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INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies. AIMS: This study investigated memantines impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in-person and remotely across 13 sites in the United States. Participants were randomized to memantine (20 mg twice daily) or placebo in a 2:1 ratio and completed 36 weeks of treatment. The primary outcome of disease progression was assessed by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and blood was collected for biomarker analysis. RESULTS: Of the 99 participants enrolled in the study, 89 were randomized to memantine or placebo (ages 24-83 years, male-to-female ratio ~3:2). Fifty-two participants completed the study treatment with no significant differences in disease progression, biomarker changes (including neurofilament light chain [NfL]), or neuropsychiatric testing noted between the groups. Initial NfL values correlated with the rate of ALSFRS-R decline. DISCUSSION: In this study, memantine did not impact ALS disease progression or neuropsychiatric symptoms. Trials with remote enrollment may help trial participation and success.

The future of pathology is dependent on a steady stream of trained physicians entering the discipline. As such, it is critical to accurately capture employment trends for new-in-practice pathologists. Since [...], * Context.--As pathologists retire and leave the field, it is critical to accurately capture employment trends for new-in-practice pathologists. There is always interest in the job market for newly graduated pathology trainees and prospective pathology trainees, but it is unclear how the COVID-19 pandemic may have affected the job search experience. Objective.--To provide an update on trends gleaned from a survey of pathology graduates' job search experiences during the COVID-19 pandemic. Design.--We analyzed data from an annual job search survey sent by the College of American Pathologists Graduate Medical Education Committee between 2020 and 2022 to College of American Pathologists junior members and fellows in practice 3 years or less actively looking for a non-fellowship position. Various indicators of the job search experience were compared year to year and with the data previously published 2017 to 2019 and 2012 to 2016. Results.--Analysis revealed continued positive trends between the 2020 to 2022 data and the data from 2017 to 2019 and 2012 to 2016. This includes continued ease in finding positions, continued availability of jobs in the subspecialty of choice, continued satisfaction with the positions accepted, and, notably, higher starting salaries. Conclusions.--Despite the many challenges of the COVID-19 pandemic, job market trends for newly graduated pathology trainees continue to be favorable with respect to multiple indicators compared with 2 prior periods, 2017 to 2019 and 2012 to 2016. (Arch Pathol Lab Med. 2025;149:14-19; doi: 10.5858/arpa.2023-0408-CP)

Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in

In a consumer-centric environment, food products are created and focused on the consumer's experience and desires. One important food product used around the world is butter. Consumers expect that when they take their butter out of the refrigerator, it will be able to spread nicely and evenly; however, with conventional butter, which does not include any added vegetable oils, achieving a soft, spreadable butter is rare. This work seeks to contribute to the pool of knowledge regarding the role of catalysts in effecting butter spreadability. To meet consumer expectations, utilizing catalysts in the esterification process with butter oil has proven successful in changing the lipid structure, enabling the possibility of a softer butter. The comparison of utilizing no catalysts and 2 different catalysts, potassium hydroxide and calcium hydroxide, during the chemical esterification process showed that the use of potassium hydroxide catalyst resulted in the least firm and lowest solid fat content butter. These findings demonstrate the potential for industrial use of esterified butter oil using potassium hydroxide in commercial butter.

Background Research software is increasingly recognized as critical infrastructure in contemporary science. It spans a broad spectrum, including source code files, algorithms, scripts, computational workflows, and executables, all created for or during research. While research funders have developed programs, initiatives, and policies to bolster research software’s role, there has been no empirical study of how these funders prioritize support for research software. Understanding their priorities is essential to clarify where current support is concentrated and to identify strategic gaps. Methods We conducted an online mixed methods survey of international research funders (n=36) to explore their priorities in supporting research software. The survey gathered data on the specific outcomes funders emphasize in their programs and initiatives for research software. Results The survey revealed that funders place strong emphasis on developing skills, promoting software sustainability, embedding open science practices, building community and collaboration, advancing research software funding mechanisms, increasing software visibility and use, fostering innovation, and ensuring security. Conclusions The findings highlight opportunities to enhance research software’s role through increased funder attention on professional recognition for software contributions and the non-technical, social aspects of research software sustainability. Addressing these areas could lead to more effective support and development of research software, ultimately benefitting the entire research ecosystem.

Abstract Objective: This qualitative study aimed to understand facilitators and barriers to implementation of interventions to improve guideline-concordant antibiotic duration prescribing for pediatric acute otitis media (AOM). Design: Clinicians and clinic administrators participated in semi-structured qualitative interviews, and parents of children 2 years of age or older with a recent diagnosis of AOM participated in focus groups. The Practical Robust Implementation and Sustainability Model (PRISM) guided the study. Interviews were analyzed using the Rapid Assessment Process. Setting: Denver Health and Hospital Authority (Denver, CO) led the study. Recruitment occurred at Vanderbilt University Medical Center (Nashville, TN) and Washington University in St. Louis Medical Center (St. Louis, MO). Participants: Purposeful sampling was used to recruit clinicians and administrators for qualitative interviews. Convenience sampling was used to recruit parents for focus groups. Results: Thirty-one participants (15 clinicians, 4 administrators, and 12 parents) engaged in interviews and focus groups. Factors influencing antibiotic prescribing included patient history, years of practice, familiarity with the patient, concerns with patient medication adherence, and practice type. Clinicians endorsed electronic health record modifications and clinician prescribing feedback as methods to improve patient care and reduce the durations of prescribed antibiotics. Suggestions for intervention optimization and education needs were also obtained. Conclusions: Findings suggest that clinicians and administrators support reducing prescribed antibiotic durations for AOM and are receptive to the proposed interventions. More education is needed to increase parent awareness about antibiotic stewardship and AOM treatment options. Clinical trials identifier: RELAX: Reducing Length of Antibiotics for Children with Ear Infections (RELAX), NCT05608993, https://clinicaltrials.gov/study/NCT05608993.

BackgroundYoung gay, bisexual, and other men who have sex with men have been referred to as a “hard-to-reach” or “hidden” community in terms of recruiting for research studies. With widespread internet use among this group and young adults in general, web-based avenues represent an important approach for reaching and recruiting members of this community. However, little is known about how participants recruited from various web-based sources may differ from one another. ObjectiveThis study aimed to determine how young gay, bisexual, and other men who have sex with men recruited from various web-based sources differ from one another in terms of participant characteristics and study engagement. MethodsData were collected as part of a randomized controlled trial of Outsmart HPV, a web-based human papillomavirus (HPV) vaccination intervention for young gay, bisexual, and other men who have sex with men. From 2019 to 2021, we recruited young gay, bisexual, and other men who have sex with men in the United States who were aged 18-25 years and not vaccinated against HPV (n=1227) through various web-based avenues. We classified each participant as being recruited from either (1) social media (eg, Facebook, Instagram, Snapchat), (2) a dating app (eg, Grindr, Scruff), or (3) some other digital recruitment source (eg, existing research panel, university-based organization). Analyses compared participants from these 3 groups on demographic and health-related characteristics and metrics involving study engagement. ResultsMost demographic and health-related characteristics differed by web-based recruitment source, including race or ethnicity (P

IntroductionNon-typhoidal Salmonella enterica (NTS) are leading bacterial agents of foodborne illnesses and a global concern for human health. While there are over 2,600 different serovars of NTS, epidemiological data suggests that certain serovars are better at causing disease than others, resulting in the majority of reported human illnesses in the United States. To improve food safety, there is a need to rapidly detect these more pathogenic serovars to facilitate their removal from the food supply.MethodsAddressing this need, we conducted a comparative analysis of 23 closed Salmonella genomic sequences of five serotypes. The analysis pinpointed eight genes (sseK2, sseK3, gtgA/gogA, avrA, lpfB, SspH2, spvD, and invA) that in combination, identify 7 of the 10 leading Salmonella serovars attributed to human illnesses in the US each year (i.e., Serovars of Concern or SoC). A multiplex PCR assay was developed to detect the presence of these genes, with strains amplifying five or more targets designated Highly Pathogenic Salmonella, or HPS. The utility of the resulting HPS assay for identifying SoC was examined in silico, using BLAST to determine the distribution of gene targets among closed Salmonella genome sequences in GenBank (n = 2,192 representing 148 serotypes) and by assaying 1,303 Salmonella (69 serotypes), isolated from FSIS regulatory samples.Results and discussionComparison of serotypes identified by the assay as HPS, with those identified as SoC, produced an Area Under the Curve (AUC) of 92.2% with a specificity of 96% and a positive predictive value of 97.4%, indicating the HPS assay has strong ability to identify SoC. The data presented lay the groundwork for development of rapid commercial assays for the detection of SoC.

PurposeTo examine the prevalence and associations of anisometropia with spherical ametropia, cylindrical power, age, and sex.MethodsAnisometropia was analyzed for subjective refraction. In total, 134,603 refractive surgery candidates were included in the period from 2010 to 2020 at the CARE Vision Refractive Centers in Germany. Our study was approved by the local ethics committee at the University in Duesseldorf (approval date: February 9, 2021) and conducted according to the tenets of the Declaration of Helsinki and Good Clinical Practices Guidelines. The treatment contract included explicit patient consent to use medical data for scientific purposes. Correlations between anisometropia and explanatory variables were analyzed using the chi-squared test (χ2 test), nonparametric Kruskal-Wallis or Mann-Whitney U-tests, and binomial logistic regression. Power vector analysis was applied for further analysis of cylindrical power.ResultsThe median level of anisometropia (Asubj) in the whole population was 0.38 D. The prevalence of Asubj was 17.9%. In hyperopes, all explanatory variables (spherical ametropia, cylindrical power, age, sex) were independently associated with anisometropia. Asubj decreased with increasing cylindrical ametropia: an increase in cylindrical power by 7.8 D reduced the chance of observing anisometropia by half. It was also associated with male sex. Asubj decreased by half with a 16.7 D increase in spherical power and an increase in age by 22.7 years. In myopes, cylindrical power was most strongly associated with anisometropia: an increase in (negative) cylindrical power by 2.15 D doubled the chances of observing anisometropia in myopes. In addition, advancing age (double chance with an increase of 38.3 years), increasing spherical power (double chance with an increase of 8.15 D), and female sex correlated positively with increasing anisometropia in myopes.ConclusionsThis retrospective analysis gives evidence for the independent association between anisometropia and spherical power, cylindrical power, age, and sex in myopic refractive surgery candidates. The relation of anisometropia with age was positive in myopes but negative in hyperopes. The analysis of sex revealed a positive relation of female sex and anisometropia in myopes and furthermore revealed a positive relation of male sex and anisometropia in hyperopes. Further clinical research into the underlying mechanisms behind our findings is indicated.

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Objective Many individuals exposed to SARS-CoV-2 experience long-term symptoms as part of a syndrome called post-COVID condition (PCC). Research on PCC is still emerging but is urgently needed to support diagnosis, clinical treatment guidelines and health system resource allocation. In this study, we developed a method to identify PCC cases using administrative health data and report PCC prevalence and predictive factors in Manitoba, Canada.Design Cohort study.Setting Manitoba, Canada.Participants All Manitobans who tested positive for SARS-CoV-2 during population-wide PCR testing from March 2020 to December 2021 (n=66 365) and were subsequently deemed to have PCC based on International Classification of Disease-9/10 diagnostic codes and prescription drug codes (n=11 316). Additional PCC cases were identified using predictive modelling to assess patterns of health service use, including physician visits, emergency department visits and hospitalisation for any reason (n=4155).Outcomes We measured PCC prevalence as % PCC cases among Manitobans with positive tests and identified predictive factors associated with PCC by calculating odds ratios with 95% confidence intervals, adjusted for sociodemographic and clinical characteristics (aOR).Results Among 66 365 Manitobans with positive tests, we identified 15 471 (23%) as having PCC. Being female (aOR 1.64, 95% CI 1.58 to 1.71), being age 60–79 (aOR 1.33, 95% CI 1.25 to 1.41) or age 80+ (aOR 1.62, 95% CI 1.46 to 1.80), being hospitalised within 14 days of COVID-19 infection (aOR 1.95, 95% CI 1.80 to 2.10) and having a Charlson Comorbidity Index of 1+ (aOR 1.95, 95% CI 1.78 to 2.14) were predictive of PCC. Receiving 1+ doses of the COVID-19 vaccine (one dose, aOR 0.80, 95% CI 0.74 to 0.86; two doses, aOR 0.29, 95% CI 0.22 to 0.31) decreased the odds of PCC.Conclusions This data-driven approach expands our understanding of the prevalence and epidemiology of PCC and may be applied in other jurisdictions with population-based data. The study provides additional insights into risk and protective factors for PCC to inform health system planning and service delivery.

Robust inference of galaxy stellar masses from photometry is crucial for constraints on galaxy assembly across cosmic time. Here, we test a commonly used spectral energy distribution (SED) fitting code using simulated galaxies from the S phinx ^20 cosmological radiation hydrodynamics simulation with JWST NIRCam photometry forward-modeled with radiative transfer. Fitting the synthetic photometry with various star formation history models, we show that recovered stellar masses are, encouragingly, generally robust to within a factor of ∼3 for galaxies in the range M _⋆ ∼ 10 ^7 −10 ^9 M _⊙ at z = 5−10. These results are in stark contrast to recent work claiming that stellar masses can be underestimated by as much as an order of magnitude in these mass and redshift ranges. However, while >90% of masses are recovered to within 0.5 dex, there are notable systematic trends, with stellar masses typically overestimated for low-mass galaxies ( M _⋆ ≲ 10 ^8 M _⊙ ) and slightly underestimated for high-mass galaxies ( M _⋆ ≳ 10 ^9 M _⊙ ). We demonstrate that these trends arise due to the SED fitting code poorly modeling the impact of strong emission lines on broadband photometry. These systematic trends, which exist for all star formation history parameterizations tested, have a tilting effect on the inferred stellar mass function, with the number densities of massive galaxies underestimated (particularly at the lowest redshifts studied) and the number densities of lower-mass galaxies typically overestimated. Overall, this work suggests that we should be optimistic about our ability to infer the masses of high- z galaxies observed with JWST (notwithstanding contamination from active galactic nuclei) but careful when modeling the impact of strong emission lines on broadband photometry.

Introduction: Contemporary data regarding the impact of war on cardiovascular disease is scarce. The Israel-Gaza war that erupted on October 7th, 2023, provided a tragic opportunity to explore the effect of war on the epidemiology, characteristics, and management of patients with acute coronary syndrome (ACS) living in areas of active armed conflict. Methods: All patients admitted with ACS to our medical center, between October 7th, 2023, and January 6th, 2024, were retrospectively included. Crucial time intervals in the management of individuals with ACS were collected in a predetermined spreadsheet. In-hospital and 30-day outcomes were obtained from the medical records and contrasted with ACS cases admitted in the period preceding the war. Results: A total of 449 individuals (102 females [22.7 %]) with a diagnosis of ACS were recruited, 358 patients (144 STEMI and 214 NSTEMI) were admitted during the 9 months before October 7th and 91 patients (42 STEMI and 49 NSTEMI) in the 3 months after October 7th. Compared to the control period, a significant reduction in ACS admissions per month was noted (38.91 vs. 28.79, p

There is strong evidence proper nutrition is imperative for healthy infant neurodevelopment, providing the neural foundations for later cognition and behavior. Over the first years of life infants are supported by unique sources of nutrition (e.g., human milk, alternative milk sources). It is during this time that the brain undergoes its most drastic changes during postnatal development. Past research has examined associations between infant feeding and nutrition and morphological features of the brain, yet there remains a paucity of information on functional characteristics of neural activity during feeding. Within this article, we discuss how neuroimaging modalities can be optimized for researching the impacts of infant feeding and nutrition on brain function. We review past research utilizing EEG and fNIRS and describe our efforts to further develop neuroimaging approaches that allow for measurement of brain activity during active feeding with greater spatial resolution (e.g., fMRI and OPM-MEG). We also discuss current challenges, as well as the scientific and logistical limitations of each method. Once protocols have been optimized, these methods will provide the requisite insight into the underlying mechanisms of nutritional and feeding impacts on neurodevelopment, providing the missing piece in the field’s efforts to understand this essential and ubiquitous part of early life.

Objective: Growth differentiation factor 15 (GDF15) acts on the receptor dimer of GDNF family receptor alpha-like (GFRAL) and Rearranged during transfection (RET). While Gfral-expressing cells are known to be present in the area postrema and nucleus of the solitary tract (AP/NTS) located in the brainstem, the presence of Gfral-expressing cells in other sites within the central nervous system and peripheral tissues is not been fully addressed. Our objective was to thoroughly investigate whether GFRAL is expressed in peripheral tissues and in brain sites different from the brainstem. Methods: From Gfral:eGFP mice we collected tissue from 12 different tissues, including brain, and used single molecule in-situ hybridizations to identify cells within those tissues expressing Gfral. We then contrasted the results with human Gfral-expression by analyzing publicly available single-cell RNA sequencing data. Results: In mice we found readably detectable Gfral mRNA within the AP/NTS but not within other brain sites. Within peripheral tissues, we failed to detect any Gfral-labelled cells in the vast majority of examined tissues and when present, were extremely rare. Single cell sequencing of human tissues confirmed GFRAL-expressing cells are detectable in some sites outside the AP/NTS in an extremely sparse manner. Importantly, across the utilized methodologies, smFISH, genetic Gfral reporter mice and scRNA-Seq, we failed to detect Gfral-labelled cells with all three. Conclusions: Through highly sensitive and selective technologies we show Gfral expression is overwhelmingly restricted to the brainstem and expect that GDF15 and GFRAL-based therapies in development for cancer cachexia will specifically target AP/NTS cells.

Background: Intranasal administration of the neuropeptide oxytocin has been explored as a potential therapeutic agent for substance use disorder including opioid use disorder (OUD). Methods: This phase 1, crossover, randomized, double-blind, placebo-controlled trial tested the safety, tolerability, and efficacy of intranasal oxytocin (80 IU) twice a day for 7 days in participants (N = 20) with OUD who were taking an opioid agonist therapy. In the laboratory, participants underwent opioid cue exposure paired with noradrenergic activation produced by yohimbine (32.4 mg) or placebo. Assessments included, 1) subjective response: craving, withdrawal, anxiety, and stress; 2) biomedical markers: hypothalamic-pituitary-adrenal axis response (cortisol) and noradrenergic activation (α-amylase); and 3) safety measures: hemodynamics and adverse event evaluation. Generalized linear model with model-based estimator in the covariance matrix was used, with medication (oxytocin/placebo) and noradrenergic activation (yohimbine/placebo) as within-subject factors. Results: Oxytocin significantly reduced opioid-like withdrawal, anxiety symptoms, and cortisol levels elicited by cue exposure under noradrenergic activation produced by yohimbine. This effect was specific because oxytocin did not reduce craving, hemodynamics, or α-amylase levels increased by yohimbine administration. A single dose of yohimbine elicited the noradrenergic stimulation, and 7-day oxytocin administration was safe and well tolerated among individuals diagnosed with OUD and taking opioid agonist therapy. Conclusions: The findings of this study suggest that oxytocin alleviates opioid-like withdrawal symptoms and anxiety by modulating the hypothalamic-pituitary-adrenal axis.

While creativity is an established driver of profit for firms and success for individuals, not all situations are ideal for maximizing creativity. In this work, we establish a framework of ways that creators can deliberately reduce novelty in their works to make them more successful. The first way, permanent novelty reduction (PNR), is where creators decrease novelty in key aspects of their final product to make it more amenable to consumers or gatekeepers. The second way, temporary novelty reduction (TNR), involves strategically decreasing novelty in the short term to overcome environmental or functional resistance to novelty, often leading to a more creative product in the long term. Together, these two categories of novelty reduction support a new theoretical perspective: novelty reduction can play a critical role in the creative process. We develop this perspective by examining James Cameron and his team’s creative decisions during the making of one of the most successful films of all time, Avatar. [ABSTRACT FROM AUTHOR]

The article in the ILR Review honors George J. Borjas as a pioneer in the study of immigration economics and quantitative social science. Borjas' work is characterized by rigorous evidence and thoughtful analysis of migration decisions and their economic impacts. His research on immigrant selectivity, assimilation, and economic mobility across generations has had a profound influence on labor economics and empirical methodology. Borjas' approach combines deep reflection on economic theory with meticulous attention to data, making his work a valuable model for scholars in the field. [Extracted from the article]