bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary and secondary prevention of stroke
Authors: Manning Lisa , Lam Man Yee , Robinson Thompson G.
Published: March 2024

Stroke is one of the leading causes of mortality, morbidity, and disability worldwide. Stroke and transient ischaemic attack survivors are at risk of recurrent stroke, which is often more severe and disabling. Despite the success in acute treatment and rehabilitation of stroke, prevention remains the most effective way to reduce the global burden of the disease. Since preventative strategies have early effectiveness, prompt recognition of symptoms, specialist assessment and diagnosis, and initiation of these secondary prevention strategies are of utmost importance in stroke prevention. This chapter provides an overview of current primary and secondary stroke prevention strategies, highlighting the importance of rapid recognition, urgent specialist care, and evidence-based interventions, which are the cornerstones of effective management.
“No Future to Be Had”: Journeying toward Death in Toni Morrison’s Song of Solomon
Authors: Kirton Jenny
Published: March 2024

This article examines Toni Morrison’s Song of Solomon (1977) by focusing on the way that the novel’s protagonist, Milkman Dead, rejects various traditional Euro-American formulations of “progress.” I argue that Milkman’s actions uncover a legacy of loss associated with African American culture and, relatedly, buried narratives of African American history. I take a cue from dance scholar Ann Cooper Albright’s attentiveness to what she terms “the cultural hegemony of the vertical” (37) in considering Milkman’s embodied resistance to existing paradigms of progress. By positing a vertical conceptualization of racial uplift ideology, the Dead family ancestry, and the journeys North and South between Michigan and Virginia in Song of Solomon, I demonstrate how Milkman’s very corporeality comes to signify the importance of African American cultural preservation and moving “counter-to” in re-visioning liberatory, counter-hegemonic routes of progress. My reading unfolds from a critical moment in chapter 2 of Song of Solomon; in this scene, the Dead family journeys northward in Milkman’s father’s Packard toward the wealthy white neighborhoods of Honoré, meanwhile Milkman demonstrates a remarkable preoccupation with what lies behind him. Situating Milkman’s embodied opposition to the journey’s progress as a point of departure, I examine how Morrison disrupts various paradigms of progress throughout Song of Solomon.
Indian Removal and the Plantation South: Cherokee Present-Absence in Three Neo-Slave Narratives
Authors: Harris Allison N
Published: March 2024

This article contends that we must understand a constitutive, interactive ontogenesis between modern Indigenous Americans and African Americans that is irreversibly shaped by the dominance of racialized slavery and the plantation economy. Building on the work of Gina Caison and Kevin Bruyneel, I argue that the present-absence of the Cherokee in prominent African American neo-slave narratives—Toni Morrison’s Beloved (1987), Edward P. Jones’s The Known World (2003), and Colson Whitehead’s The Underground Railroad (2016)—illustrates the imaginative function of Removal in the South. I slightly modify Bruyneel’s “absent/present dynamics” to show how the Cherokee persist as a constitutive Other used by these Black authors to expose the racial logic of the Plantationocene. I assert that the three novels imagine Black and Cherokee characters not where they are “supposed” to be in order to authorize Black fugitivity, demonstrating a triangulation of the power and racial formations of Blackness, whiteness, and Indigeneity in relation to the plantation.
Coupling of radiation and magnetospheric accretion flow in ULX pulsars: radiation pressure and photon escape time
Authors: Flexer Caitlyn , Mushtukov Alexander A
Published: March 2024

The accretion flow within the magnetospheric radius of bright X-ray pulsars can form an optically thick envelope, concealing the central neutron star from the distant observer. Most photons are emitted at the surface of a neutron star and leave the system after multiple reflections by the accretion material covering the magnetosphere. Reflections cause momentum to be transferred between photons and the accretion flow, which contributes to the radiative force and should thus influence the dynamics of accretion. We employ Monte Carlo simulations and estimate the acceleration along magnetic field lines due to the radiative force as well as the radiation pressure across magnetic field lines. We demonstrate that the radiative acceleration can exceed gravitational acceleration along the field lines, and similarly, radiation pressure can exceed magnetic field pressure. Multiple reflections of X-ray photons back into the envelope tend to amplify both radiative force along the field lines and radiative pressure. We analyse the average photon escape time from the magnetosphere of a star and show that its absolute value is weakly dependent on the magnetic field strength of a star and roughly linearly dependent on the mass accretion rate being $\sim 0.1\, {\rm s}$ at $\dot{M}\sim 10^{20}\, {\rm g\, s^{-1}}$. At high mass accretion rates, the escape time can be longer than free-fall time from the inner disc radius.
Partisan Legal Traditions in the Age of Camden and Mansfield
Authors: Arvind T T , Burset Christian R
Published: March 2024

The 18th century is often treated by scholars as a period of juristic consensus. This article argues, in contrast, that the late 18th century saw the emergence of rival ‘Patriot’ and ‘Tory’ legal traditions. Through a detailed study of the jurisprudence of Lords Camden and Mansfield—who were both pillars of the law, as well as political and juristic rivals—we show that they differed systematically in their understanding of the common law, and that those differences had a partisan cast: although they were not crude attempts to instrumentalise law to political ends, their political and jurisprudential commitments influenced each other and emerged from the same intellectual roots. We place these differences in the context of the fragmentation of 18th-century Whig politics, and argue that they have important implications for how we understand and make use of the common law tradition in present-day scholarship.
Plasma ctDNA Monitoring of a PTCH1-Mutant Metastatic Adult Medulloblastoma Showing a Durable Benefit With Vismodegib
Authors: Cabezas-Camarero Santiago , García-Barberán Vanesa , Pérez-Alfayate Rebeca , Gómez del Pulgar María Elena , Cabrera-Martin Maria Nieves , Casado-Fariñas Isabel , Pérez-Segura Pedro
Published: March 2024

Adult medulloblastoma (MB) is a rare disease affecting 0.6 persons per million adults over 19 years of age. The SHH-activated/TP53-wild type is the most common subtype, accounting for 60% of adult MBs, being characterized by mutations in PTCH1, SMO, or the TERT promoter. Several small studies demonstrate objective but short-lived responses to SMO inhibitors such as vismodegib or sonidegib. Like other oncogene-addicted solid tumors, detection of the corresponding drivers through liquid biopsy could aid in the molecular diagnosis and monitoring of the disease through less invasive procedures. However, most studies have only evaluated cerebrospinal fluid as the ctDNA reservoir, and very limited evidence exists on the role of liquid biopsy in plasma in patients with primary central nervous system tumors, including MB. We present the case of a 26-year-old patient with a recurrent MB, in which next-generation sequencing (FoundationOne CDx) revealed a mutation in PTCH1, allowing the patient to be treated with vismodegib in second line, resulting in a durable benefit lasting for 1 year. Using an in-house digital PCR probe, the PTCH1 mutation could be tracked in ctDNA during treatment with first-line chemotherapy and while on treatment with vismodegib, demonstrating a precise correlation with the radiological and clinical behavior of the disease.
The Practice of Medical Dissection in Third-Century BCE Alexandria, Egypt as a Heterotopia of Deviation
Authors: Fowler Ryan C
Published: March 2024

I argue that Foucault’s notion of heterotopia is a useful way to look at the practice of systematic human dissection performed in Alexandria, Egypt in the third century BCE. Foucault’s idea provides a novel way to consider why this practice—one not documented in any other time or place within Greek or Roman antiquity, and not officially recorded as a practice again until the 14th century CE with the work of de Liuzzi and da Vigevano—might have occurred when and where it did.
Actigraphic sleep dimensions and associations with academic functioning among adolescents
Authors: Mathew Gina Marie , Reichenberger David A , Master Lindsay , Buxton Orfeu M , Chang Anne-Marie , Hale Lauren
Published: March 2024

Study Objectives

There is mixed evidence regarding associations of sleep duration with academic functioning in adolescents and a lack of research on other sleep dimensions, particularly using objective sleep measures. We examined associations of multiple actigraphic sleep dimensions with academic functioning among adolescents.

Methods

Data were from the sleep sub-study of the age 15 wave of the Future of Families and Child Wellbeing Study (n = 774–782; 52% female), a national, diverse sample of teens. Adolescents wore wrist-actigraphs for ~1 week and completed a survey reporting academic performance and school-related behavioral problems. Regression models assessed whether average sleep duration, timing, maintenance efficiency, and SD-variability were associated with self-reported academic functioning in cross-sectional analyses adjusted for demographic characteristics, depressive symptoms, and anxious symptoms.

Results

Later sleep timing (hours) and greater sleep variability (SD-hours) were associated with poorer academic outcomes, including sleep onset variability with higher odds of receiving a D or lower (OR = 1.29), sleep onset (β = −.07), sleep offset (β = −.08), and sleep duration variability (β = −.08) with fewer A grades, sleep offset with lower GPA (β = −.07), sleep offset (OR = 1.11), sleep duration variability (OR = 1.31), and sleep onset variability (OR = 1.42) with higher odds of being suspended or expelled in the past 2 years, and sleep duration variability with greater trouble at school (β = .13). Sleep duration, sleep maintenance efficiency, and sleep regularity index were not associated with academic functioning.

Conclusions

Later sleep timing and greater sleep variability are risk factors for certain academic problems among adolescents. Promoting sufficient, regular sleep timing across the week may improve adolescent academic functioning.
Cost Analysis for Robotic and Open Gastrectomy
Authors: Hirata Yuki , Lyu Heather G. , Azimuddin Ahad M. , Lu Pamela , Ajith Jeeva , Schmeisser Jason A. , Ninan Elizabeth P. , Lee Kyung Hyun , Badgwell Brian D. , Mansfield Paul , Ikoma Naruhiko
Published: March 2024

Objective:

To determine the magnitude of the perioperative costs associated with robotic gastrectomy (RG).

Background:

A robotic surgery platform has a high implementation cost and requires maintenance costs; however, whether the overall cost of RG, including all perioperative costs, is higher than conventional open gastrectomy (OG) remains unknown.

Methods:

Patients who underwent a major gastrectomy during February 2018 through December 2021 were retrospectively identified. We calculated the perioperative costs of RG and OG and compared them overall as well as in different phases, including intraoperative costs and 30-day postsurgery inpatient and outpatient costs. We investigated factors potentially associated with high cost and estimated the likelihood of RG to reduce overall cost under a Bayesian framework. All cost data were converted to ratios to the average cost of all operations performed at our center in year FY2021.

Results:

We identified 119 patients who underwent gastrectomy. The incidence of postoperative complications (Clavien-Dindo >IIIa; RG, 10% vs OG, 13%) did not significantly differ between approaches. The median length of stay was 3 days shorter for RG versus OG (4 vs 7 days, P < 0.001). Intraoperative cost ratios were significantly higher for RG (RG, 2.6 vs OG, 1.7; P < 0.001). However, postoperative hospitalization cost ratios were significantly lower for RG (RG, 2.8 vs OG, 3.9; P < 0.001). Total perioperative cost ratios were similar between groups (RG, 6.1 vs OG, 6.4; P = 0.534). The multiple Bayesian generalized linear analysis showed RG had 76.5% posterior probability of overall perioperative cost reduction (adjusted risk ratio of 0.95; 95% credible interval, 0.85–1.07).

Conclusions:

Despite increased intraoperative costs, total perioperative costs in the RG group were similar to those in the OG group because of reduced postoperative hospitalization costs.
Altered hormone expression induced genetic changes leads to breast cancer
Authors: Thakur Anchal , Rana Navya , Kumar Ranjit
Published: March 2024

Purpose of review

Breast cancer ranks first among gynecological cancer in India. It is associated with urbanization, changes in lifestyle and obesity. Hormones also play a crucial role in the development of breast cancer. Steroid hormones play critical role in development of breast cancer.

Recent finding

Breast cancer is caused due to alteration in different hormone expressions leading to genetic instability. Loss or gains of functions due to genetic instability were associated with the alterations in housekeeping genes. Up-regulation in c-myc, signal transducer and activator of transcription (STAT), CREB-regulated transcription coactivator (CRTC), and eukaryotic translation initiation factor 4E (eIF4E) may cause the development of breast cancer. Peptide hormones are commonly following the phosphoinositide 3-kinases (PI3K) pathway for activation of cell cycle causing uncontrolled proliferation. Although steroid hormones are following the Ras/Raf/mitogen-activated protein kinase (MEK) pathway, their hyper-activation of these pathways causes extracellular-signal-regulated kinase (ERK) and MAPK activation, leading to carcinogenesis.

Alteration in cell cycle proteins, oncogenes, tumor suppressor genes, transcription and translation factors lead to breast cancer. Apoptosis plays a vital role in the elimination of abnormal cells but failure in any of these apoptotic pathways may cause tumorigenesis. Hence, a complex interplay of hormonal and genetic factors is required to maintain homeostasis in breast cells. Imbalance in homeostasis of these hormone and genes may lead to breast cancer.
Tripartite motif family – its role in tumor progression and therapy resistance: a review
Authors: Zhang Yongqi , Guan Ying , Wang Shuxiang , Guan Chunyan , Liu Xiaoli
Published: March 2024

Purpose of review

In this review, we summarized published articles on the role of tripartite motif (TRIM) family members in the initiation and development of human malignancies.

Recent findings

The ubiquitin-proteasome system (UP-S) plays a critical role in cellular activities, and UP-S dysregulation contributes to tumorigenesis. One of the key regulators of the UP-S is the tripartite motif TRIM protein family, most of which are active E3 ubiquitin ligases. TRIM proteins are critical for the biological functions of cancer cells, including migration, invasion, metastasis, and therapy resistance. Therefore, it is important to understand how TRIM proteins function at the molecular level in cancer cells.

We provide a comprehensive and up-to-date overview about the role TRIMs play in cancer progression and therapy resistance. We propose TRIM family members as potential new markers and targets to overcome therapy failure.
Neoadjuvant immune checkpoint blockade enhances local and systemic tumor immunity in head and neck cancer
Authors: Zhao Ye , Wucherpfennig Kai W.
Published: March 2024

Purpose of review

Neoadjuvant (presurgical) immune checkpoint blockade (ICB) has shown promising clinical activity in head and neck cancer and other cancers, including FDA approvals for neoadjuvant approaches for triple-negative breast cancer and nonsmall cell lung cancer. Here we will review recent data from clinical trials in head and neck squamous cell carcinoma (HNSCC), including mechanistic studies highlighting local and systemic effects on T cell-mediated immunity.

Recent findings

A series of clinical trials of neoadjuvant ICB have documented evidence of clinical activity, including clinical to pathologic downstaging and pathologic response in a subset of patients. Also, emerging data suggest improved survival outcomes for patients with tumors responsive to neoadjuvant ICB. In depth mechanistic studies have documented intra-tumoral expansion of CD8 T cell populations characterized by tissue residency and cytotoxicity programs. Treatment also leads to expansion of activated CD8 T cells in the blood, many of which share TCR sequences with tumor-infiltrating T cells. The frequency of activated circulating CD8 T cell populations is correlated with the degree of pathologic response within tumors.

Even a short duration of neoadjuvant immunotherapy can enhance local and systemic tumor-reactive T cell populations. Downstaging induced by neoadjuvant ICB can reduce the extent of surgical resection in this anatomically sensitive location.
What Is in the Literature
Authors: Bromberg Mark B.
Published: March 2024

This issue of What is in the Literature focuses on the Guillain–Barré syndrome. Guillain–Barré syndrome is a monophasic illness, and there is new information about precipitating factors, changes in nerve conduction studies over time, potential biomarkers, optimal treatment, and features in uncommon patient populations.
Nodal Conduction Block and Internodal Conduction Block in Nodopathy
Authors: Oh Shin J.
Published: March 2024

Objectives:

In 2015, a new term “nodopathy” was introduced to represent a group of neuropathy because of autoantibodies at the node of Ranvier and paranodal area. This review was conducted to highlight the electrophysiologic characteristics of acute and chronic nodopathies by the newly introduced term: “nodal conduction block (CB); CB without temporal dispersion or slow nerve conduction velocity” and by introducing a new term: “internodal CB; CB with temporal dispersion or/and slow nerve conduction velocity”.

Methods:

Through PubMed searches, 23 cases of acute (<4 weeks of neuropathy) nodopathy and 12 cases of chronic (>4 weeks of neuropathy) nodopathy are identified. Two other required inclusion criteria are positive nodal antibody test and detailed nerve conduction data with or without figure. All existing data were analyzed to see whether these cases had nodal or internodal CB.

Results:

Among 23 cases of acute nodopathy, 11 had nodal CB, 9 internodal CB, and 3 mixed CB. Thus, nodal CB was observed in 61% of acute nodopathy cases and internodal CB in 52% of acute nodopathy cases. Among 12 cases of chronic nodopathy, all 12 had internodal CB.

Conclusions:

Nodal CB is the nerve conduction characteristic of acute nodopathy, but internodal CB does not rule out acute nodopathy. Internodal CB is the nerve conduction characteristic of chronic nodopathy.
Harmonizing Hearts: Exploring the Impact of Music Therapy on Cardiovascular Health
Authors: Sai Nuthalapati Bhargav , Dey Debankur , Singh Bhupinder , Anamika F.N.U. , Kanagala Sai Gautham , Garg Nikita , Jain Rohit
Published: March 2024

Music therapy (MT) is a music intervention involving a credentialed professional and a client, which has gained increasing recognition in current practices as an adjunct therapy for various conditions, including cardiovascular diseases (CVDs). MT demonstrates notable physiological as well as psychological effects leading to lowered anxiety, depression, and systolic blood pressure in patients with CVDs as well as having effects on heart rate and heart rate variability in healthy subjects. MT emerges as a promising adjunct in the prevention and rehabilitation of CVDs and its holistic impact on physiological and psychological parameters underscores its potential as a noninvasive, cost-effective intervention. Existing literature shows heterogeneity in methods in the studies such as the genre and quality of music utilized as well outcomes. While further research is warranted to optimize protocols and assess long-term effects, the current evidence highlights MT’s substantial benefits in cardiovascular health care, making it a promising asset in modern therapeutic approaches. This comprehensive review explores the multifaceted role of MT in CVDs, discussing its mechanisms and clinical applications.
Fiber and whole grain intakes in relation to liver cancer risk: An analysis in 2 prospective cohorts and systematic review and meta-analysis of prospective studies
Authors: Watling Cody Z. , Wojt Aika , Florio Andrea A. , Butera Gisela , Albanes Demetrius , Weinstein Stephanie J. , Huang Wen-Yi , Parisi Dominick , Zhang Xuehong , Graubard Barry I. , Petrick Jessica L. , McGlynn Katherine A.
Published: March 2024

Background and Aims:

The association between fiber or whole grain intakes and the risk of liver cancer remains unclear. We assessed the associations between fiber or whole grain intakes and liver cancer risk among 2 prospective studies, and systematically reviewed and meta-analyzed these results with published prospective studies.

Approach and Results:

A total of 111,396 participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and 26,085 men from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study were included. Intakes of total fiber and whole grains were estimated from validated food frequency questionnaires. Study-specific HRs and 95% CI with liver cancer risk were estimated using multivariable-adjusted Cox regression. We systematically reviewed existing literature, and studies were combined in a dose-response meta-analysis. A total of 277 (median follow-up = 15.6 y) and 165 (median follow-up = 16.0 y) cases of liver cancer were observed in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, respectively. Dietary fiber was inversely associated with liver cancer risk in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (HR10g/day: 0.69; 95% CI: 0.55–0.86). No significant associations were observed between whole grain intakes and liver cancer risk in either study. Our meta-analysis included 2383 incident liver cancer cases (7 prospective cohorts) for fiber intake and 1523 cases (5 prospective cohorts) for whole grain intake; combined HRs for liver cancer risk were 0.83 (0.76–0.91) per 10 g/day of fiber and 0.92 (0.85–0.99) per 16 g/day (1 serving) of whole grains.

Conclusions:

Dietary fiber and whole grains were inversely associated with liver cancer risk. Further research exploring potential mechanisms and different fiber types is needed.
Continuous home terlipressin infusion increases handgrip strength and reduces ascites—A prospective randomized crossover study
Authors: Terbah Ryma , Testro Adam G. , Hoermann Rudolf , Majumdar Avik , Chapman Brooke , Gow Paul J. , Sinclair Marie
Published: March 2024

Background and Aims:

Observational studies suggest a beneficial effect of continuous terlipressin infusion (CTI) on ascites and sarcopenia in decompensated cirrhosis with portal hypertension.

Approach and Results:

This single-center, prospective, cross-over study randomized 30 patients with cirrhosis, ascites, and sarcopenia to commence on 12 weeks of home CTI or 12 weeks of observation prior to cross-over. The co-primary outcomes were change in handgrip strength and paracentesis volume. Secondary outcomes included quality of life, sarcopenia measures, renal function, safety, and hospitalization. The median age of participants was 62 years (IQR: 57–64), the median Model for End-Stage Liver Disease-Sodium was 16 (12.3–20.8), and 22 (73%) were male. Handgrip strength increased by a mean adjusted difference (MAD) of 3.09 kg (95% CI: 1.11–5.08 kg) between CTI and observation (p=0.006); an 11.8% increase from baseline. The total volume of ascites drained decreased by a MAD of 11.39L (2.99–19.85, p=0.01), with 1.75 fewer episodes of paracentesis (0.925–2.59, p<0.001) on CTI. Serum creatinine decreased, urinary sodium excretion increased, and quality of life was significantly higher on CTI (all p<0.001), with an increase in Chronic Liver Disease Questionnaire score of 0.41 points (0.23–0.59). There were 7 minor line-related complications but no cardiac events or pulmonary edema.

Conclusions:

This novel study demonstrates a significant increase in handgrip strength, reduction in paracentesis volume, and improved quality of life in patients with decompensated cirrhosis treated with continuous terlipressin infusion. These findings provide a strong rationale for the use of ambulatory CTI in appropriately selected patients with cirrhosis.
Autoimmune diseases in primary sclerosing cholangitis and their first-degree relatives
Authors: Lundberg Båve Aiva , von Seth Erik , Ingre Michael , Nordenvall Caroline , Bergquist Annika
Published: March 2024

Background and Aims:

Primary sclerosing cholangitis (PSC) is linked to inflammatory bowel disease (IBD). However, there is limited overlap between IBD and PSC risk genes, but a stronger association between PSC and other autoimmune conditions. We aimed to assess the coexistence and familial association of autoimmune disorders in PSC, and the influence of autoimmune comorbidity on severe outcomes.

Approach and Results:

In a matched cohort study, 1378 individuals with PSC and 13,549 general population comparators and their first-degree relatives were evaluated. National registries provided data on diagnoses and outcomes (liver transplantation, hepatobiliary cancer, and liver-related death). The OR of autoimmune disease was estimated by logistic regression. The Fine and Gray competing risk regression estimated HRs for severe outcomes. The prevalence of non-IBD, non-autoimmune hepatitis, and autoimmune disease was 18% in PSC and 11% in comparators, OR: 1.77 (95% CI: 1.53–2.05). Highest odds were seen for celiac disease [OR: 4.36 (95% CI: 2.44–7.49)], sarcoidosis [OR: 2.74 (95% CI: 1.29–5.33)], diabetes type 1 [OR: 2.91 (95% CI: 2.05–4.05)], and autoimmune skin disease [OR: 2.15 (95% CI: 1.52–2.96)]. First-degree relatives of individuals with PSC had higher odds of developing IBD, autoimmune hepatitis, and any autoimmune disease than relatives of the comparators [OR: 3.25 (95% CI: 2.68–3.91); OR: 5.94 (95% CI: 2.82–12.02); OR: 1.34 (95% CI: 1.19–1.50)]. Autoimmune comorbidity in PSC was not associated with poorer outcomes [HR: 0.96 (95% CI: 0.71–1.28)].

Conclusions:

Individuals with PSC and their first-degree relatives had higher odds of autoimmune disease compared to matched comparators. This finding provides validation for prior genetic discoveries at a phenotypic level. Autoimmune comorbidity did not impact severe outcomes.
Antagonistic effects of the cytotoxic molecules granzyme B and TRAIL in the immunopathogenesis of sclerosing cholangitis
Authors: Kellerer Mareike , Javed Sana , Casar Christian , Will Nico , Berkhout Laura K. , Schwinge Dorothee , Krebs Christian F. , Schramm Christoph , Neumann Katrin , Tiegs Gisa
Published: March 2024

Background and Aims:

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by biliary inflammation and fibrosis. We showed an elevated interferon γ response in patients with primary sclerosing cholangitis and in multidrug resistance protein 2-deficient (Mdr2

−/−
) mice developing sclerosing cholangitis. Interferon γ induced expression of the cytotoxic molecules granzyme B (GzmB) and TRAIL in hepatic lymphocytes and mediated liver fibrosis in sclerosing cholangitis.

Approach and Results:

In patient samples and Mdr2

−/−
mice, we identified lymphocyte clusters with a cytotoxic gene expression profile using single-cell RNA-seq and cellular indexing of transcriptomes and epitopes by sequencing analyses combined with multi-parameter flow cytometry. CD8+ T cells and NK cells showed increased expression of GzmB and TRAIL in sclerosing cholangitis. Depletion of CD8+ T cells ameliorated disease severity in Mdr2
−/− mice. By using Mdr2
−/− × Gzmb
−/− and Mdr2
−/− × Tnfsf10
−/− mice, we investigated the significance of GzmB and TRAIL for disease progression in sclerosing cholangitis. Interestingly, the lack of GzmB resulted in reduced cholangiocyte apoptosis, liver injury, and fibrosis. In contrast, sclerosing cholangitis was aggravated in the absence of TRAIL. This correlated with elevated GzmB and interferon γ expression by CD8+ T cells and NK cells enhanced T-cell survival, and increased apoptosis and expansion of cholangiocytes.

Conclusions:

GzmB induces apoptosis and fibrosis in sclerosing cholangitis, whereas TRAIL regulates inflammatory and cytotoxic immune responses, subsequently leading to reduced liver injury and fibrosis.
Concurrent exercise training potentiates the effects of angiotensin-converting enzyme inhibitor on regulatory systems of blood pressure control in ovariectomized hypertensive rats
Authors: Ferreira Maycon Junior , Dias Danielle da Silva , Silva Gabriel do Carmo , de Araujo Amanda Aparecida , Dutra Marina Rascio Henriques , Bernardes Nathalia , Irigoyen Maria-Cláudia , De Angelis Kátia
Published: March 2024

Objective:

Enalapril has shown satisfactory potential in controlling increased and sustained blood pressure (BP). However, multiple dysregulated mechanisms that interact with each other and are involved in the pathophysiology of arterial hypertension may not be affected, contributing to the remaining cardiovascular risk. Using an exercise training protocol, we investigated whether adding both approaches to arterial hypertension management could promote higher modulation of regulatory mechanisms of BP in postmenopausal rats.

Methods:

Spontaneously hypertensive rats were allocated into sedentary (S) and ovariectomized groups: sedentary (OS), sedentary treated with enalapril maleate (OSE) and trained treated with enalapril maleate (OTE). Both the pharmacological and exercise training protocols lasted for 8 weeks. The BP was directly recorded. Inflammation and oxidative stress were evaluated in the cardiac tissue.

Results:

Although BP reduction was similar between OSE and OTE, trained group showed lower vasopressor systems outflow after sympathetic ganglion blocking by hexamethonium (mean BP) (OTE: −53.7 ± 9.86 vs. OS: −75.7 ± 19.2 mmHg). Bradycardic and tachycardic response were increased in OTE group (−1.4 ± 0.4 and −2.6 ± 0.4 vs. OS: −0.6 ± 0.3 and −1.3 ± 0.4 bpm/mmHg, respectively), as well as BP variability. In addition, the combination of approaches induced an increase in interleukin 10, antioxidant defense (catalase and glutathione peroxidase) and nitrite levels compared with the OS group.

Conclusion:

Despite similar BP, the inclusion of exercise training in antihypertensive drug treatment exacerbates the positive adaptations induced by enalapril alone on autonomic, inflammatory and oxidative stress profiles, probably affecting end-organ damage and remaining risk.
Dietary approach for the treatment of arterial hypertension in patients with diabetes mellitus
Authors: Barcellos Pedro Augusto M. , Dall’Agnol Angélica , Sandi Giovanna M. , Remonti Luciana R. , Silveiro Sandra P.
Published: March 2024

The association of hypertension and diabetes mellitus is extremely common, increasing the mortality risk of patients, mainly by cardiovascular causes. Regarding the blood pressure (BP) targets to be achieved, most guidelines suggest levels of 130 mmHg for SBP and of 80 mmHg for DBP. Dietary modifications are quite effective, and many studies suggest that decreasing sodium intake and increasing potassium ingestion are both valuable practices for reducing BP. This can be achieved by stimulating the ingestion of lacteous products, vegetables, and nuts. As for the ideal pharmacologic treatment for hypertension, either calcium channel blockers, diuretics or angiotensin-system blockers can be the first class of drug to be used. In this review, we summarize the evaluation of patients with diabetes mellitus and hypertension, and discuss the available therapeutic approaches, with emphasis on evidence-based dietary recommendations.
CLINICAL FEATURES AND SURGICAL OUTCOMES OF SCLERAL BUCKLE SURGERY FOR PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: MOORFIELDS BUCKLE STUDY
Authors: Muqit Mahiul MK , Macri Carmelo , Chan Weng Onn , Elnaggar Mohamed , Casswell Edward J , Ng James , Yang Elizabeth , Katta Mohamed , Anguita Rodrigo
Published: March 2024

Purpose:

Long-term study to evaluate the clinical and surgical outcomes of SB surgery for primary rhegmatogenous retinal detachment (RRD) at a large tertiary eye center.

Methods:

Non-comparative, retrospective case series of 589 eyes of 569 patients with primary RRD who underwent SB surgery between 2004 and 2022 with median follow-up of 6 months. Main outcome measures were best-corrected visual acuity (BCVA), surgical outcomes, complications, and classification of RRD.

Results:

At baseline, 447/589 (76.1%), round hole-RRD and 133/589 (22.7%) retinal dialysis-RRD. Overall primary SB success rate was 83.7% for all RD subtypes, with round hole-RD 84.8% and dialysis-RRD 81.2%. Overall, Baseline BCVA was logMAR 0.42 and final logMAR 0.26 (p<0.0001). In macula-OFF RRD, the BCVA significantly improved from 0.79 to 0.48 logMAR (p<0.0001). Macula-ON RRD patients improved from 0.19 to 0.12 logMAR (p=0.014). Binary logistic regression showed registrar surgeon grade (OR 0.09,95% CI 0.01- 0.55), and partial or complete PVD (OR 0.21,95% CI 0.10 – 0.49) associated with reduced odds of primary success. Higher surgical failure associated with low pre-fellowship SB surgeon experience (p=0.024).

Conclusion:

We report favourable visual and functional outcomes in a large series of SB for primary retinal detachment, mainly for round hole and retinal dialysis RRD patients.
Large-Scale Telemedicine Implementation for Outpatient Clinicians
Authors: Wong David , Cross Israel H. , Ramers Christian B. , Imtiaz Farah , Scott John D. , Dezan Amanda M. , Armistad Amy J. , Manteuffel Marie E. , Wagner Dennis , Hunt Richard C. , England William L. , Kwong Mei Wa , Dizon Raynald A. , Lamers Vanessa , Plotkin Ilya , Jolly B. Tilman , Jones Walter , Daly Darin D. , Yeager Megan , Riley Jinean A. , Krupinski Elizabeth A. , Solomon Andrew P. , Wibberly Katharine H. , Struminger Bruce B.
Published: March 2024

Learning collaboratives are seldom used outside of health care quality improvement. We describe a condensed, 10-week learning collaborative (“Telemedicine Hack”) that facilitated telemedicine implementation for outpatient clinicians early in the COVID-19 pandemic. Live attendance averaged 1688 participants per session. Of 1005 baseline survey respondents, 57% were clinicians with one-third identifying as from a racial/ethnic minoritized group. Practice characteristics included primary care (71%), rural settings (51%), and community health centers (28%). Of three surveys, a high of 438 (81%) of 540 clinicians had billed ≥1 video-based telemedicine visit. Our learning collaborative “sprint” is a promising model for scaling knowledge during emergencies and addressing health inequities.
Critical illness-associated limb and diaphragmatic weakness
Authors: Le Stang Valentine , Latronico Nicola , Dres Martin , Bertoni Michele
Published: March 2024

Purpose of review

In the current review, we aim to highlight the evolving evidence on the diagnosis, prevention and treatment of critical illness weakness (CIW) and critical illness associated diaphragmatic weakness (CIDW).

Recent findings

In the ICU, several risk factors can lead to CIW and CIDW. Recent evidence suggests that they have different pathophysiological mechanisms and impact on outcomes, although they share common risk factors and may overlap in several patients. Their diagnosis is challenging, because CIW diagnosis is primarily clinical and, therefore, difficult to obtain in the ICU population, and CIDW diagnosis is complex and not easily performed at the bedside. All of these issues lead to underdiagnosis of CIW and CIDW, which significantly increases the risk of complications and the impact on both short and long term outcomes. Moreover, recent studies have explored promising diagnostic techniques that are may be easily implemented in daily clinical practice. In addition, this review summarizes the latest research aimed at improving how to prevent and treat CIW and CIDW.

This review aims to clarify some uncertain aspects and provide helpful information on developing monitoring techniques and therapeutic interventions for managing CIW and CIDW.
Neuromonitoring in the ICU – what, how and why?
Authors: Mathur Rohan , Meyfroidt Geert , Robba Chiara , Stevens Robert D.
Published: March 2024

Purpose of review

We selectively review emerging noninvasive neuromonitoring techniques and the evidence that supports their use in the ICU setting. The focus is on neuromonitoring research in patients with acute brain injury.

Recent findings

Noninvasive intracranial pressure evaluation with optic nerve sheath diameter measurements, transcranial Doppler waveform analysis, or skull mechanical extensometer waveform recordings have potential safety and resource-intensity advantages when compared to standard invasive monitors, however each of these techniques has limitations. Quantitative electroencephalography can be applied for detection of cerebral ischemia and states of covert consciousness. Near-infrared spectroscopy may be leveraged for cerebral oxygenation and autoregulation computation. Automated quantitative pupillometry and heart rate variability analysis have been shown to have diagnostic and/or prognostic significance in selected subtypes of acute brain injury. Finally, artificial intelligence is likely to transform interpretation and deployment of neuromonitoring paradigms individually and when integrated in multimodal paradigms.

The ability to detect brain dysfunction and injury in critically ill patients is being enriched thanks to remarkable advances in neuromonitoring data acquisition and analysis. Studies are needed to validate the accuracy and reliability of these new approaches, and their feasibility and implementation within existing intensive care workflows.
Healthcare workers’ knowledge and risk perception regarding the first wave of COVID-19 in Khyber Pakhtunkhwa, Pakistan: an online cross-sectional survey
Authors: Ali Iftikhar , Hassan Zair , Rahat Ullah Arslan , Noman Khan Wazir Muhammad , Fida Najma , Idrees Khan Muhammad , Masood Aysha , Zulfiqar Ali Shah Sayed , Ali Waqar , Ullah Irfan , Ashraf Adnan , Hussain Arshad , Ahsan Areeba , Hemmeda Lina , Mustafa Ahmed Ghassan E. , Abbasher Hussien Mohamed Ahmed Khabab
Published: March 2024

Background:

Increased COVID-19 transmission among the populace may be caused by healthcare workers (HCWs) who lack knowledge, awareness, and good preventive practices. Additionally, it may cause elevated stress levels, anxiety, poor medical judgement, and situational overestimation.

Objectives:

The present survey aimed to assess knowledge and risk perception regarding COVID-19 among HCWs in Khyber Pakhtunkhwa (KP), Pakistan.

Methodology:

A web-based online, pre-tested questionnaire comprising 26 items was circulated via social media in April 2020 amongst HCWs in major tertiary care facilities in KP.

Results:

The study’s results, revealing both the commendable knowledge levels among HCWs about COVID-19 and their heightened risk perception, highlight the critical need for targeted interventions to address the potential impact on self-protective behaviour and mental health within this vital workforce. This insight is important for designing strategies that not only enhance HCWs’ well-being but also ensure the continued effectiveness of healthcare delivery during pandemics. The percentage mean score (PMS) of COVID-19 knowledge was 85.14±10.82. Male HCWs and those with an age older than or equal to 32 years demonstrated a higher knowledge score (85.62±11.08; P=0.032 and 87.59±7.33, P=0.021, respectively). About 76% of HCWs feared contracting COVID-19. Nearly 82% of respondents were mentally preoccupied with the pandemic and also terrified of it. ‘Of these, 81% were nurses, 87% had a job experience of 6–8 years and 54.45% were frontline workers. Feelings of panic and concern about the pandemic were found to be more in HCWs who were physicians above the age of 32, and who had 3–5 years of work experience. HCWs’ overall risk perception was found to be significantly different between males (7.04±2.26) and females (8.01±1.97), job experience of 6–10 years (8.04±177) with 3–5 years and younger than or equal to 2 years job experience (7.18±2.43,6.93±2.22), respectively, and between frontline HCWs (7.50±2.10) and non-frontline HCWs (6.84±2.40).

Conclusion:

HCWs demonstrated good knowledge about COVID-19. As the risk perception of COVID-19 among HCWs is high, it can raise concerns about their self-protective behaviour, and mental health. These issues need to be addressed.
Computer vision syndrome among Sudanese medical students: a growing medical issue in the digital world
Authors: Dafallah Mumen Abdalazim , Mohamed Ahmed Omer Ali , Ibrahim Mohamed Malaz Mustafa , Zakaria Abubakar Rawan Abdalrahman , Ebraheem Ahmed Alsiddig , Ahmed Gamal M. A.
Published: March 2024

Computer vision syndrome (CVS) refers to a set of eye-related symptoms that arise from prolonged computer usage. A survey was conducted to investigate the demographic characteristics, factors contributing to, and preventive measures against CVS. Out of 159 participants, 31.0% experienced seven or more symptoms, indicating a notable prevalence. The study found no significant correlation between age or academic years and CVS occurrence (P values of 0.481 and 0.392, respectively). However, gender exhibited a statistically significant relationship, with females students showing a higher prevalence than males (P=0.018; τ=0.105*). Notably, the distance from the screen had a highly significant inverse correlation with CVS occurrence (P=0.000; τ=−0.207**), indicating that greater distance reduced the risk. Additionally, using a screen filter (P=0.000; τ=0.184**) and adjusting screen brightness (P=0.017; τ=0.101*) were associated with CVS occurrence. Among preventive measures, only the use of an anti-glare screen showed a significant association with reducing CVS risk (P=0.018; τ=−0.099*). Given these findings, raising awareness about CVS among medical students is recommended, especially as curricula in medical colleges evolve.
Use of a Robotic Walking Device for Home and Community Mobility in Parkinson Disease: A Randomized Controlled Trial
Authors: Kegelmeyer Deb A. , Minarsch Raquel , Kostyk Sandra K. , Kline David , Smith Rachel , Kloos Anne D.
Published: March 2024

Background/Purpose:

Gait impairments in Parkinson disease (PD) contribute to decreased quality of life. This randomized controlled trial examined immediate- and longer-term effects of a single joint robotic exoskeleton device (EXOD), the Honda Walking Assist device, on gait.

Methods:

Participants (n = 45) with PD (Hoehn and Yahr stages 1-3) were randomized to a robotic-assisted gait training (RAGT) group (n = 23) or control (CON) group (n = 22). The RAGT group was tested with and without the EXOD at baseline and then received supervised in-home and community training with the EXOD twice weekly for 8 weeks. The CON group received no interventions. Outcome measures included gait speed (primary), gait endurance (6-minute walk test), perceived ease of walking, and questionnaires and logs assessing performance of daily activities, freezing of gait, and daily activity levels.

Results:

Forty participants completed the study. No significant immediate impact of EXOD usage on participants’ gait measures was found. Differences in gait speed and secondary outcome measures postintervention were not significantly different between the RAGT and CON groups. Participants with greater disease severity (worse baseline motor scores) had greater improvements in stride length during unassisted walking after the intervention than those with lower severity (mean difference: 3.22, 95% confidence interval: 0.05-6.40; P = 0.04).

Discussion and Conclusions:

All RAGT participants could use the EXOD safely. The RAGT treatment used in this mostly low impairment population of people with PD may be ineffective and/or was insufficiently dosed to see a positive treatment effect. Our findings suggest that RAGT interventions in PD may be more effective in individuals with greater motor impairments.

Video Abstract available

for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A459).
Six Square Miles of Urban America: Association Between Firearm Discharge, Injury, and Fatality
Authors: Risinger William B , Uma Chinweotuto V , Benns Matthew V , Ruther Matthew H , Nash Nicholas A , Bozeman Matthew C , Coleman Jamie J , Smith Jason W , Harbrecht Brian G , Miller Keith R
Published: March 2024

BACKGROUND:

Despite the increase in firearm injury observed across the country, significant gaps remain relevant to our understanding of how firearm exposure translates to injury. Using acoustic gunshot detection and a collaborative hospital and law enforcement firearm injury database, we sought to identify the relationship between firearm discharge and injury over time.

STUDY DESIGN:

From 2018 to 2021, instances of firearm discharge captured via acoustic detection in 6 square miles of Louisville, KY, were merged with data from the collaborative firearm injury database. Key outcomes included the total number of rounds fired, injury and fatality rates per round, and the percentage of rounds discharged from automatic weapons and high-capacity magazines.

RESULTS:

During the study period, 54,397 rounds of ammunition were discharged resulting in 914 injuries, 435 hospital admissions, 2,442 hospital days, 155 emergent operations, and 180 fatalities. For each round of ammunition fired, the risk of injury and fatality was 1.7% and 0.3%, respectively. The total number of rounds fired per month nearly tripled (614 vs 1,623, p < 0.001) leading to increased injury (15 vs 37, p < 0.001) and fatality (3 vs 7, p < 0.001). The percentage of rounds fired from automatic weapons (0 vs 6.8%, p < 0.001) and high-capacity magazines (7.6 vs 28.9%, p < 0.001) increased over time.

CONCLUSIONS:

The increased burden of firearm injury is related to an overall increase in firearm exposure as measured by the total number of rounds discharged. High-capacity magazines and automatic weaponry are being used with increasing frequency in urban America.
The plant virus transmissions database
Authors: Peters† Dick , Matsumura Emilyn E. , van Vredendaal Paulien , van der Vlugt René A.A.
Published: March 2024

Plant viruses are transmitted mechanically or by vegetative propagation, and by vectors such as arthropods, fungi, nematodes, or parasitic plants. Sources to access available information regarding plant virus transmissions are scattered and require extensive literature searches. Here, a recently created plant virus transmission database is described. This was developed to provide access to the modes of transmission and vectors of over 1600 plant viruses. The database was compiled using over 3500 publication records spanning the last 100 years. The information is publicly accessible via https://library.wur.nl/WebQuery/virus and fully searchable by virus name, taxonomic position, mode of transmission or vector.