bluuebunny/crossref_metadata_2025 huggingface dataset:
Racism and Discrimination
Authors: Goldstein Mark A. , Goldstein Myrna Chandler
Published: May 2024

Racism is ubiquitous in the United States, and it has profound effects on racial, gender, and sexual minority adolescents. It impacts the biopsychosocial health of adolescents in numerous ways including reducing opportunities for education and shelter; directly affecting cognitive and emotional processes; diminishing opportunities for healthy food, exercise, and sleep; and increasing exposure to violence. Structural racism is a driver of adolescent obesity through housing segregation that may limit food and exercise choices. A perception of discrimination among Latino adolescents has been associated with recent and lifetime use of substances. And social media platforms have been vehicles of online vicarious and individual racial discrimination against adolescents. Racism is a significant public health problem that should be dismantled. This will require dramatic changes in systematic, institutional, and individual racism as well as the concept of White privilege.
Poverty
Authors: Goldstein Mark A. , Goldstein Myrna Chandler
Published: May 2024

Forty percent of American children live in poverty or near poverty, and these economic states are associated with health disparities. Childhood poverty and family adversity affect biopsychosocial outcomes for adolescents, leading to higher chances for obesity, mental health problems, and violent behavior. Poverty may also lead to a digital divide where affected adolescents lack access to computers, smartphones, or home networks. Those adolescents living in poverty are at risk for structural racism, leading to unequal access to resources, rights, power, and protection. Immigrant children and adolescents are likely to live in poverty, and they are more likely than those not living in poverty to have impacts on their learning that are mediated by structural brain development issues. Multiple strategies are needed to modify the influence of poverty on adolescents.
Pain in the LGTBQ+ Population
Authors: Javier Noelle Marie
Published: May 2024

The LGBTQI+ community is a marginalized community that has experienced multiple barriers across multiple domains, including health care. Its members have been subjected to ongoing discriminatory practices, outright prejudice, and oppressive policies that have not ensured adequate protections from these stressors and have not allowed them to live life fully and authentically. As a result, there are numerous disparities and inequities in care that exist and have proven to be significant challenges to the delivery, access, and receipt of high-quality medical care, including pain management. It is therefore essential for all health care providers to develop a cultural lens of understanding to care for this vulnerable community. This chapter explores a multidimensional approach to pain assessment and management utilizing an adaptation of the biopsychosocial model of care. This model highlights not only the spiritual and cultural domains of the lived experiences of the LGBTQI+ individual but also the external and internal stressors as well as resources around coping and resilience that will provide a comprehensive and holistic framework for fully understanding the pain experience of this community. In addition, this chapter also discusses the multimodal approach to pain management.
Pain in Patients with Substance Use Disorders
Authors: Cheatle Martin D.
Published: May 2024

Many scholarly and public policy initiatives have been devoted to the opioid crisis, resulting in published guidelines for opioid prescribing and the identification of alternatives to opioids for pain management with the objective of reducing opioid-related deaths and reducing the number of vulnerable individuals being exposed to opioids and developing an opioid use disorder. This national focus on the risks and benefits of opioid therapy for patients with pain and the need for tapering of opioids has obscured the vulnerability of patients with pain who are susceptible to discrimination based on opioid use or having a co-occurring opioid use disorder and who may develop other forms of non-opioid use disorders. This chapter discusses the myths and facts of opioids in the pain population, the prevalence of pain and both nicotine use disorder and alcohol use disorder, and assessment and mitigation strategies.
Where’s the Lesion? (How We Localize)
Authors: Gelb Douglas J.
Published: May 2024

This chapter introduces the concept of localization, explaining that it applies to diagnostic reasoning throughout all fields of medicine but particularly emphasized in neurology. A systematic approach to localization is presented, in which each symptom is conceptualized as a damaged nervous system pathway and a lesion is localized by finding the points at which all the damaged pathways intersect. The major pathways are reviewed. Practice problems are analyzed, and a link is provided to a web-based computer tutorial allowing users to work through additional practice problems.
Stroke
Authors: Gelb Douglas J.
Published: May 2024

This chapter presents the classification, pathophysiology, and clinical presentation of ischemic and hemorrhagic stroke, including the typical clinical syndromes associated with major cerebral blood vessels. It discusses the approach to diagnosis and management, including acute restoration of blood flow with thrombolysis and/or mechanical thrombectomy, techniques to limit the deficits, and rehabilitation. It explains the major components of secondary stroke prevention (prevention of subsequent strokes after a stroke or TIA): lipid management, antiplatelet medication, blood pressure management, endarterectomy or stenting in patients with carotid stenosis, and anticoagulation in patients with atrial fibrillation. It concludes with a discussion of primary stroke prevention (prevention of stroke in patients who have never had a stroke or TIA).
Acute Mental Status Changes
Authors: Gelb Douglas J.
Published: May 2024

This chapter begins with definitions of various levels of altered consciousness, followed by a discussion of the physiology of normal and altered consciousness. It then presents a clinical approach focused on evaluating and treating potential causes in order of urgency, beginning with apnea and hypotension, then hypoxia, hypoglycemia, and opioid toxicity, then transtentorial herniation, then other common metabolic disturbances, and finally conditions such as other toxins, seizures, meningoencephalitis, posterior reversible encephalopathy syndrome (PRES), and autoimmune conditions. The chapter concludes with discussion of head trauma (including presentation of the Glasgow coma scale), increased intracranial pressure, and brain death.
Geriatric Neurology
Authors: Gelb Douglas J.
Published: May 2024

This chapter begins with a discussion of the reasons that neurologic issues in the geriatric population have some distinctive features. This is followed by a discussion of how the neurologic examination changes with aging. This is followed by a discussion of common neurologic problems experienced by older people: dizziness, gait disturbance, incontinence, dementia, and pain.
Practice Cases
Authors: Gelb Douglas J.
Published: May 2024

This chapter consists of 12 clinical vignettes and accompanying questions intended to allow the reader to practice applying the principles of localization and diagnostic reasoning covered in the first 3 chapters of the book, and to review some of the specific disorders covered in the subsequent chapters. Readers are encouraged to work through the questions on their own, and then to refer to the discussions provided at the end of the chapter.
Diagnostic values and relevant factors of lumbar posterior lesions in axial spondyloarthritis
Authors: Huang Zhixiang , Ding Jiali , Huang Lixin , Huang Xuechan , Huang Yukai , Guo Xin , Chen Shuyang , Deng Weiming , Li Tianwang
Published: May 2024

Objectives

To compare the lumbar posterior lesions between axial spondyloarthritis (axSpA) and lumbar disc herniation (LDH) patients, then their diagnostic value and related factors were evaluated.

Methods

This cross-sectional study included axSpA patients from January 2020 to September 2023. They were classified as ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) individuals. Canada–Denmark magnetic resonance imaging (MRI) scoring system was used to assess the defects of the lumbar spine. Receiver operating characteristic curve analysis was utilized to determine the value of distinguishing nr-axSpA. Linear regression analyses were adopted to find the relevant factors for lumbar posterior lesions.

Results

Ninety-six AS, 98 nr-axSpA, and 108 LDH patients were included. The Canada–Denmark scores were greater in axSpA patients, AS in particular. Furthermore, lumbar posterior lesions can distinguish AS, nr-axSpA, and LDH. Besides, lumbar posterior lesions were positively related to the similar MRI changes in their adjacent structures, but were inversely associated with the other abnormalities.

Conclusions

Lumbar posterior lesions were more serious in axSpA patients. These alterations had value in distinguishing axSpA. Lumbar posterior defects were related to their adjacent components, and they may not fully follow the MRI changing pattern of vertebral bodies and sacroiliac joints.
CGeNArate: a sequence-dependent coarse-grained model of DNA for accurate atomistic MD simulations of kb-long duplexes
Authors: Farré-Gil David , Arcon Juan Pablo , Laughton Charles A , Orozco Modesto
Published: May 2024

We present CGeNArate, a new model for molecular dynamics simulations of very long segments of B-DNA in the context of biotechnological or chromatin studies. The developed method uses a coarse-grained Hamiltonian with trajectories that are back-mapped to the atomistic resolution level with extreme accuracy by means of Machine Learning Approaches. The method is sequence-dependent and reproduces very well not only local, but also global physical properties of DNA. The efficiency of the method allows us to recover with a reduced computational effort high-quality atomic-resolution ensembles of segments containing many kilobases of DNA, entering into the gene range or even the entire DNA of certain cellular organelles.
Genomic context-dependent histone H3K36 methylation by three Drosophila methyltransferases and implications for dedicated chromatin readers
Authors: Jayakrishnan Muhunden , Havlová Magdalena , Veverka Václav , Regnard Catherine , Becker Peter B
Published: May 2024

Methylation of histone H3 at lysine 36 (H3K36me3) marks active chromatin. The mark is interpreted by epigenetic readers that assist transcription and safeguard the integrity of the chromatin fiber. The chromodomain protein MSL3 binds H3K36me3 to target X-chromosomal genes in male Drosophila for dosage compensation. The PWWP-domain protein JASPer recruits the JIL1 kinase to active chromatin on all chromosomes. Unexpectedly, depletion of K36me3 had variable, locus-specific effects on the interactions of those readers. This observation motivated a systematic and comprehensive study of K36 methylation in a defined cellular model. Contrasting prevailing models, we found that K36me1, K36me2 and K36me3 each contribute to distinct chromatin states. A gene-centric view of the changing K36 methylation landscape upon depletion of the three methyltransferases Set2, NSD and Ash1 revealed local, context-specific methylation signatures. Set2 catalyzes K36me3 predominantly at transcriptionally active euchromatin. NSD places K36me2/3 at defined loci within pericentric heterochromatin and on weakly transcribed euchromatic genes. Ash1 deposits K36me1 at regions with enhancer signatures. The genome-wide mapping of MSL3 and JASPer suggested that they bind K36me2 in addition to K36me3, which was confirmed by direct affinity measurement. This dual specificity attracts the readers to a broader range of chromosomal locations and increases the robustness of their actions.
Phenomenological characteristics of auto-induced cognitive trance and Mahorikatan® trance
Authors: Grégoire Charlotte , Sombrun Corine , Lenaif Philippe , Marie Nolwenn , Giovine Aurélie , Walter Marion , Gosseries Olivia , Vanhaudenhuyse Audrey
Published: May 2024

Trance states include various practices characterized by a modulation of consciousness, but with their own specific characteristics and induction techniques. They have been very seldom scientifically studied, and their phenomenological similarities and differences are poorly documented. This paper will focus on two types of Western trances developed after the leaders were trained in traditional shamanic communities: the auto-induced cognitive trance (AICT) and the Mahorikatan® trance (MT). Twenty-five AICT and 26 MT participants who were able to self-induce the trance state completed questionnaires about their trance practice (e.g. context of the first trance episode, frequency of practice, and consequences on personal life) and the phenomenological characteristics (i.e. emotional, physical, and cognitive) of the trance episodes they experienced. These characteristics were compared to explore similarities and differences between the two trance states. AICT and MT are characterized by the expression of different emotions, modification of various perceptions, a feeling of unicity (i.e. being completely oneself), and an expansion of consciousness. AICT participants commonly reported body movements, vocalizations, as well as increased creativity, visions of entities and/or places, and feeling of interaction with the environment. MT participants commonly reported a feeling of body dissolution. Most participants in both groups reported positive effects of their trance practice on their personal life. These results helped characterize AICT and MT, as well as their similarities and differences. Further studies should continue to explore the characteristics of such trance states, as well as their potential clinical applications.
Direct conversion of CO2 to CH4 on Pd/graphdiyne single-crystalline
Authors: Zhang Chao , Zheng Xuchen , Gao Yang , Xing Chengyu , Chen Siao , Xue Yurui , Li Yuliang
Published: May 2024

A major impediment to the development of the efficient use of artificial photosynthesis is the lack of highly selective and efficient photocatalysts toward the conversion of CO2 by sunlight energy at room temperature and ambient pressure. After many years of hard work, we finally completed the synthesis of graphdiyne-based palladium quantum dot catalysts containing high-density metal atom steps for selective artificial photosynthesis. The well-designed interface structure of the catalyst is composed of electron-donor and acceptor groups, resulting in the obvious incomplete charge-transfer phenomenon between graphdiyne and plasmonic metal nanostructures on the interface. These intrinsic characteristics are the origin of the high performance of the catalyst. Studies on its mechanism reveal that the synergism between ‘hot electron’ from local surface plasmon resonance and rapid photogenerated carrier separation at the ohmic contact interface accelerates the multi-electron reaction kinetics. The catalyst can selectively synthesize CH4 directly from CO2 and H2O with selectivity of near 100% at room temperature and pressure, and exhibits transformative performance, with an average CH4 yield of 26.2 μmol g−1 h−1 and remarkable long-term stability.
Identifying and Remediating Super-splasher Sinks to Reduce Dispersal of Pathogens From Sink Drains
Authors: Torres-Teran Maria M , Greentree David Henry , Varghese Martin Mathew , Cadnum Jennifer L , Pavis Robert L , Saade Elie A , Ray Amy J , Mack Claire , Wilson Brigid M , Donskey Curtis J
Published: May 2024

Testing for dispersal of fluorescent gel from sink drains was sensitive for detection of sinks that dispersed gram-negative bacilli outside the bowl. Reducing the flow rate of sinks with rapid water inflow and/or elimination of obstruction leading to slow outflow was effective in preventing dispersal of fluorescence and gram-negative bacilli.
N-of-1 health optimization: Digital monitoring of biomarker dynamics to gamify adherence to metabolic switching
Authors: Wang Peter , Tadeo Xavier , Chew Han Shi Jocelyn , Sapanel Yoann , Ong Yoong Hun , Leung Nicole Yong Ting , Chow Edward Kai-Hua , Ho Dean
Published: May 2024

The digital health field is experiencing substantial growth due to its potential for sustained and longitudinal deployment. In turn, this may drive improved monitoring and intervention as catalysts for behavioral change compared to traditional point-of-care practices. In particular, the increase in incidence of population health challenges such as diabetes, heart disease, fatty liver disease, and other disorders coupled with rising healthcare costs have emphasized the importance of exploring technical, economics, and implementation considerations, among others in the decentralization of health and healthcare innovations. Both healthy individuals and patients stand to benefit from continued technical advances and studies in these domains. To address these points, this study reports a N-of-1 study comprised of sustained regimens of intermittent fasting, fitness (strength and cardiovascular training), and high protein, low carbohydrate diet and parallel monitoring. These regimens were paired with serial blood ketone, blood glucose (wearable and finger stick) and blood pressure readings, as well as body weight measurements using a collection of devices. Collectively this suite of platforms and approaches were used to monitor metabolic switching from glucose to ketones as energy sources—a process associated with potential cardio- and neuroprotective functions. In addition to longitudinal biomarker dynamics, this work discusses user perspectives on the potential role of harnessing digital devices to these dynamics as potential gamification factors, as well as considerations for the role of biomarker monitoring in health regimen development, user stratification, and potentially informing downstream population-scale studies to address metabolic disease, healthy aging and longevity, among other indications.
Insights into the Complexity and Functionality of Plant Virus Protein Phosphorylation
Authors: Wu Yuansheng , Liu Na , Zheng Chengxu , Li Dongyuan , Li Shanshan , Wu Jianguo , Zhao Shanshan
Published: May 2024

Phosphorylation, the most extensive and pleiotropic form of protein posttranslation modification, is central to cellular signal transduction. Throughout the extensive co-evolution of plant hosts and viruses, modifications to phosphorylation have served multiple purposes. Such modifications highlight the evolutionary trajectories of viruses and their hosts, with pivotal roles in regulation and refinement of host-virus interactions. In plant hosts, protein phosphorylation orchestrates immune responses, enhancing the activities of defense-related proteins such as kinases and transcription factors, thereby strengthening pathogen resistance in plants. Moreover, phosphorylation influences the interactions between host and viral proteins, altering viral spread and replication within host plants. In the context of plant viruses, protein phosphorylation controls key aspects of the infection cycle, including viral protein functionality and the interplay between viruses and host plant cells, leading to effects on viral accumulation and dissemination within plant tissues. Explorations of the nuances of protein phosphorylation in plant hosts and their interactions with viruses are particularly important. This review provides a systematic summary of the biological roles of the proteins of plant viruses carrying diverse genomes in regulating infection and host responses through changes in the phosphorylation status.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
DNA methylation‐mediated 11βHSD2 downregulation drives the increases in angiotensin‐converting enzyme and angiotensin II within preeclamptic placentas
Authors: Deng Fengying , Lei Jiahui , Chen Jie , Zhao Meng , Zhao Chenxuan , Fu Mengyu , Sun Miao , Zhang Meihua , Qiu Junlan , Gao Qinqin
Published: May 2024

Preeclampsia (PE) is a complex human‐specific complication frequently associated with placental pathology. The local renin‐angiotensin system (RAS) in the human placenta, which plays a crucial role in regulating placental function, has been extensively documented. Glucocorticoids (GCs) are a class of steroid hormones. PE cases often have abnormalities in GCs levels and placental GCs barrier. Despite extensive speculation, there is currently no robust evidence indicating that GCs regulate placental RAS. This study aims to investigate these potential relationships. Plasma and placental samples were collected from both normal and PE pregnancies. The levels of angiotensin‐converting enzyme (ACE), angiotensin II (Ang II), cortisol, and 11β‐hydroxysteroid dehydrogenases (11βHSD) were analyzed. In PE placentas, cortisol, ACE, and Ang II levels were elevated, while 11βHSD2 expression was reduced. Interestingly, a positive correlation was observed between ACE and cortisol levels in the placenta. A significant inverse correlation was found between the methylation statuses within the 11βHSD2 gene promoter and its expression, meanwhile, 11βHSD2 expression was negatively correlated with cortisol and ACE levels. In vitro experiments using placental trophoblast cells confirmed that active GCs can stimulate ACE transcription and expression through the GR pathway. Furthermore, 11βHSD2 knockdown could enhance this activating effect. An in vivo study using a rat model of intrauterine GCs overexposure during mid‐to‐late gestation suggested that excess GCs in utero lead to increased ACE and Ang II levels in the placenta. Collectively, this study provides the first evidence of the relationships between 11βHSD2 expression, GCs barrier, ACE, and Ang II levels in the placenta. It not only contributes to understanding the pathological features of the placental GCs barrier and RAS under PE conditions, also provides important information for revealing the pathological mechanism of PE.
The Effect of Abdominal Massage on Bilirubin Levels in Term Infants Receiving Phototherapy
Authors: Köse Selmin , Gözen Duygu , Karadağ Aytemiz Özge Eda , Çağlayan Sabiha
Published: May 2024

Background:

The incidence of neonatal hyperbilirubinemia in Europe and the United States is estimated to be 3.2 and 4.4 per 10,000 live births, respectively. Abdominal massage for hyperbilirubinemia is considered a safe complementary treatment for infants that may increase number of defecations and decrease bilirubin levels.

Purpose:

This study was designed as a randomized controlled trial to determine the effect of abdominal massage on bilirubin levels in term infants receiving phototherapy.

Methods:

The sample consisted of 43 term newborns (intervention group: 23; control group: 20) who received phototherapy in a university hospital between June 2019 and February 2021. Information and observation forms were used for data collection. The intervention group received 6 abdominal massages over 2 days, performed 3 times a day, 6 hours apart, and lasting 5 minutes each.

Results:

Transcutaneous bilirubin levels and heart rate were significantly lower in the intervention group than in the control group at 48 hours (P = .015 and P = .033, respectively). Number of defecations was higher in the intervention group at 24 hours (P = .007) but there was no significant difference at 48 hours. The decrease in serum bilirubin between 24 and 48 hours was significantly greater in the intervention group (P = .005).

Implication for Practice and Research:

Abdominal massage was effective in reducing bilirubin levels and may increase the number of defecations. Providing massage training to the parents of infants who are discharged early could be a protective approach to prevent the rise in bilirubin levels.
Pregnancy-Related Deaths Due to Hemorrhage: Pregnancy Mortality Surveillance System, 2012–2019
Authors: Hollier Lisa M. , Busacker Ashley , Njie Fanny , Syverson Carla , Goodman David A.
Published: May 2024

Hemorrhage has been a leading cause of pregnancy-related death in the Centers for Disease Control and Prevention Pregnancy Mortality Surveillance System since 1987 when reporting began. Pregnancy Mortality Surveillance System data from 2012 to 2019 were analyzed to describe pregnancy-related deaths from hemorrhage. Pregnancy-related mortality ratios were estimated for hemorrhage overall and by hemorrhage subclassifications. Specific subclassifications of hemorrhage-related deaths were analyzed by sociodemographic characteristics. Overall, there were 606 deaths due to hemorrhage. The pregnancy-related mortality ratio for hemorrhage overall was 1.94 per 100,000 live births. Ruptured ectopic pregnancy was the most frequent subclassification (22.9%) of pregnancy-related hemorrhage deaths, followed by postpartum hemorrhage (21.2%). There were no significant trends in the pregnancy-related mortality ratio, overall or among any subclassification of hemorrhage deaths, from 2012 to 2019. Reporting subclassifications of pregnancy-related hemorrhage deaths could improve the ability to focus interventions and assess progress over time.
Inhibition of interferon regulatory factor 4 orchestrates T cell dysfunction, extending mouse cardiac allograft survival
Authors: Yuan Wenjia , Zhang Hedong , Peng Longkai , Chen Chao , Feng Chen , Tang Zhouqi , Cui Pengcheng , Li Yaguang , Li Tengfang , Qiu Xia , Cui Yan , Zeng Yinqi , Luo Jiadi , Xie Xubiao , Guo Yong , Jiang Xin , Dai Helong
Published: May 2024

Background:

T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction.

Methods:

A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of MAPK and mammalian target of Rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models.

Results:

In vitro, blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg−1·day−1) and Rapamycin (0.1 mg·kg−1·day−1) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression.

Conclusions:

Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Efficacy and safety of EUS-guided hepatogastrostomy: A systematic review and meta-analysis
Authors: Moond Vishali , Loganathan Priyadarshini , Koyani Bhargav , Khan Shahab R. , Kassab Lena L. , Chandan Saurabh , Mohan Babu P. , Broder Arkady , Adler Douglas G.
Published: May 2024

EUS-guided hepaticogastrostomy (EUS-HGS) is one of the preferred methods in biliary drainage where ERCP fails or is contraindicated. The clinical outcomes of EUS-HGS are not well studied because of variability in procedure technique. We conducted a search of multiple electronic databases and conference proceedings from inception through January 2023. The clinical outcomes studied were pooled technical success, clinical success, and adverse events. Standard meta-analysis methods were used using the random-effects model, and heterogeneity was studied by I
2 statistics. We analyzed 44 studies, which included 19 prospective and 25 retrospective studies. The pooled technical success rate of EUS-HGS was 94.4% (confidence interval [CI], 92.4%–95.9%; I
2 = 0%), and the pooled clinical success rate was 88.6% (CI, 83.7%–92.2%; I
2 = 0%). The pooled adverse outcomes with EUS-HGS were 23.8% (CI, 19.6%–28.5%; I
2 = 0%). The mild adverse event rate associated with HGS was 5.8% (4.2%–8.1%; I
2 = 0%), moderate adverse event rate was 12.1% (9.1%–15.8%; I
2 = 16%), and severe adverse event rate was 4.2% (3.0%–5.7%; I
2 = 61%), whereas fatal adverse event rate was 3.2% (1.9%–5.4%; I
2 = 62%). On subgroup analysis, the pooled rate of adverse events of EUS-guided hepaticogastrostomy with antegrade stenting was 13.3% (95% CI, 8.2%–21.0%). The pooled technical success with EUS-guided hepaticogastrostomy with antegrade stenting was 89.7% (95% CI, 82.6%–94.2%), and clinical success was 92.5% (95% CI, 77.9%–97.7%). On the basis of our analysis of EUS-HGS, the overall technical success was 94.4%, and the clinical success rate was 88.6%, and the overall adverse events were reported to be 23.8%. These data can also help improve the clinical benefits of EUS-HGS in the selected patients in whom it is performed.
Implementation of a multicomponent medication adherence promotion system is associated with a decrease in late T-cell–mediated rejection
Authors: Bonn Julie , Ambrosino Teresa , Rich Kristin , Taylor Amy , Wadhwani Sharad I.
Published: May 2024

Poor immunosuppression adherence in pediatric recipients of liver transplant (LT) contributes to late T-cell–mediated rejection (TCMR) in ~90% of cases and increases the risk of mortality. A medication adherence promotion system (MAPS) was found to reduce late rejection in pediatric recipients of kidney transplants. Using quality improvement methodology, we adapted and implemented the MAPS in our LT clinic. Our primary outcome was population-level rates of late TCMR, measured as a monthly incident rate. Three-hundred fourteen patients undergoing LT are currently cared for at our institution. One-hundred sixty-two (52%) are females with a median age of 16 years and a median age at LT of 2 years. Preimplementation, monthly rejection rates were 0.84 rejections per 100 patient-months. After iterative implementation of MAPS over 2.3 years, monthly rejection rates decreased to 0.46 rejections per 100 patient-months, a 45% decrease in late TCMR. Implementation of MAPS was associated with a sustained 45% decrease in TCMR at a single center, suggesting that quality improvement tools may help improve clinical outcomes. MAPS may be an important tool to ensure long-term allograft health. Future studies should rigorously test MAPS across a multicenter sample.
Incidental Serous Tubal Intraepithelial Carcinoma Finding in a Nepalese Patient Undergoing Opportunistic Salpingectomy and the Discovery of a BRCA1 Pathogenic Variant
Authors: Tischer Kristin M. , Yadav Siddhartha , Bell Debra , Hansen Kathleen , Veres Larissa N. , Maddy Brandon , Bakkum-Gamez Jamie N.
Published: May 2024

BACKGROUND:

Serous tubal intraepithelial carcinoma lesions are the precursor to high-grade serous ovarian carcinomas, which have the highest mortality rate among gynecologic malignancies. In women diagnosed with high-grade serous ovarian carcinoma, 20% of the carcinomas are found to be secondary to hereditary causes, with the majority being associated with germline pathogenic variants in BRCA1 and BRCA2 genes. Patients with a pathogenic variant are at high risk for developing high-grade serous ovarian carcinoma, so it is recommended that they undergo risk-reducing salpingo-oophorectomy in their 30s–40s. Opportunistic salpingectomy is the only ovarian cancer prevention method available for patients at average risk. Although serous tubal intraepithelial carcinoma lesions are rare in women at average risk, studies quote incidental serous tubal intraepithelial carcinoma lesion findings in 1–7% of patients undergoing opportunistic salpingectomy.

CASE:

A 38-year-old woman, gravida 2 para 2, of Nepalese ethnicity had an incidental finding of a serous tubal intraepithelial carcinoma lesion at the time of opportunistic salpingectomy for permanent sterilization at cesarean delivery. The serous tubal intraepithelial carcinoma lesion was found with representative sampling of the fallopian tubes because the patient was considered to be at average risk for ovarian cancer. This method is much less sensitive than the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) protocol, which is used with women known to be at high risk. This ultimately led to discovery of a BRCA1 mutation in the patient.

CONCLUSION:

The SEE-FIM protocol is used to identify serous tubal intraepithelial carcinoma lesions, but it is not routinely used on fallopian tubes of patients at average risk. Using the SEE-FIM protocol would lead to fewer missed serous tubal intraepithelial carcinoma lesions, but it is unclear how much extra cost and effort would be required to implement this protocol. There are knowledge gaps when it comes to understudied populations and hereditary breast and ovarian cancer gene prevalence. Studies show that current BRCA prediction models underestimate hereditary breast and ovarian cancer gene prevalence in Asian populations. Diagnosing serous tubal intraepithelial carcinoma lesions in understudied populations could lead to the discovery of a hereditary breast and ovarian cancer pathogenic variant that the patient may not have discovered until after a cancer diagnosis. Identification of a serous tubal intraepithelial carcinoma in a patient at average risk should lead to a referral for genetic counseling and screening.
The effect of care interruptions on mortality in adults resuming antiretroviral therapy
Authors: Moolla Haroon , Davies Mary-Ann , Davies Claire , Euvrard Jonathan , Prozesky Hans W. , Fox Matthew P. , Orrell Catherine , Von Groote Per , Johnson Leigh F. ,   for the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) Collaboration
Published: May 2024

Objective:

To estimate the relative rate of all-cause mortality amongst those on antiretroviral treatment (ART) with a history of interruptions compared with those with no previous interruptions in care.

Design:

Retrospective cohort study.

Methods:

We used data from four South African cohorts participating in the International epidemiology Databases to Evaluate AIDS Southern Africa collaboration. We included adults who started ART between 2004 and 2019. We defined a care interruption as a gap in contact longer than 180 days. Observation time prior to interruption was allocated to a ‘no interruption’ group. Observation time after interruption was allocated to one of two groups based on whether the first interruption started before 6 months of ART (’early interruption’) or later (’late interruption’). We used Cox regression to estimate hazard ratios.

Results:

Sixty-three thousand six hundred and ninety-two participants contributed 162 916 person-years of observation. There were 3469 deaths. Most participants were female individuals (67.4%) and the median age at ART initiation was 33.3 years (interquartile range: 27.5–40.7). Seventeen thousand and eleven (26.7%) participants experienced care interruptions. Those resuming ART experienced increased mortality compared with those with no interruptions: early interrupters had a hazard ratio of 4.37 (95% confidence interval (CI) 3.87–4.95) and late interrupters had a hazard ratio of 2.74 (95% CI 2.39–3.15). In sensitivity analyses, effect sizes were found to be proportional to the length of time used to define interruptions.

Conclusion:

Our findings highlight the need to improve retention in care, regardless of treatment duration. Programmes to encourage return to care also need to be strengthened.
Prevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy
Authors: Wagner Thor A. , Tierney Camlin , Huang Sharon , Nichols Sharon , Malee Kathleen M. , Montañez Nicole A. , Coletti Anne , Spiegel Hans M.L. , Krotje Chelsea , Bone Frederic , Wilkins Megan , Abuogi Lisa , Purswani Murli , Bearden Allison , Wiznia Andrew , Agwu Allison , Chadwick Ellen G. , Richman Douglas , Gandhi Monica , Mehta Patrick , Macatangay Bernard , Spector Stephen A. , Spudich Serena , Persaud Deborah , Chahroudi Ann
Published: May 2024

Objective:

Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF).

Design:

IMPAACT2015 was a U.S.-based multi-site, exploratory, observational study.

Methods:

Cognitive impairment was defined as NIH Toolbox Fluid Cognition Composite score (FCCS) more than 1 standard deviation below age-adjusted normative group mean. Cell-free HIV-RNA and cell-associated HIVpol/gag-DNA and 10 biomarkers of inflammation/neuronal injury were measured in paired CSF and blood. ART exposure concentrations were quantified in hair.

Results:

Among 24 participants, 20 had successful CSF collection and 18 also met viral suppression criteria. Nine of 18 (50%) were female sex-at-birth, and 14 of 18 (78%) were black. Median (range) age was 20 years (13–27), time on ART was 18.3 years (8.0–25.5), and FCCS was 68 (53–80). HIV-DNA was detected in PBMCs from all participants. In CSF, two of 18 (11%, 95% CI: 1.4–34.7%) participants had detectable cell-free HIV-RNA, while HIVgag or pol-DNA was detectable in 13 of 18 (72%, 95% confidence interval: 47–90). Detectable HIV-DNA in CSF was associated with male sex-at-birth (P = 0.051), lower CD4+ cell count at enrollment (P = 0.016), and higher PBMC HIVpol-DNA copies (P = 0.058). Hair antiretroviral concentrations and biomarkers were not associated with CSF HIV-DNA detection.

Conclusion:

We found that a high proportion of AYAPHIV with neurocognitive impairment had CSF cells harboring HIV-DNA during long-term virologic suppression. This evidence of persistent HIV-DNA in CSF suggests that the CNS should be considered in treatment and cure studies.
HISTOLOGICAL COMPARISON OF REPEATED MILD WEIGHT DROP AND LATERAL FLUID PERCUSSION INJURY MODELS OF TRAUMATIC BRAIN INJURY IN FEMALE AND MALE RATS
Authors: Vita Sydney M. , Cruise Shealan C. , Gilpin Nicholas W. , Molina Patricia E.
Published: May 2024

In preclinical traumatic brain injury (TBI) research, the animal model should be selected based on the research question and outcome measures of interest. Direct side-by-side comparisons of different injury models are essential for informing such decisions. Here, we used immunohistochemistry to compare the outcomes from two common models of TBI, lateral fluid percussion (LFP) and repeated mild weight drop (rmWD) in adult female and male Wistar rats. Specifically, we measured the effects of LFP and rmWD on markers of cerebrovascular and tight junction disruption, neuroinflammation, mature neurons, and perineuronal nets in the cortical site of injury, cortex adjacent to injury, dentate gyrus, and the CA 2/3 area of the hippocampus. Animals were randomized into the LFP or rmWD group. On day 1, the LFP group received a craniotomy, and on day 4, injury (or sham procedure; randomly assigned). The rmWD animals underwent either injury or isoflurane only (randomly assigned) on each of those 4 days. Seven days after injury, brains were harvested for analysis. Overall, our observations revealed that the most significant disruptions were evident in response to LFP, followed by craniotomy only, whereas rmWD animals showed the least residual changes compared with isoflurane-only controls, supporting consideration of rmWD as a mild injury. LFP led to longer-lasting disruptions, perhaps more representative of moderate TBI. We also report that craniotomy and LFP produced greater disruptions in females relative to males. These findings will assist the field in the selection of animal models based on target severity of postinjury outcomes and support the inclusion of both sexes and appropriate control groups.
The Blue Ribbon Committee II Report and Recommendations on Surgical Education and Training in the United States: 2024
Authors: Stain Steven C. , Ellison E. Christopher , Farmer Diana L. , Flynn Timothy C. , Freischlag Julie A. , Matthews Jeffrey B. , Newman Rachel W. , Chen Xiaodong , Stefanidis Dimitrios , Britt L.D. , Buyske Jo , Fisher Karen , Sachdeva Ajit K. , Turner Patricia L. ,   the Blue Ribbon Committee II
Published: May 2024

Objective:

An expert panel made recommendations to optimize surgical education and training based on the effects of contemporary challenges.

Background:

The inaugural Blue Ribbon Committee (BRC I) proposed sweeping recommendations for surgical education and training in 2004. In light of those findings, a second BRC (BRC II) was convened to make recommendations to optimize surgical training considering the current landscape in medical education.

Methods:

BRC II was a panel of 67 experts selected on the basis of experience and leadership in surgical education and training. It was organized into subcommittees which met virtually over the course of a year. They developed recommendations, along with the Steering Committee, based on areas of focus and then presented them to the entire BRC II. The Delphi method was chosen to obtain consensus, defined as ≥80% agreement among the panel. Cronbach α was computed to assess the internal consistency of 3 Delphi rounds.

Results:

Of the 50 recommendations, 31 obtained consensus in the following aspects of surgical training (# of consensus recommendation/# of proposed): Workforce (1/5); Medical Student Education (3/8); Work Life Integration (4/6); Resident Education (5/7); Goals, Structure, and Financing of Training (5/8); Education Support and Faculty Development (5/6); Research Training (7/9); and Educational Technology and Assessment (1/1). The internal consistency was good in Rounds 1 and 2 and acceptable in Round 3.

Conclusions:

BRC II used the Delphi approach to identify and recommend 31 priorities for surgical education in 2024. We advise establishing a multidisciplinary surgical educational group to oversee, monitor, and facilitate implementation of these recommendations.
Triadic Communication in Medical Encounters Including Individuals With Dementia
Authors: Wollney Easton N. , Armstrong Melissa J. , Hampton Chelsea N. , McCall-Junkin Patti , Bedenfield Noheli , Fisher Carla L. , Bylund Carma L.
Published: May 2024

Purpose:

The overall goal of this review was to identify what is known about triadic (clinician–patient–caregiver) communication in mild cognitive impairment (MCI) and dementia care settings throughout the care continuum.

Methods:

Using a structured search, we conducted a systematic scoping review of relevant published journal articles across 5 databases. Study titles/abstracts and selected full-text articles were screened by 2 investigators in Covidence systematic review software. Articles were excluded if they were not about clinical communication, focused only on caregiver–patient communication or communication in residential care, were interventional, lacked empirical data, or were not in English. Extracted data were documented using Google Forms.

Results:

The study team screened 3426 article titles and abstracts and 112 full-text articles. Forty-four articles were included in the final review. Results were categorized by 3 communication scenarios: diagnostic communication (n=22), general communication (n=16), and advanced care planning communication (n=6).

Conclusions and Relevance:

Across the included articles, the conceptualization and assessment of communication lacked homogeneity. Future directions include addressing these research gaps, establishing recommendations for clinicians to effectively communicate with individuals with dementia and caregivers, and creating and testing communication skills trainings for caregivers/family members, clinicians, and/or individuals with dementia to facilitate effective communication.
The good, the BATV, and the ugly - first report of BATV vector competence inCulex quinquefasciatusfrom the Southern United States
Authors: Clark Samantha D , Turner Erik A , Vivien Jordan M , Buras Grace B. , Christofferson Rebecca C.
Published: May 2024

Batai virus is an arbovirus with wide geographic, host, and climactic ranges. BATV infects primarily avian species but can cause disease in ruminants and humans. Louisiana is at particular risk for overlaps in natural and agricultural systems as the Mississippi Flyway passes through the state. We assessed the vector competence of LouisianaCx. quinquefasciatusfor BATV and found infection and dissemination rates of 22% and 11.1% at 7 days post-exposure (dpe), and 15.8% and 5.3% at 21dpe. The current H5N1 avian influenza outbreak in dairy cows demonstrates the importance of understanding the overlap in avian and other vertebrate species to inform public health and agricultural biosecurity. Results indicate a moderate vector competence of regional LouisianaCx. quinquefasciatusfor BATV. This study presents the first known report of vector competence of BATV in US mosquitoes and establishes the non-zero risk of its emergence in the southern US.
Use of machine learning for quantification of retinal pigment epithelium tight junctions improves assay sensitivity
Authors: Gao Yan , Bray Mark-Anthony , Twarog Michael , Xu YongYao , Buchanan Natasha , Zhang Yiyun , Medley Quintus , Saint-Geniez Magali , Prasanna Ganesh , Zhang Qin
Published: May 2024

The retinal pigment epithelium (RPE) is critical for maintaining outer retinal barrier homeostasis. In age-related macular degeneration (AMD), the RPE can undergo a dedifferentiation process that includes tight junction (TJ) loss and displacement of zonula occludens-1 (ZO-1), which may impair structural and functional integrity of the RPE barrier and contribute to disease pathogenesis. Our objective was to develop an automated and sensitive quantification method for TJ aberrations in an RPE immunofluorescence imaging assay, following treatment with TNFα or TGFβ2. However, quantifying ZO-1 morphological changes in the RPE using standard image analysis methods did not provide a satisfactory assay window. To address this challenge, we developed an imaging assay to quantify ZO-1 changes using a machine learning approach, enabling enhanced phenotypic characterization of the ZO-1 changes in RPE cells and improved assay sensitivity. We were also able to capture and quantify the reversal of these changes using etanercept, an TNFα inhibitor, with this imaging assay. Our findings indicated that this machine learning ZO-1 quantification assay could serve as a potential phenotypic readout for RPE dedifferentiation and enabling large-scale mechanistic studies.