bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibrinolysis as a Causative Mechanism for Bleeding Complications on Extracorporeal Membrane Oxygenation: A Pilot Observational Prospective Study
Authors: Helms Julie , Curtiaud Anaïs , Severac François , Tschirhart Marine , Merdji Hamid , Bourdin Matthieu , Contant Geneviève , Depasse François , Abou Rjeily Ramy , Sattler Laurent , Meziani Ferhat , Angles-Cano Eduardo 
Published: March 2024

Background
Extracorporeal membrane oxygenation (ECMO) is associated with a high risk of bleeding complications. The specific impact of ECMO on fibrinolysis remains unexplored. The objective of the current pilot observational prospective study was to investigate the longitudinal dynamics of fibrinolytic markers—i.e., changes over time—in the context of bleeding events in patients on ECMO.

Methods
Longitudinal dynamics of contact phase components (kininogen and bradykinin) and fibrinolysis markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1], their complexes [tPA•PAI-1], plasmin–antiplasmin complexes, plasminogen, and D-dimer) were measured in patients undergoing venovenous and venoarterial ECMO, before implantation, at 0, 6, and 12 h after implantation, and daily thereafter.

Results
The cohort consisted of 30 patients (214 ECMO days). The concentrations of tPA, D-dimer, plasmin–antiplasmin complexes, PAI-1, and tPA•PAI-1 complexes were increased, whereas plasminogen decreased compared to normal values. A noteworthy divergence was observed between hemorrhagic and nonhemorrhagic patients: in bleeding patients, D-dimer, plasmin–antiplasmin, tPA, PAI-1, and tPA•PAI-1 followed an increasing kinetics before hemorrhage and then decreased to their baseline level; conversely, nonbleeding patients showed a decreasing kinetics in these markers. Also, D-dimer and tPA followed an increasing kinetics in bleeding patients compared to nonbleeding patients (median values for D-dimer dynamics: 1,080 vs. –440 ng/ml, P = 0.05; tPA dynamics: 0.130 vs. 0.100 nM, P = 0.038), and both markers significantly increased the day before hemorrhage. A tPA concentration above 0.304 nM was associated with bleeding events (odds ratio, 4.92; 95% CI, 1.01 to 24.08; P = 0.049).

Conclusions
Contact activation induces fibrinolysis in ECMO patients, especially in patients experiencing bleeding. This finding supports the role of this mechanism as a possible causal factor for hemorrhages during ECMO and open new avenues for novel therapeutic perspectives.

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Use of 3D-Printed Implants in Complex Foot and Ankle Reconstruction
Authors: Brown Matthew , Cush Gerard , Adams Samuel B. 
Published: March 2024

Summary:
Treatment of traumatic critical-sized bone defects remains a challenge for orthopaedic surgeons. Autograft remains the gold standard to address bone loss, but for larger defects, different strategies must be used. The use of 3D-printed implants to address lower extremity trauma and bone loss is discussed with current techniques including bone transport, Masquelet, osteomyocutaneous flaps, and massive allografts. Considerations and future directions of implant design, augmentation, and optimization of the peri-implant environment to maximize patient outcome are reviewed.
Return to Activities of Daily Living After Fusion to the Pelvis for Adult Spinal Deformity
Authors: Maayan Omri , Zhang Bo , Fourman Mitchell S. , Clohisy John , Pajak Anthony , Nakarai Hiroyuki , Kazarian Gregory S. , Du Jerry , Merrill Robert , Kaidi Austin , Knopp Rachel , Akosman Izzet , Samuel Justin , Andrews Leah , Pratyush Shahi  , Lovecchio Francis C. , Kim Han Jo 
Published: March 2024

Study Design.
Cross-sectional survey and retrospective review of prospectively collected data.

Objective.
To investigate return to activities among patients with adult spinal deformity (ASD) after long-segment fusion to the pelvis.

Background.
No prior studies have assessed the extent and timing of return to employment, driving, and walking among a single cohort of patients with ASD.

Patients and Methods.
Patients who underwent thoracolumbar ASD surgery between 2016 and 2021 with ≥ 1-year follow-up were included (posterior-only, ≥3 levels of fusion to pelvis). A cross-sectional survey was implemented to evaluate preoperative and postoperative activity tolerance. Patients were categorized into (1) better/unchanged or (2) worse groups based on their postoperative activity tolerance to allow for comparison of demographics and perioperative variables.

Results.
Ninety-five patients were included [mean age: 64.3 ± 10.1 yr; body mass index (BMI): 27.3 ± 6.1 kg/m2; levels fused: 8 (range: 3–16); follow-up: 43.5 mo]. Most patients endorsed improved capacity to walk (improved: 64.2%, unchanged: 17.9%, worse: 17.9%) and navigate stairs (improved: 52.6%, unchanged: 33.7%, worse: 13.7%) postoperatively. Seventy-five (97.4%) patients returned to driving (4.1 ± 10.8 mo) and 44 (88.0%) patients returned to work (5.4 ± 8.0 mo). Patients with decreased walking tolerance were more likely to have greater lumbar lordosis correction (37.2 ± 10.5° vs. 18.6 ± 16.7°, P = 0.02) and worse Patient-Reported Outcomes Measurement Information System–Physical Function at long-term follow-up (40.2 ± 11.0 vs. 48.0 ± 9.6, P = 0.03). Patients with decreased ability to navigate stairs were more likely to have undergone revision fusion (69.2% vs. 28.0%, P = 0.003) and have greater BMI (30.7 ± 5.8 vs. 26.7 ± 6.0 kg/m2, P = 0.04). Patients requiring the use of a postoperative assistive walking device were more likely to have undergone revision fusion (66.7% vs. 27.5%, P = 0.003), exhibit greater BMI (31.4 ± 7.2 vs. 26.5 ± 5.6 kg/m2, P = 0.004), longer operative times (285.1 ± 79.9 vs. 244.5 ± 63.4 min, P = 0.03), and worse Patient-Reported Outcomes Measurement Information System–Physical Function at long-term follow-up (39.9 ± 5.1 vs. 47.7 ± 10.5, P = 0.04).

Conclusion.
Despite the reduced range of motion caused by spinopelvic fusion, a majority of patients are able to successfully return to activities of daily living after deformity surgery.
Low Rates of Colorectal Cancer Screening in Our Patients' First-Degree Relatives: Are We Failing Them?
Authors: Almanzar Anyelin , Dahmani Sophia L , Shoucair Sami , Alnajjar Said , Zheng Christina , Gupta Vinay , Lisle David 
Published: March 2024

BACKGROUND:
Guidelines recommend screening those with a family history of early-onset colorectal cancer at age 40 or 10 years before the age of their relative’s diagnosis. Currently, there is no literature reporting the screening rate in these individuals and no protocols are in place to identify and target this population for screening awareness.

OBJECTIVE:
Assess adherence to current screening guidelines among FDRs of patients with early-onset colorectal cancer.

DESIGN:
Retrospective and qualitative study involving a telephone survey where patients were asked about relative’s screening status and barriers to screening.

SETTINGS:
Two community-based institutions between January 2018-December 2021.

PATIENTS:
Individuals diagnosed with early-onset colorectal cancer who had undergone surgery at our institutions.

MAIN OUTCOME MEASURES:
Rate of screening in first-degree relatives of our patients with early-onset colorectal cancer. Other factors measured included demographics, clinicopathologic characteristics and screening barriers.

RESULTS:
Thirty-six patients were identified. Survey response rate was 66.6% (n=24). A total of 88 first-degree relatives who met criteria for screening resulted, with 67.1% (n=59) having a known screening status. Of the 59 with known screening status, it was reported that only 44% (n=26) have undergone screening. Patients of African American race, stage III/IV disease, Medicare/Medicaid and living within Baltimore City County were more likely to have family members with unknown or no screening. Lack of insurance coverage was the most common barrier noted 12.5% (n=3); whereas 54.1% (n=13) reported no barriers to screening.

LIMITATIONS:
Retrospective design.

CONCLUSIONS:
Most first-degree relatives of patients diagnosed with early-onset colorectal cancer do not undergo colorectal cancer screening. This could be attributed to the lack of protocols that could guarantee these individuals are informed of their elevated risk and the different options available for screening. Furthermore, our study suggests that racial and socioeconomic disparities exist among high-risk patients who should pursue screening. See Video Abstract.
Identification of group differences in predictive anticipatory biasing of pain during uncertainty: preparing for the worst but hoping for the best
Authors: Strigo Irina A. , Kadlec Molly , Mitchell Jennifer M. , Simmons Alan N. 
Published: March 2024

Abstract
Pain anticipation during conditions of uncertainty can unveil intrinsic biases, and understanding these biases can guide pain treatment interventions. This study used machine learning and functional magnetic resonance imaging to predict anticipatory responses in a pain anticipation experiment. One hundred forty-seven participants that included healthy controls (n = 57) and individuals with current and/or past mental health diagnosis (n = 90) received cues indicating upcoming pain stimuli: 2 cues predicted high and low temperatures, while a third cue introduced uncertainty. Accurate differentiation of neural patterns associated with specific anticipatory conditions was observed, involving activation in the anterior short gyrus of the insula and the nucleus accumbens. Three distinct response profiles emerged: subjects with a negative bias towards high pain anticipation, those with a positive bias towards low pain anticipation, and individuals whose predictions during uncertainty were unbiased. These profiles remained stable over one year, were consistent across diagnosed psychopathologies, and correlated with cognitive coping styles and underlying insula anatomy. The findings suggest that individualized and stable pain anticipation occurs in uncertain conditions.
Effect of esketamine combined with pregabalin on acute postsurgical pain in patients who underwent resection of spinal neoplasms: a randomized controlled trial
Authors: Zhou Yang , Sun Wanchen , Fu Yuxuan , Wang Jing , Fan Jingyi , Liang Yuchao , Jia Wenqing , Han Ruquan 
Published: March 2024

Abstract
Moderate-to-severe acute postsurgical pain (APSP) can prolong the recovery and worsen the prognosis of patients who undergo spinal surgery. Esketamine and pregabalin may resolve APSP without causing hyperpathia or respiratory depression after surgery. However, there are other risks, such as dissociative symptoms. We designed a randomized controlled trial to investigate the effect of the combination of these 2 drugs on the incidence of APSP in patients who underwent resection of spinal neoplasms. Patients aged 18 to 65 years were randomized to receive esketamine (a bolus dose of 0.5 mg·kg−1 and an infusion dose of 0.12 mg·kg−1·h−1 for 48 hours after surgery) combined with oral pregabalin (75-150 mg/day, starting 2 hours before surgery and ending at 2 weeks after surgery) or an identical volume of normal saline and placebo capsules. The primary outcome was the proportion of patients with moderate-to-severe APSP (visual analog scale score ≥ 40) during the first 48 hours after surgery. Secondary outcomes included the incidence of drug-related adverse events. A total of 90 patients were randomized. The incidence of moderate-to-severe APSP in the combined group (27.3%) was lower than that in the control group (60.5%) during the first 48 hours after surgery (odds ratio = 0.25, 95% CI = 0.10-0.61; P = 0.002). The occurrence of mild dissociative symptoms was higher in the combined group than in the control group (18.2% vs 0%). In conclusion, esketamine combined with pregabalin could effectively alleviate APSP after spinal surgery, but an analgesic strategy might increase the risk of mild dissociative symptoms.
Enhancing regional control in p16-negative oropharyngeal cancer: A propensity score-matched analysis of upfront neck dissection and definitive chemoradiotherapy
Authors: Lee Tsung-Lun , Fang Wei-Chen , Lee I.-Cheng , Lirng Jiing-Feng , Chang Chia-Fan , Hsu Yen-Bin , Chu Pen-Yuan , Wang Yi-Fen , Yang Muh-Hwa , Chang Peter Mu-Hsin , Wang Ling-Wei , Tai Shyh-Kuan 
Published: March 2024

Background:
The presence of p16 and neck disease is important predictors of prognosis for oropharyngeal squamous cell carcinoma (OPSCC). Patients who are p16-negative and have clinically node-positive (cN+) disease generally have worse oncologic outcomes. This study aimed to investigate whether upfront neck dissection (UFND) could provide potential benefits for patients with cN+ p16-negative OPSCC.

Methods:
Through this retrospective study, 76 patients with cN+ p16-negative OPSCC were analyzed, those who received either definite concurrent chemoradiotherapy (CCRT group) or UFND followed by chemoradiotherapy (UFND group). The primary endpoints were regional recurrence-free survival (RRFS), disease-specific survival (DSS), and overall survival (OS). Factors associated with survival were evaluated by univariate and multivariate analysis. Survival between the two groups was compared by propensity score-matched analysis.

Results:
Matched 23 patients in each group through propensity analysis, the UFND group showed a significantly better 5-year RRFS (94.1% vs 61.0%, p = 0.011) compared to the CCRT group. Univariate analysis revealed that UFND was the sole factor associated with regional control (hazard ratio [HR] = 0.110; 95% CI, 0.014-0.879; p = 0.037). Furthermore, the study found that the CCRT group was associated with a higher dose of radiotherapy and exhibited a significantly higher risk of mortality due to pneumonia.

Conclusion:
The study indicated that UFND followed by CCRT may be a potential treatment option for patients with cN+ p16-negative OPSCC, as it can reduce the risk of regional recurrence. Additionally, the study highlights that definite CCRT is connected to a larger dose of radiotherapy and a higher risk of fatal pneumonia. These findings could be beneficial in informing clinical decision-making and improving treatment outcomes for patients with OPSCC.
Genomic and immune microenvironment features influencing chemoimmunotherapy response in gastric cancer with peritoneal metastasis: a retrospective cohort study
Authors: Yu Pengfei , Ding Guangyu , Huang Xingmao , Wang Chenxuan , Fang Jingquan , Huang Ling , Ye Zeyao , Xu Qi , Wu Xiaoying , Yan Junrong , Ou Qiuxiang , Du Yian , Cheng Xiangdong 
Published: March 2024

Background:
Patients with peritoneal metastasis (PM) from gastric cancer (GC) exhibit poor prognosis. Chemoimmunotherapy offers promising clinical benefits; however, its efficacy and predictive biomarkers in a conversion therapy setting remain unclear. The authors aimed to retrospectively evaluate chemoimmunotherapy efficacy in a conversion therapy setting for GC patients with PM and establish a prediction model for assessing clinical benefits.

Materials and methods:
A retrospective evaluation of clinical outcomes encompassed 55 GC patients with PM who underwent chemoimmunotherapy in a conversion therapy setting. Baseline PM specimens were collected for genomic and transcriptomic profiling. Clinicopathological factors, gene signatures, and tumor immune microenvironment were evaluated to identify predictive markers and develop a prediction model.

Results:
Chemoimmunotherapy achieved a 41.8% objective response rate and 72.4% R0 resection rate in GC patients with PM. Patients with conversion surgery showed better overall survival (OS) than those without the surgery (median OS: not reached vs 7.82 m, P<0.0001). Responders to chemoimmunotherapy showed higher ERBB2 and ERBB3 mutation frequencies, CTLA4 and HLA-DQB1 expression, and CD8+ T cell infiltration, but lower CDH1 mutation and naïve CD4+ T cell infiltration, compared to nonresponders. A prediction model was established integrating CDH1 and ERBB3 mutations, HLA-DQB1 expression, and naïve CD4+ T cell infiltration (AUC=0.918), which were further tested using an independent external cohort (AUC=0.785).

Conclusion:
This exploratory study comprehensively evaluated clinicopathological, genomic, and immune features and developed a novel prediction model, providing a rational basis for the selection of GC patients with PM for chemoimmunotherapy-involved conversion therapy.
An anti-infection and biodegradable TFRD-loaded porous scaffold promotes bone regeneration in segmental bone defects: experimental studies
Authors: Lin Haixiong , Li Zige , Xie Zhenze , Tang Shengyao , Huang Minling , Feng Junjie , Wei Yuhan , Shen Zhen , Zhou Ruoyu , Feng Yuanlan , Chen Huamei , Ren Yueyi , Huang Feng , Wang Xiaotong , Jiang Ziwei 
Published: March 2024

Background:
Addressing segmental bone defects remains a complex task in orthopedics, and recent advancements have led to the development of novel drugs to enhance the bone regeneration. However, long-term oral administration can lead to malnutrition and poor patient compliance. Scaffolds loaded with medication are extensively employed to facilitate the restoration of bone defects.

Methods:
Inspired by the local application of total flavonoids of Rhizoma Drynariae (TFRD) in the treatment of fracture, a novel 3D-printed HA/CMCS/PDA/TFRD scaffold with anti-infection, biodegradable and induced angiogenesis was designed, and to explore its preclinical value in segmental bone defect of tibia.

Results:
The scaffold exhibited good degradation and drug release performance. In vitro, the scaffold extract promoted osteogenesis by enhancing bone-related gene/protein expression and mineral deposition in BMSCs. It also stimulated endothelial cell migration and promoted angiogenesis through the upregulation of specific genes and proteins associated with cell migration and tube formation. This may be attributed to the activation of the PI3k/AKT/HIF-1α pathway, facilitating the processes of osteogenesis and angiogenesis. Furthermore, the HA/CMCS/PDA/TFRD scaffold was demonstrated to alleviate infection, enhance angiogenesis, promote bone regeneration, and increase the maximum failure force of new formed bone in a rat model of segmental bone defects.

Conclusion:
Porous scaffolds loaded with TFRD can reduce infection, be biodegradable, and induce angiogenesis, presenting a novel approach for addressing tibial segmental bone defects.
Association between PEMT rs7946 and blood pressure levels in Chinese adolescents
Authors: Su Guo Ming , Guo Qi Wei , Shen Yi Lin , Cai Jia Jing , Chen Xu , Lin Jia , Fang Ding Zhi 
Published: March 2024

Objectives
This study was to explore blood pressure levels in Chinese adolescents with different genotypes of phosphatidylethanolamine N-methyltransferase (PEMT) gene (PEMT) rs7946, as well as effects of dietary intake on blood pressure levels with different genders and different genotypes of PEMT rs7946.

Methods

PEMT rs7946 genotypes were identified by PCR-restriction fragment length polymorphism and verified by DNA sequencing. Blood pressure was measured using a standard mercury sphygmomanometer. Dietary intakes were analyzed based on a 3-day diet diary, and dietary components were calculated using computer software.

Results
A total of 721 high school students (314 males and 407 females) at the age of 16.86 ± 0.59 years were included. The A allele carriers of PEMT rs7946 had increased levels of SBP, DBP, mean arterial pressure (MAP) and pulse pressure (PP) than the GG homozygotes in the female subjects. There were significant interactions between PEMT rs7946 and gender on SBP and MAP levels, regardless of whether an unadjusted or adjusted model was used. When dietary intake was taken into account, fat intake was positively associated with SBP and PP in the male GG homozygotes, while protein intake was positively associated with PP in the female A allele carriers of PEMT rs7946.

Conclusion
This study suggests that PEMT rs7946 is significantly associated with blood pressure levels in human being. There might be interactions among PEMT rs7946, gender, and dietary intake on blood pressure levels in the adolescent population.
Cost-effectiveness of Accepting Kidneys From Deceased Donors With Common Cancers—A Modeling Study
Authors: Shah Karan K. , Hedley James A. , Robledo Kristy P. , Wyld Melanie , Webster Angela C. , Morton Rachael L. 
Published: March 2024

Background.
The disparity between the demand for and supply of kidney transplants has resulted in prolonged waiting times for patients with kidney failure. A potential approach to address this shortage is to consider kidneys from donors with a history of common cancers, such as breast, prostate, and colorectal cancers.

Methods.
We used a patient-level Markov model to evaluate the outcomes of accepting kidneys from deceased donors with a perceived history of breast, prostate, or colorectal cancer characterized by minimal to intermediate transmission risk. Data from the Australian transplant registry were used in this analysis. The study compared the costs and quality-adjusted life years (QALYs) from the perspective of the Australian healthcare system between the proposed practice of accepting these donors and the conservative practice of declining them. The model simulated outcomes for 1500 individuals waitlisted for a deceased donor kidney transplant for a 25-y horizon.

Results.
Under the proposed practice, when an additional 15 donors with minimal to intermediate cancer transmission risk were accepted, QALY gains ranged from 7.32 to 20.12. This translates to an approximate increase of 7 to 20 additional years of perfect health. The shift in practice also led to substantial cost savings, ranging between $1.06 and $2.3 million.

Conclusions.
The proposed practice of accepting kidneys from deceased donors with a history of common cancers with minimal to intermediate transmission risk offers a promising solution to bridge the gap between demand and supply. This approach likely results in QALY gains for recipients and significant cost savings for the health system.
Multi-ancestry Genome-Wide Association Study of Early Childhood Caries
Authors: Shrestha P , Graff M , Gu Y , Wang Y , Avery CL , Ginnis J , Simancas-Pallares MA , Ferreira Zandoná AG , Ahn HS , Nguyen KN , Lin DY , Preisser JS , Slade GD , Marazita ML , North KE , Divaris K 
Published: March 2024

AbstractEarly childhood caries (ECC) is the most common non-communicable childhood disease. It is an important health problem with known environmental and social/behavioral influences that lacks evidence for specific associated genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multi-ancestry population of U.S. preschool-age children (n=6,103) participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used ICDAS criteria to measure ECC with the primary trait using the dmfs index with decay classified as macroscopic enamel loss (ICDAS ≥3). We estimated heritability, concordance rates, and conducted genome-wide association analyses to estimate overall genetic effects; the effects stratified by sex, household water fluoride, and dietary sugar; and leveraged the combined gene/gene-environment effects using the 2-degree-of-freedom (2df) joint test. The common genetic variants explained 24% of the phenotypic variance (heritability) of the primary ECC trait and the concordance rate was higher with a higher degree of relatedness. We identified 21 novel non-overlapping genome-wide significant loci for ECC. Two loci, namelyRP11-856F16.2(rs74606067) andSLC41A3(rs71327750) showed evidence of association with dental caries in external cohorts, namely the GLIDE consortium adult cohort (n=∼487,000) and the GLIDE pediatric cohort (n=19,000), respectively. The gene-based tests identifiedTAAR6as a genome-wide significant gene. Implicated genes have relevant biological functions including roles in tooth development and taste. These novel associations expand the genomics knowledge base for this common childhood disease and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations of oral health.