bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amino acid sites related to the PB2 subunits of IDV affect polymerase activity
Authors: Wang Yutian , Sun Weiyang , Wang Zhenfei , Zhao Menglin , Zhang Xinghai , Kong Yunyi , Wang Xuefeng , Feng Na , Wang Tiecheng , Yan Feihu , Zhao Yongkun , Xia Xianzhu , Yang Songtao , Gao Yuwei 
Published: November 2021

Abstract
Background
In 2011, a new influenza virus, named Influenza D Virus (IDV), was isolated from pigs, and then cattle, presenting influenza-like symptoms. IDV is one of the causative agents of Bovine Respiratory Disease (BRD), which causes high morbidity and mortality in feedlot cattle worldwide. To date, the molecular mechanisms of IDV pathogenicity are unknown. Recent IDV outbreaks in cattle, along with serological and genetic evidence of IDV infection in humans, have raised concerns regarding the zoonotic potential of this virus. Influenza virus polymerase is a determining factor of viral pathogenicity to mammals.

Methods
Here we take a prospective approach to this question by creating a random mutation library about PB2 subunit of the IDV viral polymerase to test which amino acid point mutations will increase viral polymerase activity, leading to increased pathogenicity of the virus.

Results
Our work shows some exact sites that could affect polymerase activities in influenza D viruses. For example, two single-site mutations, PB2-D533S and PB2-G603Y, can independently increase polymerase activity. The PB2-D533S mutation alone can increase the polymerase activity by 9.92 times, while the PB2-G603Y mutation increments the activity by 8.22 times.

Conclusion
Taken together, our findings provide important insight into IDV replication fitness mediated by the PB2 protein, increasing our understanding of IDV replication and pathogenicity and facilitating future studies.
The role of family history of Cancer in Oral Cavity Cancer
Authors: Fantozzi Paolo Junior , Bavarian Roxanne , Tamayo Ibon , Bind Marie-Abele , Woo Sook-Bin , Villa Alessandro 
Published: November 2021

Abstract
Objectives
Oral and oropharyngeal squamous cell carcinoma (SCC) is the 10th most common cancer in the United States (8th in males, 13th in females), with an estimated 54,010 new cases expected in 2021, and is primarily associated with smoked tobacco, heavy alcohol consumption, areca nut use and persistent high-risk human papillomavirus (HPV). Family history of cancer (FHC) and family history of head and neck cancer (FHHNC) have been reported to play an important role in the development of OSCC. We aimed to investigate the role of FHC, FHHNC and personal history of cancer in first/second degree-relatives as co-risk factors for oral cancer.

Methods
This was a retrospective study of patients diagnosed with OSCC at the Division of Oral Medicine and Dentistry at Brigham and Women’s Hospital and at the Division of Head and Neck Oncology at Dana Farber Cancer Institute. Conditional logistic regressions were performed to examine whether OSCC was associated with FHC and FHHNC of FDRs and SDRs, personal history of cancer and secondary risk factors.

Results
Overall, we did not find an association between FHC, FHHNC and OSCC risk, whereas patients with a cancer history in one of their siblings were 1.6-times more likely to present with an OSCC. When secondary risk factors were considered, patients with a history of oral leukoplakia and dysplasia had a 16-times higher risk of having an OSCC.

Conclusions
Our study confirmed that a previous history of oral leukoplakia or dysplasia was an independent risk factor for OSCC. A positive family history of cancer in one or more siblings may be an additional risk factor for OSCC.
Analysis of clinical patient-specific pre-treatment quality assurance with the new helical tomotherapy platform, following the AAPM TG-218 report
Authors: Fusella Marco , Cavinato Samuele , Germani Alessandra , Paiusco Marta , Pivato Nicola , Rossato Marco Andrea , Scott Anthony , Scaggion Alessandro 
Published: November 2021

Abstract
Purpose
This study presents patient-specific quality assurance (QA) results from the first 395 clinical cases for the new helical TomoTherapy® platform (Radixact) coupled with dedicated Precision TPS.

Methods
The passing rate of the Gamma Index (GP%) of 395 helical QA of patient-specific tomotherapy, acquired with ArcCHECK, is presented, analysed and correlated to various parameters of the plan. Following TG-218 recommendations, the clinic specific action limit (ALcs) and tolerance limit (TLcs) were calculated for our clinic and monitored during the analysed period.

Results
The mean values ​​(± 1 standard deviation) of GP% (3%/2 mm) (both global and local normalization) are: 97.6% and 90.9%, respectively. The proposed ALcs and TLcs, after a period of two years’ process monitoring are 89.4% and 91.1% respectively.

Conclusions
The phantom measurements closely match the planned dose distributions, demonstrating that the calculation accuracy of the new Precision TPS and the delivery accuracy of the Radixact unit are adequate, with respect to international guidelines and reports. Furthermore, a first correlation with the planning parameters was made. Action and tolerance limits have been set for the new Radixact Linac.
Measuring Duchenne muscular dystrophy impact: development of a proxy-reported measure derived from PROMIS item banks
Authors: Schwartz Carolyn E. , Stark Roland B. , Cella David , Borowiec Katrina , Gooch Katherine L. , Audhya Ivana F. 
Published: November 2021

Abstract
Background
Person-reported outcomes measurement development for rare diseases has lagged behind that of more common diseases. In studies of caregivers of patients with rare diseases, one relies on proxy report to characterize this disability. It is important to measure the child’s disability accurately and comprehensively because it affects caregiver burden. We aimed to create a condition-specific caregiver proxy-report measure for Duchenne Muscular Dystrophy (DMD) in order to understand the impact of DMD on the caregiver. Drawing on relevant item banks from the Patient-Reported Outcome Measurement Information System (PROMIS), we sought to confirm their reliability and validity in the target sample of DMD caregivers.

Methods
This web-based study recruited DMD caregivers via Rare Patient Voice, patient-advocacy groups, and word of mouth. Recruitment was stratified by age of the caregiver’s child with DMD, which broadly represents stages of DMD progression: 2–7, 8–12, 13–17, and > 18. Telephone interviews with DMD parent-caregivers pretested possible measures for content validity. The web-based study utilized an algorithm to categorize respondents’ ambulatory status for tailored administration of PROMIS Parent-Proxy items as well as some new items developed based on caregiver interviews. Item response theory analyses were implemented.

Results
The study sample included 521 DMD caregivers representing equally the four age strata. The proxy-report measure included the following domains: fatigue impact, strength impact, cognitive function, upper extremity function, positive affect, negative affect, sleep-device symptoms, and mobility. The first five domains had strong psychometric characteristics (unidimensionality; acceptable model fit; strong standardized factor loadings; high marginal reliability). Negative Affect, covering anger, anxiety, depressive symptoms, and psychological stress, fit a bifactor model with good model fit, high marginal reliability, and strong factor loadings. The Sleep-device symptoms domain was not unidimensional, and the mobility domain did not have a simple structure due to residual correlations among items at opposite end of the mobility-disability continuum. These two domain scores were retained as clinimetric indices (i.e., uncalibrated scales), to achieve the overall goal of having a content-valid DMD-specific measure across all stages of disease severity.

Conclusions
The present study derived a DMD-specific proxy-report measure from PROMIS item banks and supplemental items that could potentially be utilized in caregiver research across all stages of the care recipient’s DMD. Future research will focus on assessing the responsiveness and validity of the measure over time and its comparison to DMD patient self-report.
Humanitarian surgical service utilization by a host country population: comparing surgery patterns between refugees and Tanzanians using an interrupted time-series analysis
Authors: Enumah Zachary Obinna , Rapaport Sarah , Ngude Hilary , Yenokyan Gayane , Lekey Amber , Winch Peter J. , Stevens Kent A. 
Published: November 2021

Abstract
Background
While current estimates suggest that up to three million additional surgical procedures are needed to meet the needs of forcibly displaced populations, literature on surgical care for refugee or forced migrant populations has often focused on acute phase and war-related trauma or violence with insufficient attention to non-war related pathologies. To our knowledge, no study has compared refugee versus host population utilization of surgical services in a refugee camp-based hospital over such an extended period of twenty years. The aim of this paper is to first describe the patterns of surgical care by comparing refugee and host population utilization of surgical services in Nyarugusu refugee camp between 2000 and 2020, then evaluate the impact of a large influx of refugees in 2015 on refugee and host population utilization.

Methods
The study was based on a retrospective review of surgical logbooks in Nyarugusu refugee camp (Kigoma, Tanzania) between 2000 and 2020. We utilized descriptive statistics and multiple group, interrupted time series methodology to assess baseline utilization of surgical services by a host population (Tanzanians) compared to refugees and trends in utilization before and after a large influx of Burundian refugees in 2015.

Results
A total of 10,489 operations were performed in Nyarugusu refugee camp between 2000 and 2020. Refugees underwent the majority of procedures in this dataset (n = 7,767, 74.0%) versus Tanzanians (n = 2,722, 26.0%). The number of surgeries increased over time for both groups. The top five procedures for both groups included caesarean section, bilateral tubal ligation, herniorrhaphy, exploratory laparotomy and hysterectomy. In our time series model, refugees had 3.21 times the number of surgeries per quarter at baseline when compared to Tanzanians. The large influx of Burundian refugees in 2015 impacted surgical output significantly with a 38% decrease (IRR = 0.62, 95% CI 0.46–0.84) in surgeries in the Tanzanian group and a non-significant 20% increase in the refugee group (IRR = 1.20, 95% CI 0.99–1.46). The IRR for the difference-in-difference (ratio of ratios of post versus pre-intervention slopes between refugees and Tanzanians) was 1.04 (95% CI 1.00–1.07), and this result was significant (p=0.028).

Conclusions
Surgical care in conflict and post-conflict settings is not limited to war or violence related trauma but instead includes a large burden of obstetrical and general surgical pathology. Host population utilization of surgical services in Nyarugusu camp accounted for over 25% of all surgeries performed, suggesting some host population benefit of the protracted refugee situation in western Tanzania. Host population utilization of surgical services was apparently different after a large influx of refugees from Burundi in 2015.
Born to survive: how cancer cells resist CAR T cell therapy
Authors: Lemoine Jean , Ruella Marco , Houot Roch 
Published: November 2021

AbstractAlthough chimeric antigen receptor T cells demonstrated remarkable efficacy in patients with chemo-resistant hematologic malignancies, a significant portion still resist or relapse. This immune evasion may be due to CAR T cells dysfunction, a hostile tumor microenvironment, or resistant cancer cells. Here, we review the intrinsic resistance mechanisms of cancer cells to CAR T cell therapy and potential strategies to circumvent them.
Global, regional, and national cancer incidence and death for 29 cancer groups in 2019 and trends analysis of the global cancer burden, 1990–2019
Authors: Lin Longfei , Li Zhiyong , Yan Lei , Liu Yuling , Yang Hongjun , Li Hui 
Published: November 2021

Abstract
Background and aims
Cancer will soon become the leading cause of death in every country in the twenty-first century. This study aimed to analyze the mortality and morbidity of 29 types of cancer in 204 countries or regions from 1990 to 2019 to guide global cancer prevention and control.

Methods
Detailed information for 29 cancer groups was collected from the Global Burden of Disease Study in 2019. The age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of the 29 cancer groups were calculated based on sex, age, region, and country. In addition, separate analyses were performed for major cancer types.

Results
In 2019, more than 10 million people died from cancer, which was approximately twice the number in 1990. Tracheal, bronchus, and lung (TBL) cancers collectively showed the highest death rate, and the ASDR of pancreatic cancer increased by 24%, which was cancer with the highest case fatality rate (CFR). The global cancer ASIR showed an increasing trend, with testicular cancer, thyroid cancer, and malignant skin melanoma showing a significant increase. The ASDR and ASIR of cancer in males were about 1.5 times higher than that in females. Individuals over 50 years had the highest risk of developing cancer, with incidences and deaths in this age group accounting for more than 85% of cancers in all age groups. Asia has the heaviest cancer burden due to its high population density, with esophageal cancer in this region accounting for 53% of the total fatalities related to this type of cancer in the world. In addition, the mortality and morbidity of most cancers increased with the increase in the development or socio-demographic index (SDI) in the SDI regions based on the World Bank's Human Development Index (HDI), with cancer characteristics varying in the different countries globally.

Conclusions
The global cancer burden continues to increase, with substantial mortality and morbidity differences among the different regions, ages, countries, gender, and cancer types. Effective and locally tailored cancer prevention and control measures are essential in reducing the global cancer burden in the future.
The effect of the COVID-19 pandemic on the epidemiology of positive blood cultures in Swiss intensive care units: a nationwide surveillance study
Authors: Damonti Lauro , Kronenberg Andreas , Marschall Jonas , Jent Philipp , Sommerstein Rami , De Kraker Marlieke E. A. , Harbarth Stephan , Gasser Michael , Buetti Niccolò 
Published: November 2021

Abstract
Background
Evidence about the impact of the pandemic of COVID-19 on the incidence rates of blood cultures contaminations and bloodstream infections in intensive care units (ICUs) remains scant. The objective of this study was to investigate the nationwide epidemiology of positive blood cultures drawn in ICUs during the first two pandemic waves of COVID-19 in Switzerland.

Methods
We analyzed data on positive blood cultures among ICU patients, prospectively collected through a nationwide surveillance system (ANRESIS), from March 30, 2020, to May 31, 2021, a 14-month timeframe that included a first wave of COVID-19, which affected the French and Italian-speaking regions, an interim period (summer 2020) and a second wave that affected the entire country. We used the number of ICU patient-days provided by the Swiss Federal Office of Public Health as denominator to calculate incidence rates of blood culture contaminations and bloodstream infections (ICU-BSI). Incidence rate ratios comparing the interim period with the second wave were determined by segmented Poisson regression models.

Results
A total of 1099 blood culture contaminations and 1616 ICU-BSIs were identified in 52 ICUs during the study. Overall, more episodes of blood culture contaminations and ICU-BSI were observed during the pandemic waves, compared to the interim period. The proportions of blood culture contaminations and ICU-BSI were positively associated with the ICU occupancy rate, which was higher during the COVID-19 waves. During the more representative second wave (versus interim period), we observed an increased incidence of blood culture contaminations (IRR 1.57, 95% CI 1.16–2.12) and ICU-BSI (IRR 1.20, 95% CI 1.03–1.39).

Conclusions
An increase in blood culture contaminations and ICU-BSIs was observed during the second COVID-19 pandemic wave, especially in months when the ICU burden of COVID-19 patients was high.
Cellulase production and efficient saccharification of biomass by a new mutant Trichoderma afroharzianum MEA-12
Authors: Peng Zhi-Qing , Li Chuang , Lin Yi , Wu Sheng-Shan , Gan Li-Hui , Liu Jian , Yang Shu-Liang , Zeng Xian-Hai , Lin Lu 
Published: November 2021

AbstractBackgroundCellulase plays a key role in converting cellulosic biomass into fermentable sugar to produce chemicals and fuels, which is generally produced by filamentous fungi. However, most of the filamentous fungi obtained by natural breeding have low secretory capacity in cellulase production, which are far from meeting the requirements of industrial production. Random mutagenesis combined with adaptive laboratory evolution (ALE) strategy is an effective method to increase the production of fungal enzymes.ResultsThis study obtained a mutant ofTrichoderma afroharzianumby exposures to N-methyl-N’-nitro-N-nitrosoguanidine (MNNG), Ethyl Methanesulfonate (EMS), Atmospheric and Room Temperature Plasma (ARTP) and ALE with high sugar stress. TheT. afroharzianummutant MEA-12 produced 0.60, 5.47, 0.31 and 2.17 IU/mL FPase, CMCase, pNPCase and pNPGase, respectively. These levels were 4.33, 6.37, 4.92 and 4.15 times higher than those of the parental strain, respectively. Also, it was found thatT. afroharzianumhad the same carbon catabolite repression (CCR) effect as otherTrichodermain liquid submerged fermentation. In contrast, the mutant MEA-12 can tolerate the inhibition of glucose (up to 20 mM) without affecting enzyme production under inducing conditions. Interestingly, crude enzyme from MEA-12 showed high enzymatic hydrolysis efficiency against three different biomasses (cornstalk, bamboo and reed), when combined with cellulase fromT. reeseiRut-C30. In addition, the factors that improved cellulase production by MEA-12 were clarified.ConclusionsOverall, compound mutagenesis combined with ALE effectively increased the production of fungal cellulase. A super-producing mutant MEA-12 was obtained, and its cellulase could hydrolyze common biomasses efficiently, in combination with enzymes derived from model strainT. reesei, which provides a new choice for processing of bioresources in the future.
Translocating lipopolysaccharide correlates with the severity of enterovirus A71-induced HFMD by promoting pro-inflammation and viral IRES activity
Authors: Wang Yuya , Dan Kena , Xue Xiaoling , Yang Xiongbo , Feng Xujiao , Yang Qingqing , Yang Jing , Chen Bangtao 
Published: November 2021

Abstract
Background
The increase of inflammation-inducing enterobacteria was recently observed in severe hand, foot, and mouth disease (HFMD) caused by Enterovirus A71 (EV-A71). This study aimed to verify the occurrence of bacterial translocation (BT) and further explore the contributory role of BT to severity of EV-A71-mediated HFMD cases.

Methods
Serum specimens from 65 mild and 65 severe EV-A71-associated HFMD cases and 65 healthy children were collected. EV-A71 VP1 in serum, inflammatory mediators including C-reactive protein, IL-1β, IL-6, interferon-γ and tumor necrosis factor-α, BT related biomarkers including Claudin-3, intestinal fatty acid binding protein, lipopolysaccharide (LPS), soluble CD14 (sCD14) and endotoxin core antibody were measured by ELISA. Bacterial DNA (BactDNA) fragments were quantified by quantified PCR (qPCR). Rhabdomyosarcoma (RD) or SH-SY5Y cells, infected with LPS-pre-incubated EV-A71 or transfected with plasmid containing viral 2Apro or mRNA containing viral internal ribosomal entry site (IRES), were post-treated with or without LPS in vitro. EV-A71 RNA and viral or cellular proteins were determined by qPCR and western blot, respectively.

Results
Compared to mild HFMD patients, remarkably higher inflammatory mediators as well as BT-related biomarkers except BactDNA were observed in severe HFMD cases (all P < 0.05). In severe HFMD group, circulating concentrations of LPS and sCD14 showed statistical correlations with inflammation indices (all P < 0.05), serum levels of EV-A71 VP1 were found to be positively correlated with serum LPS (r = 0.341, P = 0.005) and serum sCD14 (r = 0.458, P < 0.001). In vitro, EV-A71 attachment and internalization were only slightly promoted by LPS pre-incubation; however, EV-A71 proliferation and viral 2Apro-mediated IRES activity were significantly accelerated by LPS post-treatment.

Conclusions
Our results collectively indicate that gut-derived translocating LPS contributes to the severity of EV-A71-induced HFMD by driving inflammatory response and viral proliferation via viral 2Apro-mediated IRES.
Constructing a cell microenvironment with biomaterial scaffolds for stem cell therapy
Authors: Zhao Xiaotong , Li Qiong , Guo Zhikun , Li Zongjin 
Published: November 2021

AbstractStem cell therapy is widely recognized as a promising strategy for exerting therapeutic effects after injury in degenerative diseases. However, limitations such as low cell retention and survival rates after transplantation exist in clinical applications. In recent years, emerging biomaterials that provide a supportable cellular microenvironment for transplanted cells have optimized the therapeutic efficacy of stem cells in injured tissues or organs. Advances in the engineered microenvironment are revolutionizing our understanding of stem cell-based therapies by co-transplanting with synthetic and tissue-derived biomaterials, which offer a scaffold for stem cells and propose an unprecedented opportunity to further employ significant influences in tissue repair and regeneration.