bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Function as Immunoglobulins and Hormones
Authors: James Dominika Lipowska , Jowza Maryam
Published: May 2024

All living things depend on proteins for their existence. Proteins are some of the most structurally complex biological molecules, whose three-dimensional configuration is inherently correlated with their function. Proteins serve a wide array of physiological processes within the human body; they not only are the primary building blocks of many tissues, but also serve as hormones coordinating physiological activities, as well as carrying immune function as immunoglobulins. Protein hormones are specific proteins involved in cell signaling and communication. They are secreted by endocrine organs and are involved in regulation of many biological processes such as growth, metabolism, sexual development, and procreation. Protein hormones vary in size and structure and as such can be divided into amines, peptides, proteins, and glycoproteins. Immunoglobulins, otherwise known as antibodies, are immunologically specialized plasma proteins produced by B cells, which are essential to proper function of humoral immunity. Antibodies serve two main immunological functions: recognition and identification of pathogens and their destruction. There are five distinct antibody classes, which differ in structure and function: IgG, IgM, IgA, IgE, IgD. Structure of immunoglobulins is based on their peptide chain amino acid sequences and defines their role and antigen-binding specificity. Each antibody is capable of recognizing specific antigens. Pathogen neutralization may occur via antibody mediated processes such as cellular lysis, phagocytosis, opsonization, and complement activation.
Sleep
Authors: Goldstein Mark A. , Goldstein Myrna Chandler
Published: May 2024

Good quality and quantity of sleep are of the utmost importance for the development of adolescents. However, large numbers of adolescents are not obtaining sufficient sleep. There is a sizeable body of research that has found that adolescents with sleep issues have worse outcomes for physical, mental, social, and academic performance than their peers who obtain appropriate sleep. The use of electronic media including computers, smartphones, and tablets has a profound effect on sleep. Adolescents with disturbed sleep may have anxiety issues as well as depression. In addition, sleep issues may lead to adolescent substance use, and the use of substances may lead to sleep problems. Other issues for adolescents with sleep disturbances include increased risks for obesity, mood disorders, suicidal ideation, drowsy driving, and poor academic performance.
Obesity
Authors: Goldstein Mark A. , Goldstein Myrna Chandler
Published: May 2024

Obesity is a global issue in adolescents, especially in high-income countries such as the United States. Factors such as limited physical activities, disrupted sleep, increased screen time, and even remote learning during the COVID-19 pandemic have exacerbated the situation. Adolescents may develop high blood pressure, type 2 diabetes, and diminished self-esteem if they have obesity. Studies have determined that obesity is a risk factor for anxiety and depression in adolescents. Through social media adolescents may be exposed to advertisements with high-calorie, low-nutrient foods and beverages that could lead to dietary changes promoting weight gain. Prevention efforts for adolescents include less screen time, more physical activities, healthier diets, mandatory school-based physical education, and increased accessibility to parks and playgrounds.
Pain in Infants and Children
Authors: Harrison Denise , Bueno Mariana , Pope Nicole Marie
Published: May 2024

Sick and preterm newborns and hospitalized infants and children are especially vulnerable to pain. Vulnerabilities relate to repeated painful procedures required during hospitalizations, immature developmental stages, parental separation, lack of known effective pain treatment at different ages, and, where evidence exists, lack of consistent use of the evidence. In addition, this population is at risk of long-term pain consequences, including fear and anxiety related to needles and medical care. Reducing the burden of pain and involving parents in pain care are priorities for reducing vulnerabilities in newborns and young children. When painful procedures are required, breastfeeding, skin-to-skin, and small volumes of sweet solutions are recommended for newborns and young infants. Facilitating the use of effective distraction techniques and applying topical anesthetics are recommended for young children. The social communication model of pain and the model of parent involvement in infant pain management are used to understand pain from a biopsychosocial perspective.
Pain in Women
Authors: Dodman Keisha G. , Berken Allison M. , Barreveld Antje M.
Published: May 2024

Although gender equality has significantly evolved over centuries, sociocultural disparities as well as important biological differences persist between women and men. Recognizing biological differences as well as potential biases toward women is essential to providing optimal health care. This chapter provides an overview of the history of pain in women as well as the genetic, biological, and psychosocial underpinnings of chronic pain in this vulnerable population. The chapter provides a brief review of pain states specific to the female sex and chronic pain diseases more commonly seen in women. The chapter asserts that it is imperative for the health care community to recognize biases, gendered norms, and barriers to pain care in women to guarantee improved access to contemporary, informed, and compassionate diagnosis and treatment.
Pain in Cognitive Impairment
Authors: Geppert Cynthia M. A. , Cardon Karen E.
Published: May 2024

This chapter examines challenges in identifying, accurately assessing, and appropriately managing chronic pain in patients with cognitive impairment. It specifically focuses on three subgroups: dementia (multiple types are reviewed), developmental delay, and traumatic brain injury. The chapter provides a review of the clinical presentation and specific features of pain epidemiology, common comorbidities, and risk factors for pain in these populations, as well as treatment considerations. Much of the chapter focuses on a discussion of models of vulnerability in the three cohorts, along with examining difficulties in accurately assessing pain, and the many challenges to safe and appropriate patient-centered pain care. It concludes with a discussion of pathways to improved care for patients with cognitive impairment, including addressing the broader social context, advocacy, research, education, and accessible and integrated health care.
Pain in Military Personnel
Authors: Wilson Sara M. , Byrne Taylor J.
Published: May 2024

The military has been described as the most engrossing and demanding institution in American society. Unique experiences of the service member include special training requirements, frequent relocations, geographic isolation from support structures, deployments, redeployments, integrating from the military to the civilian workforce, and financial stressors. Despite these unique experiences, the military population is not classically considered a vulnerable population. This chapter highlights several aspects of the military population that promote vulnerability in the context of health care, specifically regarding the development of chronic pain. In addition to vulnerability due to the institutional nature of service, military-specific requirements and exposures increase service members’ vulnerability to developing illness and injury at an increased rate compared to the general population. These unique exposures increase the rate of chronic pain conditions, depression, post-traumatic stress disorder (PTSD), and traumatic brain injury. Approximately half of all veterans enrolled in the Veterans Affairs (VA) health care system experience chronic pain compared to 30% of the U.S. population. Furthermore, compared to nonveterans, veterans with chronic pain suffer from more complex pain syndromes, often associated with comorbid conditions such as depression and PTSD. This chapter explores the vulnerability of the military population, the impact of chronic pain in this unique population, and both risk factors and protective factors for developing chronic pain. It also outlines many of the strategies and programs the U.S. Department of Defense and VA have instituted to improve chronic pain measurement and outcomes.
Pain and Torture
Authors: Asgary Ramin , de C. Williams Amanda C.
Published: May 2024

Addressing physical and psychological pain, common among survivors of maltreatment and torture, requires comprehensive approaches. Refugees and asylum seekers are at a particularly high risk. In host societies, there might be a lack of recognition, experience, and structural support and related policies in both health care and social systems to meet their needs. Access to care is complicated because survivors are often in precarious situations, struggling with legal status, accommodation, finances, and basic necessities. The concept of vulnerability, inadequate social support and isolation, health care and social system barriers, health care professionals’ accountability and ethics, and social responsibility and corresponding level of accountability all pose further challenges and opportunities. Survivors who experience pain, usually persistent, have difficulty accessing appropriate assessment and treatment: Pain from torture is complex and poorly understood, and it may correspond poorly to accounts of injury. Pain may be inappropriately assigned to psychological causes, in the context of a high psychosocial burden among survivors. Expert assessment and treatment are needed but often limited and insufficient. They require the establishment of trust for survivors to disclose their history and develop a shared understanding of pain. Treatment, especially for chronic pain, is difficult to implement and follow, given other competing demands or barriers. It requires a multidisciplinary approach to further connect care to other forms of support beyond direct treatment. Comprehensive and specialized centers have been successful and warrant further exploration and investment.
Pain in Extreme Situations
Authors: Gelfand Harold J. , Tracy Erin A. , Bell Austin G.
Published: May 2024

Management of pain in victims of armed conflict and natural disasters is a particularly challenging aspect of casualty care. These events impose significant traumatic stress on individuals and communities, altering environments such that routine medical systems are disrupted, thus demanding specialized responses to meet the unique challenges in providing care to victims. Injury patterns can vary greatly depending on the nature of the incident, and they can encompass multiple organ systems across a wide range of patient age and comorbidity. Appropriate and timely pain management has a significant impact on outcome and persistent disability in those suffering trauma, requiring systems and resources to be developed in advance of need. Among such programs is the Joint Trauma System (JTS) of the U.S. military. The JTS has developed evidence-based policies and guidelines directing the resources and care to be used in the combat and disaster environment. Included is doctrine on the provision of analgesic care and monitoring for casualties based on degree and nature of injury. It is a moral and clinical imperative that pain be addressed as close to the time of injury as possible; this is reflected in JTS clinical practice guidelines and is driving research and development of new analgesic modalities that can be safely provided to wounded at the point of injury. Chronic pain has a significant socioeconomic impact on both medical need and dependence on social services. Early and appropriate pain intervention can help diminish this burden on victims and society.
Pain in Low-Income Nations
Authors: Workneh Rediet Shimeles , Nyirigira Gaston , Faponle Fola , Sutton Olivia , Amaefuna Steven , Tomobi Oluwakemi , Finley Allen , Sampson John
Published: May 2024

Chronic pain is a major public health issue, particularly in people in low- and middle-income countries (LMICs). Pain management in Africa is a critical health care issue, given the high prevalence of pain and limited access to pain medications in many African countries. In many cases, pain is undertreated, leading to suffering and decreased quality of life. The associated challenges are complex, including cultural beliefs and attitudes toward pain, inadequate training of health care professionals in pain management, limited availability and affordability of pain medications, and regulatory barriers to their use. Addressing these challenges requires a multifaceted approach that involves advocacy, education, policy reform, and increased access to medications. Improved pain management in Africa has the potential to improve the quality of life for millions, enhance the effectiveness of health care systems, and reduce the burden of pain-related disability and mortality. To address these challenges, several strategies can be employed, including improving access to pain medications through policy changes, increasing health care provider training in pain management, implementing multidisciplinary pain management programs, and addressing cultural attitudes toward pain and pain management. These are all necessary steps toward better management of chronic pain in LMICs. This chapter focuses on the African continent as a representation of challenges in many LMICs.
Cancer Pain
Authors: Ma Shuran , Christiansen Sandy
Published: May 2024

Pain is a common symptom of cancer, even in survivors. Despite this, there is a large disparity in pain control among vulnerable patient populations. Pediatric and geriatric patients are more likely to have difficulty expressing their pain and are dependent on caregivers. Different races may be more reluctant to report pain or treat pain, especially in the setting of medical disease such as cancer. Lower income and limited access to health care also prevent patients from receiving the pain treatments they need. When cancer pain is not adequately treated, it leads to not only poorer quality of life for the patient and their caregivers but also economic burden on the health care system from emergency department visits and hospitalizations. Solutions to this disparity include education and support to patients, family members, and health care providers. Telehealth has also been able to bridge the care gap for those who have limited access to health care resources. Finally, the World Health Organization has published guidelines to support primary care physicians in the management of patients’ cancer pain.
Pain in Sickle Cell Disease
Authors: Mulchan Siddika S. , Coco Megan , Boruchov Donna
Published: May 2024

Pain is the hallmark symptom of sickle cell disease. Vaso-occlusive pain crises are multifactorial in origin. Medical and psychological complications affect the perception of pain. A biopsychosocial model of pain uses a holistic approach to conceptualize the factors that contribute to the pain experience. Sickle cell disease predominantly affects people of color, and perceived injustice as well as health-related stigma and racial bias have all contributed to feelings of mistrust and often lead to negative health outcomes for individuals with sickle cell disease. The opioid crisis in the United States has inadvertently had a negative effect on access to pain medications for people with sickle cell disease. Mood disorders and pain catastrophizing also negatively impact pain crises in sickle cell disease. Remediation and treatment of pain in sickle cell disease include the development of coping skills and psychological adjustment skills and the guidance of a multidisciplinary health care team that includes physicians, nurse practitioners, nurses, social workers, and psychologists.
Pain in People Living with HIV
Authors: George Mary Catherine , Douglas Sotonye , Coyle Kaitlyn , Griffiths Shanna-Kay Christa , Robinson-Papp Jessica
Published: May 2024

Treating pain in people living with HIV, despite advances in HIV treatment, continues to be challenging due to pervasive stigma, coupled social and economic challenges, creating complexity in providing sufficient pain care. These challenges include gender, racial, and ethnic minority status, substance use disorders, and trauma. This chapter discusses the vulnerabilities experienced by some people living with HIV and how they might contribute to the experience of chronic pain, reviews the types of chronic pain that are common in people living with HIV and approaches to treatment, and discusses how the lens of vulnerability might be applied to a conceptual model of pain in people living with HIV to identify novel treatment strategies.
Managing Pain in Patients on Long-Term Opioids
Authors: Sandbrink Friedhelm
Published: May 2024

This chapter addresses key clinical issues related to opioid prescribing, including benefits and risks in the treatment of chronic pain, and provides clinical strategies to optimize safety and effectiveness, based on recently published guidelines by the Centers for Disease Control and Prevention and by the U.S. Department of Veterans Affairs and U.S. Department of Defense. Whereas opioids have wide efficacy and utility in the treatment of acute and cancer-related pain, their use for chronic non–cancer-related pain is controversial because risks of long-term opioid therapy generally outweigh the potential benefits. A careful evaluation of the patient may assist in assessing risk prior to initiating opioid therapy. Patients with a history of substance use disorder and other mental health disorders are particularly vulnerable, as are younger patients, the frail or elderly, and people with medical conditions such as sleep apnea. Opioid therapy is initiated with short-acting opioids and prescribed at the lowest effective dosage and duration based on clinical indication. Risk mitigation strategies include prescription drug monitoring programs, urine drug testing, patient education and clear communication of safety expectations (e.g., informed consent), naloxone co-prescribing, and close monitoring and reassessment. Dosage escalations and co-prescribing with benzodiazepines should be avoided. Opioid tapering must be individualized, and sudden discontinuation should be avoided. Opioid therapy with buprenorphine is an emerging strategy associated with lower risk for overdose. Patients with suspected opioid use disorder should not be abandoned but, rather, carefully assessed and supported by providing evidence-based therapy including medication such as buprenorphine.
Movement Disorders
Authors: Selwa Linda M. , Gelb Douglas J.
Published: May 2024

This chapter begins with a general approach to movement disorders, a set of definitions, and a classification system. This is followed by detailed discussion of the clinical manifestations, pathophysiology, and approach to diagnosis and management of major movement disorders: essential tremor; Parkinson disease (PD); other parkinsonian syndromes—including dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA); hereditary ataxias—including Friedreich ataxia, ataxia telangiectasia, spinocerebellar ataxias, episodic ataxias, and fragile X-associated tremor/ataxia syndrome (FXTAS); Huntington disease; tardive dyskinesias; dystonias; Wilson disease; and Tourette syndrome. The misfolded proteins associated with these disorders are emphasized.
On the origin of mixed morphology supernova remnants: linking their properties to the evolution of a red supergiant progenitor star
Authors: Chiotellis Alexandros , Zapartas Emmanouil , Meyer Dominique M -A
Published: May 2024

Mixed-morphology supernova remnants (MMSNRs) are characterized by a shell-like morphology in the radio and centrally peaked thermal emission in the X-ray band. The nature of this peculiar class of supernova remnants (SNRs) remains a controversial issue. In this work, by pairing the predictions of stellar evolution theory with two-dimensional hydrodynamic simulations, we show that the mixed morphology properties of an SNR can arise by the interaction of the SNR with the circumstellar medium shaped by a red supergiant progenitor star, embedded in a dense environment. As a study case, we model the circumstellar medium formation and the subsequent interaction of the SNR with it of a $15~\rm {\rm M}_{\odot }$ progenitor star. The reflected shock, formed by the collision of the SNR with the density walls of the surrounding circumstellar cavity, accumulates and re-shocks the supernova ejecta at the centre of the remnant, increasing its temperature so that the gas becomes X-ray bright. Such a formation mechanism may naturally explain the nature of MMSNRs resulted from Type II supernovae without the demand of additional physical mechanisms and/or ambient medium inhomogeneities. We discuss alternative evolutionary paths that potentially could be ascribed for the MMSNR formation within the framework of the reflected shock model.
Radiomics-based prediction of local control in patients with brain metastases following postoperative stereotactic radiotherapy
Authors: Buchner Josef A , Kofler Florian , Mayinger Michael , Christ Sebastian M , Brunner Thomas B , Wittig Andrea , Menze Bjoern , Zimmer Claus , Meyer Bernhard , Guckenberger Matthias , Andratschke Nicolaus , El Shafie Rami A , Debus Jürgen , Rogers Susanne , Riesterer Oliver , Schulze Katrin , Feldmann Horst J , Blanck Oliver , Zamboglou Constantinos , Ferentinos Konstantinos , Bilger-Zähringer Angelika , Grosu Anca L , Wolff Robert , Piraud Marie , Eitz Kerstin A , Combs Stephanie E , Bernhardt Denise , Rueckert Daniel , Wiestler Benedikt , Peeken Jan C
Published: May 2024

Background

Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the risk of local failure (LF) persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk.

Methods

Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of BMs (AURORA) retrospective study (training cohort: 253 patients from 2 centers; external test cohort: 99 patients from 5 centers). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (T2-FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameter set previously determined by internal 5-fold cross-validation and tested on the external test set.

Results

The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan–Meier analysis (P < .001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively.

Conclusions

A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow-up routines or intensified therapy.
Dietary Magnesium Intake in Relation to Depression in Adults: A GRADE-Assessed Systematic Review and Dose–Response Meta-analysis of Epidemiologic Studies
Authors: Hajhashemy Zahra , Shirani Fatemeh , Askari Gholamreza
Published: May 2024

Context

The relation of magnesium (Mg) intake with depression was previously investigated by meta-analyses. However, due to limited data, a dose–response analysis was not performed.

Objective

Considering the recently published articles, a systematic review and dose–response meta-analysis was conducted to summarize the relation of dietary Mg intake with depression in adults.

Data Sources

Medline (PubMed), ISI Web of Science, Scopus, and Google Scholar were comprehensively searched up to August 2023.

Data Extraction

Observational studies that reported the relation of dietary Mg intake and depression in adults were included and their data were extracted.

Data Analysis

A total of 63 214 participants from 10 cross-sectional and 3 cohort studies were included in the current study. Pooling 15 effect sizes from 12 studies (including 50 275 participants) revealed that individuals with the highest Mg intake had a 34% lower risk of depression, compared with those with the lowest Mg intake (RR: 0.66; 95% CI: 0.57, 0.78). Moreover, the linear dose–response analysis revealed that each 100-mg/d increment in Mg intake was associated with a 7% reduced risk of depression (RR: 0.93; 95% CI: 0.90, 0.96). Additionally, based on nonlinear dose–response analysis, increasing Mg intake from 170 to 370 mg/d was associated with a reduced risk of depression. Analyses were also conducted on 9 studies (49 558 participants) with representative populations, and similar results were found in the meta-analysis (RR: 0.71; 95% CI: 0.61, 0.83) and linear (RR: 0.93; 95% CI: 0.90, 0.96) and nonlinear dose–response analysis.

Conclusion

The current study shows an inverse dose–dependent association between dietary Mg intakes and risk of depression in both a general and representative population of adults in a dose–response manner.

Systematic Review Registration

PROSPERO registration no. CRD42024506570.
Olaparib for childhood tumors harboring defects in DNA damage repair genes: arm H of the NCI-COG Pediatric MATCH trial
Authors: Glade Bender Julia L , Pinkney Kerice , Williams Paul M , Roy-Chowdhuri Sinchita , Patton David R , Coffey Brent D , Reid Joel M , Piao Jin , Saguilig Lauren , Alonzo Todd A , Berg Stacey L , Ramirez Nilsa C , Fox Elizabeth , Weigel Brenda J , Hawkins Douglas S , Mooney Margaret M , Takebe Naoko , Tricoli James V , Janeway Katherine A , Seibel Nita L , Parsons Donald W
Published: May 2024

Background

The National Cancer Institute-Children’s Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) precision oncology platform trial enrolled children aged 1-21 years with treatment-refractory solid tumors and predefined actionable genetic alterations. Patients with tumors harboring alterations in DNA damage repair (DDR) genes were assigned to receive olaparib.

Methods

Tumor and blood samples were submitted for centralized molecular testing. Tumor and germline sequencing were conducted in parallel. Olaparib was given twice daily for 28-day cycles starting at a dose 30% lower than the adult recommended phase 2 dose (RP2D). The primary endpoint was the objective response.

Results

Eighteen patients matched (1.5% of those screened) based on the presence of a deleterious gene alteration in BRCA1/2, RAD51C/D, or ATM detected by tumor sequencing without germline subtraction or analysis of loss of heterozygosity (LOH). Eleven (61%) harbored a germline mutation, with only one exhibiting LOH. Six patients enrolled and received the olaparib starting dose of 135 mg/m2/dose. Two participants were fully evaluable; 4 were inevaluable because <85% of the prescribed dose was administered during cycle 1. There were no dose-limiting toxicities or responses. Minimal hematologic toxicity was observed.

Conclusion

Most DDR gene alterations detected in Pediatric MATCH were germline, monoallelic, and unlikely to confer homologous recombination deficiency predicting sensitivity to olaparib monotherapy. The study closed due to poor accrual.

ClinicalTrials.gov Identifier

NCT03233204. IRB approved: initial July 24, 2017.
Deep learning-based multi-modal data integration enhancing breast cancer disease-free survival prediction
Authors: Wang Zehua , Lin Ruichong , Li Yanchun , Zeng Jin , Chen Yongjian , Ouyang Wenhao , Li Han , Jia Xueyan , Lai Zijia , Yu Yunfang , Yao Herui , Su Weifeng
Published: May 2024

Background

The prognosis of breast cancer is often unfavorable, emphasizing the need for early metastasis risk detection and accurate treatment predictions. This study aimed to develop a novel multi-modal deep learning model using preoperative data to predict disease-free survival (DFS).

Methods

We retrospectively collected pathology imaging, molecular and clinical data from The Cancer Genome Atlas and one independent institution in China. We developed a novel Deep Learning Clinical Medicine Based Pathological Gene Multi-modal (DeepClinMed-PGM) model for DFS prediction, integrating clinicopathological data with molecular insights. The patients included the training cohort (n = 741), internal validation cohort (n = 184), and external testing cohort (n = 95).

Result

Integrating multi-modal data into the DeepClinMed-PGM model significantly improved area under the receiver operating characteristic curve (AUC) values. In the training cohort, AUC values for 1-, 3-, and 5-year DFS predictions increased to 0.979, 0.957, and 0.871, while in the external testing cohort, the values reached 0.851, 0.878, and 0.938 for 1-, 2-, and 3-year DFS predictions, respectively. The DeepClinMed-PGM's robust discriminative capabilities were consistently evident across various cohorts, including the training cohort [hazard ratio (HR) 0.027, 95% confidence interval (CI) 0.0016–0.046, P < 0.0001], the internal validation cohort (HR 0.117, 95% CI 0.041–0.334, P < 0.0001), and the external cohort (HR 0.061, 95% CI 0.017–0.218, P < 0.0001). Additionally, the DeepClinMed-PGM model demonstrated C-index values of 0.925, 0.823, and 0.864 within the three cohorts, respectively.

Conclusion

This study introduces an approach to breast cancer prognosis, integrating imaging and molecular and clinical data for enhanced predictive accuracy, offering promise for personalized treatment strategies.
Reinterpretation of the post-26 ka Taupō Rhyolitic Magmatic System (New Zealand) as Deep and Vertically Extensive Based on Isotope Thermometry and Measured and Modeled Zircon Destinies
Authors: Bindeman Ilya N
Published: May 2024

Taupō volcanic zone, the site of the 26 ka Oruanui supereruption, produced ~70 km3 of new rhyolites since 11 ka, culminating in 50 km3 Taupō eruption 1.8 ka. Major phenocrysts decrease from 4 to 1 vol%, and Oruanui and post-Oruanui ignimbrites all have identical high-δ18Omelt values of 7.39 ± 0.1‰ and lack low-δ18O values despite overlapping calderas. The Δ’17O values are −0.07‰, lower than the mantle and indicate source contamination of high-δ18O, low-Δ’17O metasediments, and limited interaction with high-Δ’17O hydrothermally altered crust. Previously published U-Th-Pb zircon ages demonstrate their diversity spanning 104–105 years for each unit. Zircon crystal size distribution shows a decrease in abundance and the mean size, and some units lack small (<~10 um) zircons suggesting that zircons were both growing and dissolving in the coexisting magma generation areas. Isotope thermometry indicates heating of the system from ~812 ± 35°C to 874 ± 36°C past zircon saturation in 1.8 ka eruption. We advocate that a deep vertically continuous and laterally discontinuous silicic magma system at the base of the Taupō rift, rather than a shallow batholith or an evolving mush, drives volcanism at Taupō. To explain the post-Oruanui magma production, rift-base silicic magma origin and moderate (~2 km3/1000 years) rhyodacitic magma flux from a growing and heating liquid magma body creates a sufficient solution for the most recent magmatism.
Unraveling the Prefrontal Cortex-Basolateral Amygdala Pathway’s Role on Schizophrenia’s Cognitive Impairments: A Multimodal Study in Patients and Mouse Models
Authors: Liang Jiaquan , Chen Lei , Li Yongbiao , Chen Yuewen , Yuan Lin , Qiu Yue , Ma Shuangshuang , Fan Fangcheng , Cheng Yong
Published: May 2024

Background and Hypothesis

This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques.

Study Design

This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA.

Study Results

Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients.

Conclusions

Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method.
Csn-miR156d targeting CsSPL1 plays an important role in flowering and anthocyanin metabolism of tea plant
Authors: Lin Qingqing , Li Hui , He Hu , Wang Pu , Wang Mingle , Zhao Hua , Wang Yu , Ni Dejiang , Fang Yanni , Guo Fei
Published: May 2024

miR156 play important roles in regulation of plant growth and development, secondary metabolite synthesis and other biological processes by targeting the SQUAMOSA promoter binding protein-like (SPL) family. Our previous sequencing data analysis suggested that Csn-miR156d may regulate flowering and anthocyanin accumulation by cleavage and degradation of the expression of the SPL in tea plant, but it remains to be elucidated. In this study, 5′RLM-RACE experiment, tobacco transient transformation, qRT-PCR and antisense oligonucleotide (asODN) were used to verify that CsSPL1 is the target gene of Csn-miR156d. Stable transformation of Arabidopsis revealed that Csn-miR156d could delay flowering by negatively regulating the transcript levels of FT, AP1, FUL and SOC1, while overexpression of CsSPL1 showed an opposite effect. Additionally, overexpression of Csn-miR156d in Arabidopsis could enhance the transcription of the anthocyanin biosynthesis-related structural genes DFR, ANS, F3H, UGT78D2 and LDOX, as well as regulatory genes PAP1, MYB113, GL3, MYB11 and MYB12, leading to anthocyanin accumulation. Moreover, asODN experiment revealed that Csn-miR156d could increase the anthocyanin content in tea plant. These results suggest that Csn-miR156d regulates flowering and anthocyanin accumulation in tea plant by suppressing the expression of CsSPL1. Our study provides new insights into the development and anthocyanin accumulation in tea plant and lays a theoretical foundation for further research on the molecular mechanism of miRNAs in regulating tea plant growth and secondary metabolism.
A Narrative Review of NICU Implementation of Evidence-Based Early Relational Health Interventions
Authors: Darilek Umber , Finley Erin , McGrath Jacqueline
Published: May 2024

Background:

Early relational health (ERH) interventions in the neonatal intensive care unit (NICU) buffer infants from toxic stress effects. Implementation science (IS) can guide successful uptake of evidence-based practice (EBP) ERH interventions. It is unknown if implementors of ERH interventions currently use the resources of IS to improve implementation.

Purpose:

A narrative review of recent literature on implementation of ERH EBPs was completed to understand (a) which ERH interventions are currently being implemented in NICUs globally, (b) whether clinical implementors of ERH interventions have adopted the resources of IS, (c) existence of implementation gaps, and (d) implementation outcomes of ERH interventions in contemporary literature.

Data Sources:

Scopus, PubMed, and CINHAL were searched for original research regarding implementation of dyadic ERH interventions using key words related to IS and ERH.

Study Selection:

For inclusion, ERH EBPs had to have been implemented exclusively in NICU settings, contained data addressing an IS domain, printed in English within the last 5 years. Twenty-four studies met inclusion criteria.

Data Extraction:

Studies were distilled for intervention, IS domains addressed, location, aims, design, sample, and outcomes.

Results:

Eleven ERH interventions were described in the literature. Few studies utilized the resources of IS, indicating variable degrees of success in implementation. Discussions of implementation cost were notably missing

Implications for Practice and Research:

Implementors of ERH interventions appear to be largely unfamiliar with IS resources. More work is needed to reach clinicians with the tools and resources of IS to improve implementation outcomes.
Reducing Noise in the NICU
Authors: Gennattasio Annmarie , Carter Brigit , Maffei Diana , Turner Barbara , Weinberger Barry , Boyar Vitaliya
Published: May 2024

Background:

In the neonatal intensive care unit (NICU), elevated noise negatively impacts the neurodevelopmental environment, interrupts sleep, and can affect brain development in neonates. The American Academy of Pediatrics recommends that noise levels in the NICU should not exceed 45 dB.

Purpose:

The project aims were to: (1) decrease average noise level by 10% from baseline and (2) decrease exposure to severe noise (>65 dB) to <5% of the time.

Methods:

This quality improvement project was conducted during 2021-2022 as a pre/post observational design in a Level IV NICU in New York City. We monitored sound levels for 20-24 h, 5 d/wk. Quality improvement interventions included: novel approaches to staff education, visual cues for when noise thresholds were exceeded, parent education, including access to personal decibel meters, technical improvements to vital sign monitors and entry doors, and defined quiet times (HUSH) for 2 h each 12-hour shift.

Results:

Education efforts and technical improvements successfully reduced median noise levels within the stepdown unit (P < .001), though not in the acute care NICU. In contrast, the implementation of 2-hour periods of enforced “quiet time” every 12 h effectively reduced both median noise levels and the incidence of severe noise (>65 dB) in both locations.

Implications for practice and research:

The HUSH strategy may be a sustainable way to decrease noise in the NICU. Future projects should prioritize education and dedicated quiet times to align with recommended standards, while research should explore the long-term developmental impacts of excessive noise levels on neonatal growth.
Gene therapy using retrovirally transduced human chondrocytes expressing TGF-β1: a systematic review of early results are not promising!
Authors: Kumar Vishal , Patel Sandeep , Baburaj Vishnu , Neradi Deepak , Kaushal Aditya
Published: May 2024

Background:

Gene therapy is a promising ortho-biologic product for Osteoarthritis (OA) knee with some level 2 and 3 studies. There is a need to evaluate the safety and efficacy of this therapy with a systematic review by pooling the data from the limited clinical trials to give an early idea of the product.

Methods:

Pubmed, Embase, and Scopus were searched for articles related to gene therapy use in human trials for osteoarthritis using mesh terms. After screening, seven RCTs were included in this review. Clinical outcomes with IKDC scores, VAS, and adverse effects were analyzed.

Results:

All studies reported significant improvement in functional outcomes measured with IKDC scores. VAS scores showed mixed results. WOMAC scores and WORMS scoring reported no significant difference between the treatment and placebo groups, but the progression of OA was decreased in the treatment group.

Conclusion:

Gene therapy could potentially improve knee-related functional outcomes and alleviate pain. While some studies indicate positive effects on knee morphology, further research is needed in this regard. Adverse events, though generally manageable, require ongoing vigilance. Gene therapy holds the potential to enhance the quality of life for individuals with osteoarthritis knee.
Contemporary treatments for mid-substance achilles tendinopathy: a review
Authors: Kanneganti Naethan , Gao Angela , Laughlin Richard T.
Published: May 2024

Mid-substance Achilles tendinopathy is primarily a degenerative condition that frequently affects quality of life, especially for patients wanting to continue a high level of activity. It can differ from insertional Achilles tendinopathy both in terms of its epidemiology as well as its management strategies. Currently, numerous treatment options exist in the literature for this fairly common musculoskeletal condition. However, many of these treatments remain experimental with no substantial evidence for efficacy. A number of these options, including regenerative and biologic medicines, have nonetheless demonstrated improvements in patient-reported outcomes and promising potential. As such, there remains no standard approach for management beyond stretching/exercise therapy. This article reviewed the current literature surrounding treatment options and provided summaries and recommendations of eight treatment modalities for this condition. It is intended to serve as a general review as well as an objective evaluation of recent evidence that may provide some guidance for healthcare providers when discussing treatment options with patients.
Atrial Fibrillation and Cognitive Disorders
Authors: Barkhordarian Maryam , Montazerin Sahar Memar , Tran Hadrian Hoang-Vu , Amin Toka , Frishman William H. , Aronow Wilbert S.
Published: May 2024

The prevalence of atrial fibrillation among older adults is increasing. Research has indicated that atrial fibrillation is linked to cognitive impairment disorders such as Alzheimer and vascular dementia, as well as Parkinson disease. Various mechanisms are believed to be shared between atrial fibrillation and cognitive impairment disorders. The specific pathologies and mechanisms of different cognitive disorders are still being studied. Potential mechanisms include cerebral hypoperfusion, ischemic or hemorrhagic infarction, and cerebrovascular reactivity to carbon dioxide. Additionally, circulatory biomarkers and certain infectious organisms appear to be involved. This review offers an examination of the overlapping epidemiology between atrial fibrillation and cognitive disorders, explores different cognitive disorders and their connections with this arrhythmia, and discusses trials and guidelines for preventing and treating atrial fibrillation in patients with cognitive disorders. It synthesizes existing knowledge on the management of atrial fibrillation and identifies areas that require further investigation to bridge the gap in understanding the complex relationship between dementia and atrial fibrillation.
Pan-cancer single-cell landscape of drug-metabolizing enzyme genes
Authors: Mao Wei , Zhou Tao , Zhang Feng , Qian Maoxiang , Xie Jianqiang , Li Zhengyan , Shu Yang , Li Yuan , Xu Heng
Published: May 2024

Objective

Varied expression of drug-metabolizing enzymes (DME) genes dictates the intensity and duration of drug response in cancer treatment. This study aimed to investigate the transcriptional profile of DMEs in tumor microenvironment (TME) at single-cell level and their impact on individual responses to anticancer therapy.

Methods

Over 1.3 million cells from 481 normal/tumor samples across 9 solid cancer types were integrated to profile changes in the expression of DME genes. A ridge regression model based on the PRISM database was constructed to predict the influence of DME gene expression on drug sensitivity.

Results

Distinct expression patterns of DME genes were revealed at single-cell resolution across different cancer types. Several DME genes were highly enriched in epithelial cells (e.g. GPX2, TST and CYP3A5) or different TME components (e.g. CYP4F3 in monocytes). Particularly, GPX2 and TST were differentially expressed in epithelial cells from tumor samples compared to those from normal samples. Utilizing the PRISM database, we found that elevated expression of GPX2, CYP3A5 and reduced expression of TST was linked to enhanced sensitivity of particular chemo-drugs (e.g. gemcitabine, daunorubicin, dasatinib, vincristine, paclitaxel and oxaliplatin).

Conclusion

Our findings underscore the varied expression pattern of DME genes in cancer cells and TME components, highlighting their potential as biomarkers for selecting appropriate chemotherapy agents.
Acellular Fish Skin Grafts for Treatment of Periocular Skin Defects
Authors: Wang Diane , Maliakkal Janice , Sadat Omar , Codrea Vlad , Nguyen John
Published: May 2024

Purpose:

To describe the outcomes of acellular fish skin grafts for repair of periocular anterior lamella skin defects after Mohs surgery for skin cancers.

Methods:

Following the institutional review board approval, the authors conducted a retrospective chart review of patients treated with acellular fish skin grafts between January 2022 and December 2023. Indication was to repair defects after Mohs excision of basal cell carcinoma and squamous cell carcinoma. Demographics, smoking and diabetes status, diagnosis, defect location, graft size, and complications were evaluated. Outcomes were analyzed using the scar cosmesis assessment and rating scale.

Results:

Six patients (3 females and 3 males) with a mean age of 60.8 (range 44–80) had Mohs surgery for basal cell carcinoma (4) and squamous cell carcinoma (2). Location of defects included eyebrow (3 cases), lateral nasal wall (1 case), lower eyelid (1 case), and medial lower eyelid/nasal wall (1 case). Defect size ranged from 8 × 10 mm to 30 × 40 mm. Two patients had more than 1 application of xenograft. One patient developed a mild cicatricial ectropion. No other postoperative complications were seen, and all had good wound healing and cosmetically acceptable results.

Conclusions:

In this pilot study, acellular fish skin xenografts are shown to be promising skin graft substitutes in patients with Mohs defects and decrease the need for autologous skin harvesting or allogenic skin donation.