bluuebunny/crossref_metadata_2025 huggingface dataset:
TARGETING CANCER STEM CELLS WITH A CDK2 INHIBITOR IN GLIOBLASTOMA
Authors: Mahmnoudian Elham , Qu Dianbo , Lotfipour Farzaneh , Jahani-Asl Arezu
Published: July 2023

Glioblastoma (GB) is the most common and aggressive adult brain tumor with no cure. Brain tumor stem cells (BTSCs) are a rare population of self-renewing multipotent stem cells in GB that contribute to tumorigenesis, therapeutic resistance, and tumour recurrence. Here, we report a CDK2 inhibitor that suppresses BTSCs via OSM/OSMR/STAT3 signalling pathway. To begin with, we performed high throughput screening (HTS) of ~8400 compounds including FDA-approved drugs in patient derived human BTSCs that naturally harbour EGFRvIII mutation and elevated STAT3 phosphorylation, in search of compounds that can suppress EGFRvIII/OSMR/STAT3 oncogenic pathway. The screen led to the identification of a panel of CDK inhibitors that possessed important characteristics including a) ability to cross the blood-brain barrier with mall molecular weights of 277-566 kDa, b) low Topological Polar Surface Area (TPSA) of 76-115 A°, c) a low number of Hydrogen Bond Donors (HBDs) (1-4), and d) cLogP values ranging from 2-4. Following counter screens, we focused on a CDK2 inhibitor that significantly and most efficiently reduced OSM/OSMR signalling and STAT3 activation. Importantly, we found that the compound inhibited the self-renewal and growth of BTSCs in EGFRvIII subtype of BTSCs. This research has led to future investigation on in vivo assessment of this CDK2 inhibitor in combination with ionizing radiation and chemotherapy in preclinical models of GB.
Machine learning phases of an Abelian gauge theory
Authors: Peng Jhao-Hong , Tseng Yuan-Heng , Jiang Fu-Jiun
Published: July 2023

The phase transition of the two-dimensional U(1) quantum link model on the triangular lattice is investigated by employing a supervised neural network (NN) consisting of only one input layer, one hidden layer of two neurons, and one output layer. No information on the studied model is used when the NN training is conducted. Instead, two artificially made configurations are considered as the training set. Interestingly, the obtained NN not only estimates the critical point accurately but also uncovers the physics correctly. The results presented here imply that a supervised NN, which has a very simple architecture and is trained without any input from the investigated model, can identify the targeted phase structure with high precision.
Social mobility and education policy: a district-level analysis of legislative behavior
Authors: Bellani Luna , Berriochoa Kattalina M , Fabella Vigile Marie
Published: July 2023

A vast literature has examined how perceptions of mobility shape demand for redistribution. These studies generally refer to contemporaneous tax policies demanded by those directly impacted. But social mobility is often measured as changes across generations. To account for these intergenerational effects, our analysis focuses on educational policies. We examine how social mobility at the district level explains legislative support for inclusive education policies. We first develop an electoral competition model where voters are altruistic parents, politicians are office seeking and the future economic status of the children is affected both by the degree of income mobility and by public education policies. We then analyze a newly compiled dataset of roll-call votes on California education legislation matched with electoral district levels of income mobility. In line with the model, our analysis suggests that upward mobility in a district negatively predicts legislative support for redistributive education bills.
Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry Identification of Metabolites in Winterberry Fruit Putatively Associated with Natural Disease Resistance to Diaporthe ilicicola
Authors: Emanuel Isabel B. , Cooperstone Jessica L. , Hand Francesca Peduto
Published: July 2023

Winterberry holly ( Ilex verticillata) is an ornamental plant popularly used in landscape design and sold as cut branches for fall and winter seasonal decoration. Latent fruit rot of winterberry is an emerging disease caused by the fungus Diaporthe ilicicola, which can result in up to 100% crop loss. Diaporthe ilicicola infects open flowers in spring, but symptom onset does not occur until the end of the growing season when the fruit is fully mature. This study was conducted to identify compounds displaying significant variation in abundance during fruit maturation and that may be putatively associated with natural disease resistance observed when the fruit is immature. Winterberry ‘Sparkleberry’ fruits collected at four timepoints during the 2018 and 2019 seasons were extracted in methanol and analyzed using high resolution ultra-high performance liquid chromatography-tandem mass spectrometry. The results showed a distinct separation of metabolic profiles based on fruit phenological stage. The top 100 features that were differentially expressed between immature and mature fruit were selected from both electrospray ionization (ESI) (−) and ESI (+) datasets for annotation. Eleven compounds shown to decrease throughout the season included cinnamic acids, a triterpenoid, terpene lactones, stilbene glycosides, a cyanidin glycoside, and a furopyran. Nine compounds shown to accumulate throughout the season included chlorogenic acid derivatives, hydrolysable tannins, flavonoid glycosides, and a triterpene saponin. Future research will further confirm the exact identity of the compounds of interest and determine whether they are biologically active toward D. ilicicola or I. verticillata. The results could inform breeding programs, chemical management programs, and novel antifungal compound development pipelines.
Hearing Aid Delay Effects on Neural Phase Locking
Authors: Zhou Mary , Soleimanpour Roksana , Mahajan Aakriti , Anderson Samira
Published: July 2023

Objectives:

This study was designed to examine the effects of hearing aid delay on the neural representation of the temporal envelope. It was hypothesized that the comb-filter effect would disrupt neural phase locking, and that shorter hearing aid delays would minimize this effect.

Design:

Twenty-one participants, ages 50 years and older, with bilateral mild-to-moderate sensorineural hearing loss were recruited through print advertisements in local senior newspapers. They were fitted with three different sets of hearing aids with average processing delays that ranged from 0.5 to 7 msec. Envelope-following responses (EFRs) were recorded to a 50-msec /da/ syllable presented through a speaker placed 1 meter in front of the participants while they wore the three sets of hearing aids with open tips. Phase-locking factor (PLF) and stimulus-to-response (STR) correlations were calculated from these recordings.

Results:

Recordings obtained while wearing hearing aids with a 0.5-msec processing delay showed higher PLF and STR correlations compared with those with either 5-msec or 7-msec delays. No differences were noted between recordings of hearing aids with 5-msec and 7-msec delays. The degree of difference between hearing aids was greater for individuals who had milder degrees of hearing loss.

Conclusions:

Hearing aid processing delays disrupt phase locking due to mixing of processed and unprocessed sounds in the ear canal when using open domes. Given previous work showing that better phase locking correlates with better speech-in-noise performance, consideration should be given to reducing hearing aid processing delay in the design of hearing aid algorithms.
Prophylactic Administration of Vasopressors Prior to Emergency Intubation in Critically Ill Patients: A Secondary Analysis of Two Multicenter Clinical Trials
Authors: Fuchita Mikita , Pattee Jack , Russell Derek W. , Driver Brian E. , Prekker Matthew E. , Barnes Christopher R. , Brewer Joseph M. , Doerschug Kevin C. , Gaillard John P. , Gandotra Sheetal , Ghamande Shekhar , Gibbs Kevin W. , Hughes Christopher G. , Janz David R. , Khan Akram , Mitchell Steven H. , Page David B. , Rice Todd W. , Self Wesley H. , Smith Lane M. , Stempek Susan B. , Trent Stacy A. , Vonderhaar Derek J. , West Jason R. , Whitson Micah R. , Williamson Kayla , Semler Matthew W. , Casey Jonathan D. , Ginde Adit A. ,   for the Pragmatic Critical Care Research Group
Published: July 2023

OBJECTIVE:

Hypotension affects approximately 40% of critically ill patients undergoing emergency intubation and is associated with an increased risk of death. The objective of this study was to examine the association between prophylactic vasopressor administration and the incidence of peri-intubation hypotension and other clinical outcomes.

DESIGN:

A secondary analysis of two multicenter randomized clinical trials. The clinical effect of prophylactic vasopressor administration was estimated using a one-to-one propensity-matched cohort of patients with and without prophylactic vasopressors.

SETTING:

Seven emergency departments and 17 ICUs across the United States.

PATIENTS:

One thousand seven hundred ninety-eight critically ill patients who underwent emergency intubation at the study sites between February 1, 2019, and May 24, 2021.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was peri-intubation hypotension defined as a systolic blood pressure less than 90 mm Hg occurring between induction and 2 minutes after tracheal intubation. A total of 187 patients (10%) received prophylactic vasopressors prior to intubation. Compared with patients who did not receive prophylactic vasopressors, those who did were older, had higher Acute Physiology and Chronic Health Evaluation II scores, were more likely to have a diagnosis of sepsis, had lower pre-induction systolic blood pressures, and were more likely to be on continuous vasopressor infusions prior to intubation. In our propensity-matched cohort, prophylactic vasopressor administration was not associated with reduced risk of peri-intubation hypotension (41% vs 32%; p = 0.08) or change in systolic blood pressure from baseline (–12 vs –11 mm Hg; p = 0.66).

CONCLUSIONS:

The administration of prophylactic vasopressors was not associated with a lower incidence of peri-intubation hypotension in our propensity-matched analysis. To address potential residual confounding, randomized clinical trials should examine the effect of prophylactic vasopressor administration on peri-intubation outcomes.
Effect of down-regulation of let-7c/g on triggering a double-negative feedback loop and promoting restenosis
Authors: Zhang Qian , Zhou Xiaojun , Li Xianzhi , Yao Shuai , Jiang Shan , Zhang Rui , Zou Zhiwei , Liao Lin , Dong Jianjun
Published: July 2023

Background:

Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are the main causes of restenosis (RS) in diabetic lower extremity arterial disease (LEAD). However, the relevant pathogenic mechanisms are poorly understood.

Methods:

In this study, we introduced a "two-step injury protocol" rat RS model, which started with the induction of atherosclerosis (AS) and was followed by percutaneous transluminal angioplasty (PTA). Hematoxylin-eosin (HE) staining and immunohistochemistry staining were used to verify the form of RS. Two-step transfection was performed, with the first transfection of Lin28a followed by a second transfection of let-7c and let-7g, to explore the possible mechanism by which Lin28a exerted effects. 5-ethynyl-2΄-deoxyuridine (EdU) and Transwell assay were performed to evaluate the ability of proliferation and migration of VSMCs. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the expression of Lin28a protein and let-7 family members.

Results:

Using a combination ofin vitroandin vivoexperiments, we discovered that let-7c, let-7g, and microRNA98 (miR98) were downstream targets of Lin28a. More importantly, decreased expression of let-7c/let-7g increased Lin28a, leading to further inhibition of let-7c/let-7g. We also found an increased level of let-7d in the RS pathological condition, suggesting that it may function as a protective regulator of the Lin28a/let-7 loop by inhibiting the proliferation and migration of VSMCs.

Conclusion:

These findings indicated the presence of a double-negative feedback loop consisting of Lin28a and let-7c/let-7g, which may be responsible for the vicious behavior of VSMCs in RS.
Content Validity of a Novel Scar Assessment Tool Evaluating the Career and Sexual Well-being Impact of Scars
Authors: Garg Stuti P. , Weissman Joshua P. , Chwa Emily S. , Galiano Robert D.
Published: July 2023

Background:

Currently, patient reported outcome scales used to assess scar impact focus solely on psychosocial well-being, symptoms, and appearance. There remains a need to develop a broadened measure of scar impact on patients, focusing on sexual and career aspects. This study investigates the content validity of the novel Career and Sexual Well-being (CS) Scar Impact Scale.

Method:

The CS scale contains five questions and was developed from previous patient thematic analysis interviews describing scar impact, and covers self-conscious behavior, new partners, hiding of the scar, being hindered in the workplace, and concerns regarding unprofessional appearance. Cognitive interviews and established guidelines were used to ensure that the scale was comprehensive, reproducible, and easily understandable.

Results:

In total, 86 patients completed cognitive interviews. Patients had a clear understanding of the questions and elicited their intent in the interviews. An estimated 86% of patients rated the CS scale coverage of scar impact on career and sexual health at a three or above out of four; 95% said the specific instructions were clear, and 92% stated it took them less than 4 minutes to complete the scale. After the first round of interviews, a question about “perception/self-consciousness in a professional environment” was added based on patient suggestions.

Conclusions:

The CS scar scale demonstrated face validity, acceptability, and field-readiness through cognitive interviewing of patients at our institution. Sexual well-being and career performance are important yet often neglected themes with which scars should be assessed. Usage of these tools would serve to improve current scar scales.
Patient Outcomes after Fat Grafting to the Radiated Chest Wall before Delayed Two-stage Alloplastic Breast Reconstruction
Authors: Wenger Robert , Retrouvey Helene , Metcalfe Kelly , Semple John L.
Published: July 2023

Background:

Two-stage alloplastic breast reconstruction in patients having received mastectomy and radiation is associated with a high rate of complications. Fat grafting has been shown to mitigate the effects of radiation on the chest wall to allow for alloplastic reconstruction. In this study, we assess the outcomes (after a mean follow-up of 28 months), including complications and revisional procedures, of women who had fat grafting to the radiated chest wall before two-stage implant-based breast reconstruction.

Methods:

A retrospective chart review was performed on consecutive patients seeking delayed implant-based reconstruction after simple mastectomy and postmastectomy radiation therapy between 2011 and 2015. All patients underwent two sessions of fat grafting to the radiated chest wall before inserting a tissue expander and subsequent exchange to a silicone implant.

Results:

Twenty patients were included in the study. No reconstructive failures were recorded. The short-term complication rate was 5%, with one hematoma leading to a revisional procedure. The mean follow-up after reconstruction was 28 months. During follow-up, two patients (10%) developed capsular contracture grade IV with implant malposition, leading to capsular revision and implant exchange. Four patients (20%) underwent additional fat grafting for contour deformities.

Conclusions:

Fat grafting before two-stage alloplastic breast reconstruction in patients treated with mastectomy and postmastectomy radiation therapy may provide an alternate method of alloplastic reconstruction in a select group of patients who are not suitable for autogenous reconstruction. Follow-up data show that additional surgery may be required for correction of implant malposition and capsular contracture.
Making an MPCT: Building and Sustaining a Multicultural Psychology Consultation Team (MPCT) Within an Academic Medical Center
Authors: Pinder-Amaker Stephanie , Winer Jeffrey P. , Wadsworth Lauren P. , Nevins Caitlin M. , Peckham Andrew , Nota Jacob A. , Beard Courtney
Published: July 2023

The synergistic epidemics of COVID-19, racial injustice, and health inequities sparked an unprecedented commitment from US hospital systems and treatment settings to address health disparities by increasing access to care for historically oppressed and underserved communities. However, the inability of hospital systems to actually provide multiculturally responsive care and, more broadly, to consistently practice cultural humility will only exacerbate patient distrust and the deleterious health and social outcomes we seek to mitigate. This perspective article describes the development of a multidisciplinary team of mental health providers committed to delivering culturally responsive mental health treatment while promoting inclusive workplace environments. We outline the Multicultural Psychology Consultation Team’s (MPCT) origin, design, process, and structure and discuss successes and challenges in maintaining the model in its first two years. We recommend that systemic infusion of cultural humility, multiculturally responsive clinical care, and support for providers delivering care be prioritized in concert with efforts to increase access to care for diverse patients. We offer MPCT as a model for supporting these aims.
Sodium-Glucose Cotransporter-2 Inhibitors in Depression
Authors: Liebers David T. , Ebina Wataru , Iosifescu Dan V.
Published: July 2023

Novel treatment strategies that refract existing treatment algorithms for depressive disorders are being sought. Abnormal brain bioenergetic metabolism may represent an alternative, therapeutically targetable neurobiological basis for depression. A growing body of research points to endogenous ketones as candidate neuroprotective metabolites with the potential to enhance brain bioenergetics and improve mood. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally approved for the treatment of diabetes, induce ketogenesis and are associated with mood improvement in population-based studies. In this column, we highlight the rationale for the hypothesis that ketogenesis induced by SGLT2 inhibitors may be an effective treatment for depressive disorders.
Safety and efficacy of a laser refractive procedure in eyes with previous keratoplasty: systematic review and meta-analysis
Authors: Alsubhi Abdulrahman Hameed , Alhindi Nawaf , Abukhudair Abdulrahman , Alsulami Abdulrahman , Seraj Hadeel , Morfeq Hussein
Published: July 2023

Post-keratoplasty (KP) patients' visual acuity can be severely limited by ametropia. Irregular astigmatisms are frequently encountered in these patients and is commonly associated with high degrees of hyperopia or myopia. This systematic review investigates the safety and efficacy of laser refractive surgery for post KP vision correction. 31 studies with 683 participants (732 eyes) enrolled in this review. Mean astigmatism improved significantly (mean difference [MD] = −2.70, 95% CI, −3.13 to −2.28, P < .0001). As well as Mean spherical equivalent (MD = −3.35, 95% CI, −3.92 to −2.78, P < .0001). From 586 participants 5.8% lost 2 or more lines of corrected distance visual acuity after treatment. The proportion of eyes with 20/40 uncorrected distance visual acuity or better was reported and the percentage was 46.79% overall. Laser refractive procedures (laser in situ keratomileusis [LASIK] or photorefractive keratectomy [PRK] or transepithelial PRK) on eyes with corneal transplantation were found to be relatively safe and effective. Our systematic review shows there is improvement in all outcomes. Main adverse effects were haze for PRK and epithelial ingrowth for LASIK.
Validation of the U60EH Wrist Electronic Blood Pressure Monitor in general population according to the ISO 81060-2:2018/AMD 1:2020 Protocol
Authors: Mu Sicong , Zhu Min , Ma Liping , Fang Lixiu
Published: July 2023

Objective

To evaluate the accuracy of the U60EH Wrist Electronic Blood Pressure Monitor in general population according to the Universal Standard (ISO 81060-2:2018/AMD 1:2020).

Methods

Subjects were recruited to fulfill the age, gender, blood pressure (BP) and cuff distribution criteria of the Universal Standard in a general population using the same arm sequential BP measurement method. A single cuff for wrist sizes 13.5–21.5 cm was used on this test device.

Results

According to Criterion 1, the mean difference of SBP between the test device and the reference device was 1.51 mmHg, with an SD of 6.48 mmHg. The mean difference of DBP was −0.44 mmHg, with an SD of 5.98 mmHg. The mean difference of both SBP and DBP was less than 5 mmHg, and the SD was less than 8 mmHg, which met the requirements. According to Criterion 2, the mean difference of SBP between the test device and the reference device was 1.51 mmHg, and the SD was 5.88 mmHg, which was less than 6.78 mmHg and met the requirements. The mean difference of DBP was −0.44 mmHg, and the SD was 5.22 mmHg, which was less than 6.93 mmHg and met the requirements.

Conclusion

All results passed the Standard (ISO 81060-2:2018/AMD 1:2020) requirements. The U60EH Wrist Electronic Blood Pressure Monitor can be recommended for home and clinical use.
Evaluation of the Inflammatory Response After Eradication of Helicobacter pylori in Patients With Familial Mediterranean Fever
Authors: Altunok Murat , Albayrak Fatih
Published: July 2023

Purpose:

Evaluation of the inflammatory response after Helicobacter pylori (Hp) eradication in patients with Familial Mediterranean Fever (FMF) during the non-attack period and determining whether there is a change in the ongoing inflammation during the non-attack period.

Materials and Methods:

Sixty-four patients, who have not been eradicated for Hp in the last 2 years, diagnosed with FMF, and evaluated in the non-attack period, were included in the study. Hp eradication therapy was administered to patients who were found to be Hp-positive. C-reactive protein (CRP), high-sensitive C-reactive protein (hs-CRP), interleukin-6, interleukin-8, tumor necrosis factor-alpha, and serum amyloid A values were compared between the groups before and after eradication.

Results:

CRP and hs-CRP levels were found to be statistically higher in the FMF group than in the control group. A statistically significant decrease was found in the values of CRP and hs-CRP, in the number of patients with attacks, and in attack frequency after eradication in the Infected Patients compared to the values before eradication.

Conclusions:

We determined a decrease in CRP and hs-CRP values, the number of patients with attacks, and attack frequency with the eradication of Infected Patients. In patients with FMF, in whom it has been proven by different studies that the inflammation continues during the non-attack period, it may be recommended to investigate the presence of Hp infection, which is thought to contribute to this inflammation and to give Hp eradication therapy to patients who are found positive to reduce the development of secondary complications caused by chronic inflammation.
Aerobic Exercise Improves Cortical Inhibitory Function After Stroke: A Preliminary Investigation
Authors: Palmer Jacqueline A. , Whitaker Alicen A , Payne Aiden M. , Bartsch Bria L. , Reisman Darcy S. , Boyne Pierce E. , Billinger Sandra A.
Published: July 2023

Background and Purpose:

Aerobic exercise can elicit positive effects on neuroplasticity and cognitive executive function but is poorly understood after stroke. We tested the effect of 4 weeks of aerobic exercise training on inhibitory and facilitatory elements of cognitive executive function and electroencephalography markers of cortical inhibition and facilitation. We investigated relationships between stimulus-evoked cortical responses, blood lactate levels during training, and aerobic fitness postintervention.

Methods:

Twelve individuals with chronic (>6 months) stroke completed an aerobic exercise intervention (40 minutes, 3×/wk). Electroencephalography and motor response times were assessed during congruent (response facilitation) and incongruent (response inhibition) stimuli of a Flanker task. Aerobic fitness capacity was assessed as

during a treadmill test pre- and postintervention. Blood lactate was assessed acutely (<1 minute) after exercise each week. Cortical inhibition (N2) and facilitation (frontal P3) were quantified as peak amplitudes and latencies of stimulus-evoked electroencephalographic activity over the frontal cortical region.

Results:

Following exercise training, the response inhibition speed increased while response facilitation remained unchanged. A relationship between earlier cortical N2 response and faster response inhibition emerged postintervention. Individuals who produced higher lactate during exercise training achieved faster response inhibition and tended to show earlier cortical N2 responses postintervention. There were no associations between

and metrics of behavioral or neurophysiologic function.

Discussion and Conclusions:

These preliminary findings provide novel evidence for selective benefits of aerobic exercise on inhibitory control during the initial 4-week period after initiation of exercise training and implicate a potential therapeutic effect of lactate on poststroke inhibitory control.

Video Abstract available for more insights from the authors (see the video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A450).
Topical Review: Methodological Variables in Clinical and Laboratory Measurements of Fixation Disparity
Authors: Fogt Nick
Published: July 2023

Significance

Fixation disparity is a small vergence error that does not disrupt fusion. Fixation disparity measures correlate with binocular symptoms. This paper covers methodological differences between clinical fixation disparity measurement devices, findings when objective and subjective fixation disparities are compared, and the potential impact of binocular capture on fixation disparity measurements.

Fixation disparity is a small vergence error that occurs in non-strabismic individuals and does not disrupt fusion. This paper reviews clinical fixation disparity variables and their clinical diagnostic value. Clinical devices that are used to measure these variables are described as are studies in which the output from these devices have been compared. Methodological differences between the devices such as the location of the fusional stimulus, the rate at which judgments of dichoptic alignment are made, and the strength of the accommodative stimulus are all considered. In addition, the paper covers theories of the neural origins of fixation disparity and control systems models incorporating fixation disparity. Studies in which objective fixation disparities (oculomotor portion of fixation disparity assessed with an eye tracker) and subjective fixation disparities (sensory portion of fixation disparity assessed psychophysically with dichoptic Nonius lines) have been compared are also examined, and consideration is given to why some investigators find differences in these measures while other investigators do not. The conclusion thus far is that there are likely complex interactions between vergence adaptation, accommodation, and the location of the fusional stimulus that lead to differences in objective and subjective fixation disparity measures. Finally, capture of the visual direction of monocular stimuli by adjacent fusional stimuli and the implications for fixation disparity measures are considered.
Impact Of Community Privilege On Access To Care Among Patients Following Complex Cancer Surgery
Authors: Munir Muhammad Musaab , Endo Yutaka , Alaimo Laura , Moazzam Zorays , Lima Henrique A , Woldesenbet Selamawit , Azap Lovette , Beane Joal , Kim Alex , Dillhoff Mary , Cloyd Jordan , Ejaz Aslam , Pawlik Timothy M.
Published: July 2023

Objective:

We sought to define the impact of community privilege on variations in travel patterns and access to care at high-volume hospitals for complex surgical procedures.

Background:

With increased emphasis on centralization of high-risk surgery, social determinants of health (SDOH) play a critical role in preventing equitable access to care. Privilege is a right, benefit, advantage, or opportunity that positively impacts all SDOH.

Methods:

The California Office of State-wide Health Planning Database identified patients who underwent esophagectomy (ES), pneumonectomy (PN), pancreatectomy (PA), or proctectomy (PR) for a malignant diagnosis between 2012 and 2016 and was merged using ZIP codes with the Index of Concentration of Extremes, a validated metric of both spatial polarization and privilege obtained from the American Community Survey. Clustered multivariable regression was performed to assess the probability of undergoing care at a high-volume center, bypassing the nearest and high-volume center, and total real driving time and travel distance.

Results:

Among 25,070 patients who underwent a complex oncologic operation (ES: n=1,216, 4.9%; PN: n=13,247, 52.8%; PD: n=3,559, 14.2%; PR: n=7,048, 28.1%), 5,019 (20.0%) individuals resided in areas with the highest privilege (i.e., White, high-income homogeneity), whereas 4,994 (19.9%) individuals resided in areas of the lowest privilege (i.e., Black, low-income homogeneity). Median travel distance was 33.1 miles (interquartile range [IQR] 14.4–72.2) and travel time was 16.4 minutes (IQR 8.3–30.2). Roughly, three-quarters of patients (overall: 74.8%, ES: 35.0%; PN: 74.3%; PD: 75.2%; LR: 82.2%) sought surgical care at a high-volume center. On multivariable regression, patients residing in the least advantaged communities were less likely to undergo surgery at a high-volume hospital (overall: odds ratio [OR] 0.65, 95% confidence interval [CI] 0.52–0.81). Of note, individuals in the least privileged areas had longer travel distances (28.5 miles, 95%CI 21.2-35.8) and times (10.4 m, 95%CI 7.6-13.1) to reach the destination facility, as well as over 70% greater odds of bypassing a high-volume hospital to undergo surgical care at a low-volume center (OR 1.74, 95% CI 1.29-2.34) versus individuals living in the highest privileged areas.

Conclusions and Relevance:

Privilege had a marked effect on access to complex oncologic surgical care at high-volume centers. This highlights the need to focus on privilege as a key social determinant of health that influences patient access to and utilization of healthcare resources.
Averaging plus learning models and their asymptotics
Authors: Popescu Ionel , Vaidya Tushar
Published: July 2023

We develop original models to study interacting agents in financial markets and in social networks. Within these models, randomness is vital as a form of shock or news that decays with time. Agents learn from their observations and learning ability to interpret news or private information in time-varying networks. Under general assumptions on the noise, a limit theorem is developed for the generalized averaging framework for certain type of conditions governing the learning. In this context, the agents’ beliefs (properly scaled) converge in distribution that is not necessarily normal. Fresh insights are gained not only from proposing a new setting for social learning models but also from using different techniques to study discrete-time random linear dynamical systems.
Exceptionally high respiration rates in the reactive surface layer of sediments underlying oxygen-deficient bottom waters
Authors: van de Velde Sebastiaan J. , Hylén Astrid , Eriksson Mats , James Rebecca K. , Kononets Mikhail Y. , Robertson Elizabeth K. , Hall Per O. J.
Published: July 2023

Organic carbon (OC) burial efficiency, which relates the OC burial rate to respiration in the seafloor, is a critical parameter in the reconstruction of past marine primary productivities. The current accepted theory is that sediments underlying oxygen-deficient (anoxic) bottom waters have low respiration rates and high OC burial efficiencies. By combining novel
in situ
measurements in anoxic basins with reaction-transport modelling, we demonstrate that sediments underlying anoxic bottom waters have much higher respiration rates than commonly assumed. A major proportion of the carbon respiration is concentrated in the top millimeter—the so-called ‘reactive surface layer’—which is likely a feature in approximately 15% of the coastal seafloor. When re-evaluating previously published data in light of our results, we conclude that the impact of bottom-water anoxia on OC burial efficiencies in marine sediments is small. Consequently, reconstructions of past marine primary productivity in a predominantly anoxic ocean based on OC burial rates might be underestimated by up to an order of magnitude.
Dollo meets Bergmann: morphological evolution in secondary aquatic mammals
Authors: Farina B. M. , Faurby S. , Silvestro D.
Published: July 2023

Secondary transitions to aquatic environments are common among vertebrates, and aquatic lineages display several adaptations to this realm, some of which might make these transitions irreversible. At the same time, discussions about secondary transitions often focus only on the marine realm, comparing fully terrestrial with fully aquatic species. This, however, captures only a fraction of land-to-water transitions, and freshwater and semi-aquatic groups are often neglected in macroevolutionary studies. Here, we use phylogenetic comparative methods to unravel the evolution of different levels of aquatic adaptations across all extant mammals, testing if aquatic adaptations are irreversible and if they are related to relative body mass changes. We found irreversible adaptations consistent with Dollo's Law in lineages that rely strongly on aquatic environments, while weaker adaptations in semi-aquatic lineages, which still allow efficient terrestrial movement, are reversible. In lineages transitioning to aquatic realms, including semi-aquatic ones, we found a consistent trend towards an increased relative body mass and a significant association with a more carnivorous diet. We interpret these patterns as the result of thermoregulation constraints associated with the high thermal conductivity of water leading to body mass increase consistently with Bergmann's rule and to a prevalence of more nutritious diets.
Occurrence and prevalence of bacteria on door handles at the University of Port Harcourt Teaching Hospital and the multidrug resistance implications
Authors: Edi Deinmo , Ejiohuo Ovinuchi , Ordinioha Best
Published: July 2023

Background. The coronavirus disease 2019 (COVID-19) pandemic has heightened concerns regarding transmitting hospital-acquired infections through high-contact points in healthcare facilities, such as door handles, which can serve as reservoirs for pathogenic micro-organisms. With the increased infectivity of the serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, there is greater awareness of the risk of multidrug-resistant bacteria on these surfaces, necessitating strict surveillance prevention protocols.

Objective. This study assesses the occurrence and prevalence of bacteria on toilet door handles at the University of Port Harcourt Teaching Hospital in Nigeria and the multidrug resistance implications. We examined the hospital infection level and overall sanitary conditions.

Method. Experimental data from our study on hospital door handles in different locations were assessed. Eighty-six samples were collected from toilet door handles at the University of Port Harcourt Teaching Hospital. Ethical approval was obtained from the hospital departments and the university research ethics committee. Samples from private offices and doors without handles were excluded. Bacteria were isolated from the samples, and antibiotic sensitivity testing was performed.

Result. Of the 329 bacteria isolated, 55.5 % were Gram-positive and 44.4 % Gram-negative. The most prevalent bacteria were

Staphylococcus epidermidis

, followed by

Bacillus

sp. The prevalence of multidrug-resistant bacteria was also low, with

Enterococcus

sp. having the highest prevalence of 28.57%, followed by

Micrococcus

sp. at 3.45 % and

S. epidermidis

at 1.96 %.

Conclusion. The results show that, despite the occurrence of pathogenic micro-organisms, there has been a reduction in the prevalence of multidrug-resistant bacteria strains. This study can be used as an example for environmental microbiological surveillance in suspected outbreak investigations and assessment of sanitary conditions and the prevalence of multidrug-resistant bacteria in healthcare facilities.
Strategies for Improving the Performance of Prediction Models for Response to Immune Checkpoint Blockade Therapy in Cancer
Authors: Zeng Tiantian , Zhang Jason , Stromberg Arnold , Chen Jin , Wang Chi
Published: July 2023

Immune checkpoint blockade (ICB) therapy holds promise for bringing long-lasting clinical gains for the treatment of cancer. However, studies show that only a fraction of patients respond to the treatment. In this regard, it is valuable to develop gene expression signatures based on RNA sequencing (RNAseq) data and machine learning methods to predict patients’ response to the ICB therapy, which contributes to more personalized treatment strategy and better management of cancer patients. However, due to the limited sample size of ICB trials with RNAseq data available and the vast number of candidate gene expression features, it is challenging to develop well-performed gene expression signatures. In this study, we used several published melanoma datasets and investigated approaches that can improve the construction of gene expression-based prediction models. We found that merging datasets from multiple studies and incorporating prior biological knowledge yielded prediction models with higher predictive accuracies. Our finding suggests that these two strategies are of high value to identify ICB response biomarkers in future studies.
An Exploratory Study of the Association Between Preoperative Pain Catastrophizing Scale Scores and Postoperative Pain Experience in Total Knee Arthroplasty
Authors: Gill Christopher , Giuliano Karen
Published: July 2023

Introduction

Opiate misuse is increasingly common and can result from a single opiate exposure. High pain catastrophizing scores have been linked with greater reported pain and increased opiate use in outpatient studies, but this association has not previously been established in a perioperative setting.

Methods

A quantitative, cross-sectional pilot study was conducted on 21 patients undergoing total knee arthroplasty surgery. Pain Catastrophizing Scale (PCS) scores and patients’ ASA Physical Status classifications were collected prior to surgery. Postoperative pain scores were measured using an 11-point numeric rating scale (NRS) and postoperative opiate consumption was measured using modified morphine equivalents (MMEs). Data were analyzed using Spearman rank correlation coefficients.

Results

Significant correlations were found between NRS pain scores at 6 hours post-surgery and 48 hours post-surgery (.455); and NRS pain scores at 6 hours post-surgery and opiate consumption within the first 24 hours post-surgery (.591). A significant correlation was also found between ASA Physical Status classification and total opiate consumption (.522). While rumination scores within the Pain Catastrophizing Scale were also moderately positively correlated with reported pain scores 12 hours post-surgery (.41) and morphine dosing at 48 hours (.40), they were not significant.

Conclusions

Early preemptive pain management is an important component of overall postoperative pain management and to reduce opiate use. Results support that the ASA Physical Status classification scores may be helpful in identifying patients at risk for high opiate use. For the PCS, more data are needed to determine the clinical usefulness of the PCS as an adjunct to overall postoperative pain management.
Later-life Mortality and the Repeal of Federal Prohibition
Authors: Jacks David S. , Pendakur Krishna , Shigeoka Hitoshi , Wray Anthony
Published: July 2023

Despite a recent and dramatic re-evaluation of the health consequences of alcohol consumption, very little is known about the effects of in utero exposure to alcohol on long-run outcomes such as later-life mortality. Here, we investigate how state by year variation in alcohol control arising from the repeal of federal prohibition affects mortality for cohorts born in the 1930s. We find that individuals born in wet states experienced higher later-life mortality than individuals born in dry states, translating into a 3.3% increase in mortality rates between 1990 and 2004 for affected cohorts.
OncoCTMiner: streamlining precision oncology trial matching via molecular profile analysis
Authors: Xu Quan , Liu Yueyue , Sun Dawei , Huang Xiaoqian , Li Feihong , Zhai JinCheng , Li Yang , Zhou Qiming , Niu Beifang
Published: July 2023

OncoCTMiner is an innovative platform that streamlines precision oncology trial matching by integrating genetic profile analysis and clinical data. It utilizes manual tagging and automated entity recognition to identify six major biomedical concepts within clinical trial records. The platform currently contains a database of over 457,000 clinical trials, enabling quick and advanced search functionalities. Additionally, OncoCTMiner features an automated matching system based on genetic profiles and clinical data, providing real-time matching reports for suitable clinical trials. This platform aims to enhance patient enrollment in precision oncology trials, facilitating the development of personalized cancer therapies.

Availability and Implementation

OncoCTMiner is available athttps://oncoctminer.chosenmedinfo.com.

Contact

niubf@cnic.cnorqimingzhou@chosenmedtech.com

Supplementary information

Supplementary data are available atmedRxivonline.

Graphic Abstract

Graphic abstract:

A) OncoCTMiner’s role in precision oncology trial enrollment. B) OncoCTMiner takes clinical and genetic profiles as inputs and utilizes a trial matching and filtering system to generate a report of matched trials. C) Strategy for building the clinical trial eligibility criteria database. D) Automatic matching strategy for genomics-driven oncology trials.
Glutamatergic neuronal activity regulates angiogenesis and blood-retinal barrier maturation via Norrin/β-catenin signaling
Authors: Biswas Saptarshi , Shahriar Sanjid , Bachay Galina , Arvanitis Panos , Jamoul Danny , Brunken William J. , Agalliu Dritan
Published: July 2023

Interactions among neuronal, glial and vascular components are crucial for retinal angiogenesis and blood-retinal barrier (BRB) maturation. Although synaptic dysfunction precedes vascular abnormalities in many retinal pathologies, how neuronal activity, specifically glutamatergic activity, regulates retinal angiogenesis and BRB maturation remains unclear. Usingin vivogenetic studies in mice, single-cell RNA-sequencing and functional validation, we show that deep plexus angiogenesis and paracellular BRB maturation are delayed inVglut1-/-retinas where neurons fail to release glutamate. In contrast, deep plexus angiogenesis and paracellular BRB maturation are accelerated inGnat1-/-retinas where constitutively depolarized rods release excessive glutamate. Norrin expression and endothelial Norrin/β-catenin signaling are downregulated inVglut1-/-retinas, and upregulated inGnat1-/-retinas. Pharmacological activation of endothelial Norrin/β-catenin signaling inVglut1-/-retinas rescued defects in deep plexus angiogenesis and paracellular BRB maturation. Our findings demonstrate that glutamatergic neuronal activity regulates retinal angiogenesis and BRB maturation by modulating endothelial Norrin/β-catenin signaling.
Polygenic architecture of flowering time and its relationship with local environments in the grassBrachypodium distachyon
Authors: Minadakis Nikolaos , Kaderli Lars , Horvath Robert , Bourgeois Yann , Xu Wenbo , Thieme Michael , Woods Daniel P. , Roulin Anne C.
Published: July 2023

Synchronizing the timing of reproduction with the environment is crucial in the wild. Among the multiple mechanisms annual plants evolved to sense their environment, the requirement of cold-mediated vernalization is a major process that prevents individuals from flowering during winter. In many annual plants including crops, both a long and short vernalization requirement can be observed within species, resulting in so-called early-(spring) and late (winter)-flowering genotypes. Here, using the grass modelBrachypodium distachyon, we explored the link between flowering time-related trait (vernalization requirement and flowering time), environmental variation, and diversity at flowering-time genes by combining measurements under greenhouse and outdoor conditions. These experiments confirmed thatB. distachyonnatural accessions display large differences regarding vernalization requirements and ultimately flowering time. We underline significant, albeit quantitative effects of current environmental conditions on flowering time-related traits. While disentangling the confounding effects of population structure on flowering time-related traits remains challenging, population genomics analyses indicate that well-characterized flowering-time genes may contribute significantly to flowering time variation and display signs of polygenic selection. Flowering-time genes, however, do not colocalize with GWAs peaks obtained with outdoor measurements, suggesting that additional genetic factors contribute to flowering time variation in the wild. Altogether, our study fosters our understanding of the polygenic architecture of flowering time in a natural grass system and opens new avenues of research to investigate the gene-by-environment interaction at play for this trait.

Article Summary

Synchronizing the timing of reproduction with the environment is crucial in the wild. We used here the modelBrachypodium distachyonto expand our knowledge on the adaptive potential and polygenic architecture of flowering time in wild grasses. While genetic factors play an important role in flowering time variation in our species, we showed that flowering time correlates with environmental variables and is therefore a locally adapted trait.