bluuebunny/crossref_metadata_2025_split huggingface dataset:
Procoagulant platelet activation promotes venous thrombosis
Authors: Kaiser Rainer , Dewender Robin , Mulkers Maité , Stermann Julia , Rossaro Dario , Di Fina Lea , Li Lukas , Gold Christoph , Schmid Michael , Kääb Lily , Eivers Luke , Akgöl Sezer , Yue Keyang , Kammerer Lisa , Loew Quentin , Anjum Afra , Escaig Raphael , Akhalkatsi Anastassia , Laun Lisa , Kranich Jan , Brocker Thomas , Mueller Tonina T. , Krächan Angelina , Gmeiner Jonas , Pekayvaz Kami , Thienel Manuela , Massberg Steffen , Stark Konstantin , Kilani Badr , Nicolai Leo 
Published: October 2024

Abstract
Platelets are key players in cardiovascular disease, and platelet aggregation represents a central pharmacologic target, particularly in secondary prevention. However, inhibition of adenosine diphosphate and thromboxane signaling has low efficacy in preventing venous thromboembolism, necessitating the inhibition of the plasmatic coagulation cascade in this disease entity. Anticoagulation carries a significantly higher risk of bleeding complications, highlighting the need of alternative therapeutic approaches. We hypothesized that procoagulant activation (PA) of platelets promotes venous thrombus formation and that targeting PA could alleviate venous thrombosis. Here, we found elevated levels of procoagulant platelets in the circulation and in thrombi of patients with deep vein thrombosis (DVT) and pulmonary embolism, and in mice developing DVT following inferior vena cava stenosis. Furthermore, we detected PA of recruited platelets within murine venous thrombi and human pulmonary emboli. Mice with platelet-specific deficiency in central pathways of PA—cyclophilin D and transmembrane protein 16F—were more resistant toward low flow–induced venous thrombosis. Finally, we found that a clinically approved carbonic anhydrase inhibitor, methazolamide, reduced platelet procoagulant activity and alleviated murine thrombus formation without affecting trauma-associated hemostasis. These findings identify an essential role of platelet procoagulant function in venous thrombosis and delineate novel pharmacologic strategies targeting platelets in the prevention of venous thromboembolism.
Wunderlich syndrome in pregnancy: life threatening bleeding renal angiomyolipoma in first and third trimesters—two case reports and literature review
Authors: Khor Vincent , Mohd Naim Mohd Yakob , Fahmy Omar , Lee Christopher Kheng Siang , Azli Saiful , Rahim Ezamin Abdul , Kamis Mohd Fandi Al Khafiz , Khairul-Asri Mohd Ghani 
Published: October 2024

Abstract
Background
Renal angiomyolipoma (AML) is a prevalent benign tumour of the kidney. However, Wunderlich syndrome, marked by retroperitoneal haemorrhage, remains a rare and critical complication of large AMLs. During pregnancy, AMLs demonstrate an accelerated growth pattern and pose an elevated risk of rupture, leading to massive retroperitoneal haemorrhage. This report presents two compelling cases of life-threatening bleeding AML during the first and third trimesters, shedding light on the urgent need for heightened awareness and management strategies in pregnant women with AML. These cases underscore the novel and crucial aspect of the increased vulnerability of AMLs in pregnancy, emphasizing the importance of timely diagnosis and intervention.

Cases presentation
The first patient is a 37-year-old lady who presented at 27 weeks of gestation with foetal distress, abdominal pain and hypovolemic shock. Emergency Caesarean section was performed for possible abruptio placenta, and a large non-expanding retroperitoneal hematoma was found intra-operatively. Post-delivery computed tomography (CT) angiography assessment showed left perinephric hematoma from bleeding AML at the lower pole. She was hemodynamically unstable after CT and underwent an emergency nephrectomy. Post-operative recovery was uneventful. The second patient is a 30-year-old lady who presented with right abdominal pain at 11 weeks of gestation with hypotension and an actively bleeding ruptured AML found on the abdominal MRI. She underwent angioembolization at 12 weeks of pregnancy with a radiation shield to protect the foetus. She recovered well after the procedure and continued her pregnancy. Her baby was born healthy at term with no evidence of any congenital malformation.

Conclusions
When dealing with renal angiomyolipoma during pregnancy, multidisciplinary team management is crucial for the best management care. Stable cases can be treated conservatively, while unstable cases may require angioembolization or nephrectomy. The management plan should prioritize the best outcomes for both the mother and foetus. During the first trimester, angioembolization is safe and effective in controlling bleeding. However, minimizing radiation exposure is crucial, especially during organogenesis. Tailored interventions are essential to optimize outcomes in this unique patient population.
Molecular characterisation of virulence genes in bacterial pathogens from daycare centres in Ile-Ife, Nigeria: implications for infection control
Authors: Wilkie Eunice Damilola , Alao Jude Oluwapelumi , Sotala Toyosi Teniola , Oluduro Anthonia Olufunke 
Published: October 2024

Abstract
Background
Daycare centres play a critical role in early childhood development but are high-risk environments for infectious disease transmission due to close physical contact, shared toys, inadequate hygiene, and poor ventilation. These risks are especially concerning in low- and middle-income countries (LMICs) like Nigeria, where resources for infection control may be limited. This study aimed to identify and characterise virulence genes in bacterial isolates from daycare centres in Ile-Ife, Nigeria, to assess infection risks.

Methods
Between November 2017 and July 2019, 233 samples were collected from 76 children, 33 daycare workers, and 124 fomites in 17 daycare centres. The bacterial isolates were analysed using conventional PCR and RAPD analysis to detect the presence of virulence genes. The frequency of crucial virulence genes and the prevalence of each bacterial species were recorded.

Results
Key virulence genes were detected, including fimH in Klebsiella species (22.73% of Gram-negative isolates), algD in Pseudomonas aeruginosa (50%), and icaA and cna in Staphylococcus aureus (16.67%). Staphylococcus aureus was the most prevalent species (35%), followed by Klebsiella (28%) and Pseudomonas aeruginosa (20%).

Conclusion
This study highlights the presence of virulent bacterial pathogens in daycare environments, posing a severe infection risk to children. To mitigate these risks, it is essential to implement enhanced infection control measures, such as regular microbial screening, improved hand hygiene practices, and disinfection protocols for fomites. Training programs for daycare workers on hygiene practices and routine monitoring could also significantly reduce infection transmission. These interventions are vital for safeguarding the health of daycare children in Nigeria and similar settings globally.
Oscillating US Department of Defense policies and medical record documentation of gender dysphoria in service members: an observational time-series analysis
Authors: Highland Krista B. , Klein David A. , Rogers Sydney , Velosky Alexander G. , Roberts Christina , Larson Noelle S. 
Published: October 2024

Abstract
Background
United States military policies regarding service by transgender service members have shifted several times within the past decade. The relationships between policy changes and electronic health record documentation of gender dysphoria, a current and historic policy requisite for gender affirming care receipt, in active duty service members remain unknown.

Methods
Bayesian estimator of abrupt change, seasonality, and trend models identified changepoints in the proportion of service members who had new and then historical medical record documentation consistent with gender dysphoria from January 2015 to August 2022. Changepoints were evaluated as they related to salient military policy-related events.

Results
Approximately 3,853 active duty and activated National Guard or Reserve service members received a documented diagnosis corresponding to gender dysphoria from January 2015 to August 2022. Four significant changepoints were identified across both time series. Salient historical events that occurred during the changepoint periods were identified for contextualization.

Conclusions
Clinical documentation of gender dysphoria oscillated with changes to policies and public statements by government leaders, which may in turn, impact military recruitment and retention. This study highlights the need for equitable policies that optimize the strength of a diverse military force. Equity-oriented monitoring is needed to continually examine the impact of military service policies on readiness and retention to support actionable, data-driven improvements to policies and their implementation.
A qualitative study on rehabilitation services at primary health care: insights from primary health care stakeholders in low-resource contexts
Authors: Charumbira Maria Y , Kaseke Farayi , Conradie Thandi , Berner Karina , Louw Quinette A 
Published: October 2024

Abstract
Background
The chasm between rehabilitation needs and available rehabilitation services is widening. In most low-resource contexts, there are inadequate rehabilitation professionals at primary health care (PHC), leaving nonrehabilitation primary care providers’ (PCPs) and district rehabilitation professionals and managers to address patients’ rehabilitation needs. This study explored rehabilitation and non-rehabilitation PCPs’ and managers’ perspectives on the situation of rehabilitation service provision in PHC settings and the challenges experienced in providing rehabilitation care.

Methods
In this descriptive, exploratory qualitative study, individual semi-structured interviews and focus group discussions were conducted with purposefully sampled PCPs in Manicaland, Zimbabwe and Eastern Cape, South Africa. The transcripts were analysed thematically using Atlas.ti. version 22.2®.

Results
Thirty-six PCPs (29 nonrehabilitation and 7 rehabilitation) and one district manager participated in the study. The current PHC rehabilitation services in the two low-resource contexts were described as inadequate, if not nonexistent. District rehabilitation professionals attempted to fill the gap through outreach and home visits, but resource limitations, particularly in Zimbabwe, often hampered this strategy. The nonrehabilitation PCPs took on task-shifting roles in the identification, referral, and education of patients with rehabilitation needs in the absence of rehabilitation professionals at PHC. Challenges encountered in providing rehabilitation care at PHC included unsupportive leadership, human resource shortages, lack of comprehensive PHC rehabilitation guidelines, no or delayed rehabilitation referral, lack of clear communication strategies, and users’ low demand for PHC rehabilitation.

Conclusion
Tailored approaches, including context-specific rehabilitation guidance for existing task-shifting models, increased investment in rehabilitation and increased rehabilitation awareness, are needed to establish basic rehabilitation services in the described contexts because they are mostly absent. Importantly, the PHC systems in which rehabilitation is to be nested need to be strengthened.
Active CNS delivery of oxycodone in healthy and endotoxemic pigs
Authors: Bällgren Frida , Bergfast Tilda , Ginosyan Aghavni , Mahajan Jessica , Lipcsey Miklós , Hammarlund-Udenaes Margareta , Syvänen Stina , Loryan Irena 
Published: October 2024

Abstract
Background
The primary objective of this study was to advance our understanding of active drug uptake at brain barriers in higher species than rodents, by examining oxycodone brain concentrations in pigs.

Methods
This was investigated by a microdialysis study in healthy and endotoxemic conditions to increase the understanding of inter-species translation of putative proton-coupled organic cation (H+/OC) antiporter-mediated central nervous system (CNS) drug delivery in health and pathology, and facilitate the extrapolation to humans for improved CNS drug treatment in patients. Additionally, we sought to evaluate the efficacy of lumbar cerebrospinal fluid (CSF) exposure readout as a proxy for brain unbound interstitial fluid (ISF) concentrations. By simultaneously monitoring unbound concentrations in blood, the frontal cortical area, the lateral ventricle (LV), and the lumbar intrathecal space in healthy and lipopolysaccharide (LPS)-induced inflammation states within the same animal, we achieved exceptional spatiotemporal resolution in mapping oxycodone transport across CNS barriers.

Results
Our findings provide novel evidence of higher unbound oxycodone concentrations in brain ISF compared to blood, yielding an unbound brain-to-plasma concentration ratio (Kp,uu,brain) of 2.5. This supports the hypothesis of the presence of the H+/OC antiporter system at the blood–brain barrier (BBB) in pigs. Despite significant physiological changes, reflected in pig Sequential Organ Failure Assessment, pSOFA scores, oxycodone blood concentrations and its active net uptake across the BBB remained nearly unchanged during three hours of i.v. infusion of 4 µg/kg/h LPS from Escherichia coli (O111:B4). Mean Kp,uu,LV values indicated active uptake also at the blood-CSF barrier in healthy and endotoxemic pigs. Lumbar CSF concentrations showed minimal inter-individual variability during the experiment, with a mean Kp,uu,lumbarCSF of 1.5. LPS challenge caused a slight decrease in Kp,uu,LV, while Kp,uu,lumbarCSF remained unaffected.

Conclusions
This study enhances our understanding of oxycodone pharmacokinetics and CNS drug delivery in both healthy and inflamed conditions, providing crucial insights for translating these findings to clinical settings.
Long-term outcome of autologous haematopoietic stem cell transplantation in patients with systemic sclerosis: a comparison with patients treated with rituximab and with traditional immunosuppressive agents
Authors: Del Papa Nicoletta , Cavalli Silvia , Rindone Andrea , Onida Francesco , Saporiti Giorgia , Minniti Antonina , Pellico Maria Rosa , Iannone Claudia , Trignani Giorgia , D’Angelo Nicoletta , Sette Manuel , Greco Raffaella , Vitali Claudio , Caporali Roberto 
Published: October 2024

Abstract
Background
Autologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there is still a paucity of data comparing AHSCT with rituximab (RTX). Aim of the study is to retrospectively compare, in patients with dcSSc, the effectiveness of AHSCT with that of RTX and CIT.

Methods
Thirty-five dcSSc AHSCT-treated patients were compared with 29 and 36 matched cases treated with RTX and CIT, respectively. The patients were followed up for 5 years by assessing selected outcome measures every year. Overall survival, modified Rodnan skin score (mRSS), lung function tests (FVC and DLCO), and the revised EUSTAR Activity Index (REAI) were the outcome measures chosen to evaluate the therapy efficacy.

Results
AHSCT was significantly more effective than RTX and CIT in prolonging survival, inducing a rapid reduction of the mRSS and REAI and maintaining the baseline level of lung function tests for a longer time. RTX therapy was also superior to CIT in reducing REAI, mRSS and in saving lung function.

Conclusion
AHSCT is more effective than both RTX and CIT in prolonging survival and inducing prolonged remission in patients with rapidly progressive dcSSc.
Revisiting Virchow’s triad: exploring the cellular and molecular alterations in cerebral venous congestion
Authors: Zhou Chen , Zhou Yifan , Ma Wei , Liu Lu , Zhang Weiyue , Li Hui , Wu Chuanjie , Chen Jian , Wu Di , Jiang Huimin , Ji Xunming 
Published: October 2024

Abstract
Background
Cerebral venous thrombosis (CVT) is a rare but serious condition that can lead to significant morbidity and mortality. Virchow’s triad elucidates the role of blood hypercoagulability, blood flow dynamics, and endothelial damage in the pathogenesis of CVT. Cerebral venous congestion (CVC) increases the risk of cerebral venous sinus thrombosis and can lead to recurrent episodes and residual symptoms. However, the precise mechanism by which blood congestion leads to thrombosis remains unclear. Our objective was to investigate the cellular and molecular alterations linked to CVC through analysis of the pathological morphology of venous sinus endothelial cells and transcriptomic profiling.

Results
This study demonstrated a remarkable correlation between CVC and the phenotypic transformation of endothelial cells from an anticoagulant to a procoagulant state. The findings revealed that cerebral venous stasis results in tortuous dilatation of the venous sinuses, with slow blood flow and elevated pressure in the sinuses and damaged endothelial cells of the retroglenoid and internal jugular vein ligation (JVL) rat model. Mechanistically, analysis of transcriptomic results of cerebral venous sinus endothelial cells showed significant activation of platelet activation, complement and coagulation cascades pathway in the JVL rats. Furthermore, the expression of von Willebrand factor (vWF) and coagulation factor VIII (F8) in the complement and coagulation cascades and Fgg and F2 in the platelet activation was increased in the cerebral venous sinuses of JVL rats than in sham rats, suggesting that endothelial cell injury in the venous sinus induced by CVC has a prothrombotic effect. In addition, endothelial cell damage accelerates coagulation and promotes platelet activation. Significantly, the concentrations of vWF, F2 and F8 in venous sinus blood of patients with internal jugular vein stenosis were higher than in their peripheral blood.

Conclusion
Collectively, our data suggest that CVC can induce endothelial cell damage, which then exhibits a procoagulant phenotype and ultimately increases the risk of CVT. This research contributes to our understanding of the pathophysiology of CVC associated with procoagulant factors and reexamines the components of Virchow’s triad in the context of CVC.
Contrasting responses of an invasive plant to herbivory of native and introduced insects
Authors: Fu Qiu-Yue , Wei Guan-Wen , Wang Mo-Zhu , Cui Yuan , Dong Bi-Cheng , Yu Fei-Hai 
Published: October 2024

Abstract
Background
Interactions between alien plants and insect herbivores in introduced ranges may determine their invasion success. However, few studies have investigated whether alien plants respond differently to native and introduced herbivores in their introduced ranges and whether genotypes of alien plants matter. We conducted a greenhouse experiment to examine the effects of herbivory by a native insect (Spodoptera litura), by an introduced insect (S. frugiperda), and simultaneously by both insect species on growth, morphology, and biomass allocation of 17 genotypes of an invasive alien clonal plant Hydrocotyle verticillata, and used selection gradient analysis to test which herbivory conditions favor selection of a specific leaf or root trait value.

Results
Different genotypes of H. verticillata showed significant variation in growth, morphology, and biomass allocation, but their responses to herbivory were relatively consistent. All three herbivory treatments significantly decreased total mass and stolon mass, but herbivory of S. frugiperda increased specific leaf area. Herbivory of S. litura and simultaneous herbivory of both insect species also decreased leaf mass, petiole mass, root mass, and ramet mass. Selection gradient analysis showed that leaf and root traits varied under different herbivory treatments. To achieve greater fitness, as measured by total mass and/or number of ramets, H. verticillata favored larger leaf area under herbivory by S. frugiperda, larger leaf area and lower specific leaf area under herbivory by S. litura, and larger leaf area, lower specific leaf area, and lower root-to-shoot ratio under simultaneous herbivory.

Conclusions
H. verticillata demonstrated contrasting responses to herbivory by native and introduced insects, showing a remarkable ability to coordinate leaf trait plasticity and optimize biomass allocation. This strategy allows H. verticillata to achieve greater fitness under various herbivory conditions, potentially contributing to its invasion success. These findings highlight the importance of plant–herbivore interactions in shaping invasion dynamics and underscore the complex adaptive mechanism that enables invasive plants to establish and spread in introduced ranges.
Lobar graft evaluation in cadaveric lobar lung redo transplantation after living-donor lobar lung transplantation: a case report
Authors: Watanabe Yui , Watanabe Tatsuaki , Hirama Takashi , Murai Sho , Ueda Kazunori , Oishi Hisashi , Akiba Miki , Watanabe Toshikazu , Suzuki Takaya , Notsuda Hirotsugu , Onodera Ken , Togo Takeo , Niikawa Hiromichi , Noda Masafumi , Okada Yoshinori 
Published: October 2024

Abstract
Background
Lung transplantation is a vital option for patients with end-stage lung disease. However, it faces a significant challenge due to the shortage of compatible donors, which particularly affects individuals with small chest cavities and pediatric patients. The novel approach of cadaveric lobar lung transplantation is a promising solution to alleviate the donor shortage crisis. Both the mid-term and long-term outcomes of lobar lung transplantation are comparable to those of standard lung transplantation. However, patients undergoing lobar lung transplantation reported a significantly higher rate of primary graft dysfunction compared to patients undergoing standard lung transplantation. Therefore, careful donor selection is critical to improve outcomes after lobar transplantation. However, no established method exists to evaluate each lung lobar graft of deceased donors. This case report describes a case of cadaveric lobar lung transplantation to overcome size mismatch and donor shortage, with particular emphasis on lobar graft evaluation.

Case presentation
A 39-year-old woman with scleroderma-related respiratory failure was listed for deceased donor lung transplantation due to a rapidly progressing disease. Faced with a long waiting list and impending mortality, she underwent bilateral living-donor lobar lung transplantation donated by her relatives. Post-transplant complications included progressive pulmonary vein obstruction and pleural effusion, which ultimately required retransplantation. An oversized donor with pneumonia in the bilateral lower lobes was allocated. Lung ultrasound was used to evaluate each lung lobar graft during procurement. The right upper and middle lobes and left upper lobe were confirmed to be transplantable, and lobar lung redo transplantation was performed. The patient’s post-transplant course was uneventful, and she was discharged home and returned to her daily activities.

Conclusions
This case highlights the clinical impact of cadaveric lobar lung transplantation as a feasible and effective strategy to overcome the shortage of donor lungs, especially in patients with small thoracic cavities. By establishing donor lung evaluation techniques and overcoming anatomical and logistical challenges, cadaveric lobar lung transplantation can significantly expand the donor pool and offer hope to those previously considered ineligible for transplantation.