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Sperm cryopreservation and biobanking are emerging as tools for supporting genetic management of small and threatened populations in amphibian conservation programs. However, there is little to no evidence demonstrating reproductive maturity and viability of offspring generated with cryopreserved sperm, potentially limiting widespread integration of these technologies. The purpose of this report is to demonstrate that amphibian sperm can be cryopreserved and thawed to successfully produce individuals of an F1 generation that can reach adulthood and reproductive maturity, to generating viable gametes and an F2 generation. Species-specific exogenous hormones were administered to both F0 and F1 adults to stimulate spermiation and oviposition in the eastern tiger salamander (Ambystoma tigrinum), dusky gopher frog (Lithobates sevosa), and Puerto Rican crested toad (Peltophryne lemur). Sperm cells collected non-lethally from F0 adults were cryopreserved, thawed, and used for in vitro fertilization (IVF) to produce F1 offspring. Individuals of the F1 generation are shown to reach adulthood, express viable gametes, and produce offspring through facilitated breeding, or IVF. The production of amphibian F2 generations shown here demonstrates that amphibian sperm collected non-lethally can be banked and used to generate reproductively viable animals of subsequent generations, thus maintaining valuable genetic linages and diversity in threatened amphibian species. The incredible value that cryopreservation of sperm has for long-term genetic management aids in the sustainability of both in situ and ex situ conservation efforts for this taxon.

Simple Summary: Assisted reproductive technologies are key components in augmenting captive breeding programs for at-risk amphibian species. Although numerous studies show that these reproductive technologies are successful in generating offspring, there is very little research investigating the reproductive viability of those individuals. It is crucial to gain insight on the reproductive potential of offspring generated using assisted reproductive technologies when those individuals are to be used for future breeding, or wild release. We report three instances where amphibian offspring generated using a suite of assisted reproductive technologies were monitored through reproductive maturity and subsequently produced an F2 generation. Sperm cryopreservation and biobanking are emerging as tools for supporting genetic management of small and threatened populations in amphibian conservation programs. However, there is little to no evidence demonstrating reproductive maturity and viability of offspring generated with cryopreserved sperm, potentially limiting widespread integration of these technologies. The purpose of this report is to demonstrate that amphibian sperm can be cryopreserved and thawed to successfully produce individuals of an F1 generation that can reach adulthood and reproductive maturity, to generating viable gametes and an F2 generation. Species-specific exogenous hormones were administered to both F0 and F1 adults to stimulate spermiation and oviposition in the eastern tiger salamander (Ambystoma tigrinum), dusky gopher frog (Lithobates sevosa), and Puerto Rican crested toad (Peltophryne lemur). Sperm cells collected non-lethally from F0 adults were cryopreserved, thawed, and used for in vitro fertilization (IVF) to produce F1 offspring. Individuals of the F1 generation are shown to reach adulthood, express viable gametes, and produce offspring through facilitated breeding, or IVF. The production of amphibian F2 generations shown here demonstrates that amphibian sperm collected non-lethally can be banked and used to generate reproductively viable animals of subsequent generations, thus maintaining valuable genetic linages and diversity in threatened amphibian species. The incredible value that cryopreservation of sperm has for long-term genetic management aids in the sustainability of both in situ and ex situ conservation efforts for this taxon. [ABSTRACT FROM AUTHOR]

Artificial intelligence is rapidly changing our world at an exponential rate and its transformative power has extensively reached important sectors like healthcare. In the fight against cancer, AI proved to be a novel and powerful tool, offering new hope for prevention and early detection. In this review, we will comprehensively explore the medical applications of AI, including early cancer detection through pathological and imaging analysis, risk stratification, patient triage, and the development of personalized prevention approaches. However, despite the successful impact AI has contributed to, we will also discuss the myriad of challenges that we have faced so far toward optimal AI implementation. There are problems when it comes to the best way in which we can use AI systemically. Having the correct data that can be understood easily must remain one of the most significant concerns in all its uses including sharing information. Another challenge that exists is how to interpret AI models because they are too complicated for people to follow through examples used in their developments which may affect trust, especially among medical professionals. Other considerations like data privacy, algorithm bias, and equitable access to AI tools have also arisen. Finally, we will evaluate possible future directions for this promising field that highlight AI's capacity to transform preventative cancer care., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: Consent to publish has been received from all participants. Ethics approval: This is a literature review, no ethical approval is required., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This article introduces an innovative adaptation of interpersonal psychotherapy tailored to the needs of individuals identifying as gender diverse and navigating the complexities of gender transition. The few available therapeutic models designed for this population are reviewed, and the novel intervention, grounded in clinical insights and empirical research, is presented. Key components of this adaptation include expanding the interpersonal inventory with targeted processing questions and developing a disclosure timeline-a structured tool designed to guide patients through gender transition-while bolstering social support, reducing distress, and improving interpersonal effectiveness. An illustrative case vignette is included to elucidate the practical applications of this approach and to underscore essential therapeutic considerations., Competing Interests: The authors report no financial relationships with commercial interests.

Competing Interests: Declaration of competing interest None

Peripheral glia are important regulators of diverse physiologic functions yet their molecular distinctions and locations in almost all visceral organs are not well-understood. We performed a systematic analysis of peripheral glia, focusing on the lung and leveraging single cell RNA sequencing (scRNA-seq) analysis to characterize their cellular and molecular features. Using in vivo lineage studies, we characterized the anatomic, cellular, and molecular features of the Sox10+ glial lineage of the mouse lung. Using high-resolution imaging, we quantified the distribution and cellular morphologies of myelinating, non-myelinating, satellite, and terminal glial cells with their intricate extensions along peripheral nerves, including terminals at specialized neurosensory structures within the lung. Spatial analysis of selectively expressed myelinating (periaxin/Prx, claudin 19/Cldn) or non-myelinating (sodium channel/Scn7a) glial cell genes identified by scRNA-seq analysis revealed molecularly distinct populations surrounding myelinated nerve fibers in the lung. To extend this analysis to primates and other organs, we extracted rare peripheral glial cells in whole organism scRNA-seq atlases of mouse lemur and human. Our cross-species data analysis and integration of scRNA-seq data of ~700 peripheral glial cells from mouse, mouse lemur, and human glial cells identified conserved gene expression of molecularly distinct peripheral glial cell populations. This foundational knowledge facilitates subsequent functional studies targeting molecularly distinct subsets of peripheral glia and integrating them into organ-specific disorders of autonomic dysregulation. In addition, our cross-species analysis identifying conserved gene expression patterns and glial networks in extrapulmonary organs provides a valuable resource for studying the functional role of peripheral glia in multiorgan human diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hall et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Technology, distance learning, and social media have changed the landscape of physical therapy education. Modifications are needed to meet the needs of applicants and align with the current healthcare environment., Purpose: To identify the most important factors students consider when selecting a physical therapist education program., Methods: A survey including free response options was shared with physical therapist education program students by chairpersons and through student interest groups., Results: 545 responses representing 46 states and all CAPTE geographical regions were analyzed. The most important factors when selecting a program were: location (65.9%), tuition (64.8%), perception of physical therapy education quality (39.1%), and national board pass rate (34.1%). The least important factors were: technology utilization (74.3%), class size (46.1%), and national ranking/ reputation (45.1%). Also, the majority of respondents preferred in-person educational delivery (94.7%). 75.4% reported program length was not a factor in applying to a program., Conclusions: Programs should seek to meet the needs of applicants with consideration of meaningful elements in choosing a program. Students ranked "location" and "tuition" as primary considerations for choosing a program, which may be related to curtailing debt by living at home while in school. "Program quality," over "reputation/ranking," suggests the importance of a robust curriculum, which is viewed as a predictor of passing the National Physical Therapy Examination (NPTE).

Background: Valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) is quickly becoming a routine and effective means by which to treat degenerated bioprosthetic valves. A known complication of ViV-TAVI is patient-prosthesis mismatch, which substantially affects survival. Bioprosthetic valve fracture is a method by which to reduce the risk of patient-prosthesis mismatch and post-ViV-TAVI transvalvular gradients. This study sought to determine the safety and efficacy of post-ViV-TAVI bioprosthetic valve fracture., Methods: Patients with a history of surgical aortic valve replacement undergoing ViV-TAVI bioprosthetic valve fracture (N = 25) at the corresponding institution from 2015 to 2022 were cataloged for a retrospective analysis. The implanted transcatheter valves were Medtronic Evolut R, Evolut PRO, and Evolut PRO+. Gradients were assessed before and after implantation and after fracturing using transthoracic echocardiogram., Results: The mean left ventricular ejection fraction of patients who underwent fracturing was 55.04%. The average (SD) peak and mean (SD) transvalvular gradients before the intervention were 68.17 (19.09) mm Hg and 38.98 (14.37) mm Hg, respectively. After ViV-TAVI, the same gradients were reduced to 27.25 (12.27) mm Hg and 15.63 (6.47) mm Hg, respectively. After bioprosthetic valve fracture, the gradients further decreased to 17.59 (7.93) mm Hg and 8.860 (3.334) mm Hg, respectively. The average reduction in peak gradient associated with fracturing was 12.07 mm Hg (95% CI, 5.73-18.41 mm Hg; P = .001). The average reduction in mean gradient associated with valve fracturing was 6.97 mm Hg (95% CI, 3.99-9.74 mm Hg; P < .001)., Conclusion: Bioprosthetic valve fracture is a viable option for reducing residual transvalvular gradients after ViV-TAVI and should be considered in patients with elevated gradients (>20 mm Hg) or with concern for patient-prosthesis mismatch in patients who have an unacceptable risk for a redo sternotomy and surgical aortic valve replacement., Competing Interests: Conflict of Interest Disclosure: The authors report no financial relationships or conflicts of interest regarding the content herein., (© 2024 The Authors. Published by The Texas Heart Institute®.)

Introduction: Patients with metastatic colorectal cancer (mCRC) often require multidisciplinary interventions due to the diversity of symptoms. Palliative treatment offers benefits including improved quality of life, yet sociodemographic disparities influence its utilization. This study aims to characterize these disparities in palliative treatment use among mCRC patients., Methods: Utilizing data from the National Cancer Database, we identified patients diagnosed with mCRC between 2016 and 2020. Patients were categorized by metastatic site: peritoneal, liver, lung, or bone/brain/lymph node. Palliative treatment rates were compared across metastatic sites as well as patient and hospital factors., Results: A total of 106,241 patients were identified as having mCRC, with 19,208 (18.08%) receiving palliative treatment; 24.0% of patients with multiple metastatic disease and 14.0% of those with solely peritoneal metastases (PM) utilized palliative treatment (p < 0.001). Furthermore, patients over 75 years of age had a significantly decreased likelihood of receiving palliative treatment compared with younger patients (p = 0.0002). Hispanic patients did not differ significantly from non-Hispanic White populations (p = 0.47). Those in the highest education quartile demonstrated a higher degree of palliative treatment use compared with the lowest education quartile (p = 0.0081)., Conclusion: Among patients with mCRC, those with multiple sites of metastatic disease tend to receive higher rates of palliative treatment compared with those with oligometastatic disease. Patients with PM had the lowest rate of receiving palliative treatment. Other determinates of utilizing palliative treatment include younger age groups and higher education. Further research is warranted to understand the patterns of disparities in palliative treatment use among mCRC patients., Competing Interests: Disclosures: Shaina Sedighim, Rhami Khorfan, Jordan Shin, Aaqil Khan, Yixuan Irene Tang, Amy Y. Li, Maheswari Senthil, Michael P. O’Leary, and Oliver S. Eng have no relevant conflicts of interest to declare that may be relevant to the contents of this study., (© 2024. Society of Surgical Oncology.)

Activation of microglia, the resident immune cells of the central nervous system, leading to the subsequent release of pro-inflammatory cytokines, has been linked to cardiac remodeling, autonomic disbalance, and cognitive deficits in heart failure (HF). While previous studies emphasized the role of hippocampal Angiotensin II (AngII) signaling in HF-induced microglial activation, unanswered mechanistic questions persist. Evidence suggests significant interactions between microglia and local microvasculature, potentially affecting blood-brain barrier integrity and cerebral blood flow regulation. Still, whether the microglial-vascular interface is affected in the brain during HF remains unknown. Using a well-established ischemic HF rat model, we demonstrate the increased abundance of vessel-associated microglia (VAM) in HF rat hippocampi, along with an increased expression of AngII AT1a receptors. Acute AngII administration to sham rats induced microglia recruitment to brain capillaries, along with increased expression of TNFα. Conversely, administering an AT1aR blocker to HF rats prevented the recruitment of microglia to blood vessels, normalizing their levels to those in healthy rats. These results highlight the critical importance of a rather understudied phenomenon (i.e., microglia-vascular interactions in the brain) in the context of the pathophysiology of a highly prevalent cardiovascular disease, and unveil novel potential therapeutic avenues aimed at mitigating neuroinflammation in cardiovascular diseases., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Illuminating the precise stepwise genetic programs directing cardiac development provides insights into the mechanisms of congenital heart disease and strategies for cardiac regenerative therapies. Here, we integrate in vitro and in vivo human single-cell multi-omic studies with high-throughput functional genomic screening to reveal dynamic, cardiac-specific gene regulatory networks (GRNs) and transcriptional regulators during human cardiomyocyte development. Interrogating developmental trajectories reconstructed from single-cell data unexpectedly reveal divergent cardiomyocyte lineages with distinct gene programs based on developmental signaling pathways. High-throughput functional genomic screens identify key transcription factors from inferred GRNs that are functionally relevant for cardiomyocyte lineages derived from each pathway. Notably, we discover a critical heat shock transcription factor 1 (HSF1)-mediated cardiometabolic GRN controlling cardiac mitochondrial/metabolic function and cell survival, also observed in fetal human cardiomyocytes. Overall, these multi-modal genomic studies enable the systematic discovery and validation of coordinated GRNs and transcriptional regulators controlling the development of distinct human cardiomyocyte populations., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Efficient DNA double strand break (DSB) repair is necessary for genomic stability and determines efficacy of DNA damaging cancer therapeutics. Spatiotemporal dynamics and post-translational modifications of repair proteins at DSBs dictate repair efficacy. Here, we identified a non-canonical function of GCN5 in regulating both HR and NHEJ repair post genotoxic stress. Mechanistically, genotoxic stress induced GCN5 recruitment to DSBs. GCN5 PARylation by PARP1 was essential for its recruitment, acetyltransferase activity and DSB repair function. Liquid chromatography-mass spectrometry (LC-MS) identified DNA-PKcs as part of GCN5 interactome. In-vitro acetyltransferase assays revealed that GCN5 acetylates DNA-PKcs at K3241 residue, a prerequisite for DNA-PKcs S2056 phosphorylation and DSB recruitment. Alongside, ChIP-qPCR revealed GCN5 mediates transcription of PRKDC via H3K27Ac acetylation in its promoter region (- 710 to - 554). Genetic perturbation of GCN5 also decreased CHEK1, NBN1, TP53BP1, POL-L transcription and abrogated ATM, BRCA1 activation. Accordingly, GCN5 loss led to persistent ɣ-H2AX foci formation, compromised in-vivo HR-NHEJ and caused GBM radio-sensitization. Importantly, PARP1 inhibition phenocopied GCN5 loss. Together, this study identifies an untraversed DSB repair function of GCN5 and provides mechanistic insights into transcriptional as well as post-translational regulation of pivotal HR-NHEJ factors. Alongside, it highlights the translational importance of PARP1-GCN5 axis in mediating GBM radio-resistance., (© 2024. The Author(s).)

Organ procurement organizations (OPOs) face increasing regulatory scrutiny, and the performance of predictive models used to assess OPO performance is critical. We sought to determine whether adding deceased donor physiological and critical care data to the existing Scientific Registry of Transplant Recipients (SRTR) heart yield model would improve the model's performance. Donor data and heart transplanted (yes/no), the outcome of interest, were obtained from the United Network for Organ Sharing Donor Management Goal (DMG) Registry for 19 141 donors after brain death, from 25 OPOs. The data were split into training and testing portions. Multivariable LASSO regression was used to develop a statistical model incorporating DMG data elements with the existing components of the SRTR model. The DMG + SRTR and SRTR models were applied to the test data to compare the predictive performance of the models. The sensitivity (84%-86%) and specificity (84%-86%) were higher for the DMG + SRTR model compared to the SRTR model (71%-75% and 76%-77%, respectively). For the DMG + SRTR model, the C-statistic was 0.92 to 0.93 compared to 0.80 to 0.81 for the SRTR model. DMG data elements improve the predictive performance of the heart yield model. The addition of DMG data elements to the Organ Procurement and Transplantation Network data collection requirements should be considered., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Published by Elsevier Inc.)

Cutaneous plaques and squamous cell carcinoma (SCC) are common in captive North American snow leopards (SLs) ( Panthera uncia ). Our objective was to determine whether these lesions are potentially associated with papillomavirus(es). Polymerase chain reaction (PCR) was performed on 3 cutaneous plaques using degenerate primers for papillomaviruses. A putatively novel papillomavirus was identified that shared 76% sequence identity to Felis catus papillomavirus 2 . Specific PCR for this virus was performed on 5 cutaneous SCC samples and 7 normal skin samples, which were all positive. In situ hybridization for this putatively novel virus was performed, which revealed strong hybridization signals within hyperplastic cells in cutaneous plaques (n = 3) and within neoplastic cells in cutaneous SCC samples (n = 5). No hybridization signals were identified within normal skin. Ultimately, identification of a causal viral agent in the development of plaques and SCC in SLs will help guide therapeutic intervention and lay the foundation for development of prophylactic vaccines., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.