bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Analysis of Incidence, Therapeutic Strategies, and In-hospital Mortality of Mallory-Weiss Syndrome in Germany
Authors: Mertens Alexander , Essing Tobias , Roderburg Christoph , Luedde Tom , Kandler Jennis , Loosen Sven H.
Published: September 2023

Background:

Mallory-Weiss syndrome (MWS) is a rare cause of upper gastrointestinal bleeding from gaging or vomiting-induced mucosal lacerations at the gastroesophageal junction. Most cases do not require urgent endoscopic intervention due to the mostly self-limiting course. For more severe cases, different hemostasis techniques have been used. In small MWS cohorts, overall mortality was ~5%, but comprehensive data, as well as population-based incidence, treatment recommendations, and outcome parameters such as in-hospital mortality and adverse events, are largely lacking.

Methods:

We evaluated current epidemiological trends, therapeutic strategies, and in-hospital Mortality of MWS in Germany based on standardized hospital discharge data provided by the German Federal Statistical Office from 2010 to 2019.

Results:

A total of 59,291 MWS cases, predominately male (62%), were included into analysis. The mean number of MWS cases in Germany was 5929/year and decreased continuously during the observation period (−4.1%/y). The overall annual incidence rate (as hospitalization cases per 100,000 persons) was 7.5 with the highest incidence rate in the New Federal States (8.7). The most common comorbidities were reflux esophagitis (23.6%), diaphragmatic hernia (19.7%), and alcohol abuse (10.9%). The most frequent complication was bleeding anemia (26%), whereas hypovolemic shock (2.9%) was rare. Endoscopic injection was the most commonly performed endoscopic therapy (13.7%), followed by endoscopic clipping (12.8%), whereas the need for surgical therapy was rare (0.1%). Endoscopic combination therapies were used predominantly as a combination of injection and clipping. The overall in-hospital mortality was 2.7% and did not differ through the observation period. The presence of hypovolemic shock, acute kidney injury, sepsis, artificial ventilation, adult respiratory distress syndrome, bleeding anemia, and female sex was associated with a significantly worse prognosis.

Conclusion:

Our study gives a detailed insight into the incidence, patient-related risk factors, endoscopic treatment, and overall in-hospital mortality as well as regional differences in a large MWS collective in Germany. Furthermore, we were able to identify mortality-associated complications and their impact.
EpCAM, Ki67, and ESM1 Predict Hepatocellular Carcinoma Recurrence After Liver Transplantation
Authors: Hemida Aiat Shaban , Taie Doha Maher , El-Wahed Moshira Mohamed Abd , Shabaan Mohammed Ibrahim , Tantawy Mona Saeed , Ehsan Nermine Ahmed
Published: September 2023

Liver transplantation (LT) is a good therapeutic decision, cures hepatocellular carcinoma (HCC) and promotes survival of cases with unrespectable HCC based on the Milan criteria. HCC still recur after LT. Identifying high risk tissue markers that predict recurrence becomes important for LT decision-making. Little is known regarding use of tissue expression of epithelial cell adhesion molecule (EpCAM) to predict HCC recurrence. This study investigates the role of EpCAM, Ki67, and endothelial-cell-specific molecule-1 (ESM1) as immunohistochemical markers to predict HCC recurrence after LT. It included 52 explanted HCC tissues from Egyptian patients who had undergone LT for HCC according to Milan criteria. Immunohistochemical staining was done on paraffin-embedded formalin-fixed tissue sections. HCC recurrence occurred in 13.5% cases. Positive EpCAM expression in HCC, was significantly associated with HCC recurrence, (P=0.011), achieving 71.43% sensitivity, 84.44% specificity and 78.8% accuracy in predicting recurrence. High Ki67 percentage was significantly associated with HCC recurrence, (P=0.005), achieving 57.14% sensitivity, 86.67% specificity and 82.69% accuracy in predicting HCC recurrence. ESM1 showed significant association with HCC recurrence (P=0.041), with 71.43% sensitivity, 71.11% specificity and 71.15% accuracy in predicting HCC recurrence. EpCAM score and Ki67 percentage showed positive correlation. In conclusion, it is suggested that large tumor size (≥3 cm), advanced pathologic staging and Ki67 could be stratified as high risk predictors of HCC recurrence after LT. Although higher classes of Child-Turcotte-Pugh classification, high serum alpha-fetoprotein, microvascular invasion, positive EpCAM and ESM1 are stratified as lower risk predictors of HCC recurrence after LT.
Editor’s Choice Articles for September
Authors: Tasker Robert C.
Published: September 2023

The September 2023 issue and this year has already proven to be important for improving our understanding of pediatric acute respiratory distress syndrome (PARDS);Pediatric Critical Care Medicine(PCCM) has published 16 articles so far. Therefore, my three Editor’s Choice articles this month highlight yet morePCCMmaterial about PARDS by covering the use of noninvasive ventilation (NIV), the trajectory in cytokine profile during illness, and a new look at lung mechanics. ThePCCMConnections for Readers give us the opportunity to focus on some clinical biomarkers of severity and mortality risk during critical illness.
Perceptions of Controversies and Unresolved Issues in the 2014 FIGO Staging System for Endometrial Cancer: Survey Results From Members of the International Society of Gynecological Pathologists and International Gynecologic Cancer Society
Authors: Kayraklioglu Neslihan , Katsakhyan Levon , Cohen Paul A. , Singh Naveena , Rabban Joseph T. , Matias-Guiu Xavier
Published: September 2023

Long-standing controversial and unresolved issues in the current “International Federation of Gynecology and Obstetrics” staging system for endometrial cancer are well-recognized by pathologists and clinicians alike and exist primarily as a result of limitations to the existing literature. To guide the design of future outcome-based studies specifically aimed at resolving such gaps, the International Society of Gynecologic Pathologists developed a survey of the current perceptions of pathologists (n = 172) and clinicians (n= 135) from the International Society of Gynecological Pathologists and from the International Gynecologic Cancer Society on areas for potential refinement of the current International Federation of Gynecology and Obstetrics staging system. The highest priority issues for pathologists and clinicians alike were the need to determine whether stage IIIA patients (ovarian/fallopian tube involvement) can be reliably separated into favorable versus unfavorable outcome groups to avoid over-treatment of the former group and to determine whether stage IIIC patients (lymph node metastases) can be separated into favorable versus unfavorable outcome groups based on the size of lymph node metastases. The majority of pathologists and clinicians viewed lymphovascular space invasion as an independent prognostic variable and favored incorporating lymphovascular space invasion into staging, though the level of support did not meet the threshold of 75% in support that we used to define a formal consensus. While pathologists did agree on the prognostic value of reporting the extent of lymphovascular space invasion, there was no consensus on the diagnostic criteria to distinguish focal versus substantial involvement. The majority of pathologists and clinicians viewed that a universally accepted protocol for sentinel lymph node ultra-staging is lacking. Both survey groups conveyed a slight preference for incorporating tumor histotype and molecular classification into staging but the support was short of the 75% threshold for formal consensus. Collectively, this survey permits the International Society of Gynecological Pathologists to develop a pathologist and clinician-driven long-term strategy for prioritizing and designing outcome-based studies specifically targeted to resolving controversial and unresolved issues in the International Federation of Gynecology and Obstetrics staging of endometrial cancer.
SATB2 Cytoplasmic Expression is Characteristic of a Subset of Ovarian Stromal Cells and Sex Cord Stromal Tumors
Authors: Al-Hussaini Maysa , McCluggage W. Glenn
Published: September 2023

Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear transcription factor that shows consistent nuclear staining in colorectal adenocarcinoma and osteosarcoma. Following the observation of cytoplasmic staining with this marker in luteinized ovarian stromal cells, we studied the expression of SATB2 in ovarian stromal cells, various types of follicular cysts, and sex cord-stromal tumors. Eighty-five cases were stained for SATB2. Ovarian hilar Leydig cells (n = 12), luteinized stromal cells (n = 10), corpora lutea (n = 4), luteinized follicular cysts (n = 4), and stromal hyperthecosis (n = 6) exhibited consistent, usually diffuse, granular cytoplasmic staining. In addition, Leydig cell tumors (n = 1) and steroid cell tumors (n = 4) showed diffuse cytoplasmic staining. SATB2 also exhibited cytoplasmic staining in most Sertoli-Leydig cell tumors (n = 16) and gynandroblastomas (n = 3) confined to the Leydig cell component. Adult granulosa cell tumors (n = 14), juvenile granulosa cell tumors (n = 3), sex cord tumors with annular tubules (n = 3), cellular fibromas (n = 3), sclerosing stromal tumors (n = 1), and thecomas (n = 1) were negative apart from cytoplasmic staining in associated luteinized stromal cells. SATB2 cytoplasmic staining has not been previously described in these lesions but is characteristic of a variety of ovarian stromal cells and sex cord-stromal tumors, in particular, those exhibiting luteinization or a Leydig or steroid cell component. SATB2 staining may be of value in identifying luteinized or Leydig cells when these are morphologically inconspicuous.
Examination of the Current Impact Factor of the Journal of Craniofacial Surgery and Analysis of its Change by Years
Authors: Bahşi İlhan
Published: September 2023

In the Journal Citation Reports, it is shared various metrics from the previous year for the journals indexed in the Web of Science. On June 28, 2023, the 2022 data of the journals were shared. In this study, it was aimed to comprehensively examine the current impact factor of the Journal of Craniofacial Surgery, which has an important place in its field, and to determine the change observed in the impact factor values over the years. In conclusion, it has been observed that the values of the journal impact factor of the Journal of Craniofacial Surgery have been on an increasing trend, especially in the last 10 years. On the other hand, this value showed a slight decrease in 2022 data, but a similar decrease was observed in many journals in the literature. It is thought that the decreases in journal impact factor for 2022 data may be due to more general reasons, not journal scale. In addition, the values of the impact factor of the Journal of Craniofacial Surgery for the years 1997 to 2022 show that it has maintained its current position in the field of science for a long time.
Perfecting the Outcome of Nasal Bone Fracture in the Pediatric Population With a Navigation System
Authors: Park Tae Hwan
Published: September 2023

Background:

The trend of using navigation systems for treating facial bone fractures is increasing. Nevertheless, any detailed recommendation on using a navigation system to treat nasal bone fracture has never been discussed. Plastic surgeons are prone to do closed reduction of nasal bone fractures with remnant posttraumatic edema in the pediatric population. This study hypothesized that the navigation system benefits this population’s treatment of nasal bone fractures.

Methods:

The authors evaluated the medical records, plain x-ray, and facial computed tomography scans of 44 pediatric patients (below the age of 18) with nasal bone fractures treated with a closed reduction from May 2021 to December 2022. Preoperative and postoperative computed tomography scan were used to assess the outcome.

Results:

The average age for 44 pediatric nasal bone fracture patients was 10. Fifteen were female, while males were 29. All cases were successfully corrected clinically and radiologically without noticeable complications.

Conclusions:

Using navigation systems to correct nasal bone fractures provides additional benefits for the pediatric population. This technique is especially useful if the fracture is located at the junction between the nasal bone and nasal process of the maxilla and is combined with concurrent old nasal bone fractures.
Recovery of Third, Fourth, and Sixth Cranial Nerve Palsies in Pituitary Adenoma and Meningioma Patients
Authors: Lu Li-Pei J. , Pelsma Iris C. M. , de Vries Friso , van Hulst-Ginjaar Saskia P. A. , van Furth Wouter R. , Verstegen Marco J. T. , Fisher Fleur L. , Zamanipoor Najafadabadi Amir H. , Biermasz Nienke R. , van der Meeren Stijn W. , Notting Irene C.
Published: September 2023

Background:

This retrospective, observational cohort study aimed to determine recovery rate and recovery time of ocular motor nerve palsies (OMP) of third (CN III), fourth (CN IV), or sixth cranial nerves (CN VI)—and associated prognostic factors—in meningioma and pituitary adenoma (PA) patients.

Methods:

A total of 25 meningioma (28 eyes) and 33 PA patients (36 eyes), treated at the Leiden University Medical Center in the Netherlands from January 1, 1978 to January 31, 2021, were included. OMPs were evaluated according to a newly created recovery scale using on-clinical and orthoptic examinations, which were performed every 3–4 months until palsy recovery, or at 18 months follow-up.

Results:

Recovery rates of CN III (meningioma 23.5% vs PA 92.3%), CN IV (meningioma 20% vs PA 100%), and CN VI (meningioma 60% vs PA 100%) palsies were observed at 18 months follow-up, with differences between the 2 tumor types being observed in the treated patients only. Median recovery time of all OMPs combined was significantly longer in meningioma patients (37.9 ± 14.3 months vs 3.3 ± 0.1 months; P < 0.001). No significant protective or risk factors for recovery rate or time were identified.

Conclusions:

OMP recovery rates in treated patients were more favorable in patients with PA compared with patients with meningiomas, independent of OMP cause. With these new insights in OMP recovery, more accurate prognoses and appropriate follow-up strategies can be determined for meningioma and PA patients with OMPs.
Peter John Lawrenson. 12 March 1933—27 October 2017
Authors: Turner Michael J.
Published: September 2023

Born in Prescot, Lancashire, Peter Lawrenson rose from relatively humble origins to become a leading figure in the world of electrical motors and generators—first as an academic and latterly as a businessman. Noteworthy research throughout the 1960s quickly earned him a personal chair at the University of Leeds, and for a number of years he was head of department at the university's School of Electrical & Electronic Engineering. He is particularly remembered for pioneering the application of numerical methods to electromagnetic field problems, and for promoting and commercializing the switched reluctance motor, which—via the business, Switched Reluctance Drives Ltd, that he co-founded with research colleagues—was transformed from a laboratory curiosity to a commercially viable and highly efficient alternative to conventional electrical machines. A leading figure in the Institution of Electrical Engineers (IEE, latterly the IET), he also served with distinction as IEE president in 1992.
Mathematical modelling with Bayesian inference to quantitatively characterize therapeutic cell behaviour in nerve tissue engineering
Authors: Berg Maxime , Eleftheriadou Despoina , Phillips James B. , Shipley Rebecca J.
Published: September 2023

Cellular engineered neural tissues have significant potential to improve peripheral nerve repair strategies. Traditional approaches depend on quantifying tissue behaviours using experiments in isolation, presenting a challenge for an overarching framework for tissue design. By comparison, mathematical cell–solute models benchmarked against experimental data enable computational experiments to be performed to test the role of biological/biophysical mechanisms, as well as to explore the impact of different design scenarios and thus accelerate the development of new treatment strategies. Such models generally consist of a set of continuous, coupled, partial differential equations relying on a number of parameters and functional forms. They necessitate dedicatedin vitroexperiments to be informed, which are seldom available and often involve small datasets with limited spatio-temporal resolution, generating uncertainties. We address this issue and propose a pipeline based on Bayesian inference enabling the derivation of experimentally informed cell–solute models describing therapeutic cell behaviour in nerve tissue engineering. We apply our pipeline to three relevant cell types and obtain models that can readily be used to simulate nerve repair scenarios and quantitatively compare therapeutic cells. Beyond parameter estimation, the proposed pipeline enables model selection as well as experiment utility quantification, aimed at improving both model formulation and experimental design.
Neuronal branching is increasingly asymmetric near synapses, potentially enabling plasticity while minimizing energy dissipation and conduction time
Authors: Desai-Chowdhry Paheli , Brummer Alexander B. , Mallavarapu Samhita , Savage Van M.
Published: September 2023

Neurons’ primary function is to encode and transmit information in the brain and body. The branching architecture of axons and dendrites must compute, respond and make decisions while obeying the rules of the substrate in which they are enmeshed. Thus, it is important to delineate and understand the principles that govern these branching patterns. Here, we present evidence that asymmetric branching is a key factor in understanding the functional properties of neurons. First, we derive novel predictions for asymmetric scaling exponents that encapsulate branching architecture associated with crucial principles such as conduction time, power minimization and material costs. We compare our predictions with extensive data extracted from images to associate specific principles with specific biophysical functions and cell types. Notably, we find that asymmetric branching models lead to predictions and empirical findings that correspond to different weightings of the importance of maximum, minimum or total path lengths from the soma to the synapses. These different path lengths quantitatively and qualitatively affect energy, time and materials. Moreover, we generally observe that higher degrees of asymmetric branching—potentially arising from extrinsic environmental cues and synaptic plasticity in response to activity—occur closer to the tips than the soma (cell body).
Uniform approximations and effective boundary conditions for a high-contrast elastic interface
Authors: Chapman C. J. , Mogilevskaya S. G.
Published: September 2023

A difficulty in the theory of a thin elastic interface is that series expansions in its thickness become disordered in the high-contrast limit, i.e. when the interface is much softer or much stiffer than the media on either side. We provide a mathematical analysis of such series for an annular coating around a cylindrical fibre embedded in an elastic matrix subject to biaxial forcing. We determine the order of magnitude of successive terms in the series, and hence the terms that need to be retained in order to ensure that every neglected term is smaller in order of magnitude than at least one retained term. In this way, we obtain uniform approximations for quantities such as the jump in the displacement and stress across the coating, and explain some peculiarities that have been observed in numerical work. A key finding is that it is essential to distinguish three types of boundary-value problem, corresponding to ‘distant forcing’, ‘localized forcing’ and ‘the homogeneous problem’, since they give different patterns of disorder in the corresponding series expansions. This provides a meaningful correspondence between physical principles and our mathematical results.
On the problem of comparing graded metamaterials
Authors: Davies Bryn , Fehertoi-Nagy Lili , Putley Henry J.
Published: September 2023

We use a simple effective model, obtained through the application of high-frequency homogenization, to tackle the fundamental question of how the choice of gradient function affects the performance of a graded metamaterial. This approach provides a unified framework for comparing gradient functions efficiently and in a way that allows us to draw conclusions that apply to a range of different wave regimes. We consider the specific problem of single-frequency localization, for which the appropriate effective model is a one-dimensional Schrödinger equation. Our analytic results both corroborate those of existing studies (which use either expensive full-field wave simulations or black-box numerical optimization algorithms) and extend them to other metamaterial regimes. Based on our analysis, we are able to propose a design strategy for optimizing monotonically graded metamaterials and offer an explanation for the lack of a universal optimal gradient function.
MatchMaps: Non-isomorphous difference maps for X-ray crystallography
Authors: Brookner Dennis E. , Hekstra Doeke R.
Published: September 2023

Conformational change mediates the biological functions of macromolecules. Crystal-lographic measurements can map these changes with extraordinary sensitivity as a function of mutations, ligands, and time. The isomorphous difference map remains the gold standard for detecting structural differences between datasets. Isomorphous difference maps combine the phases of a chosen reference state with the observed changes in structure factor amplitudes to yield a map of changes in electron density. Such maps are much more sensitive to conformational change than structure refinement is, and are unbiased in the sense that observed differences do not depend on refinement of the perturbed state. However, even minute changes in unit cell properties can render isomorphous difference maps useless. This is unnecessary. Here we describe a generalized procedure for calculating observed difference maps that retains the high sensitivity to conformational change and avoids structure refinement of the perturbed state. We have implemented this procedure in an open-source python package, MatchMaps, that can be run in any software environment supporting PHENIX and CCP4. Through examples, we show that MatchMaps “rescues” observed difference electron density maps for poorly-isomorphous crystals, corrects artifacts in nominally isomorphous difference maps, and extends to detecting differences across copies within the asymmetric unit, or across altogether different crystal forms.

Synopsis

MatchMaps is a generalization of the isomorphous difference map allowing for computation of difference maps between poorly-isomorphous and non-isomorphous pairs of crystallographic datasets. MatchMaps is implemented as a simple-to-use, python-based command-line interface.
Evaluation oftrans- andcis-4-[18F]fluorogabapentin for brain PET imaging
Authors: Zhou Yu-Peng , Normandin Marc D. , Belov Vasily , Macdonald-Soccorso Marina T. , Moon Sung-Hyun , Sun Yang , Fakhri Georges El , Guehl Nicolas J. , Brugarolas Pedro
Published: September 2023

Gabapentin, a selective ligand for the α2δ subunit of voltage-dependent calcium channels, is an anticonvulsant medication used in the treatment of neuropathic pain, epilepsy and other neurological conditions. We recently described two radiofluorinated derivatives of gabapentin (trans-4-[18F]fluorogabapentin, [18F]tGBP4F, andcis-4-[18F]fluorogabapentin, [18F]cGBP4F) and showed that these compounds accumulate in the injured nerves in a rodent model of neuropathic pain. Given the use of gabapentin in brain diseases, here we investigate whether these radiofluorinated derivatives of gabapentin can be used for imaging α2δ receptors in the brain. Specifically, we developed automated radiosynthesis methods for [18F]tGBP4F and [18F]cGBP4F and conducted dynamic PET imaging in adult rhesus macaques with and without preadministration of pharmacological doses of gabapentin. Both radiotracers showed very high metabolic stability, negligible plasma protein binding and slow accumulation in the brain. [18F]tGBP4F, the isomer with higher binding affinity, showed low brain uptake and could not be displaced whereas [18F]cGBP4F showed moderate brain uptake and could be partially displaced. Kinetic modeling of brain regional time-activity curves using a metabolite-corrected arterial input function shows that a 1-tissue compartment model accurately fits the data. Graphical analysis using Logan or multilinear analysis 1 produced similar results as compartmental modeling indicating robust quantification. This study advances our understanding of how gabapentinoids work and provides an important advancement towards imaging α2δ receptors in the brain.
Metabolic evolution of pyranopterin-dependent biochemistry
Authors: Goldford Joshua E. , Murali Ranjani , Valentine Joan Selverstone , Fischer Woodward W.
Published: September 2023

Molybdenum (Mo)-dependent biochemistry is essential for many key metabolic pathways. However, theory and geological evidence suggests that its solubility during long intervals with low dioxygen would have limited its availability on early Earth. We developed models of metabolic evolution and found that reactions employing tungsten (W)-dependent biochemistry likely preceded Mo-dependent reactions, where Mo-usage increased dramatically after the production of dioxygen. Consistent with this finding, we analyzed genomes from over 65,000 phylogenetically diverse microbes and metagenomes from an environmental dataset, and we observed that dioxygen-utilizing prokaryotes living in aerobic niches are enriched with Mo-dependent enzymes as compared to anaerobic microbes. As an independent evaluation of this hypothesis, we combined protein language models, machine learning, and phylogenomic analysis to build a classifier for W- or Mo-pterin dependence in the DMSO reductase superfamily, and we found that W-pterin-dependent enzymes cluster near the root of the tree and that a subset of late-evolving aldehyde oxidoreductases (AORs) from aerobes are predicted to rely on Mo instead of W. Overall, our combination of metabolic modeling, phenotypic analysis, machine learning, and phylogenomic analysis suggest that Mo-pterin-dependent biochemistry likely derived from W-pterin-dependent biochemistry, and that Mo-usage increased drastically after the rise of oxygen.
3Dmapper: A Command Line Tool For BioBank-scale Mapping Of Variants To Protein Structures
Authors: Ruiz-Serra Victoria , Valentini Samuel , Madroñero Sergi , Valencia Alfonso , Porta-Pardo Eduard
Published: September 2023

The interpretation of genomic data is crucial to understand the molecular mechanisms of biological processes. Protein structures play a vital role in facilitating this interpretation by providing functional context to genetic coding variants. However, mapping genes to proteins is a tedious and error-prone task due to inconsistencies in data formats. Over the past two decades, numerous tools and databases have been developed to automatically map annotated positions and variants to protein structures. However, most of these tools are web-based and not well-suited for large-scale genomic data analysis. To address this issue, we introduce 3Dmapper, a standalone command-line tool developed in Python and R. It systematically maps annotated protein positions and variants to protein structures, providing a solution that is both efficient and reliable. 3Dmapper is freely available on GitHub athttps://github.com/vicruiser/3Dmapper.
Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86
Authors: Yang Sijie , Yu Yuanling , Jian Fanchong , Song Weiliang , Yisimayi Ayijiang , Chen Xiaosu , Xu Yanli , Wang Peng , Wang Jing , Yu Lingling , Niu Xiao , Wang Jing , Xiao Tianhe , An Ran , Wang Yao , Gu Qingqing , Shao Fei , Jin Ronghua , Shen Zhongyang , Wang Youchun , Cao Yunlong
Published: September 2023

The recently identified SARS-CoV-2 variant, BA.2.86, which carries a substantial number of Spike mutations, has raised a global alarm. An immediate assessment of its antigenic properties and infectivity is necessary. Here, we reveal the distinct antigenicity of BA.2.86 compared with previous variants including XBB.1.5. BA.2.86 significantly evades convalescent plasma from XBB breakthrough infection (BTI) and reinfections. Key mutations that mediate the enhanced resistance include N450D, K356T, L452W, A484K, V483del, and V445H on the RBD, while BA.2.86’s NTD mutations and E554K on SD1 also largely contribute. However, we found that BA.2.86 pseudovirus exhibits compromised efficiency of infecting HEK293T-hACE2 cells compared to XBB.1.5 and EG.5, which may be caused by K356T, V483del, and E554K, and could potentially limit BA.2.86’s transmissibility. In sum, it appears that BA.2.86 has traded its infectivity for higher immune evasion during long-term host-viral evolution. Close attention should be paid to monitoring additional mutations that could improve BA.2.86’s infectivity.
Prosocial Decision-Making and Human Brain: A Graph Theory Analysis on Resting-State Functional Magnetic Resonance Image
Authors: Xu Jinwei , Sun Delin
Published: September 2023

Prosocial behavior is the cornerstone of a harmonious society. However, the functional organization of the brain underlying prosocial decision-making needs to be further explored. Here, we used graph theory analysis to investigate the brain functional connectivity derived from functional magnetic resonance imaging (fMRI) scans during rest in 55 female Chinese university students. The behavioral responses were collected in another fMRI scan during which participants completed an economic exchange game task by making multiple choices between a prosocial and a selfish option against either human counterparts (i.e., social environment) or robot counterparts (i.e., non-social environment). We found that making more prosocial decisions is accompanied by a longer path length in the right anterior superior temporal gyrus (aSTG), higher degree centrality in the posterior cingulate cortex (PCC), and higher betweenness centrality in the left aSTG. Our results suggest that human prosocial decisions are associated with greater inter-regional collaborations that are dominated by a few core nodes within the brain network ofTheory of Mind(ToM). Moreover, an individual’s preference for making prosocial decisions could be uncovered by graph theory analysis of the functional brain network even without explicit task requirements.
The anterior cingulate cortex is involved in intero-exteroceptive integration for spatial image transformation of the self-body
Authors: Sasaoka Takafumi , Hirose Kenji , Maekawa Toru , Inui Toshio , Yamawaki Shigeto
Published: September 2023

Spatial image transformation of the self-body is a fundamental function of visual perspective-taking. Recent research underscores the significance of integration of intero-exteroceptive information to construct representations of our embodied self. This raises the intriguing hypothesis that interoceptive processing might be involved in the spatial image transformation of our self-body. To test this hypothesis, the present study used functional magnetic resonance imaging to measure brain activity during an arm laterality judgment (ALJ) task. In this task, participants were tasked with discerning whether the outstretched arm of a human figure, viewed from the front or back, was the right or left hand. The reaction times for the ALJ task proved longer when the stimulus presented orientations of 0°, 90°, and 270° relative to the upright orientation, and when the front view presented as compared to the back view. Corresponding to the increased reaction time, increased brain activity was manifested in a cluster centered on the dorsal anterior cingulate cortex (ACC). Furthermore, this cluster of brain activity exhibited overlap with regions where the difference in activation between the front and back views positively correlated with the participants’ interoceptive sensitivity, as assessed through the heartbeat detection task, within the pregenual ACC. These results suggest that the ACC plays an important role in integrating intero-exteroceptive cues for the purpose of spatially transforming the image of our self-body.
Tropical montane gradients elucidate the contributions of functional traits to competitive and environmental fitness
Authors: Mungee Mansi , Pandit Rohan , Athreya Ramana
Published: September 2023

Functional traits can be classified as alpha or beta, based on their relative importance in determining a species’ competitive and environmental fitness, respectively. However, the link between a trait and its contribution to a particular aspect of fitness is not always straight-forward. We investigated phylogenetic and functional diversity for bird communities along a 200-2800 m elevational transect in the eastern Himalayas. We hypothesized that beta traits, associated with environmental tolerances, would exhibit a directional change in mean values, while alpha traits, linked to competitive strategies, would show a decrease in dispersion with elevation. Our findings showed that most functional traits exhibited a decrease in dispersion with elevation. However, surprisingly, the mean values of these traits also exhibited a significant relationship with elevation, suggesting their involvement in both competitive and environmental fitness. Furthermore, we observed that morphological traits, traditionally considered beta traits associated with environmental tolerance, were influenced more strongly by resource availability and habitat structure rather than aspects of temperature or air density. These results challenge the simplistic classification of traits as either alpha or beta. We suggest that future studies should carefully analyze the variation in mean values and dispersion of individual traits before assigning them solely to a particular category of fitness. The results contribute to a broader understanding of the complex interactions between functional traits, fitness, and environmental conditions in Himalayan bird communities.
The CNS Microenvironment Promotes Leukemia Cell Survival by Disrupting Tumor Suppression and Cell Cycle Regulation in Pediatric T-cell Acute Lymphoblastic Leukemia
Authors: Enlund Sabina , Sinha Indranil , Neofytou Christina , Amor Amanda Ramilo , Papadakis Konstantinos , Nilsson Anna , Jiang Qingfei , Hermanson Ola , Holm Frida
Published: September 2023

A major obstacle in improving survival in pediatric T-cell acute lymphoblastic leukemia is understanding how to predict and treat leukemia relapse in the CNS. Leukemia cells are capable of infiltrating and residing within the CNS, where they interact with the microenvironment and remain sheltered from systemic treatment. These cells can survive in the CNS niche, by hijacking the microenvironment and disrupting normal functions, thus promoting malignant transformation. While the protective effects of the bone marrow niche have been widely studied, the mechanisms behind leukemia infiltration into the CNS and the role of the CNS niche in leukemia cell survival remain unknown.

We have identified a dysregulated gene expression profile in CNS infiltrated T-ALL and CNS relapse, promoting cell survival, chemoresistance and disease progression. Furthermore, we discovered that interactions between leukemia cells and CNS microenvironment induce epigenetic alterations, such as changes in gene regulation and histone modifications, including H3K36me3 levels.

These findings can be utilized to predict CNS infiltration and CNS relapse, therefore avoiding overtreatment and adverse effects caused by CNS directed therapy. Additionally, the identified genetic drivers of disease progression can serve as a first step towards identifying therapeutic targets, to sensitize the CNS niche to current therapeutic strategies.
Evaluation of Bayesian Linear Regression Models as a Fine Mapping tool
Authors: Shrestha Merina , Bai Zhonghao , Gholipourshahraki Tahereh , Hjelholt Astrid J. , Hu Sile , Kjølby Mads , Rohde Palle D. , Sørensen Peter
Published: September 2023

Our aim was to evaluate Bayesian Linear Regression (BLR) models with BayesC and BayesR priors as a fine mapping tool and compare them to the state-of-the-art external models: FINEMAP, SuSIE-RSS, SuSIE-Inf and FINEMAP-Inf. Based on extensive simulations, we evaluated the different models based on F1classification score. The different models were applied on quantitative and binary UK Biobank (UKB) phenotypes and evaluated based upon predictive accuracy and features of credible sets (CSs). We used over 533K genotyped and 6.6 million imputed single nucleotide polymorphisms (SNPs) for simulations and UKB phenotypes respectively, from over 335K UKB White British Unrelated samples. We simulated phenotypes from low (GA1) to moderate (GA2) polygenicity, heritability (h2) of 10% and 30%, causal SNPs (π) of 0.1% and 1% sampled genome-wide, and disease prevalence (PV) of 5% and 15%. Single marker summary statistics and in-sample linkage disequilibrium were used to fit models in regions defined by lead SNPs. BayesR improved the F1score, averaged across all simulations, between 27.26% and 13.32% relative to the external models. Predictive accuracy quantified as variance explained (R2), averaged across all the UKB quantitative phenotypes, with BayesR was decreased by 5.32% (SuSIE-Inf) and 3.71% (FINEMAP-Inf), and was increased by 7.93% (SuSIE-RSS) and 8.3% (BayesC). Area under the receiver operating characteristic curve averaged across all the UKB binary phenotypes, with BayesR was increased between 0.40% and 0.05% relative to the external models. SuSIE-RSS and BayesR, demonstrated the highest number of CSs, with BayesC and BayesR exhibiting the smallest average median size CSs in the UKB phenotypes. The BLR models performed similar to the external models. Specifically, BayesR’s performance closely aligned with SuSIE-Inf and FINEMAP-Inf models. Collectively, our findings from both simulations and application of the models in the UKB phenotypes support that the BLR models are efficient fine mapping tools.
Galvanic vs. Pulsatile Effects on Decision-Making Networks: Reshaping the Neural Activation Landscape
Authors: Adkisson Paul , Steinhardt Cynthia R. , Fridman Gene Y.
Published: September 2023

I.

Primarily due to safety concerns, biphasic pulsatile stimulation is the present standard for electrical excitation of neural tissue with a diverse set of applications. While pulses have been shown to be effective to achieve functional outcomes, they have well-known deficits. Due to recent technical advances, galvanic stimulation, delivery of current for extended periods of time (>1s), has re-emerged as an alternative to pulsatile stimulation. In this paper, we use a winner-take-all decision-making cortical network model to investigate differences between pulsatile and galvanic stimulation in the context of a perceptual decision-making task. Based on previous work, we hypothesized that galvanic stimulation would produce more spatiotemporally distributed, network-sensitive neural responses, while pulsatile stimulation would produce highly synchronized activation of a limited group of neurons. Our resultsin-silicosupport these hypotheses for low-amplitude galvanic stimulation but deviate when galvanic amplitudes are large enough to directly activate or block nearby neurons. We conclude that with careful parametrization, galvanic stimulation could overcome some limitations of pulsatile stimulation to deliver more naturalistic firing patterns in the group of targeted neurons.
New tree shrew Parkinson’s model: a cost-effective alternative to monkey models
Authors: Li Hao , Mei Leyi , Nie Xiupeng , Wu Liping , Ren Xiaofeng , Lv Longbao , Yang Jitong , Cao Haonan , Wu Jing , Zhang Yuhua , Hu Yingzhou , Wang Wenchao , Turck Christoph W. , Shi Bingyin , Li Jiali , Xu Lin , Hu Xintian
Published: September 2023

The surge in demand for experimental monkeys has led to a rapid increase in their associated costs. Consequently, there is a growing need for the development of a cost-effective model for Parkinson’s disease (PD) that exhibits all core clinical and pathological phenotypes of PD. Evolutionarily, tree shrews (Tupaia belangeri) are much closer to primates in comparison to rodents and share more similar PD-related brain structures and movement ability with monkeys. As such, tree shrews represent an ideal small animal species for modeling PD. To develop a tree shrew PD model, we used the 1-Methyl-4-phenylpyridinium (MPP+) metabolite, derived from the well-established PD modeling drug 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to induce lesions in the dopaminergic neurons of the unilateral substantia nigra. After determining the optimal modeling dosage, the tree shrews consistently exhibited and maintained all classic clinical manifestations of PD for a 5-month period. The symptoms closely resembled the ones observed in PD monkeys and included bradykinesia, rest tremor, postural instability, and apomorphine-induced rotations, a classic phenotype of unilateral PD models. Immunostaining showed a significant loss of dopaminergic neurons (approximately 95%) in the substantia nigra on the lesioned side of the brain, a crucial pathological marker of PD. Further cytomorphological analysis revealed that the size of nigral dopaminergic neurons in tree shrews exceeded that of rodents and more closely approximated that of macaques. Based on the principle that structure determines function, the morphological similarity between tree shrews and monkeys may be an important structural basis for the manifestation of the highly similar phenotypes between monkey and tree shrew PD models. Collectively, this study successfully developed a PD model in a small animal species that faithfully recapitulated the classical clinical symptoms and key pathological indicators of PD monkeys. In addition to the well-recognized monkey models, the tree shrew model provides a novel avenue for the evaluation of PD treatments and underlying mechanisms.
A molecular atlas of plastid and mitochondrial evolution from algae to angiosperms
Authors: Raval Parth K. , MacLeod Alexander I. , Gould Sven B.
Published: September 2023

Algae and plants carry two organelles of endosymbiotic origin that have been co-evolving in their host cells for more than a billion years. The biology of plastids and mitochondria can differ significantly across major lineages and organelle changes likely accompanied the adaptation to new ecological niches such as the terrestrial habitat. Based on organelle proteome data and the genomes of 168 phototrophic (Archaeplastida) versus a broad range of 518 non-phototrophic eukaryotes, we screened for changes in plastid and mitochondrial biology across one billion years of evolution. Taking into account 331,571 protein families (or orthogroups), we identify 31,625 protein families that are unique to primary plastid-bearing eukaryotes. 1906 and 825 protein families are predicted to operate in plastids and mitochondria, respectively. Tracing the evolutionary history of these protein families through evolutionary time uncovers the significant remodeling the organelles experienced from algae to land plants. The analyses of gained orthogroups identifies molecular adaptations of organelle biology that connect to the diversification of major lineages and facilitated major transitions from chlorophytes en route to the global greening and origin of angiosperms.
Eavesdropping and audience effect in fighting fruit flies reveal feedback between social information use and production
Authors: Hutchins Marina , Saltz Julia
Published: September 2023

Social information use and production occur simultaneously during social learning events; however, these two processes are often studied independently. We propose that social information use and production represent a feedback loop: eavesdroppers influence the behaviors of those being observed, which then alters the eavesdroppers’ social decisions. Here, we usedDrosophila melanogasterto investigate the relationship between social information use and production in an aggressive context. We tested whether paired males altered their aggression when they were observed by (i) a male; (ii) a female, or; (iii) no one. Next, we allowed each individual eavesdropper to interact with the paired males that they just observed, and measured their social behaviors. In addition, we tested how naïve flies responded when interacting with paired males. We found that paired males reduced their aggression when observed by a male, representing a change in social information production. In response, male eavesdroppers were overall less aggressive towards the more aggressive of the paired males they had observed, but their response to social information was also modulated by their genotype. In contrast, female eavesdroppers did not elicit changes to the behavior of the paired males, nor did we find evidence that they used the social information collected to make mating decisions. Overall, we found support for the feedback loop in males, but not females: information was exchanged bi-directionally during eavesdropping events, resulting in the modification of behavior by all parties. Utilizing the social information feedback framework can contribute to a better understanding of how social behaviors and animal communication are expressed and evolve.

Competing Interests

None

Significance Statement

Animals often observe the social interactions that occur between others, but the effects of both watching and being watched on behavior are rarely studied together. Using a novel approach, we studied how an audience influenced and learned from an aggressive contest in fruit flies. A male audience caused contest participants to decrease their aggression, and the male who was watching later showed decreased aggression toward the contest winner. Surprisingly, we did not see any effect of a female audience on male-male aggression, and females’ later behavior was not altered by observing a contest. Together, these results show how observing a fight led to changes in both the behavior of the contest participants and the male audience, thus suppressing group levels of aggressive behavior. Accounting for this interaction between social information use and production is necessary to understand social behaviors.
STAT3 is a genetic modifier of TGF-beta induced EMT in KRAS mutant pancreatic cancer
Authors: D’Amico Stephen , Kirillov Varvara , Petrenko Oleksi , Reich Nancy C.
Published: September 2023

Oncogenic mutations in KRAS are among the most common in cancer. Classical models suggest that loss of epithelial characteristics and the acquisition of mesenchymal traits are associated with cancer aggressiveness and therapy resistance. However, the mechanistic link between these phenotypes and mutant KRAS biology remains to be established. Here we identify STAT3 as a genetic modifier of TGF-beta-induced epithelial to mesenchymal transition. Gene expression profiling of pancreatic cancer cells identifies more than 200 genes commonly regulated by STAT3 and oncogenic KRAS. Functional classification of STAT3 responsive program reveals its major role in tumor maintenance and epithelial homeostasis. The signatures of STAT3-activated cell states can be projected onto human KRAS mutant tumors, suggesting that they faithfully reflect characteristics of human disease. These observations have implications for therapeutic intervention and tumor aggressiveness.

Significance

The identification of the molecular and genetic characteristics of tumors is essential for understanding disease progression and aggressiveness. KRAS mutations are the most frequent oncogenic drivers in human cancer. In this study we demonstrate that the ubiquitously expressed transcription factor STAT3 is a genetic modifier of TGF-beta-induced EMT, and thereby oncogenic KRAS dependency. Bothin vitroandin vivostudies demonstrate that STAT3 responsive program is an inherent part of oncogenic KRAS outcome.