bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurobiological mechanisms of electroconvulsive therapy for depression: Insights into hippocampal volumetric increases from clinical and preclinical studies
Authors: Abe Yoshifumi , Erchinger Vera J. , Ousdal Olga Therese , Oltedal Leif , Tanaka Kenji F. , Takamiya Akihiro
Published: January 2024

Depression is a highly prevalent and disabling psychiatric disorder. The hippocampus, which plays a central role in mood regulation and memory, has received considerable attention in depression research. Electroconvulsive therapy (ECT) is the most effective treatment for severe pharmacotherapy‐resistant depression. Although the working mechanism of ECT remains unclear, recent magnetic resonance imaging (MRI) studies have consistently reported increased hippocampal volumes following ECT. The clinical implications of these volumetric increases and the specific cellular and molecular significance are not yet fully understood. This narrative review brings together evidence from animal models and human studies to provide a detailed examination of hippocampal volumetric increases following ECT. In particular, our preclinical MRI research using a mouse model is consistent with human findings, demonstrating a marked increase in hippocampal volume following ECT. Notable changes were observed in the ventral hippocampal CA1 region, including dendritic growth and increased synaptic density at excitatory synapses. Interestingly, inhibition of neurogenesis did not affect the ECT‐related hippocampal volumetric increases detected on MRI. However, it remains unclear whether these histological and volumetric changes would be correlated with the clinical effect of ECT. Hence, future research on the relationships between cellular changes, ECT‐related brain volumetric changes, and antidepressant effect could benefit from a bidirectional translational approach that integrates human and animal models. Such translational research may provide important insights into the mechanisms and potential biomarkers associated with ECT‐induced hippocampal volumetric changes, thereby advancing our understanding of ECT for the treatment of depression.

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‘It's very values driven’: A qualitative systematic review of the meaning of compassion according to healthcare professionals
Authors: Marshman Cameron , Allen Jacqui , Ling Debbie , Brand Gabrielle
Published: January 2024

Aims and Objectives

To explore the meaning ascribed to the concept of compassion by healthcare professionals.

Background

Compassion is universally regarded as the foundation of healthcare, a core value of healthcare organisations, and essential to the provision of quality care. Despite increasing research on compassion in healthcare, how healthcare professionals understand compassion remains unclear.

Design

A systematic review of qualitative studies was conducted and is reported following PRISMA guidelines.

Method

Medline, Emcare, PsychINFO and CINAHL were searched to November 2021 for qualitative studies in English that explored healthcare professionals' understandings of compassion. Included studies were appraised for quality before data were extracted and thematically analysed.

Findings

Seventeen papers met the inclusion criteria. An overarching theme, ‘It's very values driven’ underpins the four main themes identified: (1) ‘It's about people and working with them’: Compassion as being human, (2) ‘There is this feeling’: Compassion as being present, (3) ‘If I don't understand them, I won't be able to help’: Compassion as understanding, (4) ‘Wanting to help in some way’: Compassion as action.

Conclusions

Healthcare professional participants reported compassion as motivated by values and inherent to humanistic healthcare practice. The meanings healthcare professions described were varied and contextual. Qualitative research should further explore healthcare practitioners' experiences of compassion as part of their practice to inform health professions education, policy, and practice.

Relevance to Clinical Practice

To practice with compassion, healthcare professionals require supportive and humanistic organisations that honour each person's humanity and encourage people to be human and compassionate to each other as well as to patients, their families and/or carers.

Healthcare professionals need to reflect on what compassion means to them, how it is situated within their unique practice context, and how compassion can enhance clinical practice.

No Patient or Public Contribution

This systematic review had no patient or public contribution.
Comparison of force profiles from two musculoskeletal palpation methods: A methodological study
Authors: Pillai Rajath Sasidharan , Kothari Simple Futarmal , Svensson Peter , Castrillon Eduardo
Published: January 2024

Background

The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) protocol recommends a 5 s and 1 kg force dynamic palpation around the lateral condylar pole of the temporomandibular joint. However, the accuracy and precision of the generated force are not known.

Objective

To assess and compare the force profiles generated from dynamic palpation manually and using a palpometer, based on the forces and time recommendations suggested by the DC/TMD protocol.

Methods

Nineteen healthy adults applied forces of 0.5 kg, 1.0 kg and 2.0 kg on a calibrated force sensor in a circular motion within target times of 2 s and 5 s. Participants used their right index finger for manual palpation and a calibrated palpometer for device‐assisted palpation. Ten repetitions of each target force at both target times were applied. Time taken to complete each application was recorded. Repeated measures analysis of variance was used for analysis of accuracy measured as the relative difference between targeted force and actual force values and precision measured as the coefficient of variation (CV) within the 10 repeated measurements.

Results

Accuracy was significantly lower (better) and precision higher (lower CV) with the palpometer than with manual palpation (p < .001). There were significant differences in accuracy and precision between the different forces but not palpation times. Most participants could not achieve the target times and tended to be faster, irrespective of the palpation method (p > .063).

Conclusion

A palpometer is a more accurate and precise palpation method for dynamic force assessment compared to manual palpation; however, it remains difficult to standardize the palpation duration.
Substance Use Screening, Brief Intervention, and Referral to Treatment in Urban Settings: Barriers and Facilitators to Implementation With Minoritized Youth
Authors: Fisher Sycarah , Benner Kalea , Huang Hannah , Day Elizabeth
Published: January 2024

Background

Substance use in minoritized youth is associated with negative long‐term health and life outcomes. The present study explores perspectives of school stakeholders at urban minority‐serving schools regarding integration of an evidence‐based intervention, screening, brief intervention, and referral to treatment (SBIRT) into existing school prevention models.

Methods

Twenty‐two participants were interviewed using the Consolidated Framework for Implementation Research to identify barriers and facilitators to SBIRT implementation. Qualitative data were transcribed, coded, and analyzed.

Results

Four major themes related to barriers to SBIRT implementation included: lack of training, unclear role expectations, student confidentiality, and punitive school climates. The 3 major facilitators included: the feasibility of the intervention, its fit within multi‐tiered systems of support, and the districts increasing collaboration with community mental health providers. These major themes along with other minor themes are discussed.

Implications for School Health Policy, Practice, and Equity

SBIRT implementation within low‐income, minority‐serving schools may reduce substance use disparities among minoritized youth, improving health and life outcomes. Recommendations addressed training, school climate, and student engagement, highlighting a collaborative and supportive approach involving all stakeholders.

Conclusions

While SBIRT implementation has barriers and facilitators, overall, school staff were optimistic about implementation. In light of these findings, additional research should embed SBIRT in these settings.
Unravelling the mystery of endemic versus translocated populations of the endangered Australian lungfish (Neoceratodus forsteri)
Authors: Biello Roberto , Ghirotto Silvia , Schmidt Daniel J. , Fuselli Silvia , Roberts David T. , Espinoza Tom , Hughes Jane M. , Bertorelle Giorgio
Published: January 2024

The Australian lungfish is a primitive and endangered representative of the subclass Dipnoi. The distribution of this species is limited to south‐east Queensland, with some populations considered endemic and others possibly descending from translocations in the late nineteenth century shortly after European discovery. Attempts to resolve the historical distribution of this species have met with conflicting results based on descriptive genetic studies. Understanding if all populations are endemic or some are the result of, or influenced by, translocation events, has implications for conservation management. In this work, we analysed the genetic variation at three types of markers (mtDNA genomes, 11 STRs and 5196 nuclear SNPs) using the approximate Bayesian computation (ABC) algorithm to compare several demographic models. We postulated different contributions of Mary River and Burnett River gene pools into the Brisbane River and North Pine River populations, related to documented translocation events. We ran the analysis for each marker type separately, and we also estimated the posterior probabilities of the models combining the markers. Nuclear SNPs have the highest power to correctly identify the true model among the simulated datasets (where the model was known), but different marker types typically provided similar answers. The most supported demographic model able to explain the real dataset implies that an endemic gene pool is still present in the Brisbane and North Pine Rivers and coexists with the gene pools derived from past documented translocation events. These results support the view that ABC modelling can be useful to reconstruct complex historical translocation events with contemporary implications, and will inform ongoing conservation efforts for the endangered and iconic Australian lungfish.
Retinal vascular dynamics: A window for observing an irregular heartbeat. A case report
Authors: Heitmar Rebekka , Kirchhoff Paulus , Blann Andrew , Kotliar Konstantin
Published: January 2024

Objective

We aimed to characterize several aspects of retinal vascular dynamics in a patient with arrythmia in order to elicit additional diagnostic information on microvascular dysfunction.

Methods

A 68‐year‐old male patient with arrythmia and an age‐ and gender‐matched control subject underwent ocular examination including dynamic retinal vessel assessment with flicker light provocation. Retinal vessel diameters were measured continuously following a standard protocol (IMEDOS Systems, Jena, Germany). The data were evaluated using methods of signal analysis.

Results

Retinal vessel response following flicker provocation as well as local structural and functional behavior of retinal vessels were comparable between both individuals. The arrhythmia case demonstrated irregular arterial and venous heart rate (HR) pulsation with an average frequency of 1 Hz. Moreover, the case showed a higher magnitude and larger periods of low‐frequency retinal vessel oscillations as well as lower periodicity of both HR pulsations and low‐frequency vasomotions.

Conclusions

Besides numerical examination of irregular HR pulsations in case of arrhythmia, from the direct noninvasive assessment of retinal vessel dynamics one can derive more detailed information on microvascular function including the whole spectrum of retinal arterial and venous pulsations and vasomotions. This may have implications for health screening not limited to atrial fibrillation.
Myopericytoma of the mouth floor: The diagnostic and therapeutic challenge—A case report and literature review
Authors: Hamdy Omar , Mahmoud Aya , Attia Samar , Megahed Nirmeen , Elged Basma , Mansour Manar , Awny Shadi , Ezat Mohamed
Published: January 2024

Myopericytoma is defined as a rare benign myxoid tumour that is usually found in distal extremities. However, it may rarely affect the oral cavity. Few cases of oral myopericytoma were reported in the literature. A 56‐year‐old female patient presented with a mouth floor lesion. A wedge biopsy performed from the lesion revealed an atypical round cell proliferation, which may be plasmablastic lymphoma or plasmacytoma. Post‐contrast neck MRI described a well‐defined lobulated lesion at the right sublingual region measuring 14 × 21 mm. Transoral wide local excision of the ulcer was performed, and reconstruction of the defect was done using an inferiorly‐based nasolabial flap. Microscopic examination of the excised swelling revealed a tumour proliferation formed of bland‐looking spindle cells alternating with fibroblasts and intervening vascular spaces. No detected mitosis or necrosis in the examined material. IHC staining of the tumour cells was positive for Caldesmon and alpha smooth muscle actin, while Ki67 was positive in 3% of cellularity. Desmin, ALK, B‐catenin, ERG, CD31, and CD138 showed a negative reaction. This led to the diagnosis of bland spindle cell proliferation suggestive of oral myopericytoma with free all surgical margins. Myoepricytoma is a rare benign tumour that rarely affects the oral cavity. Surgical excision is the mainstay of treatment. Local flaps constitute a good choice for the reconstruction of the resection defect.
Dynamic Anterior Stabilization with Hill‐Sachs Remplissage Can be Employed in Skeletally Immature Patients—Operative Technique
Authors: Neculau Diana‐Cosmina , Avram George Mihai , Simion Cosmin , Predescu Vlad , Obada Bogdan , Popescu Ion‐Andrei
Published: January 2024

Background

Numerous studies indicate that glenoid bony augmentation raises the risk of complications during and after surgery. On the other hand, repairing the labrum alone in cases with subcritical glenoid bone loss results in recurrent instability and persistent apprehension. As a result, recent advancements in shoulder instability surgery prioritize fully restoring the anterior shoulder restraint.

Operative Technique

A novel method for treating recurrent anterior shoulder instability with subcritical glenoid bone loss and off‐track Hill‐Sachs lesion in skeletally immature patients is suggested: the use of dynamic anterior stabilization technique incorporating the long head of the biceps tendon onto the anterior glenoid rim via trans‐subscapular transfer, in conjunction with Hill‐Sachs remplissage. A practical, step‐by‐step surgical technique for a complete reconstruction of the anterior capsule‐labral‐ligamentous complex is provided. This involves utilizing a soft‐tissue dynamic anterior sling, achieved through the trans‐subscapularis transfer of the long head of the biceps tendon at the glenoid level. The procedure concludes with a Hill‐Sachs remplissage to further prevent off‐track events and alleviate apprehension.

Conclusion

Dynamic anterior stabilization is a suitable approach for addressing recurring anterior shoulder instability in skeletally immature patients who have subcritical glenoid bone loss and bipolar bone lesions.
Contact allergy to subcutaneous implantable cardioverter defibrillator in a child with Brugada syndrome
Authors: Ciriello Giovanni Domenico , Colonna Diego , Correra Anna , Romeo Emanuele , Russo Maria Giovanna , Sarubbi Berardo
Published: January 2024

Allergic reactions to components of cardiac implantable electronic devices are rare and often go undiagnosed, which can lead to a misdiagnosis of device infection. Contact allergy to subcutaneous implantable cardioverter defibrillator (S‐ICD) is extremely rare. In this report, we present a case of cobalt‐related contact allergy in a pediatric patient with Brugada syndrome who underwent S‐ICD implantation.
Evaluation of the use of chamomile in isolation and in association with laser photobiomodulation in the healing of rats oral mucosa
Authors: Fortuna Tila , Dantas Juliana Borges , Santana Rejane Conceição , Della Cella Hortência Resende , de Jesus Campos Elisângela , Martins Gabriela Botelho
Published: January 2024

Laser photobiomodulation (LPBM) has been shown to be one of the possible modulating agents of inflammation. Similarly, medicinal plants, such as chamomile (Matricaria recutita) are also used with the same purpose. To evaluate tissue repair in the dorsum of the tongue of rats under topical use of chamomile alone and in association with LPBM. Seventy‐five male Wistar rats received a standardized wound on the dorsum of the tongue and were allocated into experimental groups: Control (G1), Chamomile Fluid extract (G2), Chamomile Infusion (G3), Laser (G4), Chamomile Infusion + Laser (G5). Euthanasia was done on days 3, 7, and 14 after surgery. Ulcers were evaluated and measured with a caliper. Sections stained with hematoxylin and eosin and Picrosirius Red allowed evaluation of edema, inflammatory infiltrate, cellularity, and re‐epithelialization and characterization of total collagen. Histomorphometric analysis of the percentage of total collagen, the distance from the basal layer to the epithelial surface, and the thickness of the stratum corneum were performed. The G2 and G4 groups modulated the exudative and proliferative phases of inflammation, both clinically and histologically. The G3 and G5 groups did not show significant differences in relation to the G1 group in most of the evaluated parameters. Chamomile fluid extract and LPBM alone showed better clinical and histological responses for tissue repair than the association between these therapeutic modalities. There were differences in the parameters of clinical, histological, and histomorphometric patterns between the experimental groups of the present investigation. The LPBM proved to be superior in the performed analysis.
Daniel Billy et al v Australia (Torres Strait Islanders Petition): Climate change inaction as a human rights violation
Authors: Lentner Gabriel M. , Cenin Weronika
Published: January 2024

This case note analyses in detail the decision of the United Nations Human Rights Committee (HRComm) in Daniel Billy et al v Australia. The decision concerned a communication brought by members of an indigenous peoples' group from the Torres Strait Islands in the state of Queensland, Australia. The applicants claimed that their human rights had been violated as a result of the State's failure to take mitigation and adaptation measures to combat the effects of climate change. The HRComm's finding of a violation of the applicants' human rights deserves a closer look, as it has broader implications for future climate change‐related human rights litigation. While the HRComm missed the opportunity to consider the State's human rights obligations concerning climate change mitigation, this decision represents an important milestone in climate change litigation, as it confirms a State's obligation to protect a community from adverse climate change effects and recognises the specific vulnerabilities of indigenous peoples and their cultures to its impacts.
Safety and efficacy of blood flow restriction exercise in individuals with neurological disorders: A systematic review
Authors: Jønsson Anette Bach , Krogh Søren , Laursen Henrik Sehested , Aagaard Per , Kasch Helge , Nielsen Jørgen Feldbæk
Published: January 2024

Objectives

This systematic review evaluated the safety and efficacy of blood flow restriction exercise (BFRE) on skeletal muscle size, strength, and functional performance in individuals with neurological disorders (ND).

Methods

A literature search was performed in PubMed, CINAHL, and Embase. Two researchers independently assessed eligibility and performed data extraction and quality assessments. Eligibility criteria: Study populations with ND, BFRE as intervention modality, outcome measures related to safety or efficacy.

Results

Out of 443 studies identified, 16 were deemed eligible for review. Three studies examined the efficacy and safety of BFRE, one study focused on efficacy results, and 12 studies investigated safety. Disease populations included spinal cord injury (SCI), inclusion body myositis (sIBM), multiple sclerosis (MS), Parkinson's disease (PD), and stroke. A moderate‐to‐high risk of bias was presented in the quality assessment. Five studies reported safety concerns, including acutely elevated pain and rating of perceived exertion levels, severe fatigue, muscle soreness, and cases of autonomic dysreflexia. Two RCTs reported a significant between‐group difference in physical function outcomes, and two RCTs reported neuromuscular adaptations.

Conclusion

BFRE seems to be a potentially safe and effective training modality in individuals with ND. However, the results should be interpreted cautiously due to limited quality and number of studies, small sample sizes, and a general lack of heterogeneity within and between the examined patient cohorts.
Determination of the clinical relevance of donor epitope‐specific HLA‐antibodies in kidney transplantation
Authors: Kardol‐Hoefnagel Tineke , Senejohnny Danial Mohammadi , Kamburova Elena G. , Wisse Bram W. , Reteig Leon , Gruijters Maartje L. , Joosten Irma , Allebes Wil A. , van der Meer Arnold , Hilbrands Luuk B. , Baas Marije C. , Spierings Eric , Hack Cornelis E. , van Reekum Franka E. , van Zuilen Arjan D. , Verhaar Marianne C. , Bots Michiel L. , Drop Adriaan C. A. D. , Plaisier Loes , Melchers Rowena C. A. , Seelen Marc A. J. , Sanders Jan Stephan , Hepkema Bouke G. , Lambeck Annechien J. A. , Bungener Laura B. , Roozendaal Caroline , Tilanus Marcel G. J. , Voorter Christina E. , Wieten Lotte , van Duijnhoven Elly M. , Gelens Mariëlle A. C. J. , Christiaans Maarten H. L. , van Ittersum Frans J. , Nurmohamed Shaikh A. , Lardy Neubury M. , Swelsen Wendy , van der Pant Karlijn A. M. I. , van der Weerd Neelke C. , ten Berge Ineke J. M. , Hoitsma Andries , van der Boog Paul J. M. , de Fijter Johan W. , Betjes Michiel G. H. , Roelen Dave L. , Claas Frans H. , Bemelman Frederike J. , Senev Aleksandar , Naesens Maarten , Heidt Sebastiaan , Otten Henny G.
Published: January 2024

In kidney transplantation, survival rates are still partly impaired due to the deleterious effects of donor specific HLA antibodies (DSA). However, not all luminex‐defined DSA appear to be clinically relevant. Further analysis of DSA recognizing polymorphic amino acid configurations, called eplets or functional epitopes, might improve the discrimination between clinically relevant vs. irrelevant HLA antibodies. To evaluate which donor epitope‐specific HLA antibodies (DESAs) are clinically important in kidney graft survival, relevant and irrelevant DESAs were discerned in a Dutch cohort of 4690 patients using Kaplan–Meier analysis and tested in a cox proportional hazard (CPH) model including nonimmunological variables. Pre‐transplant DESAs were detected in 439 patients (9.4%). The presence of certain clinically relevant DESAs was significantly associated with increased risk on graft loss in deceased donor transplantations (p < 0.0001). The antibodies recognized six epitopes of HLA Class I, 3 of HLA‐DR, and 1 of HLA‐DQ, and most antibodies were directed to HLA‐B (47%). Fifty‐three patients (69.7%) had DESA against one donor epitope (range 1–5). Long‐term graft survival rate in patients with clinically relevant DESA was 32%, rendering DESA a superior parameter to classical DSA (60%). In the CPH model, the hazard ratio (95% CI) of clinically relevant DESAs was 2.45 (1.84–3.25) in deceased donation, and 2.22 (1.25–3.95) in living donation. In conclusion, the developed model shows the deleterious effect of clinically relevant DESAs on graft outcome which outperformed traditional DSA‐based risk analysis on antigen level.
Locked out? Navigating the geographies of precarity on Britain's waterways
Authors: Herman Agatha , Yarwood Richard
Published: January 2024

Motivations for living on the UK's waterways range from lifestyle to financial, but increasing numbers have been pushed aboard in response to current, and longstanding, cost‐of‐living and housing crises. However, while more affordable than living on land, our qualitative investigation reveals a diversity of practices and experiences of marginalisation on the waterways, drawing out the impacts of temporal and spatial fluidity to inform our understanding of precarity in a mobile world. The waterways are a contested and politicised space with diverse actors seeking to delineate legitimate practices and users. Liveaboard boaters practice residential subjectivities in what others designate as leisure spaces. Resistance to such powerful claims to the waterways is not necessarily chosen or active and yet has become implicit to boaters' everyday practices. The mobility and liminality offered by boat living, experienced by some as a chosen freedom and others as a restrictive imposition, presents opportunities for resistance to powerful interests but also social marginalisation and stigmatisation. Through a focus on moorings, we highlight the legal and spatial grey areas regularly inhabited by all boaters. In seemingly secure marinas, we expose a hidden world of housing precarity with residential boaters' living in the shadows of these leisure‐designed spaces, resulting in no stability, security or statutory rights. For boaters out on the waterways, precarity continued, albeit with different manifestations. Powerful local actors mobilise narratives that disembed boaters from the waterways through the absence and poor maintenance of essential facilities alongside the loss of legal, safe mooring sites. Precarity emerges as not something restricted to ‘vulnerable groups’ but an ever present ontological condition. As such it is critical to understand how individuals and communities are responding to their implicit vulnerability, and the opportunities and challenges that mobility offers to the development and practice of this agency.
Cytologic features of canine melanotroph and corticotroph pituitary adenomas
Authors: Furtado Adriana P. , DeCourcey Michelle , Miller Margaret A. , Chen Annie V. , Martin Linda G. , Guess Sarah C. , Wardrop K. Jane , de Souza Cleverson , Owen Tina J.
Published: January 2024

Background

The introduction of intraoperative cytology revolutionized neurosurgical procedures in human medicine, providing real‐time diagnostic guidance to surgeons and contributing to improved patient outcomes. In the realm of veterinary medicine, the understanding of pituitary tumors in dogs and cats remains limited due to challenges in obtaining antemortem samples of central nervous system lesions.

Objectives

The aim of this study was to describe the cytologic features of pituitary adenomas in 12 dogs that underwent hypophysectomy.

Methods

The series included nine melanotroph adenomas and three corticotroph adenomas. Definitive diagnosis was based on histopathology and immunohistochemistry.

Results

Cytologically, the adenomas had high numbers of bare nuclei and intact cells that were round to polygonal and situated individually or in small clusters. The intact cells had round to oval, eccentric nuclei with finely stippled chromatin and one to three prominent nucleoli and ample to abundant lightly basophilic to amphophilic, grainy cytoplasm with distinct borders, and variable numbers of discrete vacuoles. Mild‐to‐moderate anisocytosis and anisokaryosis, occasional binucleation, rare and atypical mitotic figures, and nuclear molding were also observed.

Conclusions

The results suggest that intraoperative cytology of canine pituitary adenomas holds promise as a valuable diagnostic tool, aiding swift differentiation from other sellar masses before histologic confirmation. Cytologic characterization of pituitary adenomas in dogs is exceptionally rare in the scientific literature, making this study one of the first to offer a comprehensive description of these cytologic features.
Association of leukergy (in vitro leukocyte aggregation) with systemic inflammation in dogs and cats (2017–2022)
Authors: Nolen‐Walston Rose D. , Stefanoski Darko , Conrado Francisco O.
Published: January 2024

Background

Leukergy is the phenomenon of aggregation of leukocytes on a peripheral blood film, and in humans, it is used as an indicator of systemic inflammation and infection.

Objectives

To assess the association of leukergy on blood film examination with biochemical and clinical evidence of systemic inflammation, infection, neoplasia, or specific organ system disease.

Methods

A case–control study using retrospective analysis (2017–2022) identified all canine and feline patients that had been presented to an academic referral center with a finding of leukergy on peripheral blood film and an equal number of species‐matched controls.

Results

A total of 127 cases (canine n = 44, feline n = 83) were identified, as well as 127 controls. Feline samples were 7.6× more likely to exhibit leukergy (0.019%) than canine (0.0025%). A positive association was noted between leukergy and higher globulin concentrations in dogs (marginal difference 0.5 mg/dL, P = .016) and cats (marginal difference 0.67 mg/dL, P = <.001). Cats with leukergy had higher WBC counts and were less likely to be diagnosed with cardiac or urinary tract disease than controls. Dogs with leukergy had lower WBC counts and were more likely to be febrile but were less likely to have urinary tract disease than controls. No association was found with neutrophil toxic change or band forms, systemic antimicrobial therapy, or signalment.

Conclusions

We conclude that there is a positive association between increased globulin concentrations and leukergy and inconsistent associations between leukergy and other markers of inflammation or infection. Leukergy is rare overall but markedly more common in cats than dogs.
Neutrophil depletion attenuates acute renal injury after exhaustive exercise in mice
Authors: Mizokami Tsubasa , Shimada Michiko , Suzuki Katsuhiko
Published: January 2024

Prolonged intense exercise induces acute renal injury; however, the precise mechanism remains unclear. We investigated the effects of neutrophil depletion in male C57BL/6J mice. Male C57BL/6J mice were divided into four groups: sedentary with control antibody; sedentary with antineutrophil antibody; exhaustive exercise with control antibody; and exhaustive exercise with antineutrophil antibody. Antineutrophil (1A8) or control antibody was administered i.p. to the mice before they ran on a treadmill. Plasma levels of creatinine and blood urea nitrogen (BUN) were measured. Renal histology was assessed 24 h after exhaustive exercise, and the concentration of kidney injury molecule (KIM)‐1 was measured using an enzyme‐linked immunosorbent assay. The expression levels of inflammatory cytokines were measured using qRT‐PCR. Furthermore, NADPH oxidase activity and the hydrogen peroxide concentration in the kidney were measured. Immediately after exhaustive exercise, plasma BUN was significantly increased, but creatinine was not. The increase in BUN after exercise was suppressed by 1A8 treatment. The pathological changes manifested as congested and swollen glomeruli and nuclear infiltration after exhaustive exercise. These changes were suppressed by treatment with the 1A8 antibodies. The KIM‐1 concentration increased after exhaustive exercise but was reduced by the 1A8 antibodies. Treatment with the 1A8 antibody also decreased exhaustive exercise‐induced inflammation and reactive oxygen species levels in the kidney. These results suggest that neutrophils contribute to exercise‐induced acute renal injury by regulating inflammation and oxidative stress.
Induced degradation of lineage-specific oncoproteins drives the therapeutic vulnerability of small cell lung cancer to PARP inhibitors
Authors: Kim Chiho , Wang Xu-Dong , Liu Zhengshuai , Hao Jianwei , Wang Shuai , Li Peng , Zi Zhenzhen , Ding Qing , Jang Seoyeon , Kim Jiwoong , Luo Yikai , Huffman Kenneth E. , Pal Choudhuri Shreoshi , del Rio Sofia , Cai Ling , Liang Han , Drapkin Benjamin J. , Minna John D. , Yu Yonghao
Published: January 2024

Although
BRCA1/2
mutations are not commonly found in small cell lung cancer (SCLC), a substantial fraction of SCLC shows clinically relevant response to PARP inhibitors (PARPis). However, the underlying mechanism(s) of PARPi sensitivity in SCLC is poorly understood. We performed quantitative proteomic analyses and identified proteomic changes that signify PARPi responses in SCLC cells. We found that the vulnerability of SCLC to PARPi could be explained by the degradation of lineage-specific oncoproteins (e.g., ASCL1). PARPi-induced activation of the E3 ligase HUWE1 mediated the ubiquitin-proteasome system (UPS)–dependent ASCL1 degradation. Although PARPi induced a general DNA damage response in SCLC cells, this signal generated a cell-specific response in ASCL1 degradation, leading to the identification of HUWE1 expression as a predictive biomarker for PARPi. Combining PARPi with agents targeting these pathways markedly improved therapeutic response in SCLC. The degradation of lineage-specific oncoproteins therefore represents a previously unidentified mechanism for PARPi efficacy in SCLC.
Single-shot digital optical fluorescence phase conjugation through forward multiple-scattering samples
Authors: Wu Tengfei , Zhang Yixuan , Blochet Baptiste , Arjmand Payvand , Berto Pascal , Guillon Marc
Published: January 2024

Aberrations and multiple scattering in biological tissues critically distort light beams into highly complex speckle patterns. In this regard, digital optical phase conjugation (DOPC) is a promising technique enabling in-depth focusing. However, DOPC becomes challenging when using fluorescent guide stars for four main reasons: the low photon budget available, the large spectral bandwidth of the fluorescent signal, the Stokes shift between the emission and the excitation wavelength, and the absence of reference beam preventing holographic measurement. Here, we demonstrate the possibility to focus a laser beam through multiple-scattering samples by measuring speckle fields in a single acquisition step with a reference-free, high-resolution wavefront sensor. By taking advantage of the large spectral bandwidth of forward multiply scattering samples, digital fluorescence phase conjugation is achieved to focus a laser beam at the excitation wavelength while measuring the broadband speckle field arising from a micrometer-sized fluorescent bead.
Co-evolution of gene transfer agents and their alphaproteobacterial hosts
Authors: Kogay Roman , Zhaxybayeva Olga
Published: January 2024

Gene transfer agents (GTAs) are enigmatic elements that resemble small viruses and are known to be produced during nutritional stress by some bacteria and archaea. The production of GTAs is regulated by quorum sensing, under which a small fraction of the population acts as GTA producers, while the rest becomes GTA recipients. In contrast to canonical viruses, GTAs cannot propagate themselves because they package pieces of the producing cell’s genome. In alphaproteobacteria, GTAs are mostly vertically inherited and reside in their hosts’ genomes for hundreds of millions of years. While GTAs’ ability to transfer genetic material within a population and their long-term preservation suggest an increased fitness of GTA-producing microbes, the associated benefits and type of selection that maintains GTAs are poorly understood. By comparing rates of evolutionary change in GTA genes to the rates in gene families abundantly present across 293 alphaproteobacterial genomes, we detected 59 gene families that likely co-evolve with GTA genes. These gene families are predominantly involved in stress response, DNA repair, and biofilm formation. We hypothesize that biofilm formation enables the physical proximity of GTA-producing cells, limiting GTA-derived benefits only to a group of closely related cells. We further conjecture that the population structure of biofilm-forming sub-populations ensures that the trait of GTA production is maintained despite the inevitable rise of “cheating” genotypes. Because release of GTA particles kills the producing cell, maintenance of GTAs is an exciting example of social evolution in a microbial population.

IMPORTANCE

Gene transfer agents (GTAs) are viruses domesticated by some archaea and bacteria as vehicles for carrying pieces of the host genome. Produced under certain environmental conditions, GTA particles can deliver DNA to neighboring, closely related cells. The function of GTAs remains uncertain. While making GTAs is suicidal for a cell, GTA-encoding genes are widespread in genomes of alphaproteobacteria. Such GTA persistence implies functional benefits but raises questions about how selection maintains this lethal trait. By showing that GTA genes co-evolve with genes involved in stress response, DNA repair, and biofilm formation, we provide support for the hypothesis that GTAs facilitate DNA exchange during the stress conditions and present a model for how GTAs persist in biofilm-forming bacterial populations despite being lethal.
Nucleolin–RNA interaction modulates rotavirus replication
Authors: Hernández-Guzmán Jey , Arias Carlos F. , López Susana , Sandoval-Jaime Carlos
Published: January 2024

Viruses rely on cellular proteins to carry out their replicative cycle. In the case of rotavirus, the involvement of cellular RNA-binding proteins during the replicative cycle is a poorly studied field. In this work, we demonstrate for the first time the interaction between nucleolin and viral RNA of rotavirus RRV. Nucleolin is a cellular protein that has a role in the metabolism of ribosomal rRNA and ribosome biogenesis, which seems to have regulatory effects on the quantity of viral particles and viral RNA copies of rotavirus RRV. Our study adds a new component to the current model of rotavirus replication, where cellular proteins can have a negative regulation on rotavirus replication.
Sudden-onset, non-traumatic large volume pneumocephalus following presentation of acute bacterial meningitis
Authors: Krez Alexandra , Malinzak Michael , Feeney Colby
Published: January 2024

A man in his 30s, with sinonasal undifferentiated carcinoma status post resection 6 years prior, presented with acute onset of fever, headache and altered mentation. The patient was diagnosed with bacteremia and meningitis due toStreptococcus pneumoniae. A standard antibiotic and corticosteroid regimen was started. Brain MRI showed an encephalocele abutting the superolateral nasopharynx mucosa. After several days of clinical improvement, the patient’s mental status and headache acutely relapsed. A CT head venogram showed a large volume pneumocephalus originating from the region of a surgical defect. Management included external ventricular drain placement followed by right pterional craniotomy with skull base packing. Skull base defects increase the risk of life-threatening conditions such as bacterial meningitis and pneumocephalus. It is crucial for clinicians to be aware of the possibility of cranial surgical defects developing years after surgery.
Compound volvulus: ileosigmoid knot
Authors: Pattanaik Sushila Kumar , Pattanaik Prasoon , Nanda Binaya Kumar
Published: January 2024

Compound volvulus, also known as ileosigmoid knot, is a rare cause of intestinal obstruction due to twisting of the small bowel around the large bowel or vice-versa. It poses a diagnostic dilemma due to the presence of features of closed-loop obstruction of both the small and large bowel. Being a surgical emergency due to the rapid progression to gangrene of involved segments leading to septicaemia, early suspicion of the disease entity, adequate resuscitation and prompt treatment are the need of the hour. Three cases encountered and managed in our setting are described here with a review of the literature.
Deep learning model for extensive smartphone-based diagnosis and triage of cataracts and multiple corneal diseases
Authors: Ueno Yuta , Oda Masahiro , Yamaguchi Takefumi , Fukuoka Hideki , Nejima Ryohei , Kitaguchi Yoshiyuki , Miyake Masahiro , Akiyama Masato , Miyata Kazunori , Kashiwagi Kenji , Maeda Naoyuki , Shimazaki Jun , Noma Hisashi , Mori Kensaku , Oshika Tetsuro
Published: January 2024

Aim

To develop an artificial intelligence (AI) algorithm that diagnoses cataracts/corneal diseases from multiple conditions using smartphone images.

Methods

This study included 6442 images that were captured using a slit-lamp microscope (6106 images) and smartphone (336 images). An AI algorithm was developed based on slit-lamp images to differentiate 36 major diseases (cataracts and corneal diseases) into 9 categories. To validate the AI model, smartphone images were used for the testing dataset. We evaluated AI performance that included sensitivity, specificity and receiver operating characteristic (ROC) curve for the diagnosis and triage of the diseases.

Results

The AI algorithm achieved an area under the ROC curve of 0.998 (95% CI, 0.992 to 0.999) for normal eyes, 0.986 (95% CI, 0.978 to 0.997) for infectious keratitis, 0.960 (95% CI, 0.925 to 0.994) for immunological keratitis, 0.987 (95% CI, 0.978 to 0.996) for cornea scars, 0.997 (95% CI, 0.992 to 1.000) for ocular surface tumours, 0.993 (95% CI, 0.984 to 1.000) for corneal deposits, 1.000 (95% CI, 1.000 to 1.000) for acute angle-closure glaucoma, 0.992 (95% CI, 0.985 to 0.999) for cataracts and 0.993 (95% CI, 0.985 to 1.000) for bullous keratopathy. The triage of referral suggestion using the smartphone images exhibited high performance, in which the sensitivity and specificity were 1.00 (95% CI, 0.478 to 1.00) and 1.00 (95% CI, 0.976 to 1.000) for ‘urgent’, 0.867 (95% CI, 0.683 to 0.962) and 1.00 (95% CI, 0.971 to 1.000) for ‘semi-urgent’, 0.853 (95% CI, 0.689 to 0.950) and 0.983 (95% CI, 0.942 to 0.998) for ‘routine’ and 1.00 (95% CI, 0.958 to 1.00) and 0.896 (95% CI, 0.797 to 0.957) for ‘observation’, respectively.

Conclusions

The AI system achieved promising performance in the diagnosis of cataracts and corneal diseases.
Prognostic value of right ventricular dyssynchrony in adults with repaired tetralogy of Fallot
Authors: Papa Andrea , Nussbaumer Clement , Goulouti Eleni , Schwitz Fabienne , Wustmann Kerstin , Tobler Daniel , Greutmann Matthias , Schwerzmann Markus
Published: January 2024

Objective

Residual sequelae after surgical repair of tetralogy of Fallot (rTOF) affect clinical outcome. We investigated the prognostic impact of right ventricular (RV) dyssynchrony in adults with rTOF years after the surgical repair.

Methods

Patients from the Swiss Adult Congenital HEart disease Registry were included. NT-proBNP levels, echocardiography, exercise testing and MRI data were collected. An offline strain analysis to quantify RV-ventricular and interventricular dyssynchrony was performed. The standard deviation of the time-to-peak shortening (TTP) of six RV segments defined the RV Dyssynchrony Index (RVDI). Maximal difference of TTP between RV and left ventricular segments defined the interventricular shortening delay (IVSD). Predictors of a composite adverse event (arrhythmias, hospitalisation for heart failure and death) were identified by multivariate Cox regression analysis. Their median values were used to create a risk score.

Results

Out of 285 included patients (mean age 34±14 years), 33 patients (12%) experienced an adverse event during a mean follow-up of 48±21 months. No correlation was found between RVDI, IVSD and clinical events. NT-proBNP, right atrial area and peak heart rate were independent predictors of outcomes. After 4 years-follow-up, no adverse events occurred in patients at low risk (score=0 points), while an adverse event occurred in 62% of patients at high risk (score=3 points, p<0.001).

Conclusion

In our cohort of adults with rTOF, surrogates of RV dyssynchrony did not correlate with outcomes. A multimodality approach was effective in predicting the risk for adverse events.
Effect of high-intensity interval training in physiotherapy primary care for patients with inflammatory arthritis: the ExeHeart randomised controlled trial
Authors: Nordén Kristine Røren , Semb Anne Grete , Dagfinrud Hanne , Hisdal Jonny , Sexton Joseph , Fongen Camilla , Bakke Emilie , Ødegård Sigrid , Skandsen Jon , Blanck Thalita , Metsios George S , Tveter Anne Therese
Published: January 2024

Objectives

To assess the effect of high-intensity interval training (HIIT) delivered in physiotherapy primary care on the primary outcome of cardiorespiratory fitness (CRF) in patients with inflammatory arthritis (IA). Additionally, to explore the effects of HIIT on secondary outcomes, including cardiovascular disease (CVD) risk factors and disease activity.

Methods

Single-blinded randomised controlled trial with 60 patients randomly assigned to either a control group receiving usual care or an exercise group receiving usual care and 12 weeks of individualised HIIT at 90%–95% peak heart rate. Outcomes were assessed at baseline, 3 months and 6 months post baseline and included CRF measured as peak oxygen uptake (VO2peak), classic CVD risk factors, disease activity, anthropometry and patient-reported physical activity, pain, fatigue, disease impact and exercise beliefs and self-efficacy.

Results

Intention-to-treat analysis demonstrated a significant between-group difference in VO2peakat 3 months (2.5 mL/kg/min, 95% CI 0.9 to 4.0) and 6 months (2.6 mL/kg/min, 95% CI 0.8 to 4.3) in favour of the exercise group. A beneficial change in self-reported physical activity in favour of the exercise group was observed at 3 and 6 months. The HIIT intervention was well-tolerated with minimal adverse events and no apparent impact on disease activity. Differences in secondary outcomes related to CVD risk factors, disease impact, pain, fatigue and exercise beliefs and self-efficacy were generally small and non-significant.

Conclusion

After 12 weeks of supervised HIIT delivered in physiotherapy primary care, patients with IA demonstrated a favourable improvement in CRF, with sustained effects at 6-month follow-up.

Trial registration number

NCT04922840.