bluuebunny/crossref_metadata_2025 huggingface dataset:
The decision aid is the easy part: workflow challenges of shared decision making in cancer care
Authors: Salwei Megan E , Ancker Jessica S , Weinger Matthew B
Published: July 2023

Delivering high-quality, patient-centered cancer care remains a challenge. Both the National Academy of Medicine and the American Society of Clinical Oncology recommend shared decision making to improve patient-centered care, but widespread adoption of shared decision making into clinical care has been limited. Shared decision making is a process in which a patient and the patient’s health-care professional weigh the risks and benefits of different options and come to a joint decision on the best course of action for that patient on the basis of their values, preferences, and goals for care. Patients who engage in shared decision making report higher quality of care, whereas patients who are less involved in these decisions have statistically significantly higher decisional regret and are less satisfied. Decision aids can improve shared decision making—for example, by eliciting patient values and preferences that can then be shared with clinicians and by providing patients with information that may influence their decisions. However, integrating decision aids into the workflows of routine care is challenging. In this commentary, we explore 3 workflow-related barriers to shared decision making: the who, when, and how of decision aid implementation in clinical practice. We introduce readers to human factors engineering and demonstrate its potential value to decision aid design through a case study of breast cancer surgical treatment decision making. By better employing the methods and principles of human factors engineering, we can improve decision aid integration, shared decision making, and ultimately patient-centered cancer outcomes.
Event-by-event approach to the oxygen-effect-incorporated stochastic microdosimetric kinetic model for hypofractionated multi-ion therapy
Authors: Inaniwa Taku , Kanematsu Nobuyuki
Published: July 2023

An oxygen-effect-incorporated stochastic microdosimetric kinetic (OSMK) model was previously developed to estimate the survival fraction of cells exposed to charged-particle beams with wide dose and linear energy transfer (LET) ranges under various oxygen conditions. In the model, hypoxia-induced radioresistance was formulated based on the dose-averaged radiation quality. This approximation may cause inaccuracy in the estimation of the biological effectiveness of the radiation with wide variation in energy deposited to a sensitive volume per event, such as spread-out Bragg peak (SOBP) beams. The purpose of this study was to apply an alternative approach so as to consider the energy depositions on an event-by-event basis. The production probability of radiation-induced lesions per energy was formulated with oxygen partial pressure to account for the hypoxia-induced radioresistance. The reduction in the oxygen enhancement ratio for high-LET radiations was modeled by reducing the sensitive-volume size and increasing the saturation energy in microdosimetry. The modified OSMK model was tested against the reported survival data of three cell lines exposed to six species of ions with wide dose and LET ranges under aerobic and hypoxic conditions. The model reasonably reproduced the reported cell survival data. To evaluate the event-by-event approach, survival distributions of Chinese hamster ovary cells exposed to SOBP beams were estimated using the original and modified OSMK models. The differences in the estimated survival distributions between the models were marginal even under extreme hypoxia. The event-by-event approach improved the theoretical validity of the OSMK model. However, the original OSMK model can still provide an accurate estimation of the biological effectiveness of therapeutic radiations.
A rare case of femoral hernia containing a strangulated appendix: a case report, operating techniques and literature review
Authors: Jebamani Jennifer , Ivanov Bogdan , Ejtehadi Farshid
Published: July 2023

Femoral hernias accounting for 2–4% of all hernias rarely involve appendicitis, known as De Garengeout hernia, with only a few reported cases. We present a case of a 66-year-old woman with acute right groin pain but no signs of intestinal obstruction. Physical examination revealed a tender, partially reducible mass in the right groin. Computed tomography scan confirmed a femoral hernia containing incarcerated bowel loops, leading to urgent surgical intervention. The McEvedys approach was used for appendicectomy and hernia repair. The patient recovered without complications. Strangulated femoral hernia with the appendix is a rare condition posing diagnostic challenges. Early recognition is crucial to prevent complications like perforation and abscess formation. Cross-sectional imaging aids in diagnosis. Surgical intervention, either open or laparoscopic, is the preferred treatment, based on surgeon expertise and patient-specific factors. Timely diagnosis and prompt surgery minimise complications.
Signal communication during microbial modulation of root system architecture
Authors: Li Yucong , Chen Yu , Fu Yansong , Shao Jiahui , Liu Yunpeng , Xuan Wei , Xu Guohua , Zhang Ruifu
Published: July 2023

Every living organism on Earth depends on its interactions with other organisms. In the rhizosphere, plants and microorganisms constantly exchange signals and influence each other’s behavior. Recent studies have shown that many beneficial rhizosphere microbes can produce specific signaling molecules that affect plant root architecture and therefore could have substantial effects on above-ground growth. This review examines these chemical signals and summarizes their mechanisms of action, with the aim of enhancing our understanding of plant–microbe interactions and providing references for the comprehensive development and utilization of these active components in agricultural production. In addition, we highlight future research directions and challenges, such as searching for microbial signals to induce primary root development.
On the Construction of Jewishness and the Inescapable Jewish Fate: The Cases of Werner and Gershom Scholem
Authors: Zadoff Mirjam , Zadoff Noam
Published: July 2023

The two youngest brothers of the Scholem family, Werner and Gerhard (later Gershom), became prominent personalities, each in his field. Werner was one of the leaders of the KPD, the German Communist Party, and Gershom became the founder of the field of Kabbalah research at the Hebrew University, Jerusalem. As a result of this prominence, both brothers were confronted throughout their lives with reactions to their physical appearance, which was perceived by the people they met as typically Jewish. These reactions came to reflect their exceptional position as political, philosophical and scholarly vanguards. Both Werner and Gershom were well aware of the reactions that their faces evoked, and each of them dealt with these ascriptions in different ways at different times: by either ignoring or employing them as they pursued their social and political goals, the brothers defined—and redefined—their relationship to Germany and developed a performative level of Jewishness. This article explores the questions: in what sense did their physical appearance in the eyes of others shape the self-perception of the two youngest Scholem brothers? And to what extent did this perception influence their complex relationship to Germany and Germans during the height of their public fame in Germany—in Werner's case the Weimar Republic and Nazi Germany, and for Gershom the post-war period? Although both of them were proponents of utopian ideas that offered a kind of salvation to the Jewish condition in turn-of-the-century Europe, this article argues that their looks and habitus determined their German-Jewish fate.
Kinematic lensing inference – I. Characterizing shape noise with simulated analyses
Authors: R. S. Pranjal , Krause Elisabeth , Huang Hung-Jin , Huff Eric , Xu Jiachuan , Eifler Tim , Everett Spencer
Published: July 2023

The unknown intrinsic shape of source galaxies is one of the largest uncertainties of weak gravitational lensing (WL). It results in the so-called shape noise at the level of $\sigma _\epsilon ^{\mathrm{WL}} \approx 0.26$, whereas the shear effect of interest is of the order of per cent. Kinematic lensing (KL) is a new technique that combines photometric shape measurements with resolved spectroscopic observations to infer the intrinsic galaxy shape and directly estimate the gravitational shear. This paper presents a KL inference pipeline that jointly forward-models galaxy imaging and slit spectroscopy to extract the shear signal. We build a set of realistic mock observations and show that the KL inference pipeline can robustly recover the input shear. To quantify the shear measurement uncertainty for KL, we average the shape noise over a population of randomly oriented disc galaxies and estimate it to be $\sigma _\epsilon ^{\mathrm{KL}}\approx 0.022\!-\!0.038$ depending on emission-line signal-to-noise ratio. This order of magnitude improvement over traditional WL makes a KL observational programme feasible with existing spectroscopic instruments. To this end, we characterize the dependence of KL shape noise on observational factors and discuss implications for the survey strategy of future KL observations. In particular, we find that prioritizing quality spectra of low-inclination galaxies is more advantageous than maximizing the overall number density.
Probing the IC/CMB interpretation for the X-ray knots of AGNs through VHE observations
Authors: Rahman Amal A , Sahayanathan S , Malik Zahoor , Subha P A
Published: July 2023

The detection of hard X-ray spectra (spectral index <2) from the kiloparsec-scale jet of active galactic nuclei cannot be accounted for by the synchrotron emission mechanism from the electron distribution responsible for the radio/optical emission. Alternate explanations are the inverse Compton scattering of cosmic microwave background photons (IC/CMB) or synchrotron emission from a second electron population. When the X-ray emission is interpreted as an IC/CMB process, the Compton spectrum often peaks at GeV energy and many sources are predicted to be Fermi candidate sources. The absence of significant gamma-ray flux from some of these galaxies by Fermi disfavours the IC/CMB interpretation of the high-energy emission. We extend this study to predict the very-high-energy (VHE) gamma-ray emission due to the IC/CMB model, which can be investigated by the Cherenkov Telescope Array Observatory (CTAO). The model parameters deciding the broad-band spectral energy distribution are estimated using an analytical approximation of the emissivity functions. The emission model is extrapolated to VHE and then compared with the CTAO sensitivity. For this particular study, we have selected 18 knots with harder X-ray spectra and for which the IC/CMB model for X-ray emission has been suggested.
Modelling dynamically driven global cloud formation microphysics in the HAT-P-1b atmosphere
Authors: Lee Elspeth K H
Published: July 2023

Insight into the formation and global distribution of cloud particles in exoplanet atmospheres continues to be a key problem to tackle going into the JWST era. Understanding microphysical cloud processes and atmospheric feedback mechanisms in three-dimensional (3D) has proven to be a challenging prospect for exoplaneteers. In an effort to address the large computational burden of coupling these models in 3D simulations, we develop an open source, lightweight, and efficient microphysical cloud model for exoplanet atmospheres. ‘Mini-cloud’ is a microphysical based cloud model for exoplanet condensate clouds that can be coupled to contemporary general circulation models (GCMs) and other time-dependent simulations. We couple mini-cloud to the Exo-FMS GCM and use a prime JWST target, the hot Jupiter HAT-P-1b, as a test case for the cloud formation module. After 1000+ of days of integration with mini-cloud, our results show a complex 3D cloud structure with cloud properties relating closely the dynamical and temperature properties of the atmosphere. Current transit and emission spectra data are best fit with a reduced cloud particle number density compared to the nominal simulation, with our simulated JWST NIRISS SOSS spectra showing promising prospects for characterizing the atmosphere in detail. Overall, our study is another small step in first principles 3D exoplanet cloud formation microphysical modelling. We suggest that additional physics not included in the present model, such as coagulation, are required to reduce the number density of particles to appropriately observed levels.
Examining NHD versus QHD in the GCM THOR with non-grey radiative transfer for the hot Jupiter regime
Authors: Noti Pascal A , Lee Elspeth K H , Deitrick Russell , Hammond Mark
Published: July 2023

Global circulation models (GCMs) play an important role in contemporary investigations of exoplanet atmospheres. Different GCMs evolve various sets of dynamical equations, which can result in obtaining different atmospheric properties between models. In this study, we investigate the effect of different dynamical equation sets on the atmospheres of hot Jupiter exoplanets. We compare GCM simulations using the quasi-primitive dynamical equations (QHD) and the deep Navier-Stokes equations (NHD) in the GCM THOR. We utilize a two-stream non-grey ‘picket-fence’ scheme to increase the realism of the radiative transfer calculations. We perform GCM simulations covering a wide parameter range grid of system parameters in the population of exoplanets. Our results show significant differences between simulations with the NHD and QHD equation sets at lower gravity, higher rotation rates, or at higher irradiation temperatures. The chosen parameter range shows the relevance of choosing dynamical equation sets dependent on system and planetary properties. Our results show the climate states of hot Jupiters seem to be very diverse, where exceptions to prograde superrotation can often occur. Overall, our study shows the evolution of different climate states that arise just due to different selections of Navier-Stokes equations and approximations. We show the divergent behaviour of approximations used in GCMs for Earth but applied for non Earth-like planets.
Inferring Human Immunodeficiency Virus 1 Proviral Integration Dates With Bayesian Inference
Authors: Jones Bradley R , Joy Jeffrey B
Published: July 2023

Human immunodeficiency virus 1 (HIV) proviruses archived in the persistent reservoir currently pose the greatest obstacle to HIV cure due to their evasion of combined antiretroviral therapy and ability to reseed HIV infection. Understanding the dynamics of the HIV persistent reservoir is imperative for discovering a durable HIV cure. Here, we explore Bayesian methods using the software BEAST2 to estimate HIV proviral integration dates. We started with within-host longitudinal HIV sequences collected prior to therapy, along with sequences collected from the persistent reservoir during suppressive therapy. We built a BEAST2 model to estimate integration dates of proviral sequences collected during suppressive therapy, implementing a tip date random walker to adjust the sequence tip dates and a latency-specific prior to inform the dates. To validate our method, we implemented it on both simulated and empirical data sets. Consistent with previous studies, we found that proviral integration dates were spread throughout active infection. Path sampling to select an alternative prior for date estimation in place of the latency-specific prior produced unrealistic results in one empirical data set, whereas on another data set, the latency-specific prior was selected as best fitting. Our Bayesian method outperforms current date estimation techniques with a root mean squared error of 0.89 years on simulated data relative to 1.23–1.89 years with previously developed methods. Bayesian methods offer an adaptable framework for inferring proviral integration dates.
The Enigma of Interpersonal Justice in Private Law Theory
Authors: Tan Zhong Xing
Published: July 2023

The purpose of this article is to establish that contemporary private law theory has located no foolproof conception of interpersonal justice. I examine four accounts and find them wanting: the instrumentalist deterrence and loss-spreading approaches of economists; Kantian right and corrective justice; critical and social justice accounts; and the human flourishing approach. If my critiques are justified, this leaves us with the enigma of ‘interpersonal justice’. I consider three options going forward, rejecting the suggestion that we should abandon the search for a theoretical concept or be content with a modus vivendi. I sketch a third option, ‘emancipating interpersonal justice’, drawing from the resources of contractualist philosophy, to suggest that interpersonal justice is not a unitary concept or single regulative idea but a framework for determining what we owe each other in different spheres of interaction, and propose how this might illume certain questions of private law theory.
The current state and future of T-cell exhaustion research
Authors: Jenkins Edward , Whitehead Toby , Fellermeyer Martin , Davis Simon J , Sharma Sumana
Published: July 2023

‘Exhaustion’ is a term used to describe a state of native and redirected T-cell hypo-responsiveness resulting from persistent antigen exposure during chronic viral infections or cancer. Although a well-established phenotype across mice and humans, exhaustion at the molecular level remains poorly defined and inconsistent across the literature. This is, in part, due to an overreliance on surface receptors to define these cells and explain exhaustive behaviours, an incomplete understanding of how exhaustion arises, and a lack of clarity over whether exhaustion is the same across contexts, e.g. chronic viral infections versus cancer. With the development of systems-based genetic approaches such as single-cell RNA-seq and CRISPR screens applied to in vivo data, we are moving closer to a consensus view of exhaustion, although understanding how it arises remains challenging given the difficulty in manipulating the in vivo setting. Accordingly, producing and studying exhausted T-cells ex vivo are burgeoning, allowing experiments to be conducted at scale up and with high throughput. Here, we first review what is currently known about T-cell exhaustion and how it’s being studied. We then discuss how improvements in their method of isolation/production and examining the impact of different microenvironmental signals and cell interactions have now become an active area of research. Finally, we discuss what the future holds for the analysis of this physiological condition and, given the diversity of ways in which exhausted cells are now being generated, propose the adoption of a unified approach to clearly defining exhaustion using a set of metabolic-, epigenetic-, transcriptional-, and activation-based phenotypic markers, that we call ‘M.E.T.A’.
Day-to-day fluctuations of fatigue severity in individuals with knee osteoarthritis: an ecological momentary assessment approach
Authors: Heijman Michelle W J , van den Ende Cornelia H M , Peters Yvonne A S , Mahler Elien A M , Popa Calin D , Vriezekolk Johanna E
Published: July 2023

Objective

The variable course of fatigue adds to the disease burden of patients with OA yet it has been poorly understood. This study aimed to describe within-person fluctuations of fatigue severity and explore its associations with pain, positive affect, negative affect, sleep, and perceived exertion of physical activity.

Methods

Individuals with chronic knee pain or a clinical diagnosis of knee OA ≥40 years of age completed daily assessments about fatigue, pain, positive affect, negative affect, sleep, perceived exertion of physical activity (numeric rating scale 0–10), and overwhelming fatigue (yes/no) on a smartphone over 14 days. Within-person fluctuations of fatigue severity were described by the probability of acute changes (PACs) and s.d.s. Associations with pain, positive affect, negative affect, sleep, and perceived exertion of physical activity were explored using multilevel models.

Results

Forty-nine individuals were included (mean age 63.4 years; 82% female). PACs and s.d.s of within-person daily fatigue fluctuations ranged from 0.00 to 0.80 and 0.35 to 2.95, respectively. Within-person associations of fatigue severity were moderate for positive affect [β = −0.57 (95% CI −0.67, −0.47)], weak for pain [β = 0.41 (95% CI 0.29, 0.53)] and negative affect [β = 0.40 (95% CI 0.21, 0.58)], and negligible for sleep [β = −0.13 (95% CI −0.18, −0.08)] and perceived exertion of physical activity [β = 0.18 (95% CI 0.09, 0.26)].

Conclusion

Some individuals showed almost stable day-to-day levels of fatigue severity, whereas others experienced a substantial number of clinically relevant fluctuations. To reduce the burden of daily fatigue fluctuations, our results suggest that pain, positive and negative affect rather than sleep and perceived exertion of physical activity should be considered as potential targets.
Twenty-five years of novel drug approvals in rheumatology
Authors: Henry Kathryn , Anumolu Natalie , Putman Michael
Published: July 2023

The field of rheumatology has experienced dozens of novel drug approvals in the past two and a half decades, but the regulatory mechanisms underpinning these decisions are not well understood. In the USA, the Food and Drug Administration (FDA) evaluates the safety and efficacy of novel drugs through the New Drug Application (NDA) process. When additional content expertise is required to evaluate scientific or technical matters, the FDA may convene Human Drug Advisory Committees. To better understand the landscape of rheumatology NDAs and the FDA use of advisory committees, we performed a review of all rheumatic disease drug applications from 1996 to 2021 that were granted approval by the FDA. Our review identified 31 NDAs, seven of which utilized an advisory committee. The indications for using advisory committees and their influence on ultimate approvals was not clear. Recommendations to improve transparency and increase public trust in FDA decisions are provided.
Anti-survival motor neuron complex antibodies as a novel biomarker for pulmonary arterial hypertension and interstitial lung disease in mixed connective tissue disease
Authors: Todoroki Yasuyuki , Satoh Minoru , Kubo Satoshi , Kosaka Shunpei , Fukuyo Shunsuke , Nakatsuka Keisuke , Saito Kazuyoshi , Tanaka Shin , Nakayamada Shingo , Tanaka Yoshiya
Published: July 2023

Objective

The presence of anti-U1 RNP antibodies (Abs) is critical for diagnosing MCTD. The aim of this study is to evaluate the clinical relevance of anti-survival motor neuron (SMN) complex Abs, which often coexist with anti-U1 RNP Abs.

Methods

A total of 158 newly diagnosed consecutive cases of SLE, SSc or MCTD with anti-U1 RNP Abs were enrolled in this multicentre observational study between April 2014 and August 2022. Serum anti-SMN complex Abs were screened by immunoprecipitation of 35S-methionine-labelled cell extracts, and associations between anti-SMN complex Abs positivity and clinical characteristics were analysed.

Results

Anti-SMN complex Abs were detected in 36% of MCTD patients, which was significantly higher than that in SLE (8%) or SSc (12%). Among MCTD patients classified based on the combination of the clinical features of SLE, SSc and idiopathic inflammatory myopathies, anti-SMN complex Abs showed the highest prevalence in a subset with clinical features of all three components. Anti-SMN complex Abs–positive MCTD had a higher prevalence of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), which are related to poor prognosis, than negative patients. Moreover, all three cases of death within 1 year of the treatment were positive for anti-SMN complex Abs.

Conclusions

Anti-SMN complex Abs is the first biomarker of a typical subset of MCTD which bears organ damages such as PAH and ILD.
“I was called everything but a student”: Blackness and the Social Death of Student Status
Authors: Lofton Richard
Published: July 2023

Using the conceptual tools of anti-Blackness and the Black habitus to analyze the interviews of 38 Black youth who lived and grew up in Baltimore City, this study contends that the negative associations placed on Black youth continue to dehumanize them and prevent them from the full embodiment of student status. This article explores Blackness and its relationship with the privileges and immunities of student status within America’s collective consciousness. Through the voices of Black youth, this article provides evidence that Black students in Baltimore have not been fully granted the immunity of student status. Instead, Black youth participants describe harm in their schools and neighborhoods, as well as a tenuous relationship between Blackness and “studentness.”
Looks Matter: Are U.S. Schools of Social Work Representing Diversity on Their Websites?
Authors: Ogbonnaya Ijeoma Nwabuzor , Wike Traci L , Bouchard Leah M , Carver Ann Turnlund
Published: July 2023

Public administration researchers have found that passive diversity leads to active diversity. However, whether this relationship holds in schools of social work is uncertain. Understanding this relationship in schools of social work can inform methods used by schools of social work to foster diversity and inclusion. Authors examined the relationship between passive and active diversity representation among 31 randomly selected school of social work websites. Quantitative content analysis revealed that the three most common passive diversity characteristics were (1) having tenure-track faculty of color, (2) images of diverse persons, and (3) faculty with diversity-focused research. The top three active diversity characteristics were (1) no GRE admissions requirement, (2) a woman dean/director, and (3) scholarship/fellowships opportunities. Least represented were student demographics and pronouns in faculty profiles. Most notable bivariate findings were the positive associations between a dean/director of color and tenured faculty of color and the relationship between faculty with diversity-focused research and tenured faculty of color. Greater representation of deans/directors of color in schools of social work is critical for the career advancement of faculty of color. To attract more faculty of color, schools of social work should use their websites to promote hiring opportunities for scholars conducting diversity-focused research. Future research exploring additional diversity characteristics on schools of social work websites and whether these characteristics translate to more inclusive environments is needed.
Fluid resuscitation in acute pancreatitis
Authors: Yang Allison L. , Vege Santhi Swaroop
Published: July 2023

Purpose of review

The purpose of the review is to critically evaluate the evidence from the literature to establish the current perspective on fluid resuscitation (FR) in acute pancreatitis (AP). We will review the rationale, type of fluid, rate of administration, total volume, duration, monitoring, ideal outcomes to be studied in clinical trials and recommendations for future studies.

Recent findings

FR remains the key component of supportive therapy in AP. The paradigm has shifted from administration of aggressive fluid resuscitation towards more moderate FR strategies. Lactated Ringer's remains the preferred fluid for resuscitation. There remain critical gaps in knowledge regarding the end point(s) to indicate adequate resuscitation, and accurate assessments of fluid sequestration and intravascular volume deficit in AP.

There is insufficient evidence to state that goal-directed therapy, using any of the parameters to guide fluid administration, reduces the risk of persistent organ failure, infected pancreatic necrosis, or mortality in AP, as well as the most appropriate method for the same.
Patient Satisfaction and Scar Quality Following Upper Blepharoplasty Using a Simplified Preoperative Marking Technique
Authors: Dossan Aina , Doskaliyev Aidos , Dzhumabekov Auyeskhan , Nuspekova Dinara
Published: July 2023

One of the most popular plastic surgical interventions both abroad and in Kazakhstan is blepharoplasty. Plastic surgeons continue to debate various methods for performing this operation; however, some of the methods used by plastic surgeons for preoperative marking of the upper eyelid skin may not be suited to the type of incision that should be used on the eyelids of individuals from Kazakhstan. For this reason, the surgery may not achieve the desired results. We conducted a study of patients from Kazakhstan who underwent upper blepharoplasty using a simplified technique for eyelid marking that we developed at our plastic surgery center. We used the Patient-Reported Outcome Measure Questionnaire (PROM-Q) to measure patient satisfaction and the Patient and Observer Scar Assessment Scale (POSAS) to measure scar quality. The results of our study showed that the majority of patients who underwent upper blepharoplasty performed by surgeons using our method of preoperative marking were extremely satisfied with the effect. The patients noted rapid tissue repair and minimal scarring. We concluded that the use of a simplified marking technique can significantly help aesthetic surgeons performing upper blepharoplasty by reducing the risk for negative postoperative effects.
Oxidative Stress Status and Its Relationship to Skin Aging
Authors: Varga Rachel , Gross Jeffrey
Published: July 2023

Skin and cellular aging are impacted by various toxins in our environment such as air pollution, water contamination, an increased prevalence of light-emitting diodes, electromagnetic frequencies, various yeast and other fungi, parasitic infections, and mold and heavy metal toxicity. Basic topical skin care is insufficient to adequately protect an individual's integumentary system and other organs from these types of daily cellular stressors. These stressors impact the level of oxidative stress
status (OSS). OSS is measurable through biomarker analysis of various body fluids including blood, saliva, urine, and breath. This poses a unique assessment challenge for aesthetic practitioners as the OSS of a patient impacts their overall aging process. Aesthetic practitioners observe the aging process through visual assessment of a patient's skin quality, skin barrier function, and the presence of solar lentigines, erythema, edema, telangiectasia, loss of collagen and elastin, bone density, and redistribution of subcutaneous tissue. Mitigating a patient's daily exposure to OS and its impacts on the skin, other organ tissues, and metabolism poses a unique challenge in medical aesthetic treatment planning. For this reason, the use of stem cells and exosomes is gaining popularity in aesthetic medicine. The purpose of this literature review is to highlight currently available research, applications, limitations, and mitigation strategies in reducing OSS on the integumentary system and aging processes.
Beyond the hype: large language models propagate race-based medicine
Authors: Omiye Jesutofunmi A. , Lester Jenna , Spichak Simon , Rotemberg Veronica , Daneshjou Roxana
Published: July 2023

Importance

Large language models (LLMs) are being integrated into healthcare systems; but these models recapitulate harmful, race-based medicine.

Objective

The objective of this study is to assess whether four commercially available large language models (LLMs) propagate harmful, inaccurate, race-based content when responding to eight different scenarios that historically included race-based medicine or widespread misconceptions around race.

Evidence Review

Questions were derived from discussion among 4 physician experts and prior work on race-based medical misconceptions of medical trainees.

Findings

We assessed four large language models with eight different questions that were interrogated five times each with a total of forty responses per a model. All models had examples of perpetuating race-based medicine in their responses. Models were not always consistent in their responses when asked the same question repeatedly.

Conclusions and Relevance

LLMs are being proposed for use in the healthcare setting, with some models already connecting to electronic health record systems. However, this study shows that based on our findings, these LLMs could potentially cause harm by perpetuating debunked, racist concepts.
Alterations of the gut microbiome are associated with epigenetic age acceleration and physical fitness
Authors: Torma Ferenc , Kerepesi Csaba , Jokai Matyas , Bakonyi Peter , Koltai Erika , Babszki Gergely , Ligeti Balazs , Kalcsevszki Regina , McGreevy Kristen M. , Horvath Steve , Radak Zsolt
Published: July 2023

Epigenetic clocks can measure aging and predict the incidence of diseases and mortality. Higher levels of physical fitness are associated with a slower aging process and a healthier lifespan. Microbiome alterations occur in various diseases and during the aging process, yet their relation to epigenetic clocks is not explored. To fill this gap, we collected metagenomic, epigenetic and exercise-related data from physically fit individuals and applying epigenetic clocks, we examined the relationship between gut flora, epigenetic age acceleration and physical fitness. We revealed that an increased entropy in the gut microbiome is associated with accelerated epigenetic aging, lower fitness or impaired health status. We also observed that, in general, accelerated epigenetic aging can be linked to the abundance of pro-inflammatory and other pathogenic bacteria and decelerated epigenetic aging or high fitness level can be linked to the abundance of anti-inflammatory bacteria. Overall our data suggest that alterations in the microbiome can be associated with epigenetic age acceleration and physical fitness.
RNA-sequencing first approach generates new diagnostic candidates in Mendelian disorders
Authors: Jaramillo Oquendo Carolina , Wai Htoo A , Rich Will , Bunyan David J. , Thomas N. Simon , Hunt David , Lord Jenny , Douglas Andrew G L , Baralle Diana
Published: July 2023

Background

RNA-sequencing is increasingly being used as a complementary tool to DNA sequencing in diagnostics where DNA analysis has been uninformative. RNA-sequencing allows us to identify alternative splicing and aberrant gene expression allowing for improved interpretation of variants of unknown significance (VUS). Additionally, RNA-sequencing provides the opportunity not only to look at the splicing effects of known VUSs but also to scan the transcriptome for abnormal splicing events and expression abnormalities in other relevant genes that may be the cause of a patient’s phenotype.

Methods

Using RNA from patient blood, we have systematically assessed transcriptomic profiles of 87 patients with suspected Mendelian disorders, 38% of which did not have a candidate sequence variant. Cases with VUSs and known events were assessed first followed by assessment of cases with no VUS. Each VUS was visually inspected using the Integrative Genomics Viewer (IGV) to search for splicing abnormalities. Once aberrant splicing was identified in cases with VUS, multiple open-source alternative splicing tools (MAJIQ, rMATS-turbo, FRASER2 and LeafCutterMD) were used to investigate if they would identify what was observed in IGV. Expression outliers were detected using OUTRIDER. To find diagnoses in cases without a VUS or gene of interest, two separate strategies were used. The first was a genotype to phenotype approach using variant calls obtained from the RNA-sequencing and overlapping those calls with results from splicing tools. The second strategy involved using phenotype information available to filter results from splicing tools.

Results

Using RNA-sequencing only, we were able to assess 71% of VUSs and detect aberrant splicing in 14/48 patients with a VUS. Furthermore, we identified four new diagnoses by detecting novel aberrant splicing events in patients with no candidate sequence variants from prior genomic DNA testing (n=33) or those in which the candidate VUS did not affect splicing (n=23) and identified one additional diagnosis through detection of skewed X-inactivation.

Conclusion

We demonstrate the identification of novel diagnoses using an RNA-sequencing first approach in patients without candidate VUSs. Furthermore, we demonstrate the utility of blood-based RNA analysis in improving diagnostic yields and highlight optimal approaches for such analysis.
The Influence of the Amino Acid Transporter LAT1 on Patient Prognosis and the Relationships between Tumor Immunometabolic and Proliferative Features Depend on Menopausal Status in Breast Cancer
Authors: Ramshankar Gautham , Liu Ryan , Perry Rachel J.
Published: July 2023

L-type Amino Acid Transporter 1 (LAT1) facilitates the uptake of specific essential amino acids, and due to this quality, it has been correlated to worse patient outcomes in various cancer types. However, the relationship between LAT1 and various clinical factors, including menopausal status, in mediating LAT1’s prognostic effects remains incompletely understood. This is particularly true in the unique subset of tumors that are both obesity-associated and responsive to immunotherapy, including breast cancer. To close this gap, we employed 6 sets of transcriptomic data using the Kaplan-Meier model in the Xena Functional Genomics Explorer, demonstrating that higher LAT1 expression diminishes breast cancer patients’ survival probability.

Additionally, we analyzed 3′-Deoxy-3′-18F-Fluorothymidine positron emission tomography-computed tomography (18F-FLT PET-CT) images found on The Cancer Imaging Archive (TCIA). After separating all patients based on menopausal status, we correlated the measured18F-FLT uptake with various clinical parameters quantifying body composition, tumor proliferation, and immune cell infiltration. By analyzing a wealth of deidentified, open-access data, the current study investigates the impact of LAT1 expression on breast cancer prognosis, along with the menopausal status-dependent associations between tumor proliferation, immunometabolism, and systemic metabolism.
A 3’UTR Insertion Is a Candidate Causal Variant at theTMEM106BLocus Associated with Increased Risk for FTLD-TDP
Authors: Chemparathy Augustine , Le Guen Yann , Zeng Yi , Gorzynski John , Jensen Tanner , Yang Chengran , Kasireddy Nandita , Talozzi Lia , Belloy Michael E. , Stewart Ilaria , Gitler Aaron D. , Wagner Anthony D. , Mormino Elizabeth , Henderson Victor W. , Wyss-Coray Tony , Ashley Euan , Cruchaga Carlos , Greicius Michael D.
Published: July 2023

Background and Objectives

Single nucleotide variants nearTMEM106Bassociate with risk of frontotemporal lobar dementia with TDP-43 inclusions (FTLD-TDP) and Alzheimer’s disease (AD) in genome-wide association studies (GWAS), but the causal variant at this locus remains unclear. Here we asked whether a novel structural variant onTMEM106Bis the causal variant.

Methods

An exploratory analysis identified structural variants on neurodegeneration-related genes. Subsequent analyses focused on anAluelement insertion on the 3’UTR ofTMEM106B. This study included data from longitudinal aging and neurogenerative disease cohorts at Stanford University, case-control cohorts in the Alzheimer’s Disease Sequencing Project (ADSP), and expression and proteomics data from Washington University in St. Louis (WUSTL). 432 individuals from two Stanford aging cohorts were whole-genome long-read and short-read sequenced. 16,906 samples from ADSP were short-read sequenced. Genotypes, transcriptomics, and proteomics data were available in 1,979 participants from an aging and dementia cohort at WUSTL. Selection criteria were specific to each cohort. In primary analyses, the linkage disequilibrium between theTMEM106Blocus variants in the FTLD-TDP GWAS and the 3’UTR insertion was estimated. We then estimated linkage by ancestry in the ADSP and evaluated the effect of theTMEM106Blead variant on mRNA and protein levels.

Results

The primary analysis included 432 participants (52.5% females, age range 45-92 years old). We identified a 316 bpAluinsertion overlapping theTMEM106B3’UTR tightly linked with top GWAS variants rs3173615(C) and rs1990622(A). In ADSP European-ancestry participants, this insertion is in equivalent linkage with rs1990622(A) (R2=0.962, D’=0.998) and rs3173615(C) (R2=0.960, D’=0.996). In African-ancestry participants, the insertion is in stronger linkage with rs1990622(A) (R2=0.992, D’=0.998) than with rs3173615(C) (R2=0.811, D’=0.994). In public datasets, rs1990622 was consistently associated with TMEM106B protein levels but not with mRNA expression. In the WUSTL dataset, rs1990622 is associated with TMEM106B protein levels in plasma and cerebrospinal fluid, but not withTMEM106BmRNA expression.

Discussion

We identified a novelAluelement insertion in the 3’UTR ofTMEM106Bin tight linkage with the lead FTLD-TDP risk variant. The lead variant is associated with TMEM106B protein levels, but not expression. The 3’UTR insertion is a lead candidate for the causal variant at this complex locus, pending confirmation with functional studies.
Comparison of Adverse Effects Related to the Use of Epidural Anesthesia versus Spinal Anesthesia in Cesarean Section Patients at the Plaza de la Salud General Hospital in Santo Domingo, Dominican Republic, During the Period January-December 2021: A Retrospective Study
Authors: Alcántara Mariam , Hernández Alba Rebecca
Published: July 2023

Objectives

This study aimed to investigate the two different types of regional anesthesia for a cesarean section and to analyze the various perioperative and postoperative side effects related to them.

Design

We retrospectively included those patients who required a cesarean section under regional anesthesia

Setting

Hospital General Plaza de la Salud from January 2021 to December 2021.

Participants

A total of 202 cesarean sections were analyzed. Spinal anesthesia was used in 195 participants and epidural anesthesia in 7; both groups were then compared.

Results

Perioperative results revealed that spinal anesthesia had a shorter total anesthesia time, more frequent hypotensive episodes, and a higher perioperative ephedrine administration rate. Regarding the postoperative results, the Apgar scores of the newborns recorded at one minute and at 5 minutes were similar in both groups.

Conclusions

For patients who required a cesarean section under regional anesthesia, the use of spinal anesthesia led to a shorter anesthetic time, however it is associated with greater hemodynamic changes and ephedrine administration compared with epidural anesthesia.
Classification of the Attempted Arm and Hand Movements of Patients with Spinal Cord Injury Using Deep Learning Approach
Authors: Makouei Sahar Taghi Zadeh , Uyulan Caglar
Published: July 2023

The primary objective of this research is to improve the average classification performance for specific movements in patients with cervical spinal cord injury (SCI). The study utilizes a low-frequency multi-class electroencephalography (EEG) dataset obtained from the Institute of Neural Engineering at Graz University of Technology. The research combines convolutional neural network (CNN) and long-short-term memory (LSTM) architectures to uncover strong neural correlations between temporal and spatial aspects of the EEG signals associated with attempted arm and hand movements.

To achieve this, three different methods are used to select relevant features, and the proposed model’s robustness against variations in the data is validated using 10-fold cross-validation (CV). Furthermore, the study explores the potential for subject-specific adaptation in an online paradigm, extending the proof-of-concept for classifying movement attempts.

In summary, this research aims to make valuable contributions to the field of neuro-technology by developing EEG-controlled assistive devices using a generalized brain-computer interface (BCI) and deep learning (DL) framework. The focus is on capturing high-level spatiotemporal features and latent dependencies to enhance the performance and usability of EEG-based assistive technologies.
Joint Association of Albuminuria and Left Ventricular Hypertrophy with Incident Heart Failure in High-Risk Adults with Hypertension: a SPRINT substudy
Authors: Ahmad Muhammad Imtiaz , Kazibwe Richard , Soliman Mai Z. , Singh Sanjay , Chen Lin Y. , Soliman Elsayed Z.
Published: July 2023

Background

Albuminuria and left ventricular hypertrophy (LVH) are independent predictors of heart failure (HF), however their combined effect on risk of HF has not been explored previously.

Objectives

To examine the joint associations of albuminuria and electrocardiographic (ECG) LVH with incident acute decompensated HF (ADHF), and whether albuminuria/LVH combinations modified the effects of blood pressure control strategy in reducing the risk of ADHF.

Methods

8,511 participants from the SPRINT (Systolic Blood Pressure Intervention Trial) were included. ECG-LVH was present if any of the following criteria: Cornell voltage, Cornell voltage product, or Sokolow Lyon were present. Albuminuria was defined as urine albumin-creatinine ratio (UACR) ≥30 mg/g. ADHF was defined as hospitalization or emergency visit for ADHF. Cox proportional hazard models were used to examine the association of neither LVH, nor albuminuria (reference), either LVH or albuminuria, and both (LVH + albuminuria) with incident ADHF.

Results

Over a median follow-up of 3.2 years, 182 cases of ADHF occurred. In adjusted models, concomitant albuminuria and LVH were associated with higher risk of ADHF than either albuminuria or LVH in isolation (HR (95% CI): 4.95 (3.22-7.62), 2.04 (1.39-3.00), and 1.47 (0.93-2.32), respectively (additive interactionp=0.01). The effect of intensive blood pressure in decreasing ADHF attenuated among participants with co-existing albuminuria and LVH without any interaction between treatment group assignment and albuminuria/LVH categories (interaction p-value= 0.26).

Conclusions

Albuminuria and LVH are additive predictors of ADHF. The effect of intensive blood pressure control in decreasing ADHF risk did not vary significantly across albuminuria/LVH combinations.

URL:https://www.clinicaltrials.gov; Unique identifier:NCT01206062