bluuebunny/crossref_metadata_2025 huggingface dataset:
Research progress on lung cancer stem cells in epidermal growth factor receptor–tyrosine kinase inhibitor targeted therapy resistance in lung adenocarcinoma
Authors: Zhang Hong , Wang Yanbin , Yuan Xianglin , Zou Yanmei , Xiong Hua
Published: January 2024

Lung cancer is the leading cause of cancer-related deaths globally. In recent years, with the widespread use of genetic testing, epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR-TKI)–targeted drugs have been efficacious to patients with lung adenocarcinoma exhibiting EGFR mutations. However, resistance to treatment is inevitable and eventually leads to tumor progression, recurrence, and reduction in the overall treatment efficacy. Lung cancer stem cells play a crucial role in the development of resistance toward EGFR-TKI–targeted therapy for lung adenocarcinoma. Lung cancer stem cells possess self-renewal, multilineage differentiation, and unlimited proliferation capabilities, which efficiently contribute to tumor formation and ultimately lead to tumor recurrence and metastasis. In this study, we evaluated the origin, markers, stemness index, relevant classic studies, resistance mechanisms, related signaling pathways, and strategies for reversing lung cancer stem cell resistance to EGFR-TKIs to provide new insights on delaying or reducing resistance and to improve the treatment efficacy of patients with EGFR-mutated lung adenocarcinoma in the future.
Efficacy, Safety, and Complications of Pigtail Thoracostomy for the Treatment of Pediatric Pleuropneumonia
Authors: Tamary Oren , Yaari Arnon , Prokocimer-Yair Zafnat , Feldman Roi , Berant Ron , Jacob Ron , Samuel Nir
Published: January 2024

Objective

Pigtail thoracostomy (PT) has become the mainstay technique for the drainage of pediatric pleuropneumonic effusions (PLPe). However, its efficacy and complication profile has been questioned when compared with video-assisted thoracoscopic surgery and larger bore traditional tube thoracostomy. The aim of this study was to assess the efficacy, safety, and complications associated with PT.

Methods

A cross-sectional study at a freestanding tertiary children's hospital. We extracted the medical records of all children aged younger than 18 years treated with PT for PLPe from June 2016 to June 2020. The primary efficacy outcome was treatment failure defined as the need for a repeat drainage procedure, thoracostomy, or video-assisted thoracoscopic surgery. Secondary efficacy outcomes were length of hospital stay (LOS) and duration of in situ PT. The primary safety outcomes were adverse events during or after insertion. We also recorded any associated complications.

Results

During the study period, 55 children required PT. The median age was 25 months (interquartile range, 14–52) and 58.2% were boys. Eight (14.4%) were bacteremic or in septic shock. There were no adverse events related to insertion. Forty-two (76.3%) children were treated with fibrinolysis. There were 2 (3.6%) treatment failures. The median LOS and PT durations were 13 and 4 days (interquartile ranges, 10–14.8, 3–6.7), respectively. Eight (14.4%) children experienced complications that were nonoperatively managed.

Conclusions

Our findings suggest that PT drainage offers a safe and highly effective option for managing PLPe and carries a very low failure rate.
Liposomal Bupivacaine Use During Orthognathic Surgery in Cleft Lip and Palate Patients
Authors: Layon Sarah A. , Burns Heather R. , Williams Austin D. , Ding Yang , Mohammad Shazia , Buchanan Edward P.
Published: January 2024

Introduction:

Effective pain management is crucial in cleft lip and palate (CLP) patients undergoing orthognathic surgery for earlier recovery and decreased opioid reliance. Liposomal bupivacaine (Exparel) is a local anesthetic that provides extended postoperative analgesia in adult patients; however, research on its use in adolescents is limited. This study explores the efficacy of liposomal bupivacaine for postoperative pain management in adolescent CLP patients undergoing orthognathic surgery.

Methods:

The authors performed a retrospective chart review at their institution between July 2020 and December 2022 to identify patients who underwent LeFort I or mandibular osteotomy. Two cohorts were compared: patients who received liposomal bupivacaine and patients who received standard pain medications alone. Outcome measures included intraoperative pain medications, length of stay, breakthrough opioid use, time to first oral intake, volume of oral intake, and opioids prescribed at discharge.

Results:

This study included 22 patients who underwent orthognathic surgery. The liposomal bupivacaine group (n=10) demonstrated earlier and greater oral intake during hospitalization compared with controls (n=12). The most significant difference was observed in total breakthrough opioid use, with an average of 8.60 morphine milligram equivalents for liposomal bupivacaine patients compared with 35.1 morphine milligram equivalents for controls (P=0.037).

Conclusions:

This study provides the first analysis of liposomal bupivacaine use in adolescent CLP patients undergoing orthognathic surgery, demonstrating a significant reduction in postoperative opioid consumption compared with controls. These results may guide future studies of liposomal bupivacaine within CLP patients, potentially as a component of enhanced recovery after surgery guidelines, as well as in cost-analysis studies.
Nationwide, County-Level Analysis of the Patterns, Trends, and System-Level Predictors of Opioid Prescribing in Surgery in the US: Social Determinants and Access to Mental Health Services Matter
Authors: Gaitanidis Apostolos , Dorken Gallastegi Ander , Van Erp Inge , Gebran Anthony , Velmahos George C , Kaafarani Haytham MA
Published: January 2024

BACKGROUND:

The diversion of unused opioid prescription pills to the community at large contributes to the opioid epidemic in the US. In this county-level population-based study, we aimed to examine the US surgeons’ opioid prescription patterns, trends, and system-level predictors in the peak years of the opioid epidemic.

STUDY DESIGN:

Using the Medicare Part D database (2013 to 2017), the mean number of opioid prescriptions per beneficiary (OPBs) was determined for each US county. Opioid-prescribing patterns were compared across counties. Multivariable linear regression was performed to determine relationships between county-level social determinants of health (demographic, eg median age and education level; socioeconomic, eg median income; population health status, eg percentage of current smokers; healthcare quality, eg rate of preventable hospital stays; and healthcare access, eg healthcare costs) and OPBs.

RESULTS:

Opioid prescription data were available for 1,969 of 3,006 (65.5%) US counties, and opioid-related deaths were recorded in 1,384 of 3,006 counties (46%). Nationwide, the mean OPBs decreased from 1.08 ± 0.61 in 2013 to 0.87 ± 0.55 in 2017; 81.6% of the counties showed the decreasing trend. County-level multivariable analyses showed that lower median population age, higher percentages of bachelor’s degree holders, higher percentages of adults reporting insufficient sleep, higher healthcare costs, fewer mental health providers, and higher percentages of uninsured adults are associated with higher OPBs.

CONCLUSIONS:

Opioid prescribing by surgeons decreased between 2013 and 2017. A county’s suboptimal access to healthcare in general and mental health services in specific may be associated with more opioid prescribing after surgery.
Safety of noninvasive brain stimulation in children
Authors: Salehinejad Mohammad Ali , Siniatchkin Michael
Published: January 2024

Purpose of review

Noninvasive brain stimulation (NIBS) is a promising method for altering cortical excitability with clinical implications. It has been increasingly used in children, especially in neurodevelopmental disorders. Yet, its safety and applications in the developing brain require further investigation. This review aims to provide an overview of the safety of commonly used NIBS techniques in children, including transcranial electrical stimulation (tES) and transcranial magnetic stimulation (TMS). Safety data for other NIBS methods is not reported in this review.

Recent findings

In line with studies from the last decade, findings in the last 2 years (2022–2023) support the safety of NIBS in children and adolescents within the currently applied protocols. Both tES and TMS are well tolerated, if safety rules, including exclusion criteria, are applied.

We briefly discussed developmental aspects of stimulation parameters that need to be considered in the developing brain and provided an up-to-date overview of tES/TMS applications in children and adolescents. Overall, the safety profile of tES/TMS in children is good. For both the tES and TMS applications, epilepsy and active seizure disorder should be exclusion criteria to prevent potential seizures. Using child-sized earplugs is required for TMS applications. We lack large randomized double-blind trials

and longitudinal studies to establish the safety of NIBS in children.

Video abstract

http://links.lww.com/YCO/A78.
Oral Complications in Patients With Psychiatric Illness Undergoing Electroconvulsive Therapy in Istanbul, Turkey
Authors: Oflezer Ceyhan , Oflezer Özlem , Canbek Özge , Eskil Çiçek Özlem , Bahadır Hakan
Published: January 2024

Objective

Despite advances in pharmacotherapy, electroconvulsive therapy (ECT) remains a mainstay treatment option in psychiatry. This study aims to determine the occurrence of oral injury from ECT modified with the use of an inexpensive, disposable, hand-made oral protector customized to the dental needs of the individual patient.

Method

Based on data collected between January 1, 2013, and December 31, 2018, registered patients who had received ECT were evaluated retrospectively. We investigated the incidence of oral complications such as dental fractures, dental avulsion, temporomandibular joint dislocation, jaw pain, and soft tissue, lip, and tongue injuries in a single center.

Results

There were 1750 male patients (59.6%) and 1187 female patients (40.4%), with a mean age of 35.20 ± 11.59 years. The incidence of oral injury was 0.1% per patient (4/2937) and 0.01% per session (4/22135). Oral complication characteristics included mucosal abrasion in 2 patients, dental fracture in 1 patient, and tooth avulsion in one. No dental fracture or avulsion in our patient population has resulted in aspiration. We found no evidence of jaw pain, temporomandibular joint dislocation, or injury to the lip or tongue.

Conclusion

Our results demonstrate a minimum risk of oral complications during ECT and also provide additional justification for an adequate oral assessment by the ECT team before the procedure.
Deinococcus rhizophilus sp.nov., isolated from rhizosphere soil
Authors: Gao Fengzhi , Li Heng , Tang Kai , Zhang Tingting , Bao Runze , Feng Fuying
Published: January 2024

A spherical, pink, aerobic, Gram-stain-positive bacterial strain (MIMF12T) was isolated from rhizosphere soil collected in the Inner Mongolia Autonomous Region, PR China. Cellular growth of the strain was observed at pH 6.0–8.0 (optimum, pH 7.0), at 20–37 °C (optimum, 28 °C) and with 0–1 % (w/v) NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain MIMF12T was most closely related to

Deinococcus terrestris

SDU3-2T with a similarity value of 96.0 %. The respiratory quinone was menaquinone 8, the major fatty acids were C15 : 1
 ω6c and C17 : 1
 ω8c, and the major polar lipids were composed of two aminophospholipids, one phospholipid and four unidentified lipids. The G+C content of the genomic DNA was 70.1 mol%. The average nucleotide identity and digital DNA–DNA hybridization values between strain MIMF12T and the closest related type strain SDU3-2T were 88.1 and 52.1 %, respectively. The discovery that MIMF12T differs not only from validly named species in the genus

Deinococcus

, but also from currently unnamed species in the GDTB, gives us new insights into the genus. Based on phenotypic, chemotaxonomic and phylogenetic characteristics, strain MIMF12T represents a novel species of the genus

Deinococcus

, for which the name Deinococcus rhizophilus sp. nov. is proposed. The type strain is MIMF12T (=CGMCC 1.61579T=KCTC 43572T).
Microbial Primer: The bacterial flagellum – how bacteria swim
Authors: Armitage Judith P.
Published: January 2024

Bacteria swim using membrane-spanning, electrochemical gradient-powered motors that rotate semi-rigid helical filaments. This primer provides a brief overview of the basic synthesis, structure and operation of these nanomachines. Details and variations on the basic system can be found in suggested further reading.
BAMBI: Integrativebiostatistical andartificial-intelligencemodels discover coding and non-coding RNA genes asbiomarkers
Authors: Zhou Peng , Li Zixiu , Liu Feifan , Kwon Euijin , Hsieh Tien-Chan , Ye Shangyuan , Vasudevan Shobha , Lee JungAe , Zhou Chan
Published: January 2024

Accurate disease diagnosis and prognosis are crucial for effective treatment management and improving patient outcomes. However, accurately detecting early signs of certain diseases or recurrence remains challenging. Existing machine-learning methods for identifying gene expression biomarkers have several limitations, including poor performance on independent test datasets, inability to directly process omics data, and difficulty in identifying noncoding RNA genes as biomarkers. Additionally, these methods may not provide sufficient biological interpretation of their results, and the panel biomarkers they identify may not be suitable for clinical application. To address these limitations, we have developed a new computational method called BAMBI, which integrates multiple machine-learning algorithms and statistical approaches to identify putative coding and noncoding genes as biomarkers for disease diagnosis and prognosis. We evaluated BAMBI ability to identify diagnostic and prognostic biomarkers by analyzing multiple RNA-seq datasets from cancerous and non-cancerous diseases at population levels. The results from BAMBI demonstrate significant biological interpretability and state-of-the-art prediction performance. When the singular gene identified by BAMBI is used as a diagnostic biomarker, it achieves a balance accuracy exceeding 95% in studies of both breast cancer and psoriasis. Additionally, the prognostic biomarkers that BAMBI identifies from RNA-seq data of Acute Myeloid Leukemia (AML) patients significantly correlate with the survival rates in an independent AML patient cohort. Additionally, BAMBI outperforms existing methods by delivering more robust results, identifying biomarkers with fewer genes, and simultaneously achieving superior prediction accuracy. We have implemented BAMBI into user-friendly software for the research community. In summary, BAMBI serves as a more reliable pipeline for identifying both coding and noncoding genes as biosignature markers, enhancing the accuracy of disease diagnosis and prognosis. BAMBI is available viahttps://github.com/CZhouLab/BAMBI.
Age-Related Decline in Blood-Brain Barrier Function is More Pronounced in Males than Females in Parietal and Temporal Regions
Authors: Shao Xingfeng , Shou Qinyang , Felix Kimberly , Ojogho Brandon , Jiang Xuejuan , Gold Brian T. , Herting Megan M , Goldwaser Eric L , Kochunov Peter , Hong L. Elliot , Pappas Ioannis , Braskie Meredith , Kim Hosung , Cen Steven , Jann Kay , Wang Danny JJ
Published: January 2024

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8 to 92 years old, using a non-invasive diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.

Significance statement

The blood-brain barrier (BBB) serves as a critical protection mechanism for the CNS. A natural decline of BBB function with aging has been reported in both animal and human studies, with possible differences in BBB function by sex. Using our MRI technique, DP-pCASL that measures water exchange rate (kw) without contrast in 186 participants from diverse race and age groups, we identified age and sex-specific patterns in BBB kw especially in parietal and temporal regions. We observed of a decline in kw beginning in the early 60s, especially in males. Our study unveils the dynamic spatiotemporal pattern of kw differences with age and sex, which serve as a foundation for understanding aberrations of BBB function in neurodegenerative and other brain disorders.
Indicators to assess interannual variability in marine connectivity processes: a semi-theoretical approach
Authors: Clavel-Henry Morane , Bahamon Nixon , Aguzzi Jacopo , Navarro Joan , López Miguel , Company Joan B.
Published: January 2024

Oceanographic connectivity in an effective network of protected areas is crucial for restoring and stabilising marine populations. However, temporal variability of connectivity is rarely considered as a criterion in designing and evaluating marine conservation planning. In this study, indicators were defined to characterise occurrence, strength and frequency of the temporal variability in connectivity in a northwestern Mediterranean Sea area. Indicators were tested on semi-theoretically-estimated connections provided by the runs of a passive particle transport model in a climatological year and in three years between 2006 - 2020, showing large deviation from the climatological year. The indicators compared the temporal variability in connectivity of four zones, highlighting differences in connectivity due to their locations and the mesoscale hydrodynamics, and identifying areas that require further investigation. The three indicators also showed that the temporal variability in connectivity was influenced by the duration and depth of particle transport, although no consistent pattern was observed in the indicator variations of the compared zones. Provided that specific objectives will be given when parameterising transport models (i.e., selection of focus species and time period), indicators of temporal variability in connectivity have potential to support, and correctly implement, spatial conservation planning, prioritise the protection of marine resources, and measure the effectiveness of Marine Protected Areas, in line with a long-term vision of ocean management.
CEL: A Continual Learning Model for Disease Outbreak Prediction by Leveraging Domain Adaptation via Elastic Weight Consolidation
Authors: Aslam Saba , Rasool Abdur , Wu Hongyan , Li Xiaoli
Published: January 2024

Continual learning, the ability of a model to learn over time without forgetting previous knowledge and, therefore, be adaptive to new data, is paramount in dynamic fields such as disease outbreak prediction. Deep neural networks, i.e., LSTM, are prone to error due to catastrophic forgetting. This study introduces a novel CEL model forcontinual learning by leveraging domain adaptation viaElastic Weight Consolidation (EWC). This model aims to mitigate the catastrophic forgetting phenomenon in a domain incremental setting. The Fisher Information Matrix (FIM) is constructed with EWC to develop a regularization term that penalizes changes to important parameters, namely, the important previous knowledge. CEL’s performance is evaluated on three distinct diseases, Influenza, Mpox, and Measles, with different metrics. The high R-squared values during evaluation and reevaluation outperform the other state-of-the-art models in several contexts, indicating that CEL adapts to incremental data well. CEL’s robustness and reliability are underscored by its minimal 65% forgetting rate and 18% higher memory stability compared to existing benchmark studies. This study highlights CEL’s versatility in disease outbreak prediction, addressing evolving data with temporal patterns. It offers a valuable model for proactive disease control with accurate, timely predictions.
Unveiling the role of Tdark genes in genetic diseases and phenotypes through bioinformatics-based functional enrichment and network analyses
Authors: Kafita Doris , Dzobo Kevin , Nkhoma Panji , Sinkala Musalula
Published: January 2024

In recent years, there has been growing interest in understanding the role of dark genes in genetic diseases and phenotypes. Despite their lack of functional characterisation, dark genes account for a significant portion of the human genome and are believed to play a role in regulating gene expression and cellular processes. We investigated the role of dark genes in genetic diseases and phenotypes by conducting integrative network analyses and functional enrichment studies across multiple large-scale molecular datasets. Our investigation revealed a predominant association of both dark and light genes with psoriasis. Furthermore, we found that the transcription factors UBTF and NFE2L2 are potential regulators of both dark and light genes associated with tuberculosis. In contrast, the transcription factors SUZ12 and TP63 are potential regulators of both dark and light genes associated with interstitial cystitis. Further network analysis of dark genes, includingCALHM6, HCP5, PRRG4, DDX60LandRASA2,revealed a notably high weighted degree of association with genetic diseases and phenotypes. Moreover, our analysis revealed that numerous genetic diseases and phenotypes, including psoriasis, pick disease, tuberculosis, ulcerative colitis, interstitial cystitis, and Crohn’s disease, exhibited shared gene linkages. Additionally, we conducted a protein-protein interaction analysis to reveal 16 dark genes that encode hub proteins, includingR3HDM2, RPUSD4, FASTKD5, andMRPL15,that could play a role in many genetic diseases and phenotypes, and are widely expressed across body tissues. Our findings contribute to the understanding of the genetic basis of diseases and provide potential therapeutic targets for future research. Identifying dysregulated dark genes in disease states can lead to new strategies for prevention, diagnosis, and treatment, thus advancing our understanding of disease mechanisms.
Pulsed low-dose-rate radiation (PLDR) reduces the tumor-promoting responses induced by conventional chemoradiation in pancreatic cancer-associated fibroblasts
Authors: Franco-Barraza Janusz , Luong Tiffany , Wong Jessica K. , Raghavan Kristopher , Handorf Elizabeth , Vendramini-Costa Débora B. , Francescone Ralph , Gardiner Jaye C. , Meyer Joshua E. , Cukierman Edna
Published: January 2024

Pancreatic cancer is becoming increasingly deadly, with treatment options limited due to, among others, the complex tumor microenvironment (TME). This short communications study investigates pulsed low-dose-rate radiation (PLDR) as a potential alternative to conventional radiotherapy for pancreatic cancer neoadjuvant treatment.

Our ex vivo research demonstrates that PLDR, in combination with chemotherapy, promotes a shift from tumor-promoting to tumor-suppressing properties in a key component of the pancreatic cancer microenvironment we called CAFu (cancer-associated fibroblasts and selfgenerated extracellular matrix functional units). This beneficial effect translates to reduced desmoplasia (fibrous tumor expansion) and suggests PLDR’s potential to improve total neoadjuvant therapy effectiveness.

To comprehensively assess this functional shift, we developed the HOST-Factor, a single score integrating multiple biomarkers. This tool provides a more accurate picture of CAFu function compared to individual biomarkers and could be valuable for guiding and monitoring future therapeutic strategies.

Our findings support the ongoingNCT04452357clinical trial testing PLDR safety and TME normalization potential in pancreatic cancer patients. The HOST-Factor will be used in samples collected from this trial to validate its potential as a key tool for personalized medicine in this aggressive disease.
Vaping and smoking cue reactivity in young adult electronic cigarette users who have never smoked combustible cigarettes: A functional neuroimaging study
Authors: Liu Jiaying , Shi Zhenhao , Fabbricatore Jessica L. , McMains Joshua T. , Worsdale Allison , Jones Erin C. , Wang Yidi , Sweet Lawrence H.
Published: January 2024

Introduction

The rapid growth in the use of electronic cigarettes (e-cigarettes) among young adults who have never smoked combustible cigarettes is concerning, as it raises the potential for chronic vaping and nicotine addiction. A key characteristic of drug addiction is the elevated neural response to conditioned drug-related cues (i.e., cue reactivity). Generalized reactivity to both vaping and smoking cues may signify an increased risk for smoking initiation in non- smoking vapers. In this study, we used functional magnetic resonance imaging (fMRI) to evaluate brain responses to vaping and smoking cues in young adult never-smoking vapers.

Methods

Sixty-six young adult never-smoking vapers underwent functional MRI while viewing visual cues pertaining to vaping, smoking, and nicotine-unrelated unconditioned reward (i.e., food). A priori region-of-interest analysis combined with exploratory whole-brain analysis was performed to characterize neural reactivity to vaping and smoking cues in comparison to food cues.

Results

The medial prefrontal cortex and the posterior cingulate cortex, regions that play a key role in drug cue reactivity, showed significantly increased neural response to vaping cues compared to food cues. The posterior cingulate cortex additionally showed increased neural responses to smoking cues compared to food cues.

Conclusions

Despite never having smoked combustible cigarettes, young adult vapers exhibited heightened neural susceptibility to both vaping and smoking cues within brain systems associated with cue reactivity. The findings shed light on the mechanisms underlying nicotine addiction and smoking initiation risk in this critical population and may contribute to the development of science-based interventions and regulatory measures in the future.

IMPLICATIONS

The escalating vaping prevalence among US never-smoking young adults is alarming, due to its potential ramifications for nicotine addiction development. Nicotine addiction is characterized by elevated neural response to conditioned nicotine-related cues. Using functional neuroimaging, we showed that young adult non-smoking vapers exhibited heightened neural susceptibility to both vaping and smoking cues within brain systems previously associated with cue reactivity. Such cross-reactivity to both types of nicotine cues may serve as the mechanism underlying nicotine addiction and smoking initiation risk in this population. Our findings may contribute to the development of science-based interventions and regulatory measures addressing the vaping epidemic.
PathFinder: a novel graph transformer model to infer multi-cell intra- and inter-cellular signaling pathways and communications
Authors: Feng Jiarui , Province Michael , Li Guangfu , Payne Philip R.O. , Chen Yixin , Li Fuhai
Published: January 2024

Recently, large-scale scRNA-seq datasets have been generated to understand the complex and poorly understood signaling mechanisms within microenvironment of Alzheimer’s Disease (AD), which are critical for identifying novel therapeutic targets and precision medicine. Though a set of targets have been identified, however, it remains a challenging to infer the core intra- and inter-multi-cell signaling communication networks using the scRNA-seq data, considering the complex and highly interactive background signaling network. Herein, we introduced a novel graph transformer model, PathFinder, to infer multi-cell intra- and inter-cellular signaling pathways and signaling communications among multi-cell types. Compared with existing models, the novel and unique design of PathFinder is based on the divide-and-conquer strategy, which divides the complex signaling networks into signaling paths, and then score and rank them using a novel graph transformer architecture to infer the intra- and inter-cell signaling communications. We evaluated PathFinder using scRNA-seq data of APOE4-genotype specific AD mice models and identified novel APOE4 altered intra- and inter-cell interaction networks among neurons, astrocytes, and microglia. PathFinder is a general signaling network inference model and can be applied to other omics data-driven signaling network inference.
Nonlinear relationship between platelet count and 30-day in-hospital mortality in ICU stroke patients: a multicenter retrospective cohort study
Authors: Wang Lan-xiang , Liu Ren-li , Zhou Pan , Hu Hao-fei , Deng Zhe
Published: January 2024

Background

Evidence of the relationship between platelet count and 30-day in-hospital mortality in ICU stroke patients is still scarce. Therefore, the purpose of this study was to explore the relationship between platelet count and 30-day in-hospital mortality among ICU stroke patients.

Methods

We conducted a multicenter retrospective cohort study using data from 8029 ICU stroke patients in the US eICU-CRD v2.0 database from 2014 to 2015. Utilizing binary logistic regression, smooth curve fitting, and subgroup analyses, we examined the link between platelet count and 30-day in-hospital mortality.

Results

The 30-day in-hospital mortality prevalence was 14.02%, and the mean platelet count of 223×109/L. Adjusting for covariates, our findings revealed an inverse association between platelet count and 30-day in-hospital mortality (OR = 0.975, 95% CI: 0.966, 0.984). Subgroup analyses supported the robustness of these results. Moreover, a nonlinear relationship was observed between platelet count and 30-day in-hospital mortality, with the inflection point at 163×109/L. On the left side of the inflection point, the effect size (OR) was 0.92 (0.89, 0.95), while on the right side, the relationship was not statistically significant.

Conclusion

This study establishes an independent negative association between platelet count and 30-day in-hospital mortality in ICU stroke patients. Furthermore, a nonlinear relationship with a saturation effect was identified, suggesting that maintaining the platelet count around 163×109/L can reduce 30-day in-hospital mortality in these patients.
Pixel walking along the boreal forest–Arctic tundra ecotone: Large scale ground-truthing of satellite-derived greenness (NDVI)
Authors: Wong Russell E. , Berner Logan T. , Sullivan Patrick F. , Potter Christopher S. , Dial Roman J.
Published: January 2024

Satellite remote sensing of climate-driven changes in terrestrial ecosystems continues to improve, yet interpreting and rigorously validating these changes requires extensive ground-truthed data. Satellite measurements of vegetation indices, such as the Normalized Difference Vegetation Index (NDVI, or vegetation greenness), indicate widespread vegetation change in the Arctic that is associated with rapid warming. Plot-based studies have indicated greater vegetation greenness generally corresponds to greater plant biomass and deciduous shrub cover. However, the spatial scale of traditional plot-based sampling is much smaller than the resolution of most satellite imagery and thus does not fully describe how plant characteristics such as structure and taxonomic composition relate to satellite measurements of greenness. To improve interpretation of Landsat measurements of vegetation greenness in the Arctic, we developed and implemented a method that links satellite measurements with ground-based vegetation classifications. Here we describe data collected across the central Brooks Range of Alaska by field sampling hundreds of Landsat pixels per day, with a field campaign total of 23,213 pixels (30 m). Our example dataset shows that vegetation with the greatest Landsat greenness was taller than 1m, woody, and deciduous; vegetation with lower greenness tended to be shorter, evergreen, or non-woody. We also show that understory vegetation influences Landsat greenness. Our methods advance efforts to inform satellite data with ground-based vegetation observations using field samples at spatial scales more closely matched to the resolution of remotely sensed imagery.
Kalium channelrhodopsins effectively inhibit neurons in the small model animals
Authors: Ott Stanislav , Xu Sangyu , Lee Nicole , Hong Ivan Hee Kean , Anns Jonathan , Suresh Danesha Devini , Zhang Zhiyi , Zhang Xianyuan , Harion Raihanah , Ye Weiying , Chandramouli Vaishnavi , Jesuthasan Suresh , Saheki Yasunori , Claridge-Chang Adam
Published: January 2024

The analysis of neural circuits has been revolutionized by optogenetic methods. Light-gated chloride-conducting anion channelrhodopsins (ACRs)—recently emerged as powerful neuron inhibitors. For cells or sub-neuronal compartments with high intracellular chloride concentrations, however, a chloride conductance can have instead an activating effect. The recently discovered light-gated, potassium-conducting, kalium channelrhodopsins (KCRs) might serve as an alternative in these situations, with potentially broad application. As yet, KCRs have not been shown to confer potent inhibitory effects in the small genetically tractable animals. Here, we evaluated the utility of KCRs to suppress behavior and inhibit neural activity inDrosophila,C. elegans, and zebrafish. In direct comparisons with ACR1, a KCR1 variant with enhanced plasma-membrane trafficking displayed comparable potency, but with improved properties that include reduced toxicity and superior efficacy in putative high-chloride cells. This comparative analysis of behavioral inhibition between chloride- and potassium-selective silencing tools establishes KCRs as next-generation optogenetic inhibitors forin vivocircuit analysis in behaving animals.
Reformer: Deep learning model for characterizing protein-RNA interactions from sequence at single-base resolution
Authors: Shen Xilin , Li Xiangchun
Published: January 2024

Protein-RNA interactions play an essential role in the regulation of transcription, translation, and metabolism of cellular RNA. Here, we develop Reformer, a deep learning model that predicts protein-RNA binding affinity purely from sequence. We developed Reformer with 155 RNA binding protein (RBP) targets from 3 cell lines. Reformer achieved high prediction accuracy at single-base resolution when tasking with inferring protein- and cell-type-specific binding affinity. We conducted electrophoretic mobility shift assays to validate high-impact RNA regulation mutations predicted by Reformer. In addition, Reformer learned to capture protein binding motifs that cannot be discovered by eCLIP-seq experiments. Furthermore, we demonstrated that motif signatures related to RNA processing functions are encoded within Reformer. In conclusion, Reformer will facilitate interpretation of the regulation mechanisms underlying RNA processing.
The probability of a unique gene occurrence at the tips of a phylogenetic tree in the absence of horizontal gene transfer (the last-one-out)
Authors: Bremer Nico , Martin William F. , Steel Mike
Published: January 2024

Gene loss is an important process in gene and genome evolution. If a gene is present at the root of a rooted binary phylogenetic tree and can be lost in one descendant lineage, it can be lost in other descendant lineages as well, and potentially can be lost in all of them, leading to extinction of the gene on the tree. In that case, just before the gene goes extinct in the rooted phylogeny, there will be one lineage that still retains the gene for some period of time, representing a ‘last-one-out’ distribution. If there are many (hundreds) of leaves in one clade of a phylogenetic tree, yet only one leaf possesses the gene, it will look like the result of a recent gene acquisition, even though the distribution at the tips was generated by loss. Here we derive the probability of observing last-one-out distributions under a Markovian loss model and a given gene loss rateµ. We find that the probability of observing such cases can be calculated mathematically, and can be surprisingly high, depending upon the tree and the rate of gene loss. Examples from real data show that gene loss can readily account for the observed frequency of last-one-out gene distribution patterns that might otherwise be attributed to lateral gene transfer.
Can social interactions rescue “lost” behavioural defences in an allopatric cuckoo host?
Authors: Tolman Deryk , Ronkä Katja , Kluen Edward , Campobello Daniela , Thorogood Rose
Published: January 2024

Social information use by cuckoo-hosts provides an excellent example of how social interactions within species can influence selection on another. Neighbours observe each other’s mobbing behaviour towards cuckoos, and then adjust costly defences back at their own nest in response. This may even allow naïve juveniles to ‘learn’ to recognise cuckoos, suggesting that ‘social responsiveness’ must play a key part in determining how hosts respond to changing rates of brood parasitism. However, if the ‘cultural memory’ of cuckoos is lost, can this plasticity in defences be rescued? This is fundamental for cuckoo-host coevolution, as the rates at which host defences are lost, gained, or retained determines evolutionary dynamics. Using populations of reed warblers at the northern- and southernmost extents of their range, we designed a field experiment to test whether populations allopatric to cuckoos (i) still recognise cuckoos as a threat, (ii) respond to social cues to upregulate defences, and (iii) vary in their strength of social responsiveness. We found defences and social responsiveness to be weaker in the south, where there is a much longer history of allopatry. In the north, only birds that retained recognition of cuckoos showed social responsiveness: social information about cuckoos did not increase hosts’ propensity to attack (whereas it doubled in the range core), but it did increase the strength of mobbing in the 30% of birds that recognised the cuckoo at the northern range front. Most importantly, however, experimental cuckoo eggs remained in the nest, whereas in previous experiments elsewhere the same social information increased egg rejection ten-fold. This suggests that social responsiveness is more limited at the range edges, under relaxed selection, and this would incur little immediate cost to cuckoos’ fitness if they (re)invade. Our study provides a rare example of geographic variation in social information use and highlights how current range expansions may influence the outcome of future species interactions.
GVRP: Genome Variant Refinement Pipeline for variant analysis in non-human species using machine learning
Authors: Choi Jeonghoon , Zhou Bo , Song Giltae
Published: January 2024

Many investigations of human disease require model systems such as non-human primates and their associated genome analyses. While DeepVariant excels in calling human genetic variations, its reliance on calibrating against known variants from previous population studies poses challenges for non-human species.

To address this limitation, we introduce the Genome Variant Refinement Pipeline (GVRP), employing a machine learning-based approach to refine variant calls in non-human species. Rather than training separate variant callers for each species, we employ a machine learning model to accurately identify variations and filter out false positives from DeepVariant.

In GVRP, we omit certain DeepVariant preprocessing steps and leverage the ground-truth Genome In A Bottle (GIAB) variant calls to train the machine learning model for non-human species genome variant refinement. We anticipate that GVRP will significantly expedite genome variation studies for non-human species,.
Investigation of the heterogeneity of cancer cells using single cell Ca2+profiling
Authors: Bura Amélie E. , Caussette Camille , Guéguinou Maxime , Bellanger Dorine , Robert Alison , Cancel Mathilde , Lacouette-Rata Margot , Fromont Gaëlle , Vandier Christophe , Mahéo Karine , Brouard Thierry , Crottès David
Published: January 2024

Calcium (Ca2+) is an essential and ubiquitous second messenger that controls numerous cellular functions. The regulation of intracellular Ca2+oscillations defines a Ca2+signature that is representative of the cellular identity and the phenotype of a cell. In cancers, aberrant Ca2+fluxes have been associated with characteristics such as migration, proliferation or resistance to chemotherapy. However, it remains unclear whether cancer cells have specific Ca2+signatures that are representative of their oncogenic properties. To reveal the existence of oncogenic Ca2+signatures, we develop a method combining single cell calcium imaging and unsupervised and supervised machine learning approaches. Briefly, we generated a database of 27,439 single-cell agonist-induced Ca2+responses obtained from 16 prostate and colon cancer cell lines. Graph-based unsupervised clustering was used to define and compare Ca2+signatures of cancer cell lines. A supervised neural network model trained on the collection of agonist-induced Ca2+responses successfully identify individual cancer cells and predicted some of their characteristics. We extend these methods to observe Ca2+signatures of docetaxel-resistant cancer cells and in a co-culture model mimicking the interaction of cancer cells with cancer-associated fibroblasts. Our models successfully highlight subtle changes in those Ca2+signatures and are able to distinguish individual cancer cells from fibroblasts and predict their sensitivity to Docetaxel. Taken together, this study provides a proof of concept that cancer cells can be defined by their Ca2+signature and conversely that Ca2+signaling can serve as a predictor of cancer cell characteristics.
Genome scale CRISPR screens identify actin capping proteins as key modulators of therapeutic responses to radiation and immunotherapy
Authors: Verma Nipun , Renauer Paul A. , Dong Chuanpeng , Xin Shan , Lin Qianqian , Zhang Feifei , Glazer Peter M. , Chen Sidi
Published: January 2024

Radiotherapy (RT), is a fundamental treatment for malignant tumors and is used in over half of cancer patients. As radiation can promote anti-tumor immune effects, a promising therapeutic strategy is to combine radiation with immune checkpoint inhibitors (ICIs). However, the genetic determinants that impact therapeutic response in the context of combination therapy with radiation and ICI have not been systematically investigated. To unbiasedly identify the tumor intrinsic genetic factors governing such responses, we perform a set of genome-scale CRISPR screens in melanoma cells for cancer survival in response to low-dose genotoxic radiation treatment, in the context of CD8 T cell co-culture and with anti-PD1 checkpoint blockade antibody. Two actin capping proteins,Capza3andCapg, emerge as top hits that upon inactivation promote the survival of melanoma cells in such settings.Capza3andCapgknockouts (KOs) in mouse and human cancer cells display persistent DNA damage due to impaired homology directed repair (HDR); along with increased radiation, chemotherapy, and DNA repair inhibitor sensitivity. However, when cancer cells with these genes inactivated were exposed to sublethal radiation, inactivation of such actin capping protein promotes activation of the STING pathway, induction of inhibitoryCEACAM1ligand expression and resistance to CD8 T cell killing. Patient cancer genomics analysis reveals an increased mutational burden in patients with inactivating mutations inCAPGand/orCAPZA3, at levels comparable to other HDR associated genes. There is also a positive correlation betweenCAPGexpression and activation of immune related pathways and CD8 T cell tumor infiltration. Our results unveil the critical roles of actin binding proteins for efficient HDR within cancer cells and demonstrate a previously unrecognized regulatory mechanism of therapeutic response to radiation and immunotherapy.
Methods and participant characteristics in the Cancer Risk in Vegetarians Consortium: A cross-sectional analysis across 11 prospective studies
Authors: Dunneram Yashvee , Lee Jia Yi , Watling Cody Z. , Fraser Gary E , Miles Fayth , Prabhakaran Dorairaj , Shridhar Krithiga , Kondal Dimple , Mohan Viswanathan , Ali Mohammed K. , Venkat Narayan Kabayam M. , Tandon Nikhil , Tong Tammy Y. N. , Chiu Tina H.T. , Lin Ming-Nan , Lin Chin-Lon , Yang Hsin-Chou , Liang Yu-Jen , Greenwood Darren C. , Du Huaidong , Chen Zhengming , Yu Canqing , Kakkoura Maria G. , Reeves Gillian K. , Papier Keren , Floud Sarah , Sinha Rashmi , Liao Linda M. , Loftfield Erikka , Cade Janet E. , Key Timothy J. , Perez-Cornago Aurora
Published: January 2024

Background

The associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established.

Objective

To describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies.

Methods

We harmonised individual-level data from 11 prospective cohort studies in the UK, US, India, China, and Taiwan. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics.

Results

2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China.

Conclusions

Food intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk.