bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental stress responses and adaptive evolution in the alpine ground beetle Nebria vandykei
Authors: Schoville Sean D , Farrand Zachery , Kavanaugh David H , Veire Benton , Weng Yi-Ming
Published: August 2023

The oscillating glacial–interglacial climate has had well-characterized effects on alpine species, driving rapid distributional and demographic shifts that have led to lineage diversification. It is unclear whether adaptive evolution has occurred during these rapid demographic changes, because strong genetic drift can overcome the force of selection. Here, using the alpine ground beetle Nebria vandykei, we test for evidence of adaptive evolution. Initially, we explore the genetic pathways induced during environmental stress responses through RNA sequencing, showing that cold, heat and desiccation stress activate a largely non-overlapping set of molecular pathways. Using additional transcriptome sequencing, we estimate the evolutionary relationship of N. vandykei to related species in the subgenus Catonebria and several outgroups. Phylogenetic analyses suggest that a history of admixture or very rapid diversification underlies the evolution of N. vandykei. Finally, using tests for selection polarized by high- and low-elevation relatives, we demonstrate selection acting on stress response pathways and on pathways known to function in tolerance to cold and hypoxic environments. These results support the role of environmental adaptation in alpine species despite rapid demographic change, while demonstrating that admixture might play a key role in facilitating adaptive diversification of alpine species.
Critical Narratives Or Crime Stories? The Ethics And Politics Of Narrative Research In Criminology
Authors: Bunn Rebecca
Published: August 2023

Amid growing criminological interest in narrative, there is hope that the mainstreaming of ‘narrative criminology’ will yield a more critical disposition within the discipline. This article contends that critical practice does not simply entail attending to issues of harm, power and resistance or researcher reflexivity, but grappling with the complex ethics and politics of our research practices. Focusing on the field of ‘narrative criminology’, this article explores issues of voyeurism, empathy, listening and bearing witness and poses some questions to guide ethical narrative practice within criminology. It calls for criminologists to consider how we may use narrative more responsibly within our discipline.
Determination of 11 Kinds of Hair Dyes in Hair-Dyeing Products by Liquid Chromatography–Tandem Mass Spectrometry
Authors: Gu Yu-Xiang , Chen Li-Song , Nie Lei
Published: August 2023

Eleven kinds of hair dyes were determined in hair-dyeing products by liquid chromatography–tandem mass spectrometry (MS). The samples were extracted with ultrasound in methanol for 20 min. After centrifugation, the supernatant was diluted with 10% methanol/90% water (v/v). Then, the solution was analyzed by Shim-pack Scepter C18–120 column (100 mm × 2.1 mm, 1.9 μm) plus electrospray ionization–MS/MS. Matrix-matched standard solutions were used to analyze the samples. The limits of detection were from 0.15 to 10 mg/kg, the limits of quantification were from 0.5 to 40 mg/kg and the recovery was from 79.4 to 109.2%. The protocol was selective and accurate and was satisfyingly applied to analyze hair dyes in different kinds of commercial products. 1-Hydroxyethyl-4,5-diaminopyrazole sulfate, hydroxyethyl-p-phenylenediamine sulfate, 2-methyl-5-hydroxyethylaminophenol, 5-amino-6-chloro-o-cresol, 3-nitro-p-hydroxyethylaminophenol and 2-amino-6-chloro-4-nitrophenol were detected in 10 samples with the concentrations between limits of detection and quantification to 9.27 × 104 mg/kg.
Changes in Life-Space Mobility With Loss of Relatives and Friends Among Older Adults: Results From the UAB Study of Aging
Authors: Driggers Amelia , Kennedy Richard E , Williams Beverly Rosa , Brown Cynthia J , Buys David R
Published: August 2023

Background and Objectives

Increasing age brings a greater risk of death of friends and family (hereafter referred to as loss) potentially impacting individuals’ life-space mobility (LSM) trajectory.

Research Design and Methods

Using the UAB study of aging, we examined differences in LSM trajectories of 1,000 community-dwelling older Alabamians (65 + years) with and without loss over 8.5 years. We measured LSM using UAB’s Life-Space Assessment (LSA), a validated instrument assessing movement through zones ranging from their bedroom to out of town. We assessed loss every 6 months using a standard bereavement questionnaire capturing spousal, other relative, or friend loss. We used piecewise linear mixed-effects models to compare LSA trajectories.

Results

At baseline, those who later experienced loss, compared with those who did not were younger, more likely to be female, and overall in better health. Those without loss had a baseline mean LSA score of 49.5 and a decline of 0.08 points per year (p < .001). Those with loss had a baseline LSA score of 60 and declined by 1.0 point per year before loss (p < .001), accelerating to 1.8 points per year after loss (p < .001).

Discussion and Implications

Those with loss do not experience acute decline postloss but do have an acceleration of the preexisting decline. Although additional research may explain the impact of loss on LSM; this finding suggests that more interventions such as social, mental, or health care services, may be needed for those who experience loss. Specifically, bereaved individuals may benefit from it.
Validation of an analytical method for quantitation of metonitazene and isotonitazene in plasma, blood, urine, liver and brain and application to authentic postmortem casework in New York City
Authors: Pardi Justine , Ford Sue , Cooper Gail
Published: August 2023

Starting in 2019, an emerging class of novel opioids causing public health concern was benzimidazole opioids, also known as “nitazenes.” Two nitazenes, isotonitazene and metonitazene, were detected in postmortem samples received at the New York City Office of Chief Medical Examiner. A protein precipitation extraction procedure was developed and validated for metonitazene and isotonitazene using 50 μL of blood, serum, liver, brain and urine utilizing liquid chromatography–tandem mass spectrometry. The limit of detection for both analytes was 0.10 ng/mL in plasma, blood and brain and 1.0 ng/mL for urine and liver. The developed method was applied to authentic casework in which isotonitazene was detected in 10 cases between 2021 and 2022, with femoral blood concentrations ranging from 0.11 to 12 ng/mL. Metonitazene was detected in four cases in 2022, with concentrations ranging from 0.10 to 1.5 ng/mL in femoral blood. All but one case had the presence of fentanyl and/or fentanyl analogs, and the next most commonly encountered analyte in these cases was xylazine. The manner of death was accidental for all cases with a detected nitazene, and all but one case was attributed to mixed drug intoxications. None of the cases reported the identified nitazene compound as the sole intoxicant responsible for death. The opioid crisis continues to tear apart communities throughout the world, including New York City. Continued research and communication regarding these drugs helps to fight this crisis.
Narrative and Story-telling in Darwall & Anor v Dartmoor National Park Authority
Authors: Ogden-Jones Rhiannon
Published: August 2023

Darwall & Anor v Dartmoor National Park Authority [2023] EWHC 35 (Ch) is a case framed by a particular narrative about national parks. This narrative exists separately from the explicit terms of the National Parks and Access to the Countryside Act 1949. Whilst a case comment about narrative seems unconventional, it is fundamental to understanding this case. This is because narrative shapes the legal questions asked in the case and so understanding narrative is essential to understanding the case itself. This comment places Darwall in its legal historical context, linking it to two legal questions from the case: the question of jurisdiction and the discussion of public access as a means of dispropriation. This illustrates that the legal questions in Darwall are asked as much because of the narrative that frames them, as they are of their explicit grounding in the legislation.
Assessing Mid-rotation Loblolly Pine and Competing Vegetation Responses to Post-thin Fertilization and Herbicide Application in the Southeastern United States
Authors: Young John B , Bullock Bronson P , Montes Cristian R
Published: August 2023

Mid-rotation silvicultural treatments (MRT) are commonly applied to loblolly pine (Pinus taeda L.) plantations in the southeastern United States to improve pine productivity. Competing vegetation is often present in operational plantations and limits site resource availability. The benefits of MRT for pine productivity are well known, but competing vegetation growth has not been extensively studied. Pine and competing vegetation growth within two regions of the southeastern United States was monitored for 8 years following a one-time post-thin application of either fertilization (224 kg ha-1 of nitrogen plus 28 kg ha-1 phosphorus), chemical herbicide (0.8 oz glyphosate and 0.8 oz triclopyr L-1 of water) or their combination. Fertilization significantly increased pine volume growth in the Lower Coastal Plain (LCP, 2.67-4.01 m3ha-1yr-1) and the Upper Coastal Plain/ Piedmont (UCPIE, 0.20-3.72 m3ha-1yr-1). Chemical herbicide application in both the LCP (0.34-4.87 m3 ha-1yr-1) and UCPIE (0.89-1.97 m3 ha-1yr-1) also significantly increased pine volume. Chemical herbicide application, individually and combined, did not result in significant decreases in herbaceous vegetation, but reduced woody vegetation by up to -2.40 m3 ha-1yr-1 in the LCP and -5.67 m3 ha-1yr-1 in the UCPIE. Consequently, we suggest that competing vegetation response should be considered within site-specific management plans aimed at maximizing pine productivity.
The haloes and environments of nearby galaxies (HERON) – III. A 45-kpc spiral structure in the GLSB galaxy UGC 4599
Authors: Mosenkov Aleksandr V , Rich R Michael , Fusco Michael , Kennefick Julia , Thilker David , Marchuk Alexander , Brosch Noah , West Michael , Gregg Michael , Longstaff Francis , Koch-Hansen Andreas J , Abdeen Shameer , Roque William
Published: August 2023

We use a 0.7-m telescope in the framework of the Halos and Environments of Nearby Galaxies (HERON) survey to probe low surface brightness (LSB) structures in nearby galaxies. One of our targets, UGC 4599, is usually classified as an early-type galaxy surrounded by a blue ring making it a potential Hoag’s Object analogue. Prior photometric studies of UGC 4599 were focused on its bright core and the blue ring. However, the HERON survey allows us to study its faint extended regions. With an 8-h integration, we detect an extremely faint outer disc with an extrapolated central surface brightness of μ0, d(r) = 25.5 mag arcsec−2 down to 31 mag arcsec−2 and a scale length of 15 kpc. We identify two distinct spiral arms of pitch angle ∼6○ surrounding the ring. The spiral arms are detected out to ∼45 kpc in radius and the faint disc continues to ∼70 kpc. These features are also seen in the GALEX far- and near-ultraviolet bands, in a deep u-band image from the 4.3-m Lowell Discovery Telescope (which reveals inner spiral structure emerging from the core), and in H i. We compare this galaxy to ordinary spiral and elliptical galaxies, giant low surface brightness (GLSB) galaxies, and Hoag’s Object itself using several standard galaxy scaling relations. We conclude that the pseudo-bulge and disc properties of UGC 4599 significantly differ from those of Hoag’s Object and of normal galaxies, pointing toward a GLSB galaxy nature and filamentary accretion of gas to generate its outer disc.
Unravelling the period gap using LAMOST chromospheric activity indices
Authors: Chahal Deepak , Kamath Devika , de Grijs Richard , Ventura Paolo , Chen Xiaodian
Published: August 2023

In our recent catalogue of BY Draconis (BY Dra) variables based on Zwicky Transient Facility data, we found traces of a period gap in the period–colour diagram. We combined our BY Dra data base with catalogues from the Kepler and K2 surveys, revealing a prominent period gap. Here, we use this combined ZTF–Kepler–K2 data set to investigate the origin of the period gap observed for BY Dra stars using chromospheric activity indices. We use low- and medium-resolution spectra from the LAMOST Data Release 7 to derive magnetic activity indices for the Ca ii H and K and Hα emission lines. We find a strong dependence of chromospheric activity on both stellar mass and rotation period. For partially convective K–M-type stars, the activity decreases steeply up to an age of ∼700–1000 Myr, subsequently evolving to the type of low-level saturation associated with spin-down stallation. In contrast, F–G-type stars with thinner convective envelopes exhibit constant activity with increasing age. We suspect that the observed steep decrease for partially convective stars is driven by core–envelope coupling. This mechanism reduces differential rotation at the core–envelope transition, hence leading to decreased magnetic activity. Moreover, we derive activity indices for previously known star clusters and find similar trends as regards their activity levels as a function of age. In particular, very low-level activity is observed around the location of the period gap. Therefore, we conclude that the period gap, defined by the non-detection of variable sources, is driven by a minimum in chromospheric activity.
Effects of sleep fragmentation on white matter pathology in a rat model of cerebral small vessel disease
Authors: Fu Xiang , Wan Xiao-Jie , Liu Jun-Yi , Sun Qian , Shen Yun , Li Jie , Mao Cheng-Jie , Ma Quan-Hong , Wang Fen , Liu Chun-Feng
Published: August 2023

Study Objectives

Mounting evidence indicated the correlation between sleep and cerebral small vessel disease (CSVD). However, little is known about the exact causality between poor sleep and white matter injury, a typical signature of CSVD, as well as the underlying mechanisms.

Methods

Spontaneously hypertensive rats (SHR) and control Wistar Kyoto rats were subjected to sleep fragmentation (SF) for 16 weeks. The effects of chronic sleep disruption on the deep white matter and cognitive performance were observed.

Results

SHR were validated as a rat model for CSVD. Fragmented sleep induced strain-dependent white matter abnormalities, characterized by reduced myelin integrity, impaired oligodendrocytes precursor cells (OPC) maturation and pro-inflammatory microglial polarization. Partially reversible phenotypes of OPC and microglia were observed in parallel following sleep recovery.

Conclusions

Long-term SF-induced pathological effects on the deep white matter in a rat model of CSVD. The pro-inflammatory microglial activation and the block of OPC maturation may be involved in the mechanisms linking sleep to white matter injury.
Clinical observation of liposomal doxorubicin on liver and renal function in patients with breast cancer
Authors: Li Mingliang , Wang Ling , Du Jie
Published: August 2023

Background

Doxorubicin has become the first-line antitumor drug clinically, but severely limited by multiple side effects, especially cardiotoxicity. Liposomal doxorubicin therefore replaced traditional doxorubicin for low toxicity and high efficiency. Previous studies have suggested liver and kidney may be the main organs affected by liposomal doxorubicin. Due to insufficient clinical evidence, we set out to analyze the effect of liposomal doxorubicin on liver and renal function in breast cancer patients.

Materials and Methods

Our retrospective analysis included breast cancer patients aged 30–70 years old who were assigned to two groups based on liposomal doxorubicin intake. We evaluated changes in liver and renal function. Multivariate logistic regression model was used to assess the risk factors of liver function damage.

Results

Ultimately, 631 patients for liver function analysis cohort and 611 cases for renal function analysis cohort. Patients receiving liposomal doxorubicin had significantly higher liver function damage rate compared to control group (52.20% vs 9.82%, p < 0.001), but there was no difference in the incidence of renal damage events between the two groups. Multivariate analysis shows total doses divided by body surface area is a significant, independent risk factor for liver function damage (odds ratio 1.005 [1.002–1.018], p < 0.001).

Conclusion

Liposomal doxorubicin treatment is associated with higher liver function damage in breast cancer patients, but has no effect on renal function. Together with risk factor analysis, our study underlines the importance to pay attention for patient’s age before taking liposomal doxorubicin, alongside liver function after the first and long-term treatments.
Benefits of Early Utilization of Palliative Care Consultation in Trauma Patients
Authors: Duncan Anthony J. , Holkup Lucas M. , Sang Hilla I. , Sahr Sheryl M.
Published: August 2023

OBJECTIVES:

To determine the effects of palliative care consultation if performed within 72 hours of admission on length of stay (LOS), mortality, and invasive procedures.

DESIGN:

Retrospective observational study.

SETTING:

Single-center level 1 trauma center.

PATIENTS:

Trauma patients, admitted to ICU with palliative care consultation.

INTERVENTION:

None.

MEASUREMENTS AND MAIN RESULTS:

The ICU LOS was decreased in the early palliative care (EPC) group compared with the late palliative care (LPC) group, by 6 days versus 12 days, respectively. Similarly, the hospital LOS was also shorter in the EPC group by 8 days versus 17 days in the LPC group. In addition, the EPC group had lower rates of tracheostomy (4% vs 14%) and percutaneous gastrostomy tubes (4% vs 15%) compared with the LPC group. There was no difference in mortality or discharge disposition between patients in the EPC versus LPC groups. It is noteworthy that the patients who received EPC were slightly older, but there were no other significant differences in demographics.

CONCLUSIONS:

EPC is associated with fewer procedures and a shorter amount of time spent in the hospital, with no immediate effect on mortality. These outcomes are consistent with studies that show patients’ preferences toward the end of life, which typically involve less time in the hospital and fewer invasive procedures.
Invasive fungal infections in liver diseases
Authors: Barros Nicolas , Rosenblatt Russell E. , Phipps Meaghan M. , Fomin Vladislav , Mansour Michael K.
Published: August 2023

Patients with liver diseases, including decompensated cirrhosis, alcohol-associated hepatitis, and liver transplant recipients are at increased risk of acquiring invasive fungal infections (IFIs). These infections carry high morbidity and mortality. Multiple factors, including host immune dysfunction, barrier failures, malnutrition, and microbiome alterations, increase the risk of developing IFI. Candida remains the most common fungal pathogen causing IFI. However, other pathogens, including Aspergillus, Cryptococcus, Pneumocystis, and endemic mycoses, are being increasingly recognized. The diagnosis of IFIs can be ascertained by the direct observation or isolation of the pathogen (culture, histopathology, and cytopathology) or by detecting antigens, antibodies, or nucleic acid. Here, we provide an update on the epidemiology, pathogenesis, diagnosis, and management of IFI in patients with liver disease and liver transplantation.
ROTH SPOTS IN A RENDU–OSLER–WEBER SYNDROME
Authors: Ferreira de Moura Thomas , Servettaz Amélie , Henry Adrien , Arndt Carl , Denoyer Alexandre
Published: August 2023

Purpose:

The purpose of this study was to describe the molecular diagnosis and atypical ocular presentation of a patient who suffered for a Rendu–Osler–Weber syndrome associated with juvenile polyposis syndrome.

Methods:

This is a case report of a patient who underwent fundus examination, brain MRI, and arteriography. Genetic testing was performed by next-generation sequencing.

Results:

A 35-year-old woman presented with right hemiplegia with right homonymous lateral hemianopia and homolateral complete sensory deficit. She also had Roth spots in her left fundus. Genetic testing revealed a pathogenic variation in the heterozygous state in the SMAD-4 gene (c.1245_1248del).

Conclusion:

Hereditary hemorrhagic telangiectasia also known as Rendu–Osler–Weber syndrome is a rare autosomal dominant disease, which reveals mostly with epistaxis and cutaneous telangiectasias. Our clinical case reports Roth spots in the context of hereditary hemorrhagic telangiectasia associated with juvenile polyposis syndrome. SMAD-4 mutation may explain the presence of a carotid-ophthalmic aneurysm, which is not a lesion usually found in hereditary hemorrhagic telangiectasia.
Developing and Validating a New Model to Predict the Risk of Poor Neurological Status of Acute Ischemic Stroke After Intravenous Thrombolysis
Authors: Liu Lu , Wang Weiping
Published: August 2023

Objectives:

The objective of this study was to develop and validate a predictive model for the risk of poor neurological status in in-hospital patients with acute ischemic stroke (AIS) after intravenous thrombolysis.

Methods:

This 2-center retrospective study included patients with AIS treated at the Advanced Stroke Center of the Second Hospital of Hebei Medical University and Baoding No.1 Central Hospital between January 2018 and January 2020). The neurological function status at day 7 of AIS onset was used as the endpoint of the study, which was evaluated using the National Institute of Health Stroke Scale (NIHSS) score.

Results:

A total of 878 patients were included in the study and divided into training (n=652) and validation (n=226) sets. Seven variables were selected as predictors to establish the risk model: age, NIHSS before thrombolysis (NIHSS1), NIHSS 24 hours after thrombolysis (NIHSS3), high-density lipoprotein, antiplatelet, cerebral computed tomography after thrombolysis (CT2), and lower extremity venous color Doppler ultrasound. The risk prediction model achieved good discrimination (the areas under the Receiver Operating Characteristic curve in the training and validation sets were 0.9626 and 0.9413, respectively) and calibration (in the training set Emax=0.072, Eavg=0.01, P=0.528, and in the validation set Emax=0.123, Eavg=0.019, P=0.594, respectively). The decision curve analysis showed that the model could achieve a good net benefit.

Conclusions:

The prediction model obtained in this study showed good discrimination, calibration, and clinical efficacy. This new nomogram can provide a reference for predicting the risk of poor neurological status in patients with acute ischemic stroke after intravenous thrombolysis.
Invasive Squamous Cell Carcinoma of the Cervix: A Review of Morphological Appearances Encountered in Human Papillomavirus-associated and Papillomavirus-independent Tumors and Precursor Lesions
Authors: Stolnicu Simona , Allison Douglas , Patrichi Andrei , Flynn Jessica , Iasonos Alexia , Soslow Robert A.
Published: August 2023

Cervical cancer is the fourth most common cancer among women globally. Historically, human papillomavirus (HPV) infection was considered necessary for the development of both precursor and invasive epithelial tumors of the cervix; however, studies in the last decade have shown that a significant proportion of cervical carcinomas are HPV-independent (HPVI). The 2020 World Health Organization (WHO) Classification of Female Genital Tumors separates both squamous cell carcinomas (SCCs) and endocervical adenocarcinomas (ECAs) by HPV status into HPV-associated (HPVA) and HPVI tumors. The classification further indicates that, in contrast to endocervical adenocarcinomas, HPVI and HPVA SCCs cannot be distinguished by morphological criteria alone and suggests that HPV testing or correlates thereof are required for correct classification. Moreover, while HPVA SCC precursor lesions (ie, high-grade squamous intraepithelial lesion) are well known and characterized, precursors to HPVI SCCs have only been described recently in a small number of cases. We studied 670 cases of SCCs from the International Squamous Cell Carcinoma Project (ISCCP) to analyze the reproducibility of recognition of invasive SCC growth patterns, presence of lymphovascular space invasion, tumor grade, and associations with patient outcomes. Consistent with previous studies, we found histologic growth patterns and tumor types had limited prognostic implications. In addition, we describe the wide morphologic spectrum of HPVA and HPVI SCCs and their precursor lesions, including tumor growth patterns, particular and peculiar morphologic features that can lead to differential diagnoses, and the role of ancillary studies in the diagnosis of these tumors.
Leukocytoclastic Vasculitis in an Adolescent with New-Onset Crohn’s Disease
Authors: Majluta Yeb Aldo , Dedic Evelina , Olsen Braden , Brathwaite Carole , Gomara Roberto , Hernandez Erick
Published: August 2023

Extraintestinal manifestations frequently affect patients with inflammatory bowel disease. They can involve virtually any organ, with the musculoskeletal and integumentary systems being the most common. Leukocytoclastic vasculitis is a rare extraintestinal manifestation of inflammatory bowel disease, especially at disease onset. It has been reported to occur in association with Crohn’s disease and trimethoprim/sulfamethoxazole (TMP-SMX) exposure independently. We report a case of a 14-year-old female who developed leukocytoclastic vasculitis after exposure to TMP-SMX and was ultimately diagnosed with Crohn’s disease. The patient presented with purpura, oral ulcers, abdominal pain, and intermittent bloody stools. Colonoscopy showed colonic inflammation, and biopsies revealed severe chronic active colitis with crypt abscesses. A skin biopsy confirmed the diagnosis of leukocytoclastic vasculitis. Management consisted of high-dose steroids and infliximab, with resolutions of her symptoms. This case emphasizes that extraintestinal manifestations are multifactorial in nature, with the example of an existing genetic predisposition through Crohn’s disease and a triggering factor such as TMP-SMX.
Describing and Predicting Preprocedural Anxiety in Patients Scheduled for Advanced Gastrointestinal Endoscopy During the COVID-19 Pandemic
Authors: Profit Dawn Donahue
Published: August 2023

Advanced gastrointestinal endoscopy includes a group of specialized procedures and interventions that are being performed more frequently, with little attention given to a patient's preprocedural anxiety issues. Compounding this concern, in 2020 the COVID-19 pandemic resulted in the delay of many endoscopy cases. It is unknown how this affected the anxiety of patients preparing for advanced endoscopy procedures. Patients with higher anxiety require higher doses of anesthetic medications, and experience increased pain and decreased satisfaction. The purpose of this study was to describe the biological, psychological, and social attributes of patients and identify whether social support, COVID-19-related anxiety, delay of procedure, patient's physical status, and procedural indication category were predictors of state anxiety levels in patients undergoing advanced gastrointestinal endoscopy during the COVID-19 pandemic. The research study was a cross-sectional descriptive design with 90 patients. Patients were classified into low state and high state anxiety groups. Fifty-eight percent of patients had high state anxiety scores. Using logistic regression, social support was identified as a predictor of preprocedural anxiety (odds ratio [OR] = 0.318 [95% confidence interval, CI = 0.170, 0.597, p < .001]) as less social support was associated with higher anxiety. It is imperative that strategies to maximize social support are reinforced.
Collaborative Team Training in Virtual Reality is Superior To Individual Learning For Performing Complex Open Surgery: A Randomised Controlled Trial
Authors: Edwards Thomas C , Soussi Daniella , Gupta Shubham , Khan Sikandar , Patel Arjun , Patil Amogh , Liddle Alexander D , Cobb Justin P , Logishetty Kartik
Published: August 2023

Objective:

To assess if multiplayer virtual reality (VR) training was superior to single player training for acquisition of both technical and non-technical skills in learning complex surgery.

Summary Background Data:

Superior team-work in the operating room (OR) is associated with improved technical performance and clinical outcomes. VR can successfully train OR staff individually, however VR team training has yet to be investigated.

Method:

Forty participants were randomised to individual or team VR training. Individually-trained participants practiced alongside virtual avatar counterparts, whilst teams trained live in pairs. Both groups underwent five VR training sessions over 6-weeks. Subsequently, they underwent a real-life assessment in which they performed Anterior Approach Total Hip Arthroplasty (AA-THA) surgery on a high-fidelity model with real equipment in a simulated OR. Teams performed together and individually-trained participants were randomly paired up. Videos were marked by two blinded assessors recording the NOTSS, NOTECHS II and SPLINTS scores. Secondary outcomes were procedure time and number of technical errors.

Results:

Teams outperformed individually-trained participants for non-technical skills in the real-world assessment (NOTSS 13.1±1.5 vs 10.6±1.6, P=0.002, NOTECHS-II score 51.7±5.5 vs 42.3±5.6, P=0.001 and SPLINTS 10±1.2 vs 7.9±1.6, P=0.004). They completed the assessment 28.1% faster (27.2 minutes±5.5 vs 41.8 ±8.9, P<0.001), and made fewer than half the number of technical errors (10.4±6.1 vs 22.6±5.4, P<0.001).

Conclusions:

Multiplayer training leads to faster surgery with fewer technical errors and the development of superior non-technical skills.
Living Donor Liver Transplantation for Adults With High Model for End-stage Liver Disease Score: The US Experience
Authors: Rosenthal Benjamin E. , Abt Peter L. , Schaubel Douglas E. , Reddy K. Rajender , Bittermann Therese
Published: August 2023

Background.

Outcomes after living-donor liver transplantation (LDLT) at high Model for End-stage Liver Disease (MELD) scores are not well characterized in the United States.

Methods.

This was a retrospective cohort study using Organ Procurement and Transplantation Network data in adults listed for their first liver transplant alone between 2002 and 2021. Cox proportional hazards models evaluated the association of MELD score (<20, 20–24, 25–29, and ≥30) and patient/graft survival after LDLT and the association of donor type (living versus deceased) on outcomes stratified by MELD.

Results.

There were 4495 LDLTs included with 5.9% at MELD 25–29 and 1.9% at MELD ≥30. LDLTs at MELD 25–29 and ≥30 LDLT have substantially increased since 2010 and 2015, respectively. Patient survival at MELD ≥30 was not different versus MELD <20: adjusted hazard ratio 1.67 (95% confidence interval, 0.96–2.88). However, graft survival was worse: adjusted hazard ratio (aHR) 1.69 (95% confidence interval, 1.07–2.68). Compared with deceased-donor liver transplant, LDLT led to superior patient survival at MELD <20 (aHR 0.92; P = 0.024) and 20–24 (aHR 0.70; P < 0.001), equivalent patient survival at MELD 25–29 (aHR 0.97; P = 0.843), but worse graft survival at MELD ≥30 (aHR 1.68, P = 0.009).

Conclusions.

Although patient survival remains acceptable, the benefits of LDLT may be lost at MELD ≥30.
Feasibility of Interleukin-6 Receptor Blockade in Cardiac Antibody-mediated Rejection
Authors: Pottebaum April A. , January Spenser E. , Liu Chang , Lavine Steven , Schilling Joel D. , Lavine Kory J.
Published: August 2023

Background.

Antibody-mediated rejection (AMR) remains a significant cause of heart transplant mortality with few effective therapies.

Methods.

This study aimed to describe initial experience of using interleukin-6 receptor blockade with tocilizumab in the treatment of acute cardiac AMR at Barnes-Jewish Hospital/Washington University Transplant Center from July 2017 to May 2021 (n = 7). Clinical, echocardiographic, and serum alloantibody data were analyzed before and after treatment.

Results.

All participants demonstrated marked improvement in functional status. Echocardiographic data following 4–6 mo of tocilizumab revealed significant improvements in biventricular systolic function for all participants. Consistent reductions in donor-specific HLA or angiotensin type I receptor antibodies were not observed, suggesting that tocilizumab may act downstream of antibody production. No patient experienced drug-related complications that necessitated discontinuation of therapy.

Conclusions.

These findings provide initial insights into the safety and efficacy of interleukin-6 receptor blockade in the treatment of cardiac AMR and support the design of larger prospective studies.
Management of neuropsychiatric symptoms in dementia
Authors: Devanand D.P.
Published: August 2023

Purpose of review

The purpose is to review the results and clinical implications of recent studies of neuropathology in relation to neuropsychiatric symptoms (NPS) in Alzheimer's disease and related dementias, and discuss new therapeutic approaches based on evidence from clinical trials.

Recent findings

In a large autopsy series from a national consortium, multiple neuropathologies of dementia subtypes were common and increased severity of specific NPS during life was associated with greater severity of neuropathology across diagnoses. Based on three clinical trials, brexpiprazole, which is an antipsychotic with dopamine and serotonin receptor partial agonism properties, was recently approved for the treatment of agitation in Alzheimer's dementia by the U.S. Food and Drug Administration (FDA). Its therapeutic profile indicates modest efficacy with high safety. Brexpiprazole has not been compared to other antipsychotics that are commonly prescribed to treat agitation in dementia, though none of them have been approved for this indication. Other drugs that showed positive results in Phase 2 trials are being tested in Phase 3 trials. These include cannabinoids and drug combinations that inhibit dextromethorphan metabolism peripherally, thereby increasing its bioavailability in the brain. Apathy is common in several types of dementia, and there is initial evidence that treatment with methylphenidate, a psychostimulant, may be efficacious with good tolerability.

Greater understanding of the associations between NPS and dementia subtypes can improve clinical management of these disorders. In addition to the approval of brexpiprazole to treat agitation in Alzheimer's dementia, there is optimism about other medications based on ongoing clinical trials. Along with short-term improvement, altering the adverse impact on NPS on long-term prognosis remains an important challenge for the field.
SIM-CNN: Self-Supervised Individualized Multimodal Learning for Stress Prediction on Nurses Using Biosignals
Authors: Eom Sunmin , Eom Sunwoo , Washington Peter
Published: August 2023

Precise stress recognition from biosignals is in-herently challenging due to the heterogeneous nature of stress, individual physiological differences, and scarcity of labeled data. To address these issues, we developed SIM-CNN, a self-supervised learning (SSL) method for personalized stress-recognition models using multimodal biosignals. SIM-CNN involves training a multimodal 1D convolutional neural network (CNN) that leverages SSL to utilize massive unlabeled data, optimizing individual parameters and hyperparameters for precision health. SIM-CNN is evaluated on a real-world multimodal dataset collected from nurses that consists of 1,250 hours of biosignals, 83 hours of which are explicitly labeled with stress levels. SIM-CNN is pre-trained on the unlabeled biosignal data with next-step time series forecasting and fine-tuned on the labeled data for stress classification. Compared to SVMs and baseline CNNs with an identical architecture but without self-supervised pre-training, SIM-CNN shows clear improvements in the average AUC and accuracy, but a further examination of the data also suggests some intrinsic limitations of patient-specific stress recognition using biosignals recorded in the wild.
Clinical Presentation of Psychotic Experiences in Patients with Common Mental Disorders Attending the UK Primary Care Improving Access to Psychological Therapies (IAPT) Programme
Authors: Wiedemann Anna , Stochl Jan , Russo Debra , Patel Ushma , Ashford Polly-Anna , Ali Naima , Jones Peter B , Perez Jesus
Published: August 2023

Background

Improving Access to Psychological Therapies (IAPT) services address anxiety and depression in primary care, but psychotic disorders are typically excluded. Our previous research found that 1 in 4 patients report distressing psychotic experiences (PE) alongside common mental disorders, yet little is known about their clinical presentation and their impact on recovery.

Methods

We used the Community Assessment of Psychic Experiences - Positive Scale (CAPE-P15) to determine the clinical presentation of PE within IAPT settings. We identified different classes (sub- groups) based on the reported frequencies of PE within this population using latent class analysis.

Results

A total of 2,042 IAPT patients completed the CAPE-P15. The mean age was 39.8 (± 15.3) years. We identified five distinct classes of symptom profiles, findings that PE were common, especially self-referential and persecutory ideas. Prevalence and intensity increased across classes, extending to bizarre experiences and perceptual abnormalities (hallucinations) in the fifth and least common class. Perceptual abnormalities were a strong indicator of symptom severity, and patients reporting such experiences were the least likely to achieve recovery by the end of treatment.

Limitations

We collected data from IAPT services that included self-report questionnaires, which may have affected the validity of the reported experiences. We did not collect information on negative PE.

Conclusions

Patients seeking treatment for anxiety and depression in primary care commonly experience a wide range of positive PE. Self-referential and persecutory ideation emerged as prevalent experiences; perceptual abnormalities were infrequent. Providing information about prevalence and tailoring therapy may help reduce patient distress.
Data-driven decision support for individualised cardiovascular resuscitation in sepsis: a scoping review and primer for clinicians
Authors: Catling Finneas JR , Nagendran Myura , Festor Paul , Bien Zuzanna , Harris Steve , Faisal A Aldo , Gordon Anthony C , Komorowski Matthieu
Published: August 2023

Background

We conducted a scoping review of machine learning systems that inform individualised cardiovascular resuscitation of adults in hospital with sepsis. Our study reviews the resuscitation tasks that the systems aim to assist with, system robustness and potential to improve patient care, and progress towards deployment in clinical practice. We assume no expertise in machine learning from the reader and introduce technical concepts where relevant.

Methods

This study followed thePreferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviewsguidance. MEDLINE, EMBASE, Scopus, ClinicalTrials.gov, arXiv, bioRxiv and medRxiv were systematically searched up to September 2021. We present a narrative synthesis of the included studies, which also aims to equip clinicians with an understanding of the foundational machine learning concepts necessary to interpret them.

Results

73 studies were included with 80% published after 2018. Supervised learning systems were often used to predict septic shock onset. Reinforcement learning systems were increasingly popular in the last five years, and were used to guide specific dosing of fluids and vasopressors. A minority of studies proposed systems containing biological models augmented with machine learning. Sepsis and septic shock were heterogeneously defined and 63% of studies derived their systems using a single dataset. Most studies performed only retrospective internal validation, with no further steps taken towards translating their proposed systems into clinical practice.

Conclusions

Machine learning systems can theoretically match, or even exceed, human performance when predicting patient outcomes and choosing the most suitable cardiovascular treatment strategy in sepsis. However, with some notable exceptions, the vast majority of systems to date exist only as proof of concept, with significant barriers to translation.
Harnessing extracellular vesicles for efficient siRNA deliveryin vitroandin vivo
Authors: Qiu Tao , Zhai Yanhua , Yi Yuan , Wang Xiaoyu , Hu Rui , Niu Shuiqin , Wang Chengcheng , Cui Chuang , He Xinjun , Xu Ke
Published: August 2023

To fulfill the potential of small interference RNA (siRNA) therapeutics, diverse and efficient delivery platforms for siRNA are urgently needed. Extracellular vesicles (EVs) are endogenous, cell secreted nano-vehicles which have been explored for functional siRNA delivery, yet impurities in EVs preparation and lack of efficient siRNA loading method have been limiting its further development into clinical applications. In this work, we have achieved high quality EVs production and an siRNA loading system via EVs. The prepared EV-siRNA system was able to deliver siRNA cargo to model cell lines to silence the expression of targeted genes with high potency. Furthermore, EV-siRNA administration in a tumor xenograft model significantly inhibited tumor growth. Therefore, this study establishes an innovative and efficient EV-siRNA platform for siRNA deliveryin vitroandin vivo.
Prevalence of Comorbidities among United States Adults with asthma and Their Association with Asthma Severity
Authors: Ogbu Chukwuemeka E. , Sarker Pallab , Oparanma Chisa O. , Ogbu Stella C. , Stouras Ioannis , Eze Ebube , Ndugba Chinaenye , Ujah Otobo I. , Kirby Russell S.
Published: August 2023

Introduction

The burden of comorbidities in asthma patients significantly affects management strategies and outcomes. This study aimed to analyze the prevalence and trends of comorbidities among adults with asthma and to investigate their association with persistent asthma.

Methods

The study employed data from the Asthma Call-Back Survey (ACBS) to ascertain the prevalence and trends of comorbidities in adults with asthma. Comorbidities were self-reported binary responses. Asthma severity was categorized as intermittent or persistent based on established methodologies to derive asthma severity in the ACBS. Intermittent asthma includes those with current asthma who are well-controlled without being on long-term control medication (LTCM). Persistent asthma includes those on LTCM, regardless of asthma control status, and those not on LTCM whose asthma is not well controlled or is very poorly controlled. Weighted logistic regression controlling for confounders was used to determine the association of comorbidities and asthma severity.

Results

Prevalence of comorbidities in adults with asthma were as follows: hypertension (38.4%), major depressive disorder (35.2%), diabetes (17.2%), MI (5.3%), Angina/CHD (6.0%), Stroke (5.0%), and Emphysema/Chronic bronchitis/COPD (19.0%). Prevalence of all comorbidities were higher among adults with persistent asthma compared to intermittent asthma. MI, Angina/CHD, obesity, depression, COPD/emphysema/chronic bronchitis, and hypertension were associated with increased odds of persistent asthma. No association was found between diabetes, stroke, and persistent asthma.

Conclusion

Comorbidities are associated with persistent asthma. These findings suggest a need for comprehensive healthcare strategy that address these intertwined health conditions along asthma.
Schisandrin B suppresses colon cancer growth by inducing cell cycle arrest and apoptosis via the CHOP signalling pathway
Authors: Co Vanessa Anna , El-Nezami Hani , Liu Yawen , Twum Bonsra , Dey Priyanka , Cox Paul A , Joseph Shalu , Agbodjan Roland , Sabzichi Mehdi , Draheim Roger , Wan Murphy Lam Yim
Published: August 2023

Colon cancer is among the most lethal and prevalent malignant tumours in the world, and the lack of effective therapies highlights the need for novel therapeutic approaches. Schisandrin B (Sch B), a lignan extracted from the fruitSchisandra chinensis, has been reported for its anti-cancer properties. However, no studies to date have been done to characterise the exact molecular mechanisms regarding the anti-tumorigenic effect of Sch B in colon cancer. A comprehensive analysis of the molecular mechanism for the anti-tumorigenic effect of Sch B on human colon cancer cells was performed using combination of Raman spectroscopy, RNA-seq, computational docking and molecular biological experiments. Thein vivoefficacy was evaluated by a mouse xenograft model. Sch B reduced cell proliferation and triggered apoptosis in human colon cancer cell lines. Raman spectroscopy, computational, RNA-seq, molecular and cellular studies revealed that Sch B activated unfolded protein responses by interacting with CHOP and upregulating CHOP, which thereby induced apoptosis. CHOP knockdown alleviated the Sch B-induced reduction in cell viability and apoptosis. Sch B reduced colon tumour growthin vivo. Our findings provide essential background for clinical trials examining the effects of Sch B in patients with colon cancer.
Equations describing semi-confluent cell growth (I) Analytical approximations
Authors: Hall Damien
Published: August 2023

A set of differential equations with analytical solutions are presented which can quantitatively account for the effects of variable degrees of contact inhibition on cell growth in two- and three-dimensional cultures. The developed equations can be used for comparative purposes when assessing the extent of contribution of higher order effects, such as culture geometry and nutrient depletion, on mean cell growth rate. These equations also offer experimentalists the opportunity to characterize their cell culture growth experiments using a single reductive parameter.
Cadherin Adhesion Complexes Direct Cell Aggregation in the Epithelial Transition of Wnt-Induced Nephron Progenitor Cells
Authors: Der Balint , Bugacov Helena , Briantseva Bohdana-Myroslava , McMahon Andrew P.
Published: August 2023

In the developing mammalian kidney, nephron formation is initiated by a subset of nephron progenitor cells (NPCs). Wnt input activates a β-catenin (Ctnnb1)-driven, transcriptional nephrogenic program. In conjunction, induced mesenchymal NPCs transition through a pre-tubular aggregate to an epithelial renal vesicle, the precursor for each nephron. How this critical mesenchymal-to-epithelial transition (MET) is regulated is unclear. In anin vitromouse NPC culture model, activation of the Wnt pathway results in the aggregation of induced NPCs into closely-packed, cell clusters. Genetic removal of β-catenin resulted in a failure of both Wnt pathway-directed transcriptional activation and the formation of aggregated cell clusters. Modulating extracellular Ca2+levels showed cell-cell contacts were Ca2+-dependent, suggesting a role for cadherin (Cdh)-directed cell adhesion. Molecular analysis identifiedCdh2,Cdh4andCdh11in uninduced NPCs and the up-regulation ofCdh3andCdh4accompanying the Wnt pathway-induced MET. Genetic removal of all four cadherins, and independent removal of α-catenin, which couples Cdh-β-catenin membrane complexes to the actin cytoskeleton, abolished cell aggregation in response to Wnt pathway activation. However, the β-catenin driven inductive transcriptional program was unaltered. Together with the accompanying paper (Bugacovet al., submitted), these data demonstrate that distinct cellular activities of β-catenin - transcriptional regulation and cell adhesion - combine in the mammalian kidney programs generating differentiated epithelial nephron precursors from mesenchymal nephron progenitors.

Summary statement

Our study highlights the role of Wnt–β-catenin pathway regulation of cadherin-mediated cell adhesion in the mesenchymal to epithelial transition of induced nephron progenitor cells.