bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural analysis of the female reptile reproductive system by micro-computed tomography and optical coherence tomography
Authors: Kircher Bonnie K , McCown Michaela A , Scully Deirdre M , Behringer Richard R , Larina Irina V
Published: April 2024

Volumetric data provide unprecedented structural insight to the reproductive tract and add vital anatomical context to the relationships between organs. The morphology of the female reproductive tract in non-avian reptiles varies between species, corresponding to a broad range of reproductive modes and providing valuable insight to comparative investigations of reproductive anatomy. However, reproductive studies in reptilian models, such as the brown anole studied here, have historically relied on histological methods to understand the anatomy. While these methods are highly effective for characterizing the cell types present in each organ, histological methods lose the 3D relationships between images and leave the architecture of the organ system poorly understood. We present the first comprehensive volumetric analyses of the female brown anole reproductive tract using two non-invasive, non-destructive imaging modalities: micro-computed tomography (microCT) and optical coherence tomography (OCT). Both are specialized imaging technologies that facilitate high-throughput imaging and preserve three-dimensional information. This study represents the first time that microCT has been used to study all reproductive organs in this species and the very first time that OCT has been applied to this species. We show how the non-destructive volumetric imaging provided by each modality reveals anatomical context including orientation and relationships between reproductive organs of the anole lizard. In addition to broad patterns of morphology, both imaging modalities provide the high resolution necessary to capture details and key anatomical features of each organ. We demonstrate that classic histological features can be appreciated within whole-organ architecture in volumetric imaging using microCT and OCT, providing the complementary information necessary to understand the relationships between tissues and organs in the reproductive system. This side-by-side imaging analysis using microCT and OCT allows us to evaluate the specific advantages and limitations of these two methods for the female reptile reproductive system.
Real-world data of 5-aminolaevulinic acid-mediated photodynamic therapy for Bowen disease: a 10-year retrospective study in patients with darker-coloured skin (2011–2021)
Authors: Fang Shan , Zhang Linglin , Wang Peiru , Shi Lei , Zhang Haiyan , Liao Caihe , Zhao Zijun , Zhou Zongxia , Zhao Yan , Yan Guorong , Wu Yun , Wu Yuhao , Zheng Zhe , Wang Ruiping , Liu Yeqiang , Zhang Guolong , Wang Xiuli
Published: April 2024

Background

Photodynamic therapy (PDT) has been strongly recommended as an excellent alternative treatment for Bowen disease (BD). However, reported data on 5-aminolaevulinic acid-mediated PDT (ALA-PDT) with red-light irradiation are limited and the long-term effectiveness remains to be determined, especially in dark-skinned populations.

Objectives

We aimed to review routine clinical practice in the field of BD treatment with ALA-PDT over an extended study period (2011–2021), calculate the overall clearance rate, and explore and evaluate factors that might affect the effectiveness of therapy in a real-world setting.

Methods

The medical records of patients with BD who received ALA-PDT with red-light irradiation between February 2011 and June 2021 were reviewed and summarized. Univariate and multivariate analyses of clinically relevant variables that may affect treatment outcomes were conducted to identify risk predictors.

Results

The overall clearance rate of 122 BD lesions was 89.3% with a median follow-up time of 36 months. The correlation between the effectiveness and fluorescence intensity of pre-PDT or PDT sessions was statistically significant after eliminating the interference of confounding factors. All recurrences occurred in the first 2 years following ALA-PDT.

Conclusions

ALA-PDT is an effective treatment for BD in patients with darker-coloured skin. Well-executed operations and effective pretreatment are the determinants of effectiveness. Fluorescence intensity of pre-PDT appeared to be a significant predictor of final effectiveness. In addition, 2 years of follow-up is necessary following ALA-PDT.
Obesity differs from diabetes mellitus in antibody and T-cell responses post-COVID-19 recovery
Authors: Ali Mohammad , Longet Stephanie , Neale Isabel , Rongkard Patpong , Chowdhury Forhad Uddin Hassan , Hill Jennifer , Brown Anthony , Laidlaw Stephen , Tipton Tom , Hoque Ashraful , Hassan Nazia , Hackstein Carl-Philipp , Adele Sandra , Akther Hossain Delowar , Abraham Priyanka , Paul Shrebash , Rahman Md Matiur , Alam Md Masum , Parvin Shamima , Mollah Forhadul Hoque , Hoque Md Mozammel , Moore Shona C , Biswas Subrata K , Turtle Lance , de Silva Thushan I , Ogbe Ane , Frater John , Barnes Eleanor , Tomic Adriana , Carroll Miles W , Klenerman Paul , Kronsteiner Barbara , Chowdhury Fazle Rabbi , Dunachie Susanna J
Published: April 2024

Objective: Obesity and type 2 diabetes (DM) are risk factors for severe coronavirus disease 2019 (COVID-19) outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors with overweight/obesity (Ov/Ob, BMI ≥ 23 kg/m2) and DM in Bangladesh. Methods: In this cross-sectional study, SARS-CoV-2-specific antibody and T-cell responses were investigated in 63 healthy and 75 PCR-confirmed COVID-19 recovered individuals in Bangladesh, during the pre-vaccination first wave of the COVID-19 pandemic in 2020. Results: In COVID-19 survivors, SARS-CoV-2 infection induced robust antibody and T-cell responses, which correlated with disease severity. After adjusting for age, sex, DM status, disease severity, and time since onset of symptoms, Ov/Ob was associated with decreased neutralizing antibody titers, and increased SARS-CoV-2 spike-specific IFN-γ response along with increased proliferation and IL-2 production by CD8 + T cells. In contrast, DM was not associated with SARS-CoV-2-specific antibody and T-cell responses after adjustment for obesity and other confounders. Conclusion: Ov/Ob is associated with lower neutralizing antibody levels and higher T-cell responses to SARS-CoV-2 post-COVID-19 recovery, while antibody or T-cell responses remain unaltered in DM.
Long-term Risk of Serious Infections and Mortality Among Patients Surviving Drug Use–Associated Infective Endocarditis
Authors: Figgatt Mary C , Rosen David L , Chu Vivian H , Wu Li-Tzy , Schranz Asher J
Published: April 2024

Among a statewide cohort of 1874 patients surviving hospitalization for drug use–associated endocarditis during 2017–2020, the 3-year risk of death or future hospitalization was 38% (16% for death before later infection, 14% for recurrent endocarditis, 14% for soft tissue, 9% for bacteremia, 5% for bone/joint, and 4% for spinal infections).
The “Totally ’80s” Eating Matters of Lyn Hejinian’s My Life
Authors: Seiler Claire
Published: April 2024

This essay brings the discourse of “weak theory” to bear on Lyn Hejinian’s feminist experimental poem of the 1980s, My Life. It argues that the eating matters of My Life—the poem’s steady references to eating, cooking, grocery shopping, dieting, and so forth—open up a fresh account of the poem’s feminist and cultural historicity. Bracketing accustomed readings of the poem as exemplary of poetic postmodernism or as what Hejinian calls an “open text,” the essay situates My Life instead in the 1970s-80s emergence of anorexia as both a popular and a theoretical keyword. It revalues the range of eating matters that shape the feminist poetics of Hejinian’s best-known work.
Epigenetic processes involved in response to pesticide exposure in human populations: a systematic review and meta-analysis
Authors: Rohr Paula , Karen Shimoyama , Francisco Luiza Flávia Veiga , Oliveira Marco Antônio , Santos Neto Martins Fidelis dos , Silveira Henrique C S
Published: April 2024

In recent decades, the use of pesticides in agriculture has increased dramatically. This has resulted in these substances being widely dispersed in the environment, contaminating both exposed workers and communities living near agricultural areas and via contaminated foodstuffs. In addition to acute poisoning, chronic exposure to pesticides can lead to molecular changes that are becoming better understood. Therefore, the aim of this study was to assess, through a systematic review of the literature, what epigenetic alterations are associated with pesticide exposure. We performed a systematic review and meta-analysis including case-control, cohort and cross-sectional observational epidemiological studies to verify the epigenetic changes, such as DNA methylation, histone modification and differential microRNA expression, in humans who had been exposed to any type of pesticide. Articles published between the years 2005 and 2020 were collected. Two different reviewers performed a blind selection of the studies using the Rayyan QCRI software. Post-completion, the data of selected articles were extracted and analyzed. Most of the 28 articles included evaluated global DNA methylation levels, and the most commonly reported epigenetic modification in response to pesticide exposure was global DNA hypomethylation. Meta-analysis revealed a significant negative correlation between Alu methylation levels and β-hexachlorocyclohexane, p,p'-dichlorodiphenyldichloroethane and p,p′-dichlorodiphenylethylene levels. In addition, some specific genes were reported to be hypermethylated in promoter regions, such as CDKN2AIGF2, WRAP53α and CDH1, while CDKN2B and H19 were hypomethylated due to pesticide exposure. The expression of microRNAs was also altered in response to pesticides, as miR-223, miR-518d-3p, miR-597, miR-517b and miR-133b that are associated with many human diseases. Therefore, this study provides evidence that pesticide exposure could lead to epigenetic modifications, possibly altering global and gene-specific methylation levels, epigenome-wide methylation and microRNA differential expression.
Spontaneous pregnancy-associated coronary artery dissection: a case report on diagnostic and therapeutic challenges
Authors: Haney Ailís Ceara , Siry Deborah , Hoerbrand Isabel Amber-Rose , Ehlermann Philipp , Beckendorf Jan
Published: April 2024

Background

One of the main causes of myocardial infarction during pregnancy is spontaneous coronary artery dissection. This is ascribed to hormonal changes during pregnancy leading to a weakening of the vessel wall and haemodynamic changes especially during childbirth. Management options include conservative medical treatment and percutaneous coronary intervention, depending on clinical presentation.

Case summary

A 37-year-old woman presented with typical chest pain six weeks after giving birth to her third child. Echocardiography revealed a moderate reduction in systolic function. Initial invasive coronary angiography showed no abnormalities. After cardiac magnetic resonance demonstrated extensive scar, invasive coronary angiography was repeated including intravascular imaging. A dissection of the left anterior descending artery was visualized and treated by percutaneous coronary intervention and stenting. Left ventricular function was normalized at three-month follow-up. In this educational case report, we highlight the diagnostic and therapeutic challenges when treating this special patient cohort and the importance of cardiovascular imaging.

Discussion

Pregnancy-associated spontaneous coronary dissection is a potential differential diagnosis when treating post-partum women with recent onset chest pain. Management is challenging and intravascular imaging to visualize dissection should be performed during invasive coronary angiography. Patients require interdisciplinary care within a pregnancy heart team.
Successful intervention for decompensated heart failure with complicated pathophysiologies with complex interdependence: a case report
Authors: Muraishi Makio , Noguchi Masahiko , Makihara Yu , Obunai Kotaro
Published: April 2024

Background

There is limited evidence regarding the optimal strategy for treating patients with acute decompensated heart failure complicated by severe left ventricular dysfunction, functional mitral regurgitation (FMR), and atrial septal defect (ASD) that cannot be controlled despite optimal medical treatment.

Case summary

A 72-year-old man with non-ischaemic cardiomyopathy presented with acute heart failure and recurrent atrial fibrillation. An electrocardiogram after electrical cardioversion revealed left bundle block with QRS duration of 152 ms. Transthoracic echocardiography revealed severe left ventricular dysfunction, severe FMR, and a left-to-right shunt through an iatrogenic ASD (IASD). Despite initial optimal medical therapy for heart failure, the patient’s condition was not completely controlled. After a discussion among the heart team, we performed cardiac resynchronization therapy (CRT) as the next strategy. Two weeks after CRT device implantation, heart failure was controlled, with improvement in cardiac function and FMR. The left-to-right shunts through the IASD also improved.

Discussion

When treating decompensated heart failure with complicated pathophysiologies, it is crucial to prioritize the predominant pathophysiological factor and engage in thorough discussions with the heart team regarding the most appropriate intervention.
Non-coding RNA therapeutics in the treatment of heart failure
Authors: Paterek Aleksandra , Załęska-Kocięcka Marta , Surzykiewicz Mateusz , Wojdyńska Zuzanna , Leszek Przemysław , Mączewski Michał
Published: April 2024

Non-coding RNA (ncRNA) therapeutics can target either ncRNAs or conventional messenger RNA, offering both superior pharmacokinetics and selectivity to conventional therapies and addressing new, previously unexplored pathways. Although no ncRNA has yet been approved for the treatment of heart failure, in this review we present five most promising pathways and agents that either are in human clinical trials or offer great promise in the near future.
The neglected floral polymorphism: mirror-image flowers emerge from the shadow of heterostyly
Authors: Barrett Spencer C H , Fairnie Alice L M
Published: April 2024

Morphological asymmetries in plants and animals raise intriguing questions concerning their function and how they have evolved. One of the most conspicuous asymmetries in plants involves mirror-image flowers (enantiostyly) in which styles are deflected to either the left or right sides (L or R, respectively) of the flower. Species with this floral polymorphism often possess two types of stamens (heteranthery): centrally located feeding anthers and a pollinating anther orientated in the opposite direction to the style (reciprocal enantiostyly). However, some species lack heteranthery and sex-organ reciprocity can be partial or absent (non-reciprocal enantiostyly). Many enantiostylous species have nectarless flowers and are ‘buzz-pollinated’ by pollen-collecting bees. In contrast to other stylar polymorphisms such as heterostyly, enantiostyly exists as either monomorphic or dimorphic conditions, with L and R flowers on the same plant in the former, and genetically determined floral morphs with either L or R flowers in the latter. Enantiostyly has been reliably reported from 11 angiosperm families, but in only two is there convincing evidence that dimorphic enantiostyly occurs. Various hypotheses concerning developmental or selective constraints attempt to explain the rarity of this genetic polymorphism. Experimental studies on the function of enantiostyly indicate that the reciprocity of stigmas and pollinating anthers promotes pollinator-mediated cross-pollination and limits geitonogamous selfing. Insufficient or inferior pollinator service can result in the evolutionary breakdown of enantiostyly, including reduced stigma–anther separation, increased selfing, and dissolution of heteranthery. In this article we review recent advances and knowledge gaps in understanding these curious asymmetries and discuss why they have received less attention than heterostyly.
Outcomes of different perioperative management strategies of patients on chronic anticoagulation in elective total hip and knee arthroplasty: a systematic review
Authors: Andronic Diana , Andronic Octavian , Ammann Elias , Pravin Edward , Cubberley Rachael
Published: April 2024

Introduction

There are currently different management guidelines for patients undergoing elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) that are on long-term anticoagulation. The timing of discontinuation and restarting the anticoagulation is challenging during the postoperative care, which often involves general practitioners and physiotherapists.

Methods

The systematic review followed the PRISMA guidelines and included 3 databases: PubMed/MEDLINE, EMBASE, and Web of Science Core Collection. It was registered in the International Prospective Register for Systematic Reviews and Meta-analysis (PROSPERO) under the registration number: CRD42023408906. The risk of bias assessment was performed using the Methodological index for non-randomized studies (MINORS) criteria.

Results

Six retrospective studies involving 727 patients with therapeutic anticoagulation (1,540 controls) for elective THA, TKA and revision arthroplasty have been included. The follow-up ranged from 30 days to 1 year postoperatively. All studies evaluated outcomes of warfarin therapeutic anticoagulation versus prophylactic dosages of one or more of the following: warfarin, aspirin, low-molecular-weight heparin (LMWH) and unfractionated low-dose heparin (UFH). One study did not discontinue therapeutic anticoagulation. Two studies reported no significant differences in complications between groups, whilst 3 studies had significantly higher rates of superficial wound infections, revision surgeries, postoperative haematomas, and prosthetic joint infections (PJI).

Conclusion

Different anticoagulation-related perioperative management strategies achieve different outcomes following elective arthroplasty in patients with therapeutic chronic anticoagulation. There is contradictory evidence regarding the need for the discontinuation of therapeutic warfarin. Retrospective data showed that individual risk stratification with multi-modal prophylaxis resulted in minimal complications.

Level of Evidence

Systematic Review of Level III studies.
The true complexities of “standard” family practice visits unmasked: an observational cross-sectional study in Regina
Authors: Heidel Mackenzie M M , Clay Adam T , Dash Megan , Cutts Danielle
Published: April 2024

Background

Many patients present to their family medicine clinic with more than one health concern, placing an increased demand on family physicians. Research into the average number of concerns per regular family medicine visit is limited. Recognition of the frequency that family physicians address more than one concern per visit and adapting practices accordingly is important for improving patient care.

Objective

To examine whether family physicians routinely address multiple different patient concerns during a single visit and if this is influenced by patient demographics.

Methods

This study was conducted at a multi-physician family medicine clinic in Regina, Saskatchewan, Canada. Five physicians contributed their 500 most recent charts, extending retrospectively from 1 June 2023, from in-person visits by patients over 18 years of age and billed as regular appointments without billed procedures. Each chart was reviewed for the number of concerns addressed in the visit.

Results

Fifty percent of visits addressed more than 1 concern (range = 1–8). A generalized linear mixed model using Poisson distribution showed certain physicians (incident rate ratio [IRR]: 1.192, 95% CI: 1.087–1.307, P < 0.001) and adults older than 65 years compared to adults less than 40 years (IRR 1.151, 95% CI: 1.069–1.239, P < 0.001) were more likely to present with multiple concerns, but patient sex was not a significant predictor.

Conclusions

Family physicians routinely address more than one concern per visit. Standard visit length and billing practices should be adapted to reflect this complexity.
The Association of the 24-Hour Activity Cycle Profiles With Cognition in Older Adults With Mild Cognitive Impairment: A Cross-Sectional Study
Authors: Balbim Guilherme Moraes , Falck Ryan S , Boa Sorte Silva Nárlon Cássio , Kramer Arthur F , Voss Michelle , Liu-Ambrose Teresa
Published: April 2024

Background

The relationship of cognition and the 24-h activity cycle (24-HAC), encompassing physical activity, sedentary behavior, and sleep, in older adults with mild cognitive impairment (MCI) remains uncertain. Distinct combinations of 24-HAC behaviors can characterize unique activity profiles and influence cognition. We aimed to characterize 24-HAC activity profiles in older adults with MCI and assess whether differences in cognition exist across profiles.

Methods

We conducted a cross-sectional analysis utilizing baseline data from 3 randomized controlled trials involving 253 community-dwelling older adults (55 + years) with MCI (no functional impairment, dementia diagnosis, and Montreal Cognitive Assessment score <26/30). Using MotionWatch8© wrist-worn actigraphy (+5 days), we captured the 24-HAC. Cognition was indexed by the Alzheimer’s Disease Assessment Scale Cognitive Plus (ADAS-Cog-Plus). Compositional data and latent profile analyses identified distinct 24-HAC activity profiles. Analysis of covariance examined whether 24-HAC activity profiles differed in cognition.

Results

Four distinct activity profiles were identified. Profile 1 (“Average 24-HAC,” n = 103) engaged in all 24-HAC behaviors around the sample average. Profile 2 (“Active Chillers,” n = 70) depicted lower-than-average engagement in physical activity and higher-than-average sedentary behavior. Profile 3 (“Physical Activity Masters,” n = 54) were the most active and the least sedentary. Profile 4 (“Sedentary Savants,” n = 26) were the least active and the most sedentary. Sleep was similar across profiles. There were no significant differences in ADAS-Cog-Plus scores between 24-HAC activity profiles (p > .05).

Conclusions

Older adults with MCI exhibited four 24-HAC activity profiles conforming to recommended physical activity and sleep guidelines. Nonetheless, cognition was similar across these profiles.
Racial/Ethnic Differences in Self-Reported Upper Limb Limitations Among U.S. Older Adults
Authors: Logue Cook Rachel N , Davis Matthew A , Hasson Rebecca E , Kinnett-Hopkins Dominique , Brown Susan H
Published: April 2024

Background

The development of disability related to activities of daily living (ADL) is of great concern in the aging population, particularly for Hispanic and Non-Hispanic (NH) Black older adults, where disability prevalence is greater compared to NH Whites. ADL-disability is typically measured across many functional tasks without differentiating upper- versus lower-limb limitations, hindering our understanding of disability burden. Despite the importance of the upper limbs for completing ADL and known age-related declines in function, racial/ethnic differences in upper limb function remain largely unknown.

Methods

We identified 4 292 NH White, NH Black, and Mexican American older adults (≥65) from the 2011–2018 waves of the National Health and Nutrition Examination Survey (NHANES). We classified participants as having a limitation based on their ability to complete 5 upper-limb tasks (preparing meals, eating, dressing, reaching overhead, and grasping small objects) and compared limitation rates across racial/ethnic groups.

Results

Compared to NH Whites, NH Black older adults had significantly greater odds of reporting difficulties preparing meals (odds ratio [OR]: 1.36, 95% confidence interval [95% CI]: 1.01, 1.86) and dressing (OR: 1.55, 95% CI: 1.19, 2.02), while Mexican Americans had greater difficulty preparing meals (OR: 1.70, 95% CI: 1.12, 2.58), dressing (OR: 1.63, 95% CI: 1.12, 2.36), and grasping small objects (OR: 1.48, 95% CI: 1.06, 2.07).

Conclusions

Our results demonstrate differences in self-reported upper limb ADL-disability across racial/ethnic groups, particularly for Mexican American older adults. Such findings underscore the need for routine monitoring of upper limb function throughout adulthood to identify limitations and target therapeutic interventions before independence is compromised.
How False Memory and True Memory Affect Decision Making in Older Adults: A Dissociative Account
Authors: Wang Jianqin , Gutchess Angela
Published: April 2024

Objectives

Remembering past rewarding experiences plays a crucial rule in guiding people’s decision making in the future. However, as people age, they become less accurate in remembering past events and more susceptible to forming false memories. An important question is how the decline of episodic memory and the increase of false memory may affect older adults’ decision-making performance.

Methods

The current study used a newly developed paradigm in which the Deese–Roediger–McDermott (DRM) false memory paradigm was combined with a reward learning task to create robust false memories of rewarding experiences. Participants learned that some DRM picture lists brought them a monetary reward and some DRM picture lists did not bring reward. Later, their memories were tested and decision-making preferences were measured.

Results

We found that older and younger adults had almost equivalent false and true memories under the rewarding context, but older adults showed significantly lower decision-making preferences for lure pictures and rewarded pictures than younger adults. Furthermore, true and false memories were a stronger predictor of decision-making preferences for younger than for older adults.

Discussion

These results together suggest an age-related dissociation between memory and decision making that older adults may be less efficient in using their memory to guide decision making than younger adults. Future research may further investigate its underlying mechanisms and develop potential interventions aiming at strengthening the connection between memory and decision making in older adults to help improve their decision-making performance.
Unfair knowledge practices in global health: a realist synthesis
Authors: Abimbola Seye , van de Kamp Judith , Lariat Joni , Rathod Lekha , Klipstein-Grobusch Kerstin , van der Graaf Rieke , Bhakuni Himani
Published: April 2024

Unfair knowledge practices easily beset our efforts to achieve health equity within and between countries. Enacted by people from a distance and from a position of power (‘the centre’) on behalf of and alongside people with less power (‘the periphery’), these unfair practices have generated a complex literature of complaints across various axes of inequity. We identified a sample of this literature from 12 journals and systematized it using the realist approach to explanation. We framed the outcome to be explained as ‘manifestations of unfair knowledge practices’; their generative mechanisms as ‘the reasoning of individuals or rationale of institutions’; and context that enable them as ‘conditions that give knowledge practices their structure’. We identified four categories of unfair knowledge practices, each triggered by three mechanisms: (1) credibility deficit related to pose (mechanisms: ‘the periphery’s cultural knowledge, technical knowledge and “articulation” of knowledge do not matter’), (2) credibility deficit related to gaze (mechanisms: ‘the centre’s learning needs, knowledge platforms and scholarly standards must drive collective knowledge-making’), (3) interpretive marginalization related to pose (mechanisms: ‘the periphery’s sensemaking of partnerships, problems and social reality do not matter’) and (4) interpretive marginalization related to gaze (mechanisms: ‘the centre’s learning needs, social sensitivities and status preservation must drive collective sensemaking’). Together, six mutually overlapping, reinforcing and dependent categories of context influence all 12 mechanisms: ‘mislabelling’ (the periphery as inferior), ‘miseducation’ (on structural origins of disadvantage), ‘under-representation’ (of the periphery on knowledge platforms), ‘compounded spoils’ (enjoyed by the centre), ‘under-governance’ (in making, changing, monitoring, enforcing and applying rules for fair engagement) and ‘colonial mentality’ (of/at the periphery). These context–mechanism–outcome linkages can inform efforts to redress unfair knowledge practices, investigations of unfair knowledge practices across disciplines and axes of inequity and ethics guidelines for health system research and practice when working at a social or physical distance.
Effectiveness and Safety of Semaglutide for Weight Loss in Patients With Inflammatory Bowel Disease and Obesity
Authors: Desai Aakash , Khataniar Himsikhar , Hashash Jana G , Farraye Francis A , Regueiro Miguel , Kochhar Gursimran S
Published: April 2024

Background

Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown sustained and clinically significant weight loss in the general population. There are limited data on outcomes of its use in patients with inflammatory bowel disease (IBD).

Methods

A retrospective cohort study was conducted between June 4, 2021, and December 11, 2023, using TriNetX, a U.S. multi-institutional database in patients with obesity who had IBD compared with patients without IBD. The primary aim was to assess the mean total body weight (TBW) change between 6 and 15 months from initiation of semaglutide compared with baseline between the 2 cohorts. One-to-one (1:1) propensity score matching was performed for demographics, comorbid conditions, smoking status, and mean body mass index. A 2-sample t test was performed to assess mean TBW change from baseline, with a P value <.05 considered to be statistically significant. We also compared the risk of IBD-specific outcomes with and without semaglutide use in patients with IBD.

Results

Out of 47 424 patients with IBD and obesity, 150 (0.3%) patients were prescribed semaglutide (mean age 47.4 ± 12.2 years; mean TBW 237 ± 54.8 pounds; mean body mass index 36.9 ± 6.5 kg/m2; 66% Crohn’s disease). There was no difference in mean TBW change after initiation of semaglutide in the IBD and non-IBD cohorts (−16 ± 13.4 pounds vs −18 ± 12.7 pounds; P = .24). There was no difference in mean TBW change between 6 and 12 months (−16 ± 13 pounds vs −15 ± 11.2 pounds; P = .24) and 12 and 15 months (−20 ± 13.2 pounds vs −21 ± 15.3 pounds; P = .49) between the 2 cohorts. There was no difference in the risk of oral or intravenous steroid use and any-cause hospitalization in the semaglutide group compared with the group without semaglutide use in patients with IBD.

Conclusion

Semaglutide use is effective in patients with IBD and obesity similar to patients without IBD, with >5% mean weight loss. There was no increased risk of IBD-specific adverse events with semaglutide use.
Impacts of Quaternary Climatic Changes on the Diversification of Riverine Cichlids in the Lower Congo River
Authors: Kurata Naoko P , Stiassny Melanie L J , Hickerson Michael J , Alter S Elizabeth
Published: April 2024

Synopsis

Climatic and geomorphological changes during the Quaternary period impacted global patterns of speciation and diversification across a wide range of taxa, but few studies have examined these effects on African riverine fish. The lower Congo River is an excellent natural laboratory for understanding complex speciation and population diversification processes, as it is hydrologically extremely dynamic and recognized as a continental hotspot of diversity harboring many narrowly endemic species. A previous study using genome-wide SNP data highlighted the importance of dynamic hydrological regimes to the diversification and speciation in lower Congo River cichlids. However, historical climate and hydrological changes (e.g., reduced river discharge during extended dry periods) have likely also influenced ichthyofaunal diversification processes in this system. The lower Congo River offers a unique opportunity to study climate-driven changes in river discharge, given the massive volume of water from the entire Congo basin flowing through this short stretch of the river. Here, we, for the first time, investigate the impacts of paleoclimatic factors on ichthyofaunal diversification in this system by inferring divergence times and modeling patterns of gene flow in four endemic lamprologine cichlids, including the blind cichlid, Lamprologus lethops. Our results suggest that Quaternary climate changes associated with river discharge fluctuations may have impacted the diversification of species along the system and the emergence of cryptophthalmic phenotype in some endemic species. Our study, using reduced representation sequencing (2RADseq), indicates that the lower Congo River lamprologines emerged during the Early-Middle Pleistocene transition, characterized as one of the earth’s major climatic transformation periods. Modeling results suggest that gene flow across populations and between species was not constant but occurred in temporally constrained pulses. We show that these results correlate with glacial–interglacial fluctuations. The current hyper-diverse fish assemblages of the lower Congo River riverscape likely reflect the synergistic effects of multiple drivers fueling complex evolutionary processes through time.
Influence of age and sex on longitudinal metabolic profiles and body weight trajectories in the UK Biobank
Authors: Mäkinen Ville-Petteri , Ala-Korpela Mika
Published: April 2024

Background

Accurate characterization of how age influences body weight and metabolism at different stages of life is important for understanding ageing processes. Here, we explore observational longitudinal associations between metabolic health and weight from the fifth to the seventh decade of life, using carefully adjusted statistical designs.

Methods

Body measures and biochemical data from blood and urine (220 measures) across two visits were available from 10 104 UK Biobank participants. Participants were divided into stable (within ±4% per decade), weight loss and weight gain categories. Final subgroups were metabolically matched at baseline (48% women, follow-up 4.3 years, ages 41–70; n = 3368 per subgroup) and further stratified by the median age of 59.3 years and sex.

Results

Pulse pressure, haemoglobin A1c and cystatin-C tracked ageing consistently (P < 0.0001). In women under 59, age-associated increases in citrate, pyruvate, alkaline phosphatase and calcium were observed along with adverse changes across lipoprotein measures, fatty acid species and liver enzymes (P < 0.0001). Principal component analysis revealed a qualitative sex difference in the temporal relationship between body weight and metabolism: weight loss was not associated with systemic metabolic improvement in women, whereas both age strata converged consistently towards beneficial (weight loss) or adverse (weight gain) phenotypes in men.

Conclusions

We report longitudinal ageing trends for 220 metabolic measures in absolute concentrations, many of which have not been described for older individuals before. Our results also revealed a fundamental dynamic sex divergence that we speculate is caused by menopause-driven metabolic deterioration in women.
Spatial Bayesian distributed lag non-linear models (SB-DLNM) for small-area exposure-lag-response epidemiological modelling
Authors: Quijal-Zamorano Marcos , Martinez-Beneito Miguel A , Ballester Joan , Marí-Dell’Olmo Marc
Published: April 2024

Background

Distributed lag non-linear models (DLNMs) are the reference framework for modelling lagged non-linear associations. They are usually used in large-scale multi-location studies. Attempts to study these associations in small areas either did not include the lagged non-linear effects, did not allow for geographically-varying risks or downscaled risks from larger spatial units through socioeconomic and physical meta-predictors when the estimation of the risks was not feasible due to low statistical power.

Methods

Here we proposed spatial Bayesian DLNMs (SB-DLNMs) as a new framework for the estimation of reliable small-area lagged non-linear associations, and demonstrated the methodology for the case study of the temperature-mortality relationship in the 73 neighbourhoods of the city of Barcelona. We generalized location-independent DLNMs to the Bayesian framework (B-DLNMs), and extended them to SB-DLNMs by incorporating spatial models in a single-stage approach that accounts for the spatial dependence between risks.

Results

The results of the case study highlighted the benefits of incorporating the spatial component for small-area analysis. Estimates obtained from independent B-DLNMs were unstable and unreliable, particularly in neighbourhoods with very low numbers of deaths. SB-DLNMs addressed these instabilities by incorporating spatial dependencies, resulting in more plausible and coherent estimates and revealing hidden spatial patterns. In addition, the Bayesian framework enriches the range of estimates and tests that can be used in both large- and small-area studies.

Conclusions

SB-DLNMs account for spatial structures in the risk associations across small areas. By modelling spatial differences, SB-DLNMs facilitate the direct estimation of non-linear exposure-response lagged associations at the small-area level, even in areas with as few as 19 deaths. The manuscript includes an illustrative code to reproduce the results, and to facilitate the implementation of other case studies by other researchers.
Hepatitis B Virus and Hepatitis C Virus Affect Mitochondrial Function Through Different Metabolic Pathways, Explaining Virus-Specific Clinical Features of Chronic Hepatitis
Authors: Selvamani Sakthi Priya , Khan Anis , Tay Enoch S E , Garvey Matthew , Ajoyan Harout , Diefenbach Eve , Gloss Brian S , Tu Thomas , George Jacob , Douglas Mark W
Published: April 2024

Background

Hepatitis C virus (HCV) and hepatitis B virus (HBV) cause chronic hepatitis with important clinical differences. HCV causes hepatic steatosis and insulin resistance, while HBV confers increased risk of liver cancer. We hypothesized these differences may be due to virus-specific effects on mitochondrial function.

Methods

Seahorse technology was used to investigate effects of virus infection on mitochondrial function. Cell-based assays were used to measure mitochondrial membrane potential and quantify pyruvate and lactate. Mass spectrometry was performed on mitochondria isolated from HBV-expressing, HCV-infected, and control cells cultured with isotope-labelled amino acids, to identify proteins with different abundance. Altered expression of key mitochondrial proteins was confirmed by real-time polymerase chain reaction (PCR) and western blot.

Results

Reduced mitochondrial function and ATP production were observed with HCV infection and HBV expression. HCV impaired glycolysis and fatty acid oxidation, promoting lipid accumulation whereas HBV caused lactate accumulation. In HBV-expressing cells enrichment of pyruvate dehydrogenase kinase inhibited pyruvate to acetyl-CoA conversion thereby reducing its availability for mitochondrial oxidative phosphorylation.

Conclusions

HBV and HCV impair mitochondrial function. HCV infection reduces lipid oxidation causing its accumulation and fatty liver disease. HBV infection affects pyruvate processing causing lactate accumulation, cellular stress, and increased risk of liver disease and cancer.
MyD88 in osteoclast and osteoblast lineages differentially controls bone remodeling in homeostasis and malaria
Authors: Alshaweesh Jalal , Dash Rashmi , Lee Michelle S J , Kahyaoglu Pinar , Erci Ece , Xu Mengling , Matsuo-Dapaah Julia , Del Rosario Zorrilla Camila , Aykac Kubra , Ekemen Suheyla , Kobiyama Kouji , Ishii Ken J , Coban Cevayir
Published: April 2024

Chronic bone loss is an under-recognized complication of malaria, the underlying mechanism of which remains incompletely understood. We have previously shown that persistent accumulation of Plasmodium products in the bone marrow leads to chronic inflammation in osteoblast (OB) and osteoclast (OC) precursors causing bone loss through MyD88, an adaptor molecule for diverse inflammatory signals. However, the specific contribution of MyD88 signaling in OB or OC precursors in malaria-induced bone loss remains elusive. To assess the direct cell-intrinsic role of MyD88 signaling in adult bone metabolism under physiological and infection conditions, we used the Lox-Cre system to specifically deplete MyD88 in the OB or OC lineages. Mice lacking MyD88 primarily in the maturing OBs showed a comparable decrease in trabecular bone density by microcomputed tomography to that of controls after Plasmodium yoelii non-lethal infection. In contrast, mice lacking MyD88 in OC precursors showed significantly less trabecular bone loss than controls, suggesting that malaria-mediated inflammatory mediators are primarily controlled by MyD88 in the OC lineage. Surprisingly, however, depletion of MyD88 in OB, but not in OC, precursors resulted in reduced bone mass with decreased bone formation rates in the trabecular areas of femurs under physiological conditions. Notably, insulin-like growth factor-1, a key molecule for OB differentiation, was significantly lower locally and systemically when MyD88 was depleted in OBs. Thus, our data demonstrate an indispensable intrinsic role for MyD88 signaling in OB differentiation and bone formation, while MyD88 signaling in OC lineages plays a partial role in controlling malaria-induced inflammatory mediators and following bone pathology. These findings may lead to the identification of novel targets for specific intervention of bone pathologies, particularly in malaria-endemic regions.
Establishing the Reportable Interval for Routine Clinical Laboratory Tests: A Data-Driven Strategy Leveraging Retrospective Electronic Medical Record Data
Authors: Zayed Ahmed M , Saegeman Veroniek , Delvaux Nicolas
Published: April 2024

Background

This paper presents a data-driven strategy for establishing the reportable interval in clinical laboratory testing. The reportable interval defines the range of laboratory result values beyond which reporting should be withheld. The lack of clear guidelines and methodology for determining the reportable interval has led to potential errors in reporting and patient risk.

Methods

To address this gap, the study developed an integrated strategy that combines statistical analysis, expert review, and hypothetical outlier calculations. A large data set from an accredited clinical laboratory was utilized, analyzing over 124 million laboratory test records from 916 distinct tests. The Dixon test was applied to identify outliers and establish the highest and lowest non-outlier result values for each test, which were validated by clinical pathology experts. The methodology also included matching the reportable intervals with relevant Logical Observation Identifiers Names and Codes (LOINC) and Unified Code for Units of Measure (UCUM)-valid units for broader applicability.

Results

Upon establishing the reportable interval for 135 routine laboratory tests (493 LOINC codes), we applied these to a primary care laboratory data set of 23 million records, demonstrating their efficacy with over 1% of result records identified as implausible.

Conclusions

We developed and tested a data-driven strategy for establishing reportable intervals utilizing large electronic medical record (EMR) data sets. Implementing the established interval in clinical laboratory settings can improve autoverification systems, enhance data reliability, and reduce errors in patient care. Ongoing refinement and reporting of cases exceeding the reportable limits will contribute to continuous improvement in laboratory result management and patient safety.
Distilling large language models for matching patients to clinical trials
Authors: Nievas Mauro , Basu Aditya , Wang Yanshan , Singh Hrituraj
Published: April 2024

Objective

The objective of this study is to systematically examine the efficacy of both proprietary (GPT-3.5, GPT-4) and open-source large language models (LLMs) (LLAMA 7B, 13B, 70B) in the context of matching patients to clinical trials in healthcare.

Materials and methods

The study employs a multifaceted evaluation framework, incorporating extensive automated and human-centric assessments along with a detailed error analysis for each model, and assesses LLMs’ capabilities in analyzing patient eligibility against clinical trial’s inclusion and exclusion criteria. To improve the adaptability of open-source LLMs, a specialized synthetic dataset was created using GPT-4, facilitating effective fine-tuning under constrained data conditions.

Results

The findings indicate that open-source LLMs, when fine-tuned on this limited and synthetic dataset, achieve performance parity with their proprietary counterparts, such as GPT-3.5.

Discussion

This study highlights the recent success of LLMs in the high-stakes domain of healthcare, specifically in patient-trial matching. The research demonstrates the potential of open-source models to match the performance of proprietary models when fine-tuned appropriately, addressing challenges like cost, privacy, and reproducibility concerns associated with closed-source proprietary LLMs.

Conclusion

The study underscores the opportunity for open-source LLMs in patient-trial matching. To encourage further research and applications in this field, the annotated evaluation dataset and the fine-tuned LLM, Trial-LLAMA, are released for public use.
Introduction and establishment of Euwallacea fornicatus (Coleoptera: Curculionidae: Scolytinae) in Brazil
Authors: Covre Luana S , Atkinson Thomas H , Johnson Andrew J , Flechtmann Carlos A H
Published: April 2024

Euwallacea fornicatus is an invasive tree pest able to infest healthy plants and cause damage to many host plants. This beetle has become established in several countries where it was introduced. It has now become established in Brazil, and while the original introduction site remains uncertain, there is a possibility of multiple introductions. We report the first evidence for the establishment of E. fornicatus with molecular confirmation, as well as its distribution, and host plants in Brazil. Euwallacea fornicatus has spread to main commercial avocado groves, other monocultures, and native vegetation in the country, and its pest status puts it as a threat, mainly to Brazilian avocado producers.