bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of including sprouted barley with alfalfa hay in the diet on ruminal health and performance of cow-calf pairs
Authors: Crump Zachary Cal , Alberto Anthony Fernando , Brown Bailee Lynn , Roholt Bryce Wayne , Okamoto Lillian Lelehua , Sego Mia Lynn , Spurling Ryan Arthur , Ward Robert Edward , Blackett Brady Morris , Harding Robert Lynn , Ranathunga Sanjeewa Dilshan , Thornton Kara Jean
Published: March 2024

The world population is growing exponentially, increasing demand to produce high-quality protein for human consumption. Changes in weather patterns, drought, and decreased land resources due to urbanization have increased the strain on the agriculture sector to meet world demands. An alternative method to combat these issues and continue to produce high-quality livestock feed would be through a controlled environment vertical farming system. Commonly, cereal grains, such as barley, are used in these systems to produce livestock feed. However, there is little information on the viability of feeding sprouted grains to beef cattle. Two diets of either feeder-quality alfalfa hay (n = 10 pairs; ALF) or the same alfalfa hay and sprouted barley (SB; 12.6% dry matter [DM]; n = 10 pairs) were fed for 90 d to Angus pairs with a steer calf during mid to late lactation. On days 0 and 90, body weight (BW), milk, rumen fluid, and body condition score were collected from cows and hip height and BW were recorded for calves. On day 10, BW was recorded for cows and calves and rumen fluid was collected from cows. Rumen fluid was also collected from cows on day 45. On day 55, BW was collected for both cows and calves and milk from cows. Intake was recorded throughout the trial via bunks with Vytelle technology. The PROC MIXED procedure of SAS was used to analyze all data with the day as a repeated measure to determine the main effect of diet. Individual volatile fatty acids (VFA) were measured as a percent of total VFA. No differences (P ≥ 0.16) were observed in calf BW, hip height, milk protein, fat, lactose, calf DM intake (DMI), or cow DMI. Cows fed SB tended (P = 0.08) to have a decreased somatic cell count compared to ALF. Percent butyrate was impacted by diet × day (P = 0.02), but no difference (P > 0.09) at any time points were detected. Additionally, a diet × day effect (P = 0.001) on rumen pH demonstrated that both groups stayed consistent until day 45 and then SB pH decreased the last 45 d. There was a day effect for total VFA (P = 0.0009), acetate:propionate (Ac:Pr; P < 0.0001), acetate (P < 0.0001), and propionate (P < 0.0001) demonstrating that total VFA, acetate, and Ac:Pr all increased throughout the trial, while propionate decreased. These results indicate that SB can be a potential alternative feed at this stage of production as it does not negatively impact health or production, but does affect the rumen pH and proportion of some VFA.
Whole-genome analysis reveals the diversification of Galapagos rail (Aves: Rallidae) and confirms the success of goat eradication programs
Authors: Chavez Daniel E , Hains Taylor , Espinoza-Ulloa Sebastian , Wayne Robert K , Chaves Jaime A
Published: March 2024

Similar to other insular birds around the world, the Galapagos rail (Laterallus spilonota Gould, 1841) exhibits reduced flight capacity following its colonization of the archipelago ~1.2 mya. Despite their short evolutionary history, rails have colonized seven different islands spanning the entire width of the archipelago. Galapagos rails were once common on islands with sufficiently high altitudes to support shrubs in humid habitats. After humans introduced goats, this habitat was severely reduced due to overgrazing. Habitat loss devastated some rail populations, with less than 50 individuals surviving, rendering the genetic diversity of Galapagos rail a pressing conservation concern. Additionally, one enigma is the reappearance of rails on the island of Pinta after they were considered extirpated. Our approach was to investigate the evolutionary history and geographic distribution of Galapagos rails as well as examine the genome-wide effects of historical population bottlenecks using 39 whole genomes across different island populations. We recovered an early divergence of rail ancestors leading to the isolated populations on Pinta and a second clade comprising the rest of the islands, historically forming a single landmass. Subsequently, the separation of the landmass ~900 kya may have led to the isolation of the Isabela population with more panmictic populations found on Santa Cruz and Santiago islands. We found that rails genomes contain long runs of homozygosity (>2 Mb) that could be related to the introduction of goats. Finally, our findings show that the modern eradication of goats was critical to avoiding episodes of inbreeding in most populations.
The IL-21/IL-21R signaling axis regulates CD4+ T-cell responsiveness to IL-12 to promote bacterial-induced colitis
Authors: Solaymani-Mohammadi Shahram
Published: March 2024

IL-21/IL-21R signaling dysregulation is linked to multiple chronic intestinal inflammatory disorders in humans and animal models of human diseases. In addition to its critical requirement for the generation and development of germinal center B cells, IL-21/IL-21R signaling can also regulate the effector functions of a variety of T-cell subsets. The antibody-mediated abrogation of IL-21/IL-21R signaling led to the impaired expression of IFN-γ by mucosal CD4+ T cells from human subjects with colitis, suggesting an IL-21/IL-21R–triggered positive feedback loop of the TH1 immune response in the colon. Despite recent advances in our understanding of the mechanisms underpinning the regulation of proinflammatory immune responses by the IL-21/IL-21R signaling axis, it remains unclear how this pathway or its downstream molecules contribute to inflammation during bacterial-induced colitis. This study found that IL-21 enhances the surface expression of IL-12Rβ2, but not IL-12Rβ1, in CD4+ T cells, leading to TH1 differentiation and stability. Consistently, these findings also point to an indispensable role of the IL-12Rβ2 signaling axis in promoting proinflammatory immune responses during Citrobacter rodentium–induced colitis. Genetic deletion of the IL-12Rβ2 signaling pathway led to the attenuation of C. rodentium–induced colitis in vivo. The genetic deletion of the IL-12Rβ2 signaling pathway did not alter the host's ability to respond adequately to C. rodentium infection or the ability of Il12rb2−/− mice to express antigen-specific cytokines (IFN-γ, IL-17A). IL-21 is a pleiotropic cytokine exerting a wide range of immunomodulatory functions in multiple tissues, and its direct targeting may result in undesirable off-target consequences. These findings highlight the possibility for targeted manipulations of signaling cascades downstream of main regulators of proinflammatory responses to control invading pathogens while preserving the integrity of host immune responses. A better understanding of the novel mechanisms by which IL-21/IL-21R signaling regulates bacterial-induced colitis will provide insights into the development of new therapeutic and preventive strategies to harness IL-21/IL-21R signaling or its downstream molecules to treat infectious colitis.
The below-ground biomass contributes more to wetland soil carbon pools than the above-ground biomass—a survey based on global wetlands
Authors: Pan Yueyan , Liu Jiakai , Zhang Mingxiang , Huang Peisheng , Hipesy Matt , Dai Liyi , Ma Ziwen , Zhang Fan , Zhang Zhenming
Published: March 2024

The biomass of wetland plants is highly responsive to environmental factors and plays a crucial role in the dynamics of the soil organic carbon (SOC) pool. In this study, we collected and analyzed global data on wetland plant biomass from 1980 to 2021. By examining 1134 observations from 182 published papers on wetland ecosystems, we created a comprehensive database of wetland plant above-ground biomass (AGB) and below-ground biomass (BGB). Using this database, we analyzed the biomass characteristics of different climate zones, wetland types and plant species globally. Based on this, we analyzed the differences between the biomass of different plant species and the linkage between AGB and BGB and organic carbon. Our study has revealed that wetland plant AGB is greater in equatorial regions but BGB is highest in polar areas, and lowest in arid and equatorial zones. For plant species, the BGB of the Poales is higher than the AGB but Caryophyllales, Cyperales and Lamiales have higher AGB. Moreover, our findings indicate that BGB plays a more significant role in contributing to the organic carbon pool compared to AGB. Notably, when BGB is less than 1 t C ha−1, even slight changes in biomass can have a significant impact on the organic carbon pool. And we observed that the SOC increases by 5.7 t C ha−1 when the BGB content is low, indicating that the SOC is more sensitive to changes in biomass under such circumstances. Our study provides a basis for the global response of AGB and BGB of wetland plants to organic carbon.
“This Sea of Upturned Faces”: The Rhetorical Role of Audience in Frederick Douglass’s Constitutional Interpretation at Midcentury
Authors: Mielke Laura L
Published: March 2024

On 15 May 1851, Frederick Douglass let it be known in the pages of the North Star that he had come to a new interpretation of the US Constitution as an anti-slavery document, indicating his complete break with Garrisonian abolitionists. This essay argues that Douglass’s change in understanding the Constitution was propelled not only by specific political and personal events detailed in scholarship but also by his rhetorical engagement with audience. In the years leading up to this announcement, and especially in speeches delivered during his 1845-47 British tour and an 1850-51 lecture series in Rochester, New York, Douglass explored the nature of interpretation through figures of audience, including the oratorical critic, contrasting British and American assemblies, and summoned groups. He offered audiences lessons in transformative anti-slavery and anti-racist reading, presenting himself as one who reads for and with audiences and who reads audiences themselves to break through the interpretive lens of white supremacy. The essay ends with a brief look at the implications of this argument for understanding Douglass’s best-known address, “What to the Slave Is the Fourth of July?” (1852).
International migration and shifts in subjective well-being: A longitudinal study using German panel data
Authors: Genoni Andreas , Stawarz Nico , Ette Andreas , Rüger Heiko
Published: March 2024

In many economically advanced countries, a relevant proportion of the population migrates across national boundaries every year. For these individuals, migrating abroad brings benefits (e.g. monetary returns) but also potential pitfalls, as migration is accompanied by profound changes in everyday life. However, there are mainly cross-sectional studies of individuals’ migration experiences that analyse the effects of migration on these individuals’ quality of life. This study fills this gap by examining shifts in the subjective well-being (SWB) of internationally mobile German citizens from a longitudinal perspective using data from the German Emigration and Remigration Panel Study and fixed effects panel regressions. To observe SWB over the course of actual migration events, we drew on a sample of repeat migrants: Germans who returned to Germany shortly before the panel and emigrated again during the panel. Consistent with methodologically comparable studies on internal migration, the analyses show a happiness dip before migration and an increase in SWB with the migration event. The increase is consistent, tends to be more pronounced than that observed in internal migration studies, and to some extent persists after the first few years of migration. Moreover, the results suggest that the increase in SWB systematically depends on the influence that individuals can exert on their migration decisions. Individuals without a partner show the highest increases in SWB, followed by so-called leading partners, partners of couples with a mutual migration decision, and trailing partners.
Stellar cluster formation in a Milky Way-sized galaxy at z > 4 – II. A hybrid formation scenario for the nuclear star cluster and its connection to the nuclear stellar ring
Authors: van Donkelaar Floor , Mayer Lucio , Capelo Pedro R , Tamfal Tomas , Quinn Thomas R , Madau Piero
Published: March 2024

Nuclear star clusters (NSCs) are massive star clusters found in the innermost region of most galaxies. While recent studies suggest that low-mass NSCs in dwarf galaxies form largely out of the merger of globular clusters and NSCs in massive galaxies accumulate mass primarily through central star formation, the formation channel of the Milky Way’s NSC is still uncertain. In this work, we use GigaEris, a high-resolution N-body, hydrodynamical, cosmological ‘zoom-in’ simulation, to investigate a possible formation path of the NSC in the progenitor of a Milky Way-sized galaxy, as well as its relation to the assembly and evolution of the galactic nuclear region. We study the possibility that bound, young, gas-rich, stellar clusters within a radius of 1.5 kpc of the main galaxy’s centre at z > 4 are the predecessors of the old, metal-poor stellar population of the Milky Way’s NSC. We identify 47 systems which satisfy our criteria, with a total stellar mass of 107.5 M⊙. We demonstrate that both stellar cluster accretion and in situ star formation will contribute to the formation of the NSC, providing evidence for a hybrid formation scenario for the first time in an N-body, hydrodynamical, cosmological ‘zoom-in’ simulation. Additionally, we find that the gas required for in situ star formation can originate from two pathways: gas-rich stellar clusters and gas influx driven by large-scale non-axisymmetric structures within the galaxy. This is partly supported by the presence of a stellar ring, resulting from gas dynamics, with properties similar to those of the Milky Way’s nuclear stellar disc.
XPA tumor variant leads to defects in NER that sensitize cells to cisplatin
Authors: Blee Alexandra M , Gallagher Kaitlyn S , Kim Hyun-Suk , Kim Mihyun , Kharat Suhas S , Troll Christina R , D’Souza Areetha , Park Jiyoung , Neufer P Drew , Schärer Orlando D , Chazin Walter J
Published: March 2024

Nucleotide excision repair (NER) reduces efficacy of treatment with platinum (Pt)-based chemotherapy by removing Pt lesions from DNA. Previous study has identified that missense mutation or loss of the NER genes Excision Repair Cross Complementation Group 1 and 2 (ERCC1 and ERCC2) leads to improved patient outcomes after treatment with Pt-based chemotherapies. Although most NER gene alterations found in patient tumors are missense mutations, the impact of mutations in the remaining nearly 20 NER genes is unknown. Towards this goal, we previously developed a machine learning strategy to predict genetic variants in an essential NER protein, Xeroderma Pigmentosum Complementation Group A (XPA), that disrupt repair. In this study, we report in-depth analyses of a subset of the predicted variants, including in vitro analyses of purified recombinant protein and cell-based assays to test Pt agent sensitivity in cells and determine mechanisms of NER dysfunction. The most NER deficient variant Y148D had reduced protein stability, weaker DNA binding, disrupted recruitment to damage, and degradation. Our findings demonstrate that tumor mutations in XPA impact cell survival after cisplatin treatment and provide valuable mechanistic insights to improve variant effect prediction. Broadly, these findings suggest XPA tumor variants should be considered when predicting chemotherapy response.
A new perspective on obesity: perception of fat taste and its relationship with obesity
Authors: Şeref Betül , Yıldıran Hilal
Published: March 2024

Background: Obesity, which results from a long-term positive energy balance, is affected by many factors, especially nutrition. The sensory properties of foods are associated with increased food intake through hedonic appetite. Taste perception, a component of flavor, is also responsible for increased consumption, through reward and hedonic mechanisms. Foods with high fat and energy content are among the foods that create the reward perception. The perception of fat taste, the primary taste that has recently entered the literature, may also be associated with increased food consumption and body weight. Therefore, in this review, the relationship between fat taste and obesity is examined, using the latest literature.

Results

Different hypotheses have been proposed regarding the mechanism of the relationship between fat-taste perception and obesity, such as hedonic appetite, microbiota, decreased taste perception, and increased taste threshold level. In addition, some studies examining this relationship reported significant associations between the level of fat-taste perception and obesity, whereas others did not find a significant difference.

Conclusion

Considering the prevalence and contribution to obesity of Western-style nutrition, characterized by high amounts of fat and sugar consumption, elucidating this relationship may be an essential solution for preventing and treating obesity.
Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study
Authors: Vasylyev Marta , Wit Ferdinand W N M , Jordans Carlijn C E , Soetekouw Robin , van Lelyveld Steven F L , Kootstra Gert-Jan , Delsing Corine E , Ammerlaan Heidi S M , van Kasteren Marjo E E , Brouwer Annemarie E , Leyten Eliane M S , Claassen Mark A A , Hassing Robert-Jan , den Hollander Jan G , van den Berge Marcel , Roukens Anna H E , Bierman Wouter F W , Groeneveld Paul H P , Lowe Selwyn H , van Welzen Berend J , Richel Olivier , Nellen Jeannine F , van den Berk Guido E L , van der Valk Marc , Rijnders Bart J A , Rokx Casper
Published: March 2024

Background

Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use.

Methods

Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA–suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+ T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin.

Results

The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: −3.78% [95% confidence interval {CI}, −7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, –.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued.

Conclusions

In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice.

Clinical Trials Registration

NCT04707326.
Renaming Palliative Cancer Therapies: Call It What It Is
Authors: Kopecky Kimberly E , Campbell Toby C
Published: March 2024

This commentary explores the language choices that oncology providers make when discussing cancer therapy goals.
What win–win lost: rethinking microfinance subsidy in the past and designing for the future
Authors: Morduch Jonathan , Ogden Timothy
Published: March 2024

The modern microfinance industry was built on the idea that lenders could (and should) profit while serving poor and excluded customers. This idea—that lenders could ‘win’ while customers would also ‘win’—inspired the broader field of social enterprise and opened possibilities for business-driven responses to social problems. However, in hindsight it is possible to see that not only was the idea flawed—important claims underpinning the core idea have failed to find empirical support—but the lingering belief that ‘win–win’ was right continues to handicap not only financial inclusion and consumer protection policies, but the social investment and finance industry as a whole. The win–win formulation was driven by the assertion that customers would be indifferent to the level of interest rates on loans and that it was simply access to finance that mattered most to customers. The argument was used to justify charging the highest interest rates to the most operationally expensive customers, who turned out to not coincidentally be the poorest customers. However, studies show that customers are indeed sensitive to interest rates and that high interest rates discourage borrowers. Moreover, despite charging high rates, financial data show that most lenders failed to earn profit after fully accounting for the subsidies received from donors and social investors. Microfinance and the social investment industry it helped spawn remain important tools for addressing poverty and inequality, but both sectors are overdue for a transparent reckoning of the roles of subsidy (including its benefits) and greater recognition of the potential for exclusion caused by high prices and the drive for profitability or ‘sustainability’. Muddled thinking on subsidy and prices handicapped the past but does not need to handicap the future.
Microfinance: an overview
Authors: Meki Muhammad , Quinn Simon
Published: March 2024

This paper presents a summary of this issue of the Oxford Review of Economic Policy, on microfinance. The paper explores the evolving landscape of microfinance, with particular emphasis on its broadening scope. It summarizes the four parts of this journal issue, focusing on: (i) microfinance and its providers; (ii) the challenges of taking microfinance to scale; (iii) microfinance and digital credit; and (iv) microfinance and repayment flexibility.
The value of audiovisual sexual stimulation with virtual reality in diagnosing erectile dysfunction
Authors: Huang Yan-Ping , Jing Tao , Liu Kai-Feng , Liu Wei , Zhang Ming , Zhong Da-Chuan , Liu Yi-Dong , Xu Shi-Ran , Lu Mu-Jun
Published: March 2024

Background

The traditional audiovisual sexual stimulation (AVSS) test may experience limitations including low erectile response rate and lack of unified diagnostic criteria.

Aim

We aimed to explore the clinical value of AVSS with virtual reality (VR-AVSS) test in assessing erectile function and diagnosing erectile dysfunction (ED).

Methods

Participants 18 to 60 years of age were screened for analysis in 3 clinical centers from June 2020 to March 2022. Demographic data, 5-item International Index of Erectile Function (IIEF-5), erectile hardness score (EHS), and self-reported symptom questions were collected. The ED patients and control patients were confirmed according to the IIEF-5 and EHS. All subjects watched a 60-minute erotic video by VR device during RigiScan recording. The parameters including tip average rigidity, tip effective erectile duration (duration of rigidity ≥60%, tip effective erectile duration), base average rigidity, and base effective erectile duration were evaluated.

Outcomes

The main outcome of interest was the application of VR immersion technology to improve the traditional AVSS test.

Results

A total of 301 ED cases and 100 eligible control patients were included for final analysis. Compared with control patients, ED cases had significantly lower IIEF-5 scores, EHS, positive response rate, and erectile rigidity and duration. The positive response rate of ED and control patients were 75.5% and 90.9%, respectively. The cutoff points of tip average rigidity, tip effective erectile duration, base average rigidity, and base effective erectile duration were 40.5% (sensitivity: 77.6%, specificity: 70.2%; P < .001), 4.75 minutes (sensitivity: 75.9%, specificity: 75.4%; P < .001), 48.5% (sensitivity: 77.6%, specificity: 75.1%; P < .001), and 7.75 minutes (sensitivity: 79.3%, specificity: 75.7%; P < .001).

Clinical Implications

The technological superiority of VR will enable the VR-AVSS immersion test to be a more accurate detection than traditional AVSS modes.

Strengths and Limitations

Our study applied VR immersion technology to establish the standard operation procedure for the AVSS test, which could effectively reduce the interference of adverse factors and minimize the detecting errors. However, the test data only included positive response subjects, so the true erectile status of men with a negative response to the AVSS test cannot be obtained.

Conclusions

The VR-AVSS test can effectively improve the diagnostic accuracy of ED. The average rigidity and effective erectile duration were the optimal diagnostic parameters for excluding ED.
Gender Disparity in Full Professor Rank Among Academic Physicians: A Systematic Review and Meta-Analysis
Authors: Marhoffer Elizabeth A. , Ein-Alshaeba Samer , Grimshaw Alyssa A. , Holleck Jürgen L. , Rudikoff Benjamin , Bastian Lori A. , Gunderson Craig G.
Published: March 2024

Purpose

The gender gap in promotion in academic medicine is well established. However, few studies have reported gender differences in promotion adjusted for scholarly production and national or international reputation, namely, career duration, publications, grant funding, and leadership positions. The authors performed a systematic review and meta-analysis of the differences between men and women in achieving benchmarks for promotion and analyze where such differences lie geographically and within specialties.

Method

A systematic search of Academic Search Premier, Business Source Complete, Cochrane Library, ERIC, GenderWatch, Google Scholar, Embase, MEDLINE, PubMed, Scopus, and Web of Science was conducted from inception to August 17, 2022. All studies that reported the number of male and female full professors on medical school faculty were included. The primary outcome was the adjusted odds ratio (AOR) for promotion to full professor for women compared with men.

Results

Two hundred forty-four studies met the inclusion criteria. The unadjusted OR for promotion to full professor for women was 0.38 (95% confidence interval [CI], 0.36–0.41). Sixteen studies reported an AOR. The pooled AOR of promotion for women to full professor was 0.60 (95% CI, 0.46–0.77). The AOR for promotion to full professor was 0.55 (95% CI, 0.34–0.88) in surgery and 0.80 (95% CI, 0.57–1.11) in internal medicine. Statistical heterogeneity was high (Q = 66.6, I
2 = 79.4%, P < .001). On meta-regression, 77% of the heterogeneity was from studies outside the United States, where more disparity was reported (AOR, 0.29; 95% CI, 0.22–0.38).

Conclusions

Most studies continued to find decreased promotion of women. Gender disparity was particularly notable in surgery and in studies from outside the United States. The results suggest that differences in promotion were due to differences in productivity and leadership and to gender bias.
Patients' Perspectives on Discontinuing Buprenorphine for the Treatment of Opioid Use Disorder
Authors: Wyse Jessica J. , Eckhardt Alison , Waller Dylan , Gordon Adam J. , Shull Sarah , Lovejoy Travis I. , Mackey Katherine , Morasco Benjamin J.
Published: March 2024

Objectives

Buprenorphine and other medications for opioid use disorder (OUD) are recommended as standard of care in the treatment of OUD and are associated with positive health and addiction-related outcomes. Despite benefits, discontinuation is common, with half of patients discontinuing in the first year of treatment. Addressing OUD is a major clinical priority, yet little is known about the causes of medication discontinuation from the patient perspective.

Methods

From March 2021 to April 2022, we conducted qualitative interviews with patients who had discontinued buprenorphine for the treatment of OUD within the past 12 months. Eligible participants were selected from 2 Veterans Health Administration Health Care Systems in Oregon. Coding and analysis were guided by conventional qualitative content analysis.

Results

Twenty participants completed an interview; 90% were White and 90% were male, and the mean age was 54.2 years. Before discontinuation, participants had received buprenorphine for 8.3 months on average (range, 1–40 months); 80% had received buprenorphine for less than 12 months. Qualitative analysis identified the following themes relating to discontinuation: health system barriers (eg, logistical hurdles, rules and policy violations), medication effects (adverse effects; attributed adverse effects, lack of efficacy in treating chronic pain) and desire for opioid use. Patient description of decisions to discontinue buprenorphine could be multicausal, reflecting provider or system-level barriers in interaction with patient complexity or medication ambivalence.

Conclusions

Study results identify several actionable ways OUD treatment could be modified to enhance patient retention.
A Clinical Guide to Support the Implementation of Addiction Consult Services and the Value of Teaching and Technical Assistance
Authors: Fielman Sarah , McNeely Jennifer , Fitzpatrick Amy , Kerensky Todd , Tomanovich Mary , Walley Alexander Y. , Kosakowski Sarah , King Carla , Appleton Noa , Weinstein Zoe M.
Published: March 2024

People with substance use disorders (SUDs) are increasingly admitted to general hospitals; however, many hospital systems lack both formal structures and skilled staff to provide high-quality care for inpatients with SUDs. Inpatient addiction consult services (ACSs), which are increasingly being implemented around the country, are an evidence-based strategy to add focused care for people with SUDs into the general medical setting. In 2018, New York City Health + Hospitals (H + H) launched an ACS program called Consult for Addiction Care and Treatment in Hospitals in six hospitals, supported by a team of addiction consult experts to deliver teaching and technical assistance (TTA) for the Consult for Addiction Care and Treatment in Hospitals ACSs. This commentary describes the TTA, which included site visits, introductory educational lectures, case conferences, ad hoc support, implementation assistance, and the creation of an addiction care guide. Similar TTA services could be used in the future when hospitals or systems want to launch novel clinical programs.
How Reliable Is Endoscopic Scoring of Postoperative Recurrence in Crohn Disease?: A Systematic Review and Meta-Analysis
Authors: van der Does de Willebois Eline M. L. , Bellato Vittoria , Duijvestein Marjolijn , van Dieren Susan , Danese Silvio , Sileri Pierpaolo , Buskens Christianne J. , Vignali Andrea , Bemelman Willem A.
Published: March 2024

Objective:

Guidelines advise to perform endoscopic surveillance following ileocolic resection (ICR) in Crohn disease (CD) for timely diagnosis of recurrence. This study aims to assess the variation in endoscopic recurrence (ER) rates in patients after ICR for CD using the most commonly used classification systems, the Rutgeerts score (RS) and modified Rutgeerts score (mRS) classifications.

Methods:

A systematic literature search using MEDLINE, Embase, and the Cochrane Library was performed. Randomized controlled trials and cohort studies describing ER < 12 months after an ICR for CD were included. Animal studies, reviews, case reports (<30 included patients), pediatric studies, and letters were excluded. The Newcastle–Ottawa Quality Assessment Scale and Cochrane Collaboration’s tool were used to assess risk of bias. Main outcome was the range of ER rates within 12 months postoperatively, defined as RS ≥ i2 and/or mRS ≥ i2b. A proportional meta-analysis was performed. The final search was performed on January 4, 2022. The study was registered at PROSPERO, CRD42022363208.

Results:

Seventy-six studies comprising 7751 patients were included. The weighted mean of ER rates in all included studies was 44.0% (95% confidence interval, 43.56–44.43). The overall range was 5.0% to 93.0% [interquartile range (IQR), 29.2–59.0]. The weighted means for RS and mRS were 44.0% and 41.1%, respectively. The variation in ER rates for RS and mRS were 5.0% to 93.0% (IQR, 29.0–59.5) and 19.8% to 62.9% (IQR, 37.3–46.5), respectively. Within studies reporting both RS and mRS, the weighted means for ER were 61.3% and 40.6%, respectively.

Conclusions:

This study demonstrates a major variation in ER rates after ICR for CD, suggesting a high likelihood of inadequate diagnosis of disease recurrence, with potentially impact on quality of life and health care consumption. Therefore, there is an important need to improve endoscopic scoring of recurrent disease.
Assessment of haemostasis in pregnant women
Authors: Zec Tamara , Schmartz Denis , Temmerman Pomeline , Fils Jean-François , Ickx Brigitte , Bonhomme Fanny , Van Der Linden Philippe
Published: March 2024

BACKGROUND

Contemporary guidelines pertaining to the evaluation of bleeding risk recommend conducting a comprehensive examination of both personal and family histories concerning haemorrhagic diatheses.

OBJECTIVES

We employed the standardised HEMSTOP (Hematoma, hEmorrhage, Menorrhagia, Surgery, Tooth extraction, Obstetrics, Parents) questionnaire in pregnant women to evaluate its efficacy in detecting a haemostatic disorder and predicting the risk of haemorrhage associated with delivery.

DESIGN

A single-centre retrospective observational cohort study.

SETTING

Brugmann Hospital, a tertiary university institution.

PATIENTS

All full-term parturients who underwent vaginal or caesarean delivery in our hospital between January 2020 and December 2021 were included in the study. A total of 3588 patients were enrolled.

MAIN OUTCOME MEASURES

The primary aim of this study was to assess the sensitivity and specificity of the HEMSTOP questionnaire in identifying individuals with an abnormal primary haemostatic profile. The secondary objective was to evaluate the sensitivity and specificity of the HEMSTOP questionnaire in predicting postpartum haemorrhage (PPH; defined as blood loss >1000 ml). Additionally, positive-predictive values and negative-predictive values (NPVs) were calculated.

RESULTS

The specificity and sensitivity of the HEMSTOP questionnaire to predict an abnormal standard coagulation test in pregnant women are respectively 96% [95% confidence interval (CI), 0.95 to 0.97] and 39% (95% CI, 0.20 to 0.61). Its NPV is 100%. The specificity and sensitivity of the HEMSTOP questionnaire to predict postpartum bleeding risk are respectively 96% (95% CI, 0.95 to 0.97) and 8% (95% CI, 0.06 to 0.11).

CONCLUSION

In the conditions of our study, the HEMSTOP questionnaire enables the prediction of a primary haemostatic anomaly with a specificity and sensitivity comparable to routine haemostatic assessments. These findings concur with the recommendation against the routine prescription of laboratory tests for patients lacking a history of bleeding diathesis.

TRIAL REGISTRATION

Clinical Trial NCT 05191251.
Impact of sugammadex and neostigmine on outcome after major orthopaedic surgery
Authors: Cozowicz Crispiana , Zhong Haoyan , Poeran Jashvant , Illescas Alex , Liu Jiabin , Poultsides Lazaros A. , Athanassoglou Vassilis , Memtsoudis Stavros G.
Published: March 2024

BACKGROUND

Residual neuromuscular blockade after surgery remains a major concern given its association with pulmonary complications. However, current clinical practices with and the comparative impact on perioperative risk of various reversal agents remain understudied.

OBJECTIVE

We investigated the use of sugammadex and neostigmine in the USA, and their impact on postoperative complications by examining national data,

DESIGN

This population-based retrospective study used national Premier Healthcare claims data.

SETTING AND PARTICIPANTS

Patients undergoing total hip/knee arthroplasty (THA, TKA), or lumbar spine fusion surgery between 2016 and 2019 in the United States who received neuromuscular blocking agents.

INTERVENTION

The effects of sugammadex and neostigmine for pharmacologically enhanced reversal were compared with each other and with controls who received no reversal agent.

MAIN OUTCOMES

included pulmonary complications, cardiac complications, and a need for postoperative ventilation. Mixed-effects regression models compared the outcomes between neostigmine, sugammadex, and controls. We report odds ratios (OR) and 95% confidence intervals (CI). Bonferroni-adjusted P values of 0.008 were used to indicate significance.

RESULTS

Among 361 553 patients, 74.5% received either sugammadex (20.7%) or neostigmine (53.8%). Sugammadex use increased from 4.4% in 2016 to 35.4% in 2019, whereas neostigmine use decreased from 64.5% in 2016 to 43.4% in 2019. Sugammadex versus neostigmine or controls was associated with significantly reduced odds for cardiac complications (OR 0.86, 95% CI, 0.80 to 0.92 and OR 0.83, 95% CI, 0.78 to 0.89, respectively). Both sugammadex and neostigmine versus controls were associated with reduced odds for pulmonary complications (OR 0.85, 95% CI, 0.77 to 0.94 and OR 0.91, CI 0.85 to 0.98, respectively). A similar pattern of sugammadex and neostigmine was observed for a reduction in severe pulmonary complications, including the requirement of invasive ventilation (OR 0.54, 95% CI, 0.45 to 0.64 and OR 0.53, 95% CI, 0.46 to 0.6, respectively).

CONCLUSIONS

Population-based data indicate that sugammadex and neostigmine both appear highly effective in reducing the odds of severe life-threatening pulmonary complications. Sugammadex, especially, was associated with reduced odds of cardiac complications.
Probe Electrospray Ionization Tandem Mass Spectrometry for the Detection and Quantification of Benzodiazepines
Authors: Griffeuille Pauline , El Balkhi Souleiman , Dulaurent Sylvain , Saint-Marcoux Franck
Published: March 2024

Background:

Legally prescribed benzodiazepines (BZDs) and designer BZDs are widely misused and must be determined in multiple contexts (eg, overdose, drug-facilitated sexual assaults, or driving under the influence of drugs). This study aimed to develop a method for measuring serum BZD levels using probe electrospray ionization (PESI) mass spectrometry and an isotope dilution approach.

Methods:

A tandem mass spectrometer equipped with a probe electrospray ionization source in multiple reaction monitoring mode was used. Isotope dilution was applied for quantification using a deuterated internal standard at a fixed concentration for alprazolam, bromazepam, diazepam, nordiazepam, oxazepam, temazepam, zolpidem, and zopiclone. This method included designer BZDs: clonazolam, deschloroetizolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam, meclonazepam, nifoxipam, and pyrazolam. Sample preparation was done by mixing 10 µL of serum with 500 µL of an ethanol/ammonium formate 0.01 mol/L buffer. Complete validation was performed, and the method was compared with liquid chromatography coupled with mass spectrometry (LC-MS/MS) and immunoassays (IC) by analyzing 40 real samples.

Results:

The analysis time for identification and quantification of the 18 molecules was 2.5 minutes. This method was fully validated, and the limits of quantification varied from 5 to 50 mcg/L depending on the molecule. In the 40 real samples, 100% of molecules (n = 89) were detected by both LC-MS/MS and PESI-MS/MS, and regression analysis showed excellent agreement between the 2 methods (r2 = 0.98). On IC, bromazepam and zolpidem were not detected in 2 and 1 cases, respectively.

Conclusions:

PESI-MS/MS allows serum BZD detection and measurement. Given the isotope dilution approach, a calibration curve was not required, and its performance was similar to that of LC-MS/MS, and its specificity was higher than that of IC.
Career Reflections: The Winding Path From County Mayo, Ireland to New York City
Authors: D’Alton Mary
Published: March 2024

Dr. Mary D’Alton's career journey intertwines her upbringing in County Mayo, Ireland, with impactful contributions to Obstetrics and Gynecology in New York City. From childhood lessons in community care to transformative experiences in Canada and prestigious mentorships, her leadership at Columbia University and NewYork–Presbyterian has fostered innovative initiatives addressing maternal health. Philanthropy plays a pivotal role in realizing her vision, including mental health integration within women’s health care. International reach, exemplified by a successful fellowship program with Ireland, underscores her commitment to collaboration Dr. D’Alton's reflections illuminate the transformative power of teamwork, mentorship, and innovation in advancing women’s health worldwide.
Granulomatous liver diseases
Authors: Mironova Maria , Gopalakrishna Harish , Rodriguez Franco Gian , Holland Steven M. , Koh Christopher , Kleiner David E. , Heller Theo
Published: March 2024

A granuloma is a discrete collection of activated macrophages and other inflammatory cells. Hepatic granulomas can be a manifestation of localized liver disease or be a part of a systemic process, usually infectious or autoimmune. A liver biopsy is required for the detection and evaluation of granulomatous liver diseases. The prevalence of granulomas on liver biopsy varies from 1% to 15%. They may be an incidental finding in an asymptomatic individual, or they may represent granulomatous hepatitis with potential to progress to liver failure, or in chronic disease, to cirrhosis. This review focuses on pathogenesis, histological features of granulomatous liver diseases, and most common etiologies, knowledge that is essential for timely diagnosis and intervention.
Clinical criteria accurately diagnose severe but not moderate alcohol-associated hepatitis: A systematic review and meta-analysis
Authors: Verma Nipun , Mehtani Rohit , Haiar Jacob Martin , Pradhan Pranita , Duseja Ajay , Im Gene Young , Singal Ashwani K.
Published: March 2024

Background:

The precision of clinical criteria and the utility of liver biopsy for diagnosis or prognosis remain unclear in patients with alcohol-associated hepatitis (AH). We systematically reviewed the literature to answer these questions.

Methods:

Four databases were searched for studies describing the precision of clinical criteria (National Institute on Alcohol Abuse and Alcoholism, European Association for Study of Liver, or classical) and the role of histology in AH. The precision(positive predictive value) of criteria was pooled through random-effects meta-analysis, and its variation was investigated through subgroups and meta-regression of study-level factors with their percent contribution to variation (R
2). The risk of bias among studies was evaluated through the QUADAS2 tool (PROSPERO-ID-CRD4203457250).

Results:

Of 4320 studies, 18 in the systematic review and 15 (10/5: low/high risk of bias, N=1639) were included in the meta-analysis. The pooled precision of clinical criteria was 80.2% (95% CI: 69.7–89.7, I
2:93%, p < 0.01), higher in studies with severe AH (mean-Model for End-Stage Liver Disease > 20) versus moderate AH (mean-Model for End-Stage Liver Disease < 20): 92% versus 67.1%, p < 0.01, and in studies with serum bilirubin cutoff 5 versus 3 mg/dL (88.5% vs.78.8%, p = 0.01). The factors contributing to variation in precision were Model for End-Stage Liver Disease (R
2:72.7%), upper gastrointestinal bleed (R
2:56.3%), aspartate aminotransferase:aspartate aminotransferase ratio (R
2:100%), clinical criteria (R
2:40.9%), bilirubin (R
2:22.5%), and Mallory body on histology (R
2:19.1%).

The net inter-pathologist agreement for histologic findings of AH was variable (0.33–0.97), best among 2 studies describing AH through simple and uniform criteria, including steatosis, ballooning, and neutrophilic inflammation. Few studies reported the utility of histology in estimating steroid responsiveness (N = 1) and patient prognosis (N = 4); however, very broad septa, pericellular fibrosis, and cholestasis were associated with mortality. Bilirubinostasis was associated with infection in 1 study.

Conclusions:

Clinical criteria are reasonably precise for diagnosing severe AH, while there is an unmet need for better criteria for diagnosing moderate AH. Histologic diagnosis of AH should be simple and uniform.
Meeting Report for the 2023 International Scientific Conference on Complex Lymphatic Anomalies
Authors: Dellinger Michael T. , Ferry Tiffany , Williams David , Milne Tracy , Murgia Louise , Kelly Michael
Published: March 2024

Objectives:

Complex lymphatic anomalies (CLAs) are rare diseases with variable clinical manifestations caused by the abnormal development of lymphatic vessels. The Lymphatic Malformation Institute (LMI), Lymphangiomatosis & Gorham’s Disease Alliance (LGDA), and LGD Alliance Europe sponsored an international conference on CLAs so leaders in the field could discuss recent advances in research on CLAs.

Methods:

The conference occurred in Dallas, Texas, between September 29th and September 30th, 2023. The event had 22 distinguished speakers and 38 attendees. Additional researchers, clinicians, and patients attended the conference virtually.

Results:

In this article, we summarize the key takeaways from the meeting. The conference emphasized the crucial role of the patient voice in guiding research, and attendees heard stories from patients and parents of children with CLAs. The conference covered topics such as the genetic causes of CLAs, preclinical models, clinical advances, new technologies for CLA research, lymphatic imaging, and patient-centered research. Videos of all the presentations can be found on the LGDA website.

Conclusions:

The meeting revealed that while progress has been made, many challenges still exist surrounding the diagnosis and treatment of CLAs. Sustained research efforts are necessary to fill the gaps in knowledge and improve the care and quality of life of CLA patients.