bluuebunny/crossref_metadata_2025 huggingface dataset:
Attitudes of deaf individuals towards genetic testing of genes known to cause hearing loss
Authors: Mascia Katherine L , Robin Nathaniel H
Published: November 2021

Congenital deafness is one of the most common birth defects reported. Approximately 70% of congenital deafness is non-syndromic, and approximately 80% of non-syndromic hearing loss results from a genetic cause. Middleton et al.’s1998 study highlighted the negative attitudes of culturally Deaf individuals towards genetic testing for genes known to cause hearing loss. While studies concerning genetic testing for deafness genes reference Middleton’s study, to our knowledge a re-evaluation of the attitudes of Deaf individuals towards genetic testing has not been conducted recently. The purpose of this study is to re-establish attitudes of Deaf individuals towards genetic testing of genes known to cause hearing loss. A computer-based questionnaire was distributed to members of the Deaf community. Responses of participants were recorded and analyzed. The primary investigator then attended Deaf community events and the 2015 Alabama Association of the Deaf Conference, and recruited individuals interested in participating in the study. The surveys were distributed to these individuals and their anonymous responses were analyzed. Our results show there are more positive attitudes within the Deaf community towards genetic counseling, genetic testing, and prenatal testing of genes known to cause hearing loss than were previously documented, although negative attitudes are still present. Additionally, our study shows there is a desire among members of the Deaf community to learn more about and potentially receive these services, despite the fact they are rarely offered by healthcare providers.
Scotland’s History of Animation: An Exploratory Account of the Key Figures and Influential Events
Authors: Mortimer Jonathan , Pilcher Nick , Richards Kendall
Published: November 2021

Scotland’s history of animation is a forgotten past accomplishment in the animation/VFX sector, with key influential animation professionals having had an impact both at home and abroad. Yet, to date, this history has not been meaningfully documented and such documentation can help inform policy initiatives to help nurture and develop the industry. These developments could help ensure that the importance and accomplishments of its achievements will not be forgotten or remain undeveloped. Indeed, it is argued here that Scotland suffers from historical amnesia with regard to the country’s past accomplishments and missed opportunities, but that public funding and further investment in talent development and retention can help establish the industry as a key player in society and economy. This article presents the results from an investigative literature collection and consultation with central figures in the Scottish animation industry, providing for the first time a clearer picture of the importance of animation in Scotland both for the country and for the industry worldwide. Discussing the initiatives and funding models of other European countries such as France, the article concludes by suggesting ways in which future policy initiatives could help assist Scotland’s animation industry grow and establish itself both for the future development of animation in Scotland and worldwide.
Single candidates: Ensuring a path to victory in local elections
Authors: Safa’at Muchamad Ali
Published: November 2021

This article analyzes the phenomenon of single candidates in Indonesia's 2020 local elections, where the number increased compared to the previous local elections. Although initially local elections with single candidates were not intended, by a ruling of the Constitutional Court a local election must still be carried out even if there is only a single pair of candidates. The number of single candidates has increased, as it becomes an easier and cheaper way to ensure victory, particularly for incumbents. This condition is strengthened by the culture of political parties that tend to provide support to candidates who possess a greater chance of winning in order to take control of the government and form political cartels. Although presently it has not been indicated that single candidates are a form of oligarchic rule and political dynasty, it may become an easy way to obtain political power.
Alcohol-induced Aggression
Authors: Atkinson Nigel S
Published: November 2021

Intraspecies aggression is commonly focused on securing reproductive resources such as food, territory, and mates, and it is often males who do the fighting. In humans, individual acts of overt physical aggression seem maladaptive and probably represent dysregulation of the pathways underlying aggression. Such acts are often associated with ethanol consumption. The Drosophila melanogaster model system, which has long been used to study how ethanol affects the nervous system and behavior, has also been used to study the molecular origins of aggression. In addition, ethanol-induced aggression has been demonstrated in flies. Recent publications show that ethanol stimulates Drosophila aggression in 2 ways: the odor of ethanol and the consumption of ethanol both make males more aggressive. These ethanol effects occur at concentrations that flies likely experience in the wild. A picture emerges of males arriving on their preferred reproductive site—fermenting plant matter—and being stimulated by ethanol to fight harder to secure the site for their own use. Fly fighting assays appear to be a suitable bioassay for studying how low doses of ethanol reshape neural signaling.
Whole-exome analysis of adolescents with low VWF and heavy menstrual bleeding identifies novel genetic associations
Authors: Sadler Brooke , Minard Charles G. , Haller Gabe , Gurnett Christina A. , O’Brien Sarah H. , Wheeler Allison , Jain Shilpa , Sharma Mutka , Zia Ayesha , Kulkarni Roshni , Mullins Eric , Ragni Margaret V. , Sidonio Robert , Dietrich Jennifer E. , Kouides Peter A. , Di Paola Jorge , Srivaths Lakshmi
Published: November 2021

Adolescents with low von Willebrand factor (VWF) levels and heavy menstrual bleeding (HMB) experience significant morbidity. There is a need to better characterize these patients genetically and improve our understanding of the pathophysiology of bleeding. We performed whole-exome sequencing on 86 postmenarchal patients diagnosed with low VWF levels (30-50 IU/dL) and HMB and compared them with 660 in-house controls. We compared the number of rare stop-gain/stop-loss and rare ClinVar “pathogenic” variants between cases and controls, as well as performed gene burden and gene-set burden analyses. We found an enrichment in cases of rare stop-gain/stop-loss variants in genes involved in bleeding disorders and an enrichment of rare ClinVar “pathogenic” variants in genes involved in anemias. The 2 most significant genes in the gene burden analysis, CFB and DNASE2, are associated with atypical hemolytic uremia and severe anemia, respectively. VWF also surpassed exome-wide significance in the gene burden analysis (P = 7.31 × 10−6). Gene-set burden analysis revealed an enrichment of rare nonsynonymous variants in cases in several hematologically relevant pathways. Further, common variants in FERMT2, a gene involved in the regulation of hemostasis and angiogenesis, surpassed genome-wide significance. We demonstrate that adolescents with HMB and low VWF have an excess of rare nonsynonymous and pathogenic variants in genes involved in bleeding disorders and anemia. Variants of variable penetrance in these genes may contribute to the spectrum of phenotypes observed in patients with HMB and could partially explain the bleeding phenotype. By identifying patients with HMB who possess these variants, we may be able to improve risk stratification and patient outcomes.
Biomarker signatures in cancer patients with and without venous thromboembolism events: a substudy of CASSINI
Authors: Khorana Alok A. , Barnard John , Wun Ted , Vijapurkar Ujjwala , Damaraju CV , Moore Kenneth Todd , Wildgoose Peter , McCrae Keith R.
Published: November 2021

Cancer is associated with an increased risk of venous thromboembolism (VTE). In the CASSINI study, ambulatory cancer patients with a Khorana risk score ≥2 had a reduced risk of VTE while receiving rivaroxaban. This analysis used blood samples from CASSINI to compare biomarker levels between patients with and without VTE. VTE occurred in 62 patients during the 6 months of CASSINI (cases), and they were matched by age, sex, cancer type, tumor stage, and Khorana score to 62 controls. Baseline blood samples were analyzed for 280 biomarkers, and biomarker distribution was compared using the Wilcoxon rank-sum test between groups defined by VTE occurrence and vital status. Sparse Bayesian regression modeling was used to select a joint panel of potential VTE biomarkers. Biomarkers with the largest differences in baseline distribution among cancer patients with and without VTE included decreases in stromal cell–derived factor-1 (SDF-1), thyroid-stimulating hormone (TSH), and monocyte chemotactic protein 4 and increases in growth hormone (GH) and interleukin-1 receptor type 1 (IL-1R1). Between survivors and those who died, significantly different biomarkers included ST2, IL-8, and C-reactive protein. Regression analyses also identified decreases in SDF-1 and TSH. Pathway analysis indicated enrichment of cytokine and chemokine activity with IL-1R1, SDF-1, and GH, which are the strongest predictors of VTE or death. Our analyses highlight the interactions between hemostatic and inflammatory processes and identify candidate biomarkers of cancer-associated VTE. Prospective studies will determine clinical relevance of these biomarkers. This trial was registered at www.ClinicalTrials.gov as #NCT02555878.
RETRACTED ARTICLE: Down-regulation of microRNA-342-5p or Up-regulation of Wnt3a Inhibits Angiogenesis and Maintains Atherosclerotic Plaque Stability in Atherosclerosis Mice
Authors: Sun Haixia , Feng Jinhua , Ma Yan , Cai Ding , Luo Yulu , Wang Qinggong , Li Fang , Zhang Mingyue , Hu Quanzhong
Published: November 2021

Evidence has demonstrated that microRNA-342-5p (miR-342-5p) is implicated in atherosclerosis (AS), but little is known regarding its intrinsic regulatory mechanisms. Here, we aimed to explore the effect of miR-342-5p targeting Wnt3a on formation of vulnerable plaques and angiogenesis of AS. ApoE−/− mice were fed with high-fat feed for 16 w to replicate the AS vulnerable plaque model. miR-342-5p and Wnt3a expression in aortic tissues of AS were detected. The target relationship between miR-342-5p and Wnt3a was verified. Moreover, ApoE−/− mice were injected with miR-342-5p antagomir and overexpression-Wnt3a vector to test their functions in serum lipid levels, inflammatory and oxidative stress-related cytokines, aortic plaque stability and angiogenesis in plaque of AS mice. miR-342-5p expression was enhanced and Wnt3a expression was degraded in aortic tissues of AS mice and miR-342-5p directly targeted Wnt3a. Up-regulating Wnt3a or down-regulating miR-342-5p reduced blood lipid content, inflammatory and oxidative stress levels, the vulnerability of aortic tissue plaque and inhibited angiogenesis in aortic plaque of AS mice. Functional studies show that depleting miR-342-5p can stabilize aortic tissue plaque and reduce angiogenesis in plaque in AS mice via restoring Wnt3a.
The use of perineural dexamethasone and transverse abdominal plane block for postoperative analgesia in cesarean section operations under spinal anesthesia: an observational study
Authors: Aga Abdisa , Abrar Meron , Ashebir Zewetir , Seifu Ashenafi , Zewdu Dereje , Teshome Diriba
Published: November 2021

Background

During transverses abdominal plane block (TAP) procedure to provide analgesia in cesarean section (CS) operation, the use of perineural dexamethasone as an additive agent may improve pain relief and may cause a prolonged block duration. This study aims to investigate whether perineural dexamethasone, when added to bupivacaine local anesthetic agent during a TAP block, may provide adequate pain relief without adverse events.

Methods

This is a prospective cohort study of fifty-eight patients undergoing elective CS with spinal anesthesia. We hypothesized to perform bilateral TAP block using perineural dexamethasone as an additive agent. The patients were randomly divided into two groups using a systematic random sampling method. While one group of patients received perineural dexamethasone of 8 mg additive agent together with bupivacaine 0.25% 40 ml (Group TAPD), the other group received only bupivacaine 0.25% 40 ml in TAP block (Group TAPA). The primary outcomes are the period for the first request of postoperative pain relief medication and the numerical rating scale (NRS) pain intensity scores at 2, 6, 12, and 24 h after surgery. The secondary outcomes are comparing the 24-h tramadol and diclofenac analgesic requirements and the incidences of side effects on postoperative day one. Ap-value of < 0.05 is statistically significant.

Results

The time to first analgesic request was 8.5 h (8.39–9.79) in the TAPD group versus 5.3 h (5.23–5.59) in the TAPA group, respectively. (p < 0.001) The median NRS scores were significantly reduced in the TAPD group compared to the TAPA group at 6, 12, and 24 h after surgery (p-values < 0.001). The total analgesics consumption over 24 h postoperatively was lower in Group TAPD compared to Group TAPA (p < 0.05).

Conclusion

An additive agent of perineural dexamethasone at a dose of 8 mg during bilateral TAP block for elective CS operation under spinal anesthesia provided better pain relief on postoperative day 1.
COVID-19 vaccine acceptance, hesitancy, and determinants among physicians in a university-based teaching hospital in Thailand
Authors: Sirikalyanpaiboon May , Ousirimaneechai Krittin , Phannajit Jeerath , Pitisuttithum Panyavee , Jantarabenjakul Watsamon , Chaiteerakij Roongruedee , Paitoonpong Leilani
Published: November 2021

Background

The COVID-19 vaccines provide renewed hope in the fight against the recent pandemic. To ensure widespread vaccination, it is crucial to analyze vaccine willingness and its determinants among physicians, key health care influencers. This study aimed to assess acceptance rate and identify factors associated with vaccine hesitancy among Thai physicians.

Methods

A cross-sectional online-based questionnaire was distributed to all physicians at King Chulalongkorn Memorial Hospital during March 31, 2021 to April 30, 2021 in order to assess their attitudes toward receiving the COVID-19 vaccine. Reasons for vaccine acceptance and refusal as well as predictors of vaccine hesitancy were analyzed by bivariate and multivariable analysis.

Results

A total of 705 complete responses were received with 95.6% (n = 675) of physicians expressing willingness to receive a COVID-19 vaccine. Only one of the 31 physicians (4.4%) who expressed a hesitancy or unwillingness to be vaccinated was a faculty member; the others were physicians-in-training. Approximately one-fifths of physicians surveyed were also not willing to recommend the vaccine to their family members (21.4%, n = 151) or patients (18.7%, n = 132). Using multivariable logistic regression, vaccine hesitancy was independently associated with preference for particular vaccines over the government allocated option, especially for mRNA vaccine (aOR 8.86; 95% CI 1.1–71.54; p = 0.041). Vaccine literacy showed an inverse relationship (aOR 0.34; 95% CI 0.13–0.9; p = 0.029) with vaccine hesitancy. Uncertainty of the vaccine efficacy (83.9%) and fear of adverse events (48.4%) were major concerns contributing to vaccine hesitancy.

Conclusion

This study revealed a high rate of physician willingness to take the COVID-19 vaccine especially among staffs; however, a significant proportion would not currently suggest vaccination to their families or patients. Restrictions on vaccine choice and vaccine illiteracy, together with concerns over adverse effects and uncertainty of efficacy, were associated with negative attitudes toward vaccination. To raise acceptance of the vaccination program, efforts should be made to balance individual preference for vaccine type in addition to increasing the availability of accurate data on safety and efficacy for each vaccine.
Correlation and agreement between superb micro-vascular imaging and contrast-enhanced ultrasound for assessing radiofrequency ablation treatment of thyroid nodules: a preliminary study
Authors: Lan Yu , Li Nan , Song Qing , Zhang Ming-bo , Luo Yu-kun , Zhang Yan
Published: November 2021

Background

To evaluate the correlation and agreement between superb micro-vascular imaging (SMI) mode and the contrast-enhanced ultrasound (CEUS) mode for the ablative completeness and the volumes of ablation lesions to determine the clinical application value of SMI in follow-up after radiofrequency ablation.

Methods

From April 2020 to June 2020, two radiologists used SMI and CEUS mode to measure the volume of the ablation lesion. We use intra-class correlation coefficient (ICC), scatter plots and Bland–Altman plots to evaluate the correlation and agreement of the two techniques. In addition, intra- and inter-observer reliability in volume measurement of ablation lesions with SMI mode was assessed.

Results

SMI mode and CEUS mode have good agreement in the evaluation of ablative completeness. The ICC was 0.876 and 0.928 of reader A and reader B between SMI mode and CEUS mode in terms of ablation lesions volume measurement. There was a strong correlation between the two modes in both reader A and reader B (rA = 0.808; rB = 0.882). The ICC was 0.836 for the inter-observer reliability of SMI technique. The scatter plot showed a good linear relation (r = 0.715). In the Bland–Altman plot, 4.35% (1/23) of the points was outside the 95% limits of agreement. The ICC was 0.965 for the intra-observer reliability of SMI technique, the scatter plot also showed a strong linear correlation (r = 0.965). In the Bland–Altman plot, 8.70% (2/23) of the points was outside the 95% limits of agreement.

Conclusions

SMI and CEUS have good agreement and correlation in the ablation volume measurement. SMI technology is expected to be applied as an alternative to CEUS in the clinical follow-up of ablation lesions.
Prognostication of neurologic outcome using gray-white-matter-ratio in comatose patients after cardiac arrest
Authors: Kirsch Konrad , Heymel Stefan , Günther Albrecht , Vahl Kathleen , Schmidt Thorsten , Michalski Dominik , Fritzenwanger Michael , Schulze Paul Christian , Pfeifer Rüdiger
Published: November 2021

Background

This study aimed to assess the prognostic value regarding neurologic outcome of CT neuroimaging based Gray-White-Matter-Ratio measurement in patients after resuscitation from cardiac arrest.

Methods

We retrospectively evaluated CT neuroimaging studies of 91 comatose patients resuscitated from cardiac arrest and 46 non-comatose controls. We tested the diagnostic performance of Gray-White-Matter-Ratio compared with established morphologic signs of hypoxic-ischaemic brain injury, e. g. loss of distinction between gray and white matter, and laboratory parameters, i. e. neuron-specific enolase, for the prediction of poor neurologic outcomes after resuscitated cardiac arrest. Primary endpoint was neurologic function assessed with cerebral performance category score 30 days after the index event.

Results

Gray-White-Matter-Ratio showed encouraging interobserver variability (ICC 0.670 [95% CI: 0.592–0.741] compared to assessment of established morphologic signs of hypoxic-ischaemic brain injury (Fleiss kappa 0.389 [95% CI: 0.320–0.457]) in CT neuroimaging studies. It correlated with cerebral performance category score with lower Gray-White-Matter-Ratios associated with unfavourable neurologic outcomes. A cut-off of 1.17 derived from the control population predicted unfavourable neurologic outcomes in adult survivors of cardiac arrest with 100% specificity, 50.3% sensitivity, 100% positive predictive value, and 39.3% negative predictive value. Gray-White-Matter-Ratio prognostic power depended on the time interval between circulatory arrest and CT imaging, with increasing sensitivity the later the image acquisition was executed.

Conclusions

A reduced Gray-White-Matter-Ratio is a highly specific prognostic marker of poor neurologic outcomes early after resuscitation from cardiac arrest. Sensitivity seems to be dependent on the time interval between circulatory arrest and image acquisition, with limited value within the first 12 h.
Survival impact of additional chemotherapy after adjuvant concurrent chemoradiation in patients with early cervical cancer who underwent radical hysterectomy
Authors: Kim Se Ik , Kim Jeong Yun , Wee Chan Woo , Lee Maria , Kim Hee Seung , Chung Hyun Hoon , Lee Taek Sang , Jeon Hye Won , Park Noh Hyun , Song Yong Sang , Kim Tae Hun
Published: November 2021

Background

To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH).

Methods

We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB–IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group).

Results

A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P < 0.001). The presence of pathologic risk factors was similar, except for lymph node metastasis, which was more frequent in the study group (72.1% vs. 46.0%; P = 0.001). In survival analyses, no differences in the disease-free survival (DFS; P = 0.539) and overall survival (OS; P = 0.121) were observed between the groups. Multivariate analyses adjusting for surgical approach and other factors revealed that additional chemotherapy was not associated with DFS (adjusted HR, 1.149; 95% CI, 0.552–2.391; P = 0.710) and OS (adjusted HR, 1.877; 95% CI, 0.621–5.673; P = 0.264). The recurrence patterns did not differ with additional chemotherapy. Consistent results were observed in a subset of high-risk patients (n = 139).

Conclusions

Additional chemotherapy after CCRT might not improve survival outcomes in patients with early cervical cancer who undergo RH.
The impact of disinvestment on alcohol and drug treatment delivery and outcomes: a systematic review
Authors: Roscoe Suzie , Boyd Jennifer , Buykx Penny , Gavens Lucy , Pryce Robert , Meier Petra
Published: November 2021

Background

In the context of substantial financial disinvestment from alcohol and drug treatment services in England, our aim was to review the existing evidence of how such disinvestments have impacted service delivery, uptake, outcomes and broader health and social implications.

Methods

We conducted a systematic review of quantitative and qualitative evidence (PROSPERO CRD42020187295), searching bibliographic databases and grey literature. Given that an initial scoping search highlighted a scarcity of evidence specific to substance use treatment, evidence of disinvestment from publicly funded sexual health and smoking cessation services was also included. Data on disinvestment, political contexts and impacts were extracted, analysed, and synthesized thematically.

Results

We found 20 eligible papers varying in design and quality including 10 related to alcohol and drugs services, and 10 to broader public health services. The literature provides evidence of sustained disinvestment from alcohol and drug treatment in several countries and a concurrent decline in the quantity and quality of treatment provision, but there was a lack of methodologically rigorous studies investigating the impact of disinvestment.

Conclusions

This review identified a paucity of scientific evidence quantifying the impacts of disinvestment on alcohol and drug treatment service delivery and outcomes. As the global economy faces new challenges, a stronger evidence base would enable informed policy decisions that consider the likely public health impacts of continued disinvestment.
Clinical application of robotic orthopedic surgery: a bibliometric study
Authors: Li Cheng , Wang Lei , Perka Carsten , Trampuz Andrej
Published: November 2021

Objectives

The present study aimed to evaluate the status and trends of robotic orthopedic surgery in a clinical setting using bibliometrics.

Methods

All relevant publications on the clinical use of robotic surgery in orthopedics were searched from the Web of Science database. Subsequently, data were analyzed using bibliometrics. Visualizing data of bibliographic coupling, co-citation, and co-occurrence analysis were performed using VOSviewer.

Results

In total, 224 clinical studies met the included standards between 2000 to 2019. Global publications presented an increasing annual trend, with the United States found to have the largest number of publications and robotic companies active in the field (n = 99), followed by China (n = 38), and the United Kingdom (n = 27). The institution with the most contributions was the Beijing Jishuitan Hospital in China (n = 15). The most productive scholars were Tian Wei and Mont Michael A, with 14 publications each. The top 30 most cited papers list showed 29 publications to be cited on more than 40 occassions. The journal with the most related and influential publications on robotic orthopedic surgery was the Journal of Arthroplasty. Fourteen types of robots were used, with the majority applied in knee and spinal surgery. MAKO was the most widely used robot in hip and knee surgery and Mazor in spinal surgery. Most studies were small sample populations of low-quality in this field. The top 20 most frequently used keywords were identified from 950 author keywords. Research on orthopedic robots were classified into two clusters by co-occurrence networks: spinal-related robotic surgery and joint-related robotic surgery.

Conclusions

The present bibliometric study summarizes the clinical research of orthopedic robots on study type, sample size, type of surgery, robot information, surgical site, most popular keywords, most cited papers, journals, authors, institutions, and countries. These findings may assist the scholars better understand the current status and research trends to guide future practice and directions.
Suture button versus syndesmotic screw in ankle fractures - evaluation with 3D imaging-based measurements
Authors: Hennings Robert , Souleiman Firas , Heilemann Martin , Hennings Mareike , Klengel Alexis , Osterhoff Georg , Hepp Pierre , Ahrberg Annette B.
Published: November 2021

Background

Inadequate reduction of syndesmotic injuries can result in disabling clinical outcomes. The aim of the study was to compare syndesmosis congruity after fixation by syndesmotic screws (SYS) or a suture button system (SBS) using three-dimensional (3D) computed imaging techniques.

Methods

In a retrospective single-center study, patients with unilateral stabilization of an ankle fracture with a syndesmotic injury and post-operative bilateral CT scans were analyzed using a recently established 3D method. The side-to-side differences were compared for tibio-fibular clear space (∆CS), translation angle (∆α), and vertical offset (∆z) among patients stabilized with syndesmotic screws or suture button system. Syndesmotic malreduction was defined for ∆CS > 2 mm and for |∆α| > 5°. ∆CS and ∆α were correlated with two-dimensional (2D) measurements.

Results

Eighteen patients stabilized with a syndesmosis screw and 29 stabilized with a suture button system were analyzed. After stabilization, both groups revealed mild diastasis (SYS: mean ∆CS 0.3 mm, SD 1.1 mm vs SBS: mean ∆CS 0.2 mm, SD 1.2 mm, p = 0.710). In addition, both stabilization methods showed slight dorsalization of the fibula (SYS: mean ∆α 0.5°, SD 4.6° vs SBS: mean ∆α 2.1°, SD 3.7°, p = 0.192). Also, restoration of the fibula-to-tibia length ratio also did not differ between the two groups (SYS: mean Δz of 0.5 mm, SD 2.4 mm vs SBS: mean Δz of 0 mm, SD 1.2 mm; p = 0.477). Malreduction according to high ∆α was most common (26% of cases), with equal distribution between the groups (p = 0.234). ∆CS and ∆α showed good correlation with 2D measurements (ρ = 0.567; ρ = 0.671).

Conclusion

This in vivo analysis of post-operative 3D models showed no differences in immediate post-operative alignment after syndesmotic screws or suture button system. Special attention should be paid to syndesmotic malreduction in the sagittal orientation of the fibula in relation to the tibia in radiological control of the syndesmotic congruity as well as intra-operatively.
Health management information system (HMIS) data quality and associated factors in Massaguet district, Chad
Authors: Moukénet Azoukalné , de Cola Monica Anna , Ward Charlotte , Beakgoubé Honoré , Baker Kevin , Donovan Laura , Laoukolé Jean , Richardson Sol
Published: November 2021

Background

Quality data from Health Management Information Systems (HMIS) are important for tracking the effectiveness of malaria control interventions. However, HMIS data in many resource-limited settings do not currently meet standards set by the World Health Organization (WHO). We aimed to assess HMIS data quality and associated factors in Chad.

Methods

A cross-sectional study was conducted in 14 health facilities in Massaguet district. Data on children under 15 years were obtained from the HMIS and from the external patient register covering the period January–December 2018. An additional questionnaire was administered to 16 health centre managers to collect data on contextual variables. Patient registry data were aggregated and compared with the HMIS database at district and health centre level. Completeness and accuracy indicators were calculated as per WHO guidelines. Multivariate logistic regressions were performed on the Verification Factor for attendance, suspected and confirmed malaria cases for three age groups (1 to < 12 months, 1 to < 5 years and 5 to < 15 years) to identify associations between health centre characteristics and data accuracy.

Results

Health centres achieved a high level of data completeness in HMIS. Malaria data were over-reported in HMIS for children aged under 15 years. There was an association between workload and higher odds of inaccuracy in reporting of attendance among children aged 1 to < 5 years (Odds ratio [OR]: 10.57, 95% CI 2.32–48.19) and 5– < 15 years (OR: 6.64, 95% CI 1.38–32.04). Similar association was found between workload and stock-outs in register books, and inaccuracy in reporting of malaria confirmed cases. Meanwhile, we found that presence of a health technician, and of dedicated staff for data management, were associated with lower inaccuracy in reporting of clinic attendance in children aged under five years.

Conclusion

Data completeness was high while the accuracy was low. Factors associated with data inaccuracy included high workload and the unavailability of required data collection tools. The results suggest that improvement in working conditions for clinic personnel may improve HMIS data quality. Upgrading from paper-based forms to a web-based HMIS may provide a solution for improving data accuracy and its utility for future evaluations of health interventions. Results from this study can inform the Ministry of Health and it partners on the precautions to be taken in the use of HMIS data and inform initiatives for improving its quality.
Improving random forest predictions in small datasets from two-phase sampling designs
Authors: Han Sunwoo , Williamson Brian D. , Fong Youyi
Published: November 2021

Background

While random forests are one of the most successful machine learning methods, it is necessary to optimize their performance for use with datasets resulting from a two-phase sampling design with a small number of cases—a common situation in biomedical studies, which often have rare outcomes and covariates whose measurement is resource-intensive.

Methods

Using an immunologic marker dataset from a phase III HIV vaccine efficacy trial, we seek to optimize random forest prediction performance using combinations of variable screening, class balancing, weighting, and hyperparameter tuning.

Results

Our experiments show that while class balancing helps improve random forest prediction performance when variable screening is not applied, class balancing has a negative impact on performance in the presence of variable screening. The impact of the weighting similarly depends on whether variable screening is applied. Hyperparameter tuning is ineffective in situations with small sample sizes. We further show that random forests under-perform generalized linear models for some subsets of markers, and prediction performance on this dataset can be improved by stacking random forests and generalized linear models trained on different subsets of predictors, and that the extent of improvement depends critically on the dissimilarities between candidate learner predictions.

Conclusion

In small datasets from two-phase sampling design, variable screening and inverse sampling probability weighting are important for achieving good prediction performance of random forests. In addition, stacking random forests and simple linear models can offer improvements over random forests.
Comparison of RetinaNet, SSD, and YOLO v3 for real-time pill identification
Authors: Tan Lu , Huangfu Tianran , Wu Liyao , Chen Wenying
Published: November 2021

Background

The correct identification of pills is very important to ensure the safe administration of drugs to patients. Here, we use three current mainstream object detection models, namely RetinaNet, Single Shot Multi-Box Detector (SSD), and You Only Look Once v3(YOLO v3), to identify pills and compare the associated performance.

Methods

In this paper, we introduce the basic principles of three object detection models. We trained each algorithm on a pill image dataset and analyzed the performance of the three models to determine the best pill recognition model. The models were then used to detect difficult samples and we compared the results.

Results

The mean average precision (MAP) of RetinaNet reached 82.89%, but the frames per second (FPS) is only one third of YOLO v3, which makes it difficult to achieve real-time performance. SSD does not perform as well on the indicators of MAP and FPS. Although the MAP of YOLO v3 is slightly lower than the others (80.69%), it has a significant advantage in terms of detection speed. YOLO v3 also performed better when tasked with hard sample detection, and therefore the model is more suitable for deployment in hospital equipment.

Conclusion

Our study reveals that object detection can be applied for real-time pill identification in a hospital pharmacy, and YOLO v3 exhibits an advantage in detection speed while maintaining a satisfactory MAP.
Integrated endotoxin-adsorption and antibacterial properties of platelet-membrane-coated copper silicate hollow microspheres for wound healing
Authors: Peng Zaihui , Zhang Xiaochun , Yuan Long , Li Ting , Chen Yajie , Tian Hao , Ma Dandan , Deng Jun , Qi Xiaowei , Yin Xuntao
Published: November 2021

Serious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared (CSO@PM). CSO@PM specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bacter icidal activity. Importantly, CSO@PM can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, CSO@PM stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, CSO@PM exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents.

Graphical Abstract
Severe ileum bleeding following adjuvant capecitabine chemotherapy for locally advanced colon cancer: a case report and review of the literature
Authors: Zou You , Liu Shuang , Wu Jianhong , Sun Zhen
Published: November 2021

Background

Capecitabine is a prodrug that is enzymatically converted to its active form, fluorouracil (also called 5-fluorouracil), which is commonly used as adjuvant chemotherapy in colorectal cancer patients. Severe gastrointestinal bleeding induced by capecitabine is rare. Here, we are presenting the first case report of surgery specimen assisted diagnosis of this uncommon condition.

Case presentation

A 63-year-old Chinese male with a history of colon adenocarcinoma and right hemicolectomy presented with severe lower gastrointestinal bleeding 2 days after finishing capecitabine administration during the first cycle of XELOX adjuvant chemotherapy. Because of the negative findings of active bleeding points by digital subtraction angiography (DSA) or colonoscopy, emergency laparotomy and partial enterectomy were performed. The bloody diarrhea had resolved after surgery and a terminal ileitis was diagnosed after pathological examination of the surgical specimen.

Conclusions

Terminal ileitis induced by capecitabine is likely to be underreported. It should be considered more often as a cause of severe gastrointestinal bleeding during or after treatment with capecitabine agents. Emergency surgery may achieve satisfactory outcomes if endoscopic hemostasis is ineffective.

Highlights of this case

1. Gastrointestinal bleeding following capecitabine treatment in colorectal cancer patients might be life-threatening.

2. Terminal ileitis induced by capecitabine should always be considered in the differential diagnosis of severe gastrointestinal bleeding.

3. Awareness of the risk factors such as deficiency of dihydropyrimidine dehydrogenase, advanced age, or right colectomy may aid in reducing capecitabine-related morbidity.

4. When severe bleeding occurs, emergency surgery may achieve satisfactory outcomes if medical and endoscopic interventions are ineffective.
Neoadjuvant camrelizumab plus chemotherapy in treating locally advanced esophageal squamous cell carcinoma patients: a pilot study
Authors: Yang Peng , Zhou Xiao , Yang Xuefeng , Wang Yuefeng , Sun Tao , Feng Shiying , Ma Xianyou
Published: November 2021

Background

Camrelizumab (a PD-1 inhibitor) has been used as a potential therapy in unresectable advanced esophageal squamous cell carcinoma (ESCC) along with adjuvant treatment in locally advanced ESCC, exhibiting an acceptable efficacy and safety profile. This pilot study was designed to further investigate the clinical value and tolerance of neoadjuvant camrelizumab plus chemotherapy in locally advanced ESCC.

Methods

A total of 16 patients with locally advanced ESCC were recruited. Patients received 2 cycles of neoadjuvant therapy including 2 doses of camrelizumab concurrent with 2 cycles of paclitaxel plus carboplatin followed by surgery 4 weeks afterward. Then, the treatment response after neoadjuvant therapy, R0 resection rate, tumor regression grade (TRG), and pathological complete remission (pCR) rate were measured. Besides, adverse events were documented. At last, progression-free survival (PFS) and overall survival (OS) were assessed.

Results

Generally, objective remission rate (ORR) was 81.3% whereas disease control rate (DCR) was 100% after neoadjuvant therapy. Concerning TRG grade, 31.3, 37.5, 18.8, and 12.5% patients reached TRG0, TRG1, TRG2, and TRG3, respectively. Then, pCR rate and R0 resection rate were 31.3 and 93.8%, respectively. Besides, mean PFS and OS were 18.3 months (95%CI: (16.2–20.5) months) and 19.2 months (95%CI: (17.7–20.7) months), respectively, with a 1-year PFS of 83% and OS of 90.9%. Adverse events included white blood cell decrease (37.5%), neutrophil decrease (31.3%), reactive cutaneous capillary endothelial proliferation (37.5%), and nausea or vomiting (25.0%), which were relatively mild and manageable.

Conclusion

Neoadjuvant camrelizumab plus chemotherapy exhibits good efficacy and acceptable tolerance in patients with locally advanced ESCC.
HIV-1 integrase binding to genomic RNA 5′-UTR induces local structural changes in vitro and in virio
Authors: Liu Shuohui , Koneru Pratibha C. , Li Wen , Pathirage Chathuri , Engelman Alan N. , Kvaratskhelia Mamuka , Musier-Forsyth Karin
Published: November 2021

Background

During HIV-1 maturation, Gag and Gag-Pol polyproteins are proteolytically cleaved and the capsid protein polymerizes to form the honeycomb capsid lattice. HIV-1 integrase (IN) binds the viral genomic RNA (gRNA) and impairment of IN-gRNA binding leads to mis-localization of the nucleocapsid protein (NC)-condensed viral ribonucleoprotein complex outside the capsid core. IN and NC were previously demonstrated to bind to the gRNA in an orthogonal manner in virio; however, the effect of IN binding alone or simultaneous binding of both proteins on gRNA structure is not yet well understood.

Results

Using crosslinking-coupled selective 2′-hydroxyl acylation analyzed by primer extension (XL-SHAPE), we characterized the interaction of IN and NC with the HIV-1 gRNA 5′-untranslated region (5′-UTR). NC preferentially bound to the packaging signal (Psi) and a UG-rich region in U5, irrespective of the presence of IN. IN alone also bound to Psi but pre-incubation with NC largely abolished this interaction. In contrast, IN specifically bound to and affected the nucleotide (nt) dynamics of the apical loop of the transactivation response element (TAR) and the polyA hairpin even in the presence of NC. SHAPE probing of the 5′-UTR RNA in virions produced from allosteric IN inhibitor (ALLINI)-treated cells revealed that while the global secondary structure of the 5′-UTR remained unaltered, the inhibitor treatment induced local reactivity differences, including changes in the apical loop of TAR that are consistent with the in vitro results.

Conclusions

Overall, the binding interactions of NC and IN with the 5′-UTR are largely orthogonal in vitro. This study, together with previous probing experiments, suggests that IN and NC binding in vitro and in virio lead to only local structural changes in the regions of the 5′-UTR probed here. Accordingly, disruption of IN-gRNA binding by ALLINI treatment results in local rather than global secondary structure changes of the 5′-UTR in eccentric virus particles.

Graphical Abstract
Amino acid sites related to the PB2 subunits of IDV affect polymerase activity
Authors: Wang Yutian , Sun Weiyang , Wang Zhenfei , Zhao Menglin , Zhang Xinghai , Kong Yunyi , Wang Xuefeng , Feng Na , Wang Tiecheng , Yan Feihu , Zhao Yongkun , Xia Xianzhu , Yang Songtao , Gao Yuwei
Published: November 2021

Background

In 2011, a new influenza virus, named Influenza D Virus (IDV), was isolated from pigs, and then cattle, presenting influenza-like symptoms. IDV is one of the causative agents of Bovine Respiratory Disease (BRD), which causes high morbidity and mortality in feedlot cattle worldwide. To date, the molecular mechanisms of IDV pathogenicity are unknown. Recent IDV outbreaks in cattle, along with serological and genetic evidence of IDV infection in humans, have raised concerns regarding the zoonotic potential of this virus. Influenza virus polymerase is a determining factor of viral pathogenicity to mammals.

Methods

Here we take a prospective approach to this question by creating a random mutation library about PB2 subunit of the IDV viral polymerase to test which amino acid point mutations will increase viral polymerase activity, leading to increased pathogenicity of the virus.

Results

Our work shows some exact sites that could affect polymerase activities in influenza D viruses. For example, two single-site mutations, PB2-D533S and PB2-G603Y, can independently increase polymerase activity. The PB2-D533S mutation alone can increase the polymerase activity by 9.92 times, while the PB2-G603Y mutation increments the activity by 8.22 times.

Conclusion

Taken together, our findings provide important insight into IDV replication fitness mediated by the PB2 protein, increasing our understanding of IDV replication and pathogenicity and facilitating future studies.
The role of family history of Cancer in Oral Cavity Cancer
Authors: Fantozzi Paolo Junior , Bavarian Roxanne , Tamayo Ibon , Bind Marie-Abele , Woo Sook-Bin , Villa Alessandro
Published: November 2021

Objectives

Oral and oropharyngeal squamous cell carcinoma (SCC) is the 10th most common cancer in the United States (8th in males, 13th in females), with an estimated 54,010 new cases expected in 2021, and is primarily associated with smoked tobacco, heavy alcohol consumption, areca nut use and persistent high-risk human papillomavirus (HPV). Family history of cancer (FHC) and family history of head and neck cancer (FHHNC) have been reported to play an important role in the development of OSCC. We aimed to investigate the role of FHC, FHHNC and personal history of cancer in first/second degree-relatives as co-risk factors for oral cancer.

Methods

This was a retrospective study of patients diagnosed with OSCC at the Division of Oral Medicine and Dentistry at Brigham and Women’s Hospital and at the Division of Head and Neck Oncology at Dana Farber Cancer Institute. Conditional logistic regressions were performed to examine whether OSCC was associated with FHC and FHHNC of FDRs and SDRs, personal history of cancer and secondary risk factors.

Results

Overall, we did not find an association between FHC, FHHNC and OSCC risk, whereas patients with a cancer history in one of their siblings were 1.6-times more likely to present with an OSCC. When secondary risk factors were considered, patients with a history of oral leukoplakia and dysplasia had a 16-times higher risk of having an OSCC.

Conclusions

Our study confirmed that a previous history of oral leukoplakia or dysplasia was an independent risk factor for OSCC. A positive family history of cancer in one or more siblings may be an additional risk factor for OSCC.
Analysis of clinical patient-specific pre-treatment quality assurance with the new helical tomotherapy platform, following the AAPM TG-218 report
Authors: Fusella Marco , Cavinato Samuele , Germani Alessandra , Paiusco Marta , Pivato Nicola , Rossato Marco Andrea , Scott Anthony , Scaggion Alessandro
Published: November 2021

Purpose

This study presents patient-specific quality assurance (QA) results from the first 395 clinical cases for the new helical TomoTherapy® platform (Radixact) coupled with dedicated Precision TPS.

Methods

The passing rate of the Gamma Index (GP%) of 395 helical QA of patient-specific tomotherapy, acquired with ArcCHECK, is presented, analysed and correlated to various parameters of the plan. Following TG-218 recommendations, the clinic specific action limit (ALcs) and tolerance limit (TLcs) were calculated for our clinic and monitored during the analysed period.

Results

The mean values ​​(± 1 standard deviation) of GP% (3%/2 mm) (both global and local normalization) are: 97.6% and 90.9%, respectively. The proposed ALcs and TLcs, after a period of two years’ process monitoring are 89.4% and 91.1% respectively.

Conclusions

The phantom measurements closely match the planned dose distributions, demonstrating that the calculation accuracy of the new Precision TPS and the delivery accuracy of the Radixact unit are adequate, with respect to international guidelines and reports. Furthermore, a first correlation with the planning parameters was made. Action and tolerance limits have been set for the new Radixact Linac.