bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages
Authors: Nkone Paballo , Loubser Shayne , Quinn Thomas C. , Redd Andrew D. , Ismail Arshad , Tiemessen Caroline T. , Mayaphi Simnikiwe H. 
Published: March 2022

Abstract
Background
Despite multiple attempts, there is still no effective HIV-1 vaccine available. The HIV-1 polymerase (pol) gene is highly conserved and encodes cytotoxic T-lymphocyte (CTL) epitopes. The aim of the study was to characterise HIV-1 Pol CTL epitopes in mostly sample pairs obtained during early and chronic stages of infection.

Methods
Illumina deep sequencing was performed for all samples while Sanger sequencing was only performed on baseline samples. Codons under immune selection pressure were assessed by computing nonsynonymous to synonymous mutation ratios using MEGA. Minority CTL epitope variants occurring at $$\ge$$
≥
5% were detected using low-frequency variant tool in CLC Genomics. Los Alamos HIV database was used for mapping mutations to known HIV-1 CTL epitopes.

Results
Fifty-two participants were enrolled in the study. Their median age was 28 years (interquartile range: 24–32 years) and majority of participants (92.3%) were female. Illumina minority variant analysis identified a significantly higher number of CTL epitopes (n = 65) compared to epitopes (n = 8) identified through Sanger sequencing. Most of the identified epitopes mapped to reverse transcriptase (RT) and integrase (IN) regardless of sequencing method. There was a significantly higher proportion of minority variant epitopes in RT (n = 39, 60.0%) compared to IN (n = 17, 26.2%) and PR (n = 9, 13.8%), p = 0.002 and < 0.0001, respectively. However, no significant difference was observed between the proportion of minority variant epitopes in IN versus PR, p = 0.06. Some epitopes were detected in either early or chronic HIV-1 infection whereas others were detected in both stages. Different distribution patterns of minority variant epitopes were observed in sample pairs; with some increasing or decreasing over time, while others remained constant. Some of the identified epitopes have not been previously reported for HIV-1 subtype C. There were also variants that could not be mapped to reported CTL epitopes in the Los Alamos HIV database.

Conclusion
Deep sequencing revealed many Pol CTL epitopes, including some not previously reported for HIV-1 subtype C. The findings of this study support the inclusion of RT and IN epitopes in HIV-1 vaccine candidates as these proteins harbour many CTL epitopes.
HBx inhibits DNA sensing signaling pathway via ubiquitination and autophagy of cGAS
Authors: Chen Hong , Jiang Linshan , Chen Shu , Hu Qin , Huang Ying , Wu Ying , Chen Weixian 
Published: March 2022

Abstract
Background
Cyclic GMP-AMP synthase (cGAS) is a crucial DNA sensor and plays an important role in host antiviral innate immune responses. During hepatitis B virus (HBV) infection, the cGAS signaling pathway can suppress HBV replication. As an important regulatory protein of HBV, hepatitis B virus X protein (HBx) may serve as an antagonistic character to the cGAS/STING signaling pathway. In this study, we aim to investigate the functional role of HBx in the cGAS/STING signaling pathway.

Methods
The effects of HBx on IFN-β promoter activity were measured by Dual-luciferase reporter assays. Ubiquitination and autophagy were analyzed by Western-blot and Co-immunoprecipitation assays.

Results
Our results show that HBx down-regulates IFN-I production by directly promoting ubiquitination and autophagy degradation of cGAS.

Conclusions
HBV can antagonize host cGAS DNA sensing to promote HBV replication and provide novel insights to develop novel approaches against HBV infection.
Occupational injury and associated factors among cement factories workers in central Ethiopia
Authors: Fresenbet Demissu Seyoum , Olana Ararso Tafese , Tulu Abera Shibiru , Danusa Kababa Temesgen 
Published: March 2022

Abstract
Background
The cement industry experiences accident rate is high compared to other manufacturing industries. Hence, this study was aimed to assess the occupational injury and associated factors among cement factories workers in West Shoa Zone, Oromia regional state, Ethiopia 2020.

Methods
An institution-based cross-sectional study design was employed. A total of 374 study participants were selected by using a systematic random sampling technique with K-interval. The collected data were entered into Epi-Info version 7 and analyzed by using SPSS version 21. Bivariate and multivariable binary logistic regression was used to identify the magnitude of occupational injury and the factor associated. A statistically significant association was declared at a 95% confidence interval and p-value<0.05.

Results
The study revealed that the magnitude of occupational injury among workers of cement factories was 183(48.9%). Workers found in an engineering department were 3.7 times more likely to be injured than those who were working in a clinker department [AOR: 3.72, 95% CI: 1.35-10.18]. Those workers who were working room did not have danger signs were 2.9 times more likely to be injured than their counterparts [AOR 2.99, 95% CI: 1.79-4.98). Those workers who did not use personal protective equipment were 3.7 times more likely to be injured than those who were used Personal Protective Equipments [AOR: 3.78, 95% CI: 1.76 - 8.12].

Conclusion
The magnitude of occupational injury in cement factories in the study area was high. The factories’ managers must provide adequate and quality safety materials in a timely and supervise their appropriate use and put danger signs where it is required.
MultipleXLab: A high-throughput portable live-imaging root phenotyping platform using deep learning and computer vision
Authors: Lube Vinicius , Noyan Mehmet Alican , Przybysz Alexander , Salama Khaled , Blilou Ikram 
Published: March 2022

Abstract
Background
Profiling the plant root architecture is vital for selecting resilient crops that can efficiently take up water and nutrients. The high-performance imaging tools available to study root-growth dynamics with the optimal resolution are costly and stationary. In addition, performing nondestructive high-throughput phenotyping to extract the structural and morphological features of roots remains challenging.

Results
We developed the MultipleXLab: a modular, mobile, and cost-effective setup to tackle these limitations. The system can continuously monitor thousands of seeds from germination to root development based on a conventional camera attached to a motorized multiaxis-rotational stage and custom-built 3D-printed plate holder with integrated light-emitting diode lighting. We also developed an image segmentation model based on deep learning that allows the users to analyze the data automatically. We tested the MultipleXLab to monitor seed germination and root growth of Arabidopsis developmental, cell cycle, and auxin transport mutants non-invasively at high-throughput and showed that the system provides robust data and allows precise evaluation of germination index and hourly growth rate between mutants.

Conclusion
MultipleXLab provides a flexible and user-friendly root phenotyping platform that is an attractive mobile alternative to high-end imaging platforms and stationary growth chambers. It can be used in numerous applications by plant biologists, the seed industry, crop scientists, and breeding companies.
Installation and imaging of thousands of minirhizotrons to phenotype root systems of field-grown plants
Authors: Rajurkar Ashish B. , McCoy Scott M. , Ruhter Jeremy , Mulcrone Jessica , Freyfogle Luke , Leakey Andrew D. B. 
Published: March 2022

Abstract
Background
Roots are vital to plant performance because they acquire resources from the soil and provide anchorage. However, it remains difficult to assess root system size and distribution because roots are inaccessible in the soil. Existing methods to phenotype entire root systems range from slow, often destructive, methods applied to relatively small numbers of plants in the field to rapid methods that can be applied to large numbers of plants in controlled environment conditions. Much has been learned recently by extensive sampling of the root crown portion of field-grown plants. But, information on large-scale genetic and environmental variation in the size and distribution of root systems in the field remains a key knowledge gap. Minirhizotrons are the only established, non-destructive technology that can address this need in a standard field trial. Prior experiments have used only modest numbers of minirhizotrons, which has limited testing to small numbers of genotypes or environmental conditions. This study addressed the need for methods to install and collect images from thousands of minirhizotrons and thereby help break the phenotyping bottleneck in the field.

Results
Over three growing seasons, methods were developed and refined to install and collect images from up to 3038 minirhizotrons per experiment. Modifications were made to four tractors and hydraulic soil corers mounted to them. High quality installation was achieved at an average rate of up to 84.4 minirhizotron tubes per tractor per day. A set of four commercially available minirhizotron camera systems were each transported by wheelbarrow to allow collection of images of mature maize root systems at an average rate of up to 65.3 tubes per day per camera. This resulted in over 300,000 images being collected in as little as 11 days for a single experiment.

Conclusion
The scale of minirhizotron installation was increased by two orders of magnitude by simultaneously using four tractor-mounted, hydraulic soil corers with modifications to ensure high quality, rapid operation. Image collection can be achieved at the corresponding scale using commercially available minirhizotron camera systems. Along with recent advances in image analysis, these advances will allow use of minirhizotrons at unprecedented scale to address key knowledge gaps regarding genetic and environmental effects on root system size and distribution in the field.
Dosimetric and radiobiological comparison of simultaneous integrated boost radiotherapy for early stage right side breast cancer between three techniques: IMRT, hybrid IMRT and hybrid VMAT
Authors: Bi Suyan , Zhu Rui , Dai Zhitao 
Published: March 2022

Abstract
Purpose
This study aimed at evaluating the clinical impact of full intensity-modulated radiotherapy (IMRT), hybrid IMRT (H-IMRT) and hybrid volumetric-modulated arc therapy (H-VMAT) for early-stage breast cancer with simultaneous integrated boost (SIB), in terms of plan quality and second cancer risk (SCR).

Methods
Three different plans were designed in full IMRT, hybrid IMRT, and hybrid VMAT for each of twenty patients with early-stage breast cancer. Target quality, organs at risk (OARs) sparing, and SCR were compared among the three plans for each case.

Results
In compared with H-IMRT, IMRT plans showed deterioration in terms of D2% of SIB, V10 of ipsilateral lung, and excess absolute risk (EAR) to contralateral lung (C-Lung) and esophagus. D2% and the homogeneity index (HI) of SIB, V5 of ipsilateral lung (I-Lung), the Dmean of the esophagus, the EAR to C-Lung and the esophagus with hybrid VMAT dramatically increased by 0.63%, 10%, 17.99%, 149.27%, 230.41%, and 135.29%, respectively (p = 0.024; 0.025; 0.046; 0.011; 0.000; 0.014). Dmean of the heart, the EAR to contralateral breast (C-Breast) and C-Lung by full IMRT was significantly decreased in comparison to the H-VMAT (4.67%, p = 0.033, 26.76%, p = 0.018; 48.05%, p = 0.036).

Conclusion
The results confirmed that H-IMRT could achieve better target quality and OARs sparing than IMRT and H-VMAT for SIB radiotherapy of early-stage right breast cancer. H-IMRT was the best treatment option, while H-VMAT performed the worst among the three plans in terms of SCR to peripheral OARs.
Chemoradiotherapy is an alternative choice for patients with primary mediastinal seminoma
Authors: Zhai Yirui , Chen Bo , Feng Xiaoli , Liu Kan , Wang Shulian , Hui Zhouguang , Feng Qinfu , Li Junling , Xiao Zefen , Lv Jima , Gao Yushun , Liu Yueping , Fang Hui , Wang Jianyang , Deng Lei , Liu Wenyang , Wang Wenqing , Zhou Zongmei , Li Ye-Xiong 
Published: March 2022

Abstract
Background
The low incidence of primary mediastinal seminomas has precluded the development of clinical trials on mediastinal seminomas. We investigated the clinicopathologic characteristics, prognosis of patients with primary mediastinal seminomas as well as the efficiency of nonsurgical treatments compared with treatments containing surgery.

Methods
We retrospectively collected data on the clinicopathologic characteristics, treatments, toxicities, and survival of 27 patients from a single center between 2000 and 2018. Patients were divided into two groups according to whether they received operation. Survivals were assessed using the Kaplan–Meier method. Univariate analysis was performed using the log-rank test.

Results
The median age was 28 (13–63) years. The most common symptoms were chest pain (29.6%), cough (25.9%), and dyspnea (22.2%). There were 13 and 14 patients in surgery and non-surgery group. Patients in the non-surgical group were more likely to be with poor performance scores (100% vs. 76.9%) and disease invaded to adjacent structures (100% vs. 76.9%) especially great vessels (100% vs. 46.2%).The median follow-up period was 32.23 (2.7–198.2) months. There was no significant difference of overall survival (5-year 100% vs. 100%), cancer-specific survival (5-year 100% vs. 100%), local regional survival (5-year 91.7% vs. 90.0%, p = 0.948), distant metastasis survival (5-year 90.9% vs. 100.0%, p = 0.340) and progression-free survival (82.5% vs. 90.0%, p = 0.245) between patients with and without surgery.

Conclusions
Primary mediastinal seminoma was with favorable prognosis, even though frequently invasion into adjacent structures brings difficulties to surgery administration. Chemoradiotherapy is an alternative treatment with both efficacy and safety.
MR-guided adaptive versus ITV-based stereotactic body radiotherapy for hepatic metastases (MAESTRO): a randomized controlled phase II trial
Authors: Hoegen P. , Zhang K. S. , Tonndorf-Martini E. , Weykamp F. , Regnery S. , Naumann P. , Lang K. , Ristau J. , Körber S. A. , Dreher C. , Buchele C. , Rippke C. , Renkamp C. K. , Paul K. M. , König L. , Büsch C. , Krisam J. , Sedlaczek O. , Schlemmer H.-P. , Niyazi M. , Corradini S. , Debus J. , Klüter S. , Hörner-Rieber J. 
Published: March 2022

Abstract
Background
Stereotactic body radiotherapy (SBRT) is an established local treatment method for patients with hepatic oligometastasis or oligoprogression. Liver metastases often occur in close proximity to radiosensitive organs at risk (OARs). This limits the possibility to apply sufficiently high doses needed for optimal local control. Online MR-guided radiotherapy (oMRgRT) is expected to hold potential to improve hepatic SBRT by offering superior soft-tissue contrast for enhanced target identification as well as the benefit of gating and daily real-time adaptive treatment. The MAESTRO trial therefore aims to assess the potential advantages of adaptive, gated MR-guided SBRT compared to conventional SBRT at a standard linac using an ITV (internal target volume) approach.

Methods
This trial is conducted as a prospective, randomized, three-armed phase II study in 82 patients with hepatic metastases (solid malignant tumor, 1–3 hepatic metastases confirmed by magnetic resonance imaging (MRI), maximum diameter of each metastasis ≤ 5 cm (in case of 3 metastases: sum of diameters ≤ 12 cm), age ≥ 18 years, Karnofsky Performance Score ≥ 60%). If a biologically effective dose (BED) ≥ 100 Gy (α/β = 10 Gy) is feasible based on ITV-based planning, patients will be randomized to either MRgRT or ITV-based SBRT. If a lesion cannot be treated with a BED ≥ 100 Gy, the patient will be treated with MRgRT at the highest possible dose. Primary endpoint is the non-inferiority of MRgRT at the MRIdian Linac® system compared to ITV-based SBRT regarding hepatobiliary and gastrointestinal toxicity CTCAE III or higher. Secondary outcomes investigated are local, locoregional (intrahepatic) and distant tumor control, progression-free survival, overall survival, possible increase of BED using MRgRT if the BED is limited with ITV-based SBRT, treatment-related toxicity, quality of life, dosimetric parameters of radiotherapy plans as well as morphological and functional changes in MRI. Potential prognostic biomarkers will also be evaluated.

Discussion
MRgRT is known to be both highly cost- and labor-intensive. The MAESTRO trial aims to provide randomized, higher-level evidence for the dosimetric and possible consecutive clinical benefit of MR-guided, on-table adaptive and gated SBRT for dose escalation in critically located hepatic metastases adjacent to radiosensitive OARs.

Trial registration

The study has been prospectively registered on August 30th, 2021: Clinicaltrials.gov, “Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases (MAESTRO)”, NCT05027711.
Sequential damage assessment of the posterolateral complex of the knee joint: a finite element study
Authors: Wu Cong-Cong , Ye Li-Mei , Li Xiao-Fei , Shi Lin-Jun 
Published: March 2022

Abstract
Background
The posterolateral complex (PLC), which consists of the popliteus tendon (PT), lateral collateral ligament (LCL), and popliteofibular ligament (PFL), is an indispensable structure of the knee joint. The aim of this study was to explore the functionality of the PLC by determining the specific role of each component in maintaining posterolateral knee stability.

Methods
A finite element (FE) model was generated based on previous material property data and magnetic resonance imaging of a volunteer’s knee joint. The injury order of the PLC was set as LCL, PFL, and PT. A combined compressive load of 1150 N and an anterior tibial load of 134 N was applied to the tibia to investigate tibial displacement (TD). Tibial external rotation (TER) and tibial varus angulation (TVA) were measured under bending motions of 5 and 10 Nm. The instantaneous axis of rotation (IAR) of the knee joint under different rotation motions was also recorded.

Results
The TD of the intact knee under a combined compressive load of 1150 N and an anterior tibial load of 134 N matched the values determined in previous studies. Our model showed consistent increases in TD, TVA, and TER after sequential damage of the PLC. In addition, sequential disruption caused the IAR to shift superiorly and laterally during varus rotation and medially and anteriorly during external rotation. In the dynamic damage of the PLC, LCL injury had the largest effect on TD, TVA, TER, and IAR.

Conclusions
Sequential injury of the PLC caused considerable loss of stability of the knee joint according to an FE model. The most significant structure of the PLC was the LCL.
Coronary artery bypass grafting in a patient with situs inversus totalis: a case report
Authors: Oi Atsushi , Tatsuishi Wataru , Mohara Jun , Yamamoto Toshikuni , Abe Tomonobu 
Published: March 2022

Abstract
Background
Coronary artery bypass grafting in situs inversus totalis patients has been seldom reported in the literature.

Case presentation
A 76-year-old woman visited our hospital for chest pain and dyspnea that had started about 5 years earlier. Coronary angiography revealed triple-vessel disease, and computed tomography showed situs inversus totalis. Coronary artery bypass grafting was performed. In this case, the main operating surgeon stood on the right side of the patient until cardiopulmonary bypass was established and then switched positions to the left side of the patient for anastomosis.

Conclusion
CABG was successfully completed in a patient with situs inversus totalis. The position shift helped improve the safety and ease of the surgery.
Genotype–phenotype correlation and natural history analyses in a Chinese cohort with pelizaeus–merzbacher disease
Authors: Duan Ruoyu , Ji Haoran , Yan Huifang , Wang Junyu , Zhang Yu , Zhang Qian , Li Dongxiao , Cao Binbin , Gu Qiang , Wu Ye , Jiang Yuwu , Li Ming , Wang Jingmin 
Published: March 2022

Abstract
Background
The natural history and genotype–phenotype correlation of Pelizaeus–Merzbacher disease (PMD) of Chinese patients has been rarely reported.

Method
Patients who met the criteria for PMD were enrolled in our study. Genomic analysis was conducted by multiplex ligation probe amplification (MLPA) and Sanger or whole-exome sequencing (WES). Natural history differences and genotype–phenotype correlations were analyzed.

Result
A total of 111 patients were enrolled in our follow-up study. The median follow-up interval was 53 m (1185). Among PMD patients, developmental delay was the most common sign, and nystagmus and hypotonia were the most common initial symptoms observed. A total of 78.4% of the patients were able to control their head, and 72.1% could speak words. However, few of the patients could stand (9.0%) or walk (4.5%) by themselves. Nystagmus improved in more than half of the patients, and hypotonia sometimes deteriorated to movement disorders. More PLP1 point mutations patients were categorized into severe group, while more patients with PLP1 duplications were categorized into mild group (p < 0.001). Compared to patients in mild groups, those in the severe group had earlier disease onset and had acquired fewer skills at a later age.

Conclusion
PMD patients have early disease onset with nystagmus and hypotonia followed by decreased nystagmus and movement disorders, such as spasticit. Patients with PLP1 duplication were more likely to be categorized into the mild group, whereas patients with point mutations were more likely to be categorized into the severe group.
Qualitative interviews with adults with Classic Galactosemia and their caregivers: disease burden and challenges with daily living
Authors: Randall Jason A. , Sutter Carolyn , Wang Stella , Bailey Evan , Raither Lydia , Perfetti Riccardo , Shendelman Shoshana , Burbridge Claire 
Published: March 2022

Abstract
Background
Classic Galactosemia is a rare, autosomal recessive disease in which galactose is not metabolized properly due to severe deficiency/absence of the galactose-1-phosphate uridylyltransferase (GALT) enzyme, converting to an aberrant and toxic metabolite, galactitol. Newborn screening and timely galactose-restricted diet can resolve acute symptoms and decrease fatalities. However, despite this, significant chronic, progressive morbidities remain which have a real impact upon daily life. To better understand the burden of disease, 20 in-depth qualitative interviews were undertaken with adult patients (n = 12), and their caregivers (n = 8), enrolled in the ACTION-Galactosemia trial, part of a clinical program designed to investigate the safety and efficacy of AT-007 (govorestat) in reducing toxic galactitol and long-term clinical outcomes in Classic Galactosemia.

Results
Interviews revealed the substantial burden of Classic Galactosemia on patients and families. Most adults were not able to live independently, and all required support with day-to-day activities. Short- and long-term memory difficulties and tremors were identified as the most frequently experienced and challenging symptoms. Other difficulties such as fine motor skills and slow/slurred speech contribute to the significant impact on daily activities, affecting ability to communicate and interact with others. Symptoms were first noticed in early childhood and worsened with age. Classic Galactosemia impacted all areas of daily functioning and quality of life, leading to social isolation, anxiety, anger/frustration and depression. This demonstrates the significant burden of disease and challenges associated with Classic Galactosemia.

Conclusions
The impact on both patients and caregivers underscores the severity of the unmet medical need and the importance of pharmacological intervention to halt or prevent disease progression. Any treatment that could reduce symptoms or slow functional decline would ease the burden of this condition on patients and caregivers.