bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Progressive Muscle Relaxation Exercise on Anxiety Among Male Nursing Students Undergoing Maternity Clinical Training
Authors: Toqan Dalia , Malak Malakeh Z. , Ayed Ahmad , Fashafsheh Imad , Salameh Basma , Sarhan Adnan Lutfi , Azizeh Saed , Batran Ahmad 
Published: November 2022

Introduction Student in a maternity nursing program must be engaged in practical training and they must be well prepared and directed along the way to becoming qualified professionals. Objective The study aimed to investigate the effect of progressive muscle relaxation exercise on anxiety among male nursing students undergoing maternity clinical training. Methods A quasi-experimental, pre-post study was conducted on nursing at Arab American University Palestine. The sample of the study consisted of 48 male nursing students enrolled in the maternity nursing course. They were selected through convenience sampling. This study was conducted on one group of male nursing students that received Jacobson's progressive muscle relaxation exercise for five consecutive days per week. The S-anxiety scale (STAI Form Y-1) was applied to collect data before and after the intervention. Results The magnitude of anxiety reduction after the progressive muscle relaxation exercise was greater than before ( t (47) = 21.2, p < .05). Conclusion The current study's findings indicated the influence of progressive muscle relaxation on maternity clinical setting anxiety reduction among male nursing students.
How I treat thrombotic microangiopathy in the era of rapid genomics
Authors: Doreille Alice , Rafat Cédric , Rondeau Eric , Mesnard Laurent 
Published: November 2022

AbstractThrombotic microangiopathy (TMA) encompasses various genetically-driven diseases. The emergence of ultrafast genomic sequencing has recently opened up new avenues of research for genetic investigations in the setting of intensive care units. TMA is likely to be a suitable focus for fast-track genomic sequencing. By establishing an expeditious molecular diagnosis of patients with the complement-dependent hemolytic uremic syndrome, fast-track genomic sequencing allows for the timely implementation or withdrawal of anti-C5 treatment while averting unnecessary, costly, and potentially harmful therapy in patients testing negative for the syndrome. Furthermore, genomics has the potential to reshape the taxonomic classification of TMA owing to comprehensive genomic analysis. The most significant results from such analysis can be categorized as (1) new descriptions of genetic diseases previously not recognized as associated with TMA and (2) an enrichment of the phenotypic spectrum of diseases traditionally related to TMA. The latter draws on the concept of retrophenotyping, wherein genomic investigation precedes full clinical description. By taking precedence over a phenotypic approach, an unbiased genomic-focused analysis maximizes the chances of discovering new descriptions of a given variant. Presented here are 4 cases of TMA which highlight these issues and substantiate the promise of fast-track genomic sequencing.
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

Abstract
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

Abstract:
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

Abstract
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

AbstractMost 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.