bluuebunny/crossref_metadata_2025_split huggingface dataset:
A real-world prospective cohort study of immunogenicity and reactogenicity of ChAdOx1-S[recombinant] among patients with immune-mediated dermatological diseases
Authors: Chanprapaph Kumutnart , Seree-aphinan Chutima , Rattanakaemakorn Ploysyne , Pomsoong Cherrin , Ratanapokasatit Yanisa , Setthaudom Chavachol , Thitithanyanont Arunee , Suriyo Aphinyaphiwat , Suangtamai Thanitta , Suchonwanit P ,   the COVIDVAC-DERM study group
Published: January 2023

Abstract

Background
Immunogenicity and reactogenicity of COVID-19 vaccines have been established in various groups of immunosuppressed patients; however, studies involving patients with immune-mediated dermatological diseases (IMDDs) are scarce.

Objectives
To investigate the influence of IMDDs on the development of SARS-CoV-2-specific immunity and side-effects following ChAdOx1-S[recombinant] vaccination.

Methods
This prospective cohort study included 127 patients with IMDDs and 97 participants without immune-mediated diseases who received ChAdOx1-S[recombinant]. SARS-CoV-2-specific immunity and side-effect profiles were assessed at 1 month postvaccination and compared between groups. Immunological (primary) outcomes were the percentages of participants who tested positive for neutralizing antibodies [seroconversion rate (SR)] and those who developed T-cell-mediated immunity demonstrated by an interferon-γ-releasing assay (IGRA) [positive IGRA rate (+IGRA)]. Reactogenicity-related (secondary) outcomes were the unsolicited adverse reactions and worsening of IMDD activity reflected by the uptitration of immunosuppressants during and within 1 month of vaccination.

Results
Overall, the SR for the IMDD group was similar to that of participants without immune-mediated conditions (75·6 vs. 84·5, P = 0·101), whereas + IGRA was lower (72·4 vs. 88·7, P = 0·003). Reactogenicity was similar between groups. No severe adverse reaction was reported. By stratifying the participants in the IMDD group according to individual disease, the immunogenicity of the vaccine was lowest in patients with autoimmune bullous diseases (AIBD) (SR 64·5%, +IGRA 62·9%) and highest in patients with psoriasis (SR 87·7%, +IGRA 80·7%). The reverse trend was found for vaccine-related reactions. Immunosuppressants were uptitrated in 15·8% of cases; 75% of these were patients with AIBD.

Conclusions
Among participants with IMDDs, ChAdOx1-S[recombinant] showed good immunogenicity among patients with psoriasis, but demonstrated lower levels of immunogenicity for patients with AIBD. Some patients, especially patients with AIBD, should be closely monitored as they may require treatment escalation within 1 month postvaccination.
Exploring disease comorbidities and temporal disease progression of psoriasis: an observational, retrospective, multi-database, cohort study
Authors: Rosenø Nana A L , Lørup Erik Hillo , Richardson Craig , Alarcon Ivette , Egeberg Alexander  
Published: January 2023

Abstract

Background
Comorbidities associated with psoriasis are well documented. However, few studies have explored the comorbidity trajectories that patients with psoriasis commonly experience over time. This study reports the 5-year comorbidity trajectories of patients with psoriasis.

Objectives
To determine the long-term comorbidity trajectories of patients with psoriasis in Denmark.

Methods
This observational cohort study explored the Danish National Patient Registry (DNPR) between 1999 and 2013 to identify comorbidities diagnosed 5 years prior to or after a psoriasis diagnosis. Comorbidity occurrence in patients with psoriasis (psoriasis cohort) was compared with patients without psoriasis (the N group). Comparison groups, each the same size as the psoriasis cohort, were created by selecting random patients from the N group. If a comorbidity occurrence was higher in more than nine comparison groups than in the psoriasis cohort, it was not analysed and only comorbidities that occurred in ≥ 0·8% of the psoriasis cohort were analysed. The strength of association between a psoriasis diagnosis and a comorbidity diagnosis was measured using relative risk (RR). All psoriasis and comorbidity pairs that achieved RR &gt; 1 (P &lt; 0·001) (known as a Diagnosed Pair) were tested for directionality to identify the sequence of diagnoses using a binomial test. Diagnosed Pairs with a statistically significant direction (Bonferroni corrected P-value &lt; 0·025) were then used to create comorbidity trajectory clusters 5 years before and after a psoriasis diagnosis.

Results
A total of 17 683 patients with psoriasis were compared with 10 000 comparison groups. A total of 121 comorbidities met the minimum criteria that ≥ 0·8% of the psoriasis cohort were diagnosed with the comorbidity within 5 years (before or after) of their psoriasis diagnosis. Thirty-eight of these comorbidities achieved RR &gt; 1 (P &lt; 0·001) with psoriasis, of which 19 achieved a significant direction from psoriasis to a comorbidity (including psoriasis to hypothyroidism), and four achieved a significant direction from a comorbidity diagnosis to a psoriasis diagnosis (including Crohn disease to psoriasis); four of five comorbidity trajectories with three sequential diagnoses achieved an RR &gt; 1 (P &lt; 0·001) and a significant direction from psoriasis to the first comorbidity to the second comorbidity (including psoriasis to hypertension to atrial fibrillation and flutter).

Conclusions
Comorbidity trajectories may support clinicians in conducting disease risk analyses of patients with psoriasis and help plan optimal treatment to prevent future high-risk comorbidities.
Heritability of cognitive abilities and regional brain structures in middle-aged to elderly East Asians
Authors: Lee Younghwa , Park Jun Young , Lee Jang Jae , Gim Jungsoo , Do Ah Ra , Jo Jinyeon , Park Juhong , Kim Kangjin , Park Kyungtaek , Jin Heejin , Choi Kyu Yeong , Kang Sarang , Kim Hoowon , Kim SangYun , Moon Seung Hwan , Farrer Lindsay A , Lee Kun Ho , Won Sungho 
Published: January 2023

AbstractThis study examined the single-nucleotide polymorphism heritability and genetic correlations of cognitive abilities and brain structural measures (regional subcortical volume and cortical thickness) in middle-aged and elderly East Asians (Korean) from the Gwangju Alzheimer’s and Related Dementias cohort study. Significant heritability was found in memory function, caudate volume, thickness of the entorhinal cortices, pars opercularis, superior frontal gyri, and transverse temporal gyri. There were 3 significant genetic correlations between (i) the caudate volume and the thickness of the entorhinal cortices, (ii) the thickness of the superior frontal gyri and pars opercularis, and (iii) the thickness of the superior frontal and transverse temporal gyri. This is the first study to describe the heritability and genetic correlations of cognitive and neuroanatomical traits in middle-aged to elderly East Asians. Our results support the previous findings showing that genetic factors play a substantial role in the cognitive and neuroanatomical traits in middle to advanced age. Moreover, by demonstrating shared genetic effects on different brain regions, it gives us a genetic insight into understanding cognitive and brain changes with age, such as aging-related cognitive decline, cortical atrophy, and neural compensation.
Age-dependent changes in the dynamic functional organization of the brain at rest: a cross-cultural replication approach
Authors: Yang Xi , Zhou Xinqi , Xin Fei , Becker Benjamin , Linden David , Hernaus Dennis 
Published: January 2023

Abstract
Age-associated changes in brain function play an important role in the development of neurodegenerative diseases. Although previous work has examined age-related changes in static functional connectivity, accumulating evidence suggests that advancing age is especially associated with alterations in the dynamic interactions and transitions between different brain states, which hitherto have received less attention. Conclusions of previous studies in this domain are moreover limited by suboptimal replicability of resting-state functional magnetic resonance imaging (fMRI) and culturally homogenous cohorts. Here, we investigate the robustness of age-associated changes in dynamic functional connectivity (dFC) by capitalizing on the availability of fMRI cohorts from two cultures (Western European and Chinese). In both the LEMON (Western European) and SALD (Chinese) cohorts, we consistently identify two distinct states: a more frequent segregated within-network connectivity state (state I) and a less frequent integrated between-network connectivity state (state II). Moreover, in both these cohorts, older (55–80 years) compared to younger participants (20–35 years) exhibited lower occurrence of and spent less time in state I. Older participants also tended to exhibit more transitions between networks and greater variance in global efficiency. Overall, our cross-cultural replication of age-associated changes in dFC metrics implies that advancing age is robustly associated with a reorganization of dynamic brain activation that favors the use of less functionally specific networks.
Peripheral and Portal VenousKRASctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma
Authors: Nitschke Christine , Markmann Benedikt , Walter Philipp , Badbaran Anita , Tölle Marie , Kropidlowski Jolanthe , Belloum Yassine , Goetz Mara R , Bardenhagen Jan , Stern Louisa , Tintelnot Joseph , Schönlein Martin , Sinn Marianne , van der Leest Paul , Simon Ronald , Heumann Asmus , Izbicki Jakob R , Pantel Klaus , Wikman Harriet , Uzunoglu Faik G 
Published: January 2023

AbstractBackgroundKRAS circulating tumor DNA (ctDNA) has shown biomarker potential for pancreatic ductal adenocarcinoma (PDAC) but has not been applied in clinical routine yet. We aim to improve clinical applicability of ctDNA detection in PDAC and to study the impact of blood-draw site and time point on the detectability and prognostic role of KRAS mutations.Methods221 blood samples from 108 PDAC patients (65 curative, 43 palliative) were analyzed. Baseline peripheral and tumor-draining portal venous (PV), postoperative, and follow-up blood were analyzed and correlated with prognosis.ResultsSignificantly higher KRAS mutant detection rates and copy numbers were observed in palliative compared to curative patients baseline blood (58.1% vs 24.6%; P = 0.002; and P &lt; 0.001). Significantly higher KRAS mutant copies were found in PV blood compared to baseline (P &lt; 0.05) samples. KRAS detection in pre- and postoperative and PV blood were significantly associated with shorter recurrence-free survival (all P &lt; 0.015) and identified as independent prognostic markers. KRAS ctDNA status was also an independent unfavorable prognostic factor for shorter overall survival in both palliative and curative cohorts (hazard ratio [HR] 4.9, P = 0.011; HR 6.9, P = 0.008).ConclusionsKRAS ctDNA detection is an independent adverse prognostic marker in curative and palliative PDAC patients—at all sites of blood draw and a strong follow-up marker. The most substantial prognostic impact was seen for PV blood, which could be an effective novel tool for identifying prognostic borderline patients—guiding future decision-making on neoadjuvant treatment despite anatomical resectability. In addition, higher PV mutant copy numbers contribute to an improved technical feasibility.
How Not To Design An Efficient FHE-Friendly Block Cipher: Seljuk
Authors: Ashur Tomer , Mahzoun Mohammad , Toprakhisar Dilara 
Published: January 2023

Abstract
With the rapid increase in the practical applications of secure computation protocols, increasingly more research is focused on the efficiency of the symmetric-key primitives underlying them. Whereas traditional block ciphers have evolved to be efficient with respect to certain performance metrics, secure computation protocols call for a different efficiency metric: arithmetic complexity. Arithmetic complexity is viewed through the number and layout of nonlinear operations in the circuit implemented by the protocol. Symmetric-key algorithms that are optimized for this metric are said to be algebraic ciphers. It has been shown that recently proposed algebraic ciphers are greatly efficient in ZK and MPC protocols. However, there has not been many algebraic ciphers proposed targeting Fully Homomorphic Encryption (FHE). In this paper, we evaluate the behavior of Vision when implemented as a circuit in an FHE protocol. To this end, we present a state-of-the-art comparison of AES and Vision implemented using HElib. Counterintuitively, Vision does not deliver a better performance than AES in this setting. Then, by attempting to improve a bottleneck of the FHE implementation evaluating Vision we present a new cipher: Seljuk. Despite the improvement with respect to Vision, Seljuk does not deliver the expected performance.
A chromosome-level genome assembly of theHenosepilachna vigintioctomaculataprovides insights into the evolution of ladybird beetles
Authors: Zhu Wenbo , Chi Shengqi , Wang Yanchun , Li Haorong , Wang Zhongkai , Gu Songdong , Sun Ting , Xiang Hui , You Ping , Ren Yandong 
Published: January 2023

AbstractThe ladybird beetle Henosepilachna vigintioctomaculata is an economically significant oligophagous pest that induces damage to many Solanaceae crops. An increasing number of studies have examined the population and phenotype diversity of ladybird beetles. However, few comparative genome analyses of ladybird beetle species have been conducted. Here, we obtained a high-quality chromosome-level genome assembly of H. vigintioctomaculata using various sequencing technologies, and the chromosome-level genome assembly was ~581.63 Mb, with 11 chromosomes successfully assembled. The phylogenetic analysis showed that H. vigintioctomaculata is a more ancient lineage than the other three sequenced ladybird beetles, Harmonia axyridis, Propylea japonica, and Coccinella septempunctata. We also compared positively selected genes (PSGs), transposable elements (TEs) ratios and insertion times, and key gene families associated with environmental adaptation among these ladybird beetles. The pattern of TEs evolution of H. vigintioctomaculata differs from the other three ladybird beetles. The PSGs were associated with ladybird beetles development. However, the key gene families associated with environmental adaptation in ladybird beetles varied. Overall, the high-quality draft genome sequence of H. vigintioctomaculata provides a useful resource for studies of beetle biology, especially for the invasive biology of ladybird beetles.
GIP reduces osteoclast activity and improves osteoblast survival in primary human bone cells
Authors: Hansen Morten S , Søe Kent , Christensen Line L , Fernandez-Guerra Paula , Hansen Nina W , Wyatt Rachael A , Martin Claire , Hardy Rowan S , Andersen Thomas L , Olesen Jacob B , Hartmann Bolette , Rosenkilde Mette M , Kassem Moustapha , Rauch Alexander , Gorvin Caroline M , Frost Morten 
Published: January 2023

AbstractObjectiveDrugs targeting the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) are emerging as treatments for type-2 diabetes and obesity. GIP acutely decreases serum markers of bone resorption and transiently increases bone formation markers in short-term clinical investigations. However, it is unknown whether GIP acts directly on bone cells to mediate these effects. Using a GIPR-specific antagonist, we aimed to assess whether GIP acts directly on primary human osteoclasts and osteoblasts.MethodsOsteoclasts were differentiated from human CD14+ monocytes and osteoblasts from human bone. GIPR expression was determined using RNA-seq in primary human osteoclasts and in situ hybridization in human femoral bone. Osteoclastic resorptive activity was assessed using microscopy. GIPR signaling pathways in osteoclasts and osteoblasts were assessed using LANCE cAMP and AlphaLISA phosphorylation assays, intracellular calcium imaging and confocal microscopy. The bioenergetic profile of osteoclasts was evaluated using Seahorse XF-96.ResultsGIPR is robustly expressed in mature human osteoclasts. GIP inhibits osteoclastogenesis, delays bone resorption, and increases osteoclast apoptosis by acting upon multiple signaling pathways (Src, cAMP, Akt, p38, Akt, NFκB) to impair nuclear translocation of nuclear factor of activated T cells-1 (NFATc1) and nuclear factor-κB (NFκB). Osteoblasts also expressed GIPR, and GIP improved osteoblast survival. Decreased bone resorption and improved osteoblast survival were also observed after GIP treatment of osteoclast–osteoblast co-cultures. Antagonizing GIPR with GIP(3–30)NH2 abolished the effects of GIP on osteoclasts and osteoblasts.ConclusionsGIP inhibits bone resorption and improves survival of human osteoblasts, indicating that drugs targeting GIPR may impair bone resorption, whilst preserving bone formation.
Real-time detection of acromegaly from facial images with artificial intelligence
Authors: Kizilgul Muhammed , Karakis Rukiye , Dogan Nurettin , Bostan Hayri , Yapici Muhammed Mutlu , Gul Umran , Ucan Bekir , Duman Elvan , Duger Hakan , Cakal Erman , Akin Omer 
Published: January 2023

Abstract

Objective
Despite improvements in diagnostic methods, acromegaly is still a late-diagnosed disease. In this study, it was aimed to automatically recognize acromegaly disease from facial images by using deep learning methods and to facilitate the detection of the disease.

Design
Cross-sectional, single-centre study

Methods
The study included 77 acromegaly (52.56 ± 11.74, 34 males/43 females) patients and 71 healthy controls (48.47 ± 8.91, 39 males/32 females), considering gender and age compatibility. At the time of the photography, 56/77 (73%) of the acromegaly patients were in remission. Normalized images were obtained by scaling, aligning, and cropping video frames. Three architectures named ResNet50, DenseNet121, and InceptionV3 were used for the transfer learning-based convolutional neural network (CNN) model developed to classify face images as “Healthy” or “Acromegaly”. Additionally, we trained and integrated these CNN machine learning methods to create an Ensemble Method (EM) for facial detection of acromegaly.

Results
The positive predictive values obtained for acromegaly with the ResNet50, DenseNet121, InceptionV3, and EM were calculated as 0.958, 0.965, 0.962, and 0.997, respectively. The average sensitivity, specificity, precision, and correlation coefficient values calculated for each of the ResNet50, DenseNet121, and InceptionV3 models are quite close. On the other hand, EM outperformed these three CNN architectures and provided the best overall performance in terms of sensitivity, specificity, accuracy, and precision as 0.997, 0.997, 0.997, and 0.998, respectively.

Conclusions
The present study provided evidence that the proposed AcroEnsemble Model might detect acromegaly from facial images with high performance. This highlights that artificial intelligence programs are promising methods for detecting acromegaly in the future.
Involvement of mTOR pathway in neurodegeneration in NSF-related developmental and epileptic encephalopathy
Authors: Hayashi Takahiro , Yano Naoko , Kora Kengo , Yokoyama Atsushi , Maizuru Kanako , Kayaki Taisei , Nishikawa Kinuko , Osawa Mitsujiro , Niwa Akira , Takenouchi Toshiki , Hijikata Atsushi , Shirai Tsuyoshi , Suzuki Hisato , Kosaki Kenjiro , Saito Megumu K , Takita Junko , Yoshida Takeshi 
Published: January 2023

Abstract
Membrane fusion is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. During neurotransmitter exocytosis, SNARE proteins on a synaptic vesicle and the target membrane form a complex, resulting in neurotransmitter release. N-ethylmaleimide-sensitive factor (NSF), a homohexameric ATPase, disassembles the complex, allowing individual SNARE proteins to be recycled. Recently, the association between pathogenic NSF variants and developmental and epileptic encephalopathy (DEE) was reported; however, the molecular pathomechanism of NSF-related DEE remains unclear. Here, three patients with de novo heterozygous NSF variants were presented, of which two were associated with DEE and one with a very mild phenotype. One of the DEE patients also had hypocalcemia from parathyroid hormone deficiency and neuromuscular junction impairment. Using PC12 cells, a neurosecretion model, we show that NSF with DEE-associated variants impaired the recycling of vesicular membrane proteins and vesicle enlargement in response to exocytotic stimulation. In addition, DEE-associated variants caused neurodegenerative change and defective autophagy through overactivation of the mammalian/mechanistic target of rapamycin (mTOR) pathway. Treatment with rapamycin, an mTOR inhibitor or overexpression of wild-type NSF ameliorated these phenotypes. Furthermore, neurons differentiated from patient-derived induced pluripotent stem cells showed neurite degeneration, which was also alleviated by rapamycin treatment or gene correction using genome editing. Protein structure analysis of NSF revealed that DEE-associated variants might disrupt the transmission of the conformational change of NSF monomers and consequently halt the rotation of ATP hydrolysis, indicating a dominant negative mechanism. In conclusion, this study elucidates the pathomechanism underlying NSF-related DEE and identifies a potential therapeutic approach.
Induction and Maintenance Treatment With Upadacitinib Improves Health-Related Quality of Life in Patients With Moderately to Severely Active Ulcerative Colitis: Phase 3 Study Results
Authors: Panés Julian , Loftus Edward V , Higgins Peter D R , Lindsay James O , Zhou Wen , Yao, Xuan , Ilo Dapo , Phillips Charles , Tran Jacinda , Sanchez Gonzalez Yuri , Vermeire Séverine 
Published: January 2023

Abstract

Background
We evaluated the health-related quality of life (HRQoL) benefits of upadacitinib (UPA) induction and maintenance treatment in a phase 3 study of patients with ulcerative colitis (UC) across a broad range of patient-centered outcomes.

Methods
Patients received UPA 45 mg once daily or placebo as induction treatment for 8 weeks. Patients who achieved clinical response were rerandomized to receive once daily UPA 15 mg, 30 mg, or placebo as maintenance treatment for 52 weeks. The percentages of patients reporting a clinically meaningful within-person change from baseline in the Ulcerative Colitis Symptoms Questionnaire, Inflammatory Bowel Disease Questionnaire, Work Productivity and Impairment Questionnaire, 36-Item Short Form Survey, and European Quality of Life-5 Dimension 5 Levels were evaluated at weeks 2 and 8 of induction and at weeks 0 and 52 of maintenance.

Results
Significant improvements from baseline in all HRQoL measures except the Work Productivity and Impairment Questionnaire–absenteeism were achieved with UPA (P &lt; .001) vs placebo as early as week 2 of induction. These improvements were sustained at week 52 with significantly more patients treated with either 15 mg or 30 mg UPA vs placebo achieving meaningful within-person change in the Ulcerative Colitis Symptoms Questionnaire; Inflammatory Bowel Disease Questionnaire; overall work impairment, presenteeism, and activity impairment; both 36-Item Short Form Survey Physical and Mental Component Summaries; and European Quality of Life-5 Dimension 5 Levels (P &lt; .001).

Conclusions
Induction treatment with UPA 45 mg significantly improved HRQoL measures. A significantly higher percentage of patients who responded to induction treatment with UPA maintained clinically meaningful improvements consistently across a wide range of HRQoL outcomes after 52 weeks of maintenance therapy with UPA (15 mg and 30 mg) compared with placebo. (ClinicalTrials.gov, Numbers: NCT02819635, NCT03653026).