bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empirical prediction intervals applied to short term mortality forecasts and excess deaths
Authors: Duerst Ricarda , Schöley Jonas 
Published: December 2024

Abstract

Background
In the winter of 2022/2023, excess death estimates for Germany indicated a 10% elevation, which has led to questions about the significance of this increase in mortality. Given the inherent errors in demographic forecasting, the reliability of estimating a 10% deviation is questionable. This research addresses this issue by analyzing the error distribution in forecasts of weekly deaths. By deriving empirical prediction intervals, we provide a more accurate probabilistic study of weekly expected and excess deaths compared to the use of conventional parametric intervals.

Methods
Using weekly death data from the Short-term Mortality Database (STMF) for 23 countries, we propose empirical prediction intervals based on the distribution of past out-of-sample forecasting errors for the study of weekly expected and excess deaths. Instead of relying on the suitability of parametric assumptions or the magnitude of errors over the fitting period, empirical prediction intervals reflect the intuitive notion that a forecast is only as precise as similar forecasts in the past turned out to be. We compare the probabilistic calibration of empirical skew-normal prediction intervals with conventional parametric prediction intervals from a negative-binomial GAM in an out-of-sample setting. Further, we use the empirical prediction intervals to quantify the probability of detecting 10% excess deaths in a given week, given pre-pandemic mortality trends.

Results
The cross-country analysis shows that the empirical skew-normal prediction intervals are overall better calibrated than the conventional parametric prediction intervals. Further, the choice of prediction interval significantly affects the severity of an excess death estimate. The empirical prediction intervals reveal that the likelihood of exceeding a 10% threshold of excess deaths varies by season. Across the 23 countries studied, finding at least 10% weekly excess deaths in a single week during summer or winter is not very unusual under non-pandemic conditions. These results contrast sharply with those derived using a standard negative-binomial GAM.

Conclusion
Our results highlight the importance of well-calibrated prediction intervals that account for the naturally occurring seasonal uncertainty in mortality forecasting. Empirical prediction intervals provide a better performing solution for estimating forecast uncertainty in the analyses of excess deaths compared to conventional parametric intervals.
Clonal T cell populations scarcely impair patients with rheumatic diseases: a prospective long-term follow up study
Authors: Gernert Michael , Müller Tobias , Schweiker Lukas , Schmalzing Marc , Fröhlich Matthias , Nagler Lea-Kristin , Strunz Patrick-Pascal , Labinsky Hannah , Schwaneck Eva Christina 
Published: December 2024

Abstract
Background
Clonal T cell populations are frequently detected in patients with rheumatic diseases. The relevance of this finding is often uncertain, as the clinical spectrum can range from being asymptomatic to T cell leukemia. Former studies suggested that certain anti-rheumatic drugs might influence the course of the clonal T cell populations.

Methods
A prospective long-term follow up study was performed including patients with rheumatic diseases and clonal T cell populations. Clinical features, adverse events, especially infections and cytopenias, and immunosuppressive medication were assessed. T cell populations were characterized by polymerase chain reaction, flow cytometry and stimulated cell cultures.

Results
28 Patients with rheumatoid arthritis, spondyloarthritis, or giant cell arteritis were prospectively followed for up to 7.6 years. Severe infections or cytopenias (10.7% autoimmune neutropenias) were rare. The clonal T cell populations mostly persisted over time, the tumor burden decreased in the long-term. The cytokine secretion in stimulated T cell cultures did not differ in the subgroup of RA patients with versus without clonal T cells.

Conclusion
Clonal T cell populations in patients with rheumatic diseases are common, but are rarely harmful. Feared neutropenia, infections or progression into T cell leukemia could not be detected in the long-term in our cohort.
DNA methylation-based analysis reveals accelerated epigenetic aging in giant cell-enriched adult-type glioblastoma
Authors: Cakmak Pinar , Jurmeister Philipp , Divé Iris , Zeiner Pia S. , Steinbach Joachim P. , Fenton Tim R. , Plate Karl H. , Czabanka Marcus , Harter Patrick N. , Weber Katharina J. 
Published: December 2024

Abstract
Background
Giant cell (gc)-enriched glioblastoma (gcGB) represents a distinct histological variant of isocitrate dehydrogenase wild-type adult-type glioblastoma with notable enlarged mono- or multinuclear tumor cells. While some studies suggest a survival advantage for gcGB patients, the underlying causes remain elusive. GcGBs are associated with TP53 mutations, and gcs were shown to accumulate DNA double-strand breaks and show deficient mitosis, potentially triggering cellular senescence programs. Epigenetic clocks have emerged as valuable tools for assessing tumor-induced age acceleration (DNAMethAgeAcc), which has lately proved itself as prognostic biomarker in glioblastoma. Our study aimed to comprehensively analyze the methylome and key metabolic proteins of gcGBs, hypothesizing that they undergo cellular aging programs compared to non-gcGBs.

Results
A total of 310 epigenetically classified GBs, including 26 gcGBs, and nine adults with malignant gliomas allocating to pediatric high-grade glioma molecular subclasses (summarized as “pediatric GB”) were included. DNAMethAgeAcc was computed by subtraction of chronological patient ages from DNA methylome-derived age estimations and its increase was associated with better survival within gcGB and non-gcGB. GcGBs were significantly more often allocated to the subgroup with increased DNAMethAgeAcc and demonstrated the highest DNAMethAgeAcc. Hypothetical senescence/aging-induced changes of the tumor microenvironment were addressed by tumor deconvolution, which was able to identify a cluster enriched for tumors with increased DNAMethAgeAcc. Key metabolic protein expression did not differ between gcGB and non-gcGB and tumor with versus without increased DNAMethAgeAcc but for elevated levels of one single mitochondrial marker, anti-mitochondrial protein MT-C02, in gcGBs.

Conclusions
With its sped-up epigenetic aging, gcGB presented as the epigenetic oldest GB variant in our cohort. Whereas the correlation between accelerated tumor-intrinsic epigenetic aging and cellular senescence in gcGB stays elusive, fostering epigenetic aging programs in GB might be of interest for future exploration of alternative treatment options in GB patients.
Nano-fluorescence imaging: advancing lymphatic disease diagnosis and monitoring
Authors: Han Chae Yeon , Choi Sang-Hun , Chi Soo-Hyang , Hong Ji Hyun , Cho Young-Eun , Kim Jihoon 
Published: December 2024

AbstractThe lymphatic system plays a crucial role in maintaining physiological homeostasis and regulating immune responses. Traditional imaging modalities such as magnetic resonance imaging, computerized tomography, and positron emission tomography have been widely used to diagnose disorders in the lymphatic system, including lymphedema, lymphangioma, lymphatic metastasis, and Castleman disease. Nano-fluorescence technology has distinct advantages—including naked-eye visibility, operational simplicity, portability of the laser, and real-time visibility—and serves as an innovative alternative to traditional imaging techniques. This review explores recent advancements in nano-fluorescence imaging aimed at enhancing the resolution of lymphatic structure, function, and immunity. After delineating the fundamental characteristics of lymphatic systems, it elaborates on the development of various nano-fluorescence systems (including nanoparticles incorporating fluorescent dyes and those with intrinsic fluorescence) while addressing key challenges such as photobleaching, limited tissue penetration, biocompatibility, and signal interference from biomolecules. Furthermore, this review highlights the clinical applications of nano-fluorescence and its potential integration into standard diagnostic protocols. Ongoing advancements in nanoparticle technology underscore the potential of nano-fluorescence to revolutionize the diagnosis and treatment of lymphatic disease.
Graphical abstract
Systolic blood pressure, mean arterial pressure and incident mortality in heart failure in a West-African cohort: the blood pressure paradox revisited
Authors: Oguntade Ayodipupo S. , Ogah Okechukwu S. , Adebiyi Adewole A. , Aje Akinyemi 
Published: December 2024

Abstract
Background
The prognostic relevance of blood pressure in Africans with heart failure (HF) has not been well investigated despite the different trajectories of HF in Africans compared to other ethnicities. We investigated the shape and strength of associations of systolic blood pressure (SBP) and mean arterial pressure (MAP) with incident death in Nigerian Africans with hypertensive HF.

Results
Present analyses include 118 participants (mean age 57.6 years, 55% men) with ambulatory hypertensive HF. Over a median 2.2 years of follow-up, there were 74 incident deaths. There was an inverse log-linear association between each of SBP and MAP, and incident death throughout the distribution of blood pressure studied and no J-shape effect was seen. Individuals in the bottom distribution of SBP (mean 100 mmHg) and MAP (mean 77 mmHg) had the highest cumulative incident death. Each 10 mmHg higher SBP and MAP was associated with lower risk of incident death (aHR 0.80 [95% CI: 0.70–0.91, p < 0.001] and aHR 0.78 [95% CI: 0.66–0.92, p < 0.01] respectively) which persisted despite adjustment for NHYA class, left ventricular function and systolic pulmonary artery pressure. The blood pressure paradox was partially explained by haematocrit, serum sodium, chloride and renal function (aHR SBP: 0.86 [95% CI: 0.73–1.00, p = 0.05] and aHR MAP: 0.88 [95% CI: 0.72–1.08, p = 0.22]).

Conclusions
There was a graded inverse dose−response association between each of SBP, MAP and incident death in hypertensive HF which was not fully explained by haemodynamic and clinical factors.
Effect of Vitamin D3, Omega-3 Fatty Acids, and Exercise on Serum Sclerostin Levels and Bone Turnover Markers
Authors: Tsourdi Elena , Gängler Stephanie , Kistler-Fischbacher Melanie , Rauner Martina , Dawson-Hughes Bess , Orav E John , Tsai Li-Tang , Lang Wei , Kanis John A , Theiler Robert , Egli Andreas , Bischoff-Ferrari Heike A , Hofbauer Lorenz C 
Published: December 2024

Abstract

Context
Sclerostin inhibits canonical Wnt signaling, a pathway promoting bone formation. The effects of vitamin D3, omega-3 fatty acids (omega-3s), and exercise on serum sclerostin levels and bone metabolism are unclear.

Objective
To investigate the effects of 2000 IU/day vitamin D3, 1 g/day omega-3s, and a simple home-based strength exercise program (SHEP), alone or in combination, on serum sclerostin and bone turnover marker levels.

Methods
Sclerostin, procollagen type 1 N propeptide (P1NP) and C-terminal telopeptide (β-CTx) levels were predefined secondary outcomes of DO-HEALTH, a double blind, randomized controlled trial in healthy physically active older adults in 5 European countries. Outcome measures were changes in yearly serum sclerostin, P1NP, and β-CTx levels over 3 years, adjusted for age, sex, prior falls, study site, baseline body mass index, and baseline level of the respective outcome.

Results
A total of 1848 participants were included (mean age 74.8 ± 4.4 years, 58.9% women, 41.4% 25(OH)D &lt; 20 ng/mL, 83.9% at least moderately physically active at baseline). Vitamin D3 and omega-3s supplementation alone did not change sclerostin levels significantly, while SHEP compared with control exercise (joint mobility) led to greater decrease in sclerostin levels (−1.56 pmol/L [−2.54, −0.58], P = .002). Omega-3s plus SHEP led to a greater decrease in sclerostin levels than no omega-3s/control exercise (−1.93 pmol/L [−3.31, −0.54], P = .007). For P1NP and β-CTx there were no significant effects for any of the individual treatments and treatment combinations.

Conclusion
In this 3-year prevention trial among largely vitamin D replete adults age 70 and older, SHEP alone or in combination with omega-3s reduced serum sclerostin levels, while vitamin D3 and omega-3s alone did not affect serum sclerostin levels.
The Biology and Clinical Implications of PCSK7
Authors: Sachan Vatsal , Susan-Resiga Delia , Lam Kalista , Seidah Nabil G 
Published: December 2024

Abstract
Discovered in 1996, PCSK7 is the seventh of the 9-membered proprotein convertase subtilisin-kexin (PCSK) family. This article reviews the various aspects of the multifaceted biology of PCSK7 and what makes it an exciting new target for metabolic dysfunction–associated steatotic liver disease (MASLD), affecting ∼30% of the population globally, dyslipidemia, cardiovascular disease, and likely cancer/metastasis. We will systematically review and discuss all the available epidemiological data, and structural, cell biology, and in vivo evidence that eventually led to the discovery of PCSK7 as a novel post-translational regulator of apolipoprotein B. Interestingly, PCSK7 is the only convertase, other than PCSK9, that exhibits noncanonical/nonenzymatic functions, which will be amply described in this review. The data so far have suggested that PCSK7 is a potential safe target in MASLD treatment. This was based on human epidemiological data, as well as mouse Pcsk7 knockout and mRNA translation inhibition using hepatocyte-targeted antisense oligonucleotides following a diet-induced MASLD. Additionally, of all the 9 convertases only the gene deletion of Pcsk7 and/or Pcsk9 in mice leads to healthy and fertile animals with no apparent deleterious consequences, suggesting that their pharmacological targeting is likely safe. Accordingly, the synergistic effects of inhibiting both PCSK7 and PCSK9 in a clinical setting may represent a novel therapy for various diseases. We believe that the current surge in oligonucleotide therapy, with many Food and Drug Administration–approved oligonucleotide-based drugs now available in clinics, and the urgent need for novel MASLD therapeutics present an opportune moment for this timely review article.
Pulmonary artery stent thrombosis and symptomatic pulmonary hypertension following COVID-19 infection in Alagille patient: A case report
Authors: Izhakian Shimon , Korlansky Miriam , Rosengarten Dror , Bruckheimer Elchanan , Kramer Mordechai Reuven 
Published: December 2024

BACKGROUND
Alagille syndrome is a multisystem disease that results in various vascular anomalies, commonly involving the cardiac and pulmonary systems. To the best of our knowledge, there is no literature regarding the cardiovascular outcomes of these patients in association with coronavirus disease 2019 (COVID-19).
CASE SUMMARY
A 34-year-old woman with a history of Alagille syndrome who underwent successful atrial septal defect with partial anomalous pulmonary veins and patent ductus arteriosus repair, as well as left pulmonary artery catheterization and stenting in childhood due to pulmonary stenosis. The patient was without any respiratory symptoms and was a dancer prior to contracting COVID-19. Several weeks after her COVID-19 infection, she developed left pulmonary artery stent thrombosis and subsequent symptomatic pulmonary hypertension. A treatment strategy of anticoagulation alongside pharmacological agents for pulmonary hypertension for 3 months followed by balloon pulmonary artery angioplasty to reopen the stenosis was unsuccessful.
CONCLUSION
In the era of COVID-19, patients with pulmonary vascular malformations and endovascular stents are at an increased risk for chronic thromboembolic disease. Patients may benefit from prophylactic antiplatelet or anticoagulation therapy. Stent thrombosis is a devastating phenomenon and should be treated urgently and aggressively with balloon pulmonary angioplasty, and/or a thrombolytic agent.
Accurate vector optically pumped magnetometer with microwave-driven Rabi frequency measurements
Authors: Kiehl Christopher , Menon Thanmay S. , Knappe Svenja , Thiele Tobias , Regal Cindy A. 
Published: December 2024

Robust calibration of vector optically pumped magnetometers (OPMs) is a
nontrivial task, but increasingly important for applications requiring
high-accuracy such as magnetic navigation, geophysics research, and
space exploration. Here, we showcase a vector OPM that utilizes Rabi
oscillations driven between the hyperfine manifolds of 87Rb to measure the direction of a DC
magnetic field against the polarization ellipse structure of a
microwave field. By relying solely on atomic
measurements—free-induction decay (FID) signals and Rabi measurements
across multiple atomic transitions—this sensor can detect drift in the
microwave vector reference and compensate for systematic shifts caused
by off-resonant driving, nonlinear Zeeman (NLZ) effects, and buffer
gas collisions. To facilitate deadzone-free operation, we also
introduce a Rabi measurement that utilizes dressed-state resonances
that appear during simultaneous Larmor precession and Rabi driving
(SPaR). These measurements, performed within a microfabricated vapor
cell platform, achieve an average vector accuracy of 0.46 mrad
and vector sensitivities down to 11µrad/Hz for geomagnetic field strengths near
50 µT. This performance surpasses the challenging 1-deg
(17 mrad) accuracy threshold of several contemporary OPM
methods utilizing atomic vapors with an electromagnetic vector
reference.
Do we know the chemical bond? A case for the ethical teaching of undefined paradigms
Authors: Kozuch Sebastian 
Published: December 2024

Abstract
The chemical bond is the biggest paradigm in chemistry. But at the same time it is notoriously complex to define it. Under the assumption that knowing what we do not know makes better students and lecturers, we succinctly describe three approaches to define the bond (energetic, structural, and orbital), their advantages and especially their failures. We propose that these definitions, including their theoretical, practical and even philosophical issues, should be taught to advanced undergraduate chemistry students as an essential introduction to the chemical bond module of quantum chemistry courses. This is a controversial topic due to the lack of consensus in the chemical bond community over this heavily disputed topic and the conflicting pedagogical approach; however, and maybe because of this controversy, the teaching of the definitions of the chemical bond including their open questions and challenges can be positively instructive. Moreover, we propose that teaching the uncertainties of chemistry, especially in relation to the paradigmatic chemical bond, is an ethical matter.
Aristotle’s Critique of Form-Number
Authors: Yang Daniel Sung-hyun 
Published: December 2024

Abstract
Aristotle’s classification of ideal number in Metaphysics M 6 has often been considered an unfair presentation of Plato’s actual views. I take another look at the passage and argue that Aristotle is a more careful critic than has been usually recognised. In particular, I argue that much of the scholarly discussion on the passage has failed to take account of Aristotle’s deeper concern, namely, the conditions necessary for numbers to be ordinal. I then set Aristotle’s critique within the broader context of his concern to separate Form from Number, and thus to separate metaphysical questions from mathematical ones. The latter half of the article shows some of the consequences of mixing mathematics with metaphysics from a systematic and historical point of view.
Reninoma: an unusual cause of growth failure
Authors: Vaghasia Nupoor , Jevalikar Ganesh , Kuchay Mohammad Shafi , Lipi Lipika , Mithal Ambrish 
Published: December 2024

Abstract

Objectives
Growth failure can result from various underlying causes, necessitating a thorough evaluation. Reninoma, a rare renin-secreting tumor, is an uncommon cause of hypertension, especially in paediatric patients, and has not been associated with growth failure until now.

Case presentation
An 11-year-old girl presented with complaints of poor height gain, headaches, increased thirst, and vomiting. The evaluation revealed severe hypertension and hypokalemic alkalosis. Investigations indicated renin-dependent hypertension, and imaging identified a right renal mass. Renal venous sampling confirmed renin production from the tumor. A right open partial nephrectomy was performed, resulting in the normalization of blood pressure and improved growth. Over the following years, she achieved a significant catch-up growth, regaining her original height percentile and the target adult height.

Conclusions
This case adds to the limited literature on paediatric reninoma. It highlights a rare presentation of reninoma causing hypertension and growth failure in a child. The growth failure was likely due to hypokalemic alkalosis-induced low insulin-like growth factor 1 (IGF-1) levels, a mechanism not previously documented in paediatric reninoma cases. Surgical excision of the tumor led to normalization of blood pressure and metabolic alkalosis with significant growth recovery.
Japanese speakers can infer specific sub-lexicons using phonotactic cues
Authors: Kawahara Shigeto , Kumagai Gakuji 
Published: December 2024

Abstract
Phonotactic restrictions do not usually hold uniformly across the entire lexicon of a particular language, and thus the lexicon of a natural language is often assumed to consist of different sub-lexicons. A question that arises is how specific these sub-lexicons can be. A classic, conservative approach is to posit only broad distinctions, such as the distinction between native words versus borrowed words. An alternative approach is to posit more specific miniature lexicons, such as a set of morphemes that show a particular morpheme-specific pattern or a set of loanwords from a particular language. With this general theoretical issue in mind, this paper first points out that there are phonotactic restrictions that can cue a very specific class of words in Japanese; for example, geminate /ɾɾ/ occurs almost exclusively in loanwords from Italian. Building upon these novel observations, the current experiments tested whether Japanese speakers can infer specific sets of words such as “snack names”, “Italian restaurant names”, and “German names” based on particular phonotactic cues. The results of the two experiments support the idea that the lexicon of a natural language can consist of very specific sub-lexicons, at least going beyond the often posited native versus loanword distinction.