bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for subsequent primary melanoma in patients with previous melanoma: a systematic review and meta-analysis
Authors: Smith Juliet , Cust Anne E , Lo Serigne N
Published: August 2023

Background

Compared with the general population, people with a previous melanoma are at increased risk of developing another primary melanoma. Understanding the risk factors associated with multiple primary melanomas can inform patient education and tailored surveillance.

Objectives

To examine the risk factors for subsequent primary melanoma in people with a previous melanoma, by conducting a systematic review and meta-analysis of the available data.

Methods

A systematic literature search was conducted in CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Embase and MEDLINE. Studies that reported a risk estimate or raw frequencies and conducted between 1982 and August 2022 were included. Adjusted risk estimates were prioritized over univariable risk estimates. PRISMA reporting guidelines were followed. Random effects meta-analysis was conducted to derive pooled estimates. Quality assessment was conducted by two researchers using the Newcastle-Ottawa scale. GRADE was used to rate the certainty and quality of the evidence.

Results

Data from 27 studies involving 413 181 participants were pooled and analysed. Risk factors assessed included age and sex, environmental, lifestyle, phenotypic, genetic and histopathological factors, and there was wide variation in how they were categorized and analysed. Independent risk factors identified from pooled analyses included male sex [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.40–1.53], increasing age per 10 years (HR 1.19, 95% CI 1.14–1.24), light skin colour (HR 1.44, 95% CI 1.23–1.70), family history [odds ratio (OR) 1.79, 95% CI 1.25–2.56], CDKN2A mutation (OR 5.29, 95% CI 2.70–10.37), a high or moderate naevus count [OR 2.63 (95% CI 1.61–4.30) and OR 1.64 (95% CI 1.07–2.51), respectively], one or more atypical naevi (OR 3.01, 95% CI 1.52–5.97), first lesions occurring on the head or neck, lentigo maligna subtype (HR 1.16, 95% CI 1.15–1.17), other subtype (HR 1.14, 95% CI 1.03–1.27) and inadequate sun protection (HR 1.85, 95% CI 0.98–3.50). Based on the GRADE criteria, there was high to very low confidence in the pooled effect estimates.

Conclusions

This meta-analysis identified several consistent, independent risk factors for the development of subsequent primary melanoma. These findings will help stratify the risk of subsequent melanoma, tailor skin-check schedules and inform patient education.
Compartment-driven imprinting of intestinal CD4 T cells in inflammatory bowel disease and homeostasis
Authors: Lutter Lisanne , ter Linde José J M , Brand Eelco C , Hoytema van Konijnenburg David P , Roosenboom Britt , Horjus Talabur-Horje Carmen , Oldenburg Bas , van Wijk Femke
Published: August 2023

The mucosal immune system is implicated in the etiology and progression of inflammatory bowel diseases. The lamina propria and epithelium of the gut mucosa constitute two separate compartments, containing distinct T-cell populations. Human CD4 T-cell programming and regulation of lamina propria and epithelium CD4 T cells, especially during inflammation, remain incompletely understood. We performed flow cytometry, bulk, and single-cell RNA-sequencing to profile ileal lamina propria and intraepithelial CD4 T cells (CD4CD8αα, regulatory T cells (Tregs), CD69− and CD69high Trm T cells) in controls and Crohn’s disease (CD) patients (paired non-inflamed and inflamed). Inflammation results in alterations of the CD4 T-cell population with a pronounced increase in Tregs and migrating/infiltrating cells. On a transcriptional level, inflammation within the epithelium induced T-cell activation, increased IFNγ responses, and an effector Treg profile. Conversely, few transcriptional changes within the lamina propria were observed. Key regulators including the chromatin remodelers ARID4B and SATB1 were found to drive compartment-specific transcriptional programming of CD4 T(reg) cells. In summary, inflammation in CD patients primarily induces changes within the epithelium and not the lamina propria. Additionally, there is compartment-specific CD4 T-cell imprinting, driven by shared regulators, between the lamina propria and the epithelium. The main consequence of intraepithelial adaptation, irrespective of inflammation, seems to be an overall dampening of broad (pro-inflammatory) responses and tight regulation of lifespan. These data suggest differential regulation of the lamina propria and epithelium, with a specific regulatory role in the inflamed epithelium.
A Short History of Judicial Diversity
Authors: Rackley Erika
Published: August 2023

Judicial diversity is a priority without priority. While few would argue, openly at least, against a more diverse judiciary in principle, there is still some way to go to make it a reality. And yet, despite the slow rate of progress, reigniting conversations about diversity may seem unwise in the current political moment, raising the question of whether those seeking to achieve a truly diverse judiciary have anywhere (new) to go. We seem to have reached an impasse. This article brings the insights of feminist legal history to bear on arguments for judicial diversity. Drawing on original archival research, it focuses on the establishment of the Industrial Court in 1919 and tells, for the first time, how there came to be statutory requirement for women’s presence on the court. It argues that the quality argument for diversity—that a court is stronger and its decision-making better for the inclusion of women among its members—was central to this success. It goes on to argue that in unsettling deep-seat assumptions particularly around arguments for the imposition of quotas, the history of the Industrial Court, and feminist legal history more generally, offers a way out of the impasse and a reason to keep talking about judicial diversity. This is important. For it is only by doing so that we have any chance of securing a judiciary that is truly diverse.
A novel method for measuring acute thermal tolerance in fish embryos
Authors: Cowan Zara-Louise , Andreassen Anna H , De Bonville Jeremy , Green Leon , Binning Sandra A , Silva-Garay Lorena , Jutfelt Fredrik , Sundin Josefin
Published: August 2023

Aquatic ectotherms are vulnerable to thermal stress, with embryos predicted to be more sensitive than juveniles and adults. When examining the vulnerability of species and life stages to warming, comparable methodology must be used to obtain robust conclusions. Critical thermal methodology is commonly used to characterize acute thermal tolerances in fishes, with critical thermal maximum (CTmax) referring to the acute upper thermal tolerance limit. At this temperature, fish exhibit loss of controlled locomotion due to a temperature-induced collapse of vital physiological functions. While it is relatively easy to monitor behavioural responses and measure CTmax in larval and adult fish, this is more challenging in embryos, leading to a lack of data on this life stage, or that studies rely on potentially incomparable metrics. Here, we present a novel method for measuring CTmax in fish embryos, defined by the temperature at which embryos stop moving. Additionally, we compare this measurement with the temperature of the embryos’ last heartbeat, which has previously been proposed as a method for measuring embryonic CTmax. We found that, like other life stages, late-stage embryos exhibited a period of increased activity, peaking approximately 2–3°C before CTmax. Measurements of CTmax based on last movement are more conservative and easier to record in later developmental stages than measurements based on last heartbeat, and they also work well with large and small embryos. Importantly, CTmax measurements based on last movement in embryos are similar to measurements from larvae and adults based on loss of locomotory control. Using last heartbeat as CTmax in embryos likely overestimates acute thermal tolerance, as the heart is still beating when loss of response/equilibrium is reached in larvae/adults. The last movement technique described here allows for comparisons of acute thermal tolerance of embryos between species and across life stages, and as a response variable to treatments.
Mitochondrial pannexin1 controls cardiac sensitivity to ischaemia/reperfusion injury
Authors: Rusiecka Olga M , Molica Filippo , Nielsen Morten S , Tollance Axel , Morel Sandrine , Frieden Maud , Chanson Marc , Boengler Kerstin , Kwak Brenda R
Published: August 2023

Aims

No effective therapy is available in clinics to protect the heart from ischaemia/reperfusion (I/R) injury. Endothelial cells are activated after I/R, which may drive the inflammatory response by releasing ATP through pannexin1 (Panx1) channels. Here, we investigated the role of Panx1 in cardiac I/R.

Methods and results

Panx1 was found in cardiac endothelial cells, neutrophils, and cardiomyocytes. After in vivo I/R, serum Troponin-I, and infarct size were less pronounced in Panx1−/− mice, but leukocyte infiltration in the infarct area was similar between Panx1−/− and wild-type mice. Serum Troponin-I and infarct size were not different between mice with neutrophil-specific deletion of Panx1 and Panx1fl/fl mice, suggesting that cardioprotection by Panx1 deletion rather involved cardiomyocytes than the inflammatory response. Physiological cardiac function in wild-type and Panx1−/− hearts was similar. The time to onset of contracture and time to maximal contracture were delayed in Panx1−/− hearts, suggesting reduced sensitivity of these hearts to ischaemic injury. Moreover, Panx1−/− hearts showed better recovery of left ventricle developed pressure, cardiac contractility, and relaxation after I/R. Ischaemic preconditioning failed to confer further protection in Panx1−/− hearts. Panx1 was found in subsarcolemmal mitochondria (SSM). SSM in WT or Panx1−/− hearts showed no differences in morphology. The function of the mitochondrial permeability transition pore and production of reactive oxygen species in SSM was not affected, but mitochondrial respiration was reduced in Panx1−/− SSM. Finally, Panx1−/− cardiomyocytes had a decreased mitochondrial membrane potential and an increased mitochondrial ATP content.

Conclusion

Panx1−/− mice display decreased sensitivity to cardiac I/R injury, resulting in smaller infarcts and improved recovery of left ventricular function. This cardioprotective effect of Panx1 deletion seems to involve cardiac mitochondria rather than a reduced inflammatory response. Thus, Panx1 may represent a new target for controlling cardiac reperfusion damage.
Effectiveness of aortic valve replacement in Heyde syndrome: a meta-analysis
Authors: Goltstein Lia C M J , Rooijakkers Maxim J P , Hoeks Marlijn , Li Wilson W L , van Wely Marleen H , Rodwell Laura , van Royen Niels , Drenth Joost P H , van Geenen Erwin-Jan M
Published: August 2023

Aims

Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding.

Methods and results

A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24–72 h (T2), 3–21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%–91%) at T1, 90% (74%–96%) at T2, 92% (84%–96%) at T3, and 87% (67%–96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%–81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05–0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40–0.81; P = 0.002).

Conclusion

Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.
Nitrogen-Fixing Plants Enhance and Stabilize Rhizospheric Soil Organic Carbon in Tropical Rainforests, Hainan Island, China
Authors: Yang Huai , Liu Shirong , Wang Jingxin , Schuler Jamie , Wang Yi , Luan Junwei
Published: August 2023

Nitrogen (N)-fixing plants play an important role in stimulating soil nitrogen supply, but the effect of N-fixing plants on soil organic carbon (SOC) sequestration has not been well documented. In this study, we measured rhizospheric carbon components and N content of first to second (1–2)-order and third to fifth (3–5)-order roots of N-fixing and non-N-fixing plants in a montane tropical rainforest in Hainan Island, China, to examine the effects of N-fixing plants on SOC and soil heavy fraction carbon (HFC), and to ascertain the main regulating factors. The results showed that rhizospheric SOC between (1–2) and (3–5)-order roots was 14.2% and 10.5% greater, respectively, for N-fixing plants compared with non-N-fixing plants. Similarly, the HFC was 0.9% (1–2) and 3.6% (3–5) greater for N-fixing plants than non-N-fixing plants. Redundancy analysis showed that spatial variance in rhizospheric SOC and HFC associated with 1–2-order roots was explained by specific root length (SRL) of second-order roots (55.8%) and specific leaf area (SLA) (14.6%), whereas spatial variance was better explained for 3–5 roots by total soil N (44.6%), diameter of fifth-order roots (16.4%), and leaf C (17.9%), respectively. Within the rhizospheric soil of 1–2 roots, N-fixing plants with smaller SRL of second-order roots presented greater SOC and HFC, whereas smaller SLA was associated with greater HFC. By contrast, rhizospheric soil of 3–5 roots under N-fixing plants had greater SOC and HFC levels in environments with higher total soil N and smaller diameters of fifth-order roots. Our study revealed that N-fixing plants enhanced rhizospheric SOC and HFC compared with non-N-fixing plants. The rhizospheric SOC and HFC were correlated strongly by root morphology traits, leaf morphology, and soil properties.

Study Implications: In this article, we compared rhizospheric soil of N-fixing and non-N-fixing species in a montane tropical rainforest in Hainan Island, China, to examine the effects of N-fixing plants on SOC and HFC. Our results suggest the N-fixing plants enhance and stabilize rhizospheric SOC and HFC; rhizospheric SOC and HFC for first- to second-order roots of N-fixing plants were mostly negatively regulated by SRL of second-order roots; and N-fixing plants had positive effects on rhizospheric SOC and HFC for third- to fifth-order roots through increased soil N. Understanding these mechanisms could improve and accumulation of soil C sink in tropical areas.
Post-seismic deformation of the 2008 Wenchuan earthquake reveals a misaligned rheological boundary in the lower crust along the eastern Tibetan Plateau margin
Authors: Zhao Dezheng , Qu Chunyan , Shan Xinjian , Bürgmann Roland , Chen Han , Wu Donglin , Gong Wenyu
Published: August 2023

Along the margins of orogenic plateaus, the viscous Earth structure and fault geometries play a primary role in controlling the tectonic evolution and earthquake generation. After the 2008 Mw 7.9 Wenchuan earthquake, the long-standing debate regarding the tectonics producing and maintaining prominent topography across the Longmen Shan reignited. Post-seismic deformation, representing the surface strain history in response to lithospheric stress perturbations, provides important insights into the lithospheric rheology and active structures. Here, we construct a new 3-D post-seismic deformation model for the Wenchuan earthquake, invoking viscoelastic relaxation and afterslip. Our best-fitting model indicates that the steady-state viscosities of the lower crust in the region to the immediately west of the Songpan-Ganzi terrane and beneath the Songpan-Ganzi terrane are estimated to be 4.0 × 1018 and 1.0 × 1018 Pa s, respectively. Our results, combining geophysical and geodetic observations and model analyses, highlight the prevalent parallelism between the rheological and structural boundaries of the lower crust, which diverge northward away from the trend of the Longmen Shan fault at ∼20°. This diverging rheological structure and the partially coupled upper and lower crust have broad implications for the stress build-up, strain partitioning and deformation styles along the eastern Tibetan Plateau margin.
A novel GRACE reconstructive filter to extract the mass changes in Madagascar
Authors: Jian Guangyu , Xu Chuang , Zou Fang , Huang Bo
Published: August 2023

The precise estimation of the mass changes in Madagascar is a challenge by using the Gravity Recovery and Climate Experiment (GRACE) mission Level-2 products since they are contaminated by noise. Although this issue can be alleviated by the empirical destriping method or spatial filtering, they result in potential signal distortion or signal leakage. To improve this, we propose a reconstructive filter, whose parameters are optimized by the signal-to-noise ratio. Subsequently, our optimal filter corresponding to the best signal-to-noise ratio (5.63) is used to estimate the mass changes (2002–2017) in Madagascar. Eventually, our results are compared with two reliable GRACE mascon products and other independent observations. Correspondingly, here are our major conclusions: (1) Compared with groundwater storage from the mascon products, our estimates have the highest Pearson correlation (0.5) with in situ observation and can detect the rapid increase of groundwater storage during the rainy season. (2) The Fourier spectrum analysis detects a ∼3.8-yr periodic signal in the terrestrial water storage changes in Madagascar, which is contributed from the interannual precipitation driven by climate factor (Indian Ocean Dipole) and the aliasing error for imperfect GRACE pre-process. Our work introduces an effective filter for processing GRACE Level-2 data and presents novel insights into mass changes in Madagascar.
Harnessing patient complaints to systematically monitoring healthcare concerns through disproportionality analysis
Authors: Bie Bogh Søren , Fryd Birkeland Søren , Maj-Britt Hansen Sebrina , Alexandrovna Tchijevitch Olga , Hallas Jesper , Morsø Lars
Published: August 2023

Staff observations are the most common source of data for driving improvements in care. However, the patient perspective should also be considered, and healthcare complaints offer concrete details that health organizations might otherwise overlook and that can highlight areas for learning and improvement in the healthcare system. However, because of the diverse nature of patient complaints, systematic analyses can be challenging. This study aimed to identify and prioritize areas for improvement using a data-driven approach to analysing patient complaints. The Danish version of the Healthcare Complaints Analysis Tool was used to categorize the content of complaint letters. All complaints managed by the national complaints authority, compensation claims to the Patient Compensation Association, and locally managed complaints that were filed directly at Odense University Hospital from 2017 to 2021 were included. Proportional reporting ratios (PRRs) were used to measure and display the top five signals of disproportionality and rank them by excess complaints at the hospital level and when divided into department types. The study included 6366 complaints containing 13 156 problems (on average, 2.1 problems mentioned per complaint letter). Surgical departments had the highest number of complaints (3818), followed by medical (1059), service (439), and emergency departments (239). Signal 1 of disproportionality, relating to quality problems during ward procedures, had the highest excess reporting of 1043 complaints at the hospital level and a PRR of 1.61 and was present in all department types. Signal 2, relating to safety problems during the examination and diagnosis stage, had an excess reporting of 699 problems and a PRR of 1.86 and was also present in all department types. Signal 3, relating to institutional problems during admission, had the highest PRR of 3.54 and was found in most department types. Signals 4 and 5, relating to environmental problems during ward procedures and care on the ward, respectively, had PRRs of 1.5 and 1.84 and were present in most department types. The study found that analysing patient complaints can identify potential areas for hospital improvement. The study identified recurring issues in multiple departments, including quality problems during ward procedures, safety problems during the examination, institutional problems during admission, and environmental problems on the ward. The study highlights disproportionality analysis of complaints as a valuable tool to monitor patient concerns systematically.
Activity of ceftolozane/tazobactam and imipenem/relebactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected in central and northern Europe (Belgium, Norway, Sweden, Switzerland)—SMART 2017–21
Authors: Karlowsky James A , Lob Sibylle H , Hawser Stephen P , Kothari Nimmi , Siddiqui Fakhar , Alekseeva Irina , DeRyke C Andrew , Young Katherine , Motyl Mary R , Sahm Daniel F
Published: August 2023

Objectives

To evaluate the in vitro activities of ceftolozane/tazobactam and imipenem/relebactam against clinical isolates of Gram-negative bacilli collected in four central and northern European countries (Belgium, Norway, Sweden, Switzerland) during 2017–21.

Methods

Participating clinical laboratories each collected up to 250 consecutive Gram-negative isolates per year from patients with bloodstream, intraabdominal, lower respiratory tract or urinary tract infections. MICs were determined by CLSI broth microdilution and interpreted using 2022 EUCAST breakpoints. β-Lactamase genes were identified in select β-lactam-non-susceptible isolate subsets.

Results

Ninety-five percent of all Enterobacterales (n = 4158), 95% of ESBL-positive non-carbapenem-resistant Enterobacterales (non-CRE) phenotype Escherichia coli and 85% of ESBL-positive non-CRE phenotype Klebsiella pneumoniae were ceftolozane/tazobactam susceptible. By country, 88% (Belgium), 91% (Sweden, Switzerland) and 96% (Norway) of ESBL-positive non-CRE phenotype Enterobacterales were ceftolozane/tazobactam susceptible. Greater than ninety-nine percent of non-Morganellaceae Enterobacterales and all ESBL-positive non-CRE phenotype Enterobacterales were imipenem/relebactam susceptible. Ceftolozane/tazobactam (96%) and imipenem/relebactam (95%) inhibited most Pseudomonas aeruginosa (n = 823). Both agents retained activity against ≥75% of cefepime-resistant, ceftazidime-resistant and piperacillin/tazobactam-resistant isolates; 56% and 43% of meropenem-resistant isolates were ceftolozane/tazobactam susceptible and imipenem/relebactam susceptible, respectively. By country, 94% (Belgium), 95% (Sweden) and 100% (Norway, Switzerland) of P. aeruginosa were ceftolozane/tazobactam susceptible and 93% (Sweden) to 98% (Norway, Switzerland) were imipenem/relebactam susceptible. Carbapenemase gene carriage among Enterobacterales and P. aeruginosa isolates was generally low (<1%) or completely absent with one exception: an estimated 2.7% of P. aeruginosa isolates from Belgium carried an MBL.

Conclusions

Recent clinical isolates of Enterobacterales and P. aeruginosa collected in four central and northern European countries were highly susceptible (≥95%) to ceftolozane/tazobactam and imipenem/relebactam.
The impact of protein source and grain inclusion on digestibility, fecal metabolites, and fecal microbiome in adult canines
Authors: Clark Stephanie D , Hsu Clare , McCauley Sydney R , de Godoy Maria R C , He Fei , Streeter Renee M , Taylor Emily G , Quest Bradley W
Published: August 2023

This study was conducted to determine the effect of animal protein inclusion rate and grain-free or grain-inclusive diets on macronutrient digestibility, fecal characteristics, metabolites, and microbiota in mixed-breed hounds and Beagles. Four experimental extruded kibble diets were made with varying amounts of animal protein and carbohydrates: 1) high animal protein, grain-inclusive (HA-GI), 2) low animal protein, grain-free (LA-GF), 3) low animal protein, grain-inclusive (LA-GI), and 4) high animal protein, grain-free (HA-GF). Thirty-two Beagles and 33 mixed-breed hounds were assigned to 1 of the 4 treatment groups in a completely randomized design that lasted 180 d. All diets were similar in chemical composition and well-digested by the animals. In general, for fecal metabolites, mixed-breed hounds had a greater concentration of total short-chain fatty acid (SCFA) and ammonia and lower indole concentration than Beagles (P < 0.05). In mixed-breed hounds, LA-GF had a greater (P < 0.05) total SCFA concentration than HA-GI and LA-GI; however, this was not observed in Beagles. There were greater concentrations of ammonia, phenol, and indole in HA-GI than in LA-GF (P < 0.05). Breed-affected fecal primary bile acid (BA) concentration, as mixed-breed hounds had a greater concentration of cholic acid (CA) than Beagles (P < 0.05). Mixed-breed hounds fed LA-GF resulted in greater CA concentrations than HA-GI and LA-GI (P < 0.05). Dogs who consumed LA-GF had lower fecal secondary BA content than the other groups (P < 0.05). The distribution of the fecal microbiota community differed in LA-GF compared with the other groups, with lower α-diversity. However, dogs fed LA-GF had the largest difference in composition with greater Selenomonadaceae, Veillonellaceae, Lactobacillaceae, Streptococcus, Ligilactobacillus, Megamonas, Collinsella aerofaciens, and Bifidobacterium sp. than the other groups. A significant breed effect was noted on nutrient digestibility, fecal metabolites, and microbiota. A treatment effect was observed in LA-GF as it resulted in greater fecal SCFA, lower protein fermentative end products, greater fecal primary BAs, lower fecal secondary BA concentrations, and shifts in fecal microbiota.
A second iron injection administered to piglets during lactation improves hemoglobin concentration, growth performance, and carcass characteristics at slaughter
Authors: Chevalier Tyler B , Lyons Wesley , Paczosa Duncan B , Rentfrow Gregg K , Lindemann Merlin D
Published: August 2023

An experiment was conducted to evaluate the effects of a second injection of iron dextran administered on days 6 to 8 of age. A total of 144 crossbred pigs (equal barrows and gilts; initial age 6 to 8 d; initial body weight [BW] = 2.86 ± 0.01 kg) were assigned to either the control (CON) or an added-injection treatment (+Fe). Pigs were paired by sex and BW within a litter and randomly assigned to the iron treatment within each pair. All pigs had received an initial intramuscular (IM) injection of iron dextran (200 mg Fe) <24 h after birth. Pigs assigned to the +Fe treatment received a second IM injection of iron dextran (200 mg Fe) on days 6 to 8. All pigs were weaned at 22 to 25 d, housed 6 pigs/pen, and received a common corn–soybean meal diet. BW and feed disappearance were recorded every 2 wk. Hemoglobin (Hb) concentrations were measured at birth, initiation of experiment (days 6 to 8), weaning, and the end of the nursery and end of the study. At the end of the study, 1 pig/pen (n = 12 pigs/treatment), closest to the pen mean was selected and slaughtered for carcass characteristic measures. The individual pig served as the experimental unit for BW, Hb, average daily gain (ADG), and carcass characteristic data whereas the pen served as the experimental unit for average daily feed intake, and gain/feed ratio data. The +Fe pigs had a greater Hb at weaning (13.1 vs. 10.7 g/dL, respectively; P < 0.01) and end of the nursery (12.1 vs. 11.7 g/dL, respectively; P = 0.01) compared to CON pigs. During the finisher period, +Fe pigs had a greater ADG (0.94 vs. 0.91 kg, respectively; P = 0.05) compared to CON pigs. Overall, pigs receiving the second iron injection had an ~4% increase in ADG (P = 0.04) from weaning to the end of study. The cumulative improvement in ADG from weaning to the end of study observed for +Fe group resulted in +Fe pigs having a heavier BW at the end of the study (~3 kg; P = 0.04). Following slaughter, +Fe pigs had ~7.2% heavier trimmed loin (P = 0.04) compared to the CON pigs. In conclusion, administering a second iron injection resulted in greater Hb at weaning and the end of the nursery as well as improved growth performance from weaning to the end of study weight and increased carcass weight at slaughter.
An unusual route of odontogenic infection from the mandible to the orbit through the facial spaces, resulting in blindness: a rare case report
Authors: Nashawi Faez Ebrahim , Alkheder Ahmad , Shasho Hamza Omar , Abdullah Lava , Mohsen Adham bader aldeen
Published: August 2023

Orbital infection is a rare complication of odontogenic infections, mostly originating from maxillary teeth. In our case, we present one of the unusual routes by which an odontogenic infection of a lower molar tooth has spread into the orbit. A 67-year-old uncontrolled diabetic patient was referred to our hospital with a complaint of a swollen right masseteric region and orbital infection following a dental procedure on the right mandibular third molar. Computed tomography scan and magnetic resonance imaging showed multiple abscesses localized in the masseteric and infratemporal spaces, extending into the orbital cavity through bony erosion in the lateral orbital with no sinus involvement. Improper treatment and poorly controlled diabetes resulted in the extensive spread of the infection. Clinical and radiological reevaluation has played a major role in the management of our case by elucidating the route of infection and localizing abscess foci accurately.
Left brachiocephalic venous thrombus initially presenting as acute aortic syndrome
Authors: Yang Amy , Seevanayagam Siven
Published: August 2023

Upper extremity deep venous thrombosis (UEDVT) is rare but carries significant morbidity. Primary UEDVT presents non-specifically and there are no clear diagnostic or management guidelines, which are essential for early treatment to prevent potentially devastating complications such as pulmonary embolus or post-thrombotic pain syndrome. A patient with left brachiocephalic vein UEDVT initially diagnosed radiographically as an acute aortic syndrome and referred to a cardiothoracic unit is presented. Computed tomography venogram confirmed the diagnosis of UEDVT and therapeutic anticoagulation was started. This case highlights the need for validated diagnostic and management algorithms for UEDVT. Furthermore, this relatively rare condition should be considered for patients with acute chest pain and abnormal imaging referred to surgical units.
Gastric conduit reconstruction after esophagectomy with right gastroepiploic artery absence: a case report
Authors: Charalampous C , Kofopoulos-Lymperis E , Pikouli A , Lykoudis P , Pararas N , Papaconstantinou D , Nastos C , Myoteri D , Dellaportas D
Published: August 2023

Gastric conduit reconstruction is the standard choice after esophagectomy. Conduit’s vascular supply is of primary importance mainly based on right gastroepiploic vessels. A 57-year-old male with absent right gastroepiploic artery, due to a duodenal bleeding ulcer treated with gastroduodenal artery ligation 10 years ago, was treated for gastroesophageal cancer and required esophagectomy. Surgical merits of this troublesome scenario are highlighted. Previous surgical history is highly important for patients requiring complex surgery as esophagectomy. The use of the stomach as conduit after esophagectomy is always the primary option; however vascular supply of it should not be compromised. Variations are rare and careful planning may overcome obstacles as in this case.
Some completeness results in derivational modal logic
Authors: Gougeon Quentin
Published: August 2023

Alongside the traditional Kripke semantics, modal logic also enjoys a topological interpretation, which is becoming increasingly influential. In this paper, we present various developments related to the topological derivational semantics, based on the Cantor derivative operator. We provide several characterizations of the validity of the axioms of bounded depth. We also elucidate the topological interpretation of the axioms of directedness and connectedness—which come in different forms, all of which we examine. We then prove results of soundness and completeness for all of these logics, using a range of old and new techniques.
Characteristic functions for cosmological cross-correlations
Authors: Breysse Patrick C , Chung Dongwoo T , Ihle Håvard T
Published: August 2023

We introduce a novel unbiased, cross-correlation estimator for the one-point statistics of cosmological random fields. One-point statistics are a useful tool for analysis of highly non-Gaussian density fields, while cross-correlations provide a powerful method for combining information from pairs of fields and separating them from noise and systematics. We derive a new Deconvolved Distribution Estimator that combines the useful properties of these two methods into one statistic. Using two example models of a toy Gaussian random field and a line intensity mapping survey, we demonstrate these properties quantitatively and show that the deconvolved distribution estimator can be used for inference. This new estimator can be applied to any pair of overlapping, non-Gaussian cosmological observations, including large-scale structure, the Sunyaev–Zeldovich effect, weak lensing, and many others.
Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) in Locally Advanced or Metastatic Breast Cancer: Prospective Cohort Study
Authors: Lück Hans-Joachim , Schmidt Marcus , Hesse Tobias , Hoffmann Oliver , Heinrich Bernhard J , Park-Simon Tjoung-Won , Grischke Eva-Maria , Weide Rudolf , Müller-Huesmann Harald , Lüdtke-Heckenkamp Kerstin , Fischer Dorothea , Zemlin Cosima , Kögel Matthias , Wu Jane , Schmitz Helga , Engelbrecht Christian , Jackisch Christian
Published: August 2023

Background

Eribulin, a halichondrin-class microtubule dynamics inhibitor, is a preferred treatment option for patients with advanced breast cancer who have been pretreated with an anthracycline and a taxane. Peripheral neuropathy (PN) is a common side effect of chemotherapies for breast cancer and other tumors. The Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) noninterventional postauthorization safety study assessed the incidence and severity of PN in patients with breast cancer treated with eribulin.

Patients and Methods

IRENE is an ongoing observational, single-arm, prospective, multicenter, cohort study. Adult patients (≥18 years of age) with locally advanced or metastatic breast cancer and disease progression after 1-2 prior chemotherapeutic regimen(s) for advanced disease were treated with eribulin. Patients with eribulin-induced PN (new-onset PN or worsening of preexisting PN) were monitored until death or resolution of PN. Primary endpoints included the incidence, severity, and time to resolution of eribulin-induced PN. Secondary endpoints included time to disease progression and safety.

Results

In this interim analysis (data cutoff date: July 1, 2019), 67 (32.4%) patients experienced any grade eribulin-induced PN, and 12 (5.8%) patients experienced grade ≥3 eribulin-induced PN. Median time to resolution of eribulin-induced PN was not reached. Median time to disease progression was 4.6 months (95% CI, 4.0-6.5). Treatment-emergent adverse events (TEAEs) occurred in 195 (93.8%) patients and serious TEAEs occurred in 107 (51.4%) patients.

Conclusion

The rates of any grade and grade ≥3 eribulin-induced PN observed in this real-world study were consistent with those observed in phase III randomized clinical trials. No new safety findings were observed.
The Visegrád (V4) Countries
Authors: Šturma Pavel
Published: August 2023

The difficult historical developments of three of the Visegrád (V4) countries, namely the Czech Republic, Slovakia, and Hungary, influenced the role of international lawyers, both in academia and practice. Indeed, international law and its scholarship cannot be dissociated from politics, which is also true in this part of Europe. Their legal systems and academia had their roots in the Western European traditions. However, their development suffered because of almost six decades of totalitarian regimes (Nazi and communist) between 1939 and 1989. Even though they are now part of the European organizations, their relatively long isolation probably caused them to be viewed as semi-peripheral, from the point of view of the West. At the same time, the experience of these countries contributes to a higher sensitivity to the issues of peace, Statehood, and sovereignty. Since these values were not for long present, they are not taken for granted and need to be protected.
A Novel Home-Based Study of Circadian Rhythms: Design, Rationale, and Methods for the Circadia Study
Authors: Vlasac Irma M , Bormes Gregory W , Do Elizabeth , Benkhoukha Selma S , Diallo Naby , Fryou Noah L , Gioia Siena , Akeju Oluwaseun , Joseph Clarence , Kuan Anne , Lapan Jennifer , Oluwadara David , Team the Pepper , Rahman Shadab A , Saxena Richa , Scheer Frank A J L , Westover M Brandon , Winkelman John W , Woodson Faraji , Lane Jacqueline M
Published: August 2023

The Circadia Study (Circadia) is a novel “direct-to-participant” research study investigating the genetics of circadian rhythm disorders of advanced and delayed sleep phase and non-24 hour rhythms. The goals of the Circadia Study are twofold: (i) to create an easy-to-use toolkit for at-home circadian phase assessment for patients with circadian rhythm disorders through the use of novel in-home based surveys, tests, and collection kits; and (ii) create a richly phenotyped patient resource for genetic studies that will lead to new genetic loci associated with circadian rhythm disorders revealing possible loci of interest to target in the development of therapeutics for circadian rhythm disorders. Through these goals, we aim to broaden our understanding and elucidate the genetics of circadian rhythm disorders across a diverse patient population while increasing accessibility to circadian rhythm disorder diagnostics reducing health disparities through self-directed at-home dim light melatonin onset (DLMO) collections.
Multiple Routes to Color Convergence in a Radiation of Neotropical Poison Frogs
Authors: Twomey Evan , Melo-Sampaio Paulo , Schulte Lisa M , Bossuyt Franky , Brown Jason L , Castroviejo-Fisher Santiago
Published: August 2023

Convergent evolution is defined as the independent evolution of similar phenotypes in different lineages. Its existence underscores the importance of external selection pressures in evolutionary history, revealing how functionally similar adaptations can evolve in response to persistent ecological challenges through a diversity of evolutionary routes. However, many examples of convergence, particularly among closely related species, involve parallel changes in the same genes or developmental pathways, raising the possibility that homology at deeper mechanistic levels is an important facilitator of phenotypic convergence. Using the genus Ranitomeya, a young, color-diverse radiation of Neotropical poison frogs, we set out to 1) provide a phylogenetic framework for this group, 2) leverage this framework to determine if color phenotypes are convergent, and 3) to characterize the underlying coloration mechanisms to test whether color convergence occurred through the same or different physical mechanisms. We generated a phylogeny for Ranitomeya using ultraconserved elements and investigated the physical mechanisms underlying bright coloration, focusing on skin pigments. Using phylogenetic comparative methods, we identified several instances of color convergence, involving several gains and losses of carotenoid and pterin pigments. We also found a compelling example of nonparallel convergence, where, in one lineage, red coloration evolved through the red pterin pigment drosopterin, and in another lineage through red ketocarotenoids. Additionally, in another lineage, “reddish” coloration evolved predominantly through structural color mechanisms. Our study demonstrates that, even within a radiation of closely related species, convergent evolution can occur through both parallel and nonparallel mechanisms, challenging the assumption that similar phenotypes among close relatives evolve through the same mechanisms.
Engaging Premedical Students in Medical Education Research: Benefits of Clinical Skills Observation Studies
Authors: Weingartner Laura A. , Noonan Emily J. , Shaw M. Ann , Fuselier Linda
Published: August 2023

Purpose

Observations requiring evaluation and critical thinking can be powerful learning experiences. Video-recorded standardized patient encounters are underused resources for evaluation and research. The authors engaged premedical students in medical education research reviewing standardized patient encounters. This study aims to explore participant perceptions of the research experience and how they gained clinical skills.

Method

This mixed-method study was completed between 2019 and 2022. Premedical participants coded medical students’ clinical skills in video-recorded standardized patient encounters. Each participant also completed their own new patient history in a standardized patient encounter at both the beginning and end of their research project. Participants then completed an end-of-program debrief to discuss their experiences coding the clinical skills encounters. The authors coded communication skills implemented in the pre/postencounters and completed a thematic analysis of the debrief transcripts.

Results

All 21 participants demonstrated significant clinical skills gain after their research project, which included spending more time with the patient (pre-M=5 minutes, post-M=19 minutes, t=13.2, P<.001) and asking more questions (pre-M=13, post-M=40, t=9.3, P<.001). Prior clinical experience did not influence pre- or postoutcomes, but the number of videos coded was associated with asking more questions in the postencounter. Participants described learning actively and reflected that their clinical skills research project gave them greater insight into patient-care aspects of medical school and how medical students learn.

Conclusions

These data demonstrate that observational studies in which premedical students evaluate standardized patient encounters gave the students context to medical education while enabling them to develop and transfer their own clinical skills. Studies observing standardized patient encounters provide rich insight into clinical skills development, and this work generates both research outcomes and actionable program evaluation data for medical educators. Purposefully engaging premedical students in such experiential learning opportunities benefits the students and helps cultivate early medical education pathways for these learners.
How Do Academic Medicine Pathways Differ for Underrepresented Trainees and Physicians? A Critical Scoping Review
Authors: Russel Sarah M. , Carter Taylor M. , Wright Sarah T. , Hirshfield Laura E.
Published: August 2023

Purpose

Academic medicine faces difficulty recruiting and retaining a diverse workforce. The proportion of medical students who are underrepresented in medicine (URiM) is smaller than the proportion of URiMs in the general population, and these numbers worsen with each step up the academic medicine ladder. Previously known as the “leaky pipeline,” this phenomenon may be better understood as disparate “pathways with potholes,” which acknowledges the different structural barriers that URiM trainees and faculty face in academic medicine. This critical scoping review analyzed current literature to determine what variables contribute to the inequitable “pathways and potholes” URiM physicians experience in academic medicine.

Method

The authors combined scoping review methodology with a critical lens. The comprehensive search strategy used terms about academic medicine, underrepresented groups, and leaving academic medical careers. One reviewer conducted screening, full-text review, and data extraction while in consultation with members of the research team. Data extraction focused on themes related to pathways and potholes, such as attrition, recruitment, and retention in academic medicine. Themes were iteratively merged, and quality of contribution to the field and literature gaps were noted.

Results

Included papers clustered into attrition, recruitment, and retention. Those pertaining to attrition noted that URiM faculty are less likely to get promoted even when controlling for scholarly output, and a hostile work environment may exacerbate attrition. Recruitment and retention strategies were most effective when multipronged approaches changed every step of the recruitment and promotion processes.

Conclusions

These studies provide examples of various “potholes” that can affect representation in academic medicine of URiM trainees and faculty. However, only a few studies examined the link between isolating and hostile work environments, the so-called “chilly climate,” and attrition from academic medicine. Understanding these concepts is key to producing the most effective interventions to improve diversity in medicine.
On Purpose: The Case for Alignment in Assessment
Authors: Norcini John
Published: August 2023

In this issue, Ryan and colleagues underscore the need for criterion-based assessments in the context of competency-based curricula in undergraduate medical education (UME). They also point out that the same scores are often interpreted from a norm-referenced perspective to support the admissions process for residency training. This problem is not unique to UME because in graduate medical education (GME), the same assessments are often used for both decision making and providing feedback. Unfortunately, an assessment with 2 purposes is neither optimal nor efficient for either purpose and may be accompanied by significant side effects. One approach to addressing these challenges is to develop a system of assessment that addresses both purposes but where each component is focused on a single purpose. This leads to alignment and transparency from purpose to test content and from test content to score interpretation and/or feedback. It ensures that the test material is optimized for the task, that individual assessments are constructed to enhance the validity of their scores, and that undesirable side effects are limited.