bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated Δ-9-Tetrahydrocannabinol administration dose dependently increases stablished schedule-induced drinking
Authors: Fuentes-Verdugo Esmeralda , Pellón Ricardo , Miguéns Miguel 
Published: February 2024

Abstract
Rationale
Schedule-induced drinking (SID) reproduces an excessive and repetitive behavioural pattern that has led to propose this procedure as an animal model to study compulsive behaviours. Although it is known that cannabis can cause several adverse effects, in recent years there has been great interest in the medical application of cannabis derivatives for obsessive-compulsive related disorders.

Objectives
The present study investigated the effects of repeated THC administration on rates of previously acquired SID, as well as the possible alteration of its temporal distribution along inter-food intervals.

Methods
Male Wistar rats acquired SID under a 30 min fixed-time 30-sec food delivery schedule (from 30 to 43 sessions to reach a stable level). Thereafter, 5 or 10 mg/kg daily i.p. injections of THC or vehicle were repeatedly administered for 7 days to evaluate the effects on SID.

Results
Repeated THC administration at a dose of 5 mg/kg resulted in an increase on licking. Surprisingly, no effects on SID were observed with the 10 mg/kg dose. However, magazine entries were reduced with both THC doses. THC also modified the temporal distributions of licking and magazine entries during inter-food intervals.

Conclusions
The present results show that repeated THC administration may (i) increase induced licking at moderate doses, (ii) reduce magazine entries, and (iii) affect the temporal pattern of SID. These findings suggest that THC does not appear to be beneficial to reduce compulsive behaviour in this animal model, while another collateral effect of THC —such as a greater habitual-like behaviour— needs to be considered.
Distinguishing reflex from non-reflex responses elicited by transcutaneous spinal stimulation targeting the lumbosacral cord in healthy individuals
Authors: Gordineer Elizabeth A. , Stokic Dobrivoje S. , Krenn Matthias J. 
Published: February 2024

AbstractTranscutaneous spinal stimulation (TSS) studies rely on the depolarization of afferent fibers to provide input to the spinal cord; however, this has not been routinely ascertained. Thus, we aimed to characterize the types of responses evoked by TSS and establish paired-pulse ratio cutoffs that distinguish posterior root reflexes, evoked by stimulation of afferent nerve fibers, from motor responses, evoked by stimulation of efferent nerve fibers. Twelve neurologically intact participants (six women) underwent unipolar TSS (cathode over T11-12 spinal processes, anode paraumbilically) while resting supine. In six participants, unipolar TSS was repeated 2–3 months later and also compared to a bipolar TSS configuration (cathode 2.5 cm below T11-12, anode 5 cm above cathode). EMG signals were recorded from 16 leg muscles. A paired-pulse paradigm was applied at interstimulus intervals (ISIs) of 25, 50, 100, 200, and 400 ms. Responses were categorized by three assessors into reflexes, motor responses, or their combination (mixed responses) based on the visual presence/absence of paired-pulse suppression across ISIs. The paired-pulse ratio that best discriminated between response types was derived for each ISI. These cutoffs were validated by repeating unipolar TSS 2–3 months later and with bipolar TSS. Unipolar TSS evoked only reflexes (90%) and mixed responses (10%), which were mainly recorded in the quadriceps muscles (25–42%). Paired-pulse ratios of 0.51 (25-ms ISI) and 0.47 (50-ms ISI) best distinguished reflexes from mixed responses (100% sensitivity, > 99.2% specificity). These cutoffs performed well in the repeated unipolar TSS session (100% sensitivity, > 89% specificity). Bipolar TSS exclusively elicited reflexes which were all correctly classified. These results can be utilized in future studies to ensure that the input to the spinal cord originates from the depolarization of large afferents. This knowledge can be applied to improve the design of future neurophysiological studies and increase the fidelity of neuromodulation interventions.
Most Probable Flows for Kunita SDEs
Authors: Grong Erlend , Sommer Stefan 
Published: February 2024

AbstractWe identify most probable flows for Kunita Brownian motions, i.e. stochastic flows with Eulerian noise and deterministic drifts. Such stochastic processes appear for example in fluid dynamics and shape analysis modelling coarse scale deterministic dynamics together with fine-grained noise. We treat this infinite dimensional problem by equipping the underlying domain with a Riemannian metric originating from the noise. The resulting most probable flows are compared with the non-perturbed deterministic flow, both analytically and experimentally by integrating the equations with various choice of noise structures.
Effect of Sarcopenia on the Increase in Liver Volume and Function After Portal Vein Embolization
Authors: Arntz Pieter J. W. , Olthof Pim B. , Korenblik Remon , Heil Jan , Kazemier Geert , van Delden Otto M. , Bennink Roelof J. , Damink Steven W. M. Olde , van Dam Ronald M. , Schadde Erik , Erdmann Joris I. 
Published: February 2024

Abstract
Purpose
Sarcopenia is associated with a decreased kinetic growth rate (KGR) of the future liver remnant (FLR) after portal vein embolization (PVE). However, little is known on the increase in FLR function (FLRF) after PVE. This study evaluated the effect of sarcopenia on the functional growth rate (FGR) after PVE measured with hepatobiliary scintigraphy (HBS).

Methods
All patients who underwent PVE at the Amsterdam UMC between January 2005 and August 2017 were analyzed. Functional imaging by HBS was used to determine FGR. Liver volumetry was performed using multiphase contrast computed tomography (CT). Muscle area measurement to determine sarcopenia was taken at the third lumbar level (L3).

Results
Out of the 95 included patients, 9 were excluded due to unavailable data. 70/86 (81%) patients were sarcopenic. In the multivariate logistic regression analysis, sarcopenia (p = 0.009) and FLR volume (FRLV) before PVE (p = 0.021) were the only factors correlated with KGR, while no correlation was found with FGR. 90-day mortality was similar across the sarcopenic and non-sarcopenic group (4/53 [8%] versus 1/11 [9%]; p = 1.000). The resection rates were also comparable (53/70 [75%] versus 11/16 [69%]; p = 0.542).

Conclusion
FGR after PVE as measured by HBS appears to be preserved in sarcopenic patients. This is in contrast to KGR after PVE as measured by liver volumetry which is decreased in sarcopenic patients.

Level of Evidence
Level 3b, cohort and case control studies.
ESR Essentials: Imaging in colorectal cancer—practice recommendations by ESGAR
Authors: Caruso Damiano , Polici Michela , Bellini Davide , Laghi Andrea 
Published: February 2024

Abstract
Colorectal cancer (CRC) is a significant global health concern. Diagnostic imaging, using different modalities, has a pivotal role in CRC, from early detection (i.e., screening) to follow-up. The role of imaging in CRC screening depends on each country’s approach: if an organized screening program is in place, the role of CT colonography (CTC) is limited to the study of either individuals with a positive stool test unwilling/unable to undergo colonoscopy (CC) or in patients with incomplete CC. Although CC is the most common modality to diagnose CRC, CRC can be also incidentally detected during a routine abdominal imaging examination or at the emergency room in patients presenting with intestinal occlusion/subocclusion or perforation. Staging is a crucial aspect of CRC management, guiding treatment decisions and providing valuable prognostic information. An accurate local staging is mandatory in both rectal and colon cancer to drive the appropriate therapeutic workflow. Important limitations of US, CT, and MR in N-staging can be partially solved by FDG PET/CT. Distant staging is usually managed by CT, with MR and FDG PET/CT which can be used as problem-solving techniques. Follow-up is performed according to the general recommendations of the oncological societies.

Clinical relevance statement
It is essential to summarize each phase of colorectal cancer workup, differentiating the management for colon and rectal cancer supported by the main international guidelines and literature data, with the aim to inform the community on the best practice imaging in colorectal cancer.

Key Points
• Colorectal cancer is a prevalent disease that lends itself to imaging at each stage of detection and management.
• Various imaging modalities can be used as adjuncts to, or in place of, direct visualization methods of screening and are necessary for evaluating metastatic disease.
• Reevaluation of follow-up strategies should be considered depending on patients’ individual risk of recurrence.
Astroglial calcium signaling and homeostasis in tuberous sclerosis complex
Authors: Romagnolo Alessia , Dematteis Giulia , Scheper Mirte , Luinenburg Mark J. , Mühlebner Angelika , Van Hecke Wim , Manfredi Marcello , De Giorgis Veronica , Reano Simone , Filigheddu Nicoletta , Bortolotto Valeria , Tapella Laura , Anink Jasper J. , François Liesbeth , Dedeurwaerdere Stefanie , Mills James D. , Genazzani Armando A. , Lim Dmitry , Aronica Eleonora 
Published: February 2024

AbstractTuberous Sclerosis Complex (TSC) is a multisystem genetic disorder characterized by the development of benign tumors in various organs, including the brain, and is often accompanied by epilepsy, neurodevelopmental comorbidities including intellectual disability and autism. A key hallmark of TSC is the hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway, which induces alterations in cortical development and metabolic processes in astrocytes, among other cellular functions. These changes could modulate seizure susceptibility, contributing to the progression of epilepsy and its associated comorbidities. Epilepsy is characterized by dysregulation of calcium (Ca2+) channels and intracellular Ca2+ dynamics. These factors contribute to hyperexcitability, disrupted synaptogenesis, and altered synchronization of neuronal networks, all of which contribute to seizure activity. This study investigates the intricate interplay between altered Ca2+ dynamics, mTOR pathway dysregulation, and cellular metabolism in astrocytes. The transcriptional profile of TSC patients revealed significant alterations in pathways associated with cellular respiration, ER and mitochondria, and Ca2+ regulation. TSC astrocytes exhibited lack of responsiveness to various stimuli, compromised oxygen consumption rate and reserve respiratory capacity underscoring their reduced capacity to react to environmental changes or cellular stress. Furthermore, our study revealed significant reduction of store operated calcium entry (SOCE) along with strong decrease of basal mitochondrial Ca2+ concentration and Ca2+ influx in TSC astrocytes. In addition, we observed alteration in mitochondrial membrane potential, characterized by increased depolarization in TSC astrocytes. Lastly, we provide initial evidence of structural abnormalities in mitochondria within TSC patient-derived astrocytes, suggesting a potential link between disrupted Ca2+ signaling and mitochondrial dysfunction. Our findings underscore the complexity of the relationship between Ca2+ signaling, mitochondria dynamics, apoptosis, and mTOR hyperactivation. Further exploration is required to shed light on the pathophysiology of TSC and on TSC associated neuropsychiatric disorders offering further potential avenues for therapeutic development.
High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer
Authors: Göbel Andy , Rachner Tilman D. , Hoffmann Oliver , Klotz Daniel Martin , Kasimir-Bauer Sabine , Kimmig Rainer , Hofbauer Lorenz C. , Bittner Ann-Kathrin 
Published: February 2024

Abstract
Background
Leucine-rich α-2 glycoprotein 1 (LRG-1) is a secreted glycoprotein that is mainly produced in the liver. Elevated levels of LRG-1 are found in a multitude of pathological conditions including eye diseases, diabetes, infections, autoimmune diseases, and cancer. In patients with early breast cancer (BC), high intratumoral LRG-1 protein expression levels are associated with reduced survival. In this study, we assessed serum levels of LRG-1 in patients with early BC and investigated its correlation with the presence of disseminated tumor cells (DTCs) in the bone marrow and survival outcomes.

Methods
Serum LRG-1 levels of 509 BC patients were determined using ELISA and DTCs were assessed by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. We stratified LRG-1 levels according to selected clinical parameters. Using the log-rank (Mantel–Cox) test and multivariate Cox regression analysis, Kaplan–Meier survival curves and prognostic relevance were assessed.

Results
Mean serum levels of LRG-1 were 29.70 ± 8.67 µg/ml. Age was positively correlated with LRG-1 expression (r = 0.19; p < 0.0001) and significantly higher LRG-1 levels were found in patients over 60 years compared to younger ones (30.49 ± 8.63 µg/ml vs. 28.85 ± 8.63 µg/ml; p = 0.011) and in postmenopausal patients compared to premenopausal patients (30.15 ± 8.34 µg/ml vs. 26.936.94 µg/ml; p = 0.002). Patients with no DTCs showed significantly elevated LRG-1 levels compared to the DTC-positive group (30.51 ± 8.69 µg/ml vs. 28.51 ± 8.54 µg/ml; p = 0.004). Overall and BC-specific survival was significantly lower in patients with high serum LRG-1 levels (above a cut-off of 33.63 µg/ml) compared to patients with lower LRG-1 levels during a mean follow-up of 8.5 years (24.8% vs. 11.1% BC-specific death; p = 0.0003; odds ratio 2.63, 95%CI: 1.56—4.36). Multivariate analyses revealed that LRG-1 is an independent prognostic marker for BC-specific survival (p = 0.001; hazard ratio 2.61).

Conclusions
This study highlights the potential of LRG-1 as an independent prognostic biomarker in patients with early BC.
Male sexual and reproductive health in multiple sclerosis: a scoping review
Authors: Toljan Karlo , Briggs Farren B. S. 
Published: February 2024

Abstract
Background
Multiple sclerosis (MS) is a chronic neuroinflammatory disease with highest incidence during the period of optimal reproductive health. This scoping review aimed to identify and summarize available data on sexual/reproductive health in males with MS (MwMS).

Methods
This review was based on PRISMA extension for Scoping Review. PubMed database was searched for keyword “multiple sclerosis” alongside keywords “sexual health”, “reproductive health”, “family planning”, “male fertility”, “male infertility”, “sexual dysfunction”, and “erectile dysfunction”, iteratively using the “AND” logical operator. Descriptive analysis was performed on the included articles.

Results
Thirty-four studies were included, and four topics emerged: sexual dysfunction, erectile dysfunction, fertility, and family planning. Sexual dysfunction is common in MwMS (35–72%), yet only a minority of MwMS discuss their sexual health with their treatment teams. Both MS disability and depression were associated with sexual dysfunction in MwMS, with erectile dysfunction and decreased libido as the most prevalent aspects of sexual dysfunction. Positively, phosphodiesterase-5 inhibitors appear effective for treating erectile dysfunction and improving sexual quality of life in MwMS. There may also be a relationship between MS and male infertility, though changes in sexual behavior may underlie this association. Finally, a prominent knowledge gap was observed for disease-modifying therapy use and family planning in MwMS.

Conclusion
Sexual dysfunction is common, impacted by MS severity, and associates with decreased quality of life in MwMS. Communication barriers regarding sexual and reproductive health appear to exist between MwMS and providers, as do literature gaps related to MS therapeutics and sexual/reproductive health.
An automated process for bulk downloading optical coherence tomography scans
Authors: Cnaany Yaacov , Lender Rivkah , Chowers Itay , Tiosano Liran , Shwartz Yahel , Levy Jaime 
Published: February 2024

Abstract
Objective
To develop an automated method for efficiently downloading a large number of optical coherence tomography (OCT) scans obtained using the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) platform.

Methods
The electronic medical records and OCT scans were extracted for all patients with age-related macular degeneration treated at the Hadassah University Hospital Retina Clinic between 2010 and 2021. A macro was created using Visual Basic for Applications (VBA) and Microsoft Excel to automate the export process and anonymize the OCT scans in accordance with hospital policy. OCT scans were extracted as proprietary Heidelberg E2E files.

Results
The VBA macro was used to export a total of 94,789 E2E files from 2807 patient records, with an average processing time of 4.32 min per volume scan (SD: 3.57 min). The entire export process took a total of approximately 202 h to complete over a period of 24 days. In a smaller sample, using the macro to download the scans was significantly faster than manually downloading the scans, averaging 3.88 vs. 11.08 min/file, respectively (t = 8.59, p < 0.001). Finally, we found that exporting the files during both off-clinic and working hours resulted in significantly faster processing times compared to exporting the files solely during working hours (t = 5.77, p < 0.001).

Conclusions
This study demonstrates the feasibility of using VBA and Excel to automate the process for bulk downloading data from a specific medical imaging platform. The specific steps and techniques will likely vary depending on the software used and hospital constraints and should be determined for each application.
Short-term outcomes of treatment switch to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration
Authors: Schneider Miklos , Bjerager Jakob , Hodzic-Hadzibegovic Delila , Klefter Oliver Niels , Subhi Yousif , Hajari Javad 
Published: February 2024

Abstract
Purpose
To report short-term outcomes of treatment switch to faricimab in real-world patients with aflibercept-resistant neovascular age-related macular degeneration (AMD).

Methods
Single-center, retrospective cohort study with chart-review using electronic injection database, electronic medical records, and optical coherence tomography (OCT) data from May to September 2023.

Results
A total of 50 eyes of 46 patients were analyzed. Faricimab treatment led to absence of fluid in 32% of the eyes and a reduction of fluid in 84% of the eyes. There was a statistically significant decrease in central retinal thickness (CRT) and pigment epithelial detachment (PED) height in those that responded to the switch (median difference: − 31 μm, IQR: 55, p < 0.0001 and median difference: − 21 μm, IQR: 36, p < 0.0001, respectively) and a statistically significant increase in CRT (median difference: + 19 μm, IQR: 20, p = 0.0143) and no change in PED height (median difference: + 22 μm, IQR: 64, p = 0.1508) in those that did not.
Best-corrected visual acuity (BCVA) showed marginal decrease with low statistical significance. No ocular or systemic safety events were observed.

Conclusions
Our findings suggest that switching to faricimab is generally safe and effective in patients with neovascular AMD who are otherwise difficult to treat and have residual fluid despite frequent injections with aflibercept. We observed a high rate of morphological response to the treatment switch, improvement of anatomical parameters with about one-third of patients having dry macula following a single injection, and a marginal change in BCVA. Sustainability of these results requires further investigation.

Study registration
ClinicalTrials.gov registration number: NCT06124677. Date of registration: 09/11/2023, retrospectively registered.
Inter-arm bone mass and size asymmetries in children tennis players are maturity status specific: a 9-month study on the effects of training time across pubertal change and somatic growth
Authors: Palaiothodorou Dimitria , Vagenas George 
Published: February 2024

Abstract
Purpose
Bone growth with exercise is best assessed by tennis-induced inter-arm asymmetries. Yet, the effects of training and maturation across puberty were unclear. This study explored arm bone growth across 9 months of training in 46 tennis players 7–14 years (25 boys, 21 girls).

Methods
Bone mineral content (BMC) and bone area (BA) were measured from DXA scans. Pubertal status was assessed by Tanner stage (TS) and somatic growth by maturity offset (MO). Children were grouped as pre- (TS I–I), early (TS I–II), and mid/late pubertal (TS II–III).

Results
Training time (TT) change in the three groups was 160–170, 190–230, and 200–220 h, respectively. Bone asymmetries were large in all groups (d > 0.8, P < 0.001): 5–18 g (9–21%) and 9–17 g (17–23%) in girls and boys, respectively, for BMC, and 5–15 cm2 (6–13%) and 9–15 cm2 (12–15%) in girls and boys (10–13%), respectively, for BA. BMC and BA change asymmetry peaked at pre-puberty in girls (56%, 46%) and at early puberty in boys (57%, 43%). Asymmetry gains varied with baseline asymmetry (41%) and change in TT (38%) and TS (17%) in BMC, and with baseline asymmetry (58%) and change in MO (17%) and TS (12%) in BA.

Conclusion
All bone asymmetries were substantial. Tennis-induced bone gains were higher at pre- to early puberty in girls and at early to mid/late puberty in boys. Training enhanced mostly bone mass and maturity status enhanced mostly bone size; sex was not bone-change modeling impactful. Implications are discussed considering certain limitations.
The test–retest reliability of physiological and perceptual responses during treadmill load carriage
Authors: Vickery-Howe Danielle M. , Dascombe Ben J. , Clarke Anthea C. , Drain Jace R. , Huynh Minh , Middleton Kane J. 
Published: February 2024

AbstractPurposeUnderstanding the test–retest reliability of physiological responses to load carriage influences the interpretation of those results. The aim of this study was to determine the test–retest reliability of physiological measures during loaded treadmill walking at 5.5 km h−1using the MetaMax 3B.MethodsFifteen Australian Army soldiers (9 male, 6 female) repeated two 12-min bouts of treadmill walking at 5.5 km h−1in both a 7.2 kg Control condition (MetaMax 3B, replica rifle) and a 23.2 kg Patrol condition (Control condition plus vest) across three sessions, separated by one week. Expired respiratory gases and heart rate were continuously collected, with the final 3 min of data analysed. Ratings of Perceived Exertion and Omnibus-Resistance Exercise Scale were taken following each trial. Reliability was quantified by coefficient of variation (CV), intra-class correlation coefficients (ICC), smallest worthwhile change (SWC), and standard error of the measurement.ResultsMetabolic and cardiovascular variables were highly reliable (≤ 5% CV; excellent-moderate ICC), while the respiratory variables demonstrated moderate reliability (< 8% CV; good-moderate ICC) across both conditions. Perceptual ratings had poorer reliability during the Control condition (12–45% CV; poor ICC) than the Patrol condition (7–16% CV; good ICC).ConclusionsThe test–retest reliability of metabolic and cardiovascular variables was high and relatively consistent during load carriage. Respiratory responses demonstrated moderate test–retest reliability; however, as the SWC differed with load carriage tasks, such data should be interpreted independently across loads. Perceptual measures demonstrated poor to moderate reliability during load carriage, and it is recommended that they only be employed as secondary measures.Graphical abstract