bluuebunny/crossref_metadata_2025 huggingface dataset:
Intramedullary Nailing or Percutaneous Plating in Fixing Distal Metaphyseal Fractures of the Tibia
Authors: Emily Beamish Rebecca , Barry Matthew
Published: June 2024

This is a prospective randomized trial comparing intramedullary nailing (IMN) and percutaneous locking compression plating for closed distal extra-articular tibial fractures (AO type 43A). One hundred and eleven patients were randomized to either IMN or plating. Eighty-five patients were analyzed at one year. The principal conclusions were that both IMN and plating were safe but IMN had the advantage of lower mean operative and radiation times (97.9 vs. 81.2 minutes [p < 0.001] and 3.0 vs. 2.12 minutes [p < 0.001], respectively), as well as easier implant removal. Relevant other studies including the UK FixDT trial are also discussed.
Metal-on-Metal Hip Failure
Authors: Davidson Donald , Sugand Kapil , Abdul-Jabar Hani B.
Published: June 2024

Metal-on-metal (MoM) hip bearings were marketed from the late 1990s. Their use was heralded as a solution to wear-induced osteolysis, a major cause for hip replacement failure, as well as their larger head size used to improve stability. At peak usage, 15% of all hip bearing surfaces were MoM; however, it became apparent that these hips were failing at a two- to threefold higher rate than other bearing types. It was noted that metal debris from the failing implant was being deposited within the periarticular soft tissues (metallosis), causing a locally destructive immune response, and metal ions were being leached into the bloodstream. This study aimed to determine if blood metal ion levels could detect the failed implant.
Dual Mobility and Large Femoral Head Diameter Are Implants for Safety in Total Hip Arthroplasty
Authors: Mabrouk Ahmed , van Duren Bernard H. , Sidhom Sameh A.
Published: June 2024

Instability/dislocation is a well-documented and recognized complication after primary and revision total hip arthroplasty (THA). Among available modern implant options, particular design characteristics may reduce the risk of dislocation and revision, such as big femoral head diameters (BTHA), dual mobility (DMTHA) acetabular components, and constrained liners (CTHA). This systematic review included eleven studies (nine comparative and two randomized controlled trials, 4084 patients). Postoperative dislocation and revision for any reason were compared. Network meta-analysis showed that the risk of revision and dislocation of DMTHA was significantly lower when compared to standard total hip arthroplasty (STHA). Based on short-term outcomes (0–5 years), the authors recommend using DMTHA and BTHA for safety.
Patellar Resurfacing in Total Knee Arthroplasty
Authors: Haider Zakir , Sri-Ram Kesavan
Published: June 2024

Patellar resurfacing in total knee arthroplasty remains a controversial topic. A large body of evidence exists in the form of randomized controlled trials and meta-analyses comparing total knee arthroplasty with and without patella resurfacing. This research provides conflicting evidence on measures such as anterior knee pain, efficacy, and patient outcomes, with no clear favorite. Consequently, no current guidelines or agreed-upon best practice currently exists to help guide clinicians. This chapter reviews and discusses current evidence on patellar resurfacing along with factors considered to affect postoperative outcomes in patients who have undergone patellar resurfacing in total knee arthroplasty.
Operative versus Nonoperative Treatment for Calcaneal Fractures
Authors: Park Chang , Sugand Kapil , Oguz Cenk , Allardice Garth
Published: June 2024

This is a multicenter randomized controlled trial to assess if operative treatment of closed intra-articular displaced fractures improves outcomes. One hundred and fifty-one patients were randomly allocated into the two arms of operative (n = 73) and nonoperative treatment (n = 78). The primary outcome measured was pain and function by the Kerr-Atkins score at two years postinjury. There was no statistically significant difference in pain and function at two years postinjury, and there was an increase in complications and need for reoperation in those managed operatively. Therefore, the study suggests that operative treatment is not recommended for the treatment of such fractures.
Bisphosphonates and Fractures of the Subtrochanteric or Diaphyseal Femur
Authors: Guevel Borna , Imbuldeniya Arjuna
Published: June 2024

This study is a secondary analysis of three randomized bisphosphonate trials reviewing the relationship between atypical fractures of the femoral shaft and bisphosphonate use. Several recently published case series suggest an increased risk of atypical subtrochanteric and diaphyseal fractures with long-term bisphosphonate use. Of 14 195 women in total, 284 (2%, 284/14 195) had hip or femur fractures whereby 12 (4.2%, 12/284) of these were subtrochanteric or diaphyseal fractures. The study highlighted the scarcity of these fractures even in long-term bisphosphonate use, with no significant increase in fracture risk. Wide confidence intervals, however, make it difficult to draw definitive conclusions.
Challenging Cases in Palliative Care
Authors: Dewhurst Felicity , Edmonds Polly , Gillon Suzie , Hawkins Amy , Miller Mary , Yardley Sarah
Published: June 2024

Palliative care has evolved rapidly in recent years. Not only is the field dealing with an increasingly elderly and multi-morbid population, it is also addressing a wider variety of complex diagnoses such as heart failure, renal failure, advanced lung disease, frailty, and dementia. As part of our Challenging Cases series, the cases in this book not only cover a range of physical and psychosocial problems seen in palliative care; they also reflect the core curriculum for UK specialty trainees. Each case brings together expert interpretation of the available evidence, management strategies, guidelines, and best practice, while discussing complexities in clinical decision-making and controversies in approach.
Cancer-related Bone Pain
Authors: Schuberth Anna , Mulvey Matt
Published: June 2024

This case outlines the mechanisms, clinical presentation, investigation, diagnosis, and management of cancer-related bone pain. Non-pharmacological measures including Transcutaneous Electrical Nerve Stimulation (TENS), acupuncture, and the use of aids and adaptations are reviewed. Pharmacological management of cancer-related bone pain including non-steroidal anti-inflammatory drugs (NSAIDs), strong opioids, antidepressants, anticonvulsants, corticosteroids, and bisphosphonates are discussed in detail. Other interventions including radiotherapy, interventional analgesia, and surgical aspects of cancer-related bone pain management are explored. A discussion on future advances in the field of cancer-related bone pain is also presented.
Cancer-related Neuropathic Pain
Authors: Gemmell Rebecca , Montgomery Craig
Published: June 2024

A 55-year-old man with locally advanced mesothelioma was referred to the community palliative care team with symptoms in keeping with neuropathic pain. His pain was managed with opioids and a trial of antidepressants and antiepileptic medications, achieving adequate analgesia. He had unsuccessful trials of topical capsaicin, lidocaine plasters, and TENS (transcutaneous electrical nerve stimulation). This case defines neuropathic pain, explores its aetiology in the presence of cancer and provides a strategy for pain management. Referral of patients to specialist multidisciplinary teams and consideration of interventional analgesia are also discussed. A patient-centred approach is recommended, considering individual needs and preferences, tolerance of medication and comorbidities.
Interventional Pain Management
Authors: Hetherington Lucy , Mitchell Alison
Published: June 2024

This case describes a 63-year-old woman, Marie, with metastatic skeletal disease causing pain on movement. Analgesic medical management has not been sufficient in alleviating the pain, further radiotherapy and surgical management are not possible. This case discusses goal setting with Marie and a multi-professional assessment to guide decision-making. Intrathecal drug delivery and percutaneous cervical cordotomy are discussed in detail. An interventional approach is indicated in an estimated 5–15% of patients with cancer pain and is underused.
Chronic Non-cancer Pain
Authors: Simkiss Lauri , Jones Iain
Published: June 2024

This case describes a patient with a life-limiting condition and chronic pain. The patient presents to the palliative care service with pain and a complex mixture of medical, psychological, and social factors. This case develops the argument that condition-specific management alone, offered in ‘pursuit of cure’, often fails people with chronic pain. Pain management requires a coordinated biopsychosocial approach to support patients effectively. Small incremental positive change is made possible through access to a range of enabling treatments, including some specialist treatments. This case also describes how, for patients with complex pain, specialist input is needed in order to manage their care holistically.
Nausea, Vomiting, and Hiccups
Authors: McGuigan Holly , Sutherland Anna
Published: June 2024

Nausea, vomiting, and hiccups are common symptoms in palliative care which can be challenging to assess and manage. This case describes a patient with nausea, vomiting, and hiccups and explores how management is tailored to the cause of the symptoms. It stresses the importance of regular reassessment of a patient’s symptoms to appreciate evolving and multifactorial causes. The case reviews the evidence base for different approaches to management of nausea, vomiting, and hiccups. The case discusses side effects and contraindications of different antiemetics, and more complex clinical scenarios such as prescribing in Parkinson’s disease or myasthenia gravis. Finally, it suggests future directions for research and practice.
Prescribing Review
Authors: Hatton Luke Nathaniel , Presland Melinda
Published: June 2024

Medications are prescribed to benefit patients. Regular prescribing reviews are needed to consider the benefit of stopping and changing these medications. As medications are increasingly used when patients enter the final stages of life, prescribing reviews become key in optimizing symptom control and quality of life. This case considers prescribing reviews, and their use in encouraging deprescribing. This should be considered throughout a patient’s journey, from initial diagnosis with a life-limiting condition and as the patient deteriorates, considering the risk and benefit of each medication. Optimal prescribing reviews need to consider patient’s preferences and communicate clearly with the patient and family the rationale for medication changes. This case uses a case illustration to review how complex decisions around medications can be approached and the use of off-label prescribing in palliative care. It includes suggested resources to aid deprescribing and is written for prescribers of medications.
Cultural Care
Authors: Charles Max , Koffman Jonathan
Published: June 2024

‘Cultural Care’ deals with the potential diverse challenges of providing palliative care for patients from different cultural backgrounds. Clinicians often lack awareness of how their personal culture, as well as bias and beliefs common to UK healthcare professionals, impact their practice. Admitting cultural vulnerability can improve communication and avoid the risks of making assumptions. Issues experienced by patients and relatives within consultations are discussed, including lack of understanding of the person’s belief system, approach to ‘bad news’ and other potential barriers to holistic care. Different models of communication to better understand a patient’s culture and values are suggested to reduce uncertainty, help build trust and consequently deliver individualized palliative care.
Developing Compassionate Communities
Authors: Sawyer Joseph , Sallnow Libby
Published: June 2024

Developing compassionate communities examines the changing context for end-of-life care. Changes in global demographic profiles suggest care needs will shift towards those in old age, with frailty and multiple long-term conditions. The number of people requiring care is likely to outstrip current capacity based on existing models of care. At the same time, access to care for marginalized communities remains a criticism of mainstream services. Increasingly, people are seeking alternate frameworks to meet such challenges. New public health approaches to palliative care promote compassionate communities as a potential solution. The approach seeks to foster supportive networks and resource that exists within communities to meet the anticipated practical and emotional challenges in providing end-of-life care. This case reviews aspects of this approach, discussing how clinicians can integrate core principles into their practice at an individual and systems level.
Long-Term Survival after Kidney Transplantation
Authors: Vasudev Brahm , Hariharan Sundaram
Published: June 2024

Kidney transplantation is the best option for renal replacement therapy for end-stage kidney disease (ESKD). In the United States, over three decades the number of kidney transplant (KT) performed has increased, but not enough to keep up with demand. The success of a KT is a function of patient survival and the transplanted organ’s long-term survival. Survival rates have improved due to improvements in pretransplant processes, better surgical techniques, advances in immunosuppressive therapies, and prevention and treatment of post-transplant cardiovascular diseases, infections, and tumors. Improved platforms for human leukocyte antigen and antibody testing and crossmatch techniques, legislative changes, better communication through the electronic health record system, and the introduction of telemedicine have had a positive impact on patient care. This chapter provides current long-term survival rates, pre- and post-transplant factors that affect KT survival, and methods to improve survival rates further.
Transplantation in Children
Authors: Dandamudi Raja S. , Höcker Britta , Dharnidharka Vikas
Published: June 2024

Kidney transplantation (KT) is the treatment of choice for children with end-stage kidney disease (ESKD), providing a significant survival advantage over dialysis. The field of pediatric KT continues to evolve, with improvements in management strategies including immunosuppression and antiviral therapies. The etiology of ESKD, donor-recipient size mismatch, post-transplant complications, medication nonadherence, growth and neurocognitive development, social issues, and comorbidities associated with the lower urinary tract are unique challenges in pediatric KT and are addressed in this chapter.
Tolerance after Kidney Transplantation
Authors: Rogers Natasha M. , Thomson Angus W.
Published: June 2024

For patients with advanced chronic kidney disease (CKD) or end-stage kidney disease (ESKD), kidney transplantation remains the best treatment modality. Kidney transplantation as opposed to long-term dialysis offers longer life expectancy with better quality of life and is cost-effective. There is an effort to offer kidney transplantation as the preferred modality to many recipients. In 2019, the federal government of the United States signed an Executive Order “Advancing American Kidney Health” intending to facilitate and promote kidney transplantation. In 2021, a total of 24,670 kidneys were transplanted which was a record high despite the midst of the COVID-19 pandemic. The number of patients with functioning kidney transplants continues to increase. In the USA, 239,413 patients had a functional kidney transplant in 2019 which has doubled in 20 years from 1999. The largest population with functional kidney transplants are patients aged 45-64 years.3 Many of these patients would eventually have irreversible graft failure requiring repeat transplant or long-term dialysis treatment. It is prudent to know how best to manage patients with failing kidney transplants. In this chapter, we address various clinical aspects of failing and failed kidney transplants.
3
Authors: Cohen Lewis
Published: June 2024

In this chapter, the concept of “losing context” is explored, including how patients with a dementia may sometimes try to preserve pictures, stories, and family history to hold on to their embeddedness of self and the relationships they have formed throughout their lives. The chapter also explores the paradoxical nature of dementia, specifically how advance planning needs to ideally take place before a diagnosis is given, which poses practical difficulties. Dan’s own prognosis and his decision to terminate his life is addressed within this paradox. The various opinions of philosophers, bioethicists, and disability rights activists are shared as they explore the issue of family and family members caring for people with a dementia.
7
Authors: Cohen Lewis
Published: June 2024

This chapter focuses on the life, diagnosis, and death-hastening act of Dr. Sandra Bem, a pioneering psychologist. Her diagnosis of mild cognitive impairment, or MCI, leads to a discussion of the full spectrum of dementia and how each individual has a unique set of symptoms and experiences. The reader also learns about the Hemlock Society and its goals to provide information to dying people who thought about accelerating their deaths and to pass legislation permitting carefully regulated physician-assisted dying. Dr. Kevorkian, one of the most famous physicians of this era, is discussed, along with various states’ death-with-dignity laws. The first patient Dr. Kevorkian helped to die was Janet Adkins, who had early-onset Alzheimer’s disease.
17
Authors: Cohen Lewis
Published: June 2024

This chapter continues to explore Dan’s symptoms through his own words. As his dementia progresses, Dan experiences increasing forgetfulness, fatigue, hallucinations, and emotional lability. An overview is provided of what access to voluntary assisted dying for people with dementia looks like globally. The shortcomings of the death-with-dignity laws that are available in the United States, as seen from Dan’s point-of-view, are explored. The reader learns about how members of Dan’s immediate and extended family are taking the news of his plan to hasten his death. Some of them object, and while this is distressing, Dan does not want them identified. Ethical quandaries of being an author of this book are discussed.
18
Authors: Cohen Lewis
Published: June 2024

This chapter continues to chart the progress of Dan’s advancing dementia. Alterations continue to be made to Dan’s plan. The role and method of communication with family and friends is explored. The inability to communicate that many suffering from a dementia experience is addressed with a nursing expert. The chapter also goes back in time to explore in more detail Dan’s past, including the trauma he suffered and the guilt that resulted, and the addictions and personality features that he developed as a means of coping. Dan’s psychoanalyst is interviewed, and he is confident that his patient is not depressed or lacks the capacity to make decisions.
19
Authors: Cohen Lewis
Published: June 2024

This chapter addresses the trigger that finally causes Dan to settle on a date for his overdose. He describes “time stopping” during a trip to a local park, and how he becomes disoriented and does not know where he is for a brief period. The incident is analyzed by a neurologist, who goes into more detail about the concept of getting lost and why it is such a universal and deeply traumatic symptom for those suffering from dementia. This leads to a discussion of the mark, or trigger, for intolerable suffering, which is different for every individual suffering from dementia. The complex reaction of Dan’s family to a date being chosen is shared with the reader.
27
Authors: Cohen Lewis
Published: June 2024

A day-to-day rundown is given of the progression of Dan’s symptoms after he voluntarily stops eating and drinking (VSED). The chapter also explores the interactions Dan and his husband have with hospice. On day #9 of his fast, Dan became disoriented and incoherent, and hospice services are begun. A case is made for hospice organizations to expand the symptom management protocols and specifically for the initiation of hospice in situations where people have dementia and want to employ VSED. The reader learns by the end of the chapter about the circumstances of Dan’s death and the contents of an email he addressed to his friends and family members.
29
Authors: Cohen Lewis
Published: June 2024

John deals with the distribution of Dan’s assets and possessions. He talks about his ongoing grieving process. John remarks that VSED is a readily available death-accelerating method for people with dementia or those who are seeking a nontechnological death, “But I think we need to look at it, hopefully, as a temporary, short-term answer to the problem of those who want to die.” The question of whether people suffering from dementia should be included in assisted dying laws is revisited. There is a discussion of the politics, concerns over vulnerable populations, and public stigma that attend this question. The issue of whether they should have the privacy right to resist disclosing their plan is touched upon. A memorial event is held in Kansas City and attended by several of Dan’s family to raise money for ACLU internships in his name.
Spinal Pathology and Muscle Morphologies with Chronic Low Back Pain and Lower Limb Amputation
Authors: Butowicz Courtney M , Helgeson Melvin D , Pisano Alfred J , Cook John W , Cherry Alex , Dearth Christopher L , Hendershot Brad D
Published: June 2024

Introduction

Low back pain (LBP) is highly prevalent after lower limb amputation (LLA) and contributes to substantial reductions in quality of life and function. Towards understanding pathophysiological mechanisms underlying LBP after LLA, this article compares lumbar spine pathologies and muscle morphologies between individuals with LBP, with and without LLA.

Materials and Methods

We queried electronic medical records of Service members with and without LLA who sought care for LBP at military treatment facilities between January 2002 and May 2020. Two groups with cLBP, one with (n = 15) and one without unilateral transtibial LLA (n = 15), were identified and randomly chosen from a larger sample. Groups were matched by age, mass, and sex. Lumbar muscle morphology, Pfirrmann grades, Modic changes, facet arthrosis, Meyerding grades, and lordosis angle were determined from radiographs and magnetic resonance images available in the medical record. Independent t-tests compared variables between cohorts while multiple regression models determined if intramuscular fat influenced Pfirrmann grades. Chi-square determined differences in presence of spondylolysis and facet arthrosis.

Results

Lordosis angle was larger with LLA (P = 0.01). Spondylolysis was more prevalent with LLA (P = 0.008; 40%) whereas facet arthrosis was similar between cohorts (P = 0.3). Muscle area was not different between cohorts, yet intramuscular fat was greater with LLA (P ≤ 0.05). Intramuscular fat did not influence Pfirrmann grades (P > 0.15).

Conclusions

Despite similar lumbar muscle size, those with unilateral LLA may be predisposed to progress to symptomatic spondylolisthesis and intramuscular fat. Surgical and/or rehabilitation interventions may mitigate long-term effects of diminished spinal health, decrease LBP-related disability, and improve function for individuals with LLA.
Effect of Cold vs Temperate Conditions on Physical Performance During Extended Mountain Warfare Training at Moderate Altitude
Authors: Zifchock Rebecca , Silder Amy , Murphy Robert , Duong Tony , Sessoms Pinata , Jones Douglas
Published: June 2024

Introduction

The purpose of this study was to investigate the effect of environmental conditions on body composition, upper body power, and lower body power throughout a ∼4-week military mountain training exercise. We hypothesized that countermovement jump and ballistic push-up performance would decrease as a result of extended mountain field training and that winter (cold) conditions would result in greater decrements compared to fall (temperate) conditions. We also expected to observe a strong positive correlation between changes in performance and changes in skeletal muscle mass. Finally, we expected acute changes in performance upon altitude exposure.

Materials and Methods

A total of 111 U.S. Infantry Marines (110 M; 1 F) provided written informed consent to participate in this study according to a protocol approved by the Naval Health Research Center. There were 54 participants in the fall cohort and 57 in the winter cohort. Maximum effort countermovement jump and ballistic push-up performance were assessed at different timepoints: (1) baseline at the sea level, (2) before training at ∼2100 m, (3) midpoint of training at ∼2100 m, (4) end of training at ∼2100 m, and (5) after 3 to 4 weeks of recovery at the sea level. The fall cohort trained at moderate temperatures (average day/night, 20°C/3°C), whereas the winter cohort trained under snowy winter conditions (7°C/−14°C).

Results

The results suggested that seasonal conditions did not significantly affect changes in body composition or physical performance. Furthermore, no acute effects of altitude on physical performance were detected. Training exercise did, however, cause performance decrements in countermovement jump height, countermovement jump peak power, and ballistic push-up height. Repeated measure correlation analyses suggested that there was a weak positive correlation between the decrease in skeletal muscle mass and the decrease in countermovement jump peak power throughout the training.

Conclusions

The results of our study suggest that explosive movements are negatively affected by extended military training, seemingly independent of environmental training conditions or temperature. Planning and execution of military training should account for the likelihood that warfighter physical power will decline and may not return to pretraining levels within the month following the training event. It may also be advised to consider targeted exercises to aid in recovery of muscular strength and power. Future work should consider additional factors that likely influenced the decrease in physical performance that occurs during extended military training, such as nutrition, sleep, and psychological and cognitive stresses.
A Clinical Case of Timely Diagnosis and Successful Treatment of Budd-Chiari Syndrome With Fulminant Cytolysis in the Setting of a First-time Diagnosed Myeloproliferative Disease
Authors: Husieva Svitlana A , Osyodlo Galyna V , Husiev Andrii V , Savichan Kyrylo V
Published: June 2024

The article presents a clinical case of peculiarities of clinical manifestations, diagnostic and therapeutic approaches of undiagnosed chronic myeloproliferative disease, on the background of which Budd-Chiari syndrome (BCS) developed. The results of clinical course, examination, and treatment of a patient with BCS as a manifestation of the hidden course of primary myelofibrosis with the presence of somatic mutation (V617F) in Janus-tyrosine kinase-2 (JAK2) gene in myeloid cells are presented. Standard clinical and laboratory examinations, and cytomorphologic and histologic examination of bone marrow were used. The diagnosis of BCS was confirmed by ultrasound (US) Doppler examination of the portal system vessels. Symptomatic therapy resulted in insignificant positive results. The analysis of this clinical case showed that the development of BCS was due to a chronic myeloproliferative disease that was not diagnosed before the development of thrombosis. Hepatic vein thrombosis was accompanied by the development of fulminant cytolytic syndrome. Along with symptomatic therapy, patient K., female, 32 years old, underwent transjugular intrahepatic portosystemic shunting 1 month after the first symptoms of BCS appeared, which contributed to a significant clinical effect. Seven years after the installation of 4 transjugular intrahepatic portosystemic shunts, the patient’s condition remains satisfactory. The uniqueness of this clinical case lies in the presence of 2 serious diseases at the same time: myeloproliferative pathology (primary myelofibrosis) JAK2-positive variant and BCS. Timely diagnosis of both hematological diseases and their complication in the form of hepatic vein thrombosis with fulminant cytolytic syndrome allowed timely prescription of adequate treatment with a good clinical response.
Candida glabrata (Nakaseomyces glabrata): A systematic review of clinical and microbiological data from 2011 to 2021 to inform the World Health Organization Fungal Priority Pathogens List
Authors: Beardsley Justin , Kim Hannah Yejin , Dao Aiken , Kidd Sarah , Alastruey-Izquierdo Ana , Sorrell Tania C , Tacconelli Evelina , Chakrabarti Arunaloke , Harrison Thomas S , Bongomin Felix , Gigante Valeria , Galas Marcelo , Siswanto Siswanto , Dagne Daniel Argaw , Roitberg Felipe , Sati Hatim , Morrissey C Orla , Alffenaar Jan-Willem
Published: June 2024

Recognising the growing global burden of fungal infections, the World Health Organization (WHO) established an advisory group consisting of experts in fungal diseases to develop a Fungal Priority Pathogen List. Pathogens were ranked based on their research and development needs and perceived public health importance using a series of global surveys and pathogen characteristics derived from systematic reviews. This systematic review evaluates the features and global impact of invasive disease caused by Candida glabrata (Nakaseomyces glabrata). PubMed and Web of Science were searched for studies reporting on mortality, morbidity (hospitalization and disability), drug resistance (including isolates from sterile and non-sterile sites, since these reflect the same organisms causing invasive infections), preventability, yearly incidence, diagnostics, treatability, and distribution/emergence in the last 10 years. Candida glabrata (N. glabrata) causes difficult-to-treat invasive infections, particularly in patients with underlying conditions such as immunodeficiency, diabetes, or those who have received broad-spectrum antibiotics or chemotherapy. Beyond standard infection prevention and control measures, no specific preventative measures have been described. We found that infection is associated with high mortality rates and that there is a lack of data on complications and sequelae. Resistance to azoles is common and well described in echinocandins—in both cases, the resistance rates are increasing. Candida glabrata remains mostly susceptible to amphotericin and flucytosine. However, the incidence of the disease is increasing, both at the population level and as a proportion of all invasive yeast infections, and the increases appear related to the use of antifungal agents.
Candida albicans—A systematic review to inform the World Health Organization Fungal Priority Pathogens List
Authors: Parambath Sarika , Dao Aiken , Kim Hannah Yejin , Zawahir Shukry , Alastruey Izquierdo Ana , Tacconelli Evelina , Govender Nelesh , Oladele Rita , Colombo Arnaldo , Sorrell Tania , Ramon-Pardo Pilar , Fusire Terence , Gigante Valeria , Sati Hatim , Morrissey C Orla , Alffenaar Jan-Willem , Beardsley Justin
Published: June 2024

Candida albicans is a common fungal pathogen and amongst the leading causes of invasive candidiasis globally. This systematic review examines the characteristics and global impact of invasive infections caused by C. albicans. We searched on PubMed and Web of Science for studies reporting on criteria such as mortality, morbidity, drug resistance, preventability, yearly incidence, and distribution/emergence during the period from 2016 to 2021. Our findings indicate that C. albicans is the most common Candida species causing invasive disease and that standard infection control measures are the primary means of prevention. However, we found high rates of mortality associated with infections caused by C. albicans. Furthermore, there is a lack of data on complications and sequelae. Resistance to commonly used antifungals remains rare. Although, whilst generally susceptible to azoles, we found some evidence of increasing resistance, particularly in middle-income settings—notably, data from low-income settings were limited. Candida albicans remains susceptible to echinocandins, amphotericin B, and flucytosine. We observed evidence of a decreasing proportion of infections caused by C. albicans relative to other Candida species, although detailed epidemiological studies are needed to confirm this trend. More robust data on attributable mortality, complications, and sequelae are needed to understand the full extent of the impact of invasive C. albicans infections.
North-PHASE: studying periodicity, hot spots, accretion stability, and early evolution in young stars in the Northern hemisphere
Authors: Sicilia-Aguilar A , Kahar R S , Pelayo-Baldárrago M E , Roccatagliata V , Froebrich D , Galindo-Guil F J , Campbell-White J , Kim J S , Mendigutía I , Schlueter L , Teixeira P S , Matsumura S , Fang M , Scholz A , Ábrahám P , Frasca A , Garufi A , Herbert C , Kóspál Á , Manara C F
Published: June 2024

We present the overview and first results from the North-PHASE Legacy Survey, which follows six young clusters for five years, using the 2 deg$^2$ FoV of the JAST80 telescope from the Javalambre Observatory (Spain). North-PHASE investigates stellar variability on time-scales from days to years for thousands of young stars distributed over entire clusters. This allows us to find new YSO, characterize accretion, and study inner disc evolution within the cluster context. Each region (Tr 37, Cep OB3, IC 5070, IC 348, NGC 2264, and NGC 1333) is observed in six filters (SDSS griz, u band, and J0660, which covers H$\alpha$), detecting cluster members as well as field variable stars. Tr 37 is used to prove feasibility and optimize the variability analysis techniques. In Tr 37, variability reveals 50 new YSO, most of them proper motion outliers. North-PHASE independently confirms the youth of astrometric members, efficiently distinguishes accreting and non-accreting stars, reveals the extent of the cluster populations along Tr37/IC 1396 bright rims, and detects variability resulting from rotation, dips, and irregular bursts. The proper motion outliers unveil a more complex star formation history than inferred from Gaia alone, and variability highlights previously hidden proper motion deviations in the surrounding clouds. We also find that non-YSO variables identified by North-PHASE cover a different variability parameter space and include long-period variables, eclipsing binaries, RR Lyr, and $\delta$ Scuti stars. These early results also emphasize the power of variability to complete the picture of star formation where it is missed by astrometry.
Hybrid approach predicts a lower binding energy for benzene on water ice
Authors: Clark Victoria H J , Benoit David M , Van de Sande Marie , Walsh Catherine
Published: June 2024

In this paper, we provide a highly accurate value for the binding energy of benzene to proton-ordered crystalline water ice (XIh), as a model for interstellar ices. We compare our computed value to the latest experimental data available from temperature-programmed desorption experiments and find that our binding energy value agrees well with data obtained from binding to either crystalline or amorphous ice. Importantly, our new value is lower than that used in most astrochemical networks by about nearly half its value. We explore the impact of this revised binding energy value for both an asymptotic giant branch (AGB) outflow and a protoplanetary disc. We find that the lower value of the binding energy predicted here compared with values used in the literature (4050 K versus 7587 K) leads to less depletion of gas-phase benzene in an AGB outflow, and leads to a shift outwards in the benzene snowline in the mid-plane of a protoplanetary disc. Using this new value, the AGB model predicts lower abundances of benzene in the solid phase throughout the outflow. The disc model also predicts a larger reservoir of gas-phase benzene in the inner disc, which is consistent with the recent detections of benzene for the first time in protoplanetary discs with JWST.
An ATP-responsive metal–organic framework against periodontitis via synergistic ion-interference-mediated pyroptosis
Authors: Yang Qijing , Sun Xiaolin , Ding Qihang , Qi Manlin , Liu Chengyu , Li Tingxuan , Shi Fangyu , Wang Lin , Li Chunyan , Kim Jong Seung
Published: June 2024

Periodontitis involves hyperactivated stromal cells that recruit immune cells, exacerbating inflammation. This study presents an ATP-responsive metal–organic framework (Mg/Zn-MOF) designed for periodontitis treatment, utilizing ion interference to modulate immune responses and prevent tissue destruction. Addressing the challenges of synergistic ion effects and targeted delivery faced by traditional immunomodulatory nanomaterials, the Mg/Zn-MOF system is activated by extracellular ATP—a pivotal molecule in periodontitis pathology—ensuring targeted ion release. Magnesium and zinc ions released from the framework synergistically inhibit membrane pore formation by attenuating Gasdermin D (GSDMD) expression and activation. This action curtails pyroptosis, lactate dehydrogenase and IL-1β release, thwarting the onset of inflammatory cascades. Mechanistically, Mg/Zn-MOF intervenes in both the NLRP3/Caspase-1/GSDMD and Caspase-11/GSDMD pathways to mitigate pyroptosis. In vivo assessments confirm its effectiveness in diminishing inflammatory cell infiltration and preserving collagen integrity, thereby safeguarding against periodontal tissue damage and bone loss. This investigation highlights the promise of ion-interference strategies in periodontitis immunotherapy, representing a significant stride in developing targeted therapeutic approaches.
A Tale of Two Ṭarīqas: The Iraqi and Khurasani Shāfiʿī Communities in the Fourth/Tenth and Fifth/Eleventh Centuries
Authors: Sheibani Mariam
Published: June 2024

This article provides a new account of Shāfiʿī legal history in the fourth/tenth and fifth/eleventh centuries: a tale of two ṭarīqas, or interpretive communities, one in Iraq and the other in Khurasan. I show that these two Shāfiʿī communities developed as distinct social and scholarly collectives before gradually converging in Ayyubid Damascus and eventually coalescing around one authoritative school doctrine in the Mamluk period. I reconstruct the networks of Shāfiʿī jurists in the two regions and show how and why the two groups differed in their legal reasoning and their paradigm of the madhhab (legal school). Although all of these jurists shared a transregional affiliation with the Shāfiʿī madhhab that distinguished them from jurists belonging to other legal schools, I argue that these affinities were countered by geographical boundaries and diverging local developments that led to the differentiation of the Iraqi and Khurasani Shāfiʿī communities. These insights not only complicate our understanding of what constitutes the post-formative madhhab as an institution but also demonstrate how broader intellectual and institutional developments, such as the ascendancy of Ashʿarism, the emergence of new centres of scholarship, and the introduction of the madrasa, shaped the internal workings of the madhhab.
The embodiment of the neighborhood socioeconomic environment in the architecture of the immune system
Authors: Noppert Grace A , Clarke Philippa , Stebbins Rebecca C , Duchowny Kate A , Melendez Robert , Rollings Kimberly , Aiello Allison E
Published: June 2024

There is growing recognition of the importance of immune health for understanding the origins of ageing-related disease and decline. Numerous studies have demonstrated consistent associations between the social determinants of health and immunosenescence (i.e. ageing of the immune system). Yet few studies have interrogated the relationship between neighborhood socioeconomic status (nSES) and biologically specific measures of immunosenescence. We used data from the US Health and Retirement Study to measure immunosenescence linked with neighborhood socioeconomic data from the National Neighborhood Data Archive to examine associations between indicators of nSES and immunosenescence. We found associations between both the ratio of terminally differentiated effector memory to naïve (EMRA:Naïve) CD4+ T cells and cytomegalovirus (CMV) immunoglobulin G (IgG) levels and nSES. For the CD4+ EMRA:Naïve ratio, each 1% increase in the neighborhood disadvantage index was associated with a 0.005 standard deviation higher value of the EMRA:Naïve ratio (95% CI: 0.0003, 0.01) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.05 higher standardized value of the CD4+ EMRA:Naïve ratio. The results were fully attenuated when adjusting for both individual-level SES and race/ethnicity. For CMV IgG antibodies, a 1% increase in neighborhood disadvantage was associated a 0.03 standard deviation higher value of CMV IgG antibodies (β = 0.03; 95% CI: 0.002, 0.03) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.3 higher standardized value of CMV. This association was attenuated though still statistically significant when controlling for individual-level SES and race/ethnicity. The findings from this study provide compelling initial evidence that large, nonspecific social exposures, such as neighborhood socioeconomic conditions, can become embodied in cellular processes of immune ageing.
Perceived legitimacy of agricultural support schemes: An investigation using factorial survey experiments
Authors: Glenk Klaus , Liebe Ulf , Burns Jay , Thomson Steven
Published: June 2024

Agricultural support payments are a significant position in public budgets, and the legitimacy of such payments is subject to continuing debate. The legitimacy rests on the social acceptance of citizens for support payments to farmers, which is the focus of this study. Social acceptance is investigated using evaluations of farm and farmer descriptions in a factorial survey experiment. The results reveal higher acceptance of payments for farms demonstrating enhanced animal welfare, biodiversity, and a lower carbon footprint. The acceptance of support payments is negatively associated with payment amount, but payments to farmers who are financially struggling are more accepted than payments to profitable farmers; indicating respondent preferences that align with the need justice principle. Study findings can be used to inform priorities for legitimate policies of agricultural support schemes, to identify areas of consensus or disagreement regarding social acceptance of support, and to facilitate effective communication on agricultural support policy.
Imagining the Future: Memory, Simulation, and Beliefs
Authors: Bordalo Pedro , Burro Giovanni , Coffman Katherine , Gennaioli Nicola , Shleifer Andrei
Published: June 2024

How do people form beliefs about novel risks, with which they have little or no experience? Motivated by survey data on beliefs about COVID we collected in 2020, we build a model based on the psychology of selective memory. When a person thinks about an event, different experiences compete for retrieval, and retrieved experiences are used to simulate the event based on how similar they are to it. The model predicts that different experiences interfere with each other in recall and that non-domain-specific experiences can bias beliefs based on their similarity to the assessed event. We test these predictions using data from our COVID survey and from a primed-recall experiment about cyberattack risk. In line with our theory of similarity-based retrieval and simulation, experiences and their measured similarity to the cued event help account for experience effects, priming effects, and the interaction of the two in shaping beliefs.
Stochastic Character Mapping, Bayesian Model Selection, and Biosynthetic Pathways Shed New Light on the Evolution of Habitat Preference in Cyanobacteria
Authors: Bianchini Giorgio , Hagemann Martin , Sánchez-Baracaldo Patricia
Published: June 2024

Cyanobacteria are the only prokaryotes to have evolved oxygenic photosynthesis paving the way for complex life. Studying the evolution and ecological niche of cyanobacteria and their ancestors is crucial for understanding the intricate dynamics of biosphere evolution. These organisms frequently deal with environmental stressors such as salinity and drought, and they employ compatible solutes as a mechanism to cope with these challenges. Compatible solutes are small molecules that help maintain cellular osmotic balance in high-salinity environments, such as marine waters. Their production plays a crucial role in salt tolerance, which, in turn, influences habitat preference. Among the 5 known compatible solutes produced by cyanobacteria (sucrose, trehalose, glucosylglycerol, glucosylglycerate, and glycine betaine), their synthesis varies between individual strains. In this study, we work in a Bayesian stochastic mapping framework, integrating multiple sources of information about compatible solute biosynthesis in order to predict the ancestral habitat preference of Cyanobacteria. Through extensive model selection analyses and statistical tests for correlation, we identify glucosylglycerol and glucosylglycerate as the most significantly correlated with habitat preference, while trehalose exhibits the weakest correlation. Additionally, glucosylglycerol, glucosylglycerate, and glycine betaine show high loss/gain rate ratios, indicating their potential role in adaptability, while sucrose and trehalose are less likely to be lost due to their additional cellular functions. Contrary to previous findings, our analyses predict that the last common ancestor of Cyanobacteria (living at around 3180 Ma) had a 97% probability of a high salinity habitat preference and was likely able to synthesize glucosylglycerol and glucosylglycerate. Nevertheless, cyanobacteria likely colonized low-salinity environments shortly after their origin, with an 89% probability of the first cyanobacterium with low-salinity habitat preference arising prior to the Great Oxygenation Event (2460 Ma). Stochastic mapping analyses provide evidence of cyanobacteria inhabiting early marine habitats, aiding in the interpretation of the geological record. Our age estimate of ~2590 Ma for the divergence of 2 major cyanobacterial clades (Macro- and Microcyanobacteria) suggests that these were likely significant contributors to primary productivity in marine habitats in the lead-up to the Great Oxygenation Event, and thus played a pivotal role in triggering the sudden increase in atmospheric oxygen.