bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pooling Alzheimer's disease clinical trial data to develop personalized medicine approaches is easier said than done: A proof‐of‐principle study and call to action
Authors: Dubbelman Mark A. , Vromen Eleonora M. , Tijms Betty M. , Berkhof Johannes , Ottenhoff Lois , Vijverberg Everard G. B. , Prins Niels D. , van der Flier Wiesje M. , Sikkes Sietske A. M. 
Published: August 2024

AbstractWith the advent of the first generation of disease‐modifying treatments for Alzheimer's disease, it is clearer now more than ever that the field needs to move toward personalized medicine. Pooling data from past trials may help identify subgroups most likely to benefit from specific treatments and thus inform future trial design. In this perspective, we report on our effort to pool data from past Alzheimer's disease trials to identify patients most likely to respond to different treatments. We delineate challenges and hurdles, from our proof‐of‐principle study, for which we requested access to trial datasets from various pharmaceutical companies and encountered obstacles in the process of arranging data‐sharing agreements through legal departments. Six phase I–III trials from three sponsors provided access to their data (total n = 3170), which included demographic information, vital signs, primary and secondary endpoints, and in a small subset, cerebrospinal fluid amyloid (n = 165, 5.2%) and tau (n = 212, 6.7%). Data could be analyzed only within specific data access platforms, limiting potential harmonization with data provided through other platforms. Limited overlap in terms of outcome measures, clinical and biological information hindered analyses. Thus, while it is a commendable advancement that (some) trials now allow researchers to study their data, we conclude that gaining access to past trial datasets is complicated, frustrating the field's communal effort to find the best treatments for the right individuals. We provide a plea to promote harmonization and open access to data, by urging trial sponsors and the academic research community alike to remove barriers to data access and improve collaboration through practicing open science and harmonizing outcome measures, to allow investigators to learn all there is to learn from past failures and successes.HIGHLIGHTS
Pooling data from past Alzheimer's disease clinical trials may help identify subgroups most likely to benefit from specific treatments and may help inform future trial design.
Accessing past trial datasets is complicated, frustrating the field's communal effort to find the best treatments for the right individuals.
We urge trial sponsors and the academic research community to remove data access barriers and improve collaboration through practicing open science and harmonizing outcome measures.
Formation of pulmonary vein stump thrombus after anatomical lung resection and anticoagulant therapy
Authors: Okami Jiro , Higashiyama Masahiko , Tokunaga Toshiteru , Susaki Yoshiyuki , Kusu Takashi , Nakagiri Tomoyuki , Oe Hiroshi , Nakanishi Katsuyuki 
Published: August 2024

AbstractObjectiveIt has recently been suggested that the formation of pulmonary vein stump thrombus (PVST) after anatomical lung resection is an underlying cause of arterial thromboembolism including cerebrovascular infarction. This study aimed to investigate the incidence and risk factors of PVST and to evaluate the efficacy and safety of anticoagulant therapy for PVST.MethodsPatients who underwent anatomical lung resection for malignant lung tumors were eligible for inclusion in this study. Chest contrast‐enhanced (CE) computed tomography (CT) was performed after surgery to detect PVST. If PVST was observed, patients received anticoagulant therapy. The size of the PVST was followed‐up by repeated chest CE‐CT.ResultsIn total, 176 patients were enrolled in this study. Chest CE‐CT was performed on postoperative day 1–13 (median, postoperative day 6). PVST was detected in 22 (12.5%) patients. The median size of PVST was 9.5 (4.1–33.4) mm. Thrombus was most commonly observed in patients who underwent left upper lobectomy (9/36, 25.0%). Hypertension, dyslipidemia, arteriosclerosis, and arrhythmia were not associated with PVST formation. Anticoagulant therapy was administered to all 22 patients with PVST until the PVST disappeared. The median duration between the detection and disappearance of PVST was 77 days (range: 6–146 days). During the period between the detection and disappearance of PVST, cerebrovascular infarction or arterial thromboembolic events were not observed.ConclusionsPostoperative PVST is commonly observed, especially in patients who undergo left upper lobectomy. Anticoagulant therapy for PVST was safely introduced and was efficient to improve PVST without subsequent arterial thromboembolic events.
Chemoradiotherapy and nanomedicine: Drug mechanisms and delivery systems
Authors: Molinaro Matthew , Skrodzki David , Pan Dipanjan 
Published: August 2024

AbstractRadiotherapy is an invaluable tool in the treatment of cancer. However, when used as a monotherapy, it fails to provide curative outcomes. Chemotherapy drugs are often included to boost the effects of radiation. Key classes of radiosensitizing drugs include platinum compounds, anthracyclines, antimetabolites, taxanes, topoisomerase inhibitors, alkylating agents, and DNA damage repair inhibitors. Chemoradiotherapy suffers from not only systemic toxicities from chemotherapy drugs but also synergistic radiation toxicity as well. It is critical to deliver radiosensitizing molecules to tumor cells while avoiding adjacent healthy tissues. Currently, nanomedicine provides an avenue for tumor specific delivery of radiosensitizers. Nanoscale delivery vehicles can be synthesized from lipids, polymers, or inorganic materials. Additionally, nanomedicine encompasses stimuli responsive particles including prodrug formulation for tumor specific activation. Clinically, nanomedicine and radiotherapy are intertwined with approved formulation including DOXIL and Abraxane. Though many challenges remain, the ongoing progress evidences a promising future for both nanomedicine and chemoradiotherapy.This article is categorized under:
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Holographic $$ \frac{1}{2} $$-BPS surface defects in ABJM
Authors: Lozano Yolanda , Macpherson Niall T. , Petri Nicolò , Ramírez Anayeli 
Published: August 2024

Abstract
We study the class of AdS3 × ℂℙ3 solutions to massive Type IIA supergravity with $$ \mathfrak{osp} $$
osp
(6|2) superconformal algebra recently constructed in [1]. These solutions are foliations over an interval preserving $$ \mathcal{N} $$
N
= (0, 6) supersymmetry in two dimensions, that in the massless limit can be mapped to the AdS4 × ℂℙ3 solution of ABJM/ABJ. We show that in the massive case extra NS5-D8 branes, that we interpret as $$ \frac{1}{2} $$

1
2

-BPS surface defect branes within the ABJ theory, backreact in the geometry and turn one of the 3d field theory directions onto an energy scale, generating a flow towards a 2d CFT. We construct explicit quiver field theories that we propose flow in the IR to the (0, 6) SCFTs dual to the solutions. Finally, we show that the AdS3 solutions realise geometrically, in terms of large gauge transformations, an extension to the massive case of Seiberg duality in ABJ theories proposed in the literature.
The (1,0) tensor and hypermultiplets in loop space
Authors: Bak Dongsu , Gustavsson Andreas 
Published: August 2024

Abstract
We show that the (1,0) tensor and hypermultiplet supersymmetry variations can be uplifted to loop space. Upon dimensional reduction we make contact with abelian five-dimensional super Yang-Mills, which has a nonabelian generalization that we subsequently uplift back to loop space where we conjecture a nonabelian generalization of the (1,0) supersymmetry variations and demonstrate their on-shell closure.
Association of trauma classifications to long-term outcome in blunt trauma patients
Authors: Kuorikoski Joonas , Heinänen Mikko , Brinck Tuomas , Söderlund Tim 
Published: August 2024

Abstract
Purpose
The impact of major trauma is long lasting. Although polytrauma patients are currently identified with the Berlin polytrauma criteria, data on long-term outcomes are not available. In this study, we evaluated the association of trauma classification with long-term outcome in blunt-trauma patients.

Methods
A trauma registry of a level I trauma centre was used for patient identification from 1.1.2006 to 31.12.2015. Patients were grouped as follows: (1) all severely injured trauma patients; (2) all severely injured polytrauma patients; 2a) severely injured patients with AIS ≥ 3 on two different body regions (Berlin-); 2b) severely injured patients with polytrauma and a physiological criterion (Berlin+); and (3) a non-polytrauma group. Kaplan-Meier survival analysis was performed to estimate differences in mortality between different groups.

Results
We identified 3359 trauma patients for this study. Non-polytrauma was the largest group (2380 [70.9%] patients). A total of 500 (14.9%) patients fulfilled the criteria for Berlin + definition, leaving 479 (14.3%) polytrauma patients in Berlin- group. Berlin + patients had the highest short-term mortality compared with other groups, although the difference in cumulative mortality gradually plateaued compared with the non-polytrauma patient group; at the end of the 10-year follow up, the non-polytrauma group had the greatest mortality due to the high number of patients with traumatic brain injury (TBI).

Conclusion
Excess mortality of polytrauma patients by Berlin definition occurs in the early phase (30-day mortality) and late deaths are rare. TBI causes high early mortality followed by increased long-term mortality.
Migrationshintergrund und Einsamkeit im mittleren und hohen Alter in Deutschland
Authors: Hajek André , König Hans-Helmut 
Published: August 2024

Zusammenfassung
Hintergrund
Bisher gibt es nur wenige Erkenntnisse über den Zusammenhang zwischen Migrationshintergrund und Einsamkeit im mittleren und hohen Alter in Deutschland. Ziel war daher, eine Assoziation zwischen Migrationshintergrund und Einsamkeit in dieser Gruppe darzustellen.

Methoden
Die Daten stammen aus dem Deutschen Alterssurvey (Welle 7, November 2020 bis März 2021), einer repräsentativen Stichprobe von zuhause lebenden Personen mittleren und höheren Alters. Die Stichprobe umfasste 4145 Individuen. Das mittlere Alter betrug 63,8 Jahre, 93,2 % der Befragten hatten keinen Migrationshintergrund, wohingegen ungefähr 5,9 % der Befragten einen Migrationshintergrund mit eigener Migrationserfahrung und 0,9 % einen Migrationshintergrund, aber ohne eigene Migrationserfahrung hatten. Zur Quantifizierung der Einsamkeit wurde das etablierte Instrument von De Jong Gierveld verwendet.

Ergebnisse
Multiple lineare Regressionen zeigten, dass Personen mit Migrationshintergrund und eigener Migrationserfahrung im Vergleich zu Personen ohne Migrationshintergrund eine signifikant höhere Einsamkeit aufweisen (β = 0,15, 95 % Konfidenzintervall (KI): 0,004–0,30, p < 0,05), wohingegen Personen mit Migrationshintergrund, aber ohne eigene Migrationserfahrung eine signifikant niedrigere Einsamkeit aufweisen (β = −0,27, 95 % KI: −0,52 bis −0,02, p < 0,05).

Diskussion
Personen mit Migrationshintergrund und eigener Migrationserfahrung scheinen eine Risikogruppe für hohe Einsamkeit im mittleren und hohen Alter in Deutschland darzustellen. Insofern sollte diese Gruppe bei entsprechenden Maßnahmen besonders berücksichtigt werden. Vor dem Hintergrund der aktuellen (und potenzieller künftiger) Migrationsbewegungen sind diese Ergebnisse von großer Relevanz, da insbesondere diese Gruppen von Einsamkeit betroffen sein könnten.
Modifizierte Masquelet-Plastik
Authors: Fischer C. , Schipper S. , Langwald S. , Klauke F. , Kobbe P. , Mendel T. , Hückstädt M. 
Published: August 2024

ZusammenfassungDie Rekonstruktion langstreckiger Knochendefekte infolge von primär traumatischen oder sekundär infektions- oder tumorbedingten Substanzverlusten stellt nach wie vor eine chirurgische Herausforderung dar. Die Kallusdistraktion über Segmenttransport, der vaskularisierte Knochentransfer und die induzierte Membrantechnik (IMT) stellen etablierte Verfahren der Rekonstruktion dar. In den letzten Jahrzehnten erfreut sich die IMT aufgrund ihrer Praktikabilität, Reproduzierbarkeit und Zuverlässigkeit zunehmender Popularität. Gleichsam erfuhr die Originaltechnik eine Vielzahl von Modifikationen. Die Ergebnisse stellen sich als entsprechend heterogen dar. Diese Übersicht soll die wesentlichen Grundprinzipien der IMT darlegen und einen Überblick über die verschiedenen Modifikationen und ihre Komplikationen geben.
Additive manufacturing and mechanical performance of short fiber reinforced PEEK (polyether ether ketone) thermoplastic composites in a vacuum environment
Authors: Vatandaş Bahri Barış , Gümrük Recep 
Published: August 2024

AbstractShort fiber reinforced thermoplastic composites (SFRTC) have gained popularity in the material extrusion (MEX) method, which is an additive manufacturing (AM) technology, allowing for the simpler and more cost-effective production of polymer composites. However, parts produced using MEX 3D printing technology often exhibit poor mechanical properties and surface quality compared to products manufactured using injection molding, which is one of the main disadvantages of this method. Various methods are used to overcome these challenges, such as production in a vacuum environment, heat-based processes, ultrasonic vibrations, and others. The objective of this study was to achieve parts with lower porosity and improved mechanical properties when printed in a vacuum environment compared to an atmospheric environment. Additionally, an investigation into the optimization of printing parameters was conducted to determine the parameters that yield the highest mechanical properties. For this purpose, SFRTC parts were printed at different vacuum levels (0.5, 10, 100 mbar), and they were subjected to flexural tests to determine their mechanical properties. The results showed that the flexural stress and elastic modulus of the samples produced in a 0.5 mbar vacuum environment increased by 79.75% and 39.41%, respectively, compared to samples produced in an atmospheric environment. Furthermore, the cross-sectional images of the samples were examined using an optical microscope, revealing the lowest porosity in the samples printed in 0.5 mbar vacuum environment.
Combination of low doses of mirtazapine plus venlafaxine produces antidepressant-like effects in rats, without affecting male or female sexual behavior
Authors: Álvarez-Silva Adriana , Rodríguez-Manzo Gabriela , Reyes Rebeca , Fernández-Guasti Alonso 
Published: August 2024

Abstract

Rationale
Pharmacological treatments for depression are not always effective and produce unwanted side effects. Male and female sexual dysfunction is one of these side effects, which can lead to treatment withdrawal. Combination of two antidepressants with different mechanisms of action, like mirtazapine (MTZ) and venlafaxine (VLF) have been shown to be effective for treatment-resistant depression in humans. Combination of low doses of these drugs may still exert antidepressant-like effects without altering sexual behavior.

Objectives
To investigate the potential antidepressant-like effect of the chronic administration of low doses of MTZ plus VLF combined, as well as its impact on male and female sexual behavior in rats.

Methods
The antidepressant-like effect of a 14-day treatment with combinations of MTZ plus VLF (0/0, 2.5/3.75 or 5/7.5 mg/kg) was assessed in young adult male and female rats in the forced swim test (FST). The 5/7.5 mg/kg MTZ/VLF combination was also tested in the chronic mild stress (CMS) test, in both males and females treated for 21 days. The sexual effects of this last treatment were assessed in sexually experienced males and in gonadally-intact females during proestrus.

Results
The 5/7.5 mg/kg MTZ/VLF combination produced an antidepressant-like effect in the FST and reversed the CMS-induced anhedonia in both male and female rats. This combination did not alter male sexual behavior, female proceptive and receptive behaviors or the regularity of the estrous cycle.

Conclusion
The combination of low doses of MTZ and VLF might be a promising therapeutic alternative to treat depression without affecting the sexual response.
Evaluation of the incidence, predictors, risk assessment scores and outcomes of thromboembolism in a cohort of Egyptian NHL patients - Real World Experience
Authors: El-Ashwah Shaimaa , Elashwah Salma , Khaled Omnia , Ghanem Ahmed A. , AboElfarh Hadeer Elsaeed , Selim Ramadan Ayman , Mansour Reham Osama , Shaaban Yasmine 
Published: August 2024

AbstractNon-Hodgkin’s Lymphoma (NHL) is the most common subtype of lymphoma. The incidence of venous thromboembolism (VTE) in aggressive NHL was estimated recently to be 11%. Several risk assessment scores and factors are available to help identify cancer patients at risk for developing VTE. Patients with a pathologically confirmed diagnosis of NHL were identified at the Oncology Center of Mansoura University. The study included 777 patients: 719 with DLBCL-NOS, 26 with Anaplastic-B-cell, and 32 with T-cell-rich-NHL. Data were retrospectively collected from electronic medical records, including clinical, radiological, and laboratory information related to VTE and NHL. The median age at NHL diagnosis was 53 years, (range: 18–98). There was a male predominance, 51.4% of the cases. At initial lymphoma diagnosis, VTE was identified in 46 (5.9%) patients, and 61 (7.9%) patients experienced VTE while undergoing chemotherapy. According to logistic regression analysis, a PS (performance status) ≥ 2, bulky lesions, and mediastinal masses were significant predictors of VTE at presentation, with P-values of 0.022, 0.002, and < 0.001, respectively. Meanwhile, NHL patients who developed VTE during chemotherapy had significantly poorer PS, higher absolute neutrophilic counts (ANC), neutrophil/lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lactate dehydrogenase (LDH) levels than lymphoma patients without VTE, with P-values of 0.003, 0.034, 0.049, 0.01 and 0.007, respectively, as determined by multivariate analysis. The ROC curve identified the cut-off values of 4.875 × 109/L for ANC, 2.985 for NLR, 144.85 for PLR, and 417.5 U/L for LDH as potential markers for predicting VTE in NHL patients. Patients with a PS ≥ 2 and values exceeding these cut-offs for ANC, NLR, and PLR experienced significantly higher incidences of VTE than other groups, with P-values of 0.003, < 0.001, < 0.001, and < 0.001, respectively. At the end of the follow-up, the overall survival was significantly shortened by VTE occurring during chemotherapy, hypoalbuminemia, intermediate-high and high international prognostic index (IPI) scores (intermediate-high and high), responses other than CR and relapse, all with P-values < 0.05. ECOG PS and Inflammatory markers such as NLR, PLR, and neutrophilic count could serve as predictors of the development of thrombotic events in patients with NHL-DLBCL. Additionally, the occurrence of VTE during chemotherapy is an independent poor prognostic marker for overall survival (OS).
Maximal Colourings for Graphs
Authors: Mulas Raffaella 
Published: August 2024

AbstractWe consider two different notions of graph colouring, namely, the t-periodic colouring for vertices that has been introduced in 1974 by Bondy and Simonovits, and the periodic colouring for oriented edges that has been recently introduced in the context of spectral theory of non-backtracking operators. For each of these two colourings, we introduce the corresponding colouring number which is given by maximising the possible number of colours. We first investigate these two new colouring numbers individually, and we then show that there is a deep relationship between them.
Effects of ∆-9 tetrahydrocannabinol on the small intestine altered by high fructose diet: A Histopathological study
Authors: Isildar Basak , Beydogan Alisa Bahar , Koyuturk Ece , Coskun Yazici Zeynep Mine , Koyuturk Meral , Bolkent Sema 
Published: August 2024

AbstractThe consumption of fructose is increasing day by day. Understanding the impact of increasing fructose consumption on the small intestine is crucial since the small intestine processes fructose into glucose. ∆9-Tetrahydrocannabinol (THC), a key cannabinoid, interacts with CB1 and CB2 receptors in the gastrointestinal tract, potentially mitigating inflammation. Therefore, this study aimed to investigate the effects of the high-fructose diet (HFD) on the jejunum of rats and the role of THC consumption in reversing these effects. Experiments were conducted on Sprague–Dawley rats, with the experimental groups as follows: control (C), HFD, THC, and HFD + THC. The HFD group received a 10% fructose solution in drinking water for 12 weeks. THC groups were administered 1.5 mg/kg/day of THC intraperitoneally for the last four weeks. Following sacrification, the jejunum was evaluated for mucus secretion capacity. IL-6, JNK, CB2 and PCNA expressions were assessed through immunohistochemical analysis and the ultrastructural alterations via transmission electron microscopy. The results showed that fructose consumption did not cause weight gain but triggered inflammation in the jejunum, disrupted the cell proliferation balance, and increased mucus secretion in rats. Conversely, THC treatment displayed suppressed inflammation and improved cell proliferation balance caused by HFD. Ultrastructural examinations showed that the zonula occludens structures deteriorated in the HFD group, along with desmosome shrinkage. Mitochondria were found to be increased due to THC application following HFD. In conclusion, the findings of this research reveal the therapeutic potential of THC in reversing HFD-related alterations and provide valuable insights for clinical application.
Graphical abstract
Tracing a caring transition policy for the German coal region Lusatia
Authors: Walk Paula , Koepchen Marius , Stognief Nora , Probst Johannes 
Published: August 2024

Abstract
Coal mining and generation adversely affect several ecosystems, including climate, water and land. On the other hand, questions of justice and socio-economic considerations of affected regions are crucial for a successful coal phase-out, underlining the need for a nexus perspective. This includes taking a gender perspective, which thus far has received relatively little attention. We contribute to closing this gap through our study on the coal region Lusatia in Germany, where an unprecedentedly high amount of money is spent to shape the regional transition. The allocation of these funds is the subject of a contentious debate about which societal needs are considered most urgent to be met. We conducted a critical discourse analysis examining relevant policy documents and analyzing dominant ideas about what a successful transition in Lusatia should look like. Based on feminist care theory and interviews with locally organized women, we show that concepts of care for humans and nonhumans are severely underdeveloped. To address this gap, we propose based on women’s emerging discourse four pillars of care work as social infrastructure that should be central to transition processes: (1) aftercare for social and ecological residuals of coal mining, (2) social cohesion, (3) democratic care services, and (4) caring democracy: democratic decision-making on how to care.