bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis
Authors: Menéndez-Gutiérrez María Piedad , Porcuna Jesús , Nayak Ramesh , Paredes Ana , Niu Haixia , Núñez Vanessa , Paranjpe Aditi , Gómez Manuel J. , Bhattacharjee Anukana , Schnell Daniel J. , Sánchez-Cabo Fátima , Welch John S. , Salomonis Nathan , Cancelas Jose A. , Ricote Mercedes
Published: November 2022

Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain hematopoietic fitness throughout life. In steady-state conditions, HSC exhaustion is prevented by the maintenance of most HSCs in a quiescent state, with cells entering the cell cycle only occasionally. HSC quiescence is regulated by retinoid and fatty-acid ligands of transcriptional factors of the nuclear retinoid X receptor (RXR) family. Herein, we show that dual deficiency for hematopoietic RXRα and RXRβ induces HSC exhaustion, myeloid cell/megakaryocyte differentiation, and myeloproliferative-like disease. RXRα and RXRβ maintain HSC quiescence, survival, and chromatin compaction; moreover, transcriptome changes in RXRα;RXRβ-deficient HSCs include premature acquisition of an aging-like HSC signature, MYC pathway upregulation, and RNA intron retention. Fitness loss and associated RNA transcriptome and splicing alterations in RXRα;RXRβ-deficient HSCs are prevented by Myc haploinsufficiency. Our study reveals the critical importance of RXRs for the maintenance of HSC fitness and their protection from premature aging.
Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial
Authors: Fragoso-Saavedra Sergio , Núñez Isaac , Audelo-Cruz Belem M. , Arias-Martínez Sarahi , Manzur-Sandoval Daniel , Quintero-Villegas Alejandro , Benjamín García-González H. , Carbajal-Morelos Sergio L. , PoncedeLeón-Rosales Sergio , Gotés-Palazuelos José , Maza-Larrea José A. , Rosales-de la Rosa J. Javier , Diaz-Rivera Dafne , Luna-García Edgar , Piten-Isidro Elvira , Del Río-Estrada Perla M. , Fragoso-Saavedra Mario , Caro-Vega Yanink , Batina Isabella , Islas-Weinstein León , Iruegas-Nunez David A. , Calva Juan J. , Belaunzarán-Zamudio Pablo F. , Sierra-Madero Juan , Crispín José C. , Valdés-Ferrer Sergio Iván
Published: November 2022

Background:

Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19.

Methods:

We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described.

Results:

We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44–64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24–0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively).

Conclusion:

Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.
Bone marrow mesenchymal stem cell-derived exosomes shuttling miR-150-5p alleviates mechanical allodynia in rats by targeting NOTCH2 in microglia
Authors: Li Shuangqing , Huang Ciying , Tu Chao , Chen Ruiqi , Ren Xiaolei , Qi Lin , Li Zhihong
Published: November 2022

Background

This study probes into the function and mechanism of bone marrow mesenchymal stem cell (BMSC)-derived exosomes loaded with miR-150-5p in mechanical allodynia.

Methods

BMSCs were infected with miR-150-5p inhibition lentiviruses to obtain exosomes with low miR-150-5p expression. A L5 spinal nerve ligation (SNL) model was established in rats where exosomes, NOTCH2 overexpression/inhibition plasmids, or microglial cells were intrathecally administered. Hind paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of rats were measured. TUNEL staining was used to measure the apoptotic rate in rat spinal dorsal horn (SDH), ELISA to evaluate pro-inflammatory factor levels, and RT-qPCR, western blotting, and immunohistochemistry to detect miR-150-5p and NOTCH2 expression. Immunofluorescence was used for localizing exosomes and NOTCH2 and detecting the expression of OX42, a maker for microglia. Dual luciferase reporter and RNA pull down assays were performed to validate the putative binding between miR-150-5p and NOTCH2.

Results

NOTCH2 expressed at a high level and miR-150-5p was downregulated in SDH of SNL rats. Exosomes injected were localized in rat SDH. BMSC-exosomes or NOTCH2 downregulation increased PWT and PWL of SNL rats and reduced apoptosis and inflammation in SDH. In contrast, NOTCH2 overexpression aggravated mechanical allodynia and SDH injury. Moreover, inhibiting miR-150-5p in BMSC-exosomes offset the therapeutic effects of BMSC-exosomes. Microglia activation induced mechanical allodynia in wild rats, while intrathecal injection of microglial cells incubated with BMSC-exosomes showed alleviated mechanical allodynia in SNL rats. NOTCH2 was targeted by miR-150-5p.

Conclusion

BMSC-derived exosomal miR-150-5p alleviates mechanical allodynia by targeting NOTCH2 in microglial cells.
Proteomic analysis identifies a signature of disease severity in the plasma of COVID-19 pneumonia patients associated to neutrophil, platelet and complement activation
Authors: Ciccosanti Fabiola , Antonioli Manuela , Sacchi Alessandra , Notari Stefania , Farina Anna , Beccacece Alessia , Fusto Marisa , Vergori Alessandra , D’Offizi Gianpiero , Taglietti Fabrizio , Antinori Andrea , Nicastri Emanuele , Marchioni Luisa , Palmieri Fabrizio , Ippolito Giuseppe , Piacentini Mauro , Agrati Chiara , Fimia Gian Maria
Published: November 2022

Most patients infected with SARS-CoV-2 display mild symptoms with good prognosis, while 20% of patients suffer from severe viral pneumonia and up to 5% may require intensive care unit (ICU) admission due to severe acute respiratory syndrome, which could be accompanied by multiorgan failure.

Plasma proteomics provide valuable and unbiased information about disease progression and therapeutic candidates. Recent proteomic studies have identified molecular changes in plasma of COVID-19 patients that implied significant dysregulation of several aspects of the inflammatory response accompanied by a general metabolic suppression. However, which of these plasma alterations are associated with disease severity remains only partly characterized.

A known limitation of proteomic studies of plasma samples is the large difference in the macromolecule abundance, with concentration spanning at least 10 orders of magnitude. To improve the coverage of plasma contents, we performed a deep proteomic analysis of plasma from 10 COVID-19 patients with severe/fatal pneumonia compared to 10 COVID-19 patients with pneumonia who did not require ICU admission (non-ICU). To this aim, plasma samples were first depleted of the most abundant proteins, trypsin digested and peptides subjected to a high pH reversed-phase peptide fractionation before LC–MS analysis.

These results highlighted an increase of proteins involved in neutrophil and platelet activity and acute phase response, which is significantly higher in severe/fatal COVID-19 patients when compared to non-ICU ones. Importantly, these changes are associated with a selective induction of complement cascade factors in severe/fatal COVID-19 patients. Data are available via ProteomeXchange with identifier PXD036491. Among these alterations, we confirmed by ELISA that higher levels of the neutrophil granule proteins DEFA3 and LCN2 are present in COVID-19 patients requiring ICU admission when compared to non-ICU and healthy donors.

Altogether, our study provided an in-depth view of plasma proteome changes that occur in COVID-19 patients in relation to disease severity, which can be helpful to identify therapeutic strategies to improve the disease outcome.
Automated classification of protein expression levels in immunohistochemistry images to improve the detection of cancer biomarkers
Authors: Xue Zhen-Zhen , Li Cheng , Luo Zhuo-Ming , Wang Shan-Shan , Xu Ying-Ying
Published: November 2022

Background

The expression changes of some proteins are associated with cancer progression, and can be used as biomarkers in cancer diagnosis. Automated systems have been frequently applied in the large-scale detection of protein biomarkers and have provided a valuable complement for wet-laboratory experiments. For example, our previous work used an immunohistochemical image-based machine learning classifier of protein subcellular locations to screen biomarker proteins that change locations in colon cancer tissues. The tool could recognize the location of biomarkers but did not consider the effect of protein expression level changes on the screening process.

Results

In this study, we built an automated classification model that recognizes protein expression levels in immunohistochemical images, and used the protein expression levels in combination with subcellular locations to screen cancer biomarkers. To minimize the effect of non-informative sections on the immunohistochemical images, we employed the representative image patches as input and applied a Wasserstein distance method to determine the number of patches. For the patches and the whole images, we compared the ability of color features, characteristic curve features, and deep convolutional neural network features to distinguish different levels of protein expression and employed deep learning and conventional classification models. Experimental results showed that the best classifier can achieve an accuracy of 73.72% and an F1-score of 0.6343. In the screening of protein biomarkers, the detection accuracy improved from 63.64 to 95.45% upon the incorporation of the protein expression changes.

Conclusions

Machine learning can distinguish different protein expression levels and speed up their annotation in the future. Combining information on the expression patterns and subcellular locations of protein can improve the accuracy of automatic cancer biomarker screening. This work could be useful in discovering new cancer biomarkers for clinical diagnosis and research.
Discussion on the causes of thrombolysis failure in a patient with STEMI: a case report
Authors: Qiu Lingzhi , Li Jia , Yan Hua , Guo Hui , Song Dan , Su Xi
Published: November 2022

Background

Spontaneous coronary artery dissection (SCAD) has emerged as an increasingly diagnosed cause of ST-segment elevation myocardial infarction (STEMI), which is easily missed or delayed. The effective use of coronary angiography (CAG) and advanced intracoronary imaging examinations in STEMI patients has led to increased detection of SCAD.

Case presentation

A 59-year-old woman with acute angina pectoris was diagnosed with STEMI detected by electrocardiography combined with measurement of myocardial enzymes. Due to the ongoing pandemic of coronavirus disease 2019 (COVID-19) in Wuhan, she was first given thrombolytic therapy after excluding contraindications according to the requirements of the current consensus statement; however, subsequently, both the symptoms of ongoing chest pain and the electrocardiographic results indicated the failure of thrombolytic therapy, so the intervention team administered rescue percutaneous coronary intervention treatment under third-grade protection. CAG confirmed total occlusion in the distal left anterior descending (LAD) artery, with thrombolysis in myocardial infarction (TIMI) 0 flow, whereas the left circumflex and right coronary arteries appeared normal, with TIMI 3 flow. Intravenous ultrasound (IVUS) was further performed to investigate the causes of occlusion, which verified the absence of atherosclerosis but detected SCAD with intramural haematoma. During the operation, the guidewire reached the distal end of the LAD artery smoothly, the balloon was dilated slightly, and the reflow of TIMI blood could be seen by repeated CAG. During the follow-up period of one and a half years, the patient complained of occasional, slight chest tightness. The repeated CAG showed that the spontaneous dissection in the LAD artery had healed well, with TIMI 3 flow. The repeated IVUS confirmed that the SCAD and intramural haematoma had been mostly resorbed and repaired.

Conclusion

This was a case of failed STEMI thrombolysis in our hospital during the outbreak of COVID-19. This case indicates that doctors need to consider the cause of the disease when treating STEMI patients, especially patients without traditional cardiovascular risk factors. Moreover, CAG and intracoronary imaging examinations should be actively performed to identify the aetiology and improve the treatment success rate.
Enterovirus detection in different regions of Madagascar reveals a higher abundance of enteroviruses of species C in areas where several outbreaks of vaccine-derived polioviruses occurred
Authors: Razafindratsimandresy Richter , Joffret Marie-Line , Andriamandimby Soa Fy , Andriamamonjy Seta , Rabemanantsoa Sendraharimanana , Richard Vincent , Delpeyroux Francis , Heraud Jean-Michel , Bessaud Maël
Published: November 2022

Background

Poliomyelitis outbreaks due to pathogenic vaccine-derived polioviruses (VDPVs) are threatening and complicating the global polio eradication initiative. Most of these VDPVs are genetic recombinants with non-polio enteroviruses (NPEVs) of species C. Little is known about factors favoring this genetic macroevolution process. Since 2001, Madagascar has experienced several outbreaks of poliomyelitis due to VDPVs, and most of VDPVs were isolated in the south of the island. The current study explored some of the viral factors that can promote and explain the emergence of recombinant VDPVs in Madagascar.

Methods

Between May to August 2011, we collected stools from healthy children living in two southern and two northern regions of Madagascar. Virus isolation was done in RD, HEp-2c, and L20B cell lines, and enteroviruses were detected using a wide-spectrum 5ʹ-untranslated region RT-PCR assay. NPEVs were then sequenced for the VP1 gene used for viral genotyping.

Results

Overall, we collected 1309 stools, of which 351 NPEVs (26.8%) were identified. Sequencing revealed 33 types of viruses belonging to three different species: Enterovirus A (8.5%), Enterovirus B (EV-B, 40.2%), and Enterovirus C (EV-C, 51.3%). EV-C species included coxsackievirus A13, A17, and A20 previously described as putative recombination partners for poliovirus vaccine strains. Interestingly, the isolation rate was higher among stools originating from the South (30.3% vs. 23.6%, p-value = 0.009). EV-C were predominant in southern sites (65.7%) while EV-B predominated in northern sites (54.9%). The factors that explain the relative abundance of EV-C in the South are still unknown.

Conclusions

Whatever its causes, the relative abundance of EV-C in the South of Madagascar may have promoted the infections of children by EV-C, including the PV vaccine strains, and have favored the recombination events between PVs and NPEVs in co-infected children, thus leading to the recurrent emergence of recombinant VDPVs in this region of Madagascar.
A rare case report of primary Sjögren’s syndrome with clinical characteristics similar to those of CLIPPERS
Authors: Lv ChenLing , Zhu FeiYan , Chen Chao , Wang YunLing , Guo DengJun , Zhang ZhenZhong
Published: November 2022

Background

Primary Sjögren’s syndrome (pSS) is an autoimmune inflammatory disease characterized by dryness of the eyes, mouth and other mucous membranes. Patients with pSS can also present with extraglandular manifestations, such as pulmonary, kidney and nervous system involvement. Central nervous system (CNS) manifestations have rarely been described in pSS.

Case presentation

A 33-year-old man was admitted with a one-month history of dizziness, speech disturbance, and walking instability. His brain enhanced magnetic resonance imaging (MRI) showed symmetrical, enhanced “salt-and-pepper-like” speckled lesions in the brainstem, basal ganglia, and subcortical regions, and his diagnosis was considered possible chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Further examination revealed that anti-SSA antibody was positive, and the Schirmer test and labial salivary gland histopathology were abnormal, which supported the diagnosis of pSS.

Conclusion

pSS is a chronic systemic autoimmune disease that involves neurological complications. This case suggests that CNS lesions of pSS can present with clinical and MRI findings similar to those of CLIPPERS.
Breast Cancer Subtypes in Northern Thailand and Barriers to satisfactory survival outcomes
Authors: Ditsatham Chagkrit , Sripan Patumrat , Chaiwun Benjaporn , Klunklin Pitchayaponne , Tharavichitkul Ekkasit , Chakrabandhu Somvilai , Muangwong Pooriwat , Chitapanarux Imjai
Published: November 2022

Background:

The incidence of breast cancer (BC) in Thailand has been rising at an alarming rate. The annual incidence of BC in Thailand has doubled over a span of 15 years. A retrospective study was conducted with the primary objective of assessing and comparing survival rates of patients with BC, stratified by subtype of BC.

Methods:

A retrospective study was implemented for a cohort of women receiving a diagnosis of invasive BC with the objective of assessing and comparing their overall survival, stratified by BC subtype. Thai women receiving a diagnosis of their first primary invasive BC between January 2006 and December 2015 at Chiang Mai University Hospital were studied with 3,150 cases meeting the eligible criteria.

Results:

The median follow-up time was 4.9 years (Inter Quartile Range: 2.8–7.7). The most common diagnosed subtype was luminal B-like (n = 1,147, 36.4%). It was still the most prevalent subtype (35.8%) in women younger than 40 years and the 40–60 age-group, The proportion of patients with TNBC is the highest in women aged less than 40 years with 19.3% compared to the other age categories. Finally, among women older than 60 years, the proportion of each subtype was relatively uniform. Most women received a diagnosis of stage II disease. Triple negative subtype increased overall mortality in advanced staging (stages III and IV) (aHR:1.42, 95% CI: 0.96–2.11). The 5-year overall survival rate was found in luminal A-like at 82.8%, luminal B-like at 77.6%, HER-2 enriched at 66.4% and triple negative subtype at 64.2%.

Conclusion:

The histologic subtype, correlated with age and staging influenced the OS. Our results confirmed the association of triple negative BC with poor prognosis especially in advanced stage. The adjuvant medical treatment in our country could not be accessible in some group of patients, so the results of treatment and survival especially HER-2 enriched are lower than other countries without treatment barrier.
Differential properties of KRAS transversion and transition mutations in non-small cell lung cancer: associations with environmental factors and clinical outcomes
Authors: Sato Koichi , Akamatsu Hiroaki , Koh Yasuhiro , Ogawa Koichi , Isa Shun-ichi , Ando Masahiko , Tamiya Akihiro , Kubo Akihito , Kitagawa Chiyoe , Kawaguchi Tomoya , Yamamoto Nobuyuki
Published: November 2022

Background

KRAS-mutated non-small cell lung cancer (NSCLC) accounts for 23–35% and 13–20% of all NSCLCs in white patients and East Asians, respectively, and is therefore regarded as a major therapeutic target. However, its epidemiology and clinical characteristics have not been fully elucidated because of its wide variety of mutational subtypes. Here, we focused on two distinct base substitution types: transversion mutations and transition mutations, as well as their association with environmental factors and clinical outcome.

Methods

Dataset from the Japan Molecular Epidemiology Study, which is a prospective, multicenter, and molecular study epidemiology cohort study involving 957 NSCLC patients who underwent surgery, was used for this study. Questionnaire-based detailed information on clinical background and lifestyles was also used to assess their association with mutational subtypes. Somatic mutations in 72 cancer-related genes were analyzed by next-generation sequencing, and KRAS mutations were classified into three categories: transversions (G > C or G > T; G12A, G12C, G12R, G12V), transitions (G > A; G12D, G12S, G13D), and wild-type (WT). Clinical correlations between these subtypes have been investigated, and recurrence-free survival (RFS) and overall survival (OS) were evaluated.

Results

Of the 957 patients, KRAS mutations were detected in 80 (8.4%). Of these, 61 were transversions and 19 were transitions mutations. Both pack-years of smoking and smoking duration had significant positive correlation with the occurrence of transversion mutations (p = 0.03 and < 0.01, respectively). Notably, transitions showed an inverse correlation with vegetable intake (p = 0.01). Patients with KRAS transitions had the shortest RFS and OS compared to KRAS transversions and WT. Multivariate analysis revealed that KRAS transitions, along with age and stage, were significant predictors of shorter RFS and OS (HR 2.15, p = 0.01; and HR 2.84, p < 0.01, respectively).

Conclusions

Smoking exposure positively correlated with transversions occurrence in a dose-dependent manner. However, vegetable intake negatively correlated with transitions. Overall, KRAS transition mutations are significantly poor prognostic factors among resected NSCLC patients.
Functional MRI radiomics-based assessment of pelvic bone marrow changes after concurrent chemoradiotherapy for cervical cancer
Authors: Qin Xiaohang , Wang Cong , Gong Guanzhong , Wang Lizhen , Su Ya , Yin Yong
Published: November 2022

Objectives

To quantify the dose-response relationship of changes in pelvic bone marrow (PBM) functional MR radiomic features (RF) during concurrent chemoradiotherapy (CCRT) for patients with cervical cancer and establish the correlation with hematologic toxicity to provide a basis for PBM sparing.

Methods

A total of 54 cervical cancer patients who received CCRT were studied retrospectively. Patients underwent MRI IDEAL IQ and T2 fat suppression (T2fs) scanning pre- and post-CCRT. The PBM RFs were extracted from each region of interest at dose gradients of 5–10 Gy, 10–15 Gy, 15–20 Gy, 20–30 Gy, 30–40 Gy, 40–50 Gy, and > 50 Gy, and changes in peripheral blood cell (PBC) counts during radiotherapy were assessed. The dose-response relationship of RF changes and their correlation with PBC changes were investigated.

Results

White blood cell, neutrophils (ANC) and lymphocyte counts during treatment were decreased by 49.4%, 41.4%, and 76.3%, respectively. Most firstorder features exhibited a significant dose-response relationship, particularly FatFrac IDEAL IQ, which had a maximum dose-response curve slope of 10.09, and WATER IDEAL IQ had a slope of − 7.93. The firstorder-Range in FAT IDEAL IQ and firstorder-10Percentile in T2fs, showed a significant correlation between the changes in ANC counts under the low dose gradient of 5–10 Gy (r = 0.744, -0.654, respectively, p < 0.05).

Conclusion

Functional MR radiomics can detect microscopic changes in PBM at various dose gradients and provide an objective reference for bone marrow sparing and dose limitation in cervical cancer CCRT.
Evaluating diagnostic and management agreement between audiology and ENT: a prospective inter-rater agreement study in a paediatric primary contact clinic
Authors: Eakin Jennifer , Michael Simone , Payten Christopher , Smith Tamsin , Stewart Vicky , Noonan Elle , Weir Kelly A.
Published: November 2022

Background

Ear, Nose and Throat (ENT) primary contact models of care use audiologists as the first triage point for children referred to ENT for middle ear and hearing concerns; and have shown reduced waiting time, improved ENT surgical conversion rates and increased service capacity. This study aimed to investigate ‘safety and quality’ of the model by looking at agreement between audiologists’ and an ENT’s clinical decisions. 

Methods

We performed an inter-rater agreement study on diagnosis and management decisions made by audiologists and an ENT for 50 children seen in an Australian hospital’s ENT primary contact service, and examined the nature and patterns of disagreements.

Results

Professionals agreed on at least one site-of-lesion diagnosis for all children (100%) and on the primary management for 74% (Gwet’s AC1 = 0.67). Management disagreements clustered around i) providing ‘watchful waiting’ versus sooner medical opinion (18%), and ii) providing monitoring versus discharge for children with no current symptoms (8%). There were no cases where the audiologist recommended discharge when the ENT recommended further medical opinion.

Conclusions

Our novel research provides further evidence that Audiologist-led primary contact models for children with middle ear and hearing concerns are safe as well as efficient.
A proposed feasible classification of common bile duct duplications based on a newly described variant and review of existing literature
Authors: Sheng Huixue , Chen Guiling , Yang Ming , Guan Hongmei
Published: November 2022

Background

Duplication of the common bile duct (CBD) is extremely rare among the anatomical variations in the biliary tract system, which presents a septum within the CBD or an accessory CBD. In our study, we report a rare case of duplication of the common bile duct combined congenital biliary dilatation.we present a rare case of a septum in the dilated biliary tract.

Case presentation

We reported a 5-year-old Asian girl who had history of repeated abdominal pain for 4 days and aggravated for 1 day. Magnetic resonance cholangiopancreatography (MRCP) examination revealed duplicated common bile duct (DCBD) malformation with congenital biliary dilatation and distal cholelithiasis. The patient underwent choledochal cyst resection and biliary tract reconstruction and abdominal cavity irrigation and drainage under general anesthesia. A septum was found within the common bile duct during the operation. The septum divided the extrahepatic bile duct into two parts connected to the left and right hepatic ducts respectively and the gallbladder is attached to the repeated right bile duct which was not previously reported in the literature.

Conclusions

We complement and adjust the classification of common bile duct duplication by reviewing the literature.
Effect of AI-assisted software on inter- and intra-observer variability for the X-ray bone age assessment of preschool children
Authors: Zhao Kai , Ma Shuai , Sun Zhaonan , Liu Xiang , Zhu Ying , Xu Yufeng , Wang Xiaoying
Published: November 2022

Background

With the rapid development of deep learning algorithms and the rapid improvement of computer hardware in the past few years, AI-assisted diagnosis software for bone age has achieved good diagnostic performance. The purpose of this study was to investigate the effect of AI-assisted software on residents’ inter-observer agreement and intra-observer reproducibility for the X-ray bone age assessment of preschool children.

Methods

This prospective study was approved by the Institutional Ethics Committee. Six board-certified residents interpreted 56 bone age radiographs ranging from 3 to 6 years with structured reporting by the modified TW3 method. The images were interpreted on two separate occasions, once with and once without the assistance of AI. After a washout period of 4 weeks, the radiographs were reevaluated by each resident in the same way. The reference bone age was the average bone age results of the three experts. Both TW3-RUS and TW3-Carpal were evaluated. The root mean squared error (RMSE), mean absolute difference (MAD) and bone age accuracy within 0.5 years and 1 year were used as metrics of accuracy. Interobserver agreement and intraobserver reproducibility were evaluated using intraclass correlation coefficients (ICCs).

Results

With the assistance of bone age AI software, the accuracy of residents’ results improved significantly. For interobserver agreement comparison, the ICC results with AI assistance among 6 residents were higher than the results without AI assistance on the two separate occasions. For intraobserver reproducibility comparison, the ICC results with AI assistance were higher than results without AI assistance between the 1st reading and 2nd reading for each resident.

Conclusions

For preschool children X-ray bone age assessment, in addition to improving diagnostic accuracy, bone age AI-assisted software can also increase interobserver agreement and intraobserver reproducibility. AI-assisted software can be an effective diagnostic tool for residents in actual clinical settings.
Public preferences regarding the priority setting criteria of health interventions for budget allocation: results of a survey of Iranian adults
Authors: Darvishi Ali , Daroudi Rajabali , Yaseri Mehdi , Sari Ali Akbari
Published: November 2022

Objectives

Priority setting in health directly impacts the general public as payers and final consumers, so the public preferences must be considered. The present study aimed to provide public preferences about health intervention allocation criteria for the optimal allocation of public health budget in Iran.

Methods

A choice-based survey method was used to assess the general public’s preferences regarding 8 critical criteria with a societal aspect. One thousand sixty-four adult citizens of Tehran, Iran, participated in the study. Participants were asked to allocate a hypothetical budget between the two groups with differences in allocation criteria. Public preferences were inferred from absolute majority responses i.e., more than 50% of participants’ allocation for a criterion. The Logistic Regression Model was used to investigate the factors affecting the preferences regarding the importance of allocation criteria.

Results

Based on expressed participants’ preferences, criteria of disease severity, age, daily care needs, Number of alternative interventions, individual’s economic status, and diseases with absence from work were important. Thus, 77, 69, 61, 57, 54, and 51% of participants preferred to allocate the hypothetical budget to the treatment of patients with poor economic status, treatment of patients with diseases leading to absence from work, treating patients with severe diseases, treatment of diseases in need of daily care and treatment of children’s diseases, respectively. Findings from the factors affecting participants’ preferences regarding allocation criteria also showed that people with different characteristics had different preferences.

Conclusions

Iranian general public pays special attention to the criteria of equitable allocation, including patients’ economic status, criteria with societal aspects such as absenteeism from work and the need for daily care, as well as criteria with medical aspects such as disease severity and access to alternative interventions which may sometimes be less considered in decision making.
Developmental disparities in sedentary time by period of the day among US youth: a cross-sectional study
Authors: Santiago-Rodríguez María Enid , Chen Jinsong , Pfeiffer Karin A. , Marquez David X. , Odoms-Young Angela , Bustamante Eduardo Esteban
Published: November 2022

Background

Definitive evidence shows sedentary time (ST) is an independent risk factor for chronic disease, irrespective of physical activity. Despite calls to limit youth ST, studies demonstrate a spike in ST at the transition from childhood to adolescence. Identifying periods of the day (e.g., before school, during school, afterschool, and evenings) during which ST is higher in adolescents vs. children—that is, specifying when within daily routines ST disparities emerge—may be important to inform intervention strategies, as periods of the day correspond with variations in setting and supervision. The purpose of this study was to examine device-assessed ST engagement by period of day and developmental stage in a nationally representative sample of United States youth.

Methods

Youth (N = 2,972 between 6–18 years) from the 2003–2004 and 2005–2006 waves of NHANES reported demographic variables and wore an accelerometer for seven consecutive days to determine ST. Linear regression analyses were applied to study associations between ST and developmental stage (childhood or adolescence) by period of the week and weekend days, while controlling for sex, race/ethnicity, annual family income, and body mass index.

Results

Adjusted linear regressions (p-values < 0.0001) showed that adolescents were more sedentary than children during school, afterschool, and weekday evening periods as well as all the weekend periods. However, during school (36.3 ± 7.3 vs. 28.2 ± 7.2 min/hour; b = -7.4 [-8.1, -6.6]) and afterschool periods (31.1 ± 7.7 vs. 22.7 ± 7.0 min/hour; b = -7.8 [-8.6, -7.0]) showed the largest weekly ST disparities by developmental stage. Overall, the during school and after school hours constitute most (during school = 35% and afterschool = 16%) of the weekly ST disparity between children and adolescents.

Conclusions

Our data provide interventionists with estimates of the potential for ST reduction in each setting and period of the day among US adolescents. Future research should gather information about the barriers and facilitators of ST in adolescents by period of the day to help understand factors driving disparities.
Prediction of exercise-induced desaturation in COPD patients without resting hypoxemia: a retrospective study
Authors: Yang Lulu , Shi Minghui , Situ Xuanming , He Jiaze , Qumu Shiwei , Yang Ting
Published: November 2022

Background

There is no universally accepted criterion for assessing exercise-induced desaturation (EID). The purpose of this study is to compare the two methods regularly used for determining EID in COPD patients, as well as to explore the risk factors and predictors related to EID.

Methods

The 6MWT was performed with continuous SpO2monitoring on patients with stable COPD. Using two methods (method A: “SpO2rest–SpO2min ≥ 4% and/or SpO2min < 90%”, method B: “SpO2rest–SpO2end ≥ 4% and/or SpO2end < 90%”) as EID determination criteria to assess the incidence of EID. The differences and consistency of the two methods are compared. Moreover, we collected data through the pulmonary function test, mMRC dyspnea score, COPD assessment test, BODE index and CT-defined emphysema. Univariate and multivariate logistic regression analyses were used to identify factors affecting the EID. For the parameters that predict EID in 6MWT, a receiver operating characteristic (ROC) curve analysis was employed.

Results

The analysis included 124 patients. The overall incidence of EID was 62.1% by using method A as the criterion and 51.6% by method B. All of the EID patients found by method B were included in the EID patients identified by method A, as well as 13 new-EID patients. The difference in diagnostic outcomes between the two approaches was not statistically significant (P > 0.05), but they were in excellent agreement (Kappa = 0.807,P = 0.001). Logistic regression analyses found that DLCO SB% pred, DLCO/VA% pred, CAT score, mean density, PD15, emphysema volume and %LAA were significant determinants of the EID. For predicting EID, the ROC analysis produced AUC and cutoffs of 0.689 and 50.45% (DLCO SB% pred), 0.707 and 75.0% (DLCO/VA% pred), 0.727 and 15 points (CAT score), 0.691 and − 955.00HU (PD15), 0.671 and − 856.46HU (mean density), 0.668 and 338.14 ml (emphysema volume) and 0.656 and 7.63% (%LAA), respectively.

Conclusions

Two methods evaluating EID in this research are in a good agreement, method A can find more EID patients by focusing on SpO2min.When conditions are constrained, it is also sufficient to assess EID in COPD patients by method B. In terms of the predictors of EID, DLCO SB% pred, DLCO/VA% pred, CAT score and CT-defined emphysema are all statistically significant test variables to determine EID.
The use of video consultations to support orthopedic patients' treatment at the interface of a clinic and general practitioners
Authors: K Estel , L Richter , G Weber , F Fellmer , S Märdian , C Willy , DA Back
Published: November 2022

Introduction

Video consultations have proven to be a powerful support tool for patient–doctor interactions in general, not only during the COVID-19 pandemic. This study analyzed the feasibility and usefulness of orthopedic telemedical consultations (OTCs) for orthopedic patients at the interface of a clinic and general practitioners.

Methods

The study was carried out at an orthopedic department of a German hospital between April 2020 and October 2020. After written informed consent was obtained, general practitioners (GPs) of a large adjunct health region could present their patients with orthopedic pathologies to specialists at the hospital via OTCs instead of the usual live consultation (LC). The patients, specialists and GPs were evaluated for their OTC experience and attitude (5-point Likert-scale and open questions, 19 to 27 items).

Results

A total of 89 video consultations took place with 76 patients, 16 GPs and six specialists. The average distance between the GPs/patients and the hospital was 141.9 km. The OTCs were rated as pleasant, and the experience was rated as very satisfying (average Likert-Scale rating, with 5 as strong agreement: specialists = 4.8; GPs = 4.9; patients = 4.7). Following the OTC, a LC was not necessary in 76.4% of cases. Patients with a necessary LC after an OTC showed significantly lower satisfaction with the OTC (p = 0.005). Time savings, the elimination of travel and quick contact with orthopedic consultants were positively highlighted by the participants. A total of 123 recommendations for further treatment were given, such as the initiation of physiotherapy/medication and the use of imaging diagnostics. Different technical and organizational challenges could be identified and addressed.

Discussion

The vast majority of the participants stated they had a very positive impression. In particular, the potential savings in travel and time as well as straightforward contact with specialists were rated positively. However, limitations in the assessment of initial presentations of complex medical conditions were also highlighted. Further studies on OTCs with a consultative health professional may show other fields of use for this mode of interdisciplinary remote communication.
Sagittal intervertebral rotational motion: a deep learning-based measurement on flexion–neutral–extension cervical lateral radiographs
Authors: Yan Yuting , Zhang Xinsheng , Meng Yu , Shen Qiang , He Linyang , Cheng Guohua , Gong Xiangyang
Published: November 2022

Background

The analysis of sagittal intervertebral rotational motion (SIRM) can provide important information for the evaluation of cervical diseases. Deep learning has been widely used in spinal parameter measurements, however, there are few investigations on spinal motion analysis. The purpose of this study is to develop a deep learning-based model for fully automated measurement of SIRM based on flexion–neutral–extension cervical lateral radiographs and to evaluate its applicability for the flexion–extension (F/E), flexion–neutral (F/N), and neutral–extension (N/E) motion analysis.

Methods

A total of 2796 flexion, neutral, and extension cervical lateral radiographs from 932 patients were analyzed. Radiographs from 100 patients were randomly selected as the test set, and those from the remaining 832 patients were used for training and validation. Landmarks were annotated for measuring SIRM at five segments from C2/3 to C6/7 on F/E, F/N, and N/E motion. High-Resolution Net (HRNet) was used as the main structure to train the landmark detection network. Landmark performance was assessed according to the percentage of correct key points (PCK) and mean of the percentage of correct key points (MPCK). Measurement performance was evaluated by intra-class correlation coefficient (ICC), Pearson correlation coefficient, mean absolute error (MAE), root mean square error (RMSE), and Bland-Altman plots.

Results

At a 2-mm distance threshold, the PCK for the model ranged from 94 to 100%. Compared with the reference standards, the model showed high accuracy for SIRM measurements for all segments on F/E and F/N motion. On N/E motion, the model provided reliable measurements from C3/4 to C6/7, but not C2/3. Compared with the radiologists’ measurements, the model showed similar performance to the radiologists.

Conclusions

The developed model can automatically measure SIRM on flexion–neutral–extension cervical lateral radiographs and showed comparable performance with radiologists. It may provide rapid, accurate, and comprehensive information for cervical motion analysis.
Nonunion of humeral medial condyle fracture caused by excessive functional exercise: a case report and review of the literature
Authors: Yang Liu , Xia Feng , Guo Jia-chao , Wang Xiao-lin , He Jin-peng , Shao Jing-fan
Published: November 2022

Background

Medial epicondyle fractures are one of the more common humerus fractures, but humeral medial condyle fracture (HMCF) is rare. Nonunion of medial humeral condyle fractures due to functional exercise is less common.

Case presentation

We report a 5-year-old patient with a nonunion HMCF due to excessive functional exercise, who bruised the elbow 1 year ago and had no positive findings on all imaging studies. On this physical examination, there was a snapping and palpable lump in the elbow joint during movement, but the patient did not feel any discomfort and the range of motion of the joint was normal. X rays and computed tomography (CT) showed that the left HMCF was discontinuous, the broken ends were dislocated, and the joint alignment was poor. Open reduction (OR) and screw fixation was used during the operation, and the patient recovered well at 3-month follow-up.

Conclusions

The rarity and low radiographic appearance of displaced HMCF are easily overlooked and can eventually lead to nonunion HMCF, especially when radiographically difficult to visualize before age 5 years. Therefore, regardless of whether there are signs or imaging abnormalities in the growth process of adolescents, they should be vigilant, shorten the time interval for re-examination, and early detection and timely treatment can avoid some complications caused by this.
Cortical screw placement with a spinous process clamp guide: a cadaver study accessing accuracy
Authors: Zhang Xi-nuo , Zhang Yi-qi , Liu Yu-zeng , Su Qing-jun , Guan Li , Li Dong-yue , Pei Bao-qing , Pan Ai-xing , Yang Hong-hao , Ding Hong-tao , Hai Yong , Zhou Li-jin
Published: November 2022

Background and objective

The Cortical Bone Trajectory (CBT) technique provides an alternative method for fixation in the lumbar spine in patients with osteoporosis. An accuracy CBT screw placement could improve mechanical stability and reduce complication rates.

Purpose

The purpose of this study is to explore the accuracy of cortical screw placement with the application of implanted spinous process clip (SPC) guide.

Methods and materials

Four lumbar specimens with T12-S1 were used to access the accuracy of the cortical screw. The SPC-guided planning screws were compared to the actual inserted screws by superimposing the vertebrae and screws preoperative and postoperative CT scans. According to preoperative planning, the SPC guide was adjusted to the appropriate posture to allow the K-wire drilling along the planned trajectory. Pre and postoperative 3D-CT reconstructions was used to evaluate the screw accuracy according to Gertzbein and Robbins classification. Intraclass correlation coefficients (ICCs) and Bland–Altman plots were used to examine SPC-guided agreements for CBT screw placement.

Results

A total of 48 screws were documented in the study. Clinically acceptable trajectory (grades A and B) was accessed in 100% of 48 screws in the planning screws group, and 93.8% of 48 screws in the inserted screws group (p = 0.242). The incidence of proximal facet joint violation (FJV) in the planning screws group (2.1%) was comparable to the inserted screws group (6.3%) (p = 0.617). The lateral angle and cranial angle of the planned screws (9.2 ± 1.8° and 22.8 ± 5.6°) were similar to inserted screws (9.1 ± 1.7° and 23.0 ± 5.1°, p = 0.662 and p = 0.760). Reliability evaluated by intraclass correlation coefficients and Bland–Altman showed good consistency in cranial angle and excellent results in lateral angle and distance of screw tip.

Conclusions

Compared with preoperative planning screws and the actually inserted screws, the SPC guide could achieve reliable execution for cortical screw placement.
Patients with ectopic ACTH syndrome might have a better prognosis in bronchopulmonary carcinoids with lymph node metastasis received radical surgery: a single-centre retrospective study in the last 22 years in China
Authors: Gao Chao , Zhang Jiaqi , Wang Yadong , Huang Cheng , Zhang Ye , Chen Yeye , Li Shanqing
Published: November 2022

Background

Bronchopulmonary carcinoids (BPCs) are rare malignancies but are known to be one of the most common causes of the ectopic adrenocorticotropic hormone (ACTH) syndrome. Surgery is the mainstay of therapy and one key question considering surgical treatment is the impact of local lymph node metastases. We sought to determine the risk factors and prognosis of LN metastases in resected carcinoid patients.

Methods

Data of 42 patients of BPCs with lymph node metastasis who received radical surgery in Peking Union Medical College Hospital (PUMCH) from Jan 2000 to Dec 2021 were retrospectively analysed. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier curves. Independent prognostic factors were assessed by COX hazard proportion model.

Results

It was indicated that in patients received radical surgery with local lymph node positive of BPCs, the 5-year OS and PFS rate was 74.5%, 68.3%, respectively. Multivariate Cox regression indicated that ectopic ACTH syndrome (EAS) could predict significantly to a better OS and PFS. In the subgroup analysis, the age, tumor size, Ki-67 index, histology and postoperative chemotherapy in patients with EAS had significantly differences with those without EAS.

Conclusions

Our study certified R0 resection with lymphadenectomy was effective in patients with lymph nodal positive. The ectopic ACTH syndrome was a protective factor for a better prognosis, which could provide clear evidence for operations.