bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fast and Simple Modification of Newton’s Method Avoiding Saddle Points
Authors: Truong Tuyen Trung , To Tat Dat , Nguyen Hang-Tuan , Nguyen Thu Hang , Nguyen Hoang Phuong , Helmy Maged
Published: July 2023

We propose in this paper New Q-Newton’s method. The update rule is conceptually very simple, using the projections to the vector subspaces generated by eigenvectors of positive (correspondingly negative) eigenvalues of the Hessian. The main result of this paper roughly says that if a sequence $$\{x_n\}$$

{

x
n

}

constructed by the method from a random initial point $$x_0$$

x
0

converges, then the limit point is a critical point and not a saddle point, and the convergence rate is the same as that of Newton’s method. A subsequent work has recently been successful incorporating Backtracking line search to New Q-Newton’s method, thus resolving the global convergence issue observed for some (non-smooth) functions. An application to quickly find zeros of a univariate meromorphic function is discussed, accompanied with an illustration on basins of attraction.
Equal Pay and the Equality Act 2010: An Accidental Paradox in Need of Change?
Authors: Hand James , Hooton Victoria
Published: July 2023

The approach in the United Kingdom to sex-based equal pay has for a long time been distinct from general sex discrimination and from equal pay based on other protected characteristics. This dichotomy allows for a greater focus on sex-based equal pay, in a distinct statutory regime, but also risks creating unnecessary, unintended and detrimental distinctions. This article outlines the different legislative approaches adopted in pursuit of related public policy goals regarding equality and explores, and suggests legislative and interpretative solutions to, a significant issue whereby problematic wording in the Equality Act 2010, and judicial interpretation of it, could unjustifiably leave sex-based claimants in a worse position than those with other protected characteristics with regard to both to injury to feelings and constructive dismissal.
A STEM Penalty from Affirmative Action Bans?
Authors: Mickey-Pabello David
Published: July 2023

The study investigates a tension between affirmative action scholars who hypothesize that affirmative action bans would increase underrepresented minority students’ STEM college completions and scholars who have empirically estimated declines. It also questions results that that find no existence of a STEM penalty (compared to non-STEM) caused by affirmative action bans and finds that a STEM penalty is likely, but varies from a very modest effect (using the Department of Homeland Security taxonomy) to a more substantial impact (using the National Science Foundation taxonomy). This study finds that many of the tensions between affirmative action scholars studying STEM are likely the product of model specification. It illustrates how the following have impacted the estimates: the period studied, the inclusion and exclusion of certain ban states, the measure of institutional selectivity, and most importantly, the taxonomy of STEM. Furthermore, this study builds upon prior studies by analyzing private schools and the shorter-term and longer-term impacts of the bans.
Review of Path-following Control Systems for Maritime Autonomous Surface Ships
Authors: Xu Haitong , Guedes Soares C.
Published: July 2023

A review presents the state-of-the-art path-following control systems for maritime autonomous surface ships, where the special focus is placed on the guidance subsystem and control subsystem. The path following control system is one of the basic requirements for autonomous ships since it guarantees that the ship can track the predefined path with small cross-track errors. The path following problem is firstly defined, and the cross-track error dynamics are derived from the kinematic equations of marine surface ships. The classical guidance laws are introduced, and the governing equations are also presented in this paper. A review of the guidance laws and controllers for the maritime autonomous surface ships has been carried out based on relevant journal and conference papers. Several important properties and characteristics, such as control structure, guidance law, control method, stability, environmental disturbance and vessel dynamics, are defined for the comparative analysis. Finally, the summary and a discussion on the most used technologies for the path following control of marine autonomous surface ships are presented and highlighted.
Optimality conditions and duality for E-differentiable multiobjective programming involving V-E-type I functions
Authors: Abdulaleem Najeeb , Treanţă Savin
Published: July 2023

In this paper, we introduce a new concept of sets and a new class of functions called $$\alpha$$
α
-E-invex sets and V-E-preinvex functions. Furthermore, a new concept of generalized convexity is introduced for (not necessarily) differentiable vector optimization problems. Namely, the concept of V-E-type I functions is defined for E-differentiable vector optimization problem. A number of sufficiency results are established under various types of (generalized) V-E-type I requirements. Moreover, several E-duality theorems in the sense of Mond–Weir are proved under appropriate (generalized) V-E-type I functions.
Inquiry-based mathematics education and attitudes towards mathematics: tracking profiles for teaching
Authors: Gómez-Chacón Inés M. , Bacelo Adrián , Marbán José M. , Palacios Andrés
Published: July 2023

Research on the relationships between the main constructs underlying inquiry-based learning is rarely reported in mathematics education research. Considering this as a complex problem which is worth to be investigated, the present study aims to provide some empirical evidences that might serve as an insight to support further investigations on the relationships between attitudes towards mathematics and inquiry-based learning approaches. Thus, this study adopts a descriptive research design where no variables are manipulated but observed and measured in order to identify changes depicted in data collection. An instructional design focusing on the nature of mathematical inquiry is carried out with the participation of 304 secondary and high school students, and a clustering approach is used to look at how participants are grouped around certain attitudinal profiles before and after such mathematical practice. The results show how the heterogeneity of attitudinal profiles present in the classroom evolves positively in terms of perceived usefulness of mathematics and mathematical self-concept as perception of competence in mathematics. This fact provides some basis that might be used for further research on the idea that certain forms of development in inquiry-based mathematics education (IBME) based on greater immersion in the nature and culture of mathematics can help students to improve their attitudes towards mathematics.
Patterning of Metal Halide Perovskite Thin Films and Functional Layers for Optoelectronic Applications
Authors: Lee Jin-Wook , Kang Seong Min
Published: July 2023

In recent years, metal halide perovskites have received significant attention as materials for next-generation optoelectronic devices owing to their excellent optoelectronic properties. The unprecedented rapid evolution in the device performance has been achieved by gaining an advanced understanding of the composition, crystal growth, and defect engineering of perovskites. As device performances approach their theoretical limits, effective optical management becomes essential for achieving higher efficiency. In this review, we discuss the status and perspectives of nano to micron-scale patterning methods for the optical management of perovskite optoelectronic devices. We initially discuss the importance of effective light harvesting and light outcoupling via optical management. Subsequently, the recent progress in various patterning/texturing techniques applied to perovskite optoelectronic devices is summarized by categorizing them into top-down and bottom-up methods. Finally, we discuss the perspectives of advanced patterning/texturing technologies for the development and commercialization of perovskite optoelectronic devices.
Levodopa-Carbidopa Intestinal Gel for Parkinson’s Disease over 11 years: One Center’s “Real-World” Experience
Authors: Vekhande Chetan , Hamed Moath , Tremain Genise , Mah Jennifer , Shetty Aakash , Lazarescu Adriana , Suchowersky Oksana
Published: July 2023

Background:

Levodopa-carbidopa intestinal gel (LCIG) therapy has been shown to be a safe and effective treatment for advanced Parkinson’s disease (PD). Limited data are available regarding long-term benefits and complications in Canada. Objective of the study was to review long-term experience and clinical outcomes in PD patients with LCIG therapy over 11 years in a multidisciplinary University clinic setting.

Methods:

Chart review was done on PD patients with LCIG from 2011 to 2022. Data collected: dosing, UPDRS-III motor scores, OFF times, hours with dyskinesias, MoCA, complications, discontinuation reasons, and nursing time requirements.

Results:

Thirty-three patients received LCIG therapy with a mean follow-up of 3.25±2.09 years. UPDRS-III scores showed reduction of 15% from baseline (mean 35.9) up to 4 years (mean 30.4). Daily OFF time improved from baseline (mean 7.1 ± 3.13 hours) up to 5 years (mean 3.3 ± 2.31 hours; −53.5%; p < 0.048), and dyskinesias remained stable. Nursing time averaged 22 hours per patient per year after PEG-J insertion and titration. Most common complications were PEG-J tube dislodgement and stoma site infection (0–3zero to three events/patient/year). Serious side effects were seen in four (12%) patients resulting in hospitalization and/or death. Nine patients (27.2%) discontinued the treatment due to lack of improved efficacy over oral therapy or development of dementia and 10 (30%) died of causes unrelated to LCIG infusion.

Conclusion:

Patients on LCIG showed improved motor function over 5-year follow-up. Serious complications were uncommon. Dedicated nursing time is required by LCIG-trained nurses in a multidisciplinary setting for optimum management.
Reportable infections following colon surgery in a large public healthcare system in New York City: The consequences of being a level 1 trauma center
Authors: Fornek Mary L. , Ata Subhan , Jimenez Edwin , Abdallah Marie , Sunny Subin , Lee Jennifer , Episcopia Briana , Roudnitsky Valery , Quale John
Published: July 2023

Objectives:

To examine differences in risk factors and outcomes of patients undergoing colon surgery in level 1 trauma centers versus other hospitals and to investigate the potential financial impact of these reportable infections.

Design:

Retrospective cohort study between 2015 and 2022.

Setting:

Large public healthcare system in New York City.

Participants:

All patients undergoing colon surgery; comparisons were made between (1) all patients undergoing colon surgery at the level 1 trauma centers versus patients at the other hospitals and (2) the nontrauma and trauma patients at the level 1 trauma centers versus the nontrauma patients at other hospitals.

Results:

Of 5,217 colon surgeries reported, 3,531 were at level 1 trauma centers and 1686 at other hospitals. Patients at level 1 trauma centers had significantly increased American Society of Anesthesiology (ASA) scores, durations of surgery, rates of delayed wound closure, and rates of class 4 wounds, resulting in higher SIRs (1.1 ± 0.15 vs 0.75 ± 0.18; P = .0007) compared to the other hospitals. Compared to the nontrauma patients at the other hospitals, both the nontrauma and trauma patients at the level 1 trauma centers had higher ASA scores, rates of delayed wound closure, and of class 4 wounds. The SIRs of the nontrauma patients (1.16 ± 1.29; P = .008) and trauma patients (1.26 ± 2.69; P = .066) at the level 1 trauma center were higher than the SIRs of nontrauma patients in the other hospitals (0.65 ± 1.18).

Conclusions:

Patients undergoing colon surgery at level 1 trauma centers had increased complexity of surgery compared to the patients in other hospitals. Until there is appropriate adjustment for these risk factors, the use of infections following colon surgery as a reportable quality measure should be re-evaluated.
On the onset of long-wavelength three-dimensional instability in the cylinder wake
Authors: Aleksyuk Andrey I. , Heil Matthias
Published: July 2023

We study the onset of the three-dimensional mode A instability in the near wake behind a circular cylinder. We show that long-wavelength perturbations organise in a time-shifting pattern such that the in-plane velocity in each streamwise slice corresponds to the base flow solution at shifted times. This observation introduces an additional unifying characteristic for certain mode A type instabilities. We then analyse the mechanisms which control the growth or decay of these perturbations and highlight the crucial role played by the tilting mechanism which operates via non-local interactions in a manner similar to Biot–Savart induction. We characterise its domain of influence using a Green's function-based approach which allows us to rationalise the non-trivial dependence of the growth rate on the spanwise wavenumber. We connect this behaviour to the subtle balance between the local growth of the perturbations as they are swept along by the flow and the feedback on the perturbations that are generated during the next period of the time-periodic base flow. Finally, we discuss generalisations of our findings to other types of flows.
ABELIAN GROUPS DEFINABLE IN p-ADICALLY CLOSED FIELDS
Authors: JOHNSON WILL , YAO NINGYUAN
Published: July 2023

Recall that a group G has finitely satisfiable generics (fsg) or definable f-generics (dfg) if there is a global type p on G and a small model

$M_0$

such that every left translate of p is finitely satisfiable in

$M_0$

or definable over

$M_0$

, respectively. We show that any abelian group definable in a p-adically closed field is an extension of a definably compact fsg definable group by a dfg definable group. We discuss an approach which might prove a similar statement for interpretable abelian groups. In the case where G is an abelian group definable in the standard model

$\mathbb {Q}_p$

, we show that

$G^0 = G^{00}$

, and that G is an open subgroup of an algebraic group, up to finite factors. This latter result can be seen as a rough classification of abelian definable groups in

$\mathbb {Q}_p$

.
Illusory intuitions: Challenging the claim of non-exclusivity
Authors: Handley Simon J. , Ghasemi Omid , Bialek Michal
Published: July 2023

A person who arrives at correct solutions via false premises is right and wrong simultaneously. Similarly, a person who generates “logical intuitions” through superficial heuristics can likewise be right and wrong at the same time. However, heuristics aren't guaranteed to deliver the logical solution, so the claim that system 1 can routinely produce the alleged system 2 response is unfounded.
Dual-process theory is Barbapapa
Authors: Tinghög Gustav , Koppel Lina , Västfjäll Daniel
Published: July 2023

The biggest benefit of dual-process theory lies in its role as a benchmark theory that, regardless of its empirical plausibility, serves as a starting point for better and more domain-specific models. In this sense, dual-process theory is the Barbapapa of psychological theory – a blob-shaped creature that can be reshaped and adapted to fit in the context of any human behavior.
Amah Activism: Domestic Servants and Decolonization in 1960s Malaysia and Singapore
Authors: Twomey Christina
Published: July 2023

The privatized nature of employment as a domestic servant is often inimical to collective action. Yet in the early 1960s there was significant trade union interest in the working conditions of female domestic servants in Singapore and Malaya. Studies of female domestic service in Malaya (later Malaysia) and Singapore are dominated by work focusing on Chinese-born servants before the Second World War, and migrant maids associated with economic transformation from the late 1970s. If scholarship on pre-war domestic servants leans toward an emphasis on agency, then studies of maids from the 1980s tend toward experiences of abjection. What of the intervening period, during the Cold War, when rapid decolonization introduced new factors into the demography, structure, and regulation of domestic service in Malaysia and Singapore? Did this provide opportunity for greater autonomy, mimic older colonial relationships, or herald new protections for domestic servants in the modern postcolonial state? The considerable historical literature devoted to the relationship between imperial power, colonialism, and domestic service rarely extends to the persistence and dynamics of domestic service in the era of decolonization between the 1950s and the 1970s, although it does explore the increasing feminization of the occupation. This article explores a confluence of factors—the politics of anticolonialism, economic dependence, and apprehension about the privacy of the home—that cohered in a controversy in the 1960s known as the “amah strike,” when female domestic servants in Singapore and Malaya threatened to walk off the job over a proposed change to their employment conditions.
Cold‐Season Methane Fluxes Simulated by GCP‐CH4 Models
Authors: Ito A. , Li T. , Qin Z. , Melton J. R. , Tian H. , Kleinen T. , Zhang W. , Zhang Z. , Joos F. , Ciais P. , Hopcroft P. O. , Beerling D. J. , Liu X. , Zhuang Q. , Zhu Q. , Peng C. , Chang K.‐Y. , Fluet‐Chouinard E. , McNicol G. , Patra P. , Poulter B. , Sitch S. , Riley W. , Zhu Q.
Published: July 2023

Cold‐season methane (CH4) emissions may be poorly constrained in wetland models. We examined cold‐season CH4 emissions simulated by 16 models participating in the Global Carbon Project model intercomparison and analyzed temporal and spatial patterns in simulation results using prescribed inundation data for 2000–2020. Estimated annual CH4 emissions from northern (>60°N) wetlands averaged 10.0 ± 5.5 Tg CH4 yr−1. While summer CH4 emissions were well simulated compared to in‐situ flux measurement observations, the models underestimated CH4 during September to May relative to annual total (27 ± 9%, compared to 45% in observations) and substantially in the months with subzero air temperatures (5 ± 5%, compared to 27% in observations). Because of winter warming, nevertheless, the contribution of cold‐season emissions was simulated to increase at 0.4 ± 0.8% decade−1. Different parameterizations of processes, for example, freezing–thawing and snow insulation, caused conspicuous variability among models, implying the necessity of model refinement.
The Role of Anomalous Transport in Long‐Term, Stream Water Chemistry Variability
Authors: Dentz Marco , Kirchner James W. , Zehe Erwin , Berkowitz Brian
Published: July 2023

We investigate the occurrence of anomalous (non‐Fickian) transport in an hydrological catchment system at kilometer scales and over a 36‐year period. Using spectral analysis, we examine the fluctuation scaling of long‐term time series measurements of a natural passive tracer (chloride), for rainfall and runoff. The scaling behavior can be described by a continuous time random walk (CTRW) based on a power‐law distribution of transition times, which indicates two distinct power‐law regimes in the distribution of overall travel times in the catchment. The CTRW provides a framework for assessing anomalous transport in catchments and its implications for water quality fluctuations.
Effects of the Hunga Tonga‐Hunga Ha'apai Eruption on MODIS‐Retrieved Sea Surface Temperatures
Authors: Jia Chong , Minnett Peter J.
Published: July 2023

The eruption of Hunga Tonga‐Hunga Ha'apai (HTHH) volcano on 15 January 2022 injected a great amount of H2O and a moderate amount of SO2 into the stratosphere, producing a pronounced and persistent sulfate aerosol layer centered around the mid‐stratosphere, mostly confined to Southern Hemisphere (SH) tropics. These aerosols affect the Moderate Resolution Imaging Spectroradiometer (MODIS) retrievals of sea surface temperature (SST) where negative biases reached −0.3 K and an annual mean of −0.1 K north of 40°S in the SH. The spatial and temporal evolutions of MODIS SST anomalies are presented. Radiative transfer simulations demonstrate the aerosol effect on MODIS SST retrievals by causing an additional brightness temperature (BT) deficit at 11 μm and a reduction in BT differences since the characteristic of spectral attenuation between 11 and 12 μm is opposite to that of H2O. A correction for HTHH aerosol effects in the retrieval algorithm is therefore desirable.
Resonant Waves Play an Important Role in the Increasing Heat Waves in Northern Hemisphere Mid‐Latitudes Under Global Warming
Authors: He Yang , Zhu Xiaoqian , Sheng Zheng , He Mingyuan
Published: July 2023

Extreme events have become more frequent in the Northern Hemisphere mid‐latitudes in recent decades, hugely impacting the ecosystem and society. The quasi‐resonance amplification (QRA) of planetary waves is considered one of the dynamic mechanisms leading to extreme weather. However, the specific impact of resonant waves caused by QRA on surface heat extremes is still an open issue. Here we show that the QRA of planetary waves leading to heat extremes is closely related to double jets, accompanied by the enhancement of atmospheric blocking and the weakening of planetary wave escaping into the stratosphere. Our results illustrate the important role of mid‐latitude planetary waves with zonal wavenumber m = 6–8 caused by QRA in the increasingly frequent heat waves in recent years, as it can increase the coverage area and occurrence frequency of heat extremes in mid‐latitudes and show a significant impact on preferred regions, especially in Eurasia.
Comparing Loon Superpressure Balloon Observations of Gravity Waves in the Tropics With Global Storm‐Resolving Models
Authors: Köhler Laura , Green Brian , Stephan Claudia C.
Published: July 2023

Superpressure balloons, which drift approximately on isopycnal surfaces, get displaced by gravity waves and are thus capable of detecting gravity wave signatures. The project Loon provides superpressure balloon data in the upper troposphere and lower stratosphere from 2011 to 2021. We compare Loon data from the 6 years of best data coverage with output of global storm‐resolving models from the DYnamics of the Atmospheric general circulation Modeled On Non‐hydrostatic Domains winter initiative in the tropics. We study the variance of the vertical velocity and, for the models, the gravity wave momentum flux as function of distance to closest convection. The models show large differences in the variance of the vertical wind velocity, which is crucial for calculating vertical gravity wave momentum fluxes. We find large differences between the models with respect to simulated convection, lateral propagation, and the wave background away from sources. We then sample balloons as models by optimizing the match of vertical wind distributions using a temporal low pass filter. The average distance the balloons travel during the optimum low pass filtering time turns out to correspond approximately to four times the model grid spacing. The functional dependence of the vertical velocity variance on distance to closest convection is similar between the models and the observations sampled as models. The robustness of this result across all models suggests that storm‐resolving models provide a useful resource for machine learning some characteristics of convectively generated gravity waves.
Experiments on Gravel‐Sand Transitions: Examination of Washload Deposition
Authors: Dingle Elizabeth H. , Venditti Jeremy G.
Published: July 2023

An abrupt transition in bed grain size occurs in river systems. Over a short downstream distance, often only a few channel widths, the bed surface fines from gravel (∼10 mm) to sand (∼1 mm). This is the gravel‐sand transition (GST), and it is the only abrupt downstream reduction in grain size within fluvial systems. There are several theories for the origin of the GST, including size‐selective deposition of bimodal grain size distributions and the rapid onset of washload deposition due to changes in particle suspension properties at shear velocities of ∼0.1 m/s. Here, we present a laboratory experiment examining changes in fluid and sediment dynamics across a GST. We developed a stable gravel bed reach that was just below the threshold of motion, then fed sand. We observed sand carried as washload in the gravel reach fall out of suspension, forming a sand bed and a stable GST. Shear velocity was 0.09–0.10 m/s upstream of the GST and <0.10 m/s downstream, consistent with the washload deposition hypothesis. We were then able to perturb the position of the GST by systematically varying discharge and/or sand supply, shifting it downstream with an increase in discharge or a reduction in sediment supply. A decrease in discharge or increase in sand supply caused upstream migration. Our observations support an abrupt change in washload transport conditions across a narrow range of shear velocities, consistent with the washload deposition theory and measurements taken across GSTs in natural river systems.
Update on Our Action Plan for Equity, Inclusion, and Diversity in Publishing at JGR: Biogeosciences
Authors: Xenopoulos Marguerite A. , Bond‐Lamberty Ben , Huntzinger Deborah , Desai Ankur R. , Feng Xiaojuan , Hammond William M. , Moore David J. P. , Peng Xuefeng , Sahagian Dork , Santin Cristina , Vargas Rodrigo , Wells Naomi S. , Wooden Paige
Published: July 2023

We made a commitment to better include underrepresented members of our community in the publication pipeline of JGR: Biogeosciences. This commitment consists of regular updates on our policies and practices, and concrete actions we intend to implement over the next year. So far, our progress to tackle biases and ensure equitable research in the biogeosciences has focused on improving diversity of our associate editor and reviewer pools, increasing awareness of unconscious bias in peer‐review, and promoting inclusion in global collaborations. In this update, we explore manuscript submissions and manuscript decisions by gender, and we present a pilot that aims to promote ethical and equitable global collaborations in resource‐poor settings. We end our editorial by presenting our next set of actions that we plan on completing over the next year, which include a more thorough analysis of reviewer demographics.
The role of Extracellular Genomic Materials (EGMs) in psychiatric disorders
Authors: Kurtulmuş Ayşe , Koçana Cemal Çağıl , Toprak Selin Fulya , Sözer Selçuk
Published: July 2023

Extracellular Genomic Materials (EGMs) are the nucleic acids secreted or released from all types of cells by endogenous or exogenous stimuli through varying mechanisms into the extracellular region and inevitably to all biological fluids. EGMs could be found as free, protein-bound, and/ or with vesicles. EGMs can potentially have immunophenotypic and/or genotypic characteristics of a cell of origin, travel to distant organs, and interact with the new microenvironment. To achieve all, EGMs might bi-directionally transit through varying membranes, including the blood–brain barrier. Such ability provides the transfer of any information related to the pathophysiological changes in psychiatric disorders in the brain to the other distant organ systems or vice versa. In this article, many aspects of EGMs have been elegantly reviewed, including their potential in diagnosis as biomarkers, application in treatment modalities, and functional effects in the pathophysiology of psychiatric disorders. The psychiatric disorders were studied under subgroups of Schizophrenia spectrum disorders, bipolar disorder, depressive disorders, and an autism spectrum disorders. EGMs provide a robust and promising tool in clinics for prognosis and diagnosis. The successful application of EGMs into treatment modalities might further provide encouraging outcomes for researchers and clinicians in psychiatric disorders.
Global disparities in patients with multiple myeloma: a rapid evidence assessment
Authors: Mateos Maria-Victoria , Ailawadhi Sikander , Costa Luciano J. , Grant Shakira J. , Kumar Lalit , Mohty Mohamad , Aydin Didem , Usmani Saad Z.
Published: July 2023

There are disparities in outcomes for patients with multiple myeloma (MM). We evaluated the influence of sociodemographic factors on global disparities in outcomes for patients with MM. This rapid evidence assessment (PROSPERO, CRD42021248461) followed PRISMA-P guidelines and used the PICOS framework. PubMed and Embase® were searched for articles in English from 2011 to 2021. The title, abstract, and full text of articles were screened according to inclusion/exclusion criteria. The sociodemographic factors assessed were age, sex, race/ethnicity, socioeconomic status, and geographic location. Outcomes were diagnosis, access to treatment, and patient outcomes. Of 84 articles included, 48 were US-based. Worldwide, increasing age and low socioeconomic status were associated with worse patient outcomes. In the US, men typically had worse outcomes than women, although women had poorer access to treatment, as did Black, Asian, and Hispanic patients. No consistent disparities due to sex were seen outside the US, and for most factors and outcomes, no consistent disparities could be identified globally. Too few studies examined disparities in diagnosis to draw firm conclusions. This first systematic analysis of health disparities in patients with MM identified specific populations affected, highlighting a need for additional research focused on assessing patterns, trends, and underlying drivers of disparities in MM.
Blast phase myeloproliferative neoplasm: contemporary review and 2024 treatment algorithm
Authors: Tefferi Ayalew , Alkhateeb Hassan , Gangat Naseema
Published: July 2023

Leukemic transformation in myeloproliferative neoplasms (MPN), also referred to as “blast-phase MPN”, is the most feared disease complication, with incidence estimates of 1–4% for essential thrombocythemia, 3–7% for polycythemia vera, and 9–13% for primary myelofibrosis. Diagnosis of MPN-BP requires the presence of ≥20% circulating or bone marrow blasts; a lower level of excess blasts (10–19%) constitutes “accelerated phase” disease (MPN-AP). Neither “intensive” nor “less intensive” chemotherapy, by itself, secures long-term survival in MPN-BP. Large-scale retrospective series have consistently shown a dismal prognosis in MPN-BP, with 1- and 3-year survival estimates of <20% and <5%, respectively. Allogeneic hematopoietic stem cell transplant (AHSCT) offers the possibility of a >30% 3-year survival rate and should be pursued, ideally, while the patient is still in chronic phase disease. The value of pre-transplant bridging chemotherapy is uncertain in MPN-AP while it is advised in MPN-BP; in this regard, we currently favor combination chemotherapy with venetoclax (Ven) and hypomethylating agent (HMA); response is more likely in the absence of complex/monosomal karyotype and presence of TET2 mutation. Furthermore, in the presence of an IDH mutation, the use of IDH inhibitors, either alone or in combination with Ven-HMA, can be considered. Pre-transplant clearance of excess blasts is desired but not mandated; in this regard, additional salvage chemotherapy is more likely to compromise transplant eligibility rather than improve post-transplant survival. Controlled studies are needed to determine the optimal pre- and post-transplant measures that target transplant-associated morbidity and post-transplant relapse.
Exposure to benzene and other hydrocarbons and risk of bladder cancer among male offshore petroleum workers
Authors: Shala Nita K. , Stenehjem Jo S. , Babigumira Ronnie , Liu Fei-Chih , Berge Leon A. M. , Silverman Debra T. , Friesen Melissa C. , Rothman Nathaniel , Lan Qing , Hosgood H. Dean , Samuelsen Sven O. , Bråtveit Magne , Kirkeleit Jorunn , Andreassen Bettina K. , Veierød Marit B. , Grimsrud Tom K.
Published: July 2023

Background

Occupational exposures constitute the second leading cause of urinary bladder cancer after tobacco smoking. Increased risks have been found in the petroleum industry, but high-quality exposure data are needed to explain these observations.

Methods

Using a prospective case-cohort design, we analysed 189 bladder cancer cases (1999–2017) and 2065 randomly drawn non-cases from the Norwegian Offshore Petroleum Workers cohort. Cases were identified in the Cancer Registry of Norway, while work histories (1965–1998) and lifestyle factors were recorded by questionnaire at baseline (1998). Occupational petroleum-related hydrocarbon exposures were assessed by expert-developed job-exposure matrices. Hazard ratios were estimated by weighted Cox-regressions, adjusted for age, tobacco smoking, education, and year of first employment, and with lagged exposures.

Results

Increased risks were found in benzene-exposed workers, either long-term exposure (≥18.8 years, HR = 1.89, 95% CI: 1.14–3.13;p-trend = 0.044) or high-level cumulative benzene exposure (HR = 1.60, 95% CI: 0.97–2.63;p-trend = 0.065), compared with the unexposed. Associations persisted with 20-year exposure lag. No associations were found with skin or inhalation exposure to crude oil, mineral oil (lubrication, hydraulics, turbines, drilling), or diesel exhaust.

Conclusions

The results suggest that exposures in the benzene fraction of the petroleum stream may be associated with increased bladder cancer risk.
Re-evaluation and re-analysis of 152 research exomes five years after the initial report reveals clinically relevant changes in 18%
Authors: Bartolomaeus Tobias , Hentschel Julia , Jamra Rami Abou , Popp Bernt
Published: July 2023

Iterative re-analysis of NGS results is not well investigated for published research cohorts of rare diseases. We revisited a cohort of 152 consanguineous families with developmental disorders (NDD) reported five years ago. We re-evaluated all reported variants according to diagnostic classification guidelines or our candidate gene scoring system (AutoCaSc) and systematically scored the validity of gene-disease associations (GDA). Sequencing data was re-processed using an up-to-date pipeline for case-level re-analysis. In 28/152 (18%) families, we identified a clinically relevant change. Ten previously reported (likely) pathogenic variants were re-classified as VUS/benign. In one case, the GDA (TSEN15) validity was judged as limited, and in five cases GDAs are meanwhile established. We identified 12 new disease causing variants. Two previously reported variants were missed by our updated pipeline due to alignment or reference issues. Our results support the need to re-evaluate screening studies, not only the negative cases but including supposedly solved ones. This also applies in a diagnostic setting. We highlight that the complexity of computational re-analysis for old data should be weighed against the decreasing re-testing costs. Since extensive re-analysis per case is beyond the resources of most institutions, we recommend a screening procedure that would quickly identify the majority (83%) of new variants.
Phase intensity nanoscope (PINE) opens long-time investigation windows of living matter
Authors: Cui Guangjie , Liu Yunbo , Zu Di , Zhao Xintao , Zhang Zhijia , Kim Do Young , Senaratne Pramith , Fox Aaron , Sept David , Park Younggeun , Lee Somin Eunice
Published: July 2023

Fundamental to all living organisms and living soft matter are emergent processes in which the reorganization of individual constituents at the nanoscale drives group-level movements and shape changes at the macroscale over time. However, light-induced degradation of fluorophores, photobleaching, is a significant problem in extended bioimaging in life science. Here, we report opening a long-time investigation window by nonbleaching phase intensity nanoscope: PINE. We accomplish phase-intensity separation such that nanoprobe distributions are distinguished by an integrated phase-intensity multilayer thin film (polyvinyl alcohol/liquid crystal). We overcame a physical limit to resolve sub-10 nm cellular architectures, and achieve the first dynamic imaging of nanoscopic reorganization over 250 h using PINE. We discover nanoscopic rearrangements synchronized with the emergence of group-level movements and shape changes at the macroscale according to a set of interaction rules with importance in cellular and soft matter reorganization, self-organization, and pattern formation.
Aluminum foil negative electrodes with multiphase microstructure for all-solid-state Li-ion batteries
Authors: Liu Yuhgene , Wang Congcheng , Yoon Sun Geun , Han Sang Yun , Lewis John A. , Prakash Dhruv , Klein Emily J. , Chen Timothy , Kang Dae Hoon , Majumdar Diptarka , Gopalaswamy Rajesh , McDowell Matthew T.
Published: July 2023

Metal negative electrodes that alloy with lithium have high theoretical charge storage capacity and are ideal candidates for developing high-energy rechargeable batteries. However, such electrode materials show limited reversibility in Li-ion batteries with standard non-aqueous liquid electrolyte solutions. To circumvent this issue, here we report the use of non-pre-lithiated aluminum-foil-based negative electrodes with engineered microstructures in an all-solid-state Li-ion cell configuration. When a 30-μm-thick Al94.5In5.5negative electrode is combined with a Li6PS5Cl solid-state electrolyte and a LiNi0.6Mn0.2Co0.2O2-based positive electrode, lab-scale cells deliver hundreds of stable cycles with practically relevant areal capacities at high current densities (6.5 mA cm−2). We also demonstrate that the multiphase Al-In microstructure enables improved rate behavior and enhanced reversibility due to the distributed LiIn network within the aluminum matrix. These results demonstrate the possibility of improved all-solid-state batteries via metallurgical design of negative electrodes while simplifying manufacturing processes.
Next generation pan-cancer blood proteome profiling using proximity extension assay
Authors: Álvez María Bueno , Edfors Fredrik , von Feilitzen Kalle , Zwahlen Martin , Mardinoglu Adil , Edqvist Per-Henrik , Sjöblom Tobias , Lundin Emma , Rameika Natallia , Enblad Gunilla , Lindman Henrik , Höglund Martin , Hesselager Göran , Stålberg Karin , Enblad Malin , Simonson Oscar E. , Häggman Michael , Axelsson Tomas , Åberg Mikael , Nordlund Jessica , Zhong Wen , Karlsson Max , Gyllensten Ulf , Ponten Fredrik , Fagerberg Linn , Uhlén Mathias
Published: July 2023

A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
3D printing of ultra-high viscosity resin by a linear scan-based vat photopolymerization system
Authors: Weng Zixiang , Huang Xianmei , Peng Shuqiang , Zheng Longhui , Wu Lixin
Published: July 2023

The current printing mechanism of the bottom-up vat photopolymerization 3D printing technique places a high demand on the fluidity of the UV-curable resin. Viscous high-performance acrylate oligomers are compounded with reactive diluents accordingly to prepare 3D printable UV-curable resins (up to 5000 cps of viscosity), yet original mechanical properties of the oligomers are sacrificed. In this work, an elaborated designed linear scan-based vat photopolymerization system is developed, allowing the adoption of printable UV-curable resins with high viscosity (> 600,000 cps). Briefly, this is realized by the employment of four rollers to create an isolated printing area on the resin tank, which enables the simultaneous curing of the resin and the detachment of cured part from the resin tank. To verify the applicability of this strategy, oligomer dominated UV-curable resin with great mechanical properties, but high viscosity is prepared and applied to the developed system. It is inspiring to find that high stress and strain elastomers and toughened materials could be facilely obtained. This developed vat photopolymerization system is expected to unblock the bottleneck of 3D printed material properties, and to build a better platform for researchers to prepare various materials with diversiform properties developed with 3D printing.
Automatically annotated motion tracking identifies a distinct social behavioral profile following chronic social defeat stress
Authors: Bordes Joeri , Miranda Lucas , Reinhardt Maya , Narayan Sowmya , Hartmann Jakob , Newman Emily L. , Brix Lea Maria , van Doeselaar Lotte , Engelhardt Clara , Dillmann Larissa , Mitra Shiladitya , Ressler Kerry J. , Pütz Benno , Agakov Felix , Müller-Myhsok Bertram , Schmidt Mathias V.
Published: July 2023

Severe stress exposure increases the risk of stress-related disorders such as major depressive disorder (MDD). An essential characteristic of MDD is the impairment of social functioning and lack of social motivation. Chronic social defeat stress is an established animal model for MDD research, which induces a cascade of physiological and behavioral changes. Current markerless pose estimation tools allow for more complex and naturalistic behavioral tests. Here, we introduce the open-source tool DeepOF to investigate the individual and social behavioral profile in mice by providing supervised and unsupervised pipelines using DeepLabCut-annotated pose estimation data. Applying this tool to chronic social defeat in male mice, the DeepOF supervised and unsupervised pipelines detect a distinct stress-induced social behavioral pattern, which was particularly observed at the beginning of a novel social encounter and fades with time due to habituation. In addition, while the classical social avoidance task does identify the stress-induced social behavioral differences, both DeepOF behavioral pipelines provide a clearer and more detailed profile. Moreover, DeepOF aims to facilitate reproducibility and unification of behavioral classification by providing an open-source tool, which can advance the study of rodent individual and social behavior, thereby enabling biological insights and, for example, subsequent drug development for psychiatric disorders.
Cryo-EM structure and polymorphic maturation of a viral transduction enhancing amyloid fibril
Authors: Heerde Thomas , Schütz Desiree , Lin Yu-Jie , Münch Jan , Schmidt Matthias , Fändrich Marcus
Published: July 2023

Amyloid fibrils have emerged as innovative tools to enhance the transduction efficiency of retroviral vectors in gene therapy strategies. In this study, we used cryo-electron microscopy to analyze the structure of a biotechnologically engineered peptide fibril that enhances retroviral infectivity. Our findings show that the peptide undergoes a time-dependent morphological maturation into polymorphic amyloid fibril structures. The fibrils consist of mated cross-β sheets that interact by the hydrophobic residues of the amphipathic fibril-forming peptide. The now available structural data help to explain the mechanism of retroviral infectivity enhancement, provide insights into the molecular plasticity of amyloid structures and illuminate the thermodynamic basis of their morphological maturation.
RUFY3 regulates endolysosomes perinuclear positioning, antigen presentation and migration in activated phagocytes
Authors: Char Rémy , Liu Zhuangzhuang , Jacqueline Cédric , Davieau Marion , Delgado Maria-Graciela , Soufflet Clara , Fallet Mathieu , Chasson Lionel , Chapuy Raphael , Camosseto Voahirana , Strock Eva , Rua Rejane , Almeida Catarina R. , Su Bing , Lennon-Duménil Ana-Maria , Nal Beatrice , Roquilly Antoine , Liang Yinming , Méresse Stéphane , Gatti Evelina , Pierre Philippe
Published: July 2023

Endo-lysosomes transport along microtubules and clustering in the perinuclear area are two necessary steps for microbes to activate specialized phagocyte functions. We report that RUN and FYVE domain-containing protein 3 (RUFY3) exists as two alternative isoforms distinguishable by the presence of a C-terminal FYVE domain and by their affinity for phosphatidylinositol 3-phosphate on endosomal membranes. The FYVE domain-bearing isoform (iRUFY3) is preferentially expressed in primary immune cells and up-regulated upon activation by microbes and Interferons. iRUFY3 is necessary for ARL8b + /LAMP1+ endo-lysosomes positioning in the pericentriolar organelles cloud of LPS-activated macrophages. We show that iRUFY3 controls macrophages migration, MHC II presentation and responses to Interferon-γ, while being important for intracellular Salmonella replication. Specific inactivation of rufy3 in phagocytes leads to aggravated pathologies in mouse upon LPS injection or bacterial pneumonia. This study highlights the role of iRUFY3 in controlling endo-lysosomal dynamics, which contributes to phagocyte activation and immune response regulation.
Cognitive effects of Lewy body pathology in clinically unimpaired individuals
Authors: Palmqvist Sebastian , Rossi Marcello , Hall Sara , Quadalti Corinne , Mattsson-Carlgren Niklas , Dellavalle Sofia , Tideman Pontus , Pereira Joana B. , Nilsson Maria H. , Mammana Angela , Janelidze Shorena , Baiardi Simone , Stomrud Erik , Parchi Piero , Hansson Oskar
Published: July 2023

α-Synuclein aggregates constitute the pathology of Lewy body (LB) disease. Little is known about the effects of LB pathology in preclinical (presymptomatic) individuals, either as isolated pathology or coexisting with Alzheimer’s disease (AD) pathology (β-amyloid (Aβ) and tau). We examined the effects of LB pathology using a cerebrospinal fluid α-synuclein-seed amplification assay in 1,182 cognitively and neurologically unimpaired participants from the BioFINDER study: 8% were LB positive, 26% Aβ positive (13% of those were LB positive) and 16% tau positive. LB positivity occurred more often in the presence of Aβ positivity but not tau positivity. LB pathology had independently negative effects on cross-sectional and longitudinal global cognition and memory and on longitudinal attention/executive function. Tau had cognitive effects of a similar magnitude, but these were less pronounced for Aβ. Participants with both LB and AD (Aβ and tau) pathology exhibited faster cognitive decline than those with only LB or AD pathology. LB, but not AD, pathology was associated with reduced sense of smell. Only LB-positive participants progressed to clinical LB disease over 10 years. These results are important for individualized prognosis, recruitment and choice of outcome measures in preclinical LB disease trials, but also for the design of early AD trials because >10% of individuals with preclinical AD have coexisting LB pathology.