bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance and robustness of small molecule retention time prediction with molecular graph neural networks in industrial drug discovery campaigns
Authors: Vik Daniel , Pii David , Mudaliar Chirag , Nørregaard-Madsen Mads , Kontijevskis Aleksejs 
Published: April 2024

AbstractThis study explores how machine-learning can be used to predict chromatographic retention times (RT) for the analysis of small molecules, with the objective of identifying a machine-learning framework with the robustness required to support a chemical synthesis production platform. We used internally generated data from high-throughput parallel synthesis in context of pharmaceutical drug discovery projects. We tested machine-learning models from the following frameworks: XGBoost, ChemProp, and DeepChem, using a dataset of 7552 small molecules. Our findings show that two specific models, AttentiveFP and ChemProp, performed better than XGBoost and a regular neural network in predicting RT accurately. We also assessed how well these models performed over time and found that molecular graph neural networks consistently gave accurate predictions for new chemical series. In addition, when we applied ChemProp on the publicly available METLIN SMRT dataset, it performed impressively with an average error of 38.70 s. These results highlight the efficacy of molecular graph neural networks, especially ChemProp, in diverse RT prediction scenarios, thereby enhancing the efficiency of chromatographic analysis.
Serum autotaxin is a prognostic indicator of liver-related events in patients with non-alcoholic fatty liver disease
Authors: Iwadare Takanobu , Kimura Takefumi , Okumura Taiki , Wakabayashi Shun-ichi , Nakajima Taro , Kondo Shohei , Kobayashi Hiroyuki , Yamashita Yuki , Sugiura Ayumi , Fujimori Naoyuki , Yamazaki Tomoo , Kunimoto Hideo , Shimamoto Satoshi , Igarashi Koji , Joshita Satoru , Tanaka Naoki , Umemura Takeji 
Published: April 2024

Abstract
Background
Circulating autotaxin (ATX) levels have been reported to correlate with liver inflammation activity and liver fibrosis severity in patients with non-alcoholic fatty liver disease (NAFLD). The objective of this study is to investigate whether serum ATX could predict liver-related events (LRE) in NAFLD patients.

Methods
This retrospective investigation includes 309 biopsy-proven NAFLD patients registered at Shinshu University Hospital. All patients are followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, hepatic encephalopathy, ascites, and esophagogastric varices, is investigated in relation to ATX levels at the time of liver biopsy.

Results
During the median follow-up period of 7.0 years, LRE are observed in 20 patients (6.5%). The area under the receiver operating characteristic curve and cut-off value of serum ATX for predicting LRE are 0.81 and 1.227 mg/l, respectively. Multivariate Cox proportional hazards models for LRE determine ATX and advanced fibrosis as independently associated factors. Furthermore, in a competing risk analysis that considered non-liver-related death as a competing event, ATX (HR 2.29, 95% CI 1.22–4.30, p = 0.010) is identified as an independent factor associated with LRE, along with advanced fibrosis (HR 8.01, 95% CI 2.10–30.60, p = 0.002). The predictive utility of ATX for LRE is validated in an independent cohort.

Conclusions
Serum ATX may serve as a predictive marker for LRE in patients with NAFLD.
The case for longtermism: concern for the far future as a catalyst for pro-climate action
Authors: Syropoulos Stylianos , Law Kyle Fiore , Young Liane 
Published: April 2024

AbstractAmid escalating climate challenges, we examine relationships between longtermism beliefs with policy-level and grassroots climate-protective attitudes and actions. Across four primary pre-registered studies (N = 4451) and two supplementary pilots (N = 1858), we find that a significant portion, approximately 25% of our participants, who endorse the longtermism ethical philosophy, report heightened climate change concerns. Furthermore, longtermists show stronger support for pro-climate policies, advocate for initiatives in line with climate justice for future generations and present-day minoritized groups and make proactive contributions to environmental causes and initiatives. Moreover, we find that responsibility to distant future generations drives these associations. Through a targeted intervention, we boosted intergenerational responsibility and increased donations to an environmental charity. These findings highlight how longtermism beliefs shape pro-environmental attitudes and actions, offering valuable insights for climate advocacy strategies and cultivating more widespread support for comprehensive environmental policies.
Brain mechanisms underlying the emotion processing bias in treatment-resistant depression
Authors: Fan Xiaoxu , Mocchi Madaline , Pascuzzi Bailey , Xiao Jiayang , Metzger Brian A. , Mathura Raissa K. , Hacker Carl , Adkinson Joshua A. , Bartoli Eleonora , Elhassa Salma , Watrous Andrew J. , Zhang Yue , Allawala Anusha , Pirtle Victoria , Mathew Sanjay J. , Goodman Wayne , Pouratian Nader , Bijanki Kelly R. 
Published: April 2024

AbstractDepression is associated with a cognitive bias towards negative information and away from positive information. This biased emotion processing may underlie core depression symptoms, including persistent feelings of sadness and a reduced capacity to experience pleasure. The neural mechanisms responsible for this biased emotion processing remain unknown. Here we had a unique opportunity to record stereotactic electroencephalography signals in the amygdala and prefrontal cortex (PFC) from 5 patients with treatment-resistant depression (TRD) and 12 patients with epilepsy (as control) while they participated in an affective bias task in which happy and sad faces were evaluated. First, compared with the control group, patients with TRD showed increased amygdala responses to sad faces in the early stage (around 300 ms) and decreased amygdala responses to happy faces in the late stage (around 600 ms) following the onset of faces. Furthermore, during the late stage of happy-face processing, alpha-band activity in the PFC as well as alpha-phase locking between the amygdala and the PFC were significantly greater in patients with TRD compared with the control group. The increased amygdala activation during the early stage of sad-face processing suggests an overactive bottom-up processing system in TRD. Meanwhile, the reduced amygdala response during the late stage of happy-face processing could be attributed to increased top-down inhibition by the PFC through alpha-band oscillation, which may be relieved following deep brain stimulation in the subcallosal cingulate and the ventral capsule/ventral striatum.
Verletzungen der subaxialen Halswirbelsäule
Authors: Schleicher Philipp , Pingel Andreas , Neuhoff Jonathan , Wengert Alexander , Kandziora Frank 
Published: April 2024

ZusammenfassungDie untere Halswirbelsäule (HWS) ist anfällig für Verletzungen, die 2,5–5% aller knöchernen Verletzungen ausmachen. Statistiken zeigen, dass 20–50% aller Wirbelsäulenverletzungen die HWS betreffen, wobei 50–70% auf die untere HWS entfallen. In Deutschland gab es 2018 rund 11.528 stationäre Behandlungen aufgrund von Halswirbelsäulenfrakturen, mit steigender Tendenz.Rückenmarkverletzungen bei HWS-Verletzungen treten mit etwa 10–12% auf, wobei das Risiko im Vergleich zu Brust- und Lendenwirbelverletzungen dreifach höher ist. Sportliche Aktivitäten, Verkehrsbeteiligung und Stürze über 2 m Höhe erhöhen das Risiko signifikant.Begleitverletzungen sind in bis zu 80% der Fälle vorhanden und betreffen andere Wirbelsäulenabschnitte, Schädel-Hirn-Trauma und Extremitäten. Die Segmente C5–6 und C6–7 sind am häufigsten betroffen.Die AO Spine-Klassifikation für subaxiale HWS-Verletzungen, eingeführt 2015, berücksichtigt Facettenverletzungen und neurologischen Status. Diagnostisch ist die Canadian-C-Spine-Rule relevant, während die CT für die primäre HWS-Bildgebung bevorzugt wird.Therapieoptionen umfassen konservative Ansätze für nicht dislozierte Frakturen, während operative Eingriffe, ventral oder dorsal, bei instabilen Verletzungen erforderlich sind. Die Wahl der Therapie hängt von verschiedenen Faktoren ab, darunter die Art der Verletzung und der neurologische Status.Die Prognose nach HWS-Verletzungen variiert je nach Grad der neurologischen Beteiligung. Ohne Rückenmarkverletzung erzielen die meisten Patienten gute Ergebnisse, während Rückenmarkverletzungen die Lebensqualität negativ beeinflussen. Die Rückkehr in den Beruf gelingt in vielen Fällen, und radikuläre Läsionen heilen häufig symptomfrei aus. Relevante Nackenschmerzen sind jedoch in etwa 20% der Fälle nach 2,5 Jahren zu verzeichnen.
Interferon-Inhibition beim systemischen Lupus erythematodes
Authors: Mucke Johanna 
Published: April 2024

ZUSAMMENFASSUNGTyp-I-Interferone (IFN) spielen über die Bindung an den Interferon-alpha-Rezeptor und die Aktivierung des JAK-STAT-Weges eine wichtige Rolle in der Abwehr viraler Organismen. Beim SLE findet sich eine Überproduktion von Typ-I-IFN, die zu einer vermehrten Aktivierung von B-Zellen führen. Die IFN-Level korrelieren dabei mit Krankheitsaktivität und -schwere. Typ-I-IFN stellen damit ein vielversprechendes Therapieziel dar und mit der Zulassung des IFN-alpha-Rezeptor-Inhibitors Anifrolumab zur Therapie des extrarenalen SLE steht bereits ein wirksames Medikament zur Interferon-Blockade zu Verfügung. Zudem gibt es weitere Ansätze, wie die JAK-Inhibition oder Hemmung der IFN-produzierenden plasmazytoiden dendritischen Zellen, die derzeit als mögliche Therapieziele bei SLE getestet werden.
CD38 als innovatives therapeutisches Target zur Plasmazelldepletion bei Autoimmunerkrankungen
Authors: Alexander Tobias , Ostendorf Lennard , Hiepe Falk 
Published: April 2024

ZUSAMMENFASSUNGCD38 ist ein Typ-II-Glykoprotein und Ektoenzym, das auf kurz- und langlebigen Plasmazellen stark exprimiert wird, während es auf anderen lymphoiden Zellen, myeloischen Zellen und nicht hämatopoetischen Zellen nur schwach exprimiert wird. Dieses Expressionsmuster macht CD38 zu einem interessanten Ziel für einen Plasmazell-gerichteten Therapieansatz und ist bei Multiplem Myelom bereits als Therapieoption fest verankert. Bei Autoantikörper-vermittelten Autoimmunerkrankungen zielt dieser Ansatz auf eine Depletion von antikörperproduzierenden Plasmazellen, die auf Immunsuppression und B-Zell-gerichtete Therapien, wie z. B. Rituximab, nicht ansprechen. Innerhalb der letzten Jahre wurden monoklonale Anti-CD38-Antikörper erfolgreich bei refraktären Autoimmunerkrankungen eingesetzt. Wir stellen hier die wissenschaftlichen Hintergründe und Ergebnisse der ersten Erfahrungsberichte zusammen.
Primary anastomosis closure after endoscopic ultrasound-directed transgastric intervention
Authors: Cui YongYan , Almario Jose Antonio , Bejjani Michael , Khashab Mouen A. , Irani Shayan 
Published: April 2024

Abstract
Background and study aims Endoscopic ultrasound-directed transgastric intervention (EDGI) is a technique that creates an anastomosis between the gastric pouch or jejunum to the excluded stomach in Roux-en-Y gastric bypass (RYGB) anatomy to allow access to the pancreaticobiliary system. Thus far, management of anastomosis closure at the time of lumen-apposing metal stent (LAMS) removal has varied widely. This study aimed to assess the efficacy of primary closure at the time of LAMS removal using a through-the-scope (TTS) tack-based suture system.
Patients and methods This was a two-center retrospective study of RYGB patients who underwent single-stage EDGI using a 20-mm LAMS and subsequent primary anastomosis closure with the X-tack system at the time of stent removal. Patient demographics, procedure details, clinical outcomes, and imaging findings are reported.
Results Nineteen patients (median age 63 years, 84% female) underwent single-stage EDGI with a median follow-up of 31.5 months. Adverse events occurred in two patients (11%) who had abdominal pain requiring hospitalization. The median LAMS dwell time was 32 days (range 16–86). All patients (100%) who underwent follow-up studies after LAMS removal had confirmed anastomosis closure (n = 18). Most patients had documented weight loss at the time of LAMS removal and at last follow-up (68%, n = 13).
Conclusions Single-stage EDGI is an effective approach to managing RYGB patients with pancreaticobiliary pathology. Thus far, endoscopic TTS tack-based suturing appears to have a high success rate in anastomosis closure after LAMS removal and should be considered as a primary method for preventing chronic fistulae.
Alban Köhler – Ein Rückblick zu seinem 150. Geburtstag anhand seiner „Lebenserinnerungen“ und seiner Röntgenbücher
Authors: Stuhrmann Markus 
Published: April 2024

ZusammenfassungVor 150 Jahren, am 1.3.1874, wurde Prof. Dr. Alban Köhler, Pionier in der Röntgendiagnostik und Mitgründer der Deutschen Röntgengesellschaft, geboren. Anhand seiner Lebenserinnerungen „Röntgenarztes Erdenwallen“, eine außergewöhnlich persönliche, interessante und auch humorvolle Autobiografie eines Zeitzeugen aus den Anfängen der Röntgenära, soll an Ihn erinnert werden. Ferner stehen im Mittelpunkt dieser Arbeit seine hervorragenden Röntgenbücher über die Skeletterkrankungen und Normvarianten.
A Triple Laser Combination Treatment for Facial Angiofibromata Management in Tuberous Sclerosis and Literature Review
Authors: Neamonitou F. , Neamonitos K.K. , Stavrianos S. , Neamonitos K.P. 
Published: April 2024

AbstractAngiofibromas are a common facial manifestation of tuberous sclerosis (TS). However, current treatments have proven ineffective due to high recurrence rates and noncompliance. To address this issue, we developed a new triple laser therapy protocol for more effective management of angiofibromas. We conducted tests to validate its efficacy. This is a prospective study of 10 patients with TS (4 women and 6 men, mean age 26.3 years [15–37 years]) with angiofibromata who received triple sequential laser therapy at our private dermatological clinic conducted from January 2000 to December 2022. We evaluated the outcome with the Facial Angiofibromata Severity Index (FASI) via clinical photography (0, 6 months, 1 year, and 2 years), and Dermatology Life Quality Index (DLQI). All patients had a successful recovery without any complications. Among these 10 patients, 4 experienced localized recurrences at their 6-month follow-up. These recurrences were treated with a second single carbon dioxide laser session. After 2 years of follow-up, we observed no recurring facial cutaneous manifestations. Furthermore, all patients experienced a decrease in their FASI score after treatment. According to the Visual Analogue Scale, patients reported 95% satisfaction, and DLQI indicated only a minor impact on their everyday lives. We believe that this protocol of three-step laser treatment is effective, safe, and compliable for patients with facial angiofibromata, providing a satisfactory outcome adaptable to the daily dermatological and plastic surgery practice.
Efficiency and safety of nasal positive airway pressure systems during endoscopic procedures in high-risk patients: Endo-Breath study
Authors: Kalner Alexander , Küchler Friedrich , Kavallari Ellen , Müller Martin , Seufferlein Thomas , Walter Benjamin M 
Published: April 2024

Abstract
Background and study aims Sedation of high-risk patients is a relevant issue in interventional endoscopy. This is especially because standard oximetric monitors display only hypoxia and not the preceding hypercapnia. Therefore, the question arises whether use of a nasal positive airway pressure (nPAP) system can decrease the rate of sedation-associated events.
Patients and methods A randomized, prospective trial was conducted at University Hospital Ulm, including 98 consecutive patients, identified as high-risk (American Society of Anesthesiologists physical status ≥3) and scheduled for prolonged (>15 minutes) endoscopic procedures. Patients underwent 1:1 randomization to two groups: interventional (nPAP-Mask) and control (conventional oxygen supplementation). Levels of CO2 were measured noninvasively by transcutaneous capnometry device. The primary outcome was incidence of hypoxia (SpO2 <90% over 10 seconds) and incidence of severe hypoxia was incidence of SpO2 <80% over 10 seconds. One of our secondary objectives was to determine if the nPAP-Mask could result in significant CO2 retention among high-risk patients.
Results Data analysis showed lower incidence of hypoxia in the interventional group (10/47 vs. 31/251) P <0.05. Episodes of severe hypoxia (SpO2 <80% over 10 seconds) were more frequent in the control group (8/51) compared with the intervention group (2/47) P <0.05. There was no significant difference in ΔCO2 levels in the interventional vs. control group (–6.01±7.66 vs. –7.35±8.59 mm Hg).
Conclusions In high-risk patients use of a nasal positive airway pressure system could significantly lower risk of hypoxia, especially in prolonged procedures. The nPAP-Mask does not induce CO2 retention when compared with conventional oxygen supplementation.
Therapy Combining Glucagon-Like Peptide-1 Receptor Agonist with
Sodium-Glucose Cotransporter 2 Inhibitor Suppresses Atherosclerosis in Diabetic
ApoE-Deficient Mice
Authors: Takubo Masahiro , Watanabe Kentaro , Saito Hitoki , Kohno Genta , Ishihara Hisamitsu 
Published: April 2024

Abstract
Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and
sodium-glucose cotransporter 2 inhibitors (SGLT2i) have beneficial effects on
cardiovascular disease in addition to their glucose-lowering effects. In this
study, the effects of these drugs, when used individually or in combination, on
cardiovascular atherosclerotic lesion development were compared in diabetic
ApoE-deficient (ApoE KO) hyperlipidemic mice.
Methods ApoE-KO mice were treated with streptozotocin and nicotinamide,
generating a type 2 diabetes model. The mice were randomly divided into four
groups: vehicle-treated (untreated), liraglutide (LIRA), ipragliflozin (IPRA),
and combination therapy (combo). These mice, as well as non-diabetic controls,
were fed a high-fat diet. After 8 weeks of drug administration, the heart and
aorta were removed and analyzed.
Results Atherosclerotic lesions evaluated by oil red O (ORO) staining were
significantly larger in the untreated group (13.4±0.8% of the total aortic area)
than in the non-diabetic controls (4.4±0.5%, p<0.01), while being reduced in
the combo group (6.0±1.0%, p<0.01) as compared with the untreated group. The
ORO stain-positive area in the LIRA and IPRA groups tended to be reduced but
their differences were not statistically significant. Transcript levels of
Mcp1 and Sirt1 were significantly reduced and increased,
respectively, in the combo compared with the untreated group, while no
significant changes were observed in the monotherapy groups.
Conclusions The data suggest that combination therapy with liraglutide and
ipragliflozin may be an efficient regimen for preventing the development of
atherosclerosis in diabetic mice deficient in ApoE.
The Accuracy of the S100B Protein Biomarker in the Prognosis of Patients with Acute Spinal Cord Injury
Authors: Haddadi Kaveh , Abediankenari Saeed , Ehteshami Saeed , Alipour Abbas , Majd Hassan Shayan , Jafarpour Hamed , Asadian Leila 
Published: April 2024

Abstract
Introduction The role of some biomarkers such as S100 beta (S100B) has been somewhat known in determining the severity of primary acute spinal cord injury (SCI), and today, it has been the basis of various relevant studies. Therefore, this study estimates the S100B level in serum and cerebrospinal fluid (CSF) in patients with spinal injuries.
Methods This was a descriptive-analytic study. In this study, 31 patients with acute SCI referred to Sari Imam Khomeini Hospital, Iran, were recruited. Patients were divided into two groups of complete and incomplete SCI according to the American Spinal Injury Association (ASIA). The S100B concentrations in serum and CSF levels were compared between the two groups.
Result There was only significant positive correlation between S100B CSF concentration and complete SCI based on the ASIA criterion, meaning that in cases of complete SCI the S100B CSF concentration was significantly increased correlation coefficient (CC) (cc = 0.529 and p = 0.002). Based on the results of serum S100B protein concentration, 14.70 ng/dL with a sensitivity of 66.7% and specificity of 55% was determined as cutoff for complete SCI. Also, about the CSF S100B protein level variable, concentration of 342.18 ng/dL with 100% sensitivity and 64% specificity was determined as cutoff for complete injury.
Conclusion The results of this unique study have shown that S100B were useful markers for predicting the prognosis of patients with acute SCI and cutoff points determined for serum and especially CSF concentrations can differentiate complete and incomplete SCI.
Heterokaryotypic Monochorionic Twin Pregnancy: New Perspective
Authors: Gupta Ashutosh , Aneja Anjila , Bahl Neena , Arora Rupam , Sehgal Renu Raina , Saini Pankaj 
Published: April 2024

AbstractMonozygotic twins are thought to be identical since they are created from a single fertilized egg, yet there may be differences in their congenital defects, birth weight, and genetic makeup. Asymmetric X chromosome inactivation, unequal gene imprinting, and postzygotic mitotic mistakes including nondisjunction and anaphase lag can all result in heterokaryotypic monochorionic twins. We report a monochorionic twin pregnancy that exhibited stigmata associated with trisomy 18 on postnatal examination despite a low risk of common aneuploidy (trisomy 18) on noninvasive prenatal screening. Short tandem repeat markers were used for postnatal examination to confirm high-grade mosaicism. These markers indicated mosaic trisomy 18 in twin II and normal in twin I, ruling out uniparental disomy and establishing monozygosity in both fetuses. Twin sac amniocentesis is a prenatal diagnostic procedure that can be used to identify discrepant monochorionic twins because chorionic villus sampling, single sac amniocentesis, or cordocentesis may not be able to rule out aneuploidy in the second fetus and may yield a false-negative result. For prompt zygosity diagnosis, chromosomal complement, genetic counseling, and referral for selective fetal reduction, twin sac amniocentesis is recommended.
Evaluation of Meniscal Load and Load Distribution in the Sound Canine Stifle at Different Angles of Flexion
Authors: Schmutterer Johannes Maximilian , Augat Peter , Greinwald Markus , Meyer-Lindenberg Andrea 
Published: April 2024

Abstract
Objectives The aim of the study was to investigate the contact mechanics and kinematic changes in the stifle in different standing angles.
Study Design We performed a biomechanical ex vivo study using pairs of canine cadaver hindlimbs. Motion sensors were fixed to the tibia and the femur for kinematic data acquisition. Pressure mapping sensors were placed between the femur and both menisci. Thirty percent bodyweight was applied to the limbs with the stifle in 125, 135, or 145 degrees of extension.
Results Stifle flexion angle influences femoromeniscal contact mechanics significantly. The load on both menisci was significantly higher for 125 and 135 degrees in comparison to 145 degrees. Additionally, the center of force was located significantly more caudal when comparing 125 to 145 degrees in the medial meniscus as well as in both menisci combined.
Conclusion The angle of knee flexion significantly impacts the contact mechanics between the femur and the meniscus. As the knee flexes, the load on both menisci increases