bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timed sulfonylurea modulation improves locomotor and sensory dysfunction following spinal cord injury
Authors: Xu Guo-Ying , Maskey Manjit , Wu Zizhen , Yang Qing 
Published: May 2024

AbstractTraumatic injury to the spinal cord (SCI) results in immediate necrosis and delayed secondary expansion of neurological damage, often resulting in lifelong paralysis, neurosensory dysfunction, and chronic pain. Progress hemorrhagic necrosis (PHN) and excessive excitation are the primary sources of neural injury triggered by various insults, causing neuronal cytotoxicity and the gradual enlargement of lesions. Recent approaches have involved blocking TRPM4, a contributor to PHN, using the sulfonylurea (SUR) subunits regulator glibenclamide. However, since SUR subunits are expressed in both neurons and glial cells in the spinal cord and sensory neurons, forming functional KATPchannels, the use of glibenclamide can exacerbate the development of SCI-induced chronic pain. In this study, we explored a treatment strategy involving the administration of glibenclamide, which suppresses PHN, and diazoxide, which protects against neuronal excitation and inflammation, at different time intervals post-SCI. Our goal is to determine whether this approach significantly enhances both sensory and motor function. Contusive SCI was induced at spinal segment T10 in adult male and female rats. Immunostaining, electrophysiological recordingin vitro, spectrophotometric assay, Western blot, and behavioral tests were performed to detect the outcomes. Results showed that the timed application of glibenclamide and diazoxide at various post-SCI time points significantly improved locomotor function and mitigated the development of SCI-induced chronic pain. These preclinical studies introduce a promising treatment strategy for addressing SCI-induced dysfunction.
Preoperative Brain Mapping Predicts Language Outcomes after Eloquent Tumor Resection
Authors: Muir Matthew , Noll Kyle , Prinsloo Sarah , Michener Hayley , Traylor Jeffrey I. , Kumar Vinodh A. , Ene Chibawanye I. , Ferguson Sherise , Weinberg Jeffrey S. , Lang Frederick , Taylor Brian A. , Forkel Stephanie J. , Prabhu Sujit S. 
Published: May 2024

AbstractIntroductionGlioma patients with tumors near critical language regions present significant clinical challenges. Surgeons often lack the tools to understand how each unique surgical approach may impact linguistic ability, leading to subjective decisions and unpredictable outcomes.ObjectiveWe aim to develop an approach that uses data-driven preoperative brain mapping to quantitatively predict the impact of planned resections on long-term language function.MethodsThis study included 79 consecutive patients undergoing resection of language-eloquent gliomas. Patients underwent preoperative navigated transcranial magnetic stimulation (nTMS) language mapping to identify language-positive sites (“TMS points”) and their associated white matter tracts (“TMS tracts”) as well as formal language evaluations pre and postoperatively. The resection of regions identified by preoperative mapping was correlated with persistent postoperative language deficits (PLDs).ResultsThe resection of TMS points did not predict PLDs. However, a TMS point subgroup defined by white matter connectivity significantly predicted PLDs (OR=8.74, p<.01) and exhibited a canonical group-level anatomical distribution of cortical language sites. TMS-derived tracts recapitulated normative group-level patterns of white matter connectivity defined by the Human Connectome Project (HCP). Subcortical resection of TMS tracts predicted PLDs independently of cortical resection (OR=60, p<.001). The resected TMS tract segments in patients with PLDs co-localized with normative, language-associated subcortical pathways, in contrast to the resected TMS tract segments in non-aphasic patients (p<.05). Accordingly, resecting patient- specific co-localizations between TMS tracts and normative tracts in native space predicted PLDs with an accuracy of 94% (OR=134, p<.001). Co-localization between individualized and normative tracts precisely predicted the linguistic performance of a patient intraoperatively in response to direct electrophysiological stimulation of subcortical brain.ConclusionThis study outlines a data-driven brain mapping approach that provides surgical insight by preoperatively predicting the impact of individual glioma resection on long-term language function.Key PointsWhite matter connectivity determines the long-term functionality of cortical language sites mapped by TMS.Long-term deficits in language processing result from resecting individualized subcortical regions within language-associated white matter tracts.Non-invasive TMS language mapping combined with routine preoperative imaging can predict language outcomes of individual surgical approaches with an accuracy of 94%.
Polymer-tethered quenched fluorescent probes for enhanced imaging of tumor associated proteases
Authors: Hadzima Martin , Faucher Franco , Blažková Kristýna , Yim Joshua J. , Guerra Matteo , Chen Shiyu , Woods Emily C. , Park Ki Wan , Šácha Pavel , Šubr Vladimír , Kostka Libor , Etrych Tomáš , Majer Pavel , Konvalinka Jan , Bogyo Matthew 
Published: May 2024

ABSTRACTFluorescence-based contrast agents enable real-time detection of solid tumors and their neovasculature, making them ideal for use in image-guided surgery. Several agents have entered late-stage clinical trials or secured FDA approval, suggesting they are likely to become standard of care in cancer surgeries. One of the key parameters to optimize in contrast agent is molecular size, which dictates much of the pharmacokinetic and pharmacodynamic properties of the agent. Here, we describe the development of a class of protease-activated quenched fluorescent probes in which a N-(2-hydroxypropyl)methacrylamide copolymer is used as the primary scaffold. This copolymer core provides a high degree of probe modularity to generate structures that cannot be achieved with small molecules and peptide probes. We used a previously validated cathepsin substrate and evaluated the effects of length and type of linker as well as positioning of the fluorophore/quencher pair on the polymer core. We found that the polymeric probes could be optimized to achieve increased over-all signal and tumor-to-background ratios compared to the reference small molecule probe. Our results also revealed multiple structure-activity relationship trends that can be used to design and optimize future optical imaging probes. Furthermore, they confirm that a hydrophilic polymer is an ideal scaffold for use in optical imaging contrast probes, allowing a highly modular design that enables efficient optimization to maximize probe accumulation and overall biodistribution properties.
Factors associated with utilization of preconception Sickle cell screening among women receiving antenatal care at Hoima regional referral hospital, Uganda
Authors: Kyakuha Solomon , Scovia Mbabazi G. , Mugenyi Nathan , Twineamatsiko Andrew 
Published: May 2024

AbstractIntroductionGlobally, it is estimated that over 300,000 babies are born with Sickle cell disease annually, yet the uptake of preconception sickle cell screening services is at 25% among the total population that become pregnant every year. In Uganda, about 20,000 babies are born annually but with a low utilization rate of Pre-Conception Sickle cell screening services among women at 11%. This study aimed at determining the utilization rate and factors associated with preconception sickle cell screening among pregnant women attending antenatal care at Hoima regional referral hospital, Uganda.MethodologyA hospital-based cross-section study was done, systematic sampling used, and participants subjected to a semi-structured questionnaire. 334 participants were recruited, and data was collected, entered into Epidata, and analyzed using STATA version 14.Study findingsThe utilization rate of Pre-Conception Sickle cell screening services among women receiving Ante Natal Care was at 11.4%. There was a significant association between woman’s level of education, marital status, partners support and knowledge towards Pre-Conception Sickle cell screening services.ConclusionsThe utilization rate of Pre-Conception Sickle cell screening services is low with level of education, marital status, and having familial history of sickle cell disease, partner support and awareness being significant associated factors.RecommendationThere is need to empower women to attain a formal education through adult literacy programs, massive sensitization and conducting regular health talks regarding Pre-Conception Sickle cell screening services.
Assessment of Accessibility, Availability, and Need of Cardiac Care at Primary Health Care Centres in Vadodara District of India: The CardioGram Pilot Project
Authors: Rao Shirish , Rudra Ujjaini , Arora Anoushka , Majumdar Sumanta , Gandhi Murtaza , Darooka Naitica , Motiwalla Zahra , Asri Sucharu , Shah Urmil , Shah Devarsh , Patil Dhrumil , Shah Eesha , Saksena Katya , Shah Priyansh , Bhatt Ami , Zadey Siddhesh 
Published: May 2024

AbstractBackgroundThere has been an increase in the burden of Cardiovascular Diseases (CVD), especially in rural India. Integrating screening and treatment for CVDs at the primary healthcare level has now become a necessity. Hence, this study was conducted to assess the accessibility, availability, and need for cardiac care with a special focus on ECG at Primary Healthcare Centers (PHC) in the Vadodara district of Gujarat.MethodsA cross-sectional pilot study was carried out in 34 PHCs of the Vadodara District of Gujarat, India between January to March 2022. Data regarding the accessibility of PHC, distance from the nearest Tertiary Health Centre (THC), availability of ECG, drugs, treatment protocols, competency of staff, and burden of CVD, hypertension, and diabetes was collected by interviewing the medical officer of the PHC. Distances were measured in kilometers (km) and Travel times were measured in minutes (min). Descriptive analysis was performed using MS Excel.ResultsThe average distance to reach a PHC, a Tertiary Care Center, and a Cardiac Care Center (CCC) is 14.8km, 37.1 km, and 55.5km, respectively, which accounts for 22.59 minutes, 62.3 minutes, and 85.5 minutes. Moreover, only 58% of the surveyed PHCs have the availability of ECGs, with a lesser percentage of healthcare workers(HCWs) who knew how to operate and/or read an ECG. 44.11% of the surveyed PHCs had functional ECGs and employed them where indicated. Most of the CVD cases were referred to higher centers. Six PHCs had an urgent need for ECG deployment.ConclusionAccessibility and availability of cardiac care services, especially ECGs is poor in PHCs of Vadodara district. There is an urgent need not only for services but also for efficient training of medical officers for performing, interpreting as well as managing cases of acute myocardial infarction.
Cardiac Troponin Fragmentation After Heavy Physical Exercise The MaraCat2 Study
Authors: Airaksinen K. E. Juhani , Paana Tuomas , Hellman Tapio , Vasankari Tuija , Salonen Selma , Tuominen Tuulia , Teppo Konsta , Jaakkola Samuli , Heinonen Olli J. , Wittfooth Saara 
Published: May 2024

AbstractBackgroundElevations of commercial cardiac troponin T (total cTnT) levels are common after strenuous exercise, but there is limited information on whether the troponin composition differs from myocardial infarction (MI).MethodsTroponin composition was analyzed in heparin plasma samples taken from 45 runners <1 h after marathon race and from 45 patients with Type 1 MI <12 h after the pain onset. The concentration of long molecular forms of cTnT (long cTnT) was measured with a novel upconversion luminescence assay, total cTnT was measured with a commercial high-sensitivity cTnT assay, and the ratio of long to total cTnT (troponin ratio) was determined.ResultsTotal cTnT exceeded the upper reference limit (>14 ng/l) in 37 (82%) runners. The median total and long cTnT concentrations and the troponin ratio were higher (113 ng/l vs. 25 ng/l, 57 ng/l vs. 4.1 ng/l, and 0.36 vs. 0.17, respectively) in patients with MI than in marathon runners (p <0.001 for all comparisons). Troponin ratio decreased (r = -0.497, p <0.001) in marathon runners and increased (r = 0.466, p = 0.001) in patients with MI with increasing troponin release. In the receiver operating characteristics curve analyses of all subjects with cTnT release >14ng/l and those with 15-100 ng/l, long cTnT showed good predictive power with the area under the curve 0.969 (CI95% 0.939-1.000) and 0.937 (95% CI, 0.877–0.996) in discriminating marathon runners from MI patients. The respective values for total cTnT were 0.892 (CI95% 0.823-0.960) and 0.778 (95% CI, 0.656–0.901).ConclusionsIn contrast to Type 1 MI, after strenuous exercise only a small fraction of circulating cTnT exists as intact cTnT or long molecular fragments. The difference in troponin composition could be of diagnostic value when evaluating post-exercise cTnT elevations in subjects with chest complaints.RegistrationURL:https://www.clinicaltrials.gov; Unique identifier:NCT06000930Clinical PerspectiveWhat Is New?Short cardiac troponin T (cTnT) fragments were the predominant form of cTnT release after marathon race among 45 runners in contrast to 45 patients with Type 1 myocardial infarction (MI) where intact cTnT and longer fragments are more commonly found in the circulation during the early hours after the attack also in patients with comparable troponin levels.The proportion of short cTnT components decreased (r = -0.497, p <0.001) in marathon runners and increased (r = 0.466, p = 0.001) in patients with MI with increasing troponin release.What Are the Clinical Implications?The principle of the novel immunoassay could be applied on automated platforms to allow implementation in clinical care and separate benign cTnT elevations after strenuous exercise from those of acute MI in a single sample with better accuracy than the commercial high-sensitivity cTnT test.
Versican controlled by Lmx1b regulates hyaluronate density and hydration for semicircular canal morphogenesis
Authors: Mori Yusuke , Smith Sierra , Wang Jiacheng , Munjal Akankshi 
Published: May 2024

AbstractDuring inner ear semicircular canal morphogenesis in zebrafish, patterned canal-genesis zones express genes for extracellular matrix component synthesis. These include hyaluronan and the hyaluronan-binding chondroitin sulfate proteoglycan Versican, which are abundant in the matrices of many developing organs. Charged hyaluronate polymers play a key role in canal morphogenesis through osmotic swelling. However, the developmental factor(s) that control the synthesis of the matrix components and regulation of hyaluronate density and swelling are unknown. Here, we identify the transcription factor, Lmx1b, as a positive transcriptional regulator of hyaluronan, Versican, and chondroitin synthesis genes crucial for canal morphogenesis. We show that Versican regulates hyaluronan density through its protein core, whereas the charged chondroitin side chains contribute to the osmotic swelling of hyaluronate. Versican-tuned properties of hyaluronate matrices may be a broadly used mechanism in morphogenesis with important implications for understanding diseases where these matrices are impaired, and for hydrogel engineering for tissue regeneration.Summary StatementHere, we reveal the function of the hyaluronan-binding proteoglycan, Versican, and its chondroitin sulfate side chains in tuning the density and hydration of the hyaluronate-rich ECM to generate force, under the control of the transcription factor Lmx1b for successful inner ear semicircular canal morphogenesis in zebrafish.
Topological data analysis of pattern formation of human induced pluripotent stem cell colonies
Authors: Hartsock Iryna , Park Eunbi , Toppen Jack , Bubenik Peter , Dimitrova Elena S. , Kemp Melissa L. , Cruz Daniel A. 
Published: May 2024

ABSTRACTUnderstanding the multicellular organization of stem cells is vital for determining the mechanisms that coordinate cell fate decision-making during differentiation; these mechanisms range from neighbor-to-neighbor communication to tissue-level biochemical gradients. Current methods for quantifying multicellular patterning cannot capture the spatial properties of cell colonies across all scales and typically rely on human annotation ora prioriselection of parameters. We present a computational pipeline that utilizes topological data analysis to generate quantitative, multiscale descriptors which capture the shape of data extracted from multichannel microscopy images. By applying our pipeline to certain stem cell colonies, we detected subtle differences in patterning that reflect distinct biological markers and progressive stages of differentiation. These results yield insight into directed cellular movement and morphogen-mediated, neighbor-to-neighbor signaling. Because of its broad applicability to immunofluorescence microscopy images, our pipeline is well-positioned to serve as a general-purpose tool for the quantitative study of multicellular pattern formation.
Determinants of COVID-19 data quality in the District Health Information Management System version 2 in Ahafo Region, Ghana
Authors: Aabebe Felix Gumaayiri , Adjei-Gyamfi Silas , Asobuno Clotilda , Badieko Samuel Malogae , Kuubabongnaa Blaise Bagyliku , Boakye-Boateng Samuel Kwabena , Aoki Tsunoneri , Aiga Hirotsugu 
Published: May 2024

AbstractBackgroundIn ensuring public health efforts in combating pandemics such as coronavirus disease 2019 (COVID-19), transparent data reporting that is of high quality and easily accessible is crucial for tracking epidemic progress and making informed decisions. In Ghana, no published studies have been conducted to evaluate the quality of COVID-19 data submitted onto the national web-based platform, District Health Information Management System version 2 (DHIMS-2) during the COVID-19 period. In this regard, this study seeks to assess the estimates and determinants of COVID-19 data quality in the DHIMS-2 in the Ahafo region of Ghana.MethodsA facility-based cross-sectional study design was employed, with a desk review of COVID-19 records in DHIMS-2 and primary data sources (registers and monthly reporting forms). This study involved all 23 different levels of healthcare facilities that reported on COVID-19 in the Ahafo region from March 2020 to December 2022. We assessed COVID-19 data quality using three dimensions of completeness, accuracy, and timeliness according to the World Health Organization data quality guide. Mixed-effect logistic regression was then employed to identify the determinants of COVID-19 data quality at a 95% confidence interval.ResultsThe overall COVID-19 data quality was estimated at 35.9% (95%CI=32.6%, 39.4%) while the rate of the data dimensions of timeliness, completeness, and accuracy were 50.2% (95%CI=46.7%, 53.8%), 50.6% (95%CI=47.1%, 54.2%), and 72.4% (95%CI=69.1%, 75.5%) respectively. It was found that the availability of a functional data validation team at the health facilities (AOR=18.3; 95%CI=1.62, 20.7; p= 0.019), training of data managers in COVID-19 data management (AOR=9.37; 95%CI=2.56, 34.3; p=0.001), and data managers with two-year professional training (certificate background) (AOR=3.42; 95%CI=1.95, 12.2; p=0.025) were independently associated with COVID-19 data quality.ConclusionThe overall COVID-19 data quality in the Ahafo region was quite poor. Dimensionally, while the rate of data timeliness was high, that of data completeness, and accuracy were relatively low. The interaction of the independent correlates of COVID-19 data quality requires the healthcare system to identify stringent measures to strengthen the health information system to enhance planning and decision-making, especially during disease outbreaks.
Pharmacological HDAC3 inhibition alters memory updating in young and old mice
Authors: Smies Chad W. , Bellfy Lauren , Wright Destiny S. , Bennetts Sofia S. , Urban Mark W. , Brunswick Chad A. , Shu Guanhua , Kwapis Janine L. 
Published: May 2024

AbstractLong-term memories are not stored in a stable state but must be flexible and dynamic to maintain relevance in response to new information. Existing memories are thought to be updated through the process of reconsolidation, in which memory retrieval initiates destabilization and updating to incorporate new information. Memory updating is impaired in old age, yet little is known about the mechanisms that go awry. One potential mechanism is the repressive histone deacetylase 3 (HDAC3), which is a powerful negative regulator of memory formation that contributes to age-related impairments in memory formation. Here, we tested whether HDAC3 also contributes to age-related impairments in memory updating using the Objects in Updated Locations (OUL) paradigm. We show that blocking HDAC3 immediately after updating with the pharmacological inhibitor RGFP966 ameliorated age-related impairments in memory updating in 18-m.o. mice. Surprisingly, we found that post-update HDAC3 inhibition in young (3-m.o.) mice had no effect on memory updating but instead impaired memory for the original information, suggesting that the original and updated information may compete for expression at test and HDAC3 helps regulate which information is expressed. To test this idea, we next assessed whether HDAC3 inhibition would improve memory updating in young mice given a weak, subthreshold update. Consistent with our hypothesis, we found that HDAC3 blockade strengthened the subthreshold update without impairing memory for the original information, enabling balanced expression of the original and updated information. Together, this research suggests that HDAC3 may contribute to age-related impairments in memory updating and may regulate the strength of a memory update in young mice, shifting the balance between the original and updated information at test.
Murine trypanosomiasis recapitulates transcriptomic features of acute kidney injury
Authors: Ogunsola John , Cooper Anneli , Quintana Juan F. , MacLeod Annette 
Published: May 2024

AbstractThe African trypanosome,Trypanosoma brucei,disseminates systemically in tissues of the infected host resulting in complex immunopathology. The kidneys which are important in the response to the anaemia characteristic of African trypanosomiasis, are prone to acute kidney injury (AKI) from multiple noxious stimuli. Little is known about the transcriptional responses of the kidney to trypanosome infection. To assess the tissue-specific response to infection withTrypanosoma brucei, we profiled the clinicopathologic and transcriptional responses of the kidney in BALB/C (susceptible) and C57BL/6 (tolerant) murine models, at early (7 dpi) and late (21 dpi) time points of infection. Trypanosomes in the renal interstitium, tubular necrosis and inflammation characterised early infection in both mouse strains. By late infection, we observed extensive tubular necrosis in the susceptible BALB/C but reparative tubular regeneration in the tolerant C57BL/6 mice.T.b. bruceiinfection resulted in significant increases in serum creatinine in both strains. Consistent with the clinicopathologic findings, RNA-seq detected both mouse strain- and time-dependent transcriptional responses in the kidney. These included perturbations in genes associated with solute/ion transport, upregulation of markers of tubular injury, hypoxia, glycolysis, and a profound inflammatory and immune response, mirroring the responses observed in other models of AKI. Differential tissue pathology at late time point is preceded by expansion of CD8+T cells, profound expression of transcription factors and upregulation of anti-inflammatory pathways in C57BL/6 mice. Our findings demonstrate that experimentalT. bruceiinfection-induced kidney injury (TIKI) is a model of AKI and may have clinical implications for Human African Trypanosomiasis cases, who currently are not routinely screened for markers of kidney function.