bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

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

Abstract
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

Abstract
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

AbstractGlioblastoma (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

Abstract
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

AbstractIn 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

AbstractSchumpeter'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

AbstractBackgroundOur 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.ResultsHere, 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.ConclusionOur 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

Abstract
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

AbstractSeeking 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.