bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer—a multitude of diseases
Authors: Divan Aysha , Royds Janice
Published: August 2024

This chapter examines the notion of cancer as a multitude of diseases. It shows that benign tumours are not classified as cancer because they do not metastasize and spread around the body to other organs. Prognosis depends on the type, grade, and stage of a tumour and its response to treatment. The chapter explains that cancer is a multistep process that requires multiple genetic and epigenetic changes to occur in cells that also need time to develop. It then provides an overview of the hallmarks of cancer, citing that different cancers share several common traits despite being a diverse set of diseases.
Treating cancer
Authors: Divan Aysha , Royds Janice
Published: August 2024

This chapter focuses on the treatment of cancer. It provides an overview of the treatment options currently available to cancer patients, including surgery, radiotherapy, chemotherapy, hormone therapy, and immunotherapy. Recent developments in the speed, availability, and cost of DNA sequencing make it possible to observe and respond to mutations in cancers as they occur and change the treatment options accordingly. The chapter then looks into the development of drugs for the use of cancer treatment. It then explains that as new drugs fail to reach the approval stage, there has been a renewed interest in drug repurposing of either old or existing drugs.
The Problems We Must Solve
Authors: Niesenbaum Richard
Published: August 2024

This chapter provides an overview of the issues surrounding the environment, human actions, and quality of life. It considers how to develop solutions to environmental and social problems by presenting the interdisciplinary background needed to understand many complex problems. Since climate change is directly linked to our resource use and most environmental issues, any approach to environmental problem solving must be done so within the context of global climate change. The chapter then explores the interplay between humans and the environment. It argues that environmental, economic, and social issues need to be considered in tandem to solve the problems of the people and the world.
Energy: From Fossil Fuels to a Sustainable Future
Authors: Niesenbaum Richard
Published: August 2024

This chapter discusses the use of fossil fuels from several perspectives. These perspectives include the environment, human condition, and growing energy demand. Renewable alternatives to fossil fuels have focused on innovations and technologies which enable us to meet the growing energy needs more sustainably, and identify the most sustainable options. The chapter considers the barriers that are inhibiting the transition to a renewable-based economy and ways to remove these barriers. The transition to renewable energy will require the development of smart grid technology and infrastructure. This is needed so we can effectively manage and distribute energy. The chapter suggests rethinking transportation so that we can successfully transition to renewable energy and mitigate climate change.
Sustainability at The Most Local Level—The Individual
Authors: Niesenbaum Richard
Published: August 2024

This chapter provides an overview of sustainability at the individual level. It notes that rates of depletion and degradation are accelerating with continued population growth and the associated rise in resource use and consumption. The actions of individuals can make significant strides toward the goals of sustainability even though individual action seems insufficient if we want to move toward a sustainable future. The chapter highlights how individuals can increase their power and effectiveness by collaborating with others through direct action or protest, education, citizen science, and by working directly with the government and politics. Moreover, a major limitation of the role of the individual is that sustainable choices or actions are often less accessible to the poor, disenfranchised, and less educated.
The scientific basis of therapeutics
Authors: Gaskell Elsie E.
Published: August 2024

This chapter introduces the scientific basis of therapeutics. Therapeutics is all about the interplay of physiology and pharmacology. Understanding the physiology of living organisms provides further background on the basic concepts of pharmacology, such as the effect drugs and administered therapeutic compounds have on the body. Pharmacy is complex and multidisciplinary, interlinking an array of different pharmaceutical sciences and practice-oriented disciplines. The chapter provides an overview of how drugs work in changing cellular and physiological effects by mimicking the endogenous signals. It explains that a number of different systems must communicate and harmonize their processes to coordinate the functions within the human body.
Communication systems in the body: autocoids and hormones
Authors: Elliott Peter N. C.
Published: August 2024

This chapter focuses on autocoids and hormones. It looks at them in correlation with the communication systems in the body. It explains that the four levels of communication range between nerves, autocoids, hormones, and direct communication between adjacent cells. Autocoids are responsible for the local, fine control of a range of body systems, while hormones are responsible for the control of whole body systems. Moreover, endogenous molecules, particularly autocoids and hormones, are involved in the development of symptoms of pathologies such as hay fever. The chapter then provides an overview on the drugs that are used to alleviate the symptoms of pathologies.
Homeostasis
Authors: Penson Peter , Henney Neil
Published: August 2024

This chapter examines homeostasis. Homeostasis refers to the many ways in which the body reacts to changes in its surroundings in order to maintain near-constant internal conditions, such as thermoregulation. Most mechanisms of homeostasis rely on the principle of negative feedback in order to maintain stable systems. The chapter notes that disruption of homeostasis often leads to disease states and death. The chapter then examines the diseases or conditions which are caused by defective homeostasis. It also elaborates on the feedback mechanisms to achieve homeostasis, referencing the function and significance of the sensor, control centre, and effector.
Gases
Authors: Forbes Ben
Published: August 2024

This chapter highlights the significance of the chemical and physical properties of gases when developing medicines, such as whether the gas is a volatile agent or whether a substance has a gaseous phase. The chapter examines, more generally, the properties of gases. It takes a look at transitions from solid or liquid into gaseous states. Gases have a variety of roles in pharmaceutical operations, including surface area measurement, distillation, lyophilization, and sterilization. The chapter also highlights examples of practical applications of gases and gas-based pharmaceutical dosage forms in pharmacy. It provides an overview of several gas-based dosage forms, such as pharmaceutical aerosols for respiratory drug delivery, nebulizers, foams, non-inhalation aerosols, and aerosol powder devices.
Thermodynamics
Authors: Seton Linda
Published: August 2024

This chapter explains that thermodynamics is the study of the transfer of energy during chemical and physical processes. It provides an overview of the First Law and Second Law of Thermodynamics. All chemical reactions bring about a conversion of energy. The chapter notes that enthalpy is a state function defined as the heat energy absorbed by a system at fixed pressure. It also introduces Hess's Law, which is used to calculate enthalpy changes. It looks at Gibbs energy and shows how this relates to the notions of enthalpy and entropy, before highlighting that the equilibrium constant for a reaction depends on temperature.
Disperse systems
Authors: Lawrence Jayne
Published: August 2024

This chapter looks at disperse systems. It explains that dispersions are formed from dispersed and continuous phases, each being formed from solid, liquid, or gas. Dosage forms that consist of two or more gases are always single-phase systems, so two-phase systems consisting of a liquid phase and suspended solid particles are examples of a disperse system. An understanding of disperse systems can help control the physical properties of a substance so that it is appropriate to specific formulations. The chapter also notes that DLVO theory can help with the understanding that the dispersed particles flocculate will depend on the forces between the dispersed particles.
Kinetics and drug stability
Authors: Moss Gary
Published: August 2024

This chapter examines the significance of kinetics and drug stability. Kinetic studies can provide information on the mechanism of reactions, and allow the degree of change during a process to be measured against time. Moreover, kinetics is a field that applies to the process of drug absorption, distribution, and elimination by the body. The chapter looks at reaction rates and reaction orders before considering the factors affecting the rate of reaction of dosage forms. The Arrhenius equation may be used to model the relationship between rate constants and temperature, which allows for the estimation of the expected shelf life of a drug at its normal storage temperature.
Thermal comfort inside a gable-roofed metallic shed in a higher educational institution: a case study and detailed analysis
Authors: Jaffar Abubakkar Abdul , Pandiaraj Selvakumar , Govindasamy Kumaresan , Sharma Kamal , Muthusamy Suresh , Siddiqui Mohammad Irfanul Haque , Cuce Erdem , Shah Mohd Asif
Published: August 2024

Central workshop is an integral part of any higher education institution, and it will be generally operated in a gable-roofed metallic shed. The users of the building are affected physiologically and psychologically due to the thermal discomfort conditions caused by improper ventilation. It is necessary to study the cause for discomfort and propose cost and effective methods to mitigate the problem. In this work, the thermal comfort inside a gable-roofed workshop was analyzed, and it was found that the discomfort was predominant from 2 PM to 5 PM. It was predicted that the conduction heat transfer could be reduced upto 55% with the help of passive cooling technique carried out using aluminium bubble wrap. During the life cycle cost study, the aluminium bubble wrap technique was found to be more economical over high-volume low-speed fan. The computer simulation aided in the prediction of overall heat transfer coefficient and conduction heat transfer through wall. The results from numerical study deviated by less than 0.1% when compared with that from the theoretical model.
Scaling Limit of Multi-Type Invariant Measures via the Directed Landscape
Authors: Busani Ofer , Seppäläinen Timo , Sorensen Evan
Published: August 2024

This paper studies the large scale limits of multi-type invariant distributions and Busemann functions of planar stochastic growth models in the Kardar–Parisi–Zhang (KPZ) class. We identify a set of sufficient hypotheses for convergence of multi-type invariant measures of last-passage percolation (LPP) models to the stationary horizon (SH), which is the unique multi-type stationary measure of the KPZ fixed point. Our limit theorem utilizes conditions that are expected to hold broadly in the KPZ class, including convergence of the scaled last-passage process to the directed landscape. We verify these conditions for the six exactly solvable models whose scaled bulk versions converge to the directed landscape, as shown by Dauvergne and Virág. We also present a second, more general, convergence theorem with future applications to polymer models and particle systems. Our paper is the first to show convergence to the SH without relying on information about the structure of the multi-type invariant measures of the prelimit models. These results are consistent with the conjecture that the SH is the universal scaling limit of multi-type invariant measures in the KPZ class.
Deep learning assisted quantitative analysis of Aβ and microglia in patients with idiopathic normal pressure hydrocephalus in relation to cognitive outcome
Authors: Luikku Antti J , Nerg Ossi , Koivisto Anne M , Hänninen Tuomo , Junkkari Antti , Kemppainen Susanna , Juopperi Sini-Pauliina , Sinisalo Rosa , Pesola Alli , Soininen Hilkka , Hiltunen Mikko , Leinonen Ville , Rauramaa Tuomas , Martiskainen Henna
Published: August 2024

Neuropathologic changes of Alzheimer disease (AD) including Aβ accumulation and neuroinflammation are frequently observed in the cerebral cortex of patients with idiopathic normal pressure hydrocephalus (iNPH). We created an automated analysis platform to quantify Aβ load and reactive microglia in the vicinity of Aβ plaques and to evaluate their association with cognitive outcome in cortical biopsies of patients with iNPH obtained at the time of shunting. Aiforia Create deep learning software was used on whole slide images of Iba1/4G8 double immunostained frontal cortical biopsies of 120 shunted iNPH patients to identify Iba1-positive microglia somas and Aβ areas, respectively. Dementia, AD clinical syndrome (ACS), and Clinical Dementia Rating Global score (CDR-GS) were evaluated retrospectively after a median follow-up of 4.4 years. Deep learning artificial intelligence yielded excellent (>95%) precision for tissue, Aβ, and microglia somas. Using an age-adjusted model, higher Aβ coverage predicted the development of dementia, the diagnosis of ACS, and more severe memory impairment by CDR-GS whereas measured microglial densities and Aβ-related microglia did not correlate with cognitive outcome in these patients. Therefore, cognitive outcome seems to be hampered by higher Aβ coverage in cortical biopsies in shunted iNPH patients but is not correlated with densities of surrounding microglia.
False lumen embolization and false lumen stent-graft techniques for ruptured post-dissection thoracoabdominal aneurysm
Authors: Umibe Takumi , Nishiori Hironobu , Ikeuchi Hiroki , Koizumi Shintaroh , Ueda Hideki , Matsumiya Goro
Published: August 2024

This report details the successful endovascular repair of a ruptured thoracoabdominal aortic aneurysm in a patient with chronic type B aortic dissection. The procedure consisted of thoracic endovascular aortic repair, abdominal endovascular aortic repair, false lumen (FL) embolization with Candy-Plug, and FL stent-graft technique. The approach effectively regulated FL inflow, achieving complete FL closure. The patient was discharged without major complications including spinal cord ischemia or renal failure, and the long-term outcome is also favorable with reduction of the aneurysm size. The follow-up results have shown a reduction in the aneurysm size. This less invasive method could be an option of treatments for post-dissection thoracoabdominal aortic aneurysms, especially in ruptured cases.
Complex Genomes of Early Nucleocytoviruses Revealed by Ancient Origins of Viral Aminoacyl-tRNA Synthetases
Authors: Kijima Soichiro , Hikida Hiroyuki , Delmont Tom O , Gaïa Morgan , Ogata Hiroyuki
Published: August 2024

Aminoacyl-tRNA synthetases (aaRSs), also known as tRNA ligases, are essential enzymes in translation. Owing to their functional essentiality, these enzymes are conserved in all domains of life and used as informative markers to trace the evolutionary history of cellular organisms. Unlike cellular organisms, viruses generally lack aaRSs because of their obligate parasitic nature, but several large and giant DNA viruses in the phylum Nucleocytoviricota encode aaRSs in their genomes. The discovery of viral aaRSs led to the idea that the phylogenetic analysis of aaRSs can shed light on ancient viral evolution. However, conflicting results have been reported from previous phylogenetic studies: one posited that nucleocytoviruses recently acquired their aaRSs from their host eukaryotes, while another hypothesized that the viral aaRSs have ancient origins. Here, we investigated 4,168 nucleocytovirus genomes, including metagenome-assembled genomes (MAGs) derived from large-scale metagenomic studies. In total, we identified 780 viral aaRS sequences in 273 viral genomes. We generated and examined phylogenetic trees of these aaRSs with a large set of cellular sequences to trace evolutionary relationships between viral and cellular aaRSs. The analyses suggest that the origins of some viral aaRSs predate the last common eukaryotic ancestor. Inside viral aaRS clades, we identify intricate evolutionary trajectories of viral aaRSs with horizontal transfers, losses, and displacements. Overall, these results suggest that ancestral nucleocytoviruses already developed complex genomes with an expanded set of aaRSs in the proto-eukaryotic era.
Evolution of Virus-like Features and Intrinsically Disordered Regions in Retrotransposon-derived Mammalian Genes
Authors: Cagliani Rachele , Forni Diego , Mozzi Alessandra , Fuchs Rotem , Tussia-Cohen Dafna , Arrigoni Federica , Pozzoli Uberto , De Gioia Luca , Hagai Tzachi , Sironi Manuela
Published: August 2024

Several mammalian genes have originated from the domestication of retrotransposons, selfish mobile elements related to retroviruses. Some of the proteins encoded by these genes have maintained virus-like features; including self-processing, capsid structure formation, and the generation of different isoforms through −1 programmed ribosomal frameshifting. Using quantitative approaches in molecular evolution and biophysical analyses, we studied 28 retrotransposon-derived genes, with a focus on the evolution of virus-like features. By analyzing the rate of synonymous substitutions, we show that the −1 programmed ribosomal frameshifting mechanism in three of these genes (PEG10, PNMA3, and PNMA5) is conserved across mammals and originates alternative proteins. These genes were targets of positive selection in primates, and one of the positively selected sites affects a B-cell epitope on the spike domain of the PNMA5 capsid, a finding reminiscent of observations in infectious viruses. More generally, we found that retrotransposon-derived proteins vary in their intrinsically disordered region content and this is directly associated with their evolutionary rates. Most positively selected sites in these proteins are located in intrinsically disordered regions and some of them impact protein posttranslational modifications, such as autocleavage and phosphorylation. Detailed analyses of the biophysical properties of intrinsically disordered regions showed that positive selection preferentially targeted regions with lower conformational entropy. Furthermore, positive selection introduces variation in binary sequence patterns across orthologues, as well as in chain compaction. Our results shed light on the evolutionary trajectories of a unique class of mammalian genes and suggest a novel approach to study how intrinsically disordered region biophysical characteristics are affected by evolution.
Human Immunodeficiency Virus–Induced Interferon-Stimulated Gene Expression Is Associated With Monocyte Activation and Predicts Viral Load
Authors: van Pul Lisa , van Dort Karel A , Girigorie Arginell F , Maurer Irma , Harskamp Agnes M , Kootstra Neeltje A
Published: August 2024

Background

Chronic immune activation is one of the hallmarks of human immunodeficiency virus (HIV) pathogenesis. Persistent upregulation of interferons (IFNs) and interferon-stimulated genes (ISGs) has previously been associated with chronic immune activation and HIV progression. Here a longitudinal analysis of the IFN and ISG response during HIV infection was performed to gain insights into the ongoing immune activation during HIV infection.

Methods

IFN and ISG levels were determined using quantitative polymerase chain reaction in peripheral blood mononuclear cells of people with HIV at pre-seroconversion, during acute and chronic HIV infection, and during suppressive antiretroviral therapy (ART).

Results

HIV infection induced the expression of a set of 4 ISGs—RSAD2, ISG15, IFI44L, and IFI27—which remained upregulated during chronic infection. This set of ISGs showed no clear correlations with T-cell activation as determined by co-expression of CD38 and HLA-DR. However, a strong correlation with monocyte activation marker soluble CD163 in serum was found. Furthermore, the expression of this ISG cluster was predictive of viral load before ART initiation and, on ART, expression levels normalized to pre-seroconversion levels.

Conclusions

The results presented here suggests that ISG expression is linked to monocyte activation, possibly driven by viral replication.
Facial recognition for disease diagnosis using a deep learning convolutional neural network: a systematic review and meta-analysis
Authors: Kong Xinru , Wang Ziyue , Sun Jie , Qi Xianghua , Qiu Qianhui , Ding Xiao
Published: August 2024

Background

With the rapid advancement of deep learning network technology, the application of facial recognition technology in the medical field has received increasing attention.

Objective

This study aims to systematically review the literature of the past decade on facial recognition technology based on deep learning networks in the diagnosis of rare dysmorphic diseases and facial paralysis, among other conditions, to determine the effectiveness and applicability of this technology in disease identification.

Methods

This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for literature search and retrieved relevant literature from multiple databases, including PubMed, on 31 December 2023. The search keywords included deep learning convolutional neural networks, facial recognition, and disease recognition. A total of 208 articles on facial recognition technology based on deep learning networks in disease diagnosis over the past 10 years were screened, and 22 articles were selected for analysis. The meta-analysis was conducted using Stata 14.0 software.

Results

The study collected 22 articles with a total sample size of 57 539 cases, of which 43 301 were samples with various diseases. The meta-analysis results indicated that the accuracy of deep learning in facial recognition for disease diagnosis was 91.0% [95% CI (87.0%, 95.0%)].

Conclusion

The study results suggested that facial recognition technology based on deep learning networks has high accuracy in disease diagnosis, providing a reference for further development and application of this technology.
‘We’ve Been Left Out’: women’s refuges in Northern Ireland, 1974–2008
Authors: McKimm Alice
Published: August 2024

With histories of late-twentieth-century Northern Ireland1 consumed with political violence, and studies of the contemporary women’s movements in Britain only recently shifting their focus beyond London, Northern Irish women’s refuges have been obscured from historical view. This article proposes that re-situating women’s refuges in the context of the Troubles can enrich our understanding of the refuge movements, and wider women’s activism, across the UK at the turn of the twenty-first century. Drawing from archived and original interviews as well as documentary sources, the article traces the development of the Northern Irish refuge movement over four key periods: early years (1974–83), cross-community organizing (1983–93), development (1993–8), and efforts for diversity and inclusion (1998–2008). Such a chronology challenges the perception of the 1980s as an era of division and decline for UK feminism, and highlights the value of moving away from overarching chronologies of women’s activism towards more localized timelines. Furthermore, re-contextualizing women’s refuges in the battleground of the Troubles offers new evidence of their efforts to reduce domestic abuse, bring together women from opposing communities, and rebuild a democratic society. These activities contributed to the ‘vernacular’ peace process taking place in Northern Ireland’s voluntary sector, and suggest that refuges across the UK were similarly engaged in a peace process addressing violence in the home.
Exploring the therapeutic potential of urine‐derived stem cell exosomes in temporomandibular joint osteoarthritis
Authors: Zhou Jian‐Ping , Peng Si‐Si , Xu Jie , Cheng Xing‐Wang , Wang Xiao‐Hui , Tao Jun‐Li , Dai Hong‐Wei , Cao Xin
Published: August 2024

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative ailment that causes slow cartilage degeneration, aberrant bone remodeling, and persistent discomfort, leading to a considerable reduction in the patient's life quality. Current treatment options for TMJOA have limited efficacy. This investigation aimed to explore a potential strategy for halting or reversing the progression of TMJOA through the utilization of exosomes (EXOs) derived from urine‐derived stem cells (USCs). The USC‐EXOs were obtained through microfiltration and ultrafiltration techniques, followed by their characterization using particle size analysis, electron microscopy, and immunoblotting. Subsequently, an in vivo model of TMJOA induced by mechanical force was established. To assess the changes in the cartilage of TMJOA treated with USC‐EXOs, we performed histology analysis using hematoxylin–eosin staining, immunohistochemistry, and histological scoring. Our findings indicate that the utilization of USC‐EXOs yields substantial reductions in TMJOA, while concurrently enhancing the structural integrity and smoothness of the compromised condylar cartilage surface. Additionally, USC‐EXOs exhibit inhibitory effects on osteoclastogenic activity within the subchondral bone layer of the condylar cartilage, as well as attenuated apoptosis in the rat TMJ in response to mechanical injury. In conclusion, USC‐EXOs hold considerable promise as a potential therapeutic intervention for TMJOA.
Preventing Hypothermia in Newborns With Congenital Anomalies in the Delivery Room
Authors: Heimall Lauren , Barrila-Yetman Michele , McCray Kia R. , Cestare Danielle , Duran Melissa , Wild K. Taylor , Ades Anne
Published: August 2024

Background:

Thermoregulation interventions in the delivery room have historically focused on preterm infants and studies often exclude term infants or those infants with known congenital anomalies.

Purpose:

The purpose of this quality improvement project was to reduce the rate of admission hypothermia in neonates of all gestational ages born with congenital anomalies and admitted to the intensive care unit (ICU).

Methods:

Utilizing the Institute for Healthcare Improvement model for improvement, implementation of plan, do study, act cycles focused on standardizing temperatures of the delivery room and resuscitation bed, recommendations for temperature monitoring, trialing polyethylene lined hats, and implementing a delivery room thermoregulation checklist.

Results:

Overall, the mean rate of neonates admitted to the ICU hypothermic (<36.5°C) decreased from 27% to 9% over an 8-month period.

Implications for Practice and Research:

The interventions significantly reduced the number of neonates admitted to the ICU with hypothermia. Implementation of thermoregulation bundles should apply to all neonates with congenital anomalies to decrease risks associated with hypothermia.
Infant Cervical Vestibular Evoked Myogenic Potentials: A Scoping Review
Authors: Bassett Alaina M. , Suresh Chandan
Published: August 2024

Objectives:

Children diagnosed with hearing loss typically demonstrate increased rates of vestibular loss as compared with their peers, with hearing within normal limits. Decreased vestibular function is linked with delays in gross motor development, acquisition of gross motor skills, and academic challenges. Timely development of sitting and walking gross motor skills aids in the progress of environmental exploratory activities, which have been tied to cognitive, language, and vocabulary development. Considering the time-sensitive development of gross motor skills and cognitive, language, and vocabulary development, identifying vestibular loss in infancy can support early intervention. This scoping review analyzes stimulus, recording, and participant factors relevant to assessing cervical vestibular evoked myogenic potentials (cVEMPs) in the infant population.

Design:

The scoping literature review was conducted on literature published between 2000 and 2023, focusing on articles assessing cVEMPs in infants. Two authors independently followed Preferred Reporting Items for Systematic and Meta-Analysis guidelines for title and abstract screening, full-text review, data extraction, and quality assessments. Sixteen articles meeting the inclusion criteria were included in the analysis.

Results:

The existing literature lacks consensus regarding stimulus and recording parameters for measuring infant cVEMPs. In addition, the review reveals a decrease in cVEMP response occurrence rates with the severity of hearing loss, especially in cases of severe to profound hearing loss, compared with mild to moderate sensorineural hearing loss in infants.

Conclusions:

This scoping review demonstrates the increasing use of cVEMP as a reliable tool for objectively assessing infant vestibular function. The lack of consensus in stimulus and recording parameters emphasizes the need for systematic research to establish an evidence-based protocol for cVEMP measurements in infants. Such a protocol will ensure the reliable measurement of cVEMPs in infants and enhance the effectiveness of cVEMP as part of the infant vestibular test battery. In addition, there is a necessity for a comprehensive large-scale study to evaluate the practicality and feasibility of implementing vestibular screening protocols for infants diagnosed with sensorineural hearing loss in the United States.
Iatrogenic Intraoperative Fracture in Patients With Osteogenesis Imperfecta
Authors: Georgiadis Andrew G. , Pottinger Todd J. , Sigrist Emmalynn J. , Truong Walter H.
Published: August 2024

Background:

Osteogenesis imperfecta (OI) is a genetic defect in collagen type I, phenotypically characterized by bony fragility and a propensity to high rates of childhood fracture. Fragility fractures in patients with OI have been reported with routine hospital care. In addition, there is a nonzero rate of iatrogenic fracture during orthopaedic surgery directly related to the technical steps of the procedure itself. The rate of this latter has never been explicitly investigated.

Methods:

A review of all patients at a single OI referral center was conducted, including all patients with a diagnosis of OI seen between 2013 and 2023, inclusive. All patients who underwent orthopaedic surgery of any kind were reviewed, and clinical and radiographic details of all procedures were extracted. Among the details examined were the OI subtype, surgery details, any implants used, intraoperative and hospital stay complications, modified Clavien-Dindo classification of complications, and ultimate outcome.

Results:

Eleven of 60 patients experienced an unplanned, iatrogenic intraoperative fracture during orthopaedic surgery (11/60 = 18.3%). This comprised 15 fractures among 356 total orthopaedic surgical episodes (15/356 = 4.2%). All but one fracture occurred on the operative long bone segment, all were a direct result of surgical steps, and 11 of 15 fractures occurred in the femur. Most fractures were secondary to the removal, insertion, or exchange of intramedullary implants in the lower extremity (11 of 15 fractures), most often the femur. Thirteen of 15 injuries were classified as modified Clavien-Dindo II or III, requiring modification of postop rehabilitation, additional treatments, or surgical intervention (87%). Overall, iatrogenic fracture was the most common intraoperative complication experienced in the cohort.

Conclusions:

Iatrogenic fracture during orthopaedic surgery for patients with OI is not uncommon. A sizeable minority of patients with OI undergoing orthopaedic surgery will experience unplanned fractures, most commonly in the femur, and care is altered in most instances. The risk of intraoperative fracture can be discussed with families of children with OI as part of informed consent and shared decision-making.

Level of Evidence:

Level IV—retrospective cohort series.
Hip Displacement After Triradiate Closure in Ambulatory Cerebral Palsy: Who Needs Continued Surveillance?
Authors: Lindgren Amelia M. , Asma Ali , Rogers Kenneth J. , Miller Freeman , Shrader M. Wade , Howard Jason J.
Published: August 2024

Background:

Hip surveillance in cerebral palsy (CP) is an accepted practice with evidence-based guidelines implemented. For the skeletally immature with open triradiate cartilage (TRC), recommendations for radiographic surveillance stemmed from population-based studies. For nonambulatory CP, progression of hip displacement after skeletal maturity has been reported; less is known for ambulatory CP. We aimed to determine the prevalence and risk factors associated with progressive hip displacement after TRC closure, a proxy for skeletal maturity, for ambulatory CP.

Methods:

This is a retrospective cohort study of patients with ambulatory CP (Gross Motor Function Classification System I-III), with unilateral or bilateral involvement, hypertonic motor type, regular hip surveillance (≥3 radiographs after age 10 yr, 1 before TRC closure, ≥1 after age 16 yr), and 2-year follow-up post-TRC closure. The primary outcome was migration percentage (MP). Other variables included previous preventative/reconstructive surgery, topographic pattern, sex, scoliosis, epilepsy, and ventriculoperitoneal shunt. An “unsuccessful hip” was defined by MP ≥30%, MP progression ≥10%, and/or requiring reconstructive surgery after TRC closure. Statistical analyses included chi-square and multivariate Cox regression. Kaplan-Meier survivorship curves were also determined. Receiver operating characteristic analysis was used to determine the MP threshold for progression to an “unsuccessful hip” after TRC closure.

Results:

Seventy-six patients (39.5% female) met the inclusion criteria, mean follow-up 4.7±2.1 years after TRC closure. Sixteen (21.1%) patients had an unsuccessful hip outcome. By chi-square analysis, diplegia (P=0.002) and epilepsy (P=0.04) were risk factors for an unsuccessful hip. By multivariate analysis, only first MP after TRC closure (P<0.001) was a significant risk factor for progression to an unsuccessful hip; MP ≥28% being the determined threshold (receiver operating characteristic curve analysis, area under curve: 0.845, P<0.02).

Conclusions:

The risk of MP progression after skeletal maturity is relatively high (21%), similar to nonambulatory CP. Annual hip surveillance radiographs after TRC closure should continue for Gross Motor Function Classification System I-III with an MP ≥28% after TRC closure, especially for bilateral CP and epilepsy.

Level of Evidence:

III
Transcriptomic profiling of intermediate cell carcinoma of the liver
Authors: Jang Byungchan , Kwon So Mee , Kim Jang Hyun , Kim Jung Mo , Chung Taek , Yoo Jeong Eun , Kim Haeryoung , Calderaro Julien , Woo Hyun Goo , Park Young Nyun
Published: August 2024

Background:

Intermediate cell carcinoma (Int-CA) is a rare and enigmatic primary liver cancer characterized by uniform tumor cells exhibiting mixed features of both HCC and intrahepatic cholangiocarcinoma. Despite the unique pathological features of int-CA, its molecular characteristics remain unclear yet.

Methods:

RNA sequencing and whole genome sequencing profiling were performed on int-CA tumors and compared with those of HCC and intrahepatic cholangiocarcinoma.

Results:

Int-CAs unveiled a distinct and intermediate transcriptomic feature that is strikingly different from both HCC and intrahepatic cholangiocarcinoma. The marked abundance of splicing events leading to intron retention emerged as a signature feature of int-CA, along with a prominent expression of Notch signaling. Further exploration revealed that METTL16 was suppressed within int-CA, showing a DNA copy number–dependent transcriptional deregulation. Notably, experimental investigations confirmed that METTL16 suppression facilitated invasive tumor characteristics through the activation of the Notch signaling cascade.

Conclusions:

Our results provide a molecular landscape of int-CA featured by METTL16 suppression and frequent intron retention events, which may play pivotal roles in the acquisition of the aggressive phenotype of Int-CA.
The role of patient and family advisory boards in promoting greater attention to patient social needs by U.S. acute care hospitals
Authors: Hearld Larry R. , Jennings J’Aime , Hubbard Demetria , Lee Seung-Yup , Hearld Kristine R.
Published: August 2024

Background

There is growing attention to individual-level patient social needs such as unstable housing and food insecurity. Such considerations, however, have historically been the purview of public health and have not been a priority of more traditional health care delivery organizations, such as acute care hospitals.

Purpose

The purpose of this study was to examine whether the presence of patient and family advisory boards (PFABs) among acute care community hospitals was associated with screening for and programs to address patient social needs.

Methods

We used a secondary data set derived from the American Hospital Association’s 2020 and 2021 annual surveys, along with multinomial and negative binomial regression models to assess the relationship between the presence/absence of a PFAB and the likelihood of offering and the number of areas addressed by social needs screening programs.

Results

More than half (55.9%) of all responding hospitals reported having a PFAB in 2020 (55.9%) and 2021 (52.7%). The presence of a PFAB among hospitals was significantly associated with patient social needs screening, more areas addressed by programs, and more types of partners to address these needs.

Conclusions

Community hospitals with a PFAB have more robust programs and partnerships to address patient social needs.

Practice Implications

Hospital leaders should consider going beyond simply establishing programs to address social needs but also consider comprehensiveness of these programs to recognize the intersectionality of social needs. One way to do this is to formally establish a PFAB to help hospitals better identify and prioritize the needs in local communities and design social needs programs/solutions that are patient- and family-centric.
The fibula osteoseptocutaneous flap: evolution in concepts, techniques, and technologies during mandibular reconstruction – a review
Authors: Hanba Curtis , Lin Ta-Chun , Wei Fu-Chan
Published: August 2024

The fibula-free flap has evolved from its initial description to be a reliable workhorse-free flap providing bone, soft tissue, and a reliable skin paddle. The senior author has been refining this technique since the mid-1980s and has personally performed over 950 hundred cases of the fibula-free flap. The following paragraphs detail an evolution in surgical concepts related to this technique’s refinement and serves as a roadmap detailing contemporary mandibular reconstruction.
Clinical outcomes and short-term survival of neoadjuvant immunochemotherapy for resectable esophageal cancer: a multicenter retrospective cohort study
Authors: Lan Ke , Yan Xiaolong , Lei Jie , Guo Xufeng , Zhou Yongan , Wang Xiaoping , Liu Honggang , Tian Feng , Lu Qiang , Gu Zhongping , Sun Jianyong , Yang Ende , Zhong Daixing , Wang Tao , Huang Lijun , Wang Jian , Liu Xu , Ni Yunfeng , Jiang Tao , Zhao Jinbo
Published: August 2024

Objective:

The present retrospective cohort study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy for resectable esophageal cancer and report the preliminary short-term survival.

Methods:

A multicenter, retrospective study was conducted concerning patients who received neoadjuvant PD-1 agents plus platinum-based chemotherapy between January 2019 and January 2022. The primary endpoint was the tumor pathologic complete response (pCR) rate.

Results:

Two hundred and thirteen patients with initial stage cI-IVA esophageal cancer who received neoadjuvant immunochemotherapy were identified. The complete tumor resection(R0) rate was 99.1%. The pCR rate was 31.9%, and the overall major pathological response rate was 49.8%. The 2-year DFS rate was 78.9% (95% CI: 72.9–85.4%) and the 2-years OS rate was 80.9% (95% CI: 75.3–86.9%). The incidence of TRAEs and surgical complications rate were 68.5 and 35.2%, respectively.

Conclusion:

The PD-1 agents combined with chemotherapy in the neoadjuvant treatment for resectable stage I–IVA esophageal cancer had a high pCR rate as well as good short-term survival benefits and tolerable toxicity.
Robot-assisted kidney transplantation: a propensity score-matched cohort analysis of early experience
Authors: Kim Seung J. J. , Kim Sangwan , Cho Ara , Han Ahram , Ha Jongwon , Min Sangil
Published: August 2024

Background:

Kidney transplantation is the preferred treatment for patients with end-stage kidney disease. Since the introduction of robot-assisted kidney transplantation (RAKT), several centers have applied this technique as an alternative to open kidney transplantation (OKT). The objective of this study is to analyze our early experience, focusing on surgical technique and learning curve, and postoperative outcomes of RAKT.

Methods:

The authors retrospectively reviewed 782 living donor kidney transplantation recipients between January 2018 and January 2024. A propensity score-matched cohort of 50 RAKT and 150 OKT patients was evaluated for intraoperative and postoperative variables. Shewhart control charts and CUSUM analysis were used to evaluate the technical outcomes and learning curves of RAKT. Postoperative eGFR values, complications, and biopsy results were compared for overall graft function and safety.

Results:

RAKT patients were associated with significantly longer overall operative, rewarming, and anastomosis times. Although overall postoperative eGFR trends showed comparable graft function between RAKT and OKT recipients (51.35±2.64 vs. 54.01±1.45; P=0.315), RAKT patients with extremely long rewarming times exhibited aggravated chronic scores at 1-year protocol biopsies (Δ Chronicity Index=4.45±1.92, P<0.001). CUSUM analysis of rewarming time revealed that proficiency in RAKT is achieved after ~15 cases.

Conclusions:

Despite longer anastomosis and ischemic times, even during the early stages of RAKT adoption, the RAKT group did not differ significantly in graft function or postoperative complications from the OKT group.
Quantile regression in the field of liver transplantation: A case study–based tutorial
Authors: Jiang Yue , Lieber Sarah R.
Published: August 2024

We present a tutorial on quantile regression, an underutilized yet valuable class of multivariable linear regression models that allows researchers to understand more fully the conditional distribution of response as compared to models based on conditional means. Quantile regression models are flexible, have attractive interpretations, and are implemented in most statistical software packages. Our focus is on an intuitive understanding of quantile regression models, particularly as compared with more familiar regression methods such as conditional mean models as estimated using ordinary least squares (OLS). We frame our tutorial through 2 clinical case studies in the field of liver transplantation: one in the context of estimating the recipient's financial burden after transplantation and another in estimating intraoperative blood transfusion needs. Our real-world cases demonstrate how quantile regression models give researchers a richer understanding of relationships in the data and provide a more nuanced clinical understanding compared to more commonly used linear regression models. We encourage researchers to explore quantile regression as a tool to answer relevant clinical research questions and support their more widespread adoption.
Metabolic Dysfunction-associated Steatotic Liver Disease is Becoming the Leading Driver of the Burden of Cirrhosis in China
Authors: Li Rui , Li Hang , Ye Xujun , Qin Juanjuan
Published: August 2024

Objective:

Cirrhosis and other chronic liver diseases (generally referred to as cirrhosis in this article) are major causes of morbidity and mortality in China. The disease pattern of cirrhosis caused by different etiologies has been changing due to economic development and changes in lifestyle.

Methods:

Prevalence, incidence, disability-adjusted life-years, and mortality data were retrieved from the Global Burden of Disease study, 2019. Estimated annual percentage change was used to quantify the trends in the age-standardized prevalence rate and prevalence number of cirrhosis from 1990 to 2019. We presented the results for five causes of cirrhosis, and for different age and sex groups.

Results:

Nationwide, we found that the prevalence number of liver cirrhosis increased steadily (from 3025.3×105 to 4279.8×105) from 1990 to 2019. Notably, the age-standardized prevalence rate of cirrhosis caused by metabolic dysfunction-associated steatotic liver disease (MASLD) increased throughout the study period, and MASLD has exceeded the hepatitis B virus and become the leading cause of liver cirrhosis since 1992. The highest prevalence number of MASLD occurred in the young population aged between 15 to 49 years.

Conclusion:

The prevalence of liver cirrhosis caused by hepatitis B virus decreased, whereas the prevalence of liver cirrhosis caused by MASLD increased. MASLD has become the leading cause of liver cirrhosis in China. The prevalence of liver cirrhosis increased most significantly in the young age group compared with the other age group. Preventive strategies targeting MASLD would be necessary to reduce the disease burden of cirrhosis in China, especially in the young aged generation.
ERCP in a patient with Billroth II gastrectomy: a rare case report
Authors: Al-Jawad Mohammad , Lbabidi Nour A. , Nabhan Mohammad H. , Sheikh Alan , Hamze Aya , Danial Aghyad K.
Published: August 2024

Introduction:

Gangrenous cholecystitis is a serious complication of untreated gallbladder inflammation, necessitating immediate intervention. The primary resolution involves cholecystectomy, the surgical removal of the gallbladder.

The Billroth II gastrectomy, named after Theodor Billroth, addresses gastric conditions by removing a portion of the stomach and reconnecting the remaining section to the small intestine.

Endoscopic retrograde cholangiopancreatography (ERCP) is a minimally invasive procedure that diagnoses and treats bile duct and pancreatic duct disorders, using an endoscope to access the ducts, administer contrast dye, and perform interventions like stone removal and stent placement. It aids in managing conditions such as bile duct stones, strictures, pancreatic tumors, and pancreatitis.

Case report:

A 25-year-old male with a history of gastric ulcer and Billroth II anastomosis presented with right hypochondrium pain, fever, and vomiting. Examination and imaging indicated gallbladder edema, abscess, and fluid collection. Laparotomy revealed severe adhesions around the gallbladder, which were released, and an abscess was drained. Postsurgery, a biliary fistula was suspected, leading to the proposal of an ERCP procedure. During ERCP, a plastic stent was inserted to aid bile drainage.

Discussion:

Therapeutic ERCP effectively treats biliary exudate, including in patients with Billroth II gastrectomy. Using a side-viewing duodenoscope simplifies accessing Vater’s papilla. This successful procedure had no complications, such as pancreatitis or bleeding, and the patient remained stable.

Conclusion:

ERCP in patients with a prior Billroth II gastrectomy is a risky procedure with potential complications. However, it can be considered as an alternative to avoid additional surgery if performed by experienced specialists with the necessary equipment.