julilili42/papers huggingface dataset:
A CASE OF ACUTE ZONAL OCCULT OUTER RETINOPATHY UNDER IMMUNOMODULATORY TREATMENT
2024-07-26

Purpose: To describe the clinical course and treatment response of a case of acute zonal occult outer retinopathy. Methods: This is an observational case report. The examinations included ophthalmic examination, longitudinal multimodal imaging, visual field testing, electrophysiologic recordings, serologic analyses, and whole genome sequencing. Results: In this report, the authors present the case of an otherwise healthy 33-year-old woman with bilateral acute zonal occult outer retinopathy manifestation. Other possible causes of the observed retinal lesions were ruled out by extensive diagnostic workup. Treatment with oral prednisolone therapy led to temporal disease control but progression was observed after prednisolone discontinuation. A tapered oral prednisolone therapy in combination with adalimumab initiation prevented further progression for at least 21 months. Conclusion: Diagnosis of acute zonal occult outer retinopathy is frequently complicated by the unspecific symptoms of the disease and significant number of differential diagnoses. Complete diagnostic workup is important to rule out other etiologies. Owing to the lack of randomized controlled trials, therapeutic decisions obligatorily rely on empiric treatment decisions in combination with frequent follow-up examinations.
Atmospheric and Oceanic Pathways Drive Separate Modes of Southern Hemisphere Climate in Simulations of Spontaneous Dansgaard-Oeschger-type Oscillations
2024-07-26

Dansgaard-Oeschger (DO) events are a dominant mode of millennial-scale climate variability during the last glacial period with most pronounced impacts in the North Atlantic region. In Antarctica, they manifest primarily as a muted and phase-shifted temperature signal, but recent studies suggest an additional in-phase component. Here, we analyze the Southern Hemisphere (SH) response to spontaneous DO-type oscillations in a general circulation model. Compared to Greenland temperatures, the dominant Antarctic temperature mode is inverted and delayed by ~275 years, consistent with the bipolar seesaw mechanism. However, the leading SH atmospheric circulation mode varies synchronously with Greenland temperatures. It features zonally heterogeneous anomalies induced by Pacific Walker circulation and SH Hadley cell modulations, with patterns differing notably from the leading modes of interannual variability. Comparison of simulated δ18O with speleothems and ice cores indicates a good agreement in the tropics and SH mid-latitudes but some deviations in Antarctica which warrant further research.
Misunderstanding Equality, Power, and Vulnerability: Elevating the Individual over Cohesion in Hierarchy as a Value
2024-07-26

Abstract This article explores dominant ideas of value at play in a critical incident experienced by international mission candidates on a team placement, in an Anglican community of the United Kingdom. The ethnographic analysis will compare different perspectives on how misunderstanding cultural values and social relations as theological obligations can lead to suffering. Thus, the study shows how qualitative differences in cultural values and social relations determine contrary ways of understanding theological conceptualizations of equality as a Christian idea in contact zones of international mission communities. The analysis challenges two Christian assumptions: firstly, that extending equal value to people before God is universally understood in the same way, and secondly, that individual well-being is inherently superior to ensuring social cohesion, exemplified by Korean hierarchy. Although people realize hierarchy and individualism the world over, the nuances of meaning dominating their relations to other values determine why and how people experience suffering.
A Sonic Vaccine for a White-Collar Disease
2024-07-26

Abstract Members of the Matua religion, a displaced Dalit community from Bengal, believe that the coronavirus can affect only the upper-caste/class layers of society, those who sit in air-conditioned offices and live in the big cities. Matua devotees, on the other hand, are predominantly part of an agriculturist community inhabiting multiple fringes: the borderlands of India and Bangladesh, the peripheries of unorthodox Vaishnavism, and the social margins of untouchability. Conducting remote ethnography with Matua participants based in West Bengal, Bangladesh, and the Andamans, one comes across insistent narratives of immunity and recurrent interpretations of the pandemic that fit into the onto-cosmology and sociocultural imagination of the Matua religious movement. I discuss these as dissident tales of immunity that describe COVID -19 as an urban-based white-collar disease. Matua practitioners successfully prevent it through a sonic vaccine – the practice of kīrtan – and a kind of power ( śakti ) accumulated through physical agricultural labor.
Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts
2024-07-27

Abstract INTRODUCTION Subjective cognitive decline (SCD) in amyloid‐positive (Aβ+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies. METHODS Eight hundred twenty‐one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed‐effects models. RESULTS In the combined and stratified cohorts, Aβ+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aβ− participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings. DISCUSSION Aβ+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials. Highlights SCD in amyloid‐positive (Aβ+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aβ+ older adults with SCD could be a target population for interventional trials.
OCT1 (SLC22A1) transporter kinetics and regulation in primary human hepatocyte 3D spheroids
2024-07-27

Abstract 3D spheroids of primary human hepatocytes (3D PHH) retain a differentiated phenotype with largely conserved metabolic function and proteomic fingerprint over weeks in culture. As a result, 3D PHH are gaining importance as a model for mechanistic liver homeostasis studies and in vitro to in vivo extrapolation (IVIVE) in drug discovery. However, the kinetics and regulation of drug transporters have not yet been assessed in 3D PHH. Here, we used organic cation transporter 1 (OCT1/ SLC22A1 ) as a model to study both transport kinetics and the long-term regulation of transporter activity via relevant signalling pathways. The kinetics of the OCT1 transporter was studied using the fluorescent model substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) and known OCT1 inhibitors in individual 3D PHH. For long-term studies, 3D PHH were treated with xenobiotics for seven days, after which protein expression and OCT1 function were assessed. Global proteomic analysis was used to track hepatic phenotypes as well as prototypical changes in other regulated proteins, such as P-glycoprotein and Cytochrome P450 3A4. ASP+ kinetics indicated a fully functional OCT1 transporter with a K m value of 14 ± 4.0μM as the mean from three donors. Co-incubation with known OCT1 inhibitors decreased the uptake of ASP+ in the 3D PHH spheroids by 35–52%. The long-term exposure studies showed that OCT1 is relatively stable upon activation of nuclear receptor signalling or exposure to compounds that could induce inflammation, steatosis or liver injury. Our results demonstrate that 3D PHH spheroids express physiologically relevant levels of fully active OCT1 and that its transporter kinetics can be accurately studied in the 3D PHH configuration. We also confirm that OCT1 remains stable and functional during the activation of key metabolic pathways that alter the expression and function of other drug transporters and drug-metabolizing enzymes. These results will expand the range of studies that can be performed using 3D PHH.
Michael Hatzakis, semiconductor industry pioneer
2024-07-27

Although this opinion paper tracks the career of Mike Hatzakis (as he liked to be called), and explains the impact he made on the IT industry, it is not intended to be comprehensive insofar as the work that was underway during his career is concerned. Thus, the intent is not to cite all relevant work in the field of Semiconductor lithography, where Mike made such an impact, but to provide a historic and human perspective of this remarkable man from the land of the Minotaur (Crete) and his career, the work he championed in his labs in the US and later Greece and his very human approach to science, technology, and to people.Unlabelled Image
A red button does it all: An adaptive notification badge to nudge students to close their knowledge gaps in intelligent tutoring systems
2024-07-27

Background: Intelligent tutoring systems (ITSs) often adaptively provide students with additional learning materials to close knowledge gaps recognized automatically by the system. In addition, students may be nudged with adaptive notification badges to close their knowledge gaps. Aim: This study evaluated the effectiveness of implementing an adaptive notification badge (small red button) reminding students to close their knowledge gaps. We also investigated the association between closing knowledge gaps and students’ overall performance, while controlling for other relevant factors (e.g., students’ usage behavior, system features, and teachers’ assignment types).Sample: We considered 105,081 students (in 6,668 classes working on ~25 million problems) who used an ITS for learning mathematics.Methods: We employed hierarchical linear regression analysis to evaluate whether students were more likely to close their knowledge gaps in a period in which notification badges were implemented in the ITS, as compared to a period without notification badges. Moreover, we used psychological network analysis to evaluate whether closing knowledge gaps was associated with students’ performance relative to other relevant factors.Results: Students closed 28% of their knowledge gaps when the adaptive red button notification badge nudged them but only closed 5% when there was no red button. Closing knowledge gaps predicted better student performance and was a more important predictor than students’ usage behavior, other system features, and teachers’ assignment types.Conclusions: Our study highlights the relevance of adaptive nudges within ITS for closing knowledge gaps and shows that closing knowledge gaps is linked to students’ performance.
Environmental versus litter traits as drivers of microbial decomposer functions
2024-07-28

Abstract Plant litter decomposition is a key ecosystem process with significant implications for global carbon cycling, soil fertility and plant productivity. Given that microbial decomposers are the main players in the decomposition process, it is surprising how little is known about their functional diversity in different habitats or their ability to respond to environmental changes. To fill this knowledge gap, we conducted a litterbag decomposition experiment along a pronounced climate and vegetation gradient in the Chilean Coastal Cordillera (26°S to 38°S), ranging from hyper-arid to temperate, using mixtures of four plant species, native to the respective ecosystems. We analyzed potential decomposition functions of bacterial and fungal litter communities along with their biotic (litter traits) and abiotic (meteorological conditions and soil properties) environments, to determine the relative importance of these environmental factors for microbial community functioning. We also tested the impact of the functional diversity of the decomposer communities (i.e., the diversity of decomposition related functions) on litter mass loss. Functional composition was related most strongly to the temporal variation of precipitation and radiation, explaining about 19 % and 6 % of variation in bacteria and fungi, respectively. In contrast, functional diversity was quite strongly related to litter chemical traits (C:N, C:P, tannins, phenols). Litter mass loss after six months of decomposition was not correlated to the functional diversity of decomposer communities but increased with the presence of habitat generalists like Proteobacteria , Actinobacteria , Firmicutes , and Bacteroidetes . Taken together, these results highlight i) the interplay between abiotic factors and chemical litter traits on litter microbial functions and functional diversity and ii) the importance of microbial generalists for litter decomposition across different ecosystems. These results enhance our ability to predict changes in microbial decomposer communities and litter decomposition under future climate-change scenarios.
The Santa Barbara Binary−disk Code Comparison
2024-07-29

Abstract We have performed numerical calculations of a binary interacting with a gas disk, using 11 different numerical methods and a standard binary−disk setup. The goal of this study is to determine whether all codes agree on a numerically converged solution and to determine the necessary resolution for convergence and the number of binary orbits that must be computed to reach an agreed-upon relaxed state of the binary−disk system. We find that all codes can agree on a converged solution (depending on the diagnostic being measured). The zone spacing required for most codes to reach a converged measurement of the torques applied to the binary by the disk is roughly 1% of the binary separation in the vicinity of the binary components. For our disk model to reach a relaxed state, codes must be run for at least 200 binary orbits, corresponding to about a viscous time for our parameters, 0.2( a 2 Ω B / ν ) binary orbits, where ν is the kinematic viscosity. The largest discrepancies between codes resulted from the dimensionality of the setup (3D vs. 2D disks). We find good agreement in the total torque on the binary between codes, although the partition of this torque between the gravitational torque, orbital accretion torque, and spin accretion torque depends sensitively on the sink prescriptions employed. In agreement with previous studies, we find a modest difference in torques and accretion variability between 2D and 3D disk models. We find cavity precession rates to be appreciably faster in 3D than in 2D.
Multi-omics analysis of overexpressed tumor-associated proteins: gene expression, immunopeptide presentation, and antibody response in oropharyngeal squamous cell carcinoma, with a focus on cancer-testis antigens
2024-07-29

Introduction The human leukocyte antigen complex (HLA) is essential for inducing specific immune responses to cancer by presenting tumor-associated peptides (TAP) to T cells. Overexpressed tumor associated antigens, mainly cancer-testis antigens (CTA), are outlined as essential targets for immunotherapy in oropharyngeal squamous cell carcinoma (OPSCC). This study assessed the degree to which presentation, gene expression, and antibody response (AR) of TAP, mainly CTA, are correlated in OPSCC patients to evaluate their potential as immunotherapy targets. Materials and methods Snap-frozen tumor (N Ligand/RNA =40), healthy mucosa (N RNA =6), and healthy tonsils (N Ligand =5) samples were obtained. RNA-Seq was performed using Illumina HiSeq 2500/NovaSeq 6000 and whole exome sequencing (WES) utilizing NextSeq500. HLA ligands were isolated from tumor tissue using immunoaffinity purification, UHPLC, and analyzed by tandem MS. Antibodies were measured in serum (N Ab =27) utilizing the KREXTM CT262 protein array. Data analysis focused on 312 proteins (KREXTM CT262 panel + overexpressed self-proteins). Results 183 and 94 of HLA class I and II TAP were identified by comparative profiling with healthy tonsils. Genes from 26 TAP were overexpressed in tumors compared to healthy mucosa (LFC&amp;gt;1; FDR&amp;lt;0.05). Low concordance (r=0.25; p&amp;lt;0.0001) was found between upregulated mRNA and class I TAP. The specific mode of correlation of TAP was found to be dependent on clinical parameters. A lack of correlation was observed both between mRNA and class II TAP, as well as between class II tumor-unique TAP (TAP-U) presentation and antibody response (AR) levels. Discussion This study demonstrates that focusing exclusively on gene transcript levels fails to capture the full extent of TAP presentation in OPSCC. Furthermore, our findings reveal that although CTA are presented at relatively low levels, a few CTA TAP-U show potential as targets for immunotherapy.
Probing the polarized photon content of the proton in ep collisions at the EIC
2024-07-29

We study the single-inclusive production of prompt photons in electron-proton collisions, <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" display="inline"><a:mrow><a:mi>e</a:mi><a:mi>p</a:mi><a:mo stretchy="false">→</a:mo><a:mi>γ</a:mi><a:mi>X</a:mi></a:mrow></a:math>, for kinematics relevant at the Electron-Ion Collider (EIC). We perform a perturbative calculation of the differential cross section to next-to-leading order in QCD and to lowest order in QED. We consider unpolarized collisions as well as scattering of longitudinally polarized incident electrons and protons. We show that the cross sections are sensitive to the parton distribution functions of photons inside the proton, which we find to generate the dominant contributions in certain kinematical regions at the EIC. We also investigate the effects of photon isolation on the unpolarized and polarized cross sections. Published by the American Physical Society 2024
A novel mutation in SETX and ATM causes ataxia in consanguineous Pakistani families
2024-07-29

Background &amp; Objectives: Ataxia is usually caused by cerebellar pathology or a decrease in vestibular or proprioceptive afferent input to the cerebellum. It is characterized by uncoordinated walking, truncal instability, body or head tremors, uncontrolled coordination of the hands, dysarthria, and aberrant eye movements. The objective of the current investigation was to identify the underlying genetic cause of the hereditary ataxia that affects the Pakistani population. Methods: We studied numerous consanguineous Pakistani families whose members had ataxia-related clinical symptoms to varying degrees. The families were chosen from the Punjab province, and the neurophysician conducted a clinical examination. Peripheral blood samples from both sick and healthy members of the family were taken after obtaining informed consent. Genomic DNA was used to find potential variations in probands using whole exome sequencing. The study was carried out at the University Hospital of Tübingen, Germany, and Government College University in Faisalabad, Pakistan, during 2018-2023. Results: The molecular analysis of these families identified different variants including SGCB: c.902C&gt;T, c.668G&gt;A, ATM: c.6196_6197insGAA, SPG11: c.5769del, SETX c.5525_5533del, and ATM: c.7969A&gt;T. A noteworthy mutation in ATM and SETX was observed among them, and its symptoms were shown to cause ataxia in these families. Conclusion: The current study broadens the mutation spectrum of several hereditary ataxia types and suggests the next generation sequencing in conjunction with clinical research for a more accurate diagnosis of overlapping phenotypes of this disorder in the Pakistani population. doi: https://doi.org/10.12669/pjms.40.8.9246 How to cite this: Akram R, Baig SM, Anwar H, Hussain G. A novel mutation in SETX and ATM causes ataxia in consanguineous Pakistani families. Pak J Med Sci. 2024;40(8):---------. doi: https://doi.org/10.12669/pjms.40.8.9246 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Mineralogical and Geochemical Response to Fluid Infiltration into Cambrian Orthopyroxene-Bearing Granitoids and Gneisses, Dronning Maud Land, Antarctica
2024-07-29

Fluid infiltration into Proterozoic and Early Palaeozoic dry, orthopyroxene-bearing granitoids and gneisses in Dronning Maud Land, Antarctica, has caused changes to rock appearance, mineralogy, and rock chemistry. The main mineralogical changes are the replacement of orthopyroxene by hornblende and biotite, ilmenite by titanite, and various changes in feldspar structure and composition. Geochemically, these processes resulted in general gains of Si, mostly of Al, and marginally of K and Na but losses of Fe, Mg, Ti, Ca, and P. The isotopic oxygen composition (δ18OSMOW = 6.0‰–9.9‰) is in accordance with that of the magmatic precursor, both for the host rock and infiltrating fluid. U-Pb isotopes in zircon of the altered and unaltered syenite to quartz-monzonite indicate a primary crystallization age of 520.2 ± 1.0 Ma, while titanite defines alteration at 485.5 ± 1.4 Ma. Two sets of gneiss samples yield a Rb-Sr age of 517 ± 6 Ma and a Sm-Nd age of 536 ± 23 Ma. The initial Sr and Nd isotopic ratios suggest derivation of the gneisses from a relatively juvenile source but with a very strong metasomatic effect that introduced radiogenic Sr into the system. The granitoid data indicate instead a derivation from Mid-Proterozoic crust, probably with additions of mantle components.
Diverging Development Paths between China and the West during the Early Modern Period: the Example of the Suction-Lift Pump
2024-07-29

Abstract The need to lift water by means of appropriate equipment is a global phenomenon and has preoccupied all cultures since earliest times. While most basic methods (for example, the bailing with some kind of container by means of a sweep well or a windlass) were shared all over the world, local conditions and crafting skills produced regional developments of more sophisticated devices. This essay examines the impact of the strategically motivated Jesuit transfer of knowledge about the suction-lift pump from the West to China in the early seventeenth century. There, in the face of constant drought disasters, more efficient implements to get hold of well water would seem to have been desperately needed. The nevertheless sluggish adoption of this innovative, though not yet fully mature, hydraulic technology by the responsible Chinese scholar-officials highlights some of the reasons for the emergence of the Great Divergence between China and the West.