bluuebunny/crossref_metadata_2025_split huggingface dataset:
A genome-wide association study identified PTPN2 as a population-specific susceptibility gene locus for primary biliary cholangitis
Authors: Hitomi Yuki , Ueno Kazuko , Aiba Yoshihiro , Nishida Nao , Kono Michihiro , Sugihara Mitsuki , Kawai Yosuke , Kawashima Minae , Khor Seik-Soon , Sugi Kazuhiro , Kouno Hirotaka , Kohno Hiroshi , Naganuma Atsushi , Iwamoto Satoru , Katsushima Shinji , Furuta Kiyoshi , Nikami Toshiki , Mannami Tomohiko , Yamashita Tsutomu , Ario Keisuke , Komatsu Tatsuji , Makita Fujio , Shimada Masaaki , Hirashima Noboru , Yokohama Shiro , Nishimura Hideo , Sugimoto Rie , Komura Takuya , Ota Hajime , Kojima Motoyuki , Nakamuta Makoto , Fujimori Naoyuki , Yoshizawa Kaname , Mano Yutaka , Takahashi Hironao , Hirooka Kana , Tsuruta Satoru , Sato Takeaki , Yamasaki Kazumi , Kugiyama Yuki , Motoyoshi Yasuhide , Suehiro Tomoyuki , Saeki Akira , Matsumoto Kosuke , Nagaoka Shinya , Abiru Seigo , Yatsuhashi Hiroshi , Ito Masahiro , Kawata Kazuhito , Takaki Akinobu , Arai Kuniaki , Arinaga-Hino Teruko , Abe Masanori , Harada Masaru , Taniai Makiko , Zeniya Mikio , Ohira Hiromasa , Shimoda Shinji , Komori Atsumasa , Tanaka Atsushi , Ishigaki Kazuyoshi , Nagasaki Masao , Tokunaga Katsushi , Nakamura Minoru 
Published: April 2024

Background and Aims:
Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-nonspecific) and nonshared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC.

Approach and Results:
Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) was identified as a novel PBC susceptibility gene locus through GWAS and subsequent genome-wide meta-analysis involving 2181 cases and 2699 controls from the Japanese population (GWAS-lead variant: rs8098858, p = 2.6 × 10-8). In silico and in vitro functional analyses indicated that the risk allele of rs2292758, which is a primary functional variant, decreases PTPN2 expression by disrupting Sp1 binding to the PTPN2 promoter in T follicular helper cells and plasmacytoid dendritic cells. Infiltration of PTPN2-positive T-cells and plasmacytoid dendritic cells was confirmed in the portal area of the PBC liver by immunohistochemistry. Furthermore, transcriptomic analysis of PBC-liver samples indicated the presence of a compromised negative feedback loop in vivo between PTPN2 and IFNG in patients carrying the risk allele of rs2292758.

Conclusions:

PTPN2, a novel susceptibility gene for PBC in the Japanese population, may be involved in the pathogenesis of PBC through an insufficient negative feedback loop caused by the risk allele of rs2292758 in IFN-γ signaling. This suggests that PTPN2 could be a potential molecular target for PBC treatment.
Age Suppresses the Association Between Traumatic Brain Injury Severity and Functional Outcomes: A Study Using the NIDILRR TBIMS Dataset
Authors: Winter Laraine , Moriarty Helene , Robinson Keith M. , Leiby Benjamin E. , Schmidt Krista , Whitehouse Christina R. , Swanson Randel L. 
Published: April 2024

Objectives:
Recovery from traumatic brain injury (TBI) is extremely difficult to predict, with TBI severity usually demonstrating weak predictive validity for functional or other outcomes. A possible explanation may lie in the statistical phenomenon called suppression, according to which a third variable masks the true association between predictor and outcome, making it appear weaker than it actually is. Age at injury is a strong candidate as a suppressor because of its well-established main and moderating effects on TBI outcomes. We tested age at injury as a possible suppressor in the predictive chain of effects between TBI severity and functional disability, up to 10 years post-TBI.

Setting:
Follow-up interviews were conducted during telephone interviews.

Participants:
We used data from the 2020 NDILRR Model Systems National Dataset for 4 successive follow-up interviews: year 1 (n = 10,734), year 2 (n = 9174), year 5 (n = 6,201), and year 10 (n = 3027).

Design:
Successive cross-sectional multiple regression analyses.

Main Measures:
Injury severity was operationalized using a categorical variable representing duration of posttrauma amnesia. The Glasgow Outcomes Scale—Extended (GOS-E) operationally defined functioning. Sociodemographic characteristics having significant bivariate correlations with GOS-E were included.

Results:
Entry of age at injury into the regression models significantly increases the association between TBI severity and functioning up to 10 years post-TBI.

Conclusions:
Age at injury is a suppressor variable, masking the true effect of injury severity on functional outcomes. Identifying the mediators of this suppression effect is an important direction for TBI rehabilitation research.
Risk factors of transient and permanent hypoparathyroidism after thyroidectomy: a systematic review and meta-analysis
Authors: Ning Kang , Yu Yongchao , Zheng Xinyi , Luo Zhenyu , Jiao Zan , Liu Xinyu , Wang Yiyao , Liang Yarong , Zhang Zhuoqi , Ye Xianglin , Wu Weirui , Bu Jian , Chen Qiaorong , Cheng Fuxiang , Liu Lizhen , Jiang Mingjie , Yang Ankui , Wu Tong , Yang Zhongyuan 
Published: April 2024

Background:
Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery.

Materials and methods:
Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle–Ottawa Scale was used to rate study quality. Pooled odds ratios were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 months). Publication bias was assessed using Begg’s test and Egger’s test.

Results:
A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery [total thyroidectomy (TT) vs. lobectomy], surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT, while preoperative PTH was a protective factor. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT.

Conclusion:
The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.
Comparative investigation of neoadjuvant immunotherapy versus adjuvant immunotherapy in perioperative patients with cancer: a global-scale, cross-sectional, and large-sample informatics study
Authors: Guo Song-Bin , Hu Le-Sheng , Huang Wei-Juan , Zhou Zhen-Zhong , Luo Hui-Yan , Tian Xiao-Peng 
Published: April 2024

Background:
Neoadjuvant and adjuvant immunotherapies for cancer have evolved through a series of remarkable and critical research advances; however, addressing their similarities and differences is imperative in clinical practice. Therefore, this study aimed to examine their similarities and differences from the perspective of informatics analysis.

Methods:
This cross-sectional study retrospectively analyzed extensive relevant studies published between 2014 and 2023 using stringent search criteria, excluding nonpeer-reviewed and non-English documents. The main outcome variables are publication volume, citation volume, connection strength, occurrence frequency, relevance percentage, and development percentage. Furthermore, an integrated comparative analysis was conducted using unsupervised hierarchical clustering, spatiotemporal analysis, regression statistics, and Walktrap algorithm analysis.

Results:
This analysis included 1373 relevant studies. Advancements in neoadjuvant and adjuvant immunotherapies have been promising over the last decade, with an annual growth rate of 25.18 vs. 6.52% and global collaboration (International Co-authorships) of 19.93 vs. 19.84%. Respectively, five dominant research clusters were identified through unsupervised hierarchical clustering based on machine learning, among which Cluster 4 (Balance of neoadjuvant immunotherapy efficacy and safety) and Cluster 2 (Adjuvant immunotherapy clinical trials) [Average Publication Year (APY): 2021.70±0.70 vs. 2017.54±4.59] are emerging research populations. Burst and regression curve analyses uncovered domain pivotal research signatures, including microsatellite instability (R2=0.7500, P=0.0025) and biomarkers (R2=0.6505, P=0.0086) in neoadjuvant scenarios, and the tumor microenvironment (R2=0.5571, P=0.0209) in adjuvant scenarios. The Walktrap algorithm further revealed that ‘neoadjuvant immunotherapy, nonsmall cell lung cancer (NSCLC), immune checkpoint inhibitors, melanoma’ and ‘adjuvant immunotherapy, melanoma, hepatocellular carcinoma, dendritic cells’ (Relevance Percentage: 100 vs. 100%, Development Percentage: 37.5 vs. 17.1%) are extremely relevant to this field but remain underdeveloped, highlighting the need for further investigation.

Conclusion:
This study identified pivotal research signatures and provided substantial predictions for neoadjuvant and adjuvant cancer immunotherapies. In addition, comprehensive quantitative comparisons revealed a notable shift in focus within this field, with neoadjuvant immunotherapy taking precedence over adjuvant immunotherapy after 2020; such a qualitative finding facilitate proper decision-making for subsequent research and mitigate the wastage of healthcare resources.
A quality improvement project to improve treatment of severe hypertriglyceridemia in veterans
Authors: Wool Caroline R. , Shaw Kathy , Saxon David R. 
Published: April 2024

ABSTRACT

Background:
Severe hypertriglyceridemia (sHTG) is associated with an increased risk of acute pancreatitis. Prompt recognition and treatment of sHTG is key for prevention of acute pancreatitis and its associated life-threatening complications.

Local problem:
Patients with sHTG at a primary care clinic within the Veterans Affairs Eastern Colorado Health Care System were receiving suboptimal treatment that did not align with evidence-based guidelines.

Methods:
We initiated a quality improvement (QI) project to improve the management of sHTG in an outpatient primary care clinic. Veterans with a triglyceride level between 500 and 1,500 mg/dl were included in the project.

Interventions:
Project interventions included provider education, patient education, and targeted electronic consultations (e-consults) with treatment recommendations. The primary outcome was to decrease the percentage of patients with triglycerides ≥500 mg/dl by 25%. The secondary outcome was to decrease the mean triglyceride level of the patient population by 15%.

Results:
Education on evaluation and treatment of sHTG was given to 100% (n = 21) of primary care clinicians. Overall, 72.8% (95% CI [62.6–81.6%]) of patients (n = 67) received appropriate written education materials, and 72.8% (95% CI [62.6–81.6%]) of patients (n = 67) received a targeted e-consult. The percentage of patients with sHTG decreased by 47%. Average triglyceride level decreased from 651 to 483 mg/dl (25.8% decrease).

Conclusion:
A multipronged QI project consisting of provider education, patient education, and targeted e-consults resulted in decreased triglyceride levels and improved access to specialist expertise. Clinical implications include decreased prevalence of sHTG and risk of acute pancreatitis among patients in the project.
The cost implications of Wilson disease among hospitalized patients: analysis of USA hospitals
Authors: Lee David Uihwan , Harmacinski Ashton , Bahadur Aneesh , Lee Ki Jung , Chou Hannah , Shaik Mohammed Rifat , Chou Harrison , Fan Gregory Hongyuan , Kwon Jean , Ponder Reid , Chang Kevin , Lee KeeSeok , Lominadze Zurabi 
Published: April 2024

Background and aim
In this study, we used a national cohort of patients with Wilson’s disease (WD) to investigate the admissions, mortality rates, and costs over the captured period to assess specific subpopulations at higher burden.

Methods
Patients with WD were selected using 2016–2019 National Inpatient Sample (NIS). The weighted estimates and patient data were stratified using demographics and medical characteristics. Regression curves were graphed to derive goodness-of-fit for each trend from which R
2 and P values were calculated.

Results
Annual total admissions per 100 000 hospitalizations due to WD were 1075, 1180, 1140, and 1330 (R
2 = 0.75; P = 0.13) from 2016 to 2019. Within the demographics, there was an increase in admissions among patients greater than 65 years of age (R
2 = 0.90; P = 0.05) and White patients (R
2 = 0.97; P = 0.02). Assessing WD-related mortality rates, there was an increase in the mortality rate among those in the first quartile of income (R
2 = 1.00; P < 0.001). The total cost for WD-related hospitalizations was $20.90, $27.23, $24.20, and $27.25 million US dollars for the years 2016, 2017, 2018, and 2019, respectively (R
2 = 0.47; P = 0.32). There was an increasing total cost trend for Asian or Pacific Islander patients (R
2 = 0.90; P = 0.05). Interestingly, patients with cirrhosis demonstrated a decreased trend in the total costs (R
2 = 0.97; P = 0.02).

Conclusion
Our study demonstrated that certain ethnicity groups, income classes and comorbidities had increased admissions or costs among patients admitted with WD.
Association between nonalcoholic fatty liver disease and gallstone risk in nonobese and lean individuals
Authors: Kim Nam Hee , Kang Ji Hun , Kim Hong Joo 
Published: April 2024

Purpose
The association between nonobese/lean nonalcoholic fatty liver disease (NAFLD) and gallstone formation remains unclear. We aimed to assess whether NAFLD is an independent risk factor for gallstones, even in nonobese or lean individuals.

Methods
We analyzed 265 353 asymptomatic adults who underwent abdominal ultrasonography. The risk of gallstone was assessed on the basis of obesity and NAFLD status.

Results
The overall prevalence rates of NAFLD and gallstones were 27.1% and 2.6%, respectively. The prevalence rates of NAFLD among the 195 204 nonobese and 136 194 lean participants were 14.7% and 7.4%, respectively. Individuals with NAFLD had a significantly increased risk of gallstones (adjusted odds ratio [OR], 1.23; 95% confidence interval [CI], 1.14–1.32). Moreover, NAFLD significantly increased the risk of gallstone (adjusted OR, 1.29; 95% CI, 1.17–1.41) among nonobese individuals. Lean individuals with NAFLD also exhibited a significantly increased risk of gallstones (adjusted OR, 1.20; 95% CI, 1.03–1.40). Furthermore, these findings remained consistent even in nonobese and lean individuals without insulin resistance.

Conclusion
Nonobese/lean NAFLD is an independent risk factor for gallstone formation, suggesting its role in gallstone pathogenesis, regardless of obesity status. Therefore, when hepatic steatosis is detected on abdominal ultrasonography, a more thorough evaluation of the gallstones may be necessary, even in nonobese or lean individuals.
Bilateral Multiple Fractures Obstruct Quantitation of 99mTc-Pyrophosphate Imaging for Cardiac Amyloidosis
Authors: Zhou Qin , Zuo Jiahong , Xiao Liu , Jiang Lisha , Zhao Zhen 
Published: April 2024

Abstract
A 57-year-old woman who had persistent symptoms of transthyretin cardiac amyloidosis underwent 99mTc-pyrophosphate (99mTc-PYP) scintigraphy. The 99mTc-PYP planar and SPECT/CT fusion image showed diffuse myocardial uptake and multiple fractures of the sternum and ribs. These fractures interfered with semiquantitative scores of 99mTc-PYP uptake, leading to false positive in 99mTc-PYP imaging.
The Monocle Sign on 18F-FDG PET Indicates Contralateral Peripheral Facial Nerve Palsy
Authors: Dana Fatemeh , Maurer Alexander , Muehlematter Urs J. , Husmann Lars , Schaab Jan , Mader Cäcilia E. , Beintner-Skawran Stephan , Messerli Michael , Sah Bert-Ram , Dana Masih , Dana Mohsen , Duhnsen Sjunne H. , Mueller Simon A. , Stadler Thomas , Morand Grégoire B. , Meerwein Christian , Orita Erika , Kaufmann Philipp A. , Huellner Martin W. 
Published: April 2024

Background
The aim of our study was to retrospectively analyze FDG PET/CT data in patients with facial nerve palsy (FNP) for the presence of the monocle sign.

Patients and Methods
A total of 85 patients with unilateral FNP were included into our study, thereof 73 with peripheral FNP and 12 with central FNP. FDG uptake (SUVmax, SUVmean, total lesion glycolysis) was measured in both orbicularis oculi muscles (OOMs). FDG uptake of paretic and nonparetic muscles was compared in patients with FNP (Wilcoxon test and Mann-Whitney U test) and was also compared with FDG uptake in 33 patients without FNP (Mann-Whitney U test). SUVmax ratios of OOM were compared. A receiver operating characteristic curve and Youden Index were used to determine the optimal cutoff SUVmax ratio for the prevalence of contralateral peripheral FNP.

Results
The SUVmax ratio of OOM was significantly higher in patients with peripheral FNP compared with patients with central FNP and those without FNP (1.70 ± 0.94 vs 1.16 ± 0.09 vs 1.18 ± 0.21, respectively; P < 0.001). The SUVmax ratio of OOM yielded an area under the curve (AUC) of 0.719 (95% confidence interval, 0.630–0.809), with an optimal cutoff of 1.41, yielding a specificity of 94.4% and a sensitivity of 44.1% for identifying contralateral peripheral FNP. One hundred percent specificity is achieved using a cutoff of 1.91 (sensitivity, 29.4%).

Conclusions
Asymmetrically increased FDG uptake of the OOM (the “monocle sign”) indicates contralateral peripheral FNP. A nearly 2-fold higher SUVmax represents a practically useful cutoff.
Outcomes after Surgical Microwave Ablation for the Treatment of Colorectal Liver Metastasis
Authors: Wells Alexandra B , Butano Vincent W , Phillips Michael C , Mckillop Iain H , Martinie John B , Baker Erin H , Iannitti David A 
Published: April 2024

BACKGROUND:
Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide. Of these, approximately 25% will have liver metastasis. We performed 394 microwave ablations (MWAs) and analyzed outcomes for survival and ablation failure.

STUDY DESIGN:
We conducted a retrospective review of patients who underwent a surgical MWA at a single-center high-volume institution from October 2006 to September 2022 using a prospectively maintained database. The primary outcome was overall survival.

RESULTS:
A total of 394 operations were performed on 328 patients with 842 tumors undergoing MWA. Median tumor size was 1.5 cm (range 0.4 to 7.0 cm), with the median number of tumors ablated per operation being 1 (range 1 to 11). A laparoscopic approach was used 77.9% of the time. Concomitant procedures were performed 63% of the time, most commonly hepatectomy (22.3%), cholecystectomy (17.5%), and colectomy (6.6%). Clavien-Dindo grade III or IV complication occurred in 12 patients (3.6%), and all of these patients had undergone concomitant procedures. Mortality within 30 days occurred in 4 patients (1.2%). The rate of incomplete ablation was 1.5% per tumor. Local recurrence occurred at a rate of 6.3% per tumor. Black patients were found to have a higher incidence of incomplete ablation and local recurrence. One-year survival probability was 91% (95% CI 87.9 to 94.3), with a mean overall survival of 57.6 months (95% CI 49.9 to 65.4 months).

CONCLUSIONS:
Surgical MWA offers a low-morbidity approach to treatment of colorectal liver metastasis, with low rate of failure. This large series reviews the outcomes of MWA as definitive treatment for colorectal liver metastasis.
A bispecific antibody-drug conjugate targeting pCAD and CDH17 has antitumor activity and improved tumor specificity
Authors: Synan Alyssa , Wu Nila C , Velazquez Roberto , Logel Claude , Mueller Kathrin , Green Andrew , Barzaghi-Rinaudo Patrizia , Simmons Quincey , Mercan Samuele , Shi Xingyi , Korn Joshua , McLaughlin Margaret , Tschantz William R , Hainzl Dominik , Malamas Anthony , Cebe Regis , Xie Kathleen T , D’Alessio Joseph A 
Published: April 2024

AbstractP-cadherin (pCAD) and LI-cadherin (CDH17) are cell surface proteins belonging to the cadherin superfamily that are both highly expressed in colorectal cancer. This co-expression profile presents a novel and attractive opportunity for a dual targeting approach using an antibody-drug conjugate (ADC). In this study, we used a unique avidity-drivenin vitroscreening approach to generate pCAD x CDH17 bispecific antibodies that selectively targets cells expressing both antigens over cells expressing only pCAD or only CDH17. Based off thein vitroresults we selected a lead bispecific antibody to link to the cytotoxic payload MMAE to generate a pCAD x CDH17 bispecific MMAE ADC. Inin vivodual flank mouse models, we demonstrated antitumor activity of the bispecific ADC in tumors expressing both antigens, but not in tumors expressing only pCAD or only CDH17. Overall, the preclinical data presented here suggests that a pCAD x CDH17 bispecific MMAE ADC has the potential to provide clinical benefit to colorectal cancer patients.
Functions of Direct and Indirect Pathways for Action Selection Are Quantitatively Analyzed in A Spiking Neural Network of The Basal Ganglia
Authors: Kim Sang-Yoon , Lim Woochang 
Published: April 2024

We are concerned about action selection in the basal ganglia (BG). We quantitatively analyze functions of direct pathway (DP) and indirect pathway (IP) for action selection in a spiking neural network with 3 competing channels. For such quantitative analysis, in each channel, we obtain the competition degree 𝒞d, given by the ratio of strength of DP (𝒮DP) to strength of IP (𝒮IP) (i.e., 𝒞d= 𝒮DP/𝒮IP). Then, a desired action is selected in the channel with the largest 𝒞d. Desired action selection is made mainly due to strong focused inhibitory projection to the output nucleus, SNr (substantia nigra pars reticulata) via the DP in the corresponding channel. Unlike the case of DP, there are two types of IPs; intra-channel IP and inter-channel IP, due to widespread diffusive excitation from the STN (subthalamic nucleus). The intra-channel IP serves a function of brake to suppress the desired action selection. In contrast, the inter-channel IP to the SNr in the neighboring channels suppresses competing actions, leading to highlight the desired action selection. In this way, function of the inter-channel IP is opposite to that of the intra-channel IP. However, to the best of our knowledge, no quantitative analysis for such functions of the DP and the two IPs was made. Here, through direct calculations of the DP and the intra- and the inter-channel IP presynaptic currents into the SNr in each channel, we obtain the competition degree of each channel to determine a desired action, and then functions of the DP and the intra- and inter-channel IPs are quantitatively made clear.PACS numbers87.19.lj, 87.19.lu, 87.19.rs