bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatic analysis and experimental validation of cuproptosis-related LncRNA as a novel biomarker for prognosis and immunotherapy of oral squamous cell carcinoma
Authors: Liang Shuang , Ji Lanting , Yu Zhenyuan , Cheng YaHsin , Gao Ruifang , Yan Wenpeng , Zhang Fang 
Published: February 2024

AbstractBackgroundThe novel form of regulatory cell death, cuproptosis, is characterized by proteotoxicity, which ultimately leads to cell death. Its targeting has emerged as a promising therapeutic approach for oral squamous cell carcinoma (OSCC). Long noncoding RNAs (lncRNAs) participate in epigenetic regulation and have been linked to the progression, prognosis, and treatment of OSCC. Thus, this study aimed to identify new cuproptosis-related lncRNAs (CRLs), establish predictive models for clinical prognosis, immune response, and drug sensitivity, and provide novel insights into immune escape and tumor drug resistance.MethodsThe present study screened eight CRLs (THAP9-AS1, STARD4-AS1, WDFY3-AS2, LINC00847, CDKN2A-DT, AL132800.1, GCC2-AS1, AC005746.1) using Lasso Cox regression analysis to develop an eight-CRL prognostic model. Patients were categorized into high- and low-risk groups using risk scores. To evaluate the predictive ability of the model, Kaplan-Meier analysis, ROC curves, and nomograms were employed. Furthermore, the study investigated the differences in immune function and anticancer drug sensitivity between the high- and low-risk groups. To validate the expression of CRLs in the model, OSCC cell lines were subjected to quantitative real-time fluorescence PCR (qRT-PCR).ResultsThe results of the study showed that the high-risk group had a shorter overall survival (OS) time in OSCC patients. Cox regression analysis demonstrated that the high-risk score was an independent risk factor for a poor prognosis. The validity of the model was confirmed using ROC curve analysis, and a nomogram was developed to predict the prognosis of OSCC patients. Furthermore, patients in the high-risk group with high TMB had a poorer prognosis. Patients in the low-risk group responded better to immunotherapy than those in the high-risk group. Additionally, the risk scores were significantly associated with drug sensitivity in OSCC patients. Finally, the findings of qRT-PCR supported the reliability of the proposed risk model.ConclusionThe study identified and established the 8-CRL model, which represents a novel pathway of lncRNA regulation of cuproptosis in OSCC. This model provides guidance for the prognosis and treatment of OSCC and offers a new insight into immune escape and tumor drug resistance.
Characterization and bioassay of indigenous isolates of the fall armyworm, Spodoptera frugiperda nucleopolyhedrovirus in India
Authors: Pandi Ram Kumar , Gopalsamy Sivakumar , Onkarappa Dhanyakumar , Thiruvengadam Venkatesan , Muthugounder Mohan , Nand Sushil Satya 
Published: February 2024

Abstract
Background
Maize fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is a highly migratory polyphagous insect pest that has posed itself as a very threatened insect invaded India since May 2018 and devastated the maize crop. This insect pest caused 62.5% damage on maize plants in Hassan district of Karnataka state, India. Surveys were undertaken in different parts of the country to assess the natural occurrences of all three categories of entomopathogens (bacteria, fungi, and viruses) associated with fall armyworm. Maximum occurrence of infection of entomopathogens (15.13%) was recorded from Chikkaballapura, Karnataka, followed by 12.23% from Hassan, Karnataka.

Results
Totally 13 isolates of S. frugiperda nucleopolyhedrovirus (SpfrNPV) were collected from 13 locations of the country. Electron microscopy studies clearly showed the tetrahedral shaped occlusion bodies of SpfrNPV with the size of 1.48–1.68 µm. The identity of highly virulent SpfrNPV NBAIR1 (Chikkaballapura isolate) was confirmed using conserved polyhedrin gene-specific primers and NCBI GenBank accession number was obtained (MT422725). Bioassay studies revealed that the SpfrNPV NBAIR1 Chikkaballapura isolate was highly virulent with the highest larval mortality (95.50%) and the lowest LC50 value of 2.11 × 103 OBs/ml. SpfrNPV is exclusively host specific and did not infect any other insect species other than S. frugiperda tested in this present study.

Conclusions
Among 13 isolates of SpfrNPV, SpfrNPV NBAIR1 Chikkaballapura isolate was highly virulent with respect to the larval mortality. Hence SpfrNPV NBAIR1 Chikkaballapura isolate is having a great potential to play in the management of maize fall armyworm S. frugiperda.
Primary Tumor Resection Before Systemic Therapy in Patients With Colon Cancer and Unresectable Metastases: Combined Results of the SYNCHRONOUS and CCRe-IV Trials
Authors: Rahbari Nuh N. , Biondo Sebastiano , Frago Ricardo , Feißt Manuel , Kreisler Esther , Rossion Inga , Serrano Monica , Jäger Dirk , Lehmann Monika , Sommer Florian , Dignass Axel , Bolling Claus , Vogel Ilka , Bork Ulrich , Büchler Markus W. , Folprecht Gunnar , Kieser Meinhard , Lordick Florian , Weitz Jürgen , Paty P.B. , Hermann R. , Schmoor C. 
Published: February 2024

PURPOSE Chemotherapy is established as primary treatment in patients with stage IV colorectal cancer and unresectable metastases. Data from nonrandomized clinical trials have fueled persistent uncertainty if primary tumor resection (PTR) before chemotherapy prolongs survival. We investigated the prognostic value of PTR in patients with newly diagnosed stage IV colon cancer who were not amenable to curative treatment. PATIENTS AND METHODS Patients enrolled in the multicenter, randomized SYNCHRONOUS and CCRe-IV trials were included in the analysis. Patients with colon cancer with synchronous unresectable metastases were randomly assigned at 100 sites in Austria, Germany, and Spain to undergo PTR or up-front chemotherapy (No PTR group). The chemotherapy regimen was left at discretion of the local team. Patients with tumor-related symptoms, inability to tolerate surgery and/or systemic chemotherapy, and history of another cancer were excluded. The primary end point was overall survival (OS), and the analyses were performed with intention-to-treat. RESULTS A total of 393 patients were randomly assigned to undergo PTR (n = 187) or no PTR (n = 206) between November 2011 and March 2017. Chemotherapy was not administered to 6.4% in the No PTR group and 24.1% in the PTR group. The median follow-up time was 36.7 months (95% CI, 36.6 to 37.3). The median OS was 16.7 months (95% CI, 13.2 to 19.2) in the PTR group and 18.6 months (95% CI, 16.2 to 22.3) in the No PTR group ( P = .191). Comparable OS between the study groups was further confirmed on multivariate analysis (hazard ratio, 0.944 [95% CI, 0.738 to 1.209], P = .65) and across all subgroups. Patients with serious adverse events were more common in the No PTR group (10.2% v 18.0%; P = .027). CONCLUSION Among patients with colon cancer and synchronous unresectable metastases, PTR before systemic chemotherapy was not associated with prolonged OS.
Relativistic energy density functional from momentum space to coordinate space within a coherent density fluctuation model
Authors: Yadav Praveen K. , Kumar Raj , Bhuyan M. 
Published: February 2024

Abstract
In this theoretical study, we have derived a simplified analytical expression for the binding energy per nucleon as a function of density and isospin asymmetry within the relativistic mean-field model. We have generated a new parameterization for the density-dependent DD-ME2 parameter set using the Relativistic-Hartree-Bogoliubov approach. Moreover, this work attempts to revisit the prior polynomial fitting in Kumar A. et al. Phys. Rev. C, 103 (2021) 024305 for the non-linear NL3 force parameter to provide a simplified set of equations for the energy density functional which is used for calculating the surface properties of finite nuclei. The current study improves the existing fitting procedure by effectively proposing a simpler model that provides comparably precise results while lowering the computational expense. To study the surface properties of finite nuclei with these parameterizations, we have adopted the coherent density fluctuation model, which effectively translates the quantities of nuclear matter from momentum space to coordinate space at local density. The isospin properties, such as symmetry energy and its surface and volume components, slope parameter, finite nuclear incompressibility, and surface incompressibility for even-even nuclei, are calculated for different mass regions. Moreover, we have studied the effect of density, weight function, and choice of relativistic force parameters on the surface properties. The significance of this work will help to determine the properties of nuclei along the nuclear landscape and can facilitate an improved understanding of the island of stability, heavy-ion collision, and nucleosynthesis, among others.
Higher Parametric Thyroid Feedback Quantile-based Index Is a Predictor of Type 2 Diabetes in a German Population Sample
Authors: Laclaustra Martin , Alonso-Ventura Vanesa , Schipf Sabine , Lou-Bonafonte Jose Manuel , Dörr Marcus , Trincado-Aznar Pablo , Völzke Henry , Nauck Matthias , Civeira Fernando , Ittermann Till 
Published: February 2024

Abstract

Context
Type 2 diabetes has been described to be associated with hypothyroidism but we recently found that a decrease in pituitary sensitivity to thyroid hormone is associated with diabetes, obesity, and metabolic syndrome.

Objective
We aimed to assess the longitudinal nature of this association in the population-based Study of Health in Pomerania (SHIP) in Germany.

Methods
Among a population-based sample of 4308 participants aged 20 to 79 years, 77% were followed for a period of 5 years. We studied 2542 participants without diabetes or thyroid medication at baseline and complete data in the variables of interest. Data of baseline free thyroxine (fT4) and thyrotropin (TSH) were used to calculate the Parametric Thyroid Feedback Quantile-based Index (PTFQI), which measures whether TSH remains elevated despite fT4 being high. It uses the average population response as reference. PTFQI association with incidence of type 2 diabetes over 5 years was estimated with Poisson regression models adjusted for age, sex, and body mass index (BMI).

Results
Compared with the first PTFQI quartile, incidence rate ratios for diabetes were 1.54 (95% CI, 0.97-2.46), 1.55 (0.94-2.57), and 1.97 (1.27-3.10) for the upper quartiles (P trend = .004) after adjusting for age and sex. The association remained statistically significant after additionally adjusting for BMI: 1.64 (1.05-2.59) for the fourth vs the first quartile (P trend = .043).

Conclusion
An elevation of the pituitary TSH-inhibition threshold is associated with incident type 2 diabetes independently of BMI. The PTFQI might have clinical potential for prognosis and metabolic status monitoring.
Prolactin Mediates Long-Term, Seasonal Rheostatic Regulation of Body Mass in Female Mammals
Authors: Marshall Christopher J , Blake Alexandra , Stewart Calum , Liddle T Adam , Denizli Irem , Cuthill Fallon , Evans Neil P , Stevenson Tyler J 
Published: February 2024

Abstract
A series of well-described anabolic and catabolic neuropeptides are known to provide short-term, homeostatic control of energy balance. The mechanisms that govern long-term, rheostatic control of regulated changes in energy balance are less well characterized. Using the robust and repeatable seasonal changes in body mass observed in Siberian hamsters, this report examined the role of prolactin in providing long-term rheostatic control of body mass and photoinduced changes in organ mass (ie, kidney, brown adipose tissue, uterine, and spleen). Endogenous circannual interval timing was observed after 4 months in a short photoperiod, indicated by a significant increase in body mass and prolactin mRNA expression in the pituitary gland. There was an inverse relationship between body mass and the expression of somatostatin (Sst) and cocaine- and amphetamine-regulated transcript (Cart). Pharmacological inhibition of prolactin release (via bromocriptine injection), reduced body mass of animals maintained in long photoperiods to winter–short photoperiod levels and was associated with a significant increase in hypothalamic Cart expression. Administration of ovine prolactin significantly increased body mass 24 hours after a single injection and the effect persisted after 3 consecutive daily injections. The data indicate that prolactin has pleiotropic effects on homeostatic sensors of energy balance (ie, Cart) and physiological effectors (ie, kidney, BAT). We propose that prolactin release from the pituitary gland acts as an output signal of the hypothalamic rheostat controller to regulate adaptive changes in body mass.
Estimates of differential toxin expression governing heterogeneous intracellular lifespans of Streptococcus pneumoniae
Authors: Santra Shweta , Nayak Indrani , Paladhi Ankush , Das Dibyendu , Banerjee Anirban 
Published: February 2024

ABSTRACT
Following invasion of the host cell, pore-forming toxins secreted by pathogens compromise vacuole integrity and expose the microbe to diverse intracellular defence mechanisms. However, the quantitative correlation between toxin expression levels and consequent pore dynamics, fostering the intracellular life of pathogens, remains largely unexplored. In this study, using Streptococcus pneumoniae and its secreted pore-forming toxin pneumolysin (Ply) as a model system, we explored various facets of host–pathogen interactions in the host cytosol. Using time-lapse fluorescence imaging, we monitored pore formation dynamics and lifespans of different pneumococcal subpopulations inside host cells. Based on experimental histograms of various event timescales such as pore formation time, vacuolar death or cytosolic escape time and total degradation time, we developed a mathematical model based on first-passage processes that could correlate the event timescales to intravacuolar toxin accumulation. This allowed us to estimate Ply production rate, burst size and threshold Ply quantities that trigger these outcomes. Collectively, we present a general method that illustrates a correlation between toxin expression levels and pore dynamics, dictating intracellular lifespans of pathogens.
Expanding the Use of HIPEC in Ovarian Cancer at Time of Interval Debulking Surgery to FIGO Stage IV and After 6 Cycles of Neoadjuvant Chemotherapy: A Prospective Analysis on Perioperative and Oncologic Outcomes
Authors: Ghirardi Valentina , Trozzi Rita , Scanu Francesca Romana , Giannarelli Diana , Santullo Francesco , Costantini Barbara , Naldini Angelica , Panico Camilla , Frassanito Luciano , Scambia Giovanni , Fagotti Anna 
Published: February 2024

Abstract
Background
Randomized data on patients with FIGO stage III ovarian cancer receiving ≤ 3 cycles of neoadjuvant chemotherapy (NACT) showed that hyperthermic intraperitoneal chemotherapy (HIPEC) after interval debulking surgery (IDS) improved patient’s survival. We assessed the perioperative outcomes and PFS of FIGO stage IV and/or patients receiving up to 6 cycles of NACT undergoing IDS+HIPEC.

Methods
Prospectively collected cases from January 1, 2019 to July 31, 2022 were included. Patients underwent HIPEC if: age ≥ 18 years but < 75 years, body mass index ≤ 35 kg/m2, ASA score ≤ 2, FIGO stage III/IV epithelial disease treated with up to 6 cycles of NACT, and residual disease < 2.5 mm.

Results
A total of 205 patients were included. No difference was found in baseline characteristics between FIGO Stage III and IV patients, whereas rate of stable disease after NACT (p = 0.004), mean surgical complexity score at IDS (p = 0.001), and bowel resection rate (p = 0.046) were higher in patients undergoing delayed IDS. A lower rate of patients with at least one G3–G5 postoperative complications was observed in FIGO stage IV versus FIGO stage III disease (5.3% vs. 14.0%; p = 0.052). This difference was confirmed at multivariable analysis (odds ratio [OR] 0.24; 95% confidence interval [CI] 0.07–0.80; p = 0.02), whereas age, SCS, bowel resection, and number of cycles did not affect postoperative complications. No difference in PFS was identified neither between FIGO stage III and IV patients (p = 0.44), nor between 3 and 4 versus > 4 cycles of NACT (p = 0.85).

Conclusions
Because of the absence of additional complications and positive survival outcomes, HIPEC administration can be considered in selected FIGO stage IV and patients receiving > 4 cycles of NACT.
The Multiple Odysseys in Research and Clinical Care for Neurogenetic Conditions
Authors: Wheeler Anne C. 
Published: February 2024

Abstract
Neurogenetic conditions (NGC; e.g., fragile X, Angelman, Prader-Willi syndromes) represent the cause for intellectual or developmental disabilities in up to 60% of cases. With expanded diagnostic options and an increasing focus on the development of gene therapies comes the potential of improved quality of life for individuals with NGCs and their families. However, these emerging initiatives also bring new challenges and considerations for NGC researchers and clinicians, including considerations for supporting caregivers and assuring outcome measures for clinical trials adequately reflect the lived experiences of people with NGCs. This paper summarizes the advances and current and future challenges of research and clinical service provision for people with NGCs and their caregivers.
SPARKing New Insight Into Autism Across the Lifespan
Authors: Sudnawa Khemika K. , Chung Wendy K. 
Published: February 2024

Abstract
Autism is heterogeneous at many levels, including clinical symptoms and etiology. A key strategy in studying heterogeneous conditions is having large enough sample sizes to stratify into smaller groups that are more homogeneous. SPARK and Simons Searchlight are large and growing research cohorts of individuals with autism in the United States and individuals with genetically defined neurodevelopmental conditions around the world, respectively. They both provide freely available phenotypic and genotypic data with the ability to re-contact participants through the research match program. Deep dives into each gene in Searchlight provide comprehensive natural history data to understand the differing clinical courses to inform proper clinical care, and work toward treatment for each condition. Moreover, pilots of genetically based newborn screening programs for neurogenetic disorders can provide opportunities for equitable and early diagnosis to try to improve outcomes with earlier interventions.
Virtual BUILD Research Collaboratory: A biomedical data science training using innovative pedagogy to address structures of racism and inequitable stress for undergraduates of color
Authors: Ceberio Niquo , Le Peter , Bailey Jasmón , Vernard Sonthonax , Coleman Nichole , Carrasco Yazmin P. , King Telisa , Bibbins-Domingo Kirsten , Nguyen Tung , Parangan-Smith Audrey , Uwaezuoke Kelechi , Rivers Robert C. , Watson Kenjus , Márquez-Magaña Leticia , Mehta Kala M. 
Published: February 2024

Objective
The unprecedented events of 2020 required a pivot in scientific training to better prepare the biomedical research workforce to address global pandemics, structural racism, and social inequities that devastate human health individually and erode it collectively. Furthermore, this pivot had to be accomplished in the virtual environment given the nation-wide lockdown.

Methods
These needs and context led to leveraging of the San Francisco Building Infrastructure Leading to Diversity (SF BUILD) theories of change to innovate a Virtual BUILD Research Collaboratory (VBRC). The purpose of VBRC was to train Black, Indigenous, and people of color (BIPOC) students to apply their unique perspectives to biomedical research. These training activities were evaluated using a pre-post survey design that included both validated and new psychosocial scales. A new scale was piloted to measure culturally relevant pedagogy.

Results
VBRC scholars increased science identity on two items: thinking of myself as a scientist (+1point, p = 0.006) and belonging to a community of scientists (+1point, p = 0.069). Overall, scholars perceived stress also decreased over VBRC (-2.35 points, p = 0.02). Post VBRC, scholars had high agency scores (μ = 11.02, Md = 12, range = 6–12, σ = 1.62) and cultural humility scores (μ = 22.11, Md = 23, range = 12–24, σ = 2.71). No notable race/ethnic differences were found in any measures.

Conclusions
Taken together, our innovative approach to data science training for BIPOC in unprecedented times shows promise for better preparing the workforce critically needed to address the fundamental gaps in knowledge at the intersection of public health, structural racism, and biomedical sciences.
"I think we did the best that we could in the space:” A qualitative study exploring individuals’ experiences with three unconventional environments for patients with a delayed hospital discharge
Authors: Marcinow Michelle , Cadel Lauren , Birze Arija , Sandercock Jane , Baek Junhee , Wodchis Walter , Guilcher Sara J. T. , Kuluski Kerry 
Published: February 2024

Background
Given growing hospital capacity pressures, persistent delayed discharges, and ongoing efforts to improve patient flow, the use of unconventional environments (newly created or repurposed areas for patient care) is becoming increasingly common. Despite this, little is known about individuals’ experiences in providing or receiving care in these environments.

Objectives
The objectives of this study were to: (1) describe the characteristics of three unconventional environments used to care for patients experiencing a delayed discharge, and (2) explore individuals’ experiences with the three unconventional environments.

Methods
This was a multi-method qualitative study of three unconventional environments in Ontario, Canada. Data were collected through semi-structured interviews and observations. Participants included patients, caregivers, healthcare providers, and clinical managers who had experience with delayed discharges. In-person observations of two environments were conducted. Interviews were transcribed and notes from the observations were recorded. Data were coded and analyzed thematically.

Results
Twenty-nine individuals participated. Three themes were identified for unconventional environments: (1) implications on the physical safety of patients; (2) implications on staffing models and continuity of care; and, (3) implications on team interactions and patient care. Participants discussed how the physical set-up of some unconventional spaces was not conducive to patient needs, especially those with cognitive impairment. Limited space made it difficult to maintain privacy and develop social relationships. However, the close proximity of team members allowed for more focused collaborations regarding patient care and contributed to staff fulfilment. A smaller, consistent care team and access to onsite physicians seemed to foster improved continuity of care.

Conclusions
There is potential to learn from multi-stakeholder perspectives in unconventional environments to improve experiences and optimize patient care. Key considerations include keeping hallways and patient rooms clear, having communal spaces for activities and socialization, co-locating team members to improve interactions and access to resources, and ensuring a consistent care team.