bluuebunny/crossref_metadata_2025 huggingface dataset:
Pandemics and Disaster Response
Authors: Manuel Athul , Daniel Sunitha
Published: June 2024

Pandemics and natural disasters are part of mass casualty events like earthquakes, major storms, haemorrhagic fever epidemics, or political violence, which comprise suffering in several ways requiring care of different kinds. Principles of palliative care, with the fundamental goal of relief of human suffering, need to be applied during any humanitarian emergency, particularly to those with pre-existing life-threatening illnesses, the severely injured, and those with comorbidities. People living in low- and middle-income countries (LMICs) are more vulnerable to needless suffering due to disasters. An already established palliative care network with strong roots in community is able to support patients and families in providing symptom control and psychosocial care. The trained volunteers who are part of palliative care networks can act as first responders during a humanitarian crisis to help with rescue, relief, and rehabilitation.
A Desire for Hastened Death
Authors: Payne Rebecca , Lund Samantha
Published: June 2024

‘A Desire for Hastened Death’ outlines a case of a patient with advanced cancer seeking to actively end their life by physician-assisted suicide (PAS). It gives a definition for the desire, or wish, to hasten death (DTHD/WTHD), and discusses reasons why a patient may hold this desire (e.g. fear or loss of control). Exclusion of potentially reversible contributing factors such as physical symptoms, or depression are considered. The law on assisting suicide is discussed, along with guidance on what to do if a patient asks for help in hastening their death. Whilst a large proportion of patients in palliative care may have a WTHD, healthcare workers may worry about causing distress if they ask about it.
Wellness after Kidney Transplantation
Authors: Wu Christine M. , Doshi Mona D.
Published: June 2024

There is a difference between being alive and living. Wellness in life is derived from positive relationships with family and friends, spiritual health, engagement in meaningful work, participation in hobbies, and ability to travel and engage with the world. Kidney transplant provides independence from dialysis and improved life expectancy with better quality of life, a term that encompasses the interdependent dimensions of physical, mental/emotional, social, spiritual, vocational, financial, and environmental health. This chapter will address some important aspects of long-term wellness after kidney transplantation including immunization, family planning and reproductive health, cancer screening, and return to work after transplantation. The transplant community can help patients to maximize their quality-of-life following transplantation.
Short-Term and Late Antibody-Mediated Rejection after Kidney Transplantation
Authors: Schinstock Carrie , Crespo Marta
Published: June 2024

Antibody-mediated rejection (ABMR) remains an important cause of renal allograft loss in the current era. A large multicenter observational study of over 5,000 kidney transplant recipients since 2006 showed that 30% of all death-censored allograft losses were associated with ABMR. Our understanding of ABMR has expanded in concert with advances in human leukocyte antigen (HLA) antibody detection techniques and standardization of renal allograft histology interpretation with the Banff classification, yet our treatment approach for late active and chronic ABMR remains limited. This chapter discusses various aspects of ABMR including the clinical presentations of ABMR, the mechanisms of ABMR, and treatment strategies. It also discusses the importance of microvascular inflammation and the histologic features suggestive of ABMR without detectable HLA donor-specific antibody (DSA).
Recurrent and De Novo Diseases after Kidney Transplantation
Authors: Coorey Craig P. , Chadban Steven J.
Published: June 2024

For most patients with end-stage kidney disease (ESKD), kidney transplant (KT) is the treatment of choice. KT provides a replacement kidney and immunosuppression, but in most cases does not ameliorate the underlying cause of kidney failure. As a result, both glomerular and systemic diseases can recur after KT, leading to graft dysfunction and failure with concurrent extrarenal morbidity and possibly death. Although less common, there are diseases that can occur de novo post transplantation that may also damage the kidney allograft.
Simultaneous Pancreas and Kidney Transplantation
Authors: Dunn Ty B. , Molinari Michele
Published: June 2024

End-stage kidney disease (ESKD) is a major health problem in the United States. Diabetes is a major cause of kidney failure. As of early 2023, a total of 1,924 candidates were waiting for a simultaneous pancreas kidney transplant (SPKT). One issue limiting the number of SPKTs is the availability of suitable donor pancreases—the (deceased) donor must be relatively young, lean, and free from major hemodynamic instability or multiorgan failure. Important additional constraints are deficiencies in patient and provider awareness, a national organ transportation system and waning expertise in the procurement and transplant of the pancreas. The current chapter aims to review the most recent data on the incidence, selection, and outcomes of SPKT, with an emphasis on how this transplant option can improve the quantity and quality of life for patients with kidney disease due to insulin dependent diabetes.
Management of Patients with Failing and Failed Kidney Transplant
Authors: Parajuli Sandesh , Gupta Gaurav
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 President of the United States of America 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, a record high despite the COVID-19 pandemic. The number of patients with functioning kidney transplants continues to increase. The largest population with functional kidney transplants are patients aged 45–64 years. Many of these patients would eventually have irreversible graft failure requiring repeat transplant or long-term dialysis treatment. This chapter addresses various clinical aspects of failing and failed kidney transplants.
4
Authors: Cohen Lewis
Published: June 2024

This chapter goes into Dan’s personality and his family history. Dan was a fifth-generation Kansan from a privileged background who, like his father, Wint, led an unusual life. The Winter family began as homesteaders in the Kansas Territory in the 1850s. They have continued into present day as community leaders and entrepreneurs. The chapter also explores Dan’s individual history, including the events in his childhood that influenced him to pursue social justice and the defense of civil rights in adulthood. After majoring in journalism at the University of Kansas, Dan became the president and CEO of a group of family-owned community banks located in eastern Kansas, Colorado, and New Mexico, and later he would be appointed Executive Director of the American Civil Liberties Union of Kansas and Western Missouri.
8
Authors: Cohen Lewis
Published: June 2024

In this chapter, the reader learns of Dan’s diagnosis of dementia. People’s behavior around a dementia diagnosis is explored, particularly how many put off seeking a definitive medical evaluation for a year or more. The chapter also explores the symptoms that Dan was experiencing that made him believe that he had a dementia, and it covers his initial formal diagnosis of mild cognitive impairment. A detailed discussion of the current treatments available for Alzheimer’s is also undertaken. The progressive nature of the disease is discussed, as are the dozens of disorders with different etiologies that result in dementia.
13
Authors: Cohen Lewis
Published: June 2024

Dan’s symptoms are worsening. Many of these appear to be inconsequential, but each further erodes Dan’s sense of self. Whether it is the inability to grasp the plot of a book or mistakes that occur during cooking, they are cumulatively eroding his confidence. They have resulted in Dan abandoning his involvement on the board of a local organization that deals with the unhoused. All the while, he has steadfastly avoided turning to John or his other family members regarding the death-hastening plans, partly to shield them from the psychological burden and partly to help them avoid any possible future legal entanglement. The chapter offers readers insight into what day-to-day life looks like for an individual suffering from dementia and for his caregiver. John’s feelings around Dan’s plan to accelerate the end of his life are explored and it becomes clearer as to why he supports the plan.
14
Authors: Cohen Lewis
Published: June 2024

The reader learns more about what is happening in the background while Dan is putting together his plan to overdose. This chapter opens with the line, “Dan’s situation was hardly taking place in a vacuum.” Current events included the COVID pandemic, the murder of George Floyd, the 2020 presidential election, and civil unrest and nightly protests in Portland. The chapter discusses how these larger events colored and influenced Dan’s personal decision-making. The reader learns more about the death of Dan’s father, as well as how Dan imagines his own will death happen and how his loved ones may handle the news.
20
Authors: Cohen Lewis
Published: June 2024

This chapter explores the care provided to dementia patients by neurologists and primary care physicians. It describes how most people’s treatment is in fact managed by their primary care physicians and that very few sufferers are regularly seen by neurologists at outpatient offices or memory clinics. The roles of geriatricians and geriatric psychiatrists are touched upon. The chapter provides further information on memory clinics, which are relatively new and uncommon, and gives the reader insight into how staff at memory clinics might treat Alzheimer’s patients. The growing field of neuropalliative care is also discussed, with insights shared from experts in this field.
22
Authors: Cohen Lewis
Published: June 2024

Family tensions continue to escalate. In this chapter, the reader learns that Dan remains worried about family members initiating guardianship or conservatorship proceedings to halt his plan to hasten his death. The stress and emotional strain contributes to a worsening of Dan’s symptoms and his own feelings around the loss of agency. The reader also learns that Dan decides not to employ lethal medications to hasten his death, and instead he considers voluntarily stopping eating and drinking (VSED). Finally, in an attempt to protect himself from interference, Dan connects with a right-to-die organization that is prepared to act as his legal shield against family intrusions.
24
Authors: Cohen Lewis
Published: June 2024

The reader learns that Dan communicates his new decision regarding voluntarily stopping eating and drinking to his family. Dan then discusses his situation with a hospice coordinator. She clarifies that her staff would be able to step in and offer assistance at the point when he is no longer walking or talking. Dan is asked if he still believes that for people who are dealing with Alzheimer’s, the idea of shortening life via overdose that is not medically supervised should still be considered an option. The discussion from experts on the topic illustrates the widely differing opinions on this matter.
Candida tropicalis—A systematic review to inform the World Health Organization of a fungal priority pathogens list
Authors: Keighley Caitlin , Kim Hannah Yejin , Kidd Sarah , Chen Sharon C-A , Alastruey Ana , Dao Aiken , Bongomin Felix , Chiller Tom , Wahyuningsih Retno , Forastiero Agustina , Al-Nuseirat Adi , Beyer Peter , Gigante Valeria , Beardsley Justin , Sati Hatim , Morrissey C Orla , Alffenaar Jan-Willem
Published: June 2024

In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority fungal pathogens and establish the WHO Fungal Priority Pathogens List for future research. This systematic review aimed to evaluate the features and global impact of invasive candidiasis caused by Candida tropicalis. PubMed and Web of Science were searched for studies reporting on criteria of mortality, morbidity (defined as hospitalization and disability), drug resistance, preventability, yearly incidence, diagnostics, treatability, and distribution/emergence from 2011 to 2021. Thirty studies, encompassing 436 patients from 25 countries were included in the analysis. All-cause mortality due to invasive C. tropicalis infections was 55%–60%. Resistance rates to fluconazole, itraconazole, voriconazole and posaconazole up to 40%–80% were observed but C. tropicalis isolates showed low resistance rates to the echinocandins (0%–1%), amphotericin B (0%), and flucytosine (0%–4%). Leukaemia (odds ratio (OR) = 4.77) and chronic lung disease (OR = 2.62) were identified as risk factors for invasive infections. Incidence rates highlight the geographic variability and provide valuable context for understanding the global burden of C. tropicalis infections. C. tropicalis candidiasis is associated with high mortality rates and high rates of resistance to triazoles. To address this emerging threat, concerted efforts are needed to develop novel antifungal agents and therapeutic approaches tailored to C. tropicalis infections. Global surveillance studies could better inform the annual incidence rates, distribution and trends and allow informed evaluation of the global impact of C. tropicalis infections.
Candida auris—a systematic review to inform the world health organization fungal priority pathogens list
Authors: Kim Hannah Yejin , Nguyen Thi Anh , Kidd Sarah , Chambers Joshua , Alastruey-Izquierdo Ana , Shin Jong-Hee , Dao Aiken , Forastiero Agustina , Wahyuningsih Retno , Chakrabarti Arunoloke , Beyer Peter , Gigante Valeria , Beardsley Justin , Sati Hatim , Morrissey C Orla , Alffenaar Jan-Willem
Published: June 2024

The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and Web of Science were used to find studies published from 1 January 2011 to 18 February 2021, reporting on predefined criteria including: mortality, morbidity (i.e., hospitalization and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. Thirty-seven studies were included in the final analysis. The overall and 30-day mortality rates associated with C. auris candidaemia ranged from 29% to 62% and 23% to 67%, respectively. The median length of hospital stay was 46–68 days, ranging up to 140 days. Late-onset complications of C. auris candidaemia included metastatic septic complications. Resistance rates to fluconazole were as high as 87%–100%. Susceptibility to isavuconazole, itraconazole, and posaconazole varied with MIC90 values of 0.06–1.0 mg/l. Resistance rates to voriconazole ranged widely from 28% to 98%. Resistance rates ranged between 8% and 35% for amphotericin B and 0%–8% for echinocandins. Over the last ten years, outbreaks due to C. auris have been reported in in all WHO regions. Given the outbreak potential of C. auris, the emergence and spread of MDR strains, and the challenges associated with its identification, and eradication of its environmental sources in healthcare settings, prevention and control measures based on the identified risk factors should be evaluated for their effectiveness and feasibility. Global surveillance studies could better inform the incidence rates and distribution patterns to evaluate the global burden of C. auris infections.
Cryptococcosis—a systematic review to inform the World Health Organization Fungal Priority Pathogens List
Authors: Dao Aiken , Kim Hannah Yejin , Garnham Katherine , Kidd Sarah , Sati Hatim , Perfect John , Sorrell Tania C , Harrison Thomas , Rickerts Volker , Gigante Valeria , Alastruey-Izquierdo Ana , Alffenaar Jan-Willem , Morrissey C Orla , Chen Sharon C-A , Beardsley Justin
Published: June 2024

Cryptococcosis causes a high burden of disease worldwide. This systematic review summarizes the literature on Cryptococcus neoformans and C. gattii infections to inform the World Health Organization’s first Fungal Priority Pathogen List. PubMed and Web of Science were used to identify studies reporting on annual incidence, mortality, morbidity, antifungal resistance, preventability, and distribution/emergence in the past 10 years. Mortality rates due to C. neoformans were 41%–61%. Complications included acute renal impairment, raised intracranial pressure needing shunts, and blindness. There was moderate evidence of reduced susceptibility (MIC range 16–32 mg/l) of C. neoformans to fluconazole, itraconazole, ketoconazole, voriconazole, and amphotericin B. Cryptococcus gattii infections comprised 11%–33% of all cases of invasive cryptococcosis globally. The mortality rates were 10%–23% for central nervous system (CNS) and pulmonary infections, and ∼43% for bloodstream infections. Complications described included neurological sequelae (17%–27% in C. gattii infections) and immune reconstitution inflammatory syndrome. MICs were generally low for amphotericin B (MICs: 0.25–0.5 mg/l), 5-flucytosine (MIC range: 0.5–2 mg/l), itraconazole, posaconazole, and voriconazole (MIC range: 0.06–0.5 mg/l). There is a need for increased surveillance of disease phenotype and outcome, long-term disability, and drug susceptibility to inform robust estimates of disease burden.
FATTY ACID DESATURASE4 enhances plant RNA virus replication and undergoes host vacuolar ATPase-mediated degradation
Authors: Fang Xinxin , Jia Zhaoxing , Yu Tianqi , Rui Penghuan , Zheng Hongying , Lu Yuwen , Peng Jiejun , Rao Shaofei , Wu Jian , Chen Jianping , Yan Fei , Wu Guanwei
Published: June 2024

Emerging evidence indicates that fatty acid (FA) metabolic pathways regulate host immunity to vertebrate viruses. However, information on FA signaling in plant virus infection remains elusive. In this study, we demonstrate the importance of fatty acid desaturase (FAD), an enzyme that catalyzes the rate-limiting step in the conversion of saturated FAs into unsaturated FAs, during infection by a plant RNA virus. We previously found that the rare Kua-ubiquitin-conjugating enzyme (Kua-UEV1) fusion protein FAD4 from Nicotiana benthamiana (NbFAD4) was downregulated upon turnip mosaic virus (TuMV) infection. We now demonstrate that NbFAD4 is unstable and is degraded as TuMV infection progresses. NbFAD4 is required for TuMV replication, as it interacts with TuMV replication protein 6K2 and colocalizes with viral replication complexes. Moreover, NbFAD4 overexpression dampened the accumulation of immunity-related phytohormones and FA metabolites, and its catalytic activity appears to be crucial for TuMV infection. Finally, a yeast 2-hybrid library screen identified the vacuolar H+-ATPase component ATP6V0C as involved in NbFAD4 degradation and further suppression of TuMV infection. This study reveals the intricate role of FAD4 in plant virus infection, and sheds light on a new mechanism by which a V-ATPase is involved in plant antiviral defense.
Autocratization Spillover: When Electing an Authoritarian Erodes Election Trust across Borders
Authors: Chan Ka Ming
Published: June 2024

The rich literature on election trust predominantly uses domestic determinants as explanatory factors. But given the international nature of the autocratization wave, can an autocratization event across borders erode election trust? This article argues that an authoritarian’s electoral success in a neighboring country can shatter democratic norms and demonstrate the viability of authoritarians. This autocratization event abroad can thus reduce citizens’ principled support for democracy and its political system. Consequently, citizens across borders are less likely to see democratic elections as the “only game in town” and they have less trust in elections. To test this idea, I study the spillover effects of the 2018 Brazilian presidential election, in which an authoritarian candidate won decisively. Using the AmericasBarometer in Colombia that was launched throughout this election, I find that the election trust of Colombian citizens erodes after Jair Bolsonaro’s electoral success. To probe into the mechanism, I uncover that his electoral victory leads Colombian citizens to be less supportive of the domestic political system and reduces their principled support for democracy. The causal mediation analysis demonstrates that these two variables mediate the effect of the authoritarian’s electoral success on election trust. These findings on autocratization spillover effects illustrate the importance of external autocratization events in the study of election trust.
Association of Apple Scar Skin Viroid (ASSVd) Infection with an Emerging Disease in ‘Saiwaihong’ Apples
Authors: Xu Huiyuan , Han Yongzeng , Du Yajie , Wang Baoxia , Zhan Binhui , Li Shifang , Zhang Zhixiang
Published: June 2024

A novel disease affecting small immature fruits has surfaced in ‘Saiwaihong’ apples (Malus pumila), a recently developed variety extensively cultivated across more than 20,000 ha in China. In an effort to pinpoint the causal agent(s) responsible for this ailment, RNA sequencing analysis was conducted on four symptomatic and four asymptomatic apple samples. The results revealed a diverse range of viruses and viroids, indicating mixed viral infection in diseased samples. However, a more focused examination involving 152 symptomatic and 122 asymptomatic fruit samples, using RT-PCR and dot-blotting hybridization techniques, highlighted a close association between the disease and the presence of apple scar skin viroid (ASSVd). Among the ASSVd variants obtained from diseased ‘Saiwaihong’ apples, 20 were identified, and they were either identical or closely related to isolates from various apple varieties cultivated in different regions and countries. This suggests that ASSVd isolates in ‘Saiwaihong’ might have been introduced from other apple varieties. Furthermore, the analysis indicates the possibility of two separate introductions, as the ASSVd ‘Saiwaihong’ isolates exhibited two distinct phylogenetic groups. These insights provide valuable guidance for disease control strategies and emphasize the significance of ongoing monitoring for ASSVd, both in its familiar forms and potential new variants.
Characterization and Pathogenicity of Soilborne Pathogens in Gloriosa superba: Effects of Single- and Multiple-Pathogen Coinfection on Disease Responses
Authors: Dhanabalan Shanmuga Priya , Johnson Iruthayasamy , Kumaresan Parthiban V. , Kandasamy Rajamani , Natesan Senthil , Periyannan Sambasivam , Muthusamy Karthikeyan
Published: June 2024

Glory lily (Gloriosa superba), an ornamental climbing plant, contains the bioactive compound colchicine, attracting attention from the pharmaceutical industry. However, soilborne pathogens have emerged as a serious threat to the cultivation of glory lily, leading to substantial economic losses in the southern parts of India. Among these, the three major pathogens are Macrophomina phaseolina, Fusarium oxysporum, and Agroathelia rolfsii, causing dry root rot (also referred to as charcoal rot), wilt, and stem rot, respectively. Here, we characterized these pathogens using morphological characteristics and phylogenetic analysis of DNA sequences related to the internal transcribed spacer of ribosomal DNA, calmodulin (CAL), and translation elongation factor 1-alpha (TEF-1α). Furthermore, in the pathogenicity tests, the inoculation of M. phaseolina alone resulted in lesions measuring 7.54 ± 0.01 mm on tubers and 90% seedling mortality. This severity was comparable to the simultaneous inoculation of all three pathogens, indicating the prominence of dry root rot among soilborne diseases. This study marks the first detailed investigation of soilborne pathogens combined infection in G. superba, contributing to the understanding of fungal disease complexity in medicinal plants.
Association of psychological stress with wives’ hypertension across over 10 million Chinese married female population aged 20–49 years
Authors: Zhao Zhenyan , Jia Jiajing , Lyu Xinyi , Zhang Lihua , Wang Yuanyuan , He Yuan , Peng Zuoqi , Zhang Ya , Zhang Hongguang , Wang Qiaomei , Shen Haiping , Zhang Yiping , Yan Donghai , Ma Xu , Yang Ying
Published: June 2024

Background:

Psychological stress has been reported to be a potential risk factor for hypertension among females, but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women. We examined the associations between stress within the family and hypertension among married women.

Methods:

Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects (NFPCP) across 31 provinces in China in 2016 and 2017. Perceived stress of wives or husbands was measured with a 5-point Likert-type scale, and assessed from three domains: work/life-related stress, economic stress, and overall stress. Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension.

Results:

Of 10,027,644 couples, 261,098 (2.60%) women had hypertension. The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women (P
for trend <0.001). Compared with non-stressed participants, female participants with the highest stress themselves were at a greater risk of hypertension, with adjusted odds ratio (OR) of 1.31 (95% confidence interval [CI]: 1.25–1.37); and compared with participants whose husbands had no stress, those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24 (95% CI: 1.20–1.29). Moreover, compared with non-stressed status for both couples, only-wife-stressed, only-husband-stressed, and both-stressed couples were found to be significantly associated with increased risks of wives’ hypertension, with adjusted ORs of 1.28 (95% CI: 1.25–1.31), 1.19 (95% CI: 1.17–1.21), and 1.28 (95% CI: 1.26–1.31), respectively.

Conclusion:

Moderate to severe stress in both spouses might be associated with female hypertension prevalence, which highlights the importance of paying attention to the psychological stresses of couples within the family.
Cardiovascular health in people with perinatally acquired HIV – where do we stand?
Authors: Majonga Edith D. , Henderson Merle , Ferrand Rashida A.
Published: June 2024

Purpose of review

HIV-associated cardiac disease was well recognized in the preantiretroviral (ART) era among children with perinatally-acquired HIV infection (PHIV). While ART has dramatically improved survival, it has become increasingly apparent that individuals with PHIV continue to experience multisystem co-morbidities. We review the cardiac and vascular manifestations in people growing up with PHIV in the ART era.

Recent findings

ART has resulted in a drop in incidence of serious cardiac morbidity. However, there is a substantial body of evidence that demonstrates that cardiac and vascular structural and functional abnormalities, mostly subclinical, are common in people with PHIV taking ART. Studies have considerable heterogeneity with respect to types of cardiovascular assessments used. HIV-mediated chronic inflammation and potentially effects of ART contribute to these abnormalities. The long-term clinical significance of these abnormalities remains unknown as studies have mainly been cross-sectional, but it is likely that the burden of cardiovascular disease will grow as individuals with PHIV age and the prevalence of traditional risk factors increases.

Understanding the pathogenesis of cardiovascular disease in PHIV, is critical to inform screening and interventional strategies. Longitudinal studies are also needed to understand the natural history of cardiovascular abnormalities and incidence of clinical outcomes.
Integrated and collaborative care across the spectrum of alcohol-associated liver disease and alcohol use disorder
Authors: Haque Lamia Y. , Leggio Lorenzo
Published: June 2024

The public health impact of alcohol-associated liver disease (ALD), a serious consequence of problematic alcohol use, and alcohol use disorder (AUD) is growing, with ALD becoming a major cause of alcohol-associated death overall and the leading indication for liver transplantation in the United States. Comprehensive care for ALD often requires treatment of AUD. Although there is a growing body of evidence showing that AUD treatment is associated with reductions in liver-related morbidity and mortality, only a minority of patients with ALD and AUD receive this care. Integrated and collaborative models that streamline both ALD and AUD care for patients with ALD and AUD are promising approaches to bridge this treatment gap and rely on multidisciplinary and interprofessional teams and partnerships. Here, we review the role of AUD care in ALD treatment, the effects of AUD treatment on liver-related outcomes, the impact of comorbid conditions such as other substance use disorders, obesity, and metabolic syndrome, and the current landscape of integrated and collaborative care for ALD and AUD in various treatment settings. We further review knowledge gaps and unmet needs that remain, including the role of precision medicine, the application of harm reduction approaches, the impact of health disparities, and the need for additional AUD treatment options, as well as further efforts to support implementation and dissemination.
Recompensation of cirrhosis in candidates of transplant: Tips and tricks for delisting
Authors: Tonon Marta , Gagliardi Roberta , Zeni Nicola , Piano Salvatore
Published: June 2024

Liver transplantation (LT) is the most successful treatment for patients with decompensated cirrhosis. The availability of effective and safe etiological treatments has altered the natural history of decompensated cirrhosis. Recently, the concept of recompensation has been defined. Patients who achieve recompensation may be removed from the waiting list for LT. Therefore, achieving an etiological cure is the cornerstone in the treatment of patients with decompensated cirrhosis. However, most patients improve their liver function after an etiologic cure, and only a proportion of patients achieve true recompensation after an etiological cure. Some patients maintain a condition of “MELD purgatory,” that is, an improvement in the Model for End-Stage Liver Disease score without relevant clinical improvement that prevents delisting and may be even detrimental because lower Model for End-Stage Liver Disease score delays LT. Herein, we review the available evidence regarding recompensation and the management of recompensated patients on the waiting list for LT.
Patient education and surgical decision-making in genital gender-affirming surgery
Authors: Arteaga Rebecca , Dryden Kim , Blasdel Gaines
Published: June 2024

Purpose of review

An update on the latest advances in surgical decision-making for genital gender-affirming surgery (GGAS), with an emphasis on patient education from three perspectives: surgeon-team perspectives, patient perspectives, and educational resources available to the public on social media.

Recent findings

Transgender, nonbinary, and other culturally specific gender identities (TGNB) patients overwhelmingly desire an active role in the decision-making process. New developments in patient-engagement strategies help mitigate the harm of historical gatekeeping practices by centering the needs and experiences of TGNB patients to create a prioritized research agenda for GGAS effectiveness. Patient educational resources play an integral role in navigating the complexity of GGAS-surgical options, informing patients of the technical and logistical knowledge required for GGAS surgical decision-making. Peer support experiences are a critical facilitator for patient surgical decision-making, both for informed decision-making and for psychosocial support.

Several developments have been made in examining shared-decision making, educational resources from the perspectives of both the surgical team and patients, and the role of social media in GGAS. Surgeons must continue to initiate robust conversations of patient goals, GGAS surgical options, the possible risk and benefit profiles of each option, and aftercare requirements, all while prioritizing patient-engagement strategies.
Focal Shock Waves Increase Efficacy and Prolong the Effect of Botulinum Toxin on Spasticity in Patients With Brain Injury From Stroke and Multiple Sclerosis
Authors: Déniz Antonio , Saavedra Pedro , Marrero Isabel , Hernández Jaime
Published: June 2024

Objective

The aim of the study is to assess the effects on spasticity reduction of the association between focal extracorporeal shock wave therapy and botulinum toxin type A, versus the toxin only in brain injury patients.

Design

Eighteen patients were included. The study had two phases: the first phase was observational, and botulinum toxin type A was used. The second was a prospective, deliberate intervention phase in which the toxin was injected and focal extracorporeal shock wave treatment was added (1 sessions/week, for 3 wks). The patients were followed up in the 1st, 4th, and 6th month, the Ashworth Scale criterion was applied, and for those with lower limb involvement and changes in walking, the 10-meter walk test was used.

Results

Patients treated with toxin only showed a statistically significant improvement in spasticity, with 1 point on the Ashworth Scale from week 5, which disappeared at week 17. However, the combined therapy reduced spasticity by 2 points from week 1 to week 25 (P < 0.001), with a faster result in the 10-meter gait test (P = 0.004).

Conclusions

Combined and simultaneous treatment with botulinum toxin and focal extracorporeal shock wave reduced spasticity in a more effective and prolonged way than treatment with botulinum toxin only.
In Search of a Common Language: The Standardized Electrode Nomenclature for Stereoelectroencephalography Applications
Authors: Chiu Michelle Y. , Bolton Jeffrey , Raskin Jeffrey S. , Curry Daniel J. , Weiner Howard L. , Pearl Phillip L. , Stone Scellig
Published: June 2024

Purpose:

Stereoelectroencephalography (SEEG) is widely performed on individuals with medically refractory epilepsy for whom invasive seizure localization is desired. Despite increasing adoption in many centers across the world, no standardized electrode naming convention exists, generating confusion among both clinical and research teams.

Methods:

We have developed a novel nomenclature, named the Standardized Electrode Nomenclature for SEEG Applications system. Concise, unique, informative, and unambiguous labels provide information about entry point, deep targets, and relationships between electrodes. Inter-rater agreement was evaluated by comparing original electrode names from 10 randomly sampled cases (including 136 electrodes) with those prospectively assigned by four additional blinded raters.

Results:

The Standardized Electrode Nomenclature for SEEG Application system was prospectively implemented in 40 consecutive patients undergoing SEEG monitoring at our institution, creating unique electrode names in all cases, and facilitating implantation design, SEEG recording and mapping interpretation, and treatment planning among neurosurgeons, neurologists, and neurophysiologists. The inter-rater percent agreement for electrode names among two neurosurgeons, two epilepsy neurologists, and one neurosurgical fellow was 97.5%.

Conclusions:

This standardized naming convention, Standardized Electrode Nomenclature for SEEG Application, provides a simple, concise, reproducible, and informative method for specifying the target(s) and relative position of each SEEG electrode in each patient, allowing for successful sharing of information in both the clinical and research settings. General adoption of this nomenclature could pave the way for improved communication and collaboration between institutions.
Identification of adrenergic presynaptic and postsynaptic protein locations at neuromuscular junctions, their decrease during aging, and recovery by nicotinamide mononucleotide administration
Authors: Takeno Kotaro , Watanabe Nobuhiro , Morifuji Masashi , Hotta Harumi , Nishimune Hiroshi
Published: June 2024

Neuromuscular junctions are innervated by motor and sympathetic nerves. The sympathetic modulation of motor innervation shows functional decline during aging, but the cellular and molecular mechanism of this change is not fully known. This study aimed to evaluate the effect of aging on sympathetic nerves and synaptic proteins at mouse neuromuscular junctions. Sympathetic nerves, presynaptic, and postsynaptic proteins of sympathetic nerves at neuromuscular junctions were visualized using immunohistochemistry, and aging-related changes were compared between adult-, aged-, and nicotinamide mononucleotide (NMN) administered aged mice. Sympathetic nerves were detected by anti-tyrosine hydroxylase antibody, and presynaptic protein vesicular monoamine transporter 2 colocalized with the sympathetic nerves. These two signals surrounded motor nerve terminals and acetylcholine receptor clusters. Postsynaptic neurotransmitter receptor β2-adrenergic receptors colocalized with motor nerve terminals and resided in reduced density at extrasynaptic sarcolemma. The signal intensity of the sympathetic nerve marker did not show a significant difference at neuromuscular junctions between 8.5-month-old adult mice and 25-month-old aged mice. However, the signal intensity of vesicular monoamine transporter 2 and β2-adrenergic receptors showed age-related decline at neuromuscular junctions. Interestingly, both age-related declines reverted to the adult level after 1 month of oral administration of NMN by drinking water. In contrast, NMN administration did not alter the expression level of sympathetic marker tyrosine hydroxylase at neuromuscular junctions. The results suggest a functional decline of sympathetic nerves at aged neuromuscular junctions due to decreases in presynaptic and postsynaptic proteins, which can be reverted to the adult level by NMN administration.
Barriers and facilitators for the implementation of co-created nursing innovations in a Dutch university hospital
Authors: van der Zanden Myrthe , Helder Onno , Westland Heleen , Ista Erwin
Published: June 2024

Introduction:

Escalating global nursing shortages require solutions for efficient care, fewer injuries and lost workdays. When commercial solutions are lacking, innovations developed through co-creation can be a viable alternative. However, many co-created nursing innovations are ineffectively implemented. Understanding the barriers and facilitators for the successful implementation of co-created nursing innovations is crucial.

Objective:

This study explored nurses’ perceived determinants influencing the implementation of co-created nursing innovations.

Methods:

We conducted a qualitative study using semi-structured interviews with nurses at a Dutch university hospital who were working with co-created nursing innovations. The Theoretical Domains Framework (TDF) was employed to identify the barriers and facilitators. Data analysis followed a deductive theoretical thematic analysis approach based on the 14 TDF domains. Determinants were labeled as a barrier, facilitator, or both.

Results:

Of the 14 TDF domains, 9 appeared relevant, including Intention, Professional Role and Identify, and Knowledge. The absence of a “superuser,” lack of storage space, and negative experiences during use were perceived as barriers to the implementation of nursing innovations. The importance of time-saving features, user-friendliness, reminders to use the innovation, and team enthusiasm were perceived as facilitators.

Conclusions:

Participants confirmed that the Social Influences domain, combined with Behavioral Regulation and Knowledge, were barriers to implementation, while Intentions and Reinforcements and Rewards were seen as facilitators.

Spanish abstract:

http://links.lww.com/IJEBH/A235
IntegrIBS: Evaluating the Potential and Challenges of Building a Robust IBS Classifier with Integrated Microbiome Data
Authors: Palani Dinakaran , Bapatdhar Nishad , Manchiraju Renuka , Kumar Bipin Pradeep , Ghosh Samik , Palaniappan Sucheendra K.
Published: June 2024

Irritable Bowel Syndrome (IBS) is a condition that is quite complicated and shares its symptoms with other related diseases, making it difficult to diagnose. In this study, we initially trained machine learning models on individual microbiome datasets and tested their performance on other datasets, observing variability and low precision among them. To mitigate this, we hypothesised that integrating multiple publicly available microbiome datasets will capture a wide spectrum of microbiome variations across different geographies and demographics. Utilizing this integrated dataset, the XGBoost model achieved a mean accuracy of 0.75 with a standard deviation of 0.04 in 10-fold cross-validation, demonstrating its potential for robust IBS prediction. Explainability analysis identified key bacterial taxa influencing predictions, aligning with existing literature. However, the model’s performance declined significantly when using a leave-one-dataset-out approach, where the model was trained on all but one dataset and tested on the excluded dataset. The results highlight the challenges of generalizing across diverse datasets due to biological and technical variability. These findings present a cautionary tale regarding the integration of datasets and interpretation of results, emphasizing the need for more comprehensive approaches to develop reliable diagnostic tools for IBS.
Joint Model with Random Changepoint for Longitudinal Measures and Semi-competing Risks
Authors: Wang Xuzhi , Larson Martin G. , Tripodis Yorghos , LaValley Michael P. , Liu Chunyu
Published: June 2024

Dementia displays a gradual decline in cognitive abilities, often accompanied by an accelerated cognitive decline preceding diagnosis. Changepoint models are proposed to identify when cognitive decline accelerates and how it progresses. Joint models are developed to further account for dropout due to death or dementia. Cognitive decline in dementia patients may lead to complications that have an impact on their mortality. However, few joint models consider semi-competing risks (i.e., dementia and death) by distinguishing transitions between various health states, i.e., dementia without death, death after dementia, and death without dementia. We proposed a joint model that accounts for both changepoints and semi-competing risks by combining a multivariate random changepoint model for cognitive decline with an illness-death model that estimates health state transitions. We examined the proposed model with two types of random changepoints: one with a smooth change and another with an abrupt change. We also explored a shared random effect structure and a current value structure that connect both longitudinal and survival processes. Two types of cohorts, i.e., a disease cohort and a community cohort, were generated to evaluate the models. Simulation studies showed our proposed models could effectively characterize the influence of the longitudinal process on health state transitions. In addition, the choice of changepoint formulations, association structures, and cohort types impacted model performance. Real data application in the Framingham Heart Study indicated significant associations between changepoints in cognitive trajectories and health states for dementia and death. Our method provides a flexible framework to integrate longitudinal trajectories with changepoints and semi-competing risks.
Bayesian Joint Model with Latent Time Shifts for Multivariate Longitudinal Data with Informative Dropout
Authors: Wang Xuzhi , Larson Martin G. , Tripodis Yorghos , LaValley Michael P. , Liu Chunyu
Published: June 2024

Dementia often has an insidious onset with considerable individual differences in disease manifestation. Nonlinear mixed-effects models with latent time shifts have been proposed to investigate the long-term disease progression and individual disease stages. The latent time shift is a horizontal shift in time that aligns patients along a global timeline for disease progression. However, these models ignore informative dropout due to dementia or death, which may result in biased estimates of the longitudinal parameters. To account for informative dropout due to dementia or death, we propose a multivariate nonlinear joint model with latent time shifts. This joint model uses a multivariate nonlinear mixed-effects model with latent time shifts to model the correlated longitudinal markers of cognitive decline, and simultaneously, a proportional hazards model to incorporate dropout due to dementia or death. We investigate two association structures between the longitudinal process and the time to event process: the current value structure and the shared random effect structure. We compare the proposed joint model with separate models that ignore informative dropout across various simulation settings. The proposed joint models with correctly specified association structures show the best performance. Even the models with misspecified association structures outperform the separate models that does not consider informative dropout. We conclude that our proposed joint model with latent time shifts offers more accurate and robust estimates than the latent time disease progression models that neglect informative dropout. Future research will involve incorporating competing risks and other parametrizations of the longitudinal model into this joint model framework.
Functional dissection of the conservedC. elegansLEM-3/ANKLE1 nuclease reveals a crucial requirement for the LEM-like and GIY-YIG domains for DNA bridges processing
Authors: Song Junfang , Geary Peter , Hong Ye , Rolland Stéphane G.M. , Garter Anton
Published: June 2024

Faithful chromosome segregation requires the removal of all DNA bridges physically linking chromatids before the completion of cell division. While several redundant safeguard mechanisms to process these DNA bridges exist from S-phase to late anaphase, the conserved LEM-3/ANKLE1 nuclease has been proposed to be part of a ‘last chance’ mechanism that acts at the midbody to eliminate DNA bridges that persist until late cytokinesis. We show that LEM-3 can cleave a wide range of branched DNA substrates, including flaps, forks, nicked and intact Holliday Junctions. AlphaFold modeling data suggest that the catalytic mechanism of LEM-3/ANKLE1 is conserved, mirroring the mechanism observed in bacterial GIY-YIG nucleases. We also present evidence that LEM-3 may form a homodimeric complex on the Holliday Junction DNA. LEM-3 DNA binding capacity requires both the LEM-like and the GIY-YIG nuclease domains; both are also essential for LEM-3 recruitment to the midbody and its nuclease activity. Finally, we show that preventing LEM-3 nuclear access is important to avoid toxicity, likely caused by branched DNAs cleavage during normal DNA metabolism. Our data suggest thatC. elegansLEM-3 acts as a ‘last chance catch-all’ enzyme that processes DNA bridges caused by various perturbations of DNA metabolism just before cells divide.