bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cross-sectional study of synchronous liver metastasis in patients with gastric cancer.
Authors: Zhang Haijun , Wang Tingya 
Published: July 2024

e16015 Background: The specific organ microenvironment can promote the colonization of tumor cells. However, lack of research shed light on the liver microenvironment in synchronous liver metastasis in patients with gastric cancer (synGCLM). With the epidemic of hepatitis B virus (HBV) infection in China, we aim to explore the influence of hepatitis B surface antigen (HBsAg) on the risk of synGCLM. Methods: It was a cross-sectional study that enrolled 858 cases of newly diagnosed gastric cancer (GC). SynGCLM confirmed by biopsy or imaging evaluation reported by two senior radiologists. HBsAg-positive was defined as the detection of serum HBsAg more than 10 IU/mL. The prevalence of synGCLM was compared between patients with HBsAg (HBsAg+) and those without HBsAg (HBsAg-). The risk factors for synGCLM were analyzed by univariate and multivariate logistic regression analyses. Especially in the HBsAg+ GC patients, aspartate aminotransferase to platelet ratio index (APRI), liver fibrosis-4 index (FIB-4) levels and hepatitis B e antigen (HBeAg) status were further analyzed. Results: The prevalence of synGCLM of the HBsAg+ group was 16.7%, higher compared to 7.0% of the HBsAg- group, which was of statistical significance (p = 0.014). Multivariate logistic regression analysis demonstrated that HBsAg (Odds ratio (OR) = 3.359, p = 0.008), the elevated level of carcinoembryonic antigen (CEA) (OR = 3.775, p < 0.001), alpha-fetoprotein (AFP) (OR = 6.204, p < 0.001), γ-glutamyltransferase (GGT) (OR = 5.081, p < 0.001), alkaline phosphatase (ALP) (OR = 3.968, p = 0.002) and age (OR = 1.028, p = 0.033) were risk factors for synGCLM. Among the HBsAg+ patients, both ARPI and FIB-4 were statistically higher in the patients with synGCLM (synGCLM+) compared to those without synGCLM (synGCLM-) (ARPI: p = 0.045; FIB-4: p = 0.047); HBeAg positivity was detected in 20.0% of synGCLM+ patients compared to 6.0% of synGCLM- patients, but the difference was of no significance (p = 0.190). Conclusions: HBV infection is a risk factor for synGCLM whereas elevated ARPI and FIB-4 may be pro-metastatic especially among the HBsAg+ GC patients. Age, preoperative CEA, AFP, GGT and ALP levels are associated with increased risk of synGCLM.
Fruquintinib combined with sintilimab and SOX as conversion therapy for unresectable locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): A single-arm, open-label, phase 2 clinical trial.
Authors: Ma Fei , Luo Suxia , Zhang Bin , Ma Qi , Ji Sheqing , Zhang Zhandong , Zhang Yonglei , Yang Wei , Peng Liangqun , Guo Dandan , Ren Jinjun , Zhang Yuan , Su Yueyue , Li Jing , Liu Wentao , Huang Jinxi , Yuan Weiwei 
Published: July 2024

e16021 Background: The evidence of conversion therapy for unresectable GC/GEJC is limited. Fruquintinib is an oral, highly selective VEGFR 1/2/3 inhibitor that has synergistic antitumor effects when combined with ICIs/chemotherapy. This study was conducted to evaluate the efficacy and safety of fruquintinib combined with sintilimab and SOX as a conversion therapy in patients (pts) with initially unresectable locally advanced or metastatic GC/GEJC. Methods: Eligible pts received 3 to 6 cycles of fruquintinib (4mg/d, po, qd, d1-14) combined with sintilimab (200mg, iv, d1), oxaliplatin (130 mg/m2, iv, d1) and S-1 (40-60mg based on BSA, po, bid, d1-14) every 3 weeks. One more cycle of sintilimab plus SOX was given before resection. Radiographic assessments were performed every 3 cycles and MDTs were employed to determine surgical feasibility. Primary endpoint was R0 resection rate. Secondary endpoints included pathological response, ORR, PFS, OS, and safety. Results: From May 2022 to December 2023, 34 pts (29 males/5 females) with a median age of 62 years (range: 43–76), 71% ECOG PS1, 59% GEJC were enrolled. The unresectable factors included liver metastasis 15% (5/34), peritoneal metastasis 6% (2/34), para-aortic lymph node metastasis 3% (1/34), extensive or bulky lymph nodes 53% (18/34), and local progression 38% (13/34). Five pts had more than one unresectable factors. The ORR and DCR of 29 pts who had at least one preoperative assessment were 65.5% (19 PR) and 96.6%, respectively. Among the 18 pts who had completed surgical conversion, all of them had R0 resection (100%), 2 pts (11.1%) achieved pathological complete response (pCR), and 1 pt reached AJCC-TRG1. The pathological response rate (pRR) according to JCGC (≥ Grade 1b) was 100% (18/18). Additionally, downstaging to pN0 was achieved in 13 pts (72.2%). During preoperative treatment, treatment-emergent adverse events (TEAEs) occurred in 85.3% (29/34) pts, and most events were grade 1–2. Grade 3 TEAEs included 2 cases of neutrophil count decreased, and 1 case of each (platelet count decreased, anemia, diarrhea, and immune-related pneumonitis). No severe surgery-related complication was observed. Conclusions: Fruquintinib combined with sintilimab and SOX as a conversion therapy strategy shown acceptable toxicity in unresectable GC/GEJC and induced very high R0 resection, pathological response, and downstaging rate. The study is ongoing, more data will be disclosed in the future. Clinical trial information: NCT05177068 .
Binary oncolytic adenovirus in combination with HER2-specific autologous CAR VST for treatment of advanced HER2-positive solid tumors (VISTA).
Authors: Makawita Shalini , Gibbs Jerry M , McFadden Dustin R. , Porter Caroline , Shaw Amanda Rosewell , Robertson Catherine , Woods Mae Louise , Wang Tao , Grilley Bambi J , Heslop Helen E , Brenner Malcolm K , Suzuki Masataka 
Published: July 2024

TPS2679 Background: Urgent therapies are needed for patients with refractory Human Epidermal Growth Factor Receptor 2 (HER2) positive solid malignancies. Our group has previously shown potent antitumor effect of a binary oncolytic/helper-dependent adenovirus (CAdVEC) with dual expression of IL-12 and PD-L1 blocker. Initial preclinical and clinical studies with direct tumor injection of CAdVEC has shown it to be safe and result in increased infiltration of CD8 T cells into the tumor microenvironment, with antitumor effect on locoregional and distant metastatic sites.1 Based on these results, we describe an ongoing study with addition of HER2-specific autologous chimeric antigen receptor (CAR)-T cell therapy to CAdVEC. Methods: This is a single arm, dose escalation phase I clinical trial guided by Bayesian Optimal Interval Design (BOIN) for patients with advanced HER2 positive solid tumors. Patients who are deemed unsuitable for curative treatments and progressed after at least one standard first line therapy are eligible. HER2 positivity is determined by IHC and defined as ≥2+. Patients are required to have at least one tumor site appropriate for intratumor injection and radiographically measurable disease per RECIST v1.1. Patients with autoimmune disease requiring systemic corticosteroids greater than 10mg/day and those with active/untreated CNS metastasis are excluded. Patients will receive increasing doses of CAdVEC intratumor injection alone (first two dose levels) or in combination with HER2 specific autologous CAR-T cells (dose levels 3-7). A total of 45 patients are planned. The primary endpoint of the study is to evaluate safety and maximum tolerated dose as assessed by incidence of dose limiting toxicities (DLT) of CAdVEC intratumor injection in combination with HER2-specific autologous CAR T cells. Secondary endpoints include anti-tumor activity of the combination measured by overall response rate (ORR), disease control rate (DCR), median progression free survival (PFS) and median overall survival (OS). Exploratory endpoints include assessing the immunogenicity of combination therapy by determining the impact of treatment on cellular and humoral immunity, as well as assessing long-term persistence and functional status of HER2 CAR T-cells. Correlative analysis of levels of adenovirus antibodies with clinical outcomes and immunological findings are also planned. This study is currently enrolling. 1. Wang D, Porter CE, Lim B, et al: Science Advances 9, 2023. Clinical trial information: NCT03740256 .
Denosumab Prevents Bone Loss and Microarchitectural Deterioration in Premenopausal Women With Breast Cancer Receiving Estradiol Suppression Therapy: A Randomized Controlled Trial
Authors: Ramchand Sabashini K. , Ghasem-Zadeh Ali , Hoermann Rudolf , White Shane , Yeo Belinda , Francis Prudence A. , Xu Cecilia L.H. , Coleman Olivia , Shore-Lorenti Cat , Ebeling Peter R. , Zajac Jeffrey D. , Seeman Ego , Grossmann Mathis 
Published: July 2024

PURPOSE
Suppression of ovarian function and aromatase inhibition (AI) increases disease-free survival in premenopausal women with estrogen receptor (ER)–positive early-stage breast cancer but accelerates bone loss. We therefore hypothesized that suppressing bone remodeling using denosumab (DMAB) would prevent bone loss in these women.

METHODS

In a 12-month double-blind randomized trial, 68 women with ER-positive early-stage breast cancer commencing ovarian function suppression and AI were randomly assigned to 60 mg DMAB (n = 34) or placebo (PBO; n = 34) once every 6 months (at 0 and 6 months). Volumetric bone mineral density (BMD), microarchitecture, and estimated bone strength of the distal tibia and distal radius were measured using high-resolution peripheral quantitative computed tomography, and spine and hip BMD were measured using dual-energy X-ray absorptiometry at 0, 6, and 12 months. The primary end point and treatment effect was the mean adjusted between group difference (MAD; [95% CI]) in distal tibial total volumetric BMD over 12 months, with a single
P
value tested over all time points. The study is registered with the Australian New Zealand Clinical Trials Registry (anzctr.org.au; identifier: ACTRN12616001051437).

RESULTS

Intention-to-treat analysis included all 68 randomly assigned women. Over 12 months, compared with PBO, DMAB prevented the decrease in distal tibial total BMD (MAD, 20.8 mg HA/cm
3
[95% CI, 17.3 to 24.2]), cortical BMD (42.9 mg HA/cm
3
[95% CI, 32.1 to 53.9]), trabecular BMD (3.32 mg HA/cm
3
[95% CI, 1.45 to 5.20],
P
= .004), estimated stiffness (11.6 kN/m [95% CI, 7.6 to 15.6]), and failure load (563 N [95% CI, 388 to 736]). Findings were similar at the distal radius. Decreases in BMD at the lumbar spine (MAD, 0.13 g/cm
2
[95% CI, 0.11 to 0.15]), total hip (0.08 g/cm
2
[95% CI, 0.07 to 0.09], and femoral neck (0.06 g/cm
2
[95% CI, 0.05 to 0.07]) were also prevented. All
P
< .001 unless otherwise noted.

CONCLUSION
Treatment with DMAB at commencement of estradiol suppression therapy preserves BMD, bone microarchitecture, and estimated strength, and is likely to increase fracture-free survival.
Cancer Therapy, Gonadal Function, and Fertility Preservation: Narrative Review
Authors: Eden Christopher O. , Haslam Alyson , Prasad Vinay 
Published: July 2024

PURPOSE
Fertility preservation was designed to help young patients overcome complications of cancer treatments, but its effectiveness is unknown. We sought to investigate how often patients with cancer are offered fertility preservation and if patients offered fertility preservation are more likely to have offspring.

METHODS
We searched Embase (through 2022) and PubMed (through 2022). Our broad computerized search strategy was built upon using the keywords “chemotherapy,” “radiation,” and “fertility.” The search took place on December 1, 2022. We included randomized and observational studies and excluded reviews and case reports/series.

RESULTS
Eighty-five articles that answered at least one of the research questions were included. Studies assessing fertoprotective therapies often rely on surrogate markers for fertility. Multiple factors affect these markers of fertility. The median premature ovarian failure rate among the intervention group was 18% (IQR, 12%-20%), and among the control group, it was 25% (IQR, 19%-33%). Five of 11 studies reported a significant benefit from fertoprotective therapy. Pregnancies occurred in a median of 21% (IQR, 6%-52%) of patients in the intervention group and 11% (IQR, 7-44) of patients in the control group, with three of seven studies reporting a higher percentage of pregnancies among the intervention group.

CONCLUSION
We reviewed the literature on several questions surrounding fertility preservation and found that there is limited and low-quality research on these therapies in cancer. Hence, there is a strong need for studies, especially randomized studies, that follow patients with cancer who undergo fertility preservation and assess outcomes in which patients are most interested.
Designing and Validating a Comprehensive Patient-Reported Outcomes Measure for Ambulatory Cancer Settings: The Revised Edmonton Symptom Assessment System for Cancer
Authors: Watson Linda , Link Claire , Qi Siwei , DeIure Andrea , Chmielewski Lindsi , Hildebrand April , Barbera Lisa 
Published: July 2024

PURPOSE
Patient-reported outcomes (PROs) information has been routinely collected in Cancer Care Alberta (CCA) for years using the revised Edmonton Symptom Assessment System (ESAS-r) and Canadian Problem Checklist (CPC). There was interest in combining these into a more comprehensive single measure tailored to ambulatory cancer settings. The purpose of this study was to validate an expanded and redesigned ESAS-r called the ESAS-r Cancer.

METHODS
Stakeholder engagement, a review of the literature, and 2 years of CPC data collected in the cancer program informed the addition of six symptoms to the ESAS-r. To assess and validate the measure, 1,600 randomly sampled patients were mailed paper copies of the ESAS-r Cancer, ESAS-r, and a validated, comprehensive PRO measure called the Memorial System Assessment Scale-Short Form (MSAS-SF), which is often used with patients with cancer. Canonical Correlation Analysis and exploratory factor analyses were performed to assess concurrent and construct validity of the ESAS-r Cancer against ESAS-r, using MSAS-SF as the reference measure for comparison. Cronbach α was calculated to assess reliability.

RESULTS

Four hundred and sixty-one patients (29% response rate) completed all three questionnaires. ESAS-r Cancer showed higher numerical correlation than ESAS-r and accounted for more information included on MSAS-SF, explaining slightly more variance than ESAS-r (75.2%
v
73.5%). The three-dimensional factor structure of ESAS-r Cancer outperformed the two-dimensional factor structure of ESAS-r. The reliability of ESAS-r Cancer was verified and found to be slightly higher than ESAS-r (Cronbach α = .903
v
.884).

CONCLUSION
ESAS-r Cancer is now in use with patients throughout CCA. This valid and reliable PRO measure can be used by other cancer or specialized health care programs who wish to routinely assess common symptoms.
Association Between Medicare Site-Based Payment Policy, Physician Practice Characteristics, and Vertical Integration Among Oncologists
Authors: Hu Xin , McCarthy Ian , Yabroff K. Robin , You Wen , Lipscomb Joseph , Graetz Ilana 
Published: July 2024

PURPOSE
Medicare's differential payments for services delivered in physician offices versus hospital outpatient settings incentivize hospital-physician integration (ie, vertical integration) across many specialties, but evidence for oncologists is mixed. We examined the association of Medicare site-based payment policy and physician practice characteristics, including service volume and diversity, with vertical integration among oncologists in 2013-2019.

METHODS
Using the Medicare Provider Utilization and Payment Data and Medicare Data on Provider Practice and Specialty in 2013-2019, we extracted nonintegrated medical/hematologic oncologists (hereafter oncologists) in 2013 and followed them through 2019. We quantified the incentives from Medicare site-based payment policy using the hospital-office ratio—total Medicare payments if all services were delivered in the hospital outpatient department (HOPD) versus physician office. Vertical integration was defined as billing >10% of services to HOPD in a year. Multivariable linear probability regressions estimated the association between hospital-office ratio and vertical integration in 2014-2019 with and without accounting for provider characteristics.

RESULTS

In 2013, the average hospital-office ratio was 1.63, which increased to 1.99 in 2018. A 25th-to-75th percentile increase in the hospital-office ratio was negatively associated with integration (–1.01 percentage points [ppts], 95% CI = −1.45 to −0.57,
p
< .001) not accounting for physician practice characteristics; this association was attenuated (–0.30 ppts, 95% CI = −0.67 to 0.07,
p
= .11) after adjusting for these characteristics. Higher baseline (ie, 2013) service volume (Quartile4
v
Quartile1 = –3.00 ppts, 95% CI = −4.42 to −1.59,
p
< .001), more diverse services (Quartile4
v
Quartile1 = –3.55 ppts, 95% CI = −4.97 to −2.13,
p
< .001), and urban location (–5.23 ppts, 95% CI = −6.89 to −3.57,
p
< .001) were more strongly associated with vertical integration.

CONCLUSION
Compared to Medicare site-based payment policy, oncologists' practice characteristics emerged as more potent factors for integration and should be considered to ensure the intended impacts of site-based payment reform. Our finding raises questions about the effectiveness of ongoing movements toward site-neutral payment for drug administration services to deter vertical integration in oncology.
GH Treatment in Children of Normal Height
Authors: Mendonca Berenice B , Arnhold Ivo J P 
Published: July 2024

Abstract
The increased availability of recombinant human GH (rhGH), albeit at a relatively high cost, has increased a demand for treatment of children and adolescents of normal height to increase their adult stature. There are no scientific reports on the efficacy and safety of rhGH therapy in this condition; therefore, the authors comment on the possible causes and consequences based on their personal opinion and experience. As in gigantism, when GH action and end-organ are normal, enough GH is expected to result in increased growth velocity. Short-term adverse effects related to rhGH therapy for approved indications of short stature in children have been very rare. Data on long-term adverse effects are still scarce. A small increase in height might be statistically significant but not functionally or socially relevant. Considering that an increase in height represents more a desire than a need, physicians should emphasize the normality and qualities of these children, discuss with families the alternatives, such as counseling, and refrain from supporting the concept that taller is better.
Reduced Nephrin Tyrosine Phosphorylation Enhances Insulin Secretion and Increases Glucose Tolerance With Age
Authors: Williamson Casey R , Jones Nina 
Published: July 2024

Abstract

Background
Nephrin is a transmembrane protein with well-established signaling roles in kidney podocytes, and a smaller set of secretory functions in pancreatic β cells are implicated in diabetes. Nephrin signaling is mediated in part through its 3 cytoplasmic YDxV motifs, which can be tyrosine phosphorylated by high glucose and β cell injuries. Although in vitro studies demonstrate these phosphorylated motifs can regulate β cell vesicle trafficking and insulin release, in vivo evidence of their role in this cell type remains to be determined.

Methods
To further explore the role of nephrin YDxV phosphorylation in β cells, we used a mouse line with tyrosine to phenylalanine substitutions at each YDxV motif (nephrin-Y3F) to inhibit phosphorylation. We assessed islet function via primary islet glucose-stimulated insulin secretion assays and oral glucose tolerance tests.

Results
Nephrin-Y3F mice successfully developed pancreatic endocrine and exocrine tissues with minimal structural differences. Unexpectedly, male and female nephrin-Y3F mice showed elevated insulin secretion, with a stronger increase observed in male mice. At 8 months of age, no differences in glucose tolerance were observed between wild-type (WT) and nephrin-Y3F mice. However, aged nephrin-Y3F mice (16 months of age) demonstrated more rapid glucose clearance compared to WT controls.

Conclusion
Taken together, loss of nephrin YDxV phosphorylation does not alter baseline islet function. Instead, our data suggest a mechanism linking impaired nephrin YDxV phosphorylation to improved islet secretory ability with age. Targeting nephrin phosphorylation could provide novel therapeutic opportunities to improve β cell function.
Full Endoscopic Transpedicular Discectomy for a Rostrally Migrated L5-S1 Disc Herniation in the Setting of Previous Lumbar Surgery: A Case Report With Intraoperative Video
Authors: Mambelli Dorian , Farrell Ryan , Huang Meng 
Published: July 2024

BACKGROUND AND IMPORTANCE:
The surgical management of rostral disc herniations at L5-S1 poses challenges for conventional endoscopic approaches, particularly in patients who have had previous lumbar surgery. We present a full endoscopic transpedicular discectomy (FETD), whereby a pediculotomy is created to pass an endoscope through the pedicle for intracanal access. This addresses anatomic obstacles and potential complications associated with other endoscopic and minimally invasive or open techniques. To date, this is the only article to highlight this approach with a case report and intraoperative video.

CLINICAL PRESENTATION:
A 76-year-old man with a history of L3-S1 laminectomy presented with left leg pain and a near-complete left foot drop. An MRI revealed a left paracentral rostrally migrated disc herniation arising from L5-S1 with impingement of the exiting left L5 nerve root at the inferomedial aspect of the pedicle of L5. The patient consented to the FETD procedure. Using sequential reamers of increasing diameter and a high-speed burr, a superolateral to inferomedial pediculotomy was performed. This approach allowed us to target the pathology at the point of maximum compression without traversing the prior operative field. A transforaminal endoscopic approach was not possible with the iliac crest obstructing rostral angulation. The disc was successfully removed without any intraoperative complications, and after surgery, the patient's radiculopathy resolved without any radiographic evidence of instability.

CONCLUSION:
FETD is a unique approach that demonstrates the versatility of endoscopic spine surgery, offering advantages over conventional approaches particularly for rostral disc herniations at L5-S1 in the setting of prior lumbar surgery.
Probabilistic Models and Statistics for Electronic Financial Markets in the Digital Age
Authors: Bibinger Markus 
Published: July 2024

AbstractThe scope of this manuscript is to review some recent developments in statistics for discretely observed semimartingales which are motivated by applications for financial markets. Our journey through this area stops to take closer looks at a few selected topics discussing recent literature. We moreover highlight and explain the important role played by some classical concepts of probability and statistics. We focus on three main aspects: Testing for jumps; rough fractional stochastic volatility; and limit order microstructure noise. We review jump tests based on extreme value theory and complement the literature proposing new statistical methods. They are based on asymptotic theory of order statistics and the Rényi representation. The second stage of our journey visits a recent strand of research showing that volatility is rough. We further investigate this and establish a minimax lower bound exploring frontiers to what extent the regularity of latent volatility can be recovered in a more general framework. Finally, we discuss a stochastic boundary model with one-sided microstructure noise for high-frequency limit order prices and its probabilistic and statistical foundation.