bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective inhibitors of the TrkC.T1 receptor reduce retinal inflammation and delay neuronal death in a model of retinitis pigmentosa
Authors: Brahimi Fouad , Nassour Hassan , Galan Alba , Guruswamy Revathy , Ortiz Christina , Nejatie Ali , Nedev Hinyu , Trempe Jean-Francois , Saragovi H Uri 
Published: February 2025

Abstract
The heterogeneity of receptor isoforms can cause an apparent paradox where each isoform can promote different or even opposite biological pathways. One example is the neurotrophin receptor TrkC. The trkC mRNA translates a full-length receptor tyrosine kinase (TrkC-FL) whose activation by the growth factor NT3 promotes neuronal survival. In some diseases, the trkC mRNA is spliced to a kinase-truncated isoform (TrkC.T1) whose activation by NT3 up-regulates tumor necrosis factor alpha (TNF-α) causing neurotoxicity. Since TrkC.T1 expression is significantly increased at the onset of neurodegeneration, we hypothesized that in disease TrkC.T1-mediated toxicity prevails over TrkC-FL-mediated survival. To study this, we developed small molecules that selectively antagonize NT3-driven TrkC.T1 neurotoxicity without compromising TrkC-FL survival. In a genetic mouse model of retinitis pigmentosa, therapeutic administration of TrkC.T1 antagonists prevents elevation of TNF-α and reduces photoreceptor neuronal death. This work demonstrates the importance of accounting for functional and structural heterogeneity in receptor–ligand interactions, illustrates chemical biology strategies to develop isoform-selective agents, validates TrkC.T1 as a druggable target, and expands the therapeutic concept of reducing neurotoxicity as a strategy to achieve neuroprotection.
Global consistency of urban scaling evidenced by remote sensing
Authors: Xu Zhibang , Xu Gang , Lan Ting , Li Xi , Chen Zuoqi , Cui Hao , Zhou Zhengzi , Wang Haowei , Jiao Limin , Small Christopher 
Published: February 2025

Abstract
The urban scaling theory (UST) strives for a universal taxonomy that depicts relationships among urban indicators (e.g. energy consumption, economic output) with city size. However, the lack of international agreement on city definitions and statistics complicates cross-country comparisons of urban scaling performance. Remote sensing provides a uniform standard for measuring cities around the world. To scrutinize the consistency of UST, we quantified changes in remotely sensed urban built-up areas (UBA) and nighttime lights (NTL) distributions from 11,581 cities in 61 countries spanning 2000–2020, representing urban physical elements and socioeconomic activities, respectively. We find that UBA is well described by UST in all analyzed countries, while NTL aligns with 98% of them. UST quantified by remote sensing shows greater robustness than country-dependent aggregate statistics. We also observed disparities of scaling exponents (β) among countries, with UBA all being sublinear (β &lt; 1), and NTL ranging from 0.46 to 1.22 with a median of 0.94. Both UST and rank-size distributions of urban area and population show stronger scaling relationships for countries with larger networks of built environments, (Brazil, China, Germany, Japan, Russia, United States) suggesting that both size and evolution of urban systems impact the underlying scaling processes. Comparison of scaling properties of remotely sensed UBA and NTL captures complementary physical characteristics of built environments while minimizing the Modifiable Area Unit Problem introduced using spatially aggregated metrics within administrative units. Our findings highlight the consistency of urban growth patterns while confirming the systematic socioeconomic disparities among urban systems of varying size and growth trajectory.
Feeding of a high protein, low carbohydrate diet leads to greater postprandial energy expenditure and fasted n6: n3 fatty acid ratio in lean, adult dogs compared to a moderate protein, moderate carbohydrate diet
Authors: Banton Sydney , Pezzali Júlia G , Richards Taylor , Hillyer Lyn M , Ma David W L , Pisco Jesús M , Templeman James R , Shoveller Anna K 
Published: February 2025

Abstract
High protein, low carbohydrate (HPLC) diets are often sought out by dog owners. They are reported to have beneficial effects on energy expenditure (EE), fat oxidation, and may alter the serum fatty acid profile. However, there is little to no data to support the feeding of HPLC diets to healthy adult dogs. Thus, the objective of the present study was to interrogate the health claims related to the feeding of HPLC diets to healthy adult dogs using a commercially available HPLC diet (48% of metabolizable energy (ME) from protein, 10% of ME from nitrogen-free extract; NFE), a moderate protein, moderate carbohydrate (MPMC) diet (28% of ME from protein, 39% of ME from NFE) formulated with the same ingredients as HPLC, and a commercially available, MPMC, high fiber, ‘metabolic’ (MET) diet (30% of ME from protein, 37% of ME from NFE) as a commercial control. Diets were fed to 9 healthy, large breed dogs for 42 days in a Latin square design. Fasted blood samples were collected on days -2 (baseline), 12, 26 and 40, and indirect calorimetry was performed on 8 dogs on days 20 and 39 to measure respiratory quotient (RQ) and EE. Statistics were performed in SAS Studio (version 9.4). Dogs fed HPLC had a lower RQ at fasted (0.76), 0-4 hrs (0.78) and 5-10 hrs (0.83) post-meal compared to dogs fed MET (0.80, 0.83, 0.90) and MPMC (0.80, 0.84, 0.91; P&lt;0.05). All dogs had a similar EE at fasted but dogs fed HPLC had a greater postprandial EE at 0-4 hrs (5.36 kcal/kg0.75) and 5-10 hrs (5.46 kcal/kg0.75) compared to dogs fed MPMC (4.79 and 4.84 kcal/kg0.75; P&lt;0.05). Dogs fed MET (4.98, 4.96 kcal/kg0.75) were similar to both (P&gt;0.05). Alpha-linolenic acid (ALA; 18:3n3), docosapentaenoic acid (DPA; 22:5n3) and total n3 were all greater in dogs fed MET at each week (P&lt;0.05). In contrast, total n6: n3 and arachidonic acid (ARA; 20:4n6): eicosapentaenoic acid (EPA; 20:5n3) were both greater (P&lt;0.05) in dogs fed HPLC and MPMC compared to dogs fed MET at each week. This study represents the first to assess EE and serum fatty acids in adult large breed dogs consuming a HPLC diet for 6 weeks. Consuming a HPLC diet led to potential beneficial effects of increased EE and fat oxidation after a meal, which has the potential to be useful in managing obesity, a common health concern in dogs.
Genomic surveillance and evolution of Getah virus
Authors: Shen Jiaqi , Liu Shaogui , Liu Shiqiang , Shen Shiyi , Lei Mingkai , Xu Qian , Li Wentao , He Qigai , Xu Xiaojuan , Cai Xuwang 
Published: February 2025

Abstract
Getah virus (GETV), a member of the Alphaviruses, has spread widely and is expanding its host range worldwide, posing a serious threat to public health safety and the farming industry. However, genetic monitoring of GETV is inadequate, and its evolution and transmission remain unclear. This study employed reverse transcription-polymerase chain reaction to screen pig tissue samples for the presence of GETV. Subsequent steps included DNA sequencing, phylogenetic analysis, and selection pressure assessments to elucidate the evolutionary history and transmission patterns of the virus. A total of 1382 samples were examined, with a positivity rate of 4.12% (95% confidence interval: 3.07%–5.17%) from 2022 to 2023. Subsequently, seven GETV strains were isolated and identified. A phylogenetic tree was constructed, which showed that all seven strains belonged to Group III. Phylodynamic analysis revealed that GETV evolved rapidly. Additionally, eight amino acid sites within the GETV E2 protein were identified as being under positive selection. These data provide insight into the epidemiology and evolution of GETV.
Evidence-based treatment approaches for adolescent electronic cigarette use
Authors: Solano Laura 
Published: February 2025

ABSTRACT
Electronic cigarettes (e-cigarettes) are the most commonly used tobacco product by adolescents. This article describes the harmful effects of e-cigarette use in adolescents and how to evaluate for severity of nicotine dependence. It also provides an overview of treatment approaches, including behavioral interventions, contingency interventions, pharmacologic options, school-based programs, combination and emerging approaches, and transcranial magnetic stimulation.
General Anesthesia Combined with Quadratus Lumborum Block Reduces Emergence Delirium in Children after Laparoscopic Surgery
Authors: Xie Haihang , Wei Wei , Xu Yingyi , Zhang Na , Li Bilian , Fan Yanting , Huang Fa , Gao Yu , Ma Daqing , Tan Yonghong , Zhao Tianyun 
Published: February 2025

Background:
Emergency delirium (ED) is a common and serious postoperative complication especially after pediatric surgery. Quadratus lumborum block (QLB) are critical components of the multimodal, opioid-sparing analgesia regimens, which provide effective analgesia, reduce opioid consumption, and attenuate surgical stress response. Therefore, this trial was designed to validate the hypothesis that the adjunctive use of QLB reduces the incidence of ED after laparoscopic surgery in children.

Methods:
Children aged 1-6 years who underwent laparoscopic surgery under general anesthesia were randomly divided into general anesthesia combined with QLB group (Group G+Q) or general anesthesia group (Group G). The primary outcome was the incidence of ED in postanesthesia care unit (PACU), the incidence of delirium 24 hrs postoperatively, extubation time, length of stay in PACU, opioid consumption and pain score were recorded.

Results:
From July 2020 to October 2022, 292 children were randomized and 287 completed the study. The incidence of delirium in Group G+Q were significantly lower than that in Group G in PACU (16.1% vs 47.9%, P<0.001) and 24 hrs postoperatively (3.4% vs 11.1%; P<0.05). The time of extubation time (21.2±11.4 min vs 18.2±11.8 min; P<0.05) and PACU stay in Group G were significantly longer than Group G+Q (57.2±20.3 min vs 48.9±20.4 min, P<0.01) compared with Group G.

Discussion:
General anesthesia combined with QLB can significantly reduce the incidence of ED, shorten the extubation time and PACU residence time, and improve the quality of resuscitation.
Audit on physicians’ adherence with the WHO analgesic ladder to treat postoperative pain
Authors: Asrat Banchayehu Enawgaw , Temesgen Mamaru Mollalign , Tawuye Hailu Yimer , Gebremedhn Endale Gebreegziabher 
Published: February 2025

Background:
Poorly controlled postoperative pain has many adverse effects on the patients. Pain management can be improved using the World Health Organization (WHO) analgesic ladder. However, the adherence of physicians with the WHO analgesic ladder remains unexplored in our hospital.

Objective:
To assess physicians’ adherence with WHO analgesic ladder to treat postoperative pain.

Methods:
Hospital-based cross-sectional clinical audit was conducted. Data were collected using checklist and interview. The SPSS version 25 was used for analysis and descriptive statistics used.

Results:
A total of 120 patients were included in this audit. A total of 18 (15%), 51 (42.5%), and 51 (42.5%) patients experienced mild, moderate, and severe pain, respectively. However, pain assessment was done for 3 (2.5%) of the patients. Only 33 (27.5%) of the patients with postoperative pain were treated according to the WHO analgesic ladder. Patients with mild 6 (5%) and moderate pain 63 (52.5%) were treated in accordance with the WHO analgesic ladder. About 45 (37.5%) of patients did not receive analgesia despite they experienced mild to severe pain. None of the patients with severe pain received strong opioids. Similarly, 56 (46.6%) and 21 (17.5%) of patients who experienced moderate and severe postoperative pain did not receive analgesia, respectively.

Conclusion and recommendation:
The practice of postoperative pain management is very poor in our hospital. Compared to the WHO pain management ladder, the physicians did not follow the postoperative pain management recommendation. It is recommended that training about postoperative pain assessment and management (including WHO analgesic ladder) should be provided for physicians.
Changes in Seasonal Patterns for Common Pediatric Respiratory Viruses During the COVID Pandemic
Authors: Lozy Tara , Perotte Rimma , Eigen Austin , Eigen Karen , Kourgialis Ashley , Scheinert Timothy , Nemetski Sondra Maureen 
Published: February 2025

Objectives:
Observed alterations in seasonal patterns of common pediatric respiratory viruses during and immediately after the COVID-19 pandemic had far-reaching implications for the care of ill children. Here, we quantify the effects of the pandemic and related nonpharmaceutical interventions on the prevalence and seasonality of common pediatric respiratory illnesses.

Methods:
We performed a retrospective chart review within a large health network to identify incidence rates of common respiratory viruses and compared them to historical trends. Time series analyses using seasonal autoregressive integrated moving average models were utilized to identify seasonal patterns for the different virus types and quantify deviations from expected incidence rates.

Results:
Overall, we noted a steep decline in non-COVID viral infection rates at the onset of the COVID pandemic in March 2020, largely coincident with the institution of mask mandates and lockdown measures. This trend continued until the Spring of 2021, at which time non-COVID infections resurged to rates higher than pre-COVID levels. In addition, the historically observed seasonality of these viruses was significantly disrupted by the pandemic. In particular, the historical peaks for influenza A and human metapneumovirus shifted from February and March, respectively, to bimodal peaks in December 2021 and May 2022; respiratory syncytial virus demonstrated an unprecedented Spring/Summer season in 2021; parainfluenza type 1 was unusually active in 2022, an even-numbered year; and influenza B virtually disappeared during and immediately after the pandemic.

Conclusions:
Our observations add to the growing body of literature supporting the hypothesis that human interactions are one of the key drivers of pediatric respiratory viral seasonality in addition to climate. Understanding the effect of human interactions on disease spread is crucial for the development of effective mitigation measures for future pandemics while avoiding dangerous spikes of other illnesses once those interventions are lifted.
Narrative review of the efficacy and safety of the high-concentration (179mg) capsaicin patch in peripheral neuropathic pain with recommendations for clinical practice and future research
Authors: Freynhagen Rainer , Baron Ralf , Huygen Frank , Perrot Serge 
Published: February 2025

Abstract
High-concentration capsaicin patch (HC capsaicin patch) is a locally acting treatment option for adults with peripheral neuropathic pain (pNeP) of various etiologies. Numerous clinical trials, post hoc analyses, and meta-analyses have investigated the efficacy and tolerability of the HC capsaicin patch. Despite this extensive body of research, a comprehensive narrative review covering publications on different pNeP conditions is lacking. This narrative review aims to fill the gap by analyzing 52 studies, including randomized controlled trials and real-world evidence. The results show that the HC capsaicin patch consistently provides pain relief and improves quality of life for several pNeP conditions, with increasing benefits seen with repeated treatments. It was found to be superior to placebo and comparable to standard care, regardless of the origin of the pain. Early initiation of therapy appears to improve efficacy, although patients with more prolonged pain also benefit. While the exact mechanisms of action are still unclear, there is evidence to suggest a potential benefit from nerve regeneration in some conditions. However, limited information exists regarding the alteration of treatment intervals and the variation in the size of the painful area upon re-treatment. The review also identifies variability in response rates for different types of pNeP and a lack of reliable predictors of treatment success, indicating a need for further research. In conclusion, the HC capsaicin patch is effective and well tolerated across a range of pNeP conditions, with increasing efficacy upon retreatment. It is a valuable treatment option, although more research is needed to refine its clinical use and explore its full therapeutic potential.
Ultrasound-guided rhomboid intercostal block combined with subserratus plane block vs pectoral nerve block type-2 in analgesia for breast-conserving surgery (randomized, controlled study)
Authors: Soliman Ahmed Mohamed , Kamel Mahmoud A. , khalil Asmaa Elsayed , Kotb Tamer Ahmed , Abed Sayed Mahmoud , Abdelmoneim Noha Mohamed 
Published: February 2025

Abstract

Introduction:
The most frequent malignancy in women is the breast cancer, the rhomboid intercostal and subserratus plane (RISS) block is a novel regional approach.

Objectives:
This study evaluated the analgesic efficacy of the RISS block compared to type 2 Pectoral Nerve (PECS II) block in breast cancer patients following breast-conserving surgery (BCS).

Methods:
This randomized controlled trial comprised 69 women with breast cancer scheduled for unilateral BCS under general anesthesia, randomly allocated into 3 equal groups. The RISS group had unilateral RISS block using 20 mL of 0.25% bupivacaine between rhomboid major and intercostal muscles and an equal volume between external intercostal and serratus anterior muscles. The PECs Group received a PECS II block using 20 mL of 0.25% bupivacaine between pectoralis major and minor muscles and 10 mL between pectoralis major and serratus muscles. The control group did not get any blocks. The primary outcome was total postoperative morphine consumption within 24 hours. The secondary outcomes were pain score, first request for rescue analgesia, intraoperative fentanyl consumption, and hemodynamics.

Results:
Requesting rescue morphine analgesia was significantly less frequent in the RISS and PECs groups compared to controls (5, 1, and 23 patients, respectively, P < 0.001). Similar findings were found in the need for extra intraoperative fentanyl (P < 0.001). Pain scores in the RISS and PECs groups were significantly lower than the control group, while RISS and PECs groups had comparable scores throughout the postoperative period. All hemodynamic readings were within the clinically acceptable ranges.

Conclusion:
In patients undergoing BCS, RISS and PECs II block are comparable, safe, and effective regional analgesic alternatives.
Diastolic Perfusion Pressure Predicts Response to Inotropes/Vasopressors and Benefit from Mechanical Circulatory Support in Cardiogenic Shock?
Authors: Lim Hoong Sern , Vondrakova Dagmar , Belohlavek Jan , Rokyta Richard , Ostadal Petr 
Published: February 2025

AbstractBackgroundHemodynamic response to escalation of vasoactive drugs has not been well-characterized in patients with cardiogenic shock CS. We tested the hypothesis that lower diastolic perfusion pressure (DPP=diastolic blood pressure-right atrial pressure) was associated with more limited hemodynamic response to up-titration of vasoactive drugs and with possible benefit from early mechanical circulatory support (MCS) in patients with CS.MethodsThis study consisted of two parts. (i) We evaluated the relationship between baseline DPP and changes in cardiac power output index (CPOI) in response to increase in vasoactive drugs in a cohort of patients with CS (n=93). (ii) We compared all-cause mortality based on baseline DPP in a post hoc analysis of the ECMO CS trial. CPOI responders were defined as post-escalation CPOI≥0.28 W/m2.ResultsVasoactive inotrope score escalated from 11.2±3.9 to 24.5±4.7. Escalation of vasoactive drugs was associated with increases in CPOI to 0.23±0.06 W/m2(all p<0.001).Post-escalation CPOI was directly related to baseline cardiac index and DPP. Baseline DPP discriminated CPO responders from non-responders with optimal cutoff of 37mmHg. Patients with baseline DPP≥37mmHg had greater CPOI increase and lactate clearance. In the ECMO-CS trial, patients with DPP˂37mmHg had lower mortality (HR 0.37, 95% CI 0.14-0.97, P=0.044) with immediate VA ECMO compared to early conservative management, but no significant difference in the subgroup with DPP≥37mmHg.ConclusionLower DPP was associated with more limited hemodynamic response to escalation of vasoactive drugs and potentially greater benefit from early VA-ECMO in CS.
Targeting non-canonical NF-κB signalling in CYLD cutaneous syndrome by selective inhibition of IκB kinase alpha
Authors: Hodgson Kirsty , Inns Joseph , Reynolds Gary , Stephenson Emily , Paul Andrew , Sinclair Naomi , Berretta Giacomo , Lawson Christopher , Frey Andrew Michael , Ivanova Iglika , Adam Eva , Lord Christopher J. , Cockell Simon , Coxhead Jonathan , Nagy Nikoletta , Adams David , Szell Marta , Trost Matthias , Haniffa Muzlifah , Mackay Simon P. , Perkins Neil , Rajan Neil 
Published: February 2025

AbstractCYLD cutaneous syndrome (CCS) skin tumors develop from puberty onwards, can number in the hundreds and progressively grow over time. CCS patients lack medical therapies and require repeated surgery to control tumor burden.CYLDloss of heterozygosity (LOH) drives tumor growth, and CCS tumors have previously been shown to demonstrate increased canonical NF-κB and Wnt signalling. Here, we demonstrate evidence of non-canonical NF-κB signalling in CCS tumor keratinocytes, with increased p100 to p52 processing and RelB protein expression compared to normal skin. Utilizing complementary transcriptomics and proteomics on patient derived CCS tumor cell fractions, we identify IκB kinase alpha (IKKα) as a candidate target in the non-canonical NF-κB signalling pathway. A novel, highly selective, IKKα inhibitor (SU1644) used in patient derived CCS tumor spheroid cultures demonstrated that IKKα inhibition reduced tumor spheroid viability. These data provide the pre-clinical rationale for the assessment of topical IKKα inhibitors as a novel preventative treatment for CCS.TeaserTopical IKKα inhibition emerges as a potential therapy for CYLD cutaneous syndrome by targeting non-canonical NF-κB signallingGraphical abstract