bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of cancer patient pathway on timing of radiotherapy and survival: a cohort study in glioblastoma patients
Authors: Blakstad Hanne , Mendoza Mireles Eduardo Erasmo , Kierulf-Vieira Kirsten Strømme , Singireddy Divija , Mdala Ibrahimu , Heggebø Liv Cathrine , Magelssen Henriette , Sprauten Mette , Johannesen Tom Børge , Leske Henning , Niehusmann Pitt , Skogen Karoline , Helseth Eirik , Emblem Kyrre Eeg , Vik-Mo Einar O. , Brandal Petter 
Published: May 2024

Abstract
Purpose
Glioblastoma (GBM) is an aggressive brain tumor in which primary therapy is standardized and consists of surgery, radiotherapy (RT), and chemotherapy. However, the optimal time from surgery to start of RT is unknown. A high-grade glioma cancer patient pathway (CPP) was implemented in Norway in 2015 to avoid non-medical delays and regional disparity, and to optimize information flow to patients. This study investigated how CPP affected time to RT after surgery and overall survival.

Methods
This study included consecutive GBM patients diagnosed in South-Eastern Norway Regional Health Authority from 2006 to 2019 and treated with RT. The pre CPP implementation group constituted patients diagnosed 2006–2014, and the post CPP implementation group constituted patients diagnosed 2016–2019. We evaluated timing of RT and survival in relation to CPP implementation.

Results
A total of 1212 patients with GBM were included. CPP implementation was associated with significantly better outcomes (p < 0.001). Median overall survival was 12.9 months. The odds of receiving RT within four weeks after surgery were significantly higher post CPP implementation (p < 0.001). We found no difference in survival dependent on timing of RT below 4, 4–6 or more than 6 weeks (p = 0.349). Prognostic factors for better outcomes in adjusted analyses were female sex (p = 0.005), younger age (p < 0.001), solitary tumors (p = 0.008), gross total resection (p < 0.001), and higher RT dose (p < 0.001).

Conclusion
CPP implementation significantly reduced time to start of postoperative RT. Survival was significantly longer in the period after the CPP implementation, however, timing of postoperative RT relative to time of surgery did not impact survival.
Finite Sample Rates for Logistic Regression with Small Noise or Few Samples
Authors: Kuchelmeister Felix , van de Geer Sara 
Published: May 2024

AbstractThe logistic regression estimator is known to inflate the magnitude of its coefficients if the sample size n is small, the dimension p is (moderately) large or the signal-to-noise ratio $$1/\sigma $$

1
/
σ

is large (probabilities of observing a label are close to 0 or 1). With this in mind, we study the logistic regression estimator with $$p\ll n/\log n$$

p
≪
n
/
log
n

, assuming Gaussian covariates and labels generated by the Gaussian link function, with a mild optimization constraint on the estimator’s length to ensure existence. We provide finite sample guarantees for its direction, which serves as a classifier, and its Euclidean norm, which is an estimator for the signal-to-noise ratio. We distinguish between two regimes. In the low-noise/small-sample regime ($$\sigma \lesssim (p\log n)/n$$

σ
≲
(
p
log
n
)
/
n

), we show that the estimator’s direction (and consequentially the classification error) achieve the rate $$(p\log n)/n$$

(
p
log
n
)
/
n

- up to the log term as if the problem was noiseless. In this case, the norm of the estimator is at least of order $$n/(p\log n)$$

n
/
(
p
log
n
)

. If instead $$(p\log n)/n\lesssim \sigma \lesssim 1$$

(
p
log
n
)
/
n
≲
σ
≲
1

, the estimator’s direction achieves the rate $$\sqrt{\sigma p\log n/n}$$

σ
p
log
n
/
n

, whereas its norm converges to the true norm at the rate $$\sqrt{p\log n/(n\sigma ^3)}$$

p
log
n
/
(
n

σ
3

)

. As a corollary, the data are not linearly separable with high probability in this regime. In either regime, logistic regression provides a competitive classifier.
Synthesis and Characterization of WNiFeCo, WNiFeMo, and WNiFeCoMo Compositional Complex Alloys Manufactured by Powder Metallurgy Technique
Authors: Abolkassem Shimaa A. , El-Hadad Shimaa , Mohamed Lamiaa Z. 
Published: May 2024

Abstract
The WNiFeCo, WNiFeMo, and WNiFeCoMo compositional complex alloys (CCAs) were prepared by powder metallurgy technique. The thermodynamic investigations of the CCAs proved that WNiFeCo, and WNiFeMo, are medium entropy alloys (MEAs), whereas WNiFeCoMo is a high entropy alloy (HEA). The density of the prepared specimens was estimated. The sintered CCAs were characterized by investigating their microstructures and elemental distribution using SEM and EDX analysis. The crystal structure of the different phases was identified utilizing X-ray diffraction (XRD). From XRD results, W, Fe7W6, and FeNi were observed in all CCAs, whereas Co7W6, MoNi4, and Co7Mo6 phases were found in WNiFeCoMo HEA. WNiFeCo MEA contained a Co7W6 phase, while the MoNi4 phase was observed in WNiFeCo MEA. The A7B6 phases are formed in the CCAs which have good characteristics. The hardness, Young’s modulus, and corrosion behavior were evaluated. Among the investigated CCAs, WNiFeMo MEA showed the highest relative density percentage (95%), Young’s modulus (190 GPa), hardness (451 HV), and lowest corrosion rate in 3.5% NaCl (0.22 mm/y). The surface morphology of the WNiFeCo, WNiFeMo, and WNiFeCoMo alloys displayed uniform corrosion, galvanic corrosion, and localized corrosion.
Isometric Exercise Training and Arterial Hypertension: An Updated Review
Authors: Edwards Jamie J. , Coleman Damian A. , Ritti-Dias Raphael M. , Farah Breno Q. , Stensel David J. , Lucas Sam J. E. , Millar Philip J. , Gordon Ben D. H. , Cornelissen Véronique , Smart Neil A. , Carlson Debra J. , McGowan Cheri , Swaine Ian , Pescatello Linda S. , Howden Reuben , Bruce-Low Stewart , Farmer Christopher K. T. , Leeson Paul , Sharma Rajan , O’Driscoll Jamie M. 
Published: May 2024

AbstractHypertension is recognised as a leading attributable risk factor for cardiovascular disease and premature mortality. Global initiatives towards the prevention and treatment of arterial hypertension are centred around non-pharmacological lifestyle modification. Exercise recommendations differ between professional and scientific organisations, but are generally unanimous on the primary role of traditional aerobic and dynamic resistance exercise. In recent years, isometric exercise training (IET) has emerged as an effective novel exercise intervention with consistent evidence of reductions in blood pressure (BP) superior to that reported from traditional guideline-recommended exercise modes. Despite a wealth of emerging new data and endorsement by select governing bodies, IET remains underutilised and is not widely prescribed in clinical practice. This expert-informed review critically examines the role of IET as a potential adjuvant tool in the future clinical management of BP. We explore the efficacy, prescription protocols, evidence quality and certainty, acute cardiovascular stimulus, and physiological mechanisms underpinning its anti-hypertensive effects. We end the review with take-home suggestions regarding the direction of future IET research.
Total osteocalcin levels are independently associated with worse testicular function and a higher degree of hypothalamic–pituitary–gonadal axis activation in Klinefelter syndrome
Authors: Carlomagno F. , Hasenmajer V. , Spaziani M. , Tenuta M. , Sesti F. , Tarantino C. , Pozza C. , Isidori A. M. , Gianfrilli D. 
Published: May 2024

Abstract
Purpose
The role of osteocalcin (OCN) in pubertal development, male hypogonadism, and the effect of testosterone (Te) replacement therapy (TRT) remains unclear. We aimed to investigate the total OCN (tOCN) concentrations in male patients with Klinefelter syndrome (KS), a model of adult hypergonadotropic hypogonadism.

Methods
This retrospective longitudinal study investigated 254 male patients with KS (47,XXY) between 2007 and 2021 at an academic referral center, categorized as (1) prepubertal, (2) pubertal, and (3) adults. All prepubertal patients were Te-naïve. Adult patients were subcategorized as (1) eugonadal, (2) hypogonadal, and (3) receiving TRT. We also analyzed 18 adult patients with available tOCN levels before and 3 months after TRT commencement.

Results
The tOCN levels varied throughout the lifespan according to pubertal status, were highest in eugonadal and significantly lower in TRT subjects, correlated with both LH (p = 0.017) and FSH levels (p = 0.004) in adults, and significantly declined after 3 months of TRT (p = 0.006) in the adult KS cohort. HPG-axis hormones levels demonstrated no correlation in prepubertal boys. Adjustment for age and body mass index confirmed previous results and revealed significant inverse correlations with total Te (p = 0.004), calculated free Te (p = 0.016), the Te/LH (p = 0.010), and calculated free Te/LH ratios (p = 0.031).

Conclusion
In KS, a model of male hypergonadotropic hypogonadism, tOCN levels were not associated with gonadal function during normal prepuberty and pubertal development but were associated with worse testicular function and a higher degree of HPG stimulation in adults. TRT acutely reduced tOCN levels in adults.
Influence of wax addition on feedstock processing behavior in additive manufacturing of metals by material extrusion
Authors: Forstner Thomas , Cholewa Simon , Drummer Dietmar 
Published: May 2024

AbstractThe additive manufacturing of metals by material extrusion in a multi-step process (MEX-MSt/M) represents a special process variant of the commonly used material extrusion (MEX) and is based on the processing of highly filled polymer filaments. This technology uses the geometrical freedom and fast processing given by MEX to create individual metal parts after a debinding and sintering process in a cost and time-efficient way. The filaments for MEX-MSt/M are made by incorporating metal powders, such as aluminum, stainless steel, or bronze into a polymer matrix. Due to the challenges that are assigned to the processing of highly filled polymers, like the increased viscosity of the material or clogging of the nozzle, the binder materials have to meet several requirements. Therefore, waxes are often used to enable a better extrusion behavior for MEX; however, the addition of wax also affects other crucial processing properties of the filaments. In this work, the interactions of different types and amounts of waxes on thermal, mechanical, and rheological properties were investigated to create a better understanding of the alternating effects of wax addition into highly filled filaments for processing via MEX. The study demonstrated that an increase in wax contents resulted in both a significant decrease in ductility and an overall improvement in melt flowability. The choice of waxes also affected the particle–matrix interactions, partly leading to an improved wetting of the filler particles.
Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment
Authors: Madronich S. , Bernhard G. H. , Neale P. J. , Heikkilä A. , Andersen M. P. Sulbæk , Andrady A. L. , Aucamp P. J. , Bais A. F. , Banaszak A. T. , Barnes P. J. , Bornman J. F. , Bruckman L. S. , Busquets R. , Chiodo G. , Häder D.-P. , Hanson M. L. , Hylander S. , Jansen M. A. K. , Lingham G. , Lucas R. M. , Calderon R. Mackenzie , Olsen C. , Ossola R. , Pandey K. K. , Petropavlovskikh I. , Revell L. E. , Rhodes L. E. , Robinson S. A. , Robson T. M. , Rose K. C. , Schikowski T. , Solomon K. R. , Sulzberger B. , Wallington T. J. , Wang Q.-W. , Wängberg S.-Å. , White C. C. , Wilson S. R. , Zhu L. , Neale R. E. 
Published: May 2024

AbstractThe protection of Earth’s stratospheric ozone (O3) is an ongoing process under the auspices of the universally ratified Montreal Protocol and its Amendments and adjustments. A critical part of this process is the assessment of the environmental issues related to changes in O3. The United Nations Environment Programme’s Environmental Effects Assessment Panel provides annual scientific evaluations of some of the key issues arising in the recent collective knowledge base. This current update includes a comprehensive assessment of the incidence rates of skin cancer, cataract and other skin and eye diseases observed worldwide; the effects of UV radiation on tropospheric oxidants, and air and water quality; trends in breakdown products of fluorinated chemicals and recent information of their toxicity; and recent technological innovations of building materials for greater resistance to UV radiation. These issues span a wide range of topics, including both harmful and beneficial effects of exposure to UV radiation, and complex interactions with climate change. While the Montreal Protocol has succeeded in preventing large reductions in stratospheric O3, future changes may occur due to a number of natural and anthropogenic factors. Thus, frequent assessments of potential environmental impacts are essential to ensure that policies remain based on the best available scientific knowledge.
Graphical abstract
Dissecting the neuroanatomy of creativity and curiosity: The subdivisions within networks matter
Authors: Chiou Rocco , Branzi Francesca M. , Krieger-Redwood Katya , Jefferies Elizabeth 
Published: May 2024

Abstract
Ivancovsky et al. argue that the neurocognitive mechanisms of creativity and curiosity both rely on the interplay among brain networks. Research to date demonstrates that such inter-network dynamics are further complicated by functional fractionation within networks. Investigating how networks subdivide and reconfigure in service of a task offers insights about the precise anatomy that underpins creative and curious behaviour.
Traumainformierte Psychiatrie
Authors: Zuaboni Gianfranco , Rixe Jacqueline , Schulz Michael 
Published: May 2024

Was ist zu diesem Thema bereits bekannt? Traumata sind bei Menschen, die psychiatrische Hilfe in Anspruch nehmen, weitverbreitet. Wie wird die neue Perspektive eingebracht? Die traumainformierte Betreuung und Begleitung (Trauma-Informed Care) ist ein aufkommender Ansatz, der als Basis für eine personenzentrierte und zeitgemäße Praxis der psychiatrischen Akutpflege dient. Die Herausforderung besteht darin, die zugrundeliegenden Werte in die alltägliche Pflegepraxis umzusetzen. Was sind die Auswirkungen für die Praxis? In diesem Beitrag wird der Ansatz beschrieben und die Implementierung in die tägliche Praxis der psychiatrischen Akutstationen aufgezeigt.
Seipin deficiency-induced lipid dysregulation leads to hypomyelination-associated cognitive deficits via compromising oligodendrocyte precursor cell differentiation
Authors: Cui Wenli , Yang Jing , Tu Chuanyun , Zhang Ziting , Zhao Huifang , Qiao Yan , Li Yanqiu , Yang Wulin , Lim Kah-Leong , Ma Quanhong , Zhang Chengwu , Lu Li 
Published: May 2024

AbstractSeipin is one key mediator of lipid metabolism that is highly expressed in adipose tissues as well as in the brain. Lack of Seipin gene, Bscl2, leads to not only severe lipid metabolic disorders but also cognitive impairments and motor disabilities. Myelin, composed mainly of lipids, facilitates nerve transmission and is important for motor coordination and learning. Whether Seipin deficiency-leaded defects in learning and motor coordination is underlined by lipid dysregulation and its consequent myelin abnormalities remains to be elucidated. In the present study, we verified the expression of Seipin in oligodendrocytes (OLs) and their precursors, oligodendrocyte precursor cells (OPCs), and demonstrated that Seipin deficiency compromised OPC differentiation, which led to decreased OL numbers, myelin protein, myelinated fiber proportion and thickness of myelin. Deficiency of Seipin resulted in impaired spatial cognition and motor coordination in mice. Mechanistically, Seipin deficiency suppressed sphingolipid metabolism-related genes in OPCs and caused morphological abnormalities in lipid droplets (LDs), which markedly impeded OPC differentiation. Importantly, rosiglitazone, one agonist of PPAR-gamma, substantially restored phenotypes resulting from Seipin deficiency, such as aberrant LDs, reduced sphingolipids, obstructed OPC differentiation, and neurobehavioral defects. Collectively, the present study elucidated how Seipin deficiency-induced lipid dysregulation leads to neurobehavioral deficits via impairing myelination, which may pave the way for developing novel intervention strategy for treating metabolism-involved neurological disorders.
Deep learning of left atrial structure and function provides link to atrial fibrillation risk
Authors: Pirruccello James P. , Di Achille Paolo , Choi Seung Hoan , Rämö Joel T. , Khurshid Shaan , Nekoui Mahan , Jurgens Sean J. , Nauffal Victor , Kany Shinwan ,   FinnGen, Ng Kenney , Friedman Samuel F. , Batra Puneet , Lunetta Kathryn L. , Palotie Aarno , Philippakis Anthony A. , Ho Jennifer E. , Lubitz Steven A. , Ellinor Patrick T. 
Published: May 2024

AbstractIncreased left atrial volume and decreased left atrial function have long been associated with atrial fibrillation. The availability of large-scale cardiac magnetic resonance imaging data paired with genetic data provides a unique opportunity to assess the genetic contributions to left atrial structure and function, and understand their relationship with risk for atrial fibrillation. Here, we use deep learning and surface reconstruction models to measure left atrial minimum volume, maximum volume, stroke volume, and emptying fraction in 40,558 UK Biobank participants. In a genome-wide association study of 35,049 participants without pre-existing cardiovascular disease, we identify 20 common genetic loci associated with left atrial structure and function. We find that polygenic contributions to increased left atrial volume are associated with atrial fibrillation and its downstream consequences, including stroke. Through Mendelian randomization, we find evidence supporting a causal role for left atrial enlargement and dysfunction on atrial fibrillation risk.
Copper isotopes track the Neoproterozoic oxidation of cratonic mantle roots
Authors: Chen Chunfei , Foley Stephen F. , Shcheka Svyatoslav S. , Liu Yongsheng 
Published: May 2024

AbstractThe oxygen fugacity (fO2) of the lower cratonic lithosphere influences diamond formation, melting mechanisms, and lithospheric evolution, but its redox evolution over time is unclear. We apply Cu isotopes (δ65Cu) of ~ 1.4 Ga lamproites and < 0.59 Ga silica-undersaturated alkaline rocks from the lithosphere-asthenosphere boundary (LAB) of the North Atlantic Craton to characterize fO2 and volatile speciation in their sources. The lamproites’ low δ65Cu (−0.19 to −0.12‰) show that the LAB was metal-saturated with CH4 + H2O as the dominant volatiles during the Mesoproterozoic. The mantle-like δ65Cu of the < 0.59 Ga alkaline rocks (0.03 to 0.15‰) indicate that the LAB was more oxidized, stabilizing CO2 + H2O and destabilizing metals. The Neoproterozoic oxidation resulted in an increase of at least 2.5 log units in fO2 at the LAB. Combined with previously reported high fO2 in peridotites from the Slave, Kaapvaal, and Siberia cratonic roots, this oxidation might occur in cratonic roots globally.
Cellular structure of dinosaur scales reveals retention of reptile-type skin during the evolutionary transition to feathers
Authors: Yang Zixiao , Jiang Baoyu , Xu Jiaxin , McNamara Maria E. 
Published: May 2024

AbstractFossil feathers have transformed our understanding of integumentary evolution in vertebrates. The evolution of feathers is associated with novel skin ultrastructures, but the fossil record of these changes is poor and thus the critical transition from scaled to feathered skin is poorly understood. Here we shed light on this issue using preserved skin in the non-avian feathered dinosaur Psittacosaurus. Skin in the non-feathered, scaled torso is three-dimensionally replicated in silica and preserves epidermal layers, corneocytes and melanosomes. The morphology of the preserved stratum corneum is consistent with an original composition rich in corneous beta proteins, rather than (alpha-) keratins as in the feathered skin of birds. The stratum corneum is relatively thin in the ventral torso compared to extant quadrupedal reptiles, reflecting a reduced demand for mechanical protection in an elevated bipedal stance. The distribution of the melanosomes in the fossil skin is consistent with melanin-based colouration in extant crocodilians. Collectively, the fossil evidence supports partitioning of skin development in Psittacosaurus: a reptile-type condition in non-feathered regions and an avian-like condition in feathered regions. Retention of reptile-type skin in non-feathered regions would have ensured essential skin functions during the early, experimental stages of feather evolution.
The SUN-family protein Sad1 mediates heterochromatin spatial organization through interaction with histone H2A-H2B
Authors: Sun Wenqi , Dong Qianhua , Li Xueqing , Gao Jinxin , Ye Xianwen , Hu Chunyi , Li Fei , Chen Yong 
Published: May 2024

AbstractHeterochromatin is generally associated with the nuclear periphery, but how the spatial organization of heterochromatin is regulated to ensure epigenetic silencing remains unclear. Here we found that Sad1, an inner nuclear membrane SUN-family protein in fission yeast, interacts with histone H2A-H2B but not H3-H4. We solved the crystal structure of the histone binding motif (HBM) of Sad1 in complex with H2A-H2B, revealing the intimate contacts between Sad1HBM and H2A-H2B. Structure-based mutagenesis studies revealed that the H2A-H2B-binding activity of Sad1 is required for the dynamic distribution of Sad1 throughout the nuclear envelope (NE). The Sad1-H2A-H2B complex mediates tethering telomeres and the mating-type locus to the NE. This complex is also important for heterochromatin silencing. Mechanistically, H2A-H2B enhances the interaction between Sad1 and HDACs, including Clr3 and Sir2, to maintain epigenetic identity of heterochromatin. Interestingly, our results suggest that Sad1 exhibits the histone-enhanced liquid-liquid phase separation property, which helps recruit heterochromatin factors to the NE. Our results uncover an unexpected role of SUN-family proteins in heterochromatin regulation and suggest a nucleosome-independent role of H2A-H2B in regulating Sad1’s functionality.
Ciliary tip actin dynamics regulate photoreceptor outer segment integrity
Authors: Megaw Roly , Moye Abigail , Zhang Zhixian , Newton Fay , McPhie Fraser , Murphy Laura C. , McKie Lisa , He Feng , Jungnickel Melissa K. , von Kriegsheim Alex , Tennant Peter A. , Brotherton Chloe , Gurniak Christine , Gross Alecia K. , Machesky Laura M. , Wensel Theodore G. , Mill Pleasantine 
Published: May 2024

AbstractAs signalling organelles, cilia regulate their G protein-coupled receptor content by ectocytosis, a process requiring localised actin dynamics to alter membrane shape. Photoreceptor outer segments comprise an expanse of folded membranes (discs) at the tip of highly-specialised connecting cilia, into which photosensitive GPCRs are concentrated. Discs are shed and remade daily. Defects in this process, due to mutations, cause retinitis pigmentosa (RP). Whilst fundamental for vision, the mechanism of photoreceptor disc generation is poorly understood. Here, we show membrane deformation required for disc genesis is driven by dynamic actin changes in a process akin to ectocytosis. We show RPGR, a leading RP gene, regulates actin-binding protein activity central to this process. Actin dynamics, required for disc formation, are perturbed in Rpgr mouse models, leading to aborted membrane shedding as ectosome-like vesicles, photoreceptor death and visual loss. Actin manipulation partially rescues this, suggesting the pathway could be targeted therapeutically. These findings help define how actin-mediated dynamics control outer segment turnover.