bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2Δ16 Engages ENPP1 to Promote an Immune-Cold Microenvironment in Breast Cancer
Authors: Attalla Sherif Samer , Boucher Jonathan , Proud Hailey , Taifour Tarek , Zuo Dongmei , Sanguin-Gendreau Virginie , Ling Chen , Johnson Gabriella , Li Vincent , Luo Robin B. , Kuasne Hellen , Papavasiliou Vasilios , Walsh Logan A. , Barok Mark , Joensuu Heikki , Park Morag , Roux Philippe P. , Muller William J. 
Published: June 2023

AbstractThe tumor–immune microenvironment (TIME) is a critical determinant of therapeutic response. However, the mechanisms regulating its modulation are not fully understood. HER2Δ16, an oncogenic splice variant of the HER2, has been implicated in breast cancer and other tumor types as a driver of tumorigenesis and metastasis. Nevertheless, the underlying mechanisms of HER2Δ16-mediated oncogenicity remain poorly understood. Here, we show that HER2∆16 expression is not exclusive to the clinically HER2+ subtype and associates with a poor clinical outcome in breast cancer. To understand how HER2 variants modulated the tumor microenvironment, we generated transgenic mouse models expressing either proto-oncogenic HER2 or HER2Δ16 in the mammary epithelium. We found that HER2∆16 tumors were immune cold, characterized by low immune infiltrate and an altered cytokine profile. Using an epithelial cell surface proteomic approach, we identified ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) as a functional regulator of the immune cold microenvironment. We generated a knock-in model of HER2Δ16 under the endogenous promoter to understand the role of Enpp1 in aggressive HER2+ breast cancer. Knockdown of Enpp1 in HER2Δ16-derived tumor cells resulted in decreased tumor growth, which correlated with increased T-cell infiltration. These findings suggest that HER2Δ16-dependent Enpp1 activation associates with aggressive HER2+ breast cancer through its immune modulatory function. Our study provides a better understanding of the mechanisms underlying HER2Δ16-mediated oncogenicity and highlights ENPP1 as a potential therapeutic target in aggressive HER2+ breast cancer.
β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer
Authors: Suzuki Toshiyasu , Kilbey Anna , Casa-Rodríguez Nuria , Lawlor Amy , Georgakopoulou Anastasia , Hayman Hannah , Yin Swe Kyi Lai , Nordin Anna , Cantù Claudio , Vantourout Pierre , Ridgway Rachel A. , Byrne Ryan M. , Chen Lei , Verzi Michael P. , Gay David M. , Gil Vázquez Ester , Belnoue-Davis Hayley L. , Gilroy Kathryn , Køstner Anne Helene , Kersten Christian , Thuwajit Chanitra , Andersen Ditte K. , Wiesheu Robert , Jandke Anett , Blyth Karen , Roseweir Antonia K. , Leedham Simon J. , Dunne Philip D. , Edwards Joanne , Hayday Adrian , Sansom Owen J. , Coffelt Seth B. 
Published: June 2023

Abstract
Intraepithelial lymphocytes (IEL) expressing γδ T-cell receptors (γδTCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immunosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic γδIELs. In contrast with healthy intestinal or colonic tissue, we found that γδIELs were largely absent from the microenvironment of both mouse and human tumors, and that butyrophilin-like (BTNL) molecules, which can critically regulate γδIEL through direct γδTCR interactions, were also downregulated in tumors. We then demonstrated that β-catenin activation through loss of Apc rapidly suppressed expression of the mRNA encoding the HNF4A and HNF4G transcription factors, preventing their binding to promoter regions of Btnl genes. Reexpression of BTNL1 and BTNL6 in cancer cells increased γδIEL survival and activation in coculture assays but failed to augment their cancer-killing ability in vitro or their recruitment to orthotopic tumors. However, inhibition of β-catenin signaling via genetic deletion of Bcl9/Bcl9L in either Apc-deficient or mutant β-catenin mouse models restored Hnf4a, Hnf4g, and Btnl gene expression and γδ T-cell infiltration into tumors. These observations highlight an immune-evasion mechanism specific to WNT-driven colon cancer cells that disrupts γδIEL immunosurveillance and furthers cancer progression.
Air Conditioner, or Revolutionary Cinema without a
Future
Authors: Hamblin Sarah 
Published: June 2023

Abstract
This essay is an effort to imagine new modes of revolutionary cinema in the age of the Capitalocene. Starting from the premise that the environmental volatility of this new epoch forces us to fundamentally reconsider the basic tenets of the revolutionary imagination, the essay asks what radical transformation looks like when we abandon earlier modes of resistance and visions of the future that are wedded to anthropocentric fantasies of humanity's sovereignty over nature and the promises of petromodernity. To begin answering this question, the text takes up the lo-fi Angolan Africanfuturist film Air Conditioner (Fradique 2020). Set in Luanda, Angola, where air-conditioning units across the city suddenly begin failing and falling from windows, the film dramatizes the problems of technological collapse combined with a rapidly warming climate. Resigning the legacies of colonialism and the nation's protracted conflict between communist and capitalist forces to the decaying infrastructural backdrop of the film, Air Conditioner is instead concerned with the new modes of solidarity and ideas of futurity that emerge from within these conditions of catastrophe. The film's incidental references to socialism, combined with its meandering narrative and languid pace, render it quite different in form and tone from the revolutionary anti-colonial cinemas of independence. Thus, against earlier images of revolution as a sudden rupture that harnesses the twin powers of industrialization and human agency, Air Conditioner roots itself in slowness, imagining revolution as a process of withdrawal based on the wearing out of life.
Development of Anatomic Risk Factors for ACL Injuries: A Comparison Between ACL-Injured Knees and Matched Controls
Authors: Pradhan Pratik , Kaushal Shankar G. , Kocher Mininder S. , Kiapour Ata M. 
Published: June 2023

Background: Several tibiofemoral anatomic features have been repeatedly associated with increased anterior cruciate ligament (ACL) injury risk. Previous studies have highlighted age and sex differences among these anatomic risk factors, but little is known about the normal and pathologic development of these differences during skeletal maturation. Purpose: To investigate differences in anatomic risk factors at various stages of skeletal maturation between ACL-injured knees and matched controls. Study Design: Cross-sectional study; Level of evidence, 3. Methods: After institutional review board approval, magnetic resonance imaging scans from 213 unique ACL-injured knees (age, 7-18 years, 48% female) and 239 unique asymptomatic ACL-intact knees (age, 7-18 years, 50% female) were used to measure femoral notch width, posterior slope of the lateral and medial tibial plateau, medial and lateral tibial spinal height (MTSH, LTSH), medial tibial depth, and posterior lateral meniscus-bone angle. Linear regression was performed to assess change in quantified anatomic indices with age for male and female patients in the ACL-injured cohort. Two-way analysis of variance with Holm-Sidak post hoc testing was performed to compare anatomic indices between ACL-injured knees and ACL-intact controls in each age group. Results: In the ACL-injured cohort, notch width, notch width index and medial tibial depth increased with age ( R2 > 0.1; P < .001) in both sexes. MTSH and LTSH increased with age only in boys ( R2≥ 0.09; P≤ .001), whereas meniscus-bone angle decreased with age only in girls ( R2 = 0.13; P < .001). There were no other age differences in quantified anatomic indices. Patients with ACL injury consistently had a significantly higher lateral tibial slope ( P < .01) and smaller LTSH ( P < .001) as compared with ACL-intact controls across all age groups and sexes. When compared with age- and sex-matched ACL-intact controls, ACL-injured knees had a smaller notch width (boys, 7-18 years; girls, 7-14 years; P < .05), larger medial tibial slope (boys and girls, 15-18 years; P < .01), smaller MTSH (boys, 7-14 years; girls, 11-14 years; P < .05), and larger meniscus-bone angle (girls, 7-10 years; P = .050). Conclusion: The consistent morphologic differences throughout skeletal growth and maturation suggest a developmental role in high-risk knee morphology. The observed high-risk knee morphology at an earlier age preliminarily suggests the potential of knee anatomy measurements in identifying those with a predisposition toward ACL injury.
Concomitant Triceps Surae Lengthening in Total Ankle Arthroplasty Affects the Mechanical Work at the Ankle Joint
Authors: Deleu Paul-André , Naaim Alexandre , Chèze Laurence , Dumas Raphaël , Devos Bevernage Bernhard , Birch Ivan , Leemrijse Thibaut , Besse Jean-Luc 
Published: June 2023

Background: Previous studies have examined the effect of concomitant triceps surae lengthening on ankle dorsiflexion motion at the time of total ankle arthroplasty (TAA). As plantarflexor muscle-tendon structures are important for producing positive ankle work during the propulsive phase of gait, caution should be exercised when lengthening triceps surae, as it may decrease plantarflexion strength. In order to develop an understanding of the work of the anatomical structures crossing the ankle during propulsion, joint work must be measured. The aim of this explorative study was to assess the effect of concomitant triceps surae lengthening with TAA on the resultant ankle joint work. Methods: Thirty-three patients were recruited to the study and divided into 3 groups of 11. The first group underwent both triceps surae lengthening (Strayer and TendoAchilles) and TAA (Achilles group), the second group underwent only TAA (Non-Achilles group), and the third group underwent only TAA, but had a greater radiographic prosthesis range of motion (Control group) compared to the first 2 groups. The 3 groups were matched in terms of demographic variables and walking speed. All patients underwent a 3D gait analysis 1 year after surgery to measure intersegmental joint work using a 4-segmented kinetic foot model. An analysis of variance (ANOVA) or Kruskal-Wallis test was used to compare the 3 groups. Results: The ANOVA showed significant differences between the 3 groups. Post hoc analyses suggested that (1) the Achilles group had less positive work at the ankle joint than the Non-Achilles and Control groups; (2) the Achilles group produced less positive work performed by all foot and ankle joints than the Control group; and (3) the Achilles and Non-Achilles groups absorbed less energy across all foot and ankle joints during the stance phase than the Control group. Conclusion: Concomitant triceps surae lengthening in TAA may reduce the positive work at the ankle joint. Level of Evidence: Level III, retrospective comparative study.
A rare case of hyperpigmented torpedo maculopathy
Authors: Chitturi Sai Prashanti , Venkatesh Ramesh , Handa Ashit , Mangla Rubble , Chhablani Jay 
Published: June 2023

Purpose To describe a rare presentation of torpedo maculopathy (TM). Case description A 25-year-old male was examined in the retina clinic for a macular scar in the left eye. His visual acuity was 20/20, N6 in both eyes and no past history of ocular trauma or any medical or ocular history. The anterior segment was quiet and intraocular pressure was normal. Results The patient's left eye on 78D slit lamp biomicroscopy revealed a flat, diffusely hyperpigmented fusiform torpedo-like lesion with sharp margins and surrounding hypopigmentation located predominantly temporal to the fovea, with its tip pointing towards it and just crossing the vertical foveal midline. Dilated fundus examination with binocular indirect ophthalmoscopy revealed no peripheral chorioretinal lesions or vitritis in both eyes. OCT scan through the lesion revealed gross damage to the outer retinal layers, as well as thickening of the retinal pigment epithelium and underlying shadowing, as well as a hyporeflective subretinal cleft involving the lesion. OCT also revealed outer retinal layer damage with an intact retinal pigment epithelium through the lesion's hypopigmented margins. Fundus autofluorescence image revealed a globally hypoautofluorescent lesion in the left eye, with surrounding patchy hyperautofluoroscent areas. Based on the patient history, clinical and imaging findings, other differential diagnoses such as atypical congenital hypertrophy of retinal pigment epithelium (RPE), choroidal nevus, RPE hamartoma, trauma and inflammatory conditions were ruled out. The diagnosis of TM was confirmed based on the typical lesion shape and location. Conclusion A torpedo lesion with diffuse hyperpigmentation is an unusually rare presentation.
Kommerell’s Diverticulum in a Right-Sided Aortic Arch With an Aberrant Left Subclavian Artery Hybrid Repair
Authors: Solano Antonio , Pizano Alejandro , Azam Jawaher , Gonzalez-Guardiola Gerardo , Siah Michael , Chamseddin Khalil , Prakash Vivek , Kirkwood Melissa L. , Shih Michael 
Published: June 2023

Background Kommerell’s diverticulum (KD) with a right aortic arch (RAA) and aberrant left subclavian artery (aLSCA) is a rare congenital anomaly of the aortic arch. Treatment is not well defined due to its uncommon presentation, with rupture and dissection risk rates of up to 53%. Case summary A 54-year-old male with a history of chronic obstructive pulmonary disease (COPD) and hypertension presented with difficulty breathing during exercise without dysphagia. Follow-up computerized tomography angiogram (CTA) revealed the presence of a RAA and aLSCA arising from the descending thoracic aorta with an adjacent 58 × 41-mm KD and tracheal and esophageal displacement. Due to the size of the KD, risk of rupture, unsuitable anatomy for total endovascular aortic repair (EVAR), and high COPD burden, the patient was planned to undergo a hybrid surgical repair. Left common carotid (LCCA) artery to LSCA bypass, full aortic debranching, LSCA embolization and percutaneous thoracic endovascular aortic repair (TEVAR) were performed. Successful device position and exclusion of the diverticulum and aneurysmal aorta were observed after completion thoracic aortogram. 18-month follow-up CTA demonstrated patency of the LSCA to LCCA bypass graft and arch vessel branches, as well as stable exclusion of the KD. Persistence of a type II endoleak originated at the right first posterior intercostal artery has been noted and is being followed conservatively since no sac growth has occurred. Conclusion We highlight the presence of a KD with RAA and aberrant subclavian artery, a rare congenital anatomic variation of the aortic arch with complex anatomy. Surgical planning must be individualized according to comorbidities and anatomical variations identified on imaging and 3D reconstructions.
Clinical Outcomes After Arthroscopic Microfracture Treatment of Coexisting Talar and Tibial Osteochondral Lesions
Authors: Wei Yu , Yun Xing , Song Jianing , Qi Wei , Li Jia , Liu Yujie , Quan Qi , Wei Min 
Published: June 2023

Background: Despite increased recognition of coexisting tibial and talar osteochondral lesions (OCLs), the risk factors influencing clinical outcomes remain unclear. Purpose: To report clinical follow-up results after arthroscopic microfracture surgery in patients with OCLs of the distal tibial plafond and talus and assess possible factors affecting these clinical outcomes. Study Design: Case series; Level of evidence, 4. Methods: A total of 40 patients with coexisting talar and tibial OCLs who underwent arthroscopic microfracture surgery were included. For analysis, the study used the American Orthopaedic Foot & Ankle Society (AOFAS) scale, Karlsson-Peterson scale, and visual analog scale (VAS) for pain for clinical evaluations on the day before surgery, 12 months after surgery, and at the last follow-up. A stepwise regression model and Spearman rank correlation were used to assess possible factors affecting these clinical outcomes. Results: The median follow-up time was 34.5 months (interquartile range [IQR], 26.5-54 months). At the final follow-up, the cohort included 40 patients (26 men and 14 women) with a mean age of 38.8 years (range, 19-60 years). The median AOFAS score increased from 57.5 (IQR, 47-65) before surgery to 88 (IQR, 83-92.5) at the final follow-up, the median Karlsson-Peterson score increased from 48 (IQR, 38.5-67) to 82 (IQR, 76-92), and the median VAS score improved from 5 (IQR, 4-6) to 1 (IQR, 0-2). All scale scores showed significant differences between the preoperative and final follow-up evaluations ( P < .001). In the stepwise regression model and Spearman rank correlation analysis, the grade of tibial OCL had a significant independent effect on the final postoperative AOFAS scores of the patients (β = –0.502, P = .001; r = –0.456, P = .003). The size of the tibial lesion also had a significant independent effect on the final postoperative Karlsson-Peterson scores of the patients (β = –0.444, P = .004; r = –0.357, P = .024). Conclusion: Arthroscopic microfracture treatment for coexisting talar and tibial OCLs can achieve good short- to midterm clinical outcomes. The grade and size of tibial OCLs are the main risk factors affecting the prognostic functional scores of such patients.
SBMLKinetics: a tool for annotation-independent classification of reaction kinetics for SBML models
Authors: Xu Jin 
Published: June 2023

Abstract

Background

Reaction networks are widely used as mechanistic models in systems biology to reveal principles of biological systems. Reactions are governed by kinetic laws that describe reaction rates. Selecting the appropriate kinetic laws is difficult for many modelers. There exist tools that attempt to find the correct kinetic laws based on annotations. Here, I developed annotation-independent technologies that assist modelers by focusing on finding kinetic laws commonly used for similar reactions.

Results

Recommending kinetic laws and other analyses of reaction networks can be viewed as a classification problem. Existing approaches to determining similar reactions rely heavily on having good annotations, a condition that is often unsatisfied in model repositories such as BioModels. I developed an annotation-independent approach to find similar reactions via reaction classifications. I proposed a two-dimensional kinetics classification scheme (2DK) that analyzed reactions along the dimensions of kinetics type (K type) and reaction type (R type). I identified approximately ten mutually exclusive K types, including zeroth order, mass action, Michaelis–Menten, Hill kinetics, and others. R types were organized by the number of distinct reactants and the number of distinct products in reactions. I constructed a tool, SBMLKinetics, that inputted a collection of SBML models and then calculated reaction classifications as the probability of each 2DK class. The effectiveness of 2DK was evaluated on BioModels, and the scheme classified over 95% of the reactions.

Conclusions

2DK had many applications. It provided a data-driven annotation-independent approach to recommending kinetic laws by using type common for the kind of models in combination with the R type of the reactions. Alternatively, 2DK could also be used to alert users that a kinetic law was unusual for the K type and R type. Last, 2DK provided a way to analyze groups of models to compare their kinetic laws. I applied 2DK to BioModels to compare the kinetics of signaling networks with the kinetics of metabolic networks and found significant differences in K type distributions.
Evaluating significance of European-associated index SNPs in the East Asian population for 31 complex phenotypes
Authors: Qiao Jiahao , Wu Yuxuan , Zhang Shuo , Xu Yue , Zhang Jinhui , Zeng Ping , Wang Ting 
Published: June 2023

Abstract
Background
Genome-wide association studies (GWASs) have identified many single-nucleotide polymorphisms (SNPs) associated with complex phenotypes in the European (EUR) population; however, the extent to which EUR-associated SNPs can be generalized to other populations such as East Asian (EAS) is not clear.

Results
By leveraging summary statistics of 31 phenotypes in the EUR and EAS populations, we first evaluated the difference in heritability between the two populations and calculated the trans-ethnic genetic correlation. We observed the heritability estimates of some phenotypes varied substantially across populations and 53.3% of trans-ethnic genetic correlations were significantly smaller than one. Next, we examined whether EUR-associated SNPs of these phenotypes could be identified in EAS using the trans-ethnic false discovery rate method while accounting for winner's curse for SNP effect in EUR and difference of sample sizes in EAS. We found on average 54.5% of EUR-associated SNPs were also significant in EAS. Furthermore, we discovered non-significant SNPs had higher effect heterogeneity, and significant SNPs showed more consistent linkage disequilibrium and allele frequency patterns between the two populations. We also demonstrated non-significant SNPs were more likely to undergo natural selection.

Conclusions
Our study revealed the extent to which EUR-associated SNPs could be significant in the EAS population and offered deep insights into the similarity and diversity of genetic architectures underlying phenotypes in distinct ancestral groups.
Assessment of the first presentations of common variable immunodeficiency in a large cohort of patients
Authors: Esmaeilzadeh Hossein , Jokar-Derisi Armita , Hassani Amir Hossein , Yazdani Reza , Delavari Samaneh , Abolhassani Hassan , Mortazavi Negar , Askarisarvestani Aida 
Published: June 2023

Abstract
Background
Common Variable Immunodeficiency (CVID) is a primary immunodeficiency syndrome resulting in recurrent infections, autoimmunity, and granulomatous manifestations.

Methods and materials
This retrospective study was conducted on an Iranian national registry of immunodeficient patients from 2010 to 2021. The frequency of first presentations of CVID and its association with sex, age of onset, and family history of CVID was evaluated.

Results
A total of 383 patients entered the study, 164 of whom were female, and the rest were male. The mean age of the patients was 25.3 ± 14.5 years. The most frequent first presentations of CVID were pneumonia (36.8%) and diarrhea (19.1%). Patient sex, age of onset, and family history did not make significant differences in first presentations of this disease.

Conclusion
pneumonia is the most common first presentation of CVID. Family history of CVID, the age of symptom onset, and sex made no differences in the first presentations of CVID.