bluuebunny/crossref_metadata_2025 huggingface dataset:
Zum Biegeknicken von Sandwichelementen
Authors: Janczyk Kevin , Nonn Jonas , Kuhnhenne Markus , Feldmann Markus
Published: November 2023

Sandwichelemente stellen eines der markführenden Systeme für die Gebäudehülle im Industrie‐ und Gewerbebau dar. Ein weiterer Anwendungsbereich sind bspw. Kühlräume, welche ausschließlich aus Sandwichelementen ohne Unterkonstruktion und Primärtragstruktur realisiert werden. Hierbei werden die Sandwichelemente, die als Wandelemente eingesetzt werden, axial belastet. Ein auf Spannungsnachweisen basierendes Bemessungskonzept von Sandwichelementen unter axialer Beanspruchung findet sich im Entwurf des neuen Eurocode 3 prEN 1993‐7 „Bemessung und Konstruktion von Stahlbauten – Sandwichelemente“. Ein Nachweiskonzept, welches auf den geometrischen und strukturellen Imperfektionen und der tatsächlichen Tragfähigkeit der Elemente basiert, ist weder in der Literatur noch im Entwurf der neuen Norm enthalten. Im Rahmen der vorliegenden Arbeit werden Untersuchungen zum Biegeknicken vorgestellt. Es wird eine Methode präsentiert, welche zukünftig für die Erarbeitung von Knickspannungslinien von Sandwichelementen verwendet werden kann.
Creating Pure Spaces: Edifices, Domesticity and the Temperance Movement
Authors: Ratschiller Nasim Linda Maria
Published: November 2023

This chapter argues that the religious ideal of purity could only be maintained in the long run if there were spaces where it held true in an exemplary fashion. Therefore, the Basel missionaries aspired to create pure spaces in the form of Christian villages, domestic safe havens and sobriety societies. A central policy of the Basel Mission consisted of establishing separate Christian settlements for their parishioners within rural contexts, referred to as “salems” in West Africa. The Pietist family model formed the core of the civilising project, in which women and domesticity ultimately guaranteed the perpetuation of cleanliness and purity. The struggle for what missionaries perceived as the reinvigoration of the Christian family among the poor at home and the heathens abroad was a transregional expression of Pietist purity efforts. The temperance movement offers another example of how born-again Christians in both Europe and West Africa aspired to create pure spaces, where the people they sought to protect would find shelter from the seemingly harmful consequences of modern life.
Therapiealgorithmus der Patellainstabilität
Authors: Wierer G. , Pfeiffer T. , Schlumberger M. , Dirisamer F. , Attal R. , Becher Ch. , Frings J. , Hinz M. , Kappel P. , Keshmiri A. , Liebensteiner M. , Nelitz M. , Pagenstert G. , Runer A. , Wagner D. , Zimmermann F. , Schöttle P. , Seitlinger G. , Balcarek P.
Published: November 2023

Der „AGA Therapiealgorithmus der Patellainstabilität“ (ATAPI) basiert auf der klinischen Untersuchung, der Bildgebung und dem daraus resultierenden Risikoprofil. Im ersten Schritt wird eine mögliche Flake-Fraktur mittels Bildgebung detektiert. Im zweiten Schritt wird das individuelle Risiko einer Reluxation in Abhängigkeit der vorliegenden anatomischen und epidemiologischen Parameter erfasst. Bei niedrigem Risikoprofil ohne Flake-Fraktur wird primär die konservative Therapie empfohlen. Bei vorhandener Flake-Fraktur wird eine Refixation des Fragments angestrebt. Eine zusätzliche Rekonstruktion des medialen patellofemoralen Ligaments (MPFL) senkt das Reluxationsrisiko deutlich und wird auch als Grundpfeiler der operativen Therapie gesehen. Je nach Risikoprofil werden weitere Zusatzeingriffe in Erwägung gezogen. Somit besteht auch bei Patellaluxation ohne Flake-Fraktur aber hohem Risikoprofil die Indikation zur Operation.
Comparing perfomance abstractions for collective adaptive systems
Authors: Murgia Maurizio , Pinciroli Riccardo , Trubiani Catia , Tuosto Emilio
Published: November 2023

Non-functional properties of collective adaptive systems (CAS) are of paramount relevance practically in any application. This paper compares two recently proposed approaches to quantitative modelling that exploit different system abstractions: the first is based on generalised stochastic Petri nets, and the second is based on queueing networks. Through a case study involving autonomous robots, we analyse and discuss the relative merits of the approaches. This is done by considering three scenarios which differ on the architecture used to coordinate the distributed components. Our experimental results assess a high accuracy when comparing model-based performance analysis results derived from two different quantitative abstractions for CAS.
Enzymatic synthesis of polypeptides in natural deep eutectic solvents
Authors: Hernández-Alonso Ángel , Pérez-García Vanessa , López-Medina Jared , Cedeño-Caero Luis , Trapala Jonathan , Montiel Carmina , Bustos-Jaimes Ismael , Gimeno Miquel
Published: November 2023

We are first to report the protease-catalyzed polypeptide synthesis in the natural deep eutectic solvent (DES) choline chloride/glycerol (ChCl:Gly) at a 1:2 molar ratio with 30 vol% of water using subtilisin Carlsberg (alkaline protease fromBacillus licheniformis). Poly-L-phenylalanine, poly-a-L-lysine, and the co-polypeptides poly(L-phenylalanine-a-L-lysine) as model polypeptides are produced from amino acid ester substrates in 40–70% yield and molecular weights ranging from 5 to 14 KDa according to dynamic light scattering (DLS). The natural DES is composed of 30 vol% water, whereas no polypeptides are formed at lower water contents. Poly-L-phenylalanine displays supramolecular self-assembly into homogenous nanotubes in water/isopropyl alcohol mixtures. This enzymatic route to polypeptides has advantages over previous reports in water and polar compressed fluids because of the higher molecular weights and greener process, respectively.
Cover crop effects on fibrous roots and growth of subsequent sugar beet
Authors: Grunwald Dennis , Koch Heinz-Josef
Published: November 2023

Purpose

Cover crops (CC) may increase root growth of the following main crop by improving the soil structure, however, the extent of this effect might depend on the CC species. This study aims at quantifying the effects of different CCs on sugar beet (SB; Beta vulgaris L.) fibrous roots and plant growth.

Methods

Two field trials were conducted near Göttingen, Central Germany, with SB after four CC treatments: fallow, oil radish, saia oat, and spring vetch, differing in biomass. SB root length density and biomass was analyzed to 60 cm soil depth in July, around 100 days after sowing. From June on, plants were sampled monthly to determine leaf and taproot biomass. CC biomass and SB residues were further analyzed for carbon content.

Results

SB root length density in 0–20 cm soil depth was increased by the CCs, particularly radish and oat, while in lower depths only non-significant differences were found. Differences between the CC treatments regarding SB leaf and taproot biomass were site-specific with increases in SB biomass after CCs at a site with high N supply, yet no effects on sugar yield were found for either site. Carbon input into the soil was significantly increased through CC cultivation by 47 to 85%.

Conclusion

CCs with different properties improved fibrous root and overall plant growth of SB to a different extent at sites with contrasting conditions. Future studies under diverse environmental conditions are needed to fully assess the potential benefits of CCs on following SB growth.
Effects of drug-induced sleep endoscopy in children with conventional obstructive sleep apnea–hypopnea syndrome: a systematic review and meta-analysis
Authors: Wang Xin , Chen Yong-chao , Li Lan , Pan Hong-guang , Teng Yi-shu
Published: November 2023

Purpose

This study aimed to conduct a meta-analysis and systematic review of drug-induced sleep endoscopy (DISE) in pediatric conventional obstructive sleep apnea–hypopnea syndrome (OSAHS) without previous upper airway surgery, or comorbidity, to evaluate the change in treatment strategies and to identify obstructive sites observed during DISE. This study aimed to explore the role of DISE in the management of pediatric conventional OSAHS.

Methods

A comprehensive search was conducted using both computerized and manual methods to retrieve relevant case studies on DISE-guided treatment of pediatric conventional OSAHS from databases including PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, WF, and VIP database. The search period extended from database inception to January 2023. Strict inclusion and exclusion criteria were applied to select relevant literature, and data extraction was performed accordingly. Meta-analysis was conducted using the Stata 16.0 software.

Results

A total of 761 patients from four studies were included in the meta-analysis. All pediatric patients had no history of upper airway surgery, craniofacial abnormalities, or syndromes other than OSAHS. The quality assessment revealed that the included studies were of low methodological quality and consisted of non-randomized case studies. Meta-analysis results indicated that in pediatric patients with OSAHS, the obstruction rates observed during DISE were as follows: nasopharyngeal (adenoid) obstruction 93%, soft palate obstruction 35%, oropharyngeal (tonsil) obstruction 76%, tongue base obstruction 32%, supraglottic obstruction 31%, and multi-level obstruction 60%. DISE led to a change in the conventional surgical approach in 45% (95% CI: 29–60%) of patients with OSAHS, providing individualized treatment plans. Postoperative symptoms and sleep-related parameters improved significantly compared to preoperative values, with DISE findings possibly enhancing surgical success rates and potentially avoiding unnecessary procedures.

Conclusion

In some cases, DISE may potentially lead to alterations in conventional surgical approaches for children with OSAHS who had no history of upper airway surgery, craniofacial abnormalities, or other syndromes.. The results of our meta-analysis were in favor of DISE-directed approach for pediatric conventional OSAHS. However, further high-quality randomized controlled trials (RCTs) are warranted in future research to investigate the role of DISE in the management of pediatric OSAHS.
Outcomes of Concurrent Hiatus Hernia Repair with Different Bariatric Surgery Procedures: a Systematic Review and Meta-analysis
Authors: Mills Henry , Alhindi Yousef , Idris Iskandar , Al-Khyatt Waleed
Published: November 2023

Background

Hiatus hernia (HH) is prevalent among patients with obesity. Concurrent repair is often performed during metabolic and bariatric surgery (MBS), but a consensus on the safety and effectiveness of concurrent HH repair (HHR) and MBS remains unclear. We performed a systematic review of the safety and effectiveness of concurrent HHR and MBS through the measurement of multiple postoperative outcomes.

Method

Seventeen studies relating to concurrent MBS and HHR were identified. MBS procedures included laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (LRYGB), and adjustable gastric banding (LAGB). Studies with pre- and postoperative measurements and outcomes were extracted.

Results

For LSG, 9 of 11 studies concluded concurrent procedures to be safe and effective with no increase in mortality. Reoperation and readmission rates however were increased with HHR, whilst GORD rates were seen to improve, therefore providing a solution to the predominant issue with LSG. For LRYGB, in all 5 studies, concurrent procedures were concluded to be safe and effective, with no increase in mortality, length of stay, readmission and reoperation rates. Higher complication rates were observed compared to LSG with HHR. Among LAGB studies, all 4 studies were concluded to be safe and effective with no adverse outcomes on mortality and length of stay. GORD rates were seen to decrease, and reoperation rates from pouch dilatation and gastric prolapse were observed to significantly decrease.

Conclusion

Concurrent HHR with MBS appears to be safe and effective. Assessment of MBS warrants the consideration of concurrent HHR depending on specific patient case and the surgeon’s preference.

Graphical Abstract
Clinical Trial Protocol for BEACH: A Phase 2a Study of MW189 in Patients with Acute Nontraumatic Intracerebral Hemorrhage
Authors: Avadhani Radhika , Ziai Wendy C. , Thompson Richard E. , Mould W. Andrew , Lane Karen , Nanni Angeline , Iacobelli Michael , Sharrock Matthew F. , Sansing Lauren H. , Van Eldik Linda J. , Hanley Daniel F. ,   on behalf of the BEACH trial consortium, Lord Aaron , Liptrap Elizabeth , Zuccarello Mario , Hatton Kevin , Girotra Tarun , Chang Tiffany , Mascitelli Justin , Magid-Bernstein Jessica , Babi Marc
Published: November 2023

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability of MW189 in patients with acute ICH, identify trends in potential mitigation of neuroinflammation and cerebral edema, and assess effects on functional outcomes. A total of 120 participants with nontraumatic ICH will be randomly assigned 1:1 to receive intravenous MW189 (0.25 mg/kg) or placebo (saline) within 24 h of symptom onset and every 12 h for up to 5 days or until hospital discharge. The 120-participant sample size (60 per group) will allow testing of the null hypothesis of noninferiority with a tolerance limit of 12% and assuming a “worst-case” safety assumption of 10% rate of death in each arm with 10% significance and 80% power. The primary outcome is all-cause mortality at 7 days post randomization between treatment arms. Secondary end points include all-cause mortality at 30 days, perihematomal edema volume after symptom onset, adverse events, vital signs, pharmacokinetics of MW189, and inflammatory cytokine concentrations in plasma (and cerebrospinal fluid if available). Other exploratory end points are functional outcomes collected on days 30, 90, and 180. BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute central nervous system injury.
Integrated Analysis of Chromatin and Transcriptomic Profiling Identifies PU.1 as a Core Regulatory Factor in Microglial Activation Induced by Chronic Cerebral Hypoperfusion
Authors: Zhang Zengyu , Jin Pengpeng , Guo Zimin , Tu Zhilan , Yang Hualan , Hu Mengting , Li Qinghua , Liu Xingdang , Li Weiwei , Hou Shuangxing
Published: November 2023

In addition to causing white matter lesions, chronic cerebral hypoperfusion (CCH) can also cause damage to gray matter, but the underlying molecular mechanisms remain largely unknown. In order to obtain a better understanding of the relationship between gene expression and transcriptional regulation alterations, novel upstream regulators could be identified using integration analysis of the transcriptome and epigenetic approaches. Here, a bilateral common carotid artery stenosis (BCAS) model was established for inducing CCH in mice. The spatial cognitive function of mice was evaluated, and changes in cortical microglia morphology were observed. RNA-sequencing (RNA-seq) and the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were performed on isolated mouse cortical brain tissue. Then, a systematic joint analysis of BCAS hypoperfusion-induced cortex-specific RNA-seq and ATAC-seq was conducted in order to assess the extent of the correlation between the two, and PU.1 was found to be greatly enriched through motif analysis and transcription factor annotation. Also, the core regulatory factor PU.1 induced by BCAS hypoperfusion was shown to be colocalized with microglia. Based on the above analysis, PU.1 plays a key regulatory role in microglial activation induced by CCH. And the transcriptome and epigenomic data presented in this study can help identify potential targets for future research exploring chronic hypoperfusion-induced brain injury.
Prediction of pollutant removal from aqueous solutions using magnetic photocatalysts
Authors: Abbasi Sedigheh , Tahari Mostafa , Imani Mohammad
Published: November 2023

In this research, magnetic nanocomposite (MGO@TiO2) consisting of Fe3O4, TiO2 and graphene oxide is synthesized for the photocatalytic removal of methyl orange, and its photocatalytic activity is compared with the nanohybrid (Fe3O4@TiO2) without graphene oxide. The crystalline phases of both photocatalysts are determined using X-ray diffraction patterns. The results show that the removal efficiency of methyl orange using the synthesized nanohybrid and nanocomposite is affected by the irradiation time and the pH of the suspension. Comparing the removal efficiency of methyl orange using synthesized photocatalysts shows that the photocatalytic activity of nanocomposite is much higher than that of nanohybrid. The statistical analysis of the experimental data using the response surface method led to the selection of the quadratic model as the best statistical model to estimate the removal efficiency of methyl orange. Also, the numerical and graphical methods confirmed the adequacy of the quadratic statistical model.
Treatment of paraffin deposition behavior in gas-condensate wells with chemical inhibitors
Authors: Shi Bowen , Hong Jiajun , Wang Zhihua , Chang Zhenbo , Li Feng
Published: November 2023

As deep gas-condensate reservoirs are explored, the problem of paraffin deposition is becoming more prominent. Therefore, this paper collects condensate samples from representative paraffin deposition gas-condensate wells and analyzes basic physical properties. The cold plate deposition device is employed to study paraffin deposition behavior under well conditions and to divide the critical regions for paraffin deposition in gas-condensate wells. The experimental apparatus, such as the crude oil dynamic paraffin deposition rate tester, is utilized to investigate the preventive effect of paraffin dispersants and paraffin crystal modifier. The results show that there is significant phase change behavior in gas-condensate wells and gas phase is dominant form, but there is also phase evolution. It can be identified from the experiments that paraffin deposition is mainly located in the 1000 ~ 1500 m region, and a paraffin deposition identification chart has been established. The maximum deposition rate could reach 15.50 mm/year, which matched the temperature and pressure conditions of 45 ℃ and 70 MPa. The preventive effect of paraffin crystal modifiers greatly exceeds that of paraffin dispersants, with paraffin prevention rates of 85–95% at the optimal concentrations of 0.25–0.50 wt.%. The dissolving paraffin rate can reach 0.0169 g/min. It decreases the paraffin appearance temperature approximately 40% and significantly changes the paraffin crystal morphology. Increased deposition surface area of the cold plate structural design describes the paraffin deposition. This diagram facilitates the reliable identification of paraffin deposition areas and the deposition rates in the wellbore during production. The optimum amounts of BZ and PI paraffin inhibitors are quantified. This study provides a comprehensive understanding of the paraffin deposition behavior, and scientific basis and guidance for the selection of paraffin inhibitors in gas-condensate wells.
On the spectrum of exterior algebra, and generalized exponents of small representations
Authors: Di Trani Sabino
Published: November 2023

We present some results about the irreducible representations appearing in the exterior algebra $$\Lambda \mathfrak {g}$$

Λ
g

, where $$\mathfrak {g}$$
g
is a simple Lie algebra over $${\mathbb {C}}$$
C
. For Lie algebras of type B, C or D we prove that certain irreducible representations, associated to weights characterized in a combinatorial way, appear as irreducible components of $$\Lambda \mathfrak {g}$$

Λ
g

. Moreover, we propose an analogue of a conjecture of Kostant, about irreducibles appearing in the exterior algebra of the little adjoint representation. Finally, we give some closed expressions, in type B, C and D, for generalized exponents of small representations that are fundamental representations and we propose a generalization of some results of De Concini, Möseneder Frajria, Procesi and Papi about the module of special covariants of adjoint and little adjoint type.
Hives but no urticaria—what could it be?
Authors: Sulk Mathias , Albers Carolin C. , Wulf Maria , Braun Stephan A. , Hammers Christoph M. , Heine Guido
Published: November 2023

Urticaria is a common inflammatory dermatosis characterized by transient, usually intensely itching wheals mediated by mast cells. Urticarial lesions can also be mimicked by other skin diseases. Differential diagnoses of urticaria should be considered if the single urticarial skin lesion persists for more than 24 h, if hyperpigmentation, scaling, or blistering occurs, if the lesions are not itching, or if fever or arthralgias are reported. In these cases, histologic examination and thorough serologic diagnostic may help to differentiate other dermatoses, such as vasculitis, autoimmune bullous skin diseases, drug reactions, or autoinflammatory syndromes. This article summarizes common differential diagnoses of urticaria.
The Politics of Working Life and Meaningful Waged Work
Authors: Laaser Knut , Karlsson Jan Ch.
Published: November 2023

Can waged work under capitalism be meaningful? How does this meaningfulness express itself in the politics of working life? More fundamentally, how should work be socially and economically valued, rewarded, organised and regulated to become more meaningful? Knut Laaser and Jan Ch. Karlsson address these questions and provide a novel theory of meaningful work that is deeply ingrained in Critical Social Science approaches. The authors conceptualise meaningful work as a continuum between meaningful–meaningless work that rests on objective and subjective dimensions of autonomy, dignity and recognition, all pushed and pulled by the multi-layered control and power dynamics of waged work. They challenge the tendency to promote unpolitical concepts in the scholarship of meaningful work. The explanatory power of the meaningful work framework is illustrated by the analysis of empirical case studies on Norwegian industry operators, British bank employees, Indian security guards, German university academics and Swedish cabin crew members.
The Merovingians in Historiographical Tradition
Authors: Fox Yaniv
Published: November 2023

The Merovingian centuries were a foundational period in the historical consciousness of western Europe. The memory of the ﬁrst dynasty of Frankish kings, their origin myths, accomplishments, and failures were used by generations of chroniclers, propagandists, and historians to justify a wide range of social and political agendas. The process of curating and editing the source material gave rise to a recognizable 'Merovingian narrative' with three distinct phases: meteoric ascent, stasis, and decline. Already in the seventh-century Chronicle of Fredegar, this tripartite model was invoked by a Merovingian queen to prophesy the fate of her descendants. This expert commentary sets out to understand how the story of the Merovingians was shaped through a process of continuous historiographical adaptation. It examines authors from across a millennium of historical writing and analyzes their inﬂuences and objectives, charting the often-unexpected ways in which their narratives were received and developed.
Paul and the Resurrection of Israel
Authors: Staples Jason A.
Published: November 2023

The gospel promoted by Paul has for many generations stirred passionate debate. That gospel proclaimed equal salvific access to Jews and gentiles alike. But on what basis? In making sense of such a remarkable step forward in religious history, Jason Staples reexamines texts that have proven thoroughly resistant to easy comprehension. He traces Paul's inclusive theology to a hidden strand of thinking in the earlier story of Israel. Postexilic southern Judah, he argues, did not simply appropriate the identity of the fallen northern kingdom of Israel. Instead, Judah maintained a notion of 'Israel' as referring both to the north and the ongoing reality of a broad, pan-Israelite sensibility to which the descendants of both ancient kingdoms belonged. Paul's concomitant belief was that northern Israel's exile meant assimilation among the nations – effectively a people's death – and that its restoration paradoxically required gentile inclusion to resurrect a greater 'Israel' from the dead.
Pflegen in Krisen und Katastrophen
Authors: Kibler Angelina , Gröbe Sebastian , Matthes Franziska
Published: November 2023

Zusammenfassung: Mit zunehmendem Auftreten von Krisen und Katastrophen steht auch die Pflege vor großen Herausforderungen. Um diesen Entwicklungen adäquat begegnen zu können, benötigen Pflegefachpersonen entsprechende Kompetenzen in der Katastrophenpflege. Die Integration dieses Themas in die Aus- und Weiterbildung der Pflege stand daher im Mittelpunkt eines Workshops auf dem Lernwelten Kongress 2022 in Luzern.
River Recovery from Drought Can Take Years
Authors: van Deelen Grace
Published: November 2023

Climate change has created increasingly volatile weather and a drier atmosphere, making it harder for rivers to recuperate after a drought.
An Explanation for the Metric Dependence of the Midlatitude Jet‐Waviness Change in Response to Polar Warming
Authors: Geen Ruth , Thomson Stephen I. , Screen James A. , Blackport Russell , Lewis Neil T. , Mudhar Regan , Seviour William J. M. , Vallis Geoffrey K.
Published: November 2023

Arctic amplification has been proposed to promote temperature extremes by slowing the midlatitude jet and increasing the amplitude of its meanders. Observational and modeling studies have used a variety of metrics to quantify jet waviness. These studies show conflicting changes in jet waviness depending on the metric used and period examined. Here, we evaluate common metrics for dry idealized model simulations in which we apply polar warming of varying depth and meridional extent. In all simulations, polar warming increases the spatial extent of jet meanders, but reduces the magnitudes of ridges and troughs within the wave. As a result, geometric and anomaly‐amplitude measures of jet waviness can yield opposing responses. This contrast between metrics is particularly evident when warming extends into the midlatitudes. In all simulations, midlatitude temperature anomalies weaken as the poles warm, suggesting that a wavier jet need not imply stronger temperature extremes.
Capturing the Onset of Mountain Snowmelt Runoff Using Satellite Synthetic Aperture Radar
Authors: Gagliano Eric , Shean David , Henderson Scott , Vanderwilt Seth
Published: November 2023

The timing of snowmelt runoff is critical for water resource applications, but its spatiotemporal evolution remains poorly understood. We present a scalable approach to map snowmelt runoff onset using Sentinel‐1 synthetic aperture radar data for the past 8 years with 10 m spatial resolution and a median temporal resolution of 3.9 days. A systematic analysis of stratovolcanoes in the Western United States showed that snowmelt runoff onset is strongly dependent on elevation (r = 0.81), with a median runoff onset lapse rate of 4.9 days per 100 m of elevation gain. During the 2015 snow drought, we observed snowmelt runoff onset 25 days early relative to the 2015–2022 median. We document a median shift in snowmelt runoff onset of +2.0 days later in the year per year between 2016 and 2022. Our open‐source tools can be used to create snowmelt runoff onset maps anywhere on Earth.
Seasonal and Elevational Variability in Dwarf Birch VOC Emissions in Greenlandic Tundra
Authors: Rieksta Jolanta , Li Tao , Davie‐Martin Cleo L. , Simin Tihomir , Brogaard Aeppli Laurids Christian , Høye Toke Thomas , Rasmussen Morten Arendt , Rinnan Riikka
Published: November 2023

Rising temperatures amplify biogenic volatile organic compound (VOC) emissions from Arctic vegetation, causing feedbacks to the climate system. Changes in climate also alter plant physiology and vegetation composition, all of which can influence VOC emissions. Moreover, leaf development and biotic stresses cause highly variable emissions during the growing season. Therefore, linking VOC emissions with plant traits and tracking responses to climate change might provide better understanding of VOC emission regulation under future conditions. We measured VOC emissions and other plant traits in dwarf birch (Betula glandulosa) at two elevations in Narsarsuaq, South Greenland. The measurements were performed in warming experiments that have run since 2016. We collected VOCs using the branch enclosure method from early June until late July 2019 (n = 200). Emissions of green leaf volatiles (GLVs), oxygenated monoterpenes (oMTs), and homoterpenes followed a seasonal trend. VOC emission rates and the diversity of the VOC blend decreased at the end of the measurement period. Differences in VOC emission rates between elevations were pronounced early in the season. Majority of the traits did not explain the variation in VOC emissions. We show strong seasonal variability in VOC emissions within the growing season, which is likely driven by leaf phenology. While the diversity of VOCs was greater at the milder low‐elevation site, VOC emission rates were higher or similar at the harsher high‐elevation site, showing stronger VOC emission potentials than previously assumed. Seasonal variations in the emissions of VOCs are crucial for accurate predictions of current and future VOC emissions from arctic ecosystems.
MAP kinase ERK5 modulates cancer cell sensitivity to extrinsic apoptosis induced by death-receptor agonists
Authors: Espinosa-Gil Sergio , Ivanova Saska , Alari-Pahissa Elisenda , Denizli Melek , Villafranca-Magdalena Beatriz , Viñas-Casas Maria , Bolinaga-Ayala Idoia , Gámez-García Andrés , Faundez-Vidiella Claudia , Colas Eva , Lopez-Botet Miguel , Zorzano Antonio , Lizcano José Miguel
Published: November 2023

Death receptor ligand TRAIL is a promising cancer therapy due to its ability to selectively trigger extrinsic apoptosis in cancer cells. However, TRAIL–based therapies in humans have shown limitations, mainly due inherent or acquired resistance of tumor cells. To address this issue, current efforts are focussed on dissecting the intracellular signaling pathways involved in resistance to TRAIL, to identify strategies that sensitize cancer cells to TRAIL-induced cytotoxicity. In this work, we describe the oncogenic MEK5-ERK5 pathway as a critical regulator of cancer cell resistance to the apoptosis induced by death receptor ligands. Using 2D and 3D cell cultures and transcriptomic analyses, we show that ERK5 controls the proteostasis of TP53INP2, a protein necessary for full activation of caspase-8 in response to TNFα, FasL or TRAIL. Mechanistically, ERK5 phosphorylates and induces ubiquitylation and proteasomal degradation of TP53INP2, resulting in cancer cell resistance to TRAIL. Concordantly, ERK5 inhibition or genetic deletion, by stabilizing TP53INP2, sensitizes cancer cells to the apoptosis induced by recombinant TRAIL and TRAIL/FasL expressed by Natural Killer cells. The MEK5-ERK5 pathway regulates cancer cell proliferation and survival, and ERK5 inhibitors have shown anticancer activity in preclinical models of solid tumors. Using endometrial cancer patient-derived xenograft organoids, we propose ERK5 inhibition as an effective strategy to sensitize cancer cells to TRAIL-based therapies.
Potentiation of apoptosis in drug-resistant mantle cell lymphoma cells by MCL-1 inhibitor involves downregulation of inhibitor of apoptosis proteins
Authors: Li Yijing , Lee Heng-Huan , Jiang Vivian Changying , Che Yuxuan , McIntosh Joseph , Jordan Alexa , Vargas Jovanny , Zhang Tianci , Yan Fangfang , Simmons Margaret Elizabeth , Wang Wei , Nie Lei , Yao Yixin , Jain Preetesh , Wang Michael , Liu Yang
Published: November 2023

Bruton’s tyrosine kinase inhibitors (BTKi) and CAR T-cell therapy have demonstrated tremendous clinical benefits in mantle cell lymphoma (MCL) patients, but intrinsic or acquired resistance inevitably develops. In this study, we assessed the efficacy of the highly potent and selective MCL-1 inhibitor AZD5991 in various therapy-resistant MCL cell models. AZD5991 markedly induced apoptosis in these cells. In addition to liberating BAK from the antiapoptotic MCL-1/BAK complex for the subsequent apoptosis cascade, AZD5991 downregulated inhibitor of apoptosis proteins (IAPs) through a BAK-dependent mechanism to amplify the apoptotic signal. The combination of AZD5991 with venetoclax enhanced apoptosis and reduced mitochondrial oxygen consumption capacity in MCL cell lines irrespective of their BTKi or venetoclax sensitivity. This combination also dramatically inhibited tumor growth and prolonged mouse survival in two aggressive MCL patient-derived xenograft models. Mechanistically, the augmented cell lethality was accompanied by the synergistic suppression of IAPs. Supporting this notion, the IAP antagonist BV6 induced dramatic apoptosis in resistant MCL cells and sensitized the resistant MCL cells to venetoclax. Our study uncovered another unique route for MCL-1 inhibitor to trigger apoptosis, implying that the pro-apoptotic combination of IAP antagonists and apoptosis inducers could be further exploited for MCL patients with multiple therapeutic resistance.
Distinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time
Authors: Kenny Grace , O’Reilly Sophie , Wrigley Kelly Neil , Negi Riya , Gaillard Colette , Alalwan Dana , Saini Gurvin , Alrawahneh Tamara , Francois Nathan , Angeliadis Matthew , Garcia Leon Alejandro Abner , Tinago Willard , Feeney Eoin R. , Cotter Aoife G. , de Barra Eoghan , Yousif Obada , Horgan Mary , Doran Peter , Stemler Jannik , Koehler Philipp , Cox Rebecca Jane , O’Shea Donal , Olesen Ole F. , Landay Alan , Hogan Andrew E. , Lelievre Jean-Daniel , Gautier Virginie , Cornely Oliver A. , Mallon Patrick W. G. ,   The All Ireland Infectious Diseases Cohort Study, Leon Alejandro Garcia , Feeney Eoin , de Barra Eoghan ,   VACCELERATE Consortium EU-COVAT-1-AGED Part A Study Group, Mallon Patrick
Published: November 2023

SARS-CoV-2 neutralising antibodies provide protection against COVID-19. Evidence from early vaccine trials suggested binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether these thresholds predict sufficient neutralising capacity against variants of concern (VOCs), and whether this is impacted by vaccine or infection history remains unclear. Here we analyse individuals recovered from, vaccinated or with hybrid immunity against SARS-CoV-2. An NT50 ≥ 100 IU confers protection in vaccine trials, however, as VOC induce a reduction in NT50, we use NT50 ≥ 1000 IU as a cut off for WT NT50 that would retain neutralisation against VOC. In unvaccinated convalescent participants, a receptor binding domain (RBD) IgG of 456 BAU/mL predicts an NT50 against WT of 1000 IU with an accuracy of 80% (95%CI 73–86%). This threshold maintains accuracy in determining loss of protective immunity against VOC in two vaccinated cohorts. It predicts an NT50 < 100 IU against Beta with an accuracy of 80% (95%CI 67–89%) in 2 vaccine dose recipients. In booster vaccine recipients with a history of COVID-19 (hybrid immunity), accuracy is 87% (95%CI 77–94%) in determining an NT50 of <100 IU against BA.5. This analysis provides a discrete threshold that could be used in future clinical studies.
Production of leishmanin skin test antigen from Leishmania donovani for future reintroduction in the field
Authors: Dey Ranadhir , Alshaweesh Jalal , Singh Kamaleshwar P. , Lypaczewski Patrick , Karmakar Subir , Klenow Laura , Paulini Kayla , Kaviraj Swarnendu , Kamhawi Shaden , Valenzuela Jesus G. , Singh Sanjay , Hamano Shinjiro , Satoskar Abhay R. , Gannavaram Sreenivas , Nakhasi Hira L. , Matlashewski Greg
Published: November 2023

The leishmanin skin test was used for almost a century to detect exposure and immunity to Leishmania, the causative agent of leishmaniasis, a major neglected tropical disease. Due to a lack of antigen used for the intradermal injection, the leishmanin skin test is no longer available. As leishmaniasis control programs are advancing and new vaccines are entering clinical trials, it is essential to re-introduce the leishmanin skin test. Here we establish a Leishmania donovani strain and describe the production, under Good Laboratory Practice conditions, of leishmanin soluble antigen used to induce the leishmanin skin test in animal models of infection and vaccination. Using a mouse model of cutaneous leishmaniasis and a hamster model of visceral leishmaniasis, soluble antigen induces a leishmanin skin test response following infection and vaccination with live attenuated Leishmania major (LmCen-/-). Both the CD4+ and CD8+ T-cells are necessary for the leishmanin skin test response. This study demonstrates the feasibility of large-scale production of leishmanin antigen addressing a major bottleneck for performing the leishmanin skin test in future surveillance and vaccine clinical trials.
Toxic PARP trapping upon cAMP-induced DNA damage reinstates the efficacy of endocrine therapy and CDK4/6 inhibitors in treatment-refractory ER+ breast cancer
Authors: Saatci Ozge , Cetin Metin , Uner Meral , Tokat Unal Metin , Chatzistamou Ioulia , Ersan Pelin Gulizar , Montaudon Elodie , Akyol Aytekin , Aksoy Sercan , Uner Aysegul , Marangoni Elisabetta , Sajish Mathew , Sahin Ozgur
Published: November 2023

Resistance to endocrine therapy and CDK4/6 inhibitors, the standard of care (SOC) in estrogen receptor-positive (ER+) breast cancer, greatly reduces patient survival. Therefore, elucidating the mechanisms of sensitivity and resistance to SOC therapy and identifying actionable targets are urgently needed. Here, we show that SOC therapy causes DNA damage and toxic PARP1 trapping upon generation of a functional BRCAness (i.e., BRCA1/2 deficiency) phenotype, leading to increased histone parylation and reduced H3K9 acetylation, resulting in transcriptional blockage and cell death. Mechanistically, SOC therapy downregulates phosphodiesterase 4D (PDE4D), a novel ER target gene in a feedforward loop with ER, resulting in increased cAMP, PKA-dependent phosphorylation of mitochondrial COXIV-I, ROS generation and DNA damage. However, during SOC resistance, an ER-to-EGFR switch induces PDE4D overexpression via c-Jun. Notably, combining SOC with inhibitors of PDE4D, EGFR or PARP1 overcomes SOC resistance irrespective of the BRCA1/2 status, providing actionable targets for restoring SOC efficacy.
Efficient optical plasmonic tweezer-controlled single-molecule SERS characterization of pH-dependent amylin species in aqueous milieus
Authors: Fu Wenhao , Chi Huanyu , Dai Xin , Zhu Hongni , Mesias Vince St. Dollente , Liu Wei , Huang Jinqing
Published: November 2023

It is challenging to characterize single or a few biomolecules in physiological milieus without excluding the influences of surrounding environment. Here we utilize optical plasmonic trapping to construct a dynamic nanocavity, which reduces the diffraction-limited detection volume and provides reproducible electromagnetic field enhancements to achieve high-throughput single-molecule surface-enhanced Raman spectroscopy (SERS) characterizations in aqueous environments. Specifically, we study human Islet Amyloid Polypeptide (amylin, hIAPP) under different physiological pH conditions by combining spectroscopic experiments and molecular dynamics (MD) simulations. Based on a statistically significant amount of time-dependent SERS spectra, two types of low-populated transient species of hIAPP containing either turn or β-sheet structure among its predominant helix-coil monomers are characterized during the early-stage incubation at neutral condition, which play a crucial role in driving irreversible amyloid fibril developments even after a subsequent adjustment of pH to continue the prolonged incubation at acidic condition. Our results might provide profound mechanistic insight into the pH-regulated amyloidogenesis and introduce an alternative approach for investigating complex biological processes at the single-molecule level.
Effect of recombinant human erythropoietin combined with iron sucrose on postoperative hemoglobin in patients undergoing artificial joint replacement
Authors: Yu Wenjiang , Liu Chengyan , Bi Zhiguo
Published: November 2023

With the aging of the population, an increasing number of elderly patients are opting for artificial joint replacement, leading to the exploration of various rapid rehabilitation programs in the perioperative period. In this study, we aimed to investigate the effectiveness of combining recombinant human erythropoietin and iron sucrose in altering the range and trend of postoperative hemoglobin in patients undergoing arthroplasty. Specifically, we will examine whether this combination can effectively alter the rise and fall of postoperative haemoglobin, identify the inflection point of haemoglobin change or recovery after arthroplasty, and assess the effect of treatment on serum iron in postoperative blood. We conducted a retrospective study of 138 patients who underwent unilateral total joint arthroplasty by the same surgeon in the same hospital before July 2022. The results of this study may provide valuable insights for the development of effective rehabilitation programs for patients undergoing arthroplasty.
Population-based study of the reproductive risk factors for transvaginal ultrasound diagnosed uterine fibroids in Nigerian women
Authors: Adebamowo Clement A. ,   The ACCME Research Group as part of the H3Africa Consortium, Adebamowo Sally N. , Offiong Richard , Olaniyan Olayinka , Obende Kayode , Adebayo Amos , Ologun Sanni , Alabi Bunmi , Achara Peter , Erhunmwonsere Juliet Iyosaba , Owoade Yinka , Gbolahan Tolu , Adebamowo Sally N.
Published: November 2023

There has been no previous systematic, epidemiological study of the reproductive risk factors for uterine fibroids (UF) in African populations despite African women having the highest burden of UF in the world. Improved knowledge of the associations between UF and reproductive factors would contribute to better understanding of the etiology of UF and may suggest novel opportunities for prevention and therapeutic interventions. We used nurse administered questionnaires to survey the demographic and reproductive risk factors of UF among 484 women who are members of the African Collaborative Center for Microbiome and Genomics Research (ACCME) Study Cohort in central Nigeria, and who had transvaginal ultrasound diagnosis (TVUS). We used logistic regression models to the evaluate associations between reproductive risk factors and UF, adjusted for significant covariates. In our multivariable logistic regression models, we found inverse associations with number of children (OR = 0.83, 95%CI = 0.74–0.93, p-value = 0.002), parity (OR = 0.41, 95%CI = 0.24–0.73, p-value = 0.002), history of any type of abortion (OR = 0.53, 95%CI = 0.35–0.82, p-value = 0.004), duration of use of Depot Medroxyprogesterone Acetate (DMPA) (p-value for trend = 0.02), menopausal status (OR = 0.48, 95%CI = 0.27–0.84, p-value = 0.01), and a non-linear positive association with age (OR = 1.04, 95%CI = 1.01–1.07, p-value = 0.003). Other reproductive risk factors that have been reported in other populations (age at menarche and menopause, and oral contraceptives) were not associated with UF in this study. Our study confirms some of the reproductive risk factors for UF that have been found in other populations and shows that some of them are stronger in the Nigerian population. The associations we found with DMPA suggest opportunities for further research to understand the mechanisms of action of progesterone and its analogues in the etiology of UF, their potential use for prevention and treatment of UF.
Addressing the issue of surface mechanisms and competitive effects in Cr(VI) reductive-adsorption on tin-hydroxyapatite in the presence of co-ions
Authors: Avola Tiziana , Campisi Sebastiano , Polito Laura , Arici Silvia , Ferruti Ludovica , Gervasini Antonella
Published: November 2023

Our group recently proposed an innovative sustainable reductant-adsorbent material, tin(II)-hydroxyapatite (Sn/HAP, ca. 10 wt% Sn) for the interfacial Cr(VI) reductive adsorption process. In this study, Cr(VI) removal capacity was evaluated in multi-component solutions containing representative background ions (i.e., CaCl2, Ca(NO3)2, MgSO4, Na2SO4, Fe(NO3)3, AlCl3, Zn(NO3)2, or Mn(NO3)2). Sn/HAP was able to reduce Cr(VI) with complete Cr3+ adsorption on HAP surface, except in the presence of Fe3+ and Al3+ ions. Some metal ions co-existing in solution, such as Fe3+, Al3+, Zn2+, and Mn2+, were also adsorbed on HAP surface. Reuse experiments of the Sn/HAP sample, up to 7 runs, resulted in a total amount of reduced Cr(VI) of ca. 15–18 mg g−1. Fast kinetics of Cr(VI) reductive adsorption at 25 °C in a multi-metal component solution was observed. The pseudo-second order model was in excellent agreement with the experimental kinetic data, leading to a rate constant (k25°C) value of ca. 30 M−1 s−1. The collection of adsorption isotherms of Cr3+ and Fe3+, together with TEM–EDX analysis permitted the unveiling of competitive adsorption phenomena between metal ions. The obtained results demonstrate that Sn/HAP could be an efficient material for the removal of hexavalent chromium in aqueous solutions containing high concentrations of inorganic impurities.
Reliability of resting-state EEG modulation by continuous and intermittent theta burst stimulation of the primary motor cortex: a sham-controlled study
Authors: Rodionov Andrei , Ozdemir Recep A. , Benwell Christopher S. Y. , Fried Peter J. , Boucher Pierre , Momi Davide , Ross Jessica M. , Santarnecchi Emiliano , Pascual-Leone Alvaro , Shafi Mouhsin M.
Published: November 2023

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation designed to induce changes of cortical excitability that outlast the period of TBS application. In this study, we explored the effects of continuous TBS (cTBS) and intermittent TBS (iTBS) versus sham TBS stimulation, applied to the left primary motor cortex, on modulation of resting state electroencephalography (rsEEG) power. We first conducted hypothesis-driven region-of-interest (ROI) analyses examining changes in alpha (8–12 Hz) and beta (13–21 Hz) bands over the left and right motor cortex. Additionally, we performed data-driven whole-brain analyses across a wide range of frequencies (1–50 Hz) and all electrodes. Finally, we assessed the reliability of TBS effects across two sessions approximately 1 month apart. None of the protocols produced significant group-level effects in the ROI. Whole-brain analysis revealed that cTBS significantly enhanced relative power between 19 and 43 Hz over multiple sites in both hemispheres. However, these results were not reliable across visits. There were no significant differences between EEG modulation by active and sham TBS protocols. Between-visit reliability of TBS-induced neuromodulatory effects was generally low-to-moderate. We discuss confounding factors and potential approaches for improving the reliability of TBS-induced rsEEG modulation.