bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploratory rearing is governed by hypothalamic MCH cells according to the locus coeruleus
Authors: Concetti Cristina , Viskaitis Paulius , Grujic Nikola , Duss Sian N. , Privitera Mattia , Bohacek Johannes , Peleg-Raibstein Daria , Burdakov Denis
Published: July 2023

Exploration is essential for survival because it allows animals to gather information about their environment. Rearing is a classic exploratory behavior, during which an animal transiently stands on its hind legs to sample its environment. It is widely observed in common lab conditions as well as in the wild, yet neural signals and circuits underlying this fundamental component of innate behavior remain unclear. We examined behavioral correlates of activity in hypothalamic MCH-producing neurons (MNs) – a recently characterized but still poorly understood neural type – and found that MN activation co-occurs with exploratory rears in mice. Complementary optogenetic and pharmacological manipulations indicated that MN activity selectively promotes rearing via G-protein coupled MCHR1 receptors. Furthermore, we showin vivothat activation of the locus coeruleus noradrenergic neurons rapidly inhibits MNs and suppresses rearing through MCHR1-dependent pathways. Overall, these findings define a subcortical neural module which both tracks and controls exploratory rearing.
Registered report: Age-preserved semantic memory and the CRUNCH effect manifested as differential semantic control networks: an fMRI study
Authors: Haitas Niobe , Dubuc Jade , Massé-Leblanc Camille , Chamberland Vincent , Amiri Mahnoush , Glatard Tristan , Wilson Maximiliano , Joanette Yves , Steffener Jason
Published: July 2023

Semantic memory representations are generally well maintained in aging, whereas semantic control is thought to be more affected. To explain this phenomenon, this study tested the predictions of the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH), focusing on task demands in aging as a possible framework. The CRUNCH effect would manifest itself in semantic tasks through a compensatory increase in neural activation in semantic control network regions but only up to a certain threshold of task demands. This study compares 39 younger (20–35 years old) with 39 older participants (60–75 years old) in a triad-based semantic judgment task performed in an fMRI scanner while manipulating task demand levels (low versus high) through semantic distance. In line with the CRUNCH predictions, differences in neurofunctional activation and behavioral performance (accuracy and response times) were expected in younger versus older participants in the low-versus high-demand conditions, which should be manifested in semantic control Regions of Interest (ROIs). Our older participants had intact behavioral performance, as proposed in the literature for semantic memory tasks (maintained accuracy and slower response times (RTs)). Age-invariant behavioral performance in the older group compared to the younger one is necessary to test the CRUNCH predictions. The older adults were also characterized by high cognitive reserve, as our neuropsychological tests showed. Our behavioral results confirmed that our task successfully manipulated task demands: error rates, RTs and perceived difficulty increased with increasing task demands in both age groups. We did not find an interaction between age group and task demand, or a statistically significant difference in activation between the low- and high-demand conditions for either RTs or accuracy. As for brain activation, we did not find the expected age group by task demand interaction, or a significant main effect of task demand. Overall, our results are compatible with neural activation in the semantic network and the semantic control network, largely in frontotemporoparietal regions. ROI analyses demonstrated significant effects (but no interactions) of task demand in the left and right inferior frontal gyrus, the left posterior middle temporal gyrus, the posterior inferior temporal gyrus and the prefrontal gyrus. Overall, our test did not confirm the CRUNCH predictions.
Design of artificial molecular motor inheriting directionality and scalability
Authors: Ito Kenta I. , Sato Yusuke , Toyabe Shoichi
Published: July 2023

The realization of artificial molecular motors with autonomous functionality and high performance is one of the major challenges in biophysics. Such motors provide not only new dimensions in biotechnologies but also a novel approach for the bottom-up elucidation of biological molecular motors. For practical applications, directionality and scalability are critical factors. However, the simultaneous realization of both remains a challenge. In this study, we propose a novel design of a rotary motor that can be fabricated using currently available technology, DNA origami, and validate its functionality by simulations with practical parameters. We demonstrate that the motor rotates unidirectionally and processively in the direction defined by the structural asymmetry. The motor also exhibits scalability in that increasing the number of motor legs allows for a larger speed, run length, and stall force. Because of its simple mechanism, a broad range of applications is expected.

Statement of Significance

Biological molecular motors are the most sophisticated nanomachines in nature. Despite a long research history, we have yet to understand how they work in detail. A simple and promising approach for this purpose is to build artificial molecular motors. The process of achieving them helps us to understand how biological motors are designed. Some artificial motors have already been achieved. However, each realization implements only part of the characteristics that biological motors possess. In this work, we propose a novel motor mechanism that simultaneously implements two essential characteristics: scalability and directionality. The results would help us improve the biophysics of molecular motors and contribute to achieving high-performance artificial molecular motors with possible industrial applications.
A streamlined method to obtain biologically active TcdA and TcdB toxins fromClostridioides difficile
Authors: Sapa Afi Akofa Diane , Brosse Anaïs , Coullon Héloïse , Pean de Ponfilly Gauthier , Candela Thomas , Monnier Alban Le
Published: July 2023

The major virulence factors ofClostridioides difficile(C. difficile) are enterotoxin A (TcdA) and cytotoxin B (TcdB). The study of toxins is a crucial step in exploring the virulence of this pathogen. Currently, the toxin purification process is either laborious and time-consuming inC. difficileor performed in heterologous hosts. Therefore, we propose a streamlined method to obtain functional toxins inC. difficile. TwoC. difficilestrains were generated each harboring a sequence encoding a His-tag at the 3’ end ofC. difficile630Δerm tcdAortcdBgenes. Each toxin gene is expressed using the Ptetpromoter inducible by anhydro-tetracycline. The purification yields were estimated to be 0.28 mg per liter and 0.1 mg per liter for rTcdA and rTcdB, respectively. In this study, we successfully developed a simple routine method that allows the production and purification of biologically rTcdA and rTcdB active toxins with similar activities compared to native toxins.
Harnessing Gradients for Self-Assembly of Peptide-Based Nanocapsules: A Pathway to Advanced Drug Delivery Systems
Authors: Li Haopeng , Qian Xuliang , Mohanram Harini , Han Xiao , Qi Huitang , Zou Guijin , Yuan Fenghou , Miserez Ali , Yang Qing , Liu Tian , Gao Huajian , Yu Jing
Published: July 2023

Biological systems often create materials with intricate structures to achieve specialized functions. In comparison, precise control of structures in man-made materials has been challenging. Here, we report a serendipitous discovery of insect cuticle peptides (ICPs) spontaneously forming nanocapsules through a single-step solvent exchange process, where the concentration gradient resulting from mixing of water and aceton drives the localization and self-assembly of the peptides into hollow nanocapsules. The underlying driving force is the intrinsic affinity of the peptides for a particular solvent concentration, while the diffusion of water and acetone creates a gradient interface that triggers peptide localization and self-assembly. This gradient-mediated self-assembly offers a transformative pathway towards next-generation drug delivery systems based on peptide nanocapsules.
Evolutionarily conserved fMRI network dynamics in the mouse, macaque, and human brain
Authors: Gutierrez-Barragan Daniel , Ramirez Julian S.B. , Panzeri Stefano , Xu Ting , Gozzi Alessandro
Published: July 2023

Evolutionarily relevant networks have been previously described in several mammalian species using time-averaged analyses of fMRI time-series. However, fMRI network activity is highly dynamic and continually evolves over timescales of seconds. Whether the dynamic organization of resting-state fMRI network activity is conserved across mammalian species remains unclear. Using frame-wise clustering of fMRI time-series, we find that intrinsic fMRI network dynamics in awake macaques and humans is characterized by recurrent transitions between a set of 4 dominant, neuroanatomically homologous fMRI coactivation modes (C-modes), three of which are also plausibly represented in the rodent brain. Importantly, in all species C-modes exhibit species-invariant dynamic features, including preferred occurrence at specific phases of fMRI global signal fluctuations, and a state transition structure compatible with infraslow coupled oscillator dynamics. Moreover, dominant C-mode occurrence reconstitutes the static organization of the fMRI connectome in all species, and is predictive of ranking of corresponding fMRI connectivity gradients. These results reveal a set of species-invariant principles underlying the dynamic organization of fMRI networks in mammalian species, and offer novel opportunities to relate fMRI network findings across the phylogenetic tree.
Dynamics of pax7 expression during development, muscle regeneration, andin vitrodifferentiation of satellite cells in the trout
Authors: Rallière Cécile , Jagot Sabrina , Sabin Nathalie , Gabillard Jean-Charles
Published: July 2023

Essential for muscle fiber formation and hypertrophy, muscle stem cells, also called satellite cells, reside beneath the basal lamina of the muscle fiber. Satellite cells have been commonly localized by the expression of the Paired box 7 (Pax7) due to its specificity and the availability of antibodies in tetrapods. In fish, the identification of satellite cells remains difficult due to the lack of specific antibodies in most species. Based on the development of a highly sensitivein situhybridization (RNAScope®) forpax7, we showed thatpax7+cells were detected in the undifferentiated myogenic epithelium corresponding to the dermomyotome at day 14 post-fertilization. Then, from day 24,pax7+cells gradually migrated into the deep myotome and were localized along the muscle fibers and reach their niche in satellite position of the fibres after hatching. Our results showed that 18 days after muscle injury, a large number ofpax7+cells accumulated at the wound site compared to the uninjured area. During thein vitrodifferentiation of satellite cells, the percentage ofpax7+cells decreased from 44% to 18% on day 7, and some differentiated cells still expressedpax7. Taken together, these results show the dynamic expression ofpax7genes and the follow-up of these muscle stem cells during the different situations of muscle fiber formation in trout.
Allosteric regulation of kinase activity in living cells
Authors: Godbole Shivani , Dokholyan Nikolay V.
Published: July 2023

The dysregulation of protein kinases is associated with multiple diseases due to the kinases’ involvement in a variety of cell signaling pathways. Manipulating protein kinase function, by controlling the active site, is a promising therapeutic and investigative strategy to mitigate and study diseases. Kinase active sites share structural similarities making it difficult to specifically target one kinase, allosteric control allows specific regulation and study of kinase function without directly targeting the active site. Allosteric sites are distal to the active site but coupled via a dynamic network of inter-atomic interactions between residues in the protein. Establishing an allosteric control over a kinase requires understanding the allosteric wiring of the protein. Computational techniques offer effective and inexpensive mapping of the allosteric sites on a protein. Here, we discuss methods to map and regulate allosteric communications in proteins, and strategies to establish control over kinase functions in live cells and organisms. Protein molecules, or “sensors” are engineered to function as tools to control allosteric activity of the protein as these sensors have high spatiotemporal resolution and help in understanding cell phenotypes after immediate activation or inactivation of a kinase. Traditional methods used to study protein functions, such as knockout, knockdown, or mutation, cannot offer a sufficiently high spatiotemporal resolution. We discuss the modern repertoire of tools to regulate protein kinases as we enter a new era in deciphering cellular signaling and developing novel approaches to treat diseases associated with signal dysregulation.
Innovative teaching practices during the emergency remote teaching (ERT) process: a phenomenological inquiry
Authors: Sadıç Tuğba , Bavlı Bünyamin
Published: July 2023

Purpose

The Covid-19 period has led to defining changes in the teaching process. Therefore, it is essential to explore how teachers have approached these changes, what experiences they have gained and what they have tried to change. This study aims to elucidate how innovative practices were applied in teaching – which was influenced by emergency remote teaching (ERT) – and better understand teachers' experiences related to these practices.

Design/methodology/approach

The phenomenology design, a qualitative research model, was executed in the current study. Phenomenological inquiry aims to interpret people's experiences about a specific concept designated as a phenomenon. Creswell (2020) classified two types of phenomenology: interpretive and descriptive. Interpretive phenomenology was employed in the current study as researchers collected data from individuals experiencing the phenomenon, collected and interpreted the data via excluding their own experiences.

Findings

As a result of the data interpretation, four themes related to experiences of innovative teaching practices during ERT were discovered: interpretation of innovative teaching, innovative teaching practices, needs related to innovative teaching and challenges to innovative teaching. The categories related to the interpretation of innovative teaching include positive and negative interpretation. The categories related to the second theme, innovative teaching practices, consist of characteristics of innovative teachers and innovative teaching practices employed. The categories related to the third theme, needs related to innovative teaching, are the need for guidance, training and technological infrastructure. The categories related to the fourth and final theme, challenges to innovative teaching, are barriers related to the teacher, barriers related to the learner and those related to the environment.

Originality/value

This study discovered that for teachers to practice innovative teaching, they must develop themselves, keep up-to-date and develop lifelong learning skills. Hung and Li (2017) reached a similar conclusion to the findings of this study: teachers' professional development is positively related to innovative teaching skills at a high level. The participating teachers stated that they had to rapidly improve their technological competency. It is thought that teachers developing their technological competencies will contribute to both ERT and face-to-face education at the end of the Pandemic.
Entrepreneurial borrowing overdue prediction based on stacking model transfer learning
Authors: Shengdong Mu , Yunjie Liu , Jijian Gu
Published: July 2023

Purpose

By introducing Stacking algorithm to solve the underfitting problem caused by insufficient data in traditional machine learning, this paper provides a new solution to the cold start problem of entrepreneurial borrowing risk control.

Design/methodology/approach

The authors introduce semi-supervised learning and integrated learning into the field of migration learning, and innovatively propose the Stacking model migration learning, which can independently train models on entrepreneurial borrowing credit data, and then use the migration strategy itself as the learning object, and use the Stacking algorithm to combine the prediction results of the source domain model and the target domain model.

Findings

The effectiveness of the two migration learning models is evaluated with real data from an entrepreneurial borrowing. The algorithmic performance of the Stacking-based model migration learning is further improved compared to the benchmark model without migration learning techniques, with the model area under curve value rising to 0.8. Comparing the two migration learning models reveals that the model-based migration learning approach performs better. The reason for this is that the sample-based migration learning approach only eliminates the noisy samples that are relatively less similar to the entrepreneurial borrowing data. However, the calculation of similarity and the weighing of similarity are subjective, and there is no unified judgment standard and operation method, so there is no guarantee that the retained traditional credit samples have the same sample distribution and feature structure as the entrepreneurial borrowing data.

Practical implications

From a practical standpoint, on the one hand, it provides a new solution to the cold start problem of entrepreneurial borrowing risk control. The small number of labeled high-quality samples cannot support the learning and deployment of big data risk control models, which is the cold start problem of the entrepreneurial borrowing risk control system. By extending the training sample set with auxiliary domain data through suitable migration learning methods, the prediction performance of the model can be improved to a certain extent and more generalized laws can be learned.

Originality/value

This paper introduces the thought method of migration learning to the entrepreneurial borrowing scenario, provides a new solution to the cold start problem of the entrepreneurial borrowing risk control system and verifies the feasibility and effectiveness of the migration learning method applied in the risk control field through empirical data.
The effectiveness of a training program on perceptions of caring culture among Turkish nurses: A quasi‐experimental trial
Authors: Gülşen Mehmet , Kutlu Adalet
Published: July 2023

Aim

To assess the effectiveness of a training program on perceptions of caring culture among Turkish nurses and investigate the relationships among caring culture, job satisfaction, and intention to leave.

Background

Every organisation has its on culture with its vairous components including values, symbols, practices and policies. Healthcare organizations need a favorable caring culture to support nurses and other professional working in the organisation.

Methods

This was a quasi‐experimental trial of an educational intervention conducted between October and December 2020 at a university hospital in Turkey. The sample of the study consisted of 86 nurses. A four‐week training program based on caring culture was provided for the training group. The data were collected using a Personal Information Form, the Turkish version of the Caring Culture Survey, and the Job Satisfaction Scale. Intention to leave was measured with a single question.

Findings

The mean total caring culture and personal caring scores of the training group were significantly higher after the training than before (p < 0.05). There were significant positive correlations between the mean caring culture total and subscale scores of the participants and their total job satisfaction scores. Besides, there were significant negative correlations between the caring culture total and subscale scores of the participants and their intentions to leave, but these relationships were weak or moderate (p < 0.05).

Conclusion

This training program based on caring culture can contribute to improving the caring culture perceptions of nurses. Caring culture is positively related to job satisfaction and negatively related to intentions to leave.

Implications for nursing and health policy

Healthcare organizations should prioritize creating a caring culture and designing initiatives that focus on caring culture. The perceptions of nurses about caring culture should be measured and identified regularly.
Rosacea and seborrheic dermatitis differentially respond to lactic acid sting and capsaicin tests in Chinese women
Authors: Hu Min , Tu Ying , Man Mao‐Qiang , He Yunting , Wu Pan , He Li , Gu Hua
Published: July 2023

Background

Although rosacea and seborrheic dermatitis share some symptoms of sensitive skin, whether they respond differently to lactic acid sting and capsaicin tests, common tests for diagnosis of sensitive skin, is unknown.

Objectives

To reveal the cutaneous responses to lactic acid sting (LAST) and capsaicin test (CAT) in females with either rosacea vs. seborrheic dermatitis.

Methods

A total of 60 patients with rosacea, 20 patients with seborrheic dermatitis and 40 normal controls were enrolled in the study. Their skin sensitivity to stimuli were evaluated following topical application of either 10% lactic acid solution or 0.001% capsaicin solution. Transepidermal water loss (TEWL) rates and erythema indexes were also measured on the face.

Results

In comparison to normal controls, the positive rate to either LAST or CAT was significantly higher in subjects with rosacea (p < 0.001), but not in that with seborrheic dermatitis. Similarly, individuals with rosacea displayed a higher positive rate to both LAST and CAT than those with seborrheic dermatitis and normal controls (p < 0.001). In parallel, the LAST scores and CAT scores in individuals with rosacea were significantly higher than in that with either seborrheic dermatitis or normal controls (p < 0.001). The baseline TEWL rates and erythema indexes were higher in individual with rosacea than in normal controls (p < 0.001). But the baseline TEWL rates and erythema indexes did not differ significantly between subjects with rosacea and that with seborrheic dermatitis. Moreover, LAST scores and CAT scores correlated positively with TEWL (p < 0.0001). TEWL rates were higher in CAT positive than in CAT negative subjects (p < 0.0001). Finally, erythema index correlated positively with CAT scores (p < 0.0001), but not with LAST scores (p = 0.0842).

Conclusions

Skin responses to LAST and CAT differ between individuals with rosacea and those with seborrheic dermatitis, possibly due to the differences in epidermal permeability barrier and the neurovascular hyperreactivity. The higher LAST and CAT scores, as well as positive rates of both LAST and CAT can be attributable to inferior permeability barrier and the neurovascular hyperreactivity in subjects with rosacea.
Fast backward steps and detachment of single kinesin molecules measured under a wide range of loads
Authors: Kondo Yuichi , Sasaki Kazuo , Higuchi Hideo
Published: July 2023

To understand force generation under a wide range of loads, the stepping of single kinesin molecules was measured at loads from −20 to 42 pN by optical tweezers with high temporal resolution. The optical trap has been improved to halve positional noise and increase bandwidth by using 200‐nm beads. The step size of the forward and backward steps was 8.2 nm even over a wide range of loads. Histograms of the dwell times of backward steps and detachment fit well to two independent exponential equations with fast (~0.4 ms) and slow (>3 ms) time constants, indicating the existence of a fast step in addition to the conventional slow step. The dwell times of the fast steps were almost independent of the load and ATP concentration, while those of the slow backward steps and detachment depended on those. We constructed the kinetic model to explain the fast and slow steps under a wide range of loads.
Drainage models: An evaluation of their applicability for the design of drainage systems in arid regions
Authors: Ellafi Murad , Simmons Robert , Deeks Lynda
Published: July 2023

Only 5%–10% of irrigated lands in least developed countries (LDCs) are currently drained. Although drainage simulation models (DSMs) are used to evaluate alternative designs, it is unclear which drainage model is suitable for LDCs' arid and semi‐arid regions. This study evaluates selected DSMs (ADAPT, RZWQM2, DRAINMOD, EPIC, HYDRUS‐1D, WaSim and SWAP) and critically assesses their applicability to arid and semi‐arid areas. Also, establish and apply selection criteria based on the availability of data in LDCs with Libya as a case study, and identify the most suitable model for application in Libya. DRAINMOD had the highest overall score, and alternative methods to predict missing input parameters for DRAINMOD are discussed. Evaluating the feasibility of using predicted input parameters for DSMs to design drainage systems in LDCs would help farmers, planners and decision‐makers to reduce the overall cost of drainage system and, also, make DRAINMOD a more accessible tool to evaluate different drainage designs.
On weighted-blowup formulae of genus zero orbifold Gromov–Witten invariants
Authors: Chen Bohui , Du Cheng-Yong
Published: July 2023

In this paper, we provide a new approach to prove some weighted-blowup formulae for genus zero orbifold Gromov–Witten invariants. As a consequence, we show the invariance of symplectically rational connectedness with respect to weighted-blowup along positive centers. Furthermore, we use this method to give a new proof to the genus zero relative-orbifold correspondence of Gromov–Witten invariants.
Draft genomes of 17 bacterial isolates from Louisiana raw sugarcane factory juices and biofilms
Authors: Qi Yunci , Bruni Gillian
Published: July 2023

We report the draft genomes for 17 bacterial isolates belonging to the genera
Gluconobacter
,
Leuconostoc
, and
Pantoea
that were obtained from Louisiana raw sugarcane factory juice and biofilm samples.
Serial dependencies in visual stability during self-motion
Authors: Bayer Manuel , Zimmermann Eckart
Published: July 2023

We report that visual stability during self-motion is maintained by serial dependencies between the current and the previous gaze-contingent visual velocity that was experienced during a head movement. The gaze-contingent scene displacement velocity that appears normal to us thus depends on what we have registered in the recent history of gaze shifts. Serial dependencies provide an efficient means to maintain visual stability during self-motion.
Ciliated Hepatic Foregut Cyst: Definitive Diagnosis Is Critical to the Optimal Treatment Pathway
Authors: Kato Tatsuhiro , Schammel Christine M. G. , Fenton Hubert , Trocha Steven D. , Devane A. Michael
Published: July 2023

Background. Ciliated hepatic foregut cyst (CHFC) is a rare, benign cyst of the liver, derived from the embryonic foregut epithelium. Although CHFCs are typically asymptomatic, some present with nonspecific abdominal symptoms. Imaging modalities alone are insufficient for diagnosis, with intrahepatic cholangiocarcinoma included in the differential due to nonspecific imaging features; definitive diagnosis relies on histologic confirmation. These lesions are often benign; however, larger lesions can have malignant transformation into squamous cell carcinoma (SCC), which carries a poor prognosis, thus making a definitive diagnosis, no matter what size, essential. Here, we present a case of CHFC as well as a comprehensive literature review. Given these data, we propose an algorithm for definitive diagnosis.
Supplemental Table 6 from Validating Wave 1 (2014) Urinary Cotinine and TNE-2 Cut-points for Differentiating Wave 4 (2017) Cigarette Use from Non-use in the United States Using Data from the PATH Study
Authors: Edwards Kathryn C. , Khan Asia , Sharma Eva , Wang Lanqing , Feng June , Blount Benjamin C. , Sosnoff Connie S. , Smith Danielle M. , Goniewicz Maciej L. , Pearson Jennifer , Villanti Andrea C. , Delnevo Cristine D. , Bover-Manderski Michelle T. , Hatsukami Dorothy K. , Niaura Raymond , Everard Colm , Kimmel Heather L. , Duffy Kara , Rostron Brian L. , Del Valle-Pinero Arseima Y. , van Bemmel Dana M. , Stanton Cassandra A. , Hyland Andrew
Published: July 2023

Supplemental Table 6 provides Wave 1 and Wave 4 TNE-2 cut-points for any tobacco use.
Supplemental Table 5 from Validating Wave 1 (2014) Urinary Cotinine and TNE-2 Cut-points for Differentiating Wave 4 (2017) Cigarette Use from Non-use in the United States Using Data from the PATH Study
Authors: Edwards Kathryn C. , Khan Asia , Sharma Eva , Wang Lanqing , Feng June , Blount Benjamin C. , Sosnoff Connie S. , Smith Danielle M. , Goniewicz Maciej L. , Pearson Jennifer , Villanti Andrea C. , Delnevo Cristine D. , Bover-Manderski Michelle T. , Hatsukami Dorothy K. , Niaura Raymond , Everard Colm , Kimmel Heather L. , Duffy Kara , Rostron Brian L. , Del Valle-Pinero Arseima Y. , van Bemmel Dana M. , Stanton Cassandra A. , Hyland Andrew
Published: July 2023

Supplemental Table 5 provides Wave 1 and Wave 4 cotinine cut-points for any tobacco use.
Supplemental Table 2 from Validating Wave 1 (2014) Urinary Cotinine and TNE-2 Cut-points for Differentiating Wave 4 (2017) Cigarette Use from Non-use in the United States Using Data from the PATH Study
Authors: Edwards Kathryn C. , Khan Asia , Sharma Eva , Wang Lanqing , Feng June , Blount Benjamin C. , Sosnoff Connie S. , Smith Danielle M. , Goniewicz Maciej L. , Pearson Jennifer , Villanti Andrea C. , Delnevo Cristine D. , Bover-Manderski Michelle T. , Hatsukami Dorothy K. , Niaura Raymond , Everard Colm , Kimmel Heather L. , Duffy Kara , Rostron Brian L. , Del Valle-Pinero Arseima Y. , van Bemmel Dana M. , Stanton Cassandra A. , Hyland Andrew
Published: July 2023

Supplemental Table 2 provides demographic and tobacco use characteristics of any tobacco users.
Supplementary Table S3 from HSA Adductomics Reveals Sex Differences in NHL Incidence and Possible Involvement of Microbial Translocation
Authors: Grigoryan Hasmik , Imani Partow , Sacerdote Carlotta , Masala Giovanna , Grioni Sara , Tumino Rosario , Chiodini Paolo , Dudoit Sandrine , Vineis Paolo , Rappaport Stephen M.
Published: July 2023

Supplementary Table S3: Fold changes and p-values for adducts
Supplemental Figure 1 from Validating Wave 1 (2014) Urinary Cotinine and TNE-2 Cut-points for Differentiating Wave 4 (2017) Cigarette Use from Non-use in the United States Using Data from the PATH Study
Authors: Edwards Kathryn C. , Khan Asia , Sharma Eva , Wang Lanqing , Feng June , Blount Benjamin C. , Sosnoff Connie S. , Smith Danielle M. , Goniewicz Maciej L. , Pearson Jennifer , Villanti Andrea C. , Delnevo Cristine D. , Bover-Manderski Michelle T. , Hatsukami Dorothy K. , Niaura Raymond , Everard Colm , Kimmel Heather L. , Duffy Kara , Rostron Brian L. , Del Valle-Pinero Arseima Y. , van Bemmel Dana M. , Stanton Cassandra A. , Hyland Andrew
Published: July 2023

Supplemental Figure 1 shows the analytic sample flow chart.
Supplementary Figure S1 from HSA Adductomics Reveals Sex Differences in NHL Incidence and Possible Involvement of Microbial Translocation
Authors: Grigoryan Hasmik , Imani Partow , Sacerdote Carlotta , Masala Giovanna , Grioni Sara , Tumino Rosario , Chiodini Paolo , Dudoit Sandrine , Vineis Paolo , Rappaport Stephen M.
Published: July 2023

Supplementary Figure S1: Ensemble of classification models for selection of adduct features associated with NHL incidence
Supplementary Table 4 from Sex-specific Associations between Body Mass Index and Thyroid Cancer Incidence among Korean Adults
Authors: Kim Kyoung-Nam , Kim Kyungsik , Lee Sangjun , Park Sue K.
Published: July 2023

Supplementary Table 4 shows the associations between body mass (BMI) and thyroid cancer incidence in the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) at 5-year latency
Table S9 from Using DEPendency of Association on the Number of Top Hits (DEPTH) as a Complementary Tool to Identify Novel Colorectal Cancer Susceptibility Loci
Authors: Lai John , Wong Chi Kuen , Schmidt Daniel F. , Kapuscinski Miroslaw K. , Alpen Karen , MacInnis Robert J. , Buchanan Daniel D. , Win Aung K. , Figueiredo Jane C. , Chan Andrew T. , Harrison Tabitha A. , Hoffmeister Michael , White Emily , Le Marchand Loic , Pai Rish K. , Peters Ulrike , Hopper John L. , Jenkins Mark A. , Makalic Enes
Published: July 2023

Supplementary Table S9 shows the number of risk regions that are common to both CCFR and GECCO in stage 3 DEPTH analysis, as well as whether they are detected by logistic regression analysis or were in previous CRC GWAS studies.
Table S4 from Using DEPendency of Association on the Number of Top Hits (DEPTH) as a Complementary Tool to Identify Novel Colorectal Cancer Susceptibility Loci
Authors: Lai John , Wong Chi Kuen , Schmidt Daniel F. , Kapuscinski Miroslaw K. , Alpen Karen , MacInnis Robert J. , Buchanan Daniel D. , Win Aung K. , Figueiredo Jane C. , Chan Andrew T. , Harrison Tabitha A. , Hoffmeister Michael , White Emily , Le Marchand Loic , Pai Rish K. , Peters Ulrike , Hopper John L. , Jenkins Mark A. , Makalic Enes
Published: July 2023

Supplementary Table S4 shows the number of participants filtered out at each QC stage (according to Supplementary Table S2).
Table S2 from Using DEPendency of Association on the Number of Top Hits (DEPTH) as a Complementary Tool to Identify Novel Colorectal Cancer Susceptibility Loci
Authors: Lai John , Wong Chi Kuen , Schmidt Daniel F. , Kapuscinski Miroslaw K. , Alpen Karen , MacInnis Robert J. , Buchanan Daniel D. , Win Aung K. , Figueiredo Jane C. , Chan Andrew T. , Harrison Tabitha A. , Hoffmeister Michael , White Emily , Le Marchand Loic , Pai Rish K. , Peters Ulrike , Hopper John L. , Jenkins Mark A. , Makalic Enes
Published: July 2023

Supplementary Table S2 shows the QC and harmonisation steps for both the GECCO and CCFR datasets
Figure S5 from Using DEPendency of Association on the Number of Top Hits (DEPTH) as a Complementary Tool to Identify Novel Colorectal Cancer Susceptibility Loci
Authors: Lai John , Wong Chi Kuen , Schmidt Daniel F. , Kapuscinski Miroslaw K. , Alpen Karen , MacInnis Robert J. , Buchanan Daniel D. , Win Aung K. , Figueiredo Jane C. , Chan Andrew T. , Harrison Tabitha A. , Hoffmeister Michael , White Emily , Le Marchand Loic , Pai Rish K. , Peters Ulrike , Hopper John L. , Jenkins Mark A. , Makalic Enes
Published: July 2023

Supplementary Figure S5 showing the QQ and Manhattan plots of conventional GWAS on the GECCO and CCFR datasets
Figure S3 from Using DEPendency of Association on the Number of Top Hits (DEPTH) as a Complementary Tool to Identify Novel Colorectal Cancer Susceptibility Loci
Authors: Lai John , Wong Chi Kuen , Schmidt Daniel F. , Kapuscinski Miroslaw K. , Alpen Karen , MacInnis Robert J. , Buchanan Daniel D. , Win Aung K. , Figueiredo Jane C. , Chan Andrew T. , Harrison Tabitha A. , Hoffmeister Michael , White Emily , Le Marchand Loic , Pai Rish K. , Peters Ulrike , Hopper John L. , Jenkins Mark A. , Makalic Enes
Published: July 2023

Supplementary Figure S3 shows further filtering of SNPs that had greater than 20% difference in odds ratio or P values when comparing odds ratios and P values before and after adjusting for the first four principal components.
Supplementary Table 1 from Impact of Frontline Ivosidenib on Volumetric Growth Patterns in Isocitrate Dehydrogenase–mutant Astrocytic and Oligodendroglial Tumors
Authors: Kamson David Olayinka , Puri Sushant , Sang Yingying , Shi Meihui Jessica , Blair Lindsay , Blakeley Jaishri O. , Laterra John
Published: July 2023

Supplementary Table 1 - Detailed volumetric data for each patient.
Table S1 from Results of an Open-label, Phase Ia/b Study of Pembrolizumab plus Olaratumab in Patients with Unresectable, Locally Advanced, or Metastatic Soft-Tissue Sarcoma
Authors: Schöffski Patrick , Bahleda Rastislav , Wagner Andrew J. , Burgess Melissa A. , Junker Niels , Chisamore Michael , Peterson Patrick , Szpurka Anna M. , Ceccarelli Matteo , Tap William D.
Published: July 2023

Table S1: DLT exceptions.
Supplementary Data S8 from Genomic Profiling of Metastatic Castration-Resistant Prostate Cancer Samples Resistant to Androgen Receptor Pathway Inhibitors
Authors: Menssouri Naoual , Poiraudeau Loïc , Helissey Carole , Bigot Ludovic , Sabio Jonathan , Ibrahim Tony , Pobel Cédric , Nicotra Claudio , Ngo-Camus Maud , Lacroix Ludovic , Rouleau Etienne , Tselikas Lambros , Chauchereau Anne , Blanc-Durand Félix , Bernard-Tessier Alice , Patrikidou Anna , Naoun Natacha , Flippot Ronan , Colomba Emeline , Fuerea Alina , Albiges Laurence , Lavaud Pernelle , van de Wiel Paul , den Biezen Eveline , Wesseling-Rozendaal Yvonne , Ponce Santiago , Michiels Stefan , Massard Christophe , Gautheret Daniel , Barlesi Fabrice , André Fabrice , Besse Benjamin , Scoazec Jean-Yves , Friboulet Luc , Fizazi Karim , Loriot Yohann
Published: July 2023

Supplementary Data 8 describes GSEA analysis with overexpressed and underexpressed gene sets in primary resistant samples.
Supplementary Data S7 from Genomic Profiling of Metastatic Castration-Resistant Prostate Cancer Samples Resistant to Androgen Receptor Pathway Inhibitors
Authors: Menssouri Naoual , Poiraudeau Loïc , Helissey Carole , Bigot Ludovic , Sabio Jonathan , Ibrahim Tony , Pobel Cédric , Nicotra Claudio , Ngo-Camus Maud , Lacroix Ludovic , Rouleau Etienne , Tselikas Lambros , Chauchereau Anne , Blanc-Durand Félix , Bernard-Tessier Alice , Patrikidou Anna , Naoun Natacha , Flippot Ronan , Colomba Emeline , Fuerea Alina , Albiges Laurence , Lavaud Pernelle , van de Wiel Paul , den Biezen Eveline , Wesseling-Rozendaal Yvonne , Ponce Santiago , Michiels Stefan , Massard Christophe , Gautheret Daniel , Barlesi Fabrice , André Fabrice , Besse Benjamin , Scoazec Jean-Yves , Friboulet Luc , Fizazi Karim , Loriot Yohann
Published: July 2023

Supplementary Data 7 describes the molecular features associated with response and primary resistance to ARPI.
Supplementary Data S6 from Genomic Profiling of Metastatic Castration-Resistant Prostate Cancer Samples Resistant to Androgen Receptor Pathway Inhibitors
Authors: Menssouri Naoual , Poiraudeau Loïc , Helissey Carole , Bigot Ludovic , Sabio Jonathan , Ibrahim Tony , Pobel Cédric , Nicotra Claudio , Ngo-Camus Maud , Lacroix Ludovic , Rouleau Etienne , Tselikas Lambros , Chauchereau Anne , Blanc-Durand Félix , Bernard-Tessier Alice , Patrikidou Anna , Naoun Natacha , Flippot Ronan , Colomba Emeline , Fuerea Alina , Albiges Laurence , Lavaud Pernelle , van de Wiel Paul , den Biezen Eveline , Wesseling-Rozendaal Yvonne , Ponce Santiago , Michiels Stefan , Massard Christophe , Gautheret Daniel , Barlesi Fabrice , André Fabrice , Besse Benjamin , Scoazec Jean-Yves , Friboulet Luc , Fizazi Karim , Loriot Yohann
Published: July 2023

Supplementary Data 6 describes the patients included in the RNA sequencing analysis as well as AR and NEPC scores.
Supplementary Data S11 from Genomic Profiling of Metastatic Castration-Resistant Prostate Cancer Samples Resistant to Androgen Receptor Pathway Inhibitors
Authors: Menssouri Naoual , Poiraudeau Loïc , Helissey Carole , Bigot Ludovic , Sabio Jonathan , Ibrahim Tony , Pobel Cédric , Nicotra Claudio , Ngo-Camus Maud , Lacroix Ludovic , Rouleau Etienne , Tselikas Lambros , Chauchereau Anne , Blanc-Durand Félix , Bernard-Tessier Alice , Patrikidou Anna , Naoun Natacha , Flippot Ronan , Colomba Emeline , Fuerea Alina , Albiges Laurence , Lavaud Pernelle , van de Wiel Paul , den Biezen Eveline , Wesseling-Rozendaal Yvonne , Ponce Santiago , Michiels Stefan , Massard Christophe , Gautheret Daniel , Barlesi Fabrice , André Fabrice , Besse Benjamin , Scoazec Jean-Yves , Friboulet Luc , Fizazi Karim , Loriot Yohann
Published: July 2023

Supplementary data 11 describes the GSEA analysis of paired biopsies
Supplementary Data S10 from Genomic Profiling of Metastatic Castration-Resistant Prostate Cancer Samples Resistant to Androgen Receptor Pathway Inhibitors
Authors: Menssouri Naoual , Poiraudeau Loïc , Helissey Carole , Bigot Ludovic , Sabio Jonathan , Ibrahim Tony , Pobel Cédric , Nicotra Claudio , Ngo-Camus Maud , Lacroix Ludovic , Rouleau Etienne , Tselikas Lambros , Chauchereau Anne , Blanc-Durand Félix , Bernard-Tessier Alice , Patrikidou Anna , Naoun Natacha , Flippot Ronan , Colomba Emeline , Fuerea Alina , Albiges Laurence , Lavaud Pernelle , van de Wiel Paul , den Biezen Eveline , Wesseling-Rozendaal Yvonne , Ponce Santiago , Michiels Stefan , Massard Christophe , Gautheret Daniel , Barlesi Fabrice , André Fabrice , Besse Benjamin , Scoazec Jean-Yves , Friboulet Luc , Fizazi Karim , Loriot Yohann
Published: July 2023

Supplementary data 10 describes the genomic alterations associated with secondary resistance
Supplementary Data S1 from Genomic Profiling of Metastatic Castration-Resistant Prostate Cancer Samples Resistant to Androgen Receptor Pathway Inhibitors
Authors: Menssouri Naoual , Poiraudeau Loïc , Helissey Carole , Bigot Ludovic , Sabio Jonathan , Ibrahim Tony , Pobel Cédric , Nicotra Claudio , Ngo-Camus Maud , Lacroix Ludovic , Rouleau Etienne , Tselikas Lambros , Chauchereau Anne , Blanc-Durand Félix , Bernard-Tessier Alice , Patrikidou Anna , Naoun Natacha , Flippot Ronan , Colomba Emeline , Fuerea Alina , Albiges Laurence , Lavaud Pernelle , van de Wiel Paul , den Biezen Eveline , Wesseling-Rozendaal Yvonne , Ponce Santiago , Michiels Stefan , Massard Christophe , Gautheret Daniel , Barlesi Fabrice , André Fabrice , Besse Benjamin , Scoazec Jean-Yves , Friboulet Luc , Fizazi Karim , Loriot Yohann
Published: July 2023

The supplementary Data 1 describes the clinical characteristics of patients included in the analysis.
Data from Impact of Frontline Ivosidenib on Volumetric Growth Patterns in Isocitrate Dehydrogenase–mutant Astrocytic and Oligodendroglial Tumors
Authors: Kamson David Olayinka , Puri Sushant , Sang Yingying , Shi Meihui Jessica , Blair Lindsay , Blakeley Jaishri O. , Laterra John
Published: July 2023

AbstractPurpose:
Isocitrate dehydrogenase (IDH)-mutant gliomas are usually treated with radiotherapy and chemotherapy, which increases the risk for neurocognitive sequelae during patients’ most productive years. We report our experience using off-label first-in-class mutant IDH1 inhibitor ivosidenib and its impact on tumor volume in IDH-mutant gliomas.
Experimental Design:
We retrospectively analyzed patients ages ≥18 years with radiation/chemotherapy-naïve, mutant IDH1, nonenhancing, radiographically active, grade 2/3 gliomas, and ≥2 pretreatment and ≥2 on-treatment ivosidenib MRIs. T2/FLAIR-based tumor volumes, growth rates, and progression-free survival (PFS) were analyzed. log-linear mixed-effect modeling of growth curves adjusted for grade, histology, and age was performed.
Results:
We analyzed 116 MRIs of 12 patients [10 males, median age 46 years (range: 26–60)]: 8 astrocytomas (50% grade 3) and 4 grade 2 oligodendrogliomas. Median on-drug follow-up was 13.2 months [interquartile range (IQR): 9.7–22.2]. Tolerability was 100%. A total of 50% of patients experienced ≥20% tumor volume reduction on-treatment and absolute growth rate was lower during treatment (−1.2 ± 10.6 cc/year) than before treatment (8.0 ± 7.7 cc/year; P ≤ 0.05). log-linear models in the Stable group (n = 9) showed significant growth before treatment (53%/year; P = 0.013), and volume reduction (−34%/year; P = 0.037) after 5 months on treatment. After treatment, volume curves were significantly lower than before treatment (after/before treatment ratio 0.5; P < 0.01). Median time-to-best response was 11.2 (IQR: 1.7–33.4) months, and 16.8 (IQR: 2.6–33.5) months in patients on drug for ≥1 year. PFS at 9 months was 75%.
Conclusions:
Ivosidenib was well tolerated and induced a high volumetric response rate. Responders had significant reduction in tumor growth rates and volume reductions observed after a 5-month delay. Thus, ivosidenib appears useful to control tumor growth and delay more toxic therapies in IDH-mutant nonenhancing indolently growing gliomas.
Data from Results of an Open-label, Phase Ia/b Study of Pembrolizumab plus Olaratumab in Patients with Unresectable, Locally Advanced, or Metastatic Soft-Tissue Sarcoma
Authors: Schöffski Patrick , Bahleda Rastislav , Wagner Andrew J. , Burgess Melissa A. , Junker Niels , Chisamore Michael , Peterson Patrick , Szpurka Anna M. , Ceccarelli Matteo , Tap William D.
Published: July 2023

AbstractPurpose:
The study evaluated safety and efficacy of olaratumab + pembrolizumab in patients with unresectable locally advanced/metastatic soft-tissue sarcoma (STS) with disease progression on standard treatment.
Patients and Methods:
This was open-label, multicenter, nonrandomized, phase Ia/Ib dose-escalation study followed by cohort expansion (olaratumab + pembrolizumab intravenous infusion). Primary objectives were safety and tolerability.
Results:
The majority of patients enrolled (n = 41) were female [phase Ia: 9 of 13, phase Ib/dose-expansion cohort (DEC), 17 of 28], aged < 65 years. In phases Ia and Ib, 13 and 26 patients received prior systemic therapy, respectively. Patients received olaratumab 15 mg/kg (phase Ia; cohort 1) or 20 mg/kg (phase Ia; cohort 2 and phase Ib) and pembrolizumab 200 mg (phase Ia/Ib). The median (Q1–Q3) duration of therapy (olaratumab) was 6.0 (3.0–11.9; cohort 1), 14.4 (12.4–20.9; cohort 2), and 14.0 (6.0–21.8) weeks (DEC). No dose-limiting toxicities and few grade ≥ 3 treatment-emergent adverse events [TEAE; 15 mg/kg: 2 (increased lipase); 20 mg/kg: 1 (increased lipase), 1 (colitis), 2 (diarrhea), 3 (anemia)] were reported. Two TEAEs (increased lipase) were related to study discontinuations. Twenty-one patients reported mild (grade ≤ 2) TEAEs [phase Ia, disease control rate (DCR):14.3% (1/7, cohort 1); 66.7% (4/6, cohort 2); no responses were reported; phase Ib, DCR: 53.6% (15/28); objective response rate: 21.4% (6/28; RECIST and irRECIST criteria)]. No response was observed in patients with programmed death ligand-1–positive tumors.
Conclusions:
Antitumor activity was observed in some patients in DEC, and combination was well tolerated with manageable safety profile. Further studies are warranted to evaluate the efficacy and mechanistic impact of platelet-derived growth factor receptor inhibitors with immune checkpoint modulator coadministration.