bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling the Tempest: Dermal Plasmacytoid Dendritic Cell Proliferation as the Harbinger of Acute Myeloid Leukemia
Authors: Zelman Brandon , Barragan Victor , Fathima Samreen , Gupta Rachit , Hanif Faaris , Mirza Kamran , Speiser Jodi 
Published: August 2024

Abstract:
Plasmacytoid dendritic cell neoplasms are rare neoplasms originating from plasmacytoid dendritic cells (pDCs). They are subclassified into 2 types: blastic plasmacytoid dendritic cell neoplasm and mature plasmacytoid dendritic cell proliferation. Neoplastic expansion of pDCs has also been found to be associated with myeloid neoplasia. We present the diagnostically challenging case of a 62-year-old woman who presented to the emergency department with numerous hemorrhagic nodules and papules on the face and extensor surfaces near the elbows and neutropenic fevers. The patient had a history notable for lupus erythematosus and a recently performed excisional lymph node biopsy involved by a “plasmacytoid dendritic cell proliferation.” A punch biopsy was performed, which showed a robust dermal infiltrate of atypical intermediate-sized mononuclear cells. The infiltrate was positive for CD4, CD43, and CD123. CD3 and CD8 highlighted background T cells. The infiltrate was negative for CD10, CD34, CD56, CD68, CD117, myeloperoxidase, lysozyme, TdT, and TCL-1. The findings favored a diagnosis of cutaneous involvement of the plasmacytoid dendritic cell proliferation. Given the association with acute leukemias, a subsequent bone marrow biopsy was recommended. The bone marrow biopsy was performed, which showed increased blasts (68% on a 500 differential cell count). Furthermore, immunohistochemical stains were performed, which highlighted the blasts to be positive for CD34 and BEST (alpha-naphthyl butyrate esterase) cytochemical stain. This diagnosis was consistent with bone marrow involvement of acute myelomonocytic leukemia. Given the overlapping presenting symptoms (skin lesions, adenopathy, marrow involvement) of pDC neoplasms and myeloid neoplasia and the possibility of presenting concurrently, increased awareness is of pivotal importance to help prevent potential misdiagnosis, missed diagnosis, and prompt investigation of possible associated neoplasms.
A Comparison of Parent-Reported Severe Autism With Mild/Moderate Autism Among US Children
Authors: Carbone Paul S. , Stipelman Carole H. , Villalobos Michele E. , Ellzey Allison , Stuart Ashley , Stoddard Gregory J. , Campbell Kathleen 
Published: August 2024

ABSTRACT:

Objective:
An expert commission has proposed the term “profound” autism for children on the spectrum who are minimally verbal or nonverbal and have intellectual disability (ID), behavioral challenges, and co-occurring conditions. It is unknown whether parents' rating of “severe” autism aligns with the definition of “profound” autism. Using the National Survey of Children's Health, we sought to (1) estimate the prevalence of parent-reported severe autism, (2) identify child characteristics that are associated with severe autism, (3) compare health care utilization, and (4) compare caregiver stress and resilience between families of children with severe versus mild/moderate autism.

Methods:
Parent responses on the 2018 to 2019 NSCH were used to compare school-age children with parent-reported severe autism and those with mild/moderate autism. Descriptive statistics, χ2 tests, and logistic regression were used for statistical analysis.

Results:
Among parents of 1,368 US children with autism, 10.1% characterized their child's autism as severe, a prevalence of 1 in 333. Parents of children with severe autism were more likely to report ID (45% vs 12.1%, p < 0.001), language delay (88% vs 58.7%, p < 0.001), and difficulties in dressing and bathing (67% vs 19.2%, p < 0.001). Children with severe autism had more behavioral problems and co-occurring conditions but were no more likely to see specialists or receive autism-specific behavioral therapy. Their caregivers reported more stress and less resilience.

Conclusion:
The characteristics of “profound” autism and parent-reported “severe” autism significantly overlap, allowing the use of the NSCH for studies of this vulnerable population. Children with profound/severe autism could benefit from more behavioral therapy, specialty care, and family support.
Transcutaneous electrical nerve stimulation and catheter-related bladder discomfort following transurethral resection of bladder tumour
Authors: Park Jun-Young , Yu Jihion , Kim Chan-Sik , Baek Ji-Won , Mun Taeho , Kim Young-Kug 
Published: August 2024

BACKGROUND
Catheter-related bladder discomfort (CRBD) is problematic in patients with a urinary catheter. Transcutaneous electrical nerve stimulation (TENS) is a non-invasive analgesic modality used to relieve various types of pain.

OBJECTIVES
We evaluated the effect of TENS on CRBD after transurethral resection of bladder tumours (TURBT).

DESIGN
A randomised controlled trial.

SETTING
A large university tertiary hospital, from October 2022 to March 2023.

PATIENTS
Patients requiring urinary catheterisation after TURBT.

INTERVENTION
In this randomised controlled trial, patients were randomly allocated to the TENS (n
= 56) or control (n
= 56) groups. CRBD manifests as a burning sensation with an urge to void or discomfort in the suprapubic area. Moderate to severe CRBD was defined as patients self-reporting CRBD symptoms with or without behavioural response, including attempts to remove the urinary catheter, intense verbal reactions, and flailing limbs. TENS was performed from the end of surgery to 1 h postoperatively.

MAIN OUTCOME MEASURE
The primary endpoint was considered moderate to severe CRBD immediately postoperatively. Secondary endpoints included moderate to severe CRBD at 1, 2 and 6 h postoperatively. Additionally, postoperative pain, patient satisfaction, and TENS-related adverse effects were evaluated.

RESULTS
Moderate to severe CRBD immediately postoperatively was significantly less frequent in the TENS group than in the control group: 10 (17.9%) vs. 34 (60.7%); P < 0.001; relative risk (95% CI) = 0.294 (0.161 to 0.536); absolute risk reduction = 0.43; number needed to treat = 2.3. Moderate to severe CRBD differed between the two groups at 1 h postoperatively: 1 (1.8%) vs. 16 (28.6%); P < 0.001; relative risk = 0.06 (95% CI 0.01 to 0.46); absolute risk reduction = 0.27; number needed to treat = 3.7. The TENS group exhibited a significantly lower score for postoperative pain at 1 h (1.8 ± 0.6 vs. 2.2 ± 0.4; P < 0.001, mean difference (95% CI) = 0.4 (0.2 to 0.6) and a higher score for patient satisfaction, 5.0 (4.0 to 6.0) vs. 3.0 (3.0 to 4.0); P < 0.001; median difference (95% CI) = 2.0 (1.0 to 2.0).

CONCLUSIONS
TENS reduced moderate to severe CRBD, decreased postoperative pain, and increased patient satisfaction after TURBT.

CLINICAL TRIAL REGISTRY
Clinical Research Information Service (KCT0007450)
Efficacy and safety of bintrafusp alfa in 2 phase I expansion cohorts with advanced HCC
Authors: Lim Ho Yeong , Heo Jeong , Peguero Julio A. , Ryoo Baek-Yeol , Decaens Thomas , Barlesi Fabrice , Moehler Markus H. , Jehl Genevieve , Eggleton S. Peter , Bajars Marcis , Gulley James L. 
Published: August 2024

Background and Aims:
Simultaneous inhibition of the TGF-β and programmed cell death 1 ligand 1 pathways provides a potential novel treatment approach. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β “trap”) fused to a human IgG1 monoclonal antibody blocking programmed cell death 1 ligand 1, was evaluated in patients with advanced HCC.

Approach and Results:
In this global, open-label, phase I study (NCT02517398), patients with programmed cell death 1 ligand 1–unselected HCC who failed or were intolerant to ≥1 line of sorafenib received bintrafusp alfa 1200 mg every 2 weeks in a dose-escalation (n = 38) or dose-expansion (n = 68) cohort until confirmed progression, unacceptable toxicity, or trial withdrawal. The primary endpoint was the best overall response per Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee. Secondary endpoints included investigator-assessed best overall response, safety, and pharmacokinetics. Median follow-up times (range) were 41.4 (39.8–44.2) and 38.6 (33.5–39.7) months in the dose-escalation and dose-expansion cohorts, respectively. The objective response rate was below the prespecified 20% objective response rate threshold set to evaluate the efficacy of bintrafusp alfa in both cohorts (10.5% and 8.8%, respectively). Median overall survival and progression-free survival, respectively, were 13.8 and 1.5 months in the dose-escalation cohort and 13.5 and 1.4 months in the dose-expansion cohort. Treatment-related adverse events occurred in 78.9% and 64.7% of patients in the respective cohorts (grade ≥3 in 18.4% and 25.0% of patients).

Conclusions:
Bintrafusp alfa showed moderate clinical activity and a safety profile consistent with previous studies of bintrafusp alfa in patients with advanced HCC.
Describing the Physician Associate Clinical Training Site Compensation Market
Authors: White Ryan D. 
Published: August 2024

Introduction
Inadequate clinical training site availability may inhibit physician assistant/associate (PA), advanced practice nursing (APN), and physician workforce growth. Educational institutions increasingly incentivize clinical training sites with financial compensation, with potential implications for educational costs and enrollment. This study investigated compensation trends among PA programs.

Methods
Data from the 2013 to 2019 PA Education Association Program Reports were examined. Multivariate logistic and linear regressions were estimated to identify the influence of PA program characteristics on clinical training site compensation. The effect of compensation on program enrollment was determined with a difference-in-differences estimator.

Results
Physician assistant/associate programs collectively paid nearly $19 million to clinical training sites in 2019. The percentage of programs that offer financial incentives increased from 22.2% in 2013 to 52.3% in 2019. Over this time, public institutions affiliated with academic health centers (AHCs) were least likely to offer compensation. Higher compensation rates were observed in Census divisions with greater number of programs, and programs located in New England were the most likely to offer compensation. Offering compensation did not influence growth in programs' enrollment.

Discussion
Compensation trends highlight increasing demand for PA clinical training sites, especially in areas with greater regional competition. Compensation is primarily driven by private institutions unaffiliated with AHCs. Programs likely offer compensation to maintain, rather than grow, enrollment. Additional investigation should incorporate medical school and APN program data to more fully examine the impact of these costs on learners, institutions, and the health care workforce.
Evaluating the association between time to skin grafting for truncal burn patients and complications: a comparative cohort study using the National Trauma Data Bank
Authors: Wang Szu-Han , Chien Chih-Ying , Fu Chih-Yuan , Bokhari Faran 
Published: August 2024

Background:
The split-thickness skin graft (STSG) procedure is frequently used in the reconstruction of burn-injured patients. This study assessed the impact of graft timing on associated skin complications in patients with torso burns using a comprehensive national database.

Methods:
Truncal burn (2nd-degree and 3rd-degree burns covering 20–89% TBSA) patients who underwent STSG in the National Trauma Data Bank from 2011 to 2015 were studied. The outcomes examined were graft-related complications (superficial surgical site infections, deep surgical site infections, and graft failure), overall mortality and hospital length of stay (LOS). Patients were compared based on the presence or absence of grafting complications. A linear regression model was used to assess the relationship between hospital LOS and graft timing, considering other variables.

Results:
Among the 853 studied patients, the cohort with graft complications exhibited a significantly prolonged time to STSG (413.0 h compared to 264.6 h, P<0.001) and a higher percentage of patients with pre-existing diabetes (18.5 vs. 8.0%, P=0.008). The multiple logistic regression analysis revealed that both the extended time to STSG (odds=1.001, P=0.003) and pre-existing diabetes (odds=2.790, P=0.010) significantly elevated the likelihood of complications associated with STSG. Notably, this delay did not elevate mortality risks. A positive relationship was found between grafting delay and LOS.

Conclusion:
The findings underscore that a prolonged duration to skin grafting contributes to extended hospital stays and increased graft-related complications. However, the role of grafting delay in influencing the mortality of truncal burn patients appeared inconsequential, indicating that mortality may be influenced by various factors.
Statins inhibit paclitaxel-induced PD-L1 expression and increase CD8+ T cytotoxicity for better prognosis in breast cancer
Authors: Li Lei , Wang Hongbin , Zhang Shiyuan , Gao Song , Lu Xiuxin , Pan You , Tang Wei , Huang Rong , Qiao Kun , Ning Shipeng 
Published: August 2024

Background:
In recent years, the widespread use of lipid-lowering drugs, especially statins, has attracted people’s attention. Statin use may be potentially associated with a reduced risk of breast cancer.

Objective:
To explore the relationship between statin use and cancer risk. And further explore the potential role of statins in the adjuvant treatment of breast cancer.

Methods:
Data for the Mendelian randomization portion of the study were obtained from genome-wide association studies of common cancers in the UK Biobank and FinnGen studies and from the Global Lipid Genetics Consortium’s low density lipoprotein (LDL). In addition, the impacts of statins and chemotherapy drugs on breast cancer were examined using both in vitro and in vivo models, with particular attention to the expression levels of the immune checkpoint protein PD-L1 and its potential to suppress tumor growth.

Results:
Data from about 3.8 million cancer patients and ~1.3 million LDL-measuring individuals were analyzed. Genetically proxied HMGCR inhibition (statins) was associated with breast cancer risk reduction (P=0.0005). In vitro experiments showed that lovastatin significantly inhibited paclitaxel-induced PD-L1 expression and assisted paclitaxel in suppressing tumor cell growth. Furthermore, the combination therapy involving lovastatin and paclitaxel amplified CD8+ T-cell infiltration, bolstering their tumor-killing capacity and enhancing in vivo efficacy.

Conclusion:
The utilization of statins is correlated with improved prognoses for breast cancer patients and may play a role in facilitating the transition from cold to hot tumors. Combination therapy with lovastatin and paclitaxel enhances CD8+ T-cell activity and leads to better prognostic characteristics.
The Channel Branches & Network Channels on the Tianhui Lacquered Meridian Figurine — Taking the Heart-Regulated Channel as an Example
Authors: Qi Zhou , Springer Lena 
Published: August 2024

Abstract:
Along with the surge of unearthed medical literature and cultural relics in recent years, the network of channels in the system of medical channels (meridians) during the early Western Han dynasty have become much clearer gradually. Among them, the increasing number of channel branches, network channels and needle insertion holes (acupoints) is an important feature of the development of classical channel medicine during the Western Han dynasty. This is not only a reflection of the expanding requirements of the theoretical system of the main trunk channels, but also an inevitable result of the continuous enrichment and accumulation of clinical experience. This article integrates the information about channel branches, network channels, inscriptions, dots and further relics on the Tianhui (天回) Lacquered Meridian Figurine to compare the unearthed literature of the channel genre with the transmitted classical literature about acupuncture. The "Heart-Regulated Channel" in Medical Manuscripts on Bamboo Slips from Tianhui (《天回医简》) serves as an example to explain the occurrence, development and changes of the channel branches and network channels in the early system of medical channels.
Understanding Diagnosis Delay in Children With Cancer: Evidence From a Single Institution in Jordan
Authors: Al-Nassan Anwar , Almanaseer Tariq , Malkawi Saja , Al-Bitar Farah , Jibrin Dayana , El-qurnah Omaima , Bataineh Shaima , Kamal Maen , Sweidan Salsabeel , Abu-shanab Mayada , Sultan Iyad 
Published: August 2024

Background:
This study aimed to evaluate the factors associated with diagnosis delay in children with cancer who are treated at a single institution, which caters to most children with cancer in Jordan.

Methods:
This was a cross-sectional study with a retrospective chart review of selected patients who were diagnosed from August 2018 to December 2021. Data on patient and household characteristics, medical history, and diagnostic delay were collected through structured interviews. Univariable and multivariable linear and logistic regression models were used to identify predictors of delay.

Results:
The study included a cohort of 202 patient-caregiver pairs, with a median total delay from symptom onset to treatment initiation of 47 days (interquartile range [IQR], 21 to 114 d). Notably, 86% of families pursued medical consultation within a month of recognizing symptoms. A regression model revealed CNS tumors as a significant independent predictor of increased total delay (P=0.002), with affected patients experiencing a median delay markedly longer than those with other cancer types. In addition, older patient age predicted longer total delay (P=0.025). Symptomatology played a pivotal role in the timeliness of the diagnosis; specifically, visible symptoms such as pallor, bruises, and jaundice were associated with more expedient medical attention, with significantly shorter delays (P values: 0.011, <0.001, and 0.045, respectively). Furthermore, our investigation disclosed a notable variance in symptom prevalence across different cancer categories, elucidating the complex relationship between clinical presentation and diagnostic timelines.

Conclusions:
This study highlights the importance of the diagnosis of CNS tumors, patient age, and symptoms in predicting diagnosis delay in pediatric oncology patients. These findings can inform interventions to reduce delays in diagnosis and improve outcomes for these patients. These insights are crucial for developing targeted educational programs aimed at healthcare professionals and families to accelerate the recognition and referral of pediatric cancer cases.
Reducing blood culture contamination: an environmental imperative
Authors: Gregg Sophie , Purcell Niamh , Doyle Maeve , Chan Grace 
Published: August 2024

Abstract
Blood culture (BC) investigation remains the gold standard for diagnosis of bloodstream infections. However, BC contamination can have clinical implications for the patient, cost implications for service providers and less well documented, environmental impacts. Efforts to reduce BC contamination are a longstanding theme in quality improvement initiatives in emergency departments and hospitals, prompted by the hospital costs, healthcare inefficiencies and antimicrobial stewardship efforts [1,2]. The WHO global analysis of health care waste in the context of COVID-19, has reported that tens of thousands of tonnes of extra medical waste was produced from the response to the COVID-19 pandemic, basing its estimates on the quantity of personal protective equipment (PPE) [3]. Additionally, recent literature has also shown increased BC contamination rates during the COVID-19 pandemic. Our study reviews the trend of BC contamination during the COVID-19 pandemic in our institution’s Emergency Department. We further discuss some of the potential implications of BC contamination, including potential environmental, economic and efficiency implications.
Recombinant dimeric PDZ protein inhibitors for long-term relief of chronic pain by AAV therapeutics
Authors: Noes-Holt Gith , Jensen Kathrine L. , Richner Mette , Comaposada-Baro Raquel , Sivertsen Line , Jager Sara E. , Jiménez-Fernández Lucía , Andersen Rita C. , Lilja Jamila H. , Larsen Andreas H. , Kowenicki Marco B. K. , Boesgaard Sofie P. , Houser Grace A. , Christensen Nikolaj R. , Tappe-Theodor Anke , Vægter Christian B. , Kuner Rohini , Madsen Kenneth L. , Sørensen Andreas T. 
Published: August 2024

ABSTRACTThe inadequate state of current pain treatments, the chronic nature of particularly neuropathic pain, and the high impact on quality of life render chronic pain conditions relevant for gene therapy. Here, we describe the development and application of self-assembling dimeric peptide inhibitors of the pain-associated scaffolding protein PICK1 (protein interacting with C-kinase 1) delivered by adeno-associated viral (AAV) vectors. In mice, these peptides prevented mechanical allodynia in inflammatory and neuropathic pain models and reversed neuropathic pain in advanced stages up to one year. Pain relief was obtained by targeting several relays along the somatosensory pain pathways unaccompanied by overt adverse side effects, while selective transduction of peripheral neurons was sufficient for providing full pain relief. We further confirmed PICK1 expression and peptide target engagement in mice and human donor tissue, and we conclude that AAV therapeutics, based on recombinant PICK1 inhibitors, represent a potential clinically meaningful strategy for persistent neuropathic pain conditions.One Sentence SummaryAlleviating neuropathic pain by PICK1-directed gene therapy.
A Novel Methodology to Recalibrate Pathogenic Range of SCA36 Repeat Expansions for PGT-M
Authors: Liu Fulin , Huang Wen , Liao Ling , Yang Jiyun 
Published: August 2024

AbstractBackgroundSpinocerebellar ataxia-36 (SCA36) is an inherited neurodegenerative disorder caused by the heterozygous expansion of an intronic GGCCTG hexanucleotide repeat in the NOP56 gene on chromosome 20p13. Unaffected individuals typically carry 3 to 14 repeats, whereas affected individuals carry 650 to 2,500. However, based on a single study, this pathogenic range was conservatively established, limiting its extended clinical applicability such as preimplantation genetic testing (PGT). In this study, we propose a novel methodology to recalibrate the pathogenic range of SCA36 repeat expansion.MethodsWe conducted a comprehensive literature review and collected examination data from 2012 onward. We used the gamma distribution to describe the data distribution and applied Bayesian methods to update the prior distribution with data from recent publications. Based on the recalibrated distribution, the 95% confidence interval (CI) was used to determine the new lower boundary of the pathogenic range. A pedigree was collected to validate the proposal with long-read sequencing (LRS) applied to detect the high GC content and long length of repeat expansions.ResultsOur results, based on 2 studies, indicate that the data distribution is well-described by gamma distribution. The prior, likelihood and posterior distributions within the 95% CI for the integrated research of SCA36 pathogenic repeat expansions were [446, +∞), [124, +∞), and [484, +∞), respectively. These recalibrated pathogenic ranges were validated by an authentic case: a proband diagnosed with SCA36 carrying 418 repeats and her daughter with 499 repeats, under the detection of LRS.ConclusionsTherefore, we proposed a novel methodology that integrates updated data, 95% CI using Bayesian methods and LRS for accurate detection of repeat expansions of dynamic mutations to present an up-to-date pathogenic range of SCA36, as well as other similar diseases.