leukemia treatment. The patient presented with a 1-month history of progressive, non-painful, soft tissue oral mass, 1 month after completing treatment for high-risk acute lymphoblastic leukemia. He was successfully treated for Kaposi sarcoma on a two-drug regimen (bleomycin and vincristine) with good clinical response.

Conclusion

Visceral Kaposi sarcoma as a second malignancy may occur after pediatric acute lymphoblastic leukemia treatment, but its rarity makes it unlikely to raise suspicion among clinicians, thus precluding early diagnosis and treatment. We recommend routine evaluation for Kaposi sarcoma lesions in children undergoing long-term surveillance following treatment for childhood acute leukemia.