bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic profiling of end-stage COVID-19 lung biopsies
Authors: Gindlhuber Juergen , Tomin Tamara , Wiesenhofer Florian , Zacharias Martin , Liesinger Laura , Demichev Vadim , Kratochwill Klaus , Gorkiewicz Gregor , Schittmayer Matthias , Birner-Gruenberger Ruth 
Published: December 2022

AbstractThe outbreak of a novel coronavirus (SARS-CoV-2) in 2019 led to a worldwide pandemic, which remains an integral part of our lives to this day. Coronavirus disease (COVID-19) is a flu like condition, often accompanied by high fever and respiratory distress. In some cases, conjointly with other co-morbidities, COVID-19 can become severe, leading to lung arrest and even death. Although well-known from a clinical standpoint, the mechanistic understanding of lethal COVID-19 is still rudimentary. Studying the pathology and changes on a molecular level associated with the resulting COVID-19 disease is impeded by the highly infectious nature of the virus and the concomitant sampling challenges. We were able to procure COVID-19 post-mortem lung tissue specimens by our collaboration with the BSL-3 laboratory of the Biobanking and BioMolecular resources Research Infrastructure Austria which we subjected to state-of-the-art quantitative proteomic analysis to better understand the pulmonary manifestations of lethal COVID-19. Lung tissue samples from age-matched non-COVID-19 patients who died within the same period were used as controls. Samples were subjected to parallel accumulation–serial fragmentation combined with data-independent acquisition (diaPASEF) on a timsTOF Pro and obtained raw data was processed using DIA-NN software. Here we report that terminal COVID-19 patients display an increase in inflammation, acute immune response and blood clot formation (with concomitant triggering of fibrinolysis). Furthermore, we describe that COVID-19 diseased lungs undergo severe extracellular matrix restructuring, which was corroborated on the histopathological level. However, although undergoing an injury, diseased lungs seem to have impaired proliferative and tissue repair signalling, with several key kinase-mediated signalling pathways being less active. This might provide a mechanistic link to post-acute sequelae of COVID-19 (PASC; “Long COVID”). Overall, we emphasize the importance of histopathological patient stratification when interpreting molecular COVID-19 data.
Unsupervised outlier detection applied to SARS-CoV-2 nucleotide sequences can identify sequences of common variants and other variants of interest
Authors: Hahn Georg , Lee Sanghun , Prokopenko Dmitry , Abraham Jonathan , Novak Tanya , Hecker Julian , Cho Michael , Khurana Surender , Baden Lindsey R. , Randolph Adrienne G. , Weiss Scott T. , Lange Christoph 
Published: December 2022

AbstractAs of June 2022, the GISAID database contains more than 11 million SARS-CoV-2 genomes, including several thousand nucleotide sequences for the most common variants such as delta or omicron. These SARS-CoV-2 strains have been collected from patients around the world since the beginning of the pandemic. We start by assessing the similarity of all pairs of nucleotide sequences using the Jaccard index and principal component analysis. As shown previously in the literature, an unsupervised cluster analysis applied to the SARS-CoV-2 genomes results in clusters of sequences according to certain characteristics such as their strain or their clade. Importantly, we observe that nucleotide sequences of common variants are often outliers in clusters of sequences stemming from variants identified earlier on during the pandemic. Motivated by this finding, we are interested in applying outlier detection to nucleotide sequences. We demonstrate that nucleotide sequences of common variants (such as alpha, delta, or omicron) can be identified solely based on a statistical outlier criterion. We argue that outlier detection might be a useful surveillance tool to identify emerging variants in real time as the pandemic progresses.
Overexpression of lncRNA HOXA-AS2 promotes the progression of oral squamous cell carcinoma by mediating SNX5 expression
Authors: Li Zhangyi 
Published: December 2022

AbstractBackgroundOral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers. Long non-coding RNA HOXA-AS2 (lncRNA HOXA-AS2) have been extensively studied in various cancers. However, the expression and function of HOXA-AS2 in OSCC still remain unknown. The aim of this study is to investigate the roles of HOXA-AS2 in OSCC.MethodsOSCC tissues and adjacent normal tissues were obtained from OSCC patients. RT-qPCR and Western blot assays were used to detect the expression of target genes in OSCC tissues or cells. Cells proliferation, migration and invasion were detected by CCK-8 and transwell assays, respectively. The target gene of HOXA-AS2 was confirmed by dual-luciferase reporter gene assay.ResultsWe found that HOXA-AS2 expression was remarkably upregulated in OSCC tissues and cell lines. The downregulation of HOXA-AS2 inhibited cells proliferation, migration and invasion. Our bioinformatics analysis found that HOXA-AS2 can target miR-520c-3p, which was confirmed by dual-luciferase reporter gene assay. The expression of HOXA-AS2 was found to be negatively associated with miR-520c-3p in OSCC tissues. Moreover, sorting nexin 5 (SNX5), a downstream target of miR-520c-3p, was inhibited by miR-520c-3p overexpression. SNX5 was also increased in OSCC tissues and cell lines. Additionally, we found that the higher expression of SNX5 was strongly associated with the tumor grade of OSCC patients in Oncomine database. Most importantly, the knockdown of HOXA-AS2 induced cells apoptosis by promoting autophagy by regulating SNX5.ConclusionHOXA-AS2 served an oncogene and promoted OSCC progression via the miR-520c-3p/SNX5 axis. Thus, HOXA-AS2 may be a new biomarker for diagnosis and treatment of OSCC.
Selection and validation of appropriate reference genes for RT–qPCR analysis of Nitraria sibirica under various abiotic stresses
Authors: Hu Aishuang , Yang Xiuyan , Zhu Jianfeng , Wang Xiuping , Liu Jiaxin , Wang Jiping , Wu Haiwen , Zhang Huilong , Zhang Huaxin 
Published: December 2022

Abstract
Background
Nitraria sibirica Pall. is a halophytic shrub with strong environmental adaptability that can survive in extremely saline-alkali and drought-impacted environments. Gene expression analysis aids in the exploration of the molecular mechanisms of plant responses to abiotic stresses. RT–qPCR is the most common technique for studying gene expression. Stable reference genes are a prerequisite for obtaining accurate target gene expression results in RT–qPCR analysis.

Results
In this study, a total of 10 candidate reference genes were selected from the transcriptome of N. sibirica, and their expression stability in leaves and roots under different treatment conditions (salt, alkali, drought, cold, heat and ABA) was evaluated with the geNorm, NormFinder, BestKeeper, comparative ΔCt and RefFinder programs. The results showed that the expression stability of the candidate reference genes was dependent on the tissue and experimental conditions tested. ACT7 combined with R3H, GAPDH, TUB or His were the most stable reference genes in the salt- or alkali-treated leaves, salt-treated roots and drought-treated roots, respectively; R3H and GAPDH were the most suitable combination for drought-treated leaves, heat-treated root samples and ABA-treated leaves; DIM1 and His maintained stable expression in roots under alkali stress; and TUB combined with R3H was stable in ABA-treated roots. TBCB and GAPDH exhibited stable expression in heat-treated leaves; TBCB, R3H, and ERF3A were stable in cold-treated leaves; and the three most stable reference genes for cold-treated roots were TBCB, ACT11 and DIM1. The reliability of the selected reference genes was further confirmed by evaluating the expression patterns of the NsP5CS gene under the six treatment conditions.

Conclusion
This study provides a theoretical reference for N. sibirica gene expression standardization and quantification under various abiotic stress conditions and will help to reveal the molecular mechanisms that confer stress tolerance to N. sibirica.
Quality of life in pregnancy after percutaneous closure of atrial septal defect guided by transthoracic echocardiography
Authors: Qiu Zhi-Huang , Zong Zhen-Fang , Wu Qing-Song , Xiao Jun , Chai Tian-Ci , Chen Xiao-Dong , Shen Yue , Chen Liang-Wan 
Published: December 2022

Abstract
Purpose
We evaluated quality of life (QoL) in pregnant women who underwent transthoracic echocardiography-guided percutaneous closure of atrial septal defect (ASD).

Methods
A total of 45 pregnant women underwent transthoracic echocardiography-guided percutaneous closure of ASD. We assessed QoL using the 36-Item Short Form Survey (SF-36) and compared results between pre- and post-procedure patients, as well as between those with ASD and healthy women in their second and third trimesters of pregnancy.

Results
All patients showed improved right ventricular function and were classified as Class I, post-procedure. Mean SF-36 scores of the post-procedure group were better on all sub-scales than those of the pre-procedure group (p < 0.05), with the exception of role-emotional and mental health. Mean SF-36 scores for the pre-procedure group were also lower on all sub-scales than those of healthy pregnant controls (p < 0.05), with the exception of role physical, role emotional, and mental health. There was no difference between the post-procedure group and healthy pregnant controls. In a subgroup analysis, scores were better in some dimensions (social functioning and role emotional) for post-procedure patients in the 31–40 years of age group and the group on their second or third pregnancies than those of the 20–30 years of age group and the group on their first pregnancies (p < 0.05).

Conclusion
After closure of ASD, QoL in pregnant women was improved. In a subgroup analysis, the younger women and those on their first pregnancy performed more poorly in some dimensions (social functioning and role emotional); this suggested that these groups should receive more proactive intervention.
Safety and efficacy analysis of chemoradiotherapy/radiotherapy combined with nimotuzumab for treating unresectable oesophageal squamous cell carcinoma in elderly patients: a retrospective analysis
Authors: Zhang Yu , Wang Jidong , Cui Di , Kong Lei , Wang Peng , Fu Zhixue , Su Mengmeng , Li Bin , Liang Jun 
Published: December 2022

Abstract
Objective
To investigate the safety and efficacy of chemoradiotherapy or radiotherapy combined with nimotuzumab in the treatment of unresectable oesophageal squamous cell carcinoma (ESCC) in elderly patients.

Methods
This study retrospectively analysed 54 cases of elderly patients (aged over 70 years) with unresectable ESCC in our centre between December 2016 and November 2019. The patients were treated with a radiation dose of 50–61.6 Gy (25–30 fractions) combined with nimotuzumab for targeted therapy with or without chemotherapy according to each patient’s condition. The patients were observed for quality of life, safety, side effects and survival before and after the treatment.

Results
Among the 54 patients, 26 were treated with nimotuzumab combined with chemoradiotherapy and 28 were treated with nimotuzumab combined with radiotherapy. Toxicities were mainly oesophagitis (≥ Grade 2, 38.9%), myelosuppression (≥ Grade 3, 24.1%) and hypoproteinaemia (any grade, 94.4%). The rates of complete response, partial response, disease stability and disease progression were 11.1% (6/54), 81.5% (44/54), 3.7% (2/54) and 3.7% (2/54), respectively, and the overall objective response rate was 92.6% (50/54). The median follow-up time was 35.1 months, and the 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 61.1% (1 year OS) and 35.2% (2 year OS), 42.6% (1 year PFS) and 16.7% (2 year PFS), respectively. The median OS and PFS rates were 16.0 and 10.0 months, respectively.

Conclusion
Nimotuzumab combined with chemoradiotherapy or radiotherapy was well tolerated in elderly patients with unresectable ESCC. This combination can achieve a good treatment response and enhance survival.
Development of a behavioural framework for dementia care partners’ fall risk management
Authors: Zhou Yuanjin , Berridge Clara , Hooyman Nancy R. , Sadak Tatiana , Mroz Tracy M. , Phelan Elizabeth A. 
Published: December 2022

Abstract
Background
Although older adults living with dementia (OLWD) are at high risk for falls, few strategies that effectively reduce falls among OLWD have been identified. Dementia care partners (hereinafter referred to as “care partners”) may have a critical role in fall risk management (FRM). However, little is known about the ways care partners behave that may be relevant to FRM and how to effectively engage them in FRM.

Methods
Semi-structured, in-depth interviews were conducted with 14 primary care partners (age: 48–87; 79% women; 50% spouses/partners; 64% completed college; 21% people of colour) of community-dwelling OLWD to examine their FRM behaviours, and their observations of behaviours adopted by other care partners who were secondary in the caring role.

Results
The analysis of interview data suggested a novel behavioural framework that consisted of eight domains of FRM behaviours adopted across four stages. The domains of FRM behaviours were 1. functional mobility assistance, 2. assessing and addressing health conditions, 3. health promotion support, 4. safety supervision, 5. modification of the physical environment, 6. receiving, seeking, and coordinating care, 7. learning, and 8. self-adjustment. Four stages of FRM included 1. supporting before dementia onset, 2. preventing falls, 3. preparing to respond to falls, and 4. responding to falls. FRM behaviours varied by the care partners’ caring responsibilities. Primary care partners engaged in behaviours from all eight behavioural domains; they often provided functional mobility assistance, safety supervision, and modification of the physical environment for managing fall risk. They also adopted behaviours of assessing and addressing health conditions, health promotion support, and receiving, seeking and coordinating care without realizing their relevance to FRM. Secondary care partners were reported to assist in health promotion support, safety supervision, modification of the physical environment, and receiving, seeking, and coordinating care.

Conclusions
The multi-domain and multi-stage framework derived from this study can inform the development of tools and interventions to effectively engage care partners in managing fall risk for community-dwelling OLWD.
Recent hospitalization and risk of antidepressant initiation in people with Parkinson’s disease
Authors: Hämäläinen Iida , Tiihonen Miia , Hartikainen Sirpa , Tolppanen Anna-Maija 
Published: December 2022

Abstract
Background
People with Parkinson’s disease (PD) are more likely to be hospitalized and initiate antidepressant use compared to people without PD. It is not known if hospitalization increases the risk of antidepressant initiation. We studied whether a recent hospitalization associates with antidepressant initiation in people with PD.

Methods
A nested case-control study within the nationwide register-based FINPARK cohort which includes community-dwelling Finnish residents diagnosed with PD between years 1996 and 2015 (N = 22,189) was conducted. Initiation of antidepressant use after PD diagnosis was identified from Prescription Register with 1-year washout period (cases). One matched non-initiator control for each case was identified (N = 5492 age, sex, and time since PD diagnosis-matched case-control pairs). Hospitalizations within the 14 day-period preceding the antidepressant initiation were identified from the Care Register for Health Care.

Results
The mean age at antidepressant initiation was 73.5 years with median time since PD diagnosis 2.9 years. Selective serotonin reuptake inhibitors (48.1%) and mirtazapine (35.7%) were the most commonly initiated antidepressants. Recent hospitalization was more common among antidepressant initiators than non-initiators (48.3 and 14.3%, respectively) and was associated with antidepressant initiation also after adjusting for comorbidities and use of medications during the washout (adjusted OR, 95% CI 5.85, 5.20–6.59). The initiators also had longer hospitalizations than non-initiators. PD was the most common main discharge diagnosis among both initiators (54.6%) and non-initiators (28.8%). Discharge diagnoses of mental and behavioral disorders and dementia were more common among initiators.

Conclusions
Hospitalisation is an opportunity to identify and assess depressive symptoms, sleep disorders and pain, which may partially explain the association. Alternatively, the indication for antidepressant initiation may have led to hospitalisation, or hospitalisation to aggravation of, e.g., neuropsychiatric symptoms leading to antidepressant initiation.
Virological failure among people living with HIV receiving second-line antiretroviral therapy in Pune, India
Authors: Salvi Sonali , Raichur Priyanka , Kadam Dileep , Sangle Shashikala , Gupte Nikhil , Nevrekar Neetal , Patil Sandesh , Chavan Amol , Nimkar Smita , Marbaniang Ivan , Mave Vidya 
Published: December 2022

Abstract
Background
The number of people receiving second-line antiretroviral therapy (ART) has increased as global access to ART has expanded. Data on the burden and factors associated with second-line ART virologic failure (VF) from India remain limited.

Methods
We conducted cross-sectional viral load (VL) testing among adults (≥ 18 years) who were registered at a publicly funded ART center in western India between 2014 and 2015 and had received second-line ART for at least 6 months. Sociodemographic and clinical characteristics were abstracted from routinely collected programmatic data. Logistic regression evaluated factors associated with VF (defined as VL > 1000 copies/mL).

Results
Among 400 participants, median age was 40 years (IQR 34–44), 71% (285/400) were male, and 15% (59/400) had VF. Relative to participants without VF, those with VF had lower median CD4 counts (230 vs 406 cells/mm3, p < 0.0001), lower weight at first-line failure (49 vs 52 kg, p = 0.003), were more likely to have an opportunistic infection (17% vs 3%, p < 0.0001) and less likely to have optimal ART adherence (71% vs 87%, p = 0.005). In multivariable analysis, VF was associated with opportunistic infection (aOR, 4.84; 95% CI, 1.77–13.24), lower CD4 count (aOR 4.15; 95% CI, 1.98–8.71) and lower weight at first-line failure (aOR, 2.67; 95% CI, 1.33–5.34).

Conclusions
We found second-line VF in about a sixth of participants in our setting, which was associated with nearly fivefold increased odds in the context of opportunistic infection. Weight could be a useful clinical indicator for second-line VF.
Clinical and epidemiologic evaluation of a 2020 chikungunya outbreak in Cambodia
Authors: Rachmat Agus , Kelly Gerard C. , Hontz Robert D. , Supaprom Chonthida , Heang Vireak , Hip Phireak , Garcia-Rivera Jose A. , Prom Satharath , Chhea Chhorvann , Sutherland Ian W. , Corson Karen S. , Letizia Andrew G. 
Published: December 2022

Abstract
Background
In 2020, the Kingdom of Cambodia experienced a nationwide outbreak of chikungunya virus (CHIKV). Despite an increase in the frequency of outbreaks and expanding geographic range of CHIKV, diagnostic challenges remain, and limited surveillance data of sufficient granularity are available to characterize epidemiological profiles and disease dynamics of the virus.

Methods
An ongoing and long-standing cross-sectional study of acute undifferentiated febrile illness (AUFI) in Cambodia was leveraged to describe the disease epidemiology and characterize the clinical presentation of patients diagnosed with CHIKV during the 2020 outbreak. Participants presenting with AUFI symptoms at ten study locations provided acute and convalescent blood samples and were tested for CHIKV using a reverse transcription-polymerase chain reaction (RT-PCR) and serological diagnostic methods including IgM and IgG. Acute and follow-up clinical data were also collected.

Results
From 1194 participant blood samples tested, 331 (27.7%) positive CHIKV cases were detected. Most CHIKV positive individuals (280, 84.6%) reported having a fever 3 to 4 days prior to visiting a health facility. Symptoms including chills, joint pain, nausea, vomiting, and lesions were all statistically significant among CHIKV positive participants compared to CHIKV negative AUFI participants. Cough was negatively associated with CHIKV positive participants. Positivity proportions were significantly higher among adults compared to children. No significant difference was found in positivity proportion between rainy and dry seasons during the outbreak. Positive CHIKV cases were detected in all study site provinces, with the highest test positivity proportion recorded in the rural northeast province of Kratie.

Conclusions
Surveillance data captured in this study provided a clinical and epidemiological characterization of positive CHIKV patients presenting at selected health facilities in Cambodia in 2020, and highlighted the widespread distribution of the outbreak, impacting both urban and rural locations. Findings also illustrated the importance of utilizing both RT-PCR and serological testing for effective CHIKV surveillance.
RESOLVE-DWI-based deep learning nomogram for prediction of normal-sized lymph node metastasis in cervical cancer: a preliminary study
Authors: Qian Weiliang , Li Zhisen , Chen Weidao , Yin Hongkun , Zhang Jibin , Xu Jianming , Hu Chunhong 
Published: December 2022

Abstract
Background
It is difficult to predict normal-sized lymph node metastasis (LNM) in cervical cancer clinically. We aimed to investigate the feasibility of using deep learning (DL) nomogram based on readout segmentation of long variable echo-trains diffusion weighted imaging (RESOLVE-DWI) and related patient information to preoperatively predict normal-sized LNM in patients with cervical cancer.

Methods
A dataset of MR images [RESOLVE-DWI and apparent diffusion coefficient (ADC)] and patient information (age, tumor size, International Federation of Gynecology and Obstetrics stage, ADC value and squamous cell carcinoma antigen level) of 169 patients with cervical cancer between November 2013 and January 2022 were retrospectively collected. The LNM status was determined by final histopathology. The collected studies were randomly divided into a development cohort (n = 126) and a test cohort (n = 43). A single-channel convolutional neural network (CNN) and a multi-channel CNN based on ResNeSt architectures were proposed for predicting normal-sized LNM from single or multi modalities of MR images, respectively. A DL nomogram was constructed by incorporating the clinical information and the multi-channel CNN. These models’ performance was analyzed by the receiver operating characteristic analysis in the test cohort.

Results
Compared to the single-channel CNN model using RESOLVE-DWI and ADC respectively, the multi-channel CNN model that integrating both two MR modalities showed improved performance in development cohort [AUC 0.848; 95% confidence interval (CI) 0.774–0.906] and test cohort (AUC 0.767; 95% CI 0.613–0.882). The DL nomogram showed the best performance in development cohort (AUC 0.890; 95% CI 0.821–0.938) and test cohort (AUC 0.844; 95% CI 0.701–0.936).

Conclusion
The DL nomogram incorporating RESOLVE-DWI and clinical information has the potential to preoperatively predict normal-sized LNM of cervical cancer.