bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of implant surgical guides fabricated using computer numerical control milling for edentulous jaws: a pilot clinical trial
Authors: Chai Jinyou , Liu Xiaoqian , Schweyen Ramona , Setz Jürgen , Pan Shaoxia , Liu Jianzhang , Zhou Yongsheng
Published: October 2020

Background

To evaluate the accuracy of a computer numerical control (CNC) milled surgical guide for implant placement in edentulous jaws.

Methods

Edentulous patients seeking implants treatment were recruited in this prospective cohort study. Radiographic guides with diagnostic templates were fabricated from wax-up dentures. Patients took cone-beam computed tomography (CBCT) wearing the radiopaque radiographic guides. Implant positions were virtually designed in the planning software based on the CBCT data, and the radiographic templates were converted into surgical guides using CNC milling technique. Forty-four implants were placed into 12 edentulous jaws following guided implant surgery protocol. Post-surgery CBCT scans were made for each jaw, and the deviations between the planned and actual implant positions were measured. Deviation of implant position was compared between maxilla and mandible, and between cases with and without anchor pins using independent t-test.

Results

Nine patients (3 males and 6 females) with 12 edentulous jaws were recruited. The mean age of patients was 59.2 ± 13.9 years old. All 44 implants was placed without complication and survived, the mean three dimensional linear deviation of implant position between virtual planning and actual placement was 1.53 ± 0.48 mm at the implant neck and 1.58 ± 0.49 mm at the apex. The angular deviation was 3.96 ± 3.05 degrees. No significant difference was found in the deviation of implant position between maxilla and mandible (P = 0.28 at neck, 0.08 at apex), nor between cases with and without anchor pins (P = 0.87 at neck, 0.06 at apex).

Conclusions

The guides fabricated using the CNC milling technique provided comparable accuracy as those fabricated by Stereolithography. The displacement of the guides on edentulous arch might be the main contributing factor of deviation.

Trial registration: Chinese Clinical Trial Registry, ChiCTR-ONC-17014159 (July 26, 2017).
Melatonin to prevent delirium in patients with advanced cancer: a double blind, parallel, randomized, controlled, feasibility trial
Authors: Lawlor Peter G. , McNamara-Kilian Marie T. , MacDonald Alistair R. , Momoli Franco , Tierney Sallyanne , Lacaze-Masmonteil Nathalie , Dasgupta Monidipa , Agar Meera , Pereira Jose L. , Currow David C. , Bush Shirley H.
Published: October 2020

Background

Delirium is highly problematic in palliative care (PC). Preliminary data indicate a potential role for melatonin to prevent delirium, but no randomized controlled trials (RCTs) are reported in PC.

Methods

Patients aged ≥18 years, with advanced cancer, admitted to an inpatient Palliative Care Unit (PCU), having a Palliative Performance Scale rating ≥ 30%, and for whom consent was obtained, were included in the study. Patients with delirium on admission were excluded. The main study objectives were to assess the feasibility issues of conducting a double-blind RCT of exogenous melatonin to prevent delirium in PC: recruitment, retention, procedural acceptability, appropriateness of outcome measures, and preliminary efficacy and safety data. Study participants were randomized in a double-blind, parallel designed study to receive daily melatonin 3 mg or placebo orally at 21:00 over 28 days or less if incident delirium, death, discharge or withdrawal occurred earlier. Delirium was diagnosed using the Confusion Assessment Method. Efficacy endpoints in the melatonin and placebo groups were compared using time-to-event analysis: days from study entry to onset of incident delirium.

Results

Over 16 months, 60/616 (9.7%; 95% CI: 7.5–12.4%) screened subjects were enrolled. The respective melatonin (n = 30) vs placebo (n = 30) outcomes were: incident delirium in 11/30 (36.7%; 95%CI: 19.9–56.1%) vs 10/30 (33%; 95% CI: 17.3–52.8%); early discharge (6 vs 5); withdrawal (6 vs 3); death (0 vs 1); and 7 (23%) vs 11 (37%) reached the 28-day end point. The 25th percentile time-to-event were 9 and 18 days (log rank, χ2 = 0.62, p = 0.43) in melatonin and placebo groups, respectively. No serious trial medication-related adverse effects occurred and the core study procedures were acceptable. Compared to those who remained delirium-free during their study participation, those who developed delirium (n = 21) had poorer functional (p = 0.036) and cognitive performance (p = 0.013), and in particular, poorer attentional capacity (p = 0.003) at study entry.

Conclusions

A larger double-blind RCT is feasible, but both subject accrual and withdrawal rates signal a need for multisite collaboration. The apparent trend for shorter time to incident delirium in the melatonin group bodes for careful monitoring in a larger trial.

Trial registration

Registered on July 21st 2014 with ClinicalTrials.gov: NCT02200172.
Adoption rates of electronic health records in Turkish Hospitals and the relation with hospital sizes
Authors: Kose Ilker , Rayner John , Birinci Suayip , Ulgu Mustafa Mahir , Yilmaz Ismayil , Guner Seyma ,   HIMSS Analytics Team, Mahir Suna Kirdag , Aycil Kubra , Elmas Beytiye O. , Volkan Esra , Altinbas Zeynep , Gencyurek Gizem ,   MoH Team, Zehir Esra , Gundogdu Berrin , Ozcan Mert , Vardar Ceyhan , Altinli Behcet , Hasancebi Jale Sungur
Published: October 2020

Background

Nation-wide adoption of electronic health records (EHRs) in hospitals has become a Turkish policy priority in recognition of their benefits in maintaining the overall quality of clinical care. The electronic medical record maturity model (EMRAM) is a widely used survey tool developed by the Healthcare Information and Management Systems Society (HIMSS) to measure the rate of adoption of EHR functions in a hospital or a secondary care setting. Turkey completed many standardizations and infrastructural improvement initiatives in the health information technology (IT) domain during the first phase of the Health Transformation Program between 2003 and 2017. Like the United States of America (USA), the Turkish Ministry of Health (MoH) applied a bottom-up approach to adopting EHRs in state hospitals. This study aims to measure adoption rates and levels of EHR use in state hospitals in Turkey and investigate any relationship between adoption and use and hospital size.

Methods

EMRAM surveys were completed by 600 (68.9%) state hospitals in Turkey between 2014 and 2017. The availability and prevalence of medical information systems and EHR functions and their use were measured. The association between hospital size and the availability/prevalence of EHR functions was also calculated.

Results

We found that 63.1% of all hospitals in Turkey have at least basic EHR functions, and 36% have comprehensive EHR functions, which compares favourably to the results of Korean hospitals in 2017, but unfavorably to the results of US hospitals in 2015 and 2017. Our findings suggest that smaller hospitals are better at adopting certain EHR functions than larger hospitals.

Conclusion

Measuring the overall adoption rates of EHR functions is an emerging approach and a beneficial tool for the strategic management of countries. This study is the first one covering all state hospitals in a country using EMRAM. The bottom-up approach to adopting EHR in state hospitals that was successful in the USA has also been found to be successful in Turkey. The results are used by the Turkish MoH to disseminate the nation-wide benefits of EHR functions.
TNFPred: identifying tumor necrosis factors using hybrid features based on word embeddings
Authors: Nguyen Trinh-Trung-Duong , Le Nguyen-Quoc-Khanh , Ho Quang-Thai , Phan Dinh-Van , Ou Yu-Yen
Published: October 2020

Background

Cytokines are a class of small proteins that act as chemical messengers and play a significant role in essential cellular processes including immunity regulation, hematopoiesis, and inflammation. As one important family of cytokines, tumor necrosis factors have association with the regulation of a various biological processes such as proliferation and differentiation of cells, apoptosis, lipid metabolism, and coagulation. The implication of these cytokines can also be seen in various diseases such as insulin resistance, autoimmune diseases, and cancer. Considering the interdependence between this kind of cytokine and others, classifying tumor necrosis factors from other cytokines is a challenge for biological scientists.

Methods

In this research, we employed a word embedding technique to create hybrid features which was proved to efficiently identify tumor necrosis factors given cytokine sequences. We segmented each protein sequence into protein words and created corresponding word embedding for each word. Then, word embedding-based vector for each sequence was created and input into machine learning classification models. When extracting feature sets, we not only diversified segmentation sizes of protein sequence but also conducted different combinations among split grams to find the best features which generated the optimal prediction. Furthermore, our methodology follows a well-defined procedure to build a reliable classification tool.

Results

With our proposed hybrid features, prediction models obtain more promising performance compared to seven prominent sequenced-based feature kinds. Results from 10 independent runs on the surveyed dataset show that on an average, our optimal models obtain an area under the curve of 0.984 and 0.998 on 5-fold cross-validation and independent test, respectively.

Conclusions

These results show that biologists can use our model to identify tumor necrosis factors from other cytokines efficiently. Moreover, this study proves that natural language processing techniques can be applied reasonably to help biologists solve bioinformatics problems efficiently.
Pan-cancer analysis of differential DNA methylation patterns
Authors: Shi Mai , Tsui Stephen Kwok-Wing , Wu Hao , Wei Yingying
Published: October 2020

Background

DNA methylation is a key epigenetic regulator contributing to cancer development. To understand the role of DNA methylation in tumorigenesis, it is important to investigate and compare differential methylation (DM) patterns between normal and case samples across different cancer types. However, current pan-cancer analyses call DM separately for each cancer, which suffers from lower statistical power and fails to provide a comprehensive view for patterns across cancers.

Methods

In this work, we propose a rigorous statistical model, PanDM, to jointly characterize DM patterns across diverse cancer types. PanDM uses the hidden correlations in the combined dataset to improve statistical power through joint modeling. PanDM takes summary statistics from separate analyses as input and performs methylation site clustering, differential methylation detection, and pan-cancer pattern discovery. We demonstrate the favorable performance of PanDM using simulation data. We apply our model to 12 cancer methylome data collected from The Cancer Genome Atlas (TCGA) project. We further conduct ontology- and pathway-enrichment analyses to gain new biological insights into the pan-cancer DM patterns learned by PanDM.

Results

PanDM outperforms two types of separate analyses in the power of DM calling in the simulation study. Application of PanDM to TCGA data reveals 37 pan-cancer DM patterns in the 12 cancer methylomes, including both common and cancer-type-specific patterns. These 37 patterns are in turn used to group cancer types. Functional ontology and biological pathways enriched in the non-common patterns not only underpin the cancer-type-specific etiology and pathogenesis but also unveil the common environmental risk factors shared by multiple cancer types. Moreover, we also identify PanDM-specific DM CpG sites that the common strategy fails to detect.

Conclusions

PanDM is a powerful tool that provides a systematic way to investigate aberrant methylation patterns across multiple cancer types. Results from real data analyses suggest a novel angle for us to understand the common and specific DM patterns in different cancers. Moreover, as PanDM works on the summary statistics for each cancer type, the same framework can in principle be applied to pan-cancer analyses of other functional genomic profiles. We implement PanDM as an R package, which is freely available at http://www.sta.cuhk.edu.hk/YWei/PanDM.html.
Risk factors for the critical illness in SARS-CoV-2 infection: a multicenter retrospective cohort study
Authors: Cheng Sijing , Wu Dingfeng , Li Jie , Zou Yifeng , Wan Yunle , Shen Lihan , Zhu Lixin , Shi Mang , Hou Linlin , Xu Tao , Jiao Na , Li Yichen , Huang Yibo , Tang Zhipeng , Xu Mingwei , Jiang Shusong , Li Maokun , Yan Guangjun , Lan Ping , Zhu Ruixin
Published: October 2020

Background

Prior studies reported that 5 ~ 32% COVID-19 patients were critically ill, a situation that poses great challenge for the management of the patients and ICU resources. We aim to identify independent risk factors to serve as prediction markers for critical illness of SARS-CoV-2 infection.

Methods

Fifty-two critical and 200 non-critical SARS-CoV-2 nucleic acid positive patients hospitalized in 15 hospitals outside Wuhan from January 19 to March 6, 2020 were enrolled in this study. Multivariable logistic regression and LASSO logistic regression were performed to identify independent risk factors for critical illness.

Results

Age older than 60 years, dyspnea, respiratory rate > 24 breaths per min, leukocytosis > 9.5 × 109/L, neutrophilia > 6.3 × 109/L, lymphopenia < 1.1 × 109/L, neutrophil-to-lymphocyte ratio > 3.53, fibrinogen > 4 g/L, d-dimer > 0.55 μg/mL, blood urea nitrogen > 7.1 mM, elevated aspartate transaminase, elevated alanine aminotransferase, total bilirubin > 21 μM, and Sequential Organ Failure Assessment (SOFA) score ≥ 2 were identified as risk factors for critical illness. LASSO logistic regression identified the best combination of risk factors as SOFA score, age, dyspnea, and leukocytosis. The Area Under the Receiver-Operator Curve values for the risk factors in predicting critical illness were 0.921 for SOFA score, 0.776 for age, 0.764 for dyspnea, 0.658 for leukocytosis, and 0.960 for the combination of the four risk factors.

Conclusions

Our findings advocate the use of risk factors SOFA score ≥ 2, age > 60, dyspnea and leukocytosis > 9.5 × 109/L on admission, alone or in combination, to determine the optimal management of the patients and health care resources.
Correction to: The intake assessment of diverse dietary patterns on childhood hypertension: alleviating the blood pressure and lipidemic factors with low-sodium seafood rich in omega-3 fatty acids
Authors: Izadi Anahita , Khedmat Leila , Tavakolizadeh Reza , Mojtahedi Sayed Yousef
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Designed proteinoid polymers and nanoparticles encapsulating risperidone for enhanced antipsychotic activity
Authors: Lugasi L. , Grinberg I. , Rudnick-Glick S. , Okun E. , Einat H. , Margel S.
Published: October 2020

Background

Nanoparticles (NPs) incorporating drug formulations can be used to facilitate passage through biological barriers including the blood–brain barrier (BBB) and increase drug delivery and bioavailability. Hence, NP-based administration may enhance the efficiency of current antipsychotics. Encapsulation within NPs can resolve aqueous solubility problems that not only reduce permeability through the BBB but also affect targeting. The present study describes a new drug delivery system based on proteinoid NPs to explore the possibility of improving drug efficacy. Risperidone (RSP) is a commonly used atypical antipsychotic medication, and was therefore selected for encapsulation by proteinoid NPs.

Results

Proteinoid polymers with high molecular weight and low polydispersity were synthesized froml-amino acids and poly-l-lactic acid (PLLA) by thermal step-growth polymerization mechanism. RSP-loaded proteinoid NPs were then prepared using a self-assembly process in the presence of RSP, followed by PEGylation. The optimal PEGylated RSP-loaded NPs were characterized in terms of diameter and size distribution, drug loading, ζ-potential, cytotoxicity, biodistribution, and psychopharmacological effects. The findings indicate significantly higher antipsychotic activity of drug-loaded proteinoid NPs compared to free RSP.

Conclusions

Proteinoid NPs enhance RSP delivery and may potentially increase drug efficiency by reducing dosage and side effects.
Who chooses to enroll in a new national gambling self-exclusion system? A general population survey in Sweden
Authors: Håkansson A. , Henzel V.
Published: October 2020

Background

Self-exclusion from gambling is a common method for prevention and harm reduction in hazardous gambling. However, few national self-exclusion programs, involving a large number of gambling operators and activities in a country, have been assessed scientifically. This study aimed to examine characteristics of individuals who chose to enroll in a recently introduced (January, 2019) national self-exclusion system in Sweden.

Methods

Adults and adolescents (from age 16 and above) were addressed with an online survey sent to members of the web panel of a market survey company (1940 respondents). Psychological distress, previous history of addictive disorders, sociodemographic data, and recent history of gambling patterns and over-indebtedness were recorded. Logistic regression tested associations with self-exclusion, with unadjusted analyses conducted for the sub-group of moderate-risk or problem gamblers.

Results

Four percent reported having self-excluded using the new national self-exclusion system. In logistic regression, self-exclusion was significantly associated with younger age (OR 0.65 [0.54–0.79] for increasing age groups) and with the highest level of problem gambling (OR 2.84 [1.10–7.37]). In moderate-risk or problem gamblers, in unadjusted analyses, younger age (p < 0.05) and psychological distress (p = 0.02) were associated with self-exclusion. In none- or low-risk gamblers, 3% had self-excluded, which was significantly associated with younger age (p < 0.001) and self-reported over-indebtedness (p < 0.001).

Conclusions

In a national, multi-venue online and land-based self-exclusion system, aiming to reduce the harm of problem gambling, self-exclusion is expectedly more common in problem gamblers, but also occurs among people without recent gambling problems. Further efforts may be needed in order to increase gambling self-exclusion in problem gamblers, and research in reasons for self-excluding, even in non-problem gamblers, is needed.
Assessing the effect of child’s gender on their father–mother perception of the PedsQL™ 4.0 questionnaire: an iterative hybrid ordinal logistic regression/item response theory approach with Monte Carlo simulation
Authors: Doostfatemeh Marziyeh , Ayatollahi Seyyed Mohammad Taghi , Jafari Peyman
Published: October 2020

Background

This study aimed at investigating the possible confounding effect of children’s gender on the parents’ dyads perception of their child HRQoL at both item and scale levels of PedsQLTM4.0 questionnaire.

Methods

The PedsQL™ 4.0 Generic Core Scales were completed by 573 children and their father-and-mother dyads. An iterative hybrid ordinal logistic regression/item response theory model with Monte Carlo simulation was used to detect differential item functioning (DIF) invariance across mothers/fathers and daughter/sons.

Results

Assessing DIF across mother–daughter, father–daughter, mother–son, and father–son dyads revealed that although parents and their children perceived the meaning of some items of PedsQLTM4.0 instrument differently, the pattern of fathers’ and mothers’ report does not vary much across daughters and sons.

Conclusion

In the Persian version of PedsQLTM4.0, the child’s gender is not a confounding factor in the mothers’ and fathers’ report with respect to their daughters’ and sons’ HRQoL. Hence, paternal proxy-reports can be included in studies, along with maternal proxy-reports, and the reports can be combined short of concerning children gender, when looking at parent–child agreement.
Kinase shRNA screening reveals that TAOK3 enhances microtubule-targeted drug resistance of breast cancer cells via the NF-κB signaling pathway
Authors: Lai Tsung-Ching , Fang Chih-Yeu , Jan Yi-Hua , Hsieh Hsiao-Ling , Yang Yi-Fang , Liu Chun-Yu , Chang Peter Mu-Hsin , Hsiao Michael
Published: October 2020

Background

Chemotherapy is currently one of the most effective treatments for advanced breast cancer. Anti-microtubule agents, including taxanes, eribulin and vinca-alkaloids are one of the primary major anti-breast cancer chemotherapies; however, chemoresistance remains a problem that is difficult to solve. We aimed to discover novel candidate protein targets to combat chemoresistance in breast cancer.

Methods

A lentiviral shRNA-based high-throughput screening platform was designed and developed to screen the global kinome to find new therapeutic targets in paclitaxel-resistant breast cancer cells. The phenotypes were confirmed with alternative expression in vitro and in vivo. Molecular mechanisms were investigated using global phosphoprotein arrays and expression microarrays. Global microarray analysis was performed to determine TAOK3 and genes that induced paclitaxel resistance.

Results

A serine/threonine kinase gene, TAOK3, was identified from 724 screened kinase genes. TAOK3 shRNA exhibited the most significant reduction in IC50 values in response to paclitaxel treatment. Ectopic downregulation of TAOK3 resulted in paclitaxel-resistant breast cancer cells sensitize to paclitaxel treatment in vitro and in vivo. The expression of TAOK3 also was correlated to sensitivity to two other anti-microtubule drugs, eribulin and vinorelbine. Our TAOK3-modulated microarray analysis indicated that NF-κB signaling played a major upstream regulation role. TAOK3 inhibitor, CP43, and shRNA of NF-κB both reduced the paclitaxel resistance in TAOK3 overexpressed cells. In clinical microarray databases, high TAOK3 expressed breast cancer patients had poorer prognoses after adjuvant chemotherapy.

Conclusions

Here we identified TAOK3 overexpression increased anti-microtubule drug resistance through upregulation of NF-κB signaling, which reduced cell death in breast cancer. Therefore, inhibition of the interaction between TAOK3 and NF-κB signaling may have therapeutic implications for breast cancer patients treated with anti-microtubule drugs.
Quantitative sensory phenotyping in chronic neuropathic pain patients treated with unilateral L4-dorsal root ganglion stimulation
Authors: Kinfe Thomas , von Willebrand Nico , Stadlbauer Andreas , Buchfelder Michael , Yearwood Thomas L. , Muhammad Sajjad , Chaudhry Shafqat R. , Gravius Sascha , Randau Thomas , Winder Klemens , Maihöfner Christian , Gravius Nadine , Magerl Walter
Published: October 2020

Background

In a previous study, we reported that selective dorsal root ganglion stimulation (DRGSTIM) at DRG level L4 promoted a favorable outcome for complex regional pain syndrome (CRPS) patients along with DRGSTIM-related changes of inflammatory biomarkers in blood and saliva. The impact on somatosensation is largely unknown. Herein, we assessed the quantitative sensory profile to quantify L4-DRGSTIM effects in CRPS patients.

Methods

Twelve refractory CRPS patients (4 female; 8 male; mean age 69 ± 9 years) received standardized quantitative sensory testing (QST) protocol at baseline and after 3 months of unilateral L4-DRGSTIM assessing nociceptive and non-nociceptive thermal and mechanical sensitivity of the knee affected by CRPS and the contralateral non-painful knee area.

Results

At baseline, CRPS subjects showed significantly increased thresholds for warmth, tactile and vibration detection (WDT, MDT and VDT) and exaggerated pain summation (WUR). After 3 months of unilateral L4-DRGSTIM all pain parameters exhibited trends towards normalization of sensitivity accumulating to a significant overall normalization for pain sensitivity (effect size: 0.91, p < 0.01), while with the one exception of WDT all non-nociceptive QST parameters remained unchanged. Overall change of non-nociceptive detection was negligible (effect size: 0.25, p > 0.40). Notably, reduction of pain summation (WUR) correlated significantly with pain reduction after 3 months of L4-DRGSTIM.

Conclusions

Selective L4-DRGSTIM lowered ongoing pain in CRPS patients and evoked significant normalization in the pain domain of the somatosensory profile. Thermoreception and mechanoreception remained unchanged. However, larger randomized, sham-controlled trials are highly warranted to shed more light on effects and mechanisms of dorsal root ganglion stimulation on quantitative sensory characteristics.

The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267).

https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011267
Hypoxia directed migration of human naïve monocytes is associated with an attenuation of cytokine release: indications for a key role of CCL26
Authors: Hummitzsch Lars , Berndt Rouven , Kott Matthias , Rusch Rene , Faendrich Fred , Gruenewald Matthias , Steinfath Markus , Albrecht Martin , Zitta Karina
Published: October 2020

Background

Numerous tissue-derived factors have been postulated to be involved in tissue migration of circulating monocytes. The aim of this study was to evaluate whether a defined hypoxic gradient can induce directed migration of naïve human monocytes and to identify responsible autocrine/paracrine factors.

Methods

Monocytes were isolated from peripheral blood mononuclear cells, transferred into chemotaxis chambers and subjected to a defined oxygen gradient with or without the addition of CCL26. Cell migration was recorded and secretome analyses were performed.

Results

Cell migration recordings revealed directed migration of monocytes towards the source of hypoxia. Analysis of the monocyte secretome demonstrated a reduced secretion of 70% (19/27) of the analyzed cytokines under hypoxic conditions. The most down-regulated factors were CCL26 (− 99%), CCL1 (− 95%), CX3CL1 (− 95%), CCL17 (− 85%) and XCL1 (− 83%). Administration of recombinant CCL26 abolished the hypoxia-induced directed migration of human monocytes, while the addition of CCL26 under normoxic conditions resulted in a repulsion of monocytes from the source of CCL26.

Conclusions

Hypoxia induces directed migration of human monocytes in-vitro. Autocrine/paracrine released CCL26 is involved in the hypoxia-mediated monocyte migration and may represent a target molecule for the modulation of monocyte migration in-vivo.
Role of macrophage-mediated Toll-like receptor 4–interleukin-1R signaling in ectopic tongue pain associated with tooth pulp inflammation
Authors: Kanno Kohei , Shimizu Kohei , Shinoda Masamichi , Hayashi Makoto , Takeichi Osamu , Iwata Koichi
Published: October 2020

Background

The existence of referred pain and ectopic paresthesia caused by tooth pulp inflammation may make definitive diagnosis difficult and cause misdiagnosis or mistreatment; thus, elucidation of that molecular mechanism is urgent. In the present study, we investigated the mechanisms underlying ectopic pain, especially tongue hyperalgesia, after tooth pulp inflammation.

Methods

A rat model with mandibular first molar tooth pulp exposure was employed. Tooth pulp exposure-induced heat and mechanical-evoked tongue hypersensitivity was measured, and immunohistochemical staining for Iba1, a marker of active macrophages, IL-1β, IL-1 type I receptor (IL-1RΙ), and toll-like receptor 4 in the trigeminal ganglion was performed. In addition, we investigated the effects of injections of liposomal clodronate Clophosome-A (LCCA), a selective macrophage depletion agent, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS, a toll-like receptor 4 antagonist), IL-1β, or heat shock protein 70 (Hsp70, a selective agonist of toll-like receptor 4), to examine changes in tongue hypersensitivity and in the regulation of IL-1RΙ, toll-like receptor 4, and transient receptor potential vanilloid 1 (TRPV1) biosynthesis.

Results

At day 1 after tooth pulp exposure, obvious tooth pulp inflammation was observed. Tooth pulp exposure-induced heat and mechanical tongue hypersensitivity was observed from days 1 to 3 after tooth pulp exposure. The production of IL-1β in activated macrophages and toll-like receptor 4 and IL-1RΙ expression were significantly increased in trigeminal ganglion neurons innervating the tongue following tooth pulp exposure. Intra-trigeminal ganglion injection of LCCA significantly suppressed tongue hypersensitivity; however, toll-like receptor 4 and IL-1RΙ expression in trigeminal ganglion neurons innervating the tongue was not significantly altered. Intra-trigeminal ganglion injection of LPS-RS significantly suppressed tongue hypersensitivity and reduced IL-1RΙ expression in the trigeminal ganglion neurons innervating the tongue following tooth pulp exposure. Intra-trigeminal ganglion injection of recombinant Hsp70 significantly promoted tongue hypersensitivity and increased IL-1RI expression in trigeminal ganglion neurons innervating the tongue in naive rats. Furthermore, intra-trigeminal ganglion injection of recombinant IL-1β led to tongue hypersensitivity and enhanced TRPV1 expression in trigeminal ganglion neurons innervating the tongue in naive rats.

Conclusions

The present findings suggest that the neuron-macrophage interaction mediated by toll-like receptor 4 and IL-1RI activation in trigeminal ganglion neurons affects the pathogenesis of abnormal tongue pain following tooth pulp inflammation via IL-1RI and TRPV1 signaling in the trigeminal ganglion. Further research may contribute to the establishment of new therapeutic and diagnostic methods.
Endoscopic and clinicopathological characteristics of colorectal T/NK cell lymphoma
Authors: Ishibashi Hideki , Nimura Satoshi , Hirai Fumihito , Harada Naohiko , Iwasaki Hiromi , Kawauchi Sigeto , Oshiro Yumi , Matsuyama Atsuji , Nakamura Shotaro , Takamatsu Yasushi , Yonemasu Hirotoshi , Shimokama Taturo , Takeshita Morishige
Published: October 2020

Background

Colorectal T/natural killer (NK)-cell lymphomas (TNKCL) are very rare. Endoscopic and clinicopathological characteristics of colorectal TNKCL have not been clearly demonstrated. In this study, we demonstrated the clinical characteristics of colorectal TNKCL.

Methods

Endoscopic and clinicopathological characteristics were investigated in 27 patients with colorectal monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), adult T-cell leukemia/lymphoma (ATLL), and other types of TNKCL.

Results

Nine TNKCL patients (33%) were classified as MEITL, 11 (41%) as ATLL, and seven (26%) as other. Four patients with Epstein-Barr Virus-positive (EBV+) TNKCL, two indolent T-cell lymphoproliferative disorder and one anaplastic large cell lymphoma were included in the other group. Endoscopically, six MEITL (67%) and five ATLL (46%) showed diffuse-infiltrating type, in which the main endoscopic lesion was edematous mucosa in MEITL, while aphthoid erosion and edematous mucosa were typical in ATLL. Ulcerative type was identified in four other group patients (57%), including two EBV+ TNKCL. An increase in atypical T-intraepithelial lymphocytes (T-IELs) was noted in seven MEITL (88%) and six ATLL (60%) patients, but not in the other group (0%) patients. Five MEITL patients (56%) showed features of lymphocytic proctocolitis with increased CD8+ T-IELs.

Conclusions

MEITL and ATLL occasionally invaded the colorectum, and primary involving MEITL was observed. Diffuse infiltrating type was the characteristic endoscopic finding in colorectal MEITL and ATLL, while ulcerative type was observed in the other group. Features of lymphocytic proctocolitis may be prodromal findings of MEITL.
Evaluating the suitability of hyper- and multispectral imaging to detect foliar symptoms of the grapevine trunk disease Esca in vineyards
Authors: Bendel Nele , Kicherer Anna , Backhaus Andreas , Klück Hans-Christian , Seiffert Udo , Fischer Michael , Voegele Ralf T. , Töpfer Reinhard
Published: October 2020

Background

Grapevine trunk diseases (GTDs) such as Esca are among the most devastating threats to viticulture. Due to the lack of efficient preventive and curative treatments, Esca causes severe economic losses worldwide. Since symptoms do not develop consecutively, the true incidence of the disease in a vineyard is difficult to assess. Therefore, an annual monitoring is required. In this context, automatic detection of symptoms could be a great relief for winegrowers. Spectral sensors have proven to be successful in disease detection, allowing a non-destructive, objective, and fast data acquisition. The aim of this study is to evaluate the feasibility of the in-field detection of foliar Esca symptoms over three consecutive years using ground-based hyperspectral and airborne multispectral imaging.

Results

Hyperspectral disease detection models have been successfully developed using either original field data or manually annotated data. In a next step, these models were applied on plant scale. While the model using annotated data performed better during development, the model using original data showed higher classification accuracies when applied in practical work. Moreover, the transferability of disease detection models to unknown data was tested. Although the visible and near-infrared (VNIR) range showed promising results, the transfer of such models is challenging. Initial results indicate that external symptoms could be detected pre-symptomatically, but this needs further evaluation. Furthermore, an application specific multispectral approach was simulated by identifying the most important wavelengths for the differentiation tasks, which was then compared to real multispectral data. Even though the ground-based multispectral disease detection was successful, airborne detection remains difficult.

Conclusions

In this study, ground-based hyperspectral and airborne multispectral approaches for the detection of foliar Esca symptoms are presented. Both sensor systems seem to be suitable for the in-field detection of the disease, even though airborne data acquisition has to be further optimized. Our disease detection approaches could facilitate monitoring plant phenotypes in a vineyard.
Getting to implementation: a protocol for a Hybrid III stepped wedge cluster randomized evaluation of using data-driven implementation strategies to improve cirrhosis care for Veterans
Authors: Rogal Shari S. , Yakovchenko Vera , Morgan Timothy , Bajaj Jasmohan S. , Gonzalez Rachel , Park Angela , Beste Lauren , Miech Edward J. , Lamorte Carolyn , Neely Brittney , Gibson Sandra , Malone Patrick S. , Chartier Maggie , Taddei Tamar , Garcia-Tsao Guadalupe , Powell Byron J. , Dominitz Jason A. , Ross David , Chinman Matthew J.
Published: October 2020

Background

Cirrhosis is a rapidly increasing cause of global mortality. To improve cirrhosis care, the Veterans Health Administration (VHA) developed the Hepatic Innovation Team (HIT) Collaborative to support VA Medical Centers (VAMCs) to deliver evidence-based cirrhosis care. This randomized HIT program evaluation aims to develop and assess a novel approach for choosing and applying implementation strategies to improve the quality of cirrhosis care.

Methods

Evaluation aims are to (1) empirically determine which combinations of implementation strategies are associated with successful implementation of evidence-based practices (EBPs) for Veterans with cirrhosis, (2) manualize these “data-driven” implementation strategies, and (3) assess the effectiveness of data-driven implementation strategies in increasing cirrhosis EBP uptake. Aim 1 will include an online survey of all VAMCs’ use of 73 implementations strategies to improve cirrhosis care, as defined by the Expert Recommendations for Implementing Change taxonomy. Traditional statistical as well as configurational comparative methods will both be employed to determine which combinations of implementation strategies are associated with site-level adherence to EBPs for cirrhosis. In aim 2, semi-structured interviews with high-performing VAMCs will be conducted to operationalize successful implementation strategies for cirrhosis care. These data will be used to inform the creation of a step-by-step guide to tailoring and applying the implementation strategies identified in aim 1. In aim 3, this manualized implementation intervention will be assessed using a hybrid type III stepped-wedge cluster randomized design. This evaluation will be conducted in 12 VAMCs, with four VAMCs crossing from control to intervention every 6 months, in order to assess the effectiveness of using data-driven implementation strategies to improve guideline-concordant cirrhosis care.

Discussion

Successful completion of this innovative evaluation will establish the feasibility of using early evaluation data to inform a manualized, user-friendly implementation intervention for VAMCs with opportunities to improve care. This evaluation will provide implementation support tools that can be applied to enhance the implementation of other evidence-based practices.

Trial registration

This project was registered at ClinicalTrials.Gov (NCT04178096) on 4/29/20.
Efficacy and toxicity of re-irradiation for esophageal cancer patients with locoregional recurrence: a retrospective analysis
Authors: Zhao Kaikai , Si Youjiao , Sun Liangchao , Meng Xiangjiao , Yu Jinming
Published: October 2020

Introduction

There is no standard treatment for locoregional recurrent (LR) esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy (RT) previously. This retrospective study aimed to examine the efficacy and toxicity of re-irradiation (re-RT) for ESCC patients with LR.

Patients and methods

A total of 252 patients were enrolled. Gross tumor volumes for re-RT were defined using contrast enhanced computed tomography and/or positron emission tomography/computed tomography. Overall survival (OS), after recurrence survival (ARS) and toxicities were assessed.

Results

Through a median follow-up of 38 months, the median OS and ARS were 39.0 and 13.0 months, respectively. The 6-, 12-, and 24-month ARS rates were 81.9%, 50.5%, and 21.8%, respectively. Multivariate analyses showed that chemotherapy, esophageal stenosis and recurrence-free interval (RFI) may be independent prognostic factors for ARS. The incidence of esophageal fistula/perforation (EP), radiation-induced pneumonitis and esophagorrhagia was 21.4%, 12.8% and 9.1%, respectively. RFI ≤ 12 months, esophageal stenosis and fat space between tumor and adjacent tissue disappeared were independent risk factors for the development of EP after re-RT.

Conclusions

Re-RT was feasible for LR ESCC patients after RT initially, the complication occurred in re-RT is acceptable. Patients with RFI ≤ 12 months, esophageal stenosis and fat space between tumor and adjacent tissue disappeared should be closely observed during and after re-RT.
Distally based peroneal artery perforator-plus fasciocutaneous flap in the reconstruction of soft tissue defects over the distal forefoot: a retrospectively analyzed clinical trial
Authors: Peng Ping , Luo Zhaobiao , Lv Guohua , Ni Jiangdong , Wei Jianwei , Dong Zhonggen
Published: October 2020

Background

Distally based peroneal artery perforator-plus fasciocutaneous (DPAPF) flaps are widely used for reconstructing soft-tissue defects of the lower extremity. However, reports on the reconstruction of the defects over the distal forefoot using the DPAPF flaps are scarce. Herein, we describe our experience on the reconstruction of these defects using DPAPF flaps in a considerable sample size.

Methods

Between February 2005 and August 2019, a total of 56 DPAPF flaps in 56 patients were used to reconstruct soft-tissue defects in the forefoot. In order to reduce the length of fascial pedicle and the total length of the DPAPF flaps, the ankles were fixed in dorsiflexion using a Kirschner wire before designing the flaps. The flaps were elevated by the anterograde–retrograde approach. Patient factors and flap factors were compared between the “survival” and “partial necrosis” groups.

Results

Overall, 47 flaps had survived completely in one stage. Partial necrosis developed in nine flaps, with only one remnant defect covered using a local flap. By fixing the ankles in dorsiflexion, the length of the fascial pedicle was reduced approximately 2.35 ± 0.58 cm, the total length of the flap was simultaneously shortened by the same amount as the length of the fascial pedicle. The width of the fascia pedicle varied from 3.0 cm to 6.0 cm. The fascial pedicle width > 4 cm was found in 21 flaps. The partial necrosis rate of the DPAPF flaps with the top edge located in the 8th zone was significantly lower than that in the 9th zone (p < 0.05).

Conclusions

The DPAPF flaps can be effectively used to reconstruct the defects over the distal forefoot because of convenient harvest and reliability. By fixing the ankle in dorsiflexion with Kirschner wire and widening the fascial pedicle appropriately, the top edge and LWR of the flaps will be decreased, and thus the procedures are helpful for the flaps survival.
Clinical outcomes of acute pulmonary embolectomy as the first-line treatment for massive and submassive pulmonary embolism: a single-centre study in China
Authors: QiMin Wang , LiangWan Chen , DaoZhong Chen , HanFan Qiu , ZhongYao Huang , XiaoFu Dai , XueShan Huang , Feng Lin , HuaBin Chen
Published: October 2020

Background

Acute pulmonary embolism (PE) is one of the most critical cardiovascular diseases. PE treatment ranges from anticoagulation, and systemic thrombolysis to surgical embolectomy and catheter embolectomy. Surgical pulmonary embolectmy (SPE) indications and outcomes are still controversial. Although there have been more favourable SPE reports over the past decades, SPE has not yet been considered broadly as an initial PE therapy and is still considered as a reserve or rescue treatment for acute massive PE when systemic thrombolysis fails. This study aimed to evaluate the early and midterm outcomes of SPE, which was a first-line therapy for acute central major PE in one Chinese single centre.

Methods

A retrospective review of patients who underwent SPE for acute PE was conducted.Patients with chronic thrombus or who underwent thromboendarterectomy were excluded. SPE risk factors for morbidity and mortality were reviewed, and echocardiographic examination were conducted for follow-up studies to access right ventricular function.

Results

Overall, 41 patients were included; 17 (41.5%) had submassive PE, and 24 (58.5%) had massive PE. Mean cardiopulmonary bypass time was 103.2 ± 48.9 min, and 10 patients (24.4%) underwent procedures without aortic cross-clamping. Ventilatory support time was 78 h (range, 40–336 h), intensive care unit stay was 7 days (range, 3–13 days), and hospital stay was 16 days (range, 12–23 days). Operative mortalities occurred in 3 massive PE patients, and no mortality occurred in submassive PE patients. The overall SPE mortality rate was 7.31% (3/41). If two systemic thrombolysis cases were excluded, SPE mortality was low (2.56%,1/39), evenlthough there were 2 cases of cardiac arrest preoperatively. Patients’ right ventricle function improved postoperatively in follow-ups.There were no deaths related to recurrent PE and chronic pulmonary hypertension in follow-ups, though 3 patients died of cerebral intracranial bleeding, gastric cancer,and brain cancer at 1 year, 3 years, and 8 years postoperatively, respectively.

Conclusions

SPE presented with a low mortality rate when rendered as a first-line treatment in selected massive and submassive acute PE patients. Favorable outcomes of right ventricle function were also observed in the follow-ups. SPE should play the same role as ST in algorithmic acute PE treatment.
COVID-19: What Iodine Maps From Perfusion CT can reveal—A Prospective Cohort Study
Authors: Santamarina Mario G. , Boisier Riscal Dominique , Beddings Ignacio , Contreras Roberto , Baque Martiniano , Volpacchio Mariano , Martinez Lomakin Felipe
Published: October 2020

Background

Subtraction CT angiography (sCTA) is a technique used to evaluate pulmonary perfusion based on iodine distribution maps. The aim of this study is to assess lung perfusion changes with sCTA seen in patients with COVID-19 pneumonia and correlate them with clinical outcomes.

Material and methods

A prospective cohort study was carried out with 45 RT-PCR-confirmed COVID-19 patients that required hospitalization at three different hospitals, between April and May 2020. In all cases, a basic clinical and demographic profile was obtained. Lung perfusion was assessed using sCTA. Evaluated imaging features included: Pattern predominance of injured lung parenchyma in both lungs (ground-glass opacities, consolidation and mixed pattern) and anatomical extension; predominant type of perfusion abnormality (increased perfusion or hypoperfusion), perfusion abnormality distribution (focal or diffuse), extension of perfusion abnormalities (mild, moderate and severe involvement); presence of vascular dilatation and vascular tortuosity. All participants were followed-up until hospital discharge searching for the development of any of the study endpoints. These endpoints included intensive-care unit (ICU) admission, initiation of invasive mechanical ventilation (IMV) and death.

Results

Forty-one patients (55.2 ± 16.5 years, 22 men) with RT-PCR-confirmed SARS-CoV-2 infection and an interpretable iodine map were included. Patients with perfusion anomalies on sCTA in morphologically normal lung parenchyma showed lower Pa/Fi values (294 ± 111.3 vs. 397 ± 37.7, p = 0.035), and higher D-dimer levels (1156 ± 1018 vs. 378 ± 60.2, p < 0.01). The main common patterns seen in lung CT scans were ground-glass opacities, mixed pattern with predominant ground-glass opacities and mixed pattern with predominant consolidation in 56.1%, 24.4% and 19.5% respectively. Perfusion abnormalities were common (36 patients, 87.8%), mainly hypoperfusion in areas of apparently healthy lung. Patients with severe hypoperfusion in areas of apparently healthy lung parenchyma had an increased probability of being admitted to ICU and to initiate IMV (HR of 11.9 (95% CI 1.55–91.9) and HR 7.8 (95% CI 1.05–61.1), respectively).

Conclusion

Perfusion abnormalities evidenced in iodine maps obtained by sCTA are associated with increased admission to ICU and initiation of IMV in COVID-19 patients.