bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and safety of methotrexate in the treatment of mycosis fungoides: Real‐world data from a multicentre study
Authors: Nikolaou Vasiliki , Panou Evdoxia , Tsimpidakis Antonios , Koumprentziotis Ioannis‐Alexios , Patsatsi Aikaterini , Siakantaris Marina , Kruger‐Krasagakis Sabine‐Elke , Marinos Leonidas , Georgiou Elisavet , Lampadaki Kyriaki , Velissari Aliki , Daponte Athina‐Ioanna , Doxastaki Aikaterini , Kaliampou Stella , Vaiopoulos Aristeidis , Konstandinou Iliana , Koumourtzis Marios , Lakiotaki Eleftheria , Pappa Vassiliki , Tsamaldoupis Athanasios , Stratigos Alexander , Papadavid Evangelia
Published: September 2024

Background

Methotrexate (MTX) has been a longstanding therapeutic option for mycosis fungoides (MF); however, data on its real‐world effectiveness remain limited.

Objectives

To evaluate treatment‐related outcomes of oral MTX in patients with early‐ and late‐stage MF.

Methods

This is a retrospective multicentre analysis involving MF subjects from five referral centres for cutaneous lymphomas in Greece. Data regarding the effectiveness and safety were analysed.

Results

In total, 211 MF patients were enrolled (males, 68.3%) with a median (IQR) age of diagnosis at 68.3 (56–75) years. Late‐stage (IIB‐IVB) disease was present in 124 patients (59.3%). MTX monotherapy was administered to 112 (53.1%) patients, with 99 receiving combination regimens with phototherapy, interferon and retinoids. MTX was used as first‐line regimen in 103 (48.9%) cases. An overall response rate (ORR) of 55.5% was observed with 29.9% of patients achieving complete responses. MTX demonstrated greater effectiveness as a first‐line treatment compared to subsequent use with no significant differences between monotherapy and combination therapy. The median time to best response was 3.8 months (IQR 2.3–9.9 months). Patients with erythrodermic disease (Stage III) had better ORRs compared to patients with tumour stage disease (Stage II) (61.1% vs. 44.8% respectively). The progression‐free survival (PFS) varied according to stage, with a median PFS of 17.1 months for early‐stage disease, 5.7 months for Stage IIB disease, 46 months for Stage III and 9.6 months for Stage IV disease (0.7‐.). Serious adverse (Grade 3) events leading to treatment discontinuation occurred in 14 (6.7%) cases. All patients received oral MTX once weekly with a median weekly dose of 15 mg/week (7.5–25).

Conclusion

Our findings support MTX as a viable treatment option for MF, particularly when used in the first‐line setting, offering a favourable benefit/risk profile. Response rates are stage‐dependent, with erythrodermic patients achieving superior and durable responses.
Effects of integrated traditional Chinese and Western medicine for acute pancreatitis: A real‐world study in a tertiary teaching hospital
Authors: Deng Lihui , Chen Zhiyao , Zhu Ping , Hu Cheng , Jin Tao , Wang Xinwei , Li Lan , Lin Ziqi , Guo Jia , Yang Xiaonan , Shi Na , Zhang Xiaoxin , Yang Xinmin , Jiang Kun , Ma Yun , Tan Qingyuan , Li Ling , Wang Wen , Huang Wei , Sun Xin , Xia Qing
Published: September 2024

Aim

This study aimed to evaluate whether integrated traditional Chinese medicine (TCM) and Western medicine (WM) is more effective than WM for acute pancreatitis (AP).

Methods

Patients with AP were enrolled and divided into the TCM and WM (TCM&WM) and WM groups according to the therapeutic protocol in real clinical settings. We applied 1:3 propensity score matching, which was to adjust confounding factors. The primary outcome was mortality, whereas the secondary outcomes were organ failure, organ supportive therapies, local complications, hospitalization cost, and length of hospital stay. Sensitivity and subgroup analyses were also performed.

Results

Of 5442 patients with AP, 4691 and 751 were included in the TCM&WM and WM groups, respectively. After PSM, patient baseline characteristics were well balanced. Compared with the WM group (n = 734), the TCM&WM group (n = 2096) had lower overall mortality rate (1.7% vs. 3.4%; risk ratio, 0.482; 95% confidence interval, 0.286–0.810; p = 0.005). The TCM&WM group was associated with lower risk of persistent renal failure, multiple organ failure, and infection, lower utilization of organ supportive therapies, shortened lengths of hospital and intensive care unit stay, and lower hospital costs. Sensitivity analyses showed similar results. Subgroup analysis favored TCM&WM treatment for patients aged < 60 years, with hypertriglyceridic etiology, and with admission interval between 24 and 48 h.

Conclusion

TCM&WM treatment can achieve lower risks of mortality and organ failure and better economic effectiveness in patients with AP than WM treatment. This study provides a promising alternative of TCM&WM treatment for AP in the real‐world setting.
Methodological and reporting quality of systematic reviews on aesthetics and reconstructive breast surgery: A meta‐research
Authors: Cavalcante Pedro Henrique de Mattos , Pacheco Rafael Leite , Latorraca Carolina de Oliveira Cruz , Oliveira Alex Sandro Moreira Fragoso de , Riera Rachel
Published: September 2024

Objective

To evaluate the methodological and reporting quality of systematic reviews (SR) of randomized controlled trials on esthetics and reconstructive breast surgery.

Methods

Meta‐research study with a broad search strategy was developed to retrieve all relevant systematic reviews. We evaluated the methodological and reporting guidance adopted by these reviews and assessed their adequacy to items from AMSTAR‐2 (methodological quality) and PRISMA 2020 (reporting quality). The protocol of this study was prospectively published in: https://osf.io/preprints/osf/ucpgd.

Results

After the selection process, 15 SR were included; eight (60%) referred the use of a methodological guide and five (33.3%) invertedly referred PRISMA as the methodological guide. Reporting guidelines were referred by none of the included systematic review. The median adequacy to PRISMA‐2020 items was 42.9% (Q1 – 38.1%/Q3 – 95.2%) and to AMSTAR‐2 items was 33.3% (Q1 – 23.3%/Q3 – 93.3%) which reflects overall low reporting and methodological quality of included SR. The overall confidence in the results using AMSTAR‐2 framework was critically low in 73.3% of included SR. Although a small number of SR were included, a high correlation between the methodological and reporting quality was observed (Spearmean rho = 0.96, 95% bias‐corrected confidence interval = 0.84 to 0.99).

Conclusion

Methodological and reposting quality of SR of randomized clinical trials on esthetic or reconstructive breast surgery is poor. Half of the authors referred to the use of valid guidance to plan and conduct their reviews and none of them referred the use of a guidance for reporting their results.
An integrative framework reveals widespread gene flow during the early radiation of oaks and relatives in Quercoideae (Fagaceae)
Authors: Liu Shui‐Yin , Yang Ying‐Ying , Tian Qin , Yang Zhi‐Yun , Li Shu‐Feng , Valdes Paul J. , Farnsworth Alex , Kates Heather R. , Siniscalchi Carolina M. , Guralnick Robert P. , Soltis Douglas E. , Soltis Pamela S. , Stull Gregory W. , Folk Ryan A. , Yi Ting‐Shuang
Published: September 2024

Although the frequency of ancient hybridization across the Tree of Life is greater than previously thought, little work has been devoted to uncovering the extent, timeline, and geographic and ecological context of ancient hybridization. Using an expansive new dataset of nuclear and chloroplast DNA sequences, we conducted a multifaceted phylogenomic investigation to identify ancient reticulation in the early evolution of oaks (Quercus). We document extensive nuclear gene tree and cytonuclear discordance among major lineages of Quercus and relatives in Quercoideae. Our analyses recovered clear signatures of gene flow against a backdrop of rampant incomplete lineage sorting, with gene flow most prevalent among major lineages of Quercus and relatives in Quercoideae during their initial radiation, dated to the Early‐Middle Eocene. Ancestral reconstructions including fossils suggest ancestors of Castanea + Castanopsis, Lithocarpus, and the Old World oak clade probably co‐occurred in North America and Eurasia, while the ancestors of Chrysolepis, Notholithocarpus, and the New World oak clade co‐occurred in North America, offering ample opportunity for hybridization in each region. Our study shows that hybridization—perhaps in the form of ancient syngameons like those seen today—has been a common and important process throughout the evolutionary history of oaks and their relatives. Concomitantly, this study provides a methodological framework for detecting ancient hybridization in other groups.
A severe head louse (Pediculus humanus capitis) infestation: Timeline, pathogen detection, kdr‐gene screening and morphological anomalies of lice
Authors: Eremeeva Marina E. , Durden Lance A. , Eisenstat Jonathan , Hargrove Brian C. , Mondor Edward B.
Published: September 2024

Lice are assuming an increasing importance in forensic investigations, given their capacity to provide information about an individual's care. Head louse pediculosis is a frequent condition in school‐age children and can be properly controlled using topical treatments combined with good personal hygiene. Prolonged and chronic infestations may result in more serious outcomes including severe iron deficiency anaemia. We conducted entomological and laboratory investigations of a head louse infestation in a 12‐year‐old girl who experienced severe anaemia and subsequent death. Numerous lice were found postmortem on the head, face and neck of the patient, as well as on bedding and clothing. Analysis of nits on individual hairs determined that the louse infestation had been present for at least 166 days. The lice had some morphological traits characteristic of body lice: the third antennal segment in some specimens was distinctly longer than wide, and the apices of some paratergal plates did not extend into intersegmental membranes, while other morphological features were characteristic of head or body lice. All lice were heterozygous for the T917I kdr genotype, a marker of permethrin resistance. Nineteen (79.2%, 95%CI 59.5%–90.8%) louse DNA samples tested TaqMan positive for Acinetobacter (Moraxellales; Moraxellaceae) sp. Available information and laboratory findings are further discussed regarding their possible contribution to the negative outcome of this case. We stress the impact head louse pediculosis can have on children with limited parental attention, and how severe head louse infestation may serve as warning sign of neglect, and other high‐risk situations.
Endogenous viral elements are targeted by RNA silencing pathways in banana
Authors: Duroy Pierre‐Olivier , Seguin Jonathan , Ravel Sébastien , Rajendran Rajeswaran , Laboureau Nathalie , Salmon Frédéric , Delos Jean‐Marie , Pooggin Mikhail , Iskra‐Caruana Marie‐Line , Chabannes Matthieu
Published: September 2024

Endogenous banana streak virus (eBSV) integrants derived from three distinct species, present in Musa balbisiana (B) but not Musa acuminata (A) banana genomes are able to reconstitute functional episomal viruses causing banana streak disease in interspecific triploid AAB banana hybrids but not in the diploid (BB) parent line, which harbours identical eBSV loci. Here, we investigated the regulation of these eBSV.

In‐depth characterization of siRNAs, transcripts and methylation derived from eBSV using Illumina and bisulfite sequencing were carried out on eBSV‐free Musa acuminata AAA plants and BB or AAB banana plants with eBSV.

eBSV loci produce low‐abundance transcripts covering most of the viral sequence and generate predominantly 24‐nt siRNAs. siRNA accumulation is restricted to duplicated and inverted viral sequences present in eBSV. Both siRNA‐accumulating and nonaccumulating sequences of eBSV in BB plants are heavily methylated in all three CG, CHG and CHH contexts.

Our data suggest that eBSVs are controlled at the epigenetic level in BB diploids. This regulation not only prevents their awakening and systemic infection of the plant but is also probably involved in the inherent resistance of the BB plants to mealybug‐transmitted viral infection. These findings are thus of relevance to other plant resources hosting integrated viruses.
A nitrogen‐responsive cytokinin oxidase/dehydrogenase regulates root response to high ammonium in rice
Authors: Li Lun , Jia Letian , Duan Xingliang , Lv Yuanda , Ye Chengyu , Ding Chengqiang , Zhang Yuwen , Qi Weicong , Motte Hans , Beeckman Tom , Luo Le , Xuan Wei
Published: September 2024

Plant root system is significantly influenced by high soil levels of ammonium nitrogen, leading to reduced root elongation and enhanced lateral root branching. In Arabidopsis, these processes have been reported to be mediated by phytohormones and their downstream signaling pathways, while the controlling mechanisms remain elusive in crops.

Through a transcriptome analysis of roots subjected to high/low ammonium treatments, we identified a cytokinin oxidase/dehydrogenase encoding gene, CKX3, whose expression is induced by high ammonium. Knocking out CKX3 and its homologue CKX8 results in shorter seminal roots, fewer lateral roots, and reduced sensitivity to high ammonium.

Endogenous cytokinin levels are elevated by high ammonium or in ckx3 mutants. Cytokinin application results in shorter seminal roots and fewer lateral roots in wild‐type, mimicking the root responses of ckx3 mutants to high ammonium. Furthermore, CKX3 is transcriptionally activated by type‐B RR25 and RR26, and ckx3 mutants have reduced auxin content and signaling in roots under low ammonium.

This study identified RR25/26‐CKX3‐cytokinin as a signal module that mediates root responses to external ammonium by modulating of auxin signaling in the root meristem and lateral root primordium. This highlights the critical role of cytokinin metabolism in regulating rice root development in response to ammonium.
Exploring health inequities through the actor‐network theory lens
Authors: Fisher Mar'yana , Tulloch Joanna , Petrovskaya Olga
Published: September 2024

Social theory plays an important role in the nursing discipline and nursing inquiry as it helps conceptually embed nursing in the larger picture of the social world. For example, a broad category of critical theory provides a unique lens for uncovering social conditions of inequity and oppression. Among the sociological theories, actor‐network theory (ANT) is an approach to research and analysis that has recently gained interest among nurse philosophers and researchers. Studies guided by ANT seek to understand phenomena of interest as constituted within the relationships between human and nonhuman actors to understand how care practices are co‐created/enacted and how they can be made more humane. In this paper, we describe the benefits of ANT for examining healthcare access for incarcerated individuals with life‐limiting illnesses accessing palliative care and for people using illicit drugs. We argue that attention to the materiality of care practices can contribute to efforts of advancing health equity for these groups.
The comparative politics of solidarity: Political party discourse across three welfare state regimes
Authors: Luypaert Anouk , Thijssen Peter
Published: September 2024

Party political conflict plays an essential role in shaping welfare policies, while they are simultaneously also shaped by these policies. As political parties grapple with the wicked challenges of our times, new forms of solidarity and solidarity conflicts arise across welfare regimes. Despite their significance, these dynamics have not received much recent attention. Our article aims to fill this gap. Through content analysis of party manifestos, we compare the solidarity frames of political parties within and between three distinct welfare regimes—Flanders (Belgium), Sweden, and the United States. Our results confirm our expectations drawn from political feedback literature: while party ideology influences parties' solidarity frame preferences and solidarity conflicts between parties, these preferences and conflicts are also influenced by a welfare regime's societal solidarity norms. Our article highlights the value of analyzing solidarity frames and political solidarity conflicts within welfare‐state regimes to better understand welfare politics and policies.

Related Articles

König, Pascal D. 2015. “Moral Societal Renewal or Getting the Country Back to Work: Welfare State Culture as a Resource and a Constraint for Policy Discourse.” Politics & Policy 43(5): 647–78. https://doi.org/10.1111/polp.12130.

Mioni, Michele, 2021. “The ‘Good Citizen’ as a ‘Respectable Worker:’ State, Unemployment, and Social Policy in the United Kingdom and Italy, 1930 to 1950.” Politics & Policy 49(4): 913–39. https://doi.org/10.1111/polp.12425.

Wagle, Udaya R. 2014. “The Heterogeneity Politics of the Welfare State: Changing Population Heterogeneity and Welfare State Policies in High‐Income OECD Countries, 1980‐2005.” Politics & Policy 41(6): 947–84. https://doi.org/10.1111/polp.12053.
Exponentially localized interface eigenmodes in finite chains of resonators
Authors: Ammari Habib , Barandun Silvio , Davies Bryn , Hiltunen Erik Orvehed , Kosche Thea , Liu Ping
Published: September 2024

This paper studies wave localization in chains of finitely many resonators. There is an extensive theory predicting the existence of localized modes induced by defects in infinitely periodic systems. This work extends these principles to finite‐sized systems. We consider one‐dimensional, finite systems of subwavelength resonators arranged in dimers that have a geometric defect in the structure. This is a classical wave analog of the Su–Schrieffer–Heeger model. We prove the existence of a spectral gap for defectless finite dimer structures and find a direct relationship between eigenvalues being within the spectral gap and the localization of their associated eigenmode. Then, for sufficiently large‐size systems, we show the existence and uniqueness of an eigenvalue in the gap in the defect structure, proving the existence of a unique localized interface mode. To the best of our knowledge, our method, based on Chebyshev polynomials, is the first to characterize quantitatively the localized interface modes in systems of finitely many resonators.
A Social Constructionist Critique of Genetic Determinism
Authors: Ványi Dániel
Published: September 2024

Recently genetic determinist claims have reappeared in the explanation of human psychology and to some extent they even made their way into explanations of social phenomena. In this article, I will provide a critical analysis of the genetic determinist discourse from a social constructionist perspective. First, I will examine the meaning of genetic determinism. Then I will shortly introduce the social constructionist perspective generally and it's relevance for analyzing scientific discourses. Next, I will examine the debates about genetic determinism in behavior genetics and sociogenomics and interpret these critically from a social constructionist and deconstructionist perspective. Finally, I will provide an analysis of the main social, ideological, cultural and economic factors that influence the development of genetic determinist ideas: modernity, the legitimation of social hierarchies, neoliberalism and business interests. My conclusion is that the social constructionist perspective is important in the analysis and critique of the genetic determinist discourse.
Wiener densities for the Airy line ensemble
Authors: Dauvergne Duncan
Published: September 2024

The parabolic Airy line ensemble is a central limit object in the KPZ (Kardar–Parisi–Zhang) universality class and related areas. On any compact set , the law of the recentered ensemble has a density with respect to the law of independent Brownian motions. We show
where is an explicit, tractable, non‐negative function of . We use this formula to show that is bounded above by a ‐dependent constant, give a sharp estimate on the size of the set where as , and prove a large deviation principle for . We also give density estimates that take into account the relative positions of the Airy lines, and prove sharp two‐point tail bounds that are stronger than those for Brownian motion. These estimates are a key input in the classification of geodesic networks in the directed landscape. The paper is essentially self‐contained, requiring only tail bounds on the Airy point process and the Brownian Gibbs property as inputs.
A functorial approach to monomorphism categories II: Indecomposables
Authors: Gao Nan , Külshammer Julian , Kvamme Sondre , Psaroudakis Chrysostomos
Published: September 2024

We investigate the (separated) monomorphism category of a quiver over an Artin algebra . We show that there exists an epivalence (called representation equivalence in the terminology of Auslander) from to , where is the category of finitely generated ‐modules and and denote the respective injectively stable categories. Furthermore, if has at least one arrow, then we show that this is an equivalence if and only if is hereditary. In general, the epivalence induces a bijection between indecomposable objects in and noninjective indecomposable objects in , and we show that the generalized Mimo‐construction, an explicit minimal right approximation into , gives an inverse to this bijection. We apply these results to describe the indecomposables in the monomorphism category of radical square zero Nakayama algebras, and to give a bijection between the indecomposables in the monomorphism category of two artinian uniserial rings of Loewy length 3 with the same residue field. The main tool to prove these results is the language of a free monad of an exact endofunctor on an arbitrary abelian category. This allows us to avoid the technical combinatorics arising from quiver representations. The setup also specializes to more general settings, such as representations of modulations. In particular, we obtain new results on the singularity category of the algebras that were introduced by Geiss, Leclerc, and Schröer in order to extend their results relating cluster algebras and Lusztig's semicanonical basis to symmetrizable Cartan matrices. We also recover results on the algebras that were introduced by Lu and Wang to realize groups via semiderived Hall algebras.
Regulatory Role of Collagen XI in the Establishment of Mechanical Properties of Tendons and Ligaments in Mice Is Tissue Dependent
Authors: Ye Yaping , Shetye Snehal S. , Birk David E. , Soslowsky Louis J.
Published: September 2024

Collagen XI is ubiquitous in tissues such as joint cartilage, cancellous bone, muscles, and tendons and is an important contributor during a crucial part in fibrillogenesis. The COL11A1 gene encodes one of three alpha chains of collagen XI. The present study elucidates the role of collagen XI in the establishment of mechanical properties of tendons and ligaments. We investigated the mechanical response of three tendons and one ligament tissues from wild type and a targeted mouse model null for collagen XI: Achilles tendon (ACH), the flexor digitorum longus tendon (FDL), the supraspinatus tendon (SST), and the anterior cruciate ligament (ACL). Area was substantially lower in Col11a1ΔTen/ΔTen ACH, FDL, and SST. Maximum load and maximum stress were significantly lower in Col11a1ΔTen/ΔTen ACH and FDL. Stiffness was lower in Col11a1ΔTen/ΔTen ACH, FDL, and SST. Modulus was reduced in Col11a1ΔTen/ΔTen FDL and SST (both insertion site and midsubstance). Collagen fiber distributions were more aligned under load in both wild type group and Col11a1ΔTen/ΔTen groups. Results also revealed that the effect of collagen XI knockout on collagen fiber realignment is tendon-dependent and location-dependent (insertion versus midsubstance). In summary, this study clearly shows that the regulatory role of collagen XI on tendon and ligament is tissue specific and that joint hypermobility in type II Stickler's Syndrome may in part be due to suboptimal mechanical response of the soft tissues surrounding joints.
Assessing the Thermal Damage Induced by Radiofrequency Ablation for Localized Liver Cancer
Authors: Gupta Pammi Raj , Ghosh Pradyumna
Published: September 2024

Clinical trials are already established for high-temperature treatment of localized cancer, i.e., rise of tissue temperature to more than 55 °C as an effective noninvasive method for the treatment of localized cancer. However, as the computational techniques and capacity have enhanced considerably personalized treatment planning has become a manured tool. In the present investigation, a novel treatment planning framework is being proposed for radio frequency (RF) ablation of cancer tissue based on the tomographic image-based actual model. In patient-specific modeling, different thermal parameters like temperature history during ablation, and thermal damage profile have been virtually determined based on Penne's bioheat transfer model with appropriate boundary conditions. This advancement promises to significantly enhance the capabilities of healthcare practitioners in tailoring personalized treatment strategies for their clinical cases. By leveraging simulation outcomes, clinicians can precisely determine the most effective parameters, such as ablation power and frequency. Unfortunately, the current landscape in India presents a scarcity of specialized medical experts in the field of ablation oncology. Moreover, those who practice in this niche often rely on empirical charts rather than data-driven approaches, highlighting a critical need for increased expertise and the integration of advanced simulation technology to optimize cancer tissue ablation procedures. This real-life patient-specific three-dimensional model-based heat transfer model in a data center-based approach will not only guide the medical practitioner but also a greater number of clinicians can use that. Last but not least, optimizing different operating parameters of RF in this patient-centric approach for accurate treatment has also been discussed.
Validation of a Methodology to Assess the Flutter Limit-Cycle Oscillation Amplitude of Low-Pressure Turbine Bladed Disks—Part I: Mach Number Effects
Authors: Escudero Alvaro , Rodríguez-Blanco Salvador , Corral Roque
Published: September 2024

This paper presents a methodology to estimate the vibration amplitude of fluttering low-pressure turbine (LPT) blades saturated due to friction effects. The study utilizes an analytical model that balances aerodynamic work and dry-friction work. The analytical predictions are compared against experimental results to validate the model. The first part of this paper focuses on the influence of the Mach number on the work balance between aerodynamic and mechanical components. It is observed that the vibration amplitude of low-pressure turbine rotor blades notably increases with higher Mach numbers. In addition, numerical simulations are employed to assess the influence of the Mach number on the critical damping ratio. The results demonstrate that an appropriate scaling of the critical damping ratio with the exit Mach number collapses all the damping versus interblade phase angle curves into a single curve. This finding validates the scaling of the aerodynamic damping for different pressure ratios. Unsteady pressure measurements were acquired, carefully postprocessed to extract their flutter-induced peak components, and presented in a nodal diameter (ND) by nodal diameter basis. The postprocessed data were then used to characterize the vibration amplitude observed in the experiments. The trends of the measured unsteady pressure on the casing of a rotating rig and the proposed model with the Mach number for different shaft speeds are in good agreement. The vibration amplitude and the mean unsteady pressure increase with the Mach number and exhibit a maximum with the shaft speed.
Techno-Economic Analysis of the Solid Oxide Semiclosed CO2 Cycle for Different Plant Sizes
Authors: Martinelli Matteo , Campanari Stefano , Martelli Emanuele
Published: September 2024

This work presents a detailed techno-economic evaluation of the solid oxide semiclosed CO2 (SOS-CO2) cycle, a hybrid semiclosed cycle with solid oxide fuel cells (SOFC) developed by Politecnico di Milano. for different plant sizes, ranging from large utility plants (400 MWel) to industrial applications (50 MWel). The analysis includes the design and sizing of all the cycle components, including specific design optimization models for the most critical cycle components such as the regenerative heat exchanger and the turbine. Results are compared with the performance of the Allam cycle, an oxy-combustion cycle with higher technology readiness level (TRL). The results show that the SOS-CO2 cycle maintains high efficiency over the whole size range thanks to the modularity of the fuel cell and the regenerator, which counterbalances the decrease in turbomachine efficiency at small sizes. For the utility scale plant, despite its higher specific investment cost (3761 €/kW versus 2490€/kW), the SOS-CO2 cycle appears to be competitive with the Allam cycle in terms of cost of electricity (COE) (128.4 €/MWh and 127.8 €/MWh of the Allam cycle) thanks to its higher efficiency (68.9% versus 53.1%). At smaller sizes, the higher efficiency and the lower dependance on the economies of scale make the SOS-CO2 more economically advantageous: for the 50 MWel plant, the cost of electricity of the SOS-CO2 is 175.8 €/MWh versus 205.8 €/MWh of the Allam cycle.
Briefe einer Antifaschistin: 1936
Authors: Obermayer August
Published: September 2024

Der Text besteht aus Briefen, die 1936 von Marianne Angermann in Madrid an ihre Mutter, Charlotte Angermann in Dresden, geschrieben wurden. Diese Briefe zeichnen das Leben in den ersten Monaten des Spanischen Bürgerkriegs auf, wie es Marianne erlebte, zuerst an der Universität Madrid (Instituto de Investigaciones Médicas) und dann später in einem Militärlazarett (Hospital Militar No. 6) in dem Vorort Chamartín.
Letters of an antifascist: 1940
Authors: Barton Peter
Published: September 2024

The text records the thoughts and experiences of Charlotte Angermann in Dresden in the first year of the Second World War. As there was no postal communication with Great Britain, Charlotte began to address Marianne and Franz Bielschowsky, her daughter and son-in-law, in the form of diary entries as a substitute for letter writing. Charlotte’s journal summarises the main events of 1940 from the point of view of a politically uncommitted woman on the Home Front. She writes of increased rationing, the first bombing raids and of the military deaths of acquaintances and family members.
Letters of an antifascist: 1944
Authors: Barton Peter
Published: September 2024

The text records day to day life under National Socialism as it was experienced by Charlotte Angermann, a resident of Dresden during the Second World War. Angermann writes of bombing raids on other German cities, the shortages faced by the general population and the deaths of friends and family members. The diary entries are constructed as an address to her daughter, Marianne Angermann-Bielschowsky, who was at the time in Great Britain where worked as a research under Professor Green at the University of Sheffield.
Guided combinatorial synthesis and automated characterization expedites the discovery of hard, electrically conductive PtxAu1−x films
Authors: Adams D. P. , Kothari R. , Addamane S. , Jain M. , Dorman K. , Desai S. , Sobczak C. , Kalaswad M. , Bianco N. , DelRio F. W. , Custer J. O. , Rodriguez M. A. , Boro J. , Dingreville R. , Boyce B. L.
Published: September 2024

Sputter-deposited Pt-Au thin films have been reported to develop a hard, stable, nanocrystalline structure, yet little is known about how these characteristics vary with PtxAu1−x composition and process conditions. Toward this end, this document describes an extensive, combinatorial Pt-Au thin film library including characterized film compositions, structure, and properties. Complemented by kinematic Monte Carlo simulations of codeposition, a broad range of PtxAu1−x compositions (from x ∼ 0.02 to 0.93) was first established by sputtering with varied magnetron powers and gun tilt angles. The produced films were subsequently interrogated using automated nanoindentation, x-ray reflectivity, x-ray diffraction, atomic force microscopy, surface profilometry, four-point probe sheet resistance techniques, and wavelength dispersive spectroscopy in order to determine how hardness, modulus, density, surface roughness, structure, and resistivity vary with film stoichiometry and process parameters. Combinatorial films displayed an assortment of properties with the hardness of some films exceeding values reported previously for this material system. High hardness, high modulus, and low resistivity were generally attained when using increased deposition energy and reduced angle-of-incidence processes. Overall, the research identified promising, new PtxAu1−x compositions for future study and pinpointed strategies for improved deposition.
Germline mutations in a G protein identify signaling cross-talk in T cells
Authors: Ham Hyoungjun , Jing Huie , Lamborn Ian T. , Kober Megan M. , Koval Alexey , Berchiche Yamina A. , Anderson D. Eric , Druey Kirk M. , Mandl Judith N. , Isidor Bertrand , Ferreira Carlos R. , Freeman Alexandra F. , Ganesan Sundar , Karsak Meliha , Mustillo Peter J. , Teo Juliana , Zolkipli-Cunningham Zarazuela , Chatron Nicolas , Lecoquierre François , Oler Andrew J. , Schmid Jana Pachlopnik , Kuhns Douglas B. , Xu Xuehua , Hauck Fabian , Al-Herz Waleed , Wagner Matias , Terhal Paulien A. , Muurinen Mari , Barlogis Vincent , Cruz Phillip , Danielson Jeffrey , Stewart Helen , Loid Petra , Rading Sebastian , Keren Boris , Pfundt Rolph , Zarember Kol A. , Vill Katharina , Potocki Lorraine , Olivier Kenneth N. , Lesca Gaetan , Faivre Laurence , Wong Melanie , Puel Anne , Chou Janet , Tusseau Maud , Moutsopoulos Niki M. , Matthews Helen F. , Simons Cas , Taft Ryan J. , Soldatos Ariane , Masle-Farquhar Etienne , Pittaluga Stefania , Brink Robert , Fink Danielle L. , Kong Heidi H. , Kabat Juraj , Kim Woo Sung , Bierhals Tatjana , Meguro Kazuyuki , Hsu Amy P. , Gu Jingwen , Stoddard Jennifer , Banos-Pinero Benito , Slack Maria , Trivellin Giampaolo , Mazel Benoît , Soomann Maarja , Li Samuel , Watts Val J. , Stratakis Constantine A. , Rodriguez-Quevedo Maria F. , Bruel Ange-Line , Lipsanen-Nyman Marita , Saultier Paul , Jain Rashmi , Lehalle Daphne , Torres Daniel , Sullivan Kathleen E. , Barbarot Sébastien , Neu Axel , Duffourd Yannis , Similuk Morgan , McWalter Kirsty , Blanc Pierre , Bézieau Stéphane , Jin Tian , Geha Raif S. , Casanova Jean-Laurent , Makitie Outi M. , Kubisch Christian , Edery Patrick , Christodoulou John , Germain Ronald N. , Goodnow Christopher C. , Sakmar Thomas P. , Billadeau Daniel D. , Küry Sébastien , Katanaev Vladimir L. , Zhang Yu , Lenardo Michael J. , Su Helen C.
Published: September 2024

Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in
GNAI2
, which encodes G
αi2
, a key component in heterotrimeric G protein signal transduction usually thought to regulate adenylyl cyclase–mediated cyclic adenosine monophosphate (cAMP) production. Patients with activating G
αi2
mutations had clinical presentations that included impaired immunity. Mutant G
αi2
impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant G
αi2
influenced TCR signaling by sequestering the guanosine triphosphatase (GTPase)–activating protein RASA2, thereby promoting RAS activation and increasing downstream extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)–AKT S6 signaling to drive cellular growth and proliferation.
Origin and fate of the pseudogap in the doped Hubbard model
Authors: Šimkovic Fedor , Rossi Riccardo , Georges Antoine , Ferrero Michel
Published: September 2024

The relationship between the pseudogap and underlying ground-state phases has not yet been rigorously established. We investigated the doped two-dimensional Hubbard model at finite temperature using controlled diagrammatic Monte Carlo calculations, allowing for the computation of spectral properties in the infinite-size limit and with arbitrary momentum resolution. We found three distinct regimes as a function of doping and interaction strength: a weakly correlated metal, a correlated metal with strong interaction effects, and a pseudogap regime at low doping. We show that the pseudogap forms both at weak coupling, when the magnetic correlation length is large, and at strong coupling, when it is shorter. As the temperature goes to zero, the pseudogap regime extrapolates precisely to the ordered stripe phase found by ground-state methods.
Large library docking identifies positive allosteric modulators of the calcium-sensing receptor
Authors: Liu Fangyu , Wu Cheng-Guo , Tu Chia-Ling , Glenn Isabella , Meyerowitz Justin , Kaplan Anat Levit , Lyu Jiankun , Cheng Zhiqiang , Tarkhanova Olga O. , Moroz Yurii S. , Irwin John J. , Chang Wenhan , Shoichet Brian K. , Skiniotis Georgios
Published: September 2024

Positive allosteric modulator (PAM) drugs enhance the activation of the calcium-sensing receptor (CaSR) and suppress parathyroid hormone (PTH) secretion. Unfortunately, these hyperparathyroidism-treating drugs can induce hypocalcemia and arrhythmias. Seeking improved modulators, we docked libraries of 2.7 million and 1.2 billion molecules against the CaSR structure. The billion-molecule docking found PAMs with a 2.7-fold higher hit rate than the million-molecule library, with hits up to 37-fold more potent. Structure-based optimization led to nanomolar leads. In ex vivo organ assays, one of these PAMs was 100-fold more potent than the standard of care, cinacalcet, and reduced serum PTH levels in mice without the hypocalcemia typical of CaSR drugs. As determined from cryo–electron microscopy structures, the PAMs identified here promote CaSR conformations that more closely resemble the activated state than those induced by the established drugs.
Characterization of galactose catabolic pathways in
Streptococcus agalactiae
and identification of a major galactose: phosphotransferase importer
Authors: Hiron Aurelia , Melet Morgane , Guerry Capucine , Dubois Ilona , Rong Vanessa , Gilot Philippe
Published: September 2024

We identified and characterized genomic regions of
Streptococcus agalactiae
that are involved in the Leloir and the tagatose-6-phosphate pathways for D-galactose catabolism. The accumulation of mutations in genes coding the Leloir pathway and the absence of these genes in a significant proportion of the strains suggest that this pathway may no longer be necessary for
S. agalactiae
and is heading toward extinction. In contrast, a genomic region containing genes coding for intermediates of the tagatose-6-phosphate pathway, a Gat family PTS transporter, and a DeoR/GlpR family regulator is present in the vast majority of strains. By deleting genes that code for intermediates of each of these two pathways in three selected strains, we demonstrated that the tagatose-6-phosphate pathway is their sole route for galactose catabolism. Furthermore, we showed that the Gat family PTS transporter acts as the primary importer of galactose in
S. agalactiae
. Finally, we proved that the DeoR/GlpR family regulator is a repressor of the tagatose-6-phosphate pathway and that galactose triggers the induction of this biochemical mechanism.

IMPORTANCE

S. agalactiae
, a significant pathogen for both humans and animals, encounters galactose and galactosylated components within its various ecological niches. We highlighted the capability of this bacterium to metabolize D-galactose and showed the role of the tagatose-6-phosphate pathway and of a PTS importer in this biochemical process. Since
S. agalactiae
relies on carbohydrate fermentation for energy production, its ability to uptake and metabolize D-galactose could enhance its persistence and its competitiveness within the microbiome.
Outbreak-associated
Salmonella
Baildon found in wastewater demonstrates how sewage monitoring can supplement traditional disease surveillance
Authors: M'ikanatha Nkuchia M. , Goldblum Zoe S. , Cesari Nicholas , Nawrocki Erin M. , Fu Yezhi , Kovac Jasna , Dudley Edward G.
Published: September 2024

Non-typhoidal
Salmonella
is a common cause of gastroenteritis worldwide, but current non-typhoidal
Salmonella
surveillance is suboptimal. Here, we evaluated the utility of wastewater monitoring to enhance traditional surveillance for this foodborne pathogen. In June 2022, we tested raw sewage collected twice a week from two treatment plants in central Pennsylvania for non-typhoidal
Salmonella
and characterized isolates using whole-genome sequencing. We recovered 43
Salmonella
isolates from wastewater samples, differentiated by genomic analysis into seven serovars: 16 Panama (37.2%), 9 Senftenberg (20.9%), 8 Baildon (18.6%), and 3 or fewer of four other serovars. We assessed genetic relatedness and epidemiologic links between these wastewater isolates with those from patients with salmonellosis. All
S
. Baildon isolates from wastewater were genetically similar to those associated with a known contemporaneous salmonellosis outbreak.
S
. Baildon from wastewater and 42 outbreak-related isolates in the national outbreak detection database had the same core genome multilocus sequence typing, and outbreak code differed by zero or one single polynucleotide polymorphism. One of the 42 outbreak-related isolates was obtained from a patient residing in the wastewater sample collection catchment area, which serves approximately 17000 people.
S
. Baildon is a rare serovar (reported in <1% cases nationally, over five years). Our study underscores the value of monitoring sewage from a defined population to supplement traditional surveillance methods for the evidence of
Salmonella
infections and to determine the extent of outbreaks.

IMPORTANCE

During the COVID-19 pandemic, monitoring for SARS-CoV-2 in wastewater was highly effective in identifying the variants of concern earlier than clinical surveillance methods. Here, we show that monitoring domestic sewage can also augment traditional reporting of foodborne illnesses to public health authorities. Our study detected multiple
Salmonella enterica
serovars in samples from two wastewater treatment plants in central Pennsylvania. Using whole-genome sequencing, we demonstrated that the isolates of variant
S
. Baildon clustered with those from a foodborne salmonellosis outbreak that occurred in a similar time frame. Cases were primarily from Pennsylvania, and one individual lived within the wastewater treatment catchment area. This study highlights the effectiveness of domestic sewage testing as a proactive public health strategy to track and respond to infectious disease outbreaks.
Evaluation of an expanded antibiotic resistance gene panel on prediction of antimicrobial susceptibility results for Gram-negative bacteria in blood cultures
Authors: Manuel Carmila , Maynard Richard , Simpkins Synthia , Haro Michelle , Humphries Romney
Published: September 2024

The QIAstat-Dx BCID Panels (RUO) (“QIAstat,” QIAGEN, Hilden, Germany) for identification of 13 Gram-negative bacteria and 18 antimicrobial resistance (AMR) gene groups was evaluated. The study was conducted in two phases; in phase 1, analytical performance was evaluated against 154 challenge isolates against whole genome sequencing data. In this phase, sensitivity and specificity of organism identification calls were 153/154 (99.3%) and 1,748/1,749 (99.8%), respectively. For AMR genes, sensitivity was 434/435 (99.8%) and specificity was 2,334/2,337 (99.9%). One false-negative
bla
IMP
, one false-positive
bla
CTX-M
, and two false-positive aac-6’-lb detections were noted in this challenge set of organisms. In phase 2, 101 clinical blood culture isolates of Gram-negative rods were evaluated by the multiplexed PCR versus reference broth microdilution, for the ability of identification combined with AMR genes to predict final susceptibility results. Negative predictive values were 92.8% for ampicillin resistance (100% for
Escherichia coli
), 93.4% for ceftriaxone, 97.4% for ceftazidime, and 98.7% for cefepime. In constrast, negative predictive values for current standard of care (identification plus detection of
bla
CTX-M
) ranged from 56.5% to 88.8%. This study demonstrated additive value of additional beta-lactamase genes for bacteria isolated from blood cultures.

IMPORTANCE

Prediction of Gram-negative bacteria resistance through detection of resistance genes is complex. This study evaluated a novel, direct-from-blood or bacterial isolate multiplexed PCR for the detection of 17 resistance genes, and evaluated the prediction of antimicrobial susceptibility.
The Rac1-PAK1-Arp2/3 signaling axis regulates CHIKV nsP1-induced filopodia and optimal viral genome replication
Authors: Aïqui-Reboul-Paviet Olivier , Bakhache William , Bernard Eric , Holsteyn Lise , Neyret Aymeric , Briant Laurence
Published: September 2024

Alphavirus infection induces dramatic remodeling of host cellular membranes, producing filopodia-like and intercellular extensions. The formation of filopodia-like extensions has been primarily assigned to the replication protein nsP1, which binds and reshapes the host plasma membrane when expressed alone. While reported decades ago, the molecular mechanisms behind nsP1 membrane deformation remain unknown. Using mammalian epithelial cells and Chikungunya virus (CHIKV) as models, we characterized nsP1-induced membrane deformations as highly dynamic actin-rich lamellipodia and filopodia-like extensions. Through pharmacological inhibition and genetic invalidation, we identified the critical contribution of the Rac1 GTPase and its downstream effectors PAK1 and the actin nucleator Arp2 in nsP1-induced membrane deformation. An intact Rac1-PAK1-Arp2 signaling axis was also required for optimal CHIKV genome replication. Therefore, our results designate the Rac1-PAK1-Arp2 pathway as an essential signaling node for CHIKV infection and establish a parallel requirement for host factors involved in nsP1-induced plasma membrane reshaping and assembly of a functional replication complex.

IMPORTANCE

The alphavirus nsP1 protein dramatically remodels host cellular membranes, resulting in the formation of filopodia-like extensions. Although described decades ago, the molecular mechanisms controlling these membrane deformations and their functional importance remain elusive. Our study provides mechanistic insight, uncovering the critical role of the Rac1 GTPase, along with its downstream effectors PAK1 and the actin nucleator Arp2, in the nsP1-associated phenotype. Furthermore, we demonstrate that the Rac1-PAK1-Arp2 pathway is essential for optimal CHIKV genome replication. Our findings establish a parallel in the cellular mechanisms governing nsP1-induced plasma membrane reshaping and the production of a functional replication complex in infected cells.