bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hsp90 up-regulates PD-L1 to promote HPV-positive cervical cancer via HER2/PI3K/AKT pathway
Authors: Zeng Jie , He Si-Li , Li Li-Jie , Wang Chen 
Published: October 2021

AbstractBackgroundHPV16 is the predominant cancer-causing strain that is responsible for over 50% of all cervical cancers. In this study, we aim to investigate the therapeutic effect of heat shock protein 90 (Hsp90) knockdown on HPV16+cervical cancer progression and the underlying mechanism.MethodsThe transcript and protein expression of Hsp90 in normal cervical and HPV16+cervical cancer tissues and cell lines were detected by qRT-PCR, immunohistochemistry staining and Western blot. Hsp90 knockdown clones were established using HPV16+cervical cancer cell line Caski and SiHa cells. The effect of Hsp90 knockdown on HER2/PI3K/AKT pathway and PD-L1 expression was characterized using qRT-PCR and Western blot analysis. Cell proliferation and migration were determined using MTT and transwell assays. Using mouse xenograft tumor model, the impact of Hsp90 knockdown and PD-L1 overexpression on tumor progression was evaluated.ResultsHsp90 expression was up-regulated in HPV16+cervical cancer tissues and cells. Knockdown of Hsp90 inhibited proliferation and migration of Caski and SiHa cells. PD-L1 expression in cervical cancer tissues was positively correlated with Hsp90 expression, and Hsp90 regulated PD-L1 expression via HER2/PI3K/AKT signaling pathway. The results of mouse xenograft tumor model demonstrated Hsp90 knockdown suppressed tumor formation and overexpression of PD-L1 simultaneously eliminated the cancer-suppressive effect of Hsp90 knockdown.ConclusionIn this study, we demonstrated a promising tumor-suppressive effect of Hsp90 knockdown in HPV16+cervical cancers, and investigated the underlying molecular pathway. Our results suggested that Hsp90 knockdown holds great therapeutic potential in treating HPV16+cervical cancers.
Conserved and breed-specific differences in the cervical transcriptome of sheep with divergent fertility at the follicular phase of a natural oestrus cycle
Authors: Abril-Parreño Laura , Meade Kieran G. , Krogenæs Anette Kristine , Druart Xavier , Fair Sean , Cormican Paul 
Published: October 2021

Abstract
Background
The outcome of cervical artificial insemination (AI) with frozen-thawed semen in sheep is limited by the inability of sperm to traverse the cervix of some ewe breeds. Previous research has demonstrated that cervical sperm transport is dependent on ewe breed, as sperm can traverse the cervix in greater numbers in some higher fertility ewe breeds. However, the molecular mechanisms underlying ewe breed differences in sperm transport through the cervix remain unknown. In this study, we aimed to characterise the cervical transcriptome of four European ewe breeds with known differences in pregnancy rates following cervical AI using frozen-thawed semen at the follicular phase of a natural oestrous cycle. Cervical post mortem tissue samples were collected from two Irish ewe breeds (Belclare and Suffolk; medium and low fertility, respectively) and from two Norwegian ewe breeds (Norwegian White Sheep (NWS) and Fur; high fertility compared to both Irish breeds) at the follicular phase of a natural oestrous cycle (n = 8 to 10 ewes per breed).

Results
High-quality RNA extracted from biopsies of the mid-region of the cervix was analysed by RNA-sequencing and Gene Ontology (GO). After stringent filtering (P <  0.05 and FC > 1.5), a total of 11, 1539 and 748 differentially expressed genes (DEGs) were identified in Belclare, Fur and NWS compared to the low fertility Suffolk breed, respectively. Gene ontology analysis identified significantly enriched biological processes involved in muscle contraction, extracellular matrix (ECM) development and the immune response. Gene co-expression analysis revealed similar patterns in muscle contraction and ECM development modules in both Norwegian ewe breeds, which differed to the Irish ewe breeds.

Conclusions
These breed-specific biological processes may account for impaired cervical sperm transport through the cervix in sheep during the follicular phase of the reproductive cycle. This novel and comprehensive dataset provides a rich foundation for future targeted initiatives to improve cervical AI in sheep.
Transcriptome analysis of Clavibacter michiganensis subsp. michiganensis-infected tomatoes: a role of salicylic acid in the host response
Authors: Yokotani Naoki , Hasegawa Yoshinori , Sato Masaru , Hirakawa Hideki , Kouzai Yusuke , Nishizawa Yoko , Yamamoto Eiji , Naito Yoshiki , Isobe Sachiko 
Published: October 2021

AbstractBacterial canker of tomato (Solanum lycopersicon) caused by the Gram-positive bacteriumClavibacter michiganensissubsp.michiganensis(Cmm) is an economically important disease.To understand the host defense response toCmminfection, transcriptome sequences in tomato cotyledons were analyzed by RNA-seq. Overall, 1788 and 540 genes were upregulated and downregulated upon infection, respectively. Gene Ontology enrichment analysis revealed that genes involved in the defense response, phosphorylation, and hormone signaling were over-represented by the infection. Induced expression of defense-associated genes suggested that the tomato response toCmmshowed similarities to common plant disease responses. After infection, many resistance gene analogs (RGAs) were transcriptionally upregulated, including the expressions of some receptor-like kinases (RLKs) involved in pattern-triggered immunity. The expressions ofWRKYs,NACs,HSFs, andCBP60sencoding transcription factors (TFs) reported to regulate defense-associated genes were induced after infection withCmm. Tomato genes orthologous to ArabidopsisEDS1,EDS5/SID1, andPAD4/EDS9, which are causal genes of salicylic acid (SA)-deficient mutants, were upregulated after infection withCmm. Furthermore,Cmminfection drastically stimulated SA accumulation in tomato cotyledons. Genes involved in the phenylalanine ammonia lyase pathway were upregulated, whereas metabolic enzyme gene expression in the isochorismate synthase pathway remained unchanged. Exogenously applied SA suppressed bacterial growth and induced the expression ofWRKYs, suggesting that someCmm-responsive genes are regulated by SA signaling, and SA signaling activation should improve tomato immunity againstCmm.
Predictive ability of the G8 screening test to determine probable sarcopenia and abnormal comprehensive geriatric assessment in older patients with solid malignancies
Authors: Cavusoglu Cagatay , Tahtaci Gozde , Dogrul Rana Tuna , Ileri Ibrahim , Yildirim Funda , Candemir Burcu , Kizilarslanoglu Muhammet Cemal , Uner Aytug , Goker Berna 
Published: October 2021

Abstract
Background
Pre-treatment evaluation for sarcopenia is recommended in cancer patients. New screening tests that are less time-consuming and can identify patients who will potentially benefit from geriatric assessment are being developed; the G8 geriatric screening test is one such example. We aimed to investigate whether the G8 screening test can detect probable sarcopenia and is valid and reliable compared to a comprehensive geriatric assessment (CGA) in Turkish older adults with solid cancers.

Methods
We included solid cancer patients referred to a single center. Probable sarcopenia and abnormal CGA were defined as low handgrip strength. Cut-offs for handgrip strength in the Turkish population have been previously determined to be 32 kg for males and 22 kg for females and impairment in at least one of the CGA tests, respectively. The CGA tests comprised KATZ Basic Activities of Daily Living Scale Lawton–Brody Instrumental Activities of Daily Living Scale, Mini-Mental-State Examination Scale, Geriatric Depression Scale-15, and Mini-Nutritional Assessment Short Form. Receiver operating characteristic curve analyses evaluated the test’s predictive ability. Intra-rater and inter-rater reliabilities were assessed.

Results
The median age of the 76 patients included was 72 (65–91) years. There was a moderate correlation between handgrip strength and the G8 test total score. The sensitivity and specificity of the G8 test to detect probable sarcopenia alone (cut off score = 12.5) were 50 and 92%, respectively (AUC: 0.747; p < 0.001); to determine abnormal CGA plus probable sarcopenia (cut off score = 13) were 93.33 and 86.89%, respectively (AUC: 0.939; p < 0.001); and to detect abnormal CGA alone (cut off score = 14) were 79.63 and 95.45%, respectively (AUC: 0.893; p < 0.001). The G8 test results agreed with those of CGA (κ = 0.638; p < 0.001). Both inter- and intra-rater assessments of G8 scores revealed a strong agreement (Interclass correlation coefficient = 0.979, p < 0.001 and ρ = 0.994, p < 0.001, respectively).

Conclusions
The Turkish version of the G8 test is a good screening tool to detect probable sarcopenia alone and in conjunction with abnormal CGA in older patients with solid malignancies. The G8 screening tool may thus be useful in detecting probable sarcopenia in Turkish older adults with solid cancers.
Mycobacteria avium-related peritonitis in a patient undergoing peritoneal dialysis: case report and review of the literature
Authors: Lu Jifang , Jiang Zhou , Wang Ling , Mou Shan , Yan Hao 
Published: October 2021

Abstract
Background
Mycobacteria avium (M. avium) is a species of ubiquitous slowly growing nontuberculous mycobacteria. It causes opportunistic infections. However, M. avium-related peritonitis in peritoneal dialysis (PD) patients is rare.

Case presentation
A 51-year-old female end-stage kidney disease patient undergoing PD was admitted for a noninfectious complication. She presented catheter exit site drainage and slightly increased PD effluent white cell count (WCC) with polymorphonuclear predominance on admission. Exit site infection and PD-related peritonitis were diagnosed. Repeated cultures of effluent and drainage were negative. Initial empirical antibiotics and further adjustment were not rewarding. PD was terminated 2 weeks later, however, shortly the patient developed stupor, high fever, peritoneal irritation, and spontaneous chylous ascites, and showed elevated ascitic adenosine deaminase (ADA). The manifestations persisted and the patient’s general condition deteriorated despite intensified antibiotic therapy. Massive parallel sequencing identified M. avium in ascites on hospital day 25, and 4-drug treatment with azithromycin, amikacin, rifampin, and ethambutol was initiated. Nevertheless, the patient died from sepsis on hospital day 30.

Conclusions
We report a case of PD-related M. avium peritonitis. Prolonged culture-negative peritonitis, chylous ascites, and elevated ascitic ADA may hint the possibility of mycobacterial infections. Diagnostic method allowing prompt identification of the pathogen is warranted. The prognosis can be extremely poor, and the prophylaxis and treatment should be better defined.
Recurrent primary pyogenic ventriculitis in an adult woman: a case report
Authors: Hong Shanyan , Yang Yingxia , Zhang Qianying , Zhuo Shitu , Wang Lingxing 
Published: October 2021

Abstract
Background
Recurrent primary pyogenic ventriculitis has not been reported previously. We present a unique case of recurrent primary pyogenic ventriculitis in an adult. And we believe that our study makes a significant contribution to the literature.

Case presentation
An adult woman with uncontrolled diabetes experienced two episodes of pyogenic ventriculitis caused by Escherichia coli over 4 years. She had typical imaging features, and the source of infection was undetermined. After antibiotic treatment, she recovered fully.

Conclusions
Early recognition and therapy will improve patient prognosis.
Retrospective comparison of death or neurodevelopmental outcomes in extremely low birth weight preterm infants following different management options of haemodynamically significant patent ductus arteriosus
Authors: Wu Jania Jia-Ying , Niduvaje Krishnamoorthy , Lee Le ye , Amin Zubair 
Published: October 2021

Abstract
Background
Optimal management of haemodynamically significant patent ductus arteriosus (HsPDA) in premature babies remains controversial. Our aim is to compare death and/or adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants with HsPDA who were managed with conservative [C], medical [M] and/or surgical [S] treatment, with secondary aim to examine short-term morbidities among [S] and [C] groups. The study also compared outcomes in very low birth weight (VLBW) infants with HsPDA and non-HsPDA.

Methods
A retrospective study of VLBW preterm infants born before 29 weeks in Singapore from 2007 to 2016 was conducted.

Results
A total of 474 VLBW infants were admitted in NUH from 2007 to 2016. Infants aged between 24 + 0 and 28 + 6 weeks of gestation, weighing ≤1500 g and diagnosed with patent ductus arteriosus (PDA) were included in the study, of which 172 infants (124 HsPDA and 48 non-HsPDA) were analyzed. Among infants with HsPDA, 17 infants were managed with [C], 83 with [M] and 24 with [S]. Mortality was not increased regardless of the presence of HsPDA or treatment received. Infants with non-HsPDA were less likely to have isolated speech delay (p < 0.05), but not global developmental delay (GDD). No significant differences in neurodevelopmental outcomes such as hearing loss, cerebral palsy (CP) and speech delay were found. [M + S] infants were at a higher risk of developing chronic lung disease (CLD) (OR 6.83, p < 0.05) and short-term growth failure compared to [C] infants. They were significantly shorter and had a smaller head circumference at discharge (p < 0.05). [M + S] infants also had elevated creatinine compared to those in group [C] (81.1 ± 24.1 vs 48.3 ± 11.8 umol/L, p < 0.000).

Conclusions
Compared to conservative management, infants requiring [M + S] treatment for HsPDA were more likely to have short-term complications such as CLD, elevated creatinine, and poorer growth. Despite a more turbulent postnatal course, death and/or adverse neurodevelopmental outcomes were not worse in infants managed with [M + S].
Time-varying effect of drunk driving regulations on road traffic mortality in Guangzhou, China: an interrupted time-series analysis
Authors: Xu Xiao-Han , Dong Hang , Li Li , Yang Zhou , Lin Guo-Zhen , Ou Chun-Quan 
Published: October 2021

Abstract
Background
China has introduced a series of stricter policies to criminalize drunk driving and increase penalties since May 2011. However, there is no previous study examining the time-varying impacts of drunk driving regulations on road traffic fatalities based on daily data.

Methods
We collected 6536 individual data of road traffic deaths (RTDs) in Guangzhou from 2008 to 2018. The quasi-Poisson regression models with an inclusion of the intervention variable and the interaction of intervention variable and a function of time were used to quantify the time-varying effects of these regulations.

Results
During the 11-year study period, the number of population and motor vehicles showed a steady upward trend. However, the population- and motor vehicles- standardized RTDs rose steadily before May 2011, the criminalizing drunk driving intervention was implemented and gradually declined after that. The new drunk driving intervention were associated with an average risk reduction of RTDs (ER = -9.01, 95% eCI: − 10.05% to − 7.62%) during the 7.7 years after May 2011. On average, 75.82 (95% eCI, 54.06 to 92.04) RTDs per 1 million population annually were prevented due to the drunk driving intervention.

Conclusion
These findings would provide important implications for the development of integrated intervention measures in China and other countries attempting to reduce traffic fatalities by stricter regulations on drunk driving.
An initial evaluation of the safety of a disposable oscillating positive expiratory pressure device in patients with chronic obstructive pulmonary disease: a short-term pilot study
Authors: O’Sullivan Kevin J. , Power Valerie , Linnane Barry , McGrath Deirdre , Fogarty Hilda , Ryan Martina , White Rebecca , Noonan Conor , Mulloy Eithne , O’Sullivan Leonard W. , Dunne Colum P. 
Published: October 2021

Abstract
Background
Handheld oscillating positive expiratory pressure (OPEP) devices have been a mainstay of treatment for patients with hypersecretory conditions such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) since the 1970s. Current devices are reusable and require regular cleaning and disinfection to prevent harbouring potentially pathogenic organisms. Adherence to cleaning regimens for respiratory devices is often poor and in response to this, a prototype disposable OPEP device—the ‘UL-OPEP’ (University of Limerick—Oscillating Positive Expiratory Pressure device)—was developed to mitigate the risk of contamination by pathogens. The device was previously evaluated successfully in a group of paediatric CF patients. The aim of the current study was to initially evaluate the safety of the prototype in patients with COPD over a period of 1 month to ensure no adverse events, negative impacts on lung function, exercise tolerance, or quality of life. Data on user experience of the device were also collected during post-study follow-up.

Methods
A sample of 50 volunteer participants were recruited from pulmonary rehabilitation clinics within the local hospital network. The patients were clinically stable, productive, and not current or previous users of OPEP devices. Participants were invited to use a prototype disposable OPEP device daily for a period of 1 month. Pre- and post-study lung function was assessed with standard spirometry, and exercise tolerance with the 6-min-walk-test (6MWT). Quality of life was assessed using the St. George’s Respiratory Questionnaire (SGRQ), and user experience of the prototype device evaluated using a post-study questionnaire.

Results
24 Participants completed the study: 9 were female. Overall median age was 67.5 years, range 53–85 years. Lung function, 6-min walk test, and SGRQ scores showed no significant change post-study. User feedback was positive overall.

Conclusions
The results indicate that the UL-OPEP is safe to use in patients with COPD. No adverse events were recorded during the study or in the follow-up period of 2 weeks. The device did not negatively impact patients’ lung function, exercise tolerance, or quality of life during short term use (1 month), and usability feedback received was generally positive. Larger, longer duration studies will be required to evaluate efficacy.
Registration The study was approved as a Clinical Investigation by the Irish Health Products Regulatory Authority (CRN-2209025-CI0085).
The impact of multimorbidity level and functional limitations on the accuracy of using self-reported survey data compared to administrative data to measure general practitioner and specialist visits in community-living adults
Authors: Griffith Lauren E. , Gruneir Andrea , Fisher Kathryn A. , Aljied Rumaisa , Perez Richard , Nguyen Francis , Patterson Christopher , Markle-Reid Maureen , Ploeg Jenny , Upshur Ross 
Published: October 2021

Abstract
Background
Researchers often use survey data to study the effect of health and social variables on physician use, but how self-reported physician use compares to administrative data, the gold standard, in particular within the context of multimorbidity and functional limitations remains unclear. We examine whether multimorbidity and functional limitations are related to agreement between self-reported and administrative data for physician use.

Methods
Cross-sectional data from 52,854 Ontario participants of the Canadian Community Health Survey linked to administrative data were used to assess agreement on physician use. The number of general practitioner (GP) and specialist visits in the previous year was assessed using both data sources; multimorbidity and functional limitation were from self-report.

Results
Fewer participants self-reported GP visits (84.8%) compared to administrative data (89.1%), but more self-reported specialist visits (69.2% vs. 64.9%). Sensitivity was higher for GP visits (≥90% for all multimorbidity levels) compared to specialist visits (approximately 75% for 0 to 90% for 4+ chronic conditions). Specificity started higher for GP than specialist visits but decreased more swiftly with multimorbidity level; in both cases, specificity levels fell below 50%. Functional limitations, age and sex did not impact the patterns of sensitivity and specificity seen across level of multimorbidity.

Conclusions
Countries around the world collect health surveys to inform health policy and planning, but the extent to which these are linked with administrative, or similar, data are limited. Our study illustrates the potential for misclassification of physician use in self-report data and the need for sensitivity analyses or other corrections.
Social participation in the unified health system of Brazil: an exploratory study on the adequacy of health councils to resolution 453/2012
Authors: de Cássia Costa da Silva Rita , de Novais Maykon Anderson Pires , Zucchi Paola 
Published: October 2021

Abstract
Introduction
Social participation is one of the guidelines of the Brazilian health system. Health councils are collegiate instances of participation established by Law 8.142/90. The most recent legal regulation for council organization and functioning was established through Resolution 453/2021. The institution of health councils has a permanent and deliberative nature to act in the formulation, deliberation and control of health policy implementation, including in economic and financial aspects.

Objective
To evaluate the compliance of health councils with the directives for the establishment, restructuring and operation of the councils from Brazil, based on Resolution 453/2012.

Methods
An exploratory, descriptive study that used the Health Council Monitoring System as a data source. Qualitative variables were selected to identify the characteristics related to the councils’ establishment (legal instruments for establishment), the strategies adopted for restructuring (budget allocation, existence of an executive secretariat, provision of a dedicated office) and the characteristics of the health councils’ operation (frequency of regular meetings, existence of a board of directors, the election of the board of directors).

Results
The study analyzed three groups of characteristics related to the constitution, strategies adopted for restructuring and the functioning of the councils. Regarding the constitution of the councils, the findings revealed that the vast majority was constituted in accordance with the legislation and, therefore, is in compliance with Resolution 453/2021. In the second group of characteristics that describe the restructuring of councils, the study found that less than half of registered councils are in compliance with the standard. And, finally, in the third group of characteristics, it was found that the boards have adopted different frequencies for regular meetings and approximately 50% of the boards studied have a board of directors.

Conclusions
The councils still do not meet the minimum conditions necessary to fulfil their role in the Unified Health System (SUS), as stipulated in Resolution 453/2021. This situation requires monitoring by public oversight agencies. Despite the increase in popular participation with the creation of the health councils, this study demonstrated that most councils still do not meet the minimum conditions for monitoring public health policy. The improvement of the Health Councils Monitoring System (SIACS) to become an instrument for monitoring the councils, with the definition of goals and results, may contribute to the organization of the councils and, therefore, to the realization of social participation in Brazil.