bluuebunny/crossref_metadata_2025_split huggingface dataset:
Looking for answers far away from the soma—the (un)known axonal functions of TDP-43, and their contribution to early NMJ disruption in ALS
Authors: Ionescu Ariel , Altman Topaz , Perlson Eran 
Published: May 2023

AbstractAxon degeneration and Neuromuscular Junction (NMJ) disruption are key pathologies in the fatal neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS). Despite accumulating evidence that axons and NMJs are impacted at a very early stage of the disease, current knowledge about the mechanisms leading to their degeneration remains elusive. Cytoplasmic mislocalization and accumulation of the protein TDP-43 are considered key pathological hallmarks of ALS, as they occur in ~ 97% of ALS patients, both sporadic and familial. Recent studies have identified pathological accumulation of TDP-43 in intramuscular nerves of muscle biopsies collected from pre-diagnosed, early symptomatic ALS patients. These findings suggest a gain of function for TDP-43 in axons, which might facilitate early NMJ disruption. In this review, we dissect the process leading to axonal TDP-43 accumulation and phosphorylation, discuss the known and hypothesized roles TDP-43 plays in healthy axons, and review possible mechanisms that connect TDP-43 pathology to the axon and NMJ degeneration in ALS.
Disulfidptosis: a new form of programmed cell death
Authors: Zheng Tingjin , Liu Qingbo , Xing Feiyue , Zeng Chong , Wang Weidong 
Published: May 2023

AbstractDisulfidptosis, a new form of cell death triggered by disulfide stress, is characterized by the collapse of cytoskeleton proteins and F-actin due to the intracellular accumulation of disulfides. This discovery will eventually aid in the development of therapeutic strategies against cancer.
Relationship between the morphology of osteophytes and cartilage lesions in anterior ankle impingement in athletes: a cross‐sectional study
Authors: Yabiku Hiroki , Matsui Tomohiro , Sugimoto Takeshi , Mase Yasuyoshi , Higa Kotaro , Uehara Fuminari , Toma Takashi , Azuma Chinatsu , Tome Yasunori , Nishida Kotaro , Kumai Tsukasa 
Published: May 2023

AbstractBackgroundThe present study aimed to describe the frequency and severity of tram‐track lesions in anterior ankle impingement in athletes and to evaluate the association between osteophyte morphology and severity of tram‐track lesions, the distinctive cartilage lesions associated with tibial osteophytes in anterior ankle impingement syndrome.MethodsWe evaluated 34 athletes who underwent arthroscopic osteophyte resection for anterior ankle impingement between January 2017 and March 2021.ResultsWe found tram‐track lesions in 26 athletes (76.5%). Arthroscopic findings revealed the distribution of the International Cartilage Repair Society grades of tram‐track lesions (grade 0, eight; grade 1, seven; grade 2, ten; grade 3, nine; grade 4, zero). These findings indicate that athletes with anterior ankle impingement syndrome may have more severe cartilage lesions than non‐athletes. There was a positive correlation between the International Cartilage Repair Society grade and osteophyte size (r = 0.393, p = 0.021). We divided athletes into two groups according to the presence or absence of osteophyte protrusion into the joint space. Osteophyte protrusion was present in 14 athletes (41.2%). All athletes in the protrusion‐type group had tram‐track lesions; seven (50%) had International Cartilage Repair Society grade 3. The protrusion‐type group's International Cartilage Repair Society grade was significantly higher than that of the non‐protrusion‐type group (p = 0.008). The osteophyte sizes in the two groups were not significantly different (p = 0.341).ConclusionsBased on these findings, osteophyte protrusion should be assessed when an indication of arthroscopic treatment for anterior ankle impingement syndrome is considered, particularly in athletes.
Transnasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergent intubation (Kids THRIVE): a statistical analysis plan for a randomised controlled trial
Authors: George Shane , Gibbons Kristen , Williams Tara , Humphreys Susan , Gelbart Ben , Le Marsney Renate , Craig Simon , Tingay David , Chavan Arjun , Schibler Andreas ,   for the Kids THRIVE Investigators, Cronin Joanna , Pearson Kylie , Rasmussen Katie , Acworth Jason , Hickey Leah , Delzoppo Carmel , Perkins Elizabeth , Oberender Felix , Waghorn Jessica , McCahill Courtney , Singhal Nitesh , Harper Gail , Ganu Subodh , Letton Georiga , Erikson Simon , Thomson Hannah , Schlapbach Luregn J. , Burren Juerg , Zimmerman Elisa , Ganeshalingham Anusha , Dalziel Stuart , Sherring Clarie ,   Paediatric Research in Emergency Departments International Collaborative (PREDICT),   the Australia, New Zealand Intensive Care Society Paediatric Study Group (ANZICS PSG)
Published: May 2023

AbstractThe placement of an endotracheal tube for children with acute or critical illness is a low-frequency and high-risk procedure, associated with high rates of first-attempt failure and adverse events, including hypoxaemia. To reduce the frequency of these adverse events, the provision of oxygen to the patient during the apnoeic phase of intubation has been proposed as a method to prolong the time available for the operator to insert the endotracheal tube, prior to the onset of hypoxaemia. However, there are limited data from randomised controlled trials to validate the efficacy of this technique in children. The technique known as transnasal humidified rapid insufflation ventilatory exchange (THRIVE) uses high oxygen flow rates (approximately 2 L/kg/min) delivered through nasal cannulae during apnoea. It has been shown to at least double the amount of time available for safe intubation in healthy children undergoing elective surgery. The technique and its application in real time have not previously been studied in acutely ill or injured children presenting to the emergency department or admitted to an intensive care unit. The Kids THRIVE trial is a multicentre, international, randomised controlled trial (RCT) in children less than 16 years old undergoing emergent intubation in either the intensive care unit or emergency department of participating hospitals. Participants will be randomised to receive either the THRIVE intervention or standard care (no apnoeic oxygenation) during their intubation. The primary objective of the trial is to determine if the use of THRIVE reduces the frequency of oxygen desaturation and increases the frequency of first-attempt success without hypoxaemia in emergent intubation of children compared with standard practice. The secondary objectives of the study are to assess the impact of the use of THRIVE on the rate of adverse events, length of mechanical ventilation and length of stay in intensive care. In this paper, we describe the detailed statistical analysis plan as an update of the previously published protocol.
Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression
Authors: Lin Chenhong , Chen Yeda , Zhang Feng , Zhu Peng , Yu Liangliang , Chen Wenbiao 
Published: May 2023

Abstract
Background
Cancer-associated fibroblasts (CAFs) are essential stromal components in the tumor microenvironment of hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) infection induces pathological changes such as liver fibrosis/cirrhosis and HCC. The aim of this research was to explore the novel mediators of CAFs to modulate HBV cirrhosis-HCC progression.

Methods
The single-cell transcriptome data of HCC were divided into subsets, and the significant subset related to fibrotic cells, along with biological function, and clinical information of HCC was revealed by integrated data analyses. The cell communication, cells communicated weight analysis of signaling pathways, and key genes in signaling pathways analysis of significant CAFs subclasses were conducted to discover the novel gene of CAFs. Bioinformatics, vitro and HBV transfection assays were used to verify the novel gene is an important target for promoting the progression HBV cirrhosis-HCC progression.

Results
Fibroblasts derived from HCC single-cell data could be separated into three cell subclasses (CAF0-2), of which CAF2 was associated with the HCC clinical information. Fibroblasts have opposite developmental trajectories to immune B cells and CD8 + T cells. CAF0-2 had strong interaction with B cells and CD8 + T cells, especially CAF2 had the highest interaction frequency and weight with B cells and CD8 + T cells. Moreover, PTN participated in CAF2-related pathways involved in the regulation of cell communication, and the interactions among CAF2 and PTN contributed the most to B cells and CD8 + T cells. Furthermore, the genes of PTN, SDC1, and NCL from PTN signaling were highest expression in CAF2, B cells, and CD8 + T cells, respectively, and the interaction of PTN- SDC1 and PTN- NCL contributed most to the interaction of CAF2- B cells and CAF2-CD8 + T cells. Bioinformatics and vitro experiments confirm PTN was upregulated in HCC and promoted the proliferation of tumor cells, and HBV infection could initiate PTN to perform cirrhosis-HCC progression.

Conclusion
Our findings revealed CAF was associated with hepatocarcinogenesis, and the functional importance of B cells and CD8 + T cells in modulating CAF in HCC. Importantly, PTN maybe a novel mediator of CAF to mediate HBV cirrhosis-HCC progression.
Ischemic stroke in the setting of supratherapeutic International Normalized Ratio following coronavirus disease 2019 infection: a case report
Authors: Demir Gokhan , Hommos Rama , Al-Sirhan Sally Sami , Serhan Hashem Abu , Haddadin Muhannad , Bin Rashid Umar , Chawa Yamane 
Published: May 2023

Abstract
Background
SARS-CoV-19 infection is associated with an increased risk of thrombotic events. We present a case of acute middle cerebral artery ischemic stroke in a patient with SARS-CoV-19 infection despite being on warfarin with supratherapeutic INR (International Normalized Ratio).

Case presentation
A 68-year-old Caucasian female with multiple comorbidities was admitted to the hospital with symptoms of upper respiratory tract infection. A rapid antigen test confirmed the diagnosis of COVID-19 pneumonia, and intravenous remdesivir was initiated. On the fifth day of admission, the patient experienced sudden onset confusion, slurred speech, left-sided hemiplegia, right-sided eye deviation, and left-sided facial droop. Imaging studies revealed an occlusion of the distal anterior M2 segment of the right middle cerebral artery, and an MRI of the brain confirmed an acute right MCA infarction. Notably, the patient was receiving warfarin therapy with a supratherapeutic INR of 3.2.

Conclusions
This case report highlights the potential for thromboembolic events, including stroke, in patients with COVID-19 infection, even when receiving therapeutic anticoagulation therapy. Healthcare providers should be vigilant for signs of thrombosis in COVID-19 patients, particularly those with pre-existing risk factors. Further research is necessary to understand the pathophysiology and optimal management of thrombotic complications in COVID-19 patients.
NPM3 as a novel oncogenic factor and poor prognostic marker contributes to cell proliferation and migration in lung adenocarcinoma
Authors: Wei Shan , Xing Jing , Lu Kaining , Wang Kai , Yu Wanjun 
Published: May 2023

Abstract
Background
Lung cancer is the leading cause of cancer-related deaths worldwide, and despite recent advances in targeted therapies and immunotherapies, the clinical benefit remains limited. Therefore, there is an urgent need to further investigate the molecular mechanisms underlying lung cancer. The aim of this study was to investigate the expression and function of NPM3 in the tumor microenvironment of lung adenocarcinoma (LUAD).

Methods
We utilized bioinformatics tools and databases, including UALCAN, GEPIA2, HPA, and Sangerbox, to analyze NPM3 expression in LUAD samples and its association with prognosis and mutational landscape. NPM3 expression in various cell types was assessed at the single cell level using the TISCH database. We also used algorithms such as TIMER and EPIC to explore the crosstalk between NPM3 expression and immune features. KEGG enrichment analysis was performed to identify potential signaling pathways of NPM3. Finally, we employed siRNA knockdown strategy to investigate the effect of NPM3 on LUAD cell proliferation and migration in vitro.

Results
NPM3 was significantly upregulated in LUAD tissues and was strongly associated with poor prognosis and TP53 gene mutations. Single-cell sequencing analysis revealed that NPM3 was expressed in immune cells (dendritic cells and monocytes/macrophages) in the tumor microenvironment. Moreover, NPM3 expression was negatively associated with immune B cell and CD4 T cell infiltration, as well as with several immune-related genes (including CCL22, CXCR2, CX3CR1, CCR6, HLA-DOA, HLA-DQA2). KEGG enrichment analysis indicated that NPM3 expression was associated with cell cycle, CAMs, and NSCLC pathway genes. Finally, in vitro experiments showed that NPM3 knockdown inhibited LUAD cell proliferation and migration in NCI-H1299 and SPC-A1 cells, and suppressed the expression of CCNA2 and MAD2L1.

Conclusion
Elevated NPM3 expression predicts poor clinical outcome and an immunosuppressive microenvironment in LUAD tissues. NPM3 promotes LUAD progression by promoting cell proliferation and migration, and targeting NPM3 may represent a novel therapeutic strategy for LUAD.

Graphical Abstract
Patient and public involvement in rheumatic and musculoskeletal research: an idea whose time has firmly come
Authors: Botto-van Bemden Angie , Adebajo Adewale O. , Fitzpatrick Ciarán Martin 
Published: May 2023

AbstractPatient and public involvement is an idea whose time has firmly come. It is the views of these Guest Editors that it is the right thing to do morally and improves research quality and applicability.
Impact of Newborn Screening on Adult Height in Patients With Congenital Adrenal Hyperplasia (CAH)
Authors: Hoyer-Kuhn Heike , Eckert Alexander J , Binder Gerhard , Bonfig Walter , Dübbers Angelika , Riedl Stefan , Woelfle Joachim , Dörr Helmuth G , Holl Reinhard W 
Published: May 2023

Abstract

Context
Treatment of children with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is challenging. Linear growth and adult height are compromised according to recent publications. However, most of these data were obtained in the era before CAH newborn screening.

Design
Body height of patients with classical CAH diagnosed before and after the establishment of newborn screening were analyzed retrospectively.

Patients and Methods
We identified 600 patients with classical CAH (227 male) with data on near-adult height (NAH), target height (TH), and information on newborn screening from the electronic German CAH registry (German Society for Paediatric Endocrinology and Diabetology). Newborn screening was performed in 101 (16.8%) patients. All patients received hydrocortisone with or without fludrocortisone.
To assess the effects of newborn screening, a linear regression model adjusted/stratified for sex and phenotype was used (SAS 9.4).

Results
TH corrected NAH (mean; 95% confidence interval) was closer to 0 in patients with CAH and newborn screening [−0.25 standard deviation score (SDS); −0.44 to −0.06] than in patients without newborn screening (−0.44 SDS; −0.52 to −0.36) (P = .069). Screening had no effect on NAH in female patients. In male patients, NAH was significantly better (P = .033) with screening than without screening. After stratifying for CAH phenotype, screening did not affect the NAH of patients with salt-wasting CAH. Patients with simple-virilizing CAH had a significantly better cNAH (P = .034) with screening (0.15 SDS; −0.28-0.59) than without screening (−0.35 SDS; −0.52 to −0.18).

Conclusions
Our data suggest that newborn screening might be associated with improved NAH in male CAH patients and in patients with simple-virilizing CAH.
A Pedagogy of Living
Authors: Gordon Eva Sage 
Published: May 2023

Abstract
This essay discusses the usefulness of empathetic, relational pedagogy while teaching at CUNY in the time of COVID-19 and reflects on experiences with three students early in the author's career that led her to this pedagogical approach. A terminally ill student, a student who had been shot in Tahrir Square during the Arab Spring, and a student who became paralyzed in a motorbike accident led the author to reconsider the idea of the classroom as apart from the outside world. Embracing the sometimes frightening events happening beyond the classroom walls can lead to a deeper engagement with course texts as well as to a more meaningful student-teacher relationship and a sense of the course as personally significant. By constructing classrooms as places for listening and by striving to practice antiracist pedagogy, linguistically and culturally diverse students find themselves supported, even when the world outside becomes unstable and difficult to navigate.
The Walking Class of India and English after COVID-19
Authors: Chandran K. Narayana 
Published: May 2023

Abstract
While students discovered that the elite civic conscience served to render the Indian “migrant workers” invisible, they felt that a discursive correctness of terms called for debate. This article records their overwhelming sense of ethical quandary as others and othering gained traction in classrooms where English at once endorsed and condemned such usages.
Predictors of Progression-Free Survival in Patients With Spinal Intramedullary Ependymoma: A Multicenter Retrospective Study by the Neurospinal Society of Japan
Authors: Naito Kentaro , Umebayashi Daisuke , Kurokawa Ryu , Endo Toshiki , Mizuno Masaki , Hoshimaru Minoru , Kim Phyo , Hida Kazutoshi , Takami Toshihiro 
Published: May 2023

BACKGROUND AND OBJECTIVES:
Ependymoma is the most common spinal intramedullary tumor. Although clinical outcomes have been described in the literature, most of the reports were based on limited numbers of cases or been confined to institutional experience. The objective of this study was to analyze more detailed characteristics of spinal intramedullary ependymoma (SIE) and provide clinical factors associated with progression-free survival (PFS).

METHODS:
This retrospective observational multicenter study included consecutive patients with SIE in the cervical or thoracic spine treated surgically at a total of 58 institutions between 2009 and 2020. The results of pathological diagnosis at each institute were confirmed, and patients with myxopapillary ependymoma, subependymoma, or unverified histopathology were strictly excluded from this study. Outcome measures included surgical data, surgery-related complications, postoperative systemic adverse events, postoperative adjuvant treatment, postoperative functional condition, and presence of recurrence.

RESULTS:
This study included 324 cases of World Health Organization grade II (96.4%) and 12 cases of World Health Organization grade III (3.6%). Gross total resection (GTR) was achieved in 76.5% of cases. Radiation therapy (RT) was applied after surgery in 16 cases (4.8%), all of which received local RT and 5 of which underwent chemotherapy in combination. Functional outcomes were significantly affected by preoperative neurological symptoms, tumor location, extent of tumor resection, and recurrence. Multivariate regression analysis suggested that limited extent of tumor resection or recurrence resulted in poor functional outcomes. Multiple comparisons among the groups undergoing GTR, subtotal resection and biopsy, or partial resection of the tumor showed that the probability of PFS differed significantly between GTR and other extents of resection.

CONCLUSION:
When GTR can be safely obtained in the surgery for SIE, functional maintenance and longer PFS can be expected.
Comparison of the Retrosigmoid Suprameatal and Anterior Subtemporal Transpetrosal Approaches After Full Exposure of the Internal Acoustic Meatus
Authors: Yüncü Mustafa Eren , Karadag Ali , Polat Sarper , Camlar Mahmut , Bilgin Berra , Quiñones-Hinojosa Alfredo , Middlebrooks Erik H. , Özer Fusun , Tanriover Necmettin 
Published: May 2023

BACKGROUND AND OBJECTIVES:
Surgical approaches to the ventral brainstem and petroclival regions are complex, and standard retrosigmoid and subtemporal approaches are often inadequate. Retrosigmoid suprameatal tubercle (RSMTA) and anterior subtemporal transpetrosal (ASTA) approaches may provide extended surgical exposure with less brain retraction. The objective of this study was to evaluate advantages and disadvantages of RSMTA vs ASTA, and illustrate the surgical corridors and 3-dimensional microsurgical anatomy of the related structures.

METHODS:
Four silicone-injected adult cadaver heads (8 sides) were dissected to evaluate the accessibility of lesions located at the petrous apex, ventral brainstem, and pontomedullary region using ASTA and RSTMA.

RESULTS:
Both ASTA and RSMTA provide access from the petrous apex to the ventral lower pons and pontomedullary junction. A greater extent of safely resected bone was found in ASTA vs RSMTA. ASTA provides a larger surgical view to the ventrolateral midpons, peritrigeminal region, superior neurovascular complex, pontomesencephalic junction, and posterior cavernous sinus. Meanwhile, through cranial nerve V mobilization, RSMTA provides a larger surgical view to the lower half part of the pons, ventrolateral part of the pontomedullary junction, and middle and lower neurovascular structures.

CONCLUSION:
The choice of surgical approach is determined by considering the area where the lesion originates, lesion size, the anatomic structures to which it extends, and evaluation of the area that can be surgically exposed. Our study highlights the differences between these approaches and important surgical anatomic considerations.
Dynamic Lateral Semisitting Position for Supracerebellar Approaches: Technical Note and Case Series
Authors: Durmuş Yunus Emre , Kaval Barış , Demirgil Bülent Timur , Gökalp Elif , Gurses Muhammet Enes , Varol Eyüp , Gonzalez-Lopez Pablo , Cohen-Gadol Aaron , Gungor Abuzer 
Published: May 2023

BACKGROUND:
It has always been a matter of debate which position is ideal for the supracerebellar approach. The risk of venous air embolism (VAE) is the major deterrent for surgeons and anesthesiologists, despite the fact that sitting and semisitting positions are commonly used in these operations.

OBJECTIVE:
To demonstrate a reduction on the risk of VAE and tension pneumocephalus throughout the operation period while taking advantages of the semisitting position.

METHODS:
In this study, 11 patients with various diagnoses were operated in our department using the supracerebellar approach in the dynamic lateral semisitting position. We used end-tidal carbon dioxide and arterial blood pressure monitoring to detect venous air embolism.

RESULTS:
None of the patients had clinically significant VAE in this study. No tension pneumocephalus or major complications were observed. All the patients were extubated safely after surgery.

CONCLUSION:
The ideal position, with which to apply the supracerebellar approach, is still a challenge. In our study, we presented an alternative position that has advantages of the sitting and semisitting positions with a lower risk of venous air embolism.