bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamically coupled kinetic chemistry in brown dwarf atmospheres – II. Cloud and chemistry connections in directly imaged sub-Jupiter exoplanets
Authors: Lee Elspeth K H , Tan Xianyu , Tsai Shang-Min 
Published: February 2024

ABSTRACT
With JWST slated to gain high-fidelity time-dependent data on brown dwarf atmospheres, it is highly anticipated to do the same for directly imaged, sub-Jupiter exoplanets. With this new capability, the need for a full three-dimensional (3D) understanding to explain spectral features and their time dependence is becoming a vital aspect for consideration. To examine the atmospheric properties of directly imaged sub-Jupiter exoplanets, we use the 3D Exo-FMS general circulation model to simulate a metal-enhanced generic young sub-Jupiter object. We couple Exo-FMS to a kinetic chemistry scheme, a tracer-based cloud formation scheme and a spectral radiative-transfer model to take into account the chemical and cloud feedback on the atmospheric thermochemical and dynamical properties. Our results show a highly complex feedback between clouds and chemistry on to the 3D temperature structure of the atmosphere, bringing about latitudinal differences and inducing time-dependent stormy features at photospheric pressures. This suggests a strong connection and feedback between the spatial cloud coverage and chemical composition of the atmosphere, with the temperature changes and dynamical motions induced by cloud opacity and triggered convection feedback driving chemical species behaviour. In addition, we also produce synthetic latitude-dependent and time-dependent spectra of our model to investigate atmospheric variability and periodicity in commonly used photometric bands. Overall, our efforts put the included physics in 3D simulations of exoplanets on par with contemporary 1D radiative-convective equilibrium modelling.
CDBProm: the Comprehensive Directory of Bacterial Promoters
Authors: Martinez Gustavo Sganzerla , Perez-Rueda Ernesto , Kumar Anuj , Dutt Mansi , Maya Cinthia Rodríguez , Ledesma-Dominguez Leonardo , Casa Pedro Lenz , Kumar Aditya , de Avila e Silva Scheila , Kelvin David J 
Published: February 2024

Abstract
The decreasing cost of whole genome sequencing has produced high volumes of genomic information that require annotation. The experimental identification of promoter sequences, pivotal for regulating gene expression, is a laborious and cost-prohibitive task. To expedite this, we introduce the Comprehensive Directory of Bacterial Promoters (CDBProm), a directory of in-silico predicted bacterial promoter sequences. We first identified that an Extreme Gradient Boosting (XGBoost) algorithm would distinguish promoters from random downstream regions with an accuracy of 87%. To capture distinctive promoter signals, we generated a second XGBoost classifier trained on the instances misclassified in our first classifier. The predictor of CDBProm is then fed with over 55 million upstream regions from more than 6000 bacterial genomes. Upon finding potential promoter sequences in upstream regions, each promoter is mapped to the genomic data of the organism, linking the predicted promoter with its coding DNA sequence, and identifying the function of the gene regulated by the promoter. The collection of bacterial promoters available in CDBProm enables the quantitative analysis of a plethora of bacterial promoters. Our collection with over 24 million promoters is publicly available at https://aw.iimas.unam.mx/cdbprom/
Anaplastic Lymphoma Kinase (ALK) Inhibitors Show Activity in Colorectal Cancer With ALK Rearrangements: Case Series and Literature Review
Authors: Hu Tingting , Zhan Jinbo , Li Li , He Yan , Lin Yun , Wang Jingru , Yu Haiming , Xiong Jianping , Fang Ziling , Deng Jun , Huang Shanshan , Xiang Xiaojun 
Published: February 2024

Abstract
Anaplastic lymphoma kinase (ALK) rearrangement is a well-known driver oncogene detected in approximately 5% of non–small cell lung cancer. However, ALK rearrangement is much less frequent in other solid tumors outside the lungs, such as colorectal cancer (CRC); thus, the optimal management of CRC with ALK rearrangements has yet to be established. In this report, we describe 2 cases of ALK-positive CRC, both of which benefited from ALK tyrosine kinase inhibitor (ALK-TKI) therapy. Case 1 was a postoperative patient with poorly differentiated colon adenocarcinoma, who was diagnosed with metastatic relapse shortly after surgery. Both fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab combined with 5-fluorouracil, l-leucovorin, and irinotecan (FOLFIRI) proved ineffective against the disease. The patient was then treated with ensartinib, as the CAD-ALK fusion gene was detected by genomic analysis. The patient was initially treated with ensartinib monotherapy for 9 months, then with ensartinib combined with local radiotherapy and fruquintinib for another 4 months for isolated hilar hepatic lymph node metastasis. The patient experienced disease progression with an acquired ALK G1202R resistance mutation that responded well to lorlatinib. Case 2 involved a 72-year-old man with advanced colon cancer (pT4bN2aM1b, stage IV) harboring an EML4-ALK fusion. The patient underwent resection of the right colon tumor due to intestinal obstruction, but the disease continued to progress after 12 courses of FOLFIRI and bevacizumab chemotherapy. However, the patient responded remarkably well to alectinib. Our report emphasizes the importance of gene detection in the treatment of malignant tumors, and the significance of ALK mutations in CRC.
Adrenocortical Carcinomas: Molecular Pathogenesis, Treatment Options, and Emerging Immunotherapy and Targeted Therapy Approaches
Authors: Chukkalore Divya , MacDougall Kira , Master Viraj , Bilen Mehmet Asim , Nazha Bassel 
Published: February 2024

Abstract
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy in the advanced setting with poor prognosis. This narrative review provides an overview of the epidemiology of ACC and its molecular pathogenesis with a summary of the main involved signaling pathways. We then provide an update on the clinical presentation, diagnosis, and current management strategies of both localized and metastatic disease from a multidisciplinary perspective. We highlight the debate around the use of mitotane in the adjuvant setting and review the use of combination chemotherapy with etoposide, doxorubicin, and cisplatin. The review also focuses on emerging data providing hope for the use of immune checkpoint inhibitors and targeted therapies in ACC with a summary of ongoing trials.
An auxin research odyssey: 1989–2023
Authors: Cohen Jerry D , Strader Lucia C 
Published: February 2024

Abstract
The phytohormone auxin is at times called the master regulator of plant processes and has been shown to be a central player in embryo development, the establishment of the polar axis, early aspects of seedling growth, as well as growth and organ formation during later stages of plant development. The Plant Cell has been key, since the inception of the journal, to developing an understanding of auxin biology. Auxin-regulated plant growth control is accomplished by both changes in the levels of active hormones and the sensitivity of plant tissues to these concentration changes. In this historical review, we chart auxin research as it has progressed in key areas and highlight the role The Plant Cell played in these scientific developments. We focus on understanding auxin-responsive genes, transcription factors, reporter constructs, perception, and signal transduction processes. Auxin metabolism is discussed from the development of tryptophan auxotrophic mutants, the molecular biology of conjugate formation and hydrolysis, indole-3-butyric acid metabolism and transport, and key steps in indole-3-acetic acid biosynthesis, catabolism, and transport. This progress leads to an expectation of a more comprehensive understanding of the systems biology of auxin and the spatial and temporal regulation of cellular growth and development.
Not so hidden anymore: Advances and challenges in understanding root growth under water deficits
Authors: Voothuluru Priya , Wu Yajun , Sharp Robert E 
Published: February 2024

Abstract
Limited water availability is a major environmental factor constraining plant development and crop yields. One of the prominent adaptations of plants to water deficits is the maintenance of root growth that enables sustained access to soil water. Despite early recognition of the adaptive significance of root growth maintenance under water deficits, progress in understanding has been hampered by the inherent complexity of root systems and their interactions with the soil environment. We highlight selected milestones in the understanding of root growth responses to water deficits, with emphasis on founding studies that have shaped current knowledge and set the stage for further investigation. We revisit the concept of integrated biophysical and metabolic regulation of plant growth and use this framework to review central growth-regulatory processes occurring within root growth zones under water stress at subcellular to organ scales. Key topics include the primary processes of modifications of cell wall–yielding properties and osmotic adjustment, as well as regulatory roles of abscisic acid and its interactions with other hormones. We include consideration of long-recognized responses for which detailed mechanistic understanding has been elusive until recently, for example hydrotropism, and identify gaps in knowledge, ongoing challenges, and opportunities for future research.
Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cell Therapy in Preclinical Models of Sepsis: A Systematic Review and Meta-analysis
Authors: Hum Christine , Tahir Usama , Mei Shirley H J , Champagne Josee , Fergusson Dean A , Lalu Manoj , Stewart Duncan J , Walley Keith , Marshall John , dos Santos Claudia C , Winston Brent W , Mendelson Asher A , Dave Chintan , McIntyre Lauralyn 
Published: February 2024

Abstract

Background
In preclinical studies, mesenchymal stromal cells (MSCs), including umbilical cord-derived MSCs (UC-MSCs), demonstrate the ability to modulate numerous pathophysiological processes related to sepsis; however, a systematic synthesis of the literature is needed to assess the efficacy of UC-MSCs for treating sepsis.

Objective
To examine the effects of UC-MSCs on overall mortality (primary outcome) as well as on organ dysfunction, coagulopathy, endothelial permeability, pathogen clearance, and systemic inflammation (secondary outcomes) at prespecified time intervals in preclinical models of sepsis.

Methods
A systematic search was conducted on Embase, Ovid MEDLINE, and Web of Science up to June 20, 2023. Preclinical controlled studies using in vivo sepsis models with systemic UC-MSC administration were included. Meta-analyses were conducted and expressed as odds ratios (OR) and ratios of the weighted means with 95% CI for categorical and continuous data, respectively. Risk of bias was assessed with the SYRCLE tool.

Results
Twenty-six studies (34 experiments, n = 1258 animals) were included in this review. Overall mortality was significantly reduced with UC-MSC treatment as compared to controls (OR: 0.26, 95% CI: 0.18-0.36). At various prespecified time intervals, UC-MSCs reduced surrogate measures of organ dysfunction related to the kidney, liver, and lung; reduced coagulopathy and endothelial permeability; and enhanced pathogen clearance from multiple sites. UC-MSCs also modulated systemic inflammatory mediators. No studies were rated as low risk across all SYCLE domains.

Conclusions
These results demonstrate the efficacy of UC-MSC treatment in preclinical sepsis models and highlight their potential as a therapeutic intervention for septic shock.
Within-host evolution of SARS-CoV-2: how often are de novo mutations transmitted from symptomatic infections?
Authors: Korosec Chapin S , Wahl Lindi M , Heffernan Jane M 
Published: February 2024

Abstract
Despite a relatively low mutation rate, the large number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has allowed for substantial genetic change, leading to a multitude of emerging variants. Using a recently determined mutation rate (per site replication), as well as within-host parameter estimates for symptomatic SARS-CoV-2 infection, we apply a stochastic transmission-bottleneck model to describe the survival probability of de novo SARS-CoV-2 mutations as a function of bottleneck size and selection coefficient. For narrow bottlenecks, we find that mutations affecting per-target-cell attachment rate (with phenotypes associated with fusogenicity and ACE2 binding) have similar transmission probabilities to mutations affecting viral load clearance (with phenotypes associated with humoral evasion). We further find that mutations affecting the eclipse rate (with phenotypes associated with reorganization of cellular metabolic processes and synthesis of viral budding precursor material) are highly favoured relative to all other traits examined. We find that mutations leading to reduced removal rates of infected cells (with phenotypes associated with innate immune evasion) have limited transmission advantage relative to mutations leading to humoral evasion. Predicted transmission probabilities, however, for mutations affecting innate immune evasion are more consistent with the range of clinically estimated household transmission probabilities for de novo mutations. This result suggests that although mutations affecting humoral evasion are more easily transmitted when they occur, mutations affecting innate immune evasion may occur more readily. We examine our predictions in the context of a number of previously characterized mutations in circulating strains of SARS-CoV-2. Our work offers both a null model for SARS-CoV-2 mutation rates and predicts which aspects of viral life history are most likely to successfully evolve, despite low mutation rates and repeated transmission bottlenecks.
The hidden world of fossil larvae: description and morphological insights of an immature scorpionfly (Mecoptera: Panorpidae) from the Baltic amber
Authors: Szpila Krzysztof , van de Kamp Thomas , Sontag Elżbieta , Krzemiński Wiesław , Kopeć Katarzyna , Soszyńska Agnieszka 
Published: February 2024

Abstract
So far, there has been no information of the pre-imaginal stages in the well-preserved fossil record of the Mecoptera. The first and well-preserved mecopteran larva was discovered in Eocene Baltic amber. The application of synchrotron X-ray microtomography enabled the reconstruction of the body structure with high accuracy, providing a comprehensive set of morphological data that classical stereoscopic microscopy could not capture. The larva is eruciform, with distinct segmentation of the body. All the most important morphological structures are documented, including the chaetotaxy system. Shape of antenna and annulated processes on the abdominal segments point to the third/four stage of development. There is no doubt that the larva belongs to Panorpidae, the most abundant family of extant Mecoptera. The morphological characters point to the closest affinity to larvae of Cerapanorpa and Panorpa but the fossil larva cannot be assigned to any extant genus of Panorpidae. Based on the results of synchrotron X-ray microtomography, it is possible to discuss the assignement of this larva to a lower systematic level than the family, and draw conclusions about the nature of the habitat preferences of Eocene panorpid.
μ-Opioid Receptor Activation at the Dorsal Reticular Nucleus Shifts Diffuse Noxious Inhibitory Controls to Hyperalgesia in Chronic Joint Pain in Male Rats
Authors: Pereira-Silva Raquel , Teixeira-Pinto Armando , Neto Fani L. , Martins Isabel 
Published: February 2024

Background
The dorsal reticular nucleus is a pain facilitatory area involved in diffuse noxious inhibitory control (DNIC) through opioidergic mechanisms that are poorly understood. The hypothesis was that signaling of μ-opioid receptors is altered in this area with prolonged chronic inflammatory pain and that this accounts for the loss of DNICs occurring in this condition.

Methods
Monoarthritis was induced in male Wistar rats (n = 5 to 9/group) by tibiotarsal injection of complete Freund’s adjuvant. The immunolabeling of µ-opioid receptors and the phosphorylated forms of µ-opioid receptors and cAMP response element binding protein was quantified. Pharmacologic manipulation of μ-opioid receptors at the dorsal reticular nucleus was assessed in DNIC using the Randall–Selitto test.

Results
At 42 days of monoarthritis, μ-opioid receptor labeling decreased at the dorsal reticular nucleus, while its phosphorylated form and the phosphorylated cAMP response element binding protein increased. [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin acetate (DAMGO) enhanced DNIC analgesia in normal animals (means ± SD: pre-DNIC: 126.9 ± 7.0 g; DNIC − DAMGO: 147.5 ± 8.0 g vs. DNIC + DAMGO: 198.1 ± 19.3 g; P < 0.001), whereas it produced hyperalgesia in monoarthritis (pre-DNIC: 67.8 ± 7.5 g; DNIC − DAMGO: 70.6 ± 7.7 g vs. DNIC + DAMGO: 32.2 ± 2.6 g; P < 0.001). An ultra-low dose of naloxone, which prevents the excitatory signaling of the μ-opioid receptor, restored DNIC analgesia in monoarthritis (DNIC − naloxone: 60.0 ± 6.1 g vs. DNIC + naloxone: 98.0 ± 13.5 g; P < 0.001), compared to saline (DNIC − saline: 62.5 ± 5.2 g vs. DNIC + saline: 64.2 ± 3.8 g). When injected before DAMGO, it restored DNIC analgesia and decreased the phosphorylated cAMP response element binding protein in monoarthritis.

Conclusions
The dorsal reticular nucleus is likely involved in a facilitatory pathway responsible for DNIC hyperalgesia. The shift of μ-opioid receptor signaling to excitatory in this pathway likely accounts for the loss of DNIC analgesia in monoarthritis.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Angioembolization Has Similar Efficacy and Lower Total Charges than Preperitoneal Pelvic Packing in Patients with Pelvic Ring or Acetabulum Fractures
Authors: Singh Aaron , Kotzur Travis , Koslosky Ezekial , Gonuguntla Rishi , Canseco Lorenzo , Momtaz David , Seifi Ali , Martin Case 
Published: February 2024

OBJECTIVES:
To compare cost, hospital related outcomes, and mortality between angioembolization (AE) and preperitoneal pelvic packing (PPP) in the setting of pelvic ring or acetabulum fractures.

METHODS:

Design: Retrospective database review.

Setting:
The National Inpatient Sample, years 2016-2020.

Patient Selection Criteria:
Hospitalized adult patients who underwent AE or PPP in the setting of a pelvic ring or acetabulum fracture.

Outcome Measures and Comparisons: Mortality, and hospital associated outcomes, including total charges following AE versus PPP in the setting of pelvic ring or acetabulum fractures.

RESULTS:
A total of 3,780 patients, 3,620 undergoing angioembolization and 160 undergoing PPP were included. No significant differences in mortality, LOS, time to procedure, or discharge disposition were found (p>0.05); however, PPP was associated with significantly greater charges than angioembolization (p=0.04). Patients who underwent angioembolization had a mean total charge of $250,062.88, while those undergoing PPP had a mean of total charge of $369,137.16.

CONCLUSIONS:
Despite equivalent clinical efficacy in terms of mortality and hospital related outcomes, preperitoneal pelvic packing was associated with significantly greater charges than angioembolization in the setting of pelvic ring or acetabulum fractures. This data information can inform clinical management of these patients and assist trauma centers in resource allocation.

LEVEL OF EVIDENCE:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
External Validation of Deep Learning-Based Cardiac Arrest Risk Management System for Predicting In-Hospital Cardiac Arrest in Patients Admitted to General Wards Based on Rapid Response System Operating and Nonoperating Periods: A Single-Center Study
Authors: Cho Kyung-Jae , Kim Kwan Hyung , Choi Jaewoo , Yoo Dongjoon , Kim Jeongmin 
Published: February 2024

OBJECTIVES:
The limitations of current early warning scores have prompted the development of deep learning-based systems, such as deep learning-based cardiac arrest risk management systems (DeepCARS). Unfortunately, in South Korea, only two institutions operate 24-hour Rapid Response System (RRS), whereas most hospitals have part-time or no RRS coverage at all. This study validated the predictive performance of DeepCARS during RRS operation and nonoperation periods and explored its potential beyond RRS operating hours.

DESIGN:
Retrospective cohort study.

SETTING:
In this 1-year retrospective study conducted at Yonsei University Health System Severance Hospital in South Korea, DeepCARS was compared with conventional early warning systems for predicting in-hospital cardiac arrest (IHCA). The study focused on adult patients admitted to the general ward, with the primary outcome being IHCA-prediction performance within 24 hours of the alarm.

PATIENTS:
We analyzed the data records of adult patients admitted to a general ward from September 1, 2019, to August 31, 2020.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Performance evaluation was conducted separately for the operational and nonoperational periods of the RRS, using the area under the receiver operating characteristic curve (AUROC) as the metric. DeepCARS demonstrated a superior AUROC as compared with the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS), both during RRS operating and nonoperating hours. Although the MEWS and NEWS exhibited varying performance across the two periods, DeepCARS showed consistent performance.

CONCLUSIONS:
The accuracy and efficiency for predicting IHCA of DeepCARS were superior to that of conventional methods, regardless of whether the RRS was in operation. These findings emphasize that DeepCARS is an effective screening tool suitable for hospitals with full-time RRS, part-time RRS, and even those without any RRS.