bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling citicoline's mechanisms and clinical relevance in the treatment of neuroinflammatory disorders
Authors: Cavalu Simona , Saber Sameh , Ramadan Asmaa , Elmorsy Elsayed A. , Hamad Rabab S. , Abdel‐Reheim Mustafa Ahmed , Youssef Mahmoud E. 
Published: September 2024

AbstractCiticoline, a compound produced naturally in small amounts in the human body, assumes a pivotal role in phosphatidylcholine synthesis, a dynamic constituent of membranes of neurons. Across diverse models of brain injury and neurodegeneration, citicoline has demonstrated its potential through neuroprotective and anti‐inflammatory effects. This review aims to elucidate citicoline's anti‐inflammatory mechanism and its clinical implications in conditions such as ischemic stroke, head trauma, glaucoma, and age‐associated memory impairment. Citicoline's anti‐inflammatory prowess is rooted in its ability to stabilize cellular membranes, thereby curbing the excessive release of glutamate—a pro‐inflammatory neurotransmitter. Moreover, it actively diminishes free radicals and inflammatory cytokines productions, which could otherwise harm neurons and incite neuroinflammation. It also exhibits the potential to modulate microglia activity, the brain's resident immune cells, and hinder the activation of NF‐κB, a transcription factor governing inflammatory genes. Clinical trials have subjected citicoline to rigorous scrutiny in patients grappling with acute ischemic stroke, head trauma, glaucoma, and age‐related memory impairment. While findings from these trials are mixed, numerous studies suggest that citicoline could confer improvements in neurological function, disability reduction, expedited recovery, and cognitive decline prevention within these cohorts. Additionally, citicoline boasts a favorable safety profile and high tolerability. In summary, citicoline stands as a promising agent, wielding both neuroprotective and anti‐inflammatory potential across a spectrum of neurological conditions. However, further research is imperative to delineate the optimal dosage, treatment duration, and underlying mechanisms. Moreover, identifying specific patient subgroups most likely to reap the benefits of citicoline as a new therapy remains a critical avenue for exploration.
Preconditioning with β‐hydroxybutyrate attenuates lung ischemia–reperfusion injury by suppressing alveolar macrophage pyroptosis through the SIRT1‐FOXO3 signaling pathway
Authors: Lu Fan , Wang Rurong , Cheng Yan , Li XueHan 
Published: September 2024

AbstractThe complex pathogenesis of lung ischemia–reperfusion injury (LIRI) was examined in a murine model, focusing on the role of pyroptosis and its exacerbation of lung injury. We specifically examined the levels and cellular localization of pyroptosis within the lung, which revealed alveolar macrophages as the primary site. The inhibition of pyroptosis by VX‐765 reduced the severity of lung injury, underscoring its significant role in LIRI. Furthermore, the therapeutic potential of β‐hydroxybutyrate (β‐OHB) in ameliorating LIRI was examined. Modulation of β‐OHB levels was evaluated by ketone ester supplementation and 3‐hydroxybutyrate dehydrogenase 1 (BDH‐1) gene knockout, along with the manipulation of the SIRT1‐FOXO3 signaling pathway using EX‐527 and pCMV‐SIRT1 plasmid transfection. This revealed that β‐OHB exerts lung‐protective and anti‐pyroptotic effects, which were mediated through the upregulation of SIRT1 and the enhancement of FOXO3 deacetylation, leading to decreased pyroptosis markers and lung injury. In addition, β‐OHB treatment of MH‐S cells in vitro showed a concentration‐dependent improvement in pyroptosis, linking its therapeutic benefits to specific cell mechanisms. Overall, this study highlights the significance of alveolar macrophage pyroptosis in the exacerbation of LIRI and indicates the potential of β‐OHB in mitigating injury by modulating the SIRT1‐FOXO3 signaling pathway.
Expert Panel Consensus on the Effectiveness and Implementation of Models to Support Posthospitalization Care Transitions for People With Substance Use Disorders
Authors: Incze Michael A. , Huebler Sophia , Szczotka Kathryn , Grant Sean , Kertesz Stefan G. , Gordon Adam J. 
Published: September 2024

Objectives
Hospitals are increasingly offering treatment for substance use disorders (SUDs) during medical admissions. However, there is a lack of consensus on the best approach to facilitating a successful transition to long-term medical and SUD care after hospitalization. We aimed to establish a hierarchy of existing SUD care transition models in 2 categories—effectiveness and implementation—using an expert consensus approach.

Methods
We conducted a modified online Delphi study that convened 25 interdisciplinary clinicians with experience facilitating posthospitalization care transitions for patients with SUD. Panelists rated 10 prespecified posthospitalization care transition models according to 6 criteria concerning each model’s anticipated effectiveness (eg, linkage to care, treatment retention) and implementation (eg, feasibility, acceptability). Ratings were made on a 9-point bidirectional scale. Group consensus was determined using the interpercentile range adjusted for symmetry.

Results
After 3 rounds of the Delphi process (96% retention across all 3 rounds), consensus was reached on all 60 rating criteria. Interdisciplinary addiction consult teams (ACTs) and in-reach from partnering outpatient clinics were rated highest for effectiveness. Interdisciplinary ACTs and bridge clinics were rated highest for implementation. Screening, brief intervention, and referral to treatment; protocol implementation; and postdischarge outreach received the lowest ratings overall. Feasibility of implementation was perceived as the largest challenge for all highly rated models.

Conclusions
An expert consensus approach including diverse clinician stakeholders found that interdisciplinary ACT, in-reach from partnering outpatient clinics, and bridge clinics had the greatest potential to enhance posthospitalization care transitions for patients with SUD when considering both perceived effectiveness and implementation.
Improving Estimates of the Prevalence of Opioid Use Disorder in the United States: Revising Keyes et al
Authors: Lim Tse Yang , Keyes Katherine M. , Caulkins Jonathan P. , Stringfellow Erin J. , Cerdá Magdalena , Jalali Mohammad S. 
Published: September 2024

Objectives
The United States faces an ongoing drug overdose crisis, but accurate information on the prevalence of opioid use disorder (OUD) remains limited. A recent analysis by Keyes et al used a multiplier approach with drug poisoning mortality data to estimate OUD prevalence. Although insightful, this approach made stringent and partly inconsistent assumptions in interpreting mortality data, particularly synthetic opioid (SO)–involved and non–opioid-involved mortality. We revise that approach and resulting estimates to resolve inconsistencies and examine several alternative assumptions.

Methods
We examine 4 adjustments to Keyes and colleagues’ estimation approach: (A) revising how the equations account for SO effects on mortality, (B) incorporating fentanyl prevalence data to inform estimates of SO lethality, (C) using opioid-involved drug poisoning data to estimate a plausible range for OUD prevalence, and (D) adjusting mortality data to account for underreporting of opioid involvement.

Results
Revising the estimation equation and SO lethality effect (adj. A and B) while using Keyes and colleagues’ original assumption that people with OUD account for all fatal drug poisonings yields slightly higher estimates, with OUD population reaching 9.3 million in 2016 before declining to 7.6 million by 2019. Using only opioid-involved drug poisoning data (adj. C and D) provides a lower range, peaking at 6.4 million in 2014–2015 and declining to 3.8 million in 2019.

Conclusions
The revised estimation equation presented is feasible and addresses limitations of the earlier method and hence should be used in future estimations. Alternative assumptions around drug poisoning data can also provide a plausible range of estimates for OUD population.
A Pharmacologic Evaluation of Buprenorphine in Pregnancy and the Postpartum Period
Authors: Caritis Steve N. , Venkataramanan Raman 
Published: September 2024

BackgroundThe dosing regimen in the package insert for sublingual buprenorphine is similar for pregnant and nonpregnant people despite the physiologic changes seen during pregnancy.AimsTo compare plasma buprenorphine pharmacokinetics during and after pregnancy and relate buprenorphine concentration to the pharmacodynamic endpoints of pupil diameter, Clinical Opioid Withdrawal Scale (COWS), and craving scores.Study DesignProspective cohort of 22 pregnant people undergoing 33 pharmacologic studies (6–8 hours each) during pregnancy or postpartum. Participants were on a stable daily dose of 2–8 mg sublingual buprenorphine every 6 or 8 hours. The dosing frequency was selected by the participant. On study day, baseline measurements of plasma buprenorphine, pupil diameter, COWS, and craving scores were obtained, then the usual morning dose was taken, and measurements were repeated several times over 1 dosing interval.FindingsThe dose-normalized area under the plasma buprenorphine concentration time curve was significantly (P= 0.036) lower during pregnancy (155 ± 52 ng × min/mL) than postpartum (218 ± 113 ng × min/mL). Buprenorphine trough concentrations were similar at the start (1.1 ± 0.7 ng/mL) and end of a dosing cycle (1.2 ± 0.8 ng/mL) regardless of dosing frequency. Pupillary diameter, COWS, and craving scores returned to baseline as buprenorphine concentrations approached ~1 ng/mL.ConclusionsPregnant people require a higher dose of buprenorphine to achieve concentrations comparable to nonpregnant people. There is a temporal relationship between the plasma buprenorphine concentration and the pharmacodynamic markers of pupillary diameter, COWS, and craving scores. An average plasma concentration of ~1 ng/mL was associated with the lowest level of COWS and craving scores.
Taking the Extra Listening Mile: Processing Spoken Semantic Context Is More Effortful for Older Than Young Adults
Authors: Harel-Arbeli Tami , Shaposhnik Hagit , Palgi Yuval , Ben-David Boaz M. 
Published: September 2024

Objectives:
Older adults use semantic context to generate predictions in speech processing, compensating for aging-related sensory and cognitive changes. This study aimed to gauge aging-related changes in effort exertion related to context use.

Design:
The study revisited data from Harel-Arbeli et al. (2023) that used a “visual-world” eye-tracking paradigm. Data on efficiency of context use (response latency and the probability to gaze at the target before hearing it) and effort exertion (pupil dilation) were extracted from a subset of 14 young adults (21 to 27 years old) and 13 older adults (65 to 79 years old).

Results:
Both age groups showed a similar pattern of context benefits for response latency and target word predictions, however only the older adults group showed overall increased pupil dilation when listening to context sentences.

Conclusions:
Older adults’ efficient use of spoken semantic context appears to come at a cost of increased effort exertion.
Comparing postoperative pain relief: ketorolac and Nasocalcin spray versus lidocaine and Nasocalcin spray in abdominal surgery patients
Authors: Saadat Fakhr Masoud , Qasemi Mahdiya , Rezvanfar Kiana , Hosseini Reza Shah , Amini Zahra , Amiri Koosha , Zhaleh Mahan , Tarkashvand Taraneh , Narimani Zamanabadi Mahnaz 
Published: September 2024

Objectives:
Postoperative pain management is critical for patient recovery after abdominal surgery. This study compared intravenous lidocaine and ketorolac for reducing postoperative pain and opioid use, along with Nasocalcin nasal spray.

Methods:
In this randomized controlled trial, 58 abdominal surgery patients were allocated to receive either intravenous lidocaine plus Nasocalcin spray (n=29) or intravenous ketorolac plus Nasocalcin spray (n=29) before surgery. Pain intensity (visual analog scale) and postoperative opioid consumption were assessed at 1, 6, 12, and 24 h after surgery.

Results:
Patients receiving ketorolac plus Nasocalcin spray reported significantly lower pain scores at all time points compared to lidocaine plus Nasocalcin (P<0.001). Average 24-h pain scores were 4.5 with ketorolac versus 5.1 with lidocaine. Mean opioid consumption was also lower in the ketorolac group (31.9 mg) versus the lidocaine group (43.9 mg, P<0.001).

Conclusion:
Preoperative ketorolac plus Nasocalcin nasal spray resulted in superior pain relief and less opioid use compared to lidocaine plus Nasocalcin after abdominal surgery. Ketorolac may be a more effective analgesic option, while Nasocalcin spray is a safe adjunct. These findings can inform clinical practice for optimizing postoperative analgesia.
A case of postpartum dermatomyositis with onset at three months: expanding the clinical spectrum
Authors: Shah Sandesh , Shrestha Garima , Raut Ujwal , Vaidya Monasha , Thapaliya Ritesh , Maharjan Radhika 
Published: September 2024

Introduction and importance:
Dermatomyositis (DM) is an autoimmune disorder affecting all age groups, with a higher prevalence in women. Diagnosis typically occurs around age 40. Manifestation can be acute or chronic. Diagnosis relies on clinical, laboratory, electromyography, and histopathological tests. Limited information exists regarding DM’s occurrence during pregnancy and its connection to pregnancy.

Case presentation:
A 31-year-old, 3-month postpartum female presented with features of proximal muscle weakness and generalized erythematous itchy rash. The weakness was associated with muscle tenderness. Laboratory evaluation and skin biopsy revealed features consistent with dermatomyositis. Pulmonary pathology and occult tumors were investigated. Symptoms gradually improved on steroids and azathioprine.

Clinical discussion:
The relationship between dermatomyositis and pregnancy remains poorly understood, with only a few documented cases highlighting the impact of pregnancy on the development and progression of the disease. From the available literature, it is evident that postpartum dermatomyositis is uncommon yet significant, necessitating careful attention during pregnancy to enhance outcomes for both the mother and the unborn child.

Conclusion:
Our experience highlights a rare case of postpartum dermatomyositis, with symptoms emerging 3 months after childbirth, differing from documented cases. More research is needed to understand pregnancy’s role in dermatomyositis development and improve treatment for pregnant women with autoimmune skin diseases.
Outcome of Minimally Invasive and Open Pancreatoduodenectomy in Patients with Intestinal- and Pancreatobiliary Subtype Ampullary Cancer
Authors: Uijterwijk Bas A. , Moekotte Alma , Boggi Ugo , Mazzola Michele , Koerkamp Bas Groot , Valle Raffaele Dalla , Mazzotta Alessandro , Luyer Misha , Kazemier Geert , Ielpo Benedetto , Suarez Muñoz Miguel Angel , Bolm Louisa , Björnsson Bergthor , Pessaux Patrick , Kleeff Jorg , Fusai Giuseppe Kito , Sparrelid Ernesto , Zerbi Alessandro , Lemmers Daniël H. , Alseidi Adnan , Vladimirov Miljana , Roberts Keith J. , Salvia Roberto , Soonawalla Zahir , Korkolis Dimitris , Serradilla-Martín Mario , Mavroeidis Vasileios K. , Bouwense Stefan A.W. , Besselink Marc G. , Abu Hilal Mohammed ,   for the International Study Group on non-pancreatic periampullary Cancer (ISGACA)
Published: September 2024

Objective:
To compare minimally invasive and open pancreatoduodenectomy in different subtypes of ampullary adenocarcinoma.

Summary Background Data:
Ampullary adenocarcinoma (AAC) is widely seen as the best indication for minimally invasive pancreatoduodenectomy (MIPD) due to the lack of vascular involvement and dilated bile and pancreatic duct. However, it is unknown whether outcomes of MIPD for AAC differ between the pancreatobiliary (AAC-PB) and intestinal (AAC-IT) subtypes as large studies are lacking.

Methods:
This is an international cohort study, encompassing 27 centers from 12 countries. Outcome of MIPD and open pancreatoduodenectomy (OPD) were compared in patients with AAC-IT and AAC-PB. Primary end points were R1 rate, lymph node yield, and 5-year overall survival (5yOS).

Results:
Overall, 1187 patients after MIPD for AAC were included, of whom 572 with AAC-IT (62 MIPD, 510 OPD) and 615 with AAC-PB (41 MIPD and 574 OPD). The rate of R1 resection was not significantly different between MIPD and OPD for both AAC-IT (3.4% vs 6.9%, P=0,425) and AAC-PB (9.8% vs 14.9%, P=0,625). AAC-IT, more lymph nodes were resected with MIPD group (19 vs 16, P=0.007), compared to OPD. The 5y-OS did not differ after MIPD and OPD for both AAC-IT (56.8% vs 59.5%, P=0.827 and AAC-PB (52.5% vs 44.4%, P=0.357). The rates of surgical complication between MIPD and OPD did not differ between AmpIT and AmpPB.

Discussion:
This international multicenter study found no differences in outcomes between MIPD and OPD for AAC-IT and AAC-PB. MIPD and OPD demonstrated comparable outcomes in oncological resection, survival and surgical outcomes for both subtypes of AAC.
Riverine Invertebrates Exhibit Spatial Asymmetry in Temporal Ecological Processes Across Landscapes
Authors: Lin Xiaowei , Wan Jialu , Luo Qingyi , Cai Qinghua , Chiu Ming-Chih , Resh Vincent H. 
Published: September 2024

AbstractThe environment and its variability exhibit spatial heterogeneity in influencing ecological processes and community dynamics across landscapes. However, the mechanisms remain unexplored.This study investigates relative significance of temporal ecological processes that shape invertebrate community dynamics across 15 rivers in the European Iberian Peninsula over 21 years.Spatial asymmetry in community dynamics was driven by a combination of temporal deterministic and stochastic processes (i.e., environmental filtering and temporal distance within the same locations, respectively).It is noteworthy that the relative importance of deterministic versus stochastic processes diminishes with increasing elevation.The analysis of community dynamics in diverse landscapes offers a foundation for anticipating and mitigating the consequences of prospective environmental transformation on biodiversity, thereby directing efficacious conservation strategies.
Use of equine H3N8 hemagglutinin as a broadly protective influenza vaccine immunogen
Authors: Verhoeven David , Sponseller Brett A. , Crowe James E. , Bangaru Sandhya , Webby Richard J. , Lee Brian 
Published: September 2024

AbstractAn efficacious universal influenza vaccine remains a long-sought goal for human health as current vaccines suffer from shortfalls such as mid to low efficacy and the need for yearly revisions in strains use to account for viral drift/shift. Horses undergo bi-annual vaccines for H3N8 equine influenza virus, and surveillance of sera from vaccinees demonstrated very broad reactivity and neutralization to many human seasonal influenza strains. Subsequently, vaccination of mice using the equine H3N8 Kentucky/1/91 strain of equine H3N8 vaccine induced similar broadly reactive and neutralizing serum antibodies to human seasonal strains and to high pathogenicity avian influenza strains. Challenge of mice vaccinated with equine H3N8 or recombinant hemagglutinin (HA) based on the same strain protected vaccinees from high-dose lethal virus challenges. Protection was associated with the presence of neutralizing antibodies to the HA head, esterase, and stem regions that was similar to that of antibodies generated in horses after vaccination. Vaccinated ferrets exhibited similar broadly reactive serum antibody responses that protected vaccinees from clinical signs of infection and viral-induced histopathology after challenge with influenza A/07/2009 (H1N1) pandemic virus. Taken together, these data suggest that vaccination with equine H3N8 vaccine induces broad protection against influenza without the need for non-influenza viral vectors, multiple HAs, or foreign protein scaffolds common to other universal influenza vaccine candidates.
Unraveling the Impact of Gene Length on Kinetic Parameters: Implications in Drug Target selection
Authors: Choudhuri Soham , Ghosh Bhaswar 
Published: September 2024

AbstractGene expression is a multifaceted process crucial to understanding molecular biology and pharmacology. Our research focuses on elucidating the intricate relationship between gene length and kinetic parameters, such asSi,Kon,Koff, andSKoff, which significantly influence the mean expression levels of genes.Using a two-state stochastic gene expression model implemented in Python, we analyzed single-cell transcriptomics data to predict kinetic parameters for each gene. We classified genes into short and long categories, revealing distinct patterns in the relationship between gene length and these parameters. Our results indicate that burst size plays a critical role in mean expression, highlighting its importance for identifying gene targets that require lower drug doses for therapeutic effects.
Metacognition in Putative Magno- and Parvocellular Vision
Authors: Pilipenko April , De La Torre Jessica , Nukala Vrishab , Samaha Jason 
Published: September 2024

AbstractA major distinction in early visual processing is the magnocellular (MC) and parvocellular (PC) pathways. The MC pathway preferentially processes motion, transient events, and low spatial frequencies, while the PC pathway preferentially processes color, sustained events, and high spatial frequencies. Prior work has theorized that the PC pathway more strongly contributes to conscious object recognition via projections to the ventral “what” visual pathway, whereas the MC pathway underlies non-conscious, action-oriented motion and localization processing via the dorsal stream “where/how” pathway. This invites the question: Are we equally aware of activity in both pathways? And if not, do task demands interact with which pathway is more accessible to awareness? We investigated this question in a set of two studies measuring participant’s metacognition for stimuli biased towards MC or PC processing. The “Steady/Pulsed Paradigm” presents brief stimuli under two conditions thought to favor either pathway. In the “pulsed” condition, the target appears atop a strong luminance pedestal which theoretically saturates the transient MC response and leaves the PC pathway to process the stimulus. In the “steady” condition, the stimulus is identical except the luminance pedestal is constant throughout the trial, rather than flashed alongside the target. This theoretically adapts the PC neurons and leaves MC for processing. Experiment 1 was a spatial localization task thought to rely on information relayed from the MC pathway. Using both a model-based and model-free approach to quantify participants’ metacognitive sensitivity to their own task performance, we found greater metacognition in the steady (MC-biased) condition. Experiment 2 was a fine-grained orientation-discrimination task more reliant on PC pathway information. Our results show an abolishment of the MC pathway advantage seen in Experiment 1 and suggest that the metacognitive advantage for MC processing may hold for stimulus localization tasks only. More generally, our results highlight the need to consider the possibility of differential access to low-level stimulus properties in studies of visual metacognition