bluuebunny/crossref_metadata_2025_split huggingface dataset:
Update on the immunological mechanisms of primary graft dysfunction and chronic lung allograft dysfunction
Authors: Jeong Jong Cheol , Gelman Andrew E. , Chong Anita S. 
Published: October 2024

Purpose of review
Primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) are the leading causes of graft loss in lung transplant recipients. The development of mouse lung transplant models has allowed for the genetic dissection of cellular and molecular pathways that prevent graft survival. This review provides an overview into recent mechanistic insights into PGD and CLAD.

Recent findings
Mouse orthotopic lung transplant models and investigations of human lung transplant recipeints have revealed new molecular and cellular targets that promote PGD and CLAD. Donor and recipient-derived innate immune cells promote PGD and CLAD. PGD is driven by communication between classical monocytes and tissue-resident nonclassical monocytes activating alveolar macrophages to release chemokines that recruit neutrophils. Products of cell damage trigger neutrophil NET release, which together with NK cells, antibodies and complement, that further promote PGD. The development of CLAD involves circuits that activate B cells, CD8+ T cells, classical monocytes, and eosinophils.

Summary
Effective targeted management of PGD and CLAD in lung transplant recipient to improve their long-term outcome remains a critical unmet need. Current mechanistic studies and therapeutic studies in mouse models and humans identify new possibilities for prevention and treatment.
Characterizing the Patterns of Cervical Cancer Symptom Recognition, Symptom Response, and Associated Factors Among Patients Treated in a Teaching Hospital in Ghana
Authors: Oppong Anita Frimpomaa , Nwozichi Chinomso Ugochukwu , Boakye Emelia Osei , Kyei Evans Frimpong 
Published: October 2024

Background
Cervical cancer is a major global health issue and ranks as the second leading cause of cancer-related deaths among women in Ghana.

Objective
This study aimed to explore and characterize the patterns of symptom recognition associated with cervical cancer and the symptom responses among women in Ghana.

Methods
A descriptive qualitative design utilizing 20 individual semistructured interview sessions was used. The study was conducted in one of Ghana’s major cancer treatment centers. Data were collected using face-to-face interviews. The data were analyzed using NVivo 12 and presented as themes and subthemes.

Results
Data analysis revealed 2 main themes: barriers to symptom recognition and response and facilitators of early symptom recognition and symptom response. Barriers included deficient knowledge about cervical symptoms, spiritual attributions of symptoms, preference for herbal remedies for symptoms, misdiagnosis, and seeking help through multiple facility visits. Facilitating factors of symptom response include perceived severity/identification of additional symptoms, quick referrals with some navigation within the healthcare system, and advice from women’s microcommunity.

Conclusion
The study emphasizes the need for continuous educational efforts on cervical cancer and its symptoms. Healthcare providers, patients, and the public have a part to play in the awareness and early detection of cervical cancer. Initiatives that educate women about the early symptoms of cervical cancer and the importance of screening can help with early recognition.

Implication for Practice
Educating communities about cervical cancer empowers individuals to take charge of their health and encourages supportive environments for women to seek care.
Vascular Resection for Pancreas Cancer – 10-year Experience from a Single High Volume-center
Authors: Henault David , Kunde Holden , Zatzman Cody , Bevacqua Daniela , Arshinoff Danielle LA. , Cleary Sean P. , Dawson Laura A. , Elimova Elena , Grant Robert , Hosni Ali , Jang Raymond W. , Knox Jennifer J. , Mesci Aruz , Moore Malcolm , Moulton Carol-Anne E. , Reichman Trevor W. , Shwaartz Chaya , Tsang Erica S. , McGilvray Ian D. , Gallinger Steven 
Published: October 2024

Objective & Background:
Combined pancreatic and vascular resections are increasingly performed for pancreatic ductal adenocarcinoma (PDAC). We evaluated the outcomes after pancreatectomy with non-vascular resection (NVR), venous resection (VR), and arterial resection (AR).

Methods:
Retrospective review (2011–2023) of 715 PDAC patients treated with curative-intent surgery. Associations among clinicopathological data, perioperative therapy, time to recurrence (TTR), and overall survival (OS) were evaluated.

Results:
Initial staging revealed 533 resectable, 98 borderline, and 84 locally advanced PDAC cases. Pancreaticoduodenectomy was the most common procedure (n=467). NVR was performed in 351 (58.2%) patients, VR in 181 (30.0%), and AR in 70 (11.8%). The median TTR and OS did not significantly differ according to the initial staging or type of pancreas resection. Median TTR and OS were significantly shorter for VR (14.5 and 22.7 mo) compared to NVR (18.6 and 30.5 mo, P<0.001) and AR (20.6 and 30.9 mo, P=0.004 and P=0.017). Chemotherapy or chemoradiation significantly prolonged TTR (20.1 vs. 10.2 mo, P<0.001 and 25.3 vs. 16.4 mo, P<0.001) and OS (31.5 vs. 17.2 mo, P<0.001 and 35.5 vs. 27.5 mo, P=0.030). AR was associated with higher 90-day mortality rates. In the multivariable analysis, vascular resection was not associated with OS. Perioperative therapy, pathological N0 status, and absence of perineural invasion were the key predictors of longer TTR and OS.

Conclusions:
Pancreatectomy with AR was not associated with worse oncological outcomes when controlling for perioperative therapy. However, AR was associated with higher 90-day mortality rates. Patient selection is crucial when performing AR in patients with PDAC.
Efficacy of Intraoperative vs Preoperative Indocyanine Green Administration for Near-Infrared Cholangiography During Laparoscopic Cholecystectomy: An Open-Label, Noninferiority, Randomized Controlled Trial
Authors: Lin Wenjun , Tao Haisu , Zeng Xiaojun , Wang Junfeng , Zhu Wen , Zeng Ning , Xiang Nan , Liu Jun , Fang Chihua , Yang Jian 
Published: October 2024

BACKGROUND:
Near-infrared fluorescence cholangiography improves the clinical effects of laparoscopic cholecystectomy. However, the administration of indocyanine green remains controversial. Both the intraoperative strategy (IS, 0.05 mg) and preoperative strategy (PS, 0.25 mg/kg body weight, 1 day before operation) have been shown to be superior to the standard strategy (2.5 mg, intraoperative). This trial was designed to determine whether IS offers noninferior visualization of biliary ducts compared with PS.

STUDY DESIGN:
A total of 168 eligible patients undergoing laparoscopic cholecystectomy were enrolled in this noninferiority, open-label, randomized controlled trial at Zhujiang hospital between August 2023 and November 2023. Participants were randomized in a 1:1 ratio into PS and IS groups after stratification by BMI and inflammation level. The fluorescence visualization of biliary structures was assessed by comparing the signal-to-background ratio (SBR) and surgeon evaluations.

RESULTS:
The common bile duct-liver SBR did not significantly differ between IS and PS groups (3.0 ± 0.8 vs 3.1 ± 1.2; p = 0.636). The liver fluorescence intensity of the IS group was significantly lower than that of the PS group (46.3 ± 12.9 vs 70.4 ± 26.2; p < 0.01). The visualization score of common hepatic ducts was significantly greater in the IS than in the PS group (4.1 ± 0.7 vs 3.7 ± 0.6; p< 0.01). The critical view of safety was achieved more rapidly in the IS group compared with the PS group (9.4 vs 11.0 minutes, p < 0.01).

CONCLUSIONS:
Although IS did not improve the SBR, it significantly reduced the fluorescence intensity of the liver background, potentially enhancing the surgeon’s subjective perception and thereby increasing the visualization score. Compared with PS, IS offers greater convenience and is more effective in facilitating critical view of safety exposure.
Plasma Glial Fibrillary Acidic Protein (GFAP) as a Biomarker of Acute Focal Brain Injury
Authors: Saez-Calveras Nil , Asturias Alexander , Yu James , Stopschinski Barbara , Vaquer-Alicea Jaime , O’Suilleabhain Padraig , Diamond Marc I. , Shah Bhavya R. 
Published: October 2024

AbstractObjectiveThe validation of acute brain injury biomarkers has encountered challenges such as the absence of pre-insult measurements, variability in injury timing and location, and interindividual differences. In this study, we addressed these limitations by using Magnetic Resonance-guided High-Intensity Focused Ultrasound (MRgHIFU) thalamotomy to assess plasma biomarker changes after an acute focal brain injury.MethodsThis prospective study included 30 essential tremor (ET) and tremor-dominant Parkinson’s disease (TDPD) patients undergoing MRgHIFU thalamotomy at a single academic institution. Blood samples were collected at three specific time points: pre-procedure, 1-hour post-procedure, and 48 hours post-procedure. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid-beta (Aβ40 and Aβ42), and phosphorylated tau 181 (pTau-181) were measured using the Quanterix Single Molecule Arrays (SiMoA) assay.ResultsGFAP levels significantly increased 48 hours post-MRgHIFU in all patients with a thalamotomy lesion. GFAP levels were highly sensitive (89.7%) and specific (96.6%) in detecting the presence of a HIFU lesion with a cutoff value of 216.2 pg/ml. NfL, Aβ40, and Aβ42, also showed statistically significant increases post-procedure but were less robust than GFAP. No changes were observed in pTau-181 levels post-MRgHIFU.ConclusionPlasma GFAP emerged as a highly sensitive and reliable biomarker for detecting acute brain injury following MRgHIFU thalamotomy. The significant post-procedure elevation of GFAP suggests its potential as an early diagnostic tool for focal brain injuries, particularly in acute stroke. Further research is needed to validate the GFAP injury cutoff identified in this study and to explore its broader clinical utility in the early detection of focal brain lesions.
A prospective study of pre-operative risk factors associated with extended length of stay in patients attending a pre-operative clinic in South Africa
Authors: Naidu Kuven , Kajee Nabeela , Naidu Jayseelan , Wadee Bilaal 
Published: October 2024

AbstractBackgroundPreoperative assessment clinics play a critical role in identifying, evaluating, and mitigating perioperative risks. Despite global data highlighting the importance of preoperative risk factors on surgical outcomes, there remains limited information on their impact on postoperative length of stay in South African contexts.ObjectivesThis study aimed to describe the demographic and clinical profiles of patients referred to a preoperative clinic in Johannesburg, South Africa, and to examine factors associated with postoperative length of stay (LOS).MethodsThis was a prospective cohort study conducted between 2021 and 2022 at a private clinic. Patients aged ≥18 years undergoing non-cardiac surgery were included. Data on demographics, comorbidities, surgical procedures, and clinical outcomes were collected. Statistical analysis was performed to assess relationships between preoperative risk factors, including ASA grading, Revised Cardiac Risk Index (RCRI), eGFR, Diabetes Mellitus, age, obesity and LOS.ResultsA total of 214 patients were assessed, of which 75.7% were female, with a median age of 62.5 years. Common comorbidities included hypertension (59.3%) and obesity (55%). The median LOS was 3.5 days, with 47.2% of patients staying more than 3 days postoperatively. Knee (33.2%) and hip surgeries (21%) were the most common procedures. A significant association was found between longer LOS and RCRI score ≥1 (p=0.007), as well as renal dysfunction in knee surgery patients (p=0.027) and age in patients undergoing hip surgery (p=0.049). There was no significant association between ASA grade, presence of diabetes mellitus, eGFR, age or obesity.ConclusionsIncreased RCRI scores, renal dysfunction, and age were associated with prolonged hospital stay. Findings highlight the need for targeted interventions in preoperative care to reduce LOS, particularly for high-risk patients. Further research is needed to validate these results across broader healthcare settings and to establish appropriate protocols for South African patients undergoing pre-operative assessment.
The future abundance of key bird species for pathogen transmission in the Netherlands
Authors: Dellar Martha , Sierdsema Henk , van Bodegom Peter M. , Schrama Maarten , Geerling Gertjan 
Published: October 2024

AbstractWild birds serve as reservoirs and vectors for many different pathogens and changes in their distribution and abundance due to environmental change will influence disease risk. We study three species which are highly abundant in north-western Europe and which can transmit a wide range of diseases including avian influenza and West Nile virus: blackbirds, mallards and house sparrows. Using the Netherlands as a case study, we created random forest models for predicting the distribution and abundance of these species, both now and in the future. Climate, land use and vegetative cover were all important predictors of bird abundance. The three species had different spatial distributions, largely related to their preferred habitat and food availability. In the future, mallard and house sparrow populations were predicted to increase, while there was little change for blackbirds. Quantifying the consequences of these abundance changes is complicated as there are many factors to consider, however increased pathogen reservoirs will likely increase disease risk and changes in distribution may affect local outbreak risk. The future abundance maps created in this study, and the methods used to create them, will be useful tools for disease modellers and policymakers to estimate future disease risk and to plan accordingly.
Paroxysmal Slow Wave Events as a diagnostic and predictive biomarker for post-traumatic epilepsy
Authors: van Hameren Gerben , Moradi Pooyan , Imtiaz Hamza , Parker Ellen , Mansoor Saara , Al Hadeed Laith , Albitar Mohammed , Alhosainy Ziad , Friedman Alon 
Published: October 2024

AbstractTraumatic brain injury (TBI) is a major global health concern, affecting more than 40 million people annually. While most cases are mild and present with light symptoms, repeated mild injuries can result in delayed brain pathologies, including cognitive decline, neuropsychiatric complications, and post-traumatic epilepsy (PTE). PTE refers to recurring, unprovoked seizures occurring at least one week after TBI. While the link between moderate to severe TBI and PTE is well established, the epileptogenesis after repetitive mild TBI (rmTBI) is seldom studied.Currently, there are no biomarkers to identify those at risk of developing PTE, and its diagnosis is challenging. Here, we used a rat model to study PTE following rmTBI and assessed human EEG data to identify potential biomarkers for PTE.We employed a closed head TBI model to induce rmTBI, and recorded brain activity using electrocorticography (ECoG) between 2- and 6-months post-injury. Behavioral assessments and post-mortem analysis were also conducted. In humans, we analyzed EEG recordings from the Temple University database to investigate the potential of EEG-derived features for diagnosing PTE.At 6 months post injury, 70% of rmTBI animals developed PTE, compared to 22% in the control group (P=0.01). While neurological assessments following injury did not predict PTE, paroxysmal slow wave events (PSWEs) were found to be a reliable biomarker for PTE prediction. In humans, the percentage time in PSWEs was significantly elevated in PTE patients with epileptiform activity.In conclusion, we suggest PSWEs as a non-invasive, cost-effective biomarker for PTE in rodents and human patients.
Treadmill step training promotes corticospinal tract plasticity after incomplete spinal cord injury
Authors: Eisdorfer Jaclyn T. , Nacht Hannah D. , Kowalski Tess , Thackray Joshua T. , Martinez Alana M. , Zymoro Lance , Phu Megan V. , Hirpara Ridhi R. , Danish Burhanuddin S. , Wang Riley , Khondker Adyan , Eisdorfer Adam B. , Tischfield Max , Abraira Victoria E. 
Published: October 2024

ABSTRACTSpinal cord injury (SCI) often impairs motor functions such as voluntary movement and fine motor control, with the corticospinal tract (CST) being a crucial pathway affected. While CST-targeted rehabilitation, such as treadmill training, supports motor recovery, gaps remain in understanding the topographical changes within the CST and how they correlate with behavioral outcomes. In this study, we utilized a custom Emx1Cre;LSL-SynGFP mouse line to quantify CST plasticity following moderate contusion SCI, both with and without exercise (treadmill) training. Fluorescent labeling of cortical synapses allowed for detailed visualization of descending CST rewiring, and we assessed its relationship to behavioral outcomes, including kinematics analysis and motivational state. Mice were stratified by motivational state using the Progressive Ratio Assay, and locomotor recovery was evaluated through the Basso Mouse Scale (BMS), joint/limb kinematics, and Motion Sequencing (MoSeq) analysis. Our findings indicate that treadmill training enhances CST rewiring, especially in highly motivated animals, leading to increased synaptic density in the ventral horn and improved BMS subscores. Motivation further influenced specific kinematic parameters, such as toe clearance, while treadmill training significantly improved speed by reducing the stance phase. Results suggest that while treadmill training induces broad beneficial outcomes, motivation may fine-tune recovery, influencing neural circuit and behavioral changes. This suggests multiple mechanisms converge to promote recovery—those we cannot control and those we can. These results underscore the combined role of task-specific training and also perhaps motivation in driving CST plasticity and functional recovery after SCI.
PAF1C allosterically activates CDK12/13 kinase during RNAPII transcript elongation
Authors: Lopez Martinez David , Todorovski Izabela , Noe Gonzalez Melvin , Rusimbi Charlotte , Blears Daniel , Khallou Nessrine , Han Zhong , Dirac-Svejstrup A. Barbara , Svejstrup Jesper Q. 
Published: October 2024

AbstractThe mechanisms ensuring temporally correct, site-specific phosphorylation of the RNA polymerase II C-terminal domain (CTD) by cyclin-dependent kinases (CDKs) during the transcription cycle remain poorly understood. Here, we present results fromin vitroreconstitution of CTD phosphorylation combined within vivoevidence to show that human CDK12 and CDK9 both co-phosphorylate CTD Serine 5 and Serine 2. However, only phosphorylation by CDK12 is stimulated by association with the elongation-specific factor PAF1C, in which the CDC73 subunit contains a short, conserved motif capable of association with and activation of CDK12/Cyclin K. This motif is necessary for cell proliferation and crucial for CTD phosphorylation and transcript elongation. Together, these data provide new insight into basic mechanisms ensuring CDK specificity in the RNAPII transcription cycle.One-Sentence SummaryPAF1C facilitates RNAPII phosphorylation in gene bodies through direct contacts with the active site of CDK12/13.
Bumblebees increase their learning flight altitude in dense environments
Authors: Sonntag Annkathrin , Lihoreau Mathieu , Bertrand Olivier J.N. , Egelhaaf Martin 
Published: October 2024

AbstractBumblebees rely on visual memories acquired during the first outbound flights to relocate their nest. While these learning flights have been extensively studied in sparse environments with few objects, little is known about how bees adapt their flight in more dense, cluttered, settings that better mimic their natural habitats. Here we investigated how environmental complexity influences the first outbound flights of bumblebees. In a large arena we tracked the bees’ 3D positions to examine the flight patterns, body orientations, and nest fixations across environmental conditions characterised by different object constellations around the nest entrance.In cluttered environments, bees prioritised altitude gain over horizontal distance, suggesting a strategy to overcome obstacles and visual clutter. Body orientation patterns became more diverse in dense environments, indicating a balance between nest-oriented learning and obstacle avoidance. Notably, bees consistently preferred to fixate the location of the nest entrance from elevated positions above the dense environment across all conditions.Our results reveal significant changes in 3D flight structure, body orientations, and nest fixation behaviours as object density increases. This highlights the importance of considering three-dimensional space and environmental complexity in understanding insect navigation.Summary StatementDense environments influence bumblebees’ first flights, during which they develop visual memories of their nest entrance. Manipulating nest-surrounding objects showed bees prioritise altitude gain over horizontal distance in cluttered environments.
Trade-off between search costs and accuracy in oculomotor and manual search tasks
Authors: Wagner Ilja , Tünnermann Jan , Schubö Anna , Schütz Alexander C. 
Published: October 2024

AbstractHumans must weigh various factors when choosing between competing courses of action. In case of eye movements, for example, a recent study demonstrated that the human oculomotor system trades off the temporal costs of eye movements against their perceptual benefits, when choosing between competing visual search targets. Here, we compared such trade-offs between different effectors. Participants were shown search displays with targets and distractors from two stimulus sets. In each trial, they chose which target to search for, and, after finding it, discriminated a target feature. Targets differed in their search costs (how many target-similar distractors were shown) and discrimination difficulty. Participants were rewarded or penalized based on whether the target’s feature was discriminated correctly. Additionally, participants were given limited time to complete trials. Critically, they inspected search items either by eye movements only or by manual actions (tapping a stylus on a tablet). Results show that participants traded off search costs and discrimination difficulty of competing targets for both effectors, allowing them to perform close to the predictions of an ideal observer model. However, behavioral analysis and computational modelling revealed that oculomotor search performance was more strongly constrained by decision-noise (what target to choose) and sampling-noise (what information to sample during search) than manual search. We conclude that the trade-off between search costs and discrimination accuracy constitutes a general mechanism to optimize decision-making, regardless of the effector used. However, slow-paced manual actions are more robust against the detrimental influence of noise, compared to fast-paced eye movements.New & NoteworthyHumans trade off costs and perceptual benefits of eye movements for decision-making. Is this trade-off effector-specific or does it constitute a general decision-making principle? Here, we investigated this question by contrasting eye movements and manual actions (tapping a stylus on a tablet) in a search task. We found evidence for a costs-benefits trade-off in both effectors, however, eye movements were more strongly compromised by noise at different levels of decision-making.