bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade
Authors: Ariyan Charlotte E. , Brady Mary Sue , Siegelbaum Robert H. , Hu Jian , Bello Danielle M. , Rand Jamie , Fisher Charles , Lefkowitz Robert A. , Panageas Kathleen S. , Pulitzer Melissa , Vignali Marissa , Emerson Ryan , Tipton Christopher , Robins Harlan , Merghoub Taha , Yuan Jianda , Jungbluth Achim , Blando Jorge , Sharma Padmanee , Rudensky Alexander Y. , Wolchok Jedd D. , Allison James P.
Published: March 2024

Abstract
Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a noninflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio. These changes were associated with improved survival of the mice. To translate these findings into a clinical setting, 26 patients with advanced melanoma were treated locally by isolated limb infusion with the nitrogen mustard alkylating agent melphalan followed by systemic administration of CTLA-4 blocking antibody (ipilimumab) in a phase II trial. This combination of local chemotherapy with systemic checkpoint blockade inhibitor resulted in a response rate of 85% at 3 months (62% complete and 23% partial response rate) and a 58% progression-free survival at 1 year. The clinical response was associated with increased T-cell infiltration, similar to that seen in the murine models. Together, our findings suggest that local chemotherapy combined with checkpoint blockade–based immunotherapy results in a durable response to cancer therapy. Cancer Immunol Res; 6(2); 189–200. ©2018 AACR.
Data from PVRIG and PVRL2 Are Induced in Cancer and Inhibit CD8+ T-cell Function
Authors: Whelan Sarah , Ophir Eran , Kotturi Maya F. , Levy Ofer , Ganguly Sudipto , Leung Ling , Vaknin Ilan , Kumar Sandeep , Dassa Liat , Hansen Kyle , Bernados David , Murter Benjamin , Soni Abha , Taube Janis M. , Fader Amanda Nickles , Wang Tian-Li , Shih Ie-Ming , White Mark , Pardoll Drew M. , Liang Spencer C.
Published: March 2024

Abstract
Although checkpoint inhibitors that block CTLA-4 and PD-1 have improved cancer immunotherapies, targeting additional checkpoint receptors may be required to broaden patient response to immunotherapy. PVRIG is a coinhibitory receptor of the DNAM/TIGIT/CD96 nectin family that binds to PVRL2. We report that antagonism of PVRIG and TIGIT, but not CD96, increased CD8+ T-cell cytokine production and cytotoxic activity. The inhibitory effect of PVRL2 was mediated by PVRIG and not TIGIT, demonstrating that the PVRIG–PVRL2 pathway is a nonredundant signaling node. A combination of PVRIG blockade with TIGIT or PD-1 blockade further increased T-cell activation. In human tumors, PVRIG expression on T cells was increased relative to normal tissue and trended with TIGIT and PD-1 expression. Tumor cells coexpressing PVR and PVRL2 were observed in multiple tumor types, with highest coexpression in endometrial cancers. Tumor cells expressing either PVR or PVRL2 were also present in numbers that varied with the cancer type, with ovarian cancers having the highest percentage of PVR−PVRL2+ tumor cells and colorectal cancers having the highest percentage of PVR+PVRL2− cells. To demonstrate a role of PVRIG and TIGIT on tumor-derived T cells, we examined the effect of PVRIG and TIGIT blockade on human tumor-infiltrating lymphocytes. For some donors, blockade of PVRIG increased T-cell function, an effect enhanced by combination with TIGIT or PD-1 blockade. In summary, we demonstrate that PVRIG and PVRL2 are expressed in human cancers and the PVRIG–PVRL2 and TIGIT–PVR pathways are nonredundant inhibitory signaling pathways.

See related article on p. 244
Data from LIN28/let-7/PD-L1 Pathway as a Target for Cancer Immunotherapy
Authors: Chen Yanlian , Xie Chen , Zheng Xiaohui , Nie Xin , Wang Zining , Liu Haiying , Zhao Yong
Published: March 2024

Abstract
The immunocheckpoint protein PD-1/PD-L1 is considered a promising target for cancer immunotherapeutics. However, the objective response rate using antibodies that block the interaction between PD-1 and PD-L1 was less than 40%, and the mechanism underlying regulation of PD-1/PD-L1 expression is poorly understood. In this study, we identified the miRNA let-7 that posttranscriptionally suppresses PD-L1 expression. LIN28, an RNA binding protein upregulated in most cancer cells, inhibits the biogenesis of let-7, thus promoting PD-L1 expression. Therefore, inhibition of LIN28 may be a strategy to prevent immune evasion of cancer cells. We found that treatment with a LIN28 inhibitor, the small compound C1632, increases let-7 and suppresses PD-L1 expression, leading to reactivation of antitumor immunity in vitro and in vivo. In addition, C1632 also displayed the capacity to inhibit cancer cell proliferation and tumor growth in mice. Altogether, these findings identified LIN28/let-7 as a target for PD-L1–mediated immunotherapeutics and reveal the potential of C1632 and its derivatives as promising oncotherapeutic agents.
Data from Converting Lymphoma Cells into Potent Antigen-Presenting Cells for Interferon-Induced Tumor Regression
Authors: Liao Jing , Luan Yan , Ren Zhenhua , Liu Xiaojuan , Xue Diyuan , Xu Hairong , Sun Zhichen , Yang Kaiting , Peng Hua , Fu Yang-Xin
Published: March 2024

Abstract
Anti-hCD20 is a therapeutic mAb that is clinically used to treat B-cell lymphoma. Some lymphomas are resistant to anti-hCD20; others relapse after treatment with anti-hCD20. Using a syngeneic immunocompetent mouse model, we observed that targeting lymphoma with interferon-α (IFNα) abolished resistance of B-cell lymphoma to anti-CD20 while limiting interferon (IFN)-associated systemic toxicity in the host. Control of tumors by a fusion of anti-CD20 and IFNα (anti–CD20-IFNα) depended on existing tumor-infiltrating CD8+ T cells. Although lymphomas were resistant to IFN-directed killing, IFN-exposed tumor cells became the dominant antigen-presenting cells (APC) for the reactivation of tumor-infiltrating CD8+ T cells that then controlled those lymphomas. Anti–CD20-IFNα also abolished checkpoint blockade resistance in advanced B-cell lymphoma. Our findings indicate that anti–CD20-IFNα eradicates B-cell lymphoma by employing tumor cells as APCs to reactivate tumor-infiltrating CD8+ T cells and synergizing with anti–PD-L1 treatment. Cancer Immunol Res; 5(7); 560–70. ©2017 AACR.
How Effective Is Drinking Natural Mineral Water against Heartburn from Functional Dyspepsia, Gastroesophageal Reflux Disease, or Other Causes? A Systematic Review of Clinical Intervention Studies
Authors: D’Souza Arun , Zink Katharina , Langhorst Jost , Wildner Manfred , Stupp Carolin , Keil Thomas
Published: March 2024

Background: For centuries, spring and other natural waters have been recommended as external or internal remedies for numerous diseases. For studies that examined the effects of drinking mineral waters against heartburn, gastroesophageal reflux disease (GERD), or functional dyspepsia, a systematic review is lacking. Objectives: The main aim of this systematic review was to examine the effects of drinking natural mineral waters on heartburn from various causes by identifying all published intervention studies and critically appraising their methods as well as summarizing their results. Methods: We systematically searched the largest medical literature database MEDLINE, further relevant web sources, and gray literature for randomized and nonrandomized trials, with or without control groups, up to September 2021 and no language restrictions. Further inclusion criteria were adult patients with heartburn, drinking cure with natural mineral water as the intervention, compared to no or other interventions (care-as-usual, waiting list). We defined the reduction of heartburn symptoms and duration of disease episodes as primary and quality of life as secondary outcomes. Two reviewers independently carried out the study quality assessments (risk of bias) using the National Institutes of Health-Study Quality Assessment Tools. Results: Nine trials comprising 393 patients from Italy, Russia, Ukraine, and Germany fulfilled all inclusion criteria. We identified three randomized controlled trials (all with poor methodological quality), plus six before-after (pre/post) intervention studies without a control group. The intervention groups of the three comparative trials seemed to show a stronger reduction of self-reported heartburn symptoms, and duration of heartburn episodes than the respective control groups; however, they all had poor methodological quality. Conclusion: Based on the best available evidence of clinical studies, we cannot recommend or advise against drinking natural mineral waters as a treatment for heartburn. The potential benefits of natural mineral waters that were reported in some studies with a lower evidence level (e.g., lacking a control group) should be verified by good quality randomized clinical trials with adequate comparison groups and longer follow-up periods.
Impact of Long-Term Dietary High Fat and Eicosapentaenoic Acid on Behavior and Hypothalamic-Pituitary-Adrenal Axis Activity in Amyloidogenic APPswe/PSEN1dE9 Mice
Authors: Harris Breanna N. , Yavari Mahsa , Ramalingam Latha , Mounce P. Logan , Alers Maldonado Kaylee , Chavira Angela C. , Thomas Sarah , Scoggin Shane , Biltz Caroline , Moustaid-Moussa Naima
Published: March 2024

Introduction: Alzheimer’s disease (AD) alters neurocognitive and emotional function and causes dysregulation of multiple homeostatic processes. The leading AD framework pins amyloid beta plaques and tau tangles as primary drivers of dysfunction. However, many additional variables, including diet, stress, sex, age, and pain tolerance, interact in ways that are not fully understood to impact the onset and progression of AD pathophysiology. We asked: (1) does high-fat diet, compared to low-fat diet, exacerbate AD pathophysiology and behavioral decline? And, (2) can supplementation with eicosapentaenoic (EPA)-enriched fish oil prevent high-fat-diet-induced changes? Methods: Male and female APPswePSdE9 mice, and their non-transgenic littermates, were randomly assigned to a diet condition (low-fat, high-fat, high-fat with EPA) and followed from 2 to 10 months of age. We assessed baseline corticosterone concentration during aging, pain tolerance, cognitive function, stress coping, and corticosterone response to a stressor. Results: Transgenic mice were consistently more active than non-transgenic mice but did not perform worse on either cognitive task, even though we recently reported that these same transgenic mice exhibited metabolic changes and had increased amyloid beta. Mice fed high-fat diet had higher baseline and post-stressor corticosterone, but diet did not impact cognition or pain tolerance. Sex had the biggest influence, as female mice were consistently more active and had higher corticosterone than males. Conclusion: Overall, diet, genotype, and sex did not have consistent impacts on outcomes. We found little support for predicted interactions and correlations, suggesting diet impacts metabolic function and amyloid beta levels, but these outcomes do not translate to changes in behaviors measured here.
A Case of Lateral Meningocele Syndrome without Lateral Meningoceles
Authors: Rubadeux Derek , Owens Joshua W. , Shillington Amelle
Published: March 2024

Introduction: Lateral meningocele syndrome (LMS), also known as Lehman syndrome, is caused by pathogenic variants in exon 33 of NOTCH3. Variants in this final exon of NOTCH3 interrupt the regulatory PEST domain, leading to enhanced NOTCH3 signaling due to prolonged cellular half-life. Individuals with LMS are expected to have multiple lateral meningoceles, developmental delay, neonatal hypotonia, dysmorphic facial features, and feeding difficulties. Case Presentation: We report an 8-year-old male with a history of autism, feeding difficulties, developmental delay, severe intellectual disability, and self-injurious behavior. Genetic testing revealed a NOTCH3 c.6663C>G (p.Y2221*) pathogenic variant in exon 33, consistent with a diagnosis of LMS. A follow-up spine MRI showed a ventral sacral extradural arachnoid cyst but no lateral meningoceles. This individual’s most recent exam noted multiple dysmorphic features including prominent metopic ridging, broad forehead, downslanting palpebral fissures, high-arched palate, long narrow philtrum, mild pectus excavatum, and wide-based gait. Discussion/Conclusion: This individual shares the dysmorphic facial features, ongoing G-tube dependence, failure to thrive, and developmental delay seen in other individuals with LMS. His lack of lateral meningoceles expands the phenotype for this condition, as all previously reported individuals with molecularly confirmed LMS had multiple lateral meningoceles before age 8 years with an average age of identification at 4 years.
Prevalence of Endoscopic and Histological Lesions at Upper Endoscopy: A Cross-Sectional, Multicentre Study in Clinical Practice
Authors: De Francesco Vincenzo , Zullo Angelo , Amato Arnaldo , Bergna Irene , Bendia Emanuele , Giorgini Giorgia , Buscarini Elisabetta , Manfredi Guido , Cadoni Sergio , Cannizzaro Renato , Realdon Stefano , Ciuffi Mario , Ignomirelli Orazio , Da Massa Carrara Paola , Finucci Giovanni , Di Somma Antonietta , Frandina Chiara , Loria Mariafrancesca , Galeazzi Francesca , Ferrara Francesco , Gemme Carlo , Bertetti Noemi Sara , Gentili Federica , Lotito Antonio , Germanà Bastianello , Russo Nunzia , Grande Giuseppe , Conigliaro Rita , Cravero Federico , Venezia Giovanna , Marmo Riccardo , Senneca Piera , Milano Angelo , Efthymakis Konstantinos , Monica Fabio , Montalto Paolo , Lombardi Mario , Morelli Olivia , Castellani Danilo , Nigro Daniela , Festa Roberto , Peralta Sergio , Grasso Maria , Privitera Antonino Carlo , Di Stefano Maria Emanuela , Scaccianoce Giuseppe , Loiacono Mariangela , Segato Sergio , Balzarini Marco , Usai Satta Paolo , Lai Mariantonia , Manta Raffaele
Published: March 2024

Background/Aim: Prevalence of gastroduodenal endoscopic and histological lesions may modify over time due to different factors. We assessed both macroscopic and histological lesions currently detected at upper endoscopy performed in routine practice. Patients and Methods: Clinical, endoscopic, and histological data of consecutive adult patients referred for upper endoscopy in the 28 participating centres were analysed. Only patients who underwent the first endoscopic examination were considered. Prevalence of erosive/ulcerative lesions, cancers and extensive precancerous lesions in the stomach, and Helicobacter pylori infection was computed. Results: A total of 1,431 patients underwent endoscopy for gastro-oesophageal reflux symptoms (31.5%), dyspepsia (29.4%), or alarm symptoms (18.5%). Erosive oesophagitis or Barrett’s oesophagus was detected in 210 (14.7%) cases, peptic ulcer in 49 (3.4%), and a neoplastic lesion in 17 (1.2%). H. pylori was present in 201 (22.6%) cases, and extensive precancerous lesions on gastric mucosa in 46 (5.6%) patients. Gastric lesions were more prevalent in patients aged ≥50 years (26% vs. 18%; p = 0.001), and peptic ulcers were more frequently detected in patients with H. pylori (9.4% vs. 2.3%; p = 0.001) and in males (5.8% vs. 1.6%; p = 0.001), while neoplastic lesions in patients with alarm symptoms (3.8% vs. 0.6%; p = 0.001). Conclusions: The overall endoscopic lesions were more prevalent in patients aged ≥50 years, peptic ulcer and erosions were more frequent in H. pylori-infected patients, and extensive gastric precancerous lesions were present in less than 6% of cases.
Capsular Block Syndrome after an Intravitreal Injection of Ranibizumab: A Case Report
Authors: Kim Jae Suk
Published: March 2024

Introduction: We present a case of capsular block syndrome that occurred after intravitreal injection of ranibizumab in a patient with age-related macular degeneration, which has not been reported in the literature. Case Presentation: A 78-year-old male presented with decreased visual acuity in the right eye. Slit-lamp examination findings were unremarkable; however, AMD was diagnosed based on fundus examination, fluorescein angiography, and optical coherence tomography (OCT). Subsequently, the patient was administered an intravitreal injection of ranibizumab. A slit-lamp examination revealed residual cortical material, numerous inflammatory cells, and posterior capsular distension 1 week after the injection. OCT showed an adhesion of the intraocular lens to the continuous curvilinear capsulorhexis site. The patient’s vision improved following Nd:YAG laser posterior capsulotomy. Conclusion: Meticulous cortical removal is crucial during phacoemulsification to prevent capsular block syndrome. In patients with a history of cataract surgery, verifying the absence of residual cortical material before administering an intravitreal injection of ranibizumab is important.
Human host defence peptide LL-37 suppresses TNFα-mediated matrix metalloproteinases MMP9 and MMP13, in human bronchial epithelial cells
Authors: Altieri Anthony , Marshall Courtney Lynn , Ramotar Padmanie , Lloyd Dylan , Hemshekhar Mahadevappa , Spicer Victor , van der Does Anne M. , Mookherjee Neeloffer
Published: March 2024

Introduction: TNFα-inducible matrix metalloproteinases (MMP) play a critical role in the process of airway remodelling in respiratory inflammatory disease including asthma. The cationic host defence peptide (CHDP) LL-37 is elevated in the lungs during airway inflammation. However, the impact of LL-37 on TNFα-driven processes is not well understood. Here, we examined the effect of LL-37 on TNFα-mediated responses in human bronchial epithelial cells (HBEC).
Methods: We used a Slow Off-rate Modified Aptamer-based proteomics approach to define the HBEC proteome altered in response to TNFα. Abundance of selected protein candidates and signaling intermediates were examined using immunoassays, ELISA and Western blots, and mRNA abundance was examined by qRT-PCR.
Results: Proteomics analysis revealed that 124 proteins were significantly altered, 12 proteins were enhanced by ≥2-fold compared to unstimulated cells, in response to TNFα. MMP9 was the topmost increased protein in response to TNFα, enhanced by ~10-fold and MMP13 was increased by ~3-fold, compared to unstimulated cells. Furthermore, we demonstrated that LL-37 significantly suppressed TNFα-mediated MMP9 and MMP13 in HBEC. Mechanistic data revealed that TNFα-mediated MMP9 and MMP13 production is controlled by SRC kinase, and that LL-37 enhances related upstream negative regulators namely phosphoAKT(T308) and TNFα-mediated TNFAIP3 or A20.
Conclusions: The findings of this study suggest that LL-37 may play a role in intervening in the process of airway remodeling in chronic inflammatory respiratory disease such as asthma.
The Impact of Age-Related Hearing Loss on Working Memory among Older Individuals: An Event-Related Potential Study
Authors: Madashetty Sankalpa , Palaniswamy Hari Prakash , Rajashekhar Bellur
Published: March 2024

Introduction: Age-related hearing loss (ARHL) may affect working memory (WM), which impacts problem-solving, decision-making, language comprehension, and learning. Limited research exists on how ARHL affects WM using N-back tasks, but studying this is crucial for understanding neural markers and associated cognitive processes. Our study explores the impact of ARHL on WM using behavioral and electrophysiological measures and how it correlates with speech-in-noise scores in older individuals with ARHL. Method: The study involved two groups, each with 20 participants aged 60–80. Group 1 had individuals with mild to moderate sensorineural hearing loss, while Group 2 had age- and education-matched controls with normal or near-normal hearing. Participants underwent audiological assessments and completed cognitive tests, including simple reaction time and N-back tests. During the performance of cognitive tasks, a simultaneous electroencephalography was recorded. Data analysis included behavioral and event-related potentials, source estimation, and functional connectivity analysis. Results: The study revealed significantly poor accuracy, longer reaction time, and smaller P300 amplitude among individuals with ARHL, even after controlling for general slowing. Individuals with ARHL experience compromised neural activity, particularly in the temporal and parietal regions, which are vital for cognition and WM. Furthermore, individuals with ARHL exhibited poor communication between the superior temporal gyrus and insulae regions among the brain regions mediating WM during the 1-back task. Also, the study found a strong correlation between hearing measures and WM outcomes. Conclusion: The study findings suggest that individuals with ARHL have impaired WM compared to those with normal hearing. This indicates a potential link between ARHL and cognitive decline, which could significantly affect daily life and quality of life. The widely used WM test with simultaneous EEG recording and source estimation analysis would further validate the usefulness of the study in assessing WM in this population.
Shape-Sensing Robotic-Assisted Bronchoscopy versus Computed Tomography-Guided Transthoracic Biopsy for the Evaluation of Subsolid Pulmonary Nodules
Authors: Fernandez-Bussy Sebastian , Yu Lee-Mateus Alejandra , Reisenauer Janani , Balasubramanian Prasanth , Barrios-Ruiz Alanna , Garza-Salas Ana , Chandra Nikitha C. , Koratala Anoop , Nadrous Anthony , Edell Eric S. , Bowman Andrew W. , Grage Rolf A. , Reisenauer Chris J. , Kurup Anil N. , Patel Neal M. , Chadha Ryan , Hazelett Britney N. , Abia-Trujillo David
Published: March 2024

Introduction: Lung cancer remains the leading cause of cancer death worldwide. Subsolid nodules (SSN), including ground-glass nodules (GGNs) and part-solid nodules (PSNs), are slow-growing but have a higher risk for malignancy. Therefore, timely diagnosis is imperative. Shape-sensing robotic-assisted bronchoscopy (ssRAB) has emerged as reliable diagnostic procedure, but data on SSN and how ssRAB compares to other diagnostic interventions such as CT-guided transthoracic biopsy (CTTB) are scarce. In this study, we compared diagnostic yield of ssRAB versus CTTB for evaluating SSN. Methods: A retrospective study of consecutive patients who underwent either ssRAB or CTTB for evaluating GGN and PSN with a solid component less than 6 mm from February 2020 to April 2023 at Mayo Clinic Florida and Rochester. Clinicodemographic information, nodule characteristics, diagnostic yield, and complications were compared between ssRAB and CTTB. Results: A total of 66 nodules from 65 patients were evaluated: 37 PSN and 29 GGN. Median size of PSN solid component was 5 mm (IQR: 4.5, 6). Patients were divided into two groups: 27 in the ssRAB group and 38 in the CTTB group. Diagnostic yield was 85.7% for ssRAB and 89.5% for CTTB (p = 0.646). Sensitivity for malignancy was similar between ssRAB and CTTB (86.4% vs. 88.5%; p = 0.828), with no statistical difference. Complications were more frequent in CTTB with no significant difference (8 vs. 2; p = 0.135). Conclusion: Diagnostic yield for SSN was similarly high for ssRAB and CTTB, with ssRAB presenting less complications and allowing mediastinal staging within the same procedure.
Upstream Stimulating Factor 2 Aggravates Spinal Nerve Ligation-Induced Neuropathic Pain in Mice via Regulating SNHG5/miR-181b-5p
Authors: Chen Mi , Yang Yang , Cui Jiatian , Qiu Li , Zou Xiaohua , Zeng Xianggang
Published: March 2024

Introduction: Upstream stimulating factor 2 (USF2) belongs to basic Helix-Loop-Helix-Leucine zipper transcription factor family, regulating expression of genes involved in immune response or energy metabolism network. Role of USF2 in neuropathic pain was evaluated. Methods: Mice were intraspinally injected with adenovirus for knockdown of USF2 (Ad-shUSF2) and then subjected to spinal nerve ligation (SNL) to induce neuropathic pain. Distribution and expression of USF2 were detected by western blot and immunofluorescence. Mechanical and thermal pain sensitivity were examined by paw withdrawal thresholds (PWT) and paw withdrawal latency (PWL). Chromatin immunoprecipitation (ChIP) and luciferase activity assays were performed to detect binding ability between USF2 and SNHG5. Results: The expression of USF2 was elevated and colocalized with astrocytes and microglia in L5 dorsal root ganglion (DRG) of SNL-induced mice. Injection of Ad-shUSF2 attenuated SNL-induced decrease of PWT and PWL in mice. Knockdown of USF2 increased the level of IL-10 but decreased TNF-α, IL-1β, and IL-6 in SNL-induced mice. Silence of USF2 enhanced protein expression of CD206 while reducing expression of CD16 and CD32 in SNL-induced mice. USF2 binds to promoter of SNHG5 and weakens SNL-induced up-regulation of SNHG5. SNHG5 binds to miR-181b-5p, and miR-181b-5p to interact with CXCL5. Conclusion: Silence of USF2 ameliorated neuropathic pain, suppressed activation of M1 microglia, and inhibited inflammation in SNL-induced mice through regulation of SNHG5/miR-181b-5p/CXCL5 axis. Therefore, USF2/SNHG5/miR-181b-5p/CXCL5 might be a promising target for neuropathic pain. However, the effect of USF2/SNHG5/miR-181b-5p/CXCL5 on neuropathic pain should also be investigated in further research.
Superior Sagittal Sinus Thrombectomy in Pediatric Head Injury
Authors: Johansen Phillip Mitchell , Ciavarra Bronson , McCormack Ryan , Kole Matthew , Spiegel Gary , Fletcher Stephen Alan
Published: March 2024

Introduction: Injury and subsequent thrombosis of the cerebral venous sinuses may be caused by closed head injuries secondary to a variety of different mechanisms. Skull fractures can lacerate or otherwise disrupt adjacent dural sinuses. The sequelae of such injuries may include thrombosis and either partial or total occlusion of the sinus, ultimately resulting in significant venous congestion. Sagittal sinus injury is associated with a more serious outcome due to the obligatory flow into the sinus, especially posterior to the coronal suture. In such cases, venous infarction may be a severe and life-threatening complication of head injury. Case Presentation: A 2-year-old female presented with a depressed skull fracture near the midline and a thrombus in the sagittal sinus. Anticoagulation, the standard treatment cerebral venous sinus thrombosis (CVST), was contraindicated due to intracranial hemorrhage, so immediate thrombectomy was performed with successful neurologic recovery at 9-month follow-up. To our knowledge, this case is the youngest patient documented to receive mechanical thrombectomy for superior sagittal sinus (SSS) thrombosis due to trauma. Conclusion: Closed head injuries in pediatric patients may be associated with CVST, with resulting venous drainage compromise and profound neurologic sequelae. Unlike adult patients with spontaneous CVST in which anticoagulation are the standard of care, pediatric patients experiencing traumatic CVST may have contraindications to anticoagulants. If the patient has a contraindication to anticoagulation such as intracranial bleeding, endovascular mechanical thrombectomy may be an effective intervention when performed by an experienced neurointerventionalist.
Incidence of Multiple Sclerosis in Uruguay: A Prospective Population-Based Study
Authors: Rocha Valeria , Sorondo Noelia , Gómez Fabián , Castro Lucía , Ontaneda Daniel , Ketzoian Carlos
Published: March 2024

Background: The worldwide incidence of multiple sclerosis (MS) is estimated at 0.5–10 cases per 100,000 person-years and is probably increasing. In 2014, a previous study estimated the incidence of multiple sclerosis in Uruguay at 1.2 cases per 100,000 person-years. Objectives: We conducted an observational, prospective, population-based study to determine MS incidence from diagnosis in Uruguay. Methods: The population studied included people older than 18 years of age who were living in Uruguay between July 1, 2019, and June 30, 2021. The diagnosis was based on 2017 McDonald criteria. Multiple data sources were employed including neurologists, magnetic resonance imaging centers, laboratories performing oligoclonal band testing, neurophysiology laboratories, neurorehabilitation centers, the institution Fondo Nacional de Recursos, and the MS Patients’ Association of Uruguay (EMUR). The capture-recapture method was used to estimate incidence. Results: 155 new MS cases were confirmed after review. The median age was 35 (range 18–62). Thirteen patients (8.38%) were diagnosed with late-onset MS. The crude incidence rate was 2.89 cases per 100,000 person-years, 3.95 among females, and 1.72 among male patients. The incidence rate estimated using the capture-recapture method was 3.18 (95% CI: 3.02–3.34). Conclusions: According to the Atlas of MS, Uruguay has a low incidence rate (2.0–3.99), even though it is one of the highest in Latin America. Our country aligns with the global trend of increasing incidence. Age and sex distribution were similar to other studies, with a high incidence of patients with late-onset multiple sclerosis. The capture-recapture method confirms the exhaustivity of our investigation.
Cytomorphological Disparities in Invasive Breast Cancer Cells following Neoadjuvant Endocrine Therapy and Chemotherapy
Authors: Hoshina Hideko , Sakatani Takashi , Kawamoto Yoko , Ohashi Ryuji , Takei Hiroyuki
Published: March 2024

Introduction: Neoadjuvant endocrine therapy (NAE) offers a breast-conserving surgery rate and clinical response rate similar to those of neoadjuvant chemotherapy (NAC), while presenting fewer adverse events and lower pathological complete response rates. The assessment of pathological response determines degenerative changes and predicts the prognosis of breast cancer treated with NAC. This study clarified the degenerative changes occurring in breast cancer following NAE. Methods: Our study encompassed two groups: NAE, consisting of 15 patients, and NAC, comprising 18 patients. Tissue samples were obtained from core needle biopsies and surgeries. Nuclear and cell areas were calculated using Autocell analysis. Furthermore, we assessed markers associated with microtubule depolymerization (KIF2A) and initiators of apoptosis (caspase-9). Results: In the NAC group, we observed significant increases in both cytoplasmic and cell areas. These changes in cytoplasm and cells were notably more pronounced in the NAC group compared to the NAE group. After treatment, KIF2A exhibited a decrease, with the magnitude of change being greater in the NET group than in the NAC group. However, no discernible differences were found in caspase-9 expression between the two groups. Conclusion: Our findings indicate that NAE induces condensation in cancer cells via cell cycle arrest or apoptosis. Conversely, NAC leads to cell enlargement due to the absence of microtubule depolymerization. These discrepancies underscore the importance of accounting for these distinctions when establishing criteria for evaluating pathological responses.
The Czech Home Parenteral Nutrition Registry REDNUP: Comprehensive Analysis of Adult Patients’ Data
Authors: Koudelková Kateřina , Waldauf Petr , Wohl Petr , Šenkyřík Michal , Beneš Petr , Kohout Pavel , Vejmelka Jiří , Maňák Jan , Těšínský Pavel , Novák František , Meisnerová Eva , Fencl Filip , Gojda Jan
Published: March 2024

Introduction: Home parenteral nutrition (HPN) is the primary treatment modality for patients with chronic intestinal failure, one of the least common organ failures. This article provides a retrospective analysis of the data collected on HPN patients in the Czech Republic over the past 30 years. Methods: National registry data were collected using a standardised online form based on the OASIS registry (Oley – A.S.P.E.N. Information System) across all centres providing HPN in the Czech Republic. Data collected prospectively from adult patients in the HPN program were analysed in the following categories: epidemiology, demographics, underlying syndrome, diagnosis, complications, and teduglutide therapy prevalence. Results: The registry identified a total of 1,838 adult patient records, reflecting almost 1.5 million individual catheter days. The prevalence of HPN has risen considerably over the last few decades, currently reaching 5.5 per 100,000 population. The majority of patients have short bowel syndrome and GI obstruction, with cancer being the most prevalent underlying disease. Catheter-related bloodstream infections have been the most prevalent acute complication. However, the incidence in 2022 was only 0.15 per 1,000 catheter days. The study also observed an increase in the prevalence of patients on palliative HPN over the last decade. Conclusion: This study presents a thorough analysis of data from the Czech REgistr Domaci NUtricni Podpory (REDNUP) registry. It shows an increasing prevalence of HPN, namely, in the palliative patient group. The sharing of national data can improve understanding of this rare condition and facilitate the development of international guidelines.
Pitfalls of Current Diagnostic Criteria of Tumor Lysis Syndrome
Authors: Alhamid Naji , Sabbagh Bana , Alsarraj Asmaa , Lerma Edgar , Caza Tiffany , Workeneh Biruh , Barrientos Jacqueline Claudia , Jhaveri Kenar D.
Published: March 2024

Background: Tumor Lysis syndrome (TLS) is a well-recognized medical emergency in patients with cancer diagnosis. The diagnostic criteria of TLS have been revised many times since it was recognized, but still have many drawbacks limit diagnosis accuracy. Summary: Autopsy studies in patients with perimortem diagnoses of TLS have shown that they may not have actually had TLS. Therefore, many cancer patients who are at risk for TLS, clinical and laboratory criteria may be fulfilled due to other causes of acute kidney injury. In this review, we aim to cast a spotlight on the shortcomings and pitfalls of the current diagnostic criteria for TLS, and propose a roadmap for developing a more rigorous criteria that improve on the diagnostic accuracy.
Key messages: Causes of AKI in patients with cancer other than TLS should be considered. Because current diagnostic criteria may miss those differential diagnosis, specific biomarkers that can tell when TLS is the underlying process is an important need, besides appropriate criteria that can jump over the pitfalls in the current criteria and enhance the recognition of TLS among other causes.
LLM-Assisted Data Augmentation for Chinese Dialogue-Level Dependency Parsing
Authors: Zhang Meishan , Jiang Gongyao , Liu Shuang , Chen Jing , Zhang Min
Published: March 2024

Dialogue-level dependency parsing, despite its growing academic interest, often encounters underperformance issues due to resource shortages. A potential solution to this challenge is data augmentation. In recent years, large language models (LLMs) have demonstrated strong capabilities in generation, which can facilitate data augmentation greatly. In this study, we focus on Chinese dialogue-level dependency parsing, presenting three simple and effective strategies with LLM to augment the original training instances, namely word-level, syntax-level, and discourse-level augmentations, respectively. These strategies enable LLMs to either preserve or modify dependency structures, thereby assuring accuracy while increasing the diversity of instances at different levels. We conduct experiments on the benchmark dataset released by Jiang et al. (2023) to validate our approach. Results show that our method can greatly boost the parsing performance in various settings, particularly in dependencies among elementary discourse units. Lastly, we provide in-depth analysis to show the key points of our data augmentation strategies.
Morphological and genetic diversification of pygmy and marbled newts, with the description of a new species from the wider Lisbon Peninsula (Triturus, Salamandridae)
Authors: Arntzen Jan W.
Published: March 2024

Iberian populations of large-bodied newts, with Triturus marmoratus in the north and T. pygmaeus in the south of the peninsula, were studied for external morphology, mitochondrial dna and for a panel of single nucleotide polymorphisms. This confirmed the species’ low level of interspecific hybridization and their parapatric, mosaic-like mutual range border across the peninsula. The genetic data also revealed substantial variation within T. pygmaeus, with narrow (0.43–35.2 km) clinal transitions in the very centre of Portugal. Similar clines were observed for body size and colouration pattern. Pygmy newts in the west of Portugal are larger, with a more striped (less reticulated) green dorso-lateral colouration pattern than those in the east and south of the country. The western group of populations is described as a new species, Triturus rudolfi sp. nov., on account of a long, ca. 2.5 Ma, independent evolutionary history and limited hybridization with its sister-species T. pygmaeus, suggesting selection against hybrid offspring. The range of the newly described species may be restricted to the wider Lisbon Peninsula, stretching northwards along the Atlantic coast to the river Vouga estuary. Inland, the range border may be set by the lower Tejo River, or by the currently wide area of agricultural land at either side of that river, that may accommodate a residual hybrid zone. The close contact between both pygmy newt species is effectively limited to a ca. 20 × 40 km area directly north of the town Entroncamento, where T. rudolfi sp. nov. is sandwiched in between T. marmoratus and the river Tejo.
Before Skunḫa
Authors: Ferrario Marco
Published: March 2024

The present paper seeks to offer a new interpretative scenario against the background of which to assess the dynamics underlying the interactions between the Achaemenid Empire (starting with Cyrus’ conquest of Central Asia) and the peoples of the steppes, which presided over the formation of what it is usually referred to as the frontier of the empire itself in Baktria, Sogdiana and Chorasmia.

To this end, a set of literary sources (especially Herodotus and Strabo) whose influence on the interpretation in strongly oppositional terms of the above-sketched process has been, and continues to be, very significant will be critically scrutinized. In a second step, archaeological data and comparative evidence of a historical-ethnographic nature will be added, with the overarching aim of framing the narrative of the classical sources into a broader and, as it shall be argued, more proper social, economic, and ecological context.

The outcome of such a study will hopefully be a more nuanced and complex picture of a crucial phase of Achaemenid history in Central Asia. In the light of the framework which shall be worked out in the following pages, while on the one hand the driving force and organizational capacity of the newly formed empire will emerge as decisive elements in the establishment of a new, distinctive, «imperial space» north of Baktr(i)a, on the other hand, the role of local communities in negotiating the modalities of their integration within the networks resulting from the birth and expansion of Achaemenid rule in the area will appear as having been of no less paramount importance.
Warm Arctic–Cold Eurasia (WACE) Trend: Inference from Large Ensemble Model Simulations
Authors: Jun Ye-Jun , Son Seok-Woo , Kim Hera , Park Hyo-Seok , Yoon Jin-Ho
Published: March 2024

Concurrent with global warming, the Eurasian continent has experienced frequent cold winters in recent decades. Although still debatable, such Eurasian winter cooling, which was particularly pronounced in the late twentieth century, has been attributed to internal climate variability, the process of which remains elusive. By examining multimodel large ensemble simulations, this study explores the potential sources of internal climate variability responsible for the Eurasian winter cooling trend over 1987–2006. Model simulations show a large ensemble spread in the Eurasian winter temperature trend with an ensemble mean close to zero. A comparison of the ensemble members shows that a circulation pattern favorable for the Eurasian cooling is characterized by the anticyclonic and cyclonic enhancements of sea level pressure (SLP) trend in the subarctic and Aleutian regions, respectively. This dipolar SLP trend is closely related to the deep Arctic warming, the change in midlatitude snow cover, and the enhancement of atmospheric convection over the tropical western Pacific. This result suggests that the Eurasian winter cooling is likely associated not only to the changes in mid- to high-latitude conditions but also to the changes in tropical convection. The possible mechanism of the tropically induced Aleutian low deepening is also discussed.
Examining the relationships between cognition and auditory hallucinations: A systematic review
Authors: Bell Adrienne , Toh Wei Lin , Allen Paul , Cella Matteo , Jardri Renaud , Larøi Frank , Moseley Peter , Rossell Susan L
Published: March 2024

Objective:

Auditory hallucinations (hearing voices) have been associated with a range of altered cognitive functions, pertaining to signal detection, source-monitoring, memory, inhibition and language processes. Yet, empirical results are inconsistent. Despite this, several theoretical models of auditory hallucinations persist, alongside increasing emphasis on the utility of a multidimensional framework. Thus, clarification of current evidence across the broad scope of proposed mechanisms is warranted.

Method:

A systematic search of the Web of Science, PubMed and Scopus databases was conducted. Records were screened to confirm the use of an objective behavioural cognitive task, and valid measurement of hallucinations specific to the auditory modality.

Results:

Auditory hallucinations were primarily associated with difficulties in perceptual decision-making (i.e. reduced sensitivity/accuracy for signal-noise discrimination; liberal responding to ambiguity), source-monitoring (i.e. self–other and temporal context confusion), working memory and language function (i.e. reduced verbal fluency). Mixed or limited support was observed for perceptual feature discrimination, imagery vividness/illusion susceptibility, source-monitoring for stimulus form and spatial context, recognition and recall memory, executive functions (e.g. attention, inhibition), emotion processing and language comprehension/hemispheric organisation.

Conclusions:

Findings were considered within predictive coding and self-monitoring frameworks. Of concern was the portion of studies which – despite offering auditory-hallucination-specific aims and inferences – employed modality-general measures, and/or diagnostic-based contrasts with psychologically healthy individuals. This review highlights disparities within the literature between theoretical conceptualisations of auditory hallucinations and the body of rigorous empirical evidence supporting such inferences. Future cognitive investigations, beyond the schizophrenia-spectrum, which explicitly define and measure the timeframe and sensory modality of hallucinations, are recommended.
Evaluating Public Spending Efficiency and its Determinants Towards Social Outcomes: Empirical Evidence from Indian States
Authors: Kumar Sumit , Kaur Baljit
Published: March 2024

The topic of public expenditure efficiency has gained a key position in the spheres of public policy goals. This article tries estimating the efficiency of public spending on health and education sectors across Indian states from 1990–1991 to 2016–2017. In input–output linkage, we have computed efficiency using a slacks-based measure model of data envelopment analysis through different orientations. The study also captures the externalities of public spending efficiency with some exogenous factors. It also suggests that these exogenous factors (such as good governance, per capita income and proportion of literates in the household) have significantly improved the output efficiency score of the health as well as the education sectors across Indian states.

JEL Codes: H51, H52, H21, E61
Don’t beat the messengers
Authors: Runyon Mary Hays , Runyon William
Published: March 2024

Gerald Keown taught Hebrew Scriptures as living documents, relevant to our lives and applicable to our issues. Issues of social justice, about which Dr. Keown wrote and spoke publicly, should be addressed using the principles available in scripture. In Numbers 22, the figure of Balaam and his beating of the donkey teaches that Christians should be ready to hear truth from those who have been oppressed and to engage that truth to be aware of white privilege and to participate in acts of reparation.
Willingness to Embrace COVID-19 Vaccination Amongst Residents in a Low-Income Nation: Insights From a Cross-Sectional Study on a Limited Cohort
Authors: Derseh Manaye Tamrie , Ambaye Abyou Seyfu , Yayehrad Ashagrachew Tewabe , Abebe Abinet , Wobie Yohannes , Assefa Erkihun
Published: March 2024

The global pandemic had a significant impact on countries around the world, both politically and socioeconomically. It is crucial that swift decisions and actions need to be taken to prevent negative outcomes. The development of vaccines has emerged as a potential necessity for countries worldwide. Ethiopia began vaccinating health professionals and high-risk individuals in March 2021, according to a report from the World Health Organization citing the Ethiopian Federal Ministry of Health. This study aimed to assess the determinants of willingness to receive the COVID-19 vaccine among Debre Markos city administration residents. A community-based cross-sectional study design was employed to recruit 845 individuals as a sample. Descriptive statistics and logistic regression were used as statistical analysis techniques. Among the total 845 samples, the overall response rate was 98.34%. Two hundred forty-two participants showed their willingness to receive vaccines. Age (AOR = 2.56; 95%CI = [1.87-3.23]), sex (Female) (AOR = 3.45; 95% CI = [2.07-5.26]), having children (AOR = 1.21; 95% CI = [1.02-1.90]), and Chronic Disease (AOR = 2.98; 95% CI = [1.67-3.50]) were significantly and positively associated with willingness to receive COVID 19 vaccines at 95% CI. Although most of the participants were aware of the possibility of COVID-19 to cause fever; and its transmission, only a small percentage of the total participants showed their willingness to receive the vaccine if it was available to them. Elderly and individuals with chronic diseases need to get a priority of taking those vaccinations.
Racialising age in the UK’s border regime: a case for abolishing age assessment
Authors: Rosen Rachel , Khan S.
Published: March 2024

Processes for assessing the age of young unaccompanied migrants have been roundly critiqued, with new concerns in the UK being raised about the increasing use of ‘scientific’ approaches. In this article, we suggest that, taking everything into account, analyses do not go far enough, arguing that technical questions of how ‘best’ to assess age or the new incursion of biometric measurements can obscure the political question of what work age does in hostile border regimes. As a result, the underpinning logics of age assessment – an essentialisation of age, ‘race’ and borders – are not only left in place but further augmented. We demonstrate, through a careful curation of assessment reports (that operate through the assertion of truth claims about the body, childhood and time) how such reports draw on and reproduce multiple and intersecting racist imaginaries as they are synthesised with developmental logics around childhood. Age, we argue, is being weaponised in the service of post-racial fantasies in liberal democracies, rising ethnonationalism and state retrenchment from social support.