The Peer Review Process: Past, Present, and Future.

The peer review process is a fundamental aspect of modern scientific paper publishing, underpinning essential quality control. First conceptualised in the 1700s, it is an iterative process that aims to elevate scientific literature to the highest standards whilst preventing publication of scientifically unsound, potentially misleading, and even plagiarised information. It is widely accepted that the peer review of scientific papers is an irreplaceable and fundamental aspect of the research process. However, the rapid growth of research and technology has led to a huge increase in the number of publications. This has led to increased pressure on the peer review system. There are several established peer review methodologies, ranging from single and double blind to open and transparent review, but their implementation across journals and research fields varies greatly. Some journals are testing entirely novel approaches (such as collaborative reviews), whilst others are piloting changes to established methods. Given the unprecedented growth in publication numbers, and the ensuing burden on journals, editors, and reviewers, it is imperative to improve the quality and efficiency of the peer review process. Herein we evaluate the peer review process, from its historical origins to current practice and future directions.

Variations in strength-speed-power performance across the season: do true changes occur in elite rugby players?

This study aimed to determine, through the use of a highly sensitive statistical tool, whether real changes in performance were present; and compare the rates of meaningful variations in strength, speed, and power parameters at different time-points during the competitive season in national team rugby players. Thirty-two players were assessed 5 times across the season using the following tests: squat jump and countermovement jump tests; 30-m sprint velocity; and one-repetition maximum (1RM) in the half-squat and bench-press exercises. A repeated-measures analysis of variance was conducted to test for differences between successive time-points. Individual coefficients of variation values were used to set target scores for post-measurements and examine whether changes in performance parameters were greater than the natural test variance, thus providing an indication of whether "true changes" occurred. No significant changes were detected in the vertical jump height, 1RM measures, and sprint velocity and momentum throughout the 11-month period (P > 0.05). True changes occurred much more frequently for strength-power measures than for sprint velocity and momentum. Elite rugby union players did not exhibit significant variations in neuromuscular performance across the competitive period, when a group-based analysis was conducted. However, at the individual level, "true changes" in strength-power-(but not in speed-) related qualities were consistently observed over the competitive season.

Disparities in spatiotemporal clustering of maternal mental health conditions before and during the COVID-19 pandemic.

Mounting evidence indicates the worsening of maternal mental health conditions during the COVID-19 pandemic. Mental health conditions are the leading cause of preventable death during the perinatal and postpartum periods. Our study sought to detect space-time patterns in the distribution of maternal mental health conditions in pregnant women before (2016-2019) and during (2020-2021) the COVID-19 pandemic in North Carolina, USA. Using the space-time Poisson model in SaTScan, we performed univariate and multivariate cluster analysis of emergency department (ED) visits for perinatal mood and anxiety disorders (PMAD), severe mental illness (SMI), maternal mental disorders of pregnancy (MDP), suicidal thoughts, and suicide attempts during the pre-pandemic and pandemic periods. Clusters were adjusted for age, race, and insurance type. Significant multivariate and univariate PMAD, SMI, and MDP clustering persisted across both periods in North Carolina, while univariate clustering for both suicide outcomes decreased during the pandemic. Local relative risk (RR) for all conditions increased drastically in select locations. The number of zip code tabulation areas (ZCTAs) included in clusters decreased, while the proportion of urban locations included in clusters increased for non-suicide outcomes. Average yearly case counts for all maternal mental health outcomes increased during the pandemic. Results provide contextual and spatial information concerning at-risk maternal populations with a high burden of perinatal mental health disorders before and during the pandemic and emphasize the necessity of urgent and targeted expansion of mental health resources in select communities.

Dopaminergic psychostimulants cause arousal from isoflurane-induced sedation without reversing memory impairment in rats.

BACKGROUND: Dopaminergic psychostimulants can restore arousal in anaesthetised animals, and dopaminergic signalling contributes to hippocampal-dependent memory formation. We tested the hypothesis that dopaminergic psychostimulants can antagonise the amnestic effects of isoflurane on visuospatial working memory. METHODS: Sixteen adult Sprague-Dawley rats were trained on a trial-unique nonmatching-to-location (TUNL) task which assessed the ability to identify a novel touchscreen location after a fixed delay. Once trained, the effects of low-dose isoflurane (0.3 vol%) on task performance and activity, assessed by infrared beam breaks, were assessed. We attempted to rescue deficits in performance and activity with a dopamine D1 receptor agonist (chloro-APB), a noradrenergic reuptake inhibitor (atomoxetine), and a mixed dopamine/norepinephrine releasing agent (dextroamphetamine). Anaesthetic induction, emergence, and recovery from anaesthesia were also investigated. RESULTS: Low-dose isoflurane impaired working memory in a sex-independent and intra-trial delay-independent manner as assessed by task performance, and caused an overall reduction in activity. Administration of chloro-APB, atomoxetine, or dextroamphetamine did not restore visuospatial working memory, but chloro-APB and dextroamphetamine recovered arousal to levels observed in the baseline awake state. Performance did not differ between induction and emergence. Animals recovered to baseline performance within 15 min of discontinuing isoflurane. CONCLUSIONS: Low-dose isoflurane impairs visuospatial working memory in a nondurable and delay-independent manner that potentially implicates non-hippocampal structures in isoflurane-induced memory deficits. Dopaminergic psychostimulants counteracted sedation but did not reverse memory impairments, suggesting that isoflurane-induced amnesia and isoflurane-induced sedation have distinct underlying mechanisms that can be antagonised independently.

Novel Mito-Nuclear Combinations Facilitate the Global Invasion of a Major Agricultural Crop Pest.

A fundamental understanding of the underlying mechanisms involved in biological invasions is crucial to developing effective risk assessment and control measures against invasive species. The fall armyworm (FAW), Spodoptera frugiperda, is a highly invasive pest that has rapidly spread from its native Americas into much of the Eastern Hemisphere, with a highly homogeneous nuclear genetic background. However, the exact mechanism behind its rapid introduction and propagation remains unclear. Here, a systematic investigation is conducted into the population dynamics of FAW in China from 2019 to 2021 and found that FAW individuals carrying "rice" mitochondria (FAW-mR) are more prevalent (>98%) than that with "corn" mitochondria (FAW-mC) at the initial stage of the invasion and in newly-occupied non-overwintering areas. Further fitness experiments show that the two hybrid-strains of FAW exhibit different adaptions in the new environment in China, and this may have been facilitated by amino acid changes in mitochondrial-encoded proteins. FAW-mR used increases energy metabolism, faster wing-beat frequencies, and lower wing loadings to drive greater flight performance and subsequent rapid colonization of new habitats. In contrast, FAW-mC individuals adapt with more relaxed mitochondria and shuttle energetics into maternal investment, observed as faster development rate and higher fecundity. The presence of two different mitochondria types within FAW has the potential to significantly expand the range of damage and enhance competitive advantage. Overall, the study describes a novel invasion mechanism displayed by the FAW population that facilitates its expansion and establishment in new environments.

Open and Endoscopic Endonasal Optic Nerve Decompression for Craniofacial Fibrous Dysplasia in an Adolescent: 2-Dimensional Operative Video.

Craniofacial fibrous dysplasia (CFFD) is a benign, bony disease that may affect the skull base.1,2 Most cases are asymptomatic and observed; however, advanced disease can present with cranial neuropathy or craniofacial deformity requiring intervention.3-5 A 16-year-old adolescent girl with known CFFD involving the sphenoid and frontal bones with severe bilateral optic canal narrowing developed progressive right eye visual decline and frontal cosmetic deformity. Visual acuity worsened oculus dextrus (OD) to 20/30 with a new superior nasal scotoma and 20% loss in the retinal nerve fiber layer and remained oculus sinister (OS) 20/20. The patient was recommended a staged subfrontal craniotomy for right optic decompression and simultaneous correction cosmetic deformity followed by endonasal right optic decompression. On postoperative day one, visual acuity OD improved to 20/20; however, she developed OS visual decline to 20/800. Curiously, there were no episodes of intraoperative hypotension or additional iatrogenic compression. Use of methylprednisolone led to improvement OS 20/400. Given persistent visual decline, urgent second stage endonasal bilateral optic nerve decompression, rather than unilateral, was performed. Postoperatively, vision improved to OS 20/200. At one month, her vision improved to OD 20/15 and OS returned to 20/20 with a paracentral scotoma and 29% decline in left retinal nerve fiber layer with further improvement anticipated. This video describes a multidisciplinary, multistaged approach in treatment of optic nerve compression due to CFFD in addition to the management of unanticipated contralateral visual decline. The patient consented to the procedure and publication of her image. No Institutional Review Board/ethics committee approval was necessary for this case report.

Rose Bengal diacetate-mediated antimicrobial photodynamic inactivation: potentiation by potassium iodide and acceleration of wound healing in MRSA-infected diabetic mice.

Previous studies have shown that antimicrobial photodynamic inactivation (aPDI) can be strongly potentiated by the addition of the non-toxic inorganic salt, potassium iodide (KI). This approach was shown to apply to many different photosensitizers, including the xanthene dye Rose Bengal (RB) excited by green light (540 nm). Rose Bengal diacetate (RBDA) is a lipophilic RB derivative that is easily taken up by cells and hydrolyzed to produce an active photosensitizer. Because KI is not taken up by microbial cells, it was of interest to see if aPDI mediated by RBDA could also be potentiated by KI. The addition of 100 mM KI strongly potentiated the killing of Gram-positive methicillin-resistant Staphylocccus aureus, Gram-negative Eschericia coli, and fungal yeast Candida albicans when treated with RBDA (up to 15 µM) for 2 hours followed by green light (540 nm, 10 J/cm2). Both RBDA aPDI regimens (400 µM RBDA with or without 400 mM KI followed by 20 J/cm2 green light) accelerated the healing of MRSA-infected excisional wounds in diabetic mice, without damaging the host tissue.

Intensifying Salvage Therapy in Prostate-specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy with Apalutamide, Salvage Radiation, and Docetaxel: The Phase 2 STARTAR Trial.

BACKGROUND AND OBJECTIVE: Androgen deprivation therapy (ADT) with salvage radiation therapy (RT) improves survival for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) for prostate cancer (PC), but many patients suffer further relapse. This study aims to determine the benefit of the combination of ADT, apalutamide, salvage RT, and docetaxel for high-risk PSA recurrent PC. METHODS: STARTAR is a multicenter, investigator-initiated phase 2 trial of men with PSA recurrent PC after RP. The key inclusion criteria included M0 by computed tomography/bone scan, Gleason 7 with either T3/positive margin/N1 disease or Gleason 8-10 prostate adenocarcinoma, PSA relapse (0.2-4 ng/ml) <4 yr after RP, and fewer than four positive resected lymph nodes. Patients received ADT with apalutamide for 9 mo, RT starting week 8, and then six cycles of docetaxel. The primary endpoint was 36-mo progression-free survival (PFS) with testosterone recovery and compared against the prior STREAM trial. KEY FINDINGS AND LIMITATIONS: We enrolled 39 men, including those with Gleason 8-10 (46%), pN1 (23%); the median PSA was 0.58 ng/ml. The median follow-up was 37 mo. All patients achieved undetectable PSA nadir. At 24 and 36 mo, PFS rates were 84% and 71%, respectively, which improved significantly over 3-yr 47% historic PFS and 54% enzalutamide/ADT/RT (STREAM) PFS rates (p = 0.004 and p = 0.039, respectively). Common any-grade adverse events included 98% hot flashes, 88% fatigue, 77% alopecia, 53% rash (10% G3), and 5% febrile neutropenia. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this phase 2 trial of ADT, apalutamide, salvage RT, and six cycles of docetaxel for high-risk PSA recurrence, the 3-yr PFS rate improved to 71%, indicating feasible and efficacious treatment intensification, with durable remissions beyond historic data. PATIENT SUMMARY: Prostate cancer recurrence after surgical removal of the tumor occurs often, and current treatment options to limit recurrence after surgery are only partially effective. In this study, we found that the addition of an androgen receptor inhibitor and docetaxel chemotherapy to standard postsurgery radiation therapy and androgen deprivation therapy significantly improved progression-free survival at 3 yr after treatment. These results suggest that intensification of treatment after surgery can provide long-term benefit to a subset of patients with high-risk prostate cancer.

Weight History Correlates of Resting Energy Expenditure in Women With Bulimia Nervosa.

OBJECTIVE: Among those with bulimia nervosa, weight suppression has been associated with illness severity and treatment prognosis. Although significant weight loss is known to reduce metabolic rate, the relation between weight suppression and resting energy expenditure (REE) in bulimia nervosa has not been examined. This study tested the hypothesis of an inverse relation between weight suppression and REE in a sample of women with bulimia nervosa (N = 84). METHODS: In primary analyses, linear regressions were conducted between weight suppression and REE, corrected for fat-free mass. In follow-up, exploratory analyses, stepwise linear regressions were conducted to explore the main and interaction effects of weight history and weight suppression on REE. RESULTS: Neither traditional (TWS) nor developmental weight suppression (DWS) correlated with REE. Results from exploratory analyses, however, revealed a medium-to-large inverse relation between several weight history variables and REE (highest past weight, sr2 = 0.05; lowest postmorbid weight, sr2 = 0.07; current weight, sr2 = 0.05). Additionally, DWS interacted with current (sr2 = 0.08) and highest premorbid (sr2 = 0.05) z-BMI to influence REE with a medium-to-large effect. For individuals low in current and premorbid z-BMIs, higher DWS associated with lower REE levels. However, for individuals at higher premorbid z-BMIs, higher DWS unexpectedly associated with greater REE levels. DISCUSSION: In this sample of women with bulimia nervosa, reduced REE associated with higher weights across all timepoints. If the interaction effect between DWS and z-BMI history persists in future studies, this may indicate unique challenges faced by individuals low in z-BMI and high in DWS related to weight gain and normalization of eating.

Electronic Medical Record-Based Nudge Intervention to Increase Comprehensive Molecular Genotyping in Patients With Metastatic Non-Small Cell Lung Cancer: Results From a Prospective Clinical Trial.

PURPOSE: Less than half of the patients with newly diagnosed metastatic non-small cell lung cancer (NSCLC) undergo comprehensive molecular testing. We designed an electronic medical record (EMR)-based "nudge intervention" to prompt plasma-based molecular testing at the time of initial medical oncology consultation. METHODS: A nonrandomized prospective trial was conducted at the University of Pennsylvania's academic practice and two affiliated community practices. Molecular genotyping was performed by tissue- and/or plasma-based next generation sequencing methods. Comprehensive testing was defined as testing for EGFR, ALK, BRAF, ROS1, MET, RET, KRAS, and NTRK. Guideline-concordant treatment was defined as the use of the appropriate first-line (1L) therapy as per the National Comprehensive Cancer Network (NCCN) guidelines. Proportion of patients with comprehensive molecular genotyping results available at any time, molecular results available before 1L therapy, and guideline-concordant 1L treatment were compared between the preintervention and postintervention cohorts using Fisher's exact test or Pearson's chi-squared test. RESULTS: Five hundred and thirty-three patients were included, 376 in the preintervention cohort and 157 in the postintervention cohort. After implementation of the EMR-based nudge, a higher proportion of patients underwent comprehensive molecular testing in the postintervention versus the preintervention cohort (100% v 88%, P = <.001), had results of comprehensive molecular testing available before initiating 1L treatment (97.3% v 91.6%, P = .026), and received NCCN guideline-concordant care (89.8% v 78.2%, P = .035). CONCLUSION: Across three practice sites in a large health system, implementation of a provider team-focused EMR-based nudge intervention was feasible, and led to a higher number of patients with NSCLC undergoing comprehensive molecular genotyping. These findings demonstrate that behavioral nudges can promote molecular testing and should be studied further as a tool to improve guideline-concordant care in both community and academic sites.

The Open Force Field Initiative: Open Software and Open Science for Molecular Modeling.

Force fields are a key component of physics-based molecular modeling, describing the energies and forces in a molecular system as a function of the positions of the atoms and molecules involved. Here, we provide a review and scientific status report on the work of the Open Force Field (OpenFF) Initiative, which focuses on the science, infrastructure and data required to build the next generation of biomolecular force fields. We introduce the OpenFF Initiative and the related OpenFF Consortium, describe its approach to force field development and software, and discuss accomplishments to date as well as future plans. OpenFF releases both software and data under open and permissive licensing agreements to enable rapid application, validation, extension, and modification of its force fields and software tools. We discuss lessons learned to date in this new approach to force field development. We also highlight ways that other force field researchers can get involved, as well as some recent successes of outside researchers taking advantage of OpenFF tools and data.

The role of ruminant urine and faeces in the recycling of nutrients by forages.

This study addresses the effect of using animal excreta on the nutritional content of forages, focusing on macro- and micro-element concentrations (nitrogen; N, phosphorus; P, sulphur; S, copper; Cu, zinc; Zn, manganese; Mn, selenium; Se) from animal feed to excreta, soil, and plants. Data were collected from pot and field trials using separate applications of sheep or cattle urine and faeces. Key findings indicate that soil organic carbon (SOC) and the type of excreta significantly influences nutrient uptake by forages, with varied responses among the seven elements defined above. Although urine contributes fewer micronutrients compared to faeces (as applied at a natural volume/mass basis, respectively), it notably improves forage yield and micronutrient accumulation, thus potentially delivering positive consequences at the farm level regarding economic performance and soil fertility when swards upon clayey soil types receive said urine in temperate agro-climatic regions (i.e., South West England in the current context). In contrast, faeces application in isolation hinders Se and Mn uptake, once again potentially delivering unintended consequences such as micronutrient deficiencies in areas of high faeces deposition. As it is unlikely that (b)ovine grazing fields will receive either urine or faeces in isolation, we also explored combined applications of both excreta types which demonstrates synergistic effects on N, Cu, and Zn uptake, with either synergistic or dilution effects being observed for P and S, depending largely on SOC levels. Additionally, interactions between excreta types can result in dilution or antagonistic effects on Mn and Se uptake. Notably, high SOC combined with faeces reduces Mn and Se in forages, raising concerns for grazed ruminant systems under certain biotic situations, e.g., due to insufficient soil Se levels typically observed in UK pastures for livestock growth. These findings underscore the importance of considering SOC and excreta nutritional composition when designing forage management to optimize nutrient uptake. It should be noted that these findings have potential ramifications for broader studies of sustainable agriculture through system-scale analyses, as the granularity of results reported herein elucidate gaps in knowledge which could affect, both positively and negatively, the interpretation of model-based environmental impact assessments of cattle and sheep production (e.g., in the case of increased yields [beneficial] or the requirement of additional synthetic supplementation [detrimental]).

Morphology and vocalization comparison of the Houston Toad and the Dwarf American Toad: implications for their historic range.

Documenting changes in the distribution and abundance of a given taxon requires historical data. In the absence of long-term monitoring data collected throughout the range of a taxon, conservation biologists often rely on preserved museum specimens to determine the past or present, putative geographic distribution. Distributional data for the Houston Toad (Anaxyrus houstonensis) has consistently been confounded by similarities with a sympatric congener, the Dwarf American Toad (A. americanus charlesmithi), both in monitoring data derived from chorusing surveys, and in historical data via museum specimens. In this case, misidentification can have unintended impacts on conservation efforts, where the Houston Toad is federally endangered, and the Dwarf American Toad is of least concern. Previously published reports have compared these two taxon on the basis of their male advertisement call and morphological appearance, often with the goal of using these characters to substantiate their taxonomic status prior to the advent of DNA sequencing technology. However, numerous studies report findings that contradict one another, and no consensus on the true differences or similarities can be drawn. Here, we use contemporary recordings of wild populations of each taxon to test for quantifiable differences in male advertisement call. Additionally, we quantitatively examine a subset of vouchered museum specimens representing each taxon to test previously reported differentiating morphometric characters used to distinguish among other Bufonids of East-Central Texas, USA. Finally, we assemble and qualitatively evaluate a database of photographs representing catalogued museum vouchers for each taxon to determine if their previously documented historic ranges may be larger than are currently accepted. Our findings reveal quantifiable differences between two allopatric congeners with respect to their male advertisement call, whereas we found similarities among their detailed morphology. Additionally, we report on the existence of additional, historically overlooked, museum records for the Houston Toad in the context of its putative historic range, and discuss errors associated with the curation of these specimens whose identity and nomenclature have not been consistent through time. These results bookend decades of disagreement regarding the morphology, voice, and historic distribution of these taxa, and alert practitioners of conservation efforts for the Houston Toad to previously unreported locations of occurrence.