bluuebunny/crossref_metadata_2025 huggingface dataset:
Is heat stress a growing problem for dairy cattle husbandry in the temperate regions? A case study of Baden-Württemberg in Germany
Authors: Leandro Miguel António , Stock Joana , Bennewitz Jörn , Chagunda Mizeck G G
Published: September 2024

Heat stress with measurable effects in dairy cattle is a growing concern in temperate regions. Heat stress in temperate regions differs between environments with different geophysical characteristics. Microclimates specific to each environment were found to greatly impact at what level heat stress occurs and will occur in the future. The landlocked state of Baden-Württemberg, Germany, provides several different environments, hence, a good case-study. Temperature–Humidity Index (THI) from 17 weather stations for the years 2003 to 2022 was calculated and milking yields from 22 farms for the years 2017 to 2022 were collected. The occurrences and evolving patterns of heat stress were analyzed with the use of a THI, and the effect of heat stress on milk yield was analyzed based on milking records from Automated Milking Systems. Daily average THI was calculated using hourly readings of relative humidity and ambient temperature, disregarding solar radiation and wind, as all animals were permanently stabled. Based on studies conducted in Baden-Württemberg and neighboring regions, cited ahead in the section of THI, THI = 60 was the threshold for heat stress occurrence. Findings show that the heat stress period varied between stations from 64 to 120 d with THI ≥ 60 in a year. This aligns with yearly and summer averages, also steadily increasing from May to September. The length of the heat stress period was found to increase 1 extra day every year. Extreme weather events such as heat waves did not increase the heat stress period of that year in length but increased the average THI. Milk yield was found to be significantly (α = 0.05) different between counties grouped into different zones according to heat stress severity and rate of increase in daily average THI. Future attempts at managing heat stress on dairy cattle farms in the temperate regions should account for microclimate, as geographical proximity does not mean that the increase in heat stress severity will be the same in the 2 neighboring areas.
State Liability in EU Environmental Law: Francovich is Dead, Long Live Compensation?
Authors: Stagstrup Johan P
Published: September 2024

In the milestone Francovich case, the European Court of Justice (ECJ) granted individuals, under certain conditions, a right to reparation for Member States’ breaches of EU law. While EU environmental law is rife with well-documented infringements, the Francovich principle, however, has seen little use in practice. This article examines why that is. Through an analysis of the ECJ’s Francovich-related case law, and especially the ECJ’s recent decision in C-61/21 Ministre de la Transition écologique, this study assesses the Court’s interpretation of the Francovich condition that the relevant provision must be ‘intended to confer rights’ on individuals. Against this backdrop, it is shown that the absence of EU environmental law conferring ‘Francovich rights’ is due to the principle’s incompatibility with the collective rights found in EU environmental law. Following from this, this study highlights the incorporation of compensation provisions in three key EU environmental directives as an alternative to Francovich liability and, in so doing, examines the evolving nature of private enforcement of EU environmental law.
Blood immune profiles reveal a CXCR3/CCR5 axis of dysregulation in early sepsis
Authors: Kealy David J , Wilson Julie C , Jaconelli Tom , Hogg Karen , Coop Rebecca , Forshaw Greg , Todd Neil , Yates David , Signoret Nathalie
Published: September 2024

We report on a pilot study exploring whether blood immune signatures can reveal early specific indicator profiles for patients meeting sepsis criteria upon hospital admission. We analyzed samples of sepsis-suspected patients (n = 20) and age-spanning healthy controls (n = 12) using flow cytometry–based assays. We measured inflammatory markers from plasma fractions and immunophenotyped freshly isolated unfixed peripheral blood mononucleated cells for leukocyte subset representation and expression of activation markers, including chemokine receptors. We found that besides IL-6 and sCD14, CXCR3 ligands (CXCL9 and CXCL10) separated sepsis-suspected patients from healthy controls. The abundance of CD4+ T cells was significantly reduced in patients, while they displayed substantial losses of CCR5-expressing monocytes and CXCR3/CCR5 double-positive T cells. Post hoc subgrouping of patients according to their sepsis diagnosis on discharge identified CXCR3/CCR5 double expression on T cells as a separating characteristic for confirmed cases. This work suggests a potential novel axis of dysregulation affecting CXCR3 and CCR5 in early sepsis.
Neonatal neutrophils exhibit reduced NLRP3 inflammasome activation
Authors: Wackerbarth Lou Martha , Seifert Sonja Birke , Napoli Matteo , Rohwedder Ina , Vogl Thomas , Scheiermann Christoph , Kolben Thomas , Nussbaum Claudia , Pruenster Monika , Immler Roland , Sperandio Markus
Published: September 2024

Newborns are at high risk to develop sepsis. This is linked to innate immune responses at birth which are not completely adapted to postnatal life. Neutrophils are key players of innate immunity and exhibit a marked ontogenetic regulation of their functionality. Here, we studied the NLRP3 inflammasome in neonatal neutrophils and found lower baseline expression of NLRP3, pro-caspase-1, and the K+-channel KV1.3 compared with adult neutrophils. Following stimulation with lipopolysaccharide/nigericin, apoptosis-related speck-like protein containing a caspase recruitment domain oligomerization, caspase-1 activation, and interleukin-1β (IL-1β) release were significantly reduced in neonatal compared with adult neutrophils. Similarly, stimulation of neonatal neutrophils with E-selectin led to reduced NLRP3 inflammasome activation accompanied by diminished release of the alarmin S100A8/A9. Taken together, our results strongly indicate diminished NLRP3 inflammasome activation in neonatal neutrophils leading to a significant reduction of released IL-1β and S100A8/A9. These findings identify reduced neutrophil NLRP3 inflammasome activation as a critical component contributing to the inherent susceptibility to infections in neonates.
Utility of genomic testing in children, adolescents, and young adults with cancer
Authors: Debortoli Emily , McGahan Ella , Yanes Tatiane , Berkman Jennifer , Fuentes-Bolanos Noemi , Milch Vivienne , Steinberg Julia , McInerney-Leo Aideen
Published: September 2024

Genomic testing can inform the diagnosis and personalize management of cancers in children, adolescents, and young adults (CAYA). This scoping review explored the clinical utility and impact of genomic testing in general CAYA cancer cohorts. Relevant records published in English between 2017 and 2024 were identified by searching PubMed. 36 studies (32 original articles; 4 reviews) were identified on genomic testing in CAYA cancers, most of which were advanced cancers. Studies internationally reported that approximately 16%-18% of CAYAs with cancer carry an associated pathogenic germline variant where 40% are de novo, and can guide treatment (eg, DNA repair gene variants). Somatic variants, predominantly copy number or structural rearrangements, inform diagnosis in up to 95% of primary cancers. Between 18% and 69% of patients have a somatic variant with a matched therapy, but only one third receive the genomic-guided recommendation, predominantly due to declining patient condition. Few studies evaluated the impact of matched therapies on response and survival. Combining comprehensive DNA and RNA sequencing maximises sensitivity. Circulating tumour DNA was detected in most primary cancers and shows high concordance with tumour tissue. In conclusion, genomic testing of CAYA cancers is feasible, informs diagnoses and guides personalised care. Further research is needed on response to genomic-guided treatments.
Disparities in the utilization of magnetic resonance imaging for prostate cancer detection: a population-based study
Authors: El Khoury Christiane J , Freedland Stephen J , Gandhi Krupa , Keith Scott W , Nikita Nikita , Shaver Amy , Sharma Swapnil , Kelly W M Kevin , Lu-Yao Grace
Published: September 2024

Background

Racial disparities exist in prostate cancer care and outcomes. Ultrasound-guided biopsy may miss a sizeable portion of clinically significant prostate cancer, while magnetic resonance imaging (MRI) improves its detection. This study aimed to investigate demographic and socioeconomic status–related factors influencing MRI use for prostate cancer detection.

Methods

Surveillance, Epidemiology, and End Results Program–Medicare data were used to assess use of prediagnostic MRI in 90 908 patients with a diagnosis of primary prostate cancer (2012-2019). Modified Poisson regression models adjusted for socioeconomic factors such as income, education, Medicare buy-in, and dual eligibility, were used to examine factors associated with MRI use. All statistical tests were 2 sided.

Results

Prediagnostic MRI use increased substantially between 2012 (3.8%) and 2019 (32.6%). The disparity in utilization between non-Hispanic Black and non-Hispanic White patients decreased by more than half, from 43% (relative risk [RR] = 0.57, 95% confidence interval [CI] = 0.48 to 0.67) in 2012 to 20% (RR = 0.80, 95% CI = 0.74 to 0.86) in 2019. Rural residents were 35% less likely (RR = 0.65, 95% CI = 0.61 to 0.69) to undergo MRI, while individuals in the US Census Central (vs West) region of the United States were 49% less likely (RR = 0.49, 95% CI = 0.48 to 0.51). No significant disparities in MRI use were identified between individuals 75 years of age and older and individuals aged 64 to 75 years. Socioeconomic status factors associated with MRI use were income, education, Medicare buy-in, and dual eligibility.

Conclusions

This study revealed increased MRI utilization over time, including among individuals 75 years of age and older. Racial disparities decreased, while wide urban-rural disparities remained. Targeted public health interventions should focus on geographical factors because urban or rural designations and US region were associated with the most prominent disparities. Future research should explore pathways contributing to these disparities by using a multidisciplinary approach, including geographical studies, to help eliminate health-care inequities.
Socioeconomic and urban-rural disparities in genome-matched treatment receipt and survival after genomic tumor testing
Authors: DiBiase Jessica F , Scharnetzki Elizabeth , Edelman Emily , Reed E Kate , Helbig Petra , Rueter Jens , Miesfeldt Susan , Frankenfeld Cara L , Han Paul K J , Jacobs Elizabeth A , Anderson Eric C ,   Maine Cancer Genomics Initiative Working Group, Erickson Nicholette , Movalia Mayur , Skacel Marek , Espinosa Allan , Gupta Ridhi , Kumar Rachit , Polkinghorn Richard , Darus Christopher , Remick Scot , Christman Robert , Rasmussen Karen , Thomas Christian , Brooks Philip , Chodkiewicz Catherine , Harb Antoine , Sinclair Sarah , Rubin Peter , Connelly Elizabeth , Georges Peter , Bourne Jennifer , Choquette Linda , Fasman Ken , Flewellen Cristen , Edelman Emily , Guerrette Lory , Helbig Petra , Mockus Susan , Reed Kate , Rueter Jens , Sanghavi Kunal , Anderson Eric , Awale Sumayo , DiBiase Jessica , DiPalazzo John , Fenton Anny , Frankenfeld Cara , Gutheil Caitlin , Han Paul , Hinton Ally , Kohut Michael , Leeds Susan , Lucas Lee , Scharnetzki Elizabeth , Waterston Leo , Wierda Lisbeth
Published: September 2024

Background

Emerging cancer treatments are often most available to socially advantaged individuals. This study examines the relationship of patient educational attainment, income level, and rurality to the receipt of genome-matched treatment and overall survival.

Methods

Survey and clinical data were collected from patients with cancer (n = 1258) enrolled in the Maine Cancer Genomics Initiative. Logistic regression models examined whether receipt of genome-matched treatment differed by patient education, income, and rurality. Kaplan–Meier curves and Cox regression were conducted to evaluate 12-month mortality. We completed additional exploratory analyses using Kaplan–Meier curves and Cox models stratified by receipt of genome-matched treatment. Logistic and Cox regression models were adjusted for age and gender.

Results

Educational attainment, income level, and rurality were not associated with genome-matched treatment receipt. Of 1258 patients, 462 (36.7%) died within 365 days of consent. Mortality risk was associated with lower educational attainment (hazard ratio [HR] = 1.30, 95% confidence interval [CI] = 1.06 to 1.59; P = .013). No statistically significant differences in mortality risk were observed for income level or rurality. Exploratory models suggest that patients who did not receive genome-matched treatment with lower educational attainment had higher mortality risk (HR = 1.36, 95% CI = 1.09 to 1.69; P = .006). For patients who did receive genome-matched treatment, there was no difference in mortality risk between the education groups (HR = 1.01, 95% CI = 0.56 to 1.81; P > .9).

Conclusion

Although there were no disparities in who received genome-matched treatment, we found a disparity in mortality associated with education level, which was more pronounced for patients who did not receive genome-matched treatment. Future research is warranted to investigate the intersectionality of social disadvantage with clinical outcomes to address survival disparities.
Inclusive measure development: amplifying the voices of adolescents and young adults with spina bifida in a new measure of benefit-finding and growth
Authors: Kritikos Tessa K , Smith Zoe R , Stiles-Shields Colleen , Clark Olivia E , Winning Adrien M , Encalade Alana , Hendrix Millicent , Helgeson Vicki , Holmbeck Grayson
Published: September 2024

Objective

Benefit-finding and growth is an important process across a range of medical populations. However, it has been understudied in the context of lifelong chronic conditions, such as spina bifida (SB). This study aimed to develop a new measure of benefit-finding and growth for youth with SB, confirm its factor structure, and examine its psychometric properties.

Method

To generate items for the new measure, 20 adolescents and young adults with SB completed qualitative interviews regarding their experience of living with SB. Interviews were coded for benefits. Questionnaire items were generated from these benefits, and an expert panel refined the wording of these items. The resultant 31-item measure was shared with six of the 20 participants for feedback and then piloted among 251 youth with SB. The factor structure of the measure was confirmed and reliability and convergent validity were assessed.

Results

Both a one- and four-factor structure were supported. The four factors include: Life Perspectives and Priorities, Personal Characteristics and Traits, Connections and Opportunities, and Problem Solving. Higher total and factor scores represent greater benefit-finding and growth. The measure demonstrated excellent internal consistency (α = 0.95). The new measure also showed significant positive correlations with optimism, positive affect, and life satisfaction.

Conclusions

This study produced a measure of benefit-finding and growth for youth with SB. Clinically, information about what youth with SB perceive to be their areas of strength and growth from their condition provides crucial insight into which factors to enhance in this population.
Mpox Recurrence and Tecovirimat Resistance in a Patient With Advanced Human Immunodeficiency Virus Disease
Authors: Griffith David C , Fall Amary , Carter Mihaela , Traut Caroline C , Sop Joel , Hansoti Bhakti , Gebo Kelly A , Mostafa Heba H , Blankson Joel N
Published: September 2024

We present a case of mpox recurrence in a transgender woman with AIDS. Her recurrent lesions required several courses of antiviral therapy over a 5-month period and her monkeypox viral genome was subsequently noted to have tecovirimat resistance mutations. Interestingly, she developed a robust orthopoxvirus-specific T-cell response.
On the morphology of urosome appendages and their potential function of marine planktonic copepods
Authors: Paffenhöfer G-A , Köster M
Published: September 2024

The goal of this paper is to draw the attention of biological oceanographers to the urosome of zooplankton. The methodology to determine the utilization of urosomes and their sensors for predator recognition is in its infancy. We here describe the potential utilization of setae and their activity of mostly juvenile copepods for the purpose of perceiving predators. Our morphological observations let us assume that calanoid nauplii have few means to perceive predators approaching from the rear and most likely from frontal, as their appendages are moving most of the time. This is being compared to post-nauplii, i.e. copepodid stages, and adults who possess a 2D array of setae on their urosomes, potentially able to perceive predators approaching from the rear. Detailed small-scale observations should reveal the sensor potential of urosomes of nauplii and older stages of planktonic copepods.
PDHX acetylation facilitates tumor progression by disrupting PDC assembly and activating lactylation-mediated gene expression
Authors: Jiang Zetan , Xiong Nanchi , Yan Ronghui , Li Shi-ting , Liu Haiying , Mao Qiankun , Sun Yuchen , Shen Shengqi , Ye Ling , Gao Ping , Zhang Pinggen , Jia Weidong , Zhang Huafeng
Published: September 2024

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Effectiveness of low dose cyproterone acetate compared to standard dose in feminizing hormone treatment: a single institutional retrospective pilot study
Authors: Korpaisarn Sira , Arunakul Jiraporn , Chaisuksombat Kewalin , Rattananukrom Teerapong
Published: September 2024

Background

Data regarding the effectiveness of low-dose cyproterone acetate (CPA) in testosterone suppression as feminizing hormone therapy (FHT) in individuals assigned male at birth (AMAB) are sparse.

Aim

To assess the effectiveness in testosterone suppression using low-dose CPA (<25 mg/day) compared to standard-dose CPA (25–50 mg/day) in FHT.

Methods

A retrospective cohort study of 59 individuals AMAB using CPA was done at a tertiary care center in Bangkok, Thailand between January 2014 and July 2022.

Outcomes

The main outcomes included a median time when the testosterone was suppressed (<50 ng/dL), the proportion of individuals AMAB who achieved the targeted testosterone level at 3 months, and the testosterone level at each follow-up. Changes in clinical data were assessed.

Results

Among 59 individuals AMAB, 37 initiated CPA with available testosterone levels at the 3-month follow-up. Twenty-two individuals AMAB started with low-dose CPA (12.5 mg/day), and 15 individuals AMAB started with standard-dose CPA. The median time to reach targeted testosterone was 3 months in both groups (adjusted hazard ratio 0.60, P = .489). At 3 months, 72.7% of those on low-dose CPA and 86.7% of those on standard-dose CPA achieved targeted testosterone (adjusted relative risk 0.85, P = .606). Testosterone levels at all follow-up visits were not significantly different. The standard dose group had higher high-density lipoprotein cholesterol (HDL-C) but lower low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT).

Clinical Translation

This study supports a paradigm shift toward using lower-dose CPA in FHT.

Strengths and Limitations

This is one of a few studies showing the effectiveness of low-dose CPA in testosterone suppression within 3 months. Limitations include a small sample size and missing data.

Conclusions

Testosterone suppression is comparable between CPA 12.5 mg/day and the standard dose in FHT.
Policy preferences for medical access in Japan’s remote aging municipalities: Insights from a randomized conjoint experiment
Authors: Matsumoto Azusa , Oku Kenji , Nakagawa Mariko , Saito Hisamitsu , Khan Ghulam Dastgir , Kawata Keisuke , Oki Ichiro , Atsumi Tatsuya , Yoshida Yuichiro
Published: September 2024

Improved means of transportation play a vital role in accessing medical services, particularly in remote and ageing municipalities. In this study, we identify crucial attributes for improving access to medical services in the Shinhidaka and Urakawa municipalities in Japan. Using a randomised conjoint field experiment, we identify individuals’ preferences regarding the time and means of transportation to hospitals that can provide high-level medical services, along with additional tax payments to support these services. We find, inter alia, that respondents have the highest preference for reducing emergency ambulance transportation time to high-function hospitals. We also estimate the minimum average willingness to pay for these services; respondents are willing to pay at least JPY 60,000 (approximately USD 500) additional tax per year to the municipal government if the emergency transportation time to high-function hospitals is reduced. The findings of this study provide valuable insights into addressing the challenges of improving access to medical services in remote areas with an ageing population.
Neurotoxic effects associated with chronic inhalation and oral exposure to glyphosate-based herbicide IN adult rats
Authors: Bifaroni Renata M S , Binotti Giovanna D , Bruneri Karen P , Tavares Maria Eduarda A , Ueda Rose Meire R , Rossi Renata C , Teixeira Giovana R , Corrêa Camila Renata , Nai Gisele Alborghetti
Published: September 2024

The use of glyphosate-based herbicides (GBHs) for agricultural production has increased substantially around the world, as have their residues in the environment. Its effects on the central nervous system and neurotoxicity pathways are still not fully understood. The aim of this study was to evaluate the neurotoxic effect of chronic exposure to a GBH in adult rats. Sixty adult male albino Wistar rats were allocated into 6 groups, 2 control groups, and four GBH exposure groups (n = 10/group). The animals were exposed to two concentrations of GBH, orally and by inhalation: 2.99 × 10−3 grams of active ingredient per hectare (g.a.i./ha) and 7.48 × 10−3 g.a.i./ha. The animals were exposed for six months. Behavioral studies were performed. Brain tissue was collected for histopathological, immunohistochemical, and oxidative stress analyses. Animals exposed by inhalation to GBH spent more time in the central area of the open field test, whereas animals exposed to a high oral concentration of GBH spent less time in the open arms in the elevated plus-maze test. Tissue hyperemia occurred only in animals exposed to high concentrations of GBH. There was a greater thickness of the cerebral cortex and an increase in the expression of the BCL-2 in the animals exposed by inhalation to GBH. There was no difference in the doses of malonaldehyde and protein carbonylation between exposed and unexposed groups. The exposure to GBH caused increased levels of anxiety, regardless of the route, high concentrations caused hyperemia and inhalation exposure cause increased cortex thickness and increased BCl-2 expression.
Mitochondrial membrane potential and oxidative stress interact to regulate Oma1‐dependent processing of Opa1 and mitochondrial dynamics
Authors: Fogo Garrett M. , Raghunayakula Sarita , Emaus Katlynn J. , Torres Torres Francisco J. , Wider Joseph M. , Sanderson Thomas H.
Published: September 2024

Mitochondrial form and function are regulated by the opposing forces of mitochondrial dynamics: fission and fusion. Mitochondrial dynamics are highly active and consequential during neuronal ischemia/reperfusion (I/R) injury. Mitochondrial fusion is executed at the mitochondrial inner membrane by Opa1. The balance of long (L‐Opa1) and proteolytically cleaved short (S‐Opa1) isoforms is critical for efficient fusion. Oma1 is the predominant stress‐responsive protease for Opa1 processing. In neuronal cell models, we assessed Oma1 and Opa1 regulation during mitochondrial stress. In an immortalized mouse hippocampal neuron line (HT22), Oma1 was sensitive to mitochondrial membrane potential depolarization (rotenone, FCCP) and hyperpolarization (oligomycin). Further, oxidative stress was sufficient to increase Oma1 activity and necessary for depolarization‐induced proteolysis. We generated Oma1 knockout (KO) HT22 cells that displayed normal mitochondrial morphology and fusion capabilities. FCCP‐induced mitochondrial fragmentation was exacerbated in Oma1 KO cells. However, Oma1 KO cells were better equipped to perform restorative fusion after fragmentation, presumably due to preserved L‐Opa1. We extended our investigations to a combinatorial stress of neuronal oxygen–glucose deprivation and reoxygenation (OGD/R), where we found that Opa1 processing and Oma1 activation were initiated during OGD in an ROS‐dependent manner. These findings highlight a novel dependence of Oma1 on oxidative stress in response to depolarization. Further, we demonstrate contrasting fission/fusion roles for Oma1 in the acute response and recovery stages of mitochondrial stress. Collectively, our results add intersectionality and nuance to the previously proposed models of Oma1 activity.
First-Generation Low-Income Individuals in Medicine: A Scoping Review
Authors: Zheng Sijin , Brutus Nicholas , Rivera Alexis , O’Marr Jamieson M. , Gardezi Mursal , Grimshaw Alyssa A. , Malcolm Kenyer , Marcellon Roselande , Mason Hyacinth R. , Cavallo Jaime A.
Published: September 2024

Purpose

This comprehensive scoping review of the medical literature on first-generation low-income (FGLI) individuals in medicine aimed to synthesize the highest levels of evidence to inform medical education stakeholders.

Method

Database searches were conducted in Academic Search Premier, Education Research Premier, ERIC, Ovid MEDLINE, Ovid Embase, Professional Development Collection, PubMed, Scopus, Google Scholar, and Web of Science Core Collection from database inception through March 15, 2023. English-language articles on first-generation or low-income individuals in medicine from U.S. medical schools were included. Articles were evaluated for level of evidence and themes chosen.

Results

Database searches resulted in 27,075 citations, 247 of which qualified for data extraction. The articles were classified by evidence level: level I (n = 2), level II (n = 17), level III (n = 90), level IV (n = 78), and level V (n = 60). Publications reported on 9 major outcomes: exam performance (n = 108), medical school performance (n = 63), residency and fellowship performance (n = 7), honor society status (n = 12), leave of absence (n = 9), withdrawal, dismissal, and attrition (n = 20), medical education graduation (n = 37), career choice (n = 109), and intent to practice in disadvantaged and rural communities (n = 60). Compared with their peers, FGLI individuals had lower medical school and standardized exam scores, enrollment in national medical honor societies and multiple degree programs, and graduate medical education performance and higher rates of leaves of absence, incompletion of medical education, pursuing primary care and family medicine specialties, and intent to practice in underserved communities.

Conclusions

Despite an increase in the number of FGLI individuals in medicine, there remains significant opportunity to improve their inclusion and support. Multi-institutional, prospective, risk-adjusted, observational studies are required to determine how to best support FGLI individuals through all medical career stages.
When to Radiate and When to Stop? Timing Radiographic Surveillance During Nonoperative Treatment of Pediatric Diaphyseal Clavicle Fractures
Authors: Gomez Robert W. , Jessen David , Storino Morgan , Lamb Zachary J. , Wang Nigel K. , Jain Neil , Greenhill Dustin A.
Published: September 2024

Introduction:

Conservative management of most pediatric clavicle fractures is standard. Despite a predictable nonoperative course, evidence about the timeliness of healing is lacking. The goal of this study was to identify when radiographic signs of healing should be expected during routine conservative management of closed pediatric diaphyseal clavicle fractures.

Methods:

Patients 18 years or younger with an acute diaphyseal clavicle fracture treated at a large academic multispecialty orthopaedic practice over 5 years were retrospectively reviewed. Patients who completed nonoperative management until radiographic and clinical evidence of union were included and categorized into 3 age groups: infants and toddlers (0 to 2 y old), school-aged children (3 to 9 y old), and adolescents (10 to 18 y old). Radiographic healing was analyzed within each 2- to 4-week interval.

Results:

Among 390 patients, 303 met inclusion criteria. Overall shortening and displacement averaged 0.3±0.6 centimeters and 42.6%±43.0%, respectively. Follow-up averaged 50±24 days with an orthopaedic physician and 16.3±14.8 months for a well-child check. No clinically relevant or statistically significant improvements in the number of cortices bridged were observed in infants/toddlers after 4 weeks (average 20.4±4.3 d from injury), in school-aged children after 8 weeks (average 39.7±7.9 d from injury), or in adolescents after 12 weeks (average 66.4±8.1 d from injury).

Conclusions:

This study provides an age-dependent timeline during which adequate radiographic healing should be expected in nonoperatively managed pediatric diaphyseal clavicle fractures. Radiographic protocols can be purposefully timed to visualize sufficient healing in infants and toddlers by 4 weeks, school-aged children by 8 weeks, and adolescents by 12 weeks.

Level of Evidence:

Level III.
Optimal Timing for Advanced Imaging in Childhood Bone and Joint Infection
Authors: Hunter Sarah , Brown Elsie , Crawford Haemish , Grant Cameron
Published: September 2024

Objective:

Advanced imaging in the management of childhood bone and joint infection (BJI) has the potential to improve disease outcomes. Knowledge about the optimal timing for magnetic resonance imaging (MRI) in relation to both surgically and nonsurgically managed BJI is limited. This study examines the impact of MRI timing on number of surgeries, length of stay (LOS), hospitalization cost, and disease recurrence in childhood BJI.

Methods:

This is a retrospective review of patients younger than 16 years with acute hematogenous osteomyelitis (AHO) or septic arthritis (SA) treated in the Auckland region from 2018 to 2023. Cases undergoing MRI as part of diagnostic workup were included. Treatment, hours between admission and MRI, LOS, hospitalization cost, and infection recurrence were assessed.

Results:

There were 563 cases of BJI, of which 390 met the inclusion criteria. Cases were primarily AHO (85%). The percentage of cases having MRI increased over time from 54% (2018) to 80% (2023). Locally disseminated infections such as subperiosteal abscess or adjacent septic arthritis occurred in 48%. Children with preoperative (n = 145) versus postoperative MRI (n = 60) had a lower reoperation rate (33% vs 77%, P = 0.001) and shorter LOS (14.1 vs 22.4 d, P = 0.002). Hospitalization costs appeared lower but did not differ statistically ($59,419 vs $159,353, P = 0.12). In nonoperative cases, LOS was shorter if an MRI occurred within 48 hours of admission (7.3 vs 10 d, P = 0.03). Disease recurrence was not associated with MRI timing.

Conclusion:

Overall, children with BJI who underwent MRI scans before surgery had lower reoperation rates. Children receiving MRIs within 48 hours of admission had shorter LOS.
EVALUATING LARGE LANGUAGE MODELS ON THEIR ACCURACY AND COMPLETENESS
Authors: Edalat Camellia , Kirupaharan Nila , Dalvin Lauren A. , Mishra Kapil , Marshall Rayna , Xu Hannah , Francis Jasmine H. , Berkenstock Meghan
Published: September 2024

Purpose:

To analyze the accuracy and thoroughness of three large language models (LLMs) to produce information for providers about immune checkpoint inhibitor ocular toxicities.

Methods:

Eight questions were created about the general definition of checkpoint inhibitors, their mechanism of action, ocular toxicities, and toxicity management. All were inputted into ChatGPT 4.0, Bard, and LLaMA programs. Using the six-point Likert scale for accuracy and completeness, four ophthalmologists who routinely treat ocular toxicities of immunotherapy agents rated the LLMs answers. Analysis of variance testing was used to assess significant differences among the three LLMs and a post hoc pairwise t-test. Fleiss kappa values were calculated to account for interrater variability.

Results:

ChatGPT responses were rated with an average of 4.59 for accuracy and 4.09 for completeness; Bard answers were rated 4.59 and 4.19; LLaMA results were rated 4.38 and 4.03. The three LLMs did not significantly differ in accuracy (P = 0.47) nor completeness (P = 0.86). Fleiss kappa values were found to be poor for both accuracy (−0.03) and completeness (0.01).

Conclusion:

All three LLMs provided highly accurate and complete responses to questions centered on immune checkpoint inhibitor ocular toxicities and management. Further studies are needed to assess specific immune checkpoint inhibitor agents and the accuracy and completeness of updated versions of LLMs.
Exploring Potential Challenges in Implementing a Standardized Curriculum for the Physician Associate Program in India: Insights From Stakeholder Discussions
Authors: Muraleedharan Manesh , Sundar Gomathy , Smalley Scott , Begg Philip A. , Philip Deepa C.
Published: September 2024

Introduction

This article explores the potential challenges in implementing a national-level standardized curriculum for physician associate (PA) programs in India, an initiative under the directions of the National Commission for Allied and Healthcare Professionals Act of 2021.

Methods

Initiated in August 2023, a multistage process began with emailing a draft curriculum for review to key stakeholders, followed by a virtual meeting on September 3. Key stakeholders, including faculty from various universities, participated in focus group discussions (FGDs) at the International Association of Physician Associate Educators and the Indian Association of Physician Assistants annual conference on September 21, 2023, in Gandhinagar.

Results

Four major themes emerged: (1) faculty development, (2) faculty recruitment, (3) alignment with the National Educational Policy, and (4) the necessity of master's degree programs for PAs. Challenges identified included shortage of qualified faculty, uncompetitive salaries for academic roles, and low enrollment in master's programs. Recommendations included increasing financial compensation for teaching PAs, developing more PA educators through additional master's programs, encouraging hospitals to mandate clinical and teaching roles for recruits, and introducing pedagogical training for PAs interested in teaching.

Discussion

Implementing a standardized curriculum for PAs faces significant challenges, especially in faculty recruitment and retention. Engaging a broader range of stakeholders is essential for the successful rollout of the curriculum and for meeting India's evolving health care needs.
National introduction of one-anastomosis gastric bypass in the UK National Bariatric Surgery Registry: a cohort study
Authors: Currie Andrew C. , Askari Alan , Parmar Chetan , Byrne James , Ahmed Ahmed R. , Pring Chris M. , Khan Omar A. , Small Peter K. , Mahawar Kamal
Published: September 2024

Aim:

There is a paucity of evidence regarding the national introduction of newer bariatric metabolic surgery procedures. This study assessed the impact of introducing one-anastomosis gastric bypass (OAGB) in bariatric surgical practice in the UK on 30-day postoperative morbidity and early postoperative weight loss.

Methods:

Patients who underwent primary BMS in the UK National Bariatric Surgical Registry (2010–2019) were identified. Patient characteristics, 30-day postoperative morbidity, and 12-month total body weight loss (TBWL) were also assessed. Multivariate regression was performed for associations between 30-day postoperative morbidity and 12-month TBWL, with SG as a reference. Learning effects were assessed by factoring in the institutional OAGB caseload (0–24/25–49/50+ cases).

Results:

A total of 59 226 patients underwent primary BMS during the study period (RYGB, 38 434; SG, 24 702; AGB, 12 627; OAGB, 3408; and others, 276). The 30-day postoperative morbidity was lower for OAGB 1.8% (51/2802) compared to RYGB 4.2% (1391/32 853) and SG 3.4% (725/21 333) but higher than AGB 1.2% (123/9915), while on multivariate regression, OAGB was associated with reduced morbidity once the institution caseload exceeded 50 operations (OR 0.35 (95% CI: 0.22–0.56; P<0.001) and no statistical difference to SG at lesser caseloads. Overall, 12-month greater than 25% TBWL was seen in 69.4% (27 736/39 971) (RYGB: 82.9% (17 617/21 246)), SG: 65.4% (7383/11 283)), AGB: 23.9% (1382/5572)) and OAGB: 82.9% (1328/1601)). On multivariate regression, OAGB was associated with the highest 12-month TBWL once the institution caseload exceeded 50 operations (OR 3.47 (95% CI 2.75–4.39; P<0.001).

Conclusion:

OAGB has been safely implemented in UK national bariatric surgery practice. It has lower reported postoperative morbidity and comparable weight loss to RYGB or SG, despite being offered to patients with more severe and complex obesity.
Clinical outcomes of preservation versus resection of portal/superior mesenteric vein during pancreaticoduodenectomy in pancreatic cancer patients who respond to neoadjuvant treatment: a retrospective cohort study
Authors: Chae Yoon Soo , Jung Hye-Sol , Yun Won-Gun , Han Youngmin , Cho Young Jae , Lee Mirang , Kwon Wooil , Park Joon Seong , Jang Jin-Young
Published: September 2024

Background:

R0 rates have increased as neoadjuvant treatment (NAT) has become the primary treatment for pancreatic ductal adenocarcinoma (PDAC) with venous involvement, suggesting a decrease in venous tumor infiltration. The aim of this study was to investigate the clinical outcomes of preserving the portal/superior mesenteric vein (PV/SMV) during pancreaticoduodenectomy (PD) in PDAC patients who underwent NAT.

Material and methods:

The 113 patients with resectable and borderline resectable PDAC with venous involvement who responded to NAT and underwent curative PD between 2012 and 2022 were retrospectively reviewed.

Results:

Among the 113 patients, PV/SMV preservation (PVP) was performed in 68 patients (60.2%), and PV/SMV resection (PVR) was performed in 45 patients (39.8%). There was no significant difference in the R0 rate, 5-year overall survival (OS) and recurrence-free survival between the two groups. PV/SMV stenosis within 3 months after surgery was more common in the PVR group than in the PVP group (1.5% versus 22.2%; P<0.001), and 5-year PV/SMV stenosis-free survival was significantly higher in the PVP group than in the PVR group (76.5% versus 53.4%; P=0.014). Multivariate analysis showed that gemcitabine-based neoadjuvant chemotherapy was associated with poor OS. PVR, clinically relevant postoperative pancreatic fistula, and locoregional recurrence were independent risk factors for PV/SMV stenosis.

Conclusion:

The PVP group had similar oncologic outcomes and better vessel-functional outcomes than the PVR group. Therefore, if dissection is possible and there is a high likelihood of achieving R0 resection after NAT, routine PVR may be unnecessary in PDAC patients with venous involvement.
Radiation-emitting metallic stent for unresectable Bismuth type III or IV perihilar cholangiocarcinoma: a multicenter randomized trial
Authors: Chen Qi , Ge Nai-Jian , Li Yu-Liang , Huang Ming , Li Wen-Hui , Lu Dong , Wei Ning , Lv Peng-Hua , Tu Jian-Fei , He Cheng-Jian , Wang Wu-Jie , Ding Rong , Peng Bo , Wang Xue-Jun , Wang Fu-An , Zhu Guang-Yu , Wang Yong , Chen Li , Min Jie , Guo Jin-He , Teng Gao-Jun , Lu Jian
Published: September 2024

Background and Aims:

Self-expandable metallic stents (SEMSs) have been recommended for patients with unresectable malignant biliary obstruction, while radiation-emitting metallic stents (REMSs) loaded with 125I seeds have recently been approved to provide longer patency and overall survival in malignant biliary tract obstruction. This trial is to evaluate the efficacy and safety of REMS plus hepatic arterial infusion chemotherapy (REMS-HAIC) versus SEMS plus HAIC (SEMS-HAIC) for unresectable perihilar cholangiocarcinoma (pCCA).

Materials and Methods:

This multicenter randomized controlled trial recruited patients with unresectable Bismuth type III or IV pCCA between March 2021 and January 2023. Patients were randomly assigned (1:1 ratio) to receive either REMS-HAIC or SEMS-HAIC using permuted block randomization, with a block size of six. The primary endpoint was overall survival (OS). The secondary endpoints were time to symptomatic progression (TTSP), stent patency, relief of jaundice, quality of life, and safety.

Results:

A total of 126 patients were included in the intent-to-treat population, with 63 in each group. The median OS was 10.2 months versus 6.7 months (P=0.002). The median TTSP was 8.6 months versus 5.4 months (P=0.003). The median stent patency was longer in the REMS-HAIC group than in the SEMS-HAIC group (P=0.001). The REMS-HAIC group showed better improvement in physical functioning scale (P<0.05) and fatigue symptoms (P<0.05) when compared to the SEMS-HAIC group. No significant differences were observed in relief of jaundice (85.7% vs. 84.1%; P=0.803) or the incidence of grade 3 or 4 adverse events (9.8% vs. 11.9%; P=0.721).

Conclusion:

REMS plus HAIC showed better OS, TTSP, and stent patency compared with SEMS plus HAIC in patients with unresectable Bismuth type III or IV pCCA with an acceptable safety profile.
Single-chamber atrial pacing + Micra AV implantation: A case report
Authors: Cai Yongxiang , Liu Mingjiang , Tao Jianhong , Tang Yijia , Xiong Yan
Published: September 2024

Rationale:

The use of transvenous pacing leads is associated with the risk of tricuspid valve dysfunction, mainly due to the continuous presence of the leads can have an impact on subsequent tricuspid function and possible operation injury of the tricuspid valve during implantation or operation.

Patient concerns:

A 69-year-old female with a history of syncope for 9 months was admitted to the hospital. The electrocardiogram showed sinus bradycardia, junctional escape rhythm, and a heart rate of 44 bpm. Echocardiography suggested a downward displacement and severe insufficiency of the tricuspid valve and atrial septal defect.

Diagnoses:

The cause of syncope was considered to be sick sinus syndrome. The patient was diagnosed with Ebstein anomaly and is considered a candidate for surgical intervention.

Interventions:

To avoid aggravating tricuspid insufficiency by pacing leads crossing the tricuspid valve and hindering subsequent tricuspid valve surgery, a single-chamber pacing mode with atrial pacing (AAI) lead and Micra AV was chosen for maintaining atrioventricular synchrony after multidisciplinary discussion.

Outcomes:

The patient had stable parameters and was in good general condition at 1- and 3-month outpatient follow-ups after discharge.

Lessons:

This is the first case of new implantation of single-chamber atrial pacing + leadless ventricular pacing with Micra AV, an alternative strategy to epicardial or coronary sinus system for tricuspid valve displacement and severe tricuspid regurgitation.
Mortality rate of pulmonary infection in senile dementia patients: A systematic review and meta-analysis
Authors: Yao Jianning , Liu Shunlin , Chen Qun
Published: September 2024

Background:

Dementia is estimated that this kind of neurodegenerative disease directly affects 50 million patients worldwide. About 12% to 70% death of dementia disease can be attributed to pneumonia. We aimed to evaluate the pneumonia-related mortality of dementia patients and how the frequency of pneumonia-related death varies according to the data of death (autopsy or death certificate).

Methods:

English literatures published from PubMed and Embase databases were extracted. Stata/SE 16.0 software was used for statistical analysis.

Results:

In the end, a total of 7 studies were finally included in this meta-analysis. The results showed that: (1) The total mortality rate associated with pneumonia was 24.68% (95% confidence interval [CI]: 19.07%, 30.29%); (2) The pneumonia-related mortality rate of dementia patients confirmed by autopsy was 56.14% (95% CI: 32.36%, 79.92%); (3) The pneumonia-related mortality rate of dementia patients confirmed by death certificate was 16.12% (95% CI: 9.98%, 22.26%); (4) The pneumonia-related direct mortality rate of dementia patients was 50.07% (95% CI: 34.85%, 65.30%); (5) The pneumonia-related indirect mortality rate of dementia patients was 12.43% (95% CI: 5.85%, 19.00%); (6) The hospital-reported mortality rate of dementia patients related to pneumonia was 12.66% (95% CI: 6.60%, 18.72%); (7) The mortality rate of dementia patients related to pneumonia was 17.48% (95% CI: 10.60%, 24.38%).

Conclusion:

This meta-analysis shows that the pneumonia-related mortality of dementia patients is much higher than the expectation of clinicians. The results of the study greatly warned clinicians to pay close attention to pneumonia cases of senile dementia patients.
‘Ritlecitinib: unveiling hair regrowth for alopecia areata’
Authors: Khaliq Nawal , Riaz Rumaisa , Khan Mushkbar , Iqbal Urooj , Khan Afsheen , Naaz Farheen , Akilimali Aymar
Published: September 2024

Alopecia Areata (AA) is an autoimmune disorder characterized by non-scarring hair loss on the scalp and other parts of the body. It is a complex medical condition associated with an impaired immune response in hair follicles. Various therapies are available for AA, including topical, systemic, and injectable treatments. However, their effectiveness varies, and no treatment consistently achieves and maintains remission. Therefore, this review aims to highlight the breakthrough advancement in treatment of AA i.e., the United State Food and Drug Administration (FDA) approved Ritlecitinib, the first and only oral treatment for moderate to severe alopecia areata in patients aged 12 and older. This approval represents a significant achievement in AA management, offering a targeted and effective treatment for those with more extensive hair loss.