bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidating the Role of miRNA-326 Modulating Hedgehog Signaling in Pancreatic Carcinoma
Authors: Rashid Safoora , Rashid Sumaira , Das Prasenjit , Malik Nargis , Dash Nihar Ranjan , Singh Nidhi , Pandey R. M. , Kumar Lalit , Chauhan Shyam Singh , Chosdol Kunzang , Gupta Surabhi , Saraya Anoop 
Published: November 2023

Background and Aim
Pancreatic ductal adenocarcinoma (PDAC) is one of the lethal malignancies worldwide characterized by poor prognosis. MicroRNAs (miRNAs) function as the key regulators in carcinogenesis and may act as noninvasive biomarkers in various malignancies including PDAC. The present study aimed to elucidate the role of miR-326, a known modulator of hedgehog (Hh) pathway in PDAC.

Materials and Methods
miR-326 circulating levels were assessed in 105 PDAC patients, 31 with chronic pancreatitis (CP) and 36 healthy controls by quantitative Polymerase chain reaction. The expression of miR-326 and smoothened (SMO) was checked in surgical PDAC tissue. SMO protein expression was analyzed by immunohistochemistry in different groups. Finally, the role of miR-326 as a modulator of Hh pathway was assessed in vitro.

Results
Our results demonstrate that miR-326 is downregulated in both blood and tissue of PDAC patients as compared with controls. In contrast, the target gene/protein expression of SMO is upregulated in PDAC. Moreover, the tumor stromal expression of SMO was found to be clinically associated with lymph-node metastasis and vascular encasement in PDAC. Overexpression of miR-326 in Panc1 cell line was found to induce downregulation of SMO suggesting the tumor suppressor role of miR-326 in PDAC.

Conclusions
Taken together, miR-326 acts as a tumor suppressor in PDAC by modulating Hh pathway. It may be a promising target for the development of efficient drug therapies for the treatment of PDAC
Combination of Serum CA 19-9 and Endoscopic Ultrasound Findings Can Predict Malignancy Risk in Patients With Chronic Pancreatitis Presenting With Pancreatic Head Mass
Authors: Agarwal Samagra , Gunjan Deepak , Gopi Srikanth , Saraya Anoop 
Published: November 2023

Background and Aims
Inflammatory head mass of pancreas (IMP) developing in background of chronic pancreatitis (CP) is difficult to distinguish from carcinoma pancreas. We aimed to delineate natural course of IMP and predict their malignancy risk, avoiding unnecessary biopsies.

Materials and Methods
In this retrospective single-center study, clinical records of patients with CP with diagnosed pancreatic head mass were reviewed. Clinical, laboratory, imaging, endoscopic findings, and follow-up details were retrieved from prospectively maintained database. A diagnostic nomogram was developed combining serum cancer antigen 19-9 and endoscopic ultrasound (EUS) findings to predict the risk of malignancy.

Results
We identified 107 patients with pancreatic head mass with CP of whom 87 (81.3%) were IMP and 20 (18.7%) were malignant. Patients with IMP were more frequently young males with alcohol-related CP and low CA 19-9 in comparison with those with malignancy (age IMP: 41.3 ± 11.3 vs carcinoma: 49.3 ± 14.5 years [P = 0.009]; males 89.7% vs 65% [P = 0.011]; alcoholic etiology: 71.3% vs 20% [P < 0.001]; median CA 19-9: 25.78 [interquartile range, 7.20–120.60] vs 1034.50 [106.65–7808.25] [P < 0.001]). A diagnostic nomogram combining CA 19-9 and EUS findings could identify malignancy with an optimism-corrected c-statistic of 0.905, which was better than both CA 19-9 (0.80) and EUS alone (0.826). Patients with IMP had relatively benign disease course with 40.2% biliary obstruction, 20.7% portal venous thrombosis, 14.9% gastric outlet obstruction, and 1-, 3-, and 5-year survival being 97.3%, 92.7%, and 92.0%, respectively. Surgery was required in only 12 patients (13.8%) with IMP.

Conclusions
Combination of CA 19-9 and EUS best identifies malignancy risk in patients with IMP, who have otherwise benign course.
A Shift Toward Early Oral Feeding in Acute Pancreatitis
Authors: Nammour Tarek , Lee Alice A. , McNabb-Baltar Julia , Banks Peter A. , Jin David X. 
Published: November 2023

Objectives
The 2018 American Gastroenterological Association (AGA) guidelines strongly recommended early oral feeding as tolerated in patients with acute pancreatitis (AP). We compare early oral feeding rates in AP patients hospitalized in the periods before (2013–2016, Period A) and after (2019–2020, Period B) publication of the AGA guidelines, hypothesizing increased adherence in Period B.

Methods
We performed a retrospective cohort study of AP patients presenting to the emergency department during each period. Early oral feeding was defined as diet initiation within the first 48 hours of presentation.

Results
The cohort included 276 AP cases in period A and 104 in period B. A higher percentage of patients were offered early oral feeding during period B as compared to period A (70.2% vs. 43.5%). Similarly, more patients in period B were started on solid diet as compared to period A (34.6% vs. 20.3%). On multivariable regression analysis, the independent predictors of delayed oral feeding included early opioid analgesics use (OR 0.37), presence of pancreatic necrosis (OR 0.14), and organ failure (OR 0.33).

Conclusions
More AP patients were initiated on early oral feeding in the period following the publication of the AGA guidelines. Opioid analgesics use, pancreatic necrosis, and organ failure were associated with delayed oral feeding.
BRAT1-Associated Leukodystrophy Exacerbated by Classic Hodgkin Lymphoma–Directed Therapy
Authors: Hooshmand Sara J. , Chohan Karan L. , Raghunathan Aditya , Renaud Deborah L. , Ruff Michael W. 
Published: November 2023

Introduction:
BRCA1-associated ataxia-telangiectasia–mutated activator-1 (BRAT1) is responsible for cell cycle surveillance and mitochondrial function. The implications of adult-onset BRAT1-variant and the resulting phenotypic neurocognitive and imaging features have not been previously described.

Case Report:
A 66-year-old man with a recent diagnosis of classic Hodgkin lymphoma was referred to neuro-oncology for cognitive and motor decline, and progressive cerebral white matter changes noted on magnetic resonance imaging (MRI). A neurological examination revealed global weakness, broad-based gait, and bilateral extensor plantar responses. Brain MRI demonstrated periventricular, deep, and subcortical white matter T2/FLAIR hyperintensities without contrast enhancement. Cerebral spinal fluid studies were unremarkable. A GeneDX genetic leukodystrophy panel conduction revealed a pathogenic variant (c.294dupA; p.L99TfsX92) resulting in a truncated protein of BRAT1, along with a variant of uncertain significance (c.746A>G;p.E249G). A presumptive diagnosis of late-onset leukoencephalopathy secondary to the BRAT1 variant was made. In an attempt to combat his mitochondrial dysfunction, he was initiated on a mitochondrial cocktail, including B-100 complex and coenzyme Q10. He began lymphoma-directed combination chemotherapy and developed precipitous functional decline after 2 cycles of therapy. Compared with prechemotherapy imaging, repeat positron emission tomography/computed tomography metabolic imaging showed a response after 3 cycles of chemotherapy; however, repeat brain MRI showed worsening diffuse white matter hyperintensities and cerebral atrophy.

Conclusion:
Given the variability in phenotypes and clinical onset, leukodystrophies can be a diagnostic challenge. This case demonstrated progressive BRAT1-associated leukodystrophy exacerbated by chemotherapy-induced toxic leukoencephalopathy. Mitochondrial energy deficiency in the context of multiple metabolic insults was likely underlying the progressive neurological decline observed in this case of genetic leukodystrophy.
Case Report: Remote Scleral Lens Fitting for High Toric Scleras in a Keratoconus Patient
Authors: Fadel Daddi , Gildea Cian 
Published: November 2023

ABSTRACT

SIGNIFICANCE
Technology plays a crucial role in customizing scleral lenses and improving lens alignment, especially in challenging scleral shapes. In addition, remote fitting technology allows optometrists to extend their expertise globally, empowering patients to access to customized lenses without travel expenses.

PURPOSE
The objective of this study was to document the difficulties encountered in fitting a scleral lens in a patient with keratoconus and pronounced scleral toricity. In addition, the study aimed to present the successful remote fitting achieved by using advanced technology.

CASE REPORT
An Irish male patient diagnosed with keratoconus exhibited high scleral toricity. Generally, keratoconus eyes often exhibit significant scleral asymmetry associated with cone decentration and disease severity. Improperly aligned scleral lenses can lead to regional changes in scleral shape, lens decentration, discomfort, and visual disturbances. Indeed, previous scleral lens fits were unsuccessful because of these issues. Corneoscleral profilometry was acquired in Ireland and then used in Italy to design customized lenses, which were then delivered to the patient's optometrist in Ireland. The first lenses designed and delivered demonstrated excellent overall performance without requiring adjustments.

CONCLUSIONS
This report highlights the importance of corneoscleral profilometry to increase efficiency and reduce lens reorders and chair time, and the remote fitting in overcoming barriers to accessing specialized lens fitting.
Relationship of Low-luminance Visual Acuity with Ocular Aberrations in Older Participants
Authors: Iizuka Tatsuya , Kawamorita Takushi , Handa Tomoya , Ishikawa Hitoshi 
Published: November 2023

ABSTRACT

SIGNIFICANCE
This study highlights the importance of twilight adaptation for reliable assessment of low-luminance visual acuity and understanding the relationship between low-luminance visual acuity and ocular aberrations.

PURPOSE
The human eye experiences reduced visual acuity as luminance decreases owing to reduced retinal and optical resolutions; however, the details are unclear. This study aimed to quantify the effects of refraction, pupil diameter, and ocular aberrations on visual acuity during the transition from high- to low-light environments, thereby contributing to the standardization of low-luminance visual acuity measurements.

METHODS
In total, 27 older participants with a mean age of 70.0 ± 4.1 years were included in this study. Visual acuity was measured according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol with three luminance conditions: high luminance (300 cd/m2), low luminance (10 cd/m2), and low luminance with short-term (15-minute) twilight adaptation (10 cd/m2).

RESULTS
The mean logarithm of minimum angle of resolution values of visual acuity were −0.09 ± 0.09, 0.10 ± 0.13, and 0.03 ± 0.09 at 300, 10, and 10 cd/m2 with twilight adaptation, respectively. Multiple regression analysis determined that spherical aberration (P < .005) and tetrafoil (P < .005) were significant factors associated with low-luminance visual acuity after twilight adaptation, with an adjusted R
2 value of 0.35 for this model (P < .005).

CONCLUSIONS
Although the influence of ocular aberrations on low-luminance visual acuity may be relatively modest compared with neural effects, it remains a crucial factor that should not be overlooked. The absence of twilight (or dark) adaptation can cause ocular aberrations and neural effects, potentially leading to inaccuracies in the measurement of low-luminance visual acuity.
What visuospatial perception has taught us about the pathophysiology of vestibular migraine
Authors: Arshad Qadeer , Moreno-Ajona David , Goadsby Peter J. , Kheradmand Amir 
Published: November 2023

Purpose of reviewA decade has passed since vestibular migraine (VM) was formally established as a clinical entity. During this time, VM has emerged amongst the most common cause of episodic vertigo. Like all forms of migraine, VM symptoms are most prominent during individual attacks, however many patients may also develop persistent symptoms that are less prominent and can still interfere with daily activities.Recent findingsVestibular inputs are strongly multimodal, and because of extensive convergence with other sensory information, they do not result in a distinct conscious sensation. Here we review experimental evidence that supports VM symptoms are linked to multisensory mechanisms that control body motion and position in space.SummaryMultisensory integration is a key concept for understanding migraine. In this context, VM pathophysiology may involve multisensory processes critical for motion perception, spatial orientation, visuospatial attention, and spatial awareness.
Epidemiological Profile of Crimean-Congo Hemorrhagic Fever, Iraq, 2018
Authors: Mustafa Ali Hazim , Lami Faris , Khaleel Hanan Abdulghafoor 
Published: November 2023

AbstractBackgroundCrimean-Congo hemorrhagic fever (CCHF) is a potentially fatal tick-borne disease that is widely distributed in Africa and Eurasia countries. It is caused by the CCHF virus of theNairovirusgenus of theBunyaviridaefamily.This study aims to describe the 2018 CCHF epidemic wave in Iraq and epidemiological pattern to assist implantation of preventive and control measures and adherence of physicians to the standard case definition.MethodsThis descriptive study reviewed all records of suspected and confirmed CCHF cases. Three types of data sources were used: the case investigation forms of all suspected cases, case sheets of all confirmed cases, and the laboratory results from the central public health laboratory.ResultsThe total number of suspected cases was 143. Most of the cases were males (59.4%), 15-45 years old (62.2%), and live in urban areas (58.7%). About three quarters of the cases (68.5%) did not fit the standard case definition adopted by Iraq Center of Disease Control. Most of the suspected cases were reported in Diwaniya province (20.3%). Nearly half of them (64, 44.7%) occurred in June.Only 7.0% (n=10) of suspected cases were positive when tested by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). One third of confirmed cases (3, 30.0%) occurred in Diwaniya province. During the 2018 epidemic wave, there were 10 confirmed cases with 8 deaths and 2 improved cases.ConclusionDespite the fact that CCHF is uncommon in Iraq, sporadic cases or outbreaks could occur.RecommendationsGiven the known method of transmission, banning of random livestock slaughtering and the practice of raising livestock inside residential areas are expected to have a major role in CCHF infection control.
A unique chaperoning mechanism in Class A JDPs recognizes and stabilizes mutant p53
Authors: Zoltsman Guy , Dang Thi Lieu , Kuchersky Miriam , Faust Ofrah , Silva Micael S. , Ilani Tal , Wentink Anne S. , Bukau Bernd , Rosenzweig Rina 
Published: November 2023

SUMMARYJ-domain proteins (JDPs) constitute a large family of molecular chaperones that bind a broad spectrum of substrates, targeting them to Hsp70, thus determining the specificity and activating the entire chaperone functional cycle. The malfunction of JDPs is therefore inextricably linked to myriad human disorders. Here we uncover a novel mechanism by which chaperones recognize misfolded clients, present in class-A JDPs. Through a newly-identified β-hairpin site, these chaperones detect changes in protein dynamics at the initial stages of misfolding, prior to exposure of hydrophobic regions or large structural rearrangements. The JDPs then sequester misfolding-prone proteins into large oligomeric assemblies, protecting them from aggregation. Through this mechanism, class-A JDPs bind destabilized p53 mutants, preventing clearance of these oncoproteins by Hsp70-mediated degradation, thus promoting cancer progression. Removal of the β-hairpin abrogates this protective activity while minimally affecting other chaperoning functions. This suggests the class-A JDP β-hairpin as a highly specific target for cancer therapeutics.
Middle-infrared Modulation Of Sleep By Cardiometabolic Function
Authors: Sun Yan , Xian Guang , Wang Chao , Zhang Delong 
Published: November 2023

AbstractThe interdependence of sleep and overall well-being is profound. Sleep has the capacity to regulate hematopoiesis, thereby sustaining our physiological equilibrium. Nevertheless, our understanding regarding the potential reversibility of this regulatory process remains limited. In this study, we present evidence suggesting that exposure to middle-infrared radiation (MIR) within the 5-7 mm wavelength range can elicit non-thermal biological effects within the human body. These effects are characterized by an augmentation in blood circulation, mediated through modifications in red blood cell properties. Furthermore, MIR exposure is accompanied by a reduction in homocysteine levels and suppressor T-cell populations. Importantly, daytime modulation of MIR has been shown to significantly facilitate the amelioration of insomnia symptoms during nighttime, primarily through its impact on the architecture of deep sleep. Conclusively, our investigation reveals a robust association between cardiometabolic function and human sleep, with MIR presenting a promising avenue for enhancing sleep quality by regulating both the circulatory system and the immune system. These findings pave the way for the development of therapeutic strategies aimed at mitigating prevalent sleep-related disorders by disentangling the intricate links between sleep and cardiometabolic function.
Interactome mapping reveals a role for LRP10 in autophagy and NDFIP1-mediated α-synuclein secretion
Authors: Mascaro Ana Carreras , Ferraro Federico , Boumeester Valerie , Breedveld Guido , Dekkers Dick H.W. , Vergouw Leonie J.M. , Jong Frank Jan de , Demmers Jeroen A. A. , Bonifati Vincenzo , Mandemakers Wim 
Published: November 2023

AbstractVariants in theLRP10gene have been found in a spectrum of neurodegenerative disorders, including Lewy body diseases (LBDs). In brains of LBD patients, LRP10 is found in neuronal α-synuclein-containing Lewy bodies, astrocytes, and vasculature, but not in inclusion-free neurons. Furthermore, recent work suggests that LRP10 is involved in α-synuclein processing and transmission, which is disrupted by the LBD-associatedLRP10:c.1424+5G>A variant (LRP10-Splice). In spite of the cumulating genetic and functional evidence for a role of LRP10 in neurodegenerative disorders, our knowledge about the biological processes in which LRP10 is involved is incomplete. In this work, we provide a list of LRP10 interactors identified via LRP10 co-immunoprecipitation and mass spectrometry in LRP10-overexpressing cells and induced pluripotent stem cells (iPSC)-derived astrocytes. In addition to interactors and biological processes previously associated with LRP10, we identified novel interactors and pathways that may provide new insights into LRP10 function. Based on these findings, we focused on the involvement of LRP10 in the autophagy and unconventional secretion pathways via its interaction with the autophagy receptor SQSTM1/p62 and the ubiquitin-proteasome adaptor protein NDFIP1, respectively. We demonstrate that changes in LRP10 levels, either via knock-out or overexpression, affect p62 levels and autophagy in HuTu-80 cells and iPSC-derived astrocytes. Furthermore, we found that both LRP10 and NDFIP1 stimulate α-synuclein secretion and synergistically affect intracellular α-synuclein levels. Next, we studied the LRP10 interactome and related biological processes in iPSC-derived astrocytes carrying the LRP10-Splice variant. Although various interactors and biological processes were shared between wild-type LRP10 (LRP10-WT) and LRP10-Splice, others were only found in either LRP10-WT or LRP10-Splice. Interestingly, we found that LRP10-Splice responded differently to autophagy-modulating drugs in comparison to LRP10-WT. Furthermore, we show that LRP10-Splice interferes with the LRP10-WT:NDFIP1 interaction and NDFIP1-mediated α-synuclein secretion. Finally, we investigated the interactome of a secreted LRP10 species only found in conditioned media from LRP10-Splice carrier cells, and identify biological processes that might be impacted by the secreted LRP10-Splice specific protein. In summary, this study enhances our understanding of LRP10 biology, describes LRP10 functions in autophagy and NDFIP1-mediated α-synuclein secretion, and reveals potentially interesting differences between LRP10-WT and LRP10-Splice carrier cells that might be relevant to better understand the role of LRP10 in LBDs pathogenesis.
Covert attention for uncertainty reduction during sequential inference
Authors: Domínguez-Zamora F. Javier , Horga Guillermo , Gottlieb Jacqueline P. 
Published: November 2023

ABSTRACTA major question in attention research is how the brain identifies task-relevant stimuli in the absence of exogenous instructions or cues. Recent studies propose that endogenous attention control expected information gains (EIG) or, equivalently, minimizes decision uncertainty, but the mechanisms of this process are not understood. We show that, in a task in which participants covertly attended to decision-relevant stimuli, their perceptual sensitivity (d’) for discriminating the stimuli depended on the diagnosticity of the stimuli and the participants’ prior decision uncertainty, consistent with Bayesian EIG. The fronto-parietal network, in particular left areas V3A/B and IPS1/2, integrated uncertainty with diagnosticity in a manner correlating with behavioral effects on d’, and uncertainty signals relied on interactions between this network and the medial prefrontal cortex (mPFC). The findings show that covert attention can be deployed based on EIG and reveal the neural mechanisms of this process.
Quantifying the impact of genotype-dependent gene flow on mutation fixation in subdivided populations
Authors: Marrec Loïc 
Published: November 2023

AbstractIn the wild, any population is likely to be spatially structured. Whereas we deeply understand evolutionary dynamics in well-mixed populations, our understanding of evolutionary dynamics in subdivided populations needs to be improved. In this work, I quantify the impact of genotype-dependent gene flow on the evolutionary dynamics of a subdivided population. Specifically, I build a model of a population structured as the island or the stepping stone model in which genotype-dependent gene flow is represented by individuals migrating between its sub-populations at a rate depending on their genotype. I analytically calculate the fixation probability and time of a mutation arising in the subdivided population under the low migration limit, which I validate with numerical simulations. I find that the island and the stepping stone models lead to the same fixation probability. Moreover, comparing the fixation probability in these models to the one in a well-mixed population of the same total census size allows me to identify an effective selection coefficient and population size. In the island and the stepping stone models, the effective selection coefficient differs from the selection coefficient if the wild-type and the mutant migration rates are different, whereas the effective population size equals the total census size. Finally, I show that genotype-dependent gene flow increases the fixation time, which allows for distinguishing the island and the stepping stone models, as opposed to the fixation probability.