bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship Between Arm Path, Ball Velocity, and Elbow Varus Torque in Professional Baseball Pitchers
Authors: Dowling Brittany , Hodakowski Alexander , Olmanson Bjorn A. , Cohn Matthew R. , Pauley Patrick J. , Verma Nikhil N. , Nicholson Gregory P. , Garrigues Grant E. 
Published: December 2023

Background: Currently, most pitching instructors suggest a shorter arm path—the total distance the arm travels during pitching. Theoretically, this combination allows for better body segment sequencing, a more efficient energy transfer through the kinetic chain, and increased ball velocity, while limiting elbow varus torque. Hypothesis: Shorter arm paths would be associated with increased ball velocity and decreased elbow varus torque. Study Design: Descriptive laboratory study. Methods: A total of 182 professional pitchers threw 8 to 12 fastball pitches while evaluated by 3-dimensional motion capture (480 Hz). The arm path was calculated as the total distance the hand marker traveled during the pitch. The pitch was divided into early, late, and total arm paths. A linear regression model assessed the interpitcher relationship between arm path, elbow varus torque, and ball velocity. A linear mixed-effects model with random intercepts assessed intrapitcher relationships. Results: Interpitcher comparison showed that total arm path weakly correlated with greater elbow varus torque ( P = .025). Strong correlations were found between ball velocity and early ( R2 = 0.788; P < .001), late ( R2 = 0.787; P = .024), and total arm paths ( R2 = 0.792; P < .001). Strong positive intrapitcher correlations were found between elbow varus torque and early ( R2 = 0.962; P < .001) and total arm path ( R2 = 0.964; P < .001). For individual pitchers, there was a large variation in the early (30.1 ± 15.7 cm) and late (21.4 ± 12.1 cm) arm path. For every 30-cm (11.8-inch) increase in early arm path (the mean range for an individual pitcher), there was a 1.29-N (β = 0.0429) increase in elbow varus torque and a 0.354 m/s (0.79 mph) (β = 0.0118) increase in ball velocity. Conclusion: A shorter arm path correlated with decreased elbow varus torque and decreased ball velocity in intrapitcher comparisons. Determining the individual mechanics that decrease elbow varus torque may help coaches and trainers correct these patterns. Clinical Significance: A shorter arm path during the pitch can decrease elbow varus torque, which limits the load on the medial elbow but also has a detrimental effect on ball velocity. An improved understanding of the impact of shortening arm paths on stresses on the throwing arm may help minimize injury risk.
Increasing Palliative Care Team Involvement in Pediatric Hematopoietic Stem Cell Transplant Patients
Authors: Vacek Meagan , Tarbell Lisa , List Melissa , Hall Erin Marie , Linebarger Jennifer , Ellis Kelstan , Jones Gina , Thompson Joel 
Published: December 2023

Background/Objectives:
Palliative care facilitates communication, helps with physical and psychological symptom management, and assists in goals of care and advance care planning discussions. Multiple organizations including the World Health Organization, American Academy of Pediatrics and the American Society of Clinical Oncology encourage palliative care involvement. Palliative care involvement with hematopoietic stem cell transplant (HSCT) patients has been shown to be beneficial as HSCT is associated with a high degree of morbidity and possible mortality. We sought to increase the frequency of palliative care consultations for patients planning to undergo HSCT for targeted diagnoses.
The outcome measure was percentage of patients who underwent HSCT for a targeted diagnosis who had a Palliative Care Team (PaCT) consult. Baseline data revealed 48 patients underwent HSCT from July 2020 to July 2022, 25 of whom had a targeted diagnosis. PaCT met 12 of the 25 patients (48%). Our goal is to increase the number of PaCT consults for patients receiving HSCT for our targeted diagnoses from 48% to 75% by December 2023.
Methods:
Chart review was conducted for patients who underwent HSCT from July 2020 to July 2022. Demographics documented included reason for HSCT, if PaCT was consulted, date of transplant, date of PaCT consult and living status. A targeted diagnosis list was compiled based on which patients were felt to benefit most from palliative care involvement: relapsed or refractory leukemias and lymphomas, myelodysplastic syndrome, high risk acute myeloid leukemia and metabolic disorders, such as Hurler syndrome. The first plan-do-study-act (PDSA) cycle included discussion of the project at division meetings, posting flyers in the clinic provider workrooms, and education regarding palliative care and evidence of its involvement in HSCT patients. The second PDSA cycle implemented involved revision of the HSCT referral form to include the question “Is PaCT consulted.” If the provider answers “no,” further elaboration is requested.
Results: From 1/1/23 to 7/31/23 ten patients with a targeted diagnosis underwent HSCT. Five patients (50%) received a PaCT consult prior to HSCT.
Conclusions: Palliative care involvement in pediatric oncology is well established, but its role in HSCT patients continues to be explored. As HSCT patients receive more intense therapy, have frequent deaths in intensive care units and can have limited opportunity for end of life planning due to rapidly changing clinical courses, early integration of PaCT could allow for decreased symptom burden and distress for both patients and families. Future PDSA cycle interventions include adding PaCT consultation to the transplant evaluation order set in the electronic medical record and review of the comments on the completed HSCT referral forms to identify possible barriers in the PaCT consultation process.
Changes in the Fibrinolytic System of Patients Infected with Severe Acute Respiratory Syndrome Coronavirus 2
Authors: Owaidah Tarek M , Abudouleh Esraa , al Qahtani Ahmed , Al Hazzani Amal , Khorfan Kadiga 
Published: December 2023

Introduction: In this study, coagulation and fibrinolysis parameters and their association with disease severity were investigated in coronavirus disease (COVID-19) patients. Materials and Methods: COVID-19 patients (n=446) admitted to our institute between February 21, 2021 and March 17, 2022, were recruited. Clinical data and staging were collected from all patients. Blood samples were collected and analyzed for several parameters of fibrinolysis and coagulation, including alpha-2-antiplasmin(α2AP) and plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), D dimer, and fibrinogen levels. Results: The TAFI, fibrinogen, and tPA levels were significantly higher in participants who died compared to that of patients who recovered (P&lt;0.001). However, PAI-1, tPA, and TAFI were significantly higher in patients admitted to the ICU than those of the healthy controls (P&lt;0.001 for PAI-1 and tPA; P=0.0331 for TAFI). Our results showed that stage C and D COVID-19 patients had significantly higher levels of PAI-1 (P = 0.003). Furthermore, the stage D COVID-19 patients had significantly higher tPA and TAFI values (P=0.003). Conclusions: Hypofibrinolysis was the most prevalent condition among patients with severe COVID-19. In this study, several coagulation markers were elevated, making them suitable prognostic markers for hypofibrinolysis.
Figure 1. Plasma levels of different coagulation factors in COVID-19 patients. Plasma isolated from patients that had died due to COVID-19 and those recovering from the disease (top panel).
An Innovative Dynamic Nomogram for Stratifying Survival Prognosis in Essential Thrombocythemia Patients with a History of Thrombosis
Authors: Jia Chen , Sun Ting , Fu Rongfeng , Dong Huan , Yang Renchi , Zhang Lei 
Published: December 2023

Background: Essential thrombocythemia (ET) with a previous history of thrombosis was classified as high risk according to the revised International Prognostic Score for Thrombosis in ET. However, prognostic factors are not well established in this patient population. With the aim of enhancing patient outcomes, we endeavored to develop a prognostic nomogram specifically for patients with ET and a prior history of thrombosis.
Methods: We included 318 ET with previous arterial or venous thrombosis or both from January 2008 to June 2022 in our study. We used multivariable Cox proportional hazards regression to build a dynamic prognostic nomogram for this patient population. Harrell C Index was used for nomogram discrimination. Internal validation was performed by bootstrap resampling. The area under the receiver operating characteristic curve (AUC) was used to determine the nomogram's performance.
Results: Based on the IPSET model, out of the 318 patients, 148 were categorized as having an intermediate risk (score of 1-2), while 170 patients were classified as high risk (score greater than or equal to 3). Substantial statistical significance was observed in the overall survival between these two groups, underscoring the ability of the IPSET model to stratify prognosis in essential thrombocythemia patients with a history of thrombosis .
We further used multivariable cox regression analysis and found that Age≥60 years (HR=5.68 [95% CI:1.44-22.47], p=0.013), splenomegaly (HR=5.66 [95% CI:1.74-18.43], p=0.004), abnormal karyotype (HR=5.28 [95% CI:1.38-20.25], p=0.015), white blood cell counts (HR=1.09 [95% CI:1.02-1.18], p=0.014), and hemoglobin (Hb, HR=0.97 [95% CI:0.95-0.99], p=0.006) were independently risk factors for survival. We created a nomogram as well as a web portal that enables survival predictions based on individualized parameters ( https://cae29l-jia-chen.shinyapps.io/DynNomapp/ ). The C Index of the nomogram was 0.818. The AUC of 3-year, 5-year, and 10-year survival of the nomogram were 0.854, 0.769, and 0.813, respectively. Sex biases were observed at Hb levels that contribute outcome heterogeneity in such ET patients.
Conclusions : We provided a new dynamic nomogram that can well evaluate the survival prognostication for a given ET patient with a previous history of thrombosis, with a good discrimination and excellent performance.
Caebv Disease Originates from Infected Hematopoietic Stem Cells
Authors: Wang Jingshi , Wei Na , Zhang Jia , Wu Lin , Wang Xi , Wang Zhao 
Published: December 2023

Background Chronic active Epstein-Barr Virus (EBV) disease (CAEBV) is lethal syndrome due to persistent EBV infection. When diagnosed as CAEBV, EBV infection was observed in multiple hematopoietic lineages, but the etiology of CAEBV is still elusive.
Methods Bone marrow and peripheral cells derived from five CAEBV patients, one EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) patient, and two healthy controls were analyzed. Multiple assays were applied to identify and characterize EBV-infected cells, including quantitative PCR (qPCR), PrimeFlow and single-cell RNA-sequencing (scRNA-seq). Based on scRNA-seq data, alterations in gene expression of particular cell types were analyzed between CAEBV patients and controls, and between infected and uninfected cells. One CAEBV patient was treated with allogeneic hematopoietic stem cell transplantation (HSCT), and the samples derived from this patient were analyzed again six month after HSCT.
Results EBV infected the full spectrum of the hematopoietic system including both lymphoid and myeloid lineages, so as hematopoietic stem cells (HSCs) in the CAEBV patients. EBV-infected HSCs exhibited a higher differentiation rate towards downstream lineages, and the EBV infection had an impact on both the innate and adaptive immunity, resulting in inflammatory symptoms. EBV infected cells were thoroughly removed from the hematopoietic system after HSCT.
Conclusions Token together,multiple lines of evidence presented in this study suggest that CAEBV disease originates from the infected hematopoietic stem cells.
Figure 1. EBV-infected HSCs were detected in CAEBV patients with multiple assays.
Mitoxantrone Hydrochloride Liposome Injection Combined with Carmustine, Etoposide, and Cytarabine As Conditioning of Autologous Hematopoietic Stem Cell Transplantation in NHL Patients：a Prospective Single-Arm Clinical Trial
Authors: Wang Xiaoning , Ren Juan , Zhu Huachao , Zhang Mei , He Pengcheng 
Published: December 2023

Background：High-dose chemotherapy and autologous stem-cell transplantation (ASCT) is standard consolidation therapy for aggressive lymphoma.Choosing the most effective conditioning regimen prior to ASCT can lead to longer survival in these patients.Mitoxantrone liposome is an anthraquinone antibiotic anti-tumor drug. Previous studies have shown that mitoxantrone liposome monotherapy or combined with other drugs has achieved good efficacy for T-cell lymphoma, but there are no reports of its application in conditioning.
Objective:This is a prospective single-arm clinical study to evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection combined with carmustine, etoposide, cytarabine (modified BEAM protocol) as conditioning of autologous hematopoietic stem cell transplantation for NHL patients (NCT05681403).
Methods: Patients with non-Hodgkin lymphoma who planned to undergo ASCT were eligible to participate in the trial if they were 18 to 60 years of age.The patients received mitoxantrone hydrochloride liposome injection 24 mg/m 2,ivgtt,d-7, carmustine 300 mg/m 2,ivgtt,d-6, etoposide200 mg/m 2,ivgtt,d-5~ -2,cytarabine 200 mg/m 2 q12h,ivgtt,d-5~ -2 as conditioning regimen.The primary end point was the relapse rate within three years and the secondary end point was adverse events of modified BEAM protocol.
Results：Twenty-five NHL patients (median age 39 years old,17 males and 8 females) were enrolled,including 40% DLBCL, 12% MCL, 4% primary mediastinal B-cell lymphoma,4%B lymphoblastic lymphoma,4%Marginal zone B-cell lymphoma,12% PTCL-NOS, 8% ALK +ALCL,8% NK/T lymphoma, 8% AITL,4% ALK -ALCL and 4% Sézary syndrome. 18 cases achieved complete remission before ASCT, while 7 cases received partial remission before ASCT. The median of neutrophil recovery time was 11 days(7-15) and the median of platelet recovery was 12days (7-60).Nausea,vomit,constipation,blue skin and cough were the most frequently reported conditioning related AEs (88%,16%,12%,12% and 8% of patients,respectively), and other AE included 1 case of hypoxemia, 1 case of hypotension, 1 case of palpitation, 1 case of rash. Except one patient experienced a grade 3 vomit ,the others were grade 1-2 and improved after symptomatic treatment. Nine patients experienced febrile neutropenia and 2 cases of sepsis, 4 cases of respiratory infection, and 3 cases of oral mucositis. All partial remission patients achieved complete remission post-HSCT and one of them relapsed 7 months after ASCT.The others were all in complete remission during follow-up.
Conclusion:Mitoxantrone hydrochloride liposome injection combined with carmustine, etoposide, cytarabine (modified BEAM protocol) was a well-tolerated and effective conditioning regimen for NHL and the study is ongoing and updated results will be presented in the future.
One Case of Heavy Chain Deposition Disease Treated with Dara+KD Regimen and Literature Review
Authors: Chen Meilan , Li Juan 
Published: December 2023

Background: Heavy chain deposition disease (HCDD) is a systemic disease caused by the deposition of monoclonal immunoglobulin heavy chains in tissues.It is a rare monoclonal immunoglobulin deposition disease. The mechanism of HCDD is still unclear, which may be related to the deletion of heavy chain constant region 1 and the activation of the Complement system by monoclonal heavy chains. Renal biopsy remains the gold standard for diagnosing HCDD at present. There are significant individual differences in the formation of abnormal heavy chains in HCDD patients, and FLC, M protein, and complement detection have certain reference significance for the evaluation of diagnosis and treatment processes. The chemotherapy scheme represented by Bortezomib has a certain effect. HDM/ASCT and kidney transplantation can be used as second-line treatment for some patients. At present, there is no report on the use of CD38 monoclonal antibody combined with KD regimen.
Objective: To explore the efficacy and toxicity of CD38 monoclonal antibody combined with KD regimen in the treatment of heavy chain deposition disease.
Methods: The diagnosis, treatment and efficacy of HCDD who hospitalized in the Hematology Department of the First Affiliated Hospital of Sun Yat-sen University was analyzed, and the value of CD38 monoclonal antibody combined with KD regimen in the treatment of HCDD was discussed. The patient was male, 44 years old, due to “depressed edema of both lower limbs and eyelid edema for more than two months”.
Results: Heavy chain deposition disease is a rare malignant Plasma cell disease. CD38 monoclonal antibody combined with KD regimen can rapidly alleviate the disease,.This patient got CR and obvious improvement of clinical symptoms after 1 cycle chemotherapy, and has no obvious side effects.We be expected to do 4 cycle chemothetaphy and would do ASCT.until now,this patient has got 3 cycles.
Conclusion: Heavy chain deposition disease is a rare malignant Plasma cell disease. CD38 monoclonal antibody combined with KD regimen can rapidly alleviate the disease, with fast onset time, high CR rate, obvious improvement of clinical symptoms, and no obvious side effects.
Demethylation Strategies for the Treatment of Acute Myeloid Leukemia: Targeting Protacs That Degrade DNA Methyltransferase
Authors: Zhang Nan , Xin Lilan , Wang Qian , Chen Guopeng , Ma Linlu , Liang Yuxing , Zhou Fuling 
Published: December 2023

Background
DNA methylation is crucial in the pathogenesis of acute myeloid leukemia (AML), characterized by abnormal proliferation of myeloid cells and disrupted DNA methylation patterns. These aberrant patterns contribute to the dysregulation of key genes involved in AML development and progression. Therefore, targeting DNA methyltransferases (DNMTs) to restore proper DNA methylation patterns has emerged as a promising therapeutic strategy. However, traditional demethylation therapies (e.g. azacytidine, decitabine) face challenges in effectively and selectively targeting DNMTs.
Methods
In this study, we investigated the potential of a novel approach utilizing proteolysis targeting chimeras (PROTACs) for selective degradation of DNMTs in AML cells. A series of PROTAC molecules was designed and synthesized, with GSK3685032 serving as the ligand for DNMTs. The E3 ligase CRBN was employed to mediate the proteasomal degradation process.
Results
The designed PROTACs efficiently degraded DNMTs in AML cell lines, as demonstrated by immunoblotting and immunofluorescence assays. Genome-wide DNA methylation analysis revealed a significant reduction in global DNA methylation levels following PROTAC-mediated DNMT degradation.In AML PDX models, the PROTACs effectively decreased DNMT protein levels, resulting in substantial reduction of global DNA methylation and significant inhibition of tumor growth. Furthermore, combination studies revealed synergistic effects when the PROTAC-mediated DNMT degradation was combined with standard clinical therapeutic agents.The combination approach showed enhanced therapeutic efficacy compared to either treatment alone, suggesting a potential strategy for improved AML treatment outcomes.
Conclusions
The study highlights the potential of PROTAC-mediated DNMT degradation as a promising targeted demethylation strategy for AML. This approach holds promise for improving treatment outcomes, particularly in AML patients with DNMT mutations. Further research is warranted to fully evaluate the efficacy of this approach in clinical settings.
Keywords: Acute myeloid leukemia, DNA methylation, PROTACs
Fluid-Overload Associated Large B-Cell Lymphoma Clinicopathologic Features and Determinants of Outcomes: Analysis of a Pooled Database
Authors: Graham Christopher , Gupta Supriya , Haddad Philip A 
Published: December 2023

Background:
Fluid overload-associated large B-cell lymphoma (FOLBCL) is a new WHO lymphoma entity previously known as PEL-like lymphoma or HHV8-unrelated PEL-like lymphoma. It is a rare lymphoma that arises within fluid-filled body cavities without a solid component. FOLBCL occurs in the absence of immunodeficiency and is commonly associated with conditions associated with fluid overload. It expresses mature B-cell phenotype and occasional EBV infection markers. We conducted this study to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect outcomes in this rare and newly-defined lymphoma subtype.
Methods:
To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 115 cases that fit the diagnostic criteria for FOLBCL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS).
Results:
A total of 115 patients with confirmed FOLBCL were identified. The median age was 74, with a peak incidence between 72 and 82 years. There was a male preponderance with M:F of 2. The pleural, pericardial, and peritoneal cavities were involved in 75%, 34%, and 27%, respectively. The median duration of symptoms before diagnosis was 1 month. Patients presented with constitutional symptoms and hepatosplenomegaly in 13% and 1%, respectively-no patients presented with lymph node and bone marrow involvement. The median OS of the whole group was 16 months. Patients younger than 70 had better median OS than 70 and older (24 vs. 10 months, p=0.008). The presence of any malignant peritoneal effusion was associated with worse OS when compared to effusion limited to the thoracic cavity (7 vs. 24 months, p=0.005). LDH≥500 was also associated with worse OS (p=0.02). Sex, the presence of fluid overload-causing conditions, and serum IL2R levels did not seem to impact OS. Compared to no treatment, chemotherapy had a numerically superior OS but did not reach statistical significance (19 vs. 10 months, p=0.11). However, patients that attained CR as their best response had a superior median OS (p&lt;0.0001).
Conclusions:
This study presents updated clinicopathologic data from a pooled cohort of patients with FOLBCL. It identifies the age, the primary location of cavitary disease, LDH, active therapy, and quality of response to treatment as key determinants of OS.