bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beneficial Role of Erythrocyte Sphingosine 1-Phosphate in Preventing Renal Macrophage Polarization and Fibrosis through Combating HIF-1α-Dependent Creatine Phosphate Shuttle
Authors: Xie Tingting , Chen Changhan , Wang Yiyan , Li Zhenjiang , Brown Benjamin C. , Kellems Rodney E. , Zhang Weiru , D'Alessandro Angelo , Xia Yang 
Published: December 2023

Introduction: Erythrocytes, the major reservoir and supplier for plasma sphingosine 1 phosphate (S1P), is a potent biolipid signaling via its specific receptors responsible for immune cell trafficking and function. Current evidence has revealed that erythrocyte intracellular S1P has its own function to promote oxygen (O 2) delivery to counteract tissue hypoxia.
Aim: To understand whether O 2 delivery mediated by erythrocyte S1P is involved in tissue macrophage polarization and fibrosis.
Methods and Results: Genetic ablation of erythrocyte SphK1 (the only enzyme to generate S1P in erythrocyte, eSphK1 -/-) resulted in less O 2 delivery from erythrocytes, thus leading to severe renal hypoxia, damage and fibrosis in angiotensin II induced hypertensive kidney disease mouse model. Surprisingly, although plasma S1P level was reduced to 50% in Ang II-infused eSphK1 -/- mice, these mice displayed preferentially elevated pro-fibrosis M2 macrophages surrounding the hypoxic renal tubules. Surprisingly, there was no significant difference of S1P level in either kidney or renal macrophages between Ang II-infused controls and eSphK1 -/- mice, ruling out the possibility of difference of kidney or macrophage S1P levels responsible for renal M2 macrophage polarization. Metabolically, untargeted high-throughput metabolic profiling in macrophages purified from mouse kidney revealed a substantial reduction of amino acids (AAs) and fatty acids (FAs) but increased creatine. We further validate this in vitro by 13C 6, 15N 4-labeled arginine tracer. Hypoxia (1~2% O 2) promoted increased 13C 2-labeled creatine (arginine downstream metabolite) in murine bone marrow derived macrophages (BMDMs) time dependently. At cellular and molecular level, we further demonstrated that hypoxia signaling via HIF-1a directly enhanced IL-4 induced M2 polarization of BMDMs as well as expression of Ckb (a gene encoding creatine shuttle), which can be reversed by Chrysin (an HIF-1α inhibitor). Preclinical studies revealed that chrysin rescued the severe renal damage in eSphK1 -/-mice manipulated with unilateral ureteral obstruction (UUO) and prevented development of chronic kidney disease (CKD) in the control mice. Translational research validated mouse findings in kidney tissue of CKD patients.
Conclusion: Our work has revealed that erythrocyte S1P combats HIF1α-dependent creatine shuttle, renal macrophage polarization and fibrosis and highlighted potential diagnostic and therapeutic possibilities for macrophage polarization and renal fibrosis.
Comparative Outcome Analysis of Nodular Lymphocyte-Predominant Hodgkin Lymphoma Vs Classical Hodgkin's Lymphoma - a SEER Based Study
Authors: Shah Anish , Budhathoki Pravash , Karki Ujjwal , Neupane Niraj , Khanal Sneha 
Published: December 2023

Introduction
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a slower-growing variant of Hodgkin lymphoma that is uniquely characterized by its growth pattern and cellular appearance. While patients with NLPHL tend to demonstrate more promising prognoses than their counterparts with classical Hodgkin lymphoma (CHL), recent comparative studies remain limited. The objective of this study was to investigate the disparities in survival rates between NLPHL and CHL patients, accounting for variations in patient demographics and disease attributes.
Methodology
We utilized Surveillance, Epidemiology, and End Results (SEER) 17 registries database to identify patients diagnosed with NLPHL and CHL between 2000 - 2020. Univariate survival analysis was done using a Kaplan Meir plot with a log-rank test, and the Cox proportion hazard regression model was used for multivariate survival analysis.
Results
A total of 2,723 NLPHL cases and 42,581 CHL cases were included in the study. The median age of NLPHL patients stood at 44 years, whereas for CHL patients it was observed to be 38 years. Over an 83-month median follow-up, NLPHL demonstrated superior 5-year (92.2%) and 10-year (83.84%) survival rates compared to CHL (82.45% and 75.45%, respectively). When controlled for all available characteristics, NLPHL showed a significantly higher overall survival (HR: 2.373; 95% CI, 2.131 - 2.644; P&lt;.001) than CHL. For those diagnosed with NLPHL, our data indicated that patients who underwent radiation therapy had better survival rate (HR: 1.98; 95% CI, 1.55 - 2.53; p&lt;.001). Additionally, younger age and male gender were associated with a more favorable prognosis.
Conclusion
Our analysis highlights the superior survival outcomes for NLPHL patients as compared to those with CHL, even when accounting for available patient and disease characteristics. The further enhanced survival rates observed in NLPHL patients undergoing radiation therapy suggests potential for more tailored therapeutic approaches. Factors such as younger age and male gender were also identified as indicative of a more favorable prognosis, underscoring the need for further exploration of demographic and clinical influences on survival outcomes in Hodgkin lymphomas.
National Mortality Outcomes of Acute Chest Syndrome Hospitalization during the COVID-19 Pandemic
Authors: Olafimihan Ayobami , Turk Ekrem , Ozogbo Stanley , Cuartas-Mesa Maria Cristina , Fawehinmi Praise , Shaka Hafeez 
Published: December 2023

Introduction
Sickle cell disease (SCD) is an hereditary hemoglobin disorder characterized by repeated episodes of severe acute pain, acute chest syndrome (ACS) and other complications. The average life expectancy of SCD patients remains 20 years less than the general population, and ACS is the leading cause of mortality. This retrospective study describes the effect of the COVID-19 pandemic on epidemiologic trends and outcomes of Acute Chest Syndrome.
Methods
The National Inpatient Sample (NIS) database from 2016 to 2020 was searched for hospitalizations with ACS as the principal diagnosis using Clinical Classifications Software Refined codes. The ACS admission rate for each calendar year was obtained as admission per 10,000 SCD adults hospitalized. The primary outcome was a comparison of inpatient mortality, and the secondary outcomes were the length of hospital stay (LOS) and total hospital charge (THC) between prepandemic (2019) and pandemic years (2020).
Results
In 2019 (prepandemic), there were 5,160 hospitalizations for ACS, accounting for 624 per 10,000 adult SCD hospitalizations. In 2020 (pandemic), there were 4,285 patients hospitalized for ACS, accounting for 540 per 10,000 adult SCD hospitalizations. The mean age of admission was similar for both years (31.5 vs 32 years, P=0.143), and there was no significant difference in age categories when both years were compared. The gender distribution was similar during both periods (females: 45.6 vs 46.7%, p=0.68). The racial distribution was predominantly blacks with no significant difference during both year (92 vs 92%, p=0.3). There was no significant difference in hospitalizations with regard to insurance status, hospital region, or hospital size between both years.
There was a three-fold increase in overall proportion of ACS inpatient mortality in the pandemic year of 2020 compared to the prepandemic level (0.6% vs 1.9%, P=0.009). Proportion of mortality among women had a five-fold increase (0.4% vs 2.3%, P=0.02). There was a four-fold increase in mortality proportions among the Black population (0.5% vs 2%; p=0.007). Mortality outcomes were similar over both years when stratified for income quartiles and hospital regions.
The LOS during the pandemic was similar to the prepandemic level (6.5. vs 7.4days, P=0.563). Also, there was no statistically significant difference in the total hospital charge ($61,515 vs $80,191, P=0.108).
Conclusion
This study depicts a statistically significant increase in inpatient mortality outcomes of Acute chest syndrome during the pandemic period. However, the length of hospital stay and total hospital charge were similar. Further studies need be conducted to evaluate the long-term effect of the COVID-19 pandemic on SCD.
Primary Pancreatic Lymphoma: An Analysis of the National Cancer Database
Authors: Abushalha Kamelah , Silberstein Peter T. 
Published: December 2023

Background: Primary pancreatic lymphoma (PPL) is a rare entity, accounting for fewer than 2% of extranodal malignant lymphomas and 0.5% of all pancreatic masses. Fewer than 150 cases of PPL have been reported in the English language medical literature. We aimed to utilize the National Cancer Database (NCDB) to investigate the clinicopathological features and prognostic factors in PPL.
Methods: The NCDB for Non-Hodgkin lymphoma was used to identify 2130 patients diagnosed with PPL (2004 and 2020). The database was used to examine clinicopathological features. Survival analysis was done by Kaplan-Meier. Cox proportional hazards was adopted for prognostic variable evaluation.
Results: Most PPL patients were males (58.5%) and white (87.7%), mean age at diagnosis was 67.38 years. Histologically 59.6% were diffuse large B-cell. 14.9% Follicular, 2.6 % Burkitt, & 15.8% Lymphoma NOS. Regarding treatment 71.5% of patients received chemotherapy. Immunotherapy given in 21.9%. Radiation in 12.1%, and 7.3% received some form of surgical treatment. Median survival was 85.32 months (CI 79.79-90.84). Using Cox hazard regression, the following factors were statistically significant (p&lt;0.001): Age &gt;60 (HR: 2.36,CI 1.9-2.8), increasing Charlson-Deyo Score, DLBL histology (HR:0.57,CI 0.45-0.72), stage 3 (HR:1.9,CI 1.6-2.2), Chemotherapy (HR 0.4,CI 0.34-0.46),and immunotherapy (HR 0.61,CI0.62-0.89)
Conclusion: This is the most comprehensive study to date to utilize the NCDB to study the characteristics and prognostic factors of patients with PPL. DLBL histology, chemotherapy and immunotherapy are associated with reduced risk of death.
Incidence and Prognosis of Primary Malignancies in Ataxia-Telangiectasia Patients: A Report from the Ataxia-Telangiectasia Clinical Center (ATCC)
Authors: Sharma Richa , Magnarelli Aimee , Liu Qi , Wang Fan , Yasui Yutaka , Ehrhardt Matthew J. , Lederman Howard 
Published: December 2023

Biallelic germline mutations in the ATM gene result in Ataxia-Telangiectasia (AT), a classic DNA repair disorder associated with a high incidence of primary malignancies. The lack of standardized cancer treatment approaches for patients with AT is believed to contribute to poor survival after diagnosis. Robust characterization of the incidence, outcomes, and ATM variant enrichment of large cohorts of individuals with AT who develop malignancies are needed to inform therapeutic decision-making.
The AT Clinical Center (ATCC) at Johns Hopkins Hospital is a large, retrospective cohort that prospectively collects outcomes data on individuals diagnosed with AT in the US. Standardized incidence ratios (SIRs) were used to compare cancer incidence to that of age-, sex-, and year-matched US general population using the SEER database. Standardized mortality ratios (SMRs) and mortality rate ratios were used to estimate mortality risk compared to the general population.
Among 508 total participants with AT, 84 developed cancers (16.5%): 39 non-Hodgkin lymphoma (NHL), 7 Hodgkin lymphoma, 16 leukemia (n=13 of T cell origin), and 22 carcinomas. SIRs were 355.9, 67.4, 45.6, and 18.0, respectively. Median (interquartile range) age at cancer diagnosis was 14.3 years (10.3-22.8), with NHL occurring in the youngest (12.4 years, IQR 7.3-16.7) and solid tumors in the oldest (26.3 years, IQR 18.7-29.0) individuals. The SMR was 24.6 (95% CI: 21.1-28.4) for the overall cohort of AT patients and 232.9 (95% CI: 178.1-299.2) among those with cancer. Median survival following a cancer diagnosis was 2.5 years (95% CI: 0.1-14.4). The post-cancer mortality rate ratio was 2.2 (95% CI: 1.1-4.3, p=0.025) comparing AT patients with cancer treated without dose reduction or for whom dosing was unknown (n=24) versus AT patients with cancer who received dose reduced chemotherapy (n= 38). Among those who received chemotherapy (n=62), 11/24 (45.8%, 95% CI: 25.6-67.2) treated with standard dosing and 24/38 (63%, 95% CI: 46.0-78.2) treated with reduced dosing experienced toxicity (p=0.20). ATM variant associations were detected by single variant analysis among 247 patients with AT who had confirmed biallelic ATM mutations via whole exome sequencing.
Individuals with AT are at very high-risk of primary malignancies, of which NHL is most common. Prognosis is poor regardless of standard versus dose reduced chemotherapy regimens, which calls for novel therapies.
Translation, cross-cultural adaptation and measurement proprieties of the German version of the Allodynia Symptom Checklist (ASC-12)
Authors: Marusich Tetiana , Szikszay Tibor M , Sennholz Anne , Luedtke Kerstin , Carvalho Gabriela F. 
Published: December 2023

Abstract
Background
Cutaneous allodynia is highly prevalent among migraineurs and is associated with a poor prognosis. The Allodynia Symptom Checklist (ASC-12) is a comprehensive questionnaire to identify the presence and severity of allodynia. Our aim was to translate and adapt the ASC-12 to German and evaluate its measurement properties.

Methods
Following the COSMIN guidelines, 80 migraine patients were enrolled in the study to evaluate the stages of translation (n=30) and measurement propriety assessment (n=50), respectively. After reaching a final version, the German ASC-12 was assessed for structural validity, internal consistency, test-retest reliability, construct validity and absolute agreement, using mechanical and thermal pain thresholds as reference method.

Results
The German version of the ASC-12 presented an adequate structural validity compatible with the original version of the questionnaire. Its internal consistency ranged from 0.70 to 0.80 considering the total score and the thermic, static and dynamic mechanic subdomains. The total score presented excellent reliability (ICC: 0.85) with a standard error of measurement of 1.15 points and smallest detectable change of 3.40 points. ASC-12 total scores were correlated with headache intensity (r=0.38, p=0.004), headache disability (r=0.37, p=0.004) and cold pain thresholds (r=0.28, p=0.025). The thermic allodynia ASC-12 scores were correlated with cold (r=0.36, p=0.005) and heat (r=-0.30, p=0.010) pain thresholds, while the static mechanical allodynia ASC-12 scores correlated with mechanical pain threshold (r=0.29, p=0.019) and with mechanical pain sensitivity (r=0.24 to 0.28, p< 0.045). Despite no significant bias between methods, quantitative sensory testing (QST) results and ASC-12 scores tend to disagree.

Conclusion
The German version of the ASC-12 is available for research and clinical settings and presented adequate measurement proprieties, as the original version. Despite the correlation between the ASC-12 and QST, one method cannot be replaced by the other.
HostNet: improved sequence representation in deep neural networks for virus-host prediction
Authors: Ming Zhaoyan , Chen Xiangjun , Wang Shunlong , Liu Hong , Yuan Zhiming , Wu Minghui , Xia Han 
Published: December 2023

Abstract
Background
The escalation of viruses over the past decade has highlighted the need to determine their respective hosts, particularly for emerging ones that pose a potential menace to the welfare of both human and animal life. Yet, the traditional means of ascertaining the host range of viruses, which involves field surveillance and laboratory experiments, is a laborious and demanding undertaking. A computational tool with the capability to reliably predict host ranges for novel viruses can provide timely responses in the prevention and control of emerging infectious diseases. The intricate nature of viral-host prediction involves issues such as data imbalance and deficiency. Therefore, developing highly accurate computational tools capable of predicting virus-host associations is a challenging and pressing demand.

Results
To overcome the challenges of virus-host prediction, we present HostNet, a deep learning framework that utilizes a Transformer-CNN-BiGRU architecture and two enhanced sequence representation modules. The first module, k-mer to vector, pre-trains a background vector representation of k-mers from a broad range of virus sequences to address the issue of data deficiency. The second module, an adaptive sliding window, truncates virus sequences of various lengths to create a uniform number of informative and distinct samples for each sequence to address the issue of data imbalance. We assess HostNet's performance on a benchmark dataset of “Rabies lyssavirus” and an in-house dataset of “Flavivirus”. Our results show that HostNet surpasses the state-of-the-art deep learning-based method in host-prediction accuracies and F1 score. The enhanced sequence representation modules, significantly improve HostNet's training generalization, performance in challenging classes, and stability.

Conclusion
HostNet is a promising framework for predicting virus hosts from genomic sequences, addressing challenges posed by sparse and varying-length virus sequence data. Our results demonstrate its potential as a valuable tool for virus-host prediction in various biological contexts. Virus-host prediction based on genomic sequences using deep neural networks is a promising approach to identifying their potential hosts accurately and efficiently, with significant impacts on public health, disease prevention, and vaccine development.
Comparison of intrathecal low-dose bupivacaine and morphine with intravenous patient control analgesia for postoperative analgesia for video-assisted thoracoscopic surgery
Authors: Guo Miao , Tang Suhong , Wang Yixin , Liu Fengxia , Wang Lin , Yang Dawei , Zhang Jianyou 
Published: December 2023

Abstract
Background
Thoracoscopic surgical techniques continue to advance, yet the intensity of postoperative pain remains significant, impeding swift patient recovery. This study aimed to evaluate the differences in postoperative pain and recuperation between patients receiving intrathecal morphine paired with low-dose bupivacaine and those administered general anesthesia exclusively.

Methods
This randomized controlled trial enrolled 100 patients, who were allocated into three groups: Group M (5 μg/kg morphine intrathecal injection), Group B (5 μg/kg morphine combined with bupivacaine 3 mg intrathecal injection) and Group C (intrathecal sham injection). The primary outcome was the assessment of pain relief using the Numeric Rating Scale (NRS). Additionally, intraoperative remifentanil consumption was quantified at the end of the surgery, and postoperative opioid use was determined by the number of patient-controlled analgesia (PCIA) compressions at 48 h post-surgery. Both the efficacy of the treatments and any complications were meticulously recorded.

Results
Postoperative NRS scores for both rest and exercise at 6, 12, 24, and 48 h were significantly lower in groups M and B than in group C (P<0.05). The intraoperative remifentanil dosage was significantly greater in groups M and C than in group B (P<0.05), while there was no significant difference between groups M and C (P>0.05). There was no significant difference in intraoperative propofol dosage across all three groups (P>0.05). Postoperative dosages of both sufentanil and Nonsteroidal anti‐inflammatory drugs (NSAIDs) were significantly less in groups M and B compared to group C (P<0.05). The time of first analgesic request was later in both groups M and B than in group C (P<0.05). Specific and total scores were elevated at 2 days postoperative when compared to scores at 1 day for all groups (P<0.05). Furthermore, at 1 day and 2 days postoperatively, both specific scores and total scores were higher in groups M and B compared to group C (P<0.05).

Conclusion
Intrathecal administration of morphine combined with bupivacaine has been shown to effectively ameliorate acute pain in patients undergoing thoracoscopic surgery.

Trial registration
The trial was registered on ClinicalTrials.gov: ChiCTR2200058544, registered 10/04/2022.
MicroRNA-155 targets SOCS1 to inhibit osteoclast differentiation during orthodontic tooth movement
Authors: Jiao Yao , Mi Sicong , Li Xiaoyan , Liu Yitong , Han Nannan , Xu Junji , Liu Yi , Li Song , Guo Lijia 
Published: December 2023

Abstract
Background
MicroRNA-155 (miR-155) is a multifunctional miRNA whose expression is known to be involved in a range of physiological and pathological processes. Its association with several oral diseases has been established. However, the specific role of miR-155 in orthodontic tooth movement remains unclear. In this study, we investigated the impact of miR-155 on osteoclast differentiation and orthodontic tooth movement models, aiming to explore the underlying mechanisms.

Methods
In this experiment, we utilized various agents including miR-155 mimic, miR-155 inhibitor, as well as non-specific sequences (NC mimic & NC inhibitor) to treat murine BMMNCs. Subsequently, osteoclast induction (OC) was carried out to examine the changes in the differentiation ability of monocytes under different conditions. To assess these changes, we employed RT-PCR, Western blotting, and TRAP staining techniques. For the orthodontic tooth movement model in mice, the subjects were divided into two groups: the NaCl group (injected with saline solution) and the miR-155 inhibitor group (injected with AntagomiR-155). We observed the impact of orthodontic tooth movement using stereoscopic microscopy, micro-CT, and HE staining. Furthermore, we performed RT-PCR and Western blotting analyses on the tissues surrounding the moving teeth. Additionally, we employed TargetScan to predict potential target genes of miR-155.

Results
During osteoclast induction of BMMNCs, the expression of miR-155 exhibited an inverse correlation with osteoclast-related markers. Overexpression of miR-155 led to a decrease in osteoclast-related indexes, whereas underexpression of miR-155 increased those indexes. In the mouse orthodontic tooth movement model, the rate of tooth movement was enhanced following injection of the miR-155 inhibitor, leading to heightened osteoclast activity. TargetScan analysis identified SOCS1 as a target gene of miR-155.

Conclusions
Our results suggest that miR-155 functions as an inhibitor of osteoclast differentiation, and it appears to regulate osteoclasts during orthodontic tooth movement. The regulatory mechanism of miR-155 in this process involves the targeting of SOCS1.