bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffuse midline glioma invasion and metastasis rely on cell-autonomous signaling
Authors: Bruschi Marco , Midjek Lilia , Ajlil Yassine , Vairy Stephanie , Lancien Manon , Ghermaoui Samia , Kergrohen Thomas , Verreault Maite , Idbaih Ahmed , de Biagi Carlos Alberto Oliveira , Liu Ilon , Filbin Mariella G , Beccaria Kevin , Blauwblomme Thomas , Puget Stephanie , Tauziede-Espariat Arnault , Varlet Pascale , Dangouloff-Ros Volodia , Boddaert Nathalie , Le Teuff Gwenael , Grill Jacques , Montagnac Guillaume , Elkhatib Nadia , Debily Marie-Anne , Castel David
Published: September 2023

Background

Diffuse midline gliomas (DMG) are pediatric tumors with negligible 2-year survival after diagnosis characterized by their ability to infiltrate the central nervous system. In the hope of controlling the local growth and slowing the disease, all patients receive radiotherapy. However, distant progression occurs frequently in DMG patients. Current clues as to what causes tumor infiltration circle mainly around the tumor microenvironment, but there are currently no known determinants to predict the degree of invasiveness.

Methods

In this study, we use patient-derived glioma stem cells (GSCs) to create patient-specific 3D avatars to model interindividual invasion and elucidate the cellular supporting mechanisms.

Results

We show that GSC models in 3D mirror the invasive behavior of the parental tumors, thus proving the ability of DMG to infiltrate as an autonomous characteristic of tumor cells. Furthermore, we distinguished 2 modes of migration, mesenchymal and ameboid-like, and associated the ameboid-like modality with GSCs derived from the most invasive tumors. Using transcriptomics of both organoids and primary tumors, we further characterized the invasive ameboid-like tumors as oligodendrocyte progenitor-like, with highly contractile cytoskeleton and reduced adhesion ability driven by crucial over-expression of bone morphogenetic pathway 7 (BMP7). Finally, we deciphered MEK, ERK, and Rho/ROCK kinases activated downstream of the BMP7 stimulation as actionable targets controlling tumor cell motility.

Conclusions

Our findings identify 2 new therapeutic avenues. First, patient-derived GSCs represent a predictive tool for patient stratification in order to adapt irradiation strategies. Second, autocrine and short-range BMP7-related signaling becomes a druggable target to prevent DMG spread and metastasis.
Nutrition and melanoma: the contribution of trace elements in onset, progression, and treatment of melanoma
Authors: Lei Rui , Liu Xiao , Wu Jinfeng
Published: September 2023

Melanoma is a highly malignant and drug-resistant disease that imposes a substantial economic burden on the world. There are many studies linking trace elements to diverse types of cancers, including melanoma. This review elucidates the relationship between trace elements exposure and melanoma. It was identified that copper, manganese, selenium, zinc, iron, and many other trace elements were associated with melanoma in humans. In terms of epidemiology, different elements have different correlations with melanoma. These trace elements affect the occurrence and development of melanoma through various mechanisms, such as oxidative stress and the MAPK pathway. The literature on the role of trace elements in the pathogenesis and treatment of melanoma depicts promising prospects for this field.
Impact of Primary Breast Surgery on Overall Survival of Patients With De Novo Metastatic Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Villacampa Guillermo , Papakonstantinou Andri , Fredriksson Irma , Matikas Alexios
Published: September 2023

Background

Breast surgery in cases of de novo metastatic breast cancer (MBC) is associated with improved outcomes in retrospective studies, although the results of randomized controlled trials (RCTs) are conflicting. We aimed to investigate whether surgery in this context prolongs patient survival.

Methods

We performed a systematic review of the literature to identify RCTs comparing surgery of primary breast cancer to no surgery in patients with de novo MBC. Cochrane Library, Embase, Medline (OVID), and Web of Science were searched with latest update in July 2023, while conference proceedings were manually searched. Data concerning patient and tumor characteristics, as well as outcomes, were extracted. A meta-analysis with random effects models was performed considering heterogeneity between trials.

Results

Overall, 3255 entries were identified and 5 RCTs fulfilled all inclusion criteria, which had enrolled 1381 patients. The overall estimation in the intention-to-treat population showed no benefit for patients who had surgical excision of the primary breast tumor (HR = 0.93; 95% CI, 0.76-1.14). No subgroups in terms of receptor status or patterns of metastasis seemed to benefit from surgery, except for younger/premenopausal patients (HR = 0.74, 95% CI, 0.58-0.94). Breast surgery was associated with improved local progression-free survival (HR = 0.37, 95% CI, 0.19-0.74).

Conclusion

Surgery of the primary tumor in patients with de novo MBC does not prolong survival, except possibly in younger/premenopausal patients. Breast surgery should be offered within the context of well-designed clinical trials examining the issue.
Experimental study of (p, 2p) reactions at 197 MeV on 12C, 16O, 40,48Ca, and 90Zr nuclei leading to low-lying states of residual nuclei
Authors: Noro Tetsuo , Sakaguchi Satoshi , Wakasa Tomotsugu , Dozono Masanori , Fujioka Hiroyuki , Fujita Kunihiro , Hatanaka Kichiji , Ishida Takashi , Iwamoto Chihiro , Kawase Shoichiro , Kubota Yuki , Maeda Yukie , Matsubara Hiroaki , Miki Kenjiro , Ota Shinsuke , Panin Valerii , Sakaguchi Harutaka , Sakaue Akane , Sakemi Yasuhiro , Sasano Masaki , Sekiguchi Kimiko , Shimizu Yohei , Takeda Hiroyuki , Tameshige Yuji , Tamii Atsushi , Terashima Satoru , Uesaka Tomohiro , Yang Zai-Hong , Yasuda Yusuke , Yoshida Hidetomo P , Zenihiro Juzo
Published: September 2023

We have measured the differential cross section and analyzing power for (p, 2p) reactions that lead to discrete states of residual nuclei at an incident energy of 197 MeV for five kinds of target nuclei, 12C, 16O, 40,48Ca, and 90Zr. The data are compared with distorted-wave impulse approximation calculations using two kinds of global optical potentials. The spectroscopic factors obtained from these calculations agree with those determined in (e, e′p) studies within 20%, except for one orbital of the 90Zr nucleus where the distortion effect is much greater than that for the other orbitals of 90Zr and for other target nuclei. We also observed a clear and visibly distinct j-dependence in the analyzing power.
Prevalence of acute kidney injury among dengue cases: a systematic review and meta-analysis
Authors: Bushi Ganesh , Shabil Muhammed , Padhi Bijaya Kumar , Ahmed Mohammed , Pandey Pratima , Satapathy Prakasini , Rustagi Sarvesh , Pradhan Keerti Bhusan , Al-qaim Zahraa Haleem , Sah Ranjit
Published: September 2023

Numerous studies have shown a correlation between dengue virus (DENV) infection and kidney disease. However, there is no existing meta-analysis on the prevalence of kidney diseases in the dengue population. A thorough systematic review and meta-analysis were undertaken to determine the prevalence of renal problems in people with DENV infection in order to fill this knowledge gap. A rigorous electronic literature search was carried out up to 25 January 2023 in a number of databases, including ProQuest, EBSCOhost, Scopus, PubMed and Web of Science. The search aimed to find articles that reported on the prevalence of kidney diseases in patients with DENV infection. Using the modified Newcastle–Ottawa Scale, the quality of the included studies was assessed. The meta-analysis included a total of 37 studies with 21 764 participants reporting on the prevalence of acute kidney injury (AKI) in individuals with DENV infection. The pooled prevalence of AKI in dengue patients was found to be 8% (95% confidence interval 6 to 11), with high heterogeneity across studies. The studies included are of moderate quality. The study revealed a high AKI prevalence in dengue patients, underlining the need for regular renal examination to detect AKI early and reduce hospitalization risk. Further research is needed to understand the dengue–kidney relationship and develop effective management strategies.
Assessing heat effects on respiratory mortality and location characteristics as modifiers of heat effects at a small area scale in Central-Northern Europe
Authors: Zafeiratou Sofia , Samoli Evangelia , Analitis Antonis , Gasparrini Antonio , Stafoggia Massimo , de’ Donato Francesca K. , Rao Shilpa , Zhang Siqi , Breitner Susanne , Masselot Pierre , Aunan Kristin , Schneider Alexandra , Katsouyanni Klea ,   on behalf of the EXHAUSTION project team
Published: September 2023

Background:

Heat effects on respiratory mortality are known, mostly from time-series studies of city-wide data. A limited number of studies have been conducted at the national level or covering non-urban areas. Effect modification by area-level factors has not been extensively investigated. Our study assessed the heat effects on respiratory mortality at a small administrative area level in Norway, Germany, and England and Wales, in the warm period (May–September) within 1996–2018. Also, we examined possible effect modification by several area-level characteristics in the framework of the EU-Horizon2020 EXHAUSTION project.

Methods:

Daily respiratory mortality counts and modeled air temperature data were collected for Norway, Germany, and England and Wales at a small administrative area level. The temperature-mortality association was assessed by small area-specific Poisson regression allowing for overdispersion, using distributed lag non-linear models. Estimates were pooled at the national level and overall using a random-effect meta-analysis. Age- and sex-specific models were also applied. A multilevel random-effects model was applied to investigate the modification of the heat effects by area-level factors.

Results:

A rise in temperature from the 75th to 99th percentile was associated with a 27% (95% confidence interval [CI] = 19%, 34%) increase in respiratory mortality, with higher effects for females. Increased population density and PM2.5 concentrations were associated with stronger heat effects on mortality.

Conclusions:

Our study strengthens the evidence of adverse heat effects on respiratory mortality in Northern Europe by identifying vulnerable subgroups and subregions. This may contribute to the development of targeted policies for adaptation to climate change.
Peripheral visual field shifts after intraocular lens implantation
Authors: van Vught Luc , Luyten Gregorius P.M. , Beenakker Jan-Willem M.
Published: September 2023

Purpose:

To assess whether intraocular lens (IOL) implantation induces shifts in the peripheral visual field.

Setting:

Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.

Design:

Ray-tracing study.

Methods:

Nonsequential ray-tracing simulations were performed with phakic and pseudophakic versions of the same eye model to assess potential shifts in the visual field after IOL implantation. 2 different IOL designs were evaluated and for each design 5 different axial positions and 7 different intrinsic powers were tested. The relation between the physical position of the light source and the location where the retina was illuminated was determined for each eye model. Subsequently, these relations were used to calculate whether the visual field shifts in pseudophakic eyes.

Results:

The pseudophakic visual field shift was below 1 degree for central vision in all evaluated models. For peripheral vision, the light rays in the pseudophakic eyes were refracted to a more central retinal location compared with phakic eyes, resulting in a central shift of the peripheral visual field. The magnitude of the shift depended on the IOL design and its axial position, but could be as high as 5.4 degrees towards central vision.

Conclusions:

IOL implantation tends to have little effect on the central visual field but can induce an over 5 degrees shift in the peripheral visual field. Such a shift can affect the perception of peripheral visual complaints.
Comparative evaluation of multiple nomograms for predicting postoperative vault after implantable collamer lens surgery
Authors: Moshirfar Majid , Han Kenneth D. , Jaafar Muhammed A. , Santos Jordan M. , Theis Joshua S. , Stoakes Isabella M. , Hoopes Philip C.
Published: September 2023

Purpose:

To compare the vault predictability of most available implantable collamer lens (ICL) sizing nomograms and identify which preoperative measurements are predictive of vault.

Setting:

Private practice in Draper, Utah.

Design:

Retrospective chart review.

Methods:

This study was a retrospective analysis of 209 eyes of 106 patients who underwent STAAR Surgical ICL implantation. Analyses were performed based on the availability of preoperative parameters, varying the number of eyes for each test. Mean absolute error (MAE) of predicted vs actual postoperative vault was calculated for each nomogram. The frequency of Kim, Rocamora (least absolute shrinkage and selection operator-optical coherence tomography), Russo, and Reinstein recommending the correct ICL size in instances when Parkhurst, optimized white-to-white (WTW), and STAAR could not recommend a definitive ICL size was determined. Univariate and multivariate linear regression analysis was performed between preoperative measurements and vault.

Results:

The Kim, Rocamora, Russo, and Reinstein nomograms had significantly lower MAE of predicted vs actual postoperative vault than the KSV2 and Nakamura V3 nomograms. The Russo formula most frequently recommended the correct ICL size when the Parkhurst, Optimized WTW, and STAAR nomograms could not provide ICL size recommendations. At the 0.05 significance level, anterior chamber depth (ACD), ciliary body inner diameter (CBID), and pupil diameter were the parameters found to have significant correlation with postoperative vault.

Conclusions:

The Kim, Rocamora, Russo, and Reinstein nomograms were the most predictive of vault. Additionally, ACD, CBID, and pupil diameter were found to be significantly correlated with vault and should be considered for use in future ICL sizing nomograms.
Effect of Enhanced Recovery After Surgery on the Prognosis of Patients With Hip Fractures: A Systematic Review and Meta-Analysis
Authors: Zhu Ruiqi , Yang Fengqiao , Li Caiying , Zhu Hongxia , Lin Lu , Zhao Xin
Published: September 2023

BACKGROUND:

Hip fractures, predominantly occurring in the elderly, are a significant public health concern due to associated morbidity, disability, and mortality. Prolonged bed rest following the fracture often leads to complications, further threatening patient health. Enhanced recovery after surgery, a modern approach to postoperative care, is being explored for its potential to improve outcomes and quality of life in hip fracture patients.

OBJECTIVE:

This study investigates the impact of enhanced recovery after surgery on hip fracture patients.

METHODS:

In this systematic review, we addressed the PICO question: Does the enhanced recovery after surgery program reduce 1-year mortality, readmissions, and postoperative pain and improve Harris Hip Score compared with traditional care in elderly hip fracture patients? We searched key databases and gray literature and analyzed outcomes through a meta-analysis using RevMan, Stata, and the Newcastle–Ottawa Scale for quality assessment.

RESULTS:

Nine studies involving 10,359 patients were included. Compared with the control group, the enhanced recovery after surgery group showed significant reduction in length of stay (mean difference [MD] = −2.00; 95% confidence interval [CI] [−2.87, −1.14]; p < .0001) and overall complication rate (risk ratio [RR] = 0.76; 95% CI [0.67, 0.85]; p < .0001), with a lower delirium rate (RR = 0.42; 95% CI [0.26, 0.68]; p = .004). No significant differences were observed in Harris Hip Score, pain score, 1-year mortality, readmission rate, or incidences of urinary tract infection, respiratory tract infection, and deep vein thrombosis.

CONCLUSION:

Enhanced recovery after surgery is associated with reduced length of stay, complication rate, and delirium rate in hip fracture patients.
Longitudinal Patient Outcomes in Chronic Dizziness: A Scoping Review
Authors: Canturk Toros , Bery Anand K. , Piccoli David , Pyche Jacob , Czikk Daniel , Osborne Jake , Pearson Alexander , Bhatt Chirayu , Shin John , Chow Linda , Azzi Jayson Lee , Tohme Angelina , Caulley Lisa , Lelli Daniel , Tse Darren
Published: September 2023

Background

Chronic dizziness can cause significant functional impairment. Outcome measures used in this patient population have not been examined systematically. Consequently, providers lack consensus on the ideal outcome measures to assess the impact of their interventions.

Objective and Methods

We conducted a scoping review to summarize existing literature on outcomes in chronic dizziness (with a minimum of 6 mo of patient follow-up). Among other details, we extracted and analyzed patient demographics, medical condition(s), and the specific outcome measures of each study.

Results

Of 19,426 articles meeting the original search terms, 416 met final exclusion after title/abstract and full-text review. Most studies focused on Ménière's disease (75%) and recurrent benign paroxysmal positional vertigo (21%). The most common outcome measures were hearing (62%) and number of attacks by American Academy of Otolaryngology–Head & Neck Surgery criteria (60%). A minority (35%) looked formally at quality-of-life metrics (Dizziness Handicap Index or other).

Conclusions

Ménière's disease and benign paroxysmal positional vertigo are overrepresented in literature on outcome assessment in chronic dizziness. Objective clinical measures are used more frequently than quality-of-life metrics. Future work is needed to identify the optimal outcome measures that reflect new knowledge about the most common causes of chronic dizziness (including persistent postural-perceptual dizziness and vestibular migraine) and consider what is most important to patients.
Comparison of the Omron HeartGuide to the Welch Allyn ProBP 3400 blood pressure monitor
Authors: Harfmann Brianna D. , Neph Sylvia E. , Gardner Mason M. , Plouffe Audrey A. , Vranish Jennifer R. , Montoye Alexander H.K.
Published: September 2023

Hypertension affects approximately 100 million U.S. adults and is the leading single contributing risk factor to all-cause mortality. Accurate blood pressure (BP) measurement is essential in the treatment of BP, and a number of devices exist for monitoring. Recently, a new watch-type design was released, the Omron HeartGuide (BP8000), with claims to provide clinically accurate BP measurement while also tracking activity and sleep similar to smart watches. The aim of this research was done in two studies: (1) evaluation of the HeartGuide device for measurement of resting BP and heart rate (HR); and (2) assessment of the HeartGuide for BP, HR, step-counting and sleep monitoring during activities of daily living. Study 1 compared the Omron HeartGuide to the previously validated Welch Allyn ProBP 3400 following a modified version of the Universal Standard for validation of BP measuring devices set by the AAMI/ESH/ISO. While resting HR measured by the HeartGuide was similar to Welch Allyn measures, both systolic and diastolic BP were significantly lower (P≤0.001), with differences of 10.4 (11.1) and 3.2 (10.0) mmHg, respectively. Study 2 compared HeartGuide measures to Welch Allyn measures for BP, HR, steps and sleep during various body positions (supine, seated, standing), physiological stressors (cold pressor test, lower body submersion, exercise), and free-living. The HeartGuide significantly underestimated BP though provided accurate HR during most conditions. It also significantly underestimated steps, but reported sleep measures similar to those subjectively reported. Based on the significant differences between the HeartGuide and Welch Allyn, our data indicate the HeartGuide is not a suitable replacement for existing BP monitors.
Ambulatory blood pressure monitoring in pediatric patients with sickle cell anemia
Authors: Guerrero Tinoco Gustavo Adolfo , Espitaleta Vergara Zilac , Daniels García Maria José , Domínguez-Vargas Alex
Published: September 2023

Introduction

Sickle cell anemia (SCA) is a hemoglobinopathy presenting severe endothelial damage associated with increased prevalence of hypertension (HTN). Few studies have used ambulatory blood pressure monitoring (ABPM) in pediatric patients with SCA. The aim of this study was to characterize the ABPM profile in children with SCA.

Methods

A retrospective cross-sectional study was conducted on all subjects <18 years of age with SCA who presented at a medical reference center in the city of Cartagena, Colombia. Anthropometric, clinical laboratory, treatment, and ABPM parameters, including ambulatory arterial stiffness index (AASI) were registered.

Results

The study included 79 patients, of these, 23 (29%) children had normal BP, 49 (62%) had abnormal BP and 7 (9%) had HTN. Mean age was 10.5 ± 3.6 years and 44 (56%) cases were male. Forty-eight (60%) patients had pre-HTN. Masked HTN was present in 6 (8%) patients. One (1%) had ambulatory HTN, and another one (1%) had white coat HTN. The HTA group exhibited significantly higher systolic BP and diastolic BP compared to the other groups in 24-hour BP readings, daytime BP, and night-time BP ABPM parameters (P < 0.05), except for daytime DBP (P = 0.08). Mean AASI was 0.4 ± 0.2. The HTN group had the highest AASI value compared to the other groups (P = 0.006).

Conclusion

Significant alterations in ABPM parameters are frequently observed in pediatric patients with SCA. The incorporation of ABPM, along with the assessment of AASI, is recommended for a comprehensive evaluation of cardiovascular and renal risk in SCA patients.
Virological and immunological correlates of HIV posttreatment control after temporal antiretroviral therapy during acute HIV infection
Authors: van Paassen Pien M. , van Pul Lisa , van der Straten Karlijn , Buchholtz Ninée V.J.E. , Grobben Marloes , van Nuenen Ad C. , van Dort Karel A. , Boeser-Nunnink Brigitte D. , van den Essenburg Mo D. , Burger Judith A. , van Luin Matthijs , Jurriaans Suzanne , Sanders Rogier W. , Swelsen Wendy T. , Symons Jori , Klouwens Michelle J. , Nijhuis Monique , van Gils Marit J. , Prins Jan M. , de Bree Godelieve J. , Kootstra Neeltje A.
Published: September 2023

Objective:

People with HIV rarely control viral replication after cessation of antiretroviral therapy (ART). We present a person with HIV with extraordinary posttreatment control (PTC) for over 23 years after temporary ART during acute HIV infection (AHI) leading to a new insight in factors contributing to PTC.

Design/methods:

Viral reservoir was determined by HIV qPCR, Intact Proviral DNA Assay, and quantitative viral outgrowth assay. Viral replication kinetics were determined in autologous and donor PBMC. IgG levels directed against HIV envelope and neutralizing antibodies were measured. Immune phenotyping of T cells and HIV-specific T-cell responses were analyzed by flow cytometry.

Results:

The case presented with AHI and a plasma viral load of 2.7 million copies/ml. ART was initiated 2 weeks after diagnosis and interrupted after 26 months. Replicating virus was isolated shortly after start ART. At 18 years after treatment interruption, HIV-DNA in CD4+ T cells and low levels of HIV-RNA in plasma (<5 copies/ml) were detectable. Stable HIV envelope glycoprotein-directed IgG was present during follow-up, but lacked neutralizing activity. Strong antiviral CD8+ T-cell responses, in particular targeting HIV-gag, were detected during 25 years follow-up. Moreover, we found a P255A mutation in an HLA-B∗44 : 02 restricted gag-epitope, which was associated with decreased replication.

Conclusion:

We describe an exceptional case of PTC, which is likely associated with sustained potent gag-specific CD8+ T-cell responses in combination with a replication attenuating escape mutation in gag. Understanding the initiation and preservation of the HIV-specific T-cell responses could guide the development of strategies to induce HIV control.
What Are the Ready-to-Use Endoscope Channels Hiding?
Authors: Garcia Naiara Bussolotti , Oliveira Adriana Cristina de
Published: September 2023

Contamination due to failures or omissions in the reprocessing steps of gastrointestinal endoscopes is common in clinical practice. Ensuring the proper execution of each step is a challenge for reprocessing personnel. This cross-sectional study was conducted in an endoscopy setting between March and May 2021. We performed interviews about reprocessing practices, analyzed the life history of the equipment, and performed inspections through a borescope video of gastrointestinal endoscope channels that were stored and ready for use. A borescope is a complementary tool used to validate endoscope reprocessing, evaluate the internal visualization of channels, and identify changes that can compromise the safety of its use, which are often not detected in the leak test. Thirteen biopsy channels from stored gastrointestinal endoscopes were inspected. We found that 85% had stains and grooves, 69% contained moisture, and 46% had debris. There was at least one noncompliance issue in all of the channels inspected.
Negative Pressure Wound Therapy for Patients With Complicated Mucocutaneous Separation Following Ileal Conduit Urinary Diversion
Authors: Ding Jiarong , Zhu Yiqi , Ge Huaqiang , Chen Hui , Wang Liangmei , Xie Shangxun , Zhang Shiwei , Deng Yongming , Yang Rong , Guo Hongqian
Published: September 2023

BACKGROUND:

Mucocutaneous separation (MCS) is one of the early stomal complications of ileal conduit diversion after radical cystectomy. It can result in abdominal infection and sepsis, prolonging patient recovery. Negative pressure wound therapy (NPWT) has been widely used for abdominal wounds after orthopedic and burn surgery. This case series describes its use in complicated MCS and ostomy retraction after ileal conduit diversion.

CASES:

We describe a case series of 3 patients with moderate to severe MCS with and without infection after robot-assisted radical cystectomy with ileal conduit diversion. Our patients were treated with NPWT to avoid infection and create a satisfactory environment for healing MCS. After 2 to 4 weeks of NPWT, all 3 patients had normal micturition function with no additional peristomal wounds or complications.

CONCLUSION:

Negative pressure wound therapy may be used in the management of complicated MCS after ileal conduit diversion.
Social Vulnerability and Firearm Violence: Geospatial Analysis of 5 US Cities
Authors: Polcari Ann M , Slidell Mark B , Hoefer Lea E , Henry Marion CW , Zakrison Tanya L , Rogers Selwyn O , Benjamin Andrew J
Published: September 2023

Background:

Firearm violence is now endemic to certain U.S. neighborhoods. Understanding factors that impact a neighborhood’s susceptibility to firearm violence is crucial for prevention. Using a nationally standardized measure to characterize community-level firearm violence risk has not been broadly studied but could enhance prevention efforts. Thus, we sought to examine the association between firearm violence and the social, structural, and geospatial determinants of health, as defined by the Social Vulnerability Index (SVI).

Study Design:

In this cross-sectional study, we merged 2018 SVI data on census tract with 2015-2021 shooting incidents from Baltimore (BAL), Chicago (CHI), Los Angeles (LA), New York City (NYC), and Philadelphia (PHL). We used negative binomial regression to associate the SVI with shooting incidents per 1,000 people in a census tract. Moran’s I statistics were used for geospatial analysis.

Results:

We evaluated 71,296 shooting incidents across 4,415 census tracts. Fifty-five percent of shootings occurred in 9.4% of census tracts. In all cities combined, a decile rise in SVI resulted in a 37% increase in shooting incidents (P<.001). A similar relationship existed in each city: 30% increase in BAL (P<.001), 50% in CHI (P<.001), 28% in LA (P<.001), 34% in NYC (P<.001), and 41% in PHL (P<.001). Shootings were highly clustered within the most vulnerable neighborhoods.

Conclusion:

In five major U.S. cities, firearm violence was concentrated in neighborhoods with high social vulnerability. A tool such as the SVI could be used to inform prevention efforts by directing resources to communities most in need and identifying factors on which to focus these programs and policies.
Extending susceptible-infectious-recovered-susceptible epidemics to allow for gradual waning of immunity
Authors: El Khalifi Mohamed , Britton Tom
Published: September 2023

Susceptible-infectious-recovered-susceptible (SIRS) epidemic models assume that individual immunity wanes in one leap, from complete immunity to complete susceptibility. For many diseases immunity on the contrary wanes gradually, something that has become even more evident during COVID-19 pandemic where also recently infected have a reinfection risk, and booster vaccines are given to increase immunity. Here, a novel mathematical model is presented allowing for the gradual decay of immunity following linear or exponential waning functions. The two new models and the SIRS model are compared assuming all three models have the same cumulative immunity. When no intervention is put in place, we find that the long-term prevalence is higher for the models with gradual waning. If aiming for herd immunity by continuous vaccination, it is shown that larger vaccine quantities are required when immunity wanes gradually compared with results obtained from the SIRS model, and this difference is the biggest for the most realistic assumption of exponentially waning of immunity. For parameter choices fitting to COVID-19, the critical amount of vaccine supply is about 50% higher if immunity wanes linearly, and more than 150% higher when immunity wanes exponentially, when compared with the classic SIRS epidemic model.
Fluid–structure interactions of bristled wings: the trade-off between weight and drag
Authors: Luna Lin Yuexia , Pezzulla Matteo , Reis Pedro M.
Published: September 2023

The smallest flying insects often have bristled wings resembling feathers or combs. We combined experiments and three-dimensional numerical simulations to investigate the trade-off between wing weight and drag generation. In experiments of bristled strips, a reduced physical model of the bristled wing, we found that the elasto-viscous number indicates when reconfiguration occurs in the bristles. Analysis of existing biological data suggested that bristled wings of miniature insects lie below the reconfiguration threshold, thus avoiding drag reduction. Numerical simulations of bristled strips showed that there exist optimal numbers of bristles that maximize the weighted drag when the additional volume due to the bristles is taken into account. We found a scaling relationship between the rescaled optimal numbers and the dimensionless bristle length. This result agrees qualitatively with and provides an upper bound for the bristled wing morphological data analysed in this study.
Thermotaxis in an apolar, non-neuronal animal
Authors: Zhong Grace , Kroo Laurel , Prakash Manu
Published: September 2023

Neuronal circuits are hallmarks of complex decision-making processes in the animal world. How animals without neurons process information and respond to environmental cues promises a new window into studying precursors of neuronal control and origin of the nervous system as we know it today. Robust decision making in animals, such as in chemotaxis or thermotaxis, often requires internal symmetry breaking (such as anterior–posterior (AP) axis) provided naturally by a given body plan of an animal. Here we report the discovery of robust thermotaxis behaviour in
Trichoplax adhaerens
, an early-divergent, enigmatic animal with no anterior–posterior symmetry breaking (apolar) and no known neurons or muscles. We present a quantitative and robust behavioural response assay in
Placozoa
, which presents an apolar flat geometry. By exposing
T. adhaerens
to a thermal gradient under a long-term imaging set-up, we observe robust thermotaxis that occurs over timescale of hours, independent of any circadian rhythms. We quantify that
T. adhaerens
can detect thermal gradients of at least 0.1°C cm
−1
. Positive thermotaxis is observed for a range of baseline temperatures from 17°C to 22.5°C, and distributions of momentary speeds for both thermotaxis and control conditions are well described by single exponential fits. Interestingly, the organism does not maintain a fixed orientation while performing thermotaxis. Using natural diversity in size of adult organisms (100 µm to a few millimetres), we find no apparent size-dependence in thermotaxis behaviour across an order of magnitude of organism size. Several transient receptor potential (TRP) family homologues have been previously reported to be conserved in metazoans, including in
T. adhaerens
. We discover naringenin, a known TRPM3 antagonist, inhibits thermotaxis in
T. adhaerens
. The discovery of robust thermotaxis in
T. adhaerens
provides a tractable handle to interrogate information processing in a brainless animal. Understanding how divergent marine animals process thermal cues is also critical due to rapid temperature rise in our oceans.
Spider dynamics under vertical vibration and its implications for biological vibration sensing
Authors: Wu Jun , Miller Thomas E. , Cicirello Alice , Mortimer Beth
Published: September 2023

Often overlooked, vibration transmission through the entire body of an animal is an important factor in understanding vibration sensing in animals. To investigate the role of dynamic properties and vibration transmission through the body, we used a modal test and lumped parameter modelling for a spider. The modal test used laser vibrometry data on a tarantula, and revealed five modes of the spider in the frequency range of 20–200 Hz. Our developed and calibrated model took into account the bounce, pitch and roll of the spider body and bounce of all the eight legs. We then performed a parametric study using this calibrated model, varying factors such as mass, inertia, leg stiffness, damping, angle and span to study what effect they had on vibration transmission. The results support that some biomechanical parameters can act as physical constraints on vibration sensing. But also, that the spider may actively control some biomechanical parameters to change the signal intensity it can sense. Furthermore, our analysis shows that the parameter changes in front and back legs have a greater influence on whole system dynamics, so may be of particular importance for active control mechanisms to facilitate biological sensing functions.
The prelude to industrial whaling: identifying the targets of ancient European whaling using zooarchaeology and collagen mass-peptide fingerprinting
Authors: van den Hurk Youri , Sikström Fanny , Amkreutz Luc , Bleasdale Madeleine , Borvon Aurélia , Ephrem Brice , Fernández-Rodríguez Carlos , Gibbs Hannah M. B. , Jonsson Leif , Lehouck Alexander , Cedeira Jose Martínez , Meng Stefan , Monge Rui , Moreno Marta , Nabais Mariana , Nores Carlos , Pis-Millán José Antonio , Riddler Ian , Schmölcke Ulrich , Segschneider Martin , Speller Camilla , Vretemark Maria , Wickler Stephen , Collins Matthew , Nadeau Marie-Josée , Barrett James H.
Published: September 2023

Taxonomic identification of whale bones found during archaeological excavations is problematic due to their typically fragmented state. This difficulty limits understanding of both the past spatio-temporal distributions of whale populations and of possible early whaling activities. To overcome this challenge, we performed zooarchaeology by mass spectrometry on an unprecedented 719 archaeological and palaeontological specimens of probable whale bone from Atlantic European contexts, predominantly dating from
ca
3500 BCE to the eighteenth century CE. The results show high numbers of Balaenidae (many probably North Atlantic right whale (
Eubalaena glacialis
)) and grey whale (
Eschrichtius robustus
) specimens, two taxa no longer present in the eastern North Atlantic. This discovery matches expectations regarding the past utilization of North Atlantic right whales, but was unanticipated for grey whales, which have hitherto rarely been identified in the European zooarchaeological record. Many of these specimens derive from contexts associated with mediaeval cultures frequently linked to whaling: the Basques, northern Spaniards, Normans, Flemish, Frisians, Anglo-Saxons and Scandinavians. This association raises the likelihood that early whaling impacted these taxa, contributing to their extirpation and extinction. Much lower numbers of other large cetacean taxa were identified, suggesting that what are now the most depleted whales were once those most frequently used.
Rat movements reflect internal decision dynamics in an evidence accumulation task
Authors: Kane Gary A. , Senne Ryan A. , Scott Benjamin B.
Published: September 2023

Perceptual decision-making involves multiple cognitive processes, including accumulation of sensory evidence, planning, and executing a motor action. How these processes are intertwined is unclear; some models assume that decision-related processes precede motor execution, whereas others propose that movements reflecting on-going decision processes occur before commitment to a choice. Here we develop and apply two complementary methods to study the relationship between decision processes and the movements leading up to a choice. The first is a free response pulse-based evidence accumulation task, in which stimuli continue until choice is reported. The second is a motion-based drift diffusion model (mDDM), in which movement variables from video pose estimation constrain decision parameters on a trial-by-trial basis. We find the mDDM provides a better model fit to rats’ decisions in the free response accumulation task than traditional DDM models. Interestingly, on each trial we observed a period of time, prior to choice, that was characterized by head immobility. The length of this period was positively correlated with the rats’ decision bounds and stimuli presented during this period had the greatest impact on choice. Together these results support a model in which internal decision dynamics are reflected in movements and demonstrate that inclusion of movement parameters improves the performance of diffusion-to-bound decision models.

Highlights

Development and validation of a free response pulse-based accumulation task for rats

Response times are well described by drift diffusion models

Incorporating movement data into diffusion models improves inference of latent decisions variables

Rats weight sensory evidence most strongly prior to movement
Compartmentalized SARS-CoV-2 replication in upper versus lower respiratory tract after intranasal inoculation or aerosol exposure
Authors: Fischer Robert J , Bushmaker Trenton , Williamson Brandi N. , Pérez-Pérez Lizzette , Feldmann Friederike , Lovaglio Jamie , Scott Dana , Saturday Greg , Feldmann Heinz , Munster Vincent J. , de Wit Emmie , van Doremalen Neeltje
Published: September 2023

Non-human primate models are essential for the development of vaccines and antivirals against infectious diseases. Rhesus macaques are a widely utilized infection model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We compared cellular tropism and virus replication in rhesus macaques inoculated with SARS-CoV-2 via the intranasal route, or via exposure to aerosols. Intranasal inoculation results in replication in the upper respiratory tract and limited lower respiratory tract involvement, whereas exposure to aerosols results in infection throughout the respiratory tract. In comparison to multi-route inoculation, the intranasal and aerosol inoculation routes result in reduced SARS-CoV-2 replication in the respiratory tract.
Identification of a human hematopoietic stem cell subset that retains memory of inflammatory stress
Authors: Zeng Andy G.X. , Nagree Murtaza S. , Jakobsen Niels Asger , Shah Sayyam , Murison Alex , Cheong Jin-Gyu , Turkalj Sven , Lim Isabel N.X. , Jin Liqing , Araújo Joana , Aguilar-Navarro Alicia G. , Parris Darrien , McLeod Jessica , Kim Hyerin , Lee Ho Seok , Zhang Lin , Boulanger Mason , Wagenblast Elvin , Flores-Figueroa Eugenia , Wang Bo , Schwartz Gregory W. , Shultz Leonard D. , Josefowicz Steven Z. , Vyas Paresh , Dick John E. , Xie Stephanie Z.
Published: September 2023

Inflammation activates many blood cell types, driving aging and malignancy. Yet, hematopoietic stem cells (HSCs) survive a lifetime of infection to sustain life-long blood production. To understand HSC adaptation to inflammation, we developed xenograft inflammation-recovery models and performed single cell multiomics on isolated human HSC. Two transcriptionally and epigenetically distinct HSC subsets expressing canonical HSC programs were identified. Only one showed sustained transcriptional and epigenetic changes after recovery from inflammatory treatments. This HSC inflammatory memory (HSC-iM) program is enriched in memory T cells and HSCs from recovered COVID-19 patients. Importantly, HSC-iM accumulates with age and with clonal hematopoiesis. Overall, heritable molecular alterations in a subset of human HSCs, an adaptation to long-term inflammatory stress, may predispose to heightened age-related risk of blood cancer and infection.

One-Sentence Summary

Inflammation across a lifetime rewires human HSCs to produce a distinct HSC subset with both beneficial and deleterious fitness consequences.
Guidelines For Rigorous Evaluation of Clinical LLMs For Conversational Reasoning
Authors: Johri Shreya , Jeong Jaehwan , Tran Benjamin A. , Schlessinger Daniel I. , Wongvibulsin Shannon , Cai Zhuo Ran , Daneshjou Roxana , Rajpurkar Pranav
Published: September 2023

The integration of Large Language Models (LLMs) like GPT-4 and GPT-3.5 into clinical diagnostics has the potential to transform patient-doctor interactions. However, the readiness of these models for real-world clinical application remains inadequately tested. This paper introduces the Conversational Reasoning Assessment Framework for Testing in Medicine (CRAFT-MD), a novel approach for evaluating clinical LLMs. Unlike traditional methods that rely on structured medical exams, CRAFT-MD focuses on natural dialogues, using simulated AI agents to interact with LLMs in a controlled, ethical environment. We applied CRAFT-MD to assess the diagnostic capabilities of GPT-4 and GPT-3.5 in the context of skin diseases. Our experiments revealed critical insights into the limitations of current LLMs in terms of clinical conversational reasoning, history taking, and diagnostic accuracy. Based on these findings, we propose a comprehensive set of guidelines for future evaluations of clinical LLMs. These guidelines emphasize realistic doctor-patient conversations, comprehensive history taking, open-ended questioning, and a combination of automated and expert evaluations. The introduction of CRAFT-MD marks a significant advancement in LLM testing, aiming to ensure that these models augment medical practice effectively and ethically.
Systematic identification of disease-causing promoter and untranslated region variants in 8,040 undiagnosed individuals with rare disease
Authors: Martin-Geary Alexandra C , Blakes Alexander J M , Dawes Ruebena , Findlay Scott D , Lord Jenny , Walker Susan , Talbot-Martin Jonathan , Wieder Nechama , D’Souza Elston N , Fernandes Maria , Hilton Sarah , Lahiri Nayana , Campbell Christopher , Jenkinson Sarah , DeGoede Christian G E L , Anderson Emily R , Burge Christopher B. , Sanders Stephan J , Ellingford Jamie , Baralle Diana , Banka Siddharth , Whiffin Nicola
Published: September 2023

Background

Both promoters and untranslated regions (UTRs) have critical regulatory roles, yet variants in these regions are largely excluded from clinical genetic testing due to difficulty in interpreting pathogenicity. The extent to which these regions may harbour diagnoses for individuals with rare disease is currently unknown.

Methods

We present a framework for the identification and annotation of potentially deleterious proximal promoter and UTR variants in known dominant disease genes. We use this framework to annotatede novovariants (DNVs) in 8,040 undiagnosed individuals in the Genomics England 100,000 genomes project, which were subject to strict region-based filtering, clinical review, and validation studies where possible. In addition, we performed region and variant annotation-based burden testing in 7,862 unrelated probands against matched unaffected controls.

Results

We prioritised eleven DNVs and identified an additional variant overlapping one of the eleven. Ten of these twelve variants (82%) are in genes that are a strong match to the individual’s phenotype and six had not previously been identified. Through burden testing, we did not observe a significant enrichment of potentially deleterious promoter and/or UTR variants in individuals with rare disease collectively across any of our region or variant annotations.

Conclusions

Overall, we demonstrate the value of screening promoters and UTRs to uncover additional diagnoses for previously undiagnosed individuals with rare disease and provide a framework for doing so without dramatically increasing interpretation burden.
Multimodal structural neuroimaging data unveil data-driven subtypes of treatment-resistant depression
Authors: Colombo Federica , Calesella Federico , Bravi Beatrice , Fortaner-Uyà Lidia , Monopoli Camilla , Tassi Emma , Carminati Matteo , Zanardi Raffaella , Bollettini Irene , Poletti Sara , Brambilla Paolo , Serretti Alessandro , Maggioni Eleonora , Fabbri Chiara , Benedetti Francesco , Vai Benedetta
Published: September 2023

Background

An estimated 30% of Major Depressive Disorder (MDD) patients exhibit resistance to conventional antidepressant treatments. Identifying reliable biomarkers of treatment-resistant depression (TRD) represents a major goal of precision psychiatry, which is hampered by the clinical and biological heterogeneity underlying MDD.

Methods

To parse heterogeneity and uncover biologically-driven subtypes of MDD, we applied an unsupervised data-driven framework to stratify 102 MDD patients on their neuroimaging signature, including extracted measures of cortical thickness, grey matter volumes, and white matter fractional anisotropy. Our novel analytical pipeline integrated different machine learning algorithms to harmonize neuroimaging data, perform data dimensionality reduction, and provide a stability-based relative clustering validation. The obtained clusters were then characterized for TRD, history of childhood trauma and different profiles of depressive symptoms.

Results

Our results indicated two different clusters of patients, differentiable with 67% of accuracy: 1) one cluster (n=59) was associated with a higher proportion of TRD compared to the other, and higher scores of energy-related depressive symptoms, history of childhood abuse and emotional neglect; this cluster showed a widespread reduction in cortical thickness and volumes, along with fractional anisotropy in the right superior fronto-occipital fasciculus, stria terminalis, and corpus callosum; 2) the second cluster (n=43) was associated with cognitive and affective depressive symptoms and thicker cortices and wider volumes compared to the other.

Discussion

Our stratification of MDD patients based on structural neuroimaging identified clinically-relevant subgroups of TRD with specific symptomatic and childhood trauma profiles, which are informative for tailoring personalized and more effective interventions of treatment resistance.