Miracle-dz/UniFAR-FTUs huggingface dataset:
Use and Outcomes of Induction Therapy in Well-Matched Kidney Transplant Recipients

Visual Abstract Background and objectives The optimal induction treatment in low–immune risk kidney transplant recipients is uncertain. We therefore investigated the use and outcomes of induction immunosuppression in a low-risk cohort of patients who were well matched with their donor at HLA-A, -B, -DR, -DQB1 on the basis of serologic typing. Design, setting, participants, & measurements Our study was an observational study of first adult kidney-only transplant recipients in the United States recorded by the Organ Procurement and Transplant Network. Results Among 2976 recipients, 57% were treated with T cell–depleting antibodies, 28% were treated with an IL-2 receptor antagonist, and 15% were treated without induction. There was no difference in allograft survival, death-censored graft survival, or death with function between patients treated with an IL-2 receptor antagonist and no induction therapy. In multivariable models, patients treated with T cell–depleting therapy had a similar risk of graft loss from any cause, including death (hazard ratio, 1.19; 95% confidence interval, 0.98 to 1.45), compared with patients treated with an IL-2 receptor antagonist or no induction. The findings were consistent in subgroup analyses of Black recipients, patients grouped by calculated panel reactive antibody, and donor source. The incidence of acute rejection at 1 year was low (≤5%) and did not vary between treatment groups. Conclusions Use of induction therapy with T cell–depleting therapy or IL-2 receptor antagonists in first kidney transplant recipients who are well matched with their donor at the HLA-A, -B, -DR, -DQB1 gene loci is not associated with improved post-transplant outcomes.
The Woven EndoBridge Device for the Treatment of Intracranial Aneurysms: Initial Clinical Experience within an Australian Population

Purpose Advances in endovascular technology have expanded the treatment options for intracranial aneurysms. Intrasaccular flow diversion is a relatively new technique that aims to disrupt blood inflow at the neck of the aneurysm, hence promoting intrasaccular thrombosis. The Woven EndoBridge device (WEB; MicroVention, Aliso Viejo, CA, USA) is an US Food and Drug Administration approved intrasaccular flow diverter for wide-necked aneurysms. We report the early interim clinical and radiological outcomes of patients with both ruptured and unruptured intracranial aneurysms (IAs) treated using the WEB device in an Australian population. Materials and Methods A retrospective analysis was done of patients with ruptured or unruptured IAs who received treatment with WEB across 5 Australian neuroendovascular referral centers between May 2017 and November 2020. Angiographic occlusion was assessed with time-of-flight magnetic resonance angiography. Complications were recorded and clinical outcomes were assessed using the modified Rankin scale at follow-up. Results In total, 66 aneurysms were treated in 63 patients, with successful deployment of the WEB device in 98.5% (n=65). Eighteen (26.9%) ruptured aneurysms were included. Failure of deployment occurred in a single case. Adjunct coiling and/or stenting was performed in 20.9% (n=14) cases. Sixty-two patients with 65 aneurysms using a WEB device were followed up (mean=9.1 months), and 89.4% of these had complete aneurysm occlusion while 1.5% remained patent. Functional independence was achieved in 93.5% of cases. Conclusion Early results following the use of WEB devices in Australia demonstrate safety and adequate aneurysm occlusion comparable to international literature.
Fear of predators in free-living wildlife reduces population growth over generations

Significance Accurately evaluating the total impact of predators on prey population growth rates is fundamental to forecasting the consequences of predator conservation and management. That the fear (antipredator responses) predators inspire could contribute to this total impact has only relatively recently been recognized. We experimentally demonstrate that fear itself can impact prey population growth rates in free-living wildlife, extending to transgenerational impacts reducing population growth beyond the parental generation. We report how fear may contribute considerably to the total impact of predators and why this may be the norm in birds and mammals. The critical significance of our work lies in experimentally establishing that inferring the effects of predators using data on direct killing alone risks dramatically underestimating their total impact. Correctly assessing the total impact of predators on prey population growth rates (lambda, λ) is critical to comprehending the importance of predators in species conservation and wildlife management. Experiments over the past decade have demonstrated that the fear (antipredator responses) predators inspire can affect prey fecundity and early offspring survival in free-living wildlife, but recent reviews have highlighted the absence of evidence experimentally linking such effects to significant impacts on prey population growth. We experimentally manipulated fear in free-living wild songbird populations over three annual breeding seasons by intermittently broadcasting playbacks of either predator or nonpredator vocalizations and comprehensively quantified the effects on all the components of population growth, together with evidence of a transgenerational impact on offspring survival as adults. Fear itself significantly reduced the population growth rate (predator playback mean λ = 0.91, 95% CI = 0.80 to 1.04; nonpredator mean λ = 1.06, 95% CI = 0.96 to 1.16) by causing cumulative, compounding adverse effects on fecundity and every component of offspring survival, resulting in predator playback parents producing 53% fewer recruits to the adult breeding population. Fear itself was consequently projected to halve the population size in just 5 years, or just 4 years when the evidence of a transgenerational impact was additionally considered (λ = 0.85). Our results not only demonstrate that fear itself can significantly impact prey population growth rates in free-living wildlife, comparing them with those from hundreds of predator manipulation experiments indicates that fear may constitute a very considerable part of the total impact of predators.
Functional Status and Survival in Older Nursing Home Residents With Advanced Non–Small-Cell Lung Cancer: A SEER-Medicare Analysis

PURPOSE: Many older patients with advanced lung cancer have functional limitations and require skilled nursing home care. Function, assessed using activities of daily living (ADL) scores, may help prognostication. We investigated the relationship between ADL impairment and overall survival among older patients with advanced non–small-cell lung cancer (NSCLC) receiving care in nursing homes. METHODS: Using the SEER-Medicare database linked with Minimum Data Set assessments, we identified patients age 65 years and older with NSCLC who received care in nursing homes from 2011 to 2015. We used Cox regression and Kaplan-Meier survival curves to examine the relationship between ADL scores and overall survival among all patients; among patients who received systemic cancer chemotherapy or immunotherapy within 3 months of NSCLC diagnosis; and among patients who did not receive any treatment. RESULTS: We included 3,174 patients (mean [standard deviation] age, 77 [7.4] years [range, 65-102 years]; 1,664 [52.4%] of female sex; 394 [12.4%] of non-Hispanic Black race/ethnicity), 415 (13.1%) of whom received systemic therapy, most commonly with carboplatin-based regimens (n = 357 [86%] patients). The median overall survival was 3.1 months for patients with ADL score < 14, 2.8 months for patients with ADL score between 14 and 17, 2.3 months for patients with ADL score between 18-19, and 1.8 months for patients with ADL score 20+ (log-rank P < .001). The ADL score was associated with increased risk of death (hazard ratio [HR], 1.20; 95% CI, 1.16 to 1.25 per standard deviation). One standard deviation increase in the ADL score was associated with lower overall survival rate among treated (HR, 1.14; 95% CI, 1.02 to 1.27) and untreated (HR, 1.20; 95% CI, 1.15 to 1.26) patients. CONCLUSION: ADL assessment stratified mortality outcomes among older nursing home adults with NSCLC, and may be a useful clinical consideration in this population.
Validating the US pancreas donor risk index in a Norwegian population, a retrospective observational study

Abstract Objectives Despite advances in immunosuppression and surgical technique, pancreas transplantation is still associated with a significant graft loss rate. The Pancreas Donor Risk Index (PDRI) is a pre-transplant scoring tool derived from a US population. We sought to validate the PDRI in a Norwegian population. Methods We retrospectively retrieved donor data for 344 pancreas transplants undertaken in Norway between 2000 and 2019, utilising the Scandiatransplant database, and matched these to the respective recipients. The PDRI score was calculated for each transplanted pancreas, these were then stratified into quintiles. The association between the PDRI quintiles and 1-year graft survival was calculated, and this was repeated for the different types of pancreas transplantation. The association between PDRI as a continuous variable, and graft survival was determined. Donor and recipient data were compared to the original US population. Results The overall 1-year graft survival was 82.7%. There were no significant differences in survival between the different PDRI quintiles. When viewed as a continuous variable, increased PDRI score was not associated with decreased graft survival. Significant differences between the Norwegian and US populations were found. Conclusions When applied to a Norwegian population, the PDRI score was unable to predict 1-year graft survival.
An Artificial Intelligence Approach to Predicting Unplanned Intubation Following Anterior Cervical Discectomy and Fusion

Study Design Level III retrospective database study. Objectives The purpose of this study is to determine if machine learning algorithms are effective in predicting unplanned intubation following anterior cervical discectomy and fusion (ACDF). Methods The National Surgical Quality Initiative Program (NSQIP) was queried to select patients who had undergone ACDF. Machine learning analysis was conducted in Python and multivariate regression analysis was conducted in R. C-Statistics area under the curve (AUC) and prediction accuracy were used to measure the classifier’s effectiveness in distinguishing cases. Results In total, 54 502 patients met the study criteria. Of these patients, . 51% underwent an unplanned re-intubation. Machine learning algorithms accurately classified between 72%-100% of the test cases with AUC values of between . 52-. 77. Multivariable regression indicated that the number of levels fused, male sex, COPD, American Society of Anesthesiologists (ASA) > 2, increased operating time, Age > 65, pre-operative weight loss, dialysis, and disseminated cancer were associated with increased risk of unplanned intubation. Conclusions The models presented here achieved high accuracy in predicting risk factors for re-intubation following ACDF surgery. Machine learning analysis may be useful in identifying patients who are at a higher risk of unplanned post-operative re-intubation and their treatment plans can be modified to prophylactically prevent respiratory compromise and consequently unplanned re-intubation.
Event-Related Potentials to Speech Relate to Speech Sound Production and Language in Young Children

ABSTRACT This research was funded through the American Speech and Hearing Foundation’s 2012 StudentResearch Grant in Early Childhood Language Development awarded to Vanessa Harwood as well as an anonymous generous donation to Haskins Laboratories. Electrophysiological measures of language within early childhood provide important information about neurolinguistic development. We investigated associations between amplitude and latency of the P1 and N2 event-related potential components in response to spoken pseudowords, and clinical measures of language performance within a sample of 58 typically developing children between 24 and 48 months. N2 amplitude differences between repeated and new tokens were correlated with measures of expressive and receptive language and speech sound production. Phonemic sensitivity measured by the N2 component may reflect the integrity of neural networks that are important for speech perception and production in young children.
Retention and Success of Underrepresented Minorities in STEM at University of Massachusetts Boston: A Pilot Study of the Impact of Freshman Success Communities

Today’s college graduates are facing a complex world in which the demand for a sophisticated skill set is ever increasing; this is even more salient in the Science, Technology, Engineering and Mathematics (STEM) fields. Therefore, the success of students majoring in STEM appears critical for meeting the market demand for such degrees. Unfortunately, current rates of success in STEM suggest that there are a number of challenges impeding STEM major completion, particularly for underrepresented minorities. In the academic year 2011, the share of underrepresented minorities (URM) receiving STEM degrees in the University of Massachusetts system was 8.7%. In the 15campus Massachusetts community college system, this same figure was 12.1%. In Fall 2009, the College of Science and Mathematics at the University of Massachusetts Boston started the Freshman Success Communities program to improve the experience and academic outcomes of its increasingly diverse population. This pilot study is an exploratory investigation of the program’s impact, especially on URM. It aims to illuminate the experiences of underrepresented minorities in order to generate insights to support the retention and success of such students. Findings reveal that these learning communities have a positive influence in URM students’ performance and academic experience. There appears to be a modest difference in academic achievement between URM and non-URM program participants.
Maternal platelets in missed abortion; from a clinical perspective.

Objective To assess the significance of platelet indices, mean platelet volume, and platelet distribution width in patients with missed abortion as an earlier and cost-benefit screening test. METHODS The prospective case-control study was conducted at the University Hospital, Baghdad, Iraq, from April to September 2021, and comprised women with missed abortion as well as healthy controls. Anthropometric parameters were recorded alongside complete blood count, platelet count, mean platelet volume, and platelet distribution width were evaluated and compared between the two groups. Data was analysed using Medcalc 20. RESULTS Of the 60 subjects, 30(50%) were cases with a mean age of 27.8±6.1 years, and 30(50%) were healthy controls with a mean age of 25.7±5.2 years (P>0.05). All platelets parameters were significantly high among the cases compared to the controls (P<0.05). Conclusion Platelet distribution width was found to have the highest sensitivity in predicting missed abortion.
Hyperuricaemia is an important risk factor of the erectile dysfunction: A systematic review and meta‐analysis

Serum uric acid can affect endothelial function, and hyperuricaemia‐induced endothelial dysfunction is involved in the pathogenesis of cardiovascular diseases. As endothelial dysfunction is also a main pathogenic mechanism of erectile dysfunction (ED), the present study aims to evaluate the relationship between hyperuricaemia and ED via systemic review and meta‐analysis. Five cohort studies and six cross‐sectional studies on hyperuricaemia and ED, including a total of 454,510 participants, were recruited. Odds ratio (OR) and the 95% confidence intervals (CI) were adopted to estimate the relationship between hyperuricaemia and ED. Overall risk on effects of urate‐lowering therapy (ULT) were analysed. In addition, subgroup analyses on study design, populations, age stratification and the object were conducted. In the patients with hyperuricaemia, the risk of ED was 1.59‐fold higher than (pooled OR = 1.59, 95% CI [1.29, 1.97]) the non‐hyperuricaemia counterparts. Urate‐lowing therapy (ULT) in these hyperuricaemia patients reduced the risk of ED by 27% (OR = 1.27, 95% CI [1.14, 1.41]). After subgroup analysis, the association between hyperuricaemia and ED remained significant apart from the >60 years subgroup. Hyperuricaemia is an important risk factor of ED, while ULT can reduce the risk of ED in hyperuricaemia. This study suggests that hyperuricaemia‐associated endothelial dysfunction may also underlie the pathogenesis of ED in these patients.
Gene expression profiling improves prognostication by nomogram in patients with soft‐tissue sarcomas

Dear Editor, Surgery remains the cornerstone of treatment for softtissue sarcomas (STS) [1]. However, despite adequate locoregional treatment, 30%-40% of the patients eventually develop metastases [2, 3]. Accurate risk assessment is crucial to tailor therapeutic strategies and to identify high-risk patients who may benefit from perioperative chemotherapy.Hence, several efforts have beenmade to develop prognostic nomograms that enable individual prognosis prediction; representing an important decision-making aid for oncologists and surgeons involved in sarcoma care [4–6]. The most recent nomogram, named SARCULATOR, has been adapted to retroperitoneal sarcoma and extremities STS, possibly treated with perioperative chemotherapy, to predict overall survival (OS) and metastasis-free survival (MFS) based on histological type, grade, tumor size and patient’s age with good performances on international validation cohorts [4–6]. However, patients treated for STS with similar clinical and pathological features may have distinct outcomes, suggesting the existence of underlying prognostic molecular features. Chibon et al. developed a prognostic gene expression signature named Complexity INdex in SARComas (CINSARC), which, for instance, could discriminate intermediate grade II patients with opposing prognosis [7]. Here, our objective was to investigate whether the CINSARC signature could improve the prediction of prognosis achieved by the SARCULATOR nomogram in STS patients. We included 227 adult patients who underwent curative surgery for newly-diagnosed, locally-advanced, histologically-proven STS from the extremities or the trunk wall between 1991 and 2006 in 14 centers of the French Sarcoma Group (Supplementary Table S1). Study design and method are described in details in
Palbociclib plus endocrine therapy significantly enhances overall survival of HR+/HER2− metastatic breast cancer patients compared to endocrine therapy alone in the second‐line setting: A large institutional study

Cyclin‐dependent‐kinase‐4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) is standard of care for patients with advanced hormone receptor (HR)‐positive, HER2‐negative breast cancer (BC). The Breast Medical Oncology database at MD Anderson Cancer Center (MDACC) was analyzed to assess effectiveness of the CDK4/6i palbociclib plus ET compared to ET alone. From a total of 5402 advanced HR+ HER2− BC patients referred to MDACC between 1997 and 2020, we identified eligible patients who received palbociclib in combination with first‐line (n = 778) and second‐line (n = 410) ET. We further identified “control” patients who received ET alone in the first‐line (n = 2452) and second‐line (n = 1183) settings. Propensity score matching analysis was conducted to balance baseline demographic and clinical characteristics between palbociclib and control cohorts to assess the effect of palbociclib treatment on progression‐free survival (PFS) and overall survival (OS). For propensity‐matched‐cohort in the first‐line setting (n = 708), palbociclib group had significantly longer median PFS (17.4 vs 11.1 months; P < .0001) compared to controls. Median OS (44.3 vs 40.2 months) did not show a statistically significant benefit in the first line setting. However, in the second‐line setting, with 380 propensity‐matched‐cohort, the palbociclib group had significantly longer PFS (10 vs 5 months, P < .0001) as well as OS (33 vs 24 months; P < .022), compared to controls. We conclude that in this single center analysis of a large cohort of metastatic HR+ HER2− BC patients, palbociclib in combination with ET was associated with improved PFS in both first‐line and second‐line settings and OS in the second‐line setting compared to ET alone cohort.
ABCD‐GENE Score and Clinical Outcomes Following Percutaneous Coronary Intervention: Insights from the TAILOR‐PCI Trial

Background In TAILOR‐PCI, genotype‐guided selection of P2Y12 inhibitors after percutaneous coronary intervention did not significantly reduce the risk of ischemic events at 12 months. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD‐GENE) score identifies patients with high platelet reactivity on clopidogrel at increased risk of ischemic events. The aim of this study was to investigate the value of the ABCD‐GENE score for tailoring P2Y12 inhibitor selection after percutaneous coronary intervention. Methods and Results In a post hoc analysis of the TAILOR‐PCI, outcomes were analyzed by ABCD‐GENE score and allocation to genotype‐guided or conventional P2Y12 inhibitor selection. Primary (death, myocardial infarction, or stroke) and secondary (cardiovascular death, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia) outcomes were assessed. Among 3883 patients discharged on clopidogrel in the genotype‐guided and conventional therapy groups, 15.8% and 84.2% had high (≥10 points) or low (<10) ABCD‐GENE scores, respectively. At 12 months, both the primary (5.2% versus 2.6%, P<0.001) and secondary outcomes (7.7% versus 4.6%, P=0.001) were significantly increased in patients with high ABCD‐GENE score. Among 4714 patients allocated to genotype‐guided or conventional therapy, the former did not significantly reduce the 12‐month risk of the primary and secondary outcomes in both the high and low ABCD‐GENE score groups (pinteraction=0.48 and 0.27, respectively). Conclusions Among patients with percutaneous coronary intervention on clopidogrel, the ABCD‐GENE score was helpful in identifying those at higher risk. The ABCD‐GENE score may potentially enhance the precision of tailored selection of P2Y12 inhibitors, which needs to be confirmed in prospective investigations. Clinical Trial Registration URL: http://www.clinicaltrials. gov. Unique Identifier: NCT01742117.
The development of peptide-drug conjugates (PDCs) strategies for paclitaxel

ABSTRACT Introduction Paclitaxel is a powerful and effective anti-tumor drug with wide clinical application. However, there are still some limitations, including poor water solubility, low specificity, and susceptibility to drug resistance. The peptide-drug conjugates (PDCs) represent a rising class of therapeutic drugs, which combines small-molecule chemotherapeutic drugs with highly flexible peptides through a cleavable or non-cleavable linker. When this strategy is applied, the therapeutic effects of paclitaxel can be improved. Areas covered In this review, we discuss the application of the PDCs strategy in paclitaxel, including two parts: the tumor targeting peptide-paclitaxel conjugates and the cell penetrating peptide-paclitaxel conjugates. Expert opinion Combining drugs with multifunctional peptides covalently is an effective strategy for delivering paclitaxel to tumors. Depending on different functional peptides, conjugates can increase the water solubility of paclitaxel, tumor permeability of paclitaxel, the accumulation of paclitaxel in tumor tissues, and enhance the antitumor effect of paclitaxel. In addition, due to the change of cell entry mechanism, partial conjugates can restore the therapeutic activity of paclitaxel against resistant tumors. Notably, in order to better translate into the clinical field in the future, more research should be conducted to ensure the safety and effectiveness of peptide-paclitaxel conjugates.