bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of urinary volatile organic compounds as novel diagnostic and surveillance biomarkers of bladder cancer
Authors: Lett Lauren , George Michael , Slater Rachael , De Lacy Costello Ben , Ratcliffe Norman , García-Fiñana Marta , Lazarowicz Henry , Probert Chris 
Published: March 2022

Abstract
Background
The diagnosis and surveillance of urothelial bladder cancer (UBC) require cystoscopy. There is a need for biomarkers to reduce the frequency of cystoscopy in surveillance; urinary volatile organic compound (VOC) analysis could fulfil this role. This cross-sectional study compared the VOC profiles of patients with and without UBC, to investigate metabolomic signatures as biomarkers.

Methods
Urine samples were collected from haematuria clinic patients undergoing diagnostic cystoscopy and UBC patients undergoing surveillance. Urinary headspace sampling utilised solid-phase microextraction and VOC analysis applied gas chromatography-mass spectrometry; the output underwent metabolomic analysis.

Results
The median participant age was 70 years, 66.2% were male. Of the haematuria patients, 21 had a new UBC diagnosis, 125 had no cancer. In the surveillance group, 75 had recurrent UBC, 84 were recurrence-free. A distinctive VOC profile was observed in UBC patients compared with controls. Ten VOCs had statistically significant abundances useful to classify patients (false discovery rate range 1.9 × 10−7–2.8 × 10−2). Two prediction models were evaluated using internal validation. An eight-VOC diagnostic biomarker panel achieved AUROC 0.77 (sensitivity 0.71, specificity 0.72). A six-VOC surveillance biomarker panel obtained AUROC 0.80 (sensitivity 0.71 and specificity 0.80).

Conclusions
Urinary VOC analysis could aid the diagnosis and surveillance of UBC.
Differential detection by breast density for digital breast tomosynthesis versus digital mammography population screening: a systematic review and meta-analysis
Authors: Li Tong , Houssami Nehmat , Noguchi Naomi , Zeng Aileen , Marinovich M. Luke 
Published: March 2022

Abstract
Background
We examined whether digital breast tomosynthesis (DBT) detects differentially in high- or low-density screens.

Methods
We searched six databases (2009–2020) for studies comparing DBT and digital mammography (DM), and reporting cancer detection rate (CDR) and/or recall rate by breast density. Meta-analysis was performed to pool incremental CDR and recall rate for DBT (versus DM) for high- and low-density (dichotomised based on BI-RADS) and within-study differences in incremental estimates between high- and low-density. Screening settings (European/US) were compared.

Results
Pooled within-study difference in incremental CDR for high- versus low-density was 1.0/1000 screens (95% CI: 0.3, 1.6; p = 0.003). Estimates were not significantly different in US (0.6/1000; 95% CI: 0.0, 1.3; p = 0.05) and European (1.9/1000; 95% CI: 0.3, 3.5; p = 0.02) settings (p for subgroup difference = 0.15). For incremental recall rate, within-study differences between density subgroups differed by setting (p < 0.001). Pooled incremental recall was less in high- versus low-density screens (−0.9%; 95% CI: −1.4%, −0.4%; p < 0.001) in US screening, and greater (0.8%; 95% CI: 0.3%, 1.3%; p = 0.001) in European screening.

Conclusions
DBT has differential incremental cancer detection and recall by breast density. Although incremental CDR is greater in high-density, a substantial proportion of additional cancers is likely to be detected in low-density screens. Our findings may assist screening programmes considering DBT for density-tailored screening.
Protein kinase inhibitor responses in uveal melanoma reflects a diminished dependency on PKC-MAPK signaling
Authors: Park John J. , Stewart Ashleigh , Irvine Mal , Pedersen Bernadette , Ming Zizhen , Carlino Matteo S. , Diefenbach Russell J. , Rizos Helen 
Published: March 2022

AbstractUveal melanoma (UM) is a rare cancer arising from melanocytes in the uveal tract of the eye. Despite effective primary treatment, there is no approved therapy for metastatic UM and prognosis and survival remain poor. Over 90% of UM are driven by mutations affecting the Gα subunits encoded by the GNAQ and GNA11 genes. These mutations activate downstream and targetable signaling pathways, including the protein kinase C (PKC) cascade. PKC inhibitors have been used in clinical trials for metastatic UM but have shown limited efficacy. In this study, we examined the signaling and functional effects of two PKC inhibitors (AEB071 and IDE196) in a panel of UM cell models. In response to PKC inhibition, all UM cell lines showed potent suppression of PKC activity, but this was not sufficient to predict PKC inhibitor sensitivity and only two UM cell lines showed substantial PKC inhibitor-induced cell death. The differences in UM cell responses to PKC inhibition were not attributable to the degree or timing of PKC suppression or inhibition of the downstream mitogen-activated protein kinase (MAPK) or phosphatidylinositol-3-kinase (PI3K) pathways. Instead, UM cell show complex, PKC-independent signaling pathways that contribute to their survival and resistance to targeted therapies.
Regulation of Semaphorin3A in the process of cutaneous wound healing
Authors: Zheng Yang , Jiang Feng , Wang Chao , Dong Mengjie , Wang Chundi , Yan Enshi , Wang Yi , Zhu Zaiou , Xiong Xianbin , Ding Xu , Ye Jinhai , He Yue , Zhang Hongchuang , Zhou Junbo , Zhang Wei , Wu Yunong , Song Xiaomeng 
Published: March 2022

AbstractSemaphorin 3A (Sema3A) has been recognized as a crucial regulator of morphogenesis and homeostasis over a wide range of organ systems. However, its function in cutaneous wound healing is poorly understood. In our study, we demonstrated that Sema3A adenovirus plasmids transfection limited keratinocyte proliferation and decreased migrative capacity as assessed by in vitro wound healing assay. Sema3A transduction inhibited TGF-β1-mediated keratinocyte migration and EMT process. Besides, we applied mice with K14-Cre-mediated deletion of Sema3A and found that Sema3A depletion postponed wound closure with decreased re-epithelialization and matrix growth. Contrary to the results obtained with full-length Sema3A plasmids transfection, increased keratinocyte migration with recombinant Sema3A proteins resulted in quicker closure of the wounding area after a scratch. Further, exogenously applied recombinant Sema3A worked with EGF to maintain the activation of EGFR by interacting with NRP1 and thereby regulated the internalization of the EGFR-NRP1 complex. Taken together, these results indicated a paradoxical role of autonomous and non-autonomous Sema3A expression during wound healing. Combined administration of recombinant EGF and Sema3A proteins could accelerate the process of wound repair, thus providing promising treatment prospects in the future.
Insight into the structure, physiological function, and role in cancer of m6A readers—YTH domain-containing proteins
Authors: Liao Jingyu , Wei Yi , Liang Junnan , Wen Jingyuan , Chen Xiaoping , Zhang Bixiang , Chu Liang 
Published: March 2022

AbstractYT521-B homology (YTH) domain-containing proteins (YTHDF1-3, YTHDC1-2) are the most crucial part of N6-methyladenosine (m6A) readers and play a regulatory role in almost all stages of methylated RNA metabolism and the progression of various cancers. Since m6A is identified as an essential post-transcriptional type, YTH domain-containing proteins have played a key role in the m6A sites of RNA. Hence, it is of great significance to study the interaction between YTH family proteins and m6A-modified RNA metabolism and tumor. In this review, their basic structure and physical functions in RNA transcription, splicing, exporting, stability, and degradation as well as protein translation are introduced. Then we discussed the expression regulation of YTH domain-containing proteins in cancers. Furthermore, we introduced the role of the YTH family in cancer biology and systematically demonstrated their functions in various aspects of tumorigenesis and development. To provide a more institute understanding of the role of YTH family proteins in cancers, we summarized their functions and specific mechanisms in various cancer types and presented their involvement in cancer-related signaling pathways.
Coronavirus Host Genetics South Africa (COHG-SA) database—a variant database for gene regions associated with SARS-CoV-2 outcomes
Authors: Barmania Fatima , Mellet Juanita , Ryder Megan A. , Ford Graeme , Herd Candice L. , Tamuhla Tsaone , Hendricks Candice , Giles Rachel , Kalua Thumbiko , Joubert Fourie , Tiffin Nicki , Pepper Michael S. 
Published: March 2022

AbstractThe SARS-CoV-2 virus is responsible for the COVID-19 global public health emergency, and the disease it causes is highly variable in its clinical presentation. Clinical phenotypes are heterogeneous both in terms of presentation of symptoms in the host and response to therapy. Several studies and initiatives have been established to analyse and review host genetic epidemiology associated with COVID-19. Our research group curated these articles into a web-based database using the python application-server framework Django. The database provides a searchable research tool describing current literature surrounding COVID-19 host genetic factors associated with disease outcome. This paper describes the COHG-SA database and provides an overview of the analyses that can be derived from these data.
Effective viral-mediated lung gene therapy: is airway surface preparation necessary?
Authors: McCarron Alexandra , Cmielewski Patricia , Drysdale Victoria , Parsons David , Donnelley Martin 
Published: March 2022

AbstractGene-based therapeutics are actively being pursued for the treatment of lung diseases. While promising advances have been made over the last decades, the absence of clinically available lung-directed genetic therapies highlights the difficulties associated with this effort. Largely, progress has been hindered by the presence of inherent physical and physiological airway barriers that significantly reduce the efficacy of gene transfer. These barriers include surface mucus, mucociliary action, cell-to-cell tight junctions, and the basolateral cell membrane location of viral receptors for many commonly used gene vectors. Accordingly, airway surface preparation methods have been developed to disrupt these barriers, creating a more conducive environment for gene uptake into the target airway cells. The two major approaches have been chemical and physical methods. Both have proven effective for increasing viral-mediated gene transfer pre-clinically, although with variable effect depending on the specific strategy employed. While such methods have been explored extensively in experimental settings, they have not been used clinically. This review covers the airway surface preparation strategies reported in the literature, the advantages and disadvantages of each method, as well as a discussion about applying this concept in the clinic.
Wearable sensors during drawing tasks to measure the severity of essential tremor
Authors: Ali Sheik Mohammed , Arjunan Sridhar Poosapadi , Peters James , Perju-Dumbrava Laura , Ding Catherine , Eller Michael , Raghav Sanjay , Kempster Peter , Motin Mohammod Abdul , Radcliffe P. J. , Kumar Dinesh Kant 
Published: March 2022

AbstractCommonly used methods to assess the severity of essential tremor (ET) are based on clinical observation and lack objectivity. This study proposes the use of wearable accelerometer sensors for the quantitative assessment of ET. Acceleration data was recorded by inertial measurement unit (IMU) sensors during sketching of Archimedes spirals in 17 ET participants and 18 healthy controls. IMUs were placed at three points (dorsum of hand, posterior forearm, posterior upper arm) of each participant’s dominant arm. Movement disorder neurologists who were blinded to clinical information scored ET patients on the Fahn–Tolosa–Marin rating scale (FTM) and conducted phenotyping according to the recent Consensus Statement on the Classification of Tremors. The ratio of power spectral density of acceleration data in 4–12 Hz to 0.5–4 Hz bands and the total duration of the action were inputs to a support vector machine that was trained to classify the ET subtype. Regression analysis was performed to determine the relationship of acceleration and temporal data with the FTM scores. The results show that the sensor located on the forearm had the best classification and regression results, with accuracy of 85.71% for binary classification of ET versus control. There was a moderate to good correlation (r2 = 0.561) between FTM and a combination of power spectral density ratio and task time. However, the system could not accurately differentiate ET phenotypes according to the Consensus classification scheme. Potential applications of machine-based assessment of ET using wearable sensors include clinical trials and remote monitoring of patients.
Characterization of Escherichia coli harboring colibactin genes (clb) isolated from beef production and processing systems
Authors: Guragain Manita , Schmidt John W. , Kalchayanand Norasak , Dickey Aaron M. , Bosilevac Joseph M. 
Published: March 2022

AbstractCertain strains of Escherichia coli possess and express the toxin colibactin (Clb) which induces host mutations identical to the signature mutations of colorectal cancer (CRC) that lead to tumorigenic lesions. Since cattle are a known reservoir of several Enterobacteriaceae including E. coli, this study screened for clb amongst E. coli isolated from colons of cattle-at-harvest (entering beef processing facility; n = 1430), across the beef processing continuum (feedlot to finished subprimal beef; n = 232), and in ground beef (n = 1074). Results demonstrated that clb+E. coli were present in cattle and beef. Prevalence of clb+E. coli from colonic contents of cattle and ground beef was 18.3% and 5.5%, respectively. clb+E. coli were found susceptible to commonly used meat processing interventions. Whole genome sequencing of 54 bovine and beef clb+ isolates showed clb occurred in diverse genetic backgrounds, most frequently in phylogroup B1 (70.4%), MLST 1079 (42.6%), and serogroup O49 (40.7%).
Linkage mapping, comparative genome analysis, and QTL detection for growth in a non-model teleost, the meagre Argyrosomus regius, using ddRAD sequencing
Authors: Nousias O. , Oikonomou S. , Manousaki T. , Papadogiannis V. , Angelova N. , Tsaparis D. , Tsakogiannis A. , Duncan N. , Estevez A. , Tzokas K. , Pavlidis M. , Chatziplis D. , Tsigenopoulos C. S. 
Published: March 2022

AbstractMeagre (Argyrosomus regius), is a benthopelagic species rapidly emerging in aquaculture, due to its low food to biomass conversion rate, good fillet yield and ease of production. Tracing a species genomic background along with describing the genetic basis of important traits can greatly influence both conservation strategies and production perspectives. In this study, we employed ddRAD sequencing of 266 fish from six F1 meagre families, to construct a high-density genetic map comprising 4529 polymorphic SNP markers. The QTL mapping analysis provided a genomic appreciation for the weight trait identifying a statistically significant QTL on linkage group 15 (LG15). The comparative genomics analysis with six teleost species revealed an evolutionarily conserved karyotype structure. The synteny observed, verified the already well-known fusion events of the three-spine stickleback genome, reinforced the evidence of reduced evolutionary distance of Sciaenids with the Sparidae family, reflected the evolutionary proximity withDicentrarchus labrax, traced several putative chromosomal rearrangements and a prominent putative fusion event in meagre’s LG17. This study presents novel elements concerning the genome evolutionary history of a non-model teleost species recently adopted in aquaculture, starts to unravel the genetic basis of the species growth-related traits, and provides a high-density genetic map as a tool that can help to further establish meagre as a valuable resource for research and production.
Evidence supporting a cultural evolutionary theory of prosocial religions in contemporary workplace safety data
Authors: Gu Yuqi , Mao Connie X. , Johnson Tim 
Published: March 2022

AbstractA prominent line of cultural evolutionary theory hypothesizes that religiously inspired prosocial behavior enhances the fecundity of pious groups, causing them to outcompete non-religious communities and spread their prosocial values. We present evidence concerning contemporary workplace safety, in the United States, that unexpectedly tested implications of this cultural evolutionary hypothesis. Avoiding workplace injury requires cooperation and injury influences fitness, thus cultural evolutionary theory would anticipate that religious communities should exhibit fewer workplace injuries. Indeed, we find that the proportion of a community adhering to a religion correlates negatively with rates of workplace injury in its private-sector establishments. This correlation emerges primarily when secular workplace safety authorities are not prominent, thus echoing evidence that religiously inspired prosocial behavior mainly occurs absent “earthly” sanctioning authorities. Furthermore, the percent of religiously affiliated individuals in a community correlates with safety investments, suggesting that workplace injury reductions in religious communities result from individually costly, group-benefitting cooperation.
Elderly onset age is associated with low efficacy of first anti-tumor necrosis factor treatment in patients with inflammatory bowel disease
Authors: Amano Takahiro , Shinzaki Shinichiro , Asakura Akiko , Tashiro Taku , Tani Mizuki , Otake Yuriko , Yoshihara Takeo , Iwatani Shuko , Yamada Takuya , Sakakibara Yuko , Osugi Naoto , Ishii Shuji , Egawa Satoshi , Araki Manabu , Arimoto Yuki , Nakahara Masanori , Murayama Yoko , Kobayashi Ichizo , Kinoshita Kazuo , Ogawa Hiroyuki , Hiyama Satoshi , Shibukawa Narihiro , Komori Masato , Okuda Yorihide , Kizu Takashi , Yoshii Shunsuke , Tsujii Yoshiki , Hayashi Yoshito , Inoue Takahiro , Iijima Hideki , Takehara Tetsuo 
Published: March 2022

AbstractThe outcomes of patients with elderly onset (EO) inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor (TNF) remains uncertain. The present study evaluated the efficacy and safety of anti-TNF treatment for bio-naïve EO-IBD. Elderly patients were defined as those 60 years and older, and further divided into those with EO (Elderly-EO) and those with non-elderly onset (Elderly-NEO). A total of 432 bio-naïve patients were enrolled in this multicenter observational study, comprising 55 with Elderly-EO (12.7%), 25 with Elderly-NEO (5.8%), and 352 under age 60 (Non-elderly, 81.5%). After 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in Elderly-EO than in Non-elderly (37.7% and 60.8%; P = 0.001, and 35.9% and 57.8%; P = 0.003, respectively), and comparable between Elderly-NEO and Non-elderly. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission (OR, 0.49, 95% CI 0.25–0.96) and steroid-free remission (OR, 0.51, 95% CI 0.26–0.99) after 52 weeks of anti-TNF treatment. The rate of cumulative severe adverse events was significantly higher in Elderly-EO than in Non-elderly (P = 0.007), and comparable between Elderly-NEO and Non-elderly. In conclusion, anti-TNF treatment for bio-naïve EO-IBD may be less effective and raise safety concerns.
Structural and biochemical characterization of in vivo assembled Lactococcus lactis CRISPR-Csm complex
Authors: Sridhara Sagar , Rai Jay , Whyms Charlisa , Goswami Hemant , He Huan , Woodside Walter , Terns Michael P. , Li Hong 
Published: March 2022

AbstractThe small RNA-mediated immunity in bacteria depends on foreign RNA-activated and self RNA-inhibited enzymatic activities. The multi-subunit Type III-A CRISPR-Cas effector complex (Csm) exemplifies this principle and is in addition regulated by cellular metabolites such as divalent metals and ATP. Recognition of the foreign or cognate target RNA (CTR) triggers its single-stranded deoxyribonuclease (DNase) and cyclic oligoadenylate (cOA) synthesis activities. The same activities remain dormant in the presence of the self or non-cognate target RNA (NTR) that differs from CTR only in its 3′-protospacer flanking sequence (3′-PFS). Here we employ electron cryomicroscopy (cryoEM), functional assays, and comparative cross-linking to study in vivo assembled mesophilic Lactococcus lactis Csm (LlCsm) at the three functional states: apo, the CTR- and the NTR-bound. Unlike previously studied Csm complexes, we observed binding of 3′-PFS to Csm in absence of bound ATP and analyzed the structures of the four RNA cleavage sites. Interestingly, comparative crosslinking results indicate a tightening of the Csm3-Csm4 interface as a result of CTR but not NTR binding, reflecting a possible role of protein dynamics change during activation.
SARS-CoV-2 spike protein causes cardiovascular disease independent of viral infection
Authors: Imig John D. 
Published: March 2022

Abstract
The SARS-CoV-2 virus that results in COVID-19 has been found to damage multiple organs beyond the lung. Interestingly, the SARS-CoV-2 spike (S) protein can be found circulating in the blood of COVID-19 patients. Experimental findings are demonstrating that the circulating S protein can bind to receptors resulting in inflammation and cell, tissue, and organ damage. Avolio et al. previously determined that the S protein acting through the cluster of differentiation 147 (CD147) receptor, and another unknown mechanism had detrimental effects on human cardiac pericytes (Clin Sci (Lond) (2021) 135 (24): 2667–2689. DOI: 10.1042/CS20210735). These findings support the notion that circulating SARS-CoV-2 S protein could contribute to cardiovascular disease independent of viral infection. Future studies are needed to determine the effect of the S protein on pericytes in other organs and evaluate the effectiveness of CD147 receptor-blocking therapies to decrease organ damage caused by the S protein.
Load‐independent inverse class‐E ZVS inverter and its application to wireless power transfer systems
Authors: Komanaka Ayano , Zhu Wenqi , Wei Xiuqin , Nguyen Kien , Sekiya Hiroo 
Published: March 2022

AbstractThis paper proposes a load‐independent inverse class‐E zero‐voltage switching (ZVS) inverter. The proposed inverter achieves the constant output current and the ZVS at any load resistance without any control. The waveforms and design equations of the proposed inverter are shown. Besides, a wireless‐power‐transfer system was implemented using the proposed inverter. The designed WPT system kept the constant output voltage and the ZVS against load variations, which denoted the effectiveness of the proposed inverter and validities of the analytical equations.