bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic plasticity of T cell fate decision
Authors: Pan Xiaoli , Wang Jiajia , Zhang Lianjun , Li Guideng , Huang Bo 
Published: December 2023

AbstractThe efficacy of adaptive immune responses in cancer treatment relies heavily on the state of the T cells. Upon antigen exposure, T cells undergo metabolic reprogramming, leading to the development of functional effectors or memory populations. However, within the tumor microenvironment (TME), metabolic stress impairs CD8+T cell anti-tumor immunity, resulting in exhausted differentiation. Recent studies suggested that targeting T cell metabolism could offer promising therapeutic opportunities to enhance T cell immunotherapy. In this review, we provide a comprehensive summary of the intrinsic and extrinsic factors necessary for metabolic reprogramming during the development of effector and memory T cells in response to acute and chronic inflammatory conditions. Furthermore, we delved into the different metabolic switches that occur during T cell exhaustion, exploring how prolonged metabolic stress within the TME triggers alterations in cellular metabolism and the epigenetic landscape that contribute to T cell exhaustion, ultimately leading to a persistently exhausted state. Understanding the intricate relationship between T cell metabolism and cancer immunotherapy can lead to the development of novel approaches to improve the efficacy of T cell-based treatments against cancer.
Accumulation of advanced glycation end products in skin and increased vascular ageing in the general population: the Malmö Offspring Study
Authors: Jujic Amra , Engström Gunnar , Nilsson Peter M. , Johansson Madeleine 
Published: December 2023

Objectives:
Advanced glycation end product (AGE) is an established risk marker for diabetic vascular disease, and associated with the degree of diabetes complications, renal failure, and atherosclerosis in middle-aged and older individuals. The relationship between AGEs and aortic stiffness has not been thoroughly examined in the younger general population. We aimed to evaluate the association between AGEs and aortic stiffness in the general population of young and middle-aged adults.

Methods:
We analysed cross-sectionally 2518 participants from a Swedish population-based cohort, the Malmö Offspring Study (mean age 41.8 ± 14.5 years, 52.2%). Advanced glycation end-products (AGEs) were measured by a well validated, noninvasive method using skin autofluorescence with AGE-Reader. Aortic stiffness was assessed by carotid–femoral pulse wave velocity (PWV) and augmentation index (Aix) was calibrated to a standard heart rate of 75 bpm at the arteria radialis using SphygmoCor. Multivariable linear regression was performed stratified by age to analyse the association between skin AGE and aortic stiffness.

Results:
Increased levels of AGEs were significantly associated with higher direct measurements of aortic stiffness (vascular ageing) in younger individuals (PWV β 0.55 m/s, P < 0.001) after adjustment for traditional cardiometabolic risk factors, however, not in older individuals (PWV β 0.23 m/s, P = 0.10). Indirect vascular ageing was also significantly associated with higher levels of AGEs in both younger (Aix β 7.78, P < 0.001) and older individuals (Aix β 3.69, P < 0.001).

Conclusion:
Higher levels of skin autofluorescence-AGEs are positively associated with increased vascular ageing in younger adults from the general population, independent of cardiometabolic risk factors.
OCULAR ISCHEMIC SYNDROME IN THE SETTING OF NORMAL CAROTID DUPLEX ULTRASOUND
Authors: Ghoraba Hashem H. , Yu Michael , Yu Gina , Wang Sean , Or Chris , Karaca Irmak , Nguyen Quan Dong 
Published: December 2023

Purpose:
The aim of this study was to describe two cases of ocular ischemic syndrome (OIS) that were initially ruled out because of a negative carotid duplex ultrasound but eventually confirmed by angiography studies.

Methods:
This is a case series.

Results:
Case 1: A 67-year-old woman presented with symptoms suggestive of OIS, but carotid duplex ultrasound was negative, and the patient was diagnosed with occlusive retinal vasculitis due to retinal nonperfusion and vascular leakage on fluorescein angiography. Immunosuppressive therapy was initiated, but her symptoms did not improve. Computerized tomography angiography was significant for severe osteal stenosis of the aortic arch vessels. Left common carotid angioplasty and stenting resulted in complete resolution of the symptoms and vascular leakage of the left eye. Case 2: A 41-year-old man with cryoglobulinemia-associated vasculitis complained of symptoms consistent with OIS, which was initially ruled out through a negative carotid duplex ultrasound. Fluorescein angiography revealed delayed arterial filling with poor retinal perfusion. Magnetic resonance angiography revealed ophthalmic artery stenosis, which was attributed to the underlying systemic vasculitis.

Conclusion:
Computerized tomography angiography or magnetic resonance angiography should be performed to rule out OIS if duplex ultrasound is negative in the setting of high clinical suspicion. Carotid ostial and ophthalmic artery stenoses are rare but possible causes of OIS.
ACUTE ATROPHIC EVOLUTION OF DRUSENOID PIGMENT EPITHELIUM DETACHMENT AFTER PHOTOBIOMODULATION
Authors: Battaglia Parodi Maurizio , Antropoli Alessio , Arrigo Alessandro , Cicinelli Maria Vittoria , Bianco Lorenzo , Saladino Andrea , Moretti Enea , Bandello Francesco , Mansour Ahmad 
Published: December 2023

Purpose:
The aim of this study was to report the acute onset of macular atrophy soon after photobiomodulation (PBM) administration in a patient with intermediate age-related macular degeneration.

Methods:
Optical coherence tomography was performed in the study eye before and after PBM.

Results:
A patient with drusenoid pigment epithelium detachment (D-PED) underwent PBM. A few weeks after PBM, the D-PED collapsed, resulting in complete retinal pigment epithelium and outer retinal atrophy with visual acuity worsening.

Conclusion:
Thinning of the outer retinal layers over a D-PED and posterior hypertransmission may represent bad prognostic factors for PBM, accelerating the lesion's natural history toward atrophic evolution.
RELENTLESS PLACOID CHORIORETINITIS RESPONSIVE TO INTRAVITREAL TRIAMCINOLONE AND SYSTEMIC ADALIMUMAB
Authors: Porteny Jacqueline R. , Witkin Andre J. 
Published: December 2023

Purpose:
The authors describe a case of relentless placoid chorioretinitis that was responsive to intravitreal triamcinolone and systemic adalimumab, but suboptimally responsive to oral prednisone.

Methods
: This is an interventional case report.

Results:
A 23-year-old woman presented with macular placoid chorioretinitis in the left eye and visual acuity of finger counting at 3 feet. Despite a 2-week course of 60 mg oral prednisone, the choroiditis expanded dramatically in the midperiphery. She was admitted to the hospital for high-dose IV corticosteroids, which stopped the progression of disease. After discharge, the patient was started on adalimumab and restarted oral prednisone; however, on resumption of oral prednisone 60 mg, the disease started to progress again over the next 2 weeks. An intravitreal injection of triamcinolone (intravitreal triamcinolone) 2 mg was given, which halted the progression of the disease for at least 9 weeks, at which time it was believed that the adalimumab started to also have an effect. The visual acuity 9 weeks after intravitreal triamcinolone had improved to 20/20. The patient was lost to follow-up after this point.

Conclusion:
This is a case of relentless placoid chorioretinitis that continued to progress despite high-dose oral corticosteroids, but which responded to intravitreal triamcinolone and systemic adalimumab. This indicates that intravitreal corticosteroids may represent an alternative treatment option to oral corticosteroids in the short-term management of macula-threatening noninfectious chorioretinitis, particularly in patients with a suboptimal response to oral corticosteroids.
IDENTIFICATION OF CHOROIDAL VASCULAR ABNORMALITIES IN PATIENTS WITH HEREDITARY HEMORRHAGIC TELANGIECTASIA
Authors: Luong Hanna N. , Houghton Odette M. 
Published: December 2023

Purpose:
The aim of this study was to evaluate the frequency of ocular imaging in patients with hereditary hemorrhagic telangiectasia (HHT) at a large academic medical institution, characterize the choroidal vascular changes on indocyanine green angiography and optical coherence tomography, and explore the relationship of these ocular features with HHT genotypes and systemic manifestations.

Methods:
This is a retrospective review of patients with HHT who were seen in the Mayo Clinic ophthalmology department between 2011 and 2021.

Results:
Of the 71 patients with HHT identified, 7 patients (10%) had qualifying imaging defined as radial or raster spectral-domain optical coherence tomography scans and/or indocyanine green angiography. Four patients (57%) had enlarged choroidal vessels detected on optical coherence tomography and/or indocyanine green angiography. Three patients (43%) had retinal telangiectasias. Patients with choroidal changes (mean age 67 years) had the endoglin gene mutation, gastrointestinal arteriovenous malformations, and facial and mucocutaneous telangiectasias. By contrast, patients without choroidal changes (mean age 45 years) included the activin A receptor-like kinase 1 gene mutation.

Conclusion:
Only a small proportion of patients with HHT undergo ophthalmic imaging at the authors’ institution. The presence of choroidal abnormalities is associated with the endoglin gene mutation, older age, corroborating retinal vascular changes, and increased systemic manifestations.
Do Chosen Learning Strategies Predict Academic Performance in First-Year DPT Anatomy Students?
Authors: Moulton Joy , Vecchiarelli Craig , Cheng M. Samuel 
Published: December 2023

Introduction.The purpose of this study was to identify predictors of anatomy final course grades from first-year physical therapist students' characteristics and chosen learning strategies, as indicated on the Motivated Strategies for Learning Questionnaire (MSLQ). Identifying factors that contribute to success in content intensive classes may aid in coaching successful learning strategies as students transition from undergraduate coursework to Doctor of Physical Therapy (DPT) programs.Review of Literature.Previous studies show that first-year graduate students use ineffective learning strategies that are insufficient for graduate-level study. The MSLQ correlates with academic performance at several educational levels. To date, only one study has examined the correlation of MSLQ with physical therapist students' academic performance for an anatomy course.Subjects.Thirty-nine first-year physical therapist students participated in the study (27 from a hybrid program, 12 from a traditional program).Methods.This study analyzed MSLQ scores for the total instrument, each domain, and each subscale using regression analyses to determine predictors of final anatomy grades.Results.The subscales of Self-Efficacy and Test Anxiety had significant predictive value for anatomy grades (R2= 0.455,F= 5.203,P= .029). Test Anxiety had an inverse relationship to anatomy grades, meaning lower test anxiety scores correlated with higher anatomy grades. The combination of Self-Efficacy, Test Anxiety, and Critical Thinking subscales resulted in a significant prediction of anatomy grades (R2= 0.603,F= 6.659,P= .014).Discussion and Conclusion.This study found moderate correlations between MSLQ Motivation subscales and final grades in DPT anatomy classes. Self-Efficacy and Test Anxiety subscales had the strongest correlations and were significantly predictive of anatomy grades. Faculty may benefit from using inventories like the MSLQ for first-year physical therapist students to identify motivational characteristics associated with success and to remediate students' learning strategies to prevent academic failure.
The Phenomenology of Visual and Other Nonauditory Hallucinations in Affective and Nonaffective Psychosis
Authors: Toh Wei Lin , Thomas Neil , Rossell Susan Lee 
Published: December 2023

Abstract
Nonauditory hallucinations in psychosis have not received as much attention relative to voice-hearing experiences. The current paper aimed to document the characteristics of these hallucinations in affective and nonaffective psychosis. Participants were selected from a primary voice-hearing sample, who had endorsed visual, tactile, or olfactory hallucinations (N = 55–75). A comprehensive, semistructured phenomenological interview was conducted, followed by mixed methods analysis. Visual hallucinations typically occurred daily, for a few minutes per episode, within one's direct line of sight; persons and/or animals were most commonly seen, with low controllability and mostly engendered negative affective outcomes. Tactile and olfactory hallucinations were endorsed by 46.8% and 39.0% of participants, respectively. The affective psychosis group (n = 33) reported significantly greater awareness and lower functional impairment relative to the nonaffective psychosis group (n = 42). Qualitative thematic analysis revealed notable themes and subthemes across each of these hallucinations modes. Further phenomenological investigations should be carried out in lesser known hallucination modalities, assisted by the development of appropriate assessment tools.
Integrated Endoscopic Craniosynostosis Surgery and Cranial Orthosis Program
Authors: Ravi Subhashree , Aziz Waseem , AlOlama Mohammed , Stenger Charl , AlSaadawi Ghaith , Baldrighi Carla , Ahmed Anwar , Mendonca Derek 
Published: December 2023

Introduction:
Craniosynostosis results from premature fusion of the cranial sutures. There has been a continuous evolution of surgical correction techniques from an extensive open procedure to the minimally invasive technique.

Aims and Objectives:
This novel surgical technique has never been previously done in the UAE and this article documents the experience of the first team to endoscopically correct craniosynostosis with planning, surgical techniques, and customized helmet therapy.

Methods:
A retrospective case series of 16 nonsyndromic craniosynostosis patients with unicoronal (6), sagittal (5), bicoronal (1), frontosphenoidal (2), and metopic craniosynostoses (2) was corrected endoscopically and followed up with customized cranial helmet. Preoperative and postoperative photography, along with anthropometric measurements were taken.

Results:
The mean age of all patients at the time of surgery was 101 (90–117) days, mean duration of surgery was 70 minutes (38–129), mean blood loss was 120 mL (100–150), and mean duration of hospital stay 4 days (4–5). No complications and mortality were reported. Mean number of helmets was 2 (1–3). Cranial index improved in all patients with sagittal and bicoronal craniosynostosis. Close cooperation with the orthotist ensured timely helmet therapy and accurate laser scanning documentation in head molding.

Conclusions:
This case series has demonstrated that endoscopically craniosynostosis correction is safe, effective, and reliable and is the first reported series from the Middle East. The authors believe that every patient with nonsyndromic single‑suture craniosynostosis should be offered endoscopic correction before the age of 6 months. The orthotist forms an important part of the Multi-disciplinary team, enabling successful outcomes.
Variant Mapping Application: Customize And Annotate Figures Of Voltage-Gated Sodium Channel
Authors: Wen Winnie , Mahadevan Arjun , Parrish R. Ryley , Dean Richard , Cutts Alison , Johnson JP 
Published: December 2023

AbstractVoltage-gated sodium ion channels allow for the initiation and transmission of action potentials. There is a high interest in research and drug development to selectively target these ion channels to treat epilepsy and other disorders such as pain. Scientific literature and presentations often incorporate maps of these integral membrane proteins with markers indicating gene mutations to highlight genotype/phenotype correlations. There is a need for automated tools to create high quality figures with mutation (variant) locations displayed on these channel maps. This manuscript introduces a simple application to create visualization for mutations on alpha voltage-gated sodium channels, created using the D3.js library. The application allows for mapping of variant sequences, as well as important properties like the type of variant and the phenotypes linked to the variant. It also allows for customizability and the production of high-quality images for publication. This application and code base can further be extrapolated to other ion channels as well.
SARS-CoV-2 nsp15 preferentially degrades AU-rich dsRNA via its dsRNA nickase activity
Authors: Wang Xionglue , Zhu Bin 
Published: December 2023

SUMMARYIt has been proposed that coronavirus nsp15 mediates evasion of host cell double-stranded (ds) RNA sensors via its uracil-specific endoribonuclease activity. However, how nsp15 processes viral dsRNA, commonly considered as a genome replication intermediate, remains elusive. Previous research has mainly focused on short single-stranded RNA as substrates, and whether nsp15 prefers single-stranded or double-stranded RNA for cleavage is controversial. In the present work, we prepared numerous RNA substrates, including both long substrates mimicking the viral genome and short defined RNA, to clarify the substrate preference and cleavage pattern of SARS-CoV-2 nsp15. We demonstrated that SARS-CoV-2 nsp15 preferentially cleaved flexible pyrimidine nucleotides located in AU-rich areas and mismatch-containing areas in dsRNA via a nicking manner. The AU content and distribution in dsRNA along with the RNA length affected cleavage by SARS-CoV-2 nsp15. Because coronavirus genomes generally have a high AU content, our work supported the mechanism that coronaviruses evade the antiviral response mediated by host cell dsRNA sensors by using nsp15 dsRNA nickase to directly cleave dsRNA intermediates formed during genome replication and transcription.
Choline degradation inParacoccus denitrificans: identification of sources of formaldehyde
Authors: Parekh Trusha , Tsai Marcus , Spiro Stephen 
Published: December 2023

ABSTRACTParacoccus denitrificansis a facultative methylotroph that can grow on methanol and methylamine as sole sources of carbon and energy. Both are oxidized to formaldehyde and then to formate, so growth on C1 substrates induces the expression of genes encoding enzymes required for the oxidation of formaldehyde and formate. This induction involves a histidine kinase response regulator pair (FlhSR) that is likely triggered by formaldehyde. Catabolism of some complex organic substrates (for example choline and L-proline betaine) also generates formaldehyde. Thus,flhSandflhRmutants that fail to induce expression of the formaldehyde catabolic enzymes cannot grow on methanol, methylamine and choline. Choline is oxidized to glycine via glycine betaine, dimethylglycine and sarcosine. By exploringflhSRgrowth phenotypes and the activities of a promoter and enzyme known to be up-regulated by formaldehyde, we identify the oxidative demethylations of glycine betaine, dimethylglycine and sarcosine as sources of formaldehyde. Growth on glycine betaine, dimethylglycine and sarcosine is accompanied by the production of up to three, two and one equivalents of formaldehyde, respectively. Genetic evidence implicates two orthologous monooxygenases in the oxidation of glycine betaine. Interestingly, one of these appears to be a bifunctional enzyme that also oxidizes L-proline betaine (stachydrine). We present preliminary evidence to suggest that growth on L-proline betaine induces expression of a formaldehyde dehydrogenase distinct from the enzyme induced during growth on other formaldehyde-generating substrates.IMPORTANCEThe bacterial degradation of one carbon compounds (methanol and methylamine) and of some complex multi-carbon compounds (for example, choline) generates formaldehyde. Formaldehyde is toxic and must be removed, which can be done by oxidation to formate and then to carbon dioxide. These oxidations provide a source of energy, in some species the CO2thus generated can be assimilated into biomass. Using the Gram-negative bacteriumParacoccus denitrificansas the experimental model, we infer that oxidation of choline to glycine generates up to three equivalents of formaldehyde and we identify the three steps in the catabolic pathway that are responsible. Our work sheds further light on metabolic pathways that are likely important in a variety of environmental contexts.
Discovery of new endogenous viral elements in campoplegine wasps (Ichneumonidae, Campopleginae, Campoplex) suggests a widespread nudivirus domestication event
Authors: de Araujo Alexandra Cerqueira , Leobold Matthieu , Cariou Marie , dos Santos Bernardo Ferreira , Uzbekov Rustem , Ricciardi Renato , Scaramozzino Pierluigi , Lucchi Andrea , Musset Karine , Drezen Jean-Michel , Josse Thibaut , Huguet Elisabeth 
Published: December 2023

AbstractViral endogenization is a widespread phenomenon that generally results in non-functional viral elements. In parasitoid wasps, nudiviruses have been involved in three independent domestication events and play a key role in parasitism success. In Campopleginae (Ichneumonidae), endogenized ichnovirus presence is widespread, with the exception ofVenturia canescens(Ichneumonidae Campopleginae), which is known to harbour an endogenous nudivirus that enables the wasp to produce Virus-Like-Particles (VLPs). So far, in Campopleginae, the nudivirus endogenization event was an isolated case restricted toV. canescens.Using third generation sequencing technologies, microscopy and mass spectrometry, we described new cases of domesticated nudiviruses in campoplegine wasps of the genusCampoplex. We found endogenized viruses inCampoplexgenomes which belong to the Alphanudivrius genus and derive from the same endogenization event as the virus found inV. canescens,suggesting that this integration event could be much more widespread in Campopleginae than previously thought. These nudiviruses are organised in highly conserved clusters, but this organisation appears to have changed relatively to free viruses during the domestication process. We showed thatCampoplex capitatorproduces in its ovaries VLPs that are similar morphologically toV. canescensVLPs, with almost the same protein content, except for a strikingly different virulence proteins, a sign of different evolutionary paths taken to respond to distinct evolutive pressure. While ichnovirus remnants have been previously found inV. canescens, no trace of ichnovirus could be detected inCampoplexgenomes, meaning that the evolutionary history of viral integrations in Campopleginae is more complex than previously imagined.