bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Indo-Pacific humpback dolphin (Sousa chinensis) severely injured by vessel collision: live rescue at sea, clinical care, and postmortem examination using a virtopsy-integrated approach
Authors: Kot Brian Chin Wing , Ho Heysen Hei Nam , Martelli Paolo , Churgin Sarah M. , Fernando Nimal , Lee Foo Khong , Tsui Henry Chun Lok , Chung Tabris Yik To 
Published: November 2022

AbstractBackgroundVessel collision induces blunt and sharp force traumas to aquatic animals and is a leading anthropogenic impact affecting cetaceans worldwide. Vessel collision is an important threat affecting vulnerable coastal cetaceans such as the Indo-Pacific humpback dolphins (Sousa chinensis) which reside in coastal waters of Hong Kong amongst heavy marine traffic.Case presentationA severely injured subadultS. chinensiswas sighted in the waters off southwestern Hong Kong with four gaping incision wounds on its dorsum. It was in poor body condition and seemed unable to use the fluke effectively. The deepest wound located at the caudal peduncle near the base of the fluke and exposed the underlying fractured caudal vertebrae. The dolphin was monitored in the field over three weeks and eventually captured for medical intervention as veterinary assessment indicated progressive and life-threatening deterioration. During rehabilitation, the dolphin demonstrated initial signs of improvement over the first 36 hours as supported by diagnostic tests but then deteriorated rapidly. It was humanely euthanised after three days of rehabilitation. Postmortem investigation was carried out using virtopsy (postmortem computed tomography and magnetic resonance imaging) and conventional necropsy, with special attention to the traumatic musculoskeletal injuries caused by vessel collision and also revealed acute gastrointestinal compromise and respiratory disease that further hampered the rehabilitation.ConclusionIn cetaceans, the prognosis for recovery from injuries caused by vessel collision depends on the extent, location, and gravity of the injuries (i.e., superficial, deep, penetrating, blunt vs. sharp, fresh vs. septic), as well as the health status of the individual and its ability to respond to the insult. Injuries extending deep into the vertebral column may lead to delayed death and associated welfare issues. The prognosis of this case was likely poor given the severity and location of the injuries, but the attempted rehabilitation and postmortem investigation provided valuable insights for clinical management if similar cases are encountered in the future. Being able to non-invasively assess and document traumatic injuries and other pathologies, diagnostic imaging is particularly useful in the clinical assessment and postmortem investigation (virtopsy) of cases with vessel-induced injuries.
Admission glucose as a prognostic marker for all-cause mortality and cardiovascular disease
Authors: Djupsjö Catarina , Kuhl Jeanette , Andersson Tomas , Lundbäck Magnus , Holzmann Martin J. , Nyström Thomas 
Published: November 2022

Abstract
Background
Diabetes and prediabetes are known risk factors for cardiovascular disease and associated with increased mortality risk. Whether patients with a random elevated blood glucose level but no history of diabetes are at a higher mortality and cardiovascular risk is not entirely known.

Methods
A retrospective cohort study where patients (18–80 years) with no history of diabetes between 2006 and 2016 attending the emergency department (ED) in Sweden were included. Based on the first (index) blood glucose level patients were categorized into four groups: hypoglycemia (< 3.9 mmol/L), normal glucose tolerance (NGT) (3.9–7.8 mmol/L), dysglycemia (7.8–11.1 mmol/L), and hyperglycemia (> 11.1 mmol/L). Data was collected from four nationwide registers (National Patient Register, National Cause of Death Register, Prescribed Drug Register and Statistics Sweden). Cox regression was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for all-cause mortality and cardiovascular outcomes using NGT as reference.

Results
618,694 patients were included during a mean follow-up time of 3.9 years. According to the index blood glucose level: 1871 (0.3%) had hypoglycemia, 525,636 (85%) had NGT, 77,442 (13%) had dysglycemia, and 13,745 (2%) patients had hyperglycemia, respectively. During follow-up 44,532 (7.2%) deaths occurred. After multiple adjustments, mortality risk was highest in patients with hypoglycemia HR 2.58 (2.26–2.96) followed by patients with hyperglycemia HR 1.69 (1.63–1.76) and dysglycemia HR 1.16 (1.13–1.19). Risk for cardiovascular events: i.e., myocardial infarction, stroke and heart failure, were highest among patients with hyperglycemia HR 2.28 (2.13–2.44), HR 1.62 (1.51–1.74) and HR 1.60 (1.46–1.75), respectively.

Conclusion
Patients with disturbed blood glucose level at ED admission have a higher mortality risk than patients with NGT. Patients with hyperglycemia have almost a two folded increased long-term mortality risk and more than a doubled risk for cardiovascular events compared to patients with NGT.
Activation of embryonic/germ cell-like axis links poor outcomes of gliomas
Authors: Ma Zhan , Zhang Fengyu , Xiong Ji , Zhang Haishi , Lin Hui-Kuan , Liu Chunfang 
Published: November 2022

AbstractBackgroundIt is unclear which core events drive the malignant progression of gliomas. Earlier studies have revealed that the embryonic stem (ES) cell/early PGC state is associated with tumourigenicity. This study was designed to investigate the role of ES/PGC state in poor outcomes of gliomas.MethodsCrispr-Cas9 technology, RT–PCR and animal experiments were used to investigate whether PGC-like cell formation play crucial roles in the tumorigenicity of human glioma cells. Bioinformatic analysis was used to address the link between ES/PGC developmental axis and glioma overall outcomes.ResultsHere, our findings showed that germ cell-like cells were present in human gliomas and cultured glioma cells and that the formation of germ cell-like cells was essential for glioma tumours. Bioinformatic analysis showed that the mRNA levels of genes related to embryonic/germ cell development could be detected in most gliomas. Our findings showed that the activation of genes related to reprogramming or the germ cell-like state alone seemed to be insufficient to lead to a malignant prognosis, whereas increased mRNA levels of genes related to the activation of the embryonic/germ cell-like cycle (somatic PGC-EGC-like cycle and somatic parthenogenetic embryo-like cycle) were positively correlated with malignant prognoses and poor clinical outcomes of gliomas. Genes related to the embryonic/germ cell cycle alone or in combination with the WHO grade or 1p19q codeletion status could be used to subdivide gliomas with distinct clinical behaviours.ConclusionTogether, our findings indicated that a crucial role of germ cell-like cell formation in glioma initiation as well as activation of genes related with the parthenogenetic embryo-like cycle and PGC-EGC-like cycle link to the malignant prognosis and poor outcomes of gliomas, which might provide a novel way to better understand the nature of and develop targeted therapies for gliomas as well as important markers for predicting clinical outcomes in gliomas.
Identifying novel interactions of the colon-cancer related APC protein with Wnt-pathway nuclear transcription factors
Authors: Al-Thani Nayra M. , Schaefer-Ramadan Stephanie , Aleksic Jovana , Mohamoud Yasmin A. , Malek Joel A. 
Published: December 2022

Abstract
Background
Colon cancer is often driven by mutations of the adenomatous polyposis coli (APC) gene, an essential tumor suppressor gene of the Wnt β-catenin signaling pathway. APC and its cytoplasmic interactions have been well studied. However, various groups have also observed its presence in the nucleus. Identifying novel interactions of APC in the Wnt pathway will provide an opportunity to understand APC’s nuclear role better and ultimately identify potential cancer treatment targets.

Methods
We used the all-vs-all sequencing (AVA-Seq) method to interrogate the interactome of protein fragments spanning most of the 60 Wnt β-catenin pathway proteins. Using protein fragments identified the interacting regions between the proteins with more resolution than a full-length protein approach. Pull-down assays were used to validate a subset of these interactions.

Results
74 known and 703 novel Wnt β-catenin pathway protein-protein interactions were recovered in this study. There were 8 known and 31 novel APC protein-protein interactions. Novel interactions of APC and nuclear transcription factors TCF7, JUN, FOSL1, and SOX17 were particularly interesting and confirmed in validation assays.

Conclusion
Based on our findings of novel interactions between APC and transcription factors and previous evidence of APC localizing to the nucleus, we suggest APC may compete and repress CTNNB1. This would occur through APC binding to the transcription factors (JUN, FOSL1, TCF7) to regulate the Wnt signaling pathway including through enhanced marking of CTNNB1 for degradation in the nucleus by APC binding with SOX17. Additional novel Wnt β-catenin pathway protein-protein interactions from this study could lead researchers to novel drug designs for cancer.
Insecticide resistance intensity and efficacy of synergists with pyrethroids in Anopheles gambiae (Diptera: Culicidae) from Southern Togo
Authors: Apetogbo Yawo , Ahadji-Dabla Koffi M. , Soma Dieudonné Diloma , Amoudji Adjovi D. , Koffi Edoh , Akagankou Kossivi I. , Bamogo Rabila , Ngaffo Kelly Lionelle , Maiga Samina , Atcha‑Oubou Rachid T. , Dorkenoo Ameyo M. , Vizcaino Lucrecia , Lenhart Audrey , Diabaté Abdoulaye , Dabiré Roch Kounbobr , Ketoh Guillaume Koffivi 
Published: November 2022

Abstract
Background
This study was designed to provide insecticide resistance data for decision-making in terms of resistance management plans in Togo.

Methods
The susceptibility status of Anopheles gambiae sensu lato (s.l.) to insecticides used in public health was assessed using the WHO tube test protocol. Pyrethroid resistance intensity bioassays were performed following the CDC bottle test protocol. The activity of detoxification enzymes was tested using the synergists piperonyl butoxide, S.S.S-tributlyphosphorotrithioate and ethacrinic acid. Species-specific identification of An. gambiae s.l. and kdr mutation genotyping were performed using PCR techniques.

Results
Local populations of An. gambiae s.l. showed full susceptibility to pirimiphos methyl at Lomé, Kovié, Anié, and Kpèlè Toutou. At Baguida, mortality was 90%, indicating possible resistance to pirimiphos methyl. Resistance was recorded to DDT, bendiocarb, and propoxur at all sites. A high intensity of pyrethroid resistance was recorded and the detoxification enzymes contributing to resistance were oxidases, esterases, and glutathione-s-transferases based on the synergist tests. Anopheles gambiae sensu stricto (s.s.) and Anopheles coluzzii were the main species identified. High kdr L1014F and low kdr L1014S allele frequencies were detected at all localities.

Conclusion
This study suggests the need to reinforce current insecticide-based malaria control interventions (IRS and LLINs) with complementary tools.
Therapeutic efficacy of dihydroartemisinin–piperaquine for the treatment of uncomplicated Plasmodium vivax malaria in Seacha area, Arbaminch Zuria District, South West Ethiopia
Authors: Mohammed Hussein , Sime Heven , Hailgiorgis Henok , Gubae Kale , Haile Mebrahtom , Solomon Hiwot , Etana Kebede , Girma Samuel , Bekele Worku , Chernet Melkie , Tollera Getachew , Tasew Geremew , Gidey Bokretsion , Commons Robert J. , Assefa Ashenafi 
Published: November 2022

Abstract
Background
Declining efficacy of chloroquine against Plasmodium vivax malaria has been documented in Ethiopia. Thus, there is a need to assess the efficacy of alternative schizontocidal anti-malarials such as dihydroartemisinin–piperaquine (DHA–PPQ) in P. vivax malaria-infected patients. This study was conducted to evaluate the therapeutic efficacy of DHA–PPQ drug in South West Ethiopia.

Methods
This is a single-arm, prospective therapeutic efficacy study in patients with uncomplicated P. vivax malaria. The study was conducted from May 2021 to August 2021, based on the standard World Health Organization study protocol for surveillance of anti-malarial therapeutic efficacy. The study endpoint was adequate clinical and parasitological response on day 42.

Results
A total of 86 patients with uncomplicated vivax malaria were enrolled. Of these, 79 patients completed the scheduled follow up; all showing adequate clinical and parasitological responses to day 42, with a successful cure rate of 100% (95% CI 96–100). Parasitaemias were cleared rapidly (86% by day 1 and 100% by day 3), as were clinical symptoms (100% by day 1). Gametocyte carriage decreased from 44% on Day 0 to 1% on day 1 and 0% on Day 2. Mean haemoglobin concentrations increased between day 0 (mean 12.2 g/dL) and day 42 (mean 13.3 g/dL). Treatment was well tolerated and no severe adverse events were observed.

Conclusion
In summary, treatment with DHA–PPQ demonstrated excellent efficacy for uncomplicated P. vivax, with no recurrences to day 42, and no safety concerns. This treatment, which is also effective against P. falciparum, appears to be an ideal alternative for P. vivax as part of the malaria elimination programme.
Molecular markers of dihydroartemisinin-piperaquine resistance in northwestern Thailand
Authors: Win Khine Nwe , Manopwisedjaroen Khajohnpong , Phumchuea Kanit , Suansomjit Chayanut , Chotivanich Kesinee , Lawpoolsri Saranath , Cui Liwang , Sattabongkot Jetsumon , Nguitragool Wang 
Published: November 2022

Abstract
Background
Dihydroartemisinin-piperaquine (DHA-PPQ) combination therapy is the current first-line treatment for Plasmodium falciparum malaria in Thailand. Since its introduction in 2015, resistance to this drug combination has emerged in the eastern part of the Greater Mekong Subregion including the eastern part of Thailand near Cambodia. This study aimed to assess whether the resistance genotypes have arisen the western part of country.

Methods
Fifty-seven P. falciparum-infected blood samples were collected in Tak province of northwestern Thailand between 2013 and 2019. Resistance to DHA was examined through the single nucleotide polymorphisms (SNPs) of kelch13. PPQ resistance was examined through the copy number plasmepsin-2 and the SNPs of Pfcrt.

Results
Among the samples whose kelch13 were successfully sequenced, approximately half (31/55; 56%) had mutation associated with artemisinin resistance, including G533S (23/55; 42%), C580Y (6/55; 11%), and G538V (2/55; 4%). During the study period, G533S mutation appeared and increased from 20% (4/20) in 2014 to 100% (9/9) in 2019. No plasmepsin-2 gene amplification was observed, but one sample (1/54) had the Pfcrt F145I mutation previously implicated in PPQ resistance.

Conclusions
Kelch13 mutation was common in Tak Province in 2013–2019. A new mutation G533S emerged in 2014 and rose to dominance in 2019. PPQ resistance marker Pfcrt F145I was also detected in 2019. Continued surveillance of treatment efficacy and drug resistance markers is warranted.
The right of access to healthcare: an analysis of how legal and institutional frameworks constrain or facilitate access to healthcare for residents in border areas in the East African Community
Authors: Ssengooba Freddie , Babirye Susan , Tuhebwe Doreen , Ssennyonjo Aloysius , Ssendagire Steven , Rutaroh Arthur , Mutesa Leon , Nangami Mabel 
Published: November 2022

Abstract
Background
Despite many countries working hard to attain Universal Health Coverage (UHC) and the Health-related Sustainable Development Goals, access to healthcare services has remained a challenge for communities residing along national borders in the East Africa Community (EAC). Unlike the communities in the interior, those along national borders are more likely to face access barriers and exclusion due to low health investments and inter-state rules for non-citizens. This study explored the legal and institutional frameworks that facilitate or constrain access to healthcare services for communities residing along the national borders in EAC.

Methods
This study is part of a broader research implemented in East Africa (2018–2020), employing mixed methods. For this paper, we report data from a literature review, key informant interviews and sub-national dialogues with officials involved in planning and implementing health and migration services in EAC. The documents reviewed included regional and national treaties, conventions, policies and access rules, regulations and guidelines that affect border crossing and access to healthcare services. These were retrieved from official online and physical libraries and archives.

Results
Overall, the existing laws, policies and guidelines at all levels do not explicitly deal with cross border healthcare access especially for border residents, but address citizen rights and entitlements including health within national frameworks. There is no clarity on whether these rights can be enjoyed beyond one’s country of citizenship. The review found examples of investments in shared health infrastructure to benefit all EAC member countries – a signal of closer cooperation for specialized health care, this had not been accompanied by access rule for citizens outside the host country. The focus on specialized care is unlikely to contribute to the every-day health care needs of border resident communities in remote areas of EAC. Nevertheless, the establishment of the EAC entail opportunities for increased collaboration and integration beyond the trade and customs union to included health care and other social services. The study established active cooperation aimed at disease surveillance and epidemic control among sub-national officials responsible for health and migration services across borders. Health insurance cards, national identification cards and official travel documents were found to constrain access to health services across the borders in EAC.

Conclusion
In the era of UHC, there is need to take advantage of the EAC integration to revise legal and policy frameworks to leverage existing investments and facilitate cross-border access to healthcare services for communities residing along EAC borders.
Evaluating the use of novel atherogenicity indices and insulin resistance surrogate markers in predicting the risk of coronary artery disease: a case‒control investigation with comparison to traditional biomarkers
Authors: Mahdavi-Roshan Marjan , Mozafarihashjin Mohammad , Shoaibinobarian Nargeskhatoon , Ghorbani Zeinab , Salari Arsalan , Savarrakhsh Amir , Hekmatdoost Azita 
Published: November 2022

Abstract
Background
Due to the contribution of coronary artery disease (CAD) to serious cardiovascular events, determining biomarkers that could robustly predict its risk would be of utmost importance. Thus, this research was designed to assess the value of traditional cardio-metabolic indices, and more novel atherogenicity indices and insulin resistance surrogate markers in the identification of individuals at risk of CAD.

Methods
A case‒control survey was conducted, in which 3085 individuals were enrolled. Their clinical and biochemical data were gathered at baseline. The investigated indices included the atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), lipoprotein combine index (LCI), cholesterol index (CHOLINDEX), Castelli’s risk indices-I, II (CRI-I, CRI-II), and metabolic score for insulin resistance (METS − IR). To examine the relationship between these variables and CAD risk, multiple regression analyses adjusted for potential confounders were conducted.

Results
Overall, 774 angiographically confirmed CAD patients (mean age = 54 years) were compared with 3085 controls (mean age = 51 years). Higher triglyceride, total cholesterol and fasting blood sugar levels and lower HDL-C levels were related to an elevated risk of CAD (P-for-trend < 0.001), while the direct association between increased serum LDL-C concentrations and a greater risk of CAD only became apparent when excluding those with diabetes, and statin users. Among novel indices, greater values of the majority of these markers, including AIP, CRI-I, and -II, CHOLINDEX, LCI, and TyG-index, in comparison to the lower values, significantly elevated CAD risk (P-for-trend < 0.001).

Conclusion
According to the current findings, novel atherogenicity indices and insulin resistance surrogate markers, in particular, AIP, CRI-I and II, CHOLINDEX, LCI, and TyG-index, may be useful in predicting CAD risk.
Effects of hydrogen-rich saline in neuroinflammation and mitochondrial dysfunction in rat model of sepsis-associated encephalopathy
Authors: Dumbuya John Sieh , Li Siqi , Liang Lili , Chen Yanchen , Du Jiang , Zeng Qiyi 
Published: November 2022

Abstract
Background
Sepsis-associated encephalopathy (SAE) is one of the most common types of sepsis-related organ dysfunction without overt central nervous system (CNS) infection. It is associated with higher mortality, low quality of life, and long-term neurological sequelae in suspected patients. At present there is no specific treatment for SAE rather than supportive therapy and judicious use of antibiotics, which are sometimes associated with adverse effects. Molecular hydrogen (H2) has been reported to play crucial role in regulating inflammatory responses, neuronal injury, apoptosis and mitochondrial dysfunction in adult models of SAE. Here we report the protective effect of hydrogen-rich saline in juvenile SAE rat model and its possible underling mechanism(s).

Materials and methods
Rats were challenged with lipopolysaccharide (LPS) at a dose of 8 mg/kg injected intraperitoneally to induce sepsis and hydrogen-rich saline (HRS) administered 1 h following LPS induction at a dose of 5 ml/kg. Rats were divided into: sham, sham + HRS, LPS and LPS + HRS. At 48 h, rats were sacrificed and Nissl staining for neuronal injury, TUNEL assay for apoptotic cells detection, immunohistochemistry, and ELISA protocol for inflammatory cytokines determination, mitochondrial dysfunction parameters, electron microscopy and western blot analysis were studied to examine the effect of HRS in LPS-induced septic rats.

Results
Rats treated with HRS improved neuronal injury, improvement in rats’ survival rate. ELISA analysis showed decreased TNF-α and IL-1β and increased IL-10 expression levels in the HRS-treated group. Apoptotic cells were decreased after HRS administration in septic rats. The numbers of GFAP and IBA-1positive cells were attenuated in the HRS-treated group when compared to the LPS group. Subsequently, GFAP and IBA-1 immunoreactivity were decreased after HRS treatment. Mitochondrial membrane potential detected by JC-1 dye and ATP content were decreased in septic rats, which were improved after HRS treatment, while release of ROS was increased in the LPS group reverted by HRS treatment, ameliorating mitochondrial dysfunction. Further analysis by transmission electron microscopy showed decreased number of mitochondria and synapses, and disrupted mitochondrial membrane ultrastructure in the LPS group, while HRS administration increased mitochondria and synapses number.

Conclusion
These data demonstrated that HRS can improve survival rate, attenuate neuroinflammation, astrocyte and microglial activation, neuronal injury and mitochondrial dysfunction in juvenile SAE rat model, making it a potential therapeutic candidate in treating paediatric SAE.