bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between Serum Potassium with Risk of Onset and Visual Field Progression in Patients with Primary Angle Close Glaucoma: A Cross-Sectional and Prospective Cohort Study
Authors: Qiu Yichao , Wei Jiaojiao , Yu Jian , Li Yingzhu , Shao Mingxi , Ren Jun , Cao Wenjun , Li Shengjie , Sun Xinghuai 
Published: June 2022

Evidence suggests that ion metabolism may be associated with oxidative stress in the ocular tissue in glaucoma patients. This study is aimed at determining whether serum ion levels are associated with the onset and/or visual field (VF) progression of PACG. A total of 265 PACG and 166 healthy subjects were included in the cross-sectional study. Meanwhile, 265 subjects with PACG were followed up every six months for at least two years in the cohort study. All subjects were evaluated for serum concentrations of ions (calcium, phosphorus, potassium (K+), sodium, and chlorine) and underwent VF examination. Logistic regression analysis was performed to assess the risk factors for PACG. Cox regression analyses and Kaplan-Meier survival analyses were performed to identify factors associated with VF progression in PACG subjects. In the cross-sectional study, the K+ level (

4.31
±
0.39

mmol
/
L

) was significantly higher in the PACG group than in the normal group (

4.16
±
0.35

mmol
/
L

,

P
<
0.001

). Multiple logistic regression showed that the increased K+ level was a risk factor of PACG (

OR
=
2.94

,

95
%
CI
=
1.63
–
5.32

,

P
<
0.001

). In the cohort study, there were 105 PACG subjects with progression and 160 PACG subjects without progression. The progression group had significantly higher baseline serum K+ levels (

4.41
±
0.37

mmol
/
L

) than the no progression group (

4.25
±
0.39

mmol
/
L

) (

P
=
0.002

). The increased level of K+ at baseline was associated with faster VF progression (

HR
=
2.07

,

95
%
CI
=
1.23
–
3.46

,

P
=
0.006

). PACG subjects with higher baseline K+ levels had significantly lower VF nonprogression rates (51.94%) than subjects with lower K+ levels (68.38%, log-rank test

P
=
0.01

). This study found that increased serum K+ level is a risk factor of PACG and is associated with faster VF progression in PACG, which might result from its influence on the oxidative stress process.
Associations of the Cardiometabolic Index with the Risk of Cardiovascular Disease in Patients with Hypertension and Obstructive Sleep Apnea: Results of a Longitudinal Cohort Study
Authors: Cai Xintian , Hu Junli , Wen Wen , Wang Jingyu , Wang Mengru , Liu Shasha , Zhu Qing , Hong Jing , Dang Yujie , Yao Xiaoguang , Sun Le , Zhang Delian , Luo Qin , Li Nanfang 
Published: June 2022

Purpose. We aimed to explore the relationship between the cardiometabolic index (CMI) and cardiovascular disease (CVD) and its subtypes (coronary artery disease and stroke) in patients with hypertension and obstructive sleep apnea (OSA). Methods. We conducted a retrospective cohort study enrolling 2067 participants from the Urumqi Research on Sleep Apnea and Hypertension study. The CMI was calculated as triglyceride to

high
‐
density

lipoprotein

cholesterol

ratio
×
waist
‐
to
‐
height

ratio

. Participants were divided into three groups (T1, T2, and T3) according to the tertile of CMI. The Kaplan-Meier method helped to calculate the cumulative incidence of CVD in different groups. We assessed the association of CMI with the risk of CVD and CVD subtypes by estimating hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox models. Results. During a median follow-up of 6.83 years (interquartile range: 5.92-8.00 years), 326 incident CVD were identified, including 121 incident stroke and 205 incident coronary heart disease (CHD). Overall, after adjusting for confounding variables, CMI was positively associated with the risk of new-onset CVD (per SD increment, adjusted HR: 1.31; 95% CI: 1.20, 1.43), new-onset CHD (per SD increment, adjusted HR: 1.33; 95% CI: 1.20, 1.48), and new-onset stroke (per SD increment, adjusted HR: 1.27; 95% CI: 1.10, 1.47). Similar results were obtained in various subgroup and sensitivity analyses. Adding CMI to the baseline risk model for CVD improved the

C

-index (

P
<
0.001

), continuous net reclassification improvement (

P
<
0.001

), and integrated discrimination index (

P
<
0.001

). Similar results were observed for CHD and stroke. Conclusion. There was a positive association between CMI levels and the risk of new-onset CVD in patients with hypertension and OSA. This finding suggests that CMI may help identify people at high risk of developing CVD.
Oral Cancer Prevalence, Mortality, and Costs in Medicaid and Commercial Insurance Claims Data
Authors: Tranby Eric P. , Heaton Lisa J. , Tomar Scott L. , Kelly Abigail L. , Fager Gulielma Leonard , Backley Mary , Frantsve-Hawley Julie 
Published: June 2022

Abstract

Background:
This study compared prevalence, incidence, mortality rates, treatment costs, and risk factors for oral and oropharyngeal cancer (OC/OPC) between two large United States adult cohorts in 2012–2019.

Methods:
Medicaid and commercial claims data came from the IBM Watson Health MarketScan Database. Logistic regression analyses estimated incidence and risk factors for OC/OPC. Mortality was calculated by merging deceased individuals’ files with those of the existing cancer cohort. Summing costs of outpatient and inpatient services determined costs.

Results:
Prevalence of OC/OPC in Medicaid enrollees decreased each year (129.8 cases per 100,000 enrollees in 2012 to 88.5 in 2019); commercial enrollees showed a lower, more stable prevalence (64.7 per 100,000 in 2012 and 2019). Incidence trended downward in both cohorts, with higher incidence in the Medicaid (51.4–37.6 cases per 100,000) than the commercial cohort (31.9–31.0 per 100,000). Mortality rates decreased for Medicaid enrollees during 2012–2014 but increased in the commercial cohort. OC/OPC treatment costs were higher for commercial enrollees by $8.6 million during 2016–2019. OC/OPC incidence was higher among adults who were older, male, and white; used tobacco or alcohol; or had prior human immunodeficiency virus/acquired immune deficiency syndrome diagnosis and lower among those who had seen a dentist the prior year.

Conclusions:
Medicaid enrollees experienced higher OC/OPC incidence, prevalence, and mortality compared with commercially insured adults. Having seen a dentist within the prior year was associated with a lower risk of OC/OPC diagnosis.

Impact:
Expanding Medicaid dental benefits may allow OC/OPC to be diagnosed at earlier stages through regular dental visits.
Ethnic Disparities in Early-Onset Gastric Cancer: A Population-Based Study in Texas and California
Authors: Tavakkoli Anna , Pruitt Sandi L. , Hoang Anh Q. , Zhu Hong , Hughes Amy E. , McKey Thomas A. , Elmunzer B. Joseph , Kwon Richard S. , Murphy Caitlin C. , Singal Amit G. 
Published: June 2022

AbstractBackground:Incidence rates of gastric cancer are increasing in young adults (age &lt;50 years), particularly among Hispanic persons. We estimated incidence rates of early-onset gastric cancer (EOGC) among Hispanic and non-Hispanic White persons by census tract poverty level and county-level metro/nonmetro residence.Methods:We used population-based data from the California and Texas Cancer Registries from 1995 to 2016 to estimate age-adjusted incidence rates of EOGC among Hispanic and non-Hispanic White persons by year, sex, tumor stage, census tract poverty level, metro versus nonmetro county, and state. We used logistic regression models to identify factors associated with distant stage diagnosis.Results:Of 3,047 persons diagnosed with EOGC, 73.2% were Hispanic White. Incidence rates were 1.29 [95% confidence interval (CI), 1.24–1.35] and 0.31 (95% CI, 0.29–0.33) per 100,000 Hispanic White and non-Hispanic White persons, respectively, with consistently higher incidence rates among Hispanic persons at all levels of poverty. There were no statistically significant associations between ethnicity and distant stage diagnosis in adjusted analysis.Conclusions:There are ethnic disparities in EOGC incidence rates that persist across poverty levels.Impact:EOGC incidence rates vary by ethnicity and poverty; these factors should be considered when assessing disease risk and targeting prevention efforts.
SHR-1701, a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, for Recurrent or Metastatic Cervical Cancer: A Clinical Expansion Cohort of a Phase I Study
Authors: Feng Jifeng , Tang Dihong , Wang Jing , Zhou Qi , Peng Jin , Lou Hanmei , Sun Yuping , Cai Yunlang , Chen Hongmin , Yang Junqin , Liu Pan , Wang Linna , Zou Jianjun 
Published: June 2022

Abstract

Purpose:
Patients with recurrent or metastatic cervical cancer have limited treatment options after platinum-containing treatment. We initiated a phase I study to assess SHR-1701, a novel bifunctional fusion protein composed of a mAb against programmed death ligand 1 (PD-L1) fused with the extracellular domain of TGFβ receptor II, in solid tumors (NCT03774979). Here, results from the cervical cancer cohort are presented.

Patients and Methods:
Patients with recurrent or metastatic cervical cancer who progressed during or after platinum-based therapy were enrolled to receive SHR-1701 at 30 mg/kg every 3 weeks. Primary endpoint was objective response rate (ORR) per RECIST v1.1.

Results:
In total, 32 patients were recruited. ORR was 15.6% [95% confidence interval (CI), 5.3–32.8], and disease control rate was 50.0% (95% CI, 31.9–68.1). Responses were still ongoing in 80.0% of the responders; 6-month duration of response rate was 80.0% (95% CI, 20.4–96.9). Median progression-free survival (PFS) was 2.7 months (95% CI, 1.4–4.1). Of note, as assessed by immune-modified RECIST, median PFS was 4.1 months (95% CI, 1.6–4.3). Overall survival rate at 12 months was 54.6% (95% CI, 31.8–72.7). Treatment-related adverse events of grade 3 or 4 were reported in 11 (34.4%) patients. No treatment-related deaths occurred. No difference in ORR was found between patients with PD-L1 combined positive score ≥1 or &lt;1; patients with high phosphorylated SMAD2 level in immune cells or tumor cells had numerically higher ORR.

Conclusions:
SHR-1701 exhibits encouraging antitumor activity and controllable safety in patients with recurrent or metastatic cervical cancer after platinum-based regimens, and therefore might provide another treatment option for this population.
See related commentary by Miller and Friedman, p. 5238
Low-Dose JAK3 Inhibition Improves Antitumor T-Cell Immunity and Immunotherapy Efficacy
Authors: Dammeijer Floris , van Gulijk Mandy , Klaase Larissa , van Nimwegen Menno , Bouzid Rachid , Hoogenboom Robin , Joosse Maria E. , Hendriks Rudi W. , van Hall Thorbald , Aerts Joachim G. 
Published: June 2022

Abstract
Terminal T-cell exhaustion poses a significant barrier to effective anticancer immunotherapy efficacy, with current drugs aimed at reversing exhaustion being limited. Recent investigations into the molecular drivers of T-cell exhaustion have led to the identification of chronic IL2 receptor (IL2R)–STAT5 pathway signaling in mediating T-cell exhaustion. We targeted the key downstream IL2R-intermediate JAK 3 using a clinically relevant highly specific JAK3-inhibitor (JAK3i; PF-06651600) that potently inhibited STAT5-phosphorylation in vitro. Whereas pulsed high-dose JAK3i administration inhibited antitumor T-cell effector function, low-dose chronic JAK3i significantly improved T-cell responses and decreased tumor load in mouse models of solid cancer. Low-dose JAK3i combined with cellular and peptide vaccine strategies further decreased tumor load compared with both monotherapies alone. Collectively, these results identify JAK3 as a novel and promising target for combination immunotherapy.
PPM1D in Solid and Hematologic Malignancies: Friend and Foe?
Authors: Zhang Linda , Hsu Joanne I. , Goodell Margaret A. 
Published: June 2022

Abstract
In the face of constant genomic insults, the DNA damage response (DDR) is initiated to preserve genome integrity; its disruption is a classic hallmark of cancer. Protein phosphatase Mg2+/Mn2+–dependent 1D (PPM1D) is a central negative regulator of the DDR that is mutated or amplified in many solid cancers. PPM1D overexpression is associated with increased proliferative and metastatic behavior in multiple solid tumor types and patients with PPM1D-mutated malignancies have poorer prognoses. Recent findings have sparked an interest in the role of PPM1D in hematologic malignancies. Acquired somatic mutations may provide hematopoietic stem cells with a competitive advantage, leading to a substantial proportion of mutant progeny in the peripheral blood, an age-associated phenomenon termed “clonal hematopoiesis” (CH). Recent large-scale genomic studies have identified PPM1D to be among the most frequently mutated genes found in individuals with CH. While PPM1D mutations are particularly enriched in patients with therapy-related myeloid neoplasms, their role in driving leukemic transformation remains uncertain. Here, we examine the mechanisms through which PPM1D overexpression or mutation may drive malignancy by suppression of DNA repair, cell-cycle arrest, and apoptosis. We also discuss the divergent roles of PPM1D in the oncogenesis of solid versus hematologic cancers with a view to clinical implications and new therapeutic avenues.
Loss of E-cadherin Induces IGF1R Activation and Reveals a Targetable Pathway in Invasive Lobular Breast Carcinoma
Authors: Elangovan Ashuvinee , Hooda Jagmohan , Savariau Laura , Puthanmadhomnarayanan Susrutha , Yates Megan E. , Chen Jian , Brown Daniel D. , McAuliffe Priscilla F. , Oesterreich Steffi , Atkinson Jennifer M. , Lee Adrian V. 
Published: June 2022

Abstract

No special-type breast cancer [NST; commonly known as invasive ductal carcinoma (IDC)] and invasive lobular carcinoma (ILC) are the two major histological subtypes of breast cancer with significant differences in clinicopathological and molecular characteristics. The defining pathognomonic feature of ILC is loss of cellular adhesion protein, E-cadherin (CDH1). We have previously shown that E-cadherin functions as a negative regulator of the IGF1R and propose that E-cadherin loss in ILC sensitizes cells to growth factor signaling that thus alters their sensitivity to growth factor–signaling inhibitors and their downstream activators. To investigate this potential therapeutic vulnerability, we generated CRISPR-mediated CDH1 knockout (CDH1 KO) IDC cell lines (MCF7, T47D, and ZR75.1) to uncover the mechanism by which loss of E-cadherin results in IGF pathway activation. CDH1 KO cells demonstrated enhanced invasion and migration that was further elevated in response to IGF1, serum and collagen I. CDH1 KO cells exhibited increased sensitivity to IGF resulting in elevated downstream signaling. Despite minimal differences in membranous IGF1R levels between wild-type (WT) and CDH1 KO cells, significantly higher ligand–receptor interaction was observed in the CDH1 KO cells, potentially conferring enhanced downstream signaling activation. Critically, increased sensitivity to IGF1R, PI3K, Akt, and MEK inhibitors was observed in CDH1 KO cells and ILC patient-derived organoids.

Implications:
Overall, this suggests that these targets require further exploration in ILC treatment and that CDH1 loss may be exploited as a biomarker of response for patient stratification.
Oral Contraceptives, Hormone Replacement Therapy, and Stroke Risk
Authors: Johansson Therese , Fowler Philip , Ek Weronica E. , Skalkidou Alkistis , Karlsson Torgny , Johansson Åsa 
Published: June 2022

Background:
Millions of women worldwide use exogenous hormones as oral contraceptives or hormone replacement therapy. Still, time-dependent and long-term consequences of exogenous hormones on stroke risk remains unclear.

Methods:
We examined the association between self-reported oral contraceptive and hormone replacement therapy use and stroke risk in 257 194 women from the UK Biobank, born between 1939 and 1970. Outcomes included any type of stroke, ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Exposures were analyzed as time-varying variables in Cox regression models.

Results:
During first year of oral contraceptive use, an increased event rate of any stroke was observed (hazard ratio [HR], 2.49 [95% CI, 1.44–4.30]), while the hazards were found to be comparable during remaining years of use (HR, 1.00 [95% CI, 0.86–1.14]), compared with nonusers. Similarly, first year of hormone replacement therapy use was associated with higher hazard rates of any stroke (HR, 2.12 [95% CI, 1.66–2.70]), as well as cause-specific stroke, including ischemic stroke (HR, 1.93 [95% CI, 1.05–3.57]) and subarachnoid hemorrhage (HR, 2.17 [95% CI, 1.25–3.78]), which remained increased for any stroke during remaining years of use (HR, 1.18 [95% CI, 1.05–1.31]), and after discontinuation (HR, 1.16 [95% CI, 1.02–1.32]).

Conclusions:
Oral contraceptive use and hormone replacement therapy were associated with an increased risk of stroke, especially during the first year of use, possibly due to immediate changes in hemostatic balance. This study provides new insights on the effects of hormone exposure on stroke risk and provide evidence of not only an overall risk but also a pronounced effects seen in the beginning of treatment.
Public Health Policy at Scale: Impact of a Government-Sponsored Information Campaign on Infant Mortality in Denmark
Authors: Altındağ Onur , Greve Jane , Tekin Erdal 
Published: June 2022

Abstract
We evaluate the impact of a nationwide public health intervention on deaths from sudden infant death syndrome (SIDS), using population data from Denmark in a regression discontinuity research design. The information campaign—implemented primarily through a universal nurse home visiting program—reduced infant mortality by 17.2% and saved between 11.6 and 13.5 lives over 10,000 births. The estimated effect sizes are 11–14 times larger among low-birthweight and preterm infants relative to the overall population. Improvement in infant mortality is concentrated among those with low socioeconomic status and with limited access to health information, thereby reducing health inequities at birth.
Language Training and Refugees’ Integration
Authors: Foged Mette , Hasager Linea , Peri Giovanni , Arendt Jacob Nielsen , Bolvig Iben 
Published: June 2022

Abstract
We evaluate a Danish reform focused on improving language training for those granted refugee status on or after January 1, 1999. Using a Regression Discontinuity Design, we find a significant, permanent, positive effect on earnings. This effect emerged after completion of language classes and was accompanied by additional schooling and a higher probability of working in complex jobs, consistent with language training, rather than other minor aspects of the reform, producing the results.
Outcomes of Coronary Artery By-Pass Grafting Under Dual Antiplatelet Therapy in ST Elevated Myocardial Infarction
Authors: Ipek Gokturk , Kehlibar Tamer , Keskin Muhammed , Yilmaz Hale , Ketenci Bulent , Bolca Osman 
Published: June 2022

Patients with recent myocardial infarction (MI) or percutaneous coronary interventions (PCI) have a higher ischemic risk in addition to perioperative bleeding risk when undergoing coronary artery bypass grafting (CABG). Data regarding preoperative dual antiplatelet therapy (DAPT) failed to create a clear recommendation. In the present study, we assessed the relationship between preoperative DAPT use and adverse outcomes, particularly in ST-elevation MI (STEMI) patients. We retrospectively analyzed 748 consecutive patients with STEMI who underwent subsequent CABG surgery. Patients were divided into 2 groups: those on DAPT up to the day before CABG and those discontinued DAPT >5 days before CABG. Predictors of in-hospital mortality and major bleeding were analyzed by multivariate analysis. Preoperative DAPT was not associated with in-hospital mortality (Odds Ratio (OR):1.81; 95% Confidence Interval (CI): .89-3.68, P = .10) and major bleeding (OR: 1.15; 95% CI: .63-2.08, P = .65) after multivariate analysis. However, glycoprotein (Gp) 2b/3a inhibitors were independently associated with higher major bleeding rates. Age, shock, and EF (ejection fraction) <30% were associated with in-hospital mortality. Previous MI, Gp 2b/3a inhibitors, and EF <30% were predictors of major bleeding. In conclusion, there were no association between pre-CABG DAPT use and in-hospital mortality and major bleeding.
Maternal Health Literacy, Health information‐seeking Behavior and Pregnancy Outcomes Among Iranian Pregnant Women: A Cross-Sectional Study
Authors: Sabetghadam Shadi , Keramat Afsaneh , Goli Shahrbanoo , Malary Mina , Rezaie Chamani Sedighe 
Published: June 2022

Background: Maternal health literacy (MHL) and health information-seeking behavior (HISB) could impact maternal health and pregnancy outcomes. Purpose and Research Design: This cross-sectional study investigated MHL, HISBs, and pregnancy outcomes in Iranian pregnant women. This study was also aimed to determine the predictors of MHL and pregnancy outcomes. Study smple and Data Collection: In this study, 337 randomly selected postpartum women completed three questionnaires, including a demographics form, an obstetrics history checklist, and the Maternal Health Literacy and Pregnancy Outcome Questionnaire (MHLAPQ). Results: The mean MHL and pregnancy outcome scores were 60.80 ± 9.91 and 49.88 ± 5.69, respectively. Of the participants, 56% adopted both formal and informal HISB. Education and internet HISB was associated with the odds of being in the group with higher MHL. Participants with high MHL had more than twice higher odds for better pregnancy outcomes (OR = 2.25, p < 0.004). Conclusions: Continued efforts are required to make health information sources more accessible to pregnant women to improve their health literacy and pregnancy outcomes.
Tension-free vaginal mesh for patients with pelvic organ prolapse: mid-term functional outcomes
Authors: Obinata Daisuke , Yamaguchi Kenya , Hashimoto Sho , Yoshizawa Tsuyoshi , Mochida Junichi , Takahashi Satoru 
Published: June 2022

Objective We aimed to evaluate the mid-term efficacy of tension-free vaginal mesh (TVM) for pelvic organ prolapse (POP), and observe the time course of lower urinary tract symptoms and sexual function. Methods In this retrospective study, we included 112 female patients who underwent TVM at a single center for stage 2 or higher POP, and replied to questionnaires before, and 2 and 4 years after TVM. We evaluated the anatomical cure rate, prolapse quality of life questionnaire scores, international prostate symptom scores, International Consultation on Incontinence Questionnaire-Short Form scores, and Female Sexual Function Index scores. Results The anatomical cure rate at 4 years was 89%. Voiding and storage symptoms improved in patients after TVM. We found that 25/112 patients had sexual intercourse before TVM, and among them, 15/25 (60%) continued sexual intercourse after TVM. Additionally, of the 87 patients who had no sexual intercourse before TVM, 13 resumed sexual intercourse after TVM. Conclusion Cases of TVM have decreased because of the Food and Drug Administration statements concerning mesh problems. However, this study showed relatively favorable mid-term results for lower urinary tract symptoms. Furthermore, sexual activity was restored in some patients, indicating the efficacy of TVM for sexual function.