bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethical and Medicolegal Issues: When Obstetric Patients Who Refuse Blood Products Change Their Minds
Authors: Holland E. , Richards J.L. , Lanlois W.O. , Zhu J. , Achu-Lopes R.A. , Brook K.
Published: May 2024

(Anesth Analg. 2024;138(1):89–95)

Patients with postpartum hemorrhage (PPH) often need blood transfusions, but there are groups of individuals who are morally or religiously against receiving transfused blood products. The most prominent religious group to refuse transfusions are Jehovah’s witnesses (JW); some may accept minor blood components such as albumin or cell salvage, but many refuse at least major blood components. The preferences and beliefs of these patients must be considered, along with ethical and legal implications surrounding the medical decisions during PPH. This article examines the implications, ethically and legally, of patients who are awake and able to participate in conversations about blood transfusions and change their minds about wanting to proceed, arguing that it is ethically necessary in specific circumstances for a physician to reassess a patient’s wishes mid-crisis and follow through with those decisions.
State Public Insurance Coverage Policies and Postpartum Care Among Immigrants
Authors: Steenland M.W. , Fabi R.E. , Bellerose M. , Desir A. , White M.S. , Wherry L.R.
Published: May 2024

(JAMA. 2023;330(3):238–246)

While physicians and professional medical organizations advocate for routine postpartum care for adults, some states impose restrictions on public insurance coverage for undocumented immigrants and immigrants granted legal documentation status within the past 5 years. The aim of this study was to investigate the relationship between public insurance coverage and postpartum care among low-income immigrants and to determine the difference in postpartum care receipt between immigrants and nonimmigrants.
Postpartum Navigation Decreases Severe Maternal Morbidity Most Among Black Women
Authors: Brown Z. , Messaoudi C. , Silvia E. , Bleau H. , Meskill A. , Flynn A. , Abel-Bey A.C. , Ball T.J.
Published: May 2024

(Am J Obstet Gynecol. 2023;229:160.e1–160.e8)

The United States has significant disparities across varying racial and ethnic groups for pregnancy-related deaths. Research shows that Black women and American Indian or Alaskan Native women have a 3 to 4 times higher risk of pregnancy-related death than White women do, regardless of education. Postpartum care can greatly affect how severe maternal morbidity (SMM) and maternal mortality conditions are addressed. The primary aim of this study was to determine if a postpartum navigation program lowered 30-day postpartum hospitalization admissions from all causes and hospitalization admissions from indicators of SMM. This was done using guidelines from the US Centers for Disease Control and Prevention (CDC). This study also analyzed if the effectiveness of this program transcended across patient demographics like ethnicity and race.
What a Ratchet! A Gripping Case Report of an Entrapped Finger with an Unyielding Wrench
Authors: Freedman Jonathan D. , Aglio James J. , Philippe-Auguste Michael , Slavin Blaire V. , Coelho Paulo G. , Tadisina Kashyap K. , Xu Kyle Y. , Panthaki Zubin J.
Published: May 2024

Finger entrapment with rings or ring-like objects is an uncommon possible hand emergency. In cases in which noncutting removal is ineffective, ring cutters or dental drills with carbide or diamond burs have been successfully used. However, objects composed of hard metallic alloys, such as lug nuts or wrenches, are often resistant to such equipment. In these instances, larger diameter metal cutting burrs or rasps may be more advantageous. Due to their increased size and cutting power, these tools are better suited to handle the toughness of hard metals. In this case report, we present the effective and efficient removal of a stainless steel wrench from an entrapped digit using a helicoidal rasp. Availability of this instrument within orthopedic departments may prevent the delays often described in the treatment of finger entrapment when traditional cutting equipment fails.
Three Case Reports of Adult-onset Still Disease Associated with Breast Implantation
Authors: Maitani Kosuke , Kadowaki Miki , Yamagiwa Yuko , Yasuhara Yumiko , Kozuki Shino , Otsuka Yohei , Kubo Tateki , Tomita Koichi
Published: May 2024

Autoimmune syndrome induced by adjuvants (ASIA) is an uncommon clinical condition reported by Shoenfeld et al. Although this syndrome is not scientifically validated, numerous reports on it have been published, and the manifestations are postulated to be diverse, including generalized symptoms such as chronic fatigue, myalgia, arthralgia, or dry mouth, induced by exogenous substances, specifically adjuvants, which can encompass vaccines, organisms, and silicone. Concurrently, adult-onset Still disease (AOSD) is also an infrequent ailment, characterized by spiking fever, arthritis, skin rash, lymphadenopathy, and serositis. Although the precise pathogenesis remains incompletely understood, some case reports suggest that ASIA may be at the root of AOSD development with the same instigator. In this context, we present three cases of patients diagnosed with AOSD, which possibly could be considered an association with ASIA, years after undergoing breast reconstruction with silicone breast implants. In one case, the patient solely received medical treatment due to her refusal to have the implant removed, resulting in multiple flares and severe complications related to glucocorticoid therapy. Conversely, in the other two cases, a combination of immunosuppressive therapy and silicone breast implant explantation led to the complete resolution of clinical symptoms. To the best of our knowledge, there are only 10 documented case reports of AOSD associated with silicone breast implants insertion. We believe this report serves as a complementary addition to prior research and offers further insights into the ongoing debate about whether explantation should be carried out early in the clinical course or not.
Real-World Effectiveness and Safety of Cladribine in Multiple Sclerosis: Longitudinal Data From the Nationwide Registry in Argentina
Authors: Rojas Juan Ignacio , Alonso Ricardo , Luetic Geraldine , Patrucco Liliana , Casas Magdalena , Silva Berenice , Miguez Jimena , Deri Norma , Vrech Carlos , Liwacki Susana , Piedrabuena Raúl , Silva Emanuel , Tkachuk Verónica , Burgos Marcos , Tavolini Dario , Zanga Gisela , Pinheiro Amelia Alvez , Hryb Javier , Leguizamon Felisa , Knorre Eduardo , Lopez Pablo A. , Martinez Alejandra , Carrá Adriana , Alonso Serena Marina , Cristiano Edgardo , Correale Jorge , Garcea Orlando , Fernandez Liguori Nora , Carnero Contentti Edgar
Published: May 2024

Objective

The aim was to evaluate patient profiles, effectiveness and safety of cladribine (CLAD) in patients with relapsing-remitting multiple sclerosis in Argentina.

Methods

This was a substudy included in RelevarEM (MS and neuromyelitis optica registry in Argentina, NCT03375177). Patients with MS who received CLAD tablets and were followed up for at least 24 months were included. Clinical evaluations every 3 months collect information about: a) clinical relapses; b) progression of physical disability, evaluated through Expanded Disability Status Scale, and c) new lesions found in the magnetic resonance imaging. Lymphopenia was evaluated during the follow-up and defined as grade 1: absolute lymphocyte count (ALC) 800–999/μL; grade 2: ALC 500–799/μL; grade 3: ALC 200–499/μL and grade 4: ALC <200/μL.

Results

A total of 240 patients were included from 19 centers from Argentina. The mean annualized relapse rate during the 12-month pre-CLAD initiation was 1.19 ± 0.56 versus 0.22 ± 0.18 at month 12 and 0.19 ± 0.15 at month 24 (P < 0.001). A total of 142 (59.2%) fulfilled the criteria of disease activity during the 12 months before treatment initiation, whereas 27 (11.3%) fulfilled it at month 12 and 38 (15.8%) at month 24, P < 0.001. Regarding no evidence of disease activity (NEDA), 202 (84.2%) patients achieved NEDA status at month 12 and 185 (77%) at month 24. The most frequent incidence density of lymphopenia for course 2 observed was also for grade 1, 6.1 (95% confidence interval [CI] = 5.5–7.1). The overall incidence density of lymphopenia grade 4 was 0.1 (95% CI = 0.06–0.19).

Conclusion

This information will help when choosing the best treatment option for Argentinean patients.
Effect of fluid elasticity on the emergence of oscillations in an active elastic filament
Authors: Link Kathryn G. , Guy Robert D. , Thomases Becca , Arratia Paulo E.
Published: May 2024

Many microorganisms propel themselves through complex media by deforming their flagella. The beat is thought to emerge from interactions between forces of the surrounding fluid, the passive elastic response from deformations of the flagellum and active forces from internal molecular motors. The beat varies in response to changes in the fluid rheology, including elasticity, but there are limited data on how systematic changes in elasticity alter the beat. This work analyses a related problem with fixed-strength driving force: the emergence of beating of an elastic planar filament driven by a follower force at the tip of a viscoelastic fluid. This analysis examines how the onset of oscillations depends on the strength of the force and viscoelastic parameters. Compared to a Newtonian fluid, it takes more force to induce the instability in viscoelastic fluids, and the frequency of the oscillation is higher. The linear analysis predicts that the frequency increases with the fluid relaxation time. Using numerical simulations, the model predictions are compared with experimental data on frequency changes in the bi-flagellated alga
Chlamydomonas reinhardtii
. The model shows the same trends in response to changes in both fluid viscosity and Deborah number and thus provides a possible mechanistic understanding of the experimental observations.
Combining models to generate consensus medium-term projections of hospital admissions, occupancy and deaths relating to COVID-19 in England
Authors: Manley Harrison , Bayley Thomas , Danelian Gabriel , Burton Lucy , Finnie Thomas , Charlett Andre , Watkins Nicholas A. , Birrell Paul , De Angelis Daniela , Keeling Matt , Funk Sebastian , Medley Graham , Pellis Lorenzo , Baguelin Marc , Ackland Graeme J. , Hutchinson Johanna , Riley Steven , Panovska-Griffiths Jasmina
Published: May 2024

Mathematical modelling has played an important role in offering informed advice during the COVID-19 pandemic. In England, a cross government and academia collaboration generated medium-term projections (MTPs) of possible epidemic trajectories over the future 4–6 weeks from a collection of epidemiological models. In this article, we outline this collaborative modelling approach and evaluate the accuracy of the combined and individual model projections against the data over the period November 2021–December 2022 when various Omicron subvariants were spreading across England. Using a number of statistical methods, we quantify the predictive performance of the model projections for both the combined and individual MTPs, by evaluating the point and probabilistic accuracy. Our results illustrate that the combined MTPs, produced from an ensemble of heterogeneous epidemiological models, were a closer fit to the data than the individual models during the periods of epidemic growth or decline, with the 90% confidence intervals widest around the epidemic peaks. We also show that the combined MTPs increase the robustness and reduce the biases associated with a single model projection. Learning from our experience of ensemble modelling during the COVID-19 epidemic, our findings highlight the importance of developing cross-institutional multi-model infectious disease hubs for future outbreak control.
Long-term efficacy of adoptive cell therapy is determined by host CD8+T cells and undermined by lymphodepleting preconditioning
Authors: Figueroa Diego , Vega Juan Pablo , Hernández-Oliveras Andrés , Gálvez-Cancino Felipe , Ardiles Felipe , Flores Felipe , Hidalgo Sofía , López Ximena , Gonzalez Hugo , Osorio Fabiola , Borgna Vincenzo , Lladser Alvaro
Published: May 2024

Adoptive T cell therapy (ACT) has demonstrated remarkable efficacy in treating hematological cancers. However, its efficacy against solid tumors remains limited and the emergence of cancer cells that lose expression of targeted antigens often promotes resistance to ACT. Importantly, the mechanisms underlying effective and durable ACT-mediated tumor control are incompletely understood. Here, we show that adoptive transfer of TCR-transgenic CD8+T cells eliminates established murine melanoma tumors, with concomitant accumulation of tumor-infiltrating CD8+T cells exhibiting both progenitor-exhausted and terminally-differentiated phenotypes. Interestingly, host CD8+T cells contributed to ACT-mediated elimination of primary tumors and rejected ACT-resistant melanoma cells lacking the targeted antigen. Mechanistically, ACT induced TNF-α- and cross-presenting dendritic cell-dependent tumor accumulation of endogenous CD8+T cells and effective tumor elimination. Importantly, although lymphodepleting preconditioning enhanced ACT-mediated tumor elimination, it abrogated host antitumor immunity and protection against ACT-resistant melanoma cells. Enrichment of transcriptional signatures associated with TNF-α signaling, cross-presenting dendritic cells and tumor-specific CD8+T cells in human melanoma tumors correlated with favorable responses to ACT and increased survival. Our findings reveal that long-term efficacy of ACT is determined by the interplay between transferred and endogenous CD8+T cells and is undermined by lymphodepleting preconditioning, which ultimately favors ACT resistance.
Contribution of leukocyte telomere length to major cardiovascular diseases onset: phenotypic and genetic insights from a large-scale genome-wide cross-trait analysis
Authors: Qiao Jun , Wang Qian , Zhao Yuhui , Chang Minjing , Cai Liuyang , Liu Feng , Yao Kaixin , Zheng Leilei , Tan Ning , He Pengcheng , Jegga Anil G. , Pauklin Siim , Jiang Lei , Yang Yining , Feng Yuliang
Published: May 2024

Telomere shortening, a marker of cellular aging and genomic instability, has been epidemiologically linked to an increased risk of various cardiovascular diseases (CVDs). However, shared genetic determinants involved in these associations remain unclear. We composed an atlas of the shared genetic associations between leukocyte telomere length (LTL) and six major CVDs by investigating shared genetic elements, encompassing SNPs, genes, biological pathways, and protein targets with pleiotropic implications. Extensive genetic overlaps beyond genetic correlations were observed, but no causal relationships were established. We identified 248 independent pleiotropic genomic risk loci, implicating 50 unique genes in two or more trait pairs, especially theSH2B3gene, which was further validated by a proteome-wide Mendelian Randomization study. Functional analysis demonstrated a link to both DNA biosynthetic processes and telomere maintenance mechanisms. These findings suggest a genetic link between LTL and CVDs, highlighting a shared genetic basis crucial for developing future interventions and therapeutic targets.
Germline status and micronutrient availability regulate a somatic mitochondrial quality control pathway via short-chain fatty acid metabolism
Authors: Held James P , Dbouk Nadir H , Strozak Adrianna M , Grub Lantana K , Ryou Hayeon , Schaffner Samantha H , Patel Maulik R
Published: May 2024

Reproductive status, such as pregnancy and menopause in women, profoundly influences metabolism of the body. Mitochondria likely orchestrate many of these metabolic changes. However, the influence of reproductive status on somatic mitochondria and the underlying mechanisms remain largely unexplored. We demonstrate that reproductive signals modulate mitochondria in the Caenorhabditis elegans soma. We show that the germline acts via an RNA endonuclease, HOE-1, which despite its housekeeping role in tRNA maturation, selectively regulates the mitochondrial unfolded protein response (UPRmt). Mechanistically, we uncover a fatty acid metabolism pathway acting upstream of HOE-1 to convey germline status. Furthermore, we link vitamin B12's dietary intake to the germline's regulatory impact on HOE-1-driven UPRmt. Combined, our study uncovers a germline-somatic mitochondrial connection, reveals the underlying mechanism, and highlights the importance of micronutrients in modulating this connection. Our findings provide insights into the interplay between reproductive biology and metabolic regulation.
Impact of Organic Compounds on the Stability of Influenza A Virus in deposited 1-ul droplets
Authors: Schaub Aline , David Shannon C. , Glas Irina , Klein Liviana K , Violaki Kalliopi , Terrettaz Celine , Motos Ghislain , Bluvshtein Nir , Luo Beiping , Pohl Marie O , Hugentobler Walter , Nenes Athanasios , Krieger Ulrich K , Peter Thomas , Stertz Silke , Kohn Tamar
Published: May 2024

The composition of respiratory fluids influences the stability of viruses in exhaled aerosol particles and droplets, though the role of respiratory organics in modulating virus stability remains poorly understood. This study investigates the effect of organic compounds on the stability of influenza A virus (IAV) in deposited droplets. We compare the infectivity loss of IAV at different relative humidities (RH) over the course of one hour in 1-ul droplets consisting of phosphate-buffered saline (without organics), synthetic lung fluid, or nasal mucus (both containing organics). We show that IAV stability increases with increasing organic:salt ratios. Among the various organic species, proteins are identified as the most protective component, with smaller proteins stabilizing IAV more efficiently at the same mass concentration. Organics act by both increasing the efflorescence RH and shortening the drying period until efflorescence at a given RH. This research advances our mechanistic understanding of how organics stabilize exhaled viruses and thus influence their inactivation in respiratory droplets.
A complete and dynamic tree of birds
Authors: McTavish Emily Jane , Gerbracht Jeff A. , Holder Mark T. , Iliff Marshall J. , Lepage Denis , Rasmussen Pam , Redelings Benjamin , Sanchez Reyes Luna Luisa , Miller Eliot T.
Published: May 2024

We present a complete, time-scaled, evolutionary tree of the world’s bird species. This tree unites phylogenetic estimates for 9,239 species from 262 studies published between 1990 and 2024, using the Open Tree synthesis algorithm. The remaining species are placed in the tree based on curated taxonomic information. The tips of this complete tree are aligned to the species in the Clements Taxonomy used by eBird and other resources, and cross-mapped to other taxonomic systems including the Open Tree of Life (Open Tree), National Center for Biotechnology Information (NCBI), and Global Biodiversity Information Facility (GBIF). The total number of named bird species varies between 10,824 and 11,017 across the taxonomy versions we applied (v2021, v2022 and v2023). We share complete trees for each taxonomy version. The procedure, software and data-stores we used to generate this tree are public and reproducible. The tree presented here is Aves v1.2 and can be easily updated with new phylogenetic information as new estimates are published. We demonstrate the types of large scale analyses this data resource enables by linking geographic data with the phylogeny to calculate the regional phylogenetic diversity of birds across the world. We will release updated versions of the phylogenetic synthesis and taxonomic translation tables annually. The procedure we describe here can be applied to developing complete phylogenetic estimates for any taxonomic group of interest.

Significance statement

Birds are charismatic - well loved, and highly studied. Many new phylogenies elucidating avian birds evolutionary relationships are published every year. We have united phylogenetic estimates from hundreds of studies to create a complete evolutionary tree of all birds. While a variety of resources aggregate huge collections of trait, behavior and location data for birds, previously the barriers to linking data between these data resources and bird evolutionary history have limited the opportunities to do exciting large scale analyses. We have bridged that gap, and developed a system that allows us to easily update our understanding of bird evolution as new estimates are generated. We share a workflow and the software needed to create a complete evolutionary tree for any group.
Liver-Quant: Feature-Based Image Analysis Toolkit for Automatic Quantification of Metabolic Dysfunction-Associated Steatotic Liver Disease
Authors: Farzi Mohsen , McGenity Clare , Cratchley Alyn , Leplat Leo , Bankhead Peter , Wright Alexander , Treanor Darren
Published: May 2024

Introduction

The histological assessment of liver biopsies by pathologists serves as the gold standard for diagnosing metabolic dysfunction-associated steatotic liver disease (MASLD) and staging disease progression. Various machine learning and image analysis tools have been reported to automate the quantification of fatty liver and enhance patient risk stratification. However, the current software is either not open-source or not directly applicable to the whole slide images (WSIs).

Methods

In this paper, we introduce “Liver-Quant,” an open-source Python package designed for quantifying fat and fibrosis in liver WSIs. Employing colour and morphological features, Liver-Quant measures the Steatosis Proportionate Area (SPA) and Collagen Proportionate Area (CPA). The method’s accuracy and robustness were evaluated using an internal dataset of 424 WSIs from adult patients collected retrospectively from the archives at Leeds Teaching Hospitals NHS Trust between 2016 and 2022 and an external public dataset of 109 WSIs. For each slide, semi-quantitative scores were automatically extracted from free-text pathological reports. Furthermore, we investigated the impact of three different staining dyes including Van Gieson (VG), Picro Sirius Red (PSR), and Masson’s Trichrome (MTC) on fibrosis quantification.

Results

The Spearman rank coefficient (ρ) was calculated to assess the correlation between the computed SPA/CPA values and the semi-quantitative pathologist scores. For steatosis quantification, we observed a substantial correlation (ρ=0.92), while fibrosis quantification exhibited a moderate correlation with human scores (ρ=0.51). To assess stain variation on CPA measurement, we collected N=18 cases and applied the three stains. Employing stain normalisation, an excellent agreement was observed in CPA measurements among the three stains using Bland-Altman plots. However, without stain normalisation, PSR emerged as the most effective dye due to its enhanced contrast in the Hue channel, displaying a strong correlation with human scores (ρ=0.9), followed by VG (ρ=0.8) and MTC (ρ=0.59). Additionally, we explored the impact of the apparent magnification on SPA and CPA. High resolution images collected at 0.25 microns per pixel (MPP) [apparent magnification = 40x] or 0.50 MPP [apparent magnification = 20x] were found to be essential for accurate SPA measurement, whereas for CPA measurement, low resolution images collected at 10 MPP [apparent magnification = 1x] were sufficient.

Conclusion

The Liver-Quant package offers an open-source solution for rapid and precise liver quantification in WSIs applicable to multiple histological stains.
Longitudinal automated brain volumetry vs. expert visual assessment of atrophy progression on MRI is robust but caution is advised
Authors: Gebest Max , Weiß Christel , Cho Chang-Gyu , Hausner Lucrezia , Frölich Lutz , Förster Alex , Santhanam Nandhini , Fontana Johann , Groden Christoph , Wenz Holger , Maros Máté E.
Published: May 2024

Automated tools have been proposed to quantify brain volume for suspected dementia diagnoses. However, their robustness in longitudinal, real-life cohorts remains unexplored. We investigated if expert visual assessment (EVA) of atrophy progression is reflected by automated volumetric analyses (AVA) on sequential MR-imaging. We analyzed a random subset of 20 patients with two consecutive 3D T1-weighted examinations (median follow-up 4.0 years, LQ-UQ: 2.1-5.2, range: 0.2-10). Thirteen (65%) with cognitive decline, the remaining with other neuropsychiatric diseases. EVA was performed by two blinded neuroradiologists using a 3 or 5-point Likert scale for atrophy progression (scores ±0-2: no, probable and certain progression or decrease, respectively) in dementia-relevant brain regions (frontal-, parietal-, temporal lobes, hippocampi, ventricles). Differences of AVA-volumes were normalized to baseline (delta). Inter-rater agreement of EVA scores was excellent (κ=0.92). AVA-delta and EVA showed significant global associations for the right hippocampus (p=0.035), left temporal lobe (p=0.0092), ventricle volume (p=0.0091) and a weak association for the parietal lobe (p=0.067).Post hoctesting revealed a significant link for the left hippocampus (p=0.039). In conclusion, the associations between volumetric deltas and EVA of atrophy progression were robust for certain brain regions. However, AVA-deltas showed unexpected variance, and therefore should be used with caution in individual cases, especially when acquisition protocols vary.
Prevalence, Trends, and Associated Factors of Isolated Systolic, Diastolic, and Systolic-Diastolic Hypertension in Peru: A Nine-Year Analysis of the Demographic and Family Health Survey
Authors: Vera-Ponce Víctor Juan , Zuzunaga-Montoya Fiorella E. , Vásquez-Romero Luisa Erika Milagros , Loayza-Castro Joan A. , Gutierrez De Carrillo Carmen Inés , Vigil-Ventura Enrique
Published: May 2024

Introduction

While HTN is widely seen as a primary threat to cardiovascular conditions worldwide, it is essential to recognize that not all HTN is identical.

Objective

To determine the prevalence, trend, and factors associated with each type of HTN: isolated systolic (ISH), isolated diastolic (IDH), and systolic-diastolic (SDH).

Methods

A secondary analysis of data from the Demographic and Family Health Survey from 2014– 2022 was conducted. For the analysis of associated factors, a Poisson regression model with robust variance was implemented to calculate adjusted Prevalence Ratios (aPR) along with their 95% confidence intervals.

Results

The prevalence was 7.02%, 1.55%, and 3.28% for ISH, IDH, and SDH, respectively. ISH showed a decline in 2022, unlike the other two types, which seem to be on the rise. A statistically significant association was found in men and an increased risk with age for ISH and SDH, unlike IDH, where age acts as a protective factor. Additional factors identified include smoking and excessive alcohol consumption, while a high intake of fruits/vegetables offers a protective effect. Obesity and diabetes were associated with a higher risk, and significant variations by region and altitude, as well as among ethnic groups, were observed.

Conclusions

Significant differences in the prevalence of HTN subtypes have been found, underscoring the heterogeneity of this chronic condition, both in related factors and in trends over the years.
Economic burden of depressive disorders for people living with HIV in Uganda
Authors: Katana Patrick V. , Ross Ian , Kiconco Barbra Elsa , Tenywa Patrick , Neuman Melissa , Ssembajjwe Wilber , Sekitoleko Isaac , Katumba Kenneth Roger , Kinyanda Eugene , Laurence Yoko V. , Greco Giulia
Published: May 2024

Introduction

Between 8–39 % of people living with HIV (PLWH) in sub-Saharan Africa have depressive disorders (DD). Despite considerable gains in the treatment of PLWH, DD is increasingly recognised as a threat to successful treatment and prevention. PLWH are generally known to suffer from stress and incur higher health-related costs compared to the general population due to care management demand throughout their lifespan. There have been limited studies examining healthcare costs borne by PLWH with DD specifically.

Objective

We aimed to estimate the economic burden of DD and HIV amongst PLWH and explore their mechanisms of coping with high out of pocket (OOP) health expenditure.

Methodology

This is a cost of illness study nested in an ongoing cluster-randomised trial assessing the effectiveness of integrating treatment of DD into routine HIV care in Uganda (HIV+D trial). The study is using cross-sectional data collected from 1,115 PLWH at trial baseline, using the Patient Health Questionnaire (PHQ-9) to measure DD and a structured cost questionnaire was administered. Forty public health care facilities that provide HIV care in Kalungu, Masaka and Wakiso Districts were randomly selected, and study participants were recruited amongst their patients. Eligibility criteria were patients attending the HIV clinic, aged ≥ 18 years who screen positive for DD (PHQ-9 ≥ 10). Economic costs (OOP expenditure and opportunity costs) were estimated from the household perspective.

Results

Mean monthly economic costs amongst those incurring any costs (n=1,115) were UGX 255,910 (US$ 68.64). Mean monthly OOP expenditures were UGX 94,500 (US$ 25.60). On average, respondents missed 6 days of work per month due to healthcare seeking or ill-health for any condition. Key cost drivers were facility bed charges and medication. The majority of respondents (73%) borrowed money from families and friends to cope with the economic burden. About 29.7% reported moderate (PHQ-9 15-19) and 5.12% severe (PHQ-9 ≥ 20) DD symptoms. Respondents with moderate or severe DD had slightly higher average monthly costs than those with mild DD (PHQ-10-14), but the difference was not statistically significant.

Conclusion

People living with HIV who experience DD incur in high OOP expenditure and productivity losses. The monthly OOP health expenditure is in the range of 23% of their monthly household income. Social protection mechanisms combined with the integration of the management of DD into routine HIV care could alleviate this burden.
Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring Cohort
Authors: Savin M.J. , Wang H. , Pei H. , Aiello A.E. , Assuras S. , Caspi A. , Moffitt T.E. , Muenning P.A. , Ryan C.P. , Shi B. , Stern Y. , Sugden K. , Valeri L. , Belsky D.W.
Published: May 2024

Introduction

The geroscience hypothesis proposes systemic biological aging is a root cause of cognitive decline.

Methods

We analyzed Framingham Heart Study Offspring Cohort data (n=2,296; 46% male; baseline ageM=62, SD=9, range=25-101y). We measured cognitive decline across two decades of neuropsychological-testing follow-up. We measured pace of aging using the DunedinPACE epigenetic clock. Analysis tested if participants with faster DunedinPACE values experienced more rapid preclinical cognitive decline as compared to those with slower DunedinPACE values.

Results

Participants with faster DunedinPACE had poorer cognitive functioning at baseline and experienced more rapid cognitive decline over follow-up. Results were robust to confounders and consistent across population strata. Findings were similar for the PhenoAge and GrimAge epigenetic clocks.

Discussion

Faster pace of aging is a risk factor for preclinical cognitive decline. Metrics of biological aging may inform risk stratification in clinical trials and prognosis in patient care.
Predictors of perinatal mortality in the seven major hospitals of Lusaka Zambia: A Case Control Study
Authors: Makasa Musonda , Kaonga Patrick , Jacobs Choolwe , Makasa Mpundu , Vwalika Bellington
Published: May 2024

Background

Over 2.6 million babies are lost later in pregnancy, during labour, and or in the first week of life. Global perinatal mortality reduced from 5.7 million since 2000 to 4.1 million in 2015. High-income countries account for 45% of this data. The rest are in low-income countries, 77% of which are in sub-Saharan Africa. Perinatal mortality rates for sub-Saharan Africa and Zambia are 42.95 and 33/1000 live births, respectively. The aim of this study was to determine the predictors of perinatal mortality at the seven major hospitals of Lusaka, Zambia.

Methods

This was a multi- centre unmatched case control study from September 2023 to January 2024. Cases included perinatal death (>24 weeks gestation or >500g stillborn, and death of neonate within seven days of life) and controls were live births. Stepwise multivariate logistic regression analysis determined predictors using adjusted odd ratios and p-values.

Results

The study had 630 participants, 210 cases and 420 controls were analysed: ratio 1:2. Antenatal care booking after 12 weeks gestation had almost three times odds of experiencing perinatal (AOR 2.909, 95% CI: 1.97-4.296), p <0.001 compared to those who booked early. Walking as means of reaching healthcare facility had over three odds perinatal mortality (AOR3.482, 95% CI: 1.87-6.49) than personal transport users. Anaemia during pregnancy had over three times risk of perinatal death (AOR 3.581, 95% CI: 1.72- 7.44) than those without it. History of loss of baby before birth had five fold odds to experience perinatal mortality than to those who had not (AOR 5.047, 95% CI: 2.99-8.51).

Conclusion

This study revealed that late antenatal care booking, walking, as means of transport to access health facility, anaemia in pregnancy, and previous history of loss of baby before birth perinatal death were the main predictors with statistical significance of perinatal death experience.
Understanding Diagnostic Error Patterns and Contributing Factors: A Descriptive Analysis of Medical Error Reports at a Tertiary Hospital in Kenya 2019-2021
Authors: Okutoyi Lydia , Godia Pamela , Adam Mary , Sitati Fred , Jaoko Walter
Published: May 2024

Background

Diagnostic errors in healthcare pose substantial risks, leading to increased costs, patient anxiety, and delayed diagnoses. Despite its prevalence, diagnostic errors have historically received less attention compared to other medical errors, necessitating urgent action to address these critical issues. This is more so in the low- and middle-income countries. (LMICs). This study aimed to analyze patterns and associated factors of diagnostic error reported to the Patient Safety Unit of Kenyatta National Hospital (KNH), a tertiary teaching hospital in Nairobi, Kenya.

Methods

This was a descriptive retrospective study of medical error reports(MER) forms submitted to KNH from 2019-2021.Type of medical errors, contributing factors, site, timing of error, and outcome were recorded. Descriptive statistics, chi-square tests, and logistic regression were employed to assess error types, contributing factors, and associated likelihoods.

Results

Among 640 MER forms analysed, diagnostic errors were reported in 40 percent of cases, predominantly associated with delayed diagnosis, wrong diagnosis, and failure to test. Contributing factors to MER included communication issues (36.1%), staff-related factors (48.9%), and equipment issues (15.6%). Diagnostic errors were more likely during non-working hours (OR 1.969, p < 0.047) and in Accident and Emergency department (OR 2.36, p < 0.022) within KNH.

Conclusion

Diagnostic errors represent a significant proportion of medical errors at KNH, particularly in Accident and Emergency settings. Strategies to involve more physicians in error reporting and enhance communication practices are recommended.
External UK validation of the ENDPAC model to predict pancreatic cancer risk: A registered report protocol
Authors: Price Claire A. , Claridge Hugh , de Lusignan Simon , Khalaf Natalia , Mold Freda , Smith Nadia A. S. , Winn Martyn , Lemanska Agnieszka
Published: May 2024

Introduction

Overall cancer survival has increased over recent decades, but the very low survival rates of pancreatic cancer have hardly changed in the last 50 years. This is attributed to late diagnosis. Pancreatic cancer symptoms are non-specific which makes early diagnosis challenging. Data-driven approaches, including algorithms using combinations of symptoms to predict cancer risk, can aid clinicians. A simple but effective algorithm called Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) has been developed in the United States (US). ENDPAC has not yet been used in the United Kingdom (UK), our aim is to translate ENDPAC into the UK setting. The objectives are to validate ENDPAC and report its predictive utility within primary care.

Methods

A retrospective cohort study of people with new-onset diabetes using the nationally representative Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) database. ORCHID holds over 10 million primary care electronic healthcare records. ENDPAC scores will be calculated for eligible people along with positive predictive value, negative predictive value, sensitivity and specificity of the algorithm. We will evaluate the optimal cut-off for defining people with high-risk of having pancreatic cancer.

Discussion

Once validated within the UK, ENDPAC could be implemented in practice to improve early pancreatic cancer diagnosis by using routine data. ENDPAC is currently being tested in the US in a clinical trial to evaluate its effectiveness. ENDPAC offers an automatable and inexpensive way to improve early diagnosis as part of a sequential approach to identify individuals at high-risk of having undiagnosed pancreatic cancer.

How this fits in

Pancreatic cancer is a devasting disease which is hard to diagnose. An algorithm called ENDPAC has been developed in the United States to help clinicians identify people at risk of having undiagnosed pancreatic cancer. These people can be referred for an imaging investigation to diagnose or rule out cancer. This protocol outlines a United Kingdom (UK) validation of ENDPAC so that it could be used in clinical practice in the UK.
Trends in Repeat Administration of Magnesium for an Exacerbation of Postpartum Preeclampsia: A National Survey
Authors: Dellapiana Gabriela , Thompson Keona , Gregory Kimberly D
Published: May 2024

Background

Magnesium (Mg) infusion is first-line for seizure prophylaxis in preeclampsia with severe features (PESF). Guidance is lacking regarding utility of an additional course of Mg for disease exacerbation following completion of an initial course. We aimed to determine the national trend among academic institutions for administration of a second course of Mg in patients with an exacerbation of PESF.

Methods

A REDCap survey querying response to clinical scenarios related to Mg administration was sent to Maternal-Fetal Medicine program directors (or surrogate if no response) using publicly available contact information. Participants received a $10 incentive.

Results

Responses were received from 66 of 95 institutions (69%), representing all 12 ACOG districts. An institutional protocol for postpartum Mg was reported by 70% (N=46) of respondents. Overall, 68% (N=45) would give a second course of Mg for an exacerbation of PESF, with no geographic variation (P=0.969). Most would administer a second course of Mg if the patient had a headache (N=52, 79%) or blood pressure ≥180/120 (N=35, 53%). The decision for a second course of Mg was not influenced by worsening laboratory values, gestational age at delivery, latency from delivery, or maternal demographics.

Conclusions

Although there are no standardized guidelines for seizure prophylaxis in postpartum exacerbations of PESF, this national survey suggests that most academic programs favor giving a second course of Mg, especially in patients with headache or severe BP. A randomized trial comparing outcomes in patients who did or did not receive an additional course of Mg is warranted.
Medial temporal lobe atrophy patterns in early- versus late-onset amnestic Alzheimer’s disease
Authors: Wuestefeld Anika , Pichet Binette Alexa , van Westen Danielle , Strandberg Olof , Stomrud Erik , Mattsson-Carlgren Niklas , Janelidze Shorena , Smith Ruben , Palmqvist Sebastian , Baumeister Hannah , Berron David , Yushkevich Paul A. , Hansson Oskar , Spotorno Nicola , Wisse Laura EM
Published: May 2024

Background

The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer’s disease (EOAD). Yet, detailed examination of MTL subfield volumes and drivers of atrophy in amnestic EOAD is lacking.

Methods

BioFINDER-2 participants with memory impairment, abnormal amyloid-β status and tau-PET were included. Forty-one EOAD individuals aged ≥65 years and, as comparison, late-onset AD (LOAD, ≤70 years, n=154) and Aβ-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured.

Results

AD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups, although LOAD showed thinner entorhinal cortices compared to EOAD. EOAD showed lower WMH compared to LOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity was found.

Conclusions

We found in vivo evidence for MTL atrophy in amnestic EOAD and overall similar levels to LOAD of MTL tau pathology and co-pathologies.
Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex
Authors: Fernández-Casañas María , Karanika Eleftheria , Olukoga Tomisin , Herbert Alex , Aliyaskarova Umit , Day Matthew , Chan Kok-Lung
Published: May 2024

The BTRR (BLM/TOP3A/RMI1/RMI2) complex resolves various DNA replication and recombination intermediates to suppress genome instability. Alongside PICH, they target mitotic DNA intertwinements, known as ultrafine DNA bridges, facilitating chromosome segregation. Both BLM and PICH undergo transient mitotic hyper-phosphorylation, but the biological significance of this remains elusive. Here, we uncover that during early mitosis, multiple protein kinases act together to strictly constrain the BTRR complex for the protection of centromeres. Mechanistically, CDK1 destabilises the complex and suppresses its association with PICH at the chromatin underneath kinetochores. Inactivating the BLM and TOP3A interaction compromises the UFB-binding complex mitotic functions and can prevent centromere destruction. We further unravel how different clusters of mitotic phosphorylation on BLM affect its interaction with the TOP3A/RMI1/RMI2 subcomplex and illegitimate centromere unwinding. Furthermore, we identify specific phosphorylation sites targeted by the MPS1-PLK1 axis functioning to prevent BLM hyper-activation at centromeres. Notably, unleashing such activity after sister-chromatid cohesion loss facilitates separation of entangled chromosomes. Together, our study defines a centromere protection pathway in human mitotic cells, heavily reliant on a tight spatiotemporal control of the BTRR complex.
Large scale loss-of-function mutations during chicken evolution and domestication
Authors: Wu Siwen , Wang Kun , Ge Xuehai , Dou Tengfei , Yuan Sisi , Yan Shixiong , Xu Zhiqiang , Liu Yong , Jian Zonghui , Zhao Jingying , Zhao Rouhan , Zi Xiannian , Gu Dahai , Liu Lixian , Li Qihua , Wu Dong-Dong , Jia Junjing , Ge Changrong , Su Zhengchang
Published: May 2024

Despite recent progresses, the driving force of evolution and domestication of chickens remains poorly understood. To fill this gap, we recently sequenced and assembled genomes of four distinct indigenous chickens from Yunnan, China. Unexpectedly, we found large numbers of pseudogenes which have lost their functions and are fixed in their corresponding populations, and we also found highly variable proteomes in the genomes of the four indigenous chickens as well as the sequenced wild red jungle fowl (RJF) (GRCg6a). Although the four indigenous chicken breeds are closely related to theG. g. spadiceoussubspecies, for the first time, we found that the RJF (GRCg6a) is of theG. g. bankivaorigin. Thus, the five chicken share the most recent common ancestor (MRCA) before subspeciation. Our results support a scenario that the MRCA of the four indigenous chickens and the RJF possessed at least 21,972 genes, of which 7,993 are dispensable. Each chicken has lost functions of thousands of the dispensable genes during their evolution and domestication via complete gene loss and pseudogenization. The occurring pattens of completely lost genes and pseudogenes segregate the chickens as their phylogenetic tree does. Therefore, loss-of-function mutations might play important roles in chicken evolution and domestication.
Imaging-Based Quantitative Assessment of Biomolecular Condensatesin vitroand in Cells
Authors: Bergsma Tessa , Steen Anton , Kamenz Julia L. , Gallardo Paola , Veenhoff Liesbeth M.
Published: May 2024

The formation of biomolecular condensates contributes to intracellular compartmentalization, and plays an important role in many cellular processes. The characterization of condensates is however challenging, requiring advanced biophysical or biochemical methods that are often less suitable forin vivostudies. A particular need for easily accessible yet thorough methods that enable the characterization of condensates across different experimental systems thus remains. To address this, we present PhaseMetrics, a semi-automated FIJI-based image analysis pipeline tailored for quantifying particle properties from microscopy data. Tested using the FG-domain of yeast nucleoporin Nup100, PhaseMetrics accurately assesses particle properties across diverse experimental setups, includingin vitro,Xenopusegg extracts, and cellular systems. It reliably detects changes induced by various conditions such as the presence of polyethylene glycol, 1,6-hexanediol, a salt gradient, and the molecular chaperone DNAJB6b. By enabling the accurate representation of the variability within the population and the detection of subtle changes at the single particle level, the method complements conventional biochemical assays. Combined, PhaseMetrics is an easily accessible, customizable pipeline that enables imaging-based quantitative assessment of biomolecular condensatesin vitroand in cells, providing a valuable addition to the current toolbox.
Key embrace factors for designing sustainable supply chains in Egyptian Industry 4.0
Authors: Khodair Adel
Published: May 2024

Purpose

This study explores the key embrace factors for designing supply chains in Industry 4.0 to improve sustainability practices with respect to the triple bottom line.

Design/methodology/approach

The theoretical underpinnings of this study were strengthened by a qualitative method that included an interview process within the framework of a holistic case study. Data collected through 38 remote interviews with representatives of 17 Egyptian companies that are actively using Industry 4.0.

Findings

The thematic analysis identified 6 main categories in addition to 32 economic, environmental, and social key embrace factors. Further, an integrated model was established to show how various key embrace factors can be included in the evaluation of the Supply chain. 64.7% of interviewees affirmed that these factors were deemed to be the most important and influential key factors.

Practical implications

The global contribution is mainly to facilitate additional eco-friendly initiatives to gain a competitive advantage through environmentally responsible practices, which reflects the strengthening of the sustainable supply chain with the involvement of all the interested parties.

Social implications

This study expands on previous research papers to underline 20 new global key embrace factors, including 9 social, 7 economic, and 4 environmental key embrace factors.

Originality/value

The Key embrace factors discovered and addressed in this paper provide a unique theoretical guideline to plan and popularize this integration process. The integrated approach assists in the review of existing supply chains or the creation of new ones.