bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental Analysis of Bubble Behavior and Critical Heat Flux During Pool Boiling on Vertical Circular Tubes
Authors: Pattanayak Bikash , Kothadia Hardik B.
Published: July 2023

The heat transfer during pool boiling incorporates a higher rate of heat dissipation capability at low-temperature differences. This technique is widely used in the nuclear industry for thermal management. In this study, the effect of tube diameter and length on critical heat flux (CHat atmospheric conditions in saturated water during pool boiling) is analyzed. The tubes of SS 304 are kept in the vertical orientation. The diameter of the tubes ranges from 1.2 mm to 9 mm. The experiments are performed with tubes having lengths varying from 50 mm to 1000 mm. It has been noted that tubes of smaller diameter show a greater magnitude of critical heat flux (CHF) for the given length. Compared to other tubes, the magnitude of CHF for a 1.2 mm diameter is higher. For a given diameter, a longer tube is found to have lower CHF than the ones having lesser length. The variation in the CHF magnitude is negligible for tubes with a diameter of more than 2.5 mm beyond a length of 200 mm. The location of occurrence of CHF is near the bottom end of the vertical tube. The study illustrates the behavior of bubble nucleation for various tube dimensions and heat fluxes. The inception and detachment of bubbles for different tubes are analyzed. The pool boiling regime is categorized and studied basing the behavior of the incepted and departed bubble while maintaining uniform heat flux. A mathematical relation that empirically accounts for the effect of tube dimensions , i.e., length and diameter on pool boiling CHF is proposed. The experimental CHF data obtained during pool boiling are tabulated toward contributing to the CHF databank.
Excitation of a Separated Flow by a Series of Protuberances Near the Leading Edge of a Model Aerofoil
Authors: Singh Pradeep , Sarkar S.
Published: July 2023

This article documents the manifestation of a shear layer under the excitation of a series of hemispherical protuberances near the leading edge of a constant-thickness airfoil. The experiments are performed at a Reynolds number of 1.6 × 105 based on the chord length and inlet velocity, where freestream turbulence is 1.2%. The hotwire and particle image velocimetry data are analyzed to appreciate the flow feature, illustrating the growth of perturbations, vortex dynamics, intermittency, and spectral response. A laminar separation bubble (LSB) appears near the leading edge for a smooth surface, and the shear layer is inviscidly unstable. The evolution of the shear layer significantly changes with a series of protuberances. The breakdown of the shear layer occurs almost immediately, triggering local turbulence resulting in a considerable reduction of the bubble length. However, a separation bubble of varying spanwise lengths is formed in this case. Although the power spectra of velocity fluctuations reveal the selective amplification of frequencies even with protuberances, the immediate augmentation of turbulence followed by faster decay suggests the transient growth of turbulence. The study has documented insight into features of a separation bubble subjected to leading-edge perturbations and might influence future studies on separation control over an airfoil.
Preparing to Land: Hamstring Preactivation Is Higher in Females and Is Inhibited by Fatigue
Authors: Phillips David Alan , Buckalew Bridgette Rae , Keough Bridget , Alencewicz Jacklyn Stephanie
Published: July 2023

The hamstring plays an important role in reducing loads born by the anterior cruciate ligament. As anterior cruciate ligament injuries occur rapidly after ground contact, how the hamstring is activated prior to landing can influence injury risk. The purpose was to determine sex-related differences in hamstring activation immediately before landing and the effect of fatigue on “preactivation.” Twenty-four participants (13 males and 11 females, age = 24.3 [6.5] y, mass = 72.2 [19.3] kg, height = 169 [9.7] cm) participated in this study. Participants completed a drop-vertical jump protocol before and after a lower body fatigue protocol. Hamstring electromyography (EMG) amplitude at 5 periods prior to landing, peak vertical ground reactions forces (in newtons/body weight), rate of loading (in body weight/second), and landing error scoring system were measured. Females had higher EMG amplitude before and after fatigue (P < .024), with decreased EMG amplitude for both sexes after fatigue (P = .025). There was no change on vertical ground reaction force, rate of loading, or landing error scoring system. Males and females demonstrated similar landing performance before and after fatigue but have different hamstring neuromuscular coordination strategies. The acute reduction in hamstring EMG amplitude following fatigue may increase loading on the anterior cruciate ligament.
Fighting/Fat: Fighting Game Characters and the Emptiness of Video Game Fatness
Authors: Harper Todd
Published: July 2023

The fatness of fat characters in screen media, video games included, is well understood on an aesthetic level. However, this research asks: Is there a mechanical dimension to the fatness of these characters? Fighting games, with their need for common toolsets among playable characters, offer a useful ground to explore that question. While the characters in this study did not exhibit a “mechanical fatness,” they do reveal that certain combinations of aesthetic fatness with gameplay mechanics may offer a potential site of resistance to the pervasive fatphobic tropes present in video games.
Rescuing β cells
Authors: Baek Amy E.
Published: July 2023

Loss of phosphatidylinositol transfer protein alpha underlies pancreatic β cell failure.
Fault-related sanctuaries of Mycenae (Greece): The Shaft Grave Circle A
Authors: Piccardi Luigi
Published: July 2023

Mycenae, one of the most important cities and sacred sites of antiquity in Greece, was built on a tectonic horst uplifted by active normal faults, and both faults show geologic evidence of recent coseismic slip. The Lion Gate fault, affecting the west slope of Mycenae, is described here through geological and archaeoseismological investigation. The tectonic offset since the Pliocene−Pleistocene sequence is 13−14 m. A 4−5-m-high scarp of the major splay of this fault, well preserved inside the Shaft Grave Circle A, exhibits tectonic geomorphological aspects typical of recent surface faulting.

Mycenae experienced two earthquakes in ∼60 yr during its climax, one around 1250 B.C. and the other around 1190 B.C. Seismic damage at Shaft Grave Circle A was found to have occurred on more than one occasion. One event occurred with the earthquake of 1190 B.C., or more likely with a much later one, which cut the circular parapet. Heavy damages were also registered with the earthquake of 1250 B.C. An episode of surface faulting appears to have occurred shortly before the early graves were created in Shaft Grave Circle A (late seventeenth century B.C., Middle/Late Helladic period).

The integration of available data suggests that the cults at Mycenae, particularly at Shaft Grave Circle A, deliberately chose specific sites or traits of the seismic fault as the central hub of their main sanctuaries. This occurrence was the result of a deliberate choice dictated by the fact that those sites along the fault trace were considered to be sacred and believed to be gateways to Hades.
Anaplastic bone lymphoma presenting as isolated back pain
Authors: Cefai Erika , Montanaro Gabriella , Mercieca Cecilia
Published: July 2023

A previously healthy man in his late 20s presented with a 4-week history of insidious back pain and raised inflammatory markers. Various specialists were involved in his care including general physicians, orthopaedic surgeons and rheumatologists. After numerous investigations including imaging and two bone biopsies, an unexpected diagnosis of anaplastic large cell lymphoma emerged. This case illustrates the importance of investigating back pain with red flags thoroughly using different imaging modalities and where indicated a bone biopsy.
The global health and care worker compact: evidence base and policy considerations
Authors: Friedman Eric A , Bickford Robert , Bjork Charles , Campbell James , Cometto Giorgio , Finch Alexandra , Kane Catherine , Wetter Sarah , Gostin Lawrence
Published: July 2023

Background

During the COVID-19 pandemic, and recognising the sacrifice of health and care workers alongside discrimination, violence, poor working conditions and other violations of their rights, health and safety, in 2021 the World Health Assembly requested WHO to develop a global health and care worker compact, building on existing normative documentation, to provide guidance to ‘protect health and care workers and safeguard their rights’.

Methods

A review of existing international law and other normative documents was conducted. We manually searched five main sets of international instruments: (1) International Labour Organization conventions and recommendations; (2) WHO documents; (3) United Nations (UN) human rights treaties and related documents; (4) UN Security Council and General Assembly resolutions and (5) the Geneva Conventions and Additional Protocols. We included only legal or other normative documents with a global or regional focus directly addressing or relevant to health and care workers or workers overall.

Results

More than 70 documents met our search criteria. Collectively, they fell into four domains, within which we identified 10 distinct areas: (1) preventing harm, encompassing (A) occupational hazards, (B) violence and harassment and (C) attacks in situations of fragility, conflict and violence; (2) inclusivity, encompassing (A) non-discrimination and equality; (3) providing support, encompassing (A) fair and equitable remuneration, (B) social protection and (C) enabling work environments and (4) safeguarding rights, encompassing (A) freedom of association and collective bargaining and (B) whistle-blower protections and freedom from retaliation.

Discussion

A robust legal and policy framework exists for supporting health and care workers and safeguarding their rights. Specific human rights, the right to health overall, and other binding and non-binding legal documents provide firm grounding for the compact.

However, these existing commitments are not being fully met. Implementing the compact will require more effective governance mechanisms and new policies, in partnership with health and care workers themselves.
Substantial increase in stillbirth rate during the COVID-19 pandemic: results from a population-based study in the Indian state of Bihar
Authors: Dandona Rakhi , Kumar G Anil , Akbar Md , Dora S Siva Prasad , Dandona Lalit
Published: July 2023

Introduction

We report on the stillbirth rate (SBR) and associated risk factors for births during the COVID-19 pandemic, and change in SBR between prepandemic (2016) and pandemic periods in the Indian state of Bihar.

Methods

Births between July 2020 and June 2021 (91.5% participation) representative of Bihar were listed. Stillbirth was defined as fetal death with gestation period of ≥7 months where the fetus did not show any sign of life. Detailed interviews were conducted for all stillbirths and neonatal deaths, and for 25% random sample of surviving live births. We estimated overall SBR, and during COVID-19 peak and non-peak periods per 1000 births. Multiple logistic regression models were run to assess risk factors for stillbirth. The change in SBR for Bihar from 2016 to 2020–2021 was estimated.

Results

We identified 582 stillbirths in 30 412 births with an estimated SBR of 19.1 per 1000 births (95% CI 17.7 to 20.7); SBR was significantly higher in private facility (38.4; 95% CI 34.3 to 43.0) than in public facility (8.6; 95% CI 7.3 to 10.1) births, and for COVID-19 peak (21.2; 95% CI 19.2 to 23.4) than non-peak period (16.3; 95% CI 14.2 to 18.6) births. Pregnancies with the last pregnancy trimester during the COVID-19 peak period had 40.4% (95% CI 10.3% to 70.4%) higher SBR than those who did not. Risk factor associations for stillbirths were similar between the COVID-19 peak and non-peak periods, with gestation age of <8 months with the highest odds of stillbirth followed by referred deliveries and deliveries in private health facilities. A statistically significant increase of 24.3% and 68.9% in overall SBR and intrapartum SBR was seen between 2016 and 2020–2021, respectively.

Conclusions

This study documented an increase in SBR during the COVID-19 pandemic as compared with the prepandemic period, and the varied SBR based on the intensity of the COVID-19 pandemic and by the place of delivery.
Exploring participant attrition in a longitudinal follow-up of older adults: the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton cohort
Authors: Okpara Chinenye , Adachi Jonathan , Papaioannou Alexandra , Ioannidis George , Thabane Lehana
Published: July 2023

Objective

We explored the magnitude of attrition, its pattern and risk factors for different forms of attrition in the cohort from the Global Longitudinal Study of Osteoporosis in Women.

Design

Prospective cohort study.

Setting

Participants were recruited from physician practices in Hamilton, Ontario.

Participants

Postmenopausal women aged ≥55 years who had consulted their primary care physician within the last 2 years.

Outcome measures

Time to all-cause, non-death, death, preventable and non-preventable attrition.

Results

All 3985 women enrolled in the study were included in the analyses. The mean age of the cohort was 69.4 (SD: 8.9) years. At the end of the follow-up, 30.2% (1206/3985) of the study participants had either died or were lost to follow-up. The pattern of attrition was monotone with most participants failing to return after a missed survey. The different types of attrition examined shared common risk factors including age, smoking and being frail but differed on factors such as educational level, race, hospitalisation, quality of life and being prefrail.

Conclusion

Attrition in this ageing cohort was selective to some participant characteristics. Minimising potential bias associated with such non-random attrition would require targeted measures to achieve maximum possible follow-rates among the high-risk groups identified and dealing with specific reasons for attrition in the study design and analysis.
PakSurg 1: determining the epidemiology and risk factors of surgical site infections in Pakistan—a multicentre, prospective cohort study
Authors:   PakSurg Collaborative
Published: July 2023

Introduction

Surgical site infections (SSIs) are among the the most common postoperative complications, despite being highly preventable. Multiple studies have explored the incidence and risk factors of SSIs globally. However, nationally representative data capable of informing evidence-based guidelines remain limited in Pakistan. Hence, the aim of this study is to identify the incidence and risk factors of developing SSIs following surgery and to explore existing SSI prevention practices in Pakistan.

Methods and analysis

This study is a multicentre, prospective cohort study across various sites in Pakistan. All consecutive adult patients undergoing inpatient elective surgery in a 1 month patient recruitment window from one or more of the nine eligible subspecialties will be included in the study. Patients with preoperative infections, emergency surgeries or intraoperative mortality are to be excluded. The following surgical subspecialties are included: breast surgery, cardiac surgery, colorectal surgery, cranial surgery, general surgery, obstetrics and gynaecology, orthopaedics surgery, spine surgery and vascular surgery. Each mini-team of up to three collaborators can select one of the nine subspecialties and a 1 month patient recruitment window from 20 September 2022 to 31 March 2023. Multiple mini-teams from the same sites can recruit patients across the same subspecialty in distinct patient recruitment windows. Additionally, multiple mini-teams from the same sites can recruit patients across different subspecialties in the same or distinct patient recruitment windows. The primary outcome is 30 day SSIs. Secondary outcomes include 30 day antibiotic-resistant SSIs, organ-space infections, other healthcare associated infections, reinterventions and all-cause mortality.

Ethics and dissemination

Approval was received by the Aga Khan University (AKU) Ethics Review Committee (ERC) and the National Bioethics Committee (NBC) Pakistan. The results from this study will be disseminated by the steering committee in journal publications, conference presentations and on other academic platforms. Evidence-based guidelines that result from these data will be disseminated to all surgical care providers in Pakistan through national networks.
Improving resource utilisation in SLE drug development through innovative trial design
Authors: Garces Sandra , Karis Elaine , Merrill Joan T , Askanase Anca D , Kalunian Kenneth , Mo May , Milmont Cassandra E
Published: July 2023

SLE is a complex autoimmune disease with considerable unmet need. Numerous clinical trials designed to investigate novel therapies are actively enrolling patients straining limited resources and creating inefficiencies that increase enrolment challenges. This has motivated investigators developing novel drugs and treatment strategies to consider innovative trial designs that aim to improve the efficiency of generating evidence; these strategies propose conducting fewer trials, involving smaller numbers of patients, while maintaining scientific rigour in safety and efficacy data collection and analysis. In this review we present the design of two innovative phase IIb studies investigating efavaleukin alfa and rozibafusp alfa for the treatment of SLE which use an adaptive study design. This design was selected as a case study, investigating efavaleukin alfa, in the Food and Drug Administration’s Complex Innovative Trial Design Pilot Program. The adaptive design approach includes prospectively planned modifications at predefined interim timepoints. Interim assessments of futility allow for a trial to end early when the investigational therapy is unlikely to provide meaningful treatment benefits to patients, which can release eligible patients to participate in other—potentially more promising—trials, or seek alternative treatments. Response-adaptive randomisation allows randomisation ratios to change based on accumulating data, in favour of the more efficacious dose arm(s), while the study is ongoing. Throughout the trial the placebo arm allocation ratio is maintained constant. These design elements can improve the statistical power in the estimation of treatment effect and increase the amount of safety and efficacy data collected for the optimal dose(s). Furthermore, these trials can provide the required evidence to potentially serve as one of two confirmatory trials needed for regulatory approval. This can reduce the need for multiple phase III trials, the total patient requirements, person-exposure risk, and ultimately the time and cost of investigational drug development programmes.
Mathematical modelling of micropolar thermoelastic problem with nonlocal and hyperbolic two-temperature based on Moore–Gibson–Thompson heat equation
Authors: Kumar Rajneesh , Kaushal Sachin , Kochar Arun
Published: July 2023

The aim of this article is to study a problem of thermomechanical deformation in a homogeneous, isotropic, micropolar thermoelastic half-space based on the Moore–Gibson–Thompson heat equation under the influence of nonlocal and hyperbolic two-temperature (HTT) parameters. The problem is formulated for the considered model by reducing the governing equations into 2D and then converting to dimensionless form. Laplace transform and Fourier transform techniques are employed to obtain the system of differential equations. In the transformed domain, the physical quantities like displacement components, stresses, thermodynamic temperature, and conductive temperature are calculated under the specific types of normal force and thermal source at the boundary surface. A numerical inversion technique is used to recuperate the equations in the physical domain to exhibit the influence of nonlocal and HTT in the form of graphs. Particular cases of interest are also discussed in the present problem. The present study finds applications in a wide range of problems in engineering and sciences, control theory, vibration mechanics, and continuum mechanics.
A proof of concept for matchete: an automated tool for matching effective theories
Authors: Fuentes-Martín Javier , König Matthias , Pagès Julie , Thomsen Anders Eller , Wilsch Felix
Published: July 2023

Studying the impact of new-physics models on low-energy observables necessitates matching to effective field theories at the relevant mass thresholds. We introduce the first public version of , a computer tool for matching weakly-coupled models at one-loop order. It uses functional methods to directly compute all matching contributions in a manifestly gauge-covariant manner, while simplification methods eliminate redundant operators from the output. We sketch the workings of the program and provide examples of how to match simple Standard Model extensions. The package, documentation, and example notebooks are publicly available at https://gitlab.com/matchete/matchete.
Korean Red Ginseng Relieves Inflammation and Modulates Immune Response Induced by Pseudo-Type SARS-CoV-2
Authors: Kwon Ki Woong , Kim Ji Won , Moon Seokoh , Yoon Jeong Hyeon , Youn Soo-Hyun , Hyun Sun Hee , Kim Han Gyung , Kweon Dae-Hyuk , Cho Jae Youl
Published: July 2023

Few studies have reported the therapeutic effects of Korean red ginseng (KRG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the positive effects of KRG on other viruses have been reported and the effects of KRG on pulmonary inflammatory diseases have also been studied. Therefore, this study investigated the therapeutic effects of KRG-water extract (KRG-WE) in a pseudo-type SARS-CoV-2 (PSV)-induced lung injury model. Constructing the pseudovirus, human angiotensin-converting enzyme 2 (hACE2) transgenic mice were infected via intranasal injection that had been orally administered with KRG-WE for six weeks. After 7-days post infection (dpi), the antiviral effects of KRG-WE were confirmed, followed by real-time polymerase chain reaction (PCR), western blot analysis, flow cytometric analysis, and an enzyme-linked immunoassay (ELISA). KRG-WE significantly inhibited an increase in immunoglobulin caused by PSV. Furthermore, KRG-WE effectively suppressed alveolar macrophages (AMs) inside the lungs and helped normalize the population of other immune cells. In addition, virus-induced gene expression and inflammatory signals such as nuclear factor-kappa B and other upstream molecules were downregulated. Moreover, KRG-WE also normalized gene expression and protein activity in the spleen. In conclusion, KRG-WE reduced AMs, normalized the immune response, and decreased the expression of inflammatory genes and activation of signaling pathway phosphorylation, thereby exhibiting anti-inflammatory effects and attenuating lung damage.
Pressure and flow transition over NACA airfoil with thrust optimized parabolic arcs
Authors: Devi Supriya , Nagaraja K. V. , Verma Amit
Published: July 2023

This paper presents an accurate prediction of surface drag, pressure coefficient and flow transition around a symmetric airfoil design through the implementation of finite element discretization. Skin friction coefficient has been analyzed at different Reynolds number and at various angles of attack for NACA0012 airfoil design. The transition from laminar to turbulent flow significantly impacts the separation of the boundary layer and skin friction of the airfoil, ultimately affecting its aerodynamic characteristics. The pressure distribution around the surface of NACA0012 has also been computed at several Reynolds number and different attack angles using higher order triangular meshes. Numerical evaluation of these results when compared with the experimental results demonstrates superior accuracy with higher-order finite element mesh. The investigation carried out by higher-order element meshing approach is based on the subparametric transformation of parabolic arcs of triangular element curved at one side. Moreover, the high aspect ratio meshes obtained during discretization of airfoil design have been considered for the analysis. The investigation has yielded results that closely align with experimental data, demonstrating excellent performance. The current efficient analysis of pressure and flow transition is beneficial in interpreting aerodynamic performance and flow simulations for aerospace and computational fluid dynamics applications.
Dynamic pull-down theory for the Toda oscillator
Authors: Feng Guang-Qing
Published: July 2023

The pull-down instability is a newly found phenomenon for oscillators with even nonlinearities. It is a seemingly periodic motion, which will suddenly pull down after some cycles. The phenomenon is similar to the pull-in instability in the micro-electromechanical systems. This paper restudies the well-known Toda oscillator, which is considered to be in periodic motion. Its pseudo-periodic property is studied and the pull-down instability is found for the first time ever. To this end, this paper establishes a variational principle for the Toda oscillator, and the criterion for prediction of the pull-down motion is obtained. A simple formulation to calculate the pull-down instability is proved and verified through examples. Furthermore, an approximate frequency formula is obtained by Li–He modified homotopy perturbation method.
Research on Green and Low-Carbon Development Path of China’s Automotive Industry
Authors: ZHAO Dongchang , ZHAO Mingnan , SUN Xin , ZHANG Hongjie , LIU Huanran , WU Jinlong , LEI Zhenlu , LI Jia’ang , QIAN Bing , LU Linfeng , LIN Yu , CHANG Wei
Published: July 2023

China’s automotive industry has been dedicated to a series of carbon-reduction efforts and has strived for comprehensive green and low-carbon transformation in order to achieve carbon peaking and carbon neutrality goals. On the basis of automobiles’ whole life-cycle (WLC) carbon emission accounting, this paper calculates life-cycle carbon emissions per vehicle, proposes green and low-carbon development path for China’s automotive industry, quantifies and analyzes implicated carbon-reduction potential, and puts forth suggestions for high-quality green and low-carbon development of China’s automotive industry. The first is to establish a sound standard and data management system; the second is to promote research, development and application of low-carbon materials and low-carbon technologies; the third is to accelerate the pace of fostering a new consumption model in the automotive industry. The research results can further support national policy-making regarding carbon emissions, promote corporations’ research, development and application of low-carbon technologies, encourage green and low-carbon consumption, and lead the automotive industry to achieve WLC neutrality.
A Computational Inflection for Scientific Discovery
Authors: Hope Tom , Downey Doug , Weld Daniel S. , Etzioni Oren , Horvitz Eric
Published: July 2023

Enabling researchers to leverage systems to overcome the limits of human cognitive capacity.
Sharpening Your Tools
Authors: Garfinkel Simson , Stewart Jon
Published: July 2023

Updating bulk_extractor for the 2020s.
Computer-Assisted Proofs Take on Fluid Flow
Authors: Monroe Don
Published: July 2023

Researchers use computers to show that equations can "blow up."
The Carbon Footprint of Artificial Intelligence
Authors: Kirkpatrick Keith
Published: July 2023

Looking for ways to cut the release of greenhouse gases attributable to AI use, at a time that usage is very likely to grow.
Improving Computing Education Research through Valuing Design
Authors: Shapiro R. Benjamin , DesPortes Kayla , DiSalvo Betsy
Published: July 2023

Exploring alternatives to existing research systems and methods.
Homelessness, Offending, Victimization, and Criminal Legal System Contact
Authors: McCarthy Bill , Hagan John
Published: July 2023

There is now a sizable literature on connections between homelessness, crime, and criminal legal system contact. We review studies on these relationships, focusing mostly on links between the adversity that often characterizes homelessness—the need for shelter, food, and income—and offending, victimization, and involvement with the criminal legal system. We concentrate on multivariate studies from the United States and Canada and consider research on youth and adults. We begin with a short discussion of some of the challenges of studying these relationships. We follow our review of research on homeless conditions with a summary of research that has used data from homeless samples to advance a broad array of explanations of crime; a collection that includes strain, routine activities and lifestyle exposure, differential association, social control, rational choice, life course, and criminal capital theories.
Ultra-High-Energy Gamma-Ray Astronomy
Authors: Cao Zhen , Chen Songzhan , Liu Ruoyu , Yang Ruizhi
Published: July 2023

Ultra-high-energy (UHE, >0.1 PeV) γ-ray astronomy is rapidly evolving into an expanding branch of γ-ray astronomy with the surprising discovery of 12 PeVatrons and the detection of a handful of photons above 1 PeV. Nearly all known celestial object types that have emissions in the TeV band are found also to emit UHE photons. UHE γ-rays have a well-defined horizon inside our Galaxy due to the absorption of infrared and cosmic microwave backgrounds in the Universe. In the last 30 years, traditional cosmic ray (CR) measurement techniques have enabled the detection of UHE γ-rays and opened the last observation window. For leptonic sources, UHE radiation is in the deep Klein–Nishina regime, which is largely suppressed. Therefore, UHE γ-ray detection will be helpful in locating and identifying hadronic radiation sources, tracing the historic pursuit for the origin of CRs around the knee of the spectrum. The Crab Nebula is the focus of attention with measured photon emissions up to 1 PeV. In the absence of hadronic processes, these emissions may indicate the existence of an extreme accelerator of e+ e−. Use of CR extensive air shower detection techniques broadens the field of view of the source observations, enabling measurement of UHE radiation surrounding the sources. These observations can probe the particle propagation inside and outside the accelerators and the subsequent injection/escape into the interstellar medium.
Liraglutide pretreatment attenuates sepsis-induced acute lung injury
Authors: Baer Brandon , Putz Nathan D. , Riedmann Kyle , Gonski Samantha , Lin Jason , Ware Lorraine B. , Toki Shinji , Peebles R. Stokes , Cahill Katherine N. , Bastarache Julie A.
Published: July 2023

In this study, pretreatment with liraglutide, a commonly used diabetes medication and glucagon-like peptide-1 (GLP-1) receptor agonist, attenuated sepsis-induced acute lung injury in a two-hit mouse model (sepsis + hyperoxia). Septic mice who received the drug were less sick, lived longer, and displayed reduced lung inflammation, edema, and injury. These therapeutic effects were not dependent on weight loss. GLP-1 receptor activation may hold promise as a new treatment strategy for sepsis-induced acute respiratory distress syndrome.
New insights into the natural history of bronchopulmonary dysplasia from proteomics and multiplexed immunohistochemistry
Authors: Dylag Andrew M. , Misra Ravi S. , Bandyopadhyay Gautam , Poole Cory , Huyck Heidie L. , Jehrio Matthew G. , Haak Jeannie , Deutsch Gail H. , Dvorak Carly , Olson Heather M. , Paurus Vanessa , Katzman Philip J. , Woo Jongmin , Purkerson Jeffrey M. , Adkins Joshua N. , Mariani Thomas J. , Clair Geremy C. , Pryhuber Gloria S.
Published: July 2023

We provide new insights into the natural history of bronchopulmonary dysplasia in donor human lungs after the neonatal intensive care unit hospitalization. This study provides new insights into how the proteome and histopathology of BPD changes in early childhood, uncovering novel pathways for future study.
Chitosan Biopolymer and Its Nanocomposites: Emerging Material as Adsorbent in Wastewater Treatment
Authors: Suyambulingam Indran , Gangadhar Lekshmi , Sana Siva Sankar , Divakaran Divya , Siengchin Suchart , Kurup Lekshmi A. , Iyyadurai Jenish , Albert Bernad Noble K. E.
Published: July 2023

Water pollution is a global issue because of potentially lethal toxins. Polymeric nanomaterials are making their way into water treatment processes and are being utilized to efficiently remove a variety of pollutants. Polymeric nanomaterials are a popular option for a solution because they have a high adsorption capacity and a high surface charge. Nanocomposites have recently come to the attention of those working in the field of water treatment in order to more effectively remove contaminants. Polymeric composites are based on biopolymers and are being developed. These all quickly reached the industrial standards because of their low impact on the natural world. Chitosan is one of the biopolymers that are used extensively. Moreover, it is one of the most highly preferred biopolymers. It is simple to scale up and is readily available. The incorporation of nanomaterials into the biopolymer enables better control over the shape, size, and morphology of the particle, as well as an increase in the efficiency with which contaminants are removed. This is an excellent review that examines recent developments in the formation of chitosan-based polymeric nanocomposites and their performance in removing various contaminants including heavy metals, dyes, pesticides, pharmaceutical waste, and radionuclides from water.
Figure S2 from De Novo and Histologically Transformed Small-Cell Lung Cancer Is Sensitive to Lurbinectedin Treatment Through the Modulation of EMT and NOTCH Signaling Pathways
Authors: Chakraborty Subhamoy , Coleman Charles , Manoj Parvathy , Demircioglu Deniz , Shah Nisargbhai , de Stanchina Elisa , Rudin Charles M. , Hasson Dan , Sen Triparna
Published: July 2023

Figure S2. Lurbinectedin sensitivity (IC50) correlation with MYC expression and changes in expression of NE markers.
Supplementary Table S3 from CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression
Authors: Kohlmeyer Jordan L. , Lingo Joshua J. , Kaemmer Courtney A. , Scherer Amanda , Warrier Akshaya , Voigt Ellen , Raygoza Garay Juan A. , McGivney Gavin R. , Brockman Qierra R. , Tang Amy , Calizo Ana , Pollard Kai , Zhang Xiaochun , Hirbe Angela C. , Pratilas Christine A. , Leidinger Mariah , Breheny Patrick , Chimenti Michael S. , Sieren Jessica C. , Monga Varun , Tanas Munir R. , Meyerholz David K. , Darbro Benjamin W. , Dodd Rebecca D. , Quelle Dawn E.
Published: July 2023

Supplementary Table S3. Cluster of differentiation (CD) markers used to delineate immune cell populations after gating on CD45+ live cells.
Supplementary Figure S6 from CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression
Authors: Kohlmeyer Jordan L. , Lingo Joshua J. , Kaemmer Courtney A. , Scherer Amanda , Warrier Akshaya , Voigt Ellen , Raygoza Garay Juan A. , McGivney Gavin R. , Brockman Qierra R. , Tang Amy , Calizo Ana , Pollard Kai , Zhang Xiaochun , Hirbe Angela C. , Pratilas Christine A. , Leidinger Mariah , Breheny Patrick , Chimenti Michael S. , Sieren Jessica C. , Monga Varun , Tanas Munir R. , Meyerholz David K. , Darbro Benjamin W. , Dodd Rebecca D. , Quelle Dawn E.
Published: July 2023

Supplementary Figure S6. Analysis of helper (CD4) and pan (CD3) T cells in combination therapysensitive versus combination therapy-resistant MPNSTs
Supplementary Figure S5 from CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression
Authors: Kohlmeyer Jordan L. , Lingo Joshua J. , Kaemmer Courtney A. , Scherer Amanda , Warrier Akshaya , Voigt Ellen , Raygoza Garay Juan A. , McGivney Gavin R. , Brockman Qierra R. , Tang Amy , Calizo Ana , Pollard Kai , Zhang Xiaochun , Hirbe Angela C. , Pratilas Christine A. , Leidinger Mariah , Breheny Patrick , Chimenti Michael S. , Sieren Jessica C. , Monga Varun , Tanas Munir R. , Meyerholz David K. , Darbro Benjamin W. , Dodd Rebecca D. , Quelle Dawn E.
Published: July 2023

Supplementary Figure S5. Evaluation of differentially expressed genes (DEGs) and tumor infiltrating immune cells (plasma cells and B cells) in drug-treated de novo MPNSTs.
Supplementary Figure S4 from CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression
Authors: Kohlmeyer Jordan L. , Lingo Joshua J. , Kaemmer Courtney A. , Scherer Amanda , Warrier Akshaya , Voigt Ellen , Raygoza Garay Juan A. , McGivney Gavin R. , Brockman Qierra R. , Tang Amy , Calizo Ana , Pollard Kai , Zhang Xiaochun , Hirbe Angela C. , Pratilas Christine A. , Leidinger Mariah , Breheny Patrick , Chimenti Michael S. , Sieren Jessica C. , Monga Varun , Tanas Munir R. , Meyerholz David K. , Darbro Benjamin W. , Dodd Rebecca D. , Quelle Dawn E.
Published: July 2023

Supplementary Figure S4. Predicted immune cell composition of human PNFs, ANNUBPs, and MPNSTs based on CIBERSORT analyses.
Supplementary Figure S3 from CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression
Authors: Kohlmeyer Jordan L. , Lingo Joshua J. , Kaemmer Courtney A. , Scherer Amanda , Warrier Akshaya , Voigt Ellen , Raygoza Garay Juan A. , McGivney Gavin R. , Brockman Qierra R. , Tang Amy , Calizo Ana , Pollard Kai , Zhang Xiaochun , Hirbe Angela C. , Pratilas Christine A. , Leidinger Mariah , Breheny Patrick , Chimenti Michael S. , Sieren Jessica C. , Monga Varun , Tanas Munir R. , Meyerholz David K. , Darbro Benjamin W. , Dodd Rebecca D. , Quelle Dawn E.
Published: July 2023

Supplementary Figure S3. Tumor growth kinetics of individual de novo MPNSTs during therapy
Supplementary Figure S1 from CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression
Authors: Kohlmeyer Jordan L. , Lingo Joshua J. , Kaemmer Courtney A. , Scherer Amanda , Warrier Akshaya , Voigt Ellen , Raygoza Garay Juan A. , McGivney Gavin R. , Brockman Qierra R. , Tang Amy , Calizo Ana , Pollard Kai , Zhang Xiaochun , Hirbe Angela C. , Pratilas Christine A. , Leidinger Mariah , Breheny Patrick , Chimenti Michael S. , Sieren Jessica C. , Monga Varun , Tanas Munir R. , Meyerholz David K. , Darbro Benjamin W. , Dodd Rebecca D. , Quelle Dawn E.
Published: July 2023

Supplementary Figure S1. Combination therapy co-targeting CDK4/6 and MEK acts synergistically against MPNST cells in vitro
Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients
Authors: Pascual Javier , Gil-Gil Miguel , Proszek Paula , Zielinski Christoph , Reay Alistair , Ruiz-Borrego Manuel , Cutts Rosalind , Ciruelos Gil Eva M. , Feber Andrew , Muñoz-Mateu Montserrat , Swift Claire , Bermejo Begoña , Herranz Jesus , Margeli Vila Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Liu Yuan , Fernandez-Garcia Daniel , Garcia-Murillas Isaac , Hubank Michael , Turner Nicholas C. , Martín Miguel
Published: July 2023

Purpose:

Prognostic and predictive biomarkers to cyclin-dependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA (ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy.

Experimental Design:

Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model.

Results:

201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms.

Conclusions:

We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor–positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted.
Colorectal Cancer Organoid–Stroma Biobank Allows Subtype-Specific Assessment of Individualized Therapy Responses
Authors: Farin Henner F. , Mosa Mohammed H. , Ndreshkjana Benardina , Grebbin Britta M. , Ritter Birgit , Menche Constantin , Kennel Kilian B. , Ziegler Paul K. , Szabó Lili , Bollrath Julia , Rieder Dietmar , Michels Birgitta E. , Kress Alena , Bozlar Müge , Darvishi Tahmineh , Stier Sara , Kur Ivan-Maximilano , Bankov Katrin , Kesselring Rebecca , Fichtner-Feigl Stefan , Brüne Bernhard , Goetze Thorsten O. , Al-Batran Salah-Eddin , Brandts Christian H. , Bechstein Wolf O. , Wild Peter J. , Weigert Andreas , Müller Susanne , Knapp Stefan , Trajanoski Zlatko , Greten Florian R.
Published: July 2023

In colorectal cancers, the tumor microenvironment plays a key role in prognosis and therapy efficacy. Patient-derived tumor organoids (PDTO) show enormous potential for preclinical testing; however, cultured tumor cells lose important characteristics, including the consensus molecular subtypes (CMS). To better reflect the cellular heterogeneity, we established the colorectal cancer organoid–stroma biobank of matched PDTOs and cancer-associated fibroblasts (CAF) from 30 patients. Context-specific phenotyping showed that xenotransplantation or coculture with CAFs improves the transcriptomic fidelity and instructs subtype-specific stromal gene expression. Furthermore, functional profiling in coculture exposed CMS4-specific therapeutic resistance to gefitinib and SN-38 and prognostic expression signatures. Chemogenomic library screening identified patient- and therapy-dependent mechanisms of stromal resistance including MET as a common target. Our results demonstrate that colorectal cancer phenotypes are encrypted in the cancer epithelium in a plastic fashion that strongly depends on the context. Consequently, CAFs are essential for a faithful representation of molecular subtypes and therapy responses ex vivo.

Significance:

Systematic characterization of the organoid–stroma biobank provides a resource for context dependency in colorectal cancer. We demonstrate a colorectal cancer subtype memory of PDTOs that is independent of specific driver mutations. Our data underscore the importance of functional profiling in cocultures for improved preclinical testing and identification of stromal resistance mechanisms.

This article is featured in Selected Articles from This Issue, p. 2109
Supplementary Table 1 from CCRL2 Expression by Specialized Lung Capillary Endothelial Cells Controls NK-cell Homing in Lung Cancer
Authors: Sozio Francesca , Schioppa Tiziana , Laffranchi Mattia , Salvi Valentina , Tamassia Nicola , Bianchetto-Aguilera Francisco M. , Tiberio Laura , Bonecchi Raffaella , Bosisio Daniela , Parmentier Marc , Bottazzi Barbara , Leone Roberto , Russo Eleonora , Bernardini Giovanni , Garofalo Stefano , Limatola Cristina , Gismondi Angela , Sciumè Giuseppe , Mantovani Alberto , Del Prete Annalisa , Sozzani Silvano
Published: July 2023

Supplementary Table 1
Supplementary Table S8 from Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit
Authors: Bulen Benjamin J. , Khazanov Nickolay A. , Hovelson Daniel H. , Lamb Laura E. , Matrana Marc , Burkard Mark E. , Yang Eddy Shih-Hsin , Edenfield William J. , Claire Dees Elizabeth , Onitilo Adedayo A. , Buchschacher Gary L. , Miller Alan M. , Parsons Benjamin M. , Wassenaar Timothy R. , Suga Jennifer M. , Siegel Robert D. , Irvin William , Nair Suresh , Slim Jennifer N. , Misleh Jamal , Khatri Jamil , Masters Gregory A. , Thomas Sachdev , Safa Malek M. , Anderson Daniel M. , Mowers Jonathan , Dusenbery Anna C. , Drewery Stephanie , Plouffe Komal , Reeder Travis , Vakil Hana , Patrias Lynnae , Falzetta Amanda , Hamilton Ryan , Kwiatkowski Kat , Johnson D. Bryan , Rhodes Daniel R. , Tomlins Scott A.
Published: July 2023

Supplementary Table S8 shows tumor mutation burden and Immunotherapy Response Score status by self -reported race in the Strata Clinical Molecular Database
Supplementary Table S6 from Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit
Authors: Bulen Benjamin J. , Khazanov Nickolay A. , Hovelson Daniel H. , Lamb Laura E. , Matrana Marc , Burkard Mark E. , Yang Eddy Shih-Hsin , Edenfield William J. , Claire Dees Elizabeth , Onitilo Adedayo A. , Buchschacher Gary L. , Miller Alan M. , Parsons Benjamin M. , Wassenaar Timothy R. , Suga Jennifer M. , Siegel Robert D. , Irvin William , Nair Suresh , Slim Jennifer N. , Misleh Jamal , Khatri Jamil , Masters Gregory A. , Thomas Sachdev , Safa Malek M. , Anderson Daniel M. , Mowers Jonathan , Dusenbery Anna C. , Drewery Stephanie , Plouffe Komal , Reeder Travis , Vakil Hana , Patrias Lynnae , Falzetta Amanda , Hamilton Ryan , Kwiatkowski Kat , Johnson D. Bryan , Rhodes Daniel R. , Tomlins Scott A.
Published: July 2023

Supplementary Table S6 shows the characteristics of the PD-L1 IHC cohort
Supplementary Table S2 from Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit
Authors: Bulen Benjamin J. , Khazanov Nickolay A. , Hovelson Daniel H. , Lamb Laura E. , Matrana Marc , Burkard Mark E. , Yang Eddy Shih-Hsin , Edenfield William J. , Claire Dees Elizabeth , Onitilo Adedayo A. , Buchschacher Gary L. , Miller Alan M. , Parsons Benjamin M. , Wassenaar Timothy R. , Suga Jennifer M. , Siegel Robert D. , Irvin William , Nair Suresh , Slim Jennifer N. , Misleh Jamal , Khatri Jamil , Masters Gregory A. , Thomas Sachdev , Safa Malek M. , Anderson Daniel M. , Mowers Jonathan , Dusenbery Anna C. , Drewery Stephanie , Plouffe Komal , Reeder Travis , Vakil Hana , Patrias Lynnae , Falzetta Amanda , Hamilton Ryan , Kwiatkowski Kat , Johnson D. Bryan , Rhodes Daniel R. , Tomlins Scott A.
Published: July 2023

Supplementary Table S2 shows the adjusted Cox proportional hazards models for real-world progression free survival and overall survival in the monotherapy validation cohort