bluuebunny/crossref_metadata_2025 huggingface dataset:
Carrollian partition functions and the flat limit of AdS
Authors: Kraus Per , Myers Richard M.
Published: February 2025

Abstract

The formulation of the S-matrix as a path integral with specified asymptotic boundary conditions naturally leads to the realization of a Carrollian partition function defined on the boundary of Minkowski space. This partition function, specified at past and future null infinity in the case of massless particles, generates Carrollian correlation functions that encode the S-matrix. We explore this connection, including the realization of symmetries, soft theorems arising from large gauge transformations, and the correspondence with standard momentum space amplitudes. This framework is also well-suited for embedding the Minkowski space S-matrix into the AdS/CFT duality in the large radius limit. In particular, we identify the AdS and Carrollian partition functions through a simple map between their respective asymptotic data, establishing a direct correspondence between the actions of symmetries on both sides. Our approach thus provides a coherent framework that ties together various topics extensively studied in recent and past literature.
Perturbatively exact supersymmetric partition functions of ABJM theory on Seifert manifolds and holography
Authors: Hong Junho
Published: February 2025

Abstract

We undertake a comprehensive analysis of the supersymmetric partition function of the U(N)
k
× U(N)
−k
ABJM theory on a U(1) fibration over a Riemann surface, evaluating it to all orders in the 1/N-perturbative expansion up to exponentially suppressed corrections. Through holographic duality, our perturbatively exact result is successfully matched with the regularized on-shell action of a dual Euclidean AdS4-Taub-Bolt background incorporating 4-derivative corrections, and also provides valuable insights into the logarithmic corrections that emerge from the 1-loop calculations in M-theory path integrals. In this process, we revisit the Euclidean AdS4-Taub-Bolt background carefully, elucidating the flat connection in the background graviphoton field. This analysis umambiguously determines the U(1)
R
holonomy along the Seifert fiber, thereby solidifying the holographic comparison regarding the partition function on a large subclass of Seifert manifolds.
Integrated correlators with a Wilson line in a $$ \mathcal{N} $$ = 2 quiver gauge theory at strong coupling
Authors: Pini Alessandro
Published: February 2025

Abstract

We consider the four-dimensional

$$ \mathcal{N} $$

N

= 2 quiver gauge theory arising from a ℤ2 orbifold of

$$ \mathcal{N} $$

N

= 4 super Yang-Mills with gauge group SU(2N). We study the integrated correlator between a half-BPS Wilson line and two Higgs branch operators of conformal dimension 2. Using supersymmetric localization, we resum the perturbative series for this observable and obtain exact expressions for both the planar and next-to-planar terms of its large N expansion, valid for arbitrary values of the ’t Hooft coupling. Finally, through a combination of analytical and numerical methods, we determine the leading terms of the corresponding strong-coupling expansions.
Susy breaking soft terms in the supersymmetric Pati-Salam landscape from intersecting D6-branes
Authors: Sabir Mudassar , Mansha Adeel , Li Tianjun , Wang Zhi-Wei
Published: February 2025

Abstract

We investigate the supersymmetry breaking soft terms for all the viable models in the complete landscape of three-family supersymmetric Pati-Salam models arising from intersecting D6-branes on a 𝕋6
/(ℤ2 × ℤ2) orientifold in type IIA string theory. The calculations are performed in the general scenario of u-moduli dominance with the s-moduli turned on, where the soft terms remain independent of the Yukawa couplings and the Wilson lines. The results for the trilinear coupling, gaugino-masses, squared-mass parameters of squarks, sleptons and Higgs depend on the brane wrapping numbers and the susy breaking parameters. We find that unlike the Yukawa couplings which remain unchanged for the models dual under the exchange of two SU(2) sectors, the corresponding soft term parameters only match for the trilinear coupling and the mass of the gluino. This can be explained by the internal geometry where the Yukawa interactions depend only on the triangular areas of the worldsheet instantons while the soft terms have an additional dependence on the orientation-angles of D6-branes in the three two-tori. In the special limit of parameter space we find universal masses for the Higgs and the gauginos.
Birthweight and risk of chronic kidney disease after a type 2 diabetes diagnosis in the DD2 cohort
Authors: Hansen Aleksander L. , Christiansen Christian F. , Brøns Charlotte , Engelhard Leonie M. , Hansen Torben , Nielsen Jens S. , Vestergaard Peter , Højlund Kurt , Jessen Niels , Olsen Michael H. , Sørensen Henrik T. , Rossing Peter , Thomsen Reimar W. , Vaag Allan
Published: February 2025

Aims/hypothesis

Low birthweight (LBW) is associated with younger age, less obesity and more hypertension among people recently diagnosed with type 2 diabetes, as well as increased cardiovascular morbidity and mortality risk. It is not known whether LBW is associated with an increased risk of incident chronic kidney disease (CKD) among people with a type 2 diabetes diagnosis.

Methods

Original midwife records were retrieved for 5982 participants with recently diagnosed type 2 diabetes enrolled in the Danish Center for Strategic Research in Type 2 Diabetes (DD2) cohort between 2010 and 2024. They were followed until first incident CKD diagnosis, defined as either two eGFR measurements <60 ml/min per 1.73m2 or two urine albumin/creatinine ratio (UACR) measurements >3 mg/mmol, each 90–365 days apart. Confounder-standardised 10 year risks of CKD were estimated, with death considered as a competing risk. Adjusted hazard ratios (aHRs) for CKD were computed using Cox and spline regression analyses. All analyses were controlled for differences in sex, age at enrolment, calendar year at birth, family history of diabetes and born-at-term status. Mixed-effects models were used to examine the trajectories of eGFR and UACR following enrolment.

Results

A total of 1501 incident CKD endpoints occurred, corresponding to an incidence rate of 42.4 per 1000 person-years over a median follow-up time of 8.3 years. Spline models with birthweight as a continuous measure showed progressively increasing aHRs for CKD with decreasing birthweight. The 10-year standardised risk of CKD was 36.0% in people with LBW (<2500 g) and 30.6% in people with a normal birthweight (2500–4000 g), yielding a risk difference (RD) of 5.5% (95% CI −0.5%, 11.8%) and an aHR of 1.23 (95% CI 0.98, 1.55). People with type 2 diabetes and high birthweight (>4000 g) had a similar 10-year standardised CKD risk compared with normal birthweight (33.1% and 30.6%, respectively). This yielded an RD of 2.5% (95% CI −1.6%, 6.7%) and an aHR of 1.10 (95% CI 0.93, 1.29). In mixed-effects models examining eGFR and UACR trajectories, each 1 kg decrease in birthweight was associated with a 6.6% (95% CI 1.9, 11.1) increase in UACR, whereas no association was found for eGFR.

Conclusions/interpretation

A history of LBW was associated with elevated risk of CKD among people with a recent type 2 diabetes diagnosis, although the precision of risk estimates was limited.

Graphical Abstract
The private sector is hoarding AI researchers: what implications for science?
Authors: Jurowetzki Roman , Hain Daniel S. , Wirtz Kevin , Bianchini Stefano
Published: February 2025

The migration of artificial intelligence (AI) researchers from academia to industry has recently sparked concerns about its implications for scientific progress. Can academia retain enough talent to shape AI advancements and counterbalance the growing influence of corporate AI labs? Analyzing OpenAlex data, we find a significant transition of premier talent to industry roles over the past decade, particularly to major tech firms. Young, highly cited scholars from leading institutions are the most likely to make this move. Following the transition, their research tends to show reduced novelty and impact. This industry-dominant shift in AI research highlights worries of an “AI brain drain”, the sidelining of exploratory science for commercial interests, and the potential misalignment with societal goals.
The growth and development of Nordic regional science research 1982–2022: bibliometric evidence from thirteen regional science journals
Authors: Karlsson Charlie , Hammarsssfelt Björn
Published: February 2025

In a paper published in 2020, Philip McCann gives a qualitative overview of “the Nordic contribution to regional science”, which, however, only includes contributions by Swedish regional science researchers. The purpose of this paper is to complement McCann’s overview by highlighting Nordic contributions to regional science in the period 1983–2022 through a bibliometric analysis of publications in a set of thirteen regional science journals indexed in Web of Science, using several standard bibliometric tools. Our most interesting and surprising result is that the number of “Nordic” publications in the chosen set of journals has grown more than six times faster than the total number of publications in these journals between 1983–1992 and 2013–2022. This implies that the “Nordic” regional science researchers have increased their “market share” from 1.9 to 9.1 per cent. During the same period, the share of co-authored papers increased from 50.0 to 82.9 per cent and the share of international co-authorships increased from 0 to 50.0 per cent and went from being a mainly intra-European activity to a global activity. This process is also reflected in a certain international influence on the research topics during the four periods analysed, but to a considerable extent it seems that the Nordic regional scientists have pursued their own Nordic research themes. In terms of individual research productivity, there was the expected skewed distribution with a small number of researchers with a large research output. At the institutional level, there were notable changes in the ranking of institutions in terms of number of authorships, but one institution—Umeå University—ranked among the Nordic top-2 in all four periods.
Dual microelectromembrane extraction as a tunable platform for the determination of antioxidant compounds with varied hydrophobicity in oral bioaccessibility assays of food commodities: a proof of concept
Authors: Sahragard Ali , Pagan-Galbarro Carlos , Cocovi-Solberg David J. , Miró Manuel
Published: February 2025

An automatic millifluidic dual microelectromembrane extraction (D-µEME) method as a front-end to HPLC-UV-Vis is herein proposed for the first time to facilitate the matrix clean-up of relatively polar polyphenolic acidic (PPA) antioxidants with a relatively broad range of lipophilicity (logP from −0.27 to 2.14) from simulated gastric extracts of oral bioaccessibility tests. The flow setup is amenable to handle microliter volumes of two distinct organic phases along with donor and acceptor phases unsupervised, conduct in-tube D-µEME in parallel without supporting membranes, and mix the two acceptor phases automatically prior to online HPLC-UV-Vis. The target antioxidants involve gallic acid, chlorogenic acid, 4-hydroxybenzoic acid, caffeic acid, and trans-cinnamic acid. Various solvents are explored to investigate their compatibility for simultaneous D-µEME, including 1-pentanol, 1-hexanol, 1-heptanol, 1-octanol, and 1-nonanol, as well as deep eutectic solvents, e.g., thymol/6-methyl coumarin, and ionic liquids as additives to alcohols. Notably, 1-pentanol and 1-octanol exhibit the best performances in extracting the most polar (gallic acid and chlorogenic acid) and the least polar analytes (trans-cinnamic acid), respectively, notwithstanding both solvents are amenable to retrieve analytes with medium hydrophobicity (4-hydroxybenzoic acid and caffeic acid). The effects of the voltage, the extraction time, and the sample ionic strength on the extraction recoveries are also investigated in detail. Under the selected D-µEME conditions, the overall linear ranges span from 1.25 to 80 mg/L, with limits of detection ranging from 0.2 to 3.3 mg/L. The flow-based D-µEME is resorted to oral bioaccessibility assays in the gastric phase of the target compounds from eggplant, blueberry, and coffee bean extracts, with relative extraction recoveries ranging from 71.5 to 133.5%.

Graphical abstract
Increasing chemical coverage, accuracy, and reproducibility of the processing method for polar organic chemical integrative samplers
Authors: Baglietto Matteo , MacKeown Henry , Benedetti Barbara , Di Carro Marina , Magi Emanuele
Published: February 2025

Despite their diffusion in research studies, passive samplers are rarely used in regulatory applications. To expand the employment of passive samplers in regulatory environmental studies, standardized procedures for processing each sampler type should be proposed and accepted, but currently, each study develops its own protocol based on previous knowledge and specific needs. In this work, six identical polar organic chemical integrative samplers in seawater were deployed to understand the importance of the sorbent transfer method prior to the elution step. A common “wet transfer” with ultra-pure water was compared to a less diffused “dry-transfer,” assessing recoveries and matrix effects of 38 target compounds of emerging concern, including polar pesticides, recreational and food-related substances, pharmaceuticals, industrial additives, and ultra-violet (UV) filters. The dry-transfer procedure generally allowed better recoveries, especially for the more polar compounds, without affecting matrix effects (which remained in the range 40–130%). Along with the recovery assessment, the analysis of the non-spiked sorbent extracts revealed traces of many of the targeted emerging contaminants, quantifying perfluorooctanoic acid, UV-filters, carbamazepine, diclofenac, and triclosan. Furthermore, other compounds were found below their limits of quantitation. Ten analytes were detected only in the extracts of the dry-transferred passive samplers, highlighting the importance of applying this protocol, especially when dealing with polar compounds. This refined processing method, therefore, permits a more standardized and reproducible strategy, at the same time enlarging the set of analytes which could be detected and quantified.

Graphical abstract
Phosphonylated tyrosine and cysteine disulfide adducts both generated from immunoglobulin G and human serum albumin indicate exposure to the nerve agent VX in vitro
Authors: Reuter Henrik , Steinritz Dirk , Worek Franz , John Harald
Published: February 2025

Pronase-catalyzed proteolysis is shown to produce single amino acid adducts of tyrosine (Tyr) and cysteine (Cys) obtained from both human serum albumin (HSA) and immunoglobulin G (IgG) after in vitro exposure of plasma to the nerve agent VX. Total plasma as well as isolated HSA and IgG yielded the Tyr residue phosphonylated with the ethyl methylphosphonic acid moiety, Tyr(-EMP). Furthermore, a Cys residue adducted with the diisopropylaminoethane thiol leaving group of the agent bound via a disulfide bridge, Cys(-DPAET), was also obtained from both proteins. Even though Tyr(-EMP) represents an internationally well-accepted biomarker of a VX-like agent its origin from plasma IgG has never been shown before. In addition, this is the first time that Cys(-DPAET) is presented as a biomarker of VX exposure clearly identifying the chemical nature of the V-type nerve agent’s leaving group. Both biomarkers were detected after selective affinity-based solid-phase extraction (SPE) from plasma that yielded highly purified HSA and IgG as documented by sodium dodecyl polyamide gel electrophoresis (SDS-PAGE). Both biomarkers were found in the corresponding protein bands of HSA and IgG each after in-gel proteolysis with pronase. A micro liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry method (LC-ESI HR-MS/MS) was developed for the simultaneous detection of Tyr(-EMP) and Cys(-DPAET). The time for proteolysis was optimized for maximum biomarker yield. The method showed excellent selectivity and sensitivity, and the adducted proteins and biomarkers were found to be highly stable during storage. Accordingly, the presented method sheds more light on the molecular toxicology of VX and broadens the spectrum of methods suited for biomedical verification.

Graphical Abstract
Stimulus conditions eliciting sneezing in response to bright light
Authors: Trinkl Josef , Bickerstaff Lucien , Munkwitz Stephan , Spitschan Manuel
Published: February 2025

The photic sneeze reflex (PSR) is an involuntary sneezing response to bright light exposure, affecting approximately 25% of the population. Despite its long history in scientific literature, the underlying mechanisms remain unclear. Several theories, including optic-trigeminal summation, parasympathetic hypersensitivity, and parasympathetic generalization, have been proposed, but none have been conclusively validated. Reproducing the PSR reliably in a laboratory setting is crucial for understanding its neural underpinnings, yet the specific light parameters that trigger PSR are not well-defined. This mini-review aims to consolidate current knowledge on the light stimulus parameters (intensity, spectral composition, wavelength, duration, timing, spatial configuration) that elicit the PSR. A comprehensive literature search was conducted using MEDLINE (PubMed), Google Scholar, Google Books, and Google, employing terms related to photic sneezing in multiple languages. Articles from 2020 to 2024 were screened, resulting in 167 records, with seven studies focusing on stimulus parameters included in this review. The reviewed studies, including four case reports and three laboratory experiments, consistently support that bright light can induce sneezing in susceptible individuals. However, there is significant variability in the methodologies and outcomes, limiting comparability and indicating a need for systematic investigation. No study has yet examined the parametric relationship between light parameters and the PSR. The heterogeneity of methods and findings in the existing literature highlights the lack of standardized research on the specific light parameters that trigger the PSR. This review underscores the need for controlled experiments to clarify these relationships and improve our understanding of the underlying neural mechanisms. Existing research on photic sneezing stimulus parameters is fragmented and lacks systematic approaches. Future studies should focus on standardized, parametric investigations to elucidate the light-sensitive mechanisms of the PSR.
Novel combination therapy for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma: a systematic review and network meta-analysis
Authors: Yanagisawa Takafumi , Mori Keiichiro , Matsukawa Akihiro , Kawada Tatsushi , Katayama Satoshi , Laukhtina Ekaterina , Rajwa Pawel , Quhal Fahad , Pradere Benjamin , Fukuokaya Wataru , Iwatani Kosuke , Pichler Renate , Teoh Jeremy Yuen-Chun , Moschini Marco , Krajewski Wojciech , Miki Jun , Shariat Shahrokh F. , Kimura Takahiro ,   European Association of Urology–Young Academic Urologists Urothelial Carcinoma Working Group (EAU-YAU)
Published: February 2025

Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47–0.99) and PFS (HR: 0.67, 95%CI 0.49–0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment.
Selective JAK2 pathway inhibition enhances anti-leukemic functionality in CD19 CAR-T cells
Authors: Mitsuno Kohei , Suematsu Masaya , Naito Yuki , Mayumi Azusa , Yoshida Hideki , Osone Shinya , Imamura Toshihiko , Nakazawa Yozo , Yagyu Shigeki , Iehara Tomoko
Published: February 2025

The integration of molecular targeted therapeutics with chimeric antigen receptor T (CAR-T) cell therapy represents a novel strategy to amplify the anti-tumor efficacy of immunotherapy. While CD19-targeted CAR-T cells and Janus kinase (JAK) inhibitors have independently shown efficacy against certain B-cell leukemias, such as Philadelphia chromosome-like acute lymphoblastic leukemia, the concurrent use of JAK1/2 inhibitors, such as ruxolitinib, has been implicated in reducing CAR-T cell potency by inhibiting the JAK1-dependent T cell activation pathway. This study explores the combinatorial use of a selective type II JAK2 inhibitor, CHZ868, with CD19 CAR-T cells, revealing a synergistic enhancement of anti-leukemic activity across B-cell tumor models irrespective of JAK2 mutational status. CHZ868-mediated JAK2 inhibition did not induce the exhaustion of CAR-T cells, maintaining efficacy over repeated tumor challenges and significantly extending survival in mouse models engrafted with JAK2 inhibitor-resistant leukemia cells (median survival, CD19 CAR-T + CHZ868 vs. CD19 CAR-T + DMSO: 32 days vs. 26 days, p = 0.0303). Transcriptomic analyses suggest that CHZ868 impedes CAR-T cell differentiation while preserving their proliferative capacity, a crucial factor in maintaining CAR-T cell functionality. Therefore, the selective inhibition of the JAK2 pathway may potentiate CAR-T cell therapy and offer a viable treatment strategy for patients with resistant B-cell leukemias.
Artificial intelligence-based spatial analysis of tertiary lymphoid structures and clinical significance for endometrial cancer
Authors: Suzuki Haruka , Hamada Kohei , Hamanishi Junzo , Ueda Akihiko , Murakami Ryusuke , Taki Mana , Mizuno Rin , Watanabe Koichi , Sato Hanako , Hosoe Yuko , Ito Hiroaki , Yamanoi Koji , Yoshitomi Hiroyuki , Kakiuchi Nobuyuki , Yamaguchi Ken , Matsumura Noriomi , Ogawa Seishi , Ueno Hideki , Mandai Masaki
Published: February 2025

With the incorporation of immune checkpoint inhibitors into the treatment of endometrial cancer (EC), a deeper understanding of the tumor immune microenvironment is critical. Tertiary lymphoid structures (TLSs) are considered favorable prognostic factors for EC, but the significance of their spatial distribution remains unclear. B cell receptor repertoire analysis performed using six TLS samples located at various distances from the tumor showed that TLSs in distal areas had more shared B cell clones with tumor-infiltrating lymphocytes. To comprehensively investigate the distribution of TLSs, we developed an artificial intelligence model to detect TLSs and determine their spatial locations in whole-slide images. Our model effectively quantified TLSs, and TLSs were detected in 69% of the patients with EC. We identified them as proximal or distal to the tumor margin and demonstrated that patients with distal TLSs (dTLSs) had significantly prolonged overall survival and progression-free survival (PFS) across multiple cohorts [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.36–0.88; p = 0.01 for overall survival; HR, 0.58; 95% CI, 0.40–0.84; p = 0.004 for PFS]. When analyzed by molecular subtype, patients with dTLSs in the copy-number-high EC subtype had significantly longer PFS (HR, 0.51; 95% CI, 0.29–0.91; p = 0.02). Moreover, patients with dTLSs had a higher response rate to immune checkpoint inhibitors (87.5 vs. 41.7%) and a trend toward improved PFS. Our findings indicate that the functions and prognostic implications of TLSs may vary with their locations, and dTLSs may serve as prognostic factors and predictors of treatment efficacy. This may facilitate personalized therapy for patients with EC.
Blood-based prognostic scores and early dynamics under immunotherapy to select patients with metastatic solid tumors for continuing immune check-point inhibition: a prospective longitudinal study
Authors: García-Corbacho Javier , Indacochea Alberto , Victoria Iván , Moreno Débora , Angelats Laura , González Navarro Azucena E. , Mezquita Laura , Brasó-Maristany Fara , Galván Patricia , Mellado Begoña , Viñolas Nuria , Sauri Tamara , Nogué Miquel , Adamo Barbara , Maurel Joan , Pineda Estela , Gaba Lydia , Reig Oscar , Basté Neus , Sanfeliu Esther , Juan Manel , Prat Aleix , Schettini Francesco
Published: February 2025

Introduction

Immune check-point inhibitors (ICI) were a major breakthrough in cancer care, but optimal patient selection remains elusive in most tumors.

Methods

Overall 173 adult patients with metastatic solid tumors candidates to ICI in clinical trials at our Institution were prospectively recruited. Blood samples were collected at cycle 1 (C1D1) and 2 (C2D1) and until the occurrence of progressive disease (PD). C1D1 LIPI, RMH, PMHI, NLR, dNLR, PIPO and GRIm prognostic scores were calculated. The primary endpoint was identifying the best score to predict rapid PD (≤ 4 months) with ICI using logistic regressions accounting for tumor type, and receiving operators characteristics (ROC) with area under curve (AUC), accompanied by an extensive comparison of the score performances in the prediction of overall survival (OS), progression-free survival (PFS), overall response rates (ORR) and durable clinical benefit (DCB). Secondary objectives included describing study cohort outcomes and studying the association between the selected score at C1D1, C2D1 and its dynamics with OS and PFS.

Results

C1D1 LIPI was the best predictor of rapid PD, OS and PFS, regardless of cancer type, compared to other scores. No score was associated to ORR and only RMH to DCB. Baseline LIPI detected three categories of patients with significantly different OS (p < 0.001) and PFS (p = 0.013). The same was observed at C2D1 for OS and PFS (both p = 0.020). Significant LIPI class shifts were observed in the overall population (p < 0.001), rapid progressors (p = 0.029) and non-rapid progressors (p = 0.009). Retaining a good LIPI or experiencing a shift towards a better prognostic class was associated to improved OS (p = 0.009) and PFS (p = 0.006). C2D1 LIPI, but not C1D1, remained significantly associated to rapid PD in multivariable analysis.

Conclusions

LIPI may improve patient selection for ICI and guide treatment adjustments according to on-treatment dynamics in a pancancer context.
A network aggregation model for amyloid-$$\beta $$ dynamics and treatment of Alzheimer’s diseases at the brain scale
Authors: Brennan Georgia S. , Goriely Alain
Published: February 2025

Neurodegenerative diseases are associated with the assembly of specific proteins into oligomers and fibrillar aggregates. At the brain scale, these protein assemblies can diffuse through the brain and seed other regions, creating an autocatalytic protein progression. The growth and transport of these assemblies depend on various mechanisms that can be targeted therapeutically. Here, we use spatially-extended nucleation-aggregation-fragmentation models for the dynamics of prion-like neurodegenerative protein-spreading in the brain to study the effect of different drugs on whole-brain Alzheimer’s disease progression.
No influence of patient age on operative treatment outcome of osteochondral lesions of the talus: data from the German Cartilage Registry (GCR, KnorpelRegister DGOU)
Authors: Richter Alena , Altemeier Anna , Becher Christoph , Ettinger Sarah , Güllmann Marco , Plaass Christian
Published: February 2025

Introduction

The influence of patient age on the clinical outcome of surgically treated osteochondral lesions of the talus (OCT) is controversial. Aim of this study was to evaluate the 24 months follow-up data of the German Cartilage Registry (KnorpelRegister DGOU, GCR) regarding the influence of patient age on clinical outcomes after surgical OCT treatment.

Materials and methods

303 patients met the inclusion criteria and were divided into patients < 40 years (27.1 ± 5.8 years, n = 177) and patients ≥ 40 years (50.8 ± 7.4 years, n = 126). Pre- and postoperative FAOS total scores, subscores and ΔFAOS for most frequent surgical techniques (bone marrow stimulation, matrix-augmented bone marrow stimulation, matrix-augmented bone marrow stimulation with additional bone grafting) and lesion size characteristics were evaluated for both groups. ANOVA analysis with post hoc Duncan test was applied for statistical analysis.

Results

Both patients < 40 years and patients ≥ 40 years benefit from surgical treatment of OCT showing significant changes from pre- to postoperative FAOS total score (63.8 ± 20.3 to 81.5 ± 17.8 in patients < 40 years, p < 0.001; 57.3 ± 20.1 to 74.9 ± 21.6 in patients ≥ 40 years, p < 0.001) and subscores. Younger patient group tended to higher pre- and postoperative scores. ΔFAOS was not different between both groups. Older patient group had significantly higher lesion size area and volume; proportion of additional bone grafting was increased.

Conclusion

Results of surgical therapy of OCTs are independent from patient age. There is no superiority of a specific surgical technique depending on patient age.
The prospective sonographic assessment of the lower uterine segment after cesarean section and its clinical utility
Authors: Spahn Stephan , Horky Alex , Sugiyo Dianita , Bahlmann Franz , Al Naimi Ammar
Published: February 2025

Purpose

This study aims to investigate the sonographic features of the lower uterine segment (LUS) and their association with successful vaginal birth after a cesarean section (VBAC).

Methods

This is a prospective observational cohort study of women who underwent a first cesarean section (CS). Inclusion criteria were age over 18 years and open family planning. Women with a history of any additional uterine surgery, as well as a vertical or inverted T uterotomy during the CS were excluded. A pregestational transvaginal sonography, followed by serial transabdominal ultrasound examinations at the first, second, and third trimesters upon starting a new pregnancy were performed. Each intra-gestational examination involved measuring the LUS on a sagittal plane over a length of 3 cm starting from the most inferior identifiable part of the myometrium behind a full bladder. Logistic regression was performed to test the association between measures of the LUS and successful vaginal birth after CS.

Results

96 women with a follow-up pregnancy within 2 years of the initial CS were included in the analysis. The pregestational RMT ratio was 62% and 38 (39%) women had a niche. The median thickness of the lower uterine segment was 8.34 mm (5.57–9.77), 4.75 mm (4.02–5.95), and 2.55 mm (2.01–3.55) at the first, second and third trimester, respectively. 70 women attempted VBAC and the risk of unplanned repeat CS was 37.1%. One millimeter increase in LUS thickness in the first trimester increased the odds of VBAC by 50–120% depending on the used measure (p < 0.05). This association weakened with increasing gestational age and the p values increased above 0.05.

Conclusion

There is a good chance of successful VBAC for women attempting it. The sonographic assessment of the lower uterine segment during pregnancy could be helpful in counseling these women, albeit it seems that performing ultrasound during the first trimester is more informative than second and third trimesters.
Intraoperative ABR measurements via the active middle ear implant vibrant soundbridge using different types of couplers
Authors: Cebulla Mario , Köstler Carolina , Herrmann David P. , Rak Kristen
Published: February 2025

Purpose

The Vibrant Soundbridge active middle ear implant is indicated for the treatment of different types of hearing loss. Recently, a novel system for determining implant performance based on auditory brainstem response (ABR) was developed. A reference value for the expected ABR hearing thresholds is determined on the base of a substantial number of measurements in this work.

Method

ABRs were recorded in patients following VSB surgery. A standard ABR system was employed, utilizing an implemented optimized chirp stimulus, which was transmitted directly to the VSB via the AcoustiAP transmission unit (MED-EL). The study included 104 subjects with different types of hearing loss. Six distinct VSB couplers were utilized in this cohort.

Results

ABR were recorded in all patients. The intraoperative ABR thresholds were 20.1 dB higher compared to the preoperative BC thresholds, 15.9 dB higher compared to the postoperative vibrogram, and 13.4 dB higher compared with the vibrogram thresholds determined at the first fitting. No significant differences were observed between the different couplers in either the investigated methods.

Conclusion

It can be posited that the presented intraoperative measurement reference value enhances the interpretability of ABR in VSB and should be considered, when using this method in VSB surgery.
Serum neurofilament light chain but not serum glial fibrillary acidic protein is a marker of early Huntington’s disease
Authors: Heim Beatrice , Mandler Elias , Peball Marina , Carbone Federico , Schwarzová Katarína , Demjaha Rina , Tafrali Cansu , Buchmann Arabella , Khalil Michael , Djamshidian Atbin , Seppi Klaus
Published: February 2025

Background

Huntington’s disease (HD) is caused by CAG trinucleotide expansion on chromosome 4, leading to mutant Huntingtin production. Premanifest carriers show no obvious clinical signs, and early symptoms progress slowly. Fluid biomarkers like neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), measurable in cerebrospinal fluid and serum (sNfL, sGFAP), offer potential predicting HD progression.

Objective

To assess the role of sGFAP and sNfL and clinical biomarkers in different disease stages and correlate with disease progression.

Methods

HD mutation carriers were categorized into clinical stages according to their motor symptoms and functional capacities. The Unified HD Rating Scale, cognitive assessments and olfactory tests were used to characterize the patients clinically. Furthermore, sNfL and sGFAP levels were assessed.

Results

We consecutively included 44 HD mutation carriers (13 premanifest HD (preHD), 18 in early (early HD) and 13 in advanced (advanced HD) disease stages) and 19 healthy controls (HC). Advanced HD patients performed worse on all clinical tasks and had higher sGFAP and sNfL levels compared to other groups (all p values < 0.05). We did not find difference in sGFAP levels between the preHD, early HD and HC group  (all p values > 0.05). In contrast, sNfL levels differed significantly between preHD and early HD, and HC (all p values < 0.05). ROC curve analysis revealed that the AUC of sGFAP (0.970) exhibited superior discriminatory accuracy compared to sNfL (0.791) levels in separating advanced from early HD patients. By contrast, ROC curve analysis revealed that the AUC of sNFL (0.988) exhibited superior discriminatory accuracy compared to sGFAP (0.609) levels in separating all HD mutation carriers from HC.

Conclusions

Our study indicates that sNfL can detect changes in very early and premanifest HD stages, whereas sGFAP showed differences in more advanced stages only.
Mortality in a cohort of WTC-exposed law-enforcement officers compared to non-WTC law-enforcement officers
Authors: Singh Ankura , Khalifeh Malak , Violanti John , Zeig-Owens Rachel , Todd Andrew C. , Shapiro Moshe Z. , Carwile Madeline E. , Dasaro Christopher R. , Li Jiehui , Yung Janette , Farfel Mark R. , Brackbill Robert M. , Cone James E. , Qiao Baozhen , Schymura Maria J. , Prezant David J. , Hall Charles B. , Boffetta Paolo
Published: February 2025

Purpose

World Trade Center (WTC) rescue/recovery workers were exposed to materials hazardous to health. Previous studies found lower than expected mortality among WTC rescue/recovery workers when compared to general populations, possibly due to healthy worker effects, better healthcare access and/or incomparability of the groups. We compared mortality rates in WTC-exposed law enforcement officers (LEOs) with rates in LEOs employed by the Buffalo, NY, Police Department. We also compared both cohorts to the general population.

Methods

Follow-up began at the later of one year after enrollment date or 1/1/2005 and ended at the earlier of death date or 12/31/2018. Analyses were restricted to ages 40–79 years (N = 11,476 WTC LEOs, N = 1668 non-WTC LEOs). We estimated standardized mortality ratios (SMRs) in each cohort using stratum-specific US mortality rates. Relative rates (RRs) and 95% CIs were estimated for the WTC vs. the Buffalo cohort using Poisson regression models adjusted for sex, race, age-group, and calendar-period.

Results

185 deaths were observed in the WTC cohort and 186 in the Buffalo cohort. All-cause and cause-specific SMRs were significantly lower in the WTC cohort. Similarly, the adjusted all-cause mortality RR for the WTC vs. Buffalo cohorts was 0.30 (95% CI = 0.23–0.40). The cause-specific mortality RRs were all significantly < 1.

Conclusion

We found lower overall and cause-specific mortality rates in WTC LEOs compared with both the general population and Buffalo LEOs. These results suggest that factors other than healthy worker effects, such as access to healthcare via the WTC Health Program, contribute to lower mortality rates in WTC rescue/recovery workers.
Supercell thunderstorm algorithm (STA): a nature-inspired metaheuristic algorithm for engineering optimization
Authors: Hassan Mohamed H. , Kamel Salah
Published: February 2025

In this paper, an optimization algorithm called supercell thunderstorm algorithm (STA) is proposed. STA draws inspiration from the strategies employed by storms, such as spiral motion, tornado formation, and the jet stream. It is a computational algorithm specifically designed to simulate and model the behavior of supercell thunderstorms. These storms are known for their rotating updrafts, strong wind shear, and potential for generating tornadoes. The optimization procedures of the STA algorithm are based on three distinct approaches: exploring a divergent search space using spiral motion, exploiting a convergent search space through tornado formation, and navigating through the search space with the aid of the jet stream. To evaluate the effectiveness of the proposed STA algorithm in achieving optimal solutions for various optimization problems, a series of test sequences were conducted. Initially, the algorithm was tested on a set of 23 well-established functions. Subsequently, the algorithm’s performance was assessed on more complex problems, including ten CEC2019 test functions, in the second experimental sequence. Finally, the algorithm was applied to five real-world engineering problems to validate its effectiveness. The experimental results of the STA algorithm were compared to those of contemporary metaheuristic methods. The analysis clearly demonstrates that the developed STA algorithm outperforms other methods in terms of performance.
Local solvability of the Poisson equation for closed $$G_2$$-structures
Authors: Buttsworth Timothy , Pulemotov Artem
Published: February 2025

We prove local solvability of the Poisson equation with definite right-hand side for closed

$$G_2$$

G
2

-structures.
Characterization of facial nerve outcomes following radiosurgery for vestibular schwannoma: a meta-analysis
Authors: Hovis Gabrielle E. A. , Chandla Anubhav , Pandey Aryan , Teton Zoe , Yang Isaac
Published: February 2025

Purpose

Gamma Knife radiosurgery (GKRS) is a precise and efficacious treatment modality for vestibular schwannoma (VS) with favorable cranial nerve preservation rates. This study aims to better characterize facial nerve (FN) outcomes in VS after GKRS.

Methods

A query of six medical databases was conducted following PRISMA guidelines. Eligible studies exclusively reported VS managed with single-fraction GKRS and included House-Brackmann (HB) scale assessments prior to and following GKRS. Data was analyzed using random-effects modeling, and FN preservation was defined as HB I or II at last follow-up.

Results

Data was analyzed from 15 articles with 3,155 patients at an mean age of 55.0 years. Mean tumor volume, radiation dose, follow-up, tumor control, and hearing preservation were 4.28 cm3, 13.3 Gy, 59.4 months, 92.7%, and 62.6%, respectively. The pooled FN preservation rate was 92.9%. Mean preoperative tumor volume > 2.5 cm3 and age > 60 years were significantly associated with worse preoperative FN function (p = 0.019, p = 0.023, respectively). Normal FN function (HB = 1) at last follow up was 95.8% for VS volume < 2.5 cm3 and 89.4% with larger volumes (p < 0.001). Doses ≤ 13 Gy were significantly associated with superior FN preservation (96.5%) compared to higher doses (p < 0.001). Tumor control and hearing preservation were not significantly associated with FN preservation.

Conclusion

This meta-analysis identifies tumor volume and radiation dose as prognostic factors for FN preservation. A FN preservation rate of 93% may be expected at five years after GKRS. This study provides a unique characterization of FN outcome that should be considered in the management of VS.
VIMP approach to fern’s sporophyte/gametophyte stages: taxonomic and phylogenetic electrochemical correlations
Authors: García-Martínez Eva , Estrelles Elena , Doménech-Carbó Antonio
Published: February 2025

The application of the voltammetry of immobilized particles methodology (VIMP) to microparticulate films prepared from the ethanolic extracts of different fern species in contact with aqueous acetate buffer is studied. The observed voltammetric responses can be mainly attributed to the oxidation of polyphenolic components of fern tissues. These responses provide a basis for linking the gametophyte stage to the fern sporophyte, facilitating taxonomic identification during the early developmental phase when distinguishing morphological characters are not clearly discernible. Data collected for 10 species from the Davalliaceae, Aspleniaceae, Athyriaceae, Polypodiaceae, Dryopteridaceae, Pteridaceae, and Osmundaceae families permit an electrochemical grouping consistent with taxonomic and phylogenetic data derived from available molecular genetic analysis.
Trophic position and periphyton carbon sources for macroinvertebrates in the litter patches of forested streams, with special reference to predatory species
Authors: Tachikake Shuhei , Kagaya Takashi , Norisada Mariko
Published: February 2025

Most research on lotic food webs has focused on reach-scale webs, whereas research on the structure and system openness of lotic food webs has not focused on the microhabitat scale. In forested streams, plant litter from riparian vegetation accumulates as discrete patches, forming a microhabitat for macroinvertebrates. We primarily aimed to determine the relative trophic position and contribution of periphyton to the assimilated diet of macroinvertebrate species in pool litter patches via stable isotope analysis. We specifically focused on predatory species in the context of their indirect effects on litter breakdown and estimated the range of their absolute trophic positions. The mean δ15N values of the 19 macroinvertebrate predator species considered ranged from 0.0 ‰ to 5.3 ‰. This range was greater than the overall mean enrichment factor of δ15N (Δ15N = 1.8 ‰) estimated from aquatic invertebrate predators based on five existing data sources, indicating that the absolute trophic position of predator species can extend across more than one level. The estimated periphyton contributions to the diets of predator species were almost half or more, indicating that the food webs of pool litter patches are closely connected with external periphyton-based webs. Our findings suggest that the top-down effect of predatory macroinvertebrates in litter patches is likely to be dissipated by the shift to the grazing food chains instead of cascading down to the litter.
Agroforestry across the United States: Results of the 2022 Census of Agriculture
Authors: Kellerman Todd , Feibel Samuel , Smith Matthew M. , Bentrup Gary , Batcheler Mark , MacFarland Katherine
Published: February 2025

Agroforestry offers producers climate mitigation and adaptation benefits and the opportunity to diversify income and enhance ecosystem services. Though these benefits are well-researched, few studies document agroforestry implementation through time in the United States using consistent national data sources. To fill this knowledge gap, we investigated changes in the number of farm operations with agroforestry across the United States using data from the 2017 and 2022 United States Census of Agriculture. Through this analysis, we showed that the number of farm operations with agroforestry increased by 6% nationally between 2017 (30,853) and 2022 (32,717). States with the highest percent of total farms reporting at least one type of agroforestry were Vermont (7.8%), Maine (6.0%), and New Hampshire (5.6%), while states with the lowest percent were Arizona (0.3%), Utah (0.4%), and North Dakota (0.4%). States on the eastern half of the country tended to see increases in the number of farm operations with agroforestry between census years, while states on the western half of the country saw the largest decreases. Reasons for these changes are complex and require additional analysis. Additionally, we identified potential factors that may decrease the accuracy of agroforestry census data, along with recommendations on how to improve overall data quality going forward. We outlined how national agroforestry census data can inform decision-making related to farm policies, funding, programs, research, and extension delivery. With an online supplement, we also provided detailed maps of the extent of agroforestry in all 50 states.