bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional Analysis of Lifting Effects after High-intensity Focused Ultrasound (Ultraformer-MPT) across Seven Facial Aesthetic Units Considering SonoAnatomy
Authors: Kim Jong Seo
Published: October 2024

Background:

This investigation delves deep into the lifting degree for each area of noninvasive facial rejuvenation through high-intensity focused ultrasound (HIFU). The study meticulously examines the lifting effects of HIFU treatment across seven distinct facial aesthetic-units, using advanced three-dimensional scanner analysis.

Methods:

The study examined a cohort of 50 patients treated with HIFU. Pre- and immediate posttreatment evaluations were conducted using three-dimensional scanner analysis, allowing for precise quantification of lifting effects across seven aesthetic units. Treatment protocols were tailored to leverage five cartridges with micropulsed mode options, optimizing outcomes based on sonographic anatomy.

Results:

The forehead was lifted by 1.24 mm; crow’s feet, 2.25; malar region, 2.46; posterior cheek, 3.40; jowl, 2.90; mandible, 3.09; and neck, 3.53.

Conclusions:

The forehead showed a lift of 1.24 mm, attributed to the thin tissue requiring a cautious approach to avoid discomfort. A lift of 2.25 mm in the crow’s feet area demonstrated the efficacy of HIFU in addressing fine lines and wrinkles. Significant lift of 2.47 mm in the malar region highlights HIFU’s effectiveness in addressing mid-face laxity and restoring volume to the cheeks. The most substantial lift of 3.38 mm in the posterior cheek underscores targeted energy application for enhanced lifting and contouring. Notable lifting effect of 2.90 mm in the jowl area benefits sagging along the jawline, refining facial contour. Lift of 3.10 mm in the mandible shows improvement of lower facial laxity, defining the jawline. The highest lift of 3.55 mm in the neck region addresses laxity and sagging for a defined neck profile.
MCAM is a prognostic biomarker in patients with liver cirrhosis and HCC
Authors: Stockinger Eva , Luxenburger Hendrik , Bettinger Dominik , Berlin Christopher , Obwegs David , Sagar  , Sturm Lukas , Gromak Mikhail , Gairing Simon Johannes , Foerster Friedrich , Labenz Christian , MacNelly Sabine , Boettler Tobias , Holzner Philipp , Bronsert Peter , Bengsch Bertram , Thimme Robert , Hofmann Maike , Roehlen Natascha
Published: October 2024

Background:

Despite the rising prevalence of liver cirrhosis and HCC worldwide, reliable prognostic blood biomarkers are lacking. Melanoma cell adhesion molecule (MCAM) is a cell adhesion protein, and its cleavage by metalloproteinases, known to be enriched in fibrotic and malignant diseases, results in the release of a soluble form into the blood. The aim of this study was to characterize MCAM expression in patients with chronic liver disease and to evaluate soluble MCAM (sMCAM) as a prognostic blood biomarker in patients with liver cirrhosis and HCC.

Methods:

Expression of MCAM in liver tissue was assessed using transcriptomic data sets as well as by immunohistochemical analyses in patients with liver cirrhosis and HCC. Moreover, sMCAM blood levels were determined in plasma samples from healthy controls (n = 8), patients with chronic liver disease (n = 66), liver cirrhosis (n = 236), and HCC (n = 72).

Results:

Single-cell RNA sequencing and immunohistochemistry indicated MCAM to be highly expressed by liver endothelial cells and fibroblasts. Expression was upregulated in liver tissue of patients with liver fibrosis and especially HCC independent of the underlying etiology (p < 0.05, respectively). Blood levels of sMCAM increased with fibrosis stage and peaked in patients with concomitant HCC, showing a comparable diagnostic performance as the fibrosis markers hyaluronic acid (HA) and TIMP1 for diagnosis of liver cirrhosis (AUROCsMCAM = 0.84, AUROCHA = 0.89, AUROCTIMP1 = 0.87) and as alpha-fetoprotein (AFP) for diagnosis of HCC (AUROCsMCAM = 0.72, AUROCAFP = 0.72). Finally, high sMCAM levels predicted worse survival in HCC (p < 0.001).

Conclusions:

Collectively, our study suggests sMCAM as a blood biomarker of a liver microenvironment that drives the progression of liver disease in patients with liver cirrhosis and HCC.
Predicting chronic post-traumatic head and neck pain: the role of bedside parameters
Authors: Ramon-Gonen Roni , Granovsky Yelena , Shelly Shahar
Published: October 2024

Traumatic brain injury (TBI) annually impacts 69 million individuals worldwide. Mild TBI constitutes approximately 90% of all TBIs. Chronic pain post-mTBI occurs in 29% to 58% of patients. This study aims to introduce a predictive model for chronic pain development in individuals diagnosed with mild traumatic brain injury (mTBI) immediately postinjury. We included individuals who had sustained mTBI in motor vehicle accident (MVA). All patients had initial assessments within the first 72 hours (representing the subacute period) after the injury and performed follow-ups for 1 year. Machine learning model was applied to the integrated measures of clinical pain, pain-related psychological parameters, mTBI clinical signs, and sociodemographic information. This study included 203 patients experiencing acute head or neck pain attributable to mTBI post-MVA. We categorized these patients into 2 groups: patients who progressed to develop chronic head or neck pain (n = 89, 43.8%) and patients who recovered (low/mild pain) (n = 114, 56.2%). Severity of the subacute neck pain, number of painful body areas, and education years were identified as the most significant factors predicting chronic pain. The optimized predictive model demonstrated high efficacy, with an accuracy of 83%, a sensitivity of 92%, and an area under the receiver operating characteristic curve of 0.8. Our findings indicate feasibility in predicting chronic post-MVA pain within the critical 72-hour window postinjury using simple bedside metrics. This approach offers a promising avenue for the early detection of individuals at increased risk for chronic pain, enabling the implementation of targeted early interventions.
I feel your pain: higher empathy is associated with higher posterior default mode network activity
Authors: Oliva Valeria , Riegner Gabriel , Dean Jon , Khatib Lora A. , Allen Alessandro , Barrows Daniel , Chen Conan , Fuentes Richard , Jacobson Aaron , Lopez Carolina , Mosbey Dwayne , Reyes Mikaila , Ross Jacob , Uvarova Alexandra , Liu Thomas , Mobley William , Zeidan Fadel
Published: October 2024

Empathy is characterized as the ability to share one's experience and is associated with altruism. Previous work using blood oxygen level–dependent (BOLD) functional MRI (fMRI) has found that empathy is associated with greater activation in brain mechanisms supporting mentalizing (temporoparietal junction), salience (anterior cingulate cortex; insula), and self-reference (medial prefrontal cortex; precuneus). However, BOLD fMRI has some limitations that may not reliably capture the tonic experience of empathy. To address this, the present study used a perfusion-based arterial spin labeling fMRI approach that provides direct a quantifiable measurement of cerebral blood flow (1 mL/100 g tissue/min) and is less susceptible to low-frequency fluctuations and empathy-based “carry-over” effects that may be introduced by BOLD fMRI–based block designs. Twenty-nine healthy females (mean age = 29 years) were administered noxious heat (48°C; left forearm) during arterial spin labeling fMRI. In the next 2 fMRI scans, female volunteers viewed a stranger (laboratory technician) and their romantic partner, respectively, receive pain-evoking heat (48°C; left forearm) in real-time and positioned proximal to the scanner during fMRI acquisition. Visual analog scale (0 = “not unpleasant”; 10 = “most unpleasant sensation imaginable”) empathy ratings were collected after each condition. There was significantly (P = 0.01) higher empathy while viewing a romantic partner in pain and greater cerebral blood flow in the right temporoparietal junction, amygdala, anterior insula, orbitofrontal cortex, and precuneus when compared with the stranger. Higher empathy was associated with greater precuneus and primary visual cortical activation. The present findings indicate that brain mechanisms supporting the embodiment of another's experience is associated with higher empathy.
The prognostic role of whole-body volumetric positron emission tomography/computed tomography parameters in treatment naive colorectal cancer patients with liver metastases
Authors: Karaoğlan Hüseyin , Kepenek Ferat , Kömek Halil , Kaplan İhsan , Yeprem Ömer , Kaya Ridvan , Güzel Yunus , Şenses Veysi , Kaya İpek Fulya , Can Canan
Published: October 2024

Purpose

The present study aimed to predict the prognostic role of quantitative 18F-fluorodeoxyglucose PET/computed tomography parameters such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) obtained from primary tumor, lymph node metastases, and liver metastasis (LM) in patients with colorectal LM (CLM).

Material and method

The research was designed as a retrospective study and 66 patients with CLM were enrolled between January 2017 and December 2018. Primary tumor SUVmax (PSUVmax), liver SUVmax (LSUVmax), and lymph node SUVmax (LnSUVmax) values obtained from the primary tumor, liver, and lymph nodes were recorded. In addition, total MTV (TMTV) and total TLG (TTLG) values were obtained by summing the values obtained from the primary tumor (PMTV and PTLG), lymph nodes (LnMTV and LnTLG), and liver (LMTV and LTLG). Univariate and multivariate Cox regression analysis was used to measure the effects of prognostic variables on mortality and survival.

Result

In univariate Cox regression analysis, PMTV (P = 0.001), LnMTV (P = 0.008), LnTLG (P = 0.008), LnSUVmax (P = 0.047), and TTLG (P = 0.038) were identified as prognostic factors for overall survival. No statistically significant relationship was found between MTV and TLG values of LM and overall survival. In multivariate analysis, PMTV (P = 0.022) was identified as an independent prognostic factor.

Conclusion

In conclusion, our study demonstrated that the PMTV value used in evaluating treatment-naive patients diagnosed with CLM is an independent prognostic factor for survival. Our results need to be confirmed with more studies involving more patients.
Impact of a Design Thinking Educational Activity on Graduate Students’ Knowledge, Confidence, and Perceived Benefits
Authors: Hawkins Janice , Baaki John , Tremblay Beth , Hawkins Robert J.
Published: October 2024

Background:

Design Thinking is gaining recognition as an innovative and creative approach to problem solving. Though nurse leaders need problem solving tools to address health care challenges, Design Thinking concepts are not commonly taught in nursing education. To introduce graduate level nursing students to Design Thinking, we held an educational activity focused on this content as part of required coursework.

Purpose:

The purpose was to describe and compare outcomes of a Design Thinking educational activity on students’ perceived knowledge, confidence, and benefits to nursing practice.

Methods:

Graduate level nursing students participated in a 3-hour educational activity. After the session, students completed an anonymous 10-item survey of their perceptions of the educational activity.

Results:

Students reported increased knowledge and confidence of communication strategies and Design Thinking concepts that would benefit their practice.

Conclusion:

Nurse educators should include Design Thinking teaching and learning strategies in their programs.
Acceptance and Commitment Therapy for an Emerging Adult Female With Misophonia: A Case Study
Authors: Spencer Samuel D. , Mangen Katie H. , Omar Yasmine , Storch Eric A.
Published: October 2024

Misophonia is characterized by decreased tolerance to idiosyncratic and repetitive human-generated sounds (ie, triggers), coupled with affective-based reactions that result in impairment and distress. Often having its onset in youth, misophonia can become especially prominent during key developmental periods, including emerging adulthood. While efforts to develop interventions for misophonia remain ongoing, a consensus has not yet been reached concerning recommended first-line treatments. Acceptance and commitment therapy (ACT), which has demonstrated efficacy in treating various psychiatric disorders via targeting psychological flexibility processes, represents one potentially feasible approach for addressing misophonia. This case study describes the application of an individually delivered, 12-session ACT intervention for a black female in her early 20s with misophonia. Descriptive data collected at 4 time points (pretreatment, mid-treatment, posttreatment, and at 2-month follow-up) suggested the potential promise of ACT as a treatment for misophonia, improving psychological flexibility processes and reducing secondary depression and anxiety symptoms. Findings are discussed in the context of the possible mechanisms of ACT most likely responsible for misophonia-related clinical improvement. More rigorous studies (eg, clinical trials) are needed to confirm promising findings from existing case studies.
A False-positive Diagnosis of a Lethal Serotonin Syndrome Based on Postmortem Whole-blood Levels of Sertraline: How Forensic Detective Work Uses Medical Knowledge and Clinical Pharmacology to Solve Cases
Authors: Preskorn Sheldon H. , Masolak David D.
Published: October 2024

This column is the third in a 3-part series describing cases in which general medical knowledge, including psychiatric and clinical pharmacology, was instrumental in determining whether dereliction was the direct cause of damages in a malpractice suit. This case illustrates how not taking into account the following variables can result in a false-positive diagnosis of a lethal serotonin syndrome: (a) the time course of treatment, (b) the time course of symptoms, (c) the difference between antemortem plasma and postmortem whole-blood levels of highly protein bound and highly lipophilic drugs. The case also illustrates how taking those 3 variables into account led to the conclusion that there was no dereliction in the care of the patient that was the direct cause of his death, and hence, there was no medical malpractice.
Risk Factors for Suicide Among Professional Athletes
Authors: Wilson George A. , Smith Joshua M. , New Karl J.
Published: October 2024

Background:

Suicide is a major public health concern that affects all demographics. Risk factors for suicide in professional athletes are poorly understood compared with the general population. The goal of this study was (1) to explore the current literature on risk factors for suicide in the population of professional athletes and (2) to formulate a proposed suicide risk identification tool as the first step in the production of a validated screening method specific to this population.

Methods:

A comprehensive literature search for relevant publications was carried out through 7 databases.

Results:

There is some evidence to suggest that retirement, anabolic androgenic steroid use, sexual abuse victimization, health problems, financial issues, relationship issues, having immigrant parents, having a financially disadvantaged childhood, using self-blame or behavioral disengagement as a coping strategy, changes in appetite or weight, sleep problems, reduced competitiveness, and thinking about a career after retirement are potential risk factors for suicide in this population. There is limited evidence to suggest that having a career in elite or professional sports, participation in contact sports, and participating in specific sports that are not associated with a higher suspected prevalence of performance-enhancing drug use are potential risk factors.

Conclusions:

This study identified potential risk factors for suicide among elite and professional athletes. These findings were used to help formulate a proposed suicide risk identification tool. Future research is recommended to explore and clarify specific risk factors for suicide in this population and to test the validity of the proposed tool.
Reflections on Integrating a Therapist-guided CBT Website Into Routine Clinical Practice
Authors: Lapidos Adrienne , Parikh Sagar V.
Published: October 2024

Psychotherapy remains a scarce resource for patients, as problems such as provider shortages result in waitlists and lack of timely access. In their academic medical center outpatient clinic, the coauthors piloted use of a therapist-guided CBT website, Good Days Ahead, in routine clinical practice. They reflect on the benefits and challenges of this approach in this guest column.
Diffuse Uptake of 68Ga-Pentixafor in the Breasts During the Ovulatory Phase in a Patient With SAPHO Syndrome
Authors: Xu Tingting , Wan Zibei , Chen Yue
Published: October 2024

We report a case of a woman with SAPHO syndrome who exhibited increased tracer uptake in the sternal angle on a 99mTc-MDP bone scan. This patient was enrolled in a 68Ga-pentixafor PET/CT trial for inflammatory diseases. The PET/CT showed no abnormal tracer uptake in the sternal angle. Unexpectedly, diffuse uptake of 68Ga-pentixafor was observed in both breasts, which might be due to hormonal stimulation because the woman underwent the 68Ga-pentixafor PET/CT scan during the ovulatory phase.
Lenticulostriatal Ischemia Shows Relevant SSTR Expression on PET/CT Imaging Using the Novel SSTR-Targeting Peptide 18F-SiTATE
Authors: Kunte Sophie C. , Unterrainer Lena M. , Kunz Wolfgang G. , Winkelmann Michael , Lindner Simon , Jurkschat Klaus , Wängler Carmen , Wängler Björn , Schirrmacher Ralf , Bartenstein Peter , Belka Claus , Schichor Christian , Albert Nathalie L. , Unterrainer Marcus
Published: October 2024

A 64-year-old woman with meningioma presented with left-sided lenticulostriatal ischemia following craniotomy and debulking of a sphenoid wing meningioma. For subsequent radiotherapy planning, an SSTR-targeted PET/CT using the novel ligand 18F-SiTATE was performed 2.5 months thereafter. The meningioma remnants showed transosseous, intrasellar, and perivascular extension around the internal carotid artery with strong SSTR expression. Moreover, there was focal 18F-SiTATE uptake in the left caudate and corresponding contrast enhancement due to postischemic blood-brain barrier disruption and reactive SSTR expression. Therefore, increased cortical or subcortical SSTR PET signal may be related to ischemic changes even in the subacute stage after initial stroke.
Renal Cell Carcinoma With Tumor Thrombus Extending Into the Inferior Vena Cava and the Right Atrium Demonstrated by 68Ga-DOTATATE PET/CT
Authors: Filizoglu Nuh , Ozguven Salih
Published: October 2024

Approximately 10% of all renal cell carcinoma (RCC) patients develop a venous tumor thrombus, a major negative prognostic factor. Surgical excision is commonly required for RCC patients with tumor thrombus. Accurate preoperative diagnosis and assessment of tumor thrombus level is vital because the level of thrombus may influence treatment decisions. MRI, contrast-enhanced CT, 18F-FDG PET/CT, and 68Ga-PSMA PET/CT have been used to diagnose and evaluate the extent of tumor thrombus in RCC. However, no case of RCC with inferior vena cava tumor thrombus showing 68Ga-DOTATATE uptake has been reported yet. Herein, we report a case of metastatic RCC with tumor thrombus in the inferior vena cava on 68Ga-DOTATATE PET/CT.
Differences in Scalp Tension Associated With Craniosynostosis Among Patients of Different Races
Authors: Sakamoto Yoshiaki , Arnaud Eric , Kamata Masafumi , Miwa Tomoru , Imai Keisuke , Sakahara Daisuke
Published: October 2024

Background:

Fronto-orbital advancement (FOA) is the gold standard treatment for craniosynostosis. Although FOA by gradual distraction has been practiced in Asia, it has not yet been accepted in Western countries. This may be attributable to differences in scalp tension among patients.

Patients and Methods:

The extent of skin advancement was intraoperatively measured as skin tension among 12 European (France) and 16 Asian (Japan) patients older than 6 months (age, 9.63±3.78 y) who underwent cranioplasty. Skin tension was measured at 3 points (left, right, and middle) after a zigzag bicoronal incision was made.

Results:

The skin tension measurements of European patients were as follows: left, 23.1±6.37 mm; middle, 18.5±3.85 mm; and right, 23.3±6.31 mm. Tension in the middle was significantly lower than that on the left and right (P<0.05). In contrast, the skin tension measurements of Asian patients were as follows: left, 12.8±1.49 mm; middle, 14.4±3.60 mm; and right, 13.0±1.74 mm. Tension in the middle was significantly higher than that on the left and right (P<0.05). In addition, skin tension was higher among European patients than among Asian patients.

Conclusions:

Scalp tension differed according to race. This should be considered when selecting appropriate treatment.
Nature and Determinants of Fear of Cancer Recurrence After Endoscopic Submucosal Dissection for Early Gastric Cancer
Authors: Song Nian , Zhang Xiaotao , Su Jie , Chen Lu , Jin Qianhong , Liu Chengcheng , Dai Zhengxiang
Published: October 2024

Gastric cancer is one of the most prevalent tumors in China and other countries, with high morbidity and mortality. Fear of cancer recurrence is common among cancer survivors. Fear of cancer recurrence experiences and psychological interventions have been investigated in breast and other cancers. However, this phenomenon and associated factors have not been evaluated in early gastric cancer survivors in China. The objective of this study was to investigate the nature of fear of cancer recurrence and influencing factors in Chinese patients with early gastric cancer treated with endoscopic submucosal dissection. This cross-sectional study in two centers included 312 early gastric cancer patients who answered self-report questionnaires and were treated with endoscopic submucosal dissection between June 2022 and May 2023 to assess fear of cancer recurrence. Gender, family history of gastrointestinal tumor, tumor recurrence, Helicobacter pylori infection, disease perception, and self-perceived burden were significant factors influencing fear of cancer recurrence (p < .05). More than half of early gastric cancer patients have fear of cancer recurrence, and how to deal with it has become a key issue in the postoperative care of patients. Medical professionals should address these factors to reduce fear of cancer recurrence in at-risk patients.
A systematic review and guide for using multi-response statistical models in co-infection research
Authors: Powell-Romero Francisca , Wells Konstans , Clark Nicholas J.
Published: October 2024

The simultaneous infection of organisms with two or more co-occurring pathogens, otherwise known as co-infections, concomitant infections or multiple infections, plays a significant role in the dynamics and consequences of infectious diseases in both humans and animals. To understand co-infections, ecologists and epidemiologists rely on models capable of accommodating multiple response variables. However, given the diversity of available approaches, choosing a model that is suitable for drawing meaningful conclusions from observational data is not a straightforward task. To provide clearer guidance for statistical model use in co-infection research, we conducted a systematic review to (i) understand the breadth of study goals and host–pathogen systems being pursued with multi-response models and (ii) determine the degree of crossover of knowledge among disciplines. In total, we identified 69 peer-reviewed primary studies that jointly measured infection patterns with two or more pathogens of humans or animals in natural environments. We found stark divisions in research objectives and methods among different disciplines, suggesting that cross-disciplinary insights into co-infection patterns and processes for different human and animal contexts are currently limited. Citation network analysis also revealed limited knowledge exchange between ecology and epidemiology. These findings collectively highlight the need for greater interdisciplinary collaboration for improving disease management.
Teicoplanin attenuates RNA virus infectionin vitro
Authors: Españo Erica , Kim Jiyeon , Park Seong Ok , Padasas Bill Thaddeus , Kim Sang-Hyun , Son Ju-Ho , Oh Jihee , Woo E-Eum , Lee Young-Ran , Hwang Soon Young , Eo Seong Kug , Kim Jeong-Ki
Published: October 2024

Teicoplanin (TP) is a glycopeptide antibiotic used for Gram-positive bacterial infections, and it has been reported to inhibit SARS-CoV-2 and Ebola virus entry through cathepsin inhibition. Given that TP can inhibit viruses belonging to different virus families, we aimed to expand the potential targets of TP to determine whether TP can be developed as a broad-spectrum antiviral agent. Considering the original indication of TP, we first determined the effects of TP against viruses that cause respiratory tract infections and found that TP inhibits enveloped and non-enveloped RNA viruses, namely: human and avian influenza viruses; representative coronaviruses including porcine epidemic diarrhea virus (PEDV), human coronavirus OC43 (HCoV-OC43), and SARS-CoV-2; measles virus; human respiratory syncytial virus A2; and enterovirus 71 (EV-71). Representative flaviviruses, Zika virus (ZIKV) and dengue virus serotype 2 (DENV2), were also susceptible to inhibition by TP. In contrast, TP did not attenuate infection of human adenovirus 5, a non-enveloped DNA virus. Addition of TP at the endocytosis stage but not at the attachment/binding stage of PEDV infection reduced PEDV productionin vitro, indicating cathepsin inhibition. Meanwhile, addition of TP during either the attachment/binding or the endocytosis stage of ZIKV infection reduced ZIKV particle production in host cells, andin silicomodeling suggested that TP has potential binding pockets in the envelope proteins of ZIKV and DENV2. These results show that TP can be developed as a broad-spectrum antiviral especially against RNA viruses, with potentially different targets in the replication cycle of various viruses.
Derivation and validation of a prediction rule for sedative-associated delirium during acute respiratory failure requiring mechanical ventilation
Authors: Prendergast Niall T. , Onyemekwu Chukwudi A. , Potter Kelly M. , Franz Christopher A. , Kitsios Georgios D. , McVerry Bryan J. , Pandharipande Pratik P. , Ely E. Wesley , Girard Timothy D.
Published: October 2024

Background

Delirium during acute respiratory failure is common and morbid. Pharmacologic sedation is a major risk factor for delirium, but some sedation is often necessary for the provision of safe care of mechanically ventilated patients. A simple, transparent model that predicts sedative-associated delirium in mechanically ventilated ICU patients could be used to guide decisions about personalized sedation.

Research Question

Can the risk of sedative-associated delirium be estimated in mechanically-ventilated ICU patients?

Study Design and Methods

Using the subset of patients in a previously-published ICU cohort who received mechanical ventilation, we performed backward stepwise logistic regression to derive a model predictive of sedative-associated delirium. We validated this model internally using hundredfold bootstrapping. We then validated this model externally in a separate prospective cohort of mechanically ventilated ICU patients.

Results

836 patients comprised the derivation cohort. Backwards stepwise regression produced a model with age, BMI, sepsis, SOFA, malignancy, COPD, stroke, sex, and doses of sedatives (opioids, propofol, and/or benzodiazepines) as predictors of sedative-associated delirium. The model had very good discriminative power, with an area under the receiver-operator curve (AUROC) of 0.83. Internal validation via bootstrapping showed preserved discriminatory function with an AUROC of 0.81 and graphical evidence of good calibration. External validation in a separate set of 340 patients showed good discrimination, with AUROC of 0.70.

Interpretation

Sedative-associated delirium during acute respiratory failure requiring mechanical ventilation can be predicted using a simple, transparent model, which can now be validated in a prospective study.
Prism Adaptation-Induced Modulation of Cortical Excitability of Upper and Lower Limb Muscles is Enhanced with Electrical Stimulation
Authors: Aloba Fisayo K , Hope Jasmine M , Spencer Jacob , Muthukumar Maithri , Leone Taylor M , Parikh Vyoma , Chen Peii , Borich Michael R , Kesar Trisha M
Published: October 2024

Background

Prism adaptation (PA) is a sensorimotor behavioral phenomenon. Right shifting PA induces a shift in global visuospatial motor behavior toward the left hemi-space (aftereffect) leading to immediate and transient changes in visuomotor behavior. Non-invasive sensorimotor electrical stimulation (Stim) may upregulate corticomotor excitability, is commonly used as a therapeutic adjunct during motor training, and may accentuate the effects of PA. However, the cortical plasticity mechanisms related to the behavioral effects of PA, its generalization to the lower limb, and the combinatorial effects of PA and Stim are poorly understood.

Objective

To evaluate the effects of combining PA with Stim on corticomotor excitability and visuo-spatial-motor behavior, and its generalization to the lower limb.

Methods

We used a repeated-measures design to evaluate the effects of 1 session of PA with and without Stim in 15 young able-bodied individuals (18-35 years). Before and after PA, visuomotor pointing task performance, corticomotor excitability, short-interval intra-cortical inhibition (SICI), long-interval intra-cortical inhibition (LICI), and intra-cortical facilitation (ICF) were evaluated in bilateral upper and left ankle muscles with motor-evoked potentials (MEPs) elicited from single and paired-pulse transcranial magnetic stimulation (TMS).

Results

Behaviorally, both PA+Stim and PA+Sham showed significant sensorimotor aftereffects, inducing a leftward shift in visuo-spatial and proprioceptive pointing. Neurophysiologically, suprathreshold MEP amplitude increased in the left first dorsal interossei (FDI) and left soleus following the PA+Stim condition but not the PA+Sham condition. PA+Stim showed statistical trends for inducing larger changes in ICF of the left FDI and left tibialis anterior. Additionally, compared to PA+Stim, PA+Sham induced larger changes in LICI of the left FDI and left tibialis anterior, and in SICI of the left tibialis anterior.

Conclusion

Although both PA+Stim and PA+Sham had similar behavioral aftereffects, only PA+Stim increased cortical excitability in M1 representations of the left upper and lower limb (toward the direction of the PA aftereffect), suggesting that PA+Stim may elicit greater neurophysiological changes and generalization to lower limb than PA alone.
Chagas Disease Screening: Awareness, Practices and Perceived Barriers Among Health Care Providers in Connecticut
Authors: Rayack Erica J. , Gutierrez-Torres Maria Alejandra , Lombo Bernardo , Mahoney-West Helen , Vermund Sten
Published: October 2024

Background

An estimated 288,000 people in the United States are infected with Chagas disease. Despite published recommendations for healthcare providers, the neglected nature of this disease persists, in part due to gaps in knowledge and low levels of Chagas disease awareness among healthcare providers. A survey was emailed to healthcare providers to assess knowledge of Chagas disease, screening practices, and provider-perceived barriers to screening.

Methods

The survey link was emailed to healthcare providers and department heads. Providers answered a series of questions categorized either as knowledge (K), practice (P), or perceived barriers (B), which were then scored by category. The analysis included Spearman’s rho test to measure the strength of the correlation coefficient between K and P scores and between K and B scores, Kruskal-Wallis tests to see if average K, P, and B scores were equal across specialty groups, and Pairwise Wilcoxon Rank Sum Tests to assess for a significant difference between average scores of cardiology, infectious disease, and the “other specialties” category.

Results

92 providers consented to complete the survey, 88 of whom fit the inclusion criteria of either affiliation with Yale University or YNHH. Infectious disease scored highest on average in knowledge and practices and reported lower provider-perceived barriers (0.66±0.183, 0.35±0.247, 0.42±0.365). No specialty received higher than 0.66±0.183 on average for knowledge or screening practices. Average perceived barriers to screening were highest in the “other” specialty category (0.76±0.303). There was a significant positive association between knowledge scores and screening practice scores and a significant negative association between knowledge scores and perceived barriers to screening.

Conclusions

This study revealed a knowledge deficit among healthcare providers in various specialties, which was associated with less frequent adherence to recommended screening practices for Chagas disease, as well as higher provider-perceived barriers to screening. This information can inform provider education initiatives so that patients at risk for Chagas disease may be better served in Connecticut and throughout the United States.
A novel patient-level computational model of atrial fibrillation patterns and clinical outcomes for evaluating screening strategies
Authors: Cai Minsi , Barrios-Espinosa Cristian , Rienstra Michiel , Crijns Harry J.G.M. , Schotten Ulrich , Heijman Jordi
Published: October 2024

Background

The dynamic, heterogenous nature of atrial fibrillation (AF) episodes and poor symptom-rhythm correlation make early AF detection challenging. The optimal screening strategy for early AF detection and its role in stroke prevention in different subpopulations are unknown. We developed a computational patient-level AF model able to simulate the dynamic occurrence of AF and AF-associated outcomes during the entire lifetime of a virtual patient cohort to elucidate the impact of AF screening in virtual randomized clinical trials (V-RCTs).

Methods

The Markov-like computer model has 7 clinical states (sinus rhythm, symptomatic/asymptomatic AF, each with/without previous stroke, and death). AF-related atrial remodeling was incorporated, which influenced the age-/sex-dependent transition probabilities between states. Model calibration/validation was performed by replicating a wide range of clinical studies. AF screening strategies and stroke rates in the presence of defined interventions were assessed in V-RCTs.

Results

The model simulates the entire lifetime of virtual patients with minute-level resolution and provides perfect information on the occurrence of AF episodes and clinical outcomes (stroke, death). It replicates numerous age/sex-specific episode- and population-level AF metrics, including AF incidence/prevalence, progression rates, burden, episode duration, and stroke/mortality incidence. The benefits of intermittent AF screening in V-RCTs were frequency- and duration-dependent, with systematic thrice-daily single-ECG recordings providing the highest detection rates (64.6% of AF patients being diagnosed before their symptom-based clinical diagnosis). Screening groups had comparable 5-year stroke rates and lower 25-year stroke rates than the control group. These differences were increased by more effective anticoagulation therapy, in patients with higher baseline stroke risk, or in patients with delayed clinical AF diagnosis.

Conclusions

We present a novel computational patient-level AF model consistent with a large body of real-world data, enabling for the first time the systematic assessment of AF-management strategies. Screening protocols with more frequent and longer monitoring have higher AF-detection rates, but stroke reduction in screening-detected individuals is highly dependent on patients’ and healthcare-systems’ characteristics. V-RCTs suggest that frequent AF screening with effective anticoagulation can reduce stroke incidence in patients with high likelihood of delayed AF diagnosis.
Preserving Full Spectrum Information in Imaging Mass Spectrometry Data Reduction
Authors: Moens Roger A.R. , Migas Lukasz G. , Van Ardenne Jacqueline M. , Skaar Eric P. , Spraggins Jeffrey M. , Van de Plas Raf
Published: October 2024

Motivation

Imaging mass spectrometry (IMS) has become an important tool for molecular characterization of biological tissue. However, IMS experiments tend to yield large datasets, routinely recording over 200,000 ion intensity values per mass spectrum and more than 100,000 pixels,i.e., spectra, per dataset. Traditionally, IMS data size challenges have been addressed by feature selection or extraction, such as by peak picking and peak integration. Selective data reduction techniques such as peak picking only retain certain parts of a mass spectrum, and often these describe only medium-to-high-abundance species. Since lower-intensity peaks and, for example, near-isobar species are sometimes missed, selective methods can potentially bias downstream analysis towards a subset of species in the data rather than considering all species measured.

Results

We present an alternative to selective data reduction of IMS data that achieves similar data size reduction while better conserving the ion intensity profiles across all recordedm/z-bins, thereby preserving full spectrum information. Our method utilizes a low-rank matrix completion model combined with a randomized sparse-format-aware algorithm to approximate IMS datasets. This representation offers reduced dimensionality and a data footprint comparable to peak picking, but also retains complete spectral profiles, enabling comprehensive analysis and compression. We demonstrate improved preservation of lower signal-to-noise-ratio signals and near-isobars, mitigation of selection bias, and reduced information loss compared to current state-of-the art data reduction methods in IMS.
Epidermal microstructures on the paired fins of marine sculpins suggest new functional hypotheses supporting benthic station-holding
Authors: Kane Emily A. , Garner Austin M. , Yadav Shubham , Hume L. Ann , Pesacreta Tom
Published: October 2024

Harsh environments, such as those with breaking waves and turbulent flows, present extreme challenges to organismal survival. Many animals exploiting these habitats possess adaptations to maintain position under dynamic flow conditions, such as reversible or permanent attachment systems. However, some station-holding fishes (e.g., sculpins) instead rely on morphological and behavioral modifications of their pectoral fins to increase friction with the substrate and combat drag. Despite epidermal microstructures on the fins of other benthic fishes, little exploration of pectoral fin surfaces at the microscopic scale has been undertaken in sculpins. Using scanning electron microscopy, we discovered microscopic, fibrillar projections contained within single cells on the ventral surfaces of the paired fin rays of two intertidal and two subtidal species of marine sculpins. In contrast to subtidal species, the intertidal species possessed epidermal cells with discrete channels separating groups of fibrillar projections. These features bear a striking resemblance to epidermal microstructures described in other fishes but have distinct morphological differences. We suggest the hypothesis that these previously overlooked features contribute to sculpin station-holding performance via enhanced mechanical interactions with the substrate, suggesting new taxa within which to explore potential mechanisms of underwater friction enhancement and adhesion.
SIRT4 enhances the cytotoxicity of NK cells toward hepatic stellate cells and reverses liver fibrosis via AMPKα/P-p53/NKG2DL pathway
Authors: Chen Huan , Da Binlin , Cai Zihao , Fang Rui , Xie Xiaolin , Zhang Han , Zhao Si , Zhang Ming , Wang Lei , Xu Bing , Zhuge Yuzheng , Zhang Feng
Published: October 2024

Natural killer (NK) cells exhibit antifibrotic properties in liver fibrosis (LF) by suppressing activated hepatic stellate cells (HSCs). SIRT4, a mitochondrial regulatory protein, plays a crucial role as a link between energy metabolism and cell viability. However, the role of SIRT4 in the cytotoxicity of NK cells toward HSCs remains unexplored.

In this study, we found that SIRT4 was markedly downregulated in both mouse models and patients with LF. The loss of SIRT4 reduced the cytotoxicity of NK cells against activated HSCs, while its overexpression enhanced this cytotoxicity. Mechanistically, SIRT4 activates AMPKα to promote p53 phosphorylation and facilitates its nuclear translocation, which induces the transcription of ULBP1 and ULBP2, members of the NK group 2D Legend (NKG2DL) family of molecules. Finally, overexpression of SIRT4 activated mouse hepatic NK cells and reversed LF by constructing adeno-associated viruses (AAV) that specifically target HSCs.

Thus, SIRT4 is essential for the cytotoxicity of NK cells toward HSCs, and AAV8-pGAFP-SIRT4 may serve as a therapeutic approach for managing LF.

Abstract Figure
Host specialization defines the emergence of new fungal plant pathogen populations
Authors: Fagundes Wagner C. , Hansen Rune , Rojas Barrera Idalia C. , Caliebe Frauke , Feurtey Alice , Haueisen Janine , Salimi Fatemeh , Alizadeh Alireza , Stukenbrock Eva H.
Published: October 2024

Host-driven selection can be considered a strong driver of pathogen evolution. To successfully infect, colonize and complete their life cycle, plant pathogens are under constant selective pressures imposed by hosts, leading to genetic adaptation and possibly lineage radiation or speciation. Population and comparative genomics approaches are powerful tools to identify signatures of selection associated with host specialization in pathogen genomes and further allow recapturing population histories. Implementing such approaches, we identified evolutionary signatures of divergent host specialisation in distinct lineages of the fungal pathogenZymoseptoria tritici, a major disease causing-agent of wheat. Unique collections ofZ. triticiwere isolated from wild (Aegilopsspp.) and domesticated (Triticum aestivum) host grasses in the Middle East and whole-genome sequencing was performed in a selected subset of isolates from each collection. We observed distinct population structure between the two host-diverging pathogens and identified particular genomic features in theAegilops-infecting isolates that may have shaped their evolutionary history. Phylogenomic analyses revealed thatA. cylindricaandA. tauchii-infecting populations ofZ. triticiform separate clusters, possibly reflecting incipient speciation driven by divergent host specialization. Using infection experiments, we confirm thatZ. triticiisolates collected fromAegilopsspp. only infect their respective host species and notT. aestivum. Population genomics analyses and demographic inference furthermore allowed us to detect signatures of recent selection and show that divergence of the wheat-infecting lineage likely coincided with wheat domestication. At last, we confirm a virulence-related role for one candidate effector located in a selective sweep region of theA. cylindrica-infecting pathogen. Taken together, our findings highlight the interplay between agricultural and wild hosts on the evolution of fungal plant pathogens and illustrate host specialization as a possible route of rapid pathogen emergence.
Game Changing Mutation
Authors: Hellman Ziv , Edhan Omer
Published: October 2024

We present a model of the effect of mutation on haploid sexually reproducing populations by modelling the reproductive dynamics as occurring in the context of a common interests game played by the loci, with the alleles in the role of pure actions. Absent mutations, the population will deterministically converge to a pure Nash equilibrium of the game. A novel mutation adds new alleles, hence is tantamount to a change of the game by the addition of new actions. If the new game defined by the mutation removes the former pure Nash equilibrium the game changing mutation becomes in addition a Nash equilibrium changing mutation, as the population will then move to a new equilibrium with an increase in fitness. A graph of common interests games is defined, and evolution by mutation is modelled as a path through this graph.

Short description

Novel mutation in sexual reproduction evolution modelled as population shifts between Nash equilibria in common interest games
BindCraft: one-shot design of functional protein binders
Authors: Pacesa Martin , Nickel Lennart , Schellhaas Christian , Schmidt Joseph , Pyatova Ekaterina , Kissling Lucas , Barendse Patrick , Choudhury Jagrity , Kapoor Srajan , Alcaraz-Serna Ana , Cho Yehlin , Ghamary Kourosh H. , Vinué Laura , Yachnin Brahm J. , Wollacott Andrew M. , Buckley Stephen , Westphal Adrie H. , Lindhoud Simon , Georgeon Sandrine , Goverde Casper A. , Hatzopoulos Georgios N. , Gönczy Pierre , Muller Yannick D. , Schwank Gerald , Swarts Daan C. , Vecchio Alex J. , Schneider Bernard L. , Ovchinnikov Sergey , Correia Bruno E.
Published: October 2024

Protein–protein interactions (PPIs) are at the core of all key biological processes. However, the complexity of the structural features that determine PPIs makes their design challenging. We present BindCraft, an open-source and automated pipeline forde novoprotein binder design with experimental success rates of 10-100%. BindCraft leverages the weights of AlphaFold21to generate binders with nanomolar affinity without the need for high-throughput screening or experimental optimization, even in the absence of known binding sites. We successfully designed binders against a diverse set of challenging targets, including cell-surface receptors, common allergens,de novodesigned proteins, and multi-domain nucleases, such as CRISPR-Cas9. We showcase the functional and therapeutic potential of designed binders by reducing IgE binding to birch allergen in patient-derived samples, modulating Cas9 gene editing activity, and reducing the cytotoxicity of a foodborne bacterial enterotoxin. Lastly, we utilize cell surface receptor-specific binders to redirect AAV capsids for targeted gene delivery. This work represents a significant advancement towards a “one design-one binder” approach in computational design, with immense potential in therapeutics, diagnostics, and biotechnology.