bluuebunny/crossref_metadata_2025 huggingface dataset:
All-Inside Repair of a Radial Lateral Meniscal Root Tear With an Anterior Cruciate Ligament Injury
Authors: Vadhera Amar S. , Knapik Derrick M. , Dasari Suhas P. , Singh Harsh , Verma Nikhil N. , Chahla Jorge
Published: April 2022

Background:

Root tears are functionally compromising injuries that require an anatomic repair for functional restoration of native joint mechanics. Posterior root tears of the lateral meniscus are commonly associated with anterior cruciate ligament (ACL) ruptures as lateral root tears contribute to anterolateral rotational instability. Two-tunnel transtibial root repair allows for root repair with superior pullout strength and can be combined with ACL reconstruction to treat this injury pattern.

Indications:

Two-tunnel transtibial root repair is indicated in active patients with meniscal root tears that have low-grade chondromalacia (grade II or less). It is contraindicated in patients with advanced degenerative changes (grade III-IV), severe mal-alignment, and extrusion related to advanced degenerative changes; those who cannot complete postoperative rehabilitation; and patients with significant medical comorbidities.

Technique Description:

After repairing a vertical horn tear of the posterior medial meniscus, a vertical tear of the posterior root of the lateral meniscus was observed. Following preparation of the anatomic footprint, 2 transtibial tunnels were drilled and sutures were passed and secured using a surgical button over the anterior tibial cortex. Horizontal repair of the tear was then performed using 2 all-inside devices. Subsequently, an ACL reconstruction was performed.

Results:

At 11 months postoperative, the patient has continued to progress as expected. She was able to ambulate without pain, had a symmetric and balanced gait, and was able to return to running.

Discussion/Conclusion:

Lateral meniscal root repairs using 2 transtibial tunnels and concomitant ACL reconstruction have yielded good and reliable clinical outcomes with low failure rates and low rates of revision surgery.
Favorable outcomes following allogeneic transplantation in adults with hemophagocytic lymphohistiocytosis
Authors: Gooptu Mahasweta , Kim Haesook T. , Jacobsen Eric , Fisher David C. , LaCasce Ann , Ho Vincent T. , Cutler Corey S. , Koreth John , Soiffer Robert J. , Antin Joseph H. , Berliner Nancy , Nikiforow Sarah
Published: April 2022

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome marked by a severe hyperinflammatory state characterized by aberrant T- and natural killer-cell activity leading to prolonged hypercytokinemia and can be rapidly fatal if not diagnosed and treated early. While upfront therapy is aimed at reducing hyperinflammation and controlling possible triggers, allogeneic hematopoietic stem cell transplantation (HSCT) is indicated for primary and relapsed/refractory cases to attain sustained remission. While this has been explored extensively in the pediatric population, there are limited data on adults undergoing HSCT for HLH. We analyzed transplant outcomes in an adult HLH population in the modern era who were transplanted at Dana-Farber Cancer Institute from 2010 onwards. Patients were uniformly transplanted on a reduced intensity platform incorporating early administration of alemtuzumab with standard infectious and graft-versus-host disease (GVHD) prophylaxis. Engraftment was documented for all patients. At 3 years after transplantation, overall survival (OS) was 75% (95% confidence interval [CI], 51-89) while 3-year progression-free survival (PFS) was 71% (95% CI, 46-86). The 3-year cumulative incidence of relapse was 15% (95% CI, 3.4-33). There were no isolated HLH relapses without relapse of malignancy. The cumulative incidence of nonrelapse mortality at 3 years was 15% (95% CI, 3.5-34). Infectious complications and GVHD outcomes were comparable to standard reduced-intensity conditioning (RIC) transplantation at our institute. Mixed chimerism was common but did not correlate with transplant outcomes. Our data suggest that the immune defect in HLH can be abrogated with allogeneic transplantation using a reduced intensity regimen with early administration of alemtuzumab as preconditioning, providing a potentially curative option for this difficult disease.
Bendamustine or high-dose cytarabine-based induction with rituximab in transplant-eligible mantle cell lymphoma
Authors: Villa Diego , Hoster Eva , Hermine Olivier , Klapper Wolfram , Szymczyk Michal , Bosly André , Unterhalt Michael , Rimsza Lisa M. , Ramsower Colleen A. , Freeman Ciara L. , Scott David W. , Gerrie Alina S. , Savage Kerry J. , Sehn Laurie H. , Dreyling Martin
Published: April 2022

The objective of this study was to explore differences in outcomes between first-line rituximab plus bendamustine (R-B) and R-CHOP/R-DHAP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, dexamethasone, cytarabine, cisplatin) in transplant-eligible patients with mantle cell lymphoma (MCL). A population-based cohort of 97 patients aged 18 to 65 years with stage II-IV MCL, consecutively treated with R-B was retrospectively identified at BC Cancer. Baseline characteristics, response rates, and outcomes were compared with the cohort of 232 patients with MCL randomized to the R-CHOP/R-DHAP arm of the MCL Younger trial. The primary endpoint was the hazard ratio (HR) of the progression-free survival (PFS) comparison between both groups, adjusted for MCL International Prognostic Index (MIPI), Ki67 index, and blastoid/ pleomorphic morphology. Ann Arbor stage, lactate dehydrogenase, MIPI, blastoid morphology, and MCL35 assignments were similar between both groups. The overall response rate (ORR) to R-B was 90% (54% complete response [CR]); 77% of patients proceeded to autologous stem cell transplantation (ASCT) and 78% received maintenance rituximab (MR). The ORR to R-CHOP/R-DHAP was 94% (54% CR); 78% proceeded to ASCT and 2% received MR. There were no differences in PFS in unadjusted (HR, 0.87; 95% confidence interval [CI], 0.53-1.41; P = .56) or adjusted (HR, 0.79; 95% CI, 0.45-1.37; P = .40) comparisons. There were no clear differences in secondary endpoints in unadjusted or adjusted analyses. This retrospective adjusted comparison of 2 independent cohorts of younger patients with MCL suggests that R-B with ASCT and maintenance rituximab is a feasible and effective first-line treatment, with outcomes comparable to R-CHOP/R-DHAP with ASCT.
Rivaroxaban for the treatment of noncirrhotic splanchnic vein thrombosis: an interventional prospective cohort study
Authors: Ageno Walter , Beyer Westendorf Jan , Contino Laura , Bucherini Eugenio , Sartori Maria Teresa , Senzolo Marco , Grandone Elvira , Santoro Rita , Carrier Marc , Delluc Aurélien , De Stefano Valerio , Pomero Fulvio , Donadini Marco Paolo , Tosetto Alberto , Becattini Cecilia , Martinelli Ida , Nardo Barbara , Bertoletti Laurent , Di Nisio Marcello , Lazo-Langner Alejandro , Schenone Alessandro , Riva Nicoletta
Published: April 2022

Heparins and vitamin K antagonists are the mainstay of treatment of splanchnic vein thrombosis (SVT). Rivaroxaban is a potential alternative, but data to support its use are limited. We aimed to evaluate the safety and efficacy of rivaroxaban for the treatment of acute SVT. In an international, single-arm clinical trial, adult patients with a first episode of noncirrhotic, symptomatic, objectively diagnosed SVT received rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg daily for an intended duration of 3 months. Patients with Budd-Chiari syndrome and those receiving full-dose anticoagulation for >7 days prior to enrollment were excluded. Primary outcome was major bleeding; secondary outcomes included death, recurrent SVT, and complete vein recanalization within 3 months. Patients were followed for a total of 6 months. A total of 103 patients were enrolled; 100 were eligible for the analysis. Mean age was 54.4 years; 64% were men. SVT risk factors included abdominal inflammation/infection (28%), solid cancer (9%), myeloproliferative neoplasms (9%), and hormonal therapy (9%); 43% of cases were unprovoked. JAK2 V617F mutation was detected in 26% of 50 tested patients. At 3 months, 2 patients (2.1%; 95% confidence interval, 0.6-7.2) had major bleeding events (both gastrointestinal). One (1.0%) patient died due to a non–SVT-related cause, 2 had recurrent SVT (2.1%). Complete recanalization was documented in 47.3% of patients. One additional major bleeding event and 1 recurrent SVT occurred at 6 months. Rivaroxaban appears as a potential alternative to standard anticoagulation for the treatment of SVT in non-cirrhotic patients. This trial was registered at www.clinicaltrials.gov as #NCT02627053 and at eudract.ema.europa.eu as #2014-005162-29-36.
An observational study ofPseudomonas aeruginosain adult long-term ventilation
Authors: Sobala Ruth , Carlin Hannah , Fretwell Thomas , Shakir Sufyan , Cattermole Katie , Royston Amy , McCallion Paul , Davison John , Lumb Joanna , Tedd Hilary , Messer Ben , De Soyza Anthony
Published: April 2022

Introduction

Pseudomonas aeruginosaincreases morbidity and mortality in respiratory disease. To date the long-term ventilation population does not have clear guidelines regarding its management.

Method

We undertook a retrospective observational study in a regional long-term ventilation population (837 patients). We defined the primary outcome asP. aeruginosaisolation. In addition positive cultures for copathogens (Serratia,Proteusspecies,Stenotrophomonas,Burkholderia cepaciacomplex and nontuberculous mycobacteria) were recorded.Logistic regression and odds ratios were calculated.

Results

17.6% of the cohort isolatedP. aeruginosa, and this pathogen was cultured more frequently in patients with a tracheostomy (logistic regression coefficient 2.90, p≤0.0001) and cystic fibrosis/bronchiectasis (logistic regression coefficient 2.48, p≤0.0001). 6.3% of patients were ventilatedviatracheostomy. In theP. aeruginosapositive cohort 46.9% of patients were treated with a long-term macrolide, 36.7% received a nebulised antibiotic and 21.1% received both. TracheostomisedP. aeruginosapositive patients received a nebulised antibiotic more frequently (OR 2.63, 95% CI 1.23–5.64, p=0.013). Copathogens were isolated in 33.3% of theP. aeruginosacohort. In this cohort patients with a tracheostomy grew a copathogen more frequently than those without (OR 2.75, 95% CI 1.28–5.90).

Conclusions

P. aeruginosaisolation is common within the adult long-term ventilation population and is significantly associated with tracheostomy, cystic fibrosis and bronchiectasis. Further research and international guidelines are needed to establish the prognostic impact ofP. aeruginosaand to guide on antimicrobial management. The increased risk ofP. aeruginosashould be considered when contemplating long-term ventilationviatracheostomy.
New Data and New Features of the FunRiceGenes (Functionally Characterized Rice Genes) Database: 2021 Update
Authors: Huang Fangfang , Jiang Yingru , Chen Tiantian , Li Haoran , Fu Mengjia , Wang Yazhou , Xu Yufang , Li Yang , Zhou Zhengfu , Jia Lihua , Ouyang Yidan , Yao Wen
Published: April 2022

As a major food crop and model organism, rice has been mostly studied with the largest number of functionally characterized genes among all crops. We previously built the funRiceGenes database including ~ 2800 functionally characterized rice genes and ~ 5000 members of different gene families. Since being published, the funRiceGenes database has been accessed by more than 54,400 users with over 540,000 pageviews. The funRiceGenes database has been continuously updated with newly cloned rice genes and newly published literature, based on the progress of rice functional genomics studies. Up to Nov 2021, ~ 4100 functionally characterized rice genes and ~ 6000 members of different gene families were collected in funRiceGenes, accounting for 22.3% of the 39,045 annotated protein-coding genes in the rice genome. Here, we summarized the update of the funRiceGenes database with new data and new features in the last 5 years.
Effects of Various Allelic Combinations of Starch Biosynthetic Genes on the Properties of Endosperm Starch in Rice
Authors: Fujita Naoko , Miura Satoko , Crofts Naoko
Published: April 2022

Rice endosperm accumulates large amounts of photosynthetic products as insoluble starch within amyloplasts by properly arranging structured, highly branched, large amylopectin molecules, thus avoiding osmotic imbalance. The amount and characteristics of starch directly influence the yield and quality of rice grains, which in turn influence their application and market value. Therefore, understanding how various allelic combinations of starch biosynthetic genes, with different expression levels, affect starch properties is important for the identification of targets for breeding new rice cultivars. Research over the past few decades has revealed the spatiotemporal expression patterns and allelic variants of starch biosynthetic genes, and enhanced our understanding of the specific roles and compensatory functions of individual isozymes of starch biosynthetic enzymes through biochemical analyses of purified enzymes and characterization of japonica rice mutants lacking these enzymes. Furthermore, it has been shown that starch biosynthetic enzymes can mutually and synergistically increase their activities by forming protein complexes. This review focuses on the more recent discoveries made in the last several years. Generation of single and double mutants and/or high-level expression of specific starch synthases (SSs) allowed us to better understand how the starch granule morphology is determined; how the complete absence of SSIIa affects starch structure; why the rice endosperm stores insoluble starch rather than soluble phytoglycogen; how to elevate amylose and resistant starch (RS) content to improve health benefits; and how SS isozymes mutually complement their activities. The introduction of active-type SSIIa and/or high-expression type GBSSI into ss3a ss4b, isa1, be2b, and ss3a be2b japonica rice mutants, with unique starch properties, and analyses of their starch properties are summarized in this review. High-level accumulation of RS is often accompanied by a reduction in grain yield as a trade-off. Backcrossing rice mutants with a high-yielding elite rice cultivar enabled the improvement of agricultural traits, while maintaining high RS levels. Designing starch structures for additional values, breeding and cultivating to increase yield will enable the development of a new type of rice starch that can be used in a wide variety of applications, and that can contribute to food and agricultural industries in the near future.
Small HSPs play an important role in crosstalk between HSF-HSP and ROS pathways in heat stress response through transcriptomic analysis in lilies (Lilium longiflorum)
Authors: Zhou Yunzhuan , Wang Yue , Xu Fuxiang , Song Cunxu , Yang Xi , Zhang Zhao , Yi Mingfang , Ma Nan , Zhou Xiaofeng , He Junna
Published: April 2022

Background

High temperature seriously limits the annual production of fresh cut lilies, which is one of the four major cut flowers in the global cut flower market. There were few transcriptomes focused on the gene expression of lilies under heat stress. In order to reveal the potential heat response patterns in bulbous plants and provide important genes for further genetic engineering techniques to improve thermotolerance of lily, RNA sequencing of lilies under heat treatments were conducted.

Results

In this study, seedlings of Lilium longiflorum ‘White Heaven’ were heat-treated at 37 °C for different lengths of time (0 h, 0.5 h, 1 h, 3 h, 6 h, and 12 h with a 12 h-light/12 h-dark cycle). The leaves of these lily seedlings were immediately collected after heat treatments and quickly put into liquid nitrogen for RNA sequencing. 109,364,486–171,487,430 clean reads and 55,044 unigenes including 21,608 differentially expressed genes (DEGs) (fold change ≥2) were obtained after heat treatment. The number of DEGs increased sharply during the heat treatments of 0.5 h–1 h and 1 h–3 h compared to that of other periods. Genes of the heat stress transcription factor (HSF) family and the small heat shock proteins (small HSPs, also known as HSP20) family responded to heat stress early and quickly. Compared to that of the calcium signal and hormone pathways, DEGs of the HSF-HSP pathway and reactive oxygen species (ROS) pathway were significantly and highly induced. Moreover, they had the similar expression pattern in response to heat stress. Small HSPs family genes were the major components in the 50 most highly induced genes at each heat stress treatment and involved in ROS pathway in the rapid response to heat stress. Furthermore, the barley stripe mosaic virus induced gene silencing (BSMV-VIGS) of LlHsfA2 caused a significantly reduced thermotolerance phenotype in Lilium longiflorum ‘White Heaven’, meanwhile decreasing the expression of small HSPs family genes and increasing the ROS scavenging enzyme ascorbate peroxidase (APX) genes, indicating the potential interplay between these two pathways.

Conclusions

Based on our transcriptomic analysis, we provide a new finding that small HSPs play important roles in crosstalk between HSF-HSP and ROS pathways in heat stress response of lily, which also supply the groundwork for understanding the mechanism of heat stress in bulbous plants.
Clinical features and predictors of outcome in patients with acute myocardial infarction complicated by out-of-hospital cardiac arrest
Authors: Sonoda Taketo , Wada Hideki , Ogita Manabu , Takahashi Daigo , Nishio Ryota , Yasuda Kentaro , Takeuchi Mitsuhiro , Yatsu Shoichiro , Shitara Jun , Tsuboi Shuta , Dohi Tomotaka , Suwa Satoru , Miyauchi Katsumi , Minamino Tohru
Published: April 2022

Background

Although short-term mortality of acute myocardial infarction (AMI) has decreased dramatically in the past few decades, sudden cardiac arrest remains a serious complication. The aim of the study was to assess the clinical characteristics and predictors of prognosis in AMI patients who experienced out-of-hospital cardiac arrest (OHCA).

Methods

We retrospectively registered consecutive AMI patients who were treated with emergency percutaneous coronary intervention (PCI) between 2004 and 2017. Clinical characteristics and outcomes were compared between patients with OHCA and those without OHCA.

Results

Among 2101 AMI patients, 95 (4.7%) presented with OHCA. Younger age (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.93–0.97; p < 0.0001), absence of diabetes mellitus (OR, 0.51; 95% CI, 0.30–0.85; p = 0.01) or dyslipidemia (OR, 0.56; 95% CI, 0.36–0.88; p = 0.01), left main trunk (LMT) or left anterior descending artery (LAD) as the culprit lesion (OR, 3.26; 95% CI, 1.99–5.33; p < 0.0001), and renal deficiency (OR, 3.64; 95% CI, 2.27–5.84; p < 0.0001) were significantly associated with incidence of OHCA. Thirty-day mortality was 32.6% in patients with OHCA and 4.5% in those without OHCA. Multivariate logistic analysis revealed LMT or LAD as the culprit lesion (OR, 12.18; 95% CI, 2.27–65.41; p = 0.004), glucose level (OR, 1.01; 95% CI, 1.00–1.01; p = 0.01), and renal deficiency (OR, 3.35; 95% CI, 1.07–10.53; p = 0.04) as independent predictors of 30-day mortality among AMI patients with OHCA.

Conclusions

In patients with AMI who underwent emergency PCI, 30-day mortality was six times greater in those having presented initially with OHCA compared with those without OHCA. Younger age, absence of diabetes mellitus or dyslipidemia, LMT or LAD as the culprit lesion, and renal deficiency were independent predictors of OHCA. OHCA patient with higher blood glucose level on admission, LMT or LAD as the culprit lesion, or renal deficiency showed worse clinical outcomes.
OLA1 promotes colorectal cancer tumorigenesis by activation of HIF1α/CA9 axis
Authors: Liu Yue , Kong Xiang-Xing , He Jin-Jie , Xu Yan-Bo , Zhang Jian-Kun , Zou Lu-Yang , Ding Ke-Feng , Xu Dong
Published: April 2022

Background

Obg-like ATPase 1 (OLA1) is a highly conserved GTPase, which was over expressed in a variety of malignant tumors, but its role in colorectal cancer (CRC) was poorly studied.

Patients and methods

Three public CRC gene databases were applied for OLA1 mRNA expression detection. The clinical data of 111 CRC patients were retrospectively collected from the Second Affiliated Hospital of Zhejiang University (SAHZU) for OLA1 protein expression and Kaplan-Meier Survival analysis. OLA1 stably knocked out CRC cell lines were conducted by CRISPR-Cas9 for experiments in vitro and in vivo.

Results

OLA1 was highly expressed in 84% CRC compared to matched surrounding tissues. Patients with OLA1 high expression had a significantly lower 5-year survival rate (47%) than those with OLA1 low expression (75%). OLA1 high expression was an independent factor of poor prognosis in CRC patients. OLA1-KO CRC cell lines showed lower ability of growth and tumorigenesis in vitro and in vivo. By mRNA sequence analysis, we found 113 differential express genes in OLA1-KO cell lines, of which 63 were hypoxic related. HIF1α was a key molecule in hypoxic regulation. Further molecular mechanisms showed HIF1α /CA9 mRNA and/or protein levels were heavily downregulated in OLA1-KO cell lines, which could explain the impaired tumorigenesis. According to previous studies, HIF1α was a downstream gene of GSK3β, we verified GSK3β was over-activated in OLA1-KO cell lines.

Conclusion

OLA1 was a new gene that was associated with carcinogenesis and poor outcomes in CRC by activation of HIF1α/CA9 axis, which may be interpreted by GSK3β.
Development and validation of a new method for visual acuity assesment on tablet in pediatric population: eMOVA test
Authors: Stoll Noémie , Di Foggia Elsa , Speeg-Schatz Claude , Meunier Hélène , Rimele Adam , Ancé Pascal , Moreau Pierre-Henri , Sauer Arnaud
Published: April 2022

Background

Amblyopia is a major public health concern. Its screening and management require reliable methods of visual acuity assessment. New technologies offer nowadays many tests available on different app stores for smartphone or tablet but most of them often lack of scientific validation for a medical use. The aim of our study was to attempt validating a tablet-based near visual acuity test adapted to the pediatric population: the eMOVA test (electronic Measurement Of Visual Acuity) by comparing visual acuity measured with more conventional test.

Methods

A cohort of 100 children aged 3 to 8 attending the ophthalmic-pediatric for eye examination between September 2016 and June 2017 were included in the study. Near visual acuity was assessed on participants using both the eMOVA test and a Standard test (Rossano-Weiss test). Duration of each test, its comprehension, its acceptability and the attention of the child during the test was also investigated.

Results

The eMOVA test overestimated near visual acuity by 0.06 logMAR. This difference, statistically significant, was not clinically relevant. The duration of the eMOVA test was longer than the reference test, but less discomfort and preferred by children and their parents compared to standard tests.

Conclusion

The eMOVA test appears as a reliable test to assess near visual acuity in children. By its portability and efficiency, this application proved to be a relevant tool to be used for children eye examination in daily routine at the hospital.
Characteristics of depression, anxiety, impulsivity, and aggression among various types of drug users and factors for developing severe depression: a cross-sectional study
Authors: Luo Dan , Tan Lu , Shen Danlin , Gao Zhe , Yu LiangMing , Lai Mingfeng , Xu Jiajun , Li Jing
Published: April 2022

Background

Mood disorder, impulsivity and aggression are common in drug users compared to healthy controls. However, no study has focused on the difference in various types of drug users. Therefore, the objective of this study was to explore the differences in depression, anxiety, impulsivity, and aggression among methamphetamine, heroin and polysubstance users and to further explore the risk factors for severe depression in the three groups.

Methods

Drug users over 18 years old who met the DSM-V diagnostic criteria for substance -related disorders were included in the study. All participants completed a general questionnaire, the Zung Self-Rating Depression Scale (SDS), the Zung Self-Rating Anxiety Scale (SAS), Barratt impulsiveness Scale Version 11 (BIS-11), and the Buss-Perry Aggression Questionnaire (BPAQ). One-way ANOVAs or Chi-square tests were used to test the differences among the groups, correlation analysis was used to test the relationship between drug use and other parameters, and multiple logistic regression was conducted to assess the risk factors for severe depression.

Results

A total of 1,486 participants were included, comprising 86.3% males with a mean age of 38.97 years. There was a significant difference in the percentage of severe depression and SDS scores among the three groups, but no significant difference was found in SAS, BIS-11 and BPAQ scores. Using methamphetamines, hostility and anxiety were risk factors for developing severe depression in all the participants and anxiety remained constant in the other three groups. Moreover, methamphetamine use was 2.16 and 3.35 times more likely to cause severe depression than heroin and polysubstance use, respectively. The initial age of substance use was negatively correlated with BPAQ, SAS, and SDS scores, whereas the drug use duration and addiction duration were positively correlated.

Conclusions

In this study, we found that the highest prevalence of severe depression was in participants using methamphetamines and that using methamphetamines, hostility, and anxiety were risk factors for developing severe depression. This result addressed an important gap in our knowledge of the different characteristics of depression, anxiety, impulsivity and aggression in various types of substance users and provides clinicians and policy-makers with directions for intervention and preventing relapse.
Evaluation of fully automated cephalometric measurements obtained from web-based artificial intelligence driven platform
Authors: Mahto Ravi Kumar , Kafle Dashrath , Giri Abhishek , Luintel Sanjeev , Karki Arjun
Published: April 2022

Background

Artificial Intelligence has created a huge impact in different areas of dentistry. Automated cephalometric analysis is one of the major applications of artificial intelligence in the field of orthodontics. Various automated cephalometric software have been developed which utilizes artificial intelligence and claim to be reliable. The purpose of this study was to compare the linear and angular cephalometric measurements obtained from web-based fully automated Artificial Intelligence (AI) driven platform “WebCeph”™ with that from manual tracing and evaluate the validity and reliability of automated cephalometric measurements obtained from “WebCeph”™.

Methods

Thirty pre-treatment lateral cephalograms of patients were randomly selected. For manual tracing, digital images of same cephalograms were printed using compatible X-ray printer. After calibration, a total of 18 landmarks was plotted and 12 measurements (8 angular and 4 linear) were obtained using standard protocols. The digital images of each cephalogram were uploaded to “WebCeph”™ server. After image calibration, the automated cephalometric measurements obtained through AI digitization were downloaded for each image. Intraclass correlation coefficient (ICC) was used to determine agreement between the measurements obtained from two methods. ICC value < 0.75 was considered as poor to moderate agreement while an ICC value between 0.75 and 0.90 was considered as good agreement. Agreement was rated as excellent when ICC value > 0.90 was obtained.

Results

All the measurements had ICC value above 0.75. A higher ICC value > 0.9 was obtained for seven parameters i.e. ANB, FMA, IMPA/L1 to MP (°), LL to E-line, L1 to NB (mm), L1 to NB (°), S-N to Go-Gn whereas five parameters i.e. UL to E-line, U1 to NA (mm), SNA, SNB, U1 to NA (°) showed ICC value between 0.75 and 0.90.

Conclusion

A good agreement was found between the cephalometric measurements obtained from “WebCeph”™ and manual tracing.
Prophylactic effect of topical (slow-release) and systemic curcumin nano-niosome antioxidant on oral cancer in rat
Authors: Fazli Behzad , Irani Soussan , Bardania Hassan , Moosavi Mahdieh-Sadat , Rohani Bita
Published: April 2022

Background

Oral malignancies have a significant effect on the quality of life among the affected patients. Curcumin is an antioxidant with a low bioavailability in the target tissue. Niosomes are carriers of increasing the therapeutic effects of drugs and reducing their side effects. This study aimed to determine the effective dose of curcumin niosome in the culture and then to compare its prophylactic effect in the form of mouthwash with that of its injectable form on oral cancer in rats.

Methods

This was an in-vitro and in-vivo study. Firstly, KB oral cancer cells and human umbilical vein endothelial cells (HUVEC) were treated in separate groups with free curcumin, curcumin-loaded niosomes, and the unloaded niosomes at four doses of 4, 8, 16, and 32 μg. The study rats were then divided into the following four groups: 1) no intervention, 2) only carcinogenic substance, 3) carcinogenic substance with curcumin-loaded niosome injection, and 4) carcinogenic substance with a mouthwash containing niosome.

Results

At the cellular level, a dose of 16 μg after 24 h was selected as an effective dose. In the animal phase, the use of injectable curcumin niosome was observed to significantly prevent the development of severe forms of dysplasia.

Conclusions

In this in-vitro and in-vivo study, curcumin-loaded niosome was effective in preventing the development of severe forms of dysplasia and the inhibition of the growth of cancer cells.
Clausena Harmandiana root extract attenuated cognitive impairments via reducing amyloid accumulation and neuroinflammation in Aβ1-42-induced rats
Authors: Nillert Nutchareeporn , Boonyarat Chantana , Welbat Jariya Umka , Bunreungthong Komsun , Puthongking Ploenthip , Pannangrong Wanassanun
Published: April 2022

Background

Alzheimer’s disease (AD) pathogenesis is associated with amyloid-β (Aβ)-induced neuroinflammation. In AD, the activation of microglia caused by Aβ accumulation is followed by the synthesis and release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), and ultimately leads to cognitive impairments. Clausena harmandiana (CH) is a medicinal plant in the Rutaceae family and has been used in folk medicine to relieve illnesses such as stomachache and headache, and as a health tonic. Interestingly, CH root extract (CHRE) has several anti-inflammatory and other pharmacological activities, but there are no studies in AD-like animal models.

Objectives

This study aims to evaluate the effects of CHRE on cognitive impairments, increased Aβ1–42 protein levels, and neuroinflammation in Aβ1–42-induced rats.

Methods

Forty-eight adult male Sprague-Dawley rats (250–300 g) were randomly divided into 6 groups (n = 8) of the sham control, V + Aβ, CB + Aβ CHRE125 + Aβ, CHRE250 + Aβ, and CHRE500 + Aβ. Sodium carboxymethylcellulose, Celebrex (10 mg/kg BW) and CHRE (125, 250, and 500 mg/kg BW) were given orally or without any treatment for 35 days. On day 21, aggregated Aβ1–42 at a concentration of 1 μg/μl were injected into both lateral ventricles (1 μl/side) of all treated rats, while sterilized normal saline were injected to untreated rats. Ten days later, the novel object recognition test was performed to assess their recognition memory. At the end of the test period, an overdose of thiopental sodium (120 mg/kg BW) and transcardial perfusion with 0.9% normal saline solution were used to euthanize all rats. Then Aβ1–42 protein levels and the expression of inflammatory markers (CD11b-positive microglia, IL-1β, and TNFα) were investigated in the cerebral cortex and hippocampus.

Results

Pretreatment with CHRE at all doses could attenuate short- and long-term impairments in recognition memory. Additionally, CHRE also inhibited the increase of Aβ1–42 protein levels and the expression of inflammatory markers in both brain regions as well as receiving Celebrex.

Conclusions

This suggests that preventive treatment of CHRE might be a potential therapy against cognitive impairments via reducing Aβ1–42 protein levels and neuroinflammation caused by Aβ1–42.
Addressing the role of PKD3 in the T cell compartment with knockout mice
Authors: Koutník Jiří , Neururer Verena , Gruber Thomas , Peer Sebastian , Hermann-Kleiter Natascha , Olson William J. , Labi Verena , Leitges Michael , Baier Gottfried , Siegmund Kerstin
Published: April 2022

Background

The Protein kinase D3 (PKD3) has been implicated in signal transduction downstream of the T cell receptor (TCR). However, its role for the activation of primary T lymphocytes has not been elucidated so far.

Methods

Expression of PKD isoforms in primary murine T cells was determined by RT-PCR and SDS-Page. A germline PKD3-knockout mouse line was analyzed for its immune response to OVA/alum intraperitoneal immunization. Phenotyping of the T cell compartment ex vivo as well as upon stimulation in vitro was performed by flow cytometry. Additionally, cytokine expression was assessed by flow cytometry, RT-PCR and Luminex technology.

Results

PKD expression in T cells is modulated by TCR stimulation, leading to a rapid down-regulation on mRNA and on protein level. PKD3-deficient mice respond to immunization with enhanced T follicular helper cell generation. Furthermore, peripheral PKD3-deficient CD4+ T cells express more interleukin-2 than wild type CD4+ T cells upon TCR stimulation ex vivo. However, purified naïve CD4+ T cells do not differ in their phenotype upon differentiation in vitro from wild type T cells. Moreover, we observed a shift towards an effector/memory phenotype of splenic T cells at steady state, which might explain the contradictory results obtained with pan-T cells ex vivo and naïve-sorted T cells.

Conclusion

While PKD3-deficiency in vivo in mice leads to a skewing of the T cell compartment towards a more activated phenotype, this kinase seems to be dispensable for naïve CD4+ T cell differentiation in vitro.
Microscopic nuclei classification, segmentation, and detection with improved deep convolutional neural networks (DCNN)
Authors: Alom Zahangir , Asari Vijayan K. , Parwani Anil , Taha Tarek M.
Published: April 2022

Background

Nuclei classification, segmentation, and detection from pathological images are challenging tasks due to cellular heterogeneity in the Whole Slide Images (WSI).

Methods

In this work, we propose advanced DCNN models for nuclei classification, segmentation, and detection tasks. The Densely Connected Neural Network (DCNN) and Densely Connected Recurrent Convolutional Network (DCRN) models are applied for the nuclei classification tasks. The Recurrent Residual U-Net (R2U-Net) and the R2UNet-based regression model named the University of Dayton Net (UD-Net) are applied for nuclei segmentation and detection tasks respectively. The experiments are conducted on publicly available datasets, including Routine Colon Cancer (RCC) classification and detection and the Nuclei Segmentation Challenge 2018 datasets for segmentation tasks. The experimental results were evaluated with a five-fold cross-validation method, and the average testing results are compared against the existing approaches in terms of precision, recall, Dice Coefficient (DC), Mean Squared Error (MSE), F1-score, and overall testing accuracy by calculating pixels and cell-level analysis.

Results

The results demonstrate around 2.6% and 1.7% higher performance in terms of F1-score for nuclei classification and detection tasks when compared to the recently published DCNN based method. Also, for nuclei segmentation, the R2U-Net shows around 91.90% average testing accuracy in terms of DC, which is around 1.54% higher than the U-Net model.

Conclusion

The proposed methods demonstrate robustness with better quantitative and qualitative results in three different tasks for analyzing the WSI.
Quantitative changes of upper airway in class III patients undergoing bimaxillary surgery after one-year follow-up: a retrospective study
Authors: Li Haizhen , Sun Chongke , Chen Yanlong , Sun Zhipeng , Gao Xuemei
Published: April 2022

Background

Bimaxillary surgery is often performed for class III malocclusion, and its complex influence on the upper airway has been well considered. The aim of this research was to provide a scaled formula between upper airway volume changes and bone movements in Class III patients after orthognathic surgery.

Materials and methods

Using a retrospective study design, the investigators enrolled a total of 30 class III malocclusion patients who were undergoing bimaxillary surgery as the study subjects. The subjects included 15 males and 15 females, and their average age was 23.3 ± 3.4 years. CBCT (cone beam tomography) was performed both before and one year after the surgery for each patient. The changes in the soft palate, tongue and upper airway were measured by using CBCT data that was collected before and after surgery. 3D superimposition of CBCT was performed to calculate three-dimensional jaw movements. A multiple regression analysis was used to calculate the quantitative relationship between airway volume changes and jaw movements.

Results

The nasopharynx airway volume was observed to be increased by 1064.0 ± 1336.2 mm3, whereas the retropalatal and retroglossal airway volumes were observed to be decreased by 1399.0 ± 2881.6 mm3and 1433.8 ± 3043.4 mm3, respectively, after the surgery. One millimetre forward and downward movements of the PNS resulted in increases of 626.90 mm3and 392.18 mm3in nasopharynx airway volume, respectively. Moreover, one millimetre retrogression of the B point caused decreases of 314.6 mm3and 656.6 mm3in the retropalatal and retroglossal airway volume, respectively. The changes in the soft palate contributed to the decrease in the retropalatal airway volume, whereas the tongue compensated for the decrease in the retroglossal airway volume.

Conclusion

The movements of the PNS and B points could be used to predict upper airway volumetric changes in Class III patients after maxillary advancement and mandibular setback.
Dunnigan lipodystrophy syndrome: French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins)
Authors: Mosbah H. , Donadille B. , Vatier C. , Janmaat S. , Atlan M. , Badens C. , Barat P. , Béliard S. , Beltrand J. , Ben Yaou R. , Bismuth E. , Boccara F. , Cariou B. , Chaouat M. , Charriot G. , Christin-Maitre S. , De Kerdanet M. , Delemer B. , Disse E. , Dubois N. , Eymard B. , Fève B. , Lascols O. , Mathurin P. , Nobécourt E. , Poujol-Robert A. , Prevost G. , Richard P. , Sellam J. , Tauveron I. , Treboz D. , Vergès B. , Vermot-Desroches V. , Wahbi K. , Jéru I. , Vantyghem M. C. , Vigouroux C.
Published: April 2022

Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal management and care of patients with FPLD2, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Dunnigan syndrome is characterized by a partial atrophy of the subcutaneous adipose tissue and by an insulin resistance syndrome, associated with a risk of metabolic, cardiovascular and muscular complications. Its prevalence, assessed at 1/100.000 in Europe, is probably considerably underestimated. Thorough clinical examination is key to diagnosis. Biochemical testing frequently shows hyperinsulinemia, abnormal glucose tolerance and hypertriglyceridemia. Elevated hepatic transaminases (hepatic steatosis) and creatine phosphokinase, and hyperandrogenism in women, are common. Molecular analysis of the LMNA gene confirms diagnosis and allows for family investigations. Regular screening and multidisciplinary monitoring of the associated complications are necessary. Diabetes frequently develops from puberty onwards. Hypertriglyceridemia may lead to acute pancreatitis. Early atherosclerosis and cardiomyopathy should be monitored. In women, polycystic ovary syndrome is common. Overall, the management of patients with Dunnigan syndrome requires the collaboration of several health care providers. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are described to provide such a support.
Comparison of platinum monotherapy with concurrent chemoradiation therapy versus platinum-based dual drug therapy with concurrent chemoradiation therapy for locally advanced cervical cancer: a systematic review and meta-analysis
Authors: Deng Ting , Gu Shequn , Wu Jianchi , Yu Yuanyi
Published: April 2022

Objective

To compare the survival outcomes and adverse events of patients with locally advanced cervical cancer (LACC) who received platinum monotherapy with concurrent chemoradiation therapy (CCRT) versus platinum-based dual drug therapy with CCRT.

Method

All relevant literature was screened form the PubMed, EMBASE, Web of Science, The Cochrane Library and other databases from their establishment to October 2020. The main endpoint indicators included overall survival (OS) and progression-free survival (PFS). Grade 3 and above adverse events induced by chemotherapy were also compared.

Results

This study involved 17 literature and 4,106 patients. There were 2,066 patients treated with CCRT with platinum-based dual drug therapy and 2,040 patients received CCRT with platinum monotherapy. Meta-analysis results showed that, compared to CCRT with platinum monotherapy, OS (HR = 0.68, 95% CI 0.58–0.79) and PFS (HR = 0.67, 95% CI 0.58–0.77) of LACC patients were significantly improved by CCRT with platinum-based dual drug therapy. In addition, CCRT with platinum-based dual drug therapy led to more adverse reactions such as neutropenia (OR = 4.92, 95% CI 3.55–6.84), anemia (OR = 1.99, 95% CI 1.17–3.39), diarrhea (OR = 1.70, 95% CI 1.30–2.22), leukopenia (OR = 2.42, 95%CI 1.84–3.17), thrombocytopenia (OR = 2.87, 95%CI 1.44–5.72), etc.

Conclusion

CCRT with platinum-based dual drug therapy improved OS and PFS of LACC patients relative to the CCRT with platinum monotherapy. But it also increased the adverse reactions caused by multiple chemotherapy drugs. Thus, it is crucial to select a proper chemotherapy regimen based on the actual tolerance of patients in clinical practice.
Family, personal, parental correlates and behavior disturbances in school-aged boys with attention-deficit/hyperactivity disorder (ADHD): a cross-sectional study
Authors: Hsu Yuan-Chang , Chen Chih-Tsai , Yang Hao-Jan , Chou Pesus
Published: April 2022

Background

To evaluate the relationship among family, personal, parental correlates, and behavioral disturbances in boys with attention-deficit/hyperactivity disorder (ADHD).

Methods

We performed a hospital-based cross-sectional study. School-aged boys who first visited the hospital between 2000 and 2011 with ADHD were identified. Through medical records review, demographic information, family characteristics, personal characteristics, parental characteristics, and the Child Behavior Checklist (CBCL) collected during the first outpatient visit were retrieved. A T-score higher than 63 in the internalizing or externalizing subscale of the CBCL indicated severe behavioral disturbances in each domain. Multivariable logistic regression was used to evaluate the relationship between the correlates and behavioral disturbances. Eligible patients were further classified into groups without behavioral disturbance, with either only severe internalizing or only severe externalizing behaviors, or with both behaviors. Multivariable ordinal logistic regression was used to investigate the association between the correlates and the number of types of behavioral disturbances.

Results

A total of 1855 boys with ADHD were included. In the multivariable logistic regression, family factors, including being first-born, living in a family not with both parents, and family history of mental disorder, were associated with severe internalizing and externalizing behaviors. Personal factors, including prenatal complications, perinatal complications, and medical and psychiatric comorbidities, were associated with severe internalizing behaviors, but only prenatal complications and medical comorbidities were associated with severe externalizing behaviors. Parental factors were only associated with severe externalizing behaviors. A higher paternal education level had a protective effect, but younger motherhood increased the risk. In ordinal logistic regression, these factors were also associated with more types of behavioral disturbances.

Conclusions

Multiple factors are related to behavioral disturbances in ADHD. Our study reported the association among family, personal, parental factors, severe internalizing behavior, severe externalizing behavior, and number of behavioral disturbances in boys with ADHD. However, the impacts differed as the behavior phenotypes varied. Further research is needed to better understand the heterogeneity of ADHD behavior.
The effect of treatment and clinical course during Emergency Department stay on severity scoring and predicted mortality risk in Intensive Care patients
Authors: Candel Bart G. J. , Raven Wouter , Lameijer Heleen , Thijssen Wendy A. M. H. , Termorshuizen Fabian , Boerma Christiaan , de Keizer Nicolette F. , de Jonge Evert , de Groot Bas
Published: April 2022

Background

Treatment and the clinical course during Emergency Department (ED) stay before Intensive Care Unit (ICU) admission may affect predicted mortality risk calculated by the Acute Physiology and Chronic Health Evaluation (APACHE)-IV, causing lead-time bias. As a result, comparing standardized mortality ratios (SMRs) among hospitals may be difficult if they differ in the location where initial stabilization takes place. The aim of this study was to assess to what extent predicted mortality risk would be affected if the APACHE-IV score was recalculated with the initial physiological variables from the ED. Secondly, to evaluate whether ED Length of Stay (LOS) was associated with a change (delta) in these APACHE-IV scores.

Methods

An observational multicenter cohort study including ICU patients admitted from the ED. Data from two Dutch quality registries were linked: the Netherlands Emergency department Evaluation Database (NEED) and the National Intensive Care Evaluation (NICE) registry. The ICU APACHE-IV, predicted mortality, and SMR based on data of the first 24 h of ICU admission were compared with an ED APACHE-IV model, using the most deviating physiological variables from the ED or ICU.

Results

A total of 1398 patients were included. The predicted mortality from the ICU APACHE-IV (median 0.10; IQR 0.03–0.30) was significantly lower compared to the ED APACHE-IV model (median 0.13; 0.04–0.36; p < 0.01). The SMR changed from 0.63 (95%CI 0.54–0.72) to 0.55 (95%CI 0.47–0.63) based on ED APACHE-IV. Predicted mortality risk changed more than 5% in 321 (23.2%) patients by using the ED APACHE-IV. ED LOS > 3.9 h was associated with a slight increase in delta APACHE-IV of 1.6 (95% CI 0.4–2.8) compared to ED LOS < 1.7 h.

Conclusion

Predicted mortality risks and SMRs calculated by the APACHE IV scores are not directly comparable in patients admitted from the ED if hospitals differ in their policy to stabilize patients in the ED before ICU admission. Future research should focus on developing models to adjust for these differences.