bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperthermic Intraperitoneal Chemotherapy May Damage Renal Function and Cause Serum Electrolyte Disturbance: A Retrospective Observational Study
Authors: Yu Zhiyuan , Zhao Xudong , Qiu Shuzhong , Zhou Sixin , Li Peiyu , Liu Na 
Published: May 2023

Objective:
The objective of this study was to evaluate the efficacy of postoperative hyperthermic intraperitoneal chemotherapy (HIPEC) on bone marrow hematopoiesis, liver and kidney function, and serum electrolytes for patients who underwent open radical gastrectomy, and investigate the variation tendency of above indicators.

Materials and Methods:
The clinical data of 153 patients who underwent open radical gastrectomy were retrospectively analyzed and were divided into HIPEC group (n=83) and control group (n=70). Repeated analysis of variance was used to analyze the variation tendency of bone marrow hematopoiesis, liver and kidney function, and serum electrolytes in the HIPEC and control group, respectively, and then made a comparison between the 2 groups.

Results:
There were statistical differences in alanine aminotransferase (P=0.034), phosphorus (P
+) (P<0.05), potassium (K+) (P=0.023), sodium (Na+) (P<0.001), and chloride (Cl−) (P=0.008) between HIPEC and control group. All outcome indicators changed significantly over time (P<0.05). No significant difference was found in hemoglobin, white blood cell, platelet, aspartate aminotransferase, total bilirubin, or uric acid between the 2 treatment groups at each time point. On the next day after HIPEC treatment, the levels of blood urea nitrogen, creatinine, and P
+ were higher in the HIPEC group, whereas the calcium (Ca+), magnesium (Mg+), and K+ levels of HIPEC group tended to be lower. However, the effects of HIPEC on alanine aminotransferase, Na+, and Cl− levels needed to be further explored.

Conclusions:
HIPEC treatment after open radical gastrectomy has no significant effect on hematopoietic bone marrow and liver function but may damage renal function; reduce Ca+, Mg+, K+ levels; and increase P
+ level.
What Value of Sixth Month Excess Weight Loss (Postsleeve Gastrectomy) Is Necessary for Better Sleep Quality?
Authors: Başak Fatih , Şişik Abdullah , Demirpolat Muhammed Taha , Çalişkan Yahya Kemal , Ülgür Hanife Şeyda 
Published: May 2023

Background:
Obesity, caused by caloric intake over output, is a global health problem. The relationship between sleep and obesity is discussed in the literature. Little is known about the compliance of sleep quality and patients’ weight loss. This study aimed to review how sleep quality is affected by bariatric surgery, assess whether compliance with sleep quality can be predicted after bariatric surgery, and establish its correlation with excess weight loss.

Methods:
A cross-sectional study was conducted for patients undergoing bariatric surgery (laparoscopic sleeve gastrectomy). Sleep quality was assessed with the Pittsburgh sleep quality index (PSQI) scale preoperatively and in the sixth postoperative month. A PSQI global score above 5 indicated poor sleep quality. Participants were divided into 2 groups: good and poor sleep quality. Receiver operating characteristics and logistic regression analysis were also performed to predict sleep quality.

Results:
The questionnaire was completed by 100 subjects. All PSQI components, except the sixth (sleep medication) component, improved in patients at the sixth postoperative month versus baseline values. In the receiver operating characteristic analysis to test the availability of excess weight loss (EWL%) cutoff values relative to predict successful sleepers, 65.1 of the sixth month EWL% was found for the diagnosis of successful sleeper patients with 72.6% sensitivity and 63% specificity (area under the curve: 0.706, P=0.002, 95% CI, 0.586 to 0.825).

Conclusions:
For patients undergoing weight loss surgery, while assessing the sixth postoperative month, the EWL% value over 65.1 was recommended for better sleep quality.
Learning Curve of Single-site Robotic Cholecystectomy: A Cumulative Sum Analysis
Authors: Kudsi Omar Y. , Kaoukabani Georges , Friedman Alexander , Sekigami Yurie , Bou-Ayash Naseem , Bahadir Jenna , Crawford Allison S. , Gokcal Fahri 
Published: May 2023

Background:
Minimally invasive surgery has significantly improved cosmesis and clinical outcomes after either laparoscopic or robotic cholecystectomy. In an effort to minimize the number of incisions in multiport procedures, single-site approaches have been developed. However, single-site robotic cholecystectomy (SSRC) can be technically challenging for novice surgeons. The goal of this study is to establish the learning curve (LC) of SSRC through an assessment of operative times and clinical outcomes.

Materials and Methods:
A retrospective analysis of patients undergoing SSRC over a period of 5 years was performed. Consecutive cholecystectomy cases were assessed based on the procedure setting (elective vs. emergent). Cumulative sum analysis were used to establish the LC through an evaluation of the skin-to-skin (STS) time and postoperative complications rate. Afterward, a direct comparison was performed between the established phases.

Results:
This study included a total of 259 SSRCs with an overall mean STS time of 41.1 minutes. Elective cases took on average of 38.8 minutes, whereas emergent cases spanned over 60.5 minutes (P=0.005). The cumulative sum-LC was obtained by summing the differences between each procedure’s STS time, revealing a quadratic best-fit line maximum and an inflection point between the early and late phases at case 91. A significant difference between STS time was seen between the early and late phases (53.8 vs. 30.0 min, P<0.0001). There were no significant differences in terms of postoperative complications between the 2 phases. Incisional hernia rates were comparable between the 2 phases (early: 4.4% vs. late: 2.5%, P<0.461).

Conclusions:
This is the largest study to assess the LC of SSRC through operative time and clinical outcomes. A steady decrease in STS time was observed during the completion of the first 91 consecutive cases.
Role of lipid nanodomains for inhibitory FcγRIIb function
Authors: Spiegel Franziska , Trollmann Marius F.W. , Kara Sibel , Pöhnl Matthias , Brandner Astrid F. , Nimmerjahn Falk , Lux Anja , Böckmann Rainer A. 
Published: May 2023

AbstractThe inhibitory Fcγ receptor FcγRIIb is involved in immune regulation and is known to localize to specific regions of the plasma membrane called lipid rafts. Previous studies suggested a link between the altered lateral receptor localization within the plasma membrane and the functional impairment of the FcγRIIb-I232T variant that is associated with systemic lupus erythematosus.Here, we conducted microsecond all-atom molecular dynamics simulations and IgG binding assays to investigate the lipid nano-environment of FcγRIIb monomers and of the FcγRIIb-I232T mutant within a plasma membrane model, the orientation of the FcγRIIb ectodomain, and its accessibility to IgG ligands. In contrast to previously proposed models, our simulations indicated that FcγRIIb does not favor a cholesterol-or a sphingolipid-enriched lipid environment. Interestingly, cholesterol was depleted for all studied FcγRIIb variants within a 2-3 nm environment of the receptor, counteracting the usage of raft terminology for models on receptor functionality. Instead, the receptor interacts with lipids that have poly-unsaturated fatty acyl chains and with (poly-) anionic lipids within the cytosolic membrane leaflet.We also found that FcγRIIb monomers adopt a conformation that is not suitable for binding to its IgG ligand, consistent with a lack of detectable binding of monomeric IgG in experiments on primary immune cells. However, our results propose that multivalent IgG complexes might stabilize FcγRIIb in a binding-competent conformation. We suggest differences in receptor complex formation within the membrane as a plausible cause of the altered membrane localization or clustering and the altered suppressive function of the FcγRIIb-I232T variant.Significance StatementOur study sheds new light on the molecular mechanisms underlying the regulation of immune signaling mediated by the inhibitory Fcγ receptor (FcγRIIb). By utilizing atomistic simulations and experimental assays, we demonstrate that FcγRIIb interacts with specific lipids in the plasma membrane. Notably, our findings challenge the current view of membrane heterogeneity in immune cells, as FcγRIIb is not localized in specialized membrane domains known as rafts. Rather, we propose that receptor complex formation modulates receptor localization and conformation, thereby enabling ligand binding.Our findings have important implications for understanding how immune receptors function and communicate with each other, and may provide new opportunities for developing therapeutic strategies targeting FcγRIIb in diseases such as autoimmunity and cancer.
Automated model discovery for muscle using constitutive recurrent neural networks
Authors: Wang Lucy M. , Linka Kevin , Kuhl Ellen 
Published: May 2023

AbstractThe stiffness of soft biological tissues not only depends on the applied deformation, but also on the deformation rate. To model this type of behavior, traditional approaches select a specific time-dependent constitutive model and fit its parameters to experimental data. Instead, a new trend now suggests a machine-learning based approach that simultaneously discovers both the best model and best parameters to explain given data. Recent studies have shown that feed-forward constitutive neural networks can robustly discover constitutive models and parameters for hyperelastic materials. However, feed-forward architectures fail to capture the history dependence of viscoelastic soft tissues. Here we combine a feed-forward constitutive neural network for the hyperelastic response and a recurrent neural network for the viscous response inspired by the theory of quasi-linear viscoelasticity. Our novel rheologically-informed network architecture discovers the time-independent initial stress using the feed-forward network and the time-dependent relaxation using the recurrent network. We train and test our combined network using unconfined compression relaxation experiments of passive skeletal muscle and compare our discovered model to a neo Hookean standard linear solid and to a vanilla recurrent neural network with no mechanics knowledge. We demonstrate that, for limited experimental data, our new constitutive recurrent neural network discovers models and parameters that satisfy basic physical principles and generalize well to unseen data. We discover a Mooney-Rivlin type two-term initial stored energy function that is linear in the first invariantI1and quadratic in the second invariantI2with stiffness parameters of 0.60kPa and 0.55kPa. We also discover a Prony-series type relaxation function with time constants of 0.362s, 2.54s, and 52.0s with coefficients of 0.89, 0.05, and 0.03. Our newly discovered model outperforms both the neo Hookean standard linear solid and the vanilla recurrent neural network in terms of prediction accuracy on unseen data. Our results suggest that constitutive recurrent neural networks can autonomously discover both model and parameters that best explain experimental data of soft viscoelastic tissues. Our source code, data, and examples are available athttps://github.com/LivingMatterLab.
Red Fluorescent Carbon Nanoparticles Derived fromSpinacia oleracea L.: A Versatile Tool for Bioimaging & Biomedical Applications
Authors: Barve Ketki , Singh Udisha , Kansara Krupa , Vaswani Payal , Yadav Pankaj , Kumar Ashutosh , Bhatia Dhiraj 
Published: May 2023

AbstractCarbon-based fluorescent quantum dots are an emerging class of nanoparticles for targeted bioimaging and biomedical applications. We present a facile microwave-assisted approach for synthesizing carbon nanoparticles with bright red fluorescence using ethanolic extracts ofSpinacia oleracealeaves, with a quantum yield of 94.67%. These nanoparticles, called CNPs, ranging from 15-50 nm, demonstrated fluorescence emission in the near-infrared (NIR) region between 650 and 700 nm, independent of excitation wavelength. Upon excitation at a wavelength of 410 nm, they exhibit an emission maxima peak at 672 nm. The significant uptake of CNPs in mammalian cells and zebrafish larvae highlights their potential as bioimaging agents in diverse biomedical applicationsin vivo. Further, these quantum dots enhance cellular proliferation and migration as observed by wound healing assay in mammalian cells, indicating their possible application in tissue engineering and regenerative medicine. These findings suggest that biosynthesized carbon nanoparticles possess significant potential for biomedical activities, which can serve as a robust benchmark for researchers towards promoting sustainability.
Seasonally variable thermal performance curves prevent adverse effects of heatwaves
Authors: Sasaki Matthew C. , Finiguerra Michael , Dam Hans G. 
Published: May 2023

AbstractThe increasing frequency and intensity of heatwaves may represent a significant challenge for predicting vulnerability of populations in a warming ocean. The direct impacts of heatwaves on populations depend on the relative position of environmental temperatures to the thermal performance curve optima. If thermal performance curves are static, the effects of heatwaves may therefore change seasonally over the annual temperature cycle. However, these seasonal changes in the effects of heatwaves may be dampened by corresponding variation in thermal performance curves which, in organisms with relatively short generation times, may be driven by phenotypic plasticity as well as genetic differentiation. Here we investigate the effects of seasonal timing and duration on the impacts of heatwaves in the ecologically important copepod congenersAcartia tonsaandAcartia hudsonica, and test the hypotheses that 1) seasonal variation in thermal performance curves will reduce overall population vulnerability to heatwaves, and 2) that seasonal variation in TPCs will prevent negative transgenerational effects of heatwave. We characterized seasonal variation in thermal performance curves for several fitness-related traits. These experiments uncovered strong seasonal variation in the thermal performance curves ofAcartia tonsa, and indicate that this variation buffers against negative effects of simulated heatwaves. We also quantified both direct and trans-generational effects of different duration heatwaves on copepods collected at various times throughout the season using simulated heatwave experiments. There was no consistent pattern in the transgenerational effects of parental exposure to heatwaves, which may indicate that seasonal variation in thermal performance curves reduces the effects of parental stress on offspring performance. Our results show that seasonal variation in thermal performance curves will likely play an important role in limiting the adverse effects of heatwaves on populations.
Nuclear cytoglobin associates with HMGB2 and regulates DNA damage and genome-wide transcriptional output in the vasculature
Authors: Mathai Clinton , Jourd’heuil Frances , Pham Le Gia Cat , Gilliard Kurrim , Howard Dennis , Balnis Joseph , Jaitovich Ariel , Chittur Sridar V. , Rilley Mark , Peredo-Wende Ruben , Ammoura Ibrahim , Shin Sandra J. , Barroso Margarida , Barra Jonathan , Shishkova Evgenia , Coon Joshua J. , Lopez-Soler Reynold I. , Jourd’heuil David 
Published: May 2023

AbstractIdentifying novel regulators of vascular smooth muscle cell function is necessary to further understand cardiovascular diseases. We previously identified cytoglobin, a hemoglobin homolog, with myogenic and cytoprotective roles in the vasculature. The specific mechanism of action of cytoglobin is unclear but does not seem to be related to oxygen transport or storage like hemoglobin. Herein, transcriptomic profiling of injured carotid arteries in cytoglobin global knockout mice revealed that cytoglobin deletion accelerated the loss of contractile genes and increased DNA damage. Overall, we show that cytoglobin is actively translocated into the nucleus of vascular smooth muscle cells through a redox signal driven by NOX4. We demonstrate that nuclear cytoglobin heterodimerizes with the non-histone chromatin structural protein HMGB2. Our results are consistent with a previously unknown function by which a non-erythrocytic hemoglobin inhibits DNA damage and regulates gene programs in the vasculature by modulating the genome-wide binding of HMGB2.
SEMORE: SEgmentation and MORphological fingErprinting by machine learning automates super-resolution data analysis
Authors: Bender Steen W. B. , Dreisler Marcus W. , Zhang Min , Kæstel-Hansen Jacob , Hatzakis Nikos S. 
Published: May 2023

AbstractThe morphology of protein assemblies impacts their behavior and contributes to beneficial and aberrant cellular responses. While single-molecule localization microscopy provides the required spatial resolution to investigate these assemblies, the lack of universal robust analytical tools to extract and quantify underlying structures limits this powerful technique. Here we present SEMORE, a semi-automatic machine learning framework for universal, system and input-dependent, analysis of super-resolution data. SEMORE implements a multi-layered density-based clustering module to dissect biological assemblies and amorphology fingerprintingmodule for quantification by multiple geometric and kinetics-based descriptors. We demonstrate SEMORE on simulations and diverse raw super-resolution data; time-resolved insulin aggregates and imaging of nuclear pore complexes. SEMORE extracts and quantifies all protein assemblies enabling classification of heterogeneous insulin aggregation pathways and NPC geometry in minutes. SEMORE is a general analysis platform for super-resolution data, and being the first time-awar e framework can also support the rise of 4D super-resolution data.
High-throughput bactericidal assays for monoclonal antibody screening against antimicrobial resistantNeisseria gonorrhoeae
Authors: Stazzoni Samuele , Troisi Marco , Abbiento Valentina , Sala Claudia , Andreano Emanuele , Rappuoli Rino 
Published: May 2023

ABSTRACTNeisseria gonorrhoeae(gonococcus) is an obligate human pathogen and the etiological agent of the sexually transmitted disease gonorrhea. The rapid rise in gonococcal resistance to all currently available antimicrobials has become a significant public health burden and the need to develop novel therapeutic and prophylactic tools is now a global priority. While high-throughput screening methods allowed rapid discovery of extremely potent monoclonal antibodies (mAbs) against viral pathogens, the field of bacteriology suffers from the lack of assays that allow efficient screening of large panels of samples. To address this point, we developed luminescence-based (L-ABA) and resazurin-based (R-ABA) antibody bactericidal assays that measureN. gonorrhoeaemetabolic activity as a proxy of bacterial viability. Both L-ABA and R-ABA are applicable on the large scale for the rapid identification of bactericidal antibodies and were validated by conventional methods. Implementation of these approaches will be instrumental to the development of new medications and vaccines againstN. gonorrhoeaeand other bacterial pathogens to support the fight against antimicrobial resistance.
Molecular Mechanism of Regulation of RhoA GTPase by Phosphorylation of RhoGDI
Authors: Sinha Krishnendu , Kumawat Amit , Jang Hyunbum , Nussinov Ruth , Chakrabarty Suman 
Published: May 2023

AbstractRho-specific guanine dissociation inhibitors (RhoGDIs) play a crucial role in the regulation of Rho family GTPases. They act as negative regulators that prevent the activation of Rho GTPases by forming complexes with the inactive GDP-bound state of GTPase. Release of Rho GTPase from the RhoGDI-bound complex is necessary for Rho GTPase activation. Biochemical studies provide evidence of a “phosphorylation code”, where phosphorylation of some specific residues of RhoGDI selectively releases its GTPase partner (RhoA, Rac1, Cdc42 etc.). This work attempts to understand the molecular mechanism behind this phosphorylation code. Using several microseconds long atomistic molecular dynamics (MD) simulations of the wild-type and phosphorylated states of the RhoA–RhoGDI complex, we propose a molecular-interaction-based mechanistic model for the dissociation of the complex. Phosphorylation induces major structural changes, particularly in the positively charged polybasic region (PBR) of RhoA and the negatively charged N-terminal region of RhoGDI that contribute most to the binding affinity. MM-PBSA binding free energy calculations show a significant weakening of interaction on phosphorylation at the RhoA-specific site of RhoGDI. In contrast, phosphorylation at a Rac1-specific site leads to the strengthening of the interaction confirming the presence of a phosphorylation code. RhoA-specific phosphorylation leads to a reduction in the number of contacts between the PBR of RhoA and the N-terminal region of RhoGDI, which manifests reduction of the binding affinity. Using hydrogen bond occupancy analysis and energetic perturbation network, we propose a mechanistic model for the allosteric response, i.e., long range signal propagation from the site of phosphorylation to the PBR and buried geranylgeranyl group in the form of rearrangement and rewiring of hydrogen bonds and salt bridges. Our results highlight the crucial role of specific electrostatic interactions in manifestation of the phosphorylation code.
Mcam stabilizes luminal progenitor breast cancer phenotypes via Ck2 control and Src/Akt/Stat3 attenuation
Authors: Balcioglu Ozlen , Gates Brooke L. , Freeman David W. , Hagos Berhane M. , Mehrabad Elnaz Mirzaei , Ayala-Talavera David , Spike Benjamin T. 
Published: May 2023

ABSTRACTBreast cancers are categorized into subtypes with distinctive therapeutic vulnerabilities and prognoses based on their expression of clinically targetable receptors and gene expression patterns mimicking different cell types of the normal gland. Here, we tested the role of Mcam in breast cancer cell state control and tumorigenicity in a luminal progenitor-like murine tumor cell line (Py230) that exhibits lineage and tumor subtype plasticity. Mcam knockdown Py230 cells show augmented Stat3 and Pi3K/Akt activation associated with a lineage state switch away from a hormone-sensing/luminal progenitor state toward alveolar and basal cell related phenotypes that were refractory to growth inhibition by the anti-estrogen therapeutic, tamoxifen. Inhibition of Stat3, or the upstream activator Ck2, reversed these cell state changes. Mcam binds Ck2 and acts as a regulator of Ck2 substrate utilization across multiple mammary tumor cell lines. In Py230 cells this activity manifests as increased mesenchymal morphology, migration, and Src/Fak/Mapk/Paxillin adhesion complex signalingin vitro, in contrast to Mcam’s reported roles in promoting mesenchymal phenotypes.In vivo, Mcam knockdown reduced tumor growth and take rate and inhibited cell state transition to Sox10+/neural crest like cells previously been associated with tumor aggressiveness. This contrasts with human luminal breast cancers where MCAM copy number loss is highly coupled to Cyclin D amplification, increased proliferation, and the more aggressive Luminal B subtype. Together these data indicate a critical role for Mcam and its regulation of Ck2 in control of breast cancer cell state plasticity with implications for progression, evasion of targeted therapies and combination therapy design.HIGHLIGHTSMcam is expressed by diverse breast cancer subtypes.Mcam regulates breast cancer cell state plasticity.Mcam maintains the mammary luminal progenitor state.Mcam attenuates Stat activity.Mcam dictates Ck2 substrate utilization.