bluuebunny/crossref_metadata_2025 huggingface dataset:
B meson anomalies and large $$ {B}^{+}\to {K}^{+}\nu \overline{\nu} $$ in non-universal U(1)′ models
Authors: Athron Peter , Martinez R. , Sierra Cristian
Published: February 2024

Abstract

In view of both the latest LHCb measurement of $$ {R}_{K^{\left(\ast \right)}} $$

R

K

∗

and the new 2.7σ deviation reported by Belle II on $$ {B}^{+}\to {K}^{+}\nu \overline{\nu} $$

B
+

→

K
+

ν

ν
¯

decays, we present a fit to the B meson anomalies for various one and two dimensional hypothesis including complex Wilson coefficients. We show in a model-independent way that the generic non-universal U(1)′ extensions of the SM, without flavour violation, fail to simultaneously fit those observables and corroborate that they can modify $$ \textrm{BR}\left({B}^{+}\to {K}^{+}\nu \overline{\nu}\right) $$
BR

B
+

→

K
+

ν

ν
¯

up to only a 10%. In view of this deficit, we propose a new way in which those models can accommodate the data at tree level by introducing lepton flavour violating couplings and non-diagonal elements of the charged lepton mixing matrix, with implications in future charged lepton flavour violation searches.
Lifting Klein-Gordon/Einstein solutions to general nonlinear sigma-models: the wormhole example
Authors: Brax Philippe , Burgess C. P. , Quevedo F.
Published: February 2024

Abstract

We describe a simple technique for generating solutions to the classical field equations for an arbitrary nonlinear sigma-model minimally coupled to gravity. The technique promotes an arbitrary solution to the coupled Einstein/Klein-Gordon field equations for a single scalar field σ to a solution of the nonlinear sigma-model for N scalar fields minimally coupled to gravity. This mapping between solutions does not require there to be any target-space isometries and exists for every choice of geodesic computed using the target-space metric. In some special situations — such as when the solution depends only on a single coordinate (e.g. for homogeneous time-dependent or static spherically symmetric configurations) — the general solution to the sigma-model equations can be obtained in this way. We illustrate the technique by applying it to generate Euclidean wormhole solutions for multi-field sigma models coupled to gravity starting from the simplest Giddings-Strominger wormhole, clarifying why in the wormhole case Minkowski-signature target-space geometries can arise. We reproduce in this way the well-known axio-dilaton string wormhole and we illustrate the power of the technique by generating simple perturbations to it, like those due to string or α′ corrections.
Two loop renormalization of scalar theories using a geometric approach
Authors: Jenkins Elizabeth E. , Manohar Aneesh V. , Naterop Luca , Pagès Julie
Published: February 2024

Abstract

We derive a general formula for two-loop counterterms in Effective Field Theories (EFTs) using a geometric approach. This formula allows the two-loop results of our previous paper to be applied to a wide range of theories. The two-loop results hold for loop graphs in EFTs where the interaction vertices contain operators of arbitrarily high dimension, but at most two derivatives. We also extend our previous one-loop result to include operators with an arbitrary number of derivatives, as long as there is at most one derivative acting on each field. The final result for the two-loop counterterms is written in terms of geometric quantities such as the Riemann curvature tensor of the scalar manifold and its covariant derivatives. As applications of our results, we give the two-loop counterterms and renormalization group equations for the O(n) EFT to dimension six, the scalar sector of the Standard Model Effective Field Theory (SMEFT) to dimension six, and chiral perturbation theory to order p6.
The efficacy and safety of pre-hospital plasma in patients at risk for hemorrhagic shock: an updated systematic review and meta-analysis of randomized controlled trials
Authors: Abuelazm Mohamed , Rezq Hazem , Mahmoud Abdelrahman , Tanashat Mohammad , Salah Abdelrahman , Saleh Othman , Morsi Samah , Abdelazeem Basel
Published: February 2024

Background and objective

Plasma is a critical element in hemostatic resuscitation post-injury, and its prompt administration within the prehospital setting may reduce the complications resulting from hemorrhage and shock. Our objective is to assess the efficacy and safety of prehospital plasma infusion in patients susceptible to hemorrhagic shock.

Methods

We conducted our study by aggregating randomized controlled trials (RCTs) sourced from PubMed, EMBASE, Scopus, Web of Science, and Cochrane CENTRAL up to January 29, 2023. Quality assessment was implemented using the Cochrane RoB 2 tool. Our study protocol is registered in PROSPERO under ID: CRD42023397325.

Results

Three RCTs with 760 individuals were included. There was no difference between plasma infusion and standard care groups in 24-h mortality (P = 0.11), 30-day mortality (P = 0.12), and multiple organ failure incidences (P = 0.20).

Plasma infusion was significantly better in the total 24-h volume of PRBC units (P = 0.03) and INR on arrival (P = 0.009). For all other secondary outcomes evaluated (total 24-h volume of packed FFP units, total 24-h volume of platelets units, massive transfusion, vasopressor need during the first 24 h, any adverse event, acute lung injury, transfusion reaction, and sepsis), no significant differences were observed between the two groups.

Conclusion

Plasma infusion in trauma patients at risk of hemorrhagic shock does not significantly affect mortality or the incidence of multiple organ failure. However, it may lead to reduced packed red blood cell transfusions and increased INR at hospital arrival.
Characterization of pathological changes in the olfactory system of mice exposed to methylmercury
Authors: Iijima Yuta , Miki Ryohei , Takasugi Nobumasa , Fujimura Masatake , Uehara Takashi
Published: February 2024

Methylmercury (MeHg) is a well-known environmental neurotoxicant that causes severe brain disorders such as Minamata disease. Although some patients with Minamata disease develop olfactory dysfunction, the underlying pathomechanism is largely unknown. We examined the effects of MeHg on the olfactory system using a model of MeHg poisoning in which mice were administered 30 ppm MeHg in drinking water for 8 weeks. Mice exposed to MeHg displayed significant mercury accumulation in the olfactory pathway, including the nasal mucosa, olfactory bulb, and olfactory cortex. The olfactory epithelium was partially atrophied, and olfactory sensory neurons were diminished. The olfactory bulb exhibited an increase in apoptotic cells, hypertrophic astrocytes, and amoeboid microglia, mainly in the granular cell layer. Neuronal cell death was observed in the olfactory cortex, particularly in the ventral tenia tecta. Neuronal cell death was also remarkable in higher-order areas such as the orbitofrontal cortex. Correlation analysis showed that neuronal loss in the olfactory cortex was strongly correlated with the plasma mercury concentration. Our results indicate that MeHg is an olfactory toxicant that damages the central regions involved in odor perception. The model described herein is useful for analyzing the mechanisms and treatments of olfactory dysfunction in MeHg-intoxicated patients.
Tau accumulation is associated with dopamine deficiency in vivo in four-repeat tauopathies
Authors: Ferschmann Christian , Messerschmidt Konstantin , Gnörich Johannes , Barthel Henryk , Marek Ken , Palleis Carla , Katzdobler Sabrina , Stockbauer Anna , Fietzek Urban , Finze Anika , Biechele Gloria , Rumpf Jost-Julian , Saur Dorothee , Schroeter Matthias L. , Rullmann Michael , Beyer Leonie , Eckenweber Florian , Wall Stephan , Schildan Andreas , Patt Marianne , Stephens Andrew , Classen Joseph , Bartenstein Peter , Seibyl John , Franzmeier Nicolai , Levin Johannes , Höglinger Günter U. , Sabri Osama , Brendel Matthias , Scheifele Maximilian ,   for the German Imaging Initiative for Tauopathies (GII4T)
Published: February 2024

Purpose

We hypothesized that severe tau burden in brain regions involved in direct or indirect pathways of the basal ganglia correlate with more severe striatal dopamine deficiency in four-repeat (4R) tauopathies. Therefore, we correlated [18F]PI-2620 tau-positron-emission-tomography (PET) imaging with [123I]-Ioflupane single-photon-emission-computed tomography (SPECT) for dopamine transporter (DaT) availability.

Methods

Thirty-eight patients with clinically diagnosed 4R-tauopathies (21 male; 69.0 ± 8.5 years) and 15 patients with clinically diagnosed α-synucleinopathies (8 male; 66.1 ± 10.3 years) who underwent [18F]PI-2620 tau-PET and DaT-SPECT imaging with a time gap of 3 ± 5 months were evaluated. Regional Tau-PET signals and DaT availability as well as their principal components were correlated in patients with 4R-tauopathies and α-synucleinopathies. Both biomarkers and the residuals of their association were correlated with clinical severity scores in 4R-tauopathies.

Results

In patients with 4R-tauopathies, [18F]PI-2620 binding in basal ganglia and midbrain regions was negatively associated with striatal DaT availability (i.e. globus pallidus internus and putamen (β =  − 0.464, p = 0.006, Durbin-Watson statistics = 1.824) in a multiple regression model. Contrarily, [18F]PI-2620 binding in the dentate nucleus showed no significant regression factor with DaT availability in the striatum (β = 0.078, p = 0.662, Durbin-Watson statistics = 1.686). Patients with α-synucleinopathies did not indicate any regional associations between [18F]PI-2620-binding and DaT availability. Higher DaT-SPECT binding relative to tau burden was associated with better clinical performance (β =  − 0.522, p = 0.011, Durbin-Watson statistics = 2.663) in patients with 4R-tauopathies.

Conclusion

Tau burden in brain regions involved in dopaminergic pathways is associated with aggravated dopaminergic dysfunction in patients with clinically diagnosed primary tauopathies. The ability to sustain dopamine transmission despite tau accumulation may preserve motor function.
EANM guidance document: dosimetry for first-in-human studies and early phase clinical trials
Authors: Stokke Caroline , Gnesin Silvano , Tran-Gia Johannes , Cicone Francesco , Holm Søren , Cremonesi Marta , Blakkisrud Johan , Wendler Thomas , Gillings Nic , Herrmann Ken , Mottaghy Felix M. , Gear Jonathan
Published: February 2024

The numbers of diagnostic and therapeutic nuclear medicine agents under investigation are rapidly increasing. Both novel emitters and novel carrier molecules require careful selection of measurement procedures. This document provides guidance relevant to dosimetry for first-in human and early phase clinical trials of such novel agents. The guideline includes a short introduction to different emitters and carrier molecules, followed by recommendations on the methods for activity measurement, pharmacokinetic analyses, as well as absorbed dose calculations and uncertainty analyses. The optimal use of preclinical information and studies involving diagnostic analogues is discussed. Good practice reporting is emphasised, and relevant dosimetry parameters and method descriptions to be included are listed. Three examples of first-in-human dosimetry studies, both for diagnostic tracers and radionuclide therapies, are given.
Targeting myeloperoxidase limits myeloid cell immunosuppression enhancing immune checkpoint therapy for pancreatic cancer
Authors: Basnet Angisha , Landreth Kaitlyn M. , Nohoesu Remi , Santiago Stell P. , Geldenhuys Werner J. , Boone Brian A. , Liu Tracy W.
Published: February 2024

Pancreatic ductal adenocarcinoma is a devastating disease characterized by an extreme resistance to current therapies, including immune checkpoint therapy. The limited success of immunotherapies can be attributed to a highly immunosuppressive pancreatic cancer microenvironment characterized by an extensive infiltration of immune suppressing myeloid cells. While there are several pathways through which myeloid cells contribute to immunosuppression, one important mechanism is the increased production of reactive oxygen species. Here, we evaluated the contribution of myeloperoxidase, a myeloid-lineage restricted enzyme and primary source of reactive oxygen species, to regulate immune checkpoint therapy response in preclinical pancreatic cancer models. We compared treatment outcome, immune composition and characterized myeloid cells using wild-type, myeloperoxidase-deficient, and myeloperoxidase inhibitor treated wild-type mice using established subcutaneous pancreatic cancer models. Loss of host myeloperoxidase and pharmacological inhibition of myeloperoxidase in combination with immune checkpoint therapy significantly delayed tumor growth. The tumor microenvironment and systemic immune landscape demonstrated significant decreases in myeloid cells, exhausted T cells and T regulatory cell subsets when myeloperoxidase was deficient. Loss of myeloperoxidase in isolated myeloid cell subsets from tumor-bearing mice resulted in decreased reactive oxygen species production and T cell suppression. These data suggest that myeloperoxidase contributes to an immunosuppressive microenvironment and immune checkpoint therapy resistance where myeloperoxidase inhibitors have the potential to enhance immunotherapy response. Repurposing myeloperoxidase specific inhibitors may provide a promising therapeutic strategy to expand therapeutic options for pancreatic cancer patients to include immunotherapies.
Chemokine CCL21 determines immunotherapy response in hepatocellular carcinoma by affecting neutrophil polarization
Authors: Xu Wenxin , Weng Jialei , Xu Minghao , Zhou Qiang , Liu Shaoqing , Hu Zhiqiu , Ren Ning , Zhou Chenhao , Shen Yinghao
Published: February 2024

Background

The efficacy of immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC) is poor and great heterogeneity among individuals. Chemokines are highly correlated with tumor immune response. Here, we aimed to identify an effective chemokine for predicting the efficacy of immunotherapy in HCC.

Methods

Chemokine C‐C motif ligand 21 (CCL21) was screened by transcriptomic analysis in tumor tissues from HCC patients with different responses to ICIs. The least absolute shrinkage and selection operator (LASSO) regression analysis was conducted to construct a predictive nomogram. Neutrophils in vitro and HCC subcutaneous tumor model in vivo were applied to explore the role of CCL21 on the tumor microenvironment (TME) of HCC.

Results

Transcriptome analysis showed that CCL21 level was much higher in HCC patients with response to immunotherapy. The predictive nomogram was constructed and validated as a classifier. CCL21 could inhibit N2 neutrophil polarization by suppressing the activation of nuclear factor kappa B (NF-κB) pathway. In addition, CCL21 enhanced the therapeutic efficacy of ICIs.

Conclusion

CCL21 may serve as a predictive biomarker for immunotherapy response in HCC patients. High levels of CCL21 in TME inhibit immunosuppressive polarization of neutrophils. CCL21 in combination with ICIs may offer a novel therapeutic strategy for HCC.
Successful treatment of a B/T MPAL patient by chemo-free treatment with venetoclax, azacitidine, and blinatumomab
Authors: Liu Shaoyu , Cui Qingya , Li Mengyun , Li Zheng , Chen Sifan , Wu Depei , Tang Xiaowen
Published: February 2024

B/T mixed phenotype acute leukemia (MPAL), which represents only 2–3% of all MPAL cases, is classified as a high-risk leukemia subtype. Adults diagnosed with B/T MPAL have a notably low 3-year survival rate, estimated at 20–40%. The rarity and undercharacterization of B/T MPAL present substantial challenges in identifying an optimal treatment protocol. This report aims to shed light on this issue by presenting a case in which a patient with a complex karyotype was treated using a combination of venetoclax, azacitidine, and blinatumomab. This novel, chemo-free regimen resulted in the patient achieving both hematologic and molecular complete remission, with no severe organ or hematological toxicity observed. Notably, the patient continued to maintain molecular remission for 1 year following the transplantation. Based on these findings, the combination of venetoclax, azacitidine, and blinatumomab could be considered a potential therapeutic approach for B/T MPAL patients, meriting further investigation.
Validation of resting full-cycle ratio and diastolic pressure ratio with [15O]H2O positron emission tomography myocardial perfusion
Authors: Dahdal Jorge , Bakker Frank , Svanerud Johan , Danad Ibrahim , Driessen Roel S. , Raijmakers Pieter G. , Harms Hendrik J. , Lammertsma Adriaan A. , van de Hoef Tim P. , Appelman Yolande , van Royen Niels , Knaapen Paul , de Waard Guus A.
Published: February 2024

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging and clinical trials. New invasive pressure ratios that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy. The aim of this study was to validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging. A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of resting and hyperemic myocardial perfusion. Within a 2 week period, coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. PET derived regional hyperemic myocardial blood flow (hMBF) and myocardial perfusion reserve (MPR) served as reference standards. In coronary arteries with stenoses (43%, 136 of 320), the overall diagnostic accuracies of RFR, dPR, and FFR did not differ when PET hyperemic MBF < 2.3 ml min−1 (69.9%, 70.6%, and 77.1%, respectively) and PET MPR < 2.5 (70.6%, 71.3%, and 66.9%, respectively) were considered as the reference for myocardial ischemia. Non-significant differences between the areas under the receiver operating characteristic (ROC) curve were found between the different indices. Furthermore, the integration of FFR with RFR (or dPR) does not enhance the diagnostic information already achieved by FFR in the characterization of ischemia via PET perfusion. In conclusion, the novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance comparable to FFR in assessing regional myocardial ischemia. These findings suggest that RFR and dPR may be considered as an FFR alternative for invasively guiding revascularization treatment in symptomatic patients with CAD.
In vivo study to assess fat embolism resulting from the Reamer-Irrigator-Aspirator 2 system compared to a novel aspirator-based concept for intramedullary bone graft harvesting
Authors: Laubach Markus , Bessot Agathe , Saifzadeh Siamak , Savi Flavia Medeiros , Hildebrand Frank , Bock Nathalie , Hutmacher Dietmar W. , McGovern Jacqui
Published: February 2024

Introduction

Fat embolism (FE) following intramedullary (IM) reaming can cause severe pulmonary complications and sudden death. Recently, a new harvesting concept was introduced in which a novel aspirator is used first for bone marrow (BM) aspiration and then for subsequent aspiration of morselized endosteal bone during sequential reaming (A + R + A). In contrast to the established Reamer-Irrigator-Aspirator (RIA) 2 system, the new A + R + A concept allows for the evacuation of fatty BM prior to reaming. In this study, we hypothesized that the risk of FE, associated coagulopathic reactions and pulmonary FE would be comparable between the RIA 2 system and the A + R + A concept.

Materials and methods

Intramedullary bone graft was harvested from intact femora of 16 Merino sheep (age: 1–2 years) with either the RIA 2 system (n = 8) or the A + R + A concept (n = 8). Fat intravasation was monitored with the Gurd test, coagulopathic response with D-dimer blood level concentration and pulmonary FE with histological evaluation of the lungs.

Results

The total number and average size of intravasated fat particles was similar between groups (p = 0.13 and p = 0.98, respectively). D-dimer concentration did not significantly increase within 4 h after completion of surgery (RIA 2: p = 0.82; A + R + A: p = 0.23), with an interaction effect similar between groups (p = 0.65). The average lung area covered with fat globules was similar between groups (p = 0.17).

Conclusions

The use of the RIA 2 system and the novel A + R + A harvesting concept which consists of BM evacuation followed by sequential IM reaming and aspiration of endosteal bone, resulted in only minor fat intravasation, coagulopathic reactions and pulmonary FE, with no significant differences between the groups. Our results, therefore, suggest that both the RIA 2 system and the new A + R + A concept are comparable technologies in terms of FE-related complications.
Anatomy, histology and ultrastructure of the digestive tract in Andean fish (Trichomycterus bogotensis) and ecological implications
Authors: Ortiz-Ruiz M. , López-Flórez C. , Castro-Rebolledo M. I. , Baldisserotto B. , Gómez-Ramírez E.
Published: February 2024

Trichomycterus bogotensis is one of the three species of fish that inhabit the Colombian Andes. However, several aspects of its basic biology, including its digestive system, are unknown. The morphology and histology of the digestive system are of great importance for understanding a species’ feeding habits and food preferences. Thus, this study aimed to perform a morphological description of the digestive tract of T. bogotensis. The gastrointestinal tract of seven specimens was processed for paraffin histology, high-resolution optical microscopy, and transmission electron microscopy. Anatomically, T. bogotensis exhibits a terminal mouth with villiform teeth, a narrow esophagus, a large and muscular stomach, and a short intestine. Histology and ultrastructure revealed a tissue organization similar to that reported for other Silurids, composed of four layers: mucosal, submucosal, muscular, and serosa. The anatomical and histological characteristics suggest that T. bogotensis is a benthic species with a tendency to carnivory.
Exploring predictors of dysphagia in survivors of head and neck cancer: A cross-sectional study
Authors: López-Fernández María Dolores , Fernández-Lao Carolina , Ruíz-Martínez Alba María , Fernández-Gualda Miguel Ángel , Lozano-Lozano Mario , Ortiz-Comino Lucía , Galiano-Castillo Noelia
Published: February 2024

Purpose

To evaluate the prevalence of dysphagia in survivors of head and neck cancer (sHNC) and to identify the predictors contributing to the development of dysphagia.

Methods

We enrolled 62 sHNC in a cross-sectional study to check the prevalence of dysphagia in sHNC and to evaluate which factors were influencing the presence of this side effect. Besides dysphagia, sociodemographic and clinical characteristics, oral symptoms, maximal mouth opening (MMO), sleep quality and physical condition were evaluated, and a linear regression analysis was performed to verify which of these outcomes impact dysphagia.

Results

Among all the sHNC, 85.5% presented dysphagia. The linear regression analysis confirmed that 44.9% of the variance in dysphagia was determined by coughing, MMO and sleep quality, being MMO the most powerful predictor, followed by coughing and sleep quality.

Conclusion

Dysphagia affected the great majority of sHNC. Moreover, symptoms as coughing, reduced MMO and sleep disorders may act as predictors contributing to the development of dysphagia. Our results emphasize the importance of an early and proper identification of the symptoms as well as an adequate treatment strategy to address the cluster of symptoms that sHNC undergo.
Coverage for evidence-based cancer survivorship care services
Authors: Blaes Anne H. , Abu-Khalaf Maysa M. , Bender Catherine M. , Dent Susan F. , Fung Chunkit , Smith Sophia K. , Watson Samantha , Katta Sweatha , Merrill Janette K. , Hudson Shawna V.
Published: February 2024

Purpose

The American Society of Clinical Oncology Cancer Survivorship Committee established a task force to determine which survivorship care services were being denied by public and private payers for coverage and reimbursement.

Methods

A quantitative survey instrument was developed to determine the clinical practice-reported rates of coverage denials for evidence-based cancer survivorship care services. Additionally, qualitative interviews were conducted to understand whether coverage denials were based on payer policies, cost-sharing, or prior authorization.

Results

Of 122 respondents from 50 states, respondents reported that coverage denials were common (“always,” “most of the time,” or “some of the time”) for maintenance therapies, screening for new primary cancers or cancer recurrence. Respondents reported that denials in coverage for maintenance therapies were highest for immunotherapy (41.74%) and maintenance chemotherapy (40.17%). Coverage denials for new primary cancer screenings were highest for Hodgkin lymphoma survivors needing a PET/CT scan (49.04%) and breast cancer survivors at a high risk of recurrence who needed an MRI (63.46%), respectively. More than half of survey respondents reported denials for symptom management and supportive care services. Fertility services, dental services when indicated, and mental health services were denied “always” or “most of the time” 23.1%, 22.5%, and 12.8%, respectively. Respondents reported they often had a process in place to automatically appeal denials for evidence-based services. The denial process, however, resulted in greater stress for the patient and provider.

Conclusion

Our study demonstrates that additional advocacy with payers is needed to ensure that reimbursement policies are consistent with evidence-based survivorship care services.
Validation of the AO Spine CROST (Clinician Reported Outcome Spine Trauma) in the clinical setting
Authors: Sadiqi Said , de Gendt Erin E. A. , Muijs Sander P. J. , Post Marcel W. M. , Benneker Lorin M. , Holas Martin , Tee Jin W. , Albers Christoph E. , Häckel Sonja , Svac Juraj , Bransford Richard J. , El-Sharkawi Mohammad M. , Kandziora Frank , Rajasekaran Shanmuganathan , Schnake Klaus J. , Vaccaro Alexander R. , Oner F. Cumhur
Published: February 2024

Purpose

To evaluate feasibility, internal consistency, inter-rater reliability, and prospective validity of AO Spine CROST (Clinician Reported Outcome Spine Trauma) in the clinical setting.

Methods

Patients were included from four trauma centers. Two surgeons with substantial amount of experience in spine trauma care were included from each center. Two separate questionnaires were administered at baseline, 6-months and 1-year: one to surgeons (mainly CROST) and another to patients (AO Spine PROST—Patient Reported Outcome Spine Trauma). Descriptive statistics were used to analyze patient characteristics and feasibility, Cronbach’s α for internal consistency. Inter-rater reliability through exact agreement, Kappa statistics and Intraclass Correlation Coefficient (ICC). Prospective analysis, and relationships between CROST and PROST were explored through descriptive statistics and Spearman correlations.

Results

In total, 92 patients were included. CROST showed excellent feasibility results. Internal consistency (α = 0.58–0.70) and reliability (ICC = 0.52 and 0.55) were moderate. Mean total scores between surgeons only differed 0.2–0.9 with exact agreement 48.9–57.6%. Exact agreement per CROST item showed good results (73.9–98.9%). Kappa statistics revealed moderate agreement for most CROST items. In the prospective analysis a trend was only seen when no concerns at all were expressed by the surgeon (CROST = 0), and moderate to strong positive Spearman correlations were found between CROST at baseline and the scores at follow-up (rs = 0.41–0.64). Comparing the CROST with PROST showed no specific association, nor any Spearman correlations (rs = −0.33–0.07).

Conclusions

The AO Spine CROST showed moderate validity in a true clinical setting including patients from the daily clinical practice.
Neurophysiological signatures of mild traumatic brain injury in the acute and subacute phase
Authors: Barone Valentina , de Koning Myrthe E. , van der Horn Harm J. , van der Naalt Joukje , Eertman-Meyer Carin J. , van Putten Michel J. A. M.
Published: February 2024

Background

Mild traumatic brain injury (mTBI) affects 48 million people annually, with up to 30% experiencing long-term complaints such as fatigue, blurred vision, and poor concentration. Assessing neurophysiological features related to visual attention and outcome measures aids in understanding clinical symptoms and prognostication.

Methods

We recorded EEG and eye movements in mTBI patients during a computerized task performed in the acute (< 24 h, TBI-A) and subacute phase (4–6 weeks thereafter). We estimated the posterior dominant rhythm, reaction times (RTs), fixation duration, and event-related potentials (ERPs). Clinical outcome measures were assessed using the Head Injury Symptom Checklist (HISC) and the Extended Glasgow Outcome Scale (GOSE) at 6 months post-injury. Similar analyses were performed in an age-matched control group (measured once). Linear mixed effect modeling was used to examine group differences and temporal changes within the mTBI group.

Results

Twenty-nine patients were included in the acute phase, 30 in the subacute phase, and 19 controls. RTs and fixation duration were longer in mTBI patients compared to controls (p < 0.05), but not between TBI-A and TBI-S (p < 0.05). The frequency of the posterior dominant rhythm was significantly slower in TBI-A (0.6 Hz, p < 0.05) than TBI-S. ERP mean amplitude was significantly lower in mTBI patients than in controls. Neurophysiological features did not significantly relate to clinical outcome measures.

Conclusion

mTBI patients demonstrate impaired processing speed and stimulus evaluation compared to controls, persisting up to 6 weeks after injury. Neurophysiological features in mTBI can assist in determining the extent and temporal progression of recovery.

Graphical abstract
Effect of photodynamic therapy mediated by hematoporphyrin derivatives on small cell lung cancer H446 cells and bronchial epithelial BEAS-2B cells
Authors: Lin Cunzhi , Zhang Yuanyuan , Liao Jiemei , Cui Shichao , Gao Zhe , Han Weizhong
Published: February 2024

To investigate the effects of photodynamic therapy (PDT) mediated by hematoporphyrin derivatives (HPD) on the proliferation of small cell lung cancer H446 cells and bronchial epithelial BEAS-2B cells. H446 cells and BEAS-2B cells were cultured in vitro with different concentrations of HPD(0, 5, 10, 12, 15, 20 μg/mL) for 4 h, and then irradiated with 630 nm laser with different energy densities (0, 25, 50, 75, 100 mW/cm2). Cell viability of H446 cells and BEAS-2B cells were detected by CCK8 assay. The cell apoptosis was observed with Annexin V-FTTC/PI double staining and Hoechst 33258. The RT-PCR examination was applied to detect the transcriptional changes of the mRNA of Bax、Bcl-2, and Caspase-9. The results of CCK8 showed that when the HPD was 15 μg/mL and the laser power density reached 50 mW/cm2, the cell viability was significantly decreased compared with the black control group. Hoechst 33258 staining showed that with the increase of HPD concentration, the cell density was reduced, and apoptotic cells increased. Flow cytometry assay revealed that the apoptotic rates of the HPD-PDT group of H446 cells and BEAS-2B cells were significantly different from those of the blank control group. The RT-PCR examination showed that the expression levels of Bax and Caspase-9 mRNA in the HPD-PDT group were up-regulated, while the expression levels of Bcl-2 mRNA were down-regulated significantly. HPD-PDT can inhibit H446 cells and BEAS-2B cells growth. The mechanism may be related to up-regulating the expression levels of Bax and Caspase-9 mRNA and down-regulating the expression levels of Bcl-2 mRNA.
PCDH8 is a novel prognostic biomarker in thyroid cancer and promotes cell proliferation and viability
Authors: Yang Ruida , Yang Nan , Yin Pan , Xue Zihan , Sun Feidi , Fan Ruihan , Liang JiaFu , Lv Xinru , Wu Shaobo , Sun Liankang
Published: February 2024

Protocadherin 8 (PCDH8), a calcium-dependent transmembrane protein in the protocadherin family, regulates cell adhesion and signal transduction. While some studies have provided indirect evidence that PCDH8 has cancer-promoting properties, this association is controversial. In particular, its involvement in thyroid cancer (THCA) remains unclear. We aimed to elucidate the role of PCDH8 in THCA using bioinformatic analysis. Subsequently, the results were experimentally validated. The analysis conducted using the R programming language and online web tools explored PCDH8 expression levels, prognostic, and clinical implications, and its relationship with the tumor immune microenvironment in THCA. Furthermore, we examined the association between PCDH8 and co-expressed genes, highlighting their involvement in several biological processes relevant to THCA. The potential of PCDH8 as a therapeutic target for this pathology was also explored. Immunohistochemical (IHC) staining was performed on samples from 98 patients with THCA, and experimental validation was carried out. PCDH8 was significantly elevated in cancer tissues and associated with poor prognosis, several clinical factors, and immune cell and checkpoint abundance. Cox regression and survival analyses, together with Receiver Operating Curves (ROC) indicated that PCDH8 was an independent prognostic factor for THCA. Furthermore, PCDH8 impacts cell viability and proliferation, promoting tumorigenesis. Also, it influences tumor cell sensitivity to various drugs. Thus, PCDH8 might be a potential therapeutic target for THCA. IHC, cell culture, MTT, and colony formation experiments further confirmed our findings. This analysis provided insights into the potential carcinogenic role of PCDH8 in THCA, as it impacts cell viability and proliferation. Thus, PCDH8 might play an important role in its prognosis, immune infiltration, and diagnosis.
Treatment strategies in MDA5-positive clinically amyopathic dermatomyositis: a single-center retrospective analysis
Authors: Hirsch Stefanie , Pöhler Gesa Helen , Seeliger Benjamin , Prasse Antje , Witte Torsten , Thiele Thea
Published: February 2024

Melanoma differentiation-associated protein 5 (MDA5) antibody positive amyopathic dermatomyositis (DM) is a rare inflammatory disease. So far, there is no official treatment guideline in MDA5 amyopathic dermatomyositis, but early and aggressive immunosuppressive combination treatment can induce a stable remission. We retrospectively analyzed a cohort of eight patients (male n = 5) that were diagnosed with MDA5-positive amyopathic DM. Patient data comprised demographics, CT-guided diagnosis of pulmonary involvement, pulmonary function testing including forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) data on baseline and mean long-term follow-up of 51 months (24–92 months) to evaluate treatment strategies. Depending on severity of organ involvement treatments were individualized including cyclophosphamide, immunoglobulins and plasmapheresis. Simultaneously, oral treatment with tacrolimus was commenced in four of the eight patients. Most patients received remission maintenance therapy with a combination of tacrolimus, rituximab and low dose steroids. In all patients, improvement in FVC was recorded and five patients achieved an improvement in DLCO. An improvement in the CT imaging morphological findings was observed in four patients. Awareness for the entirety of all clinical and disease-related findings of amyopathic DM is crucial, and remission maintenance is often achieved with a combination of tacrolimus and rituximab.
Overexpression of thioredoxin-like protein ACHT2 leads to negative feedback control of photosynthesis in Arabidopsis thaliana
Authors: Fukushi Yuka , Yokochi Yuichi , Hisabori Toru , Yoshida Keisuke
Published: February 2024

Thioredoxin (Trx) is a small redox mediator protein involved in the regulation of various chloroplast functions by modulating the redox state of Trx target proteins in ever-changing light environments. Using reducing equivalents produced by the photosynthetic electron transport chain, Trx reduces the disulfide bonds on target proteins and generally turns on their activities. While the details of the protein-reduction mechanism by Trx have been well investigated, the oxidation mechanism that counteracts it has long been unclear. We have recently demonstrated that Trx-like proteins such as Trx-like2 and atypical Cys His-rich Trx (ACHT) can function as protein oxidation factors in chloroplasts. Our latest study on transgenic Arabidopsis plants indicated that the ACHT isoform ACHT2 is involved in regulating the thermal dissipation of light energy. To understand the role of ACHT2 in vivo, we characterized phenotypic changes specifically caused by ACHT2 overexpression in Arabidopsis. ACHT2-overexpressing plants showed growth defects, especially under high light conditions. This growth phenotype was accompanied with the impaired reductive activation of Calvin–Benson cycle enzymes, enhanced thermal dissipation of light energy, and decreased photosystem II activity. Overall, ACHT2 overexpression promoted protein oxidation that led to the inadequate activation of Calvin–Benson cycle enzymes in light and consequently induced negative feedback control of the photosynthetic electron transport chain. This study highlights the importance of the balance between protein reduction and oxidation in chloroplasts for optimal photosynthetic performance and plant growth.
Human presence is positively related to the number of bird calls and songs: Assessment in a national park
Authors: Pérez-González Javier , Rey-Gozalo Guillermo , Hidalgo-de-Trucios Sebastián J.
Published: February 2024

Human disturbance has been shown to provoke physiological and behavioral responses in birds, so nature-based tourism might reduce bird abundance and diversity. The negative consequences of human disturbance might be expected to be maximized during eventual massive events in highly protected areas such as national parks. In this study, the consequences for soundscapes of human presence and disturbance of thousands of visitors during an ornithological fair (massive event) on the bird community of the Monfragüe National Park (Spain) were analyzed. We found that the number and diversity of bird vocalizations did not decrease during the massive event. In contrast, the presence of people in the Monfragüe National Park was associated with an increase in the number and diversity of vocalizations. The effect of human presence on the number of calls and songs differed: the number of calls mainly increased during the massive event when people were present, while the number of songs increased when people were present, particularly during the measurement campaign without the massive event. The human shield hypothesis, along with other behavioral and environmental factors, might potentially explain the results obtained.
Subgraphs of BV functions on RCD spaces
Authors: Antonelli Gioacchino , Brena Camillo , Pasqualetto Enrico
Published: February 2024

In this work, we extend classical results for subgraphs of functions of bounded variation in $$\mathbb R^n\times \mathbb R$$

R
n

×
R

to the setting of $${\textsf{X}}\times \mathbb R$$

X
×
R

, where $${\textsf{X}}$$
X
is an $${\textrm{RCD}}(K,N)$$

RCD
(
K
,
N
)

metric measure space. In particular, we give the precise expression of the push-forward onto $${\textsf{X}}$$
X
of the perimeter measure of the subgraph in $${\textsf{X}}\times \mathbb R$$

X
×
R

of a $${\textrm{BV}}$$
BV
function on $${\textsf{X}}$$
X
. Moreover, in properly chosen good coordinates, we write the precise expression of the normal to the boundary of the subgraph of a $${\textrm{BV}}$$
BV
function f with respect to the polar vector of f, and we prove change-of-variable formulas.
Wasserstein GAN-based architecture to generate collaborative filtering synthetic datasets
Authors: Bobadilla Jesús , Gutiérrez Abraham
Published: February 2024

Currently, generative applications are reshaping different fields, such as art, computer vision, speech processing, and natural language. The computer science personalization area is increasingly relevant since large companies such as Spotify, Netflix, TripAdvisor, Amazon, and Google use recommender systems. Then, it is rational to expect that generative learning will increasingly be used to improve current recommender systems. In this paper, a method is proposed to generate synthetic recommender system datasets that can be used to test the recommendation performance and accuracy of a company on different simulated scenarios, such as large increases in their dataset sizes, number of users, or number of items. Specifically, an improvement in the state-of-the-art method is proposed by applying the Wasserstein concept to the generative adversarial network for recommender systems (GANRS) seminal method to generate synthetic datasets. The results show that our proposed method reduces the mode collapse, increases the sizes of the synthetic datasets, improves their ratings distributions, and maintains the potential to choose the desired number of users, number of items, and starting size of the dataset. Both the baseline GANRS and the proposed Wasserstein-based WGANRS deep learning architectures generate fake profiles from dense, short, and continuous embeddings in the latent space instead of the sparse, large, and discrete raw samples that previous GAN models used as a source. To enable reproducibility, the Python and Keras codes are provided in open repositories along with the synthetic datasets generated to test the proposed architecture (https://github.com/jesusbobadilla/ganrs.git).

Graphical abstract
Caring records: professional insights into child-centered case note recording
Authors: Hawkes Martine , Evans Joanne , Reed Barbara
Published: February 2024

The consequences of poorly processed reports of child abuse and neglect, along with governance challenges in child protection systems, are well-documented. Recent research, inquiries and royal commissions emphasise the need for child-centered and participatory practices that support the rights and dignity of children and their families. However, the challenges of quality case recording in child protection systems and contexts remain unclear. This paper reports on the findings from a pilot study that interviewed (n = 22) and surveyed (n = 56) social work students and social work curriculum developers from Australian Universities and practitioners currently working in the Australian child protection service system. By capturing participants' professional insights, we aim to understand the embedded barriers to transforming child-centered systems by focusing on strengths and possibilities in current practices rather than reiterating deficiencies in recordkeeping. This paper reveals insights into how professionals working in the child protection system understand and are supported in child-centered case note recording and recordkeeping practices. It also identifies the possibilities for the crucial role that interdisciplinary collaboration and alignment between social work and recordkeeping informatics can play in transforming and supporting recordkeeping approaches and practices that prioritise and uphold the rights and dignity of the child.
Species and ecological communities as management surrogates for threatened biodiversity
Authors: Olivares-Rojas Javiera , Cook Carly N. , Ward Michelle S. , Walsh Jessica C.
Published: February 2024

In the face of the ongoing biodiversity crisis and limited conservation funding, surrogate approaches have become a valuable tool to represent biodiversity. Management surrogates are those that indirectly benefit an ecological system or species by representing the management requirements of co-occurring biodiversity. Recent findings highlight the cost-effective potential of surrogate species in managing threatened species, however, evaluating higher levels of biodiversity as management surrogates remains unexplored. Here, we sought to maximize conservation outcomes for threatened species and threatened ecological communities (TECs) by prioritizing management based on overlapping distributions, threats, and costs. We describe a prioritization framework for identifying TECs that could serve as cost-effective surrogates, and compare it with prioritizing threatened species only or both species and TECs. We show that when the objective is to maximize benefits for threatened species, a community approach performs poorly due to limited geographic overlap and high costs, while prioritizing species returned 7.5 times more benefits delivered to species under the same budget. Yet, if the objective is to maximize benefits across species and TECs simultaneously, a combined approach including both as surrogates delivers the greatest benefit for the same costs as a species-only approach. Range sizes and taxonomic groups significantly influenced the priority list, with threatened invertebrates and TECs of smaller ranges more likely to be selected as surrogates. Overall, this study emphasizes the importance of incorporating accurate data on factors such as threats and costs for identifying effective management surrogates, and highlights the potential benefits of prioritizing across multiple biodiversity features.
Comparison of trastuzumab emtansine, trastuzumab deruxtecan, and disitamab vedotin in a multiresistant HER2-positive breast cancer lung metastasis model
Authors: Pourjamal Negar , Yazdi Narjes , Halme Aleksi , Joncour Vadim Le , Laakkonen Pirjo , Saharinen Pipsa , Joensuu Heikki , Barok Mark
Published: February 2024

Human epidermal growth factor 2 (HER2)-positive breast cancer with lung metastases resistant to targeted agents is a common therapeutic challenge. Absence of preclinical lung metastasis models that are resistant to multiple anti-HER2 targeted drugs hampers the development of novel therapies. We established a novel HER2-positive breast cancer cell line (L-JIMT-1) with a high propensity to form lung metastases from the parenteral JIMT-1 cell line by injecting JIMT-1 cells into immunodeficient SCID mice. Lung metastases developed in all mice injected with L-JIMT-1 cells, and more rapidly and in greater numbers compared with the parental JIMT-1 cells. L-JIMT-1 cells expressed more epidermal growth factor receptor and HER2 than JIMT-1 cells. L-JIMT-1 cells were resistant to all five tyrosine kinase inhibitors tested in vitro (afatinib, erlotinib, lapatinib, sapitinib, and tucatinib). When we compared JIMT-1 and L-JIMT-1 sensitivity to three HER2-targeting antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and disitamab vedotin (DV) in vitro, JIMT-1 cells were resistant T-DXd, partially sensitive to T-DM1, and sensitive to DV, while L-JIMT-1 cells were resistant to both T-DM1 and T-DXd, but moderately sensitive to DV. In a mouse model, all three ADCs inhibited the growth of L-JIMT-1 lung metastases compared to a vehicle, but DV and T-DXd more strongly than T-DM1, and DV treatment led to the smallest tumor burden. The L-JIMT breast cancer lung metastasis model developed may be useful in the evaluation of anti-cancer agents for multiresistant HER2-positive advanced breast cancer.