bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenic variants affecting the TB5 domain of the fibrillin-1 protein: not only in geleophysic/acromicric dysplasias but also in Marfan syndrome
Authors: Arnaud Pauline , Mougin Zakaria , Baujat Genevieve , Drouin-Garraud Valérie , El Chehadeh Salima , Gouya Laurent , Odent Sylvie , Jondeau Guillaume , Boileau Catherine , Hanna Nadine , Le Goff Carine 
Published: March 2024

BackgroundMarfan syndrome (MFS) is a multisystem disease with a unique combination of skeletal, cardiovascular and ocular features. Geleophysic/acromicric dysplasias (GPHYSD/ACMICD), characterised by short stature and extremities, are described as ‘the mirror image’ of MFS. The numerousFBN1pathogenic variants identified in MFS are located all along the gene and lead to the same final pathogenic sequence. Conversely, in GPHYSD/ACMICD, the 28 known heterozygousFBN1pathogenic variants all affect exons 41–42 encoding TGFβ-binding protein-like domain 5 (TB5).MethodsSince 1996, more than 5000 consecutive probands have been referred nationwide to our laboratory for molecular diagnosis of suspected MFS.ResultsWe identified five MFS probands carrying distinct heterozygous pathogenic in-frame variants affecting the TB5 domain of FBN1. The clinical data showed that the probands displayed a classical form of MFS. Strikingly, one missense variant affects an amino acid that was previously involved in GPHYSD.ConclusionSurprisingly, pathogenic variants in the TB5 domain of FBN1 can lead to two opposite phenotypes: GPHYSD/ACMICD and MFS, suggesting the existence of different pathogenic sequences with the involvement of tissue specificity. Further functional studies are ongoing to determine the precise role of this domain in the physiopathology of each disease.
Risk-stratified monitoring for sulfasalazine toxicity: prognostic model development and validation
Authors: Abhishek Abhishek , Grainge Matthew , Card Tim , Williams Hywel C , Taal Maarten W , Aithal Guruprasad P , Fox Christopher P , Mallen Christian D , Stevenson Matthew D , Nakafero Georgina , Riley Richard 
Published: March 2024

BackgroundSulfasalazine-induced cytopenia, nephrotoxicity and hepatotoxicity is uncommon during long-term treatment. Some guidelines recommend 3 monthly monitoring blood tests indefinitely during long-term treatment while others recommend stopping monitoring after 1 year. To rationalise monitoring, we developed and validated a prognostic model for clinically significant blood, liver or kidney toxicity during established sulfasalazine treatment.DesignRetrospective cohort study.SettingUK primary care. Data from Clinical Practice Research Datalink Gold and Aurum formed independent development and validation cohorts.ParticipantsAge ≥18 years, new diagnosis of an inflammatory condition and sulfasalazine prescription.Study period1 January 2007 to 31 December 2019.OutcomeSulfasalazine discontinuation with abnormal monitoring blood-test result.AnalysisPatients were followed up from 6 months after first primary care prescription to the earliest of outcome, drug discontinuation, death, 5 years or 31 December 2019. Penalised Cox regression was performed to develop the risk equation. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination.Results8936 participants were included in the development cohort (473 events, 23 299 person-years) and 5203 participants were included in the validation cohort (280 events, 12 867 person-years). Nine candidate predictors were included. The optimism adjusted R2Dand Royston D statistic in the development data were 0.13 and 0.79, respectively. The calibration slope (95% CI) and Royston D statistic (95% CI) in validation cohort was 1.19 (0.96 to 1.43) and 0.87 (0.67 to 1.07), respectively.ConclusionThis prognostic model for sulfasalazine toxicity uses readily available data and should be used to risk-stratify blood-test monitoring during established sulfasalazine treatment.
Intravenous Thrombolysis Before Thrombectomy Improves Functional Outcome After Stroke Independent of Reperfusion Grade
Authors: Sedghi Annahita , Kaiser Daniel P. O. , Cuberi Ani , Schreckenbauer Sonja , Wojciechowski Claudia , Friehs Ingeborg , Reichmann Heinz , Barlinn Jessica , Barlinn Kristian , Puetz Volker , Siepmann Timo 
Published: March 2024

Background
We studied the association of bridging intravenous thrombolysis (IVT) before thrombectomy for anterior circulation large‐vessel occlusion and functional outcome and scrutinized its dependence on grade of reperfusion and distal thrombus migration.

Methods and Results

We included consecutive patients with anterior circulation large‐vessel occlusion from our prospective registry of thrombectomy‐eligible patients treated from January 1, 2017 to January 1, 2023 at a tertiary stroke center in Germany in this retrospective cohort study. To evaluate the association of bridging IVT and functional outcome quantified via modified Rankin Scale score at 90 days we used multivariable logistic and lasso regression including interaction terms with grade of reperfusion quantified via modified Thrombolysis in Cerebral Infarction (mTICI) scale and distal thrombus migration adjusted for demographic and cardiovascular risk profiles, clinical and imaging stroke characteristics, onset‐to‐recanalization time and distal thrombus migration. We performed sensitivity analysis using propensity score matching. In our study population of 1000 thrombectomy‐eligible patients (513 women; median age, 77 years [interquartile range, 67–84]), IVT emerged as a predictor of favorable functional outcome (modified Rankin Scale score, 0–2) independent of modified mTICI score (adjusted odds ratio, 0.49 [95% CI, 0.32–0.75];
P
=0.001). In those who underwent thrombectomy (n=812), the association of IVT and favorable functional outcome was reproduced (adjusted odds ratio, 0.49 [95% CI, 0.31–0.74];
P
=0.001) and was further confirmed on propensity score analysis, where IVT led to a 0.35‐point decrease in 90‐day modified Rankin Scale score (ß=–0.35 [95 CI%, −0.68 to 0.01];
P
=0.04). The additive benefit of IVT remained independent of modified mTICI score (ß=–1.79 [95% CI, −3.43 to –0.15];
P
=0.03) and distal thrombus migration (ß=–0.41 [95% CI, −0.69 to –0.13];
P
=0.004) on interaction analysis. Consequently, IVT showed an additive association with functional outcome in the subpopulation of patients undergoing thrombectomy who achieved successful reperfusion (mTICI ≥2b; ß=–0.46 [95% CI, −0.74 to –0.17];
P
=0.002) and remained beneficial in those with unsuccessful reperfusion (mTICI ≤2a; ß=–0.47 [95% CI, −0.96 to 0.01];
P
=0.05).

Conclusions
In thrombectomy‐eligible patients with anterior circulation large‐vessel occlusion, IVT improves functional outcome independent of grade of reperfusion and distal thrombus migration.
An Overview of the Free Energy Principle and Related Research
Authors: Zhang Zhengquan , Xu Feng 
Published: March 2024

Abstract
The free energy principle and its corollary, the active inference framework, serve as theoretical foundations in the domain of neuroscience, explaining the genesis of intelligent behavior. This principle states that the processes of perception, learning, and decision making—within an agent—are all driven by the objective of “minimizing free energy,” evincing the following behaviors: learning and employing a generative model of the environment to interpret observations, thereby achieving perception, and selecting actions to maintain a stable preferred state and minimize the uncertainty about the environment, thereby achieving decision making. This fundamental principle can be used to explain how the brain processes perceptual information, learns about the environment, and selects actions. Two pivotal tenets are that the agent employs a generative model for perception and planning and that interaction with the world (and other agents) enhances the performance of the generative model and augments perception. With the evolution of control theory and deep learning tools, agents based on the FEP have been instantiated in various ways across different domains, guiding the design of a multitude of generative models and decision-making algorithms. This letter first introduces the basic concepts of the FEP, followed by its historical development and connections with other theories of intelligence, and then delves into the specific application of the FEP to perception and decision making, encompassing both low-dimensional simple situations and high-dimensional complex situations. It compares the FEP with model-based reinforcement learning to show that the FEP provides a better objective function. We illustrate this using numerical studies of Dreamer3 by adding expected information gain into the standard objective function. In a complementary fashion, existing reinforcement learning, and deep learning algorithms can also help implement the FEP-based agents. Finally, we discuss the various capabilities that agents need to possess in complex environments and state that the FEP can aid agents in acquiring these capabilities.
Unraveling the Origins, Evolution, and Contemporary Applications of qili qiji 契理契机
Authors: Xuan Fang 
Published: March 2024

Abstract
This article presents a historical exploration of the concept of qili qiji 契理契机 (according with the [core] principles [of Buddhism] and the circumstances or capacities [of sentient beings]) in the context of Buddhist thought from the Eastern Jin era (317–420 CE) to contemporary times, examining its origins, development, and dissemination, and the progressive expansion of its definition. The study explores the significance of qili qiji in the writings and discussions of influential figures and organizations in the domain of “Buddhism for the Human Realm” (renjian fojiao 人间佛教), such as Taixu 太虚, Yin Shun 印顺, Sheng-yen 圣严, Hsing Yun 星云, Zhao Puchu 赵朴初, and the Buddhist Association of China. Lastly, the study investigates the adoption of this term beyond the Buddhist community, specifically its incorporation into the official discourse of governmental religious affairs departments and its usage within other religions such as Daoism.
The Invention and Vicissitudes of the “Three Great Marvelous Traditions” (san da youliang chuantong 三大优良传统) in Contemporary Chinese Buddhism
Authors: Krause Carsten 
Published: March 2024

Abstract
Religious life after the Cultural Revolution was more than just a revival of traditions. Much depended on the theoretical framing provided by Buddhist elites, the most prominent of whom became Zhao Puchu (1907–2000). As president of the Buddhist Association of China, he (re-)introduced the so-called renjian fojiao 人间佛教 (Buddhism for a Human Realm) as “guiding thought” and connected it with the “Three Great Marvelous Traditions,” which he identified as “equal weighting of agriculture and chan,” “strong concern for scientific research,” “friendly international exchange.” This article examines the trajectories of this construction and attempts to explore how it has been interpreted and used in official rhetoric and wider discourse over the past four decades, including possible reinterpretations after Zhao’s passing away. In a broader sense, this conceptual history may also raise the question of what the changing connotations of “tradition(s)”—old or new, dead or alive—have become in contemporary China.
Should We Confucians Be Liberals? Reflections on Roy Tseng’s Confucian Liberalism
Authors: Angle Stephen C. 
Published: March 2024

Abstract
Roy Tseng’s Confucian Liberalism: Mou Zongsan and Hegelian Liberalism is a tremendously significant work because of its improved understandings of some of Mou’s most central ideas and the opportunities it creates toward a full and appealing articulation of democratic, progressive Confucianism. After emphasizing some of Tseng’s key insights, I probe an ambiguity that might undercut Tseng’s contribution to progressive Confucianism. Is Mou’s view, or Tseng’s, a Confucian-flavored liberalism? While there are multiple, legitimate ways to draw on Tseng’s achievements, the one most apt for Confucians today is not best characterized as “Confucian liberalism.”
Acoustical Survey and Finite Element Analyses of Late Baroque Mandolin
Authors: Quintavalla Martino , Gabrielli Federico , Canevari Claudio 
Published: March 2024

Abstract
Replicating ancient musical instruments is a method to protect fragile originals from extensive playing. In the case of stringed instruments, replicas are generally realized by luthiers using identical wood species and geometry, according to dimensional surveys. Although this procedure yields a highly similar visual aspect, the intrinsic variability of wood properties does not ensure an identical sound. Therefore, acoustic surveys are a fundamental step in reproducing the sounds of original instruments. In this work, we report the acoustical survey of a late baroque mandolin preserved at Museo degli Strumenti Musicali del Castello Sforzesco di Milano. The survey was conducted using portable equipment and included measurements of the radiated sound spectrum, admittance, monopole mobility, and mode shape assignment. Finite Element Analyses (FEA) enabled the assignment of mode shapes and quantification of the effect of a crack on the structural integrity and acoustics of the instrument. This study has laid the foundation for the creation of a replica that, beyond the visual aspect, would resemble the original instrument in terms of sound to the extent feasible.
Effects of prolonged face mask use among patients with hypertension or diabetes during the COVID-19 pandemic
Authors: He Weiwei , Liu Yang , Zou Zhaoting , Cheng Chunbao , Wang Wenjing , Huang Zhixin , Wu Guannan , Zhu Weiquan , Sun Huiming 
Published: March 2024

Objective We aimed to investigate the impacts of prolonged mask use on patients with hypertension or diabetes during the COVID-19 pandemic. Methods This study included patients with hypertension or diabetes who visited the outpatient department of Nanjing Yimin Hospital between 1 February 2022 and 31 January 2023. We compared the change in blood pressure (BP) and fasting plasma glucose in patients with hypertension or diabetes and adjustments to treatment between the group with prolonged mask-wearing group (≥20 hours/week) and the control group (<20 hours/week). Results Compared with the control group of hypertensive patients, the prolonged mask-wearing group had significantly higher diastolic blood pressure (DBP) and mean arterial pressure (MAP). These two groups had had similar DBP and MAP 1 year earlier. Likewise, the prolonged mask-wearing group of patients with diabetes had a greater need than the control group for upgraded treatment to reach their therapeutic goals. Conclusions This study suggests that prolonged mask use by patients with hypertension or diabetes has negative effects on hypertension and plasma glucose control. BP and plasma glucose monitoring should be improved in these patient populations and their treatment should be adjusted in a timely manner.
Correlation between genetic alterations and clinicopathological features of papillary thyroid carcinomas
Authors: Shang Shixuan , Yang Huimin , Chen Meixiang , Wu Jin , Shi Xianjun , Li Xiangqin , Feng Ningning , Zheng Zhaoqing , Liu Hongmei , Zhang Yunzhi 
Published: March 2024

Objective To investigate the correlations between multigene alterations and clinicopathological features in papillary thyroid carcinoma (PTC) samples. Methods In this retrospective study, 111 cytological specimens of thyroid nodules, including 74 PTC samples and 37 benign samples, were analyzed using a 22-gene mutation assay employing next-generation sequencing. Clinicopathological information was retrospectively collected and analyzed. Results Gene alterations were associated with a higher rate of lymph node metastasis (LNM) and thyroid capsular invasion, a lower rate of coexisting Hashimoto's thyroiditis, the classical PTC subtype, and younger age (<45 years). Among the 22 genes tested, the BRAF mutation rates showed a significant difference between the PTC and benign groups. In the subgroup analysis, younger age (odds ratio = 12.512, 95% confidence interval: 3.126–50.087) was an independent risk factor for LNM. In further analyses, BRAF mutation was significantly associated with LNM in the older subgroup (age ≥ 45 years), suggesting that the BRAF mutation test has greater value for determining PTC prognosis in the older age group. Conclusions Our findings will provide a more comprehensive understanding of the relationship between gene mutations and PTC and may contribute to improved PTC management.
Perioperative Intravenous Dexamethasone Significantly Reduces Postoperative Opioid Requirement and Nausea After Unilateral Elective Hip Arthroscopy: A Randomized Double-blinded Placebo-controlled Trial
Authors: Kaiser Dominik , Hoch Armando , Dimitriou Dimitris , Groeber Tanja , Bomberg Hagen , Aguirre José A. , Eichenberger Urs , Zingg Patrick O. 
Published: March 2024

Background: Previous studies have shown that dexamethasone has a positive effect on postoperative pain control, opioid consumption, nausea, and vomiting and length of hospital stay after arthroplasty surgery. Purpose/Hypothesis: The purpose of this study was to assess whether adding perioperative dexamethasone to our current pain regimen after hip arthroscopy is more effective than a placebo. It was hypothesized that dexamethasone would reduce postoperative pain, reduce opioid consumption, improve subjective pain and nausea scores, and reduce the number of vomiting events. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 50 patients requiring unilateral elective hip arthroscopy were randomized to receive intravenous dexamethasone immediately before induction of anesthesia and at 8 am on the first postoperative day (2 ×12 mg) or a placebo (sodium chloride 0.9%). The patient, the surgeons, the treating anesthesiologist, and the involved nursing and physical therapy personnel were blinded to group assignment. The primary outcome was postoperative pain, and secondary outcomes were opioid consumption and nausea scores—assessed using a translated revised version of the American Pain Society Patient Outcome Questionnaire 6 hours postoperatively and on days 1 and 2—and vomiting events. A clinical follow-up was performed 12 weeks postoperatively to assess adverse events. Results: The mean age at inclusion was 29 years in both groups. Postoperative pain levels did not differ significantly in most instances. Opioid requirements during the hospitalization in the dexamethasone group were significantly lower than those in the placebo group (31.96 ± 20.56 mg vs 51.43 ± 38 mg; P = .014). Significantly fewer vomiting events were noted in the dexamethasone group (0.15 ± 0.59 vs 0.65 ± 0.91; P = .034). Descriptive data and surgical parameters did not differ significantly. Conclusion: Perioperative intravenous dexamethasone significantly reduced postoperative opioid consumption by 40% without compromising pain level and safety, as no corticosteroid-related side effects were observed. Dexamethasone may be a valuable adjuvant to a multimodal systemic pain regimen after hip arthroscopy. Registration: NCT04610398 (ClinicalTrials.gov identifier).
Selinexor for the treatment of patients with relapsed or refractory multiple myeloma
Authors: Babar Anum , Babar Maham , Zubair Hina , Shahid Arzu , Rafique Sana , Bano Maimona , Waleed Madeeha Subhan , Khan Maimoona , Inayat Arslan , Safi Danish 
Published: March 2024

Objective Multiple myeloma cells resist standard therapies due to overexpression of the transport protein, exportin 1. Selinexor is a novel drug that targets the Exportin 1 protein in these cells. Data source A comprehensive search was done, and data showing the efficacy and safety of selinexor in relapsed/refractory multiple myeloma was collected using PubMed, Google Scholar, and clincialtrials.gov. Data summary Results from the clinical trials STORM, BOSTON, and STOMP were included. Parts I and II of the STORM trial revealed a progression-free survival (PFS) of 4.7 and 3.7 months, a median duration of response of 6.2 and 4.4 months, and an overall survival of 7.3 and 8.4 months, respectively. BOSTON trial's SVd arm (selinexor, bortezomib, and dexamethasone) had a median follow-up period of 13.2 months and an mPFS of 13.93 months. The Vd arm (bortezomib and dexamethasone) had a median follow-up duration of 16.5 months and an mPFS of 9.46 months. The STOMP trial is still active and has limited data available. The SKd arm (selinexor, carfilzomib, and dexamethasone) reported an overall response rate of 66.7% in patients with triple refractory multiple myeloma, and 82% in patients with high-risk cytogenetics. The SPd arm (selinexor, pomalidomide, and dexamethasone) shows an overall response rate of 54.30% in pomalidomide naïve-nonrefractory, 35.70% in pomalidomide refractory and 60% in those dosed at RP2D. SRd arm (selinexor, lenalidomide, and dexamethasone) shows an overall response rate of 91.7% in lenalidomide naïve and 12.5% in lenalidomide refractory patients. SVd (selinexor, bortezomib, and dexamethasone) arm reported an overall response rate of 63% in all patients while the SDd arm (selinexor, daratumumab, and dexamethasone) showed an overall response rate of 69%. Conclusion To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups.
Pharmacist's role in the management of drug–drug interactions caused by nirmatrelvir/ritonavir in COVID-19 oncohematology patients
Authors: Guzmán Cordero Carlos , Sáez-Torres de Vicente María , Jiménez Espinosa Álvaro , Gago Sánchez Ana Isabel 
Published: March 2024

Objective New drugs developed for SARS-CoV-2 infection, such as nirmatrelvir/ritonavir (NMV/r), represent a potential for oncohematology patients, but also pose a challenge in managing the potential clinically relevant drug–drug interactions (pDDIs) that may arise. The aim of this study is to assess the frequency, severity, and pharmacist detection of pDDIs. Methods This prospective, observational, study spanned 8 months, involving 42 oncohematology patients prescribed NMV/r in a tertiary-level hospital. A Board Certified oncology pharmacist assessed pDDIs using three databases and made recommendations to prescribing physicians. Linear and logistic regression analyses were employed to explore the relationship between prescribed drugs and pDDIs. Results Clinically relevant pDDIs were detected in 76.2% of patients, with 18.1% of all medications involved in drug–drug interactions (DDIs). The most common drugs implicated were atorvastatin and imatinib. Micromedex® identified 63.3% of interactions as major severity, while Lexicomp® and University of Liverpool classifications were less restrictive. Pharmacists prevented most DDIs from reaching patients through different interventions, including treatment monitoring (44.2%), discontinuation (36.5%), and dose reduction (17.3%). Conclusion This study highlights the high prevalence of clinically significant pDDIs in oncohematology patients receiving NMV/r for COVID-19. Pharmacists, as integral members of the healthcare team, played a crucial role in detecting, categorizing, and mitigating these interactions. The results underscore the need for comprehensive studies to evaluate the impact of pharmacist-led interventions in optimizing drug therapy and enhancing patient safety in this vulnerable population.