bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring Implicit Political Extremism through Implicit Association Tests
Authors: Jungkunz Sebastian , Helbling Marc , Isani Mujtaba
Published: March 2024

We develop the first implicit association test (IAT) to measure general implicit extremist attitudes in Germany, Great Britain, and the Netherlands. We find that implicit extremist attitudes are positively but weakly correlated with existing explicit measures. This indicates that implicit measures capture different parts of the population, for example, cases in which associations are based on automated cognitive processes instead of conscious thought. Further results show that particularly the higher-educated and nonreligious respondents score higher on the implicit than on the explicit extremism measures. Our results highlight the importance of studying implicit attitudes of political extremism. We further provide novel insights into how to develop IATs for abstract concepts such as democracy and extremism, for the study of which we cannot use readily available images or concepts.
Exploring Symptom Responses to Upper Limb Neural Test Variations of the Radial Nerve in Patients With Lateral Epicondylalgia: An Observational Study
Authors: Albert-Lucena Daniel , Navarro-Santana Marcos José , Díaz-Arribas María José , Valera-Calero Juan Antonio , Fernández-de-las-Peñas César , Plaza-Manzano Gustavo
Published: March 2024

Objective

Clinical practice guidelines recommend the radial nerve mechanosensitivity evaluation in patients with lateral epicondylalgia. Despite different positions and sequences having been described, no research analyzed how each variation triggers symptoms associated with lateral epicondylalgia. The aim of this study was to explore the effects of different positions and sequences in the upper limb neural tension test 2b (ULNT2b) in symptom responses in patients with lateral epicondylalgia.

Methods

In this observational study, 66 patients underwent 4 test conditions: standard ULNT2b, ULNT2b proximal to distal, ULNT2B with resisted supination, and resisted supination isolated. Paresthesia sensations, symptom reproduction, pain intensity (measured using a visual analog scale), and distribution of painful symptoms data were collected.

Results

Significant differences in paresthesia sensations were observed between groups, with significant differences between the standard ULNT2B and other ULNT variations or resisted supination maneuvers. Symptom reproduction also differed significantly across groups, with significant differences between the standard ULNT2B and other ULNT or resisted supination tests. The positive/negative test and percentage of distribution of painful symptoms scores varied significantly across 4 conditions in both lateral and frontal views. Although pain intensity scores during tests were comparable among the tests, distribution of painful symptoms differed significantly.

Conclusion

Variations in the ULNT2b test can affect symptom responses in patients with lateral epicondylalgia. The standard ULNT2b test appears more effective at reproducing symptoms, intensity of paresthesia, and distribution of painful symptoms compared to other ULNT variations and the resisted supination test.

Impact

ULNT2b sequences have been shown to elicit varying responses concerning paresthesia, replication of familiar symptoms, positive/negative test results, and distribution of painful symptoms. Clinicians should consider specific test variations during the patients’ radial nerve mechanosensitivity assessment to identify aggravating factors reproducing recognizable symptoms. A control group of asymptomatic participants and the role of presence of other comorbidities, psychological factors, or the duration of symptoms were not considered in this study and might play an important role influencing the results of the tests.
Understanding Markets with Socially Responsible Consumers
Authors: Kaufmann Marc , Andre Peter , Kőszegi Botond
Published: March 2024

Many consumers care about climate change and other externalities associated with their purchases. We analyze the behavior and market effects of such “socially responsible consumers” in three parts. First, we develop a flexible theoretical framework to study competitive equilibria with rational consequentialist consumers. In violation of price taking, equilibrium feedback nontrivially dampens the impact of a person’s consumption on aggregate consumption, undermining the motive to mitigate. This leads to a new type of market failure, where even consumers who fully “internalize the externality” overconsume externality-generating goods. At the same time, socially responsible consumers change the relative effectiveness of taxes, caps, and other policies in lowering the externality. Second, since consumer beliefs about and preferences over their market impacts play a crucial role in our framework, we investigate them empirically via a tailored survey. Consistent with our model, consumers are often consequentialist, and many believe that they have a dampened impact on aggregate consumption. Inconsistent with our model, however, we also find many respondents who expect to have a one-to-one impact on aggregate consumption. Third, therefore, we analyze how such “naive” consumers modify our theoretical conclusions. They consume less than rational consumers in a single-good economy, but may consume more in a multigood economy with cross-market spillovers. A mix of naive and rational consumers may yield the worst outcomes.
Successful Clozapine Rechallenge After Clozapine-Induced Severe Anemia: A Case Report
Authors: Barros Felipe Mendonça Rocha , Tolentino Arthur Cardoso , Marques Lais Soares Ker , Schlittler Leandro Xavier de Camargo , Oliveira Karina Diniz , Dalgalarrondo Paulo , Barnes Lucas Luchesi , dos Santos Junior Amilton , Banzato Claudio Eduardo Muller
Published: March 2024

Introduction

Clozapine, a second-generation antipsychotic (SGA), is considered the gold standard medication to treat patients with treatment-resistant schizophrenia (TRS). Despite its efficacy, clozapine is associated with adverse effects, notably neutropenia and agranulocytosis. Other hematological adverse effects are less common. Severe anemia is a rare adverse effect seldom reported in the literature and is typically associated with pure red cell aplasia (PRCA). Nevertheless, the benefits of clozapine in managing TRS make rechallenge a reasonable option.

Case Report

We present the case of a 35-year-old man with TRS, resistant to previous antipsychotics, who experienced severe anemia during clozapine treatment. An investigation for clozapine-induced anemia revealed PRCA on myelogram. After discontinuing clozapine, the patient’s hemoglobin levels recovered. Subsequent treatments with olanzapine, zuclopenthixol, and aripiprazole proved ineffective, leading us to consider a clozapine rechallenge. The rechallenge, monitored for 58 days, resulted in improved psychiatric symptoms and stable hemoglobin levels. The patient remained stable during 6 months of follow-up, with no hematological changes.

Discussion

PRCA is a very rare adverse effect of clozapine. The cause of drug-induced PRCA is still unknown; for clozapine, there are no studies. Rechallenge after a severe and rare adverse effect is a complex decision. This case is the first to report a successful clozapine rechallenge following severe anemia without other blood dyscrasias, emphasizing the imperative need for close monitoring during the rechallenge process. Further study is warranted to understand the predictive factors for a successful outcome in clozapine rechallenges.
Safeguarding the property rights of Hindu women in India: analyses of legislative and judicial efforts
Authors: Singh Vijay P
Published: March 2024

Under the traditional Hindu succession system, a Hindu woman did not possess any entitlement to ancestral property, which is a significant demonstration of social and economic discrimination. To clarify, Hindu women’s property rights in India were characterised by inequality and injustice. Nevertheless, through legislative and judicial endeavours, Hindu women in India have been granted the ability to own and possess property through inheritance—a step towards empowering them and creating economic sustainability in their lives. The present study examines the legislative and judicial initiatives aimed at granting parity to Hindu women by integrating them into the coparcenary system and conferring upon them the entitlement to inherit ancestral property. Thus enabling them to achieve economic self-reliance.
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.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Use of 3D-Printed Implants in Complex Foot and Ankle Reconstruction
Authors: Brown Matthew , Cush Gerard , Adams Samuel B.
Published: March 2024

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.
Mucocutaneous Candidiasis: Insights Into the Diagnosis and Treatment
Authors: Cinicola Bianca Laura , Uva Andrea , Duse Marzia , Zicari Anna Maria , Buonsenso Danilo
Published: March 2024

Recent progress in the methods of genetic diagnosis of inborn errors of immunity has contributed to a better understanding of the pathogenesis of chronic mucocutaneous candidiasis (CMC) and potential therapeutic options. This review describes the latest advances in the understanding of the pathophysiology, diagnostic strategies, and management of chronic mucocutaneous candidiasis.
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

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

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.
A Healthcare-Academic Practice Partnership Program to Promote Student Nurse Readiness for Work
Authors: Swinton Carolyn , Deas Veronica , Worthy Karen , Lambdin Carol , Andrews Jeannette O.
Published: March 2024

Highly skilled new graduate nurses must be better prepared to face the clinical and professional challenges in today's healthcare environment. Compounding these challenges are the growing resignations of clinical faculty and experienced clinical nurses. Innovative programs are needed to bridge the knowledge-practice gap with opportunities to create pipelines to aid the future nursing workforce. A multihospital health system partnered with a local college of nursing to develop a Nursing Student Pipeline Program, which allows nursing students to perform select nursing tasks as employees of the health system. Fifty-six students have been hired to participate in the pilot program. Of the students eligible for hire and who completed the program, 24 are current employees with the healthcare system. Students, preceptors, and managers report the benefits of this program, including that participating in the program supports increasing readiness for practice upon graduation.
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.
Technical Advances Targeting Multiday Preservation of Isolated Ex Vivo Lung Perfusion
Authors: Iskender Ilker
Published: March 2024

Indications for ex vivo lung perfusion (EVLP) have evolved from assessment of questionable donor lungs to treatment of some pathologies and the logistics. Yet up to 3 quarters of donor lungs remain discarded across the globe. Multiday preservation of discarded human lungs on EVLP platforms would improve donor lung utilization rates via application of sophisticated treatment modalities, which could eventually result in zero waitlist mortality. The purpose of this article is to summarize advances made on the technical aspects of the protocols in achieving a stable multiday preservation of isolated EVLP. Based on the evidence derived from large animal and/or human studies, the following advances have been considered important in achieving this goal: ability to reposition donor lungs during EVLP; perfusate adsorption/filtration modalities; perfusate enrichment with plasma and/or donor whole blood, nutrients, vitamins, and amino acids; low-flow, pulsatile, and subnormothermic perfusion; positive outflow pressure; injury specific personalized ventilation strategies; and negative pressure ventilation. Combination of some of these advances in an automatized EVLP device capable of managing perfusate biochemistry and ventilation would likely speed up the processes of achieving multiday preservation of isolated EVLP.
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

Early 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.
Distinct spatiotemporal atrophy patterns in corticobasal syndrome are associated with different underlying pathologies
Authors: Scotton William J , Shand Cameron , Todd Emily , Bocchetta Martina , Cash David M , VandeVrede Lawren , Heuer Hilary W , Young Alexandra L , Oxtoby Neil P , Alexander Daniel C , Rowe James B , Morris Huw , Boxer Adam L , Rohrer Jonathan D , Wijeratne Peter A
Published: March 2024

Objective To identify imaging subtypes of the cortico-basal syndrome (CBS) based solely on a data-driven assessment of MRI atrophy patterns, and investigate whether these subtypes provide information on the underlying pathology. Methods We applied Subtype and Stage Inference (SuStaIn), a machine learning algorithm that identifies groups of individuals with distinct biomarker progression patterns, to a large cohort of 135 CBS cases (52 had a pathological or biomarker defined diagnosis) and 252 controls. The model was fit using volumetric features extracted from baseline T1-weighted MRI scans and validated using follow-up MRI. We compared the clinical phenotypes of each subtype and investigated whether there were differences in associated pathology between the subtypes. Results SuStaIn identified two subtypes with distinct sequences of atrophy progression; four-repeat-tauopathy confirmed cases were most commonly assigned to the Subcortical subtype (83% of CBS-PSP and 75% of CBS-CBD), while CBS-AD was most commonly assigned to the Fronto-parieto-occipital subtype (81% of CBS-AD). Subtype assignment was stable at follow-up (98% of cases), and individuals consistently progressed to higher stages (100% stayed at the same stage or progressed), supporting the model ability to stage progression. Interpretation By jointly modelling disease stage and subtype, we provide data-driven evidence for at least two distinct and longitudinally stable spatiotemporal subtypes of atrophy in CBS that are associated with different underlying pathologies. In the absence of sensitive and specific biomarkers, accurately subtyping and staging individuals with CBS at baseline has important implications for screening on entry into clinical trials, as well as for tracking disease progression.
“…but I know something’s not right here”: Exploring the diagnosis and disclosure experiences of persons living with ALS
Authors: Foldvari Kathleen M. , Stolee Paul , Neiterman Elena , Boscart Veronique , Tong Catherine
Published: March 2024

Background

Amyotrophic Lateral Sclerosis (ALS), an incurable motor neuron disease, primarily affects those between the ages of 60-79, and has an approximate post-diagnosis life--expectancy of only two to five years. The condition has an unpredictable but ultimately terminal trajectory that poses a number of challenges for patients, caregivers and healthcare providers. While the diagnosis and disclosure are critical periods for intervention and support, knowledge regarding the relational, communicational and psychodynamic forces that occur within the process of diagnostic disclosure is relatively limited.

Objectives

The purpose of this study was to explore the experiences of persons living with ALS in the diagnosis and disclosure of the condition, and the experiences of their caregivers.

Methods

We conducted a focus group and in-depth individual interviews with Canadians living with ALS (n = 9), family caregivers (n = 7), a professional caregiver (n = 1), and one past caregiver (1). The interviews were transcribed, cleaned, and anonymized, and then entered into NVivo 11 for thematic analysis.

Results

Participants discussed the diagnosis process, including the inklings and subtle changes prior to diagnosis, attempts at self-diagnosis, and the lengthy assessment process. Time was also a consideration in the disclosure process, in which participants shared how the diagnosis disclosure was the product of longstanding conversations with their care providers. It was described as rarely a shock to finally have confirmation. Additionally, participants shared their information seeking strategies and needs for a diagnosis that, for them, typically came with insufficient information on the disease, prognosis, and next steps.

Significance

This project serves as an initial step in bridging the relevant gaps in our knowledge and understanding towards improved patient-centered care practices in the diagnosis and disclosure of ALS.
Multiple paralogues and recombination mechanisms drive the high incidence of 22q11.2 Deletion Syndrome
Authors: Vervoort Lisanne , Dierckxsens Nicolas , Santos Marta Sousa , Meynants Senne , Souche Erika , Cools Ruben , Heung Tracy , Devriendt Koen , Peeters Hilde , McDonald-McGinn Donna M. , Swillen Ann , Breckpot Jeroen , Emanuel Beverly S. , Van Esch Hilde , Bassett Anne S. , Vermeesch Joris R.
Published: March 2024

The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder. Why the incidence of 22q11.2DS is much greater than that of other genomic disorders remains unknown. Short read sequencing cannot resolve the complex segmental duplicon structure to provide direct confirmation of the hypothesis that the rearrangements are caused by non-allelic homologous recombination between the low copy repeats on chromosome 22 (LCR22s). To enable haplotype-specific assembly and rearrangement mapping in LCR22 regions, we combined fiber-FISH optical mapping with whole genome (ultra-)long read sequencing or rearrangement-specific long-range PCR on 24 duos (22q11.2DS patient and parent-of-origin) comprising several different LCR22-mediated rearrangements. Unexpectedly, we demonstrate that not only different paralogous segmental duplicon but also palindromic AT-rich repeats (PATRR) are driving 22q11.2 rearrangements. In addition, we show the existence of two different inversion polymorphisms preceding rearrangement, and somatic mosaicism. The existence of different recombination sites and mechanisms in paralogues and PATRRs which are copy number expanding in the human population are a likely explanation for the high 22q11.2DS incidence.
Endogenous Precision of the Number Sense
Authors: Prat-Carrabin Arthur , Woodford Michael
Published: March 2024

The behavioral variability in psychophysical experiments and the stochasticity of sensory neurons have revealed the inherent imprecision in the brain’s representations of environmental variables1–6. Numerosity studies yield similar results, pointing to an imprecise ‘number sense’ in the brain7–13. If the imprecision in representations reflects an optimal allocation of limited cognitive resources, as suggested by efficient-coding models14–26, then it should depend on the context in which representations are elicited25,27. Through an estimation task and a discrimination task, both involving numerosities, we show that the scale of subjects’ imprecision increases, but sublinearly, with the width of the prior distribution from which numbers are sampled. This sublinear relation is notably different in the two tasks. The double dependence of the imprecision — both on the prior and on the task — is consistent with the optimization of a tradeoff between the expected reward, different for each task, and a resource cost of the encoding neurons’ activity. Comparing the two tasks allows us to clarify the form of the resource constraint. Our results suggest that perceptual noise is endogenously determined, and that the precision of percepts varies both with the context in which they are elicited, and with the observer’s objective.
Generating clinical-grade pathology reports from gigapixel whole slide images with HistoGPT
Authors: Tran Manuel , Schmidle Paul , Wagner Sophia J. , Koch Valentin , Novotny Brenna , Lupperger Valerio , Feuchtinger Annette , Böhner Alexander , Kaczmarczyk Robert , Biedermann Tilo , Comfere Nneka I. , Guo Ruifeng (Ray) , Wang Chen , Eyerich Kilian , Braun Stephan A. , Peng Tingying , Marr Carsten
Published: March 2024

Histopathology is considered the reference standard for diagnosing the presence and nature of many malignancies, including cancer. However, analyzing tissue samples and writing pathology reports is time-consuming, labor-intensive, and non-standardized. To address this problem, we present HistoGPT, the first vision language model that simultaneously generates reports from multiple pathology images. It was trained on more than 15,000 whole slide images from over 6,000 dermatology patients with corresponding pathology reports. The generated reports match the quality of human-written reports, as confirmed by a variety of natural language processing metrics and domain expert evaluations. We show that HistoGPT generalizes to six geographically diverse cohorts and can predict tumor subtypes and tumor thickness in a zero-shot fashion. Our model demonstrates the potential of an AI assistant that supports pathologists in evaluating, reporting, and understanding routine dermatopathology cases.
Mapping structural variants to rare disease genes using long-read whole genome sequencing and trait-relevant polygenic scores
Authors: LeMaster Cas , Schwendinger-Schreck Carl , Ge Bing , Cheung Warren A. , McLennan Rebecca , Johnston Jeffrey J. , Pastinen Tomi , Smail Craig
Published: March 2024

Recent studies have revealed the pervasive landscape of rare structural variants (rSVs) present in human genomes. rSVs can have extreme effects on the expression of proximal genes and, in a rare disease context, have been implicated in patient cases where no diagnostic single nucleotide variant (SNV) was found. Approaches for integrating rSVs to date have focused on targeted approaches in known Mendelian rare disease genes. This approach is intractable for rare diseases with many causal loci or patients with complex, multi-phenotype syndromes. We hypothesized that integrating trait-relevant polygenic scores (PGS) would provide a substantial reduction in the number of candidate disease genes in which to assess rSV effects. We further implemented a method for ranking PGS genes to define a set of core/key genes where a rSV has the potential to exert relatively larger effects on disease risk. Among a subset of patients enrolled in the Genomic Answers for Kids (GA4K) rare disease program (N=497), we used PacBio HiFi long-read whole genome sequencing (lrWGS) to identify rSVs intersecting genes in trait-relevant PGSs. Illustrating our approach in Autism (N=54 cases), we identified 22,019 deletions, 2,041 duplications, 87,826 insertions, and 214 inversions overlapping putative core/key PGS genes. Additionally, by integrating genomic constraint annotations from gnomAD, we observed that rare duplications overlapping putative core/key PGS genes were frequently in higher constraint regions compared to controls (P = 1×10−03). This difference was not observed in the lowest-ranked gene set (P = 0.15). Overall, our study provides a framework for the annotation of long-read rSVs from lrWGS data and prioritization of disease-linked genomic regions for downstream functional validation of rSV impacts. To enable reuse by other researchers, we have made SV allele frequencies and gene associations freely available.