bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR006: Multi-modal single-cell profiling of sarcomas from archival tissue reveals mechanisms of resistance to immune checkpoint inhibitors
Authors: Bose Sminu , Caldwell Blake , Amin Amit Dipak , Melms Johannes , Tagore Somnath , Ingham Matthew , Izar Benjamin , Schwartz Gary K. 
Published: September 2022

Abstract
Single-cell genomics is an enabling technology that may inform the molecular underpinnings of drug response and resistance in patient biopsies. These methods are difficult to implement in the study of rare diseases such as sarcomas due to specimen requirements and technical limitations. Here, we evolved novel methods that we recently reported in melanoma (Wang, Fan, et al., bioRxiv, 2022) which enable single-nucleus RNA, T cell receptor (snRNA/TCR-seq), and pool-matched whole-genome sequencing (WGS) from archival frozen sarcoma tissue. This enabled profiling of 75,716 cells and 788 matched TCR clonotypes from six patients with intimal sarcoma (INS) and undifferentiated pleomorphic sarcoma (UPS), including two matched pair samples from pre/post-immune checkpoint inhibitor (ICI). Our analysis revealed substantial transcriptional cancer cell heterogeneity driven by varying copy number alterations (CNAs). In one patient with INS with a complete response to ICI followed by an isolated recurrence, we identified a rare cancer cell clone defined by CNA (confirmed with WGS) and resulting transcriptional outputs that pre-existed and emerged during resistance. Furthermore, in a UPS patient with intrinsic resistance to ICI, we find adequate T cell clonal expansion, activation, and differentiation, suggesting appropriate T cell response to ICI dampened by intrinsic mechanisms of ICI resistance within the cancer cells. Non-negative matrix factorization (NMF) analysis identified cell states associated with either intrinsic or adaptive resistance to ICI that was distinct from resistance to doxorubicin. These observations are consistent with those previously reported from sequential biopsies obtained from KEYNOTE-001 in metastatic melanoma (Wang, Fan, et al., bioRxiv, 2022), which also revealed emergence of pre-existing populations of resistant clones defined by their underlying aneuploidy patterns. Together, these results demonstrate feasibility of implementing single-cell genomics from archival tissue to study sarcoma and propel our understanding of drug resistance. Conceptually, this work suggests that large-scale CNAs may allow us to identify cell sub-populations associated with ICI resistance in sarcoma and in other diseases.
Citation Format: Sminu Bose, Blake Caldwell, Amit Dipak Amin, Johannes Melms, Somnath Tagore, Matthew Ingham, Benjamin Izar, Gary K. Schwartz. Multi-modal single-cell profiling of sarcomas from archival tissue reveals mechanisms of resistance to immune checkpoint inhibitors [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr PR006.
Transcriptome analysis of sweet potato responses to potassium deficiency
Authors: Wang Fang , Tan Wen-Fang , Song Wei , Yang Song-Tao , Qiao Shuai 
Published: September 2022

Abstract
Background
As one of three essential nutrients, potassium is regarded as a main limiting factor for growth and development in plant. Sweet potato (Ipomoea batatas L.) is one of seven major food crops grown worldwide, and is both a nutrient-rich food and a bioenergy crop. It is a typical ‘K-favoring’ crop, and the level of potassium ion (K+) supplementation directly influences its production. However, little is known about the transcriptional changes in sweet potato genes under low-K+ conditions. Here, we analyzed the transcriptomic profiles of sweet potato roots in response to K+ deficiency to determine the effect of low-K+ stress on this economically important crop.

Results
The roots of sweet potato seedlings with or without K+ treatment were harvested and used for transcriptome analyses. The results showed 559 differently expressed genes (DEGs) in low and high K+ groups. Among the DEGs, 336 were upregulated and 223 were downregulated. These DEGs were involved in transcriptional regulation, calcium binding, redox-signaling, biosynthesis, transport, and metabolic process. Further analysis revealed previously unknow genes involved in low-K+ stress, which could be investigated further to improve low K+ tolerance in plants. Confirmation of RNA-sequencing results using qRT-PCR displayed a high level of consistency between the two experiments. Analysis showed that many auxin-, ethylene- and jasmonic acid-related genes respond to K+ deficiency, suggesting that these hormones have important roles in K+ nutrient signaling in sweet potato.

Conclusions
According to the transcriptome data of sweet potato, various DEGs showed transcriptional changes in response to low-K+ stress. However, the expression level of some kinases, transporters, transcription factors (TFs), hormone-related genes, and plant defense-related genes changed significantly, suggesting that they have important roles during K+ deficiency. Thus, this study identifies potential genes for genetic improvement of responses to low-K+ stress and provides valuable insight into the molecular mechanisms regulating low K+ tolerance in sweet potato. Further research is required to clarify the function of these DEGs under low-K+ stress.
Intracranial stenting as a bail-out option for posthemorrhagic cerebral vasospasm: a single-center experience with long-term follow-up
Authors: Khanafer Ali , Cimpoca Alexandru , Bhogal Pervinder , Bäzner Hansjörg , Ganslandt Oliver , Henkes Hans 
Published: September 2022

Abstract
Background
Cerebral vasospasm (CVS) is a leading cause of morbidity and mortality in patients after aneurysmal subarachnoid hemorrhage (aSAH). Endovascular treatment, including intraarterial infusion of drugs with vasodilation effects, and balloon- and stentriever angioplasty, are helpful but may achieve only short-term effects. There is a clinical need for long-lasting treatment of refractory recurrent vasospasm. We report our experience in stent implantation as a treatment for recurrent severe post-SAH vasospasm.

Methods
A retrospective analysis of our institutional database of 883 patients with SAH, managed between January 2010 and December 2021, was performed. Six patients were identified as having received intracranial stenting in the context of post-SAH cerebral vasospasm. All patients were initially treated with intra-arterial infusion of nimodipine and/or milrinone. Self-expanding intracranial stents were implanted during endovascular aneurysm treatment to enable access despite impaired perfusion (Group 1) or as a bail-out strategy after failed intraarterial drug infusion or mechanical treatment (Group 2). All stented patients received dual antiplatelet therapy (DAPT) for 6 months.

Results
Nine vessels in six patients with severe post-SAH vasospasm were stented. The stents were deployed in 16 vessel segments. All attempted implantations were technically successful. All patients demonstrated radiographic and clinical improvement of the vessel narrowing. No recurrent vasospasm or permanent vessel occlusion of the stented vessels was encountered. A thrombus formation in a Group 1 patient resolved under 4 mg eptifibatide IA infusion. During long-term angiographic follow-up, neither in-stent stenosis nor stent occlusion was found.

Conclusions
Endovascular implantation of self-expanding stents is a potential ultima ratio strategy for patients with severe refractory post-SAH cerebral vasospasm. Stents with reduced thrombogenicity (avoiding DAPT) and bioabsorbable self-expanding stents might further advance this concept.
The effect of the participatory heat education and awareness tools (HEAT) intervention on agricultural worker physiological heat strain: results from a parallel, comparison, group randomized study
Authors: Chavez Santos Erica , Spector June T. , Egbert Jared , Krenz Jennifer , Sampson Paul D. , Palmández Pablo , Torres Elizabeth , Blancas Maria , Carmona Jose , Jung Jihoon , Flunker John C. 
Published: September 2022

Abstract
Background
Farmworkers are at risk of heat-related illness (HRI). We sought to: 1) evaluate the effectiveness of farmworker Spanish/English participatory heat education and a supervisor decision-support mobile application (HEAT intervention) on physiological heat strain; and 2) describe factors associated with HRI symptoms reporting.

Methods
We conducted a parallel, comparison group intervention study from May–September of 2019 in Central/Eastern Washington State, USA. We used convenience sampling to recruit adult outdoor farmworkers and allocated participating crews to intervention (n = 37 participants) and alternative-training comparison (n = 38 participants) groups. We measured heat strain monthly using heart rate and estimated core body temperature to compute the maximum work-shift physiological strain index (PSImax) and assessed self-reported HRI symptoms using a weekly survey. Multivariable linear mixed effects models were used to assess associations of the HEAT intervention with PSImax, and bivariate mixed models were used to describe factors associated with HRI symptoms reported (0, 1, 2+ symptoms), with random effects for workers.

Results
We observed larger decreases in PSImax in the intervention versus comparison group for higher work exertion levels (categorized as low, low/medium-low, and high effort), after adjustment for maximum work-shift ambient Heat Index (HImax), but this was not statistically significant (interaction − 0.91 for high versus low/medium-low effort, t = − 1.60, p = 0.11). We observed a higher PSImax with high versus low/medium-low effort (main effect 1.96, t = 3.81, p < 0.001) and a lower PSImax with older age (− 0.03, t = − 2.95, p = 0.004), after covariate adjustment. There was no clear relationship between PSImax and the number of HRI symptoms reported. Reporting more symptoms was associated with older age, higher HImax, 10+ years agricultural work, not being an H-2A guest worker, and walking > 3 min to get to the toilet at work.

Conclusions
Effort level should be addressed in heat management plans, for example through work/rest cycles, rotation, and pacing, in addition to education and other factors that influence heat stress. Both symptoms and indicators of physiological heat strain should be monitored, if possible, during periods of high heat stress to increase the sensitivity of early HRI detection and prevention. Structural barriers to HRI prevention must also be addressed.

Trial registration
ClinicalTrials.gov Registration Number: NCT04234802, date first posted 21/01/2020.
A potent synthetic nanobody with broad-spectrum activity neutralizes SARS-CoV-2 virus and the Omicron variant BA.1 through a unique binding mode
Authors: Zhao Dongping , Liu Liqin , Liu Xinlin , Zhang Jinlei , Yin Yuqing , Luan Linli , Jiang Dingwen , Yang Xiong , Li Lei , Xiong Hualong , Xing Dongming , Zheng Qingbing , Xia Ningshao , Tao Yuyong , Li Shaowei , Huang Haiming 
Published: September 2022

AbstractThe major challenge to controlling the COVID pandemic is the rapid mutation rate of the SARS-CoV-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-CoV-2 variants. Here, we report a synthetic nanobody (named C5G2) obtained by phage display and subsequent antibody engineering. C5G2 has a single-digit nanomolar binding affinity to the RBD domain and inhibits its binding to ACE2 with an IC50 of 3.7 nM. Pseudovirus assays indicated that monovalent C5G2 could protect the cells from infection with SARS-CoV-2 wild-type virus and most of the viruses of concern, i.e., Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against Omicron BA.1 among all the variants, with an IC50 of 4.9 ng/mL. The cryo-EM structure of C5G2 in complex with the spike trimer showed that C5G2 binds to RBD mainly through its CDR3 at a conserved region that does not overlap with the ACE2 binding surface. Additionally, C5G2 binds simultaneously to the neighboring NTD domain of the spike trimer through the same CDR3 loop, which may further increase its potency against viral infection. Third, the steric hindrance caused by FR2 of C5G2 could inhibit the binding of ACE2 to RBD as well. Thus, this triple-function nanobody may serve as an effective drug for prophylaxis and therapy against Omicron as well as future variants.
Synthesis, biological evaluation and in-silico ADME studies of novel series of thiazolidin-2,4-dione derivatives as antimicrobial, antioxidant and anticancer agents
Authors: Kumar Harsh , Kumar Davinder , Kumar Pradeep , Thareja Suresh , Marwaha Minakshi Gupta , Navik Umashanker , Marwaha Rakesh Kumar 
Published: September 2022

Abstract
Background
A novel series of thiazolidine-2,4-dione molecules was derived and their chemical structures were established using physiochemical parameters and spectral techniques (1H-NMR, IR, MS etc.). The synthesized molecule were then evaluated for their antioxidant, anticancer and antimicrobial potential.

Results and discussion
Serial tube dilution method was employed to evaluate the antimicrobial potential against selected fungal and bacterial strains by taking fluconazole and cefadroxil as reference antifungal and antibacterial drugs respectively. 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity was used to assess the antioxidant potential of the synthesized analogues. Further, the anticancer potential of the selected molecules was assessed against DU-145 cancer cell lines using MTT assay. The drug-likeness was also evaluated by studying in-silico ADME parameters of the synthesized analogues.

Conclusion
In antioxidant evaluation studies, the analogue H5 with IC50 = 14.85 μg/mL was found to be the most active molecule. The antimicrobial evaluation outcomes suggested that the molecules H5, H13, H15 and H18 possessed moderate to promising activity against the selected species of microbial strains having MIC range 7.3 µM to 26.3 µM. The results of anticancer evaluation revealed that all the screened derivatives possess mild anticancer potential. The in-silico ADME studies revealed that all the compounds were found to be drug-like.
Gamma glutamyl transferases in association with cardiovascular risk scores in non-diabetic hypertensive Cameroonians: preliminary data from HYRICCA study
Authors: Nkeck Jan René , Ida Chemgne Marie , Koe Valerie Ndobo , Ndam Antonin Wilson Ndjitoyap , Jessica Yondo Ndedi Claudine , Manuella Eko Ondoa , Charelle Boukeu Yonta , Corine Zouague Zalbi , Andrée Ntyam Abena , Amazia Falmata , Nkeck Jériel Pascal , Samba Esther Astrid Mbono , Moor Vicky Jocelyne Ama 
Published: September 2022

Abstract
Objective
The usefulness of gamma glutamyl transferase (GGT) as biomarker of cardiovascular risk (CVR) remains unexplored in sub-Saharan Africans. To evaluate their relevance on CVR assessment in non-diabetic hypertensive Cameroonians. This was a prospective cross-sectional study on non-diabetic hypertensive adults aged 57.7 ± 10 years (62% female), without evidence of acute or chronic liver disease, in which we assessed GGT levels and correlates it with validated CVR biomarkers, CVR scores (WHO risk score, Framingham 2008, ASCVD 2013, EuroSCORE 2003, and Reynolds score), and plasma atherogenic index (PAI).

Results
We found a positive but weak association between GGT and PAI on linear regression [0.004 (0.001; 0.007); p = 0.021], which was dependent of triglycerides levels (r = 0.17; p = 0.03). We did not find a significant association between GGT levels and the results of the CVR scores studied; Although being related to atherogenic risk, as reported in literature in non-sub-Saharan Africans, GGTs would be of little value for CVR assessment in our population.
Identifying dietary patterns across age, educational level and physical activity level in a cross-sectional study: the Tromsø Study 2015 - 2016
Authors: Moe Åse Mari , Sørbye Sigrunn H. , Hopstock Laila A. , Carlsen Monica H. , Løvsletten Ola , Ytterstad Elinor 
Published: September 2022

Abstract
Background
A healthy diet can decrease the risk of several lifestyle diseases. From studying the health effects of single foods, research now focuses on examining complete diets and dietary patterns reflecting the combined intake of different foods. The main goals of the current study were to identify dietary patterns and then investigate how these differ in terms of sex, age, educational level and physical activity level (PAL) in a general Nordic population.

Methods
We used data from the seventh survey of the population-based Tromsø Study in Norway, conducted in 2015-2016. The study included 21,083 participants aged $$40-99$$

40
-
99

years, of which $$72\%$$

72
%

completed a comprehensive food frequency questionnaire (FFQ). After exclusion, the study sample included 10,899 participants with valid FFQ data. First, to cluster food variables, the participants were partitioned in homogeneous cohorts according to sex, age, educational level and PAL. Non-overlapping diet groups were then identified using repeated hierarchical cluster analysis on the food variables. Second, average standardized diet intake scores were calculated for all individuals for each diet group. The individual diet (intake) scores were then modelled in terms of age, education and PAL using regression models. Differences in diet scores according to education and PAL were investigated by pairwise hypothesis tests, controlling the nominal significance level using Tukey’s method.

Results
The cluster analysis revealed three dietary patterns, here named the Meat and Sweets diet, the Traditional diet, and the Plant-based- and Tea diet. Women had a lower intake of the Traditional diet and a higher preference for the Plant-based- and Tea diet compared to men. Preference for the Meat and Sweets diet and Traditional diet showed significant negative and positive trends as function of age, respectively. Adjusting for age, the group having high education and high PAL compared favourably with the group having low education and low PAL, having a significant lower intake of the Meat and Sweets and the Traditional diets and a significant higher intake of the Plant-based- and Tea diet.

Conclusions
Three dietary patterns (Meat and Sweets, Traditional, and Plant-based- and Tea) were found by repeated clustering of randomly sampled homogeneous cohorts of individuals. Diet preferences depended significantly on sex, age, education and PAL, showing a more unhealthy dietary pattern with lower age, low education and low PAL.
Physical Health Impairment and Exercise as Medicine in Severe Mental Disorders: A Narrative Review
Authors: Brobakken Mathias Forsberg , Nygård Mona , Wang Eivind 
Published: September 2022

Abstract
Background
Individuals with severe mental disorders (SMDs; schizophrenia spectrum disorders, bipolar disorder, and major depressive disorder) are not only suffering from their mental conditions; they also have an attenuated physical health, augmenting their overall critical condition.

Objectives
We review and critically appraise the evidence based on (1) key physiological factors relating to aerobic endurance and skeletal muscle strength; (2) implications for physical function and health; and (3) effects of training interventions with different intensities evaluated in individuals with SMDs.

Findings
Reductions in aerobic endurance factors, peak oxygen uptake (VO2peak) and walking work efficiency, are paralleled by reductions in maximal skeletal muscle strength and power. In turn, the poor aerobic endurance and muscle strength lead to impaired physical function, increased risk of lifestyle-related diseases, and ultimately early death. Exercise has the potential to counteract the attenuated physical health in people with SMDs. While aerobic endurance training is shown to increase VO2peak due to plasticity of the oxygen transport system, strength training is documented to improve maximal muscle strength, power, and walking work efficiency as a result of adaptations in neuromuscular force developing factors.

Conclusions
In conclusion, improvements in these key determinants for physical health appear to be achievable in people with SMDs despite many being challenged by motivational difficulties with attending regular exercise and have beneficial implications for physical function during activities of daily living, lifestyle-related diseases, and early death.
Normative Values for Sport-Specific Left Ventricular Dimensions and Exercise-Induced Cardiac Remodeling in Elite Spanish Male and Female Athletes
Authors: Boraita Araceli , Díaz-Gonzalez Leonel , Valenzuela Pedro L. , Heras María-Eugenia , Morales-Acuna Francisco , Castillo-García Adrián , Lucia María J. , Suja Pedro , Santos-Lozano Alejandro , Lucia Alejandro 
Published: September 2022

Abstract
Background
There is debate about the magnitude of geometrical remodeling [i.e., left ventricle (LV) cavity enlargement vs. wall thickening] in the heart of elite athletes, and no limits of normality have been yet established for different sports. We aimed to determine sex- and sport-specific normative values of LV dimensions in elite white adult athletes.

Methods
This was a single-center, retrospective study of Spanish elite athletes. Athletes were grouped by sport and its relative dynamic/static component (Mitchell’s classification). LV dimensions were measured with two-dimensional-guided M-mode echocardiography imaging to compute normative values. We also developed an online and app-based calculator (https://sites.google.com/lapolart.es/athlete-lv/welcome?authuser=0) to provide clinicians with sports- and Mitchell’s category-specific Z-scores for different LV dimensions.

Results
We studied 3282 athletes (46 different sports, 37.8% women, mean age 23 ± 6 years). The majority (85.4%) showed normal cardiac geometry, particularly women (90.9%). Eccentric hypertrophy was relatively prevalent (13.4%), and concentric remodeling or hypertrophy was a rare finding (each < 0.8% of total). The proportion of normal cardiac geometry and eccentric hypertrophy decreased and increased, respectively, with the dynamic (in both sexes) or static component (in male athletes) of the sport irrespective of the other (static or dynamic) component. The 95th percentile values of LV dimensions did not exceed the following limits in any of the Mitchell categories: septal wall thickness, 12 mm (males) and 10 mm (females); LV posterior wall, 11 mm and 10 mm; and LV end-diastolic diameter, 64 mm and 57 mm.

Conclusions
The majority of elite athletes had normal LV geometry, and although some presented with LV eccentric hypertrophy, concentric remodeling or hypertrophy was very uncommon. The present study provides sport-specific normative values that can serve to identify those athletes for whom a detailed examination might be recommendable (i.e., those exceeding the 95th percentile for their sex and sport).
An overview of the “Protecting Cantonese Movement” in Guangzhou (2010–2021)
Authors: Li Yaling , Kang Yeqin , Ding Dan , Zhang Nianqing 
Published: September 2022

AbstractA decade ago, an online survey resulted in the “Protecting Cantonese Movement” (PCM) in Guangzhou, Guangdong Province, China, around which some articles were produced. Based on the bibliometric analysis of data retrieved from the China National Knowledge Infrastructure (CNKI), the Web of Science, and Google Scholar keyword searches during 2010 and 2021, this paper reviews the PCM literature to summarize its major features and general trends. It reveals that the published journals or newspaper articles focus on interpretating PCM, analyzing its causes from sociocultural, sociolinguistic, socioeconomic and media environmental perspectives, and proposing countermeasures and suggestions at political, ideological and sociolinguistic environmental levels. It concludes that PCM is of far-reaching significance to the continuous research ranging from Cantonese preserving, promotion of Mandarin, language planning, language policy, and language conflict to language ecology.