bluuebunny/crossref_metadata_2025 huggingface dataset:
Does physical activity level have an impact on long-term treatment response in temporomandibular disorders: protocol for a prospective study
Authors: Chun Youngwoo , Jo Jung Hwan , Park Ji Woon
Published: September 2022

Background

Temporomandibular disorders (TMD) is a disease characterized by pain and dysfunction of the masticatory muscles and temporomandibular joint. Many factors have been found to be related to the disease however, the underlying mechanism is yet to be fully elucidated. Physical activity is widely known to modulate pain intensity in various pain disorders. However, literature suggesting the association between physical activity and signs and symptoms of TMD are limited.

Methods and design

The “Physical Activity in TMD (PAT)” is a prospective study on TMD patients that aims to determine how daily physical activity and sleep duration affect long-term TMD prognosis following conventional treatment. To analyze such effects, objective data on daily physical activity levels will be collected along with clinical indices including mouth opening ranges and masticatory muscle palpation responses from adult Koreans diagnosed with TMD following standardized diagnostic procedures. Well-known comorbidities of TMD will be extensively evaluated based on validated structured questionnaires on sleep quality, fatigue level, widespread pain, psychological status including depression and anxiety, autonomic symptoms, and health-related quality of life. The collected data will be analyzed according to TMD pain severity and physical activity level, and correlations among physical activity indices and long-term TMD prognosis will be investigated.

Discussion

In this longitudinal prospective study of adult Koreans diagnosed with TMD following standardized diagnostic procedures, primary outcomes include physical activity levels and long-term TMD clinical outcomes and secondary outcomes include disability from pain and related comorbidity levels. Results and analysis are ongoing. The results of this study will provide reliable data for future research and establish clinical guidelines that will allow cause-related, patient-tailored personalized medicine for TMD.

Trial registration: Clinical Research Information Service (Registration number: KCT0007107). Registered March 22 2022 https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&focus=reset_12&search_page=M&pageSize=10&page=undefined&seq=21420&status=5&seq_group=21420.
Multifunctional mesoporous silica-cerium oxide nanozymes facilitate miR129 delivery for high-quality healing of radiation-induced skin injury
Authors: Zhou Daijun , Du Min , Luo Han , Ran Fengwei , Zhao Xiang , Dong Yan , Zhang Tao , Hao Jie , Li Dong , Li Jianjun
Published: September 2022

Radiation-induced skin injury (RISI) is an important challenge for clinical treatments. The main causes of RISI include hypoxia in the wound microenvironment, reactive oxygen species (ROS) activation, and downregulation of DNA repair proteins. Here, a multiple radioresistance strategy was designed for microRNA therapy and attenuating hypoxia. A novel mesoporous silica (MS) firmly anchored and dispersed cerium (IV) oxide (CeO2) nanoparticles to form MS-CeO2 nanocomposites, which exhibit superior activity in inhibiting radiation-induced ROS and HIF-1α activation and ultimately promote RISI wound healing. The miR129 serum concentrations in patients can promote radioresistance by directly targeting RAD17 and regulating the Chk2 pathway. Subsequently, MS-CeO2 nanocomposites with miR129 were conjugated with iRGD-grafted polyoxyethylene glycol (short for nano-miR129), which increased the stability and antibacterial character, efficiently delivered miR129 to wound blood capillaries, and exhibited low toxicity. Notably, nano-miR129 promoted radioresistance and enhanced anti-ROS therapeutic efficacy in a subcutaneous RISI mouse model. Overall, this MS-CeO2 nanozyme and miR129-based multiresistance radiotherapy protection strategy provided a promising therapeutic approach for RISI.
Objectively measuring the association between the built environment and physical activity: a systematic review and reporting framework
Authors: Pontin Francesca L. , Jenneson Victoria L. , Morris Michelle A. , Clarke Graham P. , Lomax Nik M.
Published: September 2022

Background

Objective measures of built environment and physical activity provide the opportunity to directly compare their relationship across different populations and spatial contexts. This systematic review synthesises the current body of knowledge and knowledge gaps around the impact of objectively measured built environment metrics on physical activity levels in adults (≥ 18 years). Additionally, this review aims to address the need for improved quality of methodological reporting to evaluate studies and improve inter-study comparability though the creation of a reporting framework.

Methods

A systematic search of the literature was conducted following the PRISMA guidelines. After abstract and full-text screening, 94 studies were included in the final review. Results were synthesised using an association matrix to show overall association between built environment and physical activity variables. Finally, the new PERFORM (’Physical and Environmental Reporting Framework for Objectively Recorded Measures’) checklist was created and applied to the included studies rating them on their reporting quality across four key areas: study design and characteristics, built environment exposures, physical activity metrics, and the association between built environment and physical activity.

Results

Studies came from 21 countries and ranged from two days to six years in duration. Accelerometers and using geographic information system (GIS) to define the spatial extent of exposure around a pre-defined geocoded location were the most popular tools to capture physical activity and built environment respectively. Ethnicity and socio-economic status of participants were generally poorly reported. Moderate-to-vigorous physical activity (MVPA) was the most common metric of physical activity used followed by walking. Commonly investigated elements of the built environment included walkability, access to parks and green space. Areas where there was a strong body of evidence for a positive or negative association between the built environment and physical activity were identified. The new PERFORM checklist was devised and poorly reported areas identified, included poor reporting of built environment data sources and poor justification of method choice.

Conclusions

This systematic review highlights key gaps in studies objectively measuring the built environment and physical activity both in terms of the breadth and quality of reporting. Broadening the variety measures of the built environment and physical activity across different demographic groups and spatial areas will grow the body and quality of evidence around built environment effect on activity behaviour. Whilst following the PERFORM reporting guidance will ensure the high quality, reproducibility, and comparability of future research.
Identification of CD8+ T cell subsets that normalize in early-treated people living with HIV receiving antiretroviral therapy
Authors: Perdomo-Celis Federico , Arcia-Anaya David , Alzate Juan Carlos , Velilla Paula A. , Díaz Francisco J. , Posada Maria Paulina , Rugeles María T. , Taborda Natalia A.
Published: September 2022

Background

Although combined antiretroviral therapy (cART) has decreased the mortality associated with HIV infection, complete immune reconstitution is not achieved despite viral suppression. Alterations of CD8+T cells and some of their subpopulations, such as interleukin (IL)-17-producing cells, are evidenced in treated individuals and are associated with systemic inflammation and adverse disease outcomes. We sought to evaluate if different CD8+T cell subsets are differentially normalized during a clinical follow-up of people living with HIV (PLWH) receiving suppressive cART.

Methods

We explored the changes in the frequencies, activation/exhaustion phenotypes (HLA-DR, CD38, PD-1, and TIM-3), and function (total and HIV-specific cells expressing CD107a, perforin, granzyme B, interferon [IFN]-γ and IL-17) of CD8+T cells from early-treated PLWH receiving cART in a 1-year follow-up, using a multidimensional flow cytometry approach.

Results

Despite continuous cART-induced viral suppression and recovery of CD4+T cells, after a 1-year follow-up, the CD8+T cell counts, CD4:CD8 ratio, PD-1 expression, and IL-17 production by CD8+T cells exhibited incomplete normalization compared with seronegative controls. However, the proportion of CD8+T cells with an exhausted phenotype (co-expressing PD-1 andTIM-3), and cells co-expressing cytotoxic molecules (Perforin and Granzyme B), reached normalization.

Conclusions

Although suppressive cART achieves normalization of CD4+T cell counts, only particular subsets of CD8+T cells are more rapidly normalized in PLWH receiving cART, which could be routinely used as biomarkers for therapy efficiency in these patients.
A systematic quality evaluation and review of nanomaterial genotoxicity studies: a regulatory perspective
Authors: Siivola Kirsi M. , Burgum Michael J. , Suárez-Merino Blanca , Clift Martin J. D. , Doak Shareen H. , Catalán Julia
Published: September 2022

The number of publications in the field of nanogenotoxicology and the amount of genotoxicity data on nanomaterials (NMs) in several databases generated by European Union (EU) funded projects have increased during the last decade. In parallel, large research efforts have contributed to both our understanding of key physico-chemical (PC) parameters regarding NM characterization as well as the limitations of toxicological assays originally designed for soluble chemicals. Hence, it is becoming increasingly clear that not all of these data are reliable or relevant from the regulatory perspective. The aim of this systematic review is to investigate the extent of studies on genotoxicity of NMs that can be considered reliable and relevant by current standards and bring focus to what is needed for a study to be useful from the regulatory point of view. Due to the vast number of studies available, we chose to limit our search to two large groups, which have raised substantial interest in recent years: nanofibers (including nanotubes) and metal-containing nanoparticles. Focusing on peer-reviewed publications, we evaluated the completeness of PC characterization of the tested NMs, documentation of the model system, study design, and results according to the quality assessment approach developed in the EU FP-7 GUIDEnano project. Further, building on recently published recommendations for best practices in nanogenotoxicology research, we created a set of criteria that address assay-specific reliability and relevance for risk assessment purposes. Articles were then reviewed, the qualifying publications discussed, and the most common shortcomings in NM genotoxicity studies highlighted. Moreover, several EU projects under the FP7 and H2020 framework set the aim to collectively feed the information they produced into the eNanoMapper database. As a result, and over the years, the eNanoMapper database has been extended with data of various quality depending on the existing knowledge at the time of entry. These activities are highly relevant since negative results are often not published. Here, we have reviewed the NanoInformaTIX instance under the eNanoMapper database, which hosts data from nine EU initiatives. We evaluated the data quality and the feasibility of use of the data from a regulatory perspective for each experimental entry.
Expression of immune checkpoint regulators, programmed death-ligand 1 (PD-L1/PD-1), cytotoxic T lymphocyte antigen 4 (CTLA-4), and indolaimine-2, 3-deoxygenase (IDO) in uterine mesenchymal tumors
Authors: Samiei Alireza , Gjertson David W. , Memarzadeh Sanaz , Konecny Gottfried E. , Moatamed Neda A.
Published: September 2022

Background

Immune checkpoints including programmed death-ligand 1/programmed death-1/ (PD-L1/PD-1), cytotoxic T lymphocyte antigen 4 (CTLA-4), and indolaimine-2, 3-deoxygenase (IDO) have recently emerged as effective candidates for treatment against a range of human malignancies. We have investigated their expression in the uterine mesenchymal tumors.

Methods

Sixty-eight mesenchymal tumors were categorized into 6 diagnostic groups. We assessed PD-L1, PD-1, CTLA-4, and IDO expression on paraffin embedded tissue blocks of the uterine tumors using the respective antibodies. Immunohistochemical (IHC) stains were classified as positive when the reactions were present in at least 1% of the cell membranes for PD-L1/PD-1 or in cytoplasm for CTLA-4 and IDO, regardless of intensity. Student’s t-test and McNemar’s chi-square tests were carried out to analyze the results.

Results

The mesenchymal neoplasms had expressed the immune checkpoints in the tumor and/or the lymphoid cells at the rate of 49% and 54% respectively. The tumor cells were positive in 10 (18%, PD-L1), 0 (0%, PD-1), 18 (32%, CTLA-4), and 13 (23%, IDO) cases while the infiltrating lymphoid cells were positive in 10 (18%, PD-L1), 23 (40%, PD-1), 18 (32%, CTLA-4), and 13 (23%, IDO) cases. Overall, comparison of paired tumor vs lymphoid cells resulted in p-values of ≤ 0.04.

Conclusions

Nearly 50% of the uterine tumors express at least one of the immune checkpoints in tumor and/or the infiltrating lymphoid cells. However, expression of the proteins in the two cellular components are mutually exclusive. Namely, when tumor cells express an immune checkpoint, the infiltrating lymphoid cells do not, and vice versa. Since the leiomyosarcomas are reportedly resistant to the immunotherapy when PD-L1 is expressed in the tumor cells, it can be posited that presence of the IHC positive lymphoid cells may be a better indicator of response to the treatment.
PARP targeted Auger emitter therapy with [125I]PARPi-01 for triple-negative breast cancer
Authors: Ambur Sankaranarayanan Ramya , Florea Alexandru , Allekotte Susanne , Vogg Andreas T. J. , Maurer Jochen , Schäfer Laura , Bolm Carsten , Terhorst Steven , Classen Arno , Bauwens Matthias , Morgenroth Agnieszka , Mottaghy Felix M.
Published: September 2022

Background

Triple-negative breast cancer (TNBC) lacks biomarkers for targeted therapy. Auger emitters display the best therapeutic effect, if delivered directly into the nucleus proximal to DNA. The nuclear protein Poly (ADP-ribose)-Polymerase 1 (PARP1) is a suitable target against which few inhibitors (PARPi) are clinically approved for treatment of breast cancer with germline BRCA mutation (BRCAmut). In this study, a theranostic approach was investigated in a TNBC xenografted mouse model by radiolabelling a close derivative of a PARPi Olaparib (termed PARPi-01) with the Auger emitters 123/125I.

Methods

TNBC cell line MDA-MB-231 was subcutaneously implanted in female NOD/SCID mice. At a tumour size of ~ 500mm3, [123I]PARPi-01 was administered intravenously, and SPECT/CT images were obtained at 4 h or 24 h post injection (p.i). A therapy study was performed with [125I]PARPi-01 in 4 doses (10 MBq/dose, 10 days apart). Tumour growth was monitored by CT scans longitudinally once per week. Upon reaching study endpoint, tissues were harvested and stained with TUNEL assay for detection of apoptosis induction.

Results

SPECT/CT images showed rapid hepatobiliary tracer clearance at 4 h post injection (p.i.). Retention in thyroid at 24 h p.i. suggested tracer deiodination in vivo. The tumour and liver uptake were 0.2%ID/g and 2.5%ID/g, respectively. The tumour: blood ratio was 1.3. Endogenous therapy induced a significant delay in tumour growth (doubling time increased from 8.3 to 14.2 days), but no significant survival advantage. Significantly higher apoptosis ratio was observed in [125I]PARPi-01 treated tumour tissues. No radiotoxicity was detected in the liver and thyroid.

Conclusion

Considering the radio-cytotoxic effect in the tumour tissue and a delay on tumour doubling time, [125I]PARPi-01 presents a potential radiotherapeutics for treatment of TNBC. Improvements to overcome the suboptimal pharmacokinetics are necessary for its potential clinical application.
Fintech application on banking stability using Big Data of an emerging economy
Authors: Yin Fang , Jiao Xiaomei , Zhou Jincheng , Yin Xiong , Ibeke Ebuka , Iwendi Marvellous GodsPraise , Biamba Cresantus
Published: September 2022

The rapid growth and development of financial technological advancement (Fintech) services and innovations have attracted the attention of scholars who are now on a quest to analyse their impact on the banking sector. This study conducts several kinds of analyses to measure the effect of the fintech era on the stability of the Chinese banking sector. It uses Big Data and performs Pearson correlation and regression analysis on the fintech era’s transition period to measure the impact of several explanatory variables— institutional regulation, government stability, bank credit to deposit ratio, and economic growth— on the outcome variables, which includes Nonperforming loans (NPLs) and its numerical measurement in relation to the mean score of the Big Data (Z-score). This study uses yearly Big Data from 1995–2018 and revealed that compared to the first wave of the fintech era, the second wave helped in the reduction of NPLs and the enhancement of financial stability in China. This study concludes that in the second wave of the fintech era, the explanatory variables mentioned above had a positive impact on NPLs and banking stability. This work helps comprehend fintech development in modern society and the importance of its disruptive forces in developing and developed countries.
Estimating the spatial correlation and convergence of China's healthcare resources allocation: evidence from the Yangtze River Delta Region
Authors: Shen Yuqing , Sun Zesheng
Published: September 2022

Background

China’s imbalanced allocation of healthcare resources mainly arises from urban–rural and intercity differences, the solution of which has been the goal of reforms during the past decades. Estimating the spatial correlation and convergence could help to understand the impact of China’s fast-evolving medical market and the latest healthcare reforms.

Methods

The entropy weight method was used to construct a healthcare resource supply index (HRS) by using data of 41cities in a cluster in the Yangtze River Delta (YRD) from 2007 to 2019. The Dagum Gini coefficient, kernel density estimation, Moran's I, and LISA cluster map were used to characterize the spatiotemporal evolution and agglomeration of healthcare resources, and then a spatial panel model was used to perform β convergence estimation by incorporating the spatial effect, city heterogeneity, and healthcare reforms.

Results

Healthcare resources supply in the YRD region increases significantly and converges rapidly. There is a significant spatial correlation and agglomeration between provinces and cities, and a significant spatial spillover effect is also found in β convergence. No evidence is found that the latest healthcare reforms have an impact on the balanced allocation and convergence of healthcare resources.

Conclusion

China’s long-term investment in past decades has yielded a more balanced allocation and intercity convergence of healthcare resources. However, the latest healthcare reforms do not contribute to the balanced allocation of healthcare resources from the supply-side, and demand-side analysis is needed in the future studies.
Adaptation and validation of a critical thinking scale to measure the 3D critical thinking ability of EFL readers
Authors: Mohammadi Moloud , Abbasian Gholam-Reza , Siyyari Masood
Published: September 2022

Thinking has always been an integral part of human life, and it can be said that whenever humanity has been thinking, it has been practicing a kind of criticizing the issues around. This is the concept of critical thinking that enhances the ability of individuals to identify problems and find solutions. Most previous research has focused on only one aspect of critical thinking that is critical thinking skills, while two other dimensions of criticality and critical pedagogy should have also been included. In order to assure of the validity of the instrument designed by Mohammadi et al. (Characterization and Development of Critically-thinker EFL Readers’ Reading Ability: Asynchronous Webbased Collaborative vs. Question-Answer-Relationship Instructional Approach, under review), it was first adapted and then SEM modeling was used. Examination of the results of factor analysis and modeling of SEM showed that the model satisfied the fit indices (χ2/df, CFI, TLI, RMSEA), and all the factor loads are greater than 0.4 which represent that the items are defined properly. This research suggested a SEM modeling of critical thinking skills, composed of six factors measured by twenty-two indices. The results of the PLS-SEM CFA represented that it is a valid structural model to measure a critical thinking of EFL readers at three levels.
A revitalisation of European farming and the promise of the biodynamic worldview
Authors: Wright Julia
Published: September 2022

In 2020 and amidst the upsurge in discourse around de-industrialisation, a consortium of sixteen indigenous leaders and organisations released a briefing statement that urged change amongst modern regenerative farming movements. Called ‘Whitewashed Hope’, the critique encouraged these movements to go deeper than simply taking indigenous practices out of context, but rather to encompass the worldviews they represent and in doing so to enable the cultural and relational changes needed for humanity’s collective healing. This paper takes a critical analysis approach to address the question of whether the critique of regenerative agriculture holds true for biodynamic agriculture in particular. This is explored using the hypothesis that there is no evidence of a synergistic relationship between the biodynamic worldview and the indigenous worldview as characterised in the document Whitewashed Hope. Drawing from the works of Rudolf Steiner as well as from other biodynamic texts, the paper uncovers synergies that exist between biodynamic and indigenous worldviews and explores the implications for regenerative farming systems. The aim of this paper is to instigate further debate and enquiry around the underexplored topic of how our worldviews impact our farming systems and of ways to develop an expanded worldview for more revitalised farming in the European context.

Graphical Abstract
Effective flow-through polishing strategies for knob-into-hole bispecific antibodies
Authors: Chen Serene W. , Hoi Kong Meng , Mahfut Farouq Bin , Yang Yuansheng , Zhang Wei
Published: September 2022

Bispecific antibodies (bsAbs), though possessing great therapeutic potential, are extremely challenging to obtain at high purity within a limited number of scalable downstream processing steps. Complementary to Protein A chromatography, polishing strategies play a critical role at removing the remaining high molecular weight (HMW) and low molecular weight (LMW) species, as well as host cell proteins (HCP) in order to achieve a final product of high purity. Here, we demonstrate using two knob-into-hole (KiH) bsAb constructs that two flow-through polishing steps utilising Capto Butyl ImpRes and Capto adhere resins, performed after an optimal Protein A affinity chromatography step can further reduce the HCP by 17- to 35-fold as well as HMW and LMW species with respect to monomer by ~ 4–6% and ~ 1%, respectively, to meet therapeutical requirement at 30–60 mg/mL-resin (R) load. This complete flow-through polishing strategy, guided by Design of Experiments (DoE), eliminates undesirable aggregation problems associated with the higher aggregation propensity of scFv containing bsAbs that may occur in the bind and elute mode, offering an improved ease of overall process operation without additional elution buffer preparation and consumption, thus aligning well with process intensification efforts. Overall, we demonstrate that through the employment of (1) Protein A chromatography step and (2) flow-through polishing steps, a final product containing < 1% HMW species, < 1% LMW species and < 100 ppm HCP can be obtained with an overall process recovery of 56–87%.

Graphical Abstract
Development of a classifier for [18F]fluorodeoxyglucose extravasation severity using semi-quantitative readings from topically applied detectors
Authors: Perrin Steve , Kiser Jackson W. , Knowland Josh , Bowen Spencer L.
Published: September 2022

Background

Radiotracer extravasations, caused largely by faulty tracer injections, can occur in up to 23% of 18F-fluorodeoxyglucose (FDG) PET/CT scans and negatively impact radiological review and tracer quantification. Conventional radiological assessment of extravasation severity on PET has limited performance (e.g., extravasations frequently resolve before scanning) and practical drawbacks. In this study, we develop a new topical detector-based FDG extravasation severity classifier, calibrated from semi-quantitative PET measurements, and assess its performance on human subjects.

Methods

A retrospective study examined patients whose FDG injections had been monitored as part of their standard workup for PET/CT imaging. Topical uncollimated gamma ray detectors were applied proximal to the injection site and on the same location on the opposing arm, and readings were acquired continuously during radiotracer uptake. Patients were imaged with their arms in the PET field of view and total extravasation activity quantified from static PET images through a volume of interest approach. The image-derived activities were considered ground truth and used to calibrate and assess quantification of topical detector readings extrapolated to the start of PET imaging. The classifier utilizes the calibrated detector readings to produce four extravasation severity classes: none, minor, moderate, and severe. In a blinded study, a radiologist qualitatively labeled PET images for extravasation severity using the same classifications. The radiologist’s interpretations and topical detector classifications were compared to the ground truth PET results.

Results

Linear regression of log-transformed image-derived versus topical detector tracer extravasation activity estimates showed a strong correlation (R2 = 0.75). A total of 24 subject scans were cross-validated with the quantitatively based classifier through a leave-one-out methodology. For binary classification (none vs. extravasated), the topical detector classifier had the highest overall diagnostic performance for identifying extravasations. Specificity, sensitivity, accuracy, and positive predictive value were 100.0%, 80.0%, 95.8%, and 100.0%, respectively, for the topical detector classifier and 31.6%, 100.0%, 45.8%, and 27.8%, respectively, for the radiological analysis. The topical detector classifier, with an optimal detection threshold, produced a significantly higher Matthews correlation coefficient (MCC) than the radiological analysis (0.87 vs. 0.30).

Conclusions

The topical detector binary classifier, calibrated using quantitative static PET measurements, significantly improves extravasation detection compared to qualitative image analysis.
Impact of pathological complete response following neoadjuvant chemotherapy (gemcitabine, nab-paclitaxel, S-1) and radiation for borderline resectable pancreatic cancer: a case report and review of literature
Authors: Kinoshita Mitsuru , Watanabe Sota , Mizojiri Gaku , Sada Akitada , Kai Hiroki , Masuike Yasunori , Nagasawa Yoshinobu , Maruyama Kentaro , Lee Kyowon , Ohata Mai , Ishikawa Osamu , Oka Hiroshi
Published: September 2022

Background

Pancreatic cancer (PC) is a highly lethal malignancy, even if surgical resection is possible (median survival: < 30 months). The prognosis of borderline resectable pancreatic cancer (BR-PC) is even worse. There is no clear consensus on the optimal treatment strategy, including pre/postoperative therapy, for BR-PC. We report a patient with BR-PC who achieved clinical partial response with neoadjuvant chemoradiation therapy (NACRT) and underwent curative resection, resulting in pathological complete response (pCR).

Case presentation

A 71-year-old man with jaundice and liver dysfunction was referred to our department because of a 48-mm hypo-vascular mass in the pancreatic head with obstruction of the pancreatic and bile ducts and infiltration of superior mesenteric vein and portal vein. The lesion was identified as atypical cells which suggested adenocarcinoma by biopsy, and he was administered NACRT: gemcitabine and nab-paclitaxel, following S-1 and intensity modulated radiation therapy. After reduction in the tumor size (clinical partial response), pancreaticoduodenectomy was performed, and pCR achieved. Postoperative adjuvant chemotherapy with S-1 was initially administered and the patient is currently alive with no recurrence as of 2 years after surgery.

Conclusions

NACRT is a potentially useful treatment for BR-PC that may lead to pCR and help improve prognosis.
Exploring the inner roots of discharge against medical advice (DAMA) in an academic psychiatric hospital: a qualitative study
Authors: Alidoust Fatemeh , Yahyavi Seyyed Taha
Published: September 2022

Background

To explore the roots of DAMA in the Roozbeh Hospital, an academic mental hospital located in Tehran, Iran, the authors conducted a simple qualitative study. Twenty-four in-depth semi-structured interviews with families and eight with patients who were discharged against medical advice were done about the inner motivation and roots of DAMA. The sampling was convenient in trying to reach the maximum variation. The transcribed verbatim of the interviews was coded and categorized inductively by discussion. Ethical consideration was approved by the TUMS ethical committee.

Results

Findings were classified into six categories: The patient’s insistence, miss the beloved one, sense of improvement, outside hospital concerns, dissatisfaction with the quality of medical care, and worries about the hospitalization consequences.

Conclusions

Addressing the inner roots of DAMA can be an opportunity to understand better patients and their families’/relatives’ experiences and feelings. This will give a deep perspective and insight into the subject.
The need for clinical ethics consultation: a monocentric observational survey study in the intensive care unit (Consul.E.T.I. study)
Authors: Filippini Matteo , Nicoli Federico , Picozzi Mario , Latronico Nicola
Published: September 2022

Background

The current organizational structure of the Italian healthcare system does not include the institutionalization of clinical ethics services.

To describe the need for structured clinical ethics consultation services for ICU staff members in the intensive care unit (ICU), a monocentric observational survey study was performed utilizing a paper-based questionnaire.

Results

A total of 73 healthcare professionals (HCPs) responded out of a team of 84 people (87%). The results showed that the need for ethics consultation in the ICU is urgent, the institutionalization of the clinical ethics service is perceived as useful and should be a priority, and the issues on which the HCPs would like ethics consultation to focus are various and belong to “end of life” topics.

Conclusions

HCPs believe that the clinical ethicist should become an integral part of ICU healthcare teams, offering consultations similar to the other specialistic consultations carried out in hospitals.
Evaluation of a Health Care Worker Training Intervention to Improve the Early Diagnosis and Referral of Childhood Cancers in Ghana: A Qualitative Descriptive Study
Authors: Fowokan Adeleke , Afungchwi Glenn Mbah , Renner Lorna , Freccero Piera , Gupta Sumit , Denburg Avram
Published: September 2022

PURPOSE

This study sought to (1) evaluate the perceived effectiveness of an early childhood cancer warning signs and symptoms (EWSS) training intervention on health care worker (HCW) knowledge, attitudes, and clinical practice; (2) evaluate the ease of implementation of training received, including potential barriers and facilitators; and (3) provide insights into program improvements for future iterations of the intervention.

METHOD

Using a qualitative descriptive study design, we conducted in-depth, semistructured interviews with 23 purposively sampled Ghanaian HCW recipients of the EWSS training intervention. We undertook iterative thematic analysis of data concurrently with interviews and used a modified version of the theoretical framework of acceptability to guide the evaluation of the training intervention.

RESULTS

We identified six themes—affective attitude, burden, intervention coherence, perceived effectiveness, self-efficacy, and quality improvement—that structure participant perceptions of the effectiveness of the EWSS training. Participants generally had a positive attitude to the training intervention, found the content relatively easy to understand, and communicated the positive impacts of the training on their day-to-day practice. However, they also identified patient- and system-level challenges to the real-world implementation of intervention components, including patients' cultural and religious beliefs about illnesses, patients' financial constraints, and inadequately funded health systems.

CONCLUSION

Our findings suggest that although an HCW-focused training intervention has the potential to improve timely diagnosis and referral for childhood cancers in Ghana and comparable health system contexts, complementary interventions to address patient- and system-level implementation challenges are required to translate improvements in HCW knowledge to sustained impact on health outcomes for children with cancer.
Addition of Germline Testing to Tumor-Only Sequencing Improves Detection of Pathogenic Germline Variants in Men With Advanced Prostate Cancer
Authors: Berchuck Jacob E. , Boiarsky Daniel , Silver Rebecca , Sunkara Rajitha , McClure Heather M. , Tsai Harrison K. , Siegmund Stephanie , Tewari Alok K. , Nowak Jonathan A. , Lindeman Neal I. , Rana Huma Q. , Choudhury Atish D. , Pomerantz Mark M. , Freedman Matthew L. , Van Allen Eliezer M. , Taplin Mary-Ellen
Published: September 2022

PURPOSE

Guidelines recommend somatic and germline testing for men with advanced prostate cancer (PCa). Barriers to widespread implementation result in underutilization of germline testing. Somatic testing alone risks missing pathogenic germline variants (PGVs). We sought to determine whether the addition of germline testing to tumor-only sequencing improves detection of PGVs in men with advanced PCa. Secondarily, we sought to define the added value of combining somatic and germline testing to optimize detection of clinically actionable alterations.

PATIENTS AND METHODS

We analyzed results of independent germline testing and tumor-only sequencing from 100 men with advanced PCa from a prospective clinical trial (ClinicalTrials.gov identifier: NCT03328091 ). The primary outcome was the proportion of PGVs not reported with tumor-only sequencing. The secondary outcome was the association of locus-specific loss of heterozygosity for PGVs in homologous recombination genes with clinical-genomic features.

RESULTS

In the 100 men who underwent germline testing and tumor-only sequencing, 24 PGVs were identified, 17 of which were clinically actionable, in 23 patients. Tumor-only sequencing failed to report four (17%) of the PGVs. One additional PGV (4.2%) had variant allele frequency on tumor-sequencing below the threshold for follow-up germline testing. When integrating tumor-only sequencing with germling testing results, 33% of patients harbored clinically actionable alterations. Rates of locus-specific loss of heterozygosity were higher for BRCA2 PGVs in castration-resistant PCa than PGVs in other homologous recombination genes in hormone-sensitive PCa ( P = .029).

CONCLUSION

Tumor-only sequencing failed to report more than 20% of PGVs in men with advanced PCa. These findings strongly support guideline recommendations for universal germline and somatic testing in this population. Combining tumor and germline sequencing doubled the chance of detecting a clinically actionable alteration.
New CrOX (X = Cl, Br, I) monolayer with ultra-wide single spin states
Authors: Deng Xiaohui , Tang Zhenkun
Published: September 2022

The ultra-wide single spin states are of importance for ideal magnetic storage materials and spin injection sources. Here, a new type of CrOX (X = Cr, Br, I) monolayer has been revealed. We find that the basic constructive units for such new monolayers are four-coordinated, almost never being reported until now. More interestingly, they are half-metals and have an ultra-wide single spin channel in their electronic band structures. Monte Carlo simulations show that the Curie temperatures of three monolayers are relatively low, however they can be enhanced to exceed the liquid nitrogen temperature under strain or hole doping. The four-coordinated Cr compounds predicted here may open a new windows for exploring high spin-polarized half-metals.
The Scanning Fiber Endoscope: A Novel Surgical and High-Resolution Imaging Device for Intracranial Neurosurgery
Authors: Walker Gregory , Wang Alick P. , McVeigh Patrick Z. , Ivanishvilli Zurab , Siu William , Seibel Eric J. , Lesiuk Howard , Alkherayf Fahad , Drake Brian J.
Published: September 2022

BACKGROUND:

The scanning fiber endoscope (SFE) is a novel medical imaging device that has been used in various vascular beds as a form of angioscopy, as well as in tracts and duct systems for endoluminal imaging. Owing to its miniaturized form, high resolution, and flexibility, it has demonstrated success in imaging across a wide range of diagnostic applications.

OBJECTIVE:

To demonstrate, by performing a third ventriculostomy and visualizing the cranial nerves and brainstem anatomy, that, without modification, the SFE can be used through a transcranial approach in a therapeutic intraventricular neurosurgical application.

METHODS:

A 3.7 French SFE system was used without modification on a live porcine model to perform a third ventriculostomy and acquire high-resolution images of the animal's ventricular system, cranial nerves, and brainstem. A side-by-side comparison was made with one of the current standard-of-care rigid endoscopes as a context for size and image quality.

RESULTS:

High-resolution video-rate imaging was used to assist the successful, uncomplicated performance of a third ventriculostomy. High-resolution endoscopic images of the brainstem and cranial nerves were acquired.

CONCLUSION:

Although the SFE has been shown to be a superior device for imaging, here we demonstrate its first use as a potential therapeutic device in intracranial neurosurgery.
Image Segmentation of Operative Neuroanatomy Into Tissue Categories Using a Machine Learning Construct and Its Role in Neurosurgical Training
Authors: Witten Andrew J. , Patel Neal , Cohen-Gadol Aaron
Published: September 2022

BACKGROUND:

The complexity of the relationships among the structures within the brain makes efficient mastery of neuroanatomy difficult for medical students and neurosurgical residents. Therefore, there is a need to provide real-time segmentation of neuroanatomic images taken from various perspectives to assist with training.

OBJECTIVE:

To develop the initial foundation of a neuroanatomic image segmentation algorithm using artificial intelligence for education.

METHODS:

A pyramidal scene-parsing network with a convolutional residual neural network backbone was assessed for its ability to accurately segment neuroanatomy images. A data set of 879 images derived from The Neurosurgical Atlas was used to train, validate, and test the network. Quantitative assessment of the segmentation was performed using pixel accuracy, intersection-over-union, the Dice similarity coefficient, precision, recall, and the boundary F
1 score.

RESULTS:

The network was trained, and performance was assessed class wise. Compared with the ground truth annotations, the ensembled results for our artificial intelligence framework for the pyramidal scene-parsing network during testing generated a total pixel accuracy of 91.8%.

CONCLUSION:

Using the presented methods, we show that a convolutional neural network can accurately segment gross neuroanatomy images, which represents an initial foundation in artificial intelligence gross neuroanatomy that will aid future neurosurgical training. These results also suggest that our network is sufficiently robust, to an unprecedented level, for performing anatomic category recognition in a clinical setting.
Dura Management Strategies in the Surgical Treatment of Adult Chiari Type I Malformation: A Retrospective, Multicenter, Population-Based Parallel Cohort Case Series
Authors: Kristiansson Helena , Fletcher-Sandersjöö Alexander , Cesarini Kristina , Fransson Marcus , Vlachogiannis Pavlos , Burström Gustav , Hessington Amel , Bartek Jiri , Edström Erik , Holmgren Rafael T. , Sköld Mattias K. , Elmi-Terander Adrian
Published: September 2022

BACKGROUND:

Symptomatic Chiari I malformation is treated with suboccipital decompression and C1 laminectomy. However, whether the dura should be opened (durotomy) or enlarged with a graft (duraplasty) remains unclear.

OBJECTIVE:

To compare outcomes in adult Chiari I malformation patients treated with duraplasty, durotomy, or without dural opening (“mini-decompression”).

METHODS:

A retrospective, multicenter, population-based cohort study was performed of all adult patients surgically treated for a Chiari I malformation at 3 regional neurosurgical centers between 2005 and 2017. Three different dura management strategies were favored by the participating hospitals, with data stratified accordingly. The primary outcome was measured using the Chicago Chiari Outcome Scale (CCOS), dichotomized into favorable (CCOS ≥13) or unfavorable (CCOS ≤12). Propensity score matching was used to adjust for potential confounders in outcome comparisons.

RESULTS:

In total, 318 patients were included, of whom 52% were treated with duraplasty, 37% with durotomy, and 11% with mini-decompression. In total, 285 (90%) showed a favorable surgical outcome (CCOS ≥13). Duraplasty was associated with more favorable CCOS and shorter hospital stay compared with durotomy, both in unadjusted (93% vs 84%. P = .018 and 6.0 vs 8.0 days, P < .001) and adjusted analyses (92% vs 84%, P = .044 and 6.0 vs 8.0 days, P < .001). Mini-decompression was excluded from the adjusted analyses because of its small sample size.

CONCLUSION:

In this study of adult Chiari I malformation, posterior fossa decompression with duraplasty was associated with more favorable postoperative outcome, as determined by the CCOS, compared with posterior fossa decompression with durotomy alone.
Microsurgical Tubular Resection of Intradural Extramedullary Spinal Tumors With 3-Dimensional-Navigated Localization
Authors: McGrath Lynn B. , Kirnaz Sertac , Goldberg Jacob L. , Sommer Fabian , Medary Branden , Hussain Ibrahim , Härtl Roger
Published: September 2022

BACKGROUND:

The safety and efficacy of minimally invasive spine surgical (MISS) approaches have stimulated interest in adapting MISS principles for more complex pathology including intradural extramedullary (IDEM) tumors. No study has characterized a repeatable approach integrating the MISS surgical technique and 3-dimensional intraoperative navigated localization for the treatment of IDEM tumors.

OBJECTIVE:

To describe a safe and reproducible technical guide for the navigated MISS technique for the treatment of benign intradural and extradural spinal tumors.

METHODS:

Retrospective review of prospectively collected data on 20 patients who underwent navigated microsurgical tubular resection of intradural extramedullary tumors over a 5-year period. We review our approach to patient selection and report demographic and outcomes data for the cohort.

RESULTS:

Our experience demonstrates technical feasibility and safety with a 100% rate of gross total resection with no patients demonstrating recurrence during an average follow-up of 20.2 months and no instances of perioperative complications. We demonstrate favorable outcomes regarding blood loss, operative duration, and hospital length of stay.

CONCLUSION:

Navigated localization and microsurgical tubular resection of IDEM tumors is safe and effective. Adherence to MISS principles and thoughtful patient selection facilitate successful management of these patients.
Kyphoplasty of C2 Pathological Fractures Using an Anterior Midline Approach and Steerable Osteotome: Technical Note and Case Series
Authors: Krafft Paul R. , Peto Ivo , Flores-Milan Gabriel , Reeves Corey , Klein Sierra , Alikhani Puya , Tran Nam D.
Published: September 2022

BACKGROUND:

Malignant lesions involving the C2 vertebral body (axis) may be challenging to treat, and not all patients with cancer are good candidates for posterior cervical or occipitocervical instrumentation.

OBJECTIVE:

To describe a modified technique of the direct anterolateral C2 kyphoplasty using a steerable osteotome, commonly used for the treatment of thoracolumbar spinal lesions. We also report a case series of 11 patients treated with this technique at our institution.

METHODS:

The authors performed a retrospective review of all patients who underwent a C2 kyphoplasty using the anterior midline approach from 2010 to 2020. Patient demographics, tumor characteristics, pain severity (visual analog scale), Karnofsky performance status , perioperative complications, and postoperative spinal stability were assessed.

RESULTS:

The main indication for a C2 kyphoplasty was refractory neck pain. All patients tolerated the procedure well. There were no intraoperative complications. One patient developed transient dysphagia. Visual analog scale scores were 9.00 ± 1.10 preoperative and 3.73 ± 1.85 at 2 weeks and 1.67 ± 1.66 at 3 months after the procedure and continued to stay low during the remainder of the follow-up (4-60 months). The Karnofsky performance status improved from 72.73 ± 11.04 preoperatively to 82.22 ± 8.33 at 2 weeks and 86.67 ± 5.00 at 3 months after the procedure. There was no evidence of new occurrence or progression of C2 fractures.

CONCLUSION:

The anterior kyphoplasty using a steerable osteotome for tumors of the axis can result in lasting pain reduction and improved cervical stability while demonstrating a low complication rate.
Calcium and activity-dependent signaling in the developing cerebral cortex
Authors: Arjun McKinney Arpana , Petrova Ralitsa , Panagiotakos Georgia
Published: September 2022

Calcium influx can be stimulated by various intra- and extracellular signals to set coordinated gene expression programs into motion. As such, the precise regulation of intracellular calcium represents a nexus between environmental cues and intrinsic genetic programs. Mounting genetic evidence points to a role for the deregulation of intracellular calcium signaling in neuropsychiatric disorders of developmental origin. These findings have prompted renewed enthusiasm for understanding the roles of calcium during normal and dysfunctional prenatal development. In this Review, we describe the fundamental mechanisms through which calcium is spatiotemporally regulated and directs early neurodevelopmental events. We also discuss unanswered questions about intracellular calcium regulation during the emergence of neurodevelopmental disease, and provide evidence that disruption of cell-specific calcium homeostasis and/or redeployment of developmental calcium signaling mechanisms may contribute to adult neurological disorders. We propose that understanding the normal developmental events that build the nervous system will rely on gaining insights into cell type-specific calcium signaling mechanisms. Such an understanding will enable therapeutic strategies targeting calcium-dependent mechanisms to mitigate disease.