bluuebunny/crossref_metadata_2025 huggingface dataset:
Noether symmetry approach in scalar-torsion $$f(T,\phi )$$ gravity
Authors: Duchaniya L. K. , Mishra B. , Said Jackson Levi
Published: July 2023

The Noether Symmetry approach is applied to study an extended teleparallel $$f(T,\phi )$$

f
(
T
,
ϕ
)

gravity that contains the torsion scalar T and the scalar field $$\phi $$
ϕ
in the context of an Friedmann–Lemaître–Robertson–Walker space-time. We investigate the Noether symmetry approach in $$f(T,\phi )$$

f
(
T
,
ϕ
)

gravity formalism with the specific form of $$f(T,\phi )$$

f
(
T
,
ϕ
)

and analyze how to demonstrate a nontrivial Noether vector. The Noether symmetry method is a helpful resource for generating models and finding out the exact solution of the Lagrangian. In this article, we go through how the Noether symmetry approach enables us to define the form of the function $$f(T,\phi )$$

f
(
T
,
ϕ
)

and obtain exact cosmological solutions. We also find the analytical cosmological solutions to the field equations, that is consistent with the Noether symmetry. Our results demonstrate that the obtained solutions enable an accelerated expansion of the Universe. We have also obtained the present value of the Hubble parameter, deceleration parameter, and effective equation of state parameter, which is fit in the range of current cosmological observations.
An Efficient PSO-Based Algorithm for Finding Maximal Exact Match in Large DNA Sequences
Authors: Daas Mohamed Skander , Kenidra Billel , Bouanaka Hamza , Chikhi Salim
Published: July 2023

With the appearance of complete mammalian genomes, comparative approaches have experienced a recent upsurge. Searching maximal exact match is among the most used tasks in sequence searching within a larger DNA sequence or database. Many exact algorithms have been designed to deal with this problem. The best improvements made by these algorithms have led to a time and space complexity of O(n) and they remain practically less effective for large sequences. Heuristic methods will therefore be a good alternative to implement. In this work, we present an efficient heuristic algorithm based on PSO metaheuristic to deal with the problem of searching the maximal exact match of small searched sequences in large ones. The time and space complexity of the designed algorithm is of O(1). The experimental results showed the efficiency of the proposed search algorithm for finding maximal exact match in large sequences when compared with two other sequence searching algorithms.
Addressing Ancestry and Sex Bias in Pharmacogenomics
Authors: Corpas Manuel , Siddiqui Moneeza K. , Soremekun Opeyemi , Mathur Rohini , Gill Dipender , Fatumo Segun
Published: July 2023

The association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic variants and drug efficacy or toxicity, we are able to optimize pharmacological therapy according to an individual's genotype. Pharmacogenomics research has historically suffered from bias and underrepresentation of people from certain ancestry groups and of the female sex. These biases can arise from factors such as drugs and indications studied, selection of study participants, and methods used to collect and analyze data. To examine the representation of biogeographical populations in pharmacogenomic data sets, we describe individuals involved in gene-drug response studies from PharmGKB, a leading repository of drug-gene annotations, and showcase CYP2D6, a gene that metabolizes approximately 25% of all prescribed drugs. We also show how the historical underrepresentation of females in clinical trials has led to significantly more adverse drug reactions in females than in males.
CNN with Embedding Transformers for Person Reidentification
Authors: Jianwen Mo , Lunlin Mo , Hua Yuan , Leping Lin , Lingping Chen
Published: July 2023

For person reidentification (ReID), most slicing methods (such as part‐based convolutional baseline (PCB) and AlignedReID) introduce a lot of background devoid of pedestrian parts, resulting in the cross‐aliasing of features in the deep network. Besides, the resulting component features are not perfectly aligned with each other, thus affecting model performance. We propose a convolutional neural network (CNN) with embedding transformers (CET) person ReID network architecture based on the respective advantages of CNN and transformer. In CET, first, the residual transformer (RT) structure is first embedded in the backbone network of CNN to obtain a feature extractor, named transformers in CNN. The feature aliasing phenomenon is improved by utilizing transformer’s advantage in grasping the relevance of global information. Second, a feature fuse with learnable vector structure for fusing the output vector is added to the output of the transformer at the end of the network. A two branches loss structure is designed to balance the two different fusion strategies. Finally, the self‐attention mechanism in transformer is used for automatic part alignment of human body parts to solve the part alignment problem caused by inaccurate detection frames. The experimental results show that CET network architecture achieves better performance than PCB and some other block‐slicing methods.
Effectiveness of Community-Based Outreach Interventions for Individuals Living with Mental Ill-Health in Australia: A Systematic Review
Authors: Carrandi Alayna , Hu Yanan , Wayland Sarah , Maple Myfanwy
Published: July 2023

Objective. Mental ill-health is a common occurrence globally and represents a significant burden of disease. In Australia, the development and improvement of programs that connect individuals earlier in their mental ill-health journey is a national health priority. However, there are current informational gaps on community-based initiatives and their associated mental health outcomes. This review aimed to systematically identify, assess, and analyse studies reporting on community-based outreach interventions for individuals experiencing mental ill-health. Method. A systematic review of the literature was conducted across 6 electronic databases and Google Scholar on 01 November 2021 and 12 June 2022. The National Health and Medical Research Council Evidence Hierarchy was used to assess study quality, and the PAGER framework was used to synthesise and analyse the results of included studies. Results. Eighty-three studies met the inclusion criteria; 51% (n = 42 studies) incorporated digital technology, and 49% (n = 41 studies) involved nonclinical light-touch interventions. Individuals with severe mental ill-health were likely to benefit from targeted interventions, and individuals with mild to moderate symptoms of mental ill-health were likely to benefit from interventions involving high levels of engagement from participants. Conclusion. Results from this review provide an understanding of patterns related to the effectiveness of community-based outreach interventions. Knowledge from this review will inform the implementation of targeted strategies to enhance the proactive provision of mental health services in the community. Standardised outcome measures are needed to strengthen the evidence base for community-based outreach interventions, by enabling researchers and service providers to explore which type of intervention and with what intensity is best suited for participants with varying levels of mental ill-health.
An Interpretable Method for Operational Modal Analysis in Time-Frequency Representation and Its Applications to Railway Sleepers
Authors: Zeng Yuanchen , Shen Chen , Núñez Alfredo , Dollevoet Rolf , Zhang Weihua , Li Zili
Published: July 2023

Operational modal analysis (OMA) enables the identification of modal characteristics under operational loads and conditions. Traditional frequency-domain methods cannot directly capture modal changes over time, while existing time-frequency representations are not sufficiently interpretable due to spurious modes and implicit parameter design. This paper develops a new OMA method in time-frequency representation based on frequency-domain decomposition (FDD). Short-time FDD and a convolution-based strategy are proposed to obtain singular values and local mode shape similarity, respectively, which are further fused into mode indicators by a fuzzy-based strategy mimicking the modal assurance criterion. The method provides not only a global view of the modal characteristics over time and frequency but also estimates of the modal parameters. It is applicable to strongly nonstationary responses under time-varying loads and conditions. All the parameters explicitly affect the time-frequency representation, and the interpretability is enhanced by including physical information from the user’s prior knowledge in selecting parameters and peak bands. The proposed method is validated based on a study of railway sleepers under train passage. The rigid-body motions and bending modes are identified at frequencies up to 6,500 Hz in laboratory tests and 4,500 Hz in field tests at speeds up to 200 km/h. The identified natural frequencies and mode shapes agree with experimental modal analysis (EMA). The proposed method outperforms EMA in terms of broad frequency range and low measurement cost and can be potentially applied to structural health monitoring under operational conditions.
Spatiotemporal Self-Attention-Based Network Traffic Prediction in IIoT
Authors: Liu Xiaoteng , Huang Chuanhe , Abbas Ashraf M. Wasim , Huang Shidong , Chen Yirong
Published: July 2023

The sixth-generation (6G) mobile communications are considered as a future network and very closed to the Industrial Internet of Things (IIoT) due to its low latency and high throughput. Massive nodes supported by 6G make up the complexity of the network. Moreover, the heterogeneous traffic brings difficulties to the network management. Long-term network traffic matrix (TM) prediction is a crucial technology for realizing network edge intelligence and dealing with the above issues. However, predicting long-term network traffic in heterogeneous IIoT is challenging. Due to the powerful feature extraction capability over long sequences, self-attention is widely applied in language inference tasks. Motivated by these observations, we propose a self-attention traffic matrix prediction (SATMP) model for long-term network TM prediction in IIoT scenarios. SATMP consists of three components: (a) a spatial–temporal encoding for obtaining the spatial–temporal features of network TM; (b) a learnable positional encoding for providing positional correlation to the traffic sequence; and (c) a self-attention module for capturing long-term dependence. These components work together to enhance long-term prediction performance in complex networks effectively. Extensive experiments on three publicly available datasets demonstrate that SATMP is feasible and accurate in IIoT long-term network TM prediction.
Investigation of CO2-Sorption Characteristics of Readily Available Solid Materials for Indoor Direct Air Capturing
Authors: Baus Lukas , Nehr Sascha , Maeda Nobutaka
Published: July 2023

Direct air capturing (DAC) is an energy demanding process for CO2-removal from air. Ongoing research focuses on the potential of indoor air as DAC-feed to profit from currently unused energetic synergies between DAC and the built environment. In this work, we investigated the performance of three different readily available, solid DAC-adsorbers under typical indoor environmental conditions of 16-25°C, 25-60% relative humidity (RH), and CO2-concentrations of less than 800 ppm above atmospheric concentrations. The measured mass-specific CO2-adsorption capacities of K2CO3-impregnated activated carbon, polyethylenimine-snow (PEI-snow), and polyethylenimine (PEI) on silica amount to

6.5
±
0.3
 
mg
 

g

−
1

,

52.9
±
4.9
 
mg
 

g

−
1

, and

56.9
±
4.2
 
mg
 

g

−
1

, respectively. Among the three investigated adsorber materials, PEI on silica is the most promising candidate for DAC-applications as its synthesis is rather simple, the CO2-desorption is feasible at moderate conditions of about 80°C at 100 mbar, and the competing co-adsorption of water does not strongly affect the CO2-adsorption under the investigated experimental conditions.
Data from PTTG1 reprograms asparagine metabolism to promote hepatocellular carcinoma progression
Authors: Zhou Qi , Li Leijia , Sha Feifei , Lei Yiming , Tian Xuan , Chen Lingjun , Chen Yan , Liu Huiling , Guo Yunwei
Published: July 2023

Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a poor prognosis. Pituitary tumor transforming gene 1 (PTTG1) is highly expressed in HCC, suggesting it could play an important role in hepatocellular carcinogenesis. Here, we evaluated the impact of PTTG1 deficiency on HCC development using a diethylnitrosamine (DEN)-induced HCC mouse model and a hepatitis B virus regulatory X protein (HBx)-induced spontaneous HCC mouse model. PTTG1 deficiency significantly suppressed DEN- and HBx-induced hepatocellular carcinogenesis. Mechanistically, PTTG1 promoted asparagine synthetase (ASNS) transcription by binding to its promoter, and asparagine levels were correspondingly increased. The elevated levels of asparagine subsequently activated the mTOR pathway to facilitate HCC progression. In addition, asparaginase treatment reversed the proliferation induced by PTTG1 overexpression. Furthermore, HBx promoted ASNS and asparagine metabolism by upregulating PTTG1 expression. Overall, PTTG1 is involved in the reprogramming of asparagine metabolism to promote HCC progression and may serve as a therapeutic and diagnostic target for HCC.
Data from Targeting CD44 Variant 5 with an Antibody–Drug Conjugate Is an Effective Therapeutic Strategy for Intrahepatic Cholangiocarcinoma
Authors: Bei Yuncheng , He Jian , Dong Xuhui , Wang Yuxin , Wang Sijie , Guo Wan , Cai Chengjie , Xu Zhiye , Wei Jia , Liu Baorui , Zhang Nan , Shen Pingping
Published: July 2023

Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most frequent type of primary liver cancer. ICC is among the deadliest malignancies, highlighting that novel treatments are urgently needed. Studies have shown that CD44 variant isoforms, rather than the CD44 standard isoform, are selectively expressed in ICC cells, providing an opportunity for the development of an antibody–drug conjugate (ADC)–based targeted therapeutic strategy. In this study, we observed the specific expression of CD44 variant 5 (CD44v5) in ICC tumors. CD44v5 protein was expressed on the surface of most ICC tumors (103 of 155). A CD44v5-targeted ADC, H1D8–DC (H1D8–drug conjugate), was developed that comprises a humanized anti-CD44v5 mAb conjugated to the microtubule inhibitor monomethyl auristatin E (MMAE) via a cleavable valine–citrulline-based linker. H1D8–DC exhibited efficient antigen binding and internalization in cells expressing CD44v5 on the cell surface. Because of the high expression of cathepsin B in ICC cells, the drug was preferentially released in cancer cells but not in normal cells, thus inducing potent cytotoxicity at picomolar concentrations. In vivo studies showed that H1D8–DC was effective against CD44v5-positive ICC cells and induced tumor regression in patient-derived xenograft models, whereas no significant adverse toxicities were observed. These data demonstrate that CD44v5 is a bona fide target in ICC and provide a rationale for the clinical investigation of a CD44v5-targeted ADC-based approach.
Significance:
Elevated expression of CD44 variant 5 in intrahepatic cholangiocarcinoma confers a targetable vulnerability using the newly developed antibody–drug conjugate H1D8–DC, which induces potent growth suppressive effects without significant toxicity.
Data from Immune Checkpoint Inhibitors and the Exposome: Host-Extrinsic Factors Determine Response, Survival, and Toxicity
Authors: Pizzutilo Elio Gregory , Romanò Rebecca , Roazzi Laura , Agostara Alberto G. , Oresti Sara , Zeppellini Annalisa , Giannetta Laura , Cerea Giulio , Signorelli Diego , Siena Salvatore , Sartore-Bianchi Andrea
Published: July 2023

Abstract
Cancer immunotherapy, largely represented by immune checkpoint inhibitors (ICI), has led to substantial changes in preclinical cancer research and clinical oncology practice over the past decade. However, the efficacy and toxicity profiles of ICIs remain highly variable among patients, with only a fraction achieving a significant benefit. New combination therapeutic strategies are being investigated, and the search for novel predictive biomarkers is ongoing, mainly focusing on tumor- and host-intrinsic components. Less attention has been directed to all the external, potentially modifiable factors that compose the exposome, including diet and lifestyle, infections, vaccinations, and concomitant medications, that could affect the immune system response and its activity against cancer cells. We hereby provide a review of the available clinical evidence elucidating the impact of host-extrinsic factors on ICI response and toxicity.
Data from Investigation of PARP Inhibitor Resistance Based on Serially Collected Circulating Tumor DNA in Patients With BRCA-Mutated Ovarian Cancer
Authors: Kim Yoo-Na , Shim Yeeun , Seo Jieun , Choi Zisun , Lee Yong Jae , Shin Saeam , Kim Sang Wun , Kim Sunghoon , Choi Jong Rak , Lee Jung-Yun , Lee Seung-Tae
Published: July 2023

AbstractPurpose:
Patient-specific molecular alterations leading to PARP inhibitor (PARPi) resistance are relatively unexplored. In this study, we analyzed serially collected circulating tumor DNA (ctDNA) from patients with BRCA1/2 mutations who received PARPis to investigate the resistance mechanisms and their significance in postprogression treatment response and survival.
Experimental Design:
Patients were prospectively enrolled between January 2018 and December 2021 (NCT05458973). Whole-blood samples were obtained before PARPi administration and serially every 3 months until progression. ctDNA was extracted from the samples and sequenced with a 531-gene panel; gene sets for each resistance mechanism were curated.
Results:
Fifty-four patients were included in this analysis. Mutation profiles of genes in pre-PARPi samples indicating a high tumor mutational burden and alterations in genes associated with replication fork stabilization and drug efflux were associated with poor progression-free survival on PARPis. BRCA hypomorphism and reversion were found in 1 and 3 patients, respectively. Among 29 patients with matched samples, mutational heterogeneity increased postprogression on PARPis, showing at least one postspecific mutation in 89.7% of the patients. These mutations indicate non-exclusive acquired resistance mechanisms—homologous recombination repair restoration (28%), replication fork stability (34%), upregulated survival pathway (41%), target loss (10%), and drug efflux (3%). We observed poor progression-free survival with subsequent chemotherapy in patients with homologous recombination repair restoration (P = 0.003) and those with the simultaneous involvement of two or more resistance mechanisms (P = 0.040).
Conclusions:
Analysis of serial ctDNAs highlighted multiple acquired resistance mechanisms, providing valuable insights for improving postprogression treatment and survival.
Data from Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution
Authors: Rastegar Bahar , Andersson Natalie , Petersson Alexandra , Karlsson Jenny , Chattopadhyay Subhayan , Valind Anders , Jansson Caroline , Durand Geoffroy , Romerius Patrik , Jirström Karin , Holmquist Mengelbier Linda , Gisselsson David
Published: July 2023

AbstractPurpose:
While patients with intermediate-risk (IR) Wilms tumors now have an overall survival (OS) rate of almost 90%, those affected by high-stage tumors with diffuse anaplasia have an OS of only around 50%. We here identify key events in the pathogenesis of diffuse anaplasia by mapping cancer cell evolution over anatomic space in Wilms tumors.
Experimental Design:
We spatially mapped subclonal landscapes in a retrospective cohort of 20 Wilms tumors using high-resolution copy-number profiling and TP53 mutation analysis followed by clonal deconvolution and phylogenetic reconstruction. Tumor whole-mount sections (WMS) were utilized to characterize the distribution of subclones across anatomically distinct tumor compartments.
Results:
Compared with non-diffuse anaplasia Wilms tumors, tumors with diffuse anaplasia showed a significantly higher number of genetically distinct tumor cell subpopulations and more complex phylogenetic trees, including high levels of phylogenetic species richness, divergence, and irregularity. All regions with classical anaplasia showed TP53 alterations. TP53 mutations were frequently followed by saltatory evolution and parallel loss of the remaining wild-type (WT) allele in different regions. Morphologic features of anaplasia increased with copy-number aberration (CNA) burden and regressive features. Compartments demarcated by fibrous septae or necrosis/regression were frequently (73%) associated with the emergence of new clonal CNAs, although clonal sweeps were rare within these compartments.
Conclusions:
Wilms tumors with diffuse anaplasia display significantly more complex phylogenies compared with non-diffuse anaplasia Wilms tumors, including features of saltatory and parallel evolution. The subclonal landscape of individual tumors was constrained by anatomic compartments, which should be considered when sampling tissue for precision diagnostics.
Data from The GENIE BPC NSCLC cohort: a real-world repository integrating standardized clinical and genomic data for 1,846 patients with non-small cell lung cancer
Authors: Choudhury Noura J. , Lavery Jessica A. , Brown Samantha , de Bruijn Ino , Jee Justin , Tran Thinh Ngoc. , Rizvi Hira , Arbour Kathryn C. , Whiting Karissa , Shen Ronglai , Hellmann Matthew , Bedard Philippe L. , Yu Celeste , Leighl Natasha , LeNoue-Newton Michele , Micheel Christine , Warner Jeremy L. , Ginsberg Michelle S. , Plodkowski Andrew , Girshman Jeffrey , Sawan Peter , Pillai Shirin , Sweeney Shawn M. , Kehl Kenneth L. , Panageas Katherine S. , Schultz Nikolaus , Schrag Deb , Riely Gregory J.
Published: July 2023

Abstract
Purpose: We describe the clinical and genomic landscape of the non-small cell lung cancer (NSCLC) cohort of the AACR Project GENIE Biopharma Collaborative (BPC). Experimental Design: 1,846 patients with NSCLC whose tumors were sequenced from 2014 to 2018 at four institutions participating in AACR GENIE were randomly chosen for curation using the PRISSMMÔ data model. Progression-free survival (PFS) and overall survival (OS) were estimated for patients treated with standard therapies. Results: In this cohort, 44% of tumors harbored a targetable oncogenic alteration, with EGFR (20%), KRAS G12C (13%) and oncogenic fusions (ALK, RET and ROS1; 5%) as the most frequent. Median OS (mOS) on first-line platinum-based therapy without immunotherapy was 17.4 mo (95% confidence interval (CI) 14.9,19.5 mo). For second-line therapies, mOS was 9.2 mo (95% CI 7.5,11.3 mo) for immune checkpoint inhibitors (ICI) and 6.4 mo (95% CI 5.1,8.1 mo) for docetaxel +/- ramucirumab. In a subset of patients treated with ICI in the second-line or later setting, median RECIST PFS (2.5 mo; 95% CI 2.2, 2.8) and median real-world PFS based on imaging reports (2.2 mo; 95% CI 1.7,2.6) were similar. In exploratory analysis of the impact of tumor mutational burden (TMB) on survival on ICI treatment in the second-line or higher setting, TMB z-score harmonized across gene panels was associated with improved OS (univariable HR 0.85, p=0.03, n=247 patients). Conclusions: The GENIE BPC cohort provides comprehensive clinico-genomic data for patients with NSCLC, which can improve understanding of real-world patient outcomes.
Spectrum of Response to Platinum and PARP Inhibitors in Germline BRCA–Associated Pancreatic Cancer in the Clinical and Preclinical Setting
Authors: Stossel Chani , Raitses-Gurevich Maria , Atias Dikla , Beller Tamar , Glick Gorman Yulia , Halperin Sharon , Peer Eyal , Denroche Robert E. , Zhang Amy , Notta Faiyaz , Wilson Julie M. , O'Kane Grainne M. , Haimov Talmoud Elina , Amison Nora , Schvimer Michael , Salpeter Seth J. , Bar Vered , Zundelevich Adi , Tirosh Itay , Tal Rotem , Dinstag Gal , Kinar Yaron , Eliezer Yonatan , Ben-David Uri , Gavert Nancy S. , Straussman Ravid , Gallinger Steven J. , Berger Raanan , Golan Talia
Published: July 2023

Germline BRCA–associated pancreatic ductal adenocarcinoma (glBRCA PDAC) tumors are susceptible to platinum and PARP inhibition. The clinical outcomes of 125 patients with glBRCA PDAC were stratified based on the spectrum of response to platinum/PARP inhibition: (i) refractory [overall survival (OS) <6 months], (ii) durable response followed by acquired resistance (OS <36 months), and (iii) long-term responders (OS >36 months). Patient-derived xenografts (PDX) were generated from 25 patients with glBRCA PDAC at different clinical time points. Response to platinum/PARP inhibition in vivo and ex vivo culture (EVOC) correlated with clinical response. We deciphered the mechanisms of resistance in glBRCA PDAC and identified homologous recombination (HR) proficiency and secondary mutations restoring partial functionality as the most dominant resistant mechanism. Yet, a subset of HR-deficient (HRD) patients demonstrated clinical resistance. Their tumors displayed basal-like molecular subtype and were more aneuploid. Tumor mutational burden was high in HRD PDAC and significantly higher in tumors with secondary mutations. Anti–PD-1 attenuated tumor growth in a novel humanized glBRCA PDAC PDX model. This work demonstrates the utility of preclinical models, including EVOC, to predict the response of glBRCA PDAC to treatment, which has the potential to inform time-sensitive medical decisions.

Significance:

glBRCA PDAC has a favorable response to platinum/PARP inhibition. However, most patients develop resistance. Additional treatment options for this unique subpopulation are needed. We generated model systems in PDXs and an ex vivo system (EVOC) that faithfully recapitulate these specific clinical scenarios as a platform to investigate the mechanisms of resistance for further drug development.

This article is highlighted in the In This Issue feature, p. 1749
MHC Class II is Induced by IFNγ and Follows Three Distinct Patterns of Expression in Colorectal Cancer Organoids
Authors: Pickles Oliver J. , Wanigasooriya Kasun , Ptasinska Anetta , Patel Akshay J. , Robbins Helen L. , Bryer Claire , Whalley Celina M. , Tee Louise , Lal Neeraj , Pinna Claudia M.A. , Elzefzafy Nahla , Taniere Philippe , Beggs Andrew D. , Middleton Gary M.
Published: July 2023

Tumor-specific MHC class II (tsMHC-II) expression impacts tumor microenvironmental immunity. tsMHC-II positive cancer cells may act as surrogate antigen-presenting cells and targets for CD4+ T cell–mediated lysis. In colorectal cancer, tsMHC-II negativity is common, in cell lines due to CIITA promoter methylation. To clarify mechanisms of tsMHC-II repression in colorectal cancer, we analyzed colorectal cancer organoids which are epigenetically faithful to tissue of origin. 15 primary colorectal cancer organoids were treated with IFNγ ± epigenetic modifiers: flow cytometry was used for tsMHC-II expression. qRT-PCR, total RNA sequencing, nanopore sequencing, bisulfite conversion/pyrosequencing, and Western blotting was used to quantitate CIITA, STAT1, IRF1, and JAK1 expression, mutations and promoter methylation and chromatin immunoprecipitation to quantitate H3K9ac, H3K9Me2, and EZH2 occupancy at CIITA.

We define three types of response to IFNγ in colorectal cancer: strong, weak, and noninducibility. Delayed and restricted expression even with prolonged IFNγ exposure was due to IFNγ-mediated EZH2 occupancy at CIITA. tsMHC-II expression was enhanced by EZH2 and histone deacetylase inhibition in the weakly inducible organoids. Noninducibility is seen in three consensus molecular subtype 1 (CMS1) organoids due to JAK1 mutation. No organoid demonstrates CIITA promoter methylation.

Providing IFNγ signaling is intact, most colorectal cancer organoids are class II inducible. Upregulation of tsMHC-II through targeted epigenetic therapy is seen in one of fifteen organoids. Our approach can serve as a blueprint for investigating the heterogeneity of specific epigenetic mechanisms of immune suppression across individual patients in other cancers and how these might be targeted to inform the conduct of future trials of epigenetic therapies as immune adjuvants more strategically in cancer.

Significance:

Cancer cell expression of MHC class II significantly impacts tumor microenvironmental immunity. Previous studies investigating mechanisms of repression of IFNγ-inducible class II expression using cell lines demonstrate epigenetic silencing of IFN pathway genes as a frequent immune evasion strategy. Unlike cell lines, patient-derived organoids maintain epigenetic fidelity to tissue of origin. In the first such study, we analyze patterns, dynamics, and epigenetic control of IFNγ-induced class II expression in a series of colorectal cancer organoids.
Behandlungserfahrungen mit Rituximab bei Patienten mit rheumatoider Arthritis-assoziierter interstitieller Lungenerkrankung in Ankara, Türkei
Authors: Xanthouli Panagiota
Published: July 2023

Objective: To demonstrate the effects of rituximab (RTX) in patients with rheumatoid arthritis-related interstitial lung disease (RA-ILD). Methods: A total of 165 patients who used RTX for the management of rheumatoid arthritis were retrospectively scrutinised. Among these, 26 patients diagnosed with RA-ILD were analysed (61.5% male, mean age at RTX infusion 61.4 ± 6.5 years). To evaluate the efficacy of RTX on lung response, patients with pulmonary function test results and/or thorax computed tomography (chest-CT) of pre- and post-RTX were compared. Disease progression was defined as either a decline of ≥10% in forced vital capacity (FVC) and/or a decline of ≥15% in diffusion capacity of carbon monoxide (DLCO), or an increase of parenchymal involvement on chest-CT images according to the radiologists’ assessment. Results: Among 26 patients, the most common radiologic pattern was usual interstitial pneumonia (42.3%), followed by non-specific interstitial pneumonia (38.5%). Data for lung response was available in 20 patients. Median pre- and post-RTX DLCO values were 71.0% (60.0–77.0) and 63.0% (47.0–74.0), respectively (p = 0.06). Median pre- and post-RTX FVC values were 74.0% (61.0–99.0) and 84.0% (63.0–100.0), respectively (p = 0.28). Overall, stabilization or regression of RA-ILD was provided in 13 (65.0%) patients, whereas 7 patients had progressive RA-ILD. Post-RTX, 5 patients were diagnosed with RA-ILD.
Sarkopenie: Umfassende Diagnostik bei hohem Risiko für Sekundärfolgen der muskuloskelettalen Erkrankung
Authors: Adler Sabine
Published: July 2023

Einleitung: Als Sarkopenie (SP) bezeichnet man den pathologischen Verlust an Muskelmasse und -funktion. Dies stellt v. a. bei geriatrischen Patient*Innen ein erhebliches Problem dar, weil die SP mit Stürzen, Gebrechlichkeit (Frailty) und erhöhter Morbidität und Mortalität assoziiert ist. Auch Menschen mit entzündlichen und degenerativen rheumatologischen, muskuloskeletalen Erkrankungen (RMD) sind gefährdet, SP zu entwickeln. In der vorliegenden Arbeit wurde die Häufigkeit von SP in diesen Patient*Innengruppen auf der Basis aktueller SP-Definitionen untersucht. Ziel: Untersuchung der Häufigkeit und Schwere von SP bei Patient*Innen mit RMD. Method: en: Im Rahmen einer Querschnittstudie wurden konsekutiv 141 über 65-jährige Patient*Innen mit rheumatoider Arthritis (RA), Spondyloarthritis (SpA), Vaskulitiden und nichtentzündlichen RMD in einem tertiären Zentrum rekrutiert. Es wurden die Definitionen der European Working Group on Sarcopenia in Older People (EWGSOP 1 und 2) für Präsarkopenie, SP und schwere SP zugrunde gelegt. Die Magermasse als Parameter für die Muskelmasse und die Knochendichte wurden mit Dual-Röntgen-Absorptiometrie (DXA) gemessen. Die Bestimmung der Hand­griffkraft und die Short Physical Performance Battery (SPPB) wurden standardisiert durchgeführt. Die Häufigkeit von Stürzen und das Ausmaß an Gebrechlichkeit wurden anamnestisch ermittelt. Die statistischen Berechnungen wurden mit Student’s t- und Chi-Quadrat-Tests durchgeführt. Ergebnisse: Die Patient*innen waren zu 73% weiblich, mittleres Alter 73 Jahre, und 80% hatten eine entzündliche RMD. Wegen eingeschränkter Muskelfunktion hatten 58,9% der Patient*innen nach EWGSOP 2 eine wahrscheinliche SP. Wurde zusätzlich die Muskelmasse berücksichtigt, lag die SP-Häufigkeit bei 10,6% und 5,6% hatten eine schwere SP. Patient*Innen mit einer entzündlichen RMD (11,5%) hatten im Vergleich zu nichtentzündlichen (7,1%) numerisch häufiger eine SP. Die SP-Frequenz war bei RA (9,5%) und Vaskulitiden (24%) am höchsten, und bei SpA (4%) am niedrigsten. Sowohl Osteoporose (40% vs. 18,5%) als auch stattgehabte Stürze (15% vs. 8,6%) fanden sich bei Patient*Innen mit SP häufiger als ohne SP.
Der ungewöhnliche Fall einer Patientin mit Kolitis und Panzytopenie verursacht durch niedrig dosiertes Methotrexat
Authors: R Ramya , Malic Nikola , Menon Trishala , Marks Edward , Machani Sathyanarayana
Published: July 2023

Dieser Artikel fasst den Fall einer Patientin zusammen, die wegen einer Methotrexat-induzierten Kolitis im Zusammenhang mit einer Panzytopenie ins Krankenhaus eingeliefert wurde. Obwohl Methotrexat üblicherweise bei einer Vielzahl von Krankheiten eingesetzt wird, kann dieses Medikament bei einer Untergruppe von Patienten Nebenwirkungen hervorrufen. Dies ist ein atypischer Fall von chronischer Methotrexat-Einnahme in niedriger Dosierung, die zu Kolitis und Panzytopenie führte. Es ist äußerst wichtig, Patienten, die Methotrexat einnehmen, durch routinemäßige Laborkontrollen wie vollständige Blutbilder und Leberfunktionstests zu überwachen, um die Sicherheit zu gewährleisten und die Mortalität zu verringern.
Anti-inflammatorische Standarddiät essen oder eher pflanzenbasiert essen und fasten? Welcher ernährungstherapeutische Ansatz bringt bei rheumatoider Arthritis Vorteile?
Authors: Blumenstein Irina
Published: July 2023

This study aimed at comparing the nutrient supply and dietary behaviors during a plant-based diet (PBD) combined with time-restricted eating (TRE) to standard dietary recommendations in rheumatoid arthritis patients. In this open-label, randomized, controlled clinical trial, patients were assigned to either a 7-day fast followed by an 11-week PBD including TRE (A) or a 12-week anti-inflammatory diet following official German guidelines (German Nutrition Society, DGE) (B). Dietary habits were assessed by 3-day food records at weeks -1, 4 and 9 and food frequency questionnaires. 41 out of 53 participants were included in a post-hoc per protocol analysis. Both groups had similar energy, carbohydrate, sugar, fiber and protein intake at week 4. Group A consumed significantly less total saturated fat than group B (15.9 ± 7.7 vs. 23.2 ± 10.3 g/day; p = 0.02). Regarding micronutrients, group B consumed more vitamin A, B12, D, riboflavin and calcium (each p ≤ 0.02). Zinc and calcium were below recommended intakes in both groups. Cluster analysis did not show clear group allocation after three months. Hence, dietary counselling for a PBD combined with TRE compared to a standard anti-inflammatory diet does not seem to lead to two different dietary clusters, i.e., actual different dietary behaviors as expected. Larger confirmatory studies are warranted to further define dietary recommendations for RA.
Performance investigation of bridge-less power factor correction circuit with MOSFET
Authors: Khudur Khaleel Ali , Samad Nabeel Mohamed Akram , Hasan Ghanim Thiab
Published: July 2023

The aim of this paper is to study and investigate the performance of power factor correction (PFC) circuit implemented with the semi bridge-less configuration. The transistor-diode module APT50N60JCCU2 has been used in the proposed circuit and the UCC28070 controller has been used as a controlling device for the power factor correction (PFC) circuit. Testing has been performed in two steps. In the first step, the test was conducted
 on (230 Vac), while in the second step, the test was conducted on (115 Vac) as alternating input voltages. The testing results of both voltages were compared and analyzed in terms of efficiency, power factor, total harmonic distortion (THD) in order to determine the efficiency of the power factor correction circuit. The results obtained indicate that this circuit has efficiency up to 97% and a power factor close to 0.91 with the input voltage of 230 V.
Higher order model of synchronous generator
Authors: Kadiman Sugiarto , Yuliani Oni
Published: July 2023

Synchronous generator conventional model accurately describes only the stator circuit. Concerning the transients for rotor quantities, for example rotor voltage, rotor current, and rotor magneto-motor force, conceivable predetermined with acceptable accuracy if calculations are created on equivalent model properly on consideration of field and damper together with stator circuits. Unfortunately, it was recognized that simulated responses using conventional model with calculated machine parameters often did not match well with actual measured responses, particularly in the quantity’s rotor winding. For this intention, the newly method to producing the rotor circuit is to model it as well as the lines that conventionally viewed as the partition of current paths from the physical construction. Besides the physical field and damper circuits, a third circuit for the eddy currents induced in the pole surface could also be added. The all conclusions prove the correctness of synchronous generator model.
Automation of the air conditioning system for aseptic rooms of pharmaceutical production
Authors: Alvarez José Ricardo Nuñez , Vicente Raidel Fidel Linares , Zamora Yelena Pérez , Angarita Eliana Noriega , Rodríguez Rodrigo Isacc Fonnegra , Mendoza José Javier Lozano
Published: July 2023

As modern control systems are becoming more complex, and the implemented technology more sophisticated, the importance of the different characteristics of those systems, such as reliability, availability, security, and protection, is increasing. In this article, an automation design for the air conditioning system of classified areas of the Parenteral solutions plant of the eastern pharmaceutical laboratory company of Santiago de Cuba province, Cuba, is proposed because there is a lack of optimal environmental conditions for development and production of pharmaceuticals at a large scale. The proposal is focused on the design of a supervision system and automatic control of the environmental variables that influence the drug production process. The entire algorithm for the design was developed to monitor critical and non-critical variables and control values of temperature, relative humidity, differential pressure, and air velocity according to standards established by pharmaceutical companies. The design of the automation system includes, apart from the control and supervision algorithm for operation efficiency, the necessary instrumentation.
Optimized fuzzy PI controller for variable speed wind turbine using DE algorithm
Authors: Meziane Khaddouj Ben , Dib Faiza , Benaya Nabil , Boumhidi Ismail
Published: July 2023

To design an optimal fuzzy proportional-integral (PI) controller for the variable speed wind turbine systems, a new differential evolution (DE) algorithm approach is developed in this paper. We have investigated a fuzzy PI controller, in which fuzzy rules are applied to adapt the parameters of the PI controller founded on the error and its first-time derivative. The fuzzy PI controller's inputs and outputs are tuned using the DE optimization method. The superiority of the suggested (DE fuzzy PI) controller has been proved by comparing the results with (fuzzy PI) and only the PI controller applied to the wind turbine system. In comparison to a fuzzy controller with parameters selected by a human operator, the numerical validation results of the suggested approach (DE fuzzy PI) have shown good performance in terms of robustness, pursuit, and response time.
Technical, economic and social feasibility of using solar street lighting on campus
Authors: Nugraha I Made Aditya , Desnanjaya I Gusti Made Ngurah
Published: July 2023

A good and proper street lighting system on campus indirectly supports teaching and learning activities. However, these conditions still need to be developed at the Marine and Fisheries Polytechnic of Kupang due to the lack of these facilities. Therefore, a solar street lighting system was designed considering the good potential of solar energy in this region. The design of this system is carried out by measuring for a year, analyzing the energy potential, economics of the system, and the social impact of installing the system. The installation of solar street lighting on campus based on the results of an analysis of technical, economic, and social aspects gives good and feasible results. The results from the technical aspect provide that the utilization of this system provides a PR value of 85%, and can make savings of 15.99 MWh per year, and provide energy of 177.8 kWh per year. The results from the economic aspect of using this system provide an IRR value of 6%, SPBP for 8.93 years, and a net present value (NPV) of IDR 85,247,500.56. The results of the social aspects obtained from the respondents’ answers showed different and meaningful results (p<0.05) from all categories given to respondents.
Optimal location of multiple FACTS devices in N-1 contingency conditions using traditional genetic algorithm
Authors: Shankaregowda Tanuja Koppa , Byalihal Shankaralingappa Channappa
Published: July 2023

Transmission systems are prone to contingency conditions that would either occur using a generator outage or line outage. Placing and sizing the flexible ac transmission systems (FACTS) devices appropriately can reduce the effects of the contingency condition. This paper optimally locates FACTS devices in a transmission system under the N-1 contingency condition. The genetic algorithm (GA) technique is used to locate different, multiple FACTS devices (thyristor-controlled series capacitor and static VAR compensator) optimally in a power system. This optimization technique is used to locate FACTS devices on the IEEE 9 bus system. MATLAB simulation is developed and checked for both single and multiple FACTS placements. Simulation results obtained for generator outage and line outage are tabulated with the type of FACTS device/rating, location, and generation cost with line loss reduction. The optimized results observed for the cost-optimized FACTS placement problem are found to be satisfactory. The results obtained in the IEEE 9 bus system have shown improvement in a decrease of generation cost and system loss component while placement and sizing of both the FACTS devices.
A “Corte” nas redes: uma análise dos perfis dos Ministros do Supremo Tribunal Federal (STF) no Twitter
Authors: Jesus Maria Gorete Marques de , Almada Pablo Emanuel Romero , Amaral Mariana Celano de Souza
Published: July 2023

O presente artigo debate o uso de redes sociais por parte dos Ministros do Supremo Tribunal Federal (STF), tomando como base o Twitter. A pesquisa identifica uma lacuna com relação a estudos sociológicos e empíricos em direito sobre a produção de conteúdo digital em redes sociais realizada por magistrados. A hipótese é que o impacto e a qualidade do conteúdo produzido ainda precisam ser melhor estimados. O estudo utiliza-se da combinação de uma metodologia quantitativa de análise de redes sociais, com uso de métodos digitais, e de uma metodologia qualitativa para a análise do conteúdo dos posts do Twitter dos Ministros do STF. Evidenciamos que, embora haja poucas postagens dos Ministros, há constantes menções aos temas de direitos fundamentais, fato que traz esse conteúdo para os limites do direito e da política. O artigo conclui por lançar questionamentos acerca do alcance dessas postagens, bem como os debates sobre liberdade de expressão na magistratura brasileira e a crença na legitimidade democrática das instituições como o STF.
A Sociologia Digital na era do big data: apontamentos preliminares e problemáticas teórico-metodológicas na pesquisa sociológica
Authors: Castro Thiago Bicudo
Published: July 2023

Este artigo estabelece as primeiras problemáticas de uma pesquisa em andamento que articula big data e Sociologia Digital no Brasil. Explora-se o fenômeno do big data como objeto de estudo e instrumento técnico de pesquisa em Sociologia, situando-o em uma agenda de pesquisa em Sociologia Digital. Constata-se que sua apreensão e compreensão sociológica acontecem em consonância com ampliação e institucionalização da Sociologia Digital no Brasil e no mundo. O big data é entendido como um artefato sociocultural resultante do trabalho humano, mas de difícil apreensão a partir dos métodos tradicionais de análise sociológica. O objeto em questão é localizado no seio das disputas no campo científico entre as Humanidades e áreas da Tecnologia Informacional, como a Ciência de Dados. A Sociologia Digital, ao tomar o big data como um objeto de investigação e recurso técnico para análises, contribui para que novas abordagens e teorias possam ser formuladas a fim de se pensar as implicações do digital na sociedade e nas Ciências Sociais.
Redes de solidariedade e práticas de resistência através de interações online e offline entre familiares de pessoas encarceradas
Authors: Santos Alana Barros
Published: July 2023

Diversos trabalhos têm demonstrado a relevância das redes sociais online como mediadoras e produtoras de vínculos entre pessoas que convivem nos arredores das prisões. Este artigo, se propõe a avançar no campo dos estudos prisionais ao olhar etnograficamente para o contexto da Penitenciária Feminina alagoana. O principal objetivo é analisar como são produzidas redes de solidariedade e práticas de resistência entre os familiares de pessoas encarceradas, matizadas por interações online e offline. Secundariamente, reflito sobre os usos das tecnologias de comunicação e analiso como as redes sociais, especificamente um grupo de WhastApp, e os celulares têm sido articuladores das possibilidades de contato, bem como das formas de organização e de resistência entre esses sujeitos. A pesquisa foi desenvolvida por meio de trabalho etnográfico; registros de campo escritos, em áudios e imagens. Por fim, o artigo apresenta questões (in)conclusivas sobre a construção das relações em campo feita na/através da internet durante a pandemia da covid-19, indagando sobre os “saberes localizados” incógnitos da pesquisadora em um grupo de WhatsApp.
Roteiro geoturístico no Cemitério São Paulo, SP
Authors: Groppo Sofia , Ramponi Rodrigo Figueiredo , Del Lama Eliane Aparecida
Published: July 2023

Os cemitérios históricos têm grande valor patrimonial e potencial turístico. São fontes arqueológicas e artísticas que podem refletir de forma fidedigna a cultura de uma população ao longo do tempo. O Cemitério São Paulo, SP, abriga monumentos pétreos importantes feitos por escultores brasileiros e italianos. Entretanto, seu potencial turístico ainda é pouco explorado. Assim, o objetivo deste estudo foi propor um roteiro geoturístico visando agregar aos visitantes do local uma visão do  atrimônio histórico e cultural por meio do estudo das Geociências. Após revisão bibliográfica sobre o patrimônio cemiterial da Necrópole São Paulo, realizaram-se visitas in loco para levantar informações detalhadas de cada túmulo (como os tipos de pedra, seu estado de conservação e os artistas ou as marmorarias responsáveis por sua projeção e construção), sendo selecionados, com base nos critérios diversidade litológica, obras de artistas de renome e famílias e/ou personalidades  relevantes para a história municipal/estadual, 28 jazigos. A proposta visou apresentar a geodiversidade e os aspectos históricos e culturais das construções, o que resultou em um roteiro geoturístico utilizando linguagem acessível aos visitantes.