bluuebunny/crossref_metadata_2025 huggingface dataset:
To culture or not to culture: careful assessment of metabarcoding data is necessary when evaluating the microbiota of a modified-atmosphere-packaged vegetarian meat alternative throughout its shelf-life period
Authors: Duthoo E. , De Reu K. , Leroy F. , Weckx S. , Heyndrickx M. , Rasschaert G.
Published: January 2022

Background

As the increased consumption of ready-to-eat meat alternatives is a fairly recent trend, little is known about the composition and dynamics of the microbiota present on such products. Such information is nonetheless valuable in view of spoilage and food safety prevention. Even though refrigeration and modified-atmosphere-packaging (MAP) can extend the shelf-life period, microbial spoilage can still occur in these products. In the present study, the microbiota of a vegetarian alternative to poultry-based charcuterie was investigated during storage, contrasting the use of a culture-dependent method to a culture-independent metagenetic method.

Results

The former revealed that lactic acid bacteria (LAB) were the most abundant microbial group, specifically at the end of the shelf-life period, whereby Latilactobacillus sakei was the most abundant species. Metabarcoding analysis, in contrast, revealed that DNA of Xanthomonas was most prominently present, which likely was an artifact due to the presence of xanthan gum as an ingredient, followed by Streptococcus and Weissella.

Conclusions

Taken together, these results indicated that Lb. sakei was likely the most prominent specific spoilage organisms (SSO) and, additionally, that the use of metagenetic analysis needs to be interpreted with care in this specific type of product. In order to improve the performance of metagenetics in food samples with a high DNA matrix but a low bacterial DNA load, selective depletion techniques for matrix DNA could be explored.
Group-tailored feedback on online mental health screening for university students: using cluster analysis
Authors: Lee Seonmi , Lim Jiwoo , Lee Sangil , Heo Yoon , Jung Dooyoung
Published: January 2022

Background

The method by which mental health screening result reports are given affects the user’s health behavior. Lists with the distribution of scores in various mental health areas is difficult for users to understand, and if the results are negative, they may feel more embarrassed than necessary. Therefore, we propose using group-tailored feedback, grouping people of similar mental health types by cluster analysis for comprehensive explanations of multidimensional mental health.

Methods

This cross-sectional, observational study was conducted using a qualitative approach based on cluster analysis. Data were collected via a developed mental screening website, with depression, anxiety, sleep problems, perfectionism, procrastination, and attention assessed for 2 weeks in January 2020 in Korea. Participants were randomly recruited, and sample size was 174. Total was divided into 25 with severe depression/anxiety (SDA+) and 149 without severe depression/anxiety (SDA-) according to the PHQ-9 and GAD-7 criteria. Cluster analysis was conducted in each group, and an ANOVA was performed to find significant clusters. Thereafter, structured discussion was performed with mental health professionals to define the features of the clusters and construct the feedback content initially. Thirteen expert counselors were interviewed to reconstruct the content and validate the effectiveness of the developed feedback.

Results

SDA- was divided into 3 using the k-means algorithm, which showed the best performance (silhouette score = 0.32, CH score = 91.67) among the clustering methods. Perfectionism and procrastination were significant factors in discretizing the groups. SDA+ subgroups were integrated because only 25 people belonged to this group, and they need professional help rather than self-care. Mental status and treatment recommendations were determined for each group, and group names were assigned to represent their features. The developed feedback was assessed to improve mental health literacy (MHL) through integrative and understandable explanations of multidimensional mental health. Moreover, it appeared that a sense of belonging was induced to reduce reluctance to face the feedback.

Conclusions

This study suggests group-tailored feedback using cluster analysis, which identifies groups of university students by integrating multidimensions of mental health. These methods can help students increase their interest in mental health and improve MHL to enable timely help.
Predicting medical usage rate at mass gathering events in Belgium: development and validation of a nonlinear multivariable regression model
Authors: Scheers Hans , Van Remoortel Hans , Lauwers Karen , Gillebeert Johan , Stroobants Stijn , Vranckx Pascal , De Buck Emmy , Vandekerckhove Philippe
Published: January 2022

Background

Every year, volunteers of the Belgian Red Cross provide onsite medical care at more than 8000 mass gathering events and other manifestations. Today standardized planning tools for optimal preventive medical resource use during these events are lacking. This study aimed to develop and validate a prediction model of patient presentation rate (PPR) and transfer to hospital rate (TTHR) at mass gatherings in Belgium.

Methods

More than 200,000 medical interventions from 2006 to 2018 were pooled in a database. We used a subset of 28 different mass gatherings (194 unique events) to develop a nonlinear prediction model. Using regression trees, we identified potential predictors for PPR and TTHR at these mass gatherings. The additional effect of ambient temperature was studied by linear regression analysis. Finally, we validated the prediction models using two other subsets of the database.

Results

The regression tree for PPR consisted of 7 splits, with mass gathering category as the most important predictor variable. Other predictor variables were attendance, number of days, and age class. Ambient temperature was positively associated with PPR at outdoor events in summer. Calibration of the model revealed an R2 of 0.68 (95% confidence interval 0.60–0.75). For TTHR, the most determining predictor variables were mass gathering category and predicted PPR (R2 = 0.48). External validation indicated limited predictive value for other events (R2 = 0.02 for PPR; R2 = 0.03 for TTHR).

Conclusions

Our nonlinear model performed well in predicting PPR at the events used to build the model on, but had poor predictive value for other mass gatherings. The mass gathering categories “outdoor music” and “sports event” warrant further splitting in subcategories, and variables such as attendance, temperature and resource deployment need to be better recorded in the future to optimize prediction of medical usage rates, and hence, of resources needed for onsite emergency medical care.
A comparative study of the sarcopenia screening in older patients with interstitial lung disease
Authors: Hanada Masatoshi , Sakamoto Noriho , Ishimoto Hiroshi , Kido Takashi , Miyamura Takuto , Oikawa Masato , Nagura Hiroki , Takeuchi Rina , Kawazoe Yurika , Sato Shuntaro , Hassan S. Ahmed , Ishimatsu Yuji , Takahata Hideaki , Mukae Hiroshi , Kozu Ryo
Published: January 2022

Background

The Asian Working Group for Sarcopenia 2019 (AWGS 2019) is the gold standard diagnostic criteria for sarcopenia in Asian populations. The calf circumference (CalF), the strength, assistance in walking, rising from a chair, climbing stairs, and falls (SARC-F) and the SARC-CalF questionnaires for sarcopenia screening have been used by AWGS 2019. The aim of this study was to assess accuracy of these three sarcopenia screening tools in patients with interstitial lung disease.

Methods

In this cross-sectional study, stable patients with interstitial lung disease were enrolled. The SARC-F, SARC-CalF, and CalF, used in patients with interstitial lung disease, were compared to the diagnostic criteria proposed by AWGS 2019. The accuracy of screening tools was compared using sensitivity and specificity. Moreover, areas under the receiver operating characteristic curves (AUC) were computed.

Results

Seventy eight patients were analyzed, and sarcopenia was identified in 25 (32.1%) patients with interstitial lung disease by the AWGS 2019 criteria. The sensitivity of the CalF was highest (96%) of the three screening tools, while the specificity was 60%. The sensitivity of SARC-F and SARC-CalF were 24% and 68%, while the specificity were 92% and 66%, respectively. The AUCs of CalF, SARC-F, and SARC-CalF in all patients were 0.78, 0.58, and 0.67, respectively.

Conclusions

The CalF is most suitable for screening sarcopenia in patients with interstitial lung disease, while SARC-F and SARC-CalF are not.
1-year trajectories of patients undergoing primary total hip arthroplasty: Patient reported outcomes and resource needs according to education level
Authors: Gonzalez Amanda I. , Nguyen Uyen-Sa D. T. , Franklin Patricia , Barea Christophe , Hannouche Didier , Lübbeke Anne
Published: January 2022

Background

Objectives were first to evaluate by education level one-year trajectories of pain, function and general health, as well as hospital resource and medication needs in patients undergoing primary total hip arthroplasty (THA); and second, to evaluate whether outcome differences are related to existing baseline differences in health and disease severity.

Methods

We included all primary THAs from a public hospital-based prospective arthroplasty registry, performed in a high-income country 2010 to 2017. Education was classified in three levels: ≤8years of schooling (low), 9-12years (medium), and ≥13years (high). Pain and function prior to and one-year after surgery were assessed with the Western Ontario McMaster Universities score (WOMAC) and general health with the 12-item short-form health survey (SF-12).

Results

Overall 963 patients were included, 340 (35.3%) with low, 306 (31.8%) with medium, and 317 (32.9%) with high education. With increasing educational level preoperative scores for pain, function and SF-12 mental health component increased. One year after surgery improvement was observed in all education categories for WOMAC pain and function, SF-12 mental and physical component. However, absolute postoperative scores remained lower in all four domains for the low education group. After adjustment for baseline characteristics differences were much attenuated and no longer significant. There was also greater resource need in low educated patients.

Conclusions

The inferior absolute results one year after surgery in less educated patients were largely due to older age, worse preoperative health and greater symptom severity calling for greater attention to timely and equal management, for more targeted perioperative care and increased support for the lower education group.
Bioinformatics screening the novel and promising targets of curcumin in hepatocellular carcinoma chemotherapy and prognosis
Authors: Yang Tingting , Chen Yibiao , Xu Jiexuan , Li Jinyuan , Liu Hong , Liu Naihua
Published: January 2022

Background

The aim of present study was to screen the novel and promising targets of curcumin in hepatocellular carcinoma diagnosis and chemotherapy.

Methods

Potential targets of curcumin were screened from SwissTargetPrediction, ParmMapper and drugbank databases. Potential aberrant genes of hepatocellular carcinoma were screened from Genecards databases. Fifty paired hepatocellular carcinoma patients’ gene expression profiles from the GEO database were used to test potential targets of curcumin. Besides, GO analysis, KEGG pathway enrichment analysis and PPI network construction were used to explore the underlying mechanism of candidate hub genes. ROC analysis and Kaplan-Meier analysis were used to evaluate the diagnostic and prognostic value of candidate hub genes, respectively. Real-time PCR was used to verify the results of bioinformatics analysis.

Results

Bioinformatics analysis results suggested that AURKA, CDK1, CCNB1, TOP2A, CYP2B6, CYP2C9, and CYP3A4 genes served as candidate hub genes. AURKA, CDK1, CCNB1 and TOP2A were significantly upregulated and correlated with poor prognosis in hepatocellular carcinoma, AUC values of which were 95.7, 96.9, 98.1 and 96.1% respectively. There was not significant correlation between the expression of CYP2B6 and prognosis of hepatocellular carcinoma, while CYP2C9 and CYP3A4 genes were significantly downregulated and correlated with poor prognosis in hepatocellular carcinoma. AUC values of CYP2B6, CYP2C9, and CYP3A4 were 96.0, 97.0 and 88.0% respectively. In vitro, we further confirmed that curcumin significantly downregulated the expression of AURKA, CDK1, and TOP2A genes, while significantly upregulated the expression of CYP2B6, CYP2C9, and CYP3A4 genes.

Conclusions

Our results provided a novel panel of AURKA, CDK1, TOP2A, CYP2C9, and CYP3A4 candidate genes for curcumin related chemotherapy of hepatocellular carcinoma.
How technology-enhanced experiential e-learning can facilitate the development of person-centred communication skills online for health-care students: a qualitative study
Authors: Liao Faith , Murphy David , Wu Jeng-Cheng , Chen Chien-Yu , Chang Chun-Chao , Tsai Po-Fang
Published: January 2022

Background

The COVID-19 pandemic brought a new challenge to medical education—health-care students had fewer opportunities to interact with and treat real patients in clinical settings. Interpersonal communication skills are often developed through human interaction and communication in person, and few studies have proposed feasible digital solutions to develop learners’ communication skills. Consequently, understanding how medical teachers facilitate and implement online training programmes, with feasible instruments, to enhance students’ learning effectiveness when in-person training is not possible is critical.

Methods

By using a convenience sampling method, we recruited 26 health-care students from seven medical schools in Taiwan. Through semistructured interviews and the thematic analysis technique, we analysed the latent learning factors from the experience of implementing the technology-enhanced experiential e-learning tool ‘mPath’.

Results

Three themes were generated: A) transferring theory into practice, B) increasing authenticity with analytical features, and C) maintaining autonomy with nondirective learning. The features accessibility, flexibility, intractability, and visualisation with the characteristics of remote accessibility and flexibility, repetition and retrospect, feedback requesting, and visualised analytical reports were considered to enhance learning outcomes.

Conclusion

This study indicated how online training using technology could develop the participants’ person-centred communication skills and what features influenced the learning outcomes of social distancing. mPath may be a feasible online learning approach and has provided inspiration for developing health-care students’ communication skills when in-person training is not possible.
A machine learning approach for modeling decisions in the out of hospital cardiac arrest care workflow
Authors: Harford Samuel , Del Rios Marina , Heinert Sara , Weber Joseph , Markul Eddie , Tataris Katie , Campbell Teri , Vanden Hoek Terry , Darabi Houshang
Published: January 2022

Background

A growing body of research has shown that machine learning (ML) can be a useful tool to predict how different variable combinations affect out-of-hospital cardiac arrest (OHCA) survival outcomes. However, there remain significant research gaps on the utilization of ML models for decision-making and their impact on survival outcomes. The purpose of this study was to develop ML models that effectively predict hospital’s practice to perform coronary angiography (CA) in adult patients after OHCA and subsequent neurologic outcomes.

Methods

We utilized all (N = 2398) patients treated by the Chicago Fire Department Emergency Medical Services included in the Cardiac Arrest Registry to Enhance Survival (CARES) between 2013 and 2018 who survived to hospital admission to develop, test, and analyze ML models for decisions after return of spontaneous circulation (ROSC) and patient survival. ML classification models, including the Embedded Fully Convolutional Network (EFCN) model, were compared based on their ability to predict post-ROSC decisions and survival.

Results

The EFCN classification model achieved the best results across tested ML algorithms. The area under the receiver operating characteristic curve (AUROC) for CA and Survival were 0.908 and 0.896 respectively. Through cohort analyses, our model predicts that 18.3% (CI 16.4–20.2) of patients should receive a CA that did not originally, and 30.1% (CI 28.5–31.7) of these would experience improved survival outcomes.

Conclusion

ML modeling effectively predicted hospital decisions and neurologic outcomes. ML modeling may serve as a quality improvement tool to inform system level OHCA policies and treatment protocols.
Hearty recipes for health: the Hakka medicinal soup in Guangdong, China
Authors: Ding Mingyan , Shi Shi , Luo Binsheng
Published: January 2022

Background

The Hakka are a subgroup of the Han Chinese, originally from northern China and mainly living in southern China now. Over hundreds of years, the Hakka have developed their own medical practices to prevent and cure diseases, such as medicinal soup, an important characteristic of Hakka cuisine. This study aims at documenting plant taxa used to make Hakka medicinal soup, along with their associated ethnomedical knowledge.

Methods

Data on Hakka soup-making plants were collected through key-informant interviews, semi-structured interviews, participatory field collection, and direct observation. The choosing of participants has followed the snowball sampling method. Herbs used for preparing medicinal soup were purchased on the local market or collected from the wild, and voucher specimens were collected and identified. The study result was also compared with published studies on soup-making plants in other parts of Guangdong province and the Hakka areas in Fujian Province of China.

Results

Eighty-three taxa belonging to 70 genera within 38 families were listed by our informants as being used to treat 55 kinds of health problems. Most documented plants are herbaceous species, followed by shrubs and woody liana. Roots were the most frequently used plant parts for medicinal purposes, followed, in descending order, by the whole plant, rhizomes, and flowers. Most plants used to prepare medicinal soup are wild-harvested (56 species), 4 cultivated, and 23 wild harvested or cultivated. According to the comparison, 18 Hakka medicinal soup species are shown both in Fujian Province and Guangdong Province. The Hakka soup-making plants in both provinces share very similar therapeutic functions. This study helps to extend the Hakka menu in both provinces. The study comparison also showed a big difference in the herb ingredients between Guangdong Hakka medicinal soup and Cantonese slow-cooked soup.

Conclusion

Hakka medicinal soup is an important feature of the Hakka dietary culture. More studies are needed to be undertaken, especially on the efficacy and safety of this medicinal soup. Moreover, cultivation and conservation efforts are required to ensure the sustainability of the species that are used as ingredients in the soup. Consequently, further commercial development of medicinal soup should be promoted.
Differential effects of radiation fractionation regimens on glioblastoma
Authors: McKelvey Kelly J. , Hudson Amanda L. , Donaghy Heather , Stoner Shihani P. , Wheeler Helen R. , Diakos Connie I. , Howell Viive M.
Published: January 2022

Background

Radiotherapy (RT) is a mainstay of treatment for patients with glioblastoma (GB). Early clinical trials show that short course hypofractionation showed no survival benefit compared to conventional regimens with or without temozolomide chemotherapy (TMZ) but reduces the number of doses required. Concerns around delayed neurological deficits and reduced cognition from short course hypofractionated RT remain a concern. The aim of this study was to evaluate the effect of increased interfractional time using two different radiation fractionation regimens on GB.

Methods

The radiobiological effect of increasing doses 0–20 Gy x-ray photon RT on Gl261 and CT2A GB cell lines was compared by colony forming assay, DNA damage by alkaline comet assay, oxidative stress, DNA damage, cell cycle, and caspase-3/7 by MUSE® flow cytometric analyses, and protein expression by western blot analyses. Conventional (20 Gy/10 fractions) and hypofractionated (20 Gy/4 fractions spaced 72 h apart) RT regimens with and without TMZ (200 mg/kg/day) were performed in syngeneic Gl261 and CT2A intracranial mouse models using the Small Animal Radiation Research Platform (Xstrahl Inc.).

Results

X-ray photon radiation dose-dependently increased reactive oxygen species, DNA damage, autophagy, and caspase 3/7-mediated apoptotic cell death. While the conventional fractionated dose regimen of 20 Gy/10 f was effective at inducing cell death via the above mechanism, this was exceeded by a 20 Gy/4 f regimen which improved median survival and histopathology in Gl261-tumor bearing mice, and eradicated tumors in CT2A tumors with no additional toxicity.

Conclusions

Spacing of hypofractionated RT doses 72 h apart showed increased median survival and tumor control via increased activation of RT-mediated cell death, with no observed increased in radiotoxicity. This supports further exploration of differential RT fractionated regimens in GB clinical trials to reduce delayed neurological radiotoxicity.
Comparison of outcomes between Zero-p implant and anterior cervical plate interbody fusion systems for anterior cervical decompression and fusion: a systematic review and meta-analysis of randomized controlled trials
Authors: Zhang Tingxin , Guo Nana , Gao Gang , Liu Hao , Li Yanhong , Gao Feng , Zhang Qingxin , Tao Xiaoyang , Yang Wupeng , Wang Yongjiang
Published: January 2022

Purpose

The clinical outcomes of using a zero-profile for anterior cervical decompression and fusion were evaluated by comparison with anterior cervical plates.

Methods

All of the comparative studies published in the PubMed, Cochrane Library, Medline, Web of Science, EBSOChost, and EMBASE databases as of 1 October 2021 were included. All outcomes were analysed using Review Manager 5.4.

Results

Sevenrandomized controlled studies were included with a total of 528 patients, and all studies were randomized controlled studies. The meta-analysis outcomes indicated that the use of zero-profile fixation for anterior cervical decompression and fusion was better than anterior cervical plate fixation regarding the incidence of postoperative dysphagia (P < 0.05), adjacent-level ossification (P < 0.05), and operational time (P < 0.05). However, there were no statistically significant differences in intraoperative blood loss, Visual Analogue Scale, Neck Disability Index, or Japanese Orthopaedic Association scale (allP > 0.05) between the zero-profile and anterior cervical plate groups.

Conclusions

The systematic review and meta-analysis indicated that zero-profile and anterior cervical plates could result in good postoperative outcomes in anterior cervical decompression and fusion. No significant differences were found in intraoperative blood loss, Visual Analogue Scale, Neck Disability Index, or Japanese Orthopaedic Association scale.However, the zero-profile is superior to the anterior cervical plate in the following measures: incidence of postoperative dysphagia, adjacent-level ossification, and operational time.

PROSPERO registrationCRD42021278214.
A situational analysis of child and adolescent mental health services and systems in the Western Cape Province of South Africa
Authors: Mokitimi Stella , Schneider Marguerite , de Vries Petrus J.
Published: January 2022

Background

Even though child and adolescent mental health is a global health priority, services are very limited, particularly in low- and middle-income countries (LMIC), and therefore need comprehensive strengthening. This requires knowledge of the hardware elements of the system (human resources, financing, medicines, technology, organisational structure, service infrastructure, and information systems). This study sought to examine these elements of child and adolescent mental health (CAMH) services and systems in the Western Cape Province of South Africa.

Methods

The World Health Organization Assessment Instrument of Mental Health Systems (WHO-AIMS) version 2.2 of 2005 was adapted to identify key variables of interest in CAMH. Data were collected for the calendar year 2016 and focused on the public health sector. We outlined findings based on best available data across the six domains of the WHO-AIMS.

Results

In domain 1, we found no provincial CAMH policy or implementation plans to support the national CAMH policy and were unable to identify a CAMH-specific budget. In domain 2, there was no dedicated provincial leadership structure for CAMH, and no dedicated or ‘child- and adolescent-friendly’ mental health services at primary or secondary care levels. At tertiary level, there were only three specialist CAMH teams. The majority of CAMH resources were based in the City of Cape Town, with limited resources in the rural districts. Essential medicines were available in all facilities, and the majority of children and adolescents had access to free services. In domain 3, data were limited about the extent of training offered to primary healthcare staff, and little or no psychosocial interventions were available in primary care. Domain 4 identified a small and variable CAMH workforce across all levels of care. In domain 5, few public health campaigns focused on CAMH, and little evidence of formal intersectoral collaboration on CAMH was identified. Domain 6 identified significant limitations in health information systems for CAMH, including lack of child- and adolescent-specific and disaggregated data to establish baselines for policy development, monitoring, evaluation and CAMH research.

Conclusions

This study identified significant structural weaknesses in CAMH and presents a clear call for action to strengthen services and systems in the province and in South Africa. it would be important to expand research also to include provider and user perspectives for service strengthening.
The essential roles of m6A RNA modification to stimulate ENO1-dependent glycolysis and tumorigenesis in lung adenocarcinoma
Authors: Ma Lifang , Xue Xiangfei , Zhang Xiao , Yu Keke , Xu Xin , Tian Xiaoting , Miao Yayou , Meng Fanyu , Liu Xiaoxin , Guo Susu , Qiu Shiyu , Wang Yikun , Cui Jiangtao , Guo Wanxin , Li You , Xia Jinjing , Yu Yongchun , Wang Jiayi
Published: January 2022

Background

Lung adenocarcinoma (LUAD)  is the most common subtype of lung cancer. Patient prognosis is poor, and the existing therapeutic strategies for LUAD are far from satisfactory. Recently, targeting N6-methyladenosine (m6A) modification of RNA has been suggested as a potential strategy to impede tumor progression. However, the roles of m6A modification in LUAD tumorigenesis is unknown.

Methods

Global m6A levels and expressions of m6A writers, erasers and readers were evaluated by RNA methylation assay, dot blot, immunoblotting, immunohistochemistry and ELISA in human LUAD, mouse models and cell lines. Cell viability, 3D-spheroid generation, in vivo LUAD formation, experiments in cell- and patient-derived xenograft mice and survival analysis were conducted to explore the impact of m6A on LUAD. The RNA-protein interactions, translation, putative m6A sites and glycolysis were explored in the investigation of the mechanism underlying how m6A stimulates tumorigenesis.

Results

The elevation of global m6A level in most human LUAD specimens resulted from the combined upregulation of m6A writer methyltransferase 3 (METTL3) and downregulation of eraser alkB homolog 5 (ALKBH5). Elevated global m6A level was associated with a poor overall survival in LUAD patients. Reducing m6A levels by knocking out METTL3 and overexpressing ALKBH5 suppressed 3D-spheroid generation in LUAD cells and intra-pulmonary tumor formation in mice. Mechanistically, m6A-dependent stimulation of glycolysis and tumorigenesis occurred via enolase 1 (ENO1). ENO1 mRNA was m6A methylated at 359 A, which facilitated it’s binding with the m6A reader YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) and resulted in enhanced translation of ENO1. ENO1 positively correlated with METTL3 and global m6A levels, and negatively correlated with ALKBH5 in human LUAD. In addition, m6A-dependent elevation of ENO1 was associated with LUAD progression. In preclinical models, tumors with a higher global m6A level showed a more sensitive response to the inhibition of pan-methylation, glycolysis and ENO activity in LUAD.

Conclusions

The m6A-dependent stimulation of glycolysis and tumorigenesis in LUAD is at least partially orchestrated by the upregulation of METTL3, downregulation of ALKBH5, and stimulation of YTHDF1-mediated ENO1 translation. Blocking this mechanism may represent a potential treatment strategy for m6A-dependent LUAD.
Immunotherapy for glioblastoma: the promise of combination strategies
Authors: Bausart Mathilde , Préat Véronique , Malfanti Alessio
Published: January 2022

Glioblastoma (GBM) treatment has remained almost unchanged for more than 20 years. The current standard of care involves surgical resection (if possible) followed by concomitant radiotherapy and chemotherapy. In recent years, immunotherapy strategies have revolutionized the treatment of many cancers, increasing the hope for GBM therapy. However, mostly due to the high, multifactorial immunosuppression occurring in the microenvironment, the poor knowledge of the neuroimmune system and the presence of the blood−brain barrier, the efficacy of immunotherapy in GBM is still low. Recently, new strategies for GBM treatments have employed immunotherapy combinations and have provided encouraging results in both preclinical and clinical studies. The lessons learned from clinical trials highlight the importance of tackling different arms of immunity. In this review, we aim to summarize the preclinical evidence regarding combination immunotherapy in terms of immune and survival benefits for GBM management. The outcomes of recent studies assessing the combination of different classes of immunotherapeutic agents (e.g., immune checkpoint blockade and vaccines) will be discussed. Finally, future strategies to ameliorate the efficacy of immunotherapy and facilitate clinical translation will be provided to address the unmet medical needs of GBM.
The Unplugged program in Chile (“Yo Sé Lo Que Quiero”) for substance use prevention among early adolescents: study protocol for a randomized controlled trial
Authors: Gaete Jorge , Ramírez Saray , Gana Sofía , Valenzuela Daniela , Araya Ricardo
Published: January 2022

Background

Substance use is among the main contributors to disease among children and adolescents in the Americas region. The call for effective prevention of substance use among adolescents has resulted in numerous school-based programs, and particularly the Unplugged program has been proved to be successful in reducing the prevalence of different substances in seven European countries. The purpose of this study is to test the effectiveness of the Unplugged program in Chile (“Yo Sé Lo Que Quiero”).

Methods

This is a cluster randomized controlled trial, parallel-group type, where “Yo Sé Lo Que Quiero” is compared to standard school preventive curricula in control schools. A total of 70 schools and 8400 adolescents are expected to be randomized with 1:1 allocation. During formative work, the Unplugged program was culturally adapted to Chile, and the instrument to assess the primary and secondary outcomes was validated. The effectiveness of this program will be assessed using the European Drug Addiction Prevention Trial Questionnaire (EU-Dap), measuring substance use prevalence and risk and protective factors in baseline, post-intervention, and four months after the end of the intervention.

Discussion

The proposed study will be the first to test the effectiveness of a school-based substance use prevention program in Chile in a cluster randomized control trial and the first study evaluating the Unplugged program in Spanish-speaking Latin America. A model for disseminating the Unplugged program inside Europe already exists and has been implemented successfully in several countries. Thus, if the effects of the program are positive, wide implementation in Chile and Latin American countries is possible soon.

Trial registration

ClinicalTrials.govNCT04236999. Registered on January 17, 2020.
Development of a bacterial consortium from Variovorax paradoxus and Pseudomonas veronii isolates applicable in the removal of BTEX
Authors: Szentgyörgyi Flóra , Benedek Tibor , Fekete Dzsenifer , Táncsics András , Harkai Péter , Kriszt Balázs
Published: January 2022

In this study, we report on the development of a novel bacterial consortium, consisting of Variovorax paradoxus and Pseudomonas veronii isolates, applicable in the biodegradation of all six BTEX compounds (benzene, toluene, ethylbenzene, o-, m- and p-xylene) and the bioremediation of contaminated sites. The co-cultivability of the selected bacterial isolates was determined in nutrient-rich medium, as well as in BTEX amended mineral salts solution using Terminal Restriction Fragment Length Polymorphism (T-RFLP) and CFU determinations. BTEX biodegradation capacity of the two-strain consortium was assessed in mineral salts solution, where a series of BTEX depletions and supplementations occurred, as well as in a real, BTEX polluted environmental sample (contaminated groundwater) in the presence of the autochthonous bacterial community. The obtained results indicated that the developed bacterial consortium is very efficient in BTEX biodegradation. Under laboratory conditions, the acclimatized bacterial consortium completely degraded the BTEX mixture with a concentration as high as 20 mg l−1 in a mineral salt medium within a short span of 6 h. Close to in situ groundwater conditions (incubated at 15 °C under static conditions in the absence of light), groundwater microcosms containing the autochthonous bacterial community inoculated with the developed bacterial consortium showed more efficient toluene, o-, m-and p-xylene biodegradation capacity than microcosms containing solely the native microbial population originally found in the groundwater. In the inoculated microcosms, after 115 h of incubation the concentration (~ 1.7 mg l−1 each) of o-, m- and p-xylene decreased to zero, whereas in the non-inoculated microcosms the concentration of xylene isomers was still 0.2, 0.3 and 0.3 mg l−1, respectively. The allochthonous bioaugmentation of the contaminated groundwater with the obtained inoculant was successful and manifested in a better BTEX degradation rate. Our results suggest that the obtained bacterial consortium can be a new, stable and efficient bioremediation agent applicable in the synergistic elimination of BTEX compounds from contaminated sites.
How creative destruction functions in corporate entrepreneurial process: an empirical investigation of Schumpeterian concept in engineering firm settings in Pakistan
Authors: Alam Muhammad Zubair , Kousar Shazia , Rizwan Ullah Muhammad , Pervaiz Amber
Published: January 2022

Schumpeter's idea of creative destruction (CD) explains innovation functions in organisations. This paper investigates the CD concept in engineering firms by explaining how technical opportunity (TO) transforms into corporate entrepreneurship (CE) actions once opportunities have a market orientation (MO). A survey was conducted using a structured questionnaire with 132 managers of engineering firms in Pakistan. Structural Equation Modelling (SEM) using Partial Least Square (PLS) approach has been used to analyse the data. Results reveal that MO and TO exerts a positive influence on CE. MO is the reason for the emergence of TO, which corporate entrepreneurs in engineering firms exploit. CD intensifies the impact of MO on TO significantly. Opportunity recognition in engineering firms is distinguished and bounded by MO and technical viability. Engineering firms need to identify gaps in the market through naturally occurring obsolescence of products and services (CD) to create TO with appropriate MO. This study has revived a classical debate over opportunity recognition by incorporating external factors to propose the CE model. The Schumpeterian opportunity recognition process and CD have been examined for engineering firms.
High-resolution genomic surveillance elucidates a multilayered hierarchical transfer of resistance between WWTP- and human/animal-associated bacteria
Authors: Che You , Xu Xiaoqing , Yang Yu , Břinda Karel , Hanage William , Yang Chao , Zhang Tong
Published: January 2022

Background

Our interconnected world and the ability of bacteria to quickly swap antibiotic resistance genes (ARGs) make it particularly important to establish the epidemiological links of multidrug resistance (MDR) transfer between wastewater treatment plant (WWTP)- and human/animal-associated bacteria, under the One Health framework. However, evidence of ARGs exchange and potential factors that contribute to this transfer remain limited.

Results

Here, by combining culture-based population genomics and genetic comparisons with publicly available datasets, we reconstructed the complete genomes of 82 multidrug-resistant isolates from WWTPs and found that most WWTP-associated isolates were genetically distinct from their closest human/animal-associated relatives currently available in the public database. Even in the minority of lineages that were closely related, WWTP-associated isolates were characterized by quite different plasmid compositions. We identified a high diversity of circular plasmids (264 in total, of which 141 were potentially novel), which served as the main source of resistance, and showed potential horizontal transfer of ARG-bearing plasmids between WWTP- and humans/animal-associated bacteria. Notably, the potentially transferred ARGs and virulence factors (VFs) with different genetic backgrounds were closely associated with flanking insertion sequences (ISs), suggesting the importance of synergy between plasmids and ISs in mediating a multilayered hierarchical transfer of MDR and potentiating the emergence of MDR-hypervirulent clones.

Conclusion

Our findings advance the current efforts to establish potential epidemiological links of MDR transmission between WWTP- and human/animal-associated bacteria. Plasmids play an important role in mediating the transfer of ARGs and the IS-associated ARGs that are carried by conjugative plasmids should be prioritized to tackle the spread of resistance.
Synovial mast cells from knee and hip osteoarthritis: histological study and clinical correlations
Authors: Farinelli L. , Aquili A. , Mattioli-Belmonte M. , Manzotti S. , D’Angelo F. , Ciccullo C. , Gigante A.
Published: January 2022

Purpose

The aim of this study was to investigate the presence of synovial mast cells (MCs) in hip and knee tissue from osteoarthritis (OA) patients and to correlate them with clinical and radiological data.

Methods

Synovial tissue was obtained during arthroplasty from 60 patients, 30 with knee OA and 30 with hip OA. Control synovial tissue was obtained from 30 patients without OA, 15 undergoing above-knee amputation and 15 receiving a hip replacement for fracture. Before surgery, the radiographic findings were graded according to the Kellgren-Lawrence system and clinical data including pain (VAS) and functional information (KOOS and HOOS) was collected. The tissue was stained with hematoxylin–eosin and toluidine blue for histochemistry and incubated with CD117 and CD31 antibodies for immunohistochemistry. MC and vessel number and synovitis score were determined in all samples.

Results

Mean MC number, synovitis score and vessel number were significantly higher in the OA samples (p < 0.05) than in control tissue. MC number correlated with the synovitis score and disease severity in both patient groups.

Conclusions

The prevalence of MCs in synovium from OA patients and their association with synovial inflammation and pain suggest a role for them in OA pathophysiology.
Tracking Systems in Team Sports: A Narrative Review of Applications of the Data and Sport Specific Analysis
Authors: Torres-Ronda Lorena , Beanland Emma , Whitehead Sarah , Sweeting Alice , Clubb Jo
Published: January 2022

Seeking to obtain a competitive advantage and manage the risk of injury, team sport organisations are investing in tracking systems that can quantify training and competition characteristics. It is expected that such information can support objective decision-making for the prescription and manipulation of training load. This narrative review aims to summarise, and critically evaluate, different tracking systems and their use within team sports. The selection of systems should be dependent upon the context of the sport and needs careful consideration by practitioners. The selection of metrics requires a critical process to be able to describe, plan, monitor and evaluate training and competition characteristics of each sport. An emerging consideration for tracking systems data is the selection of suitable time analysis, such as temporal durations, peak demands or time series segmentation, whose best use depends on the temporal characteristics of the sport. Finally, examples of characteristics and the application of tracking data across seven popular team sports are presented. Practitioners working in specific team sports are advised to follow a critical thinking process, with a healthy dose of scepticism and awareness of appropriate theoretical frameworks, where possible, when creating new or selecting an existing metric to profile team sport athletes.
Cough associated with the detection of Mycoplasma hyopneumoniae DNA in clinical and environmental specimens under controlled conditions
Authors: Silva Ana Paula S. Poeta , Storino Gabriel Y. , Ferreyra Franco S. Matias , Zhang Min , Fano Eduardo , Polson Dale , Wang Chong , Derscheid Rachel J. , Zimmerman Jeffrey J. , Clavijo Maria J. , Arruda Bailey L.
Published: January 2022

Background

The association of cough with Mycoplasma hyopneumoniae (MHP) DNA detection in specimens was evaluated under conditions in which the MHP status of inoculated and contact-infected pen mates was closely monitored for 59 days post-inoculation (DPI).

Methods

Seven-week-old pigs (n = 39) were allocated to five rooms (with one pen). Rooms contained 9 pigs each, with 1, 3, 6, or 9 MHP-inoculated pigs, respectively, except Room 5 (three sham-inoculated pigs). Cough data (2 × week) and specimens, tracheal swabs (2 × week), oral fluids (daily), drinker wipes (~ 1 × week), and air samples (3 × week) were collected. At 59 DPI, pigs were euthanized, and lung and trachea were evaluated for gross and microscopic lesions. Predictive cough value to MHP DNA detection in drinker and oral fluid samples were estimated using mixed logistic regression.

Results

Following inoculation, MHP DNA was first detected in tracheal swabs from inoculated pigs (DPI 3), then oral fluids (DPI 8), air samples (DPI 10), and drinker wipes (21 DPI). MHP DNA was detected in oral fluids in 17 of 59 (Room 1) to 43 of 59 (Room 3) samples, drinker wipes in 4 of 8 (Rooms 2 and 3) to 5 of 8 (Rooms 1 and 4) samples, and air samples in 5 of 26 (Room 2) or 3 of 26 (Room 4) samples. Logistic regression showed that the frequency of coughing pigs in a pen was associated with the probability of MHP DNA detection in oral fluids (P < 0.01) and nearly associated with drinker wipes (P = 0.08). Pathology data revealed an association between the period when infection was first detected and the severity of gross lung lesions.

Conclusions

Dry, non-productive coughs suggest the presence of MHP, but laboratory testing and MHP DNA detection is required for confirmation. Based on the data from this study, oral fluids and drinker wipes may provide a convenient alternative for MHP DNA detection at the pen level when cough is present. This information may help practitioners in specimen selection for MHP surveillance.
Gene expression alterations from reversible to irreversible stages during coral metamorphosis
Authors: Ishii Yuu , Hatta Masayuki , Deguchi Ryusaku , Kawata Masakado , Maruyama Shinichiro
Published: January 2022

For corals, metamorphosis from planktonic larvae to sedentary polyps is an important life event, as it determines the environment in which they live for a lifetime. Although previous studies on the reef-building coral Acropora have clarified a critical time point during metamorphosis when cells are committed to their fates, as defined by an inability to revert back to their previous states as swimming larvae (here referred to as the “point of no return”), the molecular mechanisms of this commitment to a fate remain unclear. To address this issue, we analyzed the transcriptomic changes before and after the point of no return by inducing metamorphosis of Acropora tenuis with Hym-248, a metamorphosis-inducing neuropeptide. Gene Ontology and pathway enrichment analysis of the 5893 differentially expressed genes revealed that G protein-coupled receptors (GPCRs) were enriched, including GABA receptor and Frizzled gene subfamilies, which showed characteristic temporal expression patterns. The GPCRs were then classified by comparison with those of Homo sapiens, Nematostella vectensis and Platynereis dumerilii. Classification of the differentially expressed genes into modules based on expression patterns showed that some modules with large fluctuations after the point of no return were biased toward functions such as protein metabolism and transport. This result suggests that in precommitted larvae, different types of GPCR genes function to ensure a proper environment, whereas in committed larvae, intracellular protein transport and proteolysis may cause a loss of the reversibility of metamorphosis as a result of cell differentiation.
Reproducibility of radiomic features in CT images of NSCLC patients: an integrative analysis on the impact of acquisition and reconstruction parameters
Authors: Rinaldi Lisa , De Angelis Simone P. , Raimondi Sara , Rizzo Stefania , Fanciullo Cristiana , Rampinelli Cristiano , Mariani Manuel , Lascialfari Alessandro , Cremonesi Marta , Orecchia Roberto , Origgi Daniela , Botta Francesca
Published: January 2022

Background

We investigated to what extent tube voltage, scanner model, and reconstruction algorithm affect radiomic feature reproducibility in a single-institution retrospective database of computed tomography images of non-small-cell lung cancer patients.

Methods

This study was approved by the Institutional Review Board (UID 2412). Images of 103 patients were considered, being acquired on either among two scanners, at 100 or 120 kVp. For each patient, images were reconstructed with six iterative blending levels, and 1414 features were extracted from each reconstruction. At univariate analysis, Wilcoxon-Mann-Whitney test was applied to evaluate feature differences within scanners and voltages, whereas the impact of the reconstruction was established with the overall concordance correlation coefficient (OCCC). A multivariable mixed model was also applied to investigate the independent contribution of each acquisition/reconstruction parameter. Univariate and multivariable analyses were combined to analyse feature behaviour.

Results

Scanner model and voltage did not affect features significantly. The reconstruction blending level showed a significant impact at both univariate analysis (154/1414 features yielding an OCCC < 0.85) and multivariable analysis, with most features (1042/1414) revealing a systematic trend with the blending level (multiple comparisons adjusted p < 0.05). Reproducibility increased in association to image processing with smooth filters, nonetheless specific investigation in relation to clinical endpoints should be performed to ensure that textural information is not removed.

Conclusions

Combining univariate and multivariable models is allowed to identify features for which corrections may be applied to reduce the trend with the algorithm and increase reproducibility. Subsequent clustering may be applied to eliminate residual redundancy.