bluuebunny/crossref_metadata_2025 huggingface dataset:
A Gender-Affirming Approach to Contraceptive Care for Transgender and Gender-Diverse Patients
Authors: Costescu Dustin , Massarella Carys , Powers William J. , Singh Sukhbir S.
Published: May 2024

Transgender and gender-diverse (TGD) reproductive health care is a field with an abundance of misinformation and a paucity of quality literature available for both health care professionals and their patients. Clinicians often receive limited education and training in this area, and TGD individuals face many barriers to reproductive health care, including the lack of gender-affirming, inclusive, and knowledgeable clinicians as well as concerns about gender biases. As such, TGD individuals often feel uncomfortable discussing their reproductive health with their health care professionals and are deterred from seeking the appropriate care they need. Contraceptive counseling is a key component of reproductive health care but is often neglected in discussions between TGD patients and their health care professionals. Clinicians must strive to meet the contraceptive health care needs and desires of TGD patients in a gender-affirming manner within a safe and accepting space. Here, we summarize the current reproductive health care landscape and provide contemporary perspectives on how to improve contraceptive care for TGD individuals.
An Evaluation of the Performance, Patient Acceptability, and Feasibility of a Point-of-Care HIV-Syphilis Assay in an Urban Emergency Department
Authors: Maliszewski Kendall N. , Hsieh Yu-Hsiang , Curbeam Deanna , Rizkallah Ann , Perez Danielle A. , Dashler Gaby , Ricketts Erin P. , Rompalo Anne M. , Gaydos Charlotte A. , Manabe Yukari C. , Melendez Johan , Rothman Richard E.
Published: May 2024

Background

Point-of-care (POC) tests for sexually transmitted infections (STIs) permit delivery of results during the patient's emergency department (ED) encounter. We evaluated performance, patient acceptability, and feasibility of a new duplex POC test, Chembio Dual Path Platform HIV-Syphilis Assay, in an urban ED setting.

Methods

Convenience sampling approach prioritizing those considered at increased risk for an STI and/or with a history of HIV. For the performance evaluation, participants were tested for HIV/syphilis with the Chembio POC assay and the reference laboratory tests; sensitivity and specificity were determined. For the patient acceptability evaluation, participants completed pre- and post-user surveys. For the feasibility evaluation, ED clinical technicians completed a survey evaluating their perceptions regarding feasibility of use of this POC test.

Results

A total of 327 patients were consented and enrolled. The diagnostic sensitivity and specificity of the Chembio POC assay for HIV were 96.5% (95% confidence interval [CI], 90.1%–99.3%) and 99.6% (95% CI, 97.7%–100.0%), respectively, and for syphilis, the values were 93.9% (95% CI, 85.0%–98.3%) and 99.6% (95% CI, 97.9%–100.0%), respectively. Regarding patient acceptability, 87% trusted the result, and 93% reported that they were more likely to seek treatment if they received a positive STI test result in the ED rather than after the ED visit. Regarding feasibility, 90% of the technicians reported that they would recommend using the test in EDs.

Conclusions

The Chembio Dual Path Platform HIV-Syphilis POC Assay had excellent performance characteristics when evaluated in an ED population, as well as high perceived acceptability from patients, and feasibility for ED use from clinical technicians. The test may have utility for HIV-syphilis screening among high-risk ED patients.
The Shifting Face of Aesthetic Care: A Systematic Survey of Independent Medical Spa Directorship and Practitioner Trends in Florida
Authors: Soares Danny J. , Bowhay Alexis , Fakhre Fadia , Hynes Stephanie D. , Lee Alina , Yi Christina H.
Published: May 2024

Background:

The rapid proliferation of medical spas (med spas) in the United States has raised concerns over the continued shift of nonsurgical aesthetic treatments away from traditional core specialty integration and supervision, potentially affecting surgical treatment guidance and education of cosmetic surgery patients. The authors assessed trends in the growth of independent med spa facilities as well as practitioner supervision, licensing, and specialization in the state of Florida.

Methods:

The authors performed a comprehensive, statewide survey of all independent med spas in Florida by municipality using online business search engines. Information gathered included the number of locations, business stakeholders, and director or practitioner licensing and certification obtained from the Florida Division of Corporations or Department of Health databases and respective medical boards.

Results:

A total of 1038 med spas were identified, revealing a 100% increase in number relative to 2021 estimates. Nonphysician practitioners represented 84% of med spa providers, with core specialty medical director supervision present in only 22% of facilities and a large proportion of directors lacking specialty training (77%) or board certification (42%). In addition, 25% of med spas appeared to disregard state guidelines pertaining to medical directorship, autonomous nonphysician practice, and numeric or geographic restrictions on directorship, with 96% of facilities lacking licensing or registration with Florida’s Agency for Health Care Administration.

Conclusions:

Med spa growth in Florida has been explosive, with continued departure from core supervision, increasingly limited specialty training and integration, and nonadherence to state guidelines. Enhanced regulation and integrated nonphysician practitioner training are likely necessary to ensure patient safety and the cohesive practice of aesthetic medicine and surgery.
Outcomes of Centrally versus Laterally Based Tarsoconjunctival Pedicle Flap Reconstruction for Large, Full-Thickness Lower Eyelid Defects
Authors: Gur Zvi , Chan Alison , Ting Michelle , Alameddine Ramzi , Liu Catherine Y. , Korn Bobby S. , Kikkawa Don O.
Published: May 2024

Background:

The purpose of this study was to compare the outcomes of 2 types of tarsoconjunctival pedicle flaps for reconstruction of large lower eyelid defects.

Methods:

The authors performed a retrospective medical record review of consecutive patients who underwent centrally or laterally based tarsoconjunctival pedicle transconjunctival flap for lower eyelid reconstruction for defects greater than 50% of the lid margin. Full-thickness skin grafts were used for anterior lamellar reconstruction in all cases. The primary outcome measure was eyelid position, function, and satisfactory appearance.

Results:

A total of 43 patients were identified. Twenty-six patients underwent reconstruction with a centrally based tarsoconjunctival pedicle flap; 17 patients underwent reconstruction with a laterally based tarsoconjunctival pedicle flap. The average size of the lid defect was 77.7% (range, 50% to 100%) in the central group and 75% (range, 50% to 100%) in the lateral group (P = 0.604). Mean follow-up time was 61.5 weeks in the central group and 46.6 weeks in the lateral group (P = 0.765). After division of the flap and during follow-up, 27% of the centrally based group required revisional surgery, versus none in the laterally based group (P = 0.03). All the patients with centrally based flaps required second-stage flap division, whereas only 52% of patients with a laterally based flap underwent second-stage flap division (P < 0.001).

Conclusion:

For reconstruction of large lower lid defects requiring lid-sharing procedures, centrally and laterally based procedures had equivalent functional outcome, but the laterally based group had less need for revisional procedures and may not need a second-stage division of the flap.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Disappearance of “Elongated Pony Tail Sign” Following Chemoradiotherapy in a Case of Primary Cerebellopontine Angle Ependymoma With Spinal Drop Metastasis: 18F-FDG PET/CT Scan Findings
Authors: Krishna Sarin , Ashwathanaryana Abhiram G. , Mishra Rakesh Kumar , Asrani Shubham , Dewangan Vinita
Published: May 2024

Ependymomas are rare glial tumors that commonly arise from the lining cells of ventricular system and constitute ~10% of intracranial pediatric malignancies. The incidence of ependymoma in adults is rare. Due to close approximation with the ventricular system, subtentorial ependymomas are more prone to show cerebrospinal fluid metastasis compared with supratentorial ependymomas. We present a case of subtentorial cerebellopontine angle ependymoma with diffuse spinal drop metastases showing “elongated pony tail appearance” in a 69-year-old man with complete metabolic response on 18F-FDG PET/CT imaging following chemoradiotherapy.
Child-Patient Perspective on Results After Correction of Sagittal Synostosis and the Difference Between Child-Patient and Parent’s Perspectives
Authors: Kurniawan Melissa S.I.C , Kamst Nathalie W. , Mathijssen Irene M.J. , Erler Nicole S. , van Veelen Marie-Lise C.
Published: May 2024

Objective:

This study assesses the level of child-patient satisfaction with the surgical result after scaphocephaly correction and the difference between child-patient and parents' perspectives.

Methods:

A questionnaire was sent out to children between 6 and 18 years old with isolated sagittal synostosis, who had undergone either a frontobiparietal remodeling or extended strip craniotomy, and separately to their parents.

Results:

The questionnaire was completed by 96 patients, 81.2% of the patients considered their head to be similar or slightly different from others. Despite the majority being satisfied with the outcome, 33% would change the shape of their head if they could. Patients who underwent extended strip craniotomy wanted to change the back of their head more often (P = 0.002), whereas patients who underwent frontobiparietal remodeling wanted to change their forehead (P = 0.005). The patients’ own perspective on head shape was independent of the cephalic index (CI). However, patients with a relatively narrow CI received more remarks from others about their heads (P = 0.038). Parent and child agreement was 49.7% on average. Differences between child-patients and parents were found in reporting adaptive behavior.

Conclusion:

The majority of patients were satisfied with the outcome of their intervention. The child’s perspective seems to be a valuable addition to evaluate sagittal synostosis surgery as it is independent of the CI and differentiates between different surgical techniques. In addition, the patient’s perspective is comparable to the parent’s perspective, but gives more details on adaptive behavior.
VACTERL Association in Patients With Metopic Synostosis: Is There a Link?
Authors: Deek Roland , Moore Mark
Published: May 2024

VACTERL association is diagnosed based on the non-random co-occurrence of at least 3 out of 6 congenital malformations. The prevalence is thought to be less than 1 in 10,000 to 1 in 40,000. There is no known link between VACTERL association and metopic synostosis in the literature. There were 122 operated cases of metopic synostosis at our institution from 1999 to 2023, with a 2.3:1 male-to-female ratio. The authors describe the co-occurrence of VACTERL association and metopic synostosis in 3 female patients with no identifiable genetic variants. Given that VACTERL association is a diagnosis of exclusion, other rare syndromes were considered but ultimately excluded. This suggests that the co-occurrence of VACTERL association and metopic synostosis is a potentially rare finding, and underlying pathogenic variants are yet to be identified.
Beyond surviving: A scoping review of collaborative care models to inform the future of postdischarge trauma care
Authors: Ilkhani Saba , Comrie Cameron E. , Pinkes Nathaniel , Zier Carolyn L. , Gaudino Shonali G. , Slavin Mary D. , Kazis Lewis E. , Ryan Colleen M. , Schneider Jeffrey C. , Livingston David H. , Salim Ali , Anderson Geoffrey A. , Herrera-Escobar Juan P.
Published: May 2024

Trauma centers demonstrate an impressive ability to save lives, as reflected by inpatient survival rates of more than 95% in the United States. Nevertheless, we fail to allocate sufficient effort and resources to ensure that survivors and their families receive the necessary care and support after leaving the trauma center. The objective of this scoping review is to systematically map the research on collaborative care models that have been put forward to improve trauma survivorship. Of 833 articles screened, we included 16 studies evaluating eight collaborative care programs, predominantly in the United States. The majority of the programs offered care coordination and averaged 9 months in duration. Three fourths of the programs incorporated a mental health provider within their primary team. Observed outcomes were diverse: some models showed increased engagement (e.g., Center for Trauma Survivorship, trauma quality-of-life follow-up clinic), while others presented mixed mental health outcomes and varied results on pain and health care utilization. The findings of this study indicate that collaborative interventions may be effective in mental health screening, posttraumatic stress disorder and depression management, effective referrals, and improving patient satisfaction with care. A consensus on core elements and cost-effectiveness of collaborative care models is necessary to set the standard for comprehensive care in posttrauma recovery.
Resuscitation for injured patients requiring massive transfusion: A personal perspective
Authors: Lucas Charles E.
Published: May 2024

The past century has seen many advances in the field of resuscitation. This is particularly true in the subset of patients who sustain major injuries causing hemorrhagic shock (HS) and require massive transfusion of more than 10 U of blood within the first 24 hours. Controversies on how best to resuscitate these patients include the role of fresh whole blood, stored whole blood, fresh frozen plasma, platelets, colloid solutions, balanced electrolytes solution, vasopressors, and diuretics. This review summarizes the often-contradictory recommendations observed and studied by a single trauma surgeon working in a busy urban acute care center for 65 years.

LEVEL OF EVIDENCE

Level I.
Eye movements reveal age differences in how arousal modulates saliency priority but not attention processing speed
Authors: Kim Andy Jeesu , Nguyen Kristine , Mather Mara
Published: May 2024

The arousal-biased competition theory posits that inducing arousal increases attentional priority of salient stimuli while reducing priority of non-pertinent stimuli. However, unlike in young adults, older adults rarely exhibit shifts in priority under increased arousal, and prior studies have proposed different neural mechanisms to explain how arousal differentially modulates selective attention in older adults. Therefore, we investigated how the threat of unpredictable shock differentially modulates attentional control mechanisms in young and older adults by observing eye movements. Participants completed two oculomotor search tasks in which the salient distractor was typically captured by attention (singleton search) or proactively suppressed (feature search). We found that arousal did not modulate attentional priority for any stimulus among older adults nor affect the speed of attention processing in either age group. Furthermore, we observed that arousal modulated pupil sizes and found a correlation between evoked pupil responses and oculomotor function. Our findings suggest age differences in how the locus coeruleus-noradrenaline system interacts with neural networks of attention and oculomotor function.
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

Traumatic 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

Introduction

Glioma 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.

Objective

We 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.

Methods

This 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).

Results

The 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.

Conclusion

This 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 Points

White 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

Fluorescence-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

Introduction

Globally, 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.

Methodology

A 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 findings

The 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.

Conclusions

The 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.

Recommendation

There 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

Background

There 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.

Methods

A 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.

Results

The 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.

Conclusion

Accessibility 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

Background

Elevations 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).

Methods

Troponin 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.

Results

Total 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).

Conclusions

In 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.

Registration

URL:https://www.clinicaltrials.gov; Unique identifier:NCT06000930

Clinical Perspective

What 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

During 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 Statement

Here, 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

Understanding 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

Background

In 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.

Methods

A 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.

Results

The 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.

Conclusion

The 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

Long-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

The 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.
The SAVED domain of the type III CRISPR protease CalpL is a ring nuclease
Authors: Binder Sophie C. , Schneberger Niels , Engeser Marianne , Geyer Matthias , Rouillon Christophe , Hagelueken Gregor
Published: May 2024

Prokaryotic CRISPR-Cas immune systems detect and cleave foreign nucleic acids. In type III CRISPR-Cas systems, the Cas10 subunit of the activated recognition complex synthesizes cyclic oligoadenylates (cOAs), second messengers that activate downstream ancillary effector proteins. Once the viral attack has been weathered, elimination of extant cOA is essential to limit the antiviral response and to allow cellular recovery. Various families of ring nucleases have been identified, specializing in the degradation of cOAs either as standalone enzymes or as domains of effector proteins. Here we describe the ring nuclease activity inherent in the SAVED domain of the cA4-activated CRISPR Lon protease CalpL. We characterize the kinetics of cA4cleavage and identify key catalytic residues. We demonstrate that cA4-incuced oligomerization of CalpL is essential not only for activation of the protease, but is also required for nuclease activity. Further, the nuclease activity of CalpL poses a limitation to the protease reaction, indicating a mechanism for regulation of the CalpL/T/S signaling cascade. This work is the first demonstration of a catalytic SAVED domain and gives new insights into the dynamics of transcriptional adaption in CRISPR defense systems which are not aimed at abortive infection but rather at a reversible adaption to phage attack.
Cortex Folding by Combined Progenitor Expansion and Adhesion-Controlled Neuronal Migration
Authors: Chun Seung Hee , Diaz Almeida D. Santiago , Ivilinov Todorov Mihail , Straub Tobias , Ruff Tobias , Shao Wei , Yang Jianjun , Seyit-Bremer Gönül , Shen Yi-Ru , Ertürk Ali , del Toro Daniel , Shi Songhai , Klein Rüdiger
Published: May 2024

Folding of the mammalian cerebral cortex into sulcal fissures and gyral peaks is the result of complex processes that are incompletely understood. Previously we showed that genetic deletion of Flrt1/3 adhesion molecules causes folding of the smooth mouse cortex into sulci resulting from increased lateral dispersion and faster neuron migration, without progenitor expansion. Here, we find that combining theFlrt1/3double knockout with an additional genetic deletion that causes progenitor expansion, greatly enhances cortex folding. Expansion of intermediate progenitors by deletion of Cep83 results in enhanced formation of sulci. Expansion of apical progenitors by deletion of Fgf10 results in enhanced formation of gyri. Single cell transcriptomics and simulations suggest that changes in adhesive properties of cortical neurons, their proportions and densities in the cortical plate, combined with lateral dispersion during their radial migration are important folding parameters. These results identify key developmental mechanisms that cooperate to promote cortical gyrification.

HIGHLIGHTS

Cortex folding is enhanced by combining progenitor expansion and divergent migration.

Concomitant expansion of intermediate progenitors results in the formation of sulci

Concomitant expansion of apical progenitors results in the formation of gyri

Progenitors differentially affect cortical neurons with distinct adhesive properties
Succession of bacteria and archaea within the soil micro-food web
Authors: Tamang Mandip , Sikorski Johannes , van Bommel Miriam , Piecha Marc , Urich Tim , Ruess Liliane , Huber Katharina , Neumann-Schaal Meina , Pester Michael
Published: May 2024

Bacterivorous nematodes represent numerically abundant bacterial grazers in the soil micro-food web. Their trophic regulation shapes the soil microbiome, but the underlying population dynamics of bacteria and archaea are poorly understood. Here, we followed bulk soil respiration and time-resolved population dynamics (32 days) of bacterial and archaeal species in response to top-down control by a common bacterivorous soil nematode,Acrobeloides buetschlii, bottom-up control by resource amendment via maize litter as well as the combination of both. Addition of maize litter significantly increased soil respiration rates, while bacterivorous nematodes shifted the maximum rate of soil respiration from day 12 to day 6. Underlying bacterial and archaeal abundance changes could be separated into five major response types, dominating in different top-down and bottom-up control scenarios. Individual microbial species switched between response types depending on the different scenarios. In-depth analysis of these differential abundance patterns revealed a broad feeding behavior forA. buetschliion dominating populations of gram-negative bacteria (Acidobacteriota, Bacteroidota, Gemmatimonatoda, Pseudomonadota) and ammonia-oxidizing archaea (Nitrososphaerota), while discriminating against dominant populations of gram-positive bacteria (Actinobacteriota, Bacillota). Combined bottom-up control by maize litter and top-down control by nematode grazing caused a succession of soil microbiota, which was driven by population changes first in theBacteroidota, then in thePseudomonadota, and last in theAcidobacteriotaandNitrososphaerota. This mechanistic understanding of nematode grazing on soil microbiota population dynamics is essential to inform predictive models of the soil food web.
Data-driven analysis identifies female-specific social modulation deficit after chronic social defeat stress
Authors: Schuler Heike , Eid Rand S. , Wu Serena , Tse Yiu-Chung , Cvetkovska Vedrana , Lopez Joëlle , Quinn Rosalie , Zhou Delong , Meccia Juliet , Dion-Albert Laurence , Menard Caroline , Bennett Shannon N. , Peña Catherine J. , Bagot Rosemary C.
Published: May 2024

Background

Chronic social defeat stress is a widely used depression model in male mice. Several proposed adaptations extend this model to females with variable, often marginal effects. We examine the if widely used male-defined metrics of stress are suboptimal in females and reveal sex-specific adaptations.

Methods

Using a data-driven method we comprehensively classified social interaction behavior in 761 male and female mice after chronic social witness/defeat stress, examining social modulation of behavioral frequencies and associations with conventional metrics (i.e., social interaction (SI) ratio).

Results

Social stress induces distinct behavioral adaptation patterns in males and females. SI ratio leads to underpowered analyses in females with limited utility to differentiate susceptibility/resilience. Data-driven analyses reveal failure of social adaptation in stressed female mice that is captured in attenuated velocity change from no target to target tests (ΔVelocity) and validate this in three female social stress models. Combining SI ratio and ΔVelocity optimally differentiates susceptibility/ resilience in females and this metric reveals resilient-specific adaptation in a resilience-associated neural circuit in female mice.

Conclusions

We demonstrate that psychological or physical social defeat stress induces similar deficits in females that is qualitatively distinct from male deficits and inadequately sampled by male-defined metrics. We identify modulation of locomotion as a robust and easily implementable metric for rigorous research in female mice. Overall, our findings highlight the need to critically evaluate sex differences in behavior and implement sex-based considerations in preclinical model design.