bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality Among Noncoronavirus Disease 2019 Critically Ill Patients Attributable to the Pandemic in France
Authors: Payet Cécile , Polazzi Stéphanie , Rimmelé Thomas , Duclos Antoine 
Published: July 2021

Objectives:
We investigated whether the risk of death among noncoronavirus disease 2019 critically ill patients increased when numerous coronavirus disease 2019 cases were admitted concomitantly to the same hospital units.

Design:
We performed a nationwide observational study based on the medical information system from all public and private hospitals in France.

Setting:
Information pertaining to every adult admitted to ICUs or intermediate care units from 641 hospitals between January 1, 2020, and June 30, 2020 was analyzed.

Patients:
A total of 454,502 patients (428,687 noncoronavirus disease 2019 and 25,815 coronavirus disease 2019 patients) were included.

Interventions:
For each noncoronavirus disease 2019 patient, pandemic exposure during their stay was calculated per day using the proportion of coronavirus disease 2019 patients among all patients treated in ICU.

Measurements and Main Results:
We computed a multivariable logistic regression model to estimate the influence of pandemic exposure (low, moderate, and high exposure) on noncoronavirus disease 2019 patient mortality during ICU stay. We adjusted on patient and hospital confounders. The risk of death among noncoronavirus disease 2019 critically ill patients increased in case of moderate (adjusted odds ratio, 1.12; 95% CI, 1.05–1.19; p < 0.001) and high pandemic exposures (1.52; 95% CI, 1.33–1.74; p < 0.001).

Conclusions:
In hospital units with moderate or high levels of coronavirus disease 2019 critically ill patients, noncoronavirus disease deaths were at higher levels.
The impact of the coronavirus disease 2019 pandemic on the diagnosis and treatment of cancer in Northern Portugal
Authors: Morais Samantha , Antunes Luís , Rodrigues Jéssica , Fontes Filipa , Bento Maria José , Lunet Nuno 
Published: July 2021

Objectives
The coronavirus disease 2019 (COVID-19) pandemic has affected the availability of healthcare resources, and adjustments to cancer care have been necessary considering the risk of morbidity by COVID-19 and of cancer progression. This study aims to quantify the impact of the COVID-19 pandemic on the care of patients with cancer by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019.

Methods
Cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin-melanoma, breast, cervix, prostate, non-Hodgkin lymphoma, and leukemia from the Portuguese Oncology Institute of Porto, and diagnosed between 2 March and 1 July 2019 (before COVID-19) and 2020 (after COVID-19) were identified. Those with the first treatment outside the Portuguese Oncology Institute of Porto were excluded. Sociodemographic, clinical and treatment characteristics were obtained from the cancer registry database and clinical files.

Results
The absolute number of new cancer cases decreased nearly 40% after the COVID-19 pandemic (from 1430 to 866). The largest decreases were observed for cervical (−74.3%) and prostate (−71.7%) cancers. Cases were more often diagnosed at more advanced stages in 2020 (P = 0.001), and the proportion of patients not starting any treatment until 1 July was just under 20% in 2019 and nearly 40% in 2020. The median times from symptoms onset, first medical exam and first appointment to diagnosis, and from diagnosis to first appointment, multidisciplinary tumor board meeting and first treatment were shorter after COVID-19.

Conclusions
There was a notable overall decrease in cancer diagnoses after COVID-19, with changes in the characteristics of incident cases.
Risk factors of cervical cancer among ethnic minorities in Yunnan Province, China: a case–control study
Authors: Zhao Min , Gu Rong-yan , Ding Song-rui , Luo Lei , Jia Yue , Gao Chen-xin , Chen Bin , Xu Xue-bin , Chen Hong-fen 
Published: July 2021

Background
Cervical cancer is a common malignant tumor of the female reproductive system in the world, which is a serious threat to women’s life and health. According to the latest report, the incidence of cervical cancer is 11.42 per 100 000, and the mortality rate is 3.77 per 100 000 in Yunnan Province, which is still higher than the national average. Although there have been some relevant studies on the risk factors of cervical cancer in recent years, research on ethnic minorities is lacking in Yunnan Province.

Objective
To analyze and explore the related risk factors of cervical cancer in women of ethnic minorities in Yunnan Province, to provide the scientific basis for the development of cervical cancer prevention and control strategies and measures in this region.

Methods
In total 1119 cervical cancer patients diagnosed by histopathology at the Yunnan Cancer Center (Yunnan Cancer Hospital) from January 2010 to December 2019 were selected as the case group. According to the 1:1 matching principle of the case–control study, 1119 patients with nonmalignant tumors of the same nationality, the same hospital, age difference less than 3 years old, were selected as the control group. Univariate and multivariate conditional logistic regression were used for statistical analysis.

Results
Basic medical insurance for rural residents (OR = 3.659; P = 0.003), human papilloma virus (HPV) infection (OR = 90.030; P < 0.001) and concurrent reproductive tract infections (OR = 1.992; P = 0.047) were risk factors for cervical cancer. Late first marriage(OR = 0.881; P = 0.032), the number of normal childbirths ≤2 (OR = 0.480, P = 0.033) and contraception (OR = 0.291; P = 0.002) were positive factors for cervical cancer.

Conclusion
The high incidence of cervical cancer in Yunnan minority women is the result of many factors: HPV infection is the highest risk factor for cervical cancer, women with reproductive tract infections and basic medical insurance for rural residents have a higher risk for cervical cancer; Late first marriage, the number of deliveries ≤2 and contraception are positive factors for cervical cancer.
Elevated serum Dickkopf-1 is a biomarker for bone erosion in patients with psoriatic arthritis
Authors: Chung Yukchiu , Li Zhi-Chang , Sun Xiao-Lin , Liu Yan-Ying , Shao Miao , Gan Yu-Zhou , Li Yi-Min , Li Yu-Hui , Zhang Xue-Wu 
Published: July 2021

Abstract

Background:
Psoriatic arthritis (PsA) is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology. Dickkopf-1 (Dkk-1) is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation. The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients.

Methods:
Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 69 patients with PsA and 60 controls, including 39 rheumatoid arthritis (RA) patients, and 21 healthy controls (HCs). Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA. The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed. Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA.

Results:
Dkk-1 was elevated in 68.1% (47/69) of the patients with PsA, 46.2% (18/39) of RA patients, and 9.5% (2/21) of HCs. Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs. The level of serum Dkk-1 was correlated with a swollen joint count, and levels of complement components 3 and 4. Elevated Dkk-1 level (odds ratio = 4.440, 95% confidence interval: 1.246–15.817, P = 0.021) was identified as the risk factor for bone erosion in PsA.

Conclusions:
The serum level of Dkk-1 is abnormally elevated in PsA patients. The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.
Concomitant Use of Proton Pump Inhibitors With Capecitabine Based Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer
Authors: Menon Anjali , Abraham Aswin G. , Mahfouz Maria , Thachuthara Joseph J. , Usmani Nawaid , Warkentin Heather , Ghosh Sunita , Nijjar Tirath , Severin Diane , Tankel Keith , Paulson Kim , Mulder Karen , Roa Wilson , Joseph Kurian 
Published: July 2021

Aim:
Capecitabine (Cape) is routinely used for the neoadjuvant chemoradiation treatment (NACRT) of locally advanced rectal cancers (LARCs). Previous reports have suggested that the concomitant use of proton pump inhibitors (PPIs) may affect the efficacy of Cape, although the true effect of PPIs when used with Cape as a radiosensitizer for neoadjuvant radiation is unclear. The aim of our study was to evaluate the impact of concurrent PPI use along with fluorouracil (FU) and Cape based NACRT in terms of pathologic and oncological outcomes, in patients with LARC.

Methods:
LARC patients treated at our center with NACRT from 2010 to 2016 were identified. Postoperative pathology and follow-up outcomes were examined for any differences with relation to the use of PPIs concurrently with FU and Cape based NACRT and adjuvant chemotherapy regimens.

Results:
Three hundred four and 204 patients received treatment with FU and Cape based NACRT. No difference in pathologic complete response rate was noted between the 2 arms with the concurrent use of PPIs (25.8% and 25%, respectively, P=0.633); or with and without the use of PPIs in the Cape-NACRT arm specifically (20% and 20.7%, P=0.945). At a median follow-up of 5 years, no statistical difference in local or distant control was noted in the Cape-NACRT patients, with and without concomitant PPI use (P=0.411 and 0.264, respectively).
Multivariate analysis showed no association of PPI use and NACRT with Cape, in terms of local control (hazard ratio=0.001, P=0.988) or overall survival (hazard ratio=1.179, confidence interval=0.249-5.579, P=0.835).

Conclusions:
Our study revealed that there was no adverse pathologic or oncological outcome with the concurrent use of PPIs along with Cape-NACRT in the treatment of LARC. We report that it may be safe to use PPIs if essential, in this clinical setting, although it would be wise to exercise caution.
Immunological effector mechanisms in HIV-1 elite controllers
Authors: Hartana Ciputra Adijaya , Yu Xu G. 
Published: July 2021

Purpose of review
HIV-1 elite controllers encompass small populations of people infected with HIV-1 who can spontaneously control plasma viral loads below the limit of detection, in the absence of antiretroviral treatment. Antiviral immune responses are likely to contribute to such an impressive HIV-1 disease outcome. In this review, we discuss recent novel findings regarding antiviral innate and adaptive immune responses in elite controllers.

Recent findings
Elite controllers maintain a pool of infected cells in which intact HIV-1 proviruses are more frequently integrated into noncoding regions of the host genome, likely conferring a state of deep latency. This atypical viral reservoir configuration is best explained by potent antiviral immune responses that can successfully eliminate virally infected cells in which proviruses are integrated into permissive chromatin. However, identifying the specific type and nature of this immune selection pressure represents a formidable challenge. Recent studies continue to support the role of HIV-1-specific CD8+ T cells as the main driver of elite immune control of HIV-1, however, increasing evidence suggests that their role is complemented by a fine-tuned interplay with innate immune cell subsets. Therefore, the combination of different immune effector mechanisms may shape antiviral immunity in elite controllers.

Summary
Understanding the complex immune mechanisms responsible for natural, drug-free HIV-1 control represents a premier avenue to find and develop interventions for a cure of HIV-1 infection. Future single-cell assays designed to uncover the full genetic, epigenetic, transcriptional and functional complexity of antiviral immune responses in elite controllers may allow us to define correlates of antiviral immune protection in greater detail.
Psychopathology and Adaptive Functioning in Children, Adolescents, and Young Adults with Noonan Syndrome
Authors: Davico Chiara , Borgogno Marta , Campagna Filippa , D'Alessandro Rossella , Ricci Federica , Amianto Federico , Mussa Alessandro , Carli Diana , Ferrero Giovanni Battista , Vitiello Benedetto 
Published: July 2021

ABSTRACT:

Objective:
The objective of this study was to examine psychopathology and its impact on adaptive functioning in a sample of patients affected by Noonan syndrome (NS), a genetically heterogeneous condition with systemic manifestations.

Method:
Forty-two subjects affected by NS (23 males and 19 females), aged 5 to 21 years (mean 12.6 ± SD 5.1), were assessed for nonverbal cognitive abilities, with dimensional measures of psychopathology, adaptive functioning, and family quality of life.

Results:
The nonverbal intelligence quotient (IQ) mean was 99.4 ± SD 22.2, with 3 subjects (8%, 95% confidence interval [CI], 1.6%–20.9%) showing cognitive impairment (IQ<70). The Parent Child Behavior Checklist (CBCL) total psychopathology score was in the clinical range in 10% of sample and borderline in another 10%. On the Conners' Parent Rating Scales, scores suggestive of attention-deficit/hyperactivity disorder (ADHD) were in the clinical range in 20%. On the autism quotient, autism spectrum disorder symptoms were reported in 10%. Higher scores on the Adaptive Behavioral Assessment System–Second Edition and on the World Health Organization Quality of Life (26 items) were associated with lower problems on the CBCL (r = −0.63, 95% CI, −0.78 to −0.40 and r = −0.48, 95% CI, −0.69 to −0.20, respectively).

Conclusion:
Psychopathology was common in patients with NS and negatively correlated with global functioning and family quality of life. Treatable psychopathology, such as ADHD, may constitute a treatment target for improving adaptive functioning.
Circ-PRKCI Alleviates Lipopolysaccharide-induced Human Kidney 2 Cell Injury by Regulating miR-106b-5p/GAB1 Axis
Authors: Xiong Yueli , Wang Yang , Tian Hui , Li Yuanyuan , Xu Qingjie , He Zhenkun 
Published: July 2021

Abstract:
Circular RNAs act as vital regulators in diverse diseases. However, the investigation of circular RNAs in sepsis-engendered acute kidney injury remains dismal. We aimed to explore the effects of circular RNA protein kinase C iota (circ-PRKCI) in lipopolysaccharide (LPS)-mediated HK2 cell injury. Sepsis in vitro model was established by LPS treatment. Quantitative real-time polymerase chain reaction assay was conducted for determining the levels of circ-PRKCI, microRNA-106b-5p (miR-106b-5p), and growth factor receptor binding 2-associated binding protein 1 (GAB1). Cell viability and apoptosis were evaluated using Cell Counting Kit-8 assay and flow cytometry analysis, respectively. The concentrations of interleukin-6, interleukin-1β, and tumor necrosis factor-α were measured with enzyme-linked immunosorbent assay kits. The levels of oxidative stress markers were determined using relevant commercial kits. Western blot assay was conducted for B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), and GAB1 protein levels. Dual-luciferase reporter assay and RNA immunoprecipitation assay were used to verify the association between miR-106b-5p and circ-PRKCI or GAB1. We found the Circ-PRKCI level was decreased in sepsis patients and LPS-induced human kidney 2 (HK-2) cells. LPS exposure inhibited cell viability and facilitated apoptosis, inflammation, and oxidative stress in HK-2 cells. Circ-PRKCI overexpression abrogated the effects of LPS on cell apoptosis, inflammation, and oxidative stress in HK-2 cells. Furthermore, circ-PRKCI was identified as the sponge for miR-106b-5p to positively regulate GAB1 expression. Overexpression of circ-PRKCI relieved LPS-mediated HK-2 cell damage by sponging miR-106b-5p. MiR-106b-5p inhibition ameliorated the injury of HK-2 cells mediated by LPS, whereas GAB1 knockdown reversed the effect. Collectively, Circ-PRKCI overexpression attenuated LPS-induced HK-2 cell injury by regulating miR-106b-5p/GAB1 axis.
Circ-USP9X Inhibition Reduces Oxidized Low-density Lipoprotein–induced Endothelial Cell Injury via the microRNA 599/Chloride Intracellular Channel 4 Axis
Authors: Peng Huaiyu , Sun Jihu , Li Yi , Zhang Ye , Zhong Yongjin 
Published: July 2021

Abstract:
Atherosclerosis (AS) is the common pathological basis of cardiovascular disease. Circular RNA circ-USP9X (hsa_circ_0090231) has been discovered to be upregulated in oxidized low-density lipoprotein (ox-LDL)–induced human umbilical vein endothelial cells (HUVECs), but the role of circ-USP9X in ox-LDL–induced endothelial cell injury is indistinct. The purpose of the research was to investigate the role and regulatory mechanism of circ-USP9X in ox-LDL–-induced endothelial cell injury. Expression of circ-USP9X was examined by quantitative real-time polymerase chain reaction. Loss-of-function experiments were performed to assess the impacts of circ-USP9X inhibition on viability, cell cycle progression, apoptosis, and tube formation, inflammation, and oxidative stress of ox-LDL–induced HUVEC. The regulatory mechanism of circ-USP9X predicted by bioinformatics analysis and verified by dual-luciferase reporter or RNA immunoprecipitation assays. We observed that circ-USP9X was upregulated in AS patients' serum and ox-LDL–induced HUVEC. Inhibition of circ-USP9X elevated viability, promoted cell cycle progression and angiopoiesis, and decreased apoptosis, inflammation, and oxidative stress of ox-LDL–induced HUVEC. Mechanically, circ-USP9X regulated chloride intracellular channel 4 (CLIC4) messenger RNA expression by sponging microRNA (miR)-599. Furthermore, miR-599 inhibitor overturned circ-USP9X silencing-mediated influence on ox-LDL–induced HUVEC injury. Also, CLIC4 overexpression reversed miR-599 elevation–mediated effect on ox-LDL–induced HUVEC injury. In conclusion, circ-USP9X silencing decreased ox-LDL–induced endothelial cell injury via the miR-599/CLIC4 axis, which offered a novel molecular mechanism to comprehend the pathology of AS.
Global burden of cardiovascular diseases attributable to hypertension in young adults from 1990 to 2019
Authors: Liu Jing , Bu Xiang , Wei Linyan , Wang Xiqiang , Lai Lulu , Dong Caijuan , Ma Aiqun , Wang Tingzhong 
Published: July 2021

Background:
Hypertension grows into a serious public health problem among young adults, linking to a set of life-threatening cardiovascular diseases (CVDs). Young adults are not well represented in current knowledge about the CVDs burden attributable to hypertension.

Methods:
In this analysis of data from the GBD (Global Burden of Disease) study 2019, we focus on young adults and provide the first comprehensive and comparative assessment of the hypertension attributable CVDs burden, in terms of its mortality and years of living with disability (YLD) from 1990 to 2019, stratified by location, sex, and development status.

Results:
Globally in 2019, the death and YLD numbers caused by hypertension-related CVDs were 640 239 and 2 717 474 in young adults, marking a 43.0 and 86.6% increase from 1990, respectively. The corresponding mortality rate dropped by 10.5%, whereas the YLD rate increased by 16.8% during the same period. V-shaped association between CVDs burden and social development status was observed. The largest burden and the most pronounced increase were borne by middle-income countries, while high-income countries had the lowest death/YLD rate with a quicker annual decline. Men largely outpaced women in hypertension attributable CVDs mortality. Ischemic heart disease and stroke were the leading cause for death and YLD burden, correspondingly.

Conclusions:
Hypertension attributable CVDs burden in young adults has greatly increased from 1990 to 2019, with considerably spatiotemporal and sexual heterogeneity. The largest burden was borne by middle-income countries, especially by men. Establishment of geographically and sexually tailored strategies were needed to prevent hypertension-related CVDs in young adults.
ASSOCIATION BETWEEN EPIRETINAL MEMBRANE, EPIRETINAL PROLIFERATION, AND PROGNOSIS OF FULL-THICKNESS MACULAR HOLE CLOSURE
Authors: Yang Jee Myung , Choi Sang Uk , Kim Yoon Jeon , Kim Ryul , Yon Dong Keon , Lee Seung Won , Shin Jae Il , Lee Joo Yong , Kim June-Gone 
Published: July 2021

Purpose:
To demonstrate the effects of epiretinal membrane (ERM) and epiretinal proliferation on surgical outcomes for full-thickness macular hole.

Methods:
Nested case–control study with propensity score matching. Patients operated on for full-thickness macular hole between January 2011 and March 2020 were enrolled. The primary outcome was failure of the macular hole closure, and the secondary outcome was unfavorable hole closure (V or λ type closure) at 6 months after the surgery.

Results:
Five hundred and thirty-four eyes of 534 patients met the inclusion criteria. After 1:1 propensity score matching (127 pairs), patients demonstrating ERM were more likely to have a failure of hole closure (adjusted odds ratio, 2.71; 95% confidence interval, 1.19–6.14) and unfavorable hole closure (adjusted odds ratio, 2.07; 95% confidence interval, 1.16–3.71). Epiretinal membrane spanning the hole margin (hole marginal ERM) greatly increased the likelihood of unfavorable hole closure (adjusted odds ratio, 2.13; 95% confidence interval, 1.12–4.07). Patients with hole marginal-ERM + epiretinal proliferation were more likely to have a failure of hole closure (38.4%) compared with those with no ERM (11.8%).

Conclusion:
Patients with ERM had a higher risk for adverse surgical outcomes for full-thickness macular hole closure. The location of the ERM relative to the macular hole and the presence of epiretinal proliferation might affect the surgical outcomes for full-thickness macular hole closure.
Hypervirulent Klebsiella pneumoniae Infections in Pediatric Populations in Beijing (2017–2019)
Authors: Li Yue , Dong Limin , Gao Wei , Zhen Jinghui , Dong Fang , Yao Kaihu 
Published: July 2021

Background:
Hypervirulent variants of Klebsiella pnuemoniae (hvKp) are emerging globally causing life-threatening infectious diseases; however, comprehensive studies on pediatric hvKp strains and related infections are still lacking.

Methods:
Clinical data were collected from medical records. Genotype (multilocus sequence typing), capsular serotype, virulence gene profile and carbapenemase of the isolates were determined by PCR and DNA sequencing. Broth microdilution method was adopted to test the antimicrobial susceptibility. Hypermucoviscosity phenotype and the virulence of the strains were evaluated by string test and Galleria mellonella larvae killing assay.

Results:
Among 319 K. pneumoniae strains, 26 (8.2%) hvKp were identified, the detection rates in 2017, 2018 and 2019 were 1.8%, 5.2% and 11.3%. The majority of hvKp infections were found in school-age children and adolescents (57.7%). Pneumonia was the most common diagnosis (38.5%). Single fatal case was hvKp caused liver abscess complicated with bacteremia. hvKp were dominated by ST23 (30.8%) and ST11 (30.8%). Eight carbapenem-resistant hvKp (CR-hvKp) were found, which all belonged to ST11. Virulence gene profile revealed that ST11 hvKp might carry incomplete pLVPK-like plasmids, but they exhibited comparable in vivo virulence to the other hvKp.

Conclusions:
The infections caused by hvKp are not frequent among pediatric populations, but the detection rate of hvKp in pediatric populations is increasing rapidly in recent years. The emerging and dissemination of ST11 CR-hvKp should be monitored continuously.