bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 within-host diversity of human hosts and its implications for viral immune evasion
Authors: Xi Binbin , Zeng Xi , Chen Zixi , Zeng Jiong , Huang Lizhen , Du Hongli 
Published: June 2023

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving, bringing great challenges to the control of the virus. In the present study, we investigated the characteristics of SARS-CoV-2 within-host diversity of human hosts and its implications for immune evasion using about 2,00,000 high-depth next-generation genome sequencing data of SARS-CoV-2. A total of 44% of the samples showed within-host variations (iSNVs), and the average number of iSNVs in the samples with iSNV was 1.90. C-to-U is the dominant substitution pattern for iSNVs. C-to-U/G-to-A and A-to-G/U-to-C preferentially occur in 5′-CG-3′ and 5′-AU-3′ motifs, respectively. In addition, we found that SARS-CoV-2 within-host variations are under negative selection. About 15.6% iSNVs had an impact on the content of the CpG dinucleotide (CpG) in SARS-CoV-2 genomes. We detected signatures of faster loss of CpG-gaining iSNVs, possibly resulting from zinc-finger antiviral protein-mediated antiviral activities targeting CpG, which could be the major reason for CpG depletion in SARS-CoV-2 consensus genomes. The non-synonymous iSNVs in the
S
gene can largely alter the S protein’s antigenic features, and many of these iSNVs are distributed in the amino-terminal domain (NTD) and receptor-binding domain (RBD). These results suggest that SARS-CoV-2 interacts actively with human hosts and attempts to take different evolutionary strategies to escape human innate and adaptive immunity. These new findings further deepen and widen our understanding of the within-host evolutionary features of SARS-CoV-2.

IMPORTANCE

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the coronavirus disease 2019, has evolved rapidly since it was discovered. Recent studies have pointed out that some mutations in the SARS-CoV-2 S protein could confer SARS-CoV-2 the ability to evade the human adaptive immune system. In addition, it is observed that the content of the CpG dinucleotide in SARS-CoV-2 genome sequences has decreased over time, reflecting the adaptation to the human host. The significance of our research is revealing the characteristics of SARS-CoV-2 within-host diversity of human hosts, identifying the causes of CpG depletion in SARS-CoV-2 consensus genomes, and exploring the potential impacts of non-synonymous within-host variations in the
S
gene on immune escape, which could further deepen and widen our understanding of the evolutionary features of SARS-CoV-2.
Gut phageome of the giant panda (
Ailuropoda melanoleuca
) reveals greater diversity than relative species
Authors: Lu Juan , Wang Haoning , Wang Chunmei , Zhao Min , Hou Rong , Shen Quan , Yang Shixing , Ji Likai , Liu Yuwei , Wang Xiaochun , Liu Songrui , Shan Tongling , Zhang Wen 
Published: June 2023

ABSTRACT

The gut flora is a treasure house of diverse bacteriophages maintaining a harmonious and coexistent relationship with their hosts. The giant panda (
Ailuropoda melanoleuca
), as a vulnerable endemic species in China, has existed for millions of years and is regarded as a flagship species for biodiversity conservation. And yet, limited studies have analyzed the phage communities in the gut of giant pandas. Using viral metagenomic analysis, the phageomes of giant pandas and other relative species were investigated. Our study explored and compared the composition of phage communities from different animal sources. Giant pandas possessed more diverse and abundant phage communities in the gut compared with other relevant animals. Phylogenetic analyses based on the phage terminase large subunit (TerL) showed that the
Caudovirales
phages in giant pandas also presented highly genetic diversity. Our study revealed the diversity of phage communities in giant pandas and other relative species, contributing to the health maintenance of giant pandas and laying the groundwork for molecular evolution research of bacteriophages in mammals.

IMPORTANCE

Gut phageome plays an important role in shaping gut microbiomes by direct interactions with bacteria or indirect influences on the host immune system, potentially regulating host health and disease status. The giant panda (
Ailuropoda melanoleuca
) is a vulnerable and umbrella species for biodiversity conservation. Our work explored and compared the gut phageome of giant pandas and relative species, contributing to the health maintenance of giant pandas.
In-hospital therapies and determinants of treatment strategy selection in patients with atrial fibrillation and left ventricular systolic dysfunction in China: a retrospective study based on the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) project, 2015–2019
Authors: He Pengkang , Pan Yannan , Jiang Jie , Fan Fangfang , Zhou Jing , Xia Yulong , Liu Jun , Yang Na , Hao Yongchen , Li Jianping , Liu Jing , Zhao Dong , Huo Yong 
Published: June 2023

ObjectivesThe optimal treatment strategy remains debatable in patients with atrial fibrillation (AF) and heart failure. Our objectives were to summarise in-hospital therapies and determine factors associated with treatment strategy selections.DesignA retrospective study analysing the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) project from 2015 to 2019.SettingThe CCC-AF project included patients from 151 tertiary and 85 secondary hospitals across 30 provinces in China.ParticipantsPatients with AF and left ventricular systolic dysfunction (LVSD, defined as left ventricular ejection fraction<50%) were included, with 5560 patients in the study sample.MethodsPatients were classified by treatment strategies. In-hospital treatments and trends of therapies were analysed. Multiple logistic regression models were used to find determinants of treatment strategies.ResultsRhythm control therapies were used in 16.9% of patients with no significant trends (ptrend=0.175). Catheter ablation was used in 5.5% of patients, increasing from 3.3% in 2015 to 6.6% in 2019 (ptrend<0.001). Factors negatively associated with rhythm control included increased age (OR 0.973, 95% CI 0.967 to 0.980), valvular AF (OR 0.618, 95% CI 0.419 to 0.911), AF types (persistent: OR 0.546, 95% CI 0.462 to 0.645; long-standing persistent: OR 0.298, 95% CI 0.240 to 0.368), larger left atrial diameters (OR 0.966, 95% CI 0.957 to 0.976) and higher Charlson Comorbidity Index scores (CCI 1–2: OR 0.630, 95% CI 0.529 to 0.750; CCI≥3: OR 0.551, 95% CI 0.390 to 0.778). Higher platelet counts (OR 1.025, 95% CI 1.013 to 1.037) and prior rhythm control attempts (electrical cardioversion: OR 4.483, 95% CI 2.369 to 8.483; catheter ablation: OR 4.957, 95% CI 3.072 to 7.997) were positively associated with rhythm control strategies.ConclusionIn China, non-rhythm control strategy remained the dominant choice in patients with AF and LVSD. Age, AF types, prior treatments, left atrial diameters, platelet counts and comorbidities were major determinants of treatment strategies. Guideline-adherent therapies should be further promoted.Study registration numberNCT02309398.
The mediating role of sleep quality on the relationship between internet gaming disorder and perceived stress and suicidal behaviour among Indian medical students
Authors: Garg Sunny , Kharb Aakanksha , Verma Deepika , Antil Ritu , Khanna Binika , Sihag Ritika , Lamba Divya 
Published: June 2023

BackgroundIn the recent digital era, individuals with internet gaming disorder (IGD) have reported a much higher prevalence of poor sleep quality, perceived stress and suicidal behaviour. However, the underlying mechanisms for these psychological problems remain unknown.AimsThe primary aims of this study were to explore the mediating role of sleep quality on the relationship between IGD and the health outcomes of perceived stress and suicidal behaviour and to assess the prevalence and risk factors for IGD among medical students.MethodsA cross-sectional study enrolling 795 medical students from two medical colleges in a rural area of North India was conducted from April to May 2022. The study participants were chosen using a stratified random sampling approach. A self-administered questionnaire was used to collect data, including sociodemographic and personal information and gaming characteristics. The study also included the Gaming Disorder and Hazardous Gaming Scale, the Pittsburgh Sleep Quality Index, the Perceived Stress Scale-10 and the Suicide Behaviors Questionnaire–Revised to measure IGD, sleep quality, perceived stress and suicidal behaviour, respectively. Multiple logistic regression for the risk factors and Pearson’s correlation test for the relationship between variables were used. Hayes’ PROCESS macro for SPSS was employed to carry out mediation analysis.ResultsAmong the 348 gamers with a mean age of 21.03 (SD 3.27) years, the prevalence of IGD was 15.23% (95% confidence interval: 11.6% to 19.4%). In the correlational analysis, small to large (r: 0.32–0.72) significant relationships between scores of IGD and other health outcomes were established. The indirect effect (B=0.300) via sleep quality accounted for 30.62% of the total effect (B=0.982) of IGD on perceived stress (partially mediated), while sleep quality (B=0.174) accounted for 27.93% of the total effect (B=0.623) of IGD on suicidal behaviour (partially mediated). The factors of being male, living in a single-parent family, using the internet for other than academic purposes (1–3 hours and more than 3 hours/day), playing games for more than 3 hours/day and playing games with violent content were associated with IGD symptoms.ConclusionsUsing a dimensional measure, the results specified the relationship between IGD and perceived stress and suicidal behaviour by demonstrating that sleep quality meditated them. This modifiable mediating factor can be addressed by psychotherapy to mitigate the risk of perceived stress and suicidal behaviour among the future medical workforce.
System Verification and Runtime Monitoring with Multiple Weakly-Hard Constraints
Authors: Hsieh Yi-Ting , Chang Tzu-Tao , Tsai Chen-Jun , Wu Shih-Lun , Bai Ching-Yuan , Chang Kai-Chieh , Lin Chung-Wei , Kang Eunsuk , Huang Chao , Zhu Qi 
Published: June 2023

A weakly-hard fault model can be captured by an
(m,k)
constraint, where 0≤
m
≤
k
, meaning that there are at most
m
bad events (faults) among any
k
consecutive events. In this article, we use a weakly-hard fault model to constrain the occurrences of faults in system inputs. We develop approaches to verify properties for all possible values of
(m,k)
, where
k
is smaller than or equal to a given
K
, in an exact and efficient manner. By verifying all possible values of
(m,k)
, we define weakly-hard requirements for the system environment and design a runtime monitor based on counting the number of faults in system inputs. If the system environment satisfies the weakly-hard requirements, then the satisfaction of desired properties is guaranteed; otherwise, the runtime monitor can notify the system to switch to a safe mode. This is especially essential for cyber-physical systems that need to provide guarantees with limited resources and the existence of faults. Experimental results with discrete second-order control, network routing, vehicle following, and lane changing demonstrate the generality and the efficiency of the proposed approaches.
Research on the Rescue Time of the Taiwan Marathon Emergency Medical Service System Between 2013 and 2021
Authors: Hsia Tsu-I , Wei Chih-Yuan , Fann Li-Yun , Kao Wei-Fong , Chien Wu-Chien , Huang Han-Bin 
Published: June 2023

Background: While there are several studies on marathon injuries worldwide, there are no related studies on the Taipei Marathon regarding the rescue time of onsite injury cases, the incidence of out-of-hospital cardiac arrest (OHCA) cases, and the success rate of recovery of spontaneous circulation (ROSC). This study aims to fill that gap. Hypothesis: The rescue time onsite of contact injury cases was in the prime time for lifesaving. Study Design: Descriptive epidemiological study. Level of Evidence: Level 2c. Methods: This is a retrospective study of numerical and timeflow data using descriptive statistics. Our data were obtained from records of the Taipei Marathon from 2013 to 2021. These included (1) notification data, (2) the time record of the emergency care personnel in contact with patients, (3) incidence of OHCA, (4) the success rate of ROSC, (5) the location of occurrence of OHCA, and (6) emergency medical service capacity and configuration. Results: The average time taken for first contact was 1.56 minutes in OHCA cases, and the total incidence rate of OHCA in 9 years was 4 people per 100,000 people, with a 100% ROSC success rate. Further, the location of OHCA cases was mostly in Q4 of the race (66.67%), followed by Q3 (22.22%) and Q2 (1.11%). The average number of emergency care personnel per marathon was 78, spread across 6 rescue and 6 medical stations and equipped with 8 ambulances and 35 automated external defibrillators. Conclusion: Shortening the arrival time of medical personnel to the scene and implementing a complete chain of survival can improve survival rates. Other ways to provide faster and more timely emergency rescue services require further study. Clinical Relevance: Contact with patients as soon as possible, timely implementation of cardiopulmonary resuscitation, and use of an automated external defibrillator are the basic requirements of the chain of survival theory.
Secondary bile acids function through the vitamin D receptor in myeloid progenitors to promote myelopoiesis
Authors: Thompson Brandon , Lu Shan , Revilla Julio , Uddin Md Jashim , Oakland David N. , Brovero Savannah , Keles Sunduz , Bresnick Emery H. , Petri William A. , Burgess Stacey L. 
Published: June 2023

Abstract
Metabolic products of the microbiota can alter hematopoiesis. However, the contribution and site of action of bile acids is poorly understood. Here, we demonstrate that the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA), increase bone marrow myelopoiesis. Treatment of bone marrow cells with DCA and LCA preferentially expanded immunophenotypic and functional colony-forming unit–granulocyte and macrophage (CFU-GM) granulocyte-monocyte progenitors (GMPs). DCA treatment of sorted hematopoietic stem and progenitor cells (HSPCs) increased CFU-GMs, indicating that direct exposure of HSPCs to DCA sufficed to increase GMPs. The vitamin D receptor (VDR) was required for the DCA-induced increase in CFU-GMs and GMPs. Single-cell RNA sequencing revealed that DCA significantly upregulated genes associated with myeloid differentiation and proliferation in GMPs. The action of DCA on HSPCs to expand GMPs in a VDR-dependent manner suggests microbiome-host interactions could directly affect bone marrow hematopoiesis and potentially the severity of infectious and inflammatory disease.
A Fondazione Italiana Linfomi cohort study of R-COMP vs R-CHOP in older patients with diffuse large B-cell lymphoma
Authors: Arcari Annalisa , Rigacci Lugi , Tucci Alessandra , Puccini Benedetta , Usai Sara Veronica , Cavallo Federica , Fabbri Alberto , Balzarotti Monica , Pelliccia Sabrina , Luminari Stefano , Pennese Elsa , Zilioli Vittorio Ruggero , Mahmoud Abdurraouf Mokhtar , Musuraca Gerardo , Marino Dario , Sartori Roberto , Botto Barbara , Gini Guido , Zanni Manuela , Hohaus Stefan , Tarantini Giuseppe , Flenghi Leonardo , Tani Monica , Di Rocco Alice , Merli Michele , Vallisa Daniele , Pagani Chiara , Nassi Luca , Dessì Daniela , Ferrero Simone , Cencini Emanuele , Bernuzzi Patrizia , Mammi Caterina , Marcheselli Luigi , Tabanelli Valentina , Spina Michele , Merli Francesco 
Published: June 2023

Abstract
Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the most commonly used regimen for the upfront treatment of diffuse large B-cell lymphoma (DLBCL). However, it is associated with cardiotoxicity, especially in older patients. Substituting doxorubicin with non-PEGylated liposomal doxorubicin (R-COMP) may reduce the risk of cardiac events, but its efficacy has never been demonstrated in prospective trials. We describe the characteristics and outcome of patients with DLBCL aged ≥65 years prospectively enrolled in the Elderly Project by the Fondazione Italiana Linfomi and treated with full doses of R-CHOP or R-COMP per local practice. Starting from 1163 patients, 383 (55%) were treated with R-CHOP and 308 (45%) with R-COMP. Patients treated with R-COMP were older (median age, 76 vs 71 years), less frequently fit at simplified geriatric assessment (61% vs 88%; P &lt; .001), and had a more frequent baseline cardiac disorders (grade &gt;1, 32% vs 8%; P &lt; .001). Three-year progression-free survival (PFS) was similar between R-CHOP and R-COMP (70% and 64%); 3-year overall survival was 77%, and 71% respectively. R-CHOP was associated with better PFS vs R-COMP only in the Elderly Prognostic Index (EPI) low-risk group. The two groups had similar rates of treatment interruptions due to toxicities or of cardiac events (P = 1.00). We suggest R-COMP is a potentially curative treatment for older patients with intermediate- or high-risk EPI, even in the presence of a baseline cardiopathy. R-CHOP is confirmed as the standard therapy for low risk patients.
Expected effects of accident data recording technology evolution on the identification of accident causes and liability
Authors: Vida Gábor , Török Árpád 
Published: June 2023

Abstract
Background
The classic accident reconstruction process is based on information recorded manually at the scene and gathered from witness statements. Liability cannot always be determined if no objective data are available, especially for accidents at traffic lights. Even Event Data Recorder (EDR) data (speed, braking, gas/brake pedal operation, etc.) will not improve the assessment of such a liability situation significantly, since vehicle movements cannot be synchronized in time with the phase plan of the intersection control. This problem could be solved if globally synchronized time data (Global Navigation Satellite Systems) were available, or a camera recorded the signal of the given traffic lights. In our study, the technology that goes beyond EDR data was defined as EDR+ data recording technology.

Aim
The aim of this article is to rank the assessability of different types of accidents through the statistical analysis of a publicly available database, taking into account the different data recording technologies.

Methods
An in-dept statistical analysis of 124 accidents and the corresponding liability investigations is provided. Also, analysis is carried out on estimated levels of assessability if modern data recording technologies had been applied for the same accident set.

Results
This study reveals the impact of the introduction, spread and wide application of the examined types of data recording technology on assessability. It is also explored what kind of data recording technology would be necessary to ensure the level of assessability required to establish liability for accidents.

Conclusion
The flexible framework presented here is suitable for comparing the assessability of road accidents according to accident type and data recording technology.
Arteriovenous fistula in a renal allograft with gross hematuria and subsequent acute kidney injury due to urinary tract obstruction: a case report
Authors: Aoki Yujiro , Kawamura Takeshi , Shiraga Nobuyuki , Yonekura Takashi , Maeda Maho , Kurihara Sota , Sekine Yoshitaka , Shishido Seiichiro , Sakai Ken 
Published: June 2023

Abstract
Background
Arteriovenous fistula (AVF) due to renal allograft biopsy is mechanical trauma resulting from the penetration of small arteries and veins by a core needle. Most AVFs are reported to resolve asymptomatically and spontaneously. This report presents a patient with acute kidney injury (AKI) due to urinary tract obstruction caused by a bleeding AVF in a renal allograft.

Case presentation
A 22-year-old Japanese woman who underwent living-donor kidney transplantation (KT) at 3 years due to end-stage renal disease caused by focal segmental glomerulosclerosis (FSGS) presented with a renal transplant AVF (gourd-shaped; 42 × 19 × 20 mm). The AVF was unexpectedly discovered by ultrasound before a surveillance biopsy at 10 years after KT. The patient had a history of recurrent FSGS, had undergone several renal allograft biopsies after KT, and did not experience symptoms or growth of the AVF for years. Nineteen years after KT, the patient developed AKI with sudden, asymptomatic, gross hematuria and anuria. Plain computed tomography revealed a hematoma in the pelvis of the renal allograft and bladder tamponade. The AVF was successfully treated by coil embolization. Hemodialysis was performed for AKI, and graft function was gradually recovered.

Conclusions
Unexpected bleeding from a renal transplant AVF may lead to transplant dysfunction. Angiographic embolization against the ruptured renal transplant AVF may prevent rebleeding and rescue the renal allograft.
FAP, CD10, and GPR77-labeled CAFs cause neoadjuvant chemotherapy resistance by inducing EMT and CSC in gastric cancer
Authors: Zhao Zehua , Zhu Yanmei 
Published: June 2023

Abstract
Objective
A significant proportion of patients can not benefit from neoadjuvant chemotherapy (NCT) due to drug resistance. Cancer-associated fibroblasts (CAFs) influence many biological behaviours of tumors, including chemo-resistance. This study aims to explore whether CAFs expressing FAP, CD10, and GPR77 affect the efficacy of NCT and the prognosis of patients with gastric cancer, and its mechanism.

Methods
One hundred seventy-one patients with locally progressive gastric adenocarcinoma who had undergone NCT and radical surgery were collected. Immunohistochemistry was used to detect the expression of FAP, CD10, and GPR77 in CAFs; the EMT markers (N-cadherin, Snail1, and Twist1) and the CSC markers (ALDH1, CD44, and LGR5) in gastric cancer cells. The χ2 test was used to analyze the relationship between the expression of CAF, EMT, and CSC markers and the clinicopathological factors, as well as the relationship between CAF markers and EMT, and CSC markers. Logistic regression and Cox risk regression were used to analyze the relationship between the expression of CAF, EMT, and CSC markers and TRG grading and OS; Kaplan-Meier analysis was used for survival analysis and plotting the curves.

Results
The expression of CAF markers FAP, CD10, and GPR77 was closely associated with that of EMT markers; FAP and CD10 were closely related to CSC markers. In the univariate analysis of pathological response, CAF markers (FAP, CD10, GPR77), EMT markers (N-cadherin, Snail1, Twist1), and CSC markers (ALDH1, LGR5, CD44), were all closely associated with pathological response (all p < 0.05). Only Twist1 was an independent factor affecting pathological response in multifactorial analysis (p = 0.001). In a univariate analysis of OS, expression of FAP and CD10 in CAF, as well as expression of EMT biomarkers (N-cadherin, Snail1), were significant factors influencing patient prognosis (all p < 0.05). Multifactorial analysis revealed N-cadherin (p = 0.032) and Snail1 (p = 0.028), as independent prognostic factors affecting OS.

Conclusion
FAP, CD10, and GPR77 labeled CAF subgroup may lead to NCT resistance and poor prognosis by inducing EMT and CSC of gastric cancer cells in locally advanced gastric cancer patients.