bluuebunny/crossref_metadata_2025 huggingface dataset:
Renormalization group improved photon impact factors and the high energy virtual photon scattering
Authors: Colferai Dimitri , Li Wanchen , Staśto Anna M.
Published: January 2024

Abstract

We perform the renormalization group improved collinear resummation of the photon-gluon impact factors. We construct the resummed cross section for virtual photon-photon (γ∗γ∗) scattering which incorporates the impact factors and BFKL gluon Green’s function up to the next-to-leading logarithmic accuracy in energy. The impact factors include important kinematical effects which are responsible for the most singular poles in Mellin space at next-to-leading order. Further conditions on the resummed cross section are obtained by requiring the consistency with the collinear limits. Our analysis is consistent with previous impact factor calculations at NLO, apart from a new term proportional to CF that we find for the longitudinal polarization. Finally, we use the resummed cross section to compare with the LEP data on the γ∗γ∗ cross section and with previous calculations. The resummed result is lower than the leading logarithmic approximation but higher than the pure next-to-leading one, and is consistent with the experimental data.
The SUSY index beyond the Cardy limit
Authors: Mamroud Ohad
Published: January 2024

Abstract

We analyze a set of contributions to the superconformal index of 4d 𝒩 = 4 SU(N) super Yang-Mills using the Bethe Ansatz approach. These contributions dominate at the large N limit, where their leading order in N reproduces various supersymmetric Euclidean black hole saddles in the dual theory, and they also dominate for finite N in high temperature Cardy-like limits. We compute the O(N0) terms, including those exponentially suppressed in the Cardy limit, and show that there are no 1/N corrections beyond them. Under certain assumptions, it implies that the gravitational perturbative series around these black hole saddles is 1-loop exact.
Local Poincaré algebra from quantum chaos
Authors: Ouseph Shoy , Furuya Keiichiro , Lashkari Nima , Leung Kwing Lam , Moosa Mudassir
Published: January 2024

Abstract

The local two-dimensional Poincaré algebra near the horizon of an eternal AdS black hole, or in proximity to any bifurcate Killing horizon, is generated by the Killing flow and outward null translations on the horizon. In holography, this local Poincaré algebra is reflected as a pair of unitary flows in the boundary Hilbert space whose generators under modular flow grow and decay exponentially with a maximal Lyapunov exponent. This is a universal feature of many geometric vacua of quantum gravity. To explain this universality, we show that a two-dimensional Poincaré algebra emerges in any quantum system that has von Neumann subalgebras associated with half-infinite modular time intervals (modular future and past subalgebras) in a limit analogous to the near-horizon limit. In ergodic theory, quantum dynamical systems with future or past algebras are called quantum K-systems. The surprising statement is that modular K-systems are always maximally chaotic.

Interacting quantum systems in the thermodynamic limit and large N theories above the Hawking-Page phase transition are examples of physical theories with future/past subalgebras. We prove that the existence of (modular) future/past von Neumann subalgebras also implies a second law of (modular) thermodynamics and the exponential decay of (modular) correlators. We generalize our results from the modular flow to any dynamical flow with a positive generator and interpret the positivity condition as quantum detailed balance.
Hypergraphs in LHC phenomenology — the next frontier of IRC-safe feature extraction
Authors: Konar Partha , Ngairangbam Vishal S. , Spannowsky Michael
Published: January 2024

Abstract

In this study, we critically evaluate the approximation capabilities of existing infra-red and collinear (IRC) safe feature extraction algorithms, namely Energy Flow Networks (EFNs) and Energy-weighted Message Passing Networks (EMPNs). Our analysis reveals that these algorithms fall short in extracting features from any N-point correlation that isn’t a power of two, based on the complete basis of IRC safe observables, specifically C-correlators. To address this limitation, we introduce the Hypergraph Energy-weighted Message Passing Networks (H-EMPNs), designed to capture any N-point correlation among particles efficiently. Using the case study of top vs. QCD jets, which holds significant information in its 3-point correlations, we demonstrate that H-EMPNs targeting up to N=3 correlations exhibit superior performance compared to EMPNs focusing on up to N=4 correlations within jet constituents.
Inequalities for Convex Functions and Isotonic Sublinear Functionals
Authors: Otachel Zdzisław
Published: January 2024

In this paper, versions of the famous Jensen inequality for sublinear isotonic functionals are proved. The obtained results generalize classic Jessen’s and McShane’s inequalities. Applications to generalized means and to Hölder’s and Minkowski’s inequalities are also given.
Artificial intelligence (AI)—it’s the end of the tox as we know it (and I feel fine)*
Authors: Kleinstreuer Nicole , Hartung Thomas
Published: January 2024

The rapid progress of AI impacts diverse scientific disciplines, including toxicology, and has the potential to transform chemical safety evaluation. Toxicology has evolved from an empirical science focused on observing apical outcomes of chemical exposure, to a data-rich field ripe for AI integration. The volume, variety and velocity of toxicological data from legacy studies, literature, high-throughput assays, sensor technologies and omics approaches create opportunities but also complexities that AI can help address. In particular, machine learning is well suited to handle and integrate large, heterogeneous datasets that are both structured and unstructured—a key challenge in modern toxicology. AI methods like deep neural networks, large language models, and natural language processing have successfully predicted toxicity endpoints, analyzed high-throughput data, extracted facts from literature, and generated synthetic data. Beyond automating data capture, analysis, and prediction, AI techniques show promise for accelerating quantitative risk assessment by providing probabilistic outputs to capture uncertainties. AI also enables explanation methods to unravel mechanisms and increase trust in modeled predictions. However, issues like model interpretability, data biases, and transparency currently limit regulatory endorsement of AI. Multidisciplinary collaboration is needed to ensure development of interpretable, robust, and human-centered AI systems. Rather than just automating human tasks at scale, transformative AI can catalyze innovation in how evidence is gathered, data are generated, hypotheses are formed and tested, and tasks are performed to usher new paradigms in chemical safety assessment. Used judiciously, AI has immense potential to advance toxicology into a more predictive, mechanism-based, and evidence-integrated scientific discipline to better safeguard human and environmental wellbeing across diverse populations.
Factors associated with trajectories of bone marrow lesions over 4 years: data from the Osteoarthritis Initiative
Authors: Shen Ziyuan , Zhang Xiaoyue , Wang Yining , Zhu Rui , Ge Liru , Cai Guoqi
Published: January 2024

Objective

To identify bone marrow lesion (BML) trajectories over 4 years and their demographic and structural predictors in middle-aged and older adults with or at increased risk of knee osteoarthritis (OA).

Methods

A total of 614 participants (mean age 61 years, 62% female) from the Osteoarthritis Initiative cohort (OAI) were included. BMLs in 15 anatomical locations of the knee were measured annually from baseline to 4 years using the Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) method. BML trajectories were determined using latent class mixed models (LCMMs). Multinomial logistic regression was used to examine baseline characteristics that predicted BML trajectories.

Results

Three distinct BML trajectories were identified: “Mild-stable BMLs” (25.9%), “Moderate-stable BMLs” (66.4%), and “Rapid-rise BMLs” (7.7%). Compared to the “Mild-stable BMLs” trajectory, current smokers were more likely to be in the “Moderate-stable BMLs” (odds ratio [OR] 2.089, P < 0.001) and “Rapid-rise” (OR 2.462, P < 0.001) trajectories. Moreover, female sex and meniscal tears were associated with an increased risk of being in the “Rapid-rise BMLs” trajectory (OR 2.023 to 2.504, P < 0.05). Participants who had higher education levels and drank more alcohol were more likely to be in the “Rapid-rise BMLs” trajectory (OR 1.624 to 3.178, P < 0.05) and less likely to be in the “Moderate-stable BMLs” trajectory (OR 0.668 to 0.674, P < 0.05).

Conclusions

During the 4-year follow-up, most participants had relatively stable BMLs, few had enlarged BMLs, and no trajectory of decreased BMLs was identified. Sociodemographic factors, lifestyle, and knee structural pathology play roles in predicting distinct BML trajectories.
Acute and long-term toxicity in primary hypofractionated external photon radiation therapy in patients with localized prostate cancer
Authors: Lilleby Wolfgang , Kishan Amar , Geinitz Hans
Published: January 2024

Background

Compelling evidence exists for the iso-effectiveness and safety of moderate hypofractionated radiotherapy (Hypo-RT) schedules [1, 2]. However, international guidelines are not congruent regarding recommendation of ultrahypofractionated radiotherapy (UHF-RT) to all risk groups.

Methods

The current review gives an overview of clinically relevant toxicity extracted from major randomized controlled trials (RCT) trials comparing conventional to hypofractionated regimes in the primary setting of external photon radiation. Functional impairments are reported by using physician-rated and patient-reported scores using validated questionnaires.

Results

The uncertain radiobiology of the urethra/bladder when applying extreme hypofractionation may have contributed to worse acute urinary toxicity score in the Scandinavian UHF-RT and worse subacute toxicity in PACE-B. The observed trend of increased acute GI toxicity in several moderate Hypo-RT trials and one UHF-RT trial, the Scandinavian Hypo-RT PC trial, could be associated to the different planning margins and radiation dose schedules.

Conclusion

Nevertheless, Hypo-RT has gained ground for patients with localized PCa and further improvements may be achieved by inclusion of genetically assessed radiation sensitivity. Several RCTs in Hypo-RT have shown non-inferior outcome and well-tolerated treatment toxicity by physician-rated scores. In the future, we suggest that toxicity should be measured by patient-reported outcome (PRO) using comparable questionnaires.
Size of lymph-node metastases in prostate cancer patients undergoing radical prostatectomy: implication for imaging and oncologic follow-up of 2705 lymph-node positive patients
Authors: Falkenbach Fabian , Kachanov Mykyta , Leyh-Bannurah Sami-Ramzi , Maurer Tobias , Knipper Sophie , Köhler Daniel , Graefen Markus , Sauter Guido , Budäus Lars
Published: January 2024

Background

Despite modern imaging modalities, lymph-node staging before radical prostatectomy (RP) remains challenging in patients with prostate cancer (PCa). The visibility of lymph-node metastases (LNMs) is critically influenced by their size.

Objective

This study aims to describe the distribution of maximal tumor diameters (i.e., size) in LNMs of pN1-PCa at RP and its consequences on visibility in preoperative imaging and oncological outcomes.

Design, setting, and participants

A total of 2705 consecutive patients with pN1-PCa at RP, harboring a cumulative 7510 LNMs, were analyzed. Descriptive and multivariable analyses addressed the risk of micrometastases (MM)-only disease and the visibility of LNMs. Kaplan–Meier curves and Cox analyses were used for biochemical recurrence-free survival (BCRFS) stratified for MM-only disease.

Results

The median LNM size was 4.5mm (interquartile range (IQR): 2.0–9.0 mm). Of 7510 LNMs, 1966 (26%) were MM (≤ 2mm). On preoperative imaging, 526 patients (19%) showed suspicious findings (PSMA-PET/CT: 169/344, 49%). In multivariable analysis, prostate-specific antigen (PSA) (OR 0.98), age (OR 1.01), a Gleason score greater than 7 at biopsy (OR 0.73), percentage of positive cores at biopsy (OR 0.36), and neoadjuvant treatment (OR 0.51) emerged as independent predictors for less MM-only disease (p < 0.05). Patients with MM-only disease compared to those harboring larger LNMs had a longer BCRFS (median 60 versus 29 months, p < 0.0001).

Conclusion

Overall, 26% of LNMs were MM (≤ 2mm). Adverse clinical parameters were inversely associated with MM at RP. Consequently, PSMA-PET/CT did not detect a substantial proportion of LNMs. LNM size and count are relevant for prognosis.
Radiotherapy in metastatic bladder cancer
Authors: Ashley Sophie , Choudhury Ananya , Hoskin Peter , Song YeePei , Maitre Priyamvada
Published: January 2024

Purpose

To review available and emerging evidence of radiotherapy for symptom management and disease control in metastatic bladder cancer.

Methods

A literature search and subsequent cross-referencing were carried out for articles in the PubMed and Scopus databases using terms ‘radiotherapy’ OR ‘palliative radiation therapy’ with ‘metastatic bladder cancer’ OR ‘advanced bladder cancer’ between 1990 and 2023, excluding articles with no English translation.

Results

Palliative radiotherapy is an effective and accessible treatment for the alleviation of haematuria and pain due to the primary and metastatic disease. With growing recognition of oligometastatic disease state at diagnosis, response, or progression, radiotherapy can consolidate response by ablating residual or resistant lesions. Experience with other primary cancers supports positive impact of radiotherapy on disease control, quality of life, and survival in oligometastatic stage, without significant adverse effects. Alongside immune checkpoint inhibitors, fibroblast growth receptor inhibitors, and antibody–drug conjugates, the immunomodulatory potential of radiotherapy is being explored in combination with these systemic therapies for metastatic bladder cancer.

Conclusion

Radiotherapy is an effective, safe, and accessible treatment modality for palliation as well as disease control in various clinical settings of metastatic bladder cancer. Its role in oligometastatic stage in combination with systemic therapy is expected to expand with emerging evidence.
Surgical management of Rathke cleft cysts in pediatric patients: a single institution experience
Authors: Brandel Michael G. , Lin Christine , Rennert Robert C. , Plonsker Jillian H. , Khan Usman A. , Crawford John R. , Nation Javan , Levy Michael L.
Published: January 2024

Objective

Rathke cleft cysts (RCCs) are benign, epithelial-lined sellar lesions that arise from remnants of the craniopharyngeal duct. Due to their rarity in the pediatric population, data are limited regarding the natural history and optimal management of growing or symptomatic RCCs. We present our institutional experience with the surgical management of RCCs.

Methods

We performed a retrospective study of consecutive RCC patients ≤ 18 years old treated surgically at our institution between 2006 and 2022.

Results

Overall, 567 patients with a diagnosis of pituitary mass or cyst were identified. Of these, 31 had a histopathological diagnosis of RCC, 58% female and 42% male. The mean age was 13.2 ± 4.2 years. Presenting symptoms included headache (58%), visual changes (32%), and endocrinopathies or growth delay (26%); 13% were identified incidentally and subsequently demonstrated growth on serial imaging. Six percent presented with symptomatic intralesional hemorrhage. Surgical approach was transsphenoidal for 90% of patients and orbitozygomatic for 10%. Preoperative headaches resolved in 61% of patients and preoperative visual deficits improvement in 55% after surgery. New pituitary axis deficits were seen in 9.7% of patients. Only two complications occurred from a first-time surgery: one cerebrospinal fluid leak requiring lumbar drain placement, and one case of epistaxis requiring cauterization. No patients experienced new visual or neurological deficits. Patients were followed postoperatively with serial imaging at a mean follow-up was 62.9 ± 58.4 months. Recurrence requiring reoperation occurred in 32% of patients. Five-year progression-free survival was 47.9%. Except for one patient with multiple neurological deficits from a concurrent tectal glioma, all patients had a modified Rankin Scale score of 0 or 1 (good outcome) at last follow-up.

Conclusion

Due to their secretory epithelium, pediatric RCCs may demonstrate rapid growth and can cause symptoms due to local mass effect. Surgical management of symptomatic or growing pediatric RCCs via cyst fenestration or partial resection of the cyst wall can be performed safely, with good neurologic outcomes. There is a nontrivial risk of endocrinologic injury, and long-term follow up is needed due to high recurrence rates.
Impact of spring land-surface conditions over the Tibetan Plateau on the early summer Asian monsoon using an AGCM large ensemble
Authors: Takahashi Hiroshi G. , Sugimoto Shiori , Sato Tomonori
Published: January 2024

Influence of land-surface memory effects over the Tibetan Plateau on the Asian summer monsoon has long been studied, but not quantified because of the difficulty of extracting only these effects from observational data. This study examines the impact of spring land-surface conditions, including surface air temperature (SAT) and snow cover, over the Tibetan Plateau and its surrounding regions on the early stage of the Asian summer monsoon using large-ensemble experiments produced by an atmospheric global climate model (AGCM). The results show that the above-normal SAT over and around the Tibetan Plateau in May can enhance June monsoon circulation without the sea surface temperature (SST) forcing. The physical mechanism behind this involves warmed surface air over the plateau enhancing the north–south SAT gradient, leading to strengthening the Asian summer monsoon circulation and precipitation. Inter-ensemble correlation analysis indicated that SAT warming over the plateau is clearly associated with upper-tropospheric anti-cyclonic circulation anomalies in May. Also, although winter land-surface signals do not persist until late spring, SAT anomalies in March tend to persist until May, explaining 10–20% of the total SAT variance in May. Interestingly, the spring SAT impacts on June monsoon circulations vary interannually, indicating that the contribution of the land–atmosphere (L–A) coupling process to interannual monsoon variability differs from year to year. Active L–A coupling years tend to coincide with cooler SSTs with anomalous low-level divergence and upper-level convergence over and around the Maritime continent, implying that SST forcing is associated with the L–A coupling strength. Specifically, in May of the developing stage of monsoon circulation, the weak Walker circulation over the equatorial and northern Indian Ocean and undeveloped monsoon circulation are suitable for the L–A coupling to influence the development of the monsoon circulation effectively. However, the well-known oceanic events, such as El Ni$${\widetilde{n}}$$

n
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o, are found to be less connected with the interannual L–A coupling variations.
Plasma boron concentrations and risk of all-cause mortality in the general population
Authors: Stürmer Paula , Weber Katharina Susanne , Strathmann Eike Andreas , Lieb Wolfgang
Published: January 2024

Purpose

Higher dietary intake or higher circulating levels of the trace element boron have been associated with beneficial effects on human health. However, the relationship between plasma boron levels and survival in the general population is not known. Therefore, we aimed to assess the association between plasma boron concentrations and all-cause mortality in a population-based cohort from northern Germany (n = 863 individuals; median age 62.3 years, 42.8% women).

Methods

Plasma boron concentrations (median 31.9 µg/L [22.9; 43.5]) were measured by inductively coupled plasma-mass spectrometry. Cox proportional hazards regression models adjusted for relevant confounders were used to associate plasma boron concentrations with all-cause mortality.

Results

After a median follow-up time of 11 years, n = 99 individuals had died. In the overall sample, plasma boron concentrations were associated with all-cause mortality in the crude model (HR: 1.07 [95% CI 1.03–1.11] per 5-unit-increment). However, multivariable adjustment rendered the association non-significant (HR: 1.03 [95% CI 0.99–1.07]). Sex-stratified analyses revealed slightly higher mortality hazards with increasing plasma boron concentrations in women (HR: 1.11 [95% CI 1.03–1.18], pInteraction = 0.034), but not in men (HR: 1.00 [95% CI 0.95–1.06]).

Conclusion

We conclude that in a moderate-sized sample from the general population, higher plasma boron concentrations were associated with a higher risk of all-cause mortality in women, but not in men. Due to the low number of events in the female subsample (n = 27), this observation has to be interpreted with caution.
Language, cognitive, and speech in noise perception abilities of children with cochlear ımplants: a comparative analysis by implantation period and bilateral versus unilateral cochlear implants
Authors: İkiz Bozsoy Merve , Yücel Esra
Published: January 2024

Purpose

The purpose of this study was to compare the language, cognitive, and speech in noise (SiN) perception abilities of children with cochlear implants (CIs) to those of their peers with NH by grouping them according to their implantation period (12–18 months/19–24 months) and unilateral/bilateral CI use.

Methods

The sample comprised 50 children with cochlear implants (CIs) and 20 children with normal hearing (NH), ages 6–9 years. Children’s language, cognitive, and speech in noise (SiN) perception skills were assessed.

Results

Children with CIs between 12 and 18 months and 19 and 24 months performed more poorly than children with NH on language, verbal memory (VM), verbal-short-term memory (V-STM), verbal working memory (V-WM), rapid naming, and speech in noise (SiN) perception abilities measures (p < 0.001). In addition, children with CIs between 19 and 24 months performed worse on rapid naming and V-WM tasks than children with CIs between 12 and 18 months (p < 0.017). Children with unilateral and bilateral CI performed more poorly than children with NH on language, VM, V-STM, V-WM, rapid naming, and SiN perception abilities assessments (p < 0.001). Additionally children with unilateral CI users performed poorly than children with bilateral CI users on SiN perception (p < 0.017).

Conclusions

In children with congenital hearing loss (CHL), cochlear implantation between 12 and 18 months or sequential bilateral implantation is not sufficient for these children to perform like their NH peers in language, cognitive, and SiN perception abilities. In addition, intervention approaches should focus not only on increasing language skills, but also on cognitive abilities.
Optical coherence tomography angiography macular biomarkers of peripheral retinal ischemia in diabetic macular edema: secondary endpoints from the clinical study “FOVEA”
Authors: Serra Rita , Coscas Florence , Boulet Jean François , Cabral Diogo , Tran Thi Ha Chau , Pinna Antonio , Lupidi Marco , Coscas Gabriel ,   Fovea study group, Cornut Pierre-Loic , Uzzan Joel , DeBats Flore , Theron Jean-Philippe , Wolff Benjamin , Francais Catherine , Favard Catherine
Published: January 2024

Purpose

To investigate the relationship between the macular values of fractal dimension (FD) and lacunarity (LAC) on optical coherence tomography angiography (OCTA) images and the presence of peripheral retina non-perfusion areas (NPAs) on fluorescein angiography (FA) in patients with treatment-naïve diabetic macular edema (DME).

Methods

Fifty patients with treatment-naïve DME underwent a full ophthalmic examination, including best-corrected visual acuity measurement, FA, spectral-domain optical coherence tomography, and OCTA. Specifically, FA was performed to detect the presence of retinal NPAs, whereas fractal OCTA analysis was used to determine macular FD and LAC values at the level of the superficial and deep capillary plexus (SCP and DCP). FA montage frames of the posterior pole and peripheral retina, as well as macular OCTA slabs of the SCP and DCP, were obtained.

Results

Thirty (60%) eyes with FA evidence of peripheral retinal NPAs in at least one quadrant showed significantly lower FD and higher LAC in both SCP and DCP, when compared with eyes presenting a well-perfused peripheral retina. Furthermore, macular FD and LAC values were found to be significantly associated with the extent of retinal NPAs.

Conclusions

Macular FD and LAC of both SCP and DCP seem to be strongly associated with the extent of peripheral retinal NPAs, thus suggesting that may be useful predictive biomarkers of peripheral ischemia in treatment-naïve DME eyes.
The peroxisome: an update on mysteries 3.0
Authors: Kumar Rechal , Islinger Markus , Worthy Harley , Carmichael Ruth , Schrader Michael
Published: January 2024

Peroxisomes are highly dynamic, oxidative organelles with key metabolic functions in cellular lipid metabolism, such as the β-oxidation of fatty acids and the synthesis of myelin sheath lipids, as well as the regulation of cellular redox balance. Loss of peroxisomal functions causes severe metabolic disorders in humans. Furthermore, peroxisomes also fulfil protective roles in pathogen and viral defence and immunity, highlighting their wider significance in human health and disease. This has sparked increasing interest in peroxisome biology and their physiological functions. This review presents an update and a continuation of three previous review articles addressing the unsolved mysteries of this remarkable organelle. We continue to highlight recent discoveries, advancements, and trends in peroxisome research, and address novel findings on the metabolic functions of peroxisomes, their biogenesis, protein import, membrane dynamics and division, as well as on peroxisome–organelle membrane contact sites and organelle cooperation. Furthermore, recent insights into peroxisome organisation through super-resolution microscopy are discussed. Finally, we address new roles for peroxisomes in immune and defence mechanisms and in human disorders, and for peroxisomal functions in different cell/tissue types, in particular their contribution to organ-specific pathologies.
Efficacy and safety of first-line therapy in patients with HER2-positive advanced breast cancer: a network meta-analysis of randomized controlled trials
Authors: Wang Junxiao , Yu Yushuai , Lin Qisheng , Zhang Jie , Song Chuangui
Published: January 2024

Purpose

The numerous first-line treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) necessitate a comprehensive evaluation to inform clinical decision-making. We conducted a Bayesian network meta-analysis (NMA) to compare the efficacy and safety of different interventions.

Methods

We systematically searched for relevant randomized controlled trials (RCTs) in Pubmed, Embase, Cochrane Library and online abstracts from inception to June 1, 2023. NMA was performed to calculate and analyze progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events of grade 3 or higher (≥ 3 AEs).

Results

Out of the 10,313 manuscripts retrieved, we included 28 RCTs involving 11,680 patients. Regarding PFS and ORR, the combination of trastuzumab with tyrosine kinase inhibitors (TKIs) was more favorable than dual-targeted therapy. If only using trastuzumab, combination chemotherapy is superior to monochemotherapy in terms of PFS. It is important to note that the addition of anthracycline did not result in improved PFS. For patients with hormone receptor-positive HER2-positive diseases, dual-targeted combined with endocrine therapy showed better benefit in terms of PFS compared to dual-targeted alone, but it did not reach statistical significance. The comprehensive analysis of PFS and ≥ 3 AEs indicates that monochemotherapy combined with dual-targeted therapy still has the optimal balance between efficacy and safety.

Conclusion

Monochemotherapy (Docetaxel) plus dual-target (Trastuzumab and Pertuzumab) therapy remains the optimal choice among all first-line treatment options for ABC. The combination of trastuzumab with TKIs (Pyrotinib) demonstrated a significant improvement in PFS and ORR, but further data are warranted to confirm the survival benefit.
Predictive biomarkers for immunotherapy response in extensive-stage SCLC
Authors: Zhu Lin , Qin Jing
Published: January 2024

Background

Small cell lung cancer (SCLC) accounts for about 13–15% of all lung cancers, and about 70% of SCLC patients have developed extensive-stage small cell lung cancer (ES-SCLC) at the time of diagnosis because of its highgrade malignancy, easy invasion, and metastasis. In recent years, immunotherapy combined with chemotherapy has become the standard first-line treatment for ES-SCLC. However, SCLC is a relatively immune-cold lung cancer subtype with a limited number of beneficiaries and a short benefit period. Therefore, the use of biomarkers to identify populations with significant benefits from immunotherapy will help improve the efficacy and survival benefits of immunotherapy. However, predictive biomarkers suitable for clinical practice have not been established in the field of SCLC.

Purpose

In order to find the predictive biomarkers of immunotherapy for ES-SCLC, we summarized the research progress of traditional biomarkers, such as programmed cell death ligand 1 (PD-L1) and tumor mutation burden (TMB), and summarizes the research of potential biomarkers associated with prognosis, such as molecular subtypes, special gene expression, expression of major histocompatibility complex (MHC) I and II classes, tumor immune microenvironment (TIME), and circulating tumor DNA (ctDNA) .We aim to provide new insights on biomarkers.

Conclusion

The exploration of biomarkers for immunotherapy of SCLC is still very difficult, and it is clear that conventional predictive biomarkers are not suitable for SCLC. At present, the molecular subtypes defined from transcription factors may have some guiding significance, which still needs to be confirmed by prospective clinical studies. In addition, the ctDNA positivity rate of SCLC is higher than that of other tumor types, which can also solve the dilemma of the difficulty of obtaining specimens of SCLC tissues. And the dynamic change of ctDNA also has great potential to predict the curative effect of SCLC, which is worth further clinical exploration.
FSTL3 is associated with prognosis and immune cell infiltration in lung adenocarcinoma
Authors: Meng Xiangzhi , Zhao Xiaojian , Zhou Boxuan , Song Weijian , Liang Yicheng , Liang Mei , Du Minjun , Shi Jianwei , Gao Yushun
Published: January 2024

Purpose

FSTL3 expression is altered in various types of cancer. However, the role and mechanism of action of FSTL3 in lung adenocarcinoma development and tumor immunity are unknown. We investigated the association between FSTL3 expression and clinical characteristics and immune cell infiltration in lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) and a separate validation set from our hospital.

Methods

Data on immune system infiltration, gene expression, and relevant clinical information were obtained by analyzing lung adenocarcinoma sample data from TCGA database. Using online tools like GEPIA, the correlations between FSTL3 expression and prognosis, clinical stage, survival status, and tumor-infiltrating immune cells were examined. In a validation dataset, immunohistochemistry was performed to analyze FSTL3 expression and its related clinical characteristics.

Results

FSTL3 expression was markedly reduced in patients with lung adenocarcinoma. N stage, pathological stage, and overall survival were significantly correlated with FSTL3 expression. According to GSEA, FSTL3 is strongly linked to signaling pathways such as DNA replication and those involved in cell cycle regulation. Examination of TCGA database and TIMER online revealed a correlation between FSTL3 and B cell, T cell, NK cell, and neutrophil levels. The prognosis of patients with lung adenocarcinoma was significantly affected by six genes (KRT6A, VEGFC, KRT14, KRT17, SNORA12, and KRT81) related to FSTL3.

Conclusion

FSTL3 is significantly associated with the prognosis and progression of lung adenocarcinoma and the infiltration of immune cells. Thus, targeting FSTL3 and its associated genes in immunotherapy could be potentially beneficial for the treatment of lung adenocarcinoma.
Comparative morphology and function of Chloropidae (Diptera) tibial organ
Authors: Raile Riccardi Paula , de Souza Amorim Dalton , dos Santos Araújo Renan , Ferreira Martins Gustavo
Published: January 2024

The tibial organ of Chloropidae and Milichiidae flies is an obscure feature with taxonomic significance. This study provides the first in-depth investigation into the ultrastructure of the hind leg of 11 genera from all Chloropidae subfamilies using a multimodal microscopy approach. The modified dermal tissue associated with the tibial organ indicates glandular function, as evidenced by the presence of secretory vesicles containing non-proteinaceous elements, potentially indicating lipidic secretion. The overall similarity of the tibial organ between Chloropidae and Milichiidae indicates a shared homology. However, the evolutionary history of this structure is still contentious due to limitations in the phylogenetic relationships of both lineages. Moreover, our findings enable future comparative investigations of other Diptera leg organs that possess secretory ability, which could be homologous across schizophoran families, but not necessarily the organs themselves.
Inter- and intrapopulation resource use variation of marine subsidized western fence lizards
Authors: Ebersole Alexi , Bunker Marie E. , Weiss Stacey L. , Fox-Dobbs Kena
Published: January 2024

Marine resource subsidies alter consumer dynamics of recipient populations in coastal systems. The response to these subsidies by generalist consumers is often not uniform, creating inter- and intrapopulation diet variation and niche diversification that may be intensified across heterogeneous landscapes. We sampled western fence lizards, Sceloporus occidentalis, from Puget Sound beaches and coastal and inland forest habitats, in addition to the lizards’ marine and terrestrial prey items to quantify marine and terrestrial resource use with stable isotope analysis and mixing models. Beach lizards had higher average δ13C and δ15N values compared to coastal and inland forest lizards, exhibiting a strong mixing line between marine and terrestrial prey items. Across five beach sites, lizard populations received 20–51% of their diet from marine resources, on average, with individual lizards ranging between 7 and 86% marine diet. The hillslope of the transition zone between marine and terrestrial environments at beach sites was positively associated with marine-based diets, as the steepest sloped beach sites had the highest percent marine diets. Within-beach variation in transition zone slope was positively correlated with the isotopic niche space of beach lizard populations. These results demonstrate that physiography of transitional landscapes can mediate resource flow between environments, and variable habitat topography promotes niche diversification within lizard populations. Marine resource subsidization of Puget Sound beach S. occidentalis populations may facilitate occupation of the northwesternmost edge of the species range. Shoreline restoration and driftwood beach habitat conservation are important to support the unique ecology of Puget Sound S. occidentalis.
Estimating the Incidence and Prevalence of Dysphagia in New Zealand
Authors: Duncan Shnece , Menclova Andrea , Huckabee Maggie-Lee
Published: January 2024

Dysphagia imposes a substantial economic burden on global healthcare systems due to its pervasive, high-cost nature. To comprehend this burden, we must first assess dysphagia's prevalence and incidence in the general population. Existing studies on dysphagia prevalence encompass minor symptoms, while it is the severe cases that drive significant healthcare costs. We address this knowledge gap by estimating dysphagia incidence and prevalence in the New Zealand population, projecting future demographics of affected individuals. Incidence and prevalence rates of dysphagia within specific underlying medical conditions are sourced from existing literature. Median projected population estimates from Statistics New Zealand, by age, sex, and ethnicity are used to calculate dysphagia projections. Where possible, projections by age and ethnicity are provided until 2038 and projections by age and sex until 2073. In 2020, 9300 New Zealanders are estimated to have newly developed dysphagia while 1.5% of the general New Zealand population are estimated to have been living with the effects of the condition. By 2073, the number of individuals newly diagnosed annually is projected to increase to 24,500 and the prevalence of dysphagia is projected to increase to 2.6%. These results indicate that a significant number of New Zealanders are impacted by dysphagia. This number is predicted to dramatically increase in the future, mostly due to population ageing, indicating an increased burden on society and healthcare systems. Our work provides a useful starting point for countries worldwide to assess future healthcare resource demands associated with dysphagia, assisting with healthcare provision planning.
Considerations for establishing and maintaining international research collaboration: the example of chemotherapy-induced peripheral neurotoxicity (CIPN)—a white paper
Authors: Alberti Paola , Argyriou Andreas A. , Bruna Jordi , Damaj M. Imad , Faithfull Sara , Harding Alice , Hoke Ahmet , Knoerl Robert , Kolb Noah , Li Tiffany , Park Susanna B. , Staff Nathan P. , Tamburin Stefano , Thomas Simone , Smith Ellen Lavoie
Published: January 2024

Purpose

This white paper provides guidance regarding the process for establishing and maintaining international collaborations to conduct oncology/neurology-focused chemotherapy-induced peripheral neurotoxicity (CIPN) research.

Methods

An international multidisciplinary group of CIPN scientists, clinicians, research administrators, and legal experts have pooled their collective knowledge regarding recommendations for establishing and maintaining international collaboration to foster advancement of CIPN science.

Results

Experts provide recommendations in 10 categories: (1) preclinical and (2) clinical research collaboration; (3) collaborators and consortiums; (4) communication; (5) funding; (6) international regulatory standards; (7) staff training; (8) data management, quality control, and data sharing; (9) dissemination across disciplines and countries; and (10) additional recommendations about feasibility, policy, and mentorship.

Conclusion

Recommendations to establish and maintain international CIPN research collaboration will promote the inclusion of more diverse research participants, increasing consideration of cultural and genetic factors that are essential to inform innovative precision medicine interventions and propel scientific discovery to benefit cancer survivors worldwide.

Relevance to inform research policy

Our suggested guidelines for establishing and maintaining international collaborations to conduct oncology/neurology-focused chemotherapy-induced peripheral neurotoxicity (CIPN) research set forth a challenge to multinational science, clinical, and policy leaders to (1) develop simple, streamlined research designs; (2) address logistical barriers; (3) simplify and standardize regulatory requirements across countries; (4) increase funding to support international collaboration; and (5) foster faculty mentorship.
Impact of intratumoral microbiome on tumor immunity and prognosis in human pancreatic ductal adenocarcinoma
Authors: Abe Shohei , Masuda Atsuhiro , Matsumoto Tomonori , Inoue Jun , Toyama Hirochika , Sakai Arata , Kobayashi Takashi , Tanaka Takeshi , Tsujimae Masahiro , Yamakawa Kohei , Gonda Masanori , Masuda Shigeto , Uemura Hisahiro , Kohashi Shinya , Inomata Noriko , Nagao Kae , Harada Yoshiyuki , Miki Mika , Irie Yosuke , Juri Noriko , Ko Testuhisa , Yokotani Yusuke , Oka Yuki , Ota Shogo , Kanzawa Maki , Itoh Tomoo , Imai Toshio , Fukumoto Takumi , Hara Eiji , Kodama Yuzo
Published: January 2024

Background

Recent evidence suggests that the presence of microbiome within human pancreatic ductal adenocarcinoma (PDAC) tissue potentially influences cancer progression and prognosis. However, the significance of tumor-resident microbiome remains unclear. We aimed to elucidate the impact of intratumoral bacteria on the pathophysiology and prognosis of human PDAC.

Methods

The presence of intratumoral bacteria was assessed in 162 surgically resected PDACs using quantitative polymerase chain reaction (qPCR) and in situ hybridization (ISH) targeting 16S rRNA. The intratumoral microbiome was explored by 16S metagenome sequencing using DNA extracted from formalin-fixed paraffin-embedded tissues. The profile of intratumoral bacteria was compared with clinical information, pathological findings including tumor-infiltrating T cells, tumor-associated macrophage, fibrosis, and alterations in four main driver genes (KRAS, TP53, CDKN2A/p16, SMAD4) in tumor genomes.

Results

The presence of intratumoral bacteria was confirmed in 52 tumors (32%) using both qPCR and ISH. The 16S metagenome sequencing revealed characteristic bacterial profiles within these tumors, including phyla such as Proteobacteria and Firmicutes. Comparison of bacterial profiles between cases with good and poor prognosis revealed a significant positive correlation between a shorter survival time and the presence of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus. The abundance of these bacteria was correlated with a decrease in the number of tumor-infiltrating T cells positive for CD4, CD8, and CD45RO.

Conclusions

Intratumoral infection of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus is correlated with the suppressed anti-PDAC immunity and poor prognosis.
The effect of solution viscosity on the quality of electroactive nanofibers produced by electrospinning
Authors: Kočí Jan , Míka Havlík Martin , Procházka Václav , Klusoňová Nikola , Sedláčková Eliška
Published: January 2024

This work describes the modification of organic–inorganic nanofibrous templates for advanced electrotechnical applications and their filling with active particles from various materials, according to their intended use. The organic component of the templates consists of high molecular polyvinylpyrrolidone. The inorganic part is colloidal SiO2. The organic–inorganic templates produce by electrospinning can be filled with inorganic particles with diameter below 50 µm (for example, different types of spinels or electroactive nanopowders). The idea is to create a modifiable and flexible material for use as a template for electrodes or a solid electrolyte in a safe solid-state battery. The quality and properties of nanofibers are very important for advanced applications, and therefore, the optimization of the manufacturing process is needed. The most important property is the viscosity of the organic–inorganic solution for electrospinning. The influence of viscosity on the quality of nanofibrous layers was observed even with very subtle differences in viscosity. The age of the precursors and the resulting workability time also plays a significant role.

Graphical abstract
Molar incisor hypomineralization and oral health-related quality of life: a sample of 8–12-years-old children
Authors: Kisacik Seyma , Ozler Cansu Ozsin , Olmez Seval
Published: January 2024

Objectives

The study aimed to evaluate the impact of molar incisor hypomineralization (MIH) and tooth sensitivity on the oral health in terms of the quality of life (OHRQoL). In addition, the impact of tooth maturity on tooth sensitivity was evaluated in the study.

Materials and methods

Children aged 8–12 years with and without MIH participated in this descriptive cross-sectional study. They were chosen through the convenience sample technique. ThePediatric-Oral-Health-related-Quality-of-Life (POQL)scale was used to assess OHRQoL. The presence of the MIH and decayed, filled and missing teeth due to caries (using dmft/s, DMFT/S indexes) were recorded. The tooth sensitivity and dental maturity status were evaluated with theShiff-Cold-Air-Sensitivity-Scale (SCASS)andDemirjian-method, respectively. Statistical analysis of the data was performed by Pearson Chi-Square Test and Mann-WhitneyUtest (p<0.05).

Results

In this study, the participants were a total of 260 children, half were affected by the MIH. Their mean POQL scores were higher than those of the children without MIH with a statistically significantly difference in the total child scale score (p=0.014). Among the children with the MIH, child total QoL score was found to be higher in SCASS positive response group (p=0.011). The teeth with MIH (p<0.001) showed higher response to the stimulus. According to the dental age and dental maturity categories of the children with MIH, the total child scale score was found to be higher in the SCASS category (p=0.011), and the response status to the SCASS was statistically significant (p=0.042 andp=0.05, respectively).

Conclusions

Among the children with MIH, the OHRQoL was found to be negatively affected. The teeth with the MIH tend to reveal more tooth sensitivity than healthy teeth. Many conditions such as having MIH, and tooth sensitivity might have an impact on the OHRQoL. In addition, more sensitivity to the stimulus was observed in the teeth with lower tooth maturity status; the dental age and dental maturity might have effects on tooth sensitivity.

Clinical relevance

Considering the negative impacts due to MIH, the evaluation of OHRQoL is critical for dentists to employ a well-defined guide in their clinical decisions.
Characterization of matrices with bounded Graver bases and depth parameters and applications to integer programming
Authors: Briański Marcin , Koutecký Martin , Král’ Daniel , Pekárková Kristýna , Schröder Felix
Published: January 2024

An intensive line of research on fixed parameter tractability of integer programming is focused on exploiting the relation between the sparsity of a constraint matrix A and the norm of the elements of its Graver basis. In particular, integer programming is fixed parameter tractable when parameterized by the primal tree-depth and the entry complexity of A, and when parameterized by the dual tree-depth and the entry complexity of A; both these parameterization imply that A is sparse, in particular, the number of its non-zero entries is linear in the number of columns or rows, respectively. We study preconditioners transforming a given matrix to a row-equivalent sparse matrix if it exists and provide structural results characterizing the existence of a sparse row-equivalent matrix in terms of the structural properties of the associated column matroid. In particular, our results imply that the $$\ell _1$$

ℓ
1

-norm of the Graver basis is bounded by a function of the maximum $$\ell _1$$

ℓ
1

-norm of a circuit of A. We use our results to design a parameterized algorithm that constructs a matrix row-equivalent to an input matrix A that has small primal/dual tree-depth and entry complexity if such a row-equivalent matrix exists. Our results yield parameterized algorithms for integer programming when parameterized by the $$\ell _1$$

ℓ
1

-norm of the Graver basis of the constraint matrix, when parameterized by the $$\ell _1$$

ℓ
1

-norm of the circuits of the constraint matrix, when parameterized by the smallest primal tree-depth and entry complexity of a matrix row-equivalent to the constraint matrix, and when parameterized by the smallest dual tree-depth and entry complexity of a matrix row-equivalent to the constraint matrix.