bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology and outcomes associated with carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Pseudomonas aeruginosa: a retrospective cohort study
Authors: Vivo Amanda , Fitzpatrick Margaret A. , Suda Katie J. , Jones Makoto M. , Perencevich Eli N. , Rubin Michael A. , Ramanathan Swetha , Wilson Geneva M. , Evans Martin E. , Evans Charlesnika T.
Published: May 2022

Background

Carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a growing threat. The objective of this study was to describe CRAB and CRPA epidemiology and identify factors associated with mortality and length of stay (LOS) post-culture.

Methods

This was a national retrospective cohort study of Veterans with CRAB or CRPA positive cultures from 2013 to 2018, conducted at Hines Veterans Affairs Hospital. Carbapenem resistance was defined as non-susceptibility to imipenem, meropenem and/or doripenem. Multivariable cluster adjusted regression models were fit to assess the association of post-culture LOS among inpatient and long-term care (LTC) and to identify factors associated with 90-day and 365-day mortality after positive CRAB and CRPA cultures.

Results

CRAB and CRPA were identified in 1,048 and 8,204 unique patients respectively, with 90-day mortality rates of 30.3% and 24.5% and inpatient post-LOS of 26 and 27 days. Positive blood cultures were associated with an increased odds of 90-day mortality compared to urine cultures in patients with CRAB (OR 6.98, 95% CI 3.55–13.73) and CRPA (OR 2.82, 95% CI 2.04–3.90). In patients with CRAB and CRPA blood cultures, higher Charlson score was associated with increased odds of 90-day mortality. In CRAB and CRPA, among patients from inpatient care settings, blood cultures were associated with a decreased LOS compared to urine cultures.

Conclusions

Positive blood cultures and more comorbidities were associated with higher odds for mortality in patients with CRAB and CRPA. Recognizing these factors would encourage clinicians to treat these patients in a timely manner to improve outcomes of patients infected with these organisms.
Combined model of radiomics, clinical, and imaging features for differentiating focal pneumonia-like lung cancer from pulmonary inflammatory lesions: an exploratory study
Authors: Gong Jun-wei , Zhang Zhu , Luo Tian-you , Huang Xing-tao , Zhu Chao-nan , Lv Jun-wei , Li Qi
Published: May 2022

Background

Only few studies have focused on differentiating focal pneumonia-like lung cancer (F-PLC) from focal pulmonary inflammatory lesion (F-PIL). This exploratory study aimed to evaluate the clinical value of a combined model incorporating computed tomography (CT)-based radiomics signatures, clinical factors, and CT morphological features for distinguishing F-PLC and F-PIL.

Methods

In total, 396 patients pathologically diagnosed with F-PLC and F-PIL from two medical institutions between January 2015 and May 2021 were retrospectively analyzed. Patients from center 1 were included in the training (n = 242) and internal validation (n = 104) cohorts. Moreover, patients from center 2 were classified under the external validation cohort (n = 50). The clinical and CT morphological characteristics of both groups were compared first. And then, a clinical model incorporating clinical and CT morphological features, a radiomics model reflecting the radiomics signature of lung lesions, and a combined model were developed and validated, respectively.

Results

Age, gender, smoking history, respiratory symptoms, air bronchogram, necrosis, and pleural attachment differed significantly between the F-PLC and F-PIL groups (allP < 0.05). For the clinical model, age, necrosis, and pleural attachment were the most effective factors to differentiate F-PIL from F-PLC, with the area under the curves (AUCs) of 0.838, 0.819, and 0.717 in the training and internal and external validation cohorts, respectively. For the radiomics model, five radiomics features were found to be significantly related to the identification of F-PLC and F-PIL (allP < 0.001), with the AUCs of 0.804, 0.877, and 0.734 in the training and internal and external validation cohorts, respectively. For the combined model, five radiomics features, age, necrosis, and pleural attachment were independent predictors for distinguishing between F-PLC and F-PIL, with the AUCs of 0.915, 0.899, and 0.805 in the training and internal and external validation cohorts, respectively. The combined model exhibited a better performance than had the clinical and radiomics models.

Conclusions

The combined model, which incorporates CT-based radiomics signatures, clinical factors, and CT morphological characteristics, is effective in differentiating F-PLC from F-PIL.
Role of electrocardiogram findings in predicting 48-h mortality in patients with traumatic brain injury
Authors: Lee Ji Ho , Lee Dong Hun , Lee Byung Kook , Cho Yong Soo , Kim Dong Ki , Jung Yong Hun
Published: May 2022

Objective

Electrocardiogram (ECG) patterns can change, especially in patients with central nervous system disorders such as spontaneous subarachnoid hemorrhage. However, the association between the prognosis of traumatic brain injury (TBI) and ECG findings is unknown. Therefore, this study aimed to compare and to analyze ECG findings to predict early mortality in patients with TBI.

Methods

This retrospective observational study included patients with severe trauma and TBI who were admitted to the emergency department (ED) between January 2018 and December 2020. TBI was defined as an abbreviated injury scale score of the head of ≥3. We examined ECG findings, including PR prolongation (≥ 200 ms), QRS complex widening (≥ 120 ms), corrected QT interval prolongation (QTP, ≥ 480 ms), ST-segment elevation, and ST-segment depression (STD) at ED arrival. The primary outcome was 48-h mortality.

Results

Of the total patients with TBI, 1024 patients were included in this study and 48-h mortality occurred in 89 patients (8.7%). In multivariate analysis, QTP (odds ratio [OR], 2.017; confidence interval [CI], 1.203–3.382) and STD (OR, 8.428; 95% CI, 5.019–14.152) were independently associated with 48-h mortality in patients with TBI. The areas under the curve (AUCs) of the revised trauma score (RTS), injury severity score (ISS), QTP, STD, and the combination of QTP and STD were 0.790 (95% CI, 0.764–0.815), 0.632 (95% CI, 0.602–0.662), 0.605 (95% CI, 0.574–0.635), 0.723 (95% CI, 0.695–0.750), and 0.786 (95% CI, 0.759–0.811), respectively. The AUC of the combination of QTP and STD significantly differed from that of ISS, QTP, and STD, but not RTS.

Conclusion

Based on the ECG findings, QTP and STD were associated with 48-h mortality in patients with TBI.
The risk for future cerebrovascular disease in pregnant women with Moyamoya disease: a nationwide population-based study in South Korea
Authors: Jeong Yeonseong , Jung Yun Ji , Noh Eunjin , Ha Sungyeon , Hwang Jeongeun , Cho Geum Joon , Oh Min-Jeong , Kim Young-Han
Published: May 2022

Background

Physiologic changes during pregnancy affect the development of postpartum cerebrovascular disease (CVD) in women with Moyamoya disease. Due to the rare prevalence of Moyamoya disease and its large regional variations, large-scale based studies on the risk of CVD after delivery have not been conducted. This study aimed to evaluate whether women with Moyamoya disease have an increased risk of CVD after delivery.

Methods

Research data was collected from the National Health Insurance Claims Database of the Health Insurance Review and Assessment Service. Patients who delivered in Korea from 2007 to 2014 were enrolled in this study. We classified women as having CVD if they were diagnosed with any of the following conditions between delivery and December 31, 2016; cerebral infarction (I63.X in the International Classification of Diseases-10th Revision [ICD-10]) and/or intracranial hemorrhage (I61.X, I62.X in ICD-10) and/or subarachnoid hemorrhage (I60.X in ICD-10). Women with Moyamoya disease were identified as having I67.5 in ICD-10. We matched the study cohort by the ratio of 1:10 to analyze the risk CVD occurrence. The matching technique applied in this study was based on the variables of age and parity. To evaluate the adjusted hazard ratio (HR) for CVD in women with Moyamoya disease, we used multivariate Cox proportional hazard regression.

Results

Among a total of 3,611,216 Korean women who underwent delivered, we identified 412 women with Moyamoya disease diagnosis and 1420 age- and parity-matched women without Moyamoya disease (control). Compared to the control group, women with Moyamoya disease had a significantly higher rate of Cesarean section, overt DM, and essential hypertension (all p < 0.0001). Among women with Moyamoya disease, 55 (13.35%) women developed CVD within the follow-up postpartum period. The presence of Moyamoya disease was associated with an increased risk of CVD after delivery (adjusted HR 37.42; 95% confidence interval (CI) 17.50-80.02 within 2.3 years) after adjusting for pregnancy-induced hypertension, gestational diabetes mellitus, pregestational diabetes, chronic hypertension.

Conclusion

This population based study showed that the occurrence rate of CVD after delivery was higher in women with Moyamoya disease than in those without. Therefore, careful and long-term postpartum surveillance is required for women with Moyamoya disease.
HMGB1 mediates invasion and PD-L1 expression through RAGE-PI3K/AKT signaling pathway in MDA-MB-231 breast cancer cells
Authors: Amornsupak Kamolporn , Thongchot Suyanee , Thinyakul Chanida , Box Carol , Hedayat Somaieh , Thuwajit Peti , Eccles Suzanne A. , Thuwajit Chanitra
Published: May 2022

Background

High-mobility group box 1 (HMGB1) is increased in breast cancer cells as the result of exposure to the secreted substances from cancer-associated fibroblasts and plays a crucial role in cancer progression and drug resistance. Its effect, however, on the expression of programmed death ligand 1 (PD-L1) in breast cancer cells has not been investigated. This study aimed to investigate the mechanism of HMGB1 through receptors for advanced glycation end products (RAGE) on cell migration/invasion and PD-L1 expression in breast cancer cells.

Methods

A 3-dimensional (3-D) migration and invasion assay and Western blotting analysis to evaluate the function and the mechanism under recombinant HMGB1 (rHMGB1) treatment with knockdown of RAGE using shRAGE and PI3K/AKT inhibitors was performed.

Results

The results revealed that rHMGB1 induced MDA-MB-231 cell migration and invasion. The knockdown of RAGE using shRAGE and PI3K/AKT inhibitors attenuated 3-D migration and invasion in response to rHMGB1 compared to mock cells. PD-L1 up-regulation was observed in both parental MDA-MB-231 (P) and MDA-MB-231 metastasis to bone marrow (BM) cells treated with rHMGB1, and these effects were alleviated in RAGE-knock down (KD) breast cancer cells as well as in PI3K/AKT inhibitor-treated cells.

Conclusions

Collectively, these findings indicate that HMGB1-RAGE through PI3K/AKT signaling promotes not only breast cancer cell invasion but also PD-L1 expression which leads to the destruction of the effector T cells. The attenuating HMGB1-RAGE-PI3K/AKT pathway may help to attenuate breast cancer cell aggressive phenotypes.
Reproducibility of a protocol for standardized reading of chest X-rays of children household contact of patients with tuberculosis
Authors: Lozano-Acosta María Margarita , Rubiano-Arenas María Alejandra , Cadavid Lina Marcela , Vélez-Parra Guillermo , Molinares Beatriz , Marín-Pineda Diana Marcela , Arbeláez-Montoya María Patricia , Benjumea-Bedoya Dione
Published: May 2022

Background

The interpretation of the chest radiograph may vary because it depends on the reader and due to the non-specificity of findings in tuberculosis (TB). We aim to assess the reproducibility of a standardized chest radiograph reading protocol in contacts of patients with pulmonary TB under the 5 years of age.

Methods

Descriptive, cross-sectional study with children under the age of five, household contacts of patients with confirmed pulmonary TB from Medellín, Bello and Itagüí (Colombia) between Jan-01–2015 and May-31–2016. Standardized reading protocol: two radiologists, blinded independent reading, use of template (Dr. Andronikou design) in case of disagreement a third reading was performed. Kappa coefficient for intra and inter observer agreement, and prevalence ratio were estimated of sociodemographic characteristics, TB exposure and interpretation of chest X-ray.

Results

From 278 children, standardized reading found 255 (91.7%) normal X-rays, 10 (3.6%) consistent with TB, and 13 (4.7%) other alterations. Global agreement was 91.3% (Kappa = 0.51). Inter-observer agreement between readers 1–2 was 90.0% (Kappa = 0.59) and 1–3 93.2% (Kappa = 0.59). Intra-observer agreement for reader 1 was 95.5% (Kappa = 0.86), 2 84.0% (Kappa = 0.51), and 3 94.7% (Kappa = 0.68). Greater inter-observer disagreement was between readers 1–2 for soft tissue density suggestive of adenopathy (4.6%), airspace opacification (1.17%) and pleural effusion (0.58%); between readers 1–3 for soft tissue density suggestive of adenopathy (4.2%), opacification of airspace (2.5%) and cavities (0.8%).

Conclusions

Chest radiographs are an affordable tool that contributes to the diagnosis of TB, so having a standardized reading protocol showed good agreement and improves the reproducibility of radiograph interpretation.
Factors associated with a change in smoking habit during the first COVID-19 lockdown: an Italian cross-sectional study among ever-smokers
Authors: Munarini Elena , Stival Chiara , Boffi Roberto , Lugoboni Fabio , Veronese Chiara , Tinghino Biagio , Agnelli Gianna Maria , Lugo Alessandra , Gallus Silvano , Giordano Rosaria
Published: May 2022

Background

The COVID-19 pandemic and the lockdown period lasted from March to May 2020, resulted in a highly stressful situation yielding different negative health consequences, including the worsening of smoking habit.

Methods

A web-based cross-sectional study on a convenient sample of 1013 Italian ever smokers aged 18 years or more was conducted. Data were derived from surveys compiled by three different groups of people: subjects belonging to Smoking Cessation Services, Healthcare Providers and Nursing Sciences’ students. All institutions were from Northern Italy. The primary outcome self-reported worsening (relapse or increase) or improvement (quit or reduce) of smoking habit during lockdown period. Multiple unconditional (for worsening) and multinomial (for improving) logistic regressions were carried out.

Results

Among 962 participants, 56.0% were ex-smokers. Overall, 13.2% of ex-smokers before lockdown reported relapsing and 32.7% of current smokers increasing cigarette intake. Among current smokers before lockdown, 10.1% quit smoking and 13.5% decreased cigarette intake. Out of 7 selected stressors related to COVID-19, four were significantly related to relapse (OR for the highest vs. the lowest tertile ranging between 2.24 and 3.62): fear of being infected and getting sick; fear of dying due to the virus; anxiety in listening to news of the epidemic; sense of powerlessness in protecting oneself from contagion. In addition to these stressors, even the other 3 stressors were related with increasing cigarette intensity (OR ranging between 1.90 and 4.18): sense of powerlessness in protecting loved ones from contagion; fear of losing loved ones due to virus; fear of infecting other.

Conclusion

The lockdown during the COVID-19 pandemic was associated with both self-reported relapse or increase smoking habit and also quitting or reduction of it.
Community engagement on-site rapid test for chlamydia and gonorrhea among men who have sex with men: a pioneering study in Guangzhou, China
Authors: Lin Xiao-Xin , Meng Si-Yan , Ke Wu-Jian , Zhang Xiao-Hui , Wang Liu-Yuan , Liao Yu-Ying , Liu Han , Zhao Pei-Zhen , Liang Chun-Mei , Chen Hui-Ru , Long Hai-Ying , Yang Bin , Yang Li-Gang
Published: May 2022

Background

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are prevalent among men who have sex with men (MSM) in China. However, compared to syphilis and HIV, the testing rate for chlamydia and gonorrhea remains low. The purpose of this pilot study was to evaluate the feasibility for conducting rapid nucleic acid test for chlamydia and gonorrhea in MSM community-based organizations (CBO).

Method

We recruited our participants through an MSM CBO where free HV and syphilis testing were routinely provided. We collected data including social-demographic background, sexual history, chlamydia and gonorrhea testing history, and reasons for accepting this on-site rapid testing. Urine and/or anorectal swab samples were collected and tested for chlamydia and gonorrhea on-site and the testing results were delivered in about 1.5 h. Positive cases received on-site free treatment.

Results

From August 2020 to October 2020, 634 MSM visited the CBO for syphilis and HIV testing and 158 (158/634, 24.9%) accepted the on-site chlamydia and gonorrhea rapid test, 135 were finally enrolled. The positive rate fo chlamydia was 16.3% (22/135) and 3.0% (4/135) for gonorrhea, respectively. Only 19.3% participants had previously undergone chlamydia and gonorrhea testing and 68.9% (93/135) participants reported that they had heard of gonorrhea, 47.4% (64/135) had heard of chlamydia. The main reason for testing was “free for charge” (66.2%), followed by “convenient, ‘shorter waiting time” (45.2%) and “had high-risk sexual behavior recently” (16.3%).

Conclusions

This pilot study showed that the chlamydia and gonorrhea infection rate remains high among MSM, while the testing rate was low. On-site rapid testing is feasible and potentially preferred by MSM.
QTc prolongation is associated with severe desaturations in stroke patients with sleep apnea
Authors: Sillanmäki Saara , Lipponen Jukka A. , Korkalainen Henri , Kulkas Antti , Leppänen Timo , Nikkonen Sami , Töyräs Juha , Duce Brett , Suni Aaron , Kainulainen Samu
Published: May 2022

Background

Obstructive sleep apnea (OSA) is associated with vascular diseases from which stroke and sudden cardiac death are the most significant ones. It is known that disturbances of the autonomic nervous system and electrocardiographic changes are seen in patients with a previous cerebrovascular event. However, the pathophysiological cascade between breathing cessations, autonomic regulation, and cardiovascular events is not fully understood.

Methods

We aimed to investigate the acute effect of desaturation on repolarisation in OSA patients with a previous stroke. We retrospectively analysed heart-rate corrected QT (QTc) intervals before, within, and after 975 desaturations in OSA patients with a stroke history and at least moderate sleep apnea (apnea–hypopnea index ≥ 15 events/h, n = 18). For the control population (n = 18), QTc intervals related to 1070 desaturation were analysed. Desaturations were assigned to groups according to their length and duration. Groupwise comparisons and regression analyses were further executed to investigate the influence of desaturation features on repolarization.

Results

In the stroke population the QTc prolonged at least 11 ms during 27.1% of desaturations, and over 20 ms during 12.2% of desaturations. QTc was significantly prolonged during longer (> 30 s, p < 0.04) and deeper (> 7%, p < 0.03) desaturations. Less severe desaturations didn't influence QTc. In median, QTc prolonged 7.5 ms during > 45 s desaturations and 7.4 ms during > 9% deep desaturations. In the control population, QTc prolongation was observed but to a significantly lesser extent than in stroke patients. In addition, desaturation duration was found to be an independent predictor of QTc prolongation (β = 0.08, p < 0.001) among all study patients.

Conclusions

We demonstrated that longer (> 30 s) and deeper (> 7%) desaturations prolong QTc in patients with stroke history. A significant proportion of desaturations produced clinically relevant QTc prolongation. As it is known that a long QTc interval is associated with lethal arrhythmias, this finding might in part explain the pathophysiological sequelae of cardiovascular mortality in OSA patients with a history of stroke.
Acute fibrinous and organizing pneumonia in a patient with Sjögren’s syndrome and Legionella pneumonia: a case report and literature review
Authors: Lu Ye , Zheng Wei , Cao Wei , Yang Xianghong , Zhao Li , Chen Yu
Published: May 2022

Background

Acute fibrinous and organizing pneumonia (AFOP) is a rare clinicopathological condition. Studies in the literature have reported that AFOP may be associated with respiratory infections, such as respiratory syncytial virus, influenza virus, Pneumocystis jirovecii, Penicillium citrinum, and Chlamydia infections. However, AFOP associated with Legionella infection has not been reported previously. Here, we report a case of a patient with AFOP secondary to Sjögren’s syndrome and Legionella infection.

Case presentation

A 47-year-old man was admitted to the hospital because of fever, expectoration, and shortness of breath. Lung imaging showed irregular patchy consolidation. A diagnosis of Legionella pneumonia was initially considered on the basis of the patient’s history of exposure to soil before disease onset, signs of extrapulmonary involvement, and a positive Legionella urine antigen test result. However, the patient’s symptoms and lung imaging did not improve after treatment with levofloxacin, moxifloxacin, and tigecycline for Legionella infection. In addition, Sjögren’s syndrome was diagnosed on the basis of clinical manifestations and immunological indicators. Pathological changes associated with AFOP were confirmed from the results of ultrasound-guided percutaneous lung biopsy. The patient’s clinical symptoms improved rapidly after a short course of low-dose corticosteroid therapy, and lung imaging showed significant improvement.

Conclusions

The possibility of secondary AFOP should be considered when Legionella pneumonia does not improve after standard antibiotic therapy. Lung biopsy and histopathological examination are important for the adjustment of treatment strategy. Our case also highlights the importance of screening for autoimmune diseases in patients with AFOP.
Cross-species discrimination of vocal expression of emotional valence by Equidae and Suidae
Authors: Maigrot Anne-Laure , Hillmann Edna , Briefer Elodie F.
Published: May 2022

Background

Discrimination and perception of emotion expression regulate interactions between conspecifics and can lead to emotional contagion (state matching between producer and receiver) or to more complex forms of empathy (e.g., sympathetic concern). Empathy processes are enhanced by familiarity and physical similarity between partners. Since heterospecifics can also be familiar with each other to some extent, discrimination/perception of emotions and, as a result, emotional contagion could also occur between species.

Results

Here, we investigated if four species belonging to two ungulate Families, Equidae (domestic and Przewalski’s horses) and Suidae (pigs and wild boars), can discriminate between vocalizations of opposite emotional valence (positive or negative), produced not only by conspecifics, but also closely related heterospecifics and humans. To this aim, we played back to individuals of these four species, which were all habituated to humans, vocalizations from a unique set of recordings for which the valence associated with vocal production was known. We found that domestic and Przewalski’s horses, as well as pigs, but not wild boars, reacted more strongly when the first vocalization played was negative compared to positive, regardless of the species broadcasted.

Conclusions

Domestic horses, Przewalski’s horses and pigs thus seem to discriminate between positive and negative vocalizations produced not only by conspecifics, but also by heterospecifics, including humans. In addition, we found an absence of difference between the strength of reaction of the four species to the calls of conspecifics and closely related heterospecifics, which could be related to similarities in the general structure of their vocalization. Overall, our results suggest that phylogeny and domestication have played a role in cross-species discrimination/perception of emotions.
Elevated testicular apoptosis is associated with elevated sphingosine driven by gut microbiota in prediabetic sheep
Authors: Sun Yuanchao , Sun Peng , Hu Yanting , Shan Liying , Geng Qi , Gong Yutian , Fan Haitao , Zhang Teng , Zhou Yang
Published: May 2022

Background

Men with prediabetes often exhibit concomitant low-quality sperm production or even infertility, problems which urgently require improved therapeutic options. In this study, we have established a sheep model of diet-induced prediabetes that is associated with spermatogenic defects and have explored the possible underlying metabolic causes.

Results

We compared male sheep fed a normal diet with those in which prediabetes was induced by a rich diet and with a third group in which the rich diet was supplemented by melatonin. Only the rich diet group had symptoms of prediabetes, and in these sheep, we found impaired spermatogenesis characterized by a block in the development of round spermatids and an increased quantity of testicular apoptotic cells. Comparing the gut microbiomes and intestinal digest metabolomes of the three groups revealed a distinctive difference in the taxonomic composition of the microbiota in prediabetic sheep, and an altered metabolome, whose most significant feature was altered sphingosine metabolism; elevated sphingosine was also found in blood and testes. Administration of melatonin alleviated the symptoms of prediabetes, including those of impaired spermatogenesis, while restoring a more normal microbiota and metabolic levels of sphingosine. Fecal microbiota transplantation from prediabetic sheep induced elevated sphingosine levels and impaired spermatogenesis in recipient mice, indicating a causal role of gut microbiota in these phenotypes.

Conclusions

Our results point to a key role of sphingosine in the disruption of spermatogenesis in prediabetic sheep and suggest it could be a useful disease marker; furthermore, melatonin represents a potential prebiotic agent for the treatment of male infertility caused by prediabetes.
Genome-wide association study of eigenvectors provides genetic insights into selective breeding for tomato metabolites
Authors: Yang Junwei , Liang Bin , Zhang Yuemei , Liu Yun , Wang Shengyuan , Yang Qinqin , Geng Xiaolin , Liu Simiao , Wu Yaoyao , Zhu Yingfang , Lin Tao
Published: May 2022

Background

Long-term domestication and intensive breeding of crop plants aim to establish traits desirable for human needs, and characteristics related to yield, disease resistance, and postharvest storage have traditionally received considerable attention. These processes have led also to negative consequences, as is the case of loss of variants controlling fruit quality, for instance in tomato. Tomato fruit quality is directly associated to metabolite content profiles; however, a full understanding of the genetics affecting metabolite content during tomato domestication and improvement has not been reached due to limitations of the single detection methods previously employed. Here, we aim to reach a broad understanding of changes in metabolite content using a genome-wide association study (GWAS) with eigenvector decomposition (EigenGWAS) on tomato accessions.

Results

An EigenGWAS was performed on 331 tomato accessions using the first eigenvector generated from the genomic data as a “phenotype” to understand the changes in fruit metabolite content during breeding. Two independent gene sets were identified that affected fruit metabolites during domestication and improvement in consumer-preferred tomatoes. Furthermore, 57 candidate genes related to polyphenol and polyamine biosynthesis were discovered, and a major candidate gene chlorogenate: glucarate caffeoyltransferase (SlCGT) was identified, which affected the quality and diseases resistance of tomato fruit, revealing the domestication mechanism of polyphenols.

Conclusions

We identified gene sets that contributed to consumer liking during domestication and improvement of tomato. Our study reports novel evidence of selective sweeps and key metabolites controlled by multiple genes, increasing our understanding of the mechanisms of metabolites variation during those processes. It also supports a polygenic selection model for the application of tomato breeding.
Ubiquitin-like modifier 1 ligating enzyme 1 relieves cisplatin-induced premature ovarian failure by reducing endoplasmic reticulum stress in granulosa cells
Authors: Tang Xiangting , Dong Hao , Fang Zhi , Li Jingyi , Yang Qi , Yao Ting , Pan Zezheng
Published: May 2022

Background

Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1), the ligase of the UFMylation system, has recently been reported to be involved in apoptosis and endoplasmic reticulum stress (ER stress) in a variety of diseases. Premature ovarian failure (POF) is a gynecological disease that severely reduces the fertility of women, especially in female cancer patients receiving chemotherapy drugs. Whether UFL1 is involved in protection against chemotherapy-induced POF and its mechanism remain unclear.

Methods

In this study, we examined the function of UFL1 in ovarian dysfunction and granulosa cell (GC) apoptosis induced by cisplatin through histological examination and cell viability analysis. We used western blotting, quantitative real-time PCR (qPCR) and immunofluorescence (IF) to detect the expression of UFL1 and the levels of ER stress specific markers. Enzyme linked immunosorbent assays were used to detect the levels of follicle-stimulating hormone (FSH) and estrogen (E2) in ovaries and GCs. In addition, we used infection with lentiviral particle suspensions to knock down and overexpress UFL1 in ovaries and GCs, respectively.

Results

Our data showed that the expression of UFL1 was reduced in POF model ovaries, accompanied by ER stress. In vitro, cisplatin induced a stress-related increase in UFL1 expression in GCs and enhanced ER stress, which was aggravated by UFL1 knockdown and alleviated by UFL1 overexpression. Furthermore, UFL1 knockdown resulted in a decrease in ovarian follicle number, an increase in atretic follicles, and decreased expression of AMH and FSHR. Conversely, the overexpression of UFL1 reduced cisplatin-induced damage to the ovary in vitro.

Conclusions

Our research indicated that UFL1 regulates cisplatin-induced ER stress and apoptosis in GCs, and participates in protection against cisplatin-induced POF, providing a potential therapeutic target for the clinical prevention of chemotherapeutic drug-induced POF.

Graphical Abstract
Network alterations underlying anxiety symptoms in early multiple sclerosis
Authors: Ellwardt Erik , Muthuraman Muthuraman , Gonzalez-Escamilla Gabriel , Chirumamilla Venkata Chaitanya , Luessi Felix , Bittner Stefan , Zipp Frauke , Groppa Sergiu , Fleischer Vinzenz
Published: May 2022

Background

Anxiety, often seen as comorbidity in multiple sclerosis (MS), is a frequent neuropsychiatric symptom and essentially affects the overall disease burden. Here, we aimed to decipher anxiety-related networks functionally connected to atrophied areas in patients suffering from MS.

Methods

Using 3-T MRI, anxiety-related atrophy maps were generated by correlating longitudinal cortical thinning with the severity of anxiety symptoms in MS patients. To determine brain regions functionally connected to these maps, we applied a technique termed “atrophy network mapping”. Thereby, the anxiety-related atrophy maps were projected onto a large normative connectome (n = 1000) performing seed‐based functional connectivity. Finally, an instructed threat paradigm was conducted with regard to neural excitability and effective connectivity, using transcranial magnetic stimulation combined with high-density electroencephalography.

Results

Thinning of the left dorsal prefrontal cortex was the only region that was associated with higher anxiety levels. Atrophy network mapping identified functional involvement of bilateral prefrontal cortex as well as amygdala and hippocampus. Structural equation modeling confirmed that the volumes of these brain regions were significant determinants that influence anxiety symptoms in MS. We additionally identified reduced information flow between the prefrontal cortex and the amygdala at rest, and pathologically increased excitability in the prefrontal cortex in MS patients as compared to controls.

Conclusion

Anxiety-related prefrontal cortical atrophy in MS leads to a specific network alteration involving structures that resemble known neurobiological anxiety circuits. These findings elucidate the emergence of anxiety as part of the disease pathology and might ultimately enable targeted treatment approaches modulating brain networks in MS.
N-Oleoyl dopamine induces IL-10 via central nervous system TRPV1 and improves endotoxemia and sepsis outcomes
Authors: Joffre Jérémie , Wong Erika , Lawton Samira , Lloyd Elliot , Nguyen Nina , Xu Fengyun , Sempio Cristina , Kobzik Lester , Zlatanova Ivana , Schumacher Mark , Klawitter Jost , Su Hua , Rabl Katalin , Wilhelmsen Kevin , Yeh Che-Chung , Hellman Judith
Published: May 2022

Background

The transient receptor potential vanilloid 1 (TRPV1) participates in thermosensation and inflammatory pain, but its immunomodulatory mechanisms remain enigmatic.N-Oleoyl dopamine (OLDA), an endovanilloid and endocannabinoid, is a TRPV1 agonist that is produced in the central nervous system and the peripheral nervous system. We studied the anti-inflammatory effects and TRPV1-dependent mechanisms of OLDA in models of inflammation and sepsis.

Methods

Mice were challenged intratracheally or intravenously with LPS, or intratracheally withS. aureusto induce pneumonia and sepsis, and then were treated intravenously with OLDA. Endpoints included plasma cytokines, leukocyte activation marker expression, mouse sepsis scores, lung histopathology, and bacterial counts. The role of TRPV1 in the effects of OLDA was determined usingTrpv1−/−mice, and mice with TRPV1 knockdown pan-neuronally, in peripheral nervous system neurons, or in myeloid cells. Circulating monocytes/macrophages were depleted using clodronate to determine their role in the anti-inflammatory effects of OLDA in endotoxemic mice. Levels of exogenous OLDA, and of endovanilloids and endocannabinoids, at baseline and in endotoxemic mice, were determined by LC–MS/MS.

Results

OLDA administration caused an early anti-inflammatory response in endotoxemic and septic mice with high serum levels of IL-10 and decreased levels of pro-inflammatory cytokines. OLDA also reduced lung injury and improved mouse sepsis scores. Blood and lung bacterial counts were comparable between OLDA- and carrier-treated mice withS. aureuspneumonia. OLDA’s effects were reversed in mice with pan-neuronal TRPV1 knockdown, but not with TRPV1 knockdown in peripheral nervous system neurons or myeloid cells. Depletion of monocytes/macrophages reversed the IL-10 upregulation by OLDA in endotoxemic mice. Brain and blood levels of endovanilloids and endocannabinoids were increased in endotoxemic mice.

Conclusions

OLDA has strong anti-inflammatory actions in mice with endotoxemia orS. aureuspneumonia. Prior studies focused on the role of peripheral nervous system TRPV1 in modulating inflammation and pneumonia. Our results suggest that TRPV1-expressing central nervous system neurons also regulate inflammatory responses to endotoxemia and infection. Our study reveals a neuro-immune reflex that during acute inflammation is engaged proximally by OLDA acting on neuronal TRPV1, and through a multicellular network that requires circulating monocytes/macrophages, leads to the systemic production of IL-10.
Longitudinal profiling of clonal hematopoiesis provides insight into clonal dynamics
Authors: Uddin Md Mesbah , Zhou Ying , Bick Alexander G. , Burugula Bala Bharathi , Jaiswal Siddhartha , Desai Pinkal , Honigberg Michael C. , Love Shelly-Ann , Barac Ana , Hayden Kathleen M. , Manson JoAnn E. , Whitsel Eric A. , Kooperberg Charles , Natarajan Pradeep , Reiner Alexander P. , Kitzman Jacob O.
Published: May 2022

Background

Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of mutant hematopoietic stem cells, confers risk for multiple diseases of aging including hematologic cancer and cardiovascular disease. Whole-exome or genome sequencing can detect CHIP, but due to those assays’ high cost, most population studies have been cross-sectional, sequencing only a single timepoint per individual.

Results

We developed and validated a cost-effective single molecule molecular inversion probe sequencing (smMIPS) assay for detecting CHIP, targeting the 11 most frequently mutated genes in CHIP along with 4 recurrent mutational hotspots. We sequenced 548 multi-timepoint samples collected from 182 participants in the Women’s Health Initiative cohort, across a median span of 16 years. We detected 178 driver mutations reaching variant allele frequency ≥ 2% in at least one timepoint, many of which were detectable well below this threshold at earlier timepoints. The majority of clonal mutations (52.1%) expanded over time (with a median doubling period of 7.43 years), with the others remaining static or decreasing in size in the absence of any cytotoxic therapy.

Conclusions

Targeted smMIPS sequencing can sensitively measure clonal dynamics in CHIP. Mutations that reached the conventional threshold for CHIP (2% frequency) tended to continue growing, indicating that after CHIP is acquired, it is generally not lost. The ability to cost-effectively profile CHIP longitudinally will enable future studies to investigate why some CHIP clones expand, and how their dynamics relate to health outcomes at a biobank scale.
Molecular characterization of a bovine adenovirus type 7 (Bovine Atadenovirus F) strain isolated from a systemically infected calf in Germany
Authors: Jesse Sonja T. , Ciurkiewicz Malgorzata , Siesenop Ute , Spitzbarth Ingo , Osterhaus A. D. M. E. , Baumgärtner Wolfgang , Ludlow Martin
Published: May 2022

Bovine adenovirus 7 (BAdV-7) is an unclassified member of the genus Atadenovirus with a worldwide distribution and has been reported to induce clinical disease of varying severity in infected cattle, ranging from asymptomatic infections to severe enteric or respiratory disease. In this study, we used next-generation sequencing to obtain the first complete genome sequence of a European strain of BadV-7, from pooled spleen and liver tissue obtained from a deceased newborn Limousin calf. Histopathological analysis and electron microscopy showing systemic lesions in multiple organs with intranuclear amphophilic inclusions observed in endothelial cells in multiple peripheral tissues. Virus isolation was readily achieved from tissue homogenate using bovine esophagus cells (KOP-R), a strategy which should facilitate future in vitro or in vivo BAdV-7 studies. Phylogenetic analysis of available genome sequences of BAdV-7 showed that the newly identified strain groups most closely with a recent BAdV-7 strain, SD18-74, from the USA, confirming that this newly identified strain is a member of the Atadenovirus genus. The fiber gene was found to be highly conserved within BAdV-7 strains but was highly divergent in comparison to Ovine adenovirus 7 (OAdV-7) (39.56% aa sequence identity). Furthermore, we report a variable region of multiple tandem repeats between the coding regions of E4.1 and RH5 genes. In summary, the presented pathological and molecular characterization of this case suggests that further research into the worldwide molecular epidemiology and disease burden of BAdV-7 is warranted.
Combined endoscopic and radiologic intervention for management of acute perforated peptic ulcer: a randomized controlled trial
Authors: Negm Said , Mohamed Hatem , Shafiq Ahmed , AbdelKader Taha , Ismail Adel , Yassin Mahmoud , Mousa Bassam , Abozaid Mohamed , Orban Yasser A. , Al Alawi Mazoun , Farag Ahmed
Published: May 2022

Background

Peptic ulcer perforation is a common life-threatening surgical emergency. Graham omental patch is performed for plugging of perforated peptic ulcer. Many endoscopic methods have been used to treat acute perforated peptic ulcer such as over the scope clips, standard endoscopic clips, endoscopic sewing and metallic stents. The main idea in endoscopic management of acute perforated peptic ulcer is early decontamination and decrease sepsis by interventional radiologic drainage.

Methods

This is a prospective randomized controlled clinical trial. This study included patients who were developed acute perforated peptic ulcer manifestations and were admitted to our hospital between December 2019 and August 2021. Sample size was 100 patients divided into 2 equal groups. Endoscopic group (EG): included 50 patients who were subjected to endoscopic management. Surgical group (SG): included 50 patients who were subjected to surgical management.

Results

One hundred patients were randomized into 2 groups: SG (50) and EG (50). Median age of patients was 36 (range 27:54) and 47 (range 41:50) years-old in SG and EG, respectively. Males constituted 72% and 66% in SG and EG, respectively. Median length of postoperative hospital stay was 1 (range: 1–2) days in EG, while in SG was 7 (range 6–8) days. Postoperative complications in SG patients were 58% in form of fever, pneumonia, leak, abdominal abscess, renal failure and incisional hernia (11%, 5%, 5%, 3%, 2% and 3%, respectively). Postoperative complications in EG patients were 24% in form of fever, pneumonia, leak, abdominal abscess, renal failure and incisional hernia (10%, 0%, 2%, 0%, 0% and 0%, respectively).

Conclusion

Combined endoscopic and interventional radiological drainage can effectively manage acute perforated peptic ulcer without the need for general anesthesia, with short operative time, in high risk surgical patients with low incidence of morbidity & mortality.
Effect of abdominal weight training with and without cough machine assistance on lung function in the patients with prolonged mechanical ventilation: a randomized trial
Authors: Hung Tsai-Yi , Wu Wen-Lan , Kuo Ho-Chang , Liu Shih-Feng , Chang Chia-Ling , Chang Hui-Chuan , Tsai Yuh-Chyn , Liu Jui-Fang
Published: May 2022

Purpose

The patients with prolonged mechanical ventilation (PMV) have the risk of ineffective coughing and infection due to diaphragm weakness. This study aimed to explore the effect of abdominal weight training (AWT) intervention with/without cough machine (CM) assistance on lung function, respiratory muscle strength and cough ability in these patients.

Methods

Forty patients with PMV were randomly assigned to three groups: AWT group (n = 12), AWT + CM group (n = 14) and control group (n = 14). Change of maximum inspiratory pressure (MIP), Maximum expiratory pressure (MEP) and peak cough flow (PCF) between 1 day before and 2 weeks after the intervention were compared among these three groups.

Results

MIP before and after intervention in AWT group (30.50 ± 11.73 vs. 36.00 ± 10.79; p < 0.05) and AWT + CM group (29.8 ± 12.14 vs. 36.14 ± 10.42; p < 0.05) compared with control group (28.43 ± 9.74 vs 26.71 ± 10.77; p > 0.05) was significantly improved. MEP before and after intervention in AWT group (30.58 ± 15.19 vs. 41.50 ± 18.33; p < 0.05) and AWT + CM group (27.29 ± 12.76 vs 42.43 ± 16.96; p < 0.05) compared with control group (28.86 ± 10.25 vs. 29.57 ± 14.21; p > 0.05) was significantly improved. PCF before and after intervention in AWT group in AWT group (105.83 ± 16.21 vs. 114.17 ± 15.20; p < 0.05) and AWT + CM group (108.57 ± 18.85 vs. 131.79 ± 38.96; p < 0.05) compared to control group (108.57 ± 19.96 vs. 109.86 ± 17.44; p > 0.05) showed significant improvements. AWT + CM group had significantly greater improvements than control group in MIP and peak cough flow than control group (13.71 ± 11.28 vs 19.64 ± 29.90, p < 0.05).

Conclusion

AWT can significantly improve lung function, respiratory muscle strength, and cough ability in the PMV patients. AWT + CM can further improve their expiratory muscle strength and cough ability.

Trial registration ClinicalTrials.gov registry (registration number: NCT0529538 retrospectively registered on March 3, 2022).
Peer specialists deliver cognitive behavioral social skills training compared to social skills training and treatment as usual to veterans with serious mental illness: study protocol for a randomized controlled trial
Authors: Mitchell-Miland Chantele , McCarthy Sharon , Chinman Matthew
Published: May 2022

Background

Serious mental illness (SMI) affects 4.6% of the American population. While treatments are available, adherence to specific regimens is often suboptimal. Multiple organizations, such as the Substance Abuse and Mental Health Services Administration (SAMHSA), have called for more options that improve accessibility and engagement to treatment among individuals with SMI. This study protocol answers such calls by testing the effectiveness of peer specialists—individuals with SMI trained to use their experience to help others with SMI—in delivering social skills training (SST) and cognitive behavioral social skills training (CBSST), evidence-based treatments effective at engaging individuals with SMI to make behavioral and cognitive changes. Peer specialists have been shown to be adept at engaging those with SMI in treatment; however, their ability to deliver these structured treatments is unknown.

Methods

This study is a randomized, hybrid 1, research assistant-blinded, superiority trial. A total of 252 veterans with SMI will be recruited and randomized to one of three arms: CBSST-Peer vs. SST-Peer vs. treatment as usual. Participants randomized to CBSST-Peer or SST-Peer will participate in a 20-week group-based intervention that meets weekly for a 60-min class. All participants will complete 4 study assessments at baseline, 10 weeks, 20 weeks, and 32 weeks. A multidimensional battery of functional outcomes will be used with the Independent Living Skills Survey (ILSS) as the primary outcome measure. Post-study completion, veterans who participated in the CBSST-Peer or SST-Peer arms will randomly be invited to participate in focus groups, and peer specialists will complete interviews to further assess the effectiveness of each intervention.

Discussion

Improving care and outcomes for individuals with SMI is a national priority. To improve care, it is imperative to think about new ways to improve engagement and accessibility to care. This study provides an innovative solution to this problem by evaluating how two different types of treatment, delivered by peer specialists, compare to usual care. The results of the study will allow for the expansion of treatment options that improve access and engagement among veterans with SMI.