bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMOD-27. RECURRENT GLIOBLASTOMA AFTER LASER ABLATION OF THE PRIMARY TUMOR IN A PRECLINICAL ORTHOTOPIC MODEL EXHIBIT INCREASED GENETIC SIGNATURES OF CELL CYCLE AND CELL MOTILITY
Authors: Nagaraja Tavarekere , Lee Ian 
Published: November 2024

Abstract
Image-guided laser interstitial thermal therapy (LITT) is a minimally invasive tumor cytoreductive treatment for recurrent gliomas and tumors in eloquent loci. We have adapted this technique to develop an image-guided glioblastoma (GBM) ablation model, its recurrence and have tested the efficacy of imaging biomarkers in evaluating tumor ablation and recurrence. The cytopathology and molecular signatures of the primary and recurrent tumors were compared. Immune-compromised female rats were implanted with U251N tumor cells in one brain hemisphere (n=20). Tumor growth was monitored using magnetic resonance imaging (MRI). When tumors reached about 4 mm in diameter, they were ablated using a clinical LITT system (Visualase®), under MRI guidance. Five other rats implanted with U251N tumors were used as unablated controls. MRI data were acquired at 24 h post-LITT, and at 2 and 4 weeks. Rats were sacrificed for histopathology at 2 and 4 weeks, and brain sections stained for hematoxylin and eosin, human major histocompatibility complex, Ki67, a cell proliferation marker and sex determining region Y)-box 2 (SOX2), a stem cell transcription factor. An additional cohort of rats with primary (n=4) and post-LITT recurrent (n=4) U251N tumors were used for analysis of their molecular composition using RNA-Seq approach. In the treated groups, MRI showed little tumor tissue at 24 h, evidence of recurrence at 2 weeks and significant tumor tissue at 4 weeks. Tumor DCE-MRI parameters showed elevated intra-tumoral vascular permeability (i.e., Ktrans) values at pre-LITT imaging, that shifted to peri-ablation periphery at 24 h. A trend of progressive decrease in Ktrans was seen until 1-week post-ablation. Increasing Ktrans values at 2 weeks and after 4 weeks coincided with tumor recurrence. RNA-Seq data showed that cell cycle, cellular movement and inflammatory disease genes were the most differentially expressed genes in the recurrent tumors suggesting increased infiltration may primarily underlie treatment resistance.
TMOD-31. SINGLE-CELL PROFILING AND CHARACTERIZATION OF PATIENT-DERIVED XENOGRAFT GLIOBLASTOMA MODEL IN HUMANIZED MICE
Authors: Takei Jun , Furudate Ken , Iwaloye Opeyemi , Nagaoka-Kamata Yoshiko , Blucas Madison T , Azolibe Stella U , Jepson Chloe E , Saito Kiyotaka , Miller C Ryan , Van Meir Erwin G , Kamata Masakazu , Osuka Satoru 
Published: November 2024

Abstract
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults, and the current standard therapy has limited efficacy. To develop effective therapies, it is desirable to develop an animal model that can replicate the tumor heterogeneity and immune microenvironment of human GBM. Here, we describe a novel GBM mouse model established with a patient-derived xenograft (PDX) in humanized mice harboring a nearly complete human immune environment. Humanized mice were generated by engrafting human CD34+ hematopoietic stem cells from umbilical cord blood into immunocompromised mice (NSG, NSG-SGM3, and NOG-EXL) after myeloablation. NSG-SGM3 is a triple transgenic mouse encoding human IL3, GM-CSF, and SCF on the NSG strain background. NOG-EXL is a NOG strain with human IL3 and GM-CSF expression. These cytokines foster the development of the human myeloid lineage and its differentiation. NSG-SGM3 and NOG-EXL were superior in immune cell reproducibility, especially myeloid cells. Radioresistant PDX GBM cells established after repeated irradiation were injected into the forebrain of humanized mice and the same immunocompromised mice without humanization. Human PDX GBM cells formed aggressive tumors with similar growth speed in the humanized mice compared to non-humanized mice; however, their dissemination to the spinal cord was significantly suppressed in humanized mice, suggesting that human immune cells impact the spinal dissemination of GBM cells. Single-cell RNA sequencing analysis revealed infiltration of human CD4+ T, CD8+ T, NK cells, and macrophages, as well as infiltration of regulatory T and exhausted CD8+ cells into the brain tumor, reflecting the immunosuppressive landscape of recurrent human GBM. Furthermore, we found that tumor heterogeneity was increased in humanized mice compared to non-humanized mice. There was a notable rise in neural progenitor-like cell populations, indicating tumor adaptation to immune pressures. This novel GBM-PDX humanized mouse model might be highly beneficial for analyzing the interaction between human tumor cells and human immune cells, and evaluating the effect of immunotherapies.
TMOD-35. EGFRVIII OVEREXPRESSION AND LOSS OF MOUSE SPECIFIC CDKN2A IN GLIAL CELLS LEADS TO SPONTANEOUS GLIOMAGENESIS IN A NOVEL MOUSE MODEL
Authors: Singh Olivia , Voisin Mathew , Li Mira , Ali Hafsah , Wei Qingxia , Gao Andrew , Agnihotri Sameer , Burrell Kelly , Wilson Mark , Kamiri Shirin , Bunda Severa , Aldape Kenneth , Zadeh Gelareh 
Published: November 2024

Abstract
A new mouse model for the classical subtype of human glioblastoma (GBM) has been bred using Cre-mediated EGFRvIII overexpression and homozygous p19-ARF deletion, the mouse homolog of human p14ARF/CDKN2A, in GFAP expressing cells. Transgenic mice develop intraparenchymal and/or leptomeningeal brain lesions with some spinal cord invasion as early as 1 month old and 95% of mice die by 6 months due to hydrocephalus and/or paralysis. Mice with high grade tumors have worse survival and similar features to human classical GBM such as necrosis, high levels of mitosis and infiltration of tumor cells into normal brain. Immunohistochemical analysis confirms EGFRvIII overexpression and p19-ARF loss in Cre-expressing cells, along with patchy positive GFAP and high proliferation by Ki67. Bulk RNA sequencing reveals GEC3 tumors cluster closely with human classical GBM and have significant upregulation of downstream markers in the JAK/STAT and P13K/AKT pathways. Adherent and neurosphere primary culture of dissociated tumors indicate that tumor cells maintain EGFRvIII expression in culture and generate xenograft tumors by 3 weeks after intracranial injections into NODSCID mice. Xenograft tumors are reminiscent of the primary tumor, with similar histopathological features and immunohistochemical staining. Our spontaneous glioma model is a powerful tool for future studies focused on the role of the immune microenvironment on glioma recurrence and resistance.
Robustly Optimal Mechanisms for Selling Multiple Goods
Authors: Che Yeon-Koo , Zhong Weijie 
Published: November 2024

Abstract
We study robustly optimal mechanisms for selling multiple items. The seller maximizes revenue against a worst-case distribution of a buyer’s valuations within a set of distributions, called an “ambiguity” set. We identify the exact forms of robustly optimal selling mechanisms and the worst-case distributions when the ambiguity set satisfies various moment conditions on the values of subsets of goods. The analysis reveals general properties of the ambiguity set that justifies categorical bundling, which includes separate sales and pure bundling as special cases.
Prevalence and Prognosis of Coronal Malalignment Following Lateral Lumbar Interbody Fusion for Minimally Invasive Treatment of Adult Spinal Deformity
Authors: Chan Andrew K. , Sampath Shailen G. , Mummaneni Praveen V. , Park Paul , Uribe Juan S. , Turner Jay D. , Le Vivian P. , Eastlack Robert K. , Fessler Richard G. , Than Khoi D. , Fu Kai-Ming , Wang Michael Y. , Kanter Adam S. , Okonkwo David O. , Nunley Pierce D. , Anand Neel , Mundis Gregory M. , Passias Peter G. , Bess Shay , Shaffrey Christopher I. , Chou Dean ,   the International Spine Study Group
Published: November 2024

Study Design:
Retrospective analysis of prospective multicenter adult spinal deformity (ASD) database.

Objective:
To determine the prevalence and prognosis of postoperative coronal malalignment following LLIF for ASD with Qiu type A coronal alignment.

Summary of background data:
Qiu Type A coronal alignment is defined as coronal vertical axis (CVA) <30mm.1 There is concern that circumferential minimally invasive surgery (cMIS) with lateral lumbar interbody fusion (LLIF) is associated with postoperative coronal malalignment in ASD with preoperative Qiu type A patients.

Methods:
Qui type A patients undergoing cMIS with LLIF for ASD were included, with ASD defined with at least: maximum CC≥20°, SVA>5 cm, PI-LL≥10°, or PT>20°. Two year (2Y) clinical outcomes were compared for type A with 2Y CVA≥30 mm (MAL) versus <30 mm (ALIGN) and were adjusted for factors reaching P<0.05 on univariate comparisons (age, BMI, and ODI).

Results:
43 patients met inclusion criteria, of which 12 (27.9%) developed coronal malalignment and 31 (72.1%) remained coronally aligned at 2Y. At baseline, MAL were older (73.0 vs. 69.0, P=0.045), had a lower BMI (26.09 vs. 29.45, P=0.047), and were less disabled (ODI 42.83 vs. 51.69, P=0.016). Otherwise, the groups were well-matched for baseline characteristics. At 2Y, MAL had a greater 2Y SVA (mean 54.08 vs 19.00 mm, P=0.01). Clinically, MAL was associated with inferior 2Y SF-36 PCS (34.78 vs. 37.42, adj P=0.043) and 2Y SRS-22r function/activity domain (3.03 vs. 3.36, adj P=0.040), but otherwise similar in other patient-reported-outcome-metrics (adj P>0.05 for all). 2Y complications were similar between groups, including for reoperations and major and minor complications (adj P>0.05 for all).

Conclusions:
In Qui type A patients undergoing cMIS with LLIF for ASD, 27.9% develop coronal malalignment, which was associated with worse SF-36 PCS and SRS-22r function/activity. Despite radiographic malalignment, malalignment was not associated with higher 2-year complication rates including reoperations.
The Need for Institutional Policies for Innovative Therapy: Existing Approaches and Key Elements
Authors: Rao Emily , Grady Christine , Wendler David 
Published: November 2024

OBJECTIVES:
Innovative therapy is common in many areas of medicine. Yet, it is unknown whether medical centers have policies to ensure innovative therapy is conducted appropriately.

DESIGN:
We contacted three informants at leading U.S. medical centers to determine whether the center has a policy for innovative therapy and, if so, what requirements the policies include and whether the policies lack any important elements.

SETTING:
Existing policies and published recommendations.

PATIENTS:
None.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Our search found that 46 of 58 responding centers (79%) do not have a policy for innovative therapy. Of the ten policies available for review, half lack requirements to report patient outcomes, and half do not explicitly coordinate innovative therapy with research.

CONCLUSIONS:
A majority of leading U.S. medical centers do not have a policy for innovative therapy. In addition, existing policies lack important elements, especially with respect to reporting patient outcomes and coordinating innovative therapy with research. Based on the existing policies and recommendations in the literature, we thus identify eight key elements that should be included in policies for innovative therapy. Future research should assess whether these elements can be feasibly implemented and whether, in practice, they offer patients appropriate protection.
The Clinical Characteristics and Virus Shedding of Omicron Patients in a Shanghai Mobile Cabin Hospital
Authors: Wen Yuchan , Xie Qinli , Liu Xinquan , Kong Qinghao , Zhang Yan , Liu Min , Huang Jing 
Published: November 2024

Background
Information about characteristics of Omicron-infected patients and estimation of risk factors for the duration of viral shedding were unclear.

Methods
This retrospective study included asymptomatic patients and patients with mild symptoms, who were infected with Omicron and hospitalized in a Shanghai mobile cabin hospital. The clinical characteristics of those patients were summarized, and the influencing factors of severe acute respiratory syndrome coronavirus 2 virus shedding were explored.

Results
Multivariate logistic regression analysis indicated that comorbidities (odds ratio [OR], 1.991; 95% confidence interval [CI], 1.365–2.904; P = 0.000), 2 doses of vaccines (OR, 2.421; 95% CI, 1.636–3.584; P = 0.000), 3 doses of vaccine/booster shots (OR, 3.797; 95% CI, 2.607–5.529; P = 0.000), and virus shedding time (OR, 1.078; 95% CI, 1.053–1.103; P = 0.000) were associated with increased odds of mild symptoms in Omicron patients, whereas age (OR, 0.951; 95% CI, 0.940–0.963; P = 0.000) was associated with a reduced risk of mild symptoms. The median length of virus ribonucleic acid shedding time was 10 days. Being male (OR, 1.868; 95% CI, 1.488–2.345; P < 0.001), age (OR, 1.018; 95% CI, 1.008–1.028; P < 0.001), and a diagnosis of mild symptoms (OR, 1.508; 95% CI, 1.244–1.895; P < 0.001) were risk factors of prolonged shedding time in multivariate regression analysis. The cycle threshold values of nucleocapsid protein and open reading frame 1ab genes in Omicron patients with virus shedding time ≤10 days are significantly different from that in patients with virus shedding time >20 days (P < 0.001).

Conclusions
Being male, being older, and having a mild case were all risk factors for prolonged virus shedding time, and patients with high viral load may have long virus shedding time. Patients who are young, have complications, and have been vaccinated with 2 or 3 doses/enhanced vaccines with long virus shedding time increased the risk of clinical symptoms.
Intraocular lens rotational stability after cataract surgery with and without primary posterior continuous curvilinear capsulorhexis
Authors: Huang Yulong , Yu Mengting , Liu Xiaobao , Cai Yajing , Kang Chishan , Wu Wenjie 
Published: November 2024

Purpose:
To evaluate intraocular lens (IOL) rotational stability and capsular fusion process after cataract surgery with and without primary posterior continuous curvilinear capsulorhexis (PPCCC).

Setting:
Fujian Provincial Hospital, Fujian, China.

Design:
Prospective, intraindividual, randomized clinical trial.

Methods:
This study included 56 adult patients (112 eyes) with bilateral cataract undergoing phacoemulsification cataract surgery with PPCCC in 1 eye (PPCCC group) and conventional cataract surgery in the contralateral eye (NPCCC group). IOL axis orientation and fusion footprint length were measured at 1 day, 1 week, 1 month, 3 months, and 1 year postoperatively using OPD-Scan III, while the capsular bend index (CBI) was assessed at the same timepoints using Pentacam AXL.

Results:
No between-group difference was found in the absolute rotation from 1 day to 1 year (2.93 ± 1.72 vs 2.66 ± 1.61 degrees, P = .54). The absolute rotation from 1 week to 1 month in the NPCCC group was higher than that in the PPCCC group (1.65 ± 0.68 vs 1.27 ± 0.32 degrees, P = .01). At 1 month postoperatively, both fusion footprint length (9.11 ± 2.74 vs 10.67 ± 2.06 mm, P = .02) and CBI (2.92 ± 0.60 vs 3.25 ± 0.59, P = .03) were lower in the NPCCC group.

Conclusions:
Cataract surgery involving PPCCC demonstrated comparable outcomes with conventional procedures regarding long-term IOL rotational stability and therefore is a promising option for adult patients with cataract scheduled for toric IOL implantation. PPCCC slightly reduces IOL rotation in the early postoperative period, which can be attributed to accelerated capsular fusion.
Social Demographic and Clinical Predictors of Time to Clinic Presentation After a Sport-Related Concussion
Authors: Amedy Amad , Williams Kristen , Prosak Olivia L. , Anesi Trevor , Zuckerman Scott L. , Terry Douglas P. 
Published: November 2024

Objective:
To investigate the associations between clinical risk factors, social demographic and time to concussion clinic presentation after sports-related concussion in young athletes.

Design:
Retrospective cohort study.

Setting:
Multidisciplinary regional concussion center.

Patients:
Athletes ages 12 to 18 years who sustained a SRC from November 2017 to April 2022.

Independent Variables:
Independent variables included social demographic factors (ie, race, ethnicity, public vs private school, public vs private insurance), patient medical history, family medical history, acute concussion characteristics, and initial presentation elsewhere.

Main Outcome Measures:
Descriptive statistics were employed to assess for group differences. Mann–Whitney U tests, Spearman rank order correlations, and linear regressions were performed to explore associations between each independent variable and the main outcome, days to concussion clinic presentation.

Results:
A total of 945 athletes we included (age 15.8 ± 1.61, 33.7% female). Hispanic/Latino background, (P = 0.009), public insurance status (U = 47 377.0, P = 0.002), amnesia (U = 57 738.0, P = 0.002) at time of injury, family psychiatric (U = 35 091.0, P < 0.001) or migraine (U = 59 594.5, P < 0.001) histories, and personal psychiatric (U = 30 798.0, P = 0.004) or migraine (U = 34 133.5, P = 0.011) histories were associated with longer time to concussion clinic presentation. A multivariable linear regression found that initial presentation elsewhere (β = 0.37, P < 0.001), family migraine history (β = 0.18, P < 0.001), public insurance status (β = 0.09, P = 0.024), and history of learning disability (β = 0.09, P = 0.032) were the only predictors of longer time to concussion clinic presentation.

Conclusions:
Variables that predicted longer time to concussion clinic presentation included initial presentation elsewhere, public insurance status, positive family migraine history, and history of learning disability. Further research is needed to elucidate these findings and determine how they impact concussion seeking behavior.
The Effect of the Nordic Hamstring Exercise on Hamstring Muscle Activity Distribution During High-Speed Running Estimated Using Multichannel Electromyography: A Pragmatic Randomized Controlled Trial
Authors: Suskens Jozef J. M. , Maas Huub , van Dieën Jaap H. , Kerkhoffs Gino M. M. J. , Tol Johannes L. , Reurink Gustaaf 
Published: November 2024

Objective:
To evaluate the effect of the Nordic hamstring exercise on normalized muscle activity and relative contribution of the biceps femoris long head, semitendinosus, and semimembranosus through multichannel electromyography in the late-swing phase of high-speed running.

Design:
A pragmatic, 2-arm, single-center randomized controlled trial. Participants were randomly assigned to a Nordic group or control group.

Setting:
Dutch male basketball.

Participants:
Twenty injury-free players (mean age 18 ± 3 years).

Intervention:
A 12-week Nordic hamstring exercise intervention.

Main Outcome Measures:
Level of normalized muscle activity (percentage maximal voluntary isometric contraction [%MVIC]) and relative contribution (%con) of hamstring muscles for 12 weeks.

Results:
The Nordic hamstring exercise intervention did not result in significant changes for 12 weeks. For normalized muscle activity, between-group differences (compared with the control group) for 12 weeks were 11.4 %MVIC (95% confidence interval [95% CI]: −11.0, 33.8) for the biceps femoris long head, −9.4 %MVIC (95% CI: −23.3, 5.2) for the semitendinosus, and −2.7 %MVIC (95% CI: −15.8, 10.3) for the semimembranosus, P = 0.151. For relative contribution, between-group differences for 12 weeks were −6.1 %con (95% CI: −2.4, 14.6) for the biceps femoris long head, −7.0 %con (95% CI: −13.6, −0.4) for the semitendinosus, and 0.9 %con (95% CI: −9.2, 11.0) for the semimembranosus P = 0.187. Positive values are in favor of the Nordic group.

Conclusions:
A 12-week Nordic hamstring exercise intervention did not affect the level of muscle activity and relative contribution of hamstring muscles in the late-swing phase of high-speed running. Because of the low amount of data sets, results should be interpreted cautiously.
Fire dragon cupping in treating a parturient woman with gastrointestinal dysfunction after cesarean section: A case report
Authors: Zhang Huiying , Ye Chunyan , Ye Xuefen , Cai Junhong 
Published: November 2024

Rationale:
The postoperative gastrointestinal dysfunction after cesarean section is commonly presented as uncomfortable symptoms such as abdominal pain and distension. As a novel traditional Chinese medicine characteristic therapy, the fire dragon cupping can effectively enhance intestinal peristalsis and improve the gastrointestinal discomforts by using the manipulation and moxibustion heat to stimulate acupuncture points. The purpose of this report is to provide a new approach and new ideas for rapid rehabilitation of gastrointestinal dysfunction after cesarean section.

Patient concerns:
A parturient woman, 39 years old, pregnancy 4, delivery 2, underwent lower uterine segment cesarean section under intrathecal anesthesia due to scarred uterus. On the 3rd day after cesarean section, the anus still did not exhaust and defecate, so this parturient woman complained of obvious abdominal pain, abdominal distension, nausea, and vomiting.

Diagnoses:
The measured abdominal circumference was 96 cm, and the bowel sounds weakened on auscultation; the plain abdominal radiograph indicated a small amount of pneumomediastinum, thus the incomplete intestinal obstruction was considered.

Interventions:
The parturient woman was treated with fire dragon cupping treatment in her back and abdomen once a day, each time about 30 to 40 minutes, 3 consecutive days of treatment.

Outcomes:
On the 4th day after cesarean section, the parturient woman naturally had anal exhaust and defecated watery stools twice, without complaint of abdominal pain distension.

Lessons:
Under the guidance of the concept of rapid rehabilitation nursing in obstetrics, according to the principle of making gradual and orderly progress, risk management of gastrointestinal dysfunction after cesarean section is carried out in the early stage, the fire dragon cupping and individualized rehabilitation scheme are implemented, and the parturient women with gastrointestinal dysfunction after cesarean section are actively treated.