bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Screening, Incidental Detection, and Overdiagnosis
Authors: Welch H Gilbert , Bergmark Regan
Published: September 2023

Background

In the past, patients were only diagnosed with cancer because they had symptoms. Now, because of screening and incidental detection, some patients are diagnosed with cancer when they are asymptomatic. While this shift is typically viewed as desirable, it has produced an unfortunate side-effect: it is now possible to be diagnosed with a cancer not destined to cause symptoms or death—a phenomenon labeled as overdiagnosis.

Content

We begin with a brief introduction to the heterogeneity of cancer progression: at one extreme, some cancers are already systemic by the time they are detectable; at the other, some grow extremely slowly or even regress. The ensuing sections describe the evidence that the pursuit of earlier detection has led to overdiagnosis. Although rarely confirmed in an individual, overdiagnosis is readily identifiable in a long-term follow-up of a randomized trial of screening. Furthermore, 2 population signatures for overdiagnosis exist: (a) rising incidence coupled with stable mortality and (b) rising early-stage incidence coupled with stable late-stage incidence. Finally, we review the misleading feedback produced by overdiagnosis—such as rising 5-year survival rates and more cancer survivors. This feedback is erroneously interpreted as reinforcing the value of early detection, encourages more screening/incidental detection and, ironically, promotes more overdiagnosis.

Overdiagnosis is an unintended consequence of the desire to detect cancer early. Given the evolving understanding that tumor biology and host response are more relevant to prognosis than early vs late diagnosis, it is time to challenge the assertion that early diagnosis is always the best approach to curing cancer.
Transcatheter aortic valve replacement outcomes in patients with low-flow very low-gradient aortic stenosis
Authors: Ueyama Hiroki A , Chopra Lakshay , Dalsania Ankur , Prandi Francesca Romana , Sharma Samin K , Kini Annapoorna , Lerakis Stamatios
Published: September 2023

Aims

In patients with severe aortic stenosis (AS), low-flow low-gradient (LG) is a known predictor of worse outcomes. However, very LG may represent a distinct population with further cardiac dysfunction. It is unknown whether this population benefits from transcatheter aortic valve replacement (TAVR). We aimed to describe the patient characteristics and clinical outcomes of low-flow very LG severe AS.

Methods and results

This single-centre study included all patients with low-flow severe AS between 2019 and 2021. Patients were divided into groups with very LG [mean pressure gradient (MPG) ≤ 20 mmHg], LG (20 < MPG < 40 mmHg), and high-gradient (HG) (MPG ≥ 40 mmHg). Composite endpoint of all-cause mortality and heart failure rehospitalization was compared. A total of 662 patients [very LG 130 (20%); LG 339 (51%); HG 193 (29%)] were included. Median follow-up was 12 months. Very LG cohort had a higher prevalence of comorbid conditions with lower left ventricular ejection fraction (45% vs. 57% vs. 60%; P < 0.001). There was a graded increase in the risk of composite endpoint in the lower MPG strata (P < 0.001). Among those who underwent TAVR, very LG was an independent predictor of the composite endpoint (adjusted HR 2.42 [1.29–4.55]). While LG and HG cohorts had decreased risk of composite endpoint after TAVR compared with conservative management, very LG was not associated with risk reduction (adjusted HR 0.69 [0.35–1.34]).

Conclusion

Low-flow very LG severe AS represents a distinct population with significant comorbidities and worse outcomes. Further studies are needed to evaluate the short- and long-term benefits of TAVR in this population.
Elevational Goldilocks zone underlies the exceptional diversity of a large lizard radiation (Liolaemus; Liolaemidae)
Authors: Skeels Alexander , Esquerré Damien , Lipsky Daria , Pellissier Loïc , Boschman Lydian M
Published: September 2023

Mountains are among the most biodiverse regions on the planet, and how these landforms shape diversification through the interaction of biological traits and geo-climatic dynamics is integral to understanding global biodiversity. In this study, we investigate the dual roles of climate change and mountain uplift on the evolution of a hyper-diverse radiation, Liolaemus lizards, with a spatially explicit model of diversification using a reconstruction of uplift and paleotemperature in central and southern South America. The diversification model captures a hotspot for Liolaemus around 40°S in lineages with low-dispersal ability and narrow niche breadths. Under the model, speciation rates are highest in low latitudes (<35°S) and mid elevations (~1,000 m), while extinction rates are highest at higher latitudes (>35°S) and higher elevations (>2,000 m). Temperature change through the Cenozoic explained variation in speciation and extinction rates through time and across different elevational bands. Our results point to the conditions of mid elevations being optimal for diversification (i.e., Goldilocks Zone), driven by the combination of (1) a complex topography that facilitates speciation during periods of climatic change, and (2) a relatively moderate climate that enables the persistence of ectothermic lineages and buffers species from extinction.
From the Lie Operad to the Grothendieck–Teichmüller Group
Authors: Wolff Vincent
Published: September 2023

We study the deformation complex of the natural morphism from the degree $d$ shifted Lie operad to its polydifferential version, and prove that it is quasi-isomorphic to the Kontsevich graph complex $\textbf {GC}_{d}$. In particular, we show that in the case $d=2$ the Grothendieck–Teichmüller group $\textbf {GRT}_{1}$ is a symmetry group (up to homotopy) of the aforementioned morphism. We also prove that in the case $d=1$, corresponding to the usual Lie algebras, the natural morphism admits a unique homotopy non-trivial deformation, which is described explicitly with the help of the universal enveloping construction. Finally, we prove the rigidity of the strongly homotopy version of the universal enveloping functor in the Lie theory.
Rational function neural networks for learning rock physics models from field data
Authors: Sun Weitao , Yang Zhifang
Published: September 2023

Seismic wave velocity estimation is critical for understanding Earth's internal structure. Traditional rock physics models require careful physical assumptions and mathematical derivations, often facing challenges when applied to complex field data. Empirical formulas, while simple, lack a solid physical foundation. To address these limitations, we propose a data-driven approach using rational function neural networks (RafNN) for rock physics modelling. By analysing logging data, RafNN establishes a rational equation capturing the interdependencies among rock modulus, matrix stiffness, porosity, and fluid. The results show that RafNN accurately extracts the Gassmann's equation when the training data adheres to its constraints. Moreover, RafNN can derive general models from logging data that deviate from the Gassmann's equation. These data-driven models exhibit lower prediction errors while maintaining consistency with Gassmann's model. RafNN's adaptability to field data variability is a key advantage, facilitating better comprehension of the underlying mathematical and physical principles. Additionally, we explore the relationship between modulus, porosity, and compressibility, shedding light on the physical interpretation of RafNN models. Notably, RafNN derives analytical models directly from field data, reducing reliance on mathematical derivations and physical assumptions. Although further research is needed to understand the convergence theory of RafNN, this study presents a promising approach for data-driven rock physics modelling. It contributes to the exploration of Earth's heterogeneous structure and advances the field of seismic wave velocity estimation.
Pulmonary valve papillary fibroelastoma: to PE or not to PE
Authors: Kirk Frazer , Yong Matthew S , Williams Peter , Stroebel Andrie
Published: September 2023

Pulmonary valve (PV) fibroelastomas are a rare pathology, with limited anecdotal literature surrounding them. Consequently, the natural history is unclear; however, two features have remained salient; they are asymptomatic and found incidentally. Here, we describe a 52-year-old female, presenting with symptoms suggestive pulmonary embolism (PE). Pulmonary angiography revealed a filling deficit in the pulmonary trunk (PT), adjacent to the PV. Subsequent investigation found a large PV fibroelastoma. The presence of symptoms is likely secondary to right ventricular outflow tract obstruction from the lesions large size. We describe our investigation and management of the lesion. The reporting of this case challenges the existing knowledge of PV fibroelastomas.
A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas
Authors: Saijo Atsuro , Ogino Hirokazu , Butowski Nicholas A , Tedesco Meghan R , Gibson David , Watchmaker Payal B , Okada Kaori , Wang Albert S , Shai Anny , Salazar Andres M , Molinaro Annette M , Rabbitt Jane E , Shahin Maryam , Perry Arie , Clarke Jennifer L , Taylor Jennie W , Daras Mariza , Oberheim Bush Nancy Ann , Hervey-Jumper Shawn L , Phillips Joanna J , Chang Susan M , Hilf Norbert , Mayer-Mokler Andrea , Keler Tibor , Berger Mitchel S , Okada Hideho
Published: September 2023

Background

Central nervous system (CNS) WHO grade 2 low-grade glioma (LGG) patients are at high risk for recurrence and with unfavorable long-term prognosis due to the treatment resistance and malignant transformation to high-grade glioma. Considering the relatively intact systemic immunity and slow-growing nature, immunotherapy may offer an effective treatment option for LGG patients.

Methods

We conducted a prospective, randomized pilot study to evaluate the safety and immunological response of the multipeptide IMA950 vaccine with agonistic anti-CD27 antibody, varlilumab, in CNS WHO grade 2 LGG patients. Patients were randomized to receive combination therapy with IMA950 + poly-ICLC and varlilumab (Arm 1) or IMA950 + poly-ICLC (Arm 2) before surgery, followed by adjuvant vaccines.

Results

A total of 14 eligible patients were enrolled in the study. Four patients received pre-surgery vaccines but were excluded from postsurgery vaccines due to the high-grade diagnosis of the resected tumor. No regimen-limiting toxicity was observed. All patients demonstrated a significant increase of anti-IMA950 CD8+ T-cell response postvaccine in the peripheral blood, but no IMA950-reactive CD8+ T cells were detected in the resected tumor. Mass cytometry analyses revealed that adding varlilumab promoted T helper type 1 effector memory CD4+ and effector memory CD8+ T-cell differentiation in the PBMC but not in the tumor microenvironment.

Conclusion

The combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients.
Invasion dynamics of the European Collared-Dove in North America are explained by combined effects of habitat and climate
Authors: Shao Yiran , Ethier Danielle M , Bonner Simon J
Published: September 2023

Global biodiversity is increasingly threatened by the spread of invasive species. Understanding the mechanisms influencing the initial colonization and persistence of invaders is therefore needed if conservation actions are to prevent new invasions or strive to slow their spread. The Eurasian Collared-Dove (Streptopelia decaocto, EUCO) is one of the most successful avian invasive species in North America; however, to our knowledge, no study has simultaneously examined the role that climate-matching, human activity, directional propagation, and local density have in this invasion process. Our research expands upon a cellular-automata-based hierarchical model developed to assess directional invasion dynamics to further quantify the impacts of climate, elevation, and land cover type on the spread of EUCO in North America. Our results suggest that EUCO’s dispersal patterns can largely be explained by the effects of habitat, climate, and environmental conditions at different stages of the invasion process rather than some innate preferred north-westerly spread. Specifically, EUCO initially colonized warm and wet grassland habitats and tended to persist in urban areas. We also found that while EUCO were more likely to spread to the northeast of existing habitats, directional preference did not drive persistence and recolonization events. These findings highlight the importance of incorporating both neighborhood effects and environmental factors in the modelling of range-expanding species, adding to the toolset available to researchers to model invasive species spread. Further, our research demonstrates that historical records of invasive species occurrences can provide the data resources needed to disentangle the characteristics driving species invasion and enable predictions that are of critical importance to resource managers.
Conscious expectancy rather than associative strength elicits brain activity during single-cue fear conditioning
Authors: Grégoire Laurent , Robinson Tyler D , Choi Jong Moon , Greening Steven G
Published: September 2023

The neurocognitive processes underlying Pavlovian conditioning in humans are still largely debated. The conventional view is that conditioned responses (CRs) emerge automatically as a function of the contingencies between a conditioned stimulus (CS) and an unconditioned stimulus (US). As such, the associative strength model asserts that the frequency or amplitude of CRs reflects the strength of the CS–US associations. Alternatively, the expectation model asserts that the presentation of the CS triggers conscious expectancy of the US, which is responsible for the production of CRs. The present study tested the hypothesis that there are dissociable brain networks related to the expectancy and associative strength theories using a single-cue fear conditioning paradigm with a pseudo-random intermittent reinforcement schedule during functional magnetic resonance imaging. Participants’ (n = 21) trial-by-trial expectations of receiving shock displayed a significant linear effect consistent with the expectation model. We also found a positive linear relationship between the expectancy model and activity in frontoparietal brain areas including the dorsolateral prefrontal cortex (PFC) and dorsomedial PFC. While an exploratory analysis found a linear relationship consistent with the associated strength model in the insula and early visual cortex, our primary results are consistent with the view that conscious expectancy contributes to CRs.
Executive Control and Associated Brain Activity in Children With Familial High-Risk of Schizophrenia or Bipolar Disorder: A Danish Register-based Study
Authors: Johnsen Line Korsgaard , Larsen Kit Melissa , Fuglsang Søren Asp , Ver Loren van Themaat Anna Hester , Baaré William Frans Christiaan , Madsen Kathrine Skak , Madsen Kristoffer Hougaard , Hemager Nicoline , Andreassen Anna Krogh , Veddum Lotte , Greve Aja Neergaard , Nejad Ayna Baladi , Burton Birgitte Klee , Gregersen Maja , Eichele Heike , Lund Torben E , Bliksted Vibeke , Thorup Anne Amalie Elgaard , Mors Ole , Plessen Kerstin Jessica , Nordentoft Merete , Siebner Hartwig Roman
Published: September 2023

Background and Hypotheses

Impaired executive control is a potential prognostic and endophenotypic marker of schizophrenia (SZ) and bipolar disorder (BP). Assessing children with familial high-risk (FHR) of SZ or BP enables characterization of early risk markers and we hypothesize that they express impaired executive control as well as aberrant brain activation compared to population-based control (PBC) children.

Study Design

Using a flanker task, we examined executive control together with functional magnetic resonance imaging (fMRI) in 11- to 12-year-old children with FHR of SZ (FHR-SZ) or FHR of BP (FHR-BP) and PBC children as part of a register-based, prospective cohort-study; The Danish High Risk and Resilience study—VIA 11.

Study Results

We included 85 (44% female) FHR-SZ, 63 (52% female) FHR-BP and 98 (50% female) PBC in the analyses. Executive control effects, caused by the spatial visuomotor conflict, showed no differences between groups. Bayesian ANOVA of reaction time (RT) variability, quantified by the coefficient of variation (CVRT), revealed a group effect with similarly higher CVRT in FHR-BP and FHR-SZ compared to PBC (BF10 = 6.82). The fMRI analyses revealed no evidence for between-group differences in task-related brain activation. Post hoc analyses excluding children with psychiatric illness yielded same results.

Conclusion

FHR-SZ and FHR-BP at age 11–12 show intact ability to resolve a spatial visuomotor conflict and neural efficacy. The increased variability in RT may reflect difficulties in maintaining sustained attention. Since variability in RT was independent of existing psychiatric illness, it may reflect a potential endophenotypic marker of risk.
Nighttime smartphone use, sleep quality, and mental health: investigating a complex relationship
Authors: Andersen Thea Otte , Sejling Christoffer , Jensen Andreas Kryger , Drews Henning Johannes , Ritz Beate , Varga Tibor V , Rod Naja Hulvej
Published: September 2023

Study Objectives

This study investigated the complex relationship between nighttime smartphone use, sleep, and mental health among adult populations in Denmark.

Methods

Data from three interconnected samples (aged 16–89 years) from the SmartSleep Study included 5798 individuals with survey and register data; 4239 individuals also provided high-resolution smartphone tracking data. Logistic regression models and causal discovery algorithms, which suggest possible causal pathways consistent with the underlying data structure, were used to infer the relationship between self-reported and tracked nighttime smartphone use, self-reported sleep quality, mental health indicators, and register-based psychotropic medication use.

Results

Frequent self-reported nighttime smartphone use was associated with high perceived stress (OR: 2.24, 95% CI = 1.42 to 3.55) and severe depressive symptoms (OR: 2.96, 95% CI = 2.04 to 4.28). We found no clear associations between tracked nighttime smartphone use and mental health outcomes, except for the cluster that used their smartphones repeatedly during the sleep period, which was associated with severe depressive symptoms (OR = 1.69, 95% CI = 1.24 to 2.31). Poor sleep quality (vs. good sleep quality) was associated with high perceived stress (OR = 5.07, 95% CI = 3.72 to 6.90), severe depressive symptoms (OR = 9.67, 95% CI = 7.09 to 13.19), and psychotropic medication use (OR = 2.13, 95% CI = 1.36 to 3.35). The causal discovery models suggest that nighttime smartphone use affects mental health through both problematic smartphone use and poor sleep quality.

Conclusion

The complex relationship between nighttime smartphone use, sleep, and poor mental health may create a vicious circle over time, and nighttime smartphone use may constitute a potential leverage point for public health interventions aimed at improving sleep and mental health.
Detection, Characterization, and Distribution of the First Case of Pepino Mosaic Virus in Aotearoa New Zealand
Authors: Veerakone Stella , W. Waite David , Delmiglio Catia , Kanchiraopally Deepika , Kelly Michelle , Khan Subuhi , Liefting Lia , T. Lilly Sonia , Perez-Egusquiza Zoila , Tang Joe , Yan Juncong , Tomiczek Laura , Thompson Jeremy R.
Published: September 2023

Tomato (Solanum lycopersicum L., family Solanaceae) represents one of the most economically valuable horticultural crops worldwide. Tomato production is affected by numerous emerging plant viruses. We identified, for the first time in New Zealand (NZ), Pepino mosaic virus (PepMV) in greenhouse grown tomato crops using a combination of methods from electron microscopy and herbaceous indexing to RT-qPCR and high-throughput sequencing. Phylogenetic and genomic analysis of a near-complete PepMV genome determined that the detected strain belonged to the mild form of the CH2 lineage of the virus. Subsequently, a delimiting survey of PepMV was conducted, and PepMV was detected at four additional locations. PCR-derived sequences obtained from samples collected from different greenhouses and from herbaceous indicator plants were identical to the original sequence. Since PepMV has never been reported in NZ before, seed pathways are speculated to be the most likely source of entry into the country.
Revision Strategies for Cervical Disc Arthroplasty
Authors: Roth Steven G. , Robles Ortiz Marcos Joaquin , Vulapalli Meghana , Riew K. Daniel
Published: September 2023

Study Design:

Narrative review.

Objective:

To review indications and strategies for revision of cervical disc arthroplasty (CDA).

Summary of Background Data:

No data were generated as part of this review.

Methods:

A narrative review of the literature was performed.

Results:

No results were generated as part of this review.

Conclusions:

CDA is a proven, motion-sparing surgical option for the treatment of myelopathy or radiculopathy secondary to cervical degenerative disc disease. As is the case with any operation, a small percentage of CDA will require revision, which can be a technically demanding endeavor. Here we review available revision strategies and associated indications, a thorough understanding of which will aid the surgeon in finely tailoring their approach to varying presentations.
Health and Social Determinants Associated With Delay of Care Among Community-Dwelling Rural Older Adults
Authors: Decker Autumn , Weaver Raven H.
Published: September 2023

Background:

Delaying health care has the capacity to increase morbidity and premature mortality among individuals with chronic and acute health conditions, particularly for those living in rural areas.

Objective:

The objective of this study was to identify social determinants of health that are associated with delay of care (DOC) among older adults residing in rural areas across the inland northwest.

Method:

We conducted descriptive, bivariate, and regression analyses using data from a needs assessment designed to identify health needs and service delivery gaps among an economically diverse 8-county region.

Result:

Most respondents (aged 60+ years) were white, female, with health insurance coverage (n = 1226, mean = 71). Overall, 35% experienced DOC. We used logistic regression to determine the influence of age, sex, health conditions, distance from medical facility, income, and perceived quality of neighborhood on DOC. Individuals with younger age (P= .017), more chronic conditions (P< .001), lower income (P< .001), and lower perceived quality of neighborhood (P= .008) were more likely to experience DOC.

Conclusion:

These findings highlight risk factors associated with DOC, which can inform prevention efforts championed by community-based organizations, health care providers, and policy makers. Future research is needed to investigate compounding long-term effects of DOC, especially among individuals living in rural areas.
Prediction of postembolization syndrome after transarterial chemoembolization of hepatocellular carcinoma and its impact on prognosis
Authors: Roehlen Natascha , Stoehr Fabian , Müller Lukas , Luxenburger Hendrik , Gairing Simon J. , Reincke Marlene , Schultheiss Michael , Berisha Floriona , Weinmann Arndt , Foerster Friedrich , Marquardt Jens U. , Thimme Robert , Galle Peter R. , Bettinger Dominik , Kloeckner Roman
Published: September 2023

Background:

Postembolization syndrome (PES) represents the most frequent complication after transarterial chemoembolization (TACE) in patients with HCC. Given the vague definition as a symptom complex comprising abdominal pain, fever, and nausea, PES is diagnosed in heterogeneous patient cohorts with symptoms ranging from mild pain to severe deterioration of their general condition. This study aimed to evaluate predictive factors and the prognostic impact of PES with regard to different severity grades.

Methods:

A total of 954 patients treated with TACE for HCC at the University Medical Centres Mainz and Freiburg were included in this study. PES disease severity was graded as mild, moderate, or severe according to a predefined combination of symptoms. Logistic regression models were used to identify independent predictors of PES. The prognostic impact of PES was evaluated by competing risk analyses considering liver transplantation as a competing risk.

Results:

PES occurred in 616 patients (64.5%), but only 56 patients (5.9%) had severe PES, defined as moderate to severe abdominal pain requiring opioids in combination with fever and nausea. The largest tumor diameter was the strongest independent predictor of PES (OR = 1.21, 95% CI = 1.13–1.28), and severe PES (OR = 1.23, 95% CI = 1.14–1.33, p < 0.0001). Presence of liver cirrhosis was protective against PES (OR = 0.48, 95% CI = 0.27–0.84, p = 0.01). Furthermore, PES was independently associated with an impaired disease control rate (OR = 0.33, 95% CI = 0.16–0.69, p = 0.003) and severe PES with poor overall survival (subdistribution HR = 1.53, 95% CI = 0.99–2.36, p = 0.04).

Conclusions:

Tumor size and absence of liver cirrhosis are predictors of severe PES and associated with impaired prognosis in HCC patients after TACE.
Graft-versus-host disease following liver transplantation: A systematic review of literature
Authors: Kneifel Felicia , Vogel Thomas , Bormann Eike , Becker Felix , Houben Philipp , Flammang Isabelle , Slepecka Patrycja , Eichelmann Ann-Kathrin , Brockmann Jens G. , Pascher Andreas
Published: September 2023

Background:

Graft-versus-host disease following liver transplantation is a serious and usually fatal complication. Data identifying the risk factors and specifying the diagnosis and treatment options of the disease are scarce and contentious. Moreover, recommendations for therapeutic approaches are similarly sparse.

Methods:

A systematic review of the literature from 1988 to 2020 on graft-versus-host disease following liver transplantation was performed using the PubMed and MEDLINE databases. Medical subject headings, such as graft-versus-host disease and GvHD were used in combination with solid organ transplant, transplantation, or liver transplant. Following duplicate removal, 9298 articles were screened for suitability. A total of 238 full-text articles were analyzed for eligibility, resulting in 130 eligible articles for meta-analysis. Two hundred twenty-five patients developing graft-versus-host disease following liver transplantation reported herein were mainly published in case reports and case series.

Results:

Graft-versus-host disease occurred with an incidence of 1.2%. 85% developed following deceased donor liver transplant and 15% following living-related donor liver transplantation. The median follow-up period following liver transplantation was 84 days (interquartile range, 45–180). The median time from liver transplantation to graft-versus-host disease onset was 30 days (interquartile range, 21–42). The main clinical features included skin rash (59%), fever (43%), diarrhea (36%), and pancytopenia (30%). The overall mortality rate was 71%. Neither univariate (HR = 0.999; 95% CI, 0.493–2.023;p= 1.0) nor multivariate Cox regression analysis revealed a significant correlation between adaptation of immunosuppression and survival probability (HR = 1.475; 95% CI, 0.659–3.303;p= 0.3).

Conclusions:

This systematic review suggests that an increase in immunosuppressive regimen does not yield any survival benefit in patients suffering from graft-versus-host disease following liver transplantation.
Ashwagandha-induced liver injury—A case series from India and literature review
Authors: Philips Cyriac A. , Valsan Arun , Theruvath Arif H. , Ravindran Resmi , Oommen Tharun T. , Rajesh Sasidharan , Bishnu Saptarshi , Augustine Philip ,   on behalf of The Liver Research Club India
Published: September 2023

Background:

Ashwagandha herb is commonly used in Ayurveda and a “fad” dietary supplement for a host of indications based on low levels of evidence. Recently, ashwagandha was implicated in multiple reports of herb-induced liver injury (HILI), mainly from the United States. We present the first, and currently largest, series of ashwagandha-HILI from multiple centers in India.

Methods:

We retrospectively analyzed the respective institutional electronic medical records for ashwagandha-HILI. Patients consuming ashwagandha as part of multiherbal formulations or along with other known hepatotoxic supplements or medicines were excluded. All patients underwent a detailed diagnostic workup to exclude competing causes reasonably. Where possible, the implicated herbal formulation was retrieved and subjected to chemical analysis.

Results:

Out of 23 patients with liver injury from ashwagandha (January 2019 to December 2022), we report 8 patients with single-ingredient formulation-related HILI. Study cohort was male predominant, and cholestatic hepatitis was the commonest presentation. Five patients had underlying chronic liver disease; 3 presented with acute-on-chronic liver failure, and all 3 died on follow-up. In others, the liver injury was prolonged, nonetheless self-limiting. Liver biopsy revealed cholestatic features predominantly with hepatocellular necrosis and lymphocyte/eosinophil predominant portal-based inflammation. One patient progressed to chronic HILI. Chemical analysis revealed only natural phytochemicals without adulteration or contamination.

Conclusions:

Ashwagandha-HILI presents with cholestatic hepatitis and can lead to the syndrome of acute-on-chronic liver failure with high mortality in those with pre-existing liver disease. Educating the public on avoiding the use of potentially toxic and unrecommended herbal supplements can help mitigate the avoidable liver disease burden in the community.
Envelope antibody HBeIgG and HBV DNA in HBeAg-seronegative young adults in Nigeria
Authors: Olaniyan Mathew Folaranmi , Muhibi Musa Abidemi , Olaniyan Tolulope Busayo , Kanikwu Phoebe Nwamaka
Published: September 2023

Study background:

Anti-HBe and hepatitis B virus (HBV) DNA are important markers in evaluating HBV infection. Anti-HBe indicates past or current infection that persists after hepatitis B e antigen (HBeAg) clearance. Detecting anti-HBe helps identify cleared or chronic infections. HBV DNA measures viral replication, indicating infection activity. Studying these markers in HBeAg-seronegative young adults provides insights into infection dynamics, immune responses, and transmission risk. It informs clinical management and public health interventions for preventing HBV transmission and reducing the burden of liver disease.

Aim and objectives:

This cross-sectional study aimed to determine the prevalence of HBeAg seronegativity and its association with HBV infection markers among young adults in Etsako, Edo State, Nigeria.

Materials and methods:

The study population consisted of HBeAg-seronegative individuals aged 18 to 30 years. A total of 400 participants (200 females and 200 males) were randomly selected from urban and rural communities using a multistage sampling technique. Anti-HBe and HBeAg were analyzed by ELISA, whereas HBV DNA was evaluated by polymerase chain reaction.

Results:

The prevalence of HBeAg seropositivity was 28%, whereas 72% of participants were seronegative. Among the HBeAg-seronegative participants, the frequencies of anti-HBe and HBV DNA were analyzed based on various categorical variables. The results showed no significant differences in the frequency of anti-HBe and HBV DNA based on occupation, training, or other categorical variables (
P
>0.05). However, there was a significantly higher proportion of males (60%) among the total number of anti-HBe-seropositive young adults compared to females (40%) (
P
<0.05). Additionally, a significantly higher proportion of single/unmarried individuals without children (63.3%) was observed among anti-HBe-seropositive young adults compared to those who were married (25%) and those who were single/unmarried with children (12.5%,
P
<0.05).

Conclusion:

The study findings contribute to the understanding of HBeAg seronegativity and its association with anti-HBe and HBV DNA in young adults in Etsako, Edo State, Nigeria. Further research and public health interventions are warranted to better comprehend the factors influencing HBeAg seronegativity and its association with anti-HBe and HBV DNA and its implications for HBV transmission and disease progression in this population.
Psychometric Analysis of the Health Self-Care Neglect Scale
Authors: Riegel Barbara , Barbaranelli Claudio , Quinn Ryan , Matus Austin , Stawnychy Michael A. , Hirschman Karen B.
Published: September 2023

Objectives

The Health Self-Care Neglect (HSCN) scale is a measure of self-care neglect developed for use in informal caregivers, where self-care is defined as behaviors undertaken to maintain health. There was no formal psychometric analysis of the scale, so we tested a 9-item, dichotomous-response version of the HSCN scale in a sample of 250 informal caregivers of adults with chronic heart failure.

Methods

As the indicators of self-care neglect were considered formative (influencing the latent variable directly) rather than reflective (influenced by the latent variable), we used a procedure for the specification of formative measurement models. First, maximally correlated composites of indicators were identified for the latent variable, and optimal scoring weights were developed. Then, the reflective factor was tested with confirmatory factor analysis, and longitudinal invariance of the factorial structure was tested by introducing model constraints. Reliability was assessed with composite reliability model-based estimates. Concurrent validity was assessed by correlating the HSCN scale total score with the maintenance scale score of the Self-Care Inventory.

Results

Strict invariance, the highest level possible, was achieved. Reliability was 0.81 at baseline. Concurrent validity was demonstrated (r= −0.475,P< .0001).

Conclusion

The results of this analysis indicate that the HSCN scale is reliable, stable, and valid as a measure of health self-care neglect when tested in a sample of caregivers. The HSCN scale measures the successful performance of self-care, whereas existing measures of self-care reflect intention. Understanding both intention and behavior is useful, so we recommend using the HSCN scale in addition to existing measures of self-care.
Impact of functional status on 30-day resource utilization and organ system complications following index bariatric surgery: a cohort study
Authors: Holley Z. Logan , Knio Ziyad O. , Pham Long-Quan , Shakoor Unique , Zuo Zhiyi
Published: September 2023

Background:

Bariatric surgical procedures carry an appreciable risk profile despite their elective nature. Identified risk factors for procedural complications are often limited to medical comorbidities. This study assesses the impact of functional status on resource utilization and organ system complications following bariatric surgery.

Materials and methods:

This retrospective cohort study analyzed patients undergoing elective, index bariatric surgery from American College of Surgeons National Surgical Quality Improvement Program participating hospitals from 2015 to 2019 (n=65627). The primary independent variable was functional status. The primary outcome was unplanned resource utilization. Secondary outcomes included composite organ system complications and mortality. The impact of functional status was first investigated with univariate analyses. Survival and multivariate analyses were then performed on select complications with clinically and statistically significant incidence in the dependent cohort.

Results:

On univariate analysis, dependent functional status was associated with unplanned resource utilization (12.1% [27/223] vs 4.1% [2661/65404]; relative risk [RR], 2.98 [95% CI, 2.09 to 4.25];P< 0.001) and hematologic/infectious complications (6.7% [15/223] vs 2.4% [1540/65404]; RR, 2.86 [95% CI, 1.75 to 4.67;P< 0.001). Survival analysis demonstrated a significantly shorter time to both events in patients with dependent functional status (P< 0.001). On multivariate analysis, dependent functional status was an independent predictor of unplanned resource utilization (adjusted odds ratio [AOR] 2.17 [95% CI, 1.27 to 3.50];P= 0.003; model c-statistic, 0.572) and hematologic/infectious complications (AOR, 2.20 [95% CI, 1.14 to 3.86];P= 0.011; model c-statistic, 0.579).

Conclusion:

Patients with dependent functional status are at an elevated risk of unplanned resource utilization and hematologic/infectious complications following index bariatric surgery. The increased risk cannot be explained by medical comorbidities alone.
Is dynamic change in mean platelet volume related with composite endpoint development after transcatheter aortic valve replacement?
Authors: Ince Orhan , Gulsen Kamil , Ozcan Sevgi , Donmez Esra , Ziyrek Murat , Sahin Irfan , Okuyan Ertugrul
Published: September 2023

Aortic valve stenosis (AS) is the most common valvular disease, and surgical or transcatheter aortic valve replacement (TAVR) are the treatment options. Diminish in platelet production or dysfunction may occur due to shear stress, advanced age, and other coexisting diseases in AS patients. Bleeding is one of the complications of TAVR and associated with increased mortality. MPV (mean platelet volume) indicates platelet's thrombogenic activity. Overproduction or consumption of platelets in various cardiac conditions may affect MPV values. We aimed to investigate the pre and postprocedure MPV percentage change (MPV-PC) and its association with post-TAVR short-term complications.

A total of 204 patients who underwent TAVR with a diagnosis of severe symptomatic AS were included. The mean age was 78.66 ± 6.45 years, and 49.5% of patients were women. Two groups generated according to composite end point (CEP) development: CEP(+) and CEP(-).110 patients(53.9%) formed CEP(+) group.

Although baseline MPV and platelet levels were similar between groups, MPV was increased (P < 0.001) and platelet was decreased (P < 0.001) significantly following the procedure when compared to baseline. MPV-PC was significantly higher in the VARC type 2–4 bleeding (P 
= 0.036) and major vascular, access-related, or cardiac structural complication groups (P 
= 0.048) when CEP subgroups were analyzed individually. Regression analysis revealed that diabetes mellitus [P 
= 0.044, β: 1.806 odds ratio (95% confidence interval): 1.016–3.21] and MPV-PC [P 
= 0.007,β: 1.044 odds ratio (95% confidence interval): 1.012–1.077] as independent predictors of CEP development at 1 month after TAVR.

The MPV increase following TAVR may be an indicator of adverse outcomes following TAVR procedure within 1-month.
Brief Report: Changing Characteristics Among In-Hospital HIV Deaths: An 11-Year Retrospective Review of a Regional Hospital in South Africa
Authors: Lombardo Alexandra R. , Materi Joshua , Caturegli Giorgio , Milovanovic Minja , Martinson Neil , Calver Alistair , Nonyane Bareng A.S. , Golub Jonathan , Hoffmann Christopher J. , Variava Ebrahim
Published: September 2023

Background:

Elevated HIV-associated mortality persists, despite a notable decline with the expansion of antiretroviral therapy (ART). In South Africa, the relative majority of deaths occur in health facilities, providing an opportunity to track decedent characteristics.

Setting:

We analyzed data from 14,870 adult patients who died between 2008 and 2018 at Klerksdorp/Tshepong Hospital Complex in South Africa.

Methods:

Recorded data included demographics, causes of death, HIV status, ART, and tuberculosis (TB) history. We present summary statistics and results from linear, log-binomial, and multinomial regressions to quantify changes over time.

Results:

Over the study period, the median age of decedents with HIV in the hospital increased from 39.3 to 43.4 years, and there was a switch to male predominance (46%–54%). Those who died at a younger age (<40 years) remained more likely to be HIV-positive than the older age group, despite the overall proportion of HIV-positivity decreasing over time. The proportion of decedents with HIV ever started on ART increased from 21% to 67%. The proportion of HIV patients dying from TB and AIDS-defining illnesses decreased from 31% to 22%.

Conclusions:

We noted a shift in deaths over time to more men and older individuals, whereas the burden of HIV was heaviest on the younger age groups. Advanced HIV disease remained an important cause of mortality. We also observed an increase in less-traditional opportunistic illnesses among those with HIV, including malignancy, cardiovascular disease, and kidney disease. The high proportion of patients on ART who died prematurely requires further research and interventions.
Time to Treatment Initiation and HIV Viral Suppression in People Diagnosed With HIV-1 During COVID-19 Pandemic in Ex-Aquitaine, France (ANRS CO3 AQUIVIH-NA Cohort-QuAliCOV Study)
Authors: Ben Farhat Jihane , Hessamfar Mojgan , Farbos Sophie , Desclaux Arnaud , Dumondin Gilles , Ferrand Hélène , Greib Carine , Castan Bernard , Rispal Patrick , Duffau Pierre , Leleux Olivier , Perrier Adélaïde , Wittkop Linda , Bonnet Fabrice , Barger Diana
Published: September 2023

Objectives:

The COVID-19 pandemic's impact on initiation and effectiveness of antiretroviral therapy (ART) in people diagnosed with HIV remains unclear. We evaluated critical delays in HIV care in people diagnosed before and during the pandemic in ex-Aquitaine, France.

Methods:

We considered adults diagnosed with HIV-1 in 2018–2021 and enrolled in the ANRS CO3 AQUIVIH-NA and followed them until October 10, 2022 for those diagnosed during the pandemic (April 01, 2020–December 31, 2021) and until March 31, 2020 for historical controls. We compared their characteristics at inclusion and the median time between diagnosis and ART initiation, ART initiation and viral suppression, and diagnosis and virologic, suppression (effective management).

Results:

Eighty-three individuals were diagnosed during the pandemic versus 188 during the prepandemic period. Median follow-up was 549 (interquartile range: 329–713) days. Populations were similar in sex, age, HIV acquisition mode, hospital type, and clinical characteristics at diagnosis; however, fewer were foreign-born during the pandemic (15.7% versus 33.5%, P = 0.003). The probability of ART initiation, therapeutic success, and effective management was higher in people living with HIV (PLWH) diagnosed during the pandemic in adjusted analyses (hazard ratio [HR]: 2.0; 95% CI: 1.5 to 2.7; HR: 1.7; 95% CI: 1.2 to 2.3; HR: 1.8; 95% CI: 1.3 to 2.6, respectively). Those diagnosed during the pandemic were 2.3 (95% CI: 1.2 to 4.1) times more likely to be virologically suppressed within six months of diagnosis compared with historical controls.

Conclusions:

Pandemic-related reorganizations may have resulted in newly diagnosed PLWH being prioritized; however, the lower proportion of foreign-born PLWH diagnosed during the pandemic period, likely because of reduced migration and potential delays in diagnosis, may contribute to these preliminary findings.
A machine learning model derived from analysis of time-course gene-expression datasets reveal temporally stable gene markers predictive of sepsis mortality
Authors: Huang Min , Atreya Mihir R. , Holder Andre , Kamaleswaran Rishikesan
Published: September 2023

Sepsis is associated with significant mortality and morbidity among critically ill patients admitted to intensive care units (ICU) and represents a major health challenge globally. Given the significant clinical and biological heterogeneity among patients and the dynamic nature of the host immune response, identifying those at high risk of poor outcomes remains a critical challenge. Here, we performed secondary analysis of publicly available time-series gene-expression datasets from peripheral blood of patients admitted to the ICU to elucidate temporally stable gene expression markers between sepsis survivors and non-survivors. Using a limited set of genes that were determined to be temporally stable, we derived a dynamical model using a Support Vector Machine (SVM) classifier to accurately predict the mortality of sepsis patients. Our model had robust performance in a test dataset, where patients’ transcriptome was sampled at alternate time points, with an area under the curve (AUC) of 0.89 (95% CI: 0.82-0.96) upon 5-fold cross-validation. We also identified 7 potential biomarkers of sepsis mortality (STAT5A, CX3CR1, LCP1, SNRPG, RPS27L, LSM5, SHCBP1 that require future validation. Pending prospective testing, our model may be used to identify sepsis patients with high risk of mortality accounting for the dynamic nature of the disease and with potential therapeutic implications.
CEBPD REGULATES OXIDATIVE STRESS AND INFLAMMATORY RESPONSES IN HYPERTENSIVE CARDIAC REMODELING
Authors: Zhao Jinghong , Hu Jilin , Zhang Rongyi , Deng Jianping
Published: September 2023

Hypertension seems to inevitably cause cardiac remodeling, increasing the mortality of patients. This study aimed to explore the molecular mechanism of CCAAT/enhancer-binding protein delta (CEBPD)–mediated oxidative stress and inflammation in hypertensive cardiac remodeling. The hypertensive murine model was established through angiotensin-II injection, and hypertensive mice underwent overexpressed CEBPD vector injection, cardiac function evaluation, and observation of histological changes. The cell model was established by angiotensin-II treatment and transfected with overexpressed CEBPD vector. Cell viability and surface area and oxidative stress (reactive oxygen species/superoxide dismutase/lactate dehydrogenase/malondialdehyde) were assessed, and inflammatory factors (TNF-α/IL-1β/IL-6/IL-10) were determined bothin vivoandin vitro. The levels of CEBPD, miR-96-5p, inositol 1,4,5-trisphosphate receptor 1 (IP3R), natriuretic peptide B, and natriuretic peptide A, collagen I, and collagen III in tissues and cells were determined. The binding relationships of CEBPD/miR-96-5p/IP3R 3′ untranslated region were validated. CEBPD was reduced in cardiac tissue of hypertensive mice, and CEBPD upregulation improved cardiac function and attenuated fibrosis and hypertrophy, along with reductions of reactive oxygen species/lactate dehydrogenase/malondialdehyde/TNF-α/IL-1β/IL-6 and increases in superoxide dismutase/IL-10. CEBPD enriched on the miR-96-5p promoter to promote miR-96-5p expression, whereas CEBPD and miR-96-5p negatively regulated IP3R. miR-96-5p silencing/IP3R overexpression reversed the alleviative role of CEBPD overexpression in hypertensive mice. In summary, CEBPD promoted miR-96-5p to negatively regulate IP3R expression to inhibit oxidative stress and inflammation, thereby alleviating hypertensive cardiac remodeling.