bluuebunny/crossref_metadata_2025 huggingface dataset:
Clarifying misbeliefs about hydroxychloroquine (HCQ): developing the HCQ benefits versus harm decision aid (HCQ-SAFE) per low health literacy standards
Authors: Garg Shivani , Ferguson Sancia , Chewning Betty , Gomez Shelby , Keevil Jon , Bartels Christie
Published: July 2023

Background

Up to 83% of patients with SLE stop taking hydroxychloroquine (HCQ) within the first year due to knowledge gaps regarding the survival benefits of HCQ versus inflated fears of rare toxicity. Thus, there is a need for a shared decision-making tool that highlights HCQ’s significant benefits versus rare harms to improve patients’ understanding and align treatments with their values. The objective of this study was to describe development and piloting of a decision aid (HCQ-SAFE) to facilitate HCQ adherence, and safe, effective use by engaging patients in therapeutic decision-making.

Methods

HCQ-SAFE was developed via a collaborative process involving patients, clinicians, implementation scientists and health literacy experts. The initial prototype was informed by Agency for Healthcare Research and Quality (AHRQ) low literacy principles and key themes about HCQ use from six prior patient and clinician focus groups, with iterative expert and stakeholder feedback to deliver a final prototype. We implemented HCQ-SAFE in four clinics to examine usability and feasibility on Likert scales (0–7) and net promoter score (0%–100%).

Results

The final HCQ-SAFE shared decision-making laminated tool organises data using pictograms showing how HCQ use reduces risk of organ damage, early death and blood clots versus low risk of eye toxicity.

HCQ-SAFE was reviewed in all eligible patient visits (n=40) across four clinics on an average of ~8 min, including 25% non-English-speaking patients. All patients scored 100% on the knowledge post-test; no decisional conflicts were noted after using HCQ-SAFE. HCQ-SAFE garnered high clinician and patient satisfaction with 100% likelihood to recommend to peers.

Conclusions

HCQ-SAFE is a stakeholder-informed feasible shared decision-making tool that enhances communication and can potentially improve knowledge, clarify misbeliefs and engage patients in treatment decisions, including those with limited English proficiency.
Impaired regulatory function of granzyme B-producing B cells against T cell inflammatory responses in lupus mice
Authors: Xue Jimeng , Xu Liling , Zhong Hua , Bai Mingxin , Li Xin , Yao Ranran , Wang Ziye , Zhao Zhen , Li Hongchao , Zhu Huaqun , Hu Fanlei , Su Yin
Published: July 2023

Objective

Recently, a new subtype of granzyme B (GrB)-producing Breg cells has been identified, which was proven to be involved in autoimmune disease. Our recent report demonstrated that GrB-producing Breg cells were correlated with clinical and immunological features of SLE. However, the effect of GrB-producing Breg cells in lupus mice is unclear.

Methods

GrB expression in naïve and lupus mouse B cells was analysed using flow cytometry, PCR, ELISA and ELISpot assays. To study the role of GrB-producing B cells in a lupus model, GrB knockout (KO) and wild-type (WT) mice were intraperitoneally injected with monoclonal cells from the mutant mouse strain B6.C-H-2bm12 (bm12) for 2 weeks. In addition, the function of GrB-producing Breg cells in naïve and lupus mice was further explored using in vitro B cells-CD4+CD25−T cell co-culture assays with GrB blockade/KO of B cells.

Results

B cells from the spleens of WT C57BL/6 (B6) mice could express and secret GrB (p<0.001). GrB-producing Breg cells from WT mice showed their regulatory functions on CD4+CD25−T cell. While the frequency of GrB-producing Breg cells was significantly decreased (p=0.001) in lupus mice (p<0.001). Moreover, GrB-producing Breg cells in lupus mice failed to suppress T cell-mediated proinflammatory responses, partially due to the impaired capacity of downregulating the T cell receptor-zeta chain and inducing CD4+CD25−T cell apoptosis.

Conclusion

This study further revealed the function and mechanism of GrB-producing Breg cells in regulating T cell homeostasis in lupus mice and highlighted GrB-producing Breg cells as a therapeutic target in SLE.
Still ‘Cool’: tobacco industry responds to state-wide menthol ban with synthetic coolants
Authors: Page Michelle K , Paul Emily E , Leigh Noel J , Meza Leah R , Galimov Artur , Sussman Steve , Leventhal Adam , O'Connor Richard J , Goniewicz Maciej L
Published: July 2023

Introduction

In December 2022, California (CA) enforced a voter-approved regulation restricting the retail sale of flavoured tobacco products, including menthol cigarettes. Shortly after, new products emerged on the market containing similar blue and green package colours yet with ‘non-menthol’ descriptors. Using chemical analyses, we measured the content of menthol and 15 other cooling chemicals in Californian cigarettes with ‘non-menthol’ descriptors and compared concentrations to similar ‘menthol’-labelled counterparts available in New York State (NY).

Methods

A convenience sample of 10 brands and types of cigarettes in CA were purchased based on package colours suggesting a cooling effect and/or ‘non-menthol’ descriptors. The exact brand and type of cigarettes (with menthol descriptors) were purchased in NY. Cigarettes from CA were compared with equivalent cigarettes from NY on package design and colours, cigarette physical characteristics and the presence of cooling additives.

Results

Menthol was not detected in any CA cigarette, except for Maverick-green box type, while its presence was confirmed in most NY counterpart products. A synthetic cooling chemical WS-3 was not detected in any NY cigarettes but was detected in four CA brands and types with implied cooling effect, ranging from 1.24±0.04 to 1.97±0.05 mg/cigarette.

Conclusion

While manufacturers have removed menthol descriptors from CA packaging and the menthol ingredient from cigarettes, synthetic cooling chemicals detected in several CA brands suggest that cooling sensory effects may still be sustained. Policymakers must consider both the chemical ingredients themselves and sensory effects in future regulatory approaches.
Enriched rearing environment enhances fitness-related traits of salmonid fishes facing multiple biological interactions
Authors: Karvonen Anssi , Klemme Ines , Räihä Ville , Hyvärinen Pekka
Published: July 2023

To improve stocking success in threatened populations, captive-reared animals are often familiarized to natural environment. However, whether such actions improve the ability to cope with multiple biological interactions, such as competition, predation, and parasitism that impose contradicting pressures on decision-making, is not well understood. Here, we explored short-term (4 weeks) and long-term (10 months) effects of enriched rearing on fitness-related traits of Atlantic salmon ( Salmo salar). Salmon with different backgrounds of enrichment and parasite infection (eye fluke Diplostomum pseudospathaceum) were released to semi-natural ponds and monitored for activity, growth, and predation susceptibility. Fish from enriched rearing showed lower short-term activity and higher short-term growth, suggesting that they coped better with novel conditions. However, predation susceptibility and longer-term growth and survival were unaffected by rearing treatment. Importantly, parasitism did not remove the positive effect of enrichment on growth, although the infection decreased both short-term and long-term growth and survival. These results suggest that enriched rearing can enhance fitness-related traits, such as growth, of stocked fish, particularly during the critical early days, which can have important implications for stock enhancement activities.
Community-led non-invasive polar bear monitoring in the Eeyou Marine Region of James Bay, Canada: insights on distribution and body condition during the ice-free season
Authors: Langwieder Alexandra , Coxon Angela , Louttit Natasha , Varty Stephanie , Boulanger Felix , Diamond Sanford , Lameboy John , Jolly Anderson , Natawapineskum George , Okimaw Derek , Humphries Murray M.
Published: July 2023

Wildlife conservation is informed by detailed understanding of species demographics, habitat use, and interactions with environmental drivers. Challenges to collecting this information, particularly in remote places and on widely ranging species, can contribute to data deficiencies that detract from conservation status assessment and the effectiveness of management actions. Polar bears in James Bay face rapidly changing environmental conditions at the southern edge of their global range, but studying their ecology has been limited by community concerns about the methods typically used in polar bear research. Using a community-led and non-invasive approach, we deployed hair snare and camera trap sampling stations across 400 km of the Eeyou Marine Region in eastern James Bay. Stations collected >100 hair samples and thousands of photographs in one eight-week period that allowed for a novel investigation of this population’s distribution and body condition during the ice-free season. Polar bears were in average to above average body condition, and model selection of detections at stations revealed distance to mainland as a significant predictor of polar bear presence. Given its high potential, we suggest community-based monitoring using this method become a standard protocol to expand the scope and local leadership of polar bear research across the North.
Sixty years of learning and teaching physiology
Authors: Williams John A.
Published: July 2023

Teaching remains an important part of the career of academic physiologists. It is important for schools offering the Ph.D. to provide instruction and experience in teaching. The American Physiology Society has developed new programs to assist teachers and many universities have centers on learning and teaching.
Metformin reduces insulin resistance and attenuates progressive renal injury in prepubertal obese Dahl salt-sensitive rats
Authors: Ekperikpe Ubong S. , Mandal Sautan , Holt Stephen J. , Daniels Jacori K. , Johnson Tyler D. , Cooper Jonita S. , Safir Sarah M. , Cornelius Denise C. , Williams Jan M.
Published: July 2023

Childhood/prepubertal obesity is a public health concern that is associated with early signs of proteinuria. Insulin resistance has been described in obese children. However, studies investigating the role of insulin resistance during childhood obesity-associated renal injury are limited. This study provides evidence of an early relationship between insulin resistance and renal injury in a rat model of prepubertal obesity. These data also suggest that reducing insulin resistance with metformin may be renoprotective in obese children.
Hyperoside Attenuates Sepsis-Induced Acute Lung Injury (ALI) through Autophagy Regulation and Inflammation Suppression
Authors: Mai Jingyin , He Qingqing , Liu Yuting , Hou Yuting
Published: July 2023

Background. Sepsis mortality and morbidity are aggravated by acute lung injury (ALI) or acute respiratory distress syndrome. Published studies have discovered that hyperoside (HYP) has an anti-inflammatory and therapeutic effect in many diseases. However, whether HYP treatment can attenuate sepsis-induced ALI is still obscure. Methods. In this study, a cecal ligation and puncture (CLP)-induced sepsis mouse model was constructed. The mouse lungs were harvested and assessed using proteomics, immunohistochemistry, immunofluorescence, and enzyme-linked immunosorbent assay for pro-inflammatory cytokines. Human lung microvascular endothelial cells (HLMVECs) were induced with lipopolysaccharide (LPS) for the in vitro model. Results. The results showed that HYP treatment attenuated sepsis-induced ALI through an increased survival rate, decreased inflammatory factor expression, and lung tissue apoptosis. At the same time, HYP pretreatment restored angiogenesis in CLP-induced mouse lung tissues. Proteomics detection showed that Atg13 played a vital role in HYP-mediated protection against sepsis-induced ALI. The in vitro experiment showed HYP treatment attenuated LPS-induced HLMVEC damage by regulating Atg13-mediated autophagy. Inhibiting autophagy or silencing Atg13 reversed the protective effect of HYP against sepsis-induced ALI. Conclusion. Taken together, we conclude that HYP attenuated sepsis-induced ALI by regulating autophagy and inhibiting inflammation.
Artificial Intelligence Applied on Traffic Planning and Management for Rail Transport: A Review and Perspective
Authors: Zhang Jiamin , Zhang Jiarui
Published: July 2023

Artificial intelligence (AI) has received much attention in the domain of railway traffic planning and management (TPM) from academia and industries. While many promising applications have been reported, there remains a lack of detailed review of the many AI models/algorithms and their uses and adaptations in rail TPM. To fill this gap, this systematic literature review conducts, reports, and synthesizes the state-of-the-art of AI applied in railway TPM from four perspectives, i.e., the intersection between AI research fields (e.g., expert systems, data mining, and adversarial search) and rail TPM, the intersection between AI techniques (e.g., evolutionary computing and machine learning) and rail TPM, the intersection between AI applications (e.g., operations research, scheduling, and planning) and rail TPM, and the intersection between AI related disciplines (e.g., big data analytics and digital twins) and rail TPM. The study evaluates 95 research papers published during 1970–2022. Accordingly, a comprehensive synthesis of each intersection between AI and rail TPM is presented, and the practical roadmap for application of AI in rail TPM is proposed. Furthermore, the study identifies the research gaps and areas that need more investigation. The contribution helps researchers and practitioners to get a better understanding of the status quo of research stream, research development trends, and challenges for further related study.
State of the Population of Gladiolus imbricatus L. in a Molinia Meadow after Extensive Management and Abandonment
Authors: Kostrakiewicz-Gierałt Kinga , Podgórska Monika , Kłosowski Stanisław
Published: July 2023

The abandonment of seminatural Molinia meadows observed in Central and Eastern Europe during the 20th century started the secondary succession and threatened the state and persistence of populations of numerous meadow species. Considering this, the aims of the presented investigations were to study the abundance and selected traits of individuals of Gladiolus imbricatus L. in extensively used (EM) and unmanaged for at least 15 years (UM) Molinia meadows (Southern Poland, Central Europe). Altogether, 125 juvenile individuals, 21 vegetative individuals, and 119 generative individuals of Gladiolus imbricatus were investigated. The field studies showed positive correlation among the height of shoots and other traits of generative individuals in both study patches. Moreover, the greater abundance of population of Gladiolus imbricatus (especially the greater number of juveniles), as well as the greater dimensions of leaf blades, shoots, inflorescence, and number of capsules in the patch UM, indicates the appropriate state of the population. These data indicate a positive influence of abandonment and evolving secondary succession on the Gladiolus imbricatus population within the Molinia meadows.
Concurrent Ocular and Cerebral Toxoplasmosis in a Liver Transplant Patient Treated with Anti-CD40 Monoclonal Antibody
Authors: Van Den Noortgate Roos , Kiselinova Maja , Sys Céline , Accou Geraldine , Laureys Guy , Van Vlierberghe Hans , Berrevoet Frederik , Kreps Elke O.
Published: July 2023

Toxoplasma gondii, an obligate intracellular parasitic protozoon, usually causes a mild, acute infection followed by a latent asymptomatic phase with tissue cysts or a chronic form with recurrent retinochoroiditis. However, immunocompromised patients can cause disseminated disease due to the reactivation of the latent tissue cysts or due to a primary infection. Here, we present a rare case of bilateral ocular toxoplasmosis and concurrent subacute toxoplasma encephalitis in a 70-year-old patient on anti-CD40 treatment following his liver transplant. The diagnosis was confirmed by PCR of anterior chamber fluid and brain biopsy, and no other sites of disseminated disease were detected on PET-CT. The patient has been treated with sulfamethoxazole-trimethoprim 800/160 mg with virtually complete resolution of the neurological and ocular symptoms. Iatrogenic blockade of the CD40 pathway may elicit a particular susceptibility for CNS reactivation of T. gondii.
Knowledge, Attitude, and Practices (KAP) on Antibiotic Use and Disposal Ways in Sidama Region, Ethiopia: A Community-Based Cross-Sectional Survey
Authors: Sitotaw Baye , Philipos Workneh
Published: July 2023

Antibiotic resistance has been among the top public health threats elsewhere. Scientific information on knowledge, attitudes, and practices (KAP) at the community level towards antibiotic use and disposal ways is a vital step for effective intervention. This study aimed at determining the levels of KAP and associated risk factors for antibiotics in and around Hawassa City, southern Ethiopia. A community-based cross-sectional study was conducted, and data were collected using a structured questionnaire. Descriptive statistics, chi-square test, and logistic regression were used to analyze and interpret the results. A total of 504 participants with a mean age of 35.32 ± 9.03 years were included in the study. Most of the participants were urban dwellers (59.5%); more than half (55.6%) of the participants were male; most of the participants (62.7%) were at least college graduates; about half were employed (52.4%); about 41.7% of the participants had a large family size (≥7) with a mean family size of 5.7 ± 2.7; the average family monthly income was ETB 7213.71 ± 3673, and over three-fourth (74.8%) of the study participants were married. In addition, about 83.13% of the study participants heard about antibiotics; almost all of them (99.8%) had ever used antibiotics at some point in their life (75% of which used antibiotics within 6 months), and all of them could name at least one common type of antibiotic. Moreover, most of the participants (86.5%) did not receive any training related to antibiotics, and 29.4% of them obtained antibiotics without a prescription. Most participants had poor knowledge (64%), negative attitudes (60.4%), and poor practices (55%) towards antibiotic use, resistance, and disposal methods. Significant and positive linear correlations between knowledge and attitude (r = 0.539,

P
≤
0.001

), knowledge-practice (r = 0.532,

P
≤
0.001

), and attitude-practice (r = 0.786,

P
<
0.001

) were also observed. Most of the sociodemographic variables were significantly associated with the mean KAP scores of the study participants. Living in a rural area, having a large family size, and being female, married, illiterate, and farmer resulted in a very low level of knowledge. Similarly, living in a rural area, having a small family size, and being older and married resulted in a negative attitude. Furthermore, having a smaller family size, having a low family monthly income, and being married, illiterate, and self-employed resulted in poor practice. A very low level of KAP towards antibiotics among people living in and around Hawassa City calls for urgent and effective intervention strategies.
Splicing Analysis of MYO5B Noncanonical Variants in Patients with Low Gamma-Glutamyltransferase Cholestasis
Authors: Wang Li , Qiu Yi-Ling , Abuduxikuer Kuerbanjiang , Wang Neng-Li , Li Zhong-Die , Cheng Ye , Lu Yi , Xie Xin-Bao , Xing Qing-He , Wang Jian-She
Published: July 2023

Biallelic MYO5B variants have been associated with familial intrahepatic cholestasis (FIC) with low serum gamma-glutamyltransferase (GGT). Intronic or synonymous variants outside of canonical splice sites (hereinafter referred to as noncanonical variants) with uncertain significance were identified in MYO5B posing a challenge in clinical interpretation. This study is aimed at assessing the effects of these variants on premessenger RNA (pre-mRNA) splicing to improve recognition of pathogenic spliceogenic variants in MYO5B and better characterize the MYO5B genetic variation spectrum. Disease-associated MYO5B noncanonical variants were collected from the literature or newly identified low GGT cholestasis patients. In silico splicing predictions were performed to prioritize potential pathogenic variants. Minigene splicing assays were performed to determine their splicing patterns, with confirmation by blood RNA analysis in one case. Eleven (five novel) noncanonical variants with uncertain significance were identified. Minigene splicing assays revealed that three variants (c.2090+3A>T, c.2414+5G>T, and c.613-11G>A) caused complete aberrations, five variants (c.2349A>G/p.(=), c.4221G>A/p.(=), c.1322+5G>A, c.1669-35A>C, and c.3045+3A>T) caused predominant aberrations, and three variants (c.4852+11A>G, c.455+8T>C, and c.2415-6C>G) had no effect on pre-mRNA splicing. Patient-derived RNA analysis showed consistent results. Based on our results, eight variants were reclassified as likely pathogenic and three as likely benign. Combining the clinical features and the above analysis, the diagnosis of MYO5B-associated FIC could be made in three new patients. In conclusion, we characterized the splicing patterns of MYO5B noncanonical variants and suggest that RNA analysis should be routinely included in clinical diagnostics to provide essential evidence for the interpretation of variants.
A Prediction Model for Energy Production in a Solar Concentrator Using Artificial Neural Networks
Authors: Ricci Leonardo , Papurello Davide
Published: July 2023

Solar energy is widely adopted today and produced by photovoltaic or concentrator solar power (CSP). Photovoltaic technology is the most prevalent, thanks to its well-established technology and low costs. CSP technology, on the other hand, has received less attention and interest, as it requires larger investments and a considerable surface. A relevant difficulty connected to the CSP is decoupling solar randomness and energy production. This paper proposes an artificial neural network (ANN) which foresees energy production using a solar parabolic dish installed at Politecnico di Torino (Energy Center Lab). The investigation was performed using a backpropagation ANN. Different learning algorithms were used: Levenberg-Marquardt, Bayesian regularization, resilient backpropagation, and scaled conjugate gradient. Seven atmospheric condition parameters were adopted (humidity, temperature, pressure, wind velocity and direction, solar radiation, and rain), to calculate the receiver temperature as an output. Bayesian regularization was found to be the optimal model for CSP energy production. The results of this investigation suggest that the ANNs are a strong, reliable, and useful tool for predicting temperature in a CSP receiver that can be of great value in the forecasting of energy production. The outcome of this investigation can simplify energy production forecasting using readily available meteorological data.
Figure S2 from T-cell Receptor Therapy Targeting Mutant Capicua Transcriptional Repressor in Experimental Gliomas
Authors: Kilian Michael , Friedrich Mirco , Sanghvi Khwab , Green Edward , Pusch Stefan , Kawauchi Daisuke , Löwer Martin , Sonner Jana K. , Krämer Christopher , Zaman Julia , Jung Stefanie , Breckwoldt Michael O. , Willimsky Gerald , Eichmüller Stefan B. , von Deimling Andreas , Wick Wolfgang , Sahm Felix , Platten Michael , Bunse Lukas
Published: July 2023

Supplementary Figure 2: Molecular features of A2.DR1 MHC-humanized gliomas. A. Verification of the CRISPR-Cas9-mediated functional KO of p53 and Nf1 in the A2.DR1 glioma cell line. B. Copy number variations (CNVs) in the A2.DR1 glioma cell line. C. Chromosomal distribution of CNVs D. Representative immunofluorescence image of A2.DR1 glioma orthotopically injected into the brain of adult A2.DR1 mice, 20 days after injection. E. Relative expression of Cic in wild-type and CicR215W overexpressing A2.DR1 glioma cells as determined by RT-qPCR. F: Immunoblot depicting overexpression of the Cic protein in the CicR215W transfected cell line compared to the parental line (WT).
Figure S1 from T-cell Receptor Therapy Targeting Mutant Capicua Transcriptional Repressor in Experimental Gliomas
Authors: Kilian Michael , Friedrich Mirco , Sanghvi Khwab , Green Edward , Pusch Stefan , Kawauchi Daisuke , Löwer Martin , Sonner Jana K. , Krämer Christopher , Zaman Julia , Jung Stefanie , Breckwoldt Michael O. , Willimsky Gerald , Eichmüller Stefan B. , von Deimling Andreas , Wick Wolfgang , Sahm Felix , Platten Michael , Bunse Lukas
Published: July 2023

Supplementary Figure 1: T cell responses in A2.DR1 and DR4 mice after peptide vaccination with potential shared neoepitopes. A. Predicted binding affinity for selected amino acid alterations for HLA-A*0201 determined by NetMHC 4.0. B, C. Quantification of IFN-Î³ ELISpot using cells isolated from lymph nodes from vaccinated A2.DR1 mice restimulated with the indicated peptide. D. ELISpot of splenocytes from 27-mer CICR215W-vaccinated mice restimulated for 48 h with the indicated 15-mer (see also Supplementary Table 1). B, C, D Data are represented as meanâ€‰{plus minus}â€‰SEM, statistical significance was determined by unpaired two-tailed Student's t-test. E. Intracellular IFN-Î³ flow cytometric analyses after in vitro re-stimulation of splenocytes from 27-mer CICR215W-vaccinated DR4 mice gated on single, living, and CD3+ cells.
Supplementary Data 1 from Phase I Study of Acalabrutinib Plus Danvatirsen (AZD9150) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma Including Circulating Tumor DNA Biomarker Assessment
Authors: Roschewski Mark , Patel Manish R. , Reagan Patrick M. , Saba Nakhle S. , Collins Graham P. , Arkenau Hendrik-Tobias , de Vos Sven , Nuttall Barrett , Acar Melih , Burke Kathleen , White Rafael D. , Udriste Maria , Sharma Shringi , Dougherty Brian , Stetson Daniel , Jenkins David , Mortlock Andrew , Forcina Alessandra , Munugalavadla Veerendra , Flinn Ian
Published: July 2023

Supplementary Data
Supplementary Table 1: Key exclusion criteria
Supplementary Table 2: Prior systemic therapies
Supplementary Table 3: Subsequent anticancer therapy
Supplementary Table 4: Mutations by response: cell-of-origin and genetic subtyping
Supplementary Table 5: Representativeness of Study Participants
Supplementary Figure 1: Study design
Supplementary Figure 2: Plasma concentration of danvatirsen, acalabrutinib, and ACP-5862 (active metabolite of acalabrutinib) consistent with historical monotherapy data
Supplementary Figure 3: EZB-related mutations by treatment response, number of cycles on treatment, cell-of-origin, and LymphGen cluster
Supplementary Figure 4: STAT3 protein and ASO expression detection by IHC
Supplementary Figure 5: Allele frequency over time for all patients by response
Supplementary Figure 6: Copy number dynamics for all patients with available data by response
Supplementary Figure 7: Peripheral blood analysis of gene expression associated with CD19+ B-cell signaling at baseline (A) and for baseline and longitudinal samples (B), and comparison of baseline gene expression of select B- and T-cell–specific genes in PBMCs in responders and nonresponders (C)
Supplementary Figure 8: Peripheral blood analysis of gene expression associated with interferon-gamma signaling: baseline comparison (A) and baseline and longitudinal samples (B)
Supplementary Figure 9: T-cell, B-cell, and NK-cell (TBNK) flow analysis: immunophenotyping in responders and nonresponders at baseline
Supplementary Figure 10: Longitudinal immunophenotyping/immune cell population data (A) and percentage of CD4+ naïve T-cells among all CD4+ T cells (B) at each visit by treatment response
Supplementary Figure 11: Pretreatment and on-treatment levels of cytokines/chemokines
Supplementary Figure S1 from Caveolin Gene Expression Predicts Clinical Outcomes for Early-Stage HER2-Negative Breast Cancer Treated with Paclitaxel-Based Chemotherapy in the GeparSepto Trial
Authors: Williams Terence M. , Schneeweiss Andreas , Jackisch Christian , Shen Changxian , Weber Karsten E. , Fasching Peter A. , Denkert Carsten , Furlanetto Jenny , Heinmöller Ernst , Schmatloch Sabine , Karn Thomas , Szeto Christopher W. , van Mackelenbergh Marion T. , Nekljudova Valentina , Stickeler Elmar , Soon-Shiong Patrick , Schem Christian , Mairinger Thomas , Müller Volkmar , Marme Frederik , Untch Michael , Loibl Sibylle
Published: July 2023

Supplementary Figure S1. CAV1 and CAV2 before (A, C) and after (B, D) transformation of the continuous expression values.
Supplementary Figure S14 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

Subasumstat induces changes in the TME associated with Interferon Signature expression
Supplementary Figure S11 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: July 2023

Interferon Signature Expression closely matches MIL113 staining
Data from A phase Ib, open-label study evaluating the safety and efficacy of ipatasertib plus rucaparib in patients with metastatic castration-resistant prostate cancer
Authors: Pook David , Geynisman Daniel M. , Carles Joan , de Braud Filippo , Joshua Anthony M. , Perez-Gracia Jose Luis. , Pérez Casilda Llácer. , Shin Sang Joon , Fang Bruno , Barve Minal , Maruzzo Marco , Bracarda Sergio , Kim Miso , Kerloeguen Yannick , Gallo Jorge Daniel. , Maund Sophia L. , Harris Adam , Huang Kuan-Chieh , Poon Victor , Sutaria Dhruvitkumar S. , Gurney Howard
Published: July 2023

Abstract
Purpose: To report the safety and efficacy of ipatasertib (AKT inhibitor) combined with rucaparib (PARP inhibitor) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with second-generation androgen-receptor inhibitors. Patients and Methods: In this two-part phase Ib trial (NCT03840200), patients with advanced prostate, breast, or ovarian cancer received ipatasertib (300 or 400mg daily [QD]) plus rucaparib (400 or 600mg twice daily [BID]) to assess safety and identify a recommended phase 2 dose (RP2D). A Part 1 dose-escalation phase was followed by a Part 2 dose-expansion phase in which only patients with mCRPC received the RP2D. The primary efficacy endpoint was prostate-specific antigen (PSA) response (≥50% reduction) in patients with mCRPC. Patients were not selected on tumor mutational status. Results: Fifty-one patients were enrolled (Part 1=21; Part 2=30). Ipatasertib 400mg QD plus rucaparib 400mg BID was the selected RP2D, received by 37 patients with mCRPC. Grade 3/4 adverse events occurred in 46% (17/37) of patients, with one grade 4 adverse event (anemia, deemed related to rucaparib) and no deaths. Adverse events leading to treatment modification occurred in 70% (26/37). The PSA response rate was 26% (9/35), and the objective response rate per RECIST 1.1 was 10% (2/21). Median radiographic progression-free survival per Prostate Cancer Working Group 3 criteria was 5.8 months (95% CI, 4.0-8.1), and median overall survival was 13.3 months (95% CI, 10.9-not evaluable). Conclusion: Ipatasertib plus rucaparib was manageable with dose modification but did not demonstrate synergistic or additive antitumor activity in previously treated patients with mCRPC.
Data from FH variant pathogenicity promotes purine salvage pathway dependence in kidney cancer
Authors: Wilde Blake R. , Chakraborty Nishma , Matulionis Nedas , Hernandez Stephanie , Ueno Daiki , Gee Michayla E. , Esplin Edward D. , Ouyang Karen , Nykamp Keith , Shuch Brian , Christofk Heather R.
Published: July 2023

Abstract
Fumarate accumulation due to loss of fumarate hydratase (FH) drives cellular transformation. Germline FH alterations lead to hereditary leiomyomatosis and renal cell cancer (HLRCC) where patients are predisposed to an aggressive form of kidney cancer. There is an unmet need to classify FH variants by cancer-associated risk. We quantified catalytic efficiencies of 74 variants of uncertain significance. Over half were enzymatically inactive which is strong evidence of pathogenicity. We next generated a panel of HLRCC cell lines expressing FH variants with a range of catalytic activities, then correlated fumarate levels with metabolic features. We found that fumarate accumulation blocks de novo purine biosynthesis, rendering FH-deficient cells reliant on purine salvage for proliferation. Genetic or pharmacologic inhibition of the purine salvage pathway reduced HLRCC tumor growth in vivo. These findings suggest pathogenicity of patient-associated FH variants and reveal purine salvage as a targetable vulnerability in FH-deficient tumors.
Table S4 from HTLV-1 bZIP Factor-Induced Reprogramming of Lactate Metabolism and Epigenetic Status Promote Leukemic Cell Expansion
Authors: Toyoda Kosuke , Yasunaga Jun-ichirou , Shichijo Takafumi , Arima Yuichiro , Tsujita Kenichi , Tanaka Azusa , Salah Tarig , Zhang Wenyi , Hussein Osama , Sonoda Miyu , Watanabe Miho , Kurita Daisuke , Nakashima Kazutaka , Yamada Kyohei , Miyoshi Hiroaki , Ohshima Koichi , Matsuoka Masao
Published: July 2023

Experimental reagents and resources with identifiers used in this study.
Table S3 from HTLV-1 bZIP Factor-Induced Reprogramming of Lactate Metabolism and Epigenetic Status Promote Leukemic Cell Expansion
Authors: Toyoda Kosuke , Yasunaga Jun-ichirou , Shichijo Takafumi , Arima Yuichiro , Tsujita Kenichi , Tanaka Azusa , Salah Tarig , Zhang Wenyi , Hussein Osama , Sonoda Miyu , Watanabe Miho , Kurita Daisuke , Nakashima Kazutaka , Yamada Kyohei , Miyoshi Hiroaki , Ohshima Koichi , Matsuoka Masao
Published: July 2023

Oligonucleotides used in this study.
Supplementary Table S1 from A pilot study of neoadjuvant nivolumab, ipilimumab and intralesional oncolytic virotherapy for HER2-negative breast cancer
Authors: Nguyen Vina P , Campbell Katie M. , Nowicki Theodore S , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L , Chang Helena R. , Oseguera Denise K , Ribas Antoni , Glaspy John A.
Published: July 2023

Representativeness of Study Participants
Supplementary Figure S2 from A pilot study of neoadjuvant nivolumab, ipilimumab and intralesional oncolytic virotherapy for HER2-negative breast cancer
Authors: Nguyen Vina P , Campbell Katie M. , Nowicki Theodore S , Elumalai Nila , Medina Egmidio , Baselga-Carretero Ignacio , DiNome Maggie L , Chang Helena R. , Oseguera Denise K , Ribas Antoni , Glaspy John A.
Published: July 2023

Immune cell deconvolution of bulk RNA-seq data. MCPcounter was used to summarize gene expression scores for immune cell populations from bulk RNA-seq expression data across ten cell types. Each point represents one sample, and paired baseline/surgery samples are connected by a line. Individual patients and their responses are indicated by color and point shape.
Figure S4 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

X15695 derivatives attenuate AR target gene expression.
FIGURE 2 from Identification of an Imidazopyridine-based Compound as an Oral Selective Estrogen Receptor Degrader for Breast Cancer Therapy
Authors: Pan Mengwu , Solozobova Valeria , Kuznik Nane C. , Jung Nicole , Gräßle Simone , Gourain Victor , Heneka Yvonne M. , Cramer von Clausbruch Christina A. , Fuhr Olaf , Munuganti Ravi S. N. , Maddalo Danilo , Blattner Christine , Neeb Antje , Sharp Adam , Cato Laura , Weiss Carsten , Jeselsohn Rinath M. , Orian-Rousseau Veronique , Bräse Stefan , Cato Andrew C. B.
Published: July 2023

X15695 attenuates ERα-mediated target gene expression. GSEA plots of the top gene sets identified in a comparison of E2 + X15695 versus E2 (A) and X15695 versus vehicle (B) in MCF-7. C–H, Quantitative RT-PCR to detect the effect of X15695 on the expression of the indicated p53 target genes in MCF-7 cells in the presence and absence of E2. Cells were treated with the indicated concentrations of X15695 in the presence and absence of 10 nmol/L E2 for 16 hours. The data represent the mean ± SEM (n = 4; *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001; ns, not significant).
From Os Lusíadas to Luzitayonn: An analysis of Canto VII of Camoes’ epic, and its Konkani translation by Olivinho Gomes
Authors: Alberto Loraine Ethel Barreto , Silveira Irene
Published: July 2023

Luis de Camões displayed his poetic prowess in his magnum opus, The Lusiads. The masterpiece is a unique composition, a combination of historical facts and images from ancient mythology, set in exuberant places discovered by the Portuguese. The extraordinary setting, coupled with the author's opulence of poetic imagination, made The Lusiads one of the greatest epics of European literature, with over a hundred editions and translations into more than a dozen European languages (NLR, [S.d.]). This paper seeks to study the translation exercise to an Indian language (Konkani) undertaken by Olivinho Gomes in Goa. Drawing from Gomes’ translation (Luzitayonn published in 2003), our work aims to interpret select strophes from Canto VII of The Lusiads. The strophes that form the basis of this study paint iconic scenes dealing with Vasco da Gama's arrival on the Malabar Coast and move on to a eulogy of the Indian subcontinent. Many scenes are significant and have featured widely in luso iconography. While retaining ideas inherent to The Lusiads, and the flavour of Camões’ epic style writing, Gomes skilfully adapts his translation to the contemporary Indian audience. Through a deft shift of focus away from other ancient civilisations wherever possible, he attempts to (re)place India in the centre of the narrative. Canto VII of Luzitayonn appears to be retold in places through a translator’s Indian gaze. We understand, however, that this is but a feeble attempt, and Camões’ references continue to majorly structure the text.
Uma releitura de Os Lusíadas
Authors: Chauvin Jean Pierre
Published: July 2023

Parte considerável dos historiadores da literatura em língua portuguesa analisou e interpretou as epopeias sem levar em consideração os preceitos do gênero e a maneira como elas foram concebidas. O modo como Os Lusíadas (1572) foi discutido até recentemente é sintomático de uma maneira enviesada de ler. Esta resenha visa a apresentar Heroísmo na singradura dos mares (2018), que resulta da tese de doutorado do historiador Cleber Vinicius do Amaral Felipe, realizada na Universidade Federal de Uberlândia.
First photographic record of White Royal Tajuria illurgis illurgis (Hewitson, [1869]) (Insecta: Lepidoptera: Lycaenidae) from Arunachal Pradesh, India
Authors: Limbu Ruksha , Roshan Upadhaya  , Renu Gogoi  , Jyoti Gaur
Published: July 2023

Tajuria illurgis illurgis (Hewitson, [1869]), is an Indo-Malayan blue butterfly belonging to the family Lycaenidae with distribution across the Himalaya, but there is no photographic evidence of the species from Arunachal Pradesh. On 25 August 2022, a single individual of the species was photographed at an elevation of 1,344 m from Vijaynagar, Arunachal Pradesh, which is the first photographic record of the species from the state. This species is also legally protected under Schedule II of the Indian Wildlife Protection Act 1972. Our record from Vijaynagar suggests that more scientific exploration on lepidopteran community is needed in future, with the area being geopolitically important boundary of Indo-Myanmar.
Prevalence of Chronic Kidney Disease Among US Adults With Hypertension, 1999 to 2018
Authors: Zeng Xianghui , Zeng Qingfeng , Zhou Lanqian , Zhu Hengqing , Luo Jianping
Published: July 2023

BACKGROUND:

Hypertension is a major cause of end-stage renal disease. Assessing temporal trends in the prevalence of chronic kidney disease (CKD) in hypertension could provide information for public health policies and plans.

METHODS:

From the National Health and Nutrition Examination Survey from 1999 to 2018, a probability sample of adults aged ≥20 years was collected. The primary outcomes were classified according to the estimated glomerular filtration rate and urinary albumin. Trend tests were performed to assess age-standardized prevalence trends of CKD, albuminuria, and macroalbuminuria in US adults with hypertension.

RESULTS:

A total of 23 120 US adults with hypertension were included in this study. The prevalence of any CKD, albuminuria, or macroalbuminuria in hypertension remained relatively stable. However, the age-standardized prevalence of stage 1 CKD in hypertension increased from 4.9% in 2003 to 2006 to 7.0% in 2015 to 2018 (
P
=0.0077 for trend). The age-standardized prevalence of stage 3b CKD in hypertension decreased from 2.9% in 2011 to 2014 to 2.1% in 2015 to 2018 (
P
=0.0350 for trend). A similar trend was observed for the age-standardized prevalence of stages 3 to 5 CKD in hypertension, which declined from 10.9% in 2011 to 2014 to 8.9% in 2015 to 2018 (
P
=0.0160 for trend).

CONCLUSIONS:

Among US adults with hypertension, the prevalence of any CKD, albuminuria, and macroalbuminuria remained relatively stable from 1999 to 2018, whereas the hypertensive population showed an increasing trend in stage 1 CKD from 2003 to 2006 to 2015 to 2018 and a decreasing trend in the prevalence of stages 3 to 5 and 3b CKD from 2011 to 2014 to 2015 to 2018.
Tütün Eksperleri, Tütün Teknolojisi Mühendislerinin Yaptıkları Lisansüstü Tezlerin Bibliyometrik Analizi
Authors: TANRIVERDİ Haluk , ÇIKI Kartal Doğukan
Published: July 2023

Bu araştırmada, ülkemizde tütün ve teknolojisi ile ilgili tek uzmanlık kolu olan tütün eksperliği meslek mensuplarının yaptıkları lisansüstü tez çalışmaları hakkında bilgi edinilmesi amaçlanmaktadır. Türkiye’de tütün eksperliği mesleğinin tarihi geçmişi 1875’lere dayanmaktadır. Tütün eksperliği eğitiminde ise, 1928 Yılından itibaren önceleri kurs şeklinde başlayan süreç, daha sonra 1975 yılında yüksekokulu bünyesinde devam etmiştir. Tütün eksperliği mesleğinin lisans düzeyinde eğitimi 1984 yılında başlamış, ilk yüksek lisans eğitimi 1987 yılında, doktora eğitimi ise 1990 yılında elde edilmiştir. 1987-2020 Yıllarını kapsayan süreçte 52 tütün eksperi-tütün teknolojisi mühendisi lisansüstü eğitim yapmışlardır. Araştırmada tütün eksperlerinin fen ve sosyal bilim enstitülerinde 4 temel bilim alanının farklı programlarında farklı bilim dallarında lisansüstü çalışması yaparak bilim alanına katkı sundukları ortaya çıkmıştır.
The Concept of Guarding the One from the Zhuangzi 《莊子》 to Early Chan Buddhism
Authors: Zhao Wen
Published: July 2023

This paper traces the conception of “guarding the One” (shou yi 守一), an equivalent to “one-practice samādhi” from the East Mountain Teaching (dong shan fa men 東山法門) in early Chan Buddhism, back to the Zhuangzi《莊子》. “Guarding the One” and “nurturing the shen” (yang shen 養神) appear frequently in the context of Daoist spiritual training for longevity. In early medieval Chinese Buddhism, with the influence of the discourse of Daoist spiritual training and the karma theory from India, the concept of shen 神 generally developed into a pure substance of the mind. This substance of the mind also echoes the theory of Buddha-nature, and played a significant role in “Fourth Patriarch” Daoxin’s interpretation of “guarding the One”.
The Surface Atmosphere Integrated Field Laboratory (SAIL) Campaign
Authors: Feldman D. R. , Aiken A. C. , Boos W. R. , Carroll R. W. H. , Chandrasekar V. , Collis S. , Creamean J. M. , de Boer G. , Deems J. , DeMott P. J. , Fan J. , Flores A. N. , Gochis D. , Grover M. , Hill T. C. J. , Hodshire A. , Hulm E. , Hume C. C. , Jackson R. , Junyent F. , Kennedy A. , Kumjian M. , Levin E. J. T. , Lundquist J. D. , O’Brien J. , Raleigh M. S. , Reithel J. , Rhoades A. , Rittger K. , Rudisill W. , Sherman Z. , Siirila-Woodburn E. , Skiles S. M. , Smith J. N. , Sullivan R. C. , Theisen A. , Tuftedal M. , Varble A. C. , Wiedlea A. , Wielandt S. , Williams K. , Xu Z.
Published: July 2023

The science of mountainous hydrology spans the atmosphere through the bedrock and inherently crosses physical and disciplinary boundaries: land–atmosphere interactions in complex terrain enhance clouds and precipitation, while watersheds retain and release water over a large range of spatial and temporal scales. Limited observations in complex terrain challenge efforts to improve predictive models of the hydrology in the face of rapid changes. The Upper Colorado River exemplifies these challenges, especially with ongoing mismatches between precipitation, snowpack, and discharge. Consequently, the U.S. Department of Energy’s (DOE) Atmospheric Radiation Measurement (ARM) user facility has deployed an observatory to the East River Watershed near Crested Butte, Colorado, between September 2021 and June 2023 to measure the main atmospheric drivers of water resources, including precipitation, clouds, winds, aerosols, radiation, temperature, and humidity. This effort, called the Surface Atmosphere Integrated Field Laboratory (SAIL), is also working in tandem with DOE-sponsored surface and subsurface hydrologists and other federal, state, and local partners. SAIL data can be benchmarks for model development by producing a wide range of observational information on precipitation and its associated processes, including those processes that impact snowpack sublimation and redistribution, aerosol direct radiative effects in the atmosphere and in the snowpack, aerosol impacts on clouds and precipitation, and processes controlling surface fluxes of energy and mass. Preliminary data from SAIL’s first year showcase the rich information content in SAIL’s many datastreams and support testing hypotheses that will ultimately improve scientific understanding and predictability of Upper Colorado River hydrology in 2023 and beyond.