bluuebunny/crossref_metadata_2025 huggingface dataset:
SUMO-specific protease 1 exacerbates acute myeloid leukemia by enhancing beclin 1-dependent autophagy through polypyrimidine tract-binding protein 1 deSUMOylation
Authors: Xing Lina , Guo Xuefei , Zhang Xiaolei , Wang Ying , Ren Jinhai
Published: June 2024

Genetic association between SUMO-specific protease 1 (SENP1) and acute myeloid leukemia (AML) has been validated. However, the mechanism by which SENP1 affects AML proliferation, apoptosis, and autophagy remains unknown. The levels of SENP1 and polypyrimidine tract-binding protein 1 (PTBP1) were measured in patients with AML, AML cell lines, and xenograft tissues. The effects of SENP1 on AML proliferation, apoptosis, and beclin 1 (BECN1)-dependent autophagy were assessed through in vitro and in vivo loss- or gain-of-function experiments. SUMOylation analysis using immunoprecipitation (IP), RNA pull-down, RNA IP (RIP), and RNA stability assays were used to explore the molecular mechanism of SENP1 in AML development. The SENP1 level was elevated in AML samples. Silencing SENP1 impeded the development of AML, as evidenced by the inhibition of proliferation and promotion of G1-phase arrest and apoptosis resulting from SENP1 depletion in AML cells. Moreover, silencing of SENP1 restrained BECN1-depentent autophagy in AML cells. In addition, the overexpression of BECN1 or PTBP1 partially neutralized the effect of SENP1 knockdown on AML cell behavior. Mechanistically, SENP1 mediated PTBP1 deSUMOylation, which then directly interacted with BECN1 mRNA and enhanced its stability. In vivo experiments further confirmed the repressive effects of SENP1 suppression on AML development. Collectively, the SENP1/PTBP1/BECN1 signaling axis has been identified as a significant therapeutic target for enhancing AML treatment.
Evaluation of PTV margin in CBCT-based online adaptive radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma
Authors: Hirose Taka-aki , Takaki Masanori , Shibayama Yusuke , Fukunaga Jun-ichi , Kato Toyoyuki , Yoshitake Tadamasa , Ishigami Kousei
Published: June 2024

The aim of this study was to investigate planning target volume (PTV) margin in online adaptive radiation therapy (oART) for gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Four consecutive patients with gastric MALT lymphoma ﻿who received oART (30 Gy in 15 fractions) on the oART system were included in this study. One hundred and twenty cone-beam computed tomography (CBCT) scans acquired pre- and post-treatment of 60 fractions for all patients were used to evaluate intra- and interfractional motions. Patients were instructed on breath-holding at exhalation during image acquisition. To assess the intrafraction gastric motion, different PTVs were created by isotropically extending the CTV contoured on a pre-CBCT image (CTVpre) at1 mm intervals. Intrafraction motion was defined as the amount of expansion covering the contoured CTV on post-CBCT images (CTVpost). Interfractional motion was defined as the amount of reference CTV expansion that could cover each CTVpre, as well as the evaluation of the intrafractional motion. PTV margins were estimated from the cumulative proportion of fraction covering the intra- and interfractional motions. The extent of expansion covering the CTVs in 90% of fractions was adopted as the PTV margin. The PTV margin for intrafractional gastric motion using the oART system with breath-holding was 14 mm. In contrast, the PTV margin for interfractional gastric organ motion without the oART system was 25 mm. These results indicated that the oART system can reduce the PTV margin by >10 mm. Our results could be valuable data for oART cases.
Natural flavonoid glycosides Chrysosplenosides I & A rejuvenate intestinal stem cell aging via activation of PPARγ signaling
Authors: Ye Jinbao , Yan La , Yuan Yu , Fu Fang , Yuan Lu , Fan Xinxin , Zhou Juanyu , Zhu Yuedan , Liu Xingzhu , Ren Gang , Chen Haiyang
Published: June 2024

The decline in intestinal stem cell (ISC) function is a hallmark of aging, contributing to compromised intestinal regeneration and increased incidence of age-associated diseases. Novel therapeutic agents that can rejuvenate aged ISCs are of paramount importance for extending healthspan. Here, we report on the discovery of Chrysosplenosides I and A (CAs 1 & 2), flavonol glycosides from the Xizang medicinal plant Chrysosplenium axillare Maxim., which exhibit potent anti-aging effects on ISCs. Our research, using Drosophila models, reveals that CAs 1 & 2 treatments not only restrain excessive ISC proliferation, thereby preserving intestinal homeostasis, but also extend the lifespan of aging Drosophila. In aged mouse intestinal organoids, CAs 1 & 2 enhance the growth and budding of intestinal organoids, indicating improved regenerative capacity. Mechanistic investigations show that CAs 1 & 2 exert their effects by activating the peroxisome proliferator-activated receptor-gamma (PPARγ) and concurrently inhibiting the epidermal growth factor receptor (EGFR) signaling pathways. Our findings position CAs 1 & 2 as promising candidates for ameliorating ISC aging and suggest that targeting PPARγ, in particular, may offer a therapeutic strategy to counteract age-related intestinal dysfunction.
The Value of the Tip-Apex Distance in Predicting Failure of Fixation of Peritrochanteric Fractures of the Hip
Authors: George David A. , Whittingham-Jones Paul
Published: June 2024

The tip-apex distance philosophy was first coined by Baumgaertner and his coauthors in 1995, in response to failures of fixation following the use of a sliding hip screw in trochanteric fractures of the hip. The use of the tip-apex distance, based upon intraoperative anteroposterior and lateral radiographs, describes the sum of the distance from the tip of the lag screw to the apex of the femoral head, with a recommended combined value of less than 25 mm. Anything above this was shown to be highly predictive of failure by cutout of the lag screw (P = 0.0001).
How Long Does a Hip Replacement Last?
Authors: Twaij Haider , Memon Kashif , Raza Naeem
Published: June 2024

Total hip arthroplasty (THA) is a successful procedure used to manage hip osteoarthritis (OA). This study aims to identify the lifespan of a prosthesis to better inform patients. It looks at two data sets consisting of (1) a systematic review and meta-analysis conducted using Embase and Medline searches to September 2017 that provided data for forty-four series (13 212 THAs) and (2) a pooled survival and implant data from the National Joint Registry (NJR) for ninety-two series (215 676 THAs) from Australia and Finland. The twenty-five-year pooled survival of THAs from the case series was 77.6% (95% CI: 76.0–79.2) compared to 57.9% (95% CI: 57.1–58.7) from the NJR. Data from the NJR are less likely to be biased; thus patients and surgeons can expect a THA to last twenty-five years in around 58% of patients.
UK DRAFFT
Authors: Mitchell Chris , Karia Monil , Domos Peter
Published: June 2024

The Distal Radius Acute Fracture Fixation Trial (DRAFFT) is a multicenter randomized trial that compared the functional outcomes of Kirschner wire (K-wire) fixation vs. open reduction and internal fixation (ORIF) with locking plate for dorsally displaced extra-articular distal radius fractures that were reducible using a closed technique. Functional outcomes, radiographic parameters, and cost effectiveness were compared at twelve months postoperatively. Locking plates were associated with statistically significant improvement in radiographic findings of unknown clinical significance. No statistically significant difference in functional outcomes was seen at twelve-month follow-up. There was significant cost savings for K-wiring vs. ORIF.
Close Contact Casting versus Surgery for Initial Treatment of Unstable Ankle Fractures in Older Adults
Authors: Hardman John , Pearse Michael
Published: June 2024

A multicenter randomized controlled study designed to compare outcomes of operative fixation vs. close contact casting in the management of unstable ankle fractures in patients over the age of 60 years; 620 patients were randomly assigned to either treatment modality. The primary outcome was ankle function using the Olerud-Molander Ankle Score, which was equivalent at 6 months (66 for surgery vs. 64.5 for casting; p = 0.75). Quality of life, pain, and range of motion assessments were similarly comparable. A lower rate of perioperative complications and reduced overall theater time were observed in the casting group. Casting was associated with an increased rate of asymptomatic radiographic nonunion and malunion.
Primary Arthroscopic Stabilization for a First-Time Anterior Dislocation of the Shoulder
Authors: Assiotis Angelos , Singh Uppal Harpal
Published: June 2024

The investigators of this level I randomized trial from Edinburgh (Scotland) compare the clinical and functional outcomes of arthroscopic examination and lavage against arthroscopic anatomical repair of the Bankart lesion at two years after the intervention in eighty-four patients with a first-time anterior shoulder dislocation. They assess rates of recurrent instability, functional scores, range of motion, satisfaction, health service costs, and complications. They make a strong case in favor of arthroscopic repair of the Bankart lesion as they demonstrate that the risk of a further dislocation is reduced by 76% in the arthroscopic repair group compared with the lavage group. This study suggested that arthroscopic repair of a primary anterior traumatic shoulder dislocation confers improved functional outcomes and a reduced risk of recurrent instability when compared to arthroscopic lavage. This study helped to establish the significant role of arthroscopic Bankart repair in managing such patients.
Compression Plating versus Intramedullary Nailing for Humeral Shaft Fractures Requiring Operative Fixation
Authors: Morgan Catrin , Singh Kewal , Magnussen Alexander
Published: June 2024

This chapter looks at a study investigating dynamic compression plating (DCP) versus intramedullary nailing (IMN) for unstable humeral shaft fractures. This study includes forty-four patients who were randomized into two groups (i.e., DCP and IMN) with a mean follow-up of 14.3 months. The primary outcomes were function and pain, whereas the secondary outcomes were complications and need for further surgery. No difference in functional outcomes were demonstrated between DCP and IMN. A significantly higher complication and revision rate with IMN was reported. Therefore, in this study, DCP is the preferred treatment for unstable humeral shaft fractures.
Total or Partial Knee Replacement for Treating Medial Compartment Osteoarthritis
Authors: Hamilton Thomas W. , Alvand Abtin
Published: June 2024

The Total or Partial Knee Arthroplasty Trial (TOPKAT) was a pragmatic, multicenter randomized controlled trial designed to assess the clinical and cost effectiveness of total knee replacement (TKR) compared to partial knee replacement (PKR) in patients with medial compartment osteoarthritis (OA) of the knee. Randomizing 531 patients at five years, TOPKAT reported that there was no difference in functional outcomes, health-related quality of life, patient satisfaction, or revision rates between groups; however, TKR was associated with an increase in complications, particularly knee stiffness. Health economic analysis identified PKR to be more cost effective compared to TKR, and based on this the study suggested that PKR should be considered the first choice for patients with late-stage isolated medial compartment OA of the knee.
Timing of Surgical Decompression after Onset of Cauda Equina Syndrome
Authors: Wignadasan Warran , Thavarajah Dushan
Published: June 2024

Cauda equina syndrome (CES) is a rare but significant spinal surgical emergency characterized by a constellation of symptoms produced from compression of the cauda equina. The meta-analysis published by Ahn et al. (2000) aimed to determine the association between timing of surgical decompression and clinical outcomes in patients with compression of the cauda equina from a herniated lumbar disc. A total of forty-two articles met the inclusion criteria. The preoperative and postoperative data collected on 322 patients showed that there was a significant benefit in surgical decompression within forty-eight hours of onset of CES symptoms compared to decompression after forty-eight hours.
Long-Term Outcomes of Reverse Total Shoulder Arthroplasty
Authors: Tang Quen O. , Sugand Kapil , Makki Daoud
Published: June 2024

This study is a follow-up from an original report of 191 reverse total shoulder arthroplasties (RTSAs) in 186 patients. A retrospective case-series analysis was performed with at least ten years of follow-up (mean of 150 months). Prosthesis survival, radiographic evaluation, complications, and clinical outcomes were presented. Implant survivorship analysis was performed on a total of 240 prostheses. Eighty-four patients (eighty-seven RTSAs) were available for clinical outcome evaluation, and sixty-four patients (sixty-seven RSTAs) were available for radiographic assessment at final follow-up. The ten-year overall implant survivorship was 93% (revision as endpoint). Scapular notching was evident in 73% of patients. Complications were recorded in forty-seven patients (29%), with ten cases (10%) occurring after two years. The mean absolute and relative Constant scores (± standard deviation) were 55 ±16 points and 86 ±26 points respectively, which were both significant.
Diarrhoea
Authors: McConnell Robert , Connolly Michael , Butterly Leona
Published: June 2024

Diarrhoea is a debilitating problem in patients with advanced cancer. This case presents a patient with advanced cancer who has severe diarrhoea and focuses on the causes and management of diarrhoea in this patient group. Particular attention is given to cancer itself as a cause, as well as side effects of treatments, including chemotherapy, radiotherapy, surgery, and medications. The management of diarrhoea and potential complications will be discussed, looking at the specific management of chemotherapy-associated diarrhoea, bile acid malabsorption, immunotherapy-related diarrhoea using medications such as loperamide, codeine, octreotide as well as medications targeted at the cause of the diarrhoea.
De-escalation from Intensive Therapy Unit
Authors: Longwell Sarah , Wyld Lucy
Published: June 2024

This case discusses some of the key areas for clinicians to consider when providing end-of-life care for patients in intensive therapy unit (ITU). It discusses the importance of supporting early advance care planning (ACP) discussions to ensure all treatments are in line with the patient’s goals of care. It explores the unique challenges this environment poses, from symptom management and organ donation to complex decision-making. It considers the practicalities and legal framework surrounding the withdrawal of ventilation and artificial nutrition and hydration at the end of life. It highlights the importance of a patient-centred approach to end-of-life care and considers the role of the multidisciplinary team and other services, such as the Spiritual Care team, in providing this. It also discusses the role of the Hospital Palliative Care Team (HPCT) in the ITU and future models of integrating palliative care into critical care services.
Community Patient Transferred into Emergency Department/Acute Medical Unit
Authors: Copley Alice , Yardley Sarah
Published: June 2024

This chapter reviews the case of a patient attending the emergency department (ED) with dyspnoea and cough on a background of advanced terminal lung disease, who appears to be in the last weeks of life. He is transferred there by ambulance from a nursing home. The case explores the role of healthcare professionals in symptom assessment, communication, and clinical decision-making throughout the patient’s journey from ambulance attendance at the nursing home to the acute hospital setting and finally discharge to the nursing home for end-of-life care. It reviews principles of symptom control, including oxygen therapy and coordinating the discharge of a dying patient to a nursing home from the ED/acute medical unit. It also analyses why patients in the last phase of life are transferred to hospital and encourages professionals to take a patient-centred and pragmatic approach to investigation and intervention.
Giving Remote Advice to Families and Other Professional Providers
Authors: Qureshi Shaun Peter , Guppy Philippa , Osborne Georgina , Al-Qurainy Rasha
Published: June 2024

Remote consultations and remote advice-giving have become an increasingly embedded part of clinical practice in palliative care, driven by the COVID-19 pandemic. This case details how remote advice and consults can be delivered safely and effectively, explores the opportunities and challenges of telemedicine, and considers its role in developing more versatile palliative care services. There are complexities and challenges in conducting remote consultations, particularly in being able to develop a rapport with patients, which is key in palliative care, though simple strategies can be used to mitigate these. As healthcare providers and professionals become more confident with remote consultations, we are likely to further develop what can be offered remotely, which will be beneficial in enabling palliative care specialists to share their expertise across numerous sites and a wider geographical area. Building on the strong reputation of palliative care for personalized care, remote input should form part of a blended offer for patients and the wider healthcare family.
Dementia
Authors: Tolmie Kirsty , Dening Karen Harrison
Published: June 2024

Dementia is the leading cause of death in the UK and one of the major causes of disability and dependency among older people. The spectrum of symptoms in advanced dementia is comparable to those with cancer, however the symptom burden is often underestimated and patients are disproportionately underserved by specialist palliative care services. This case study explores some of the barriers people with dementia face when trying to access palliative care. It considers the physical as well as the behavioural and psychological symptoms of dementia (BPSD) and how pain is assessed and managed in patients who are unable to communicate their feelings and experiences. It explores prognostic uncertainty in dementia and presents recommendations for care including shared decision-making, avoiding burdensome interventions, spiritual and psychosocial support, and carer involvement.
Symptom Management in Organ Failure
Authors: Lister-Flynn Stephanie , Ainley Stephanie , Murphy Emma
Published: June 2024

This case explores the range of common symptoms experienced by patients with end-westage kidney disease and how these may be treated, including symptoms experienced after dialysis withdrawal. It reviews types of pain likely to be encountered and the use of opioid and non-opioid analgesics; the management of uraemic pruritus, including the evidence base for recommendations; and the psychiatric comorbidities of anxiety and depression in renal failure. It discusses the use of patient-reported outcome measures to identify symptoms and the importance of palliative and supportive care earlier in the disease course. The case includes the consideration of dialysis adequacy for symptom management, and common symptoms experienced following dialysis withdrawal at the end of life.
Rigidity
Authors: Pitsillides Constantina , Wiblin Lou
Published: June 2024

Progressive supranuclear palsy (PSP) is a rapidly progressing neurological condition which may present with a variety of clinical features such as blurred vision, falls, cognitive impairment, altered eye movements, and rigidity. This case reviews the role of dopamine agonists in the management of rigidity, the causes and management of blurred vision and highlights the importance of a multidisciplinary approach when managing patients with PSP. It also discusses cognitive impairment in patients with PSP and the use of Montreal Cognitive Assessment (MoCA). Additionally, this case also highlights key milestones, such as falls, PSP progression, and the role of palliative care services.
Goal Setting and Interdisciplinary Support and Care Planning
Authors: Tiberini Rebecca , Martin Jonathan
Published: June 2024

In this case, the importance of goal-setting and interdisciplinary support and care planning for people with advanced disease is discussed. Drawing on the practice of a hospice interdisciplinary breathlessness clinic, the case highlights issues such as the need to consider ‘concerns’ rather than just ‘problems’. The practice of person-centred goal-setting is explained, and evidence about patient experiences of this within palliative care is provided. Tips are given to help practitioners consider how to orientate their services so that establishing patient goals becomes the central focus for interdisciplinary care teams. Positive risk-taking and parallel planning are highlighted as ways to shift practice to improve the rehabilitative approaches in palliative care. This case includes video content from Lucy, who was known to hospice services due to her advanced chronic obstructive pulmonary disease. Lucy was keen for her experiences to be used in the education of healthcare professionals and the content is freely accessible via YouTube.
Grief and Bereavement
Authors: Chamberlain Charlotte , Selman Lucy
Published: June 2024

Grief is the emotional process we go through when losing someone or something important to us. It is a natural part of life and not a pathology requiring medical intervention. However, while most grief can be managed within personal social support networks, for up to 10% of people it can become prolonged, leading to anxiety, depression, increased use of medication and hospital admissions. This case describes theoretical models of grief and specific sub-types of grief (anticipatory, disenfranchised). It highlights evidence that tailored interventions (such as individual and group psychotherapy) targeted at those with prolonged grief disorder (PGD) improve outcomes for this population. Health professionals have a responsibility to support those who are recently bereaved or grieving, providing information about grief and signposting to support options. For those with risk factors for or exhibiting signs of PGD, awareness and referring to specialist services is essential to prevent further harm to patients.
Behavior and Psychosocial Functioning after Kidney Transplantation
Authors: Steel Jennifer L. , Cukor Daniel
Published: June 2024

Psychosocial and behavioral factors are considered among the determinants of health and are critical in the development and progression of chronic disease. Psychosocial factors, including anxiety, post-traumatic stress disorder (PTSD), and depression, and behavioral factors, such as diet, physical activity, and substance use, may contribute to the development of end-stage renal disease. These psychosocial and behavioral factors remain important for quality and quantity of life post–renal transplant. While psychosocial factors such as depression, sleep, anxiety, and substance use have been shown to contribute to increased risk of mortality in other chronic diseases, there is a paucity of research linking these factors to post-kidney transplant survival.
Winter's End
Authors: Cohen Lewis
Published: June 2024

Winter’s End: Dementia and Dying Well is constructed around a lengthy and detailed case history layered with the voices of approximately 100 palliative medicine practitioners, legal scholars, bioethicists, social workers, nurses, neurologists, and other authorities, primarily from North America and Europe. Arguably among the worst of all medical afflictions, the dementias slowly destroy one’s personality; take a tremendous emotional, physical, and financial toll on patients and families; and are irreversible and inexorably fatal. This book explores how and when one might prepare to foreshorten life after being diagnosed with a dementing illness while not ignoring the reality that, for most people, such actions are unthinkable and unacceptable.
2
Authors: Cohen Lewis
Published: June 2024

The author recounts the circumstances of how he first met Dan Winter and came to begin a series of interviews that would chronicle, in real-time, how Dan received his diagnosis of dementia, continued living his life, and, ultimately, sought his death. Practical matters surrounding a dementia diagnosis, such as getting personal affairs in order, are explored. The concept of memory is discussed. The reader learns more about Dan’s personal history and how the gathering of such details can provide the context needed to understand an individual’s decision to terminate their life to relieve suffering. A brief description of organizations that assist individuals in dying is included.
6
Authors: Cohen Lewis
Published: June 2024

In this chapter, the reader learns more about Dan’s personal history, particularly his coming out as a gay man and how he met his husband, John Forsgren. As a lead up to Dan’s own story, a general history of the HIV/AIDS epidemic of the 1980s also is discussed. At that time, a great number people with HIV diagnoses perished, and the embedded trauma this caused for members of the LGBTQ population resonates to this day. John’s experiences during the HIV/AIDS epidemic left a lasting impression on him. In this chapter, experts from psycho-oncology and psychiatry explore how John’s testing positive for HIV and his social activism allowed him a unique perspective on end-of-life issues.
25
Authors: Cohen Lewis
Published: June 2024

This chapter begins with a conversation between the author and Dan’s husband. In this discussion, they review the concept of family and friends (particularly a “logical” family that you build yourself) and the impact the AIDS epidemic on end-of-life issues in American society. They discuss how the decision to pursue voluntarily stopping eating and drinking (VSED) instead of a legal drug cocktail may have had a positive impact on Dan’s family. The conversation with John reveals more details about the logistics of VSED and how he’ll be supported. Most importantly, Dan later reveals to me that he is beginning his fast on the following day.
26
Authors: Cohen Lewis
Published: June 2024

This chapter follows the day-to-day, practical details of going through voluntarily stopping eating and drinking (VSED). The chapter discusses how Dan’s family is reacting to his decision to pursue VSED. These include symptom management (e.g., headaches, thirst). Also discussed is how a partner living with someone undergoing VSED handles matters like cooking, eating, and drinking. The reader learns how VSED is progressing for Dan, and the various symptoms he is experiencing. During the first few days, he remains able to walk his dog while accompanied by John, but this becomes impossible as his fatigue increases. Dan urges his family members to honestly tell his mother what is transpiring. He is exceedingly grateful when they comply with his request.
‘Intimacy as method’: Ethnographic reflections on equitable knowledge production in migration research
Authors: Cîrstea Ana-Maria , Pescinski Janina
Published: June 2024

Despite the ongoing ‘reflexive turn’ in migration studies, intimacy continues to be cropped out of methodologies. This article explores how intimacy can enable us to produce knowledge in a way that is grounded in and sensitive to our participants’ lives. We reflect on our experiences of building intimacy during our two respective ethnographic projects. While one project analyses the solidarity practices of citizens and migrants at the Franco–Italian border, the other explores the experiences of a Romanian family in London. Although researching seemingly divergent topics, we find methodological convergences and come together to propose the concept of ‘intimacy as method’. Positionality is central to intimacy, as who we are as early-career female researchers shaped how we built intimate and caring relationships with our participants. Cultivating intimacy, however, also presented challenges, including ethical considerations in how we conduct research, and how we represent our interlocutors and engage them in knowledge production. In sitting with the discomfort which is central to intimacy, we found its analytical potential as it granted us novel insights into our participants’ lives. By reflecting on both the potential and challenges of intimacy, we argue that migration researchers can use ‘intimacy as method’ to conduct more equitable research in migration studies.
Talaromyces marneffei, Coccidioides species, and Paracoccidioides species—a systematic review to inform the World Health Organization priority list of fungal pathogens
Authors: Morris Arthur J , Kim Hannah Yejin , Nield Blake , Dao Aiken , McMullan Brendan , Alastruey-Izquierdo Ana , Colombo Arnaldo Lopes , Heim Jutta , Wahyuningsih Retno , Le Thuy , Chiller Tom M , Forastiero Agustina , Chakrabarti Arunaloke , Harrison Thomas S , Bongomin Felix , Galas Marcelo , Siswanto Siswanto , Dagne Daniel Argaw , Roitberg Felipe , Gigante Valeria , Beardsley Justin , Sati Hatim , Alffenaar Jan-Willem , Morrissey Catherine Orla
Published: June 2024

The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic review aimed to evaluate the epidemiology and impact of infections caused by Talaromyces marneffei, Coccidioides species, and Paracoccidioides species. PubMed and Web of Sciences databases were searched to identify studies published between 1 January 2011 and 23 February 2021 reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 25, 17, and 6 articles were included for T. marneffei, Coccidioides spp. and Paracoccidioides spp., respectively. Mortality rates were high in those with invasive talaromycosis and paracoccidioidomycosis (up to 21% and 22.7%, respectively). Hospitalization was frequent in those with coccidioidomycosis (up to 84%), and while the duration was short (mean/median 3–7 days), readmission was common (38%). Reduced susceptibility to fluconazole and echinocandins was observed for T. marneffei and Coccidioides spp., whereas >88% of T. marneffei isolates had minimum inhibitory concentration values ≤0.015 μg/ml for itraconazole, posaconazole, and voriconazole. Risk factors for mortality in those with talaromycosis included low CD4 counts (odds ratio 2.90 when CD4 count <200 cells/μl compared with 24.26 when CD4 count <50 cells/μl). Outbreaks of coccidioidomycosis and paracoccidioidomycosis were associated with construction work (relative risk 4.4–210.6 and 5.7-times increase, respectively). In the United States of America, cases of coccidioidomycosis increased between 2014 and 2017 (from 8232 to 14 364/year). National and global surveillance as well as more detailed studies to better define sequelae, risk factors, outcomes, global distribution, and trends are required.
The hyperplane of early-type galaxies: using stellar population properties to increase the precision and accuracy of the fundamental plane as a distance indicator
Authors: D’Eugenio Francesco , Colless Matthew , van der Wel Arjen , Vaughan Sam P , Said Khaled , van de Sande Jesse , Bland-Hawthorn Joss , Bryant Julia J , Croom Scott M , López-Sánchez Ángel R , Lorente Nuria P F , Maiolino Roberto , Taylor Edward N
Published: June 2024

We use deep spectroscopy from the SAMI (Sydney-AAO Multi-object Integral) Galaxy Survey to explore the precision of the fundamental plane (FP) of early-type galaxies as a distance indicator for future single-fibre spectroscopy surveys. We study the optimal trade-off between sample size and signal-to-noise ratio (SNR), and investigate which additional observables can be used to construct hyperplanes with smaller intrinsic scatter than the FP. We add increasing levels of random noise (parametrized as effective exposure time) to the SAMI spectra to study the effect of increasing measurement uncertainties on the FP- and hyperplane-inferred distances. We find that, using direct-fit methods, the values of the FP and hyperplane best-fitting coefficients depend on the spectral SNR, and reach asymptotic values for a mean $\langle \mathrm{ SNR} \rangle =40\, \mathrm{\mathring{\rm A}}^{-1}$. As additional variables for the FP we consider three stellar-population observables: light-weighted age, stellar mass-to-light ratio, and a novel combination of Lick indices ($I_\mathrm{age}$). For an $\langle \mathrm{ SNR} \rangle =45~\mathrm{\mathring{\rm A}}^{-1}$ (equivalent to 1-h exposure on a 4-m telescope), all three hyperplanes outperform the FP as distance indicators. Being an empirical spectral index, $I_\mathrm{age}$ avoids the model-dependent uncertainties and bias underlying age and mass-to-light ratio measurements, yet yields a 10 per cent reduction of the median distance uncertainty compared to the FP. We also find that, as a by-product, the $I_\mathrm{age}$ hyperplane removes most of the reported environment bias of the FP. After accounting for the different SNR, these conclusions also apply to a 50 times larger sample from SDSS-III (Sloan Digital Sky Survey). However, in this case, only $\mathrm{ age}$ removes the environment bias.
Self-similar mass accretion history in scale-free simulations
Authors: Soltis John , Garrison Lehman H
Published: June 2024

Using a scale-free N-body simulation generated with the abacusN-body code, we test the robustness of halo mass accretion histories via their convergence to self-similarity. We compare two halo finders, rockstar and compaso. We find superior self-similarity in halo mass accretion histories determined using rockstar, with convergence to 5 per cent or better between $\sim\!\! 10^2$ and $10^5$ particles. For compaso, we find weaker convergence over a similar region, with at least 10 per cent between $\sim\!\! 10^2$ and $10^4$ particles. Furthermore, we find that the convergence to self-similarity improves as the simulation evolves, with the largest and deepest regions of convergence appearing after the scale factor quadrupled from the time at which non-linear structures begin to form. With sufficient time evolution, halo mass accretion histories are converged to self-similarity within 5 per cent with as few as $\sim\!\! 70$ particles for compaso and within 2 per cent for as few as $\sim\!\! 30$ particles for rockstar.
Coordinated DNA polymerization by Polγ and the region of LonP1 regulated proteolysis
Authors: Riccio Amanda A , Brannon Asia J , Krahn Juno M , Bouvette Jonathan , Williams Jason G , Borgnia Mario J , Copeland William C
Published: June 2024

The replicative mitochondrial DNA polymerase, Polγ, and its protein regulation are essential for the integrity of the mitochondrial genome. The intricacies of Polγ regulation and its interactions with regulatory proteins, which are essential for fine-tuning polymerase function, remain poorly understood. Misregulation of the Polγ heterotrimer, consisting of (i) PolG, the polymerase catalytic subunit and (ii) PolG2, the accessory subunit, ultimately results in mitochondrial diseases. Here, we used single particle cryo-electron microscopy to resolve the structure of PolG in its apoprotein state and we captured Polγ at three intermediates within the catalytic cycle: DNA bound, engaged, and an active polymerization state. Chemical crosslinking mass spectrometry, and site-directed mutagenesis uncovered the region of LonP1 engagement of PolG, which promoted proteolysis and regulation of PolG protein levels. PolG2 clinical variants, which disrupted a stable Polγ complex, led to enhanced LonP1-mediated PolG degradation. Overall, this insight into Polγ aids in an understanding of mitochondrial DNA replication and characterizes how machinery of the replication fork may be targeted for proteolytic degradation when improperly functioning.
Utilization of machine learning methods for prediction of acute and late rectal toxicity due to curative prostate radiotherapy
Authors: Ozkan Emine Elif , Serel Tekin Ahmet , Soyupek Arap Sedat , Kaymak Zumrut Arda
Published: June 2024

Objective

Rectal toxicity is one of the primary dose-limiting side effects of prostate cancer radiotherapy, and consequential impairment on quality of life in these patients with long survival is an important problem. In this study, we aimed to evaluate the possibility of predicting rectal toxicity with artificial intelligence model which was including certain dosimetric parameters.

Materials and methods

One hundred and thirty-seven patients with a diagnosis of prostate cancer who received curative radiotherapy for prostate +/− pelvic lymphatics were included in the study. The association of the clinical data and dosimetric data between early and late rectal toxicity reported during follow-up was evaluated. The sample size was increased to 274 patients by synthetic data generation method. To determine suitable models, 15 models were studied with machine learning algorithms using Python 2.3, Pycaret library. Random forest classifier was used with to detect active variables.

Results

The area under the curve and accuracy were found to be 0.89–0.97 and 95%–99%, respectively, with machine learning algorithms. The sensitivity values for acute and toxicity were found to be 0.95 and 0.99, respectively.

Conclusion

Early or late rectal toxicity can be predicted with a high probability via dosimetric and physical data and machine learning algorithms of patients who underwent prostate +/− pelvic radiotherapy. The fact that rectal toxicity can be predicted before treatment, which may result in limiting the dose and duration of treatment, makes us think that artificial intelligence can enter our daily practice in a short time in this sense.
Intramural Leiomyomas and Fertility
Authors: Pritts Taïna Laurore , Ogden Meghan , Parker William , Ratcliffe Jennifer , Pritts Elizabeth A.
Published: June 2024

OBJECTIVE:

To evaluate fertility outcomes based on size and number of intramural leiomyomas and outcomes after removal.

DATA SOURCES:

Online searches: MEDLINE, ClinicalTrials.gov, PubMed, Cochrane Library, and PROSPERO Library from 1994 to 2023.

METHODS OF STUDY SELECTION:

A total of 5,143 studies were identified, with inclusion of 13 study groups.

TABULATION, INTEGRATION AND RESULTS:

Outcomes for size and number of leiomyomas were reported with clinical pregnancy rates and ongoing pregnancy or live-birth rates. In data sets with maximum leiomyoma diameters of less than 6 cm for study inclusion, women with leiomyomas smaller than 3 cm had lower clinical pregnancy rates than women without leiomyomas, with an odds ratio (OR) of 0.53 (95% CI, 0.38–0.76) and, for ongoing pregnancy or live-birth rates, an OR of 0.59 (95% CI, 0.41–0.86). The ORs for clinical pregnancy rates in women with intermediately-sized leiomyomas (those between 3 cm and 6 cm) were lower than in women without leiomyomas, with an OR at 0.43 (95% CI, 0.29–0.63) and, for ongoing pregnancy or live-birth rates, an OR at 0.38 (95% CI, 0.24–0.59). In data sets without exclusion for women with larger-sized leiomyomas, clinical pregnancy rates were lower for those with leiomyomas smaller than 5 cm compared with those without leiomyomas, with an OR of 0.75 (95% CI, 0.58–0.96). Women with leiomyomas larger than 5 cm showed no differences in clinical pregnancy rate compared with women without leiomyomas, with an OR of 0.71 (95% CI, 0.32–1.58). Although women with a single leiomyoma in any location had no differences in outcomes, those with more than one leiomyoma had lower clinical pregnancy rates and ongoing pregnancy or live-birth rates, with an OR of 0.62 (95% CI, 0.44–0.86) and 0.57 (95% CI, 0.36–0.88), respectively. The clinical pregnancy rate for women undergoing myomectomy for intramural leiomyomas was no different than those with intramural leiomyomas in situ, with an OR of 1.10 (95% CI, 0.77–1.59).

CONCLUSION:

Even small intramural leiomyomas are associated with lower fertility; removal does not confer benefit. Women with more than one leiomyoma in any location have reduced fertility.
Intraoperative Ultrasonography for the Surgical Treatment of Grisel Syndrome of the Adult
Authors: Rusconi Angelo , Schembari Silvia , Peron Stefano , Ardemagni Andreana , Stefini Roberto
Published: June 2024

Study Design:

This is a narrative review and case report.

Objective:

To review the literature concerning Grisel syndrome physiopathology, diagnosis, and surgical reports, highlighting the decision-making for treatment and its timing. We describe the role of intraoperative US in the management of 2 cases of GS of the adult.

Summary of Background Data:

GS is a rare nontraumatic post inflammatory C1-C2 rotatory instability usually affecting children; adult cases are even rarer, and the role of surgical treatment is not well defined.

Case Discussion:

Case 1: A 72-year-old man with upper cervical pain and no neurological deficit; radiologic examination revealed C1-C2 spondylitis and epidural abscess. After antibiotic therapy, the patient developed cervical instability. Hence, surgical decompression and C1-C2 stabilization were performed. Case 2: An 82-year-old woman with progressive right hemiparesis. CT and MRI showed C1-C2 spondylitis with retro-odontoid epidural abscess. Atlanto-axial rotatory instability was evident so surgery was achieved. In both cases, intraoperative US was useful for localizing retro-odontoid abscess and allowing safe puncture of the collection, leading to its remarkable radiologic reduction.

Conclusion:

GS in adults remains a challenge: Patients should be closely monitored concerning neurological and inflammatory status. We describe the successful use of intraoperative US for draining retro-odontoid abscess for the first time, with satisfactory postoperative outcome without need of circumferential approach.
Transcatheter Intervention for Management of Tricuspid Regurgitation Using TriClip
Authors: Sharedalal Anmol , Zois Alexandra , Sharedalal Parija , Frishman William H. , Aronow Wilbert S.
Published: June 2024

Severe tricuspid regurgitation (TR) is an underrated, common pathology that affects over 70 million individuals worldwide. Traditionally, TR has been managed with diuretic therapies without any significant mortality benefit. The underlying cause of TR can be primary, coming from structural issues with tricuspid valve and more commonly secondary, arising from conditions affecting the right ventricle or the pulmonary circulation. Management of TR has seen few improvements until recently. Traditionally, valve replacement and surgical repair were the therapeutic options available. Tricuspid valve is a complex cardiac structure with many technical challenges for surgical intervention. Transcatheter valve interventions have proven to be safe and effective novel therapeutic options for severe TR, which reduce the severity of TR with associated improvement in quality of life. In this review, we will provide an overview of the management of severe TR utilizing transcatheter edge-to-edge repair with the TriClip device (Abbott, Santa Clara, CA).
Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice
Authors: Wang Ye , Jiang Zhi-Hui , Zhou Yu-Wei , Qiu Tian-Tian , Wang Han , Zhu Min-Sheng , Chen Xin , Zhang Xue-Na
Published: June 2024

Background:

The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown.

Methods:

Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF).

Results:

Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide–resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF.

Conclusions:

We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.
Randomized clinical trial on safety of the natriuretic peptide ularitide as treatment of refractory cirrhotic ascites
Authors: Gantzel Rasmus H. , Møller Emilie E. , Aagaard Niels K. , Watson Hugh , Jepsen Peter , Grønbæk Henning
Published: June 2024

Background:

Sodium and water retention is a mainstay of the pathophysiology leading to ascites formation in patients with advanced cirrhosis. Refractory ascites denotes the most severe ascites status with limited treatment options and a poor prognosis. We investigated the efficacy and safety of the natriuretic peptide ularitide in patients with refractory cirrhotic ascites.

Methods:

We conducted a randomized placebo-controlled trial investigating ularitide to manage refractory ascites. Until trial termination after interim analyses, we randomized 17 participants in a 2:1 ratio between ularitide (n=11) and placebo (n=6). While hospitalized, the participants received treatment for up to 48 hours. The primary efficacy endpoint was a change in renal water excretion, and secondary end points included changes in renal sodium excretion rate and body weight. The starting dose was 30 ng/kg/min, though later reduced to 20 for safety reasons.

Results:

In contrast to the study hypothesis, the mean urine production decreased after 24 hours of ularitide treatment compared with the baseline level (22.8 vs. 47.5 mL/h, p=0.04) and decreased more in participants randomized to ularitide than placebo (24.7 vs. −6.2 mL/h, p=0.05). Ularitide did not increase the renal sodium excretion rate or reduce the weight gain. The incidence rate ratio of adverse reactions in ularitide versus placebo was 8.5 (95% CI: 2–35, p=0.003). Participants treated with ularitide developed serious blood pressure reductions, impacting their renal responsiveness.

Conclusions:

Ularitide in doses of 20–30 ng/kg/min did not benefit urine production and renal sodium excretion rate in patients with refractory ascites. The participants randomized to ularitide overall developed more adverse reactions than placebo. EudraCT no. 2019-002268-28.