bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.

Summary
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.

Summary
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.
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.
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.
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.
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.

Summary
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.

Summary
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.