bluuebunny/crossref_metadata_2025 huggingface dataset:
Merging automatic differentiation and the adjoint method for photonic inverse design
Authors: Luce Alexander , Alaee Rasoul , Knorr Fabian , Marquardt Florian
Published: June 2024

Optimizing the shapes and topology of physical devices is crucial for both scientific and technological advancements, given their wide-ranging implications across numerous industries and research areas. Innovations in shape and topology optimization have been observed across a wide range of fields, notably structural mechanics, fluid mechanics, and more recently, photonics. Gradient-based inverse design techniques have been particularly successful for photonic and optical problems, resulting in integrated, miniaturized hardware that has set new standards in device performance. To calculate the gradients, there are typically two approaches: namely, either by implementing specialized solvers using automatic differentiation (AD) or by deriving analytical solutions for gradient calculation and adjoint sources by hand. In this work, we propose a middle ground and present a hybrid approach that leverages and enables the benefits of AD for handling gradient derivation while using existing, proven but black-box photonic solvers for numerical solutions. Utilizing the adjoint method, we make existing numerical solvers differentiable and seamlessly integrate them into an AD framework. Further, this enables users to integrate the optimization environment seamlessly with other autodifferentiable components such as machine learning, geometry generation, or intricate post-processing which could lead to better photonic design workflows. We illustrate the approach through two distinct photonic optimization problems: optimizing the Purcell factor of a magnetic dipole in the vicinity of an optical nanocavity and enhancing the light extraction efficiency of a µLED.
On the prediction of the turbulent flow behind cylinder arrays via echo state networks
Authors: Ghazijahani M Sharifi , Cierpka C
Published: June 2024

This study aims at the prediction of the turbulent flow behind cylinder arrays by the application of Echo State Networks (ESN). Three different arrangements of arrays of seven cylinders are chosen for the current study. These represent different flow regimes: single bluff body flow, transient flow, and co-shedding flow. This allows the investigation of turbulent flows that fundamentally originate from wake flows yet exhibit highly diverse dynamics. The data is reduced by Proper Orthogonal Decomposition (POD) which is optimal in terms of kinetic energy. The Time Coefficients of the POD Modes (TCPM) are predicted by the ESN. The network architecture is optimized with respect to its three main hyperparameters, Input Scaling (INS), Spectral Radius (SR), and Leaking Rate (LR), in order to produce the best predictions in terms of Weighted Prediction Score (WPS), a metric leveling statistic and deterministic prediction. In general, the ESN is capable of imitating the complex dynamics of turbulent flows even for longer periods of several vortex shedding cycles. Furthermore, the mutual interdependencies of the TCPM are well preserved. However, optimal hyperparameters depend strongly on the flow characteristics. Generally, as flow dynamics become faster and more intermittent, larger LR and INS values result in better predictions, whereas less clear trends for SR are observable.
Kicking the can down the road: understanding the effects of delaying the deployment of stratospheric aerosol injection
Authors: Brody Ezra , Visioni Daniele , Bednarz Ewa M , Kravitz Ben , MacMartin Douglas G , Richter Jadwiga H , Tye Mari R
Published: June 2024

Climate change is a prevalent threat, and it is unlikely that current mitigation efforts will be enough to avoid unwanted impacts. One potential option to reduce climate change impacts is the use of stratospheric aerosol injection (SAI). Even if SAI is ultimately deployed, it might be initiated only after some temperature target is exceeded. The consequences of such a delay are assessed herein. This study compares two cases, with the same target global mean temperature of ∼1.5° C above preindustrial, but start dates of 2035 or a ‘delayed’ start in 2045. We make use of simulations in the Community Earth System Model version 2 with the Whole Atmosphere Coupled Chemistry Model version 6 (CESM2-WACCM6), using SAI under the SSP2-4.5 emissions pathway. We find that delaying the start of deployment (relative to the target temperature) necessitates lower net radiative forcing (−30%) and thus larger sulfur dioxide injection rates (+20%), even after surface temperatures converge, to compensate for the extra energy absorbed by the Earth system. Southern hemisphere ozone is higher from 2035 to 2050 in the delayed start scenario, but converges to the same value later in the century. However, many of the surface climate differences between the 2035 and 2045 start simulations appear to be small during the 10–25 years following the delayed SAI start, although longer simulations would be needed to assess any longer-term impacts in this model. In addition, irreversibilities and tipping points that might be triggered during the period of increased warming may not be adequately represented in the model but could change this conclusion in the real world.
Human-induced climate change has decreased wheat production in northern Kazakhstan
Authors: Romanovska Paula , Undorf Sabine , Schauberger Bernhard , Duisenbekova Aigerim , Gornott Christoph
Published: June 2024

Northern Kazakhstan is a major wheat exporter, contributing to food security in Central Asia and beyond. However, wheat yields fluctuate and low-producing years occur frequently. It is currently unclear to what extent human-induced climate change contributes to this. The most severe low-producing year in this century was in 2010, which had severe consequences for the food security of wheat-importing countries. Here, we present a climate impact attribution study that quantifies the impact of human-induced climate change on the average wheat production and associated economic revenues in northern Kazakhstan in the 21st century and on the likelihood of a low-production year like 2010. The study uses bias-adjusted counterfactual and factual climate model data from two large ensembles of latest-generation climate models as input to a statistical subnational yield model. We consider the climate data and the yield model as fit for purpose as first, the factual climate simulations represent the observations, second, the out-of-sample validation of the yield model performs reasonably well with a mean R
2 of 0.54, and third, the results are robust under the performed sensitivity tests. Human-induced climate change has had a critical impact on wheat production, specifically through increases in daily-minimum temperatures and extreme heat. This has resulted in a decrease in yields during 2000–2019 by approximately 6.2%–8.2% (uncertainty range of two climate models) and an increased likelihood of the 2010 low-production event by 1.5–4.7 times (10th to 90th percentile uncertainty range covering both climate models). During 2000–2019, human-induced climate change caused economic losses estimated at between 96 and 180 million USD per year (10th to 90th percentile uncertainty range covering both climate models). These results highlight the necessity for ambitious global mitigation efforts and measures to adapt wheat production to increasing temperatures, ensuring regional and global food security.
Genetic, epigenetic and environmental factors in diverticular disease: systematic review
Authors: Humphrey Hannah N , Sibley Pauline , Walker Eleanor T , Keller Deborah S , Pata Francesco , Vimalachandran Dale , Daniels Ian R , McDermott Frank D
Published: June 2024

Background

Diverticulosis is a normal anatomical variant of the colon present in more than 70% of the westernized population over the age of 80. Approximately 3% will develop diverticulitis in their lifetime. Many patients present emergently, suffer high morbidity rates and require substantial healthcare resources. Diverticulosis is the most common finding at colonoscopy and has the potential for causing a significant morbidity rate and burden on healthcare. There is a need to better understand the aetiology and pathogenesis of diverticular disease. Research suggests a genetic susceptibility of 40–50% in the formation of diverticular disease. The aim of this review is to present the hypothesized functional effects of the identified gene loci and environmental factors.

Methods

A systematic literature review was performed using PubMed, MEDLINE and Embase. Medical subject headings terms used were: ‘diverticular disease, diverticulosis, diverticulitis, genomics, genetics and epigenetics’. A review of grey literature identified environmental factors.

Results

Of 995 articles identified, 59 articles met the inclusion criteria. Age, obesity and smoking are strongly associated environmental risk factors. Intrinsic factors of the colonic wall are associated with the presence of diverticula. Genetic pathways of interest and environmental risk factors were identified. The COLQ, FAM155A, PHGR1, ARHGAP15, S100A10, and TNFSF15 genes are the strongest candidates for further research.

Conclusion

There is increasing evidence to support the role of genomics in the spectrum of diverticular disease. Genomic, epigenetic and omic research with demographic context will help improve the understanding and management of this complex disease.
Single-cell RNA sequencing identifies interferon-inducible monocytes/macrophages as a cellular target for mitigating the progression of abdominal aortic aneurysm and rupture risk
Authors: Le Sheng , Wu Jia , Liu Hao , Du Yifan , Wang Dashuai , Luo Jingjing , Yang Peiwen , Ran Shuan , Hu Poyi , Chen Manhua , Ye Ping , Xia Jiahong
Published: June 2024

Aims

Abdominal aortic aneurysm (AAA) represents a life-threatening condition characterized by medial layer degeneration of the abdominal aorta. Nevertheless, knowledge regarding changes in regulators associated with aortic status remains incomplete. A thorough understanding of cell types and signalling pathways involved in the development and progression of AAAs is essential for the development of medical therapy.

Methods and results

We harvested specimens of the abdominal aorta with different pathological features in Angiotensin II (AngII)-infused ApoE−/− mice, conducted scRNA-seq, and identified a unique population of interferon-inducible monocytes/macrophages (IFNICs), which were amply found in the AAAs. Gene set variation analysis revealed that activation of the cytosolic DNA sensing cGAS-STING and JAK-STAT pathways promoted the secretion of type I interferons in monocytes/macrophages and differentiated them into IFNICs. We generated myeloid cell-specific deletion of Sting1 (Lyz2-Cre+/−; Sting1flox/flox) mice and performed bone marrow transplantation and found that myeloid cell-specific deletion of Sting1 or Ifnar1 significantly reduced the incidence of AAA, aortic rupture rate, and diameter of the abdominal aorta. Mechanistically, the activated pyroptosis- and inflammation-related signalling pathways, regulated by IRF7 in IFNICs, play critical roles in the developing AAAs.

Conclusion

IFNICs are a unique monocyte/macrophage subset implicated in the development of AAAs and aortic rupture.
A Comparative Study of Organizational Grief Support and Burnout Among Nursing Home Staff
Authors: Hawes Frances M , Wang Shuangshuang
Published: June 2024

Background and Objectives

The purpose of this study was to examine the relationship between dimensions of grief support (recognition of the relationship, acknowledgement of the loss, and inclusion of the griever) and aspects of burnout (emotional exhaustion, depersonalization, and personal accomplishment) among nursing home staff.

Research Design and Methods

Data were collected from 553 nursing home workers from 37 nursing home facilities in 5 states during fall of 2022. Responses to the Maslach Burnout Inventory and Grief Support Health Care Scale were analyzed for this study.

Results

The study found that recognizing the relationship with deceased patients led to a decrease in exhaustion and depersonalization among workers while simultaneously enhancing their sense of personal accomplishment. Including the griever in the support process lowered all burnout subscales for nursing home staff. Acknowledging the loss was associated with higher levels of personal accomplishment. Registered nurses, nurse practitioners, and physicians experienced higher levels of exhaustion and depersonalization compared to other nursing home staff. Behavioral health workers had the highest personal accomplishment, whereas direct support workers reported the lowest.

Discussion and Implications

These findings have important implications for improving the well-being of nursing home staff, emphasizing the importance of organizational grief support, and tailored interventions to address burnout among different healthcare provider roles in nursing homes.
LC–MS-MS quantification of Δ8-THC, Δ9-THC, THCV isomers and their main metabolites in human plasma
Authors: Sempio Cristina , Campos-Palomino Jorge , Klawitter Jelena , Harrison Amy , Peters Erica N , MacNair Laura , Haghdoost Mehdi , Bonn-Miller Marcel , Babalonis Shanna , Huestis Marilyn A , Christians Uwe , Klawitter Jost
Published: June 2024

In recent years, potential therapeutic applications of several different cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC), its isomer Δ8-THC and Δ9-tetrahydrocannabivarin (Δ9-THCV), have been investigated. Nevertheless, to establish dose–effect relationship and to gain knowledge of their pharmacokinetics and metabolism, sensitive and specific analytical assays are needed to measure these compounds in patients. For this reason, we developed and validated an online extraction high-performance liquid/liquid chromatography–tandem mass spectrometry (LC/LC–MS-MS) method for the simultaneous quantification of 13 cannabinoids and metabolites including the Δ8 and Δ9 isomers of THC, THCV and those of their major metabolites in human plasma. Plasma was fortified with cannabinoids at varying concentrations within the working range of the respective compound and 200 µL was extracted using a simple one-step protein precipitation procedure. The extracts were analyzed using online trapping LC/LC–atmospheric pressure chemical ionization–MS-MS running in the positive multiple reaction monitoring mode. The lower limit of quantification ranged from 0.5 to 2.5 ng/mL, and the upper limit of quantification was 400 ng/mL for all analytes. Inter-day analytical accuracy and imprecision ranged from 82.9% to 109% and 4.3% to 20.3% (coefficient of variance), respectively. Of 534 plasma samples following controlled oral administration of Δ8-THCV, 236 were positive for Δ8-THCV (median; interquartile ranges: 3.5 ng/mL; 1.8–11.9 ng/mL), 383 for the major metabolite (−)-11-nor-9-carboxy-Δ8-tetrahydrocannabivarin (Δ8-THCV-COOH) (95.4 ng/mL; 20.7–328 ng/mL), 260 for (−)-11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (Δ9-THCV-COOH) (5.8 ng/mL; 2.5–16.1 ng/mL), 157 for (−)-11-hydroxy-Δ8-tetrahydrocannabivarin (11-OH-Δ8-THCV) (1.7 ng/mL; 1.0–3.7 ng/mL), 49 for Δ8-THC-COOH (1.7 ng/mL; 1.4–2.3 ng/mL) and 42 for Δ9-THCV (1.3 ng/mL; 0.8–1.6 ng/mL). We developed and validated the first LC/LC–MS-MS assay for the specific quantification of Δ8-THC, Δ9-THC and THCV isomers and their respective metabolites in human plasma. Δ8-THCV-COOH, 11-hydroxy-Δ8-THCV and Δ9-THCV-COOH were the major Δ8-THCV metabolites in human plasma after oral administration of 98.6% pure Δ8-THCV.
Lethal carbon monoxide generated from small internal combustion engines
Authors: Hyson Brian E , Friedman Brittany M , Spear Brianna , Bishop-Freeman Sandra C
Published: June 2024

Fuel-burning small engines have the potential to emit dangerous and potentially lethal concentrations of carbon monoxide when used in poorly ventilated environments. The North Carolina Office of the Chief Medical Examiner investigated seven cases from 2013 to 2020 involving lethal carbon monoxide from small internal combustion engines. Evaluation of percent carboxyhemoglobin saturation was determined in these case studies as ratios of carboxyhemoglobin to reduced hemoglobin, using HP 8453 and Agilent 8454 UV-Visible Spectrophotometers (Agilent Technologies, Santa Clara, CA, USA). Sources of carbon monoxide included a pressure washer, a propane-powered forklift, an inboard engine boat, a motorcycle, propane and kerosene heaters, and home-use generators. It was demonstrated during a death investigation that the Dräger X-am 2000 electrochemical gas monitor often used by first responders, falsely reacted to acetylene gas, initially misleading investigators to the source of the carbon monoxide. Educating first responders about not only the hazards of these unexpected carbon monoxide sources, but the limitations of their equipment, is a valuable goal of disseminating complete medical examiner case information. The details of these cases will educate first responders, the forensic science community, and public health leaders on potential small engine sources of carbon monoxide in death investigations, responder safety, and the limitations of portable air quality monitoring equipment during death investigation.
ZW10: an emerging orchestrator of organelle dynamics during the cell division cycle
Authors: Bellah Sm Faysal , Yang Fengrui , Xiong Fangyuan , Dou Zhen , Yao Xuebiao , Liu Xing
Published: June 2024

Zeste white 10 (ZW10) was first identified as a centromere/kinetochore protein encoded by the ZW10 gene in Drosophila. ZW10 guides the spindle assembly checkpoint signaling during mitotic chromosome segregation in metazoans. Recent studies have shown that ZW10 is also involved in membrane-bound organelle interactions during interphase and plays a vital role in membrane transport between the endoplasmic reticulum and Golgi apparatus. Despite these findings, the precise molecular mechanisms by which ZW10 regulates interactions between membrane-bound organelles in interphase and the assembly of membraneless organelle kinetochore in mitosis remain elusive. Here, we highlight how ZW10 forms context-dependent protein complexes during the cell cycle. These complexes are essential for mediating membrane trafficking in interphase and ensuring the accurate segregation of chromosomes in mitosis.
Fibroblast growth factor receptor 1 gene mutation as a potential risk factor for spontaneous intracranial hemorrhage in pediatric low-grade glioma patients
Authors: Gonzalez-Vega Maxine , M. Lebert Brittany , Campion Stephani , Wagner Aaron , Aguilar-Bonilla Ana , A. Smith Amy
Published: June 2024

Background

Fibroblast growth factor receptor 1 (FGFR1) mutations have been associated with poorer prognoses in pediatric central nervous system tumor patients. A recent study highlighted a link between FGFR1 mutations and spontaneous intracranial hemorrhage (ICH), demonstrating that all patients with an FGFR1 alteration experienced hemorrhage at some point during their course of treatment.

Methods

The current study examined 50 out of 67 pediatric patients with low-grade gliomas (LGGs) who had genomic testing between 2011 and 2022 at our institution to determine whether a correlation exists between FGFR1 mutations and spontaneous ICH.

Results

We found that of the 50 patients with genomic data, 7 (14%) experienced ICH, and an additional spontaneous hemorrhage was recorded; however, no genomic testing was performed for this case. Five of the seven patients (71.4%) had an FGFR1 modification. In our patient population, 6 expressed a detectable FGFR1 mutation (66.7% [4/6] had N546K alteration, 16.7% [1/6] FGFR1 exons duplication, and 16.7% [1/6] had a variant of unknown significance [VUS]). The patient with the FGFR1 VUS had no reported spontaneous hemorrhage. Statistical analysis found a significant association between FGFR1 and spontaneous intracranial hemorrhage (P-value = < .0001). In the patient population, all cases of PTPN11 alterations (n = 3) co-occurred with FGFR1 mutations.

Conclusions

Our case series highlights this link between the FGFR1 mutation and spontaneous intracranial hemorrhage in pediatric LGGs.
Microbial and Biochemical Biofungicides Ineffective Against Alternaria Black Spot on Organic Kale
Authors: Keinath Anthony P.
Published: June 2024

In South Carolina, the disease black spot on kale is caused by the fungi Alternaria brassicicola and A. japonica. Because all kale cultivars are presumed to be susceptible, organic producers may apply biofungicides to prevent or manage black spot. Microbial and biochemical biofungicides were tested in the greenhouse (12 products) and the field (10 products) against black spot caused by both Alternaria spp. on organically produced kale. Thereafter, three biofungicides (copper hydroxide, potassium silicate, and Reynoutria sachalinensis extract) were tested in the field on three kale cultivars. Although several biofungicides reduced black spot in the greenhouse compared with the water-treated control, no biofungicides did so in the field even though they were applied preventatively before plants were inoculated. Biofungicides also did not increase the weight of healthy leaves compared with the water-treated control in any field experiment. Conversely, two biofungicides that increased the severity and incidence of black spot in the greenhouse, B. amyloliquefaciens F727 and potassium bicarbonate, reduced weights of healthy leaves in the field. On average, curly kale cultivar Winterbor had fewer diseased leaves than curly kale cultivar Darkibor, and lacinato kale cultivar Toscano had fewer diseased leaves than curly kale. Winterbor also consistently produced greater healthy leaf weight than Darkibor. Biopesticides are not recommended against black spot on organic kale.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Association of Postarrest Hypotension Burden With Unfavorable Neurologic Outcome After Pediatric Cardiac Arrest
Authors: Liu Raymond , Majumdar Tanmay , Gardner Monique M. , Burnett Ryan , Graham Kathryn , Beaulieu Forrest , Sutton Robert M. , Nadkarni Vinay M. , Berg Robert A. , Morgan Ryan W. , Topjian Alexis A. , Kirschen Matthew P.
Published: June 2024

OBJECTIVE:

Quantify hypotension burden using high-resolution continuous arterial blood pressure (ABP) data and determine its association with outcome after pediatric cardiac arrest.

DESIGN:

Retrospective observational study.

SETTING:

Academic PICU.

PATIENTS:

Children 18 years old or younger admitted with in-of-hospital or out-of-hospital cardiac arrest who had invasive ABP monitoring during postcardiac arrest care.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

High-resolution continuous ABP was analyzed up to 24 hours after the return of circulation (ROC). Hypotension burden was the time-normalized integral area between mean arterial pressure (MAP) and fifth percentile MAP for age. The primary outcome was unfavorable neurologic status (pediatric cerebral performance category ≥ 3 with change from baseline) at hospital discharge. Mann-Whitney U tests compared hypotension burden, duration, and magnitude between favorable and unfavorable patients. Multivariable logistic regression determined the association of unfavorable outcomes with hypotension burden, duration, and magnitude at various percentile thresholds from the 5th through 50th percentile for age. Of 140 patients (median age 53 [interquartile range 11–146] mo, 61% male); 63% had unfavorable outcomes. Monitoring duration was 21 (7–24) hours. Using a MAP threshold at the fifth percentile for age, the median hypotension burden was 0.01 (0–0.11) mm Hg-hours per hour, greater for patients with unfavorable compared with favorable outcomes (0 [0–0.02] vs. 0.02 [0–0.27] mm Hg-hr per hour, p < 0.001). Hypotension duration and magnitude were greater for unfavorable compared with favorable patients (0.03 [0–0.77] vs. 0.71 [0–5.01]%, p = 0.003; and 0.16 [0–1.99] vs. 2 [0–4.02] mm Hg, p = 0.001). On logistic regression, a 1-point increase in hypotension burden below the fifth percentile for age (equivalent to 1 mm Hg-hr of burden per hour of recording) was associated with increased odds of unfavorable outcome (adjusted odds ratio [aOR] 14.8; 95% CI, 1.1–200; p = 0.040). At MAP thresholds of 10th–50th percentiles for age, MAP burden below the threshold was greater in unfavorable compared with favorable patients in a dose-dependent manner.

CONCLUSIONS:

High-resolution continuous ABP data can be used to quantify hypotension burden after pediatric cardiac arrest. The burden, duration, and magnitude of hypotension are associated with unfavorable neurologic outcomes.
Nomophobia and Phubbing Levels of Nursing Students
Authors: Sahin Karaduman Gul , Basak Tulay , Santana Fialho Sim-Sim Maria Margarida , Aaberg Vicki , Bule Maria José
Published: June 2024

Today, with the enhancement in the usage of smartphones, the concepts of nomophobia and phubbing have emerged. Nomophobia refers to the fear of being deprived of smartphones/smart devices. Phubbing is the use of a person's smartphone in situations that are not appropriate for the situation, time, and place. Therefore, the study purposed to evaluate nursing students' nomophobia and phubbing scores in Turkey, Portugal, and the United States. The data were collected with the Personal Information Questionnaire, Nomophobia Scale, and Phubbing Scale from N = 446 nursing students. The mean age of the students was 22.04 ± 4.08 years, and 86.5% were women. It was found that the total nomophobia scores of the nursing students were 80.15 ± 21.96, 72.29 ± 28.09, and 99.65 ± 6.11, respectively in Turkey, Portugal, and the United States. When the countries' Nomophobia Scale total scores, “giving up convenience,” “not being able to communicate,” and “losing connectedness” scores were compared with each other, they were found to be statistically significant (P < .05). When the countries' Phubbing Scale total scores and all subscale scores were compared with each other were found to be statistically significant (P < .05). It is seen that nomophobia scores were moderate (60 ≤ NMP-Q nomophobia ≤ 99) and phubbing scores (<40) were below the level indicating addiction in all countries.
Therapeutic Drug Monitoring of Olanzapine: Effects of Clinical Factors on Plasma Concentrations in Psychiatric Patients
Authors: Ansermot Nicolas , Vathanarasa Harish , Ranjbar Setareh , Gholam Mehdi , Crettol Séverine , Vandenberghe Frederik , Gamma Franziska , Plessen Kerstin Jessica , von Gunten Armin , Conus Philippe , Eap Chin B.
Published: June 2024

Background:

Therapeutic drug monitoring (TDM) is strongly recommended for olanzapine due to its high pharmacokinetic variability. This study aimed to investigate the impact of various clinical factors on olanzapine plasma concentrations in patients with psychiatric disorders.

Methods:

The study used TDM data from the PsyMetab cohort, including 547 daily dose–normalized, steady-state, olanzapine plasma concentrations (C:D ratios) from 248 patients. Both intrinsic factors (eg, sex, age, body weight) and extrinsic factors (eg, smoking status, comedications, hospitalization) were examined. Univariate and multivariable, linear, mixed-effects models were employed, with a stepwise selection procedure based on Akaike information criterion to identify the relevant covariates.

Results:

In the multivariable model (based on 440 observations with a complete data set), several significant findings emerged. Olanzapine C:D ratios were significantly lower in smokers (β = −0.65, P < 0.001), valproate users (β = −0.53, P = 0.002), and inpatients (β = −0.20, P = 0.025). Furthermore, the C:D ratios decreased significantly as the time since the last dose increased (β = −0.040, P < 0.001). The male sex had a significant main effect on olanzapine C:D ratios (β = −2.80, P < 0.001), with significant interactions with age (β = 0.025, P < 0.001) and body weight (β = 0.017, P = 0.011). The selected covariates explained 30.3% of the variation in C:D ratios, with smoking status accounting for 7.7% and sex contributing 6.9%. The overall variation explained by both the fixed and random parts of the model was 67.4%. The model facilitated the prediction of olanzapine C:D ratios based on sex, age, and body weight.

Conclusions:

The clinical factors examined in this study, including sex, age, body weight, smoking status, and valproate comedication, remarkably influence olanzapine C:D ratios. Considering these factors, in addition to TDM and the clinical situation, could be important for dose adjustment.
Compression Therapy for Keloid Scars: A Systematic Review and Meta-analysis
Authors: Tahir Sadia M. , Ihebom Diane , Simman Richard
Published: June 2024

Background:

Keloid scars have a multitude of treatments with varying success rates. The purpose of this systematic review and meta-analysis is to study the different types of compression therapies used following surgical excision and their recurrence rates.

Methods:

A literature search was conducted using the following databases: PubMed, Embase, and Cochrane Reviews. The following keywords were used in the search: “keloid” and “compression.” The following inclusion criteria were used: (1) identifying lesion must be a keloid and (2) use of any type of compression therapy for keloid scar.

Results:

A total of 27 articles were included in the final analysis, grouped into three treatment modalities for comparison. The three treatment modalities are (1) surgical excision and compression earring, (2) surgical excision and silicone gel sheeting, and (3) surgical excision, compression earring, and silicone gel sheeting. Based on our analysis, combination treatment with compression earring device and silicone gel sheeting had the lowest recurrence rate when compared with compression earring device or silicone gel alone, but the difference in recurrence rates between the three treatment modalities was not statistically significant.

Conclusions:

There were too few studies included in each treatment modality with even fewer sample sizes, and there is a need for a greater number of studies with increased sample size to evaluate which therapy is the most efficacious in preventing keloid recurrence following surgical excision.
Research Letter: Relationship of Blood Biomarkers of Inflammation With Acute Concussion Symptoms and Recovery in the CARE Consortium
Authors: Meier Timothy B. , Huber Daniel L. , Goeckner Bryna D. , Gill Jessica M. , Pasquina Paul , Broglio Steven P. , McAllister Thomas W. , Harezlak Jaroslaw , McCrea Michael A. ,   CARE Consortium Investigators
Published: June 2024

Objective:

Determine the association of inflammatory biomarkers with clinical measures and recovery in participants with concussion.

Setting:

Multicenter study in National Collegiate Athletic Association member institutions including military service academies.

Participants:

Four hundred twenty-two participants with acute concussion.

Design:

Clinical visits and blood draws were completed preinjury and at multiple visits postconcussion (0-12 hours, 12-36 hours, and 36-60 hours postinjury). Clinical measures included Sport Concussion Assessment Tool (SCAT) symptom severity, Balance Error Scoring System, Standardized Assessment of Concussion (SAC), Brief Symptom Inventory-18 (BSI-18) scores, time to initiation of graduated return-to-play (RTP) protocol, and time to RTP. Interleukin (IL)-6, IL-10, IL-8, IL-1 receptor antagonist (RA), tumor necrosis factor (TNF), c-reactive protein, and vascular endothelial growth factor (VEGF) were measured in serum. Prespecified analyses focused on IL-6 and IL-1RA at 0 to 12 hours; exploratory analyses were conducted with false discovery rate correction.

Results:

For prespecified analyses, IL-1RA at 0 to 12 hours in female participants was positively associated with more errors on the SAC (B(standard error, SE) = 0.58(0.27), P < .05) and worse SCAT symptom severity (B(SE) = 0.96(0.44), P < .05). For exploratory analyses, higher levels of IL-1RA at 12 to 36 hours were associated with higher global (B(SE) = 0.55(0.14), q < 0.01), depression (B(SE) = 0.45(0.10), q < 0.005), and somatization scores on the BSI (B(SE) = 0.46(0.12), q < 0.01) in participants with concussion; Higher TNF at 12 to 36 hours was associated with fewer errors on the SAC (B(SE) = − 0.46(0.14), q < 0.05). Subanalyses showed similar results for male participants and participants who were athletes. No associations were discovered in nonathlete cadets. Higher IL-8 at 0 to 12 hours was associated with slower RTP in female participants (OR = 14.47; 95% confidence interval, 2.96-70.66, q < 0.05); no other associations with recovery were observed.

Conclusions:

Peripheral inflammatory markers are associated with clinical symptoms following concussion and potentially represent one mechanism for psychological symptoms observed postinjury. Current results do not provide strong support for a potential prognostic role for these markers.
Efficacy of naproxen in patients with sciatica: multicenter, randomized, double-blind, placebo-controlled trial
Authors: Grøvle Lars , Hasvik Eivind , Holst René , Sætre Anders , Brox Jens Ivar , Mathiassen Ståle , Myhre Kjersti , Holmgard Thor Einar , Haugen Anne Julsrud
Published: June 2024

This trial assessed the efficacy of naproxen in patients with sciatica in outpatient clinics across 4 Norwegian hospitals. A total of 123 adults with radiating pain below the knee (≥4 on a 0-10 numeric rating scale) and signs consistent with nerve root involvement were included. Participants were randomized to receive either naproxen 500 mg or a placebo twice daily for 10 days. The primary outcome, daily leg pain intensity measured on a 0 to 10 numeric rating scale throughout the treatment period, revealed a statistically significant difference in favor of naproxen, with an adjusted mean difference of −0.5 (95% CI −0.8 to −0.1, P = 0.015). In the naproxen group, the treatment effect was significantly related to time, and over the whole 10-day period, the average adjusted difference was −0.6 (95% CI −0.8 to −0.5). Mean numbers needed to treat for 30% and 50% improvement were 9.9 (95% CI 4.7-15.0) and 20.7 (8.7-32.7), respectively. The adjusted mean difference for back pain was −0.4 (95% CI −0.8 to 0.0), and for Roland Morris Disability Questionnaire for Sciatica, it was −1.5 (95% CI −3.0 to 0.0). No differences were found for sciatica bothersomeness or consumption of rescue medication or opioids. Participants in the naproxen group exhibited an adjusted odds ratio of 4.7 (95% CI 1.3-16.2) for improvement by 1 level on the global perceived change scale. In conclusion, naproxen treatment showed small, likely clinically unimportant benefits compared with placebo in patients with moderate-to-severe sciatica.
Outcomes of bariatric surgery in the setting of compensated advanced chronic liver disease associated with clinically significant portal hypertension: a multicenter, retrospective, cohort study on feasibility and safety
Authors: Temime Victor , Ghanem Omar M. , Heimbach Julie K. , Diwan Tayyab S. , Tranchart Hadrien , Abdallah Hussein , Blanchard Claire , Lontrichard Marie , Reche Fabian , Borel Anne-Laure , Belluzzi Amanda , Foletto Mirto , Manno Emilio , Poghosyan Tigran , Chierici Andrea , Iannelli Antonio
Published: June 2024

Background:

The obesity epidemic has led to an increase in the proportion of patients with chronic liver disease due to metabolic associated steatosic liver disease and in the prevalence of obesity in patients with cirrhosis. Metabolic and bariatric surgery (MBS) has been proven to determine weight loss, obesity-related medical problems remission, and liver steatosis, inflammation, and fibrosis improvement. However, cirrhosis and portal hypertension are well-known risk factors for increased morbidity and mortality after surgery. The aim of this study is to evaluate the safety of MBS in patients with compensated advanced chronic liver disease (cALCD) and clinically significant portal hypertension (CSPH).

Material and methods:

This is an international, multicentric, retrospective study on 63 individuals affected by obesity with cALCD and CSPH who underwent MBS in tertiary referral centers with experts hepatobiliary surgeons between January 2010 and October 2022. The primary endpoint was postoperative mortality at 90 days. The secondary endpoints included postoperative weight loss at last follow-up and postoperative complication rate. In addition, the authors performed subgroup analyses of Child-Pugh (A vs. B) score, MELD (≤9 vs. >9) score, and type of surgery.

Results:

One patient (1.6%) experienced gastric leakage and mortality. There were three (5%) reported cases of portal vein thrombosis, two (3%) postoperative acute renal failure, and one (1.6%) postoperative encephalopathy. Child-Pugh score A resulted to be a protective factor for intraoperative bleeding requiring transfusion at univariate analysis (OR: 0.73, 95% CI: 0.55–0.97, P=0.046) but not at multivariate analysis. MELD>9 score and the type of surgery did not result to be a risk factor for any postoperative complication.

Conclusion:

MBS is safe in patients with cALCD and CSPH performed in tertiary bariatric referral centers with hepatobiliary expert surgeons. Larger, prospective studies with longer follow-up periods are needed to confirm these results.
Changes in serum ghrelin and resistin levels after sleeve gastrectomy versus one anastomosis gastric bypass: prospective cohort study
Authors: Ozmen Fusun , Şahin Tevfik T. , Dolgun Anil , Ozmen M. Mahir
Published: June 2024

Introduction:

Humoral factors and neural mechanisms play a central role in the pathogenesis of obesity and in weight loss following bariatric surgery. Although various hormones and adipokines, including ghrelin and resistin, are linked to obesity, studies analyzing the changes in fasting ghrelin and resistin levels in patients following one anastomosis gastric bypass (OAGB) are lacking.

Aim:

The authors aimed to investigate resistin and ghrelin levels before and after two commonly used bariatric procedures with different mechanisms of action: sleeve gastrectomy (SG) and OAGB.

Patients and methods:

Fasting serum ghrelin and resistin levels were evaluated by using ELISA in a nonrandomized, prospective cohort study for the pattern of changes in the preoperative period and 1 week, 1 month, 3 months and, 12 months after surgery in age and sex-matched patients with BMI ≥40 kg/m2 undergoing either SG (n=40) or OAGB (n=40). Their relationships with demographic parameters such as body weight, BMI, presence of T2DM, HbA1C, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index were also evaluated.

Results:

OAGB was superior in weight control compared to the SG group. There were significant differences in resistin and ghrelin levels between the OAGB and SG groups. Ghrelin decreased more in the SG group than the preoperative values. This change in ghrelin levels was more significant at 1 year after SG [preoperative mean (range) level of 334.2 (36.6–972.1) pg/ml decreased to 84 (9.1–227) pg/ml at 1 year] whereas in the OAGB group no significant change was observed [preoperative mean (range) level of 310 (146–548) pg/ml decreased to 264 (112–418) pg/ml at 1 year]. Resistin levels decreased in both groups, especially after 3 months and onward following both operations [the mean (range) resistin levels were 2.6 (0.87–5.4) ng/ml and decreased to 1.1 (0.5–2.4) ng/ml in the SG group vs 2.48 (0.89–6.43) ng/ml decreased to 0.72 (0.35–1.8) ng/ml in OAGB group at 1 year], which was in parallel with changes in HOMA-IR index, body weight, and BMI changes at 1st year. HOMA-IR index changes were similar, but more prominent after OAGB. OAGB was als3 three months and onward), and HOMA-IR changes.

Conclusion:

This is the first study to compare fasting ghrelin and resistin levels after OAGB and SG. Although similar changes were observed, ghrelin changes were more prominent after SG, whereas resistin were observed after OAGB. OAGB was superior in T2DM control, which was in parallel with weight loss, fasting resistin levels, and HOMA-IR changes suggesting a possible effect of resistin after OAGB in glucose metabolism and insulin resistance.
New augmented reality remote for virtual guidance and education of fracture surgery: a retrospective, non-inferiority, multi-center cohort study
Authors: Liu Songxiang , Xie Mao , Gao Fei , Fang Ying , Xue Mingdi , Zuo Bingran , Wang Junwen , Hu Jialang , Liu Rong , Zhang Jiayao , Huo Tongtong , Liu Pengran , Zeng Cheng , Yew Andy , Chen Heng-Gui , Ye Zhewei
Published: June 2024

Background:

The demand for telesurgery is rapidly increasing. Augmented reality (AR) remote surgery is a promising alternative, fulfilling a worldwide need in fracture surgery. However, previous AR endoscopic and Google Glass remotes remain unsuitable for fracture surgery, and the application of remote fracture surgery has not been reported. The authors aimed to evaluate the safety and clinical effectiveness of a new AR remote in fracture surgery.

Materials and methods:

This retrospective non-inferiority cohort study was conducted at three centres. Between 1 January 2018 and 31 March 2022, 800 patients who underwent fracture surgery were eligible for participation. The study enroled 551 patients with fractures (132 patellae, 128 elbows, 126 tibial plateaus, and 165 ankles) divided into an AR group (specialists used AR to remotely guide junior doctors to perform surgeries) and a traditional non-remote group (specialists performed the surgery themselves).

Results:

Among 364 patients (182 per group) matched by propensity score, seven (3.8%) in the AR group and six (3%) in the non-remote group developed complications. The 0.005 risk difference (95% CI: −0.033 to 0.044) was below the pre-defined non-inferiority margin of a 10% absolute increase. A similar distribution in the individual components of all complications was found between the groups. Hierarchical analysis following propensity score matching revealed no statistical difference between the two groups regarding functional results at 1-year follow-up, operative time, amount of bleeding, number of fluoroscopies, and injury surgery interval. A Likert scale questionnaire showed positive results (median scores: 4–5) for safety, efficiency, and education.

Conclusion:

This study is the first to report that AR remote surgery can be as safe and effective as that performed by a specialist in person for fracture surgery, even without the physical presence of a specialist, and is associated with improving the skills and increasing the confidence of junior surgeons. This technique is promising for remote fracture surgery and other open surgeries, offering a new strategy to address inadequate medical care in remote areas.
Deciphering tertiary lymphoid structure heterogeneity reveals prognostic signature and therapeutic potentials for colorectal cancer: a multicenter retrospective cohort study
Authors: Lei Jia-Xin , Wang Runxian , Hu Chuling , Lou Xiaoying , Lv Min-Yi , Li Chenghang , Gai Baowen , Wu Xiao-Jian , Dou Ruoxu , Cai Du , Gao Feng
Published: June 2024

Background:

Tertiary lymphoid structures (TLSs) exert a crucial role in the tumor microenvironment (TME), impacting tumor development, immune escape, and drug resistance. Nonetheless, the heterogeneity of TLSs in colorectal cancer (CRC) and their impact on prognosis and treatment response remain unclear.

Methods:

The authors collected genome, transcriptome, clinicopathological information, and digital pathology images from multiple sources. An unsupervised clustering algorithm was implemented to determine diverse TLS patterns in CRC based on the expression levels of 39 TLS signature genes (TSGs). Comprehensive explorations of heterogeneity encompassing mutation landscape, TME, biological characteristics, response to immunotherapy, and drug resistance were conducted using multiomics data. TLSscore was then developed to quantitatively assess TLS patterns of individuals for further clinical applicability.

Results:

Three distinct TLS patterns were identified in CRC. Cluster 1 exhibited upregulation of proliferation-related pathways, high metabolic activity, and intermediate prognosis, while Cluster 2 displayed activation of stromal and carcinogenic pathways and a worse prognosis. Both Cluster 1 and Cluster 2 may potentially benefit from adjuvant chemotherapy. Cluster 3, characterized by the activation of immune regulation and activation pathways, demonstrated a favorable prognosis and enhanced responsiveness to immunotherapy. The authors subsequently employed a regularization algorithm to construct the TLSscore based on nine core genes. Patients with lower TLSscore trended to prolonged prognosis and a more prominent presence of TLSs, which may benefit from immunotherapy. Conversely, those with higher TLSscore exhibited increased benefits from adjuvant chemotherapy.

Conclusions:

The authors identified distinct TLS patterns in CRC and characterized their heterogeneity through multiomics analyses. The TLSscore held promise for guiding clinical decision-making and further advancing the field of personalized medicine in CRC.
Machine learning guided prediction of warfarin blood levels for personalized medicine based on clinical longitudinal data from cardiac surgery patients: a prospective observational study
Authors: Xue Ling , He Shan , Singla Rajeev K. , Qin Qiong , Ding Yinglong , Liu Linsheng , Ding Xiaoliang , Bediaga-Bañeres Harbil , Arrasate Sonia , Durado-Sanchez Aliuska , Zhang Yuzhen , Shen Zhenya , Shen Bairong , Miao Liyan , González-Díaz Humberto
Published: June 2024

Background:

Warfarin is a common oral anticoagulant, and its effects vary widely among individuals. Numerous dose-prediction algorithms have been reported based on cross-sectional data generated via multiple linear regression or machine learning. This study aimed to construct an information fusion perturbation theory and machine-learning prediction model of warfarin blood levels based on clinical longitudinal data from cardiac surgery patients.

Methods and material:

The data of 246 patients were obtained from electronic medical records. Continuous variables were processed by calculating the distance of the raw data with the moving average (MA ∆vki(s
j)), and categorical variables in different attribute groups were processed using Euclidean distance (ED ǁ∆vk(s
j)ǁ). Regression and classification analyses were performed on the raw data, MA ∆vki(s
j), and ED ǁ∆vk(s
j)ǁ. Different machine-learning algorithms were chosen for the STATISTICA and WEKA software.

Results:

The random forest (RF) algorithm was the best for predicting continuous outputs using the raw data. The correlation coefficients of the RF algorithm were 0.978 and 0.595 for the training and validation sets, respectively, and the mean absolute errors were 0.135 and 0.362 for the training and validation sets, respectively. The proportion of ideal predictions of the RF algorithm was 59.0%. General discriminant analysis (GDA) was the best algorithm for predicting the categorical outputs using the MA ∆vki(s
j) data. The GDA algorithm’s total true positive rate (TPR) was 95.4% and 95.6% for the training and validation sets, respectively, with MA ∆vki(s
j) data.

Conclusions:

An information fusion perturbation theory and machine-learning model for predicting warfarin blood levels was established. A model based on the RF algorithm could be used to predict the target international normalized ratio (INR), and a model based on the GDA algorithm could be used to predict the probability of being within the target INR range under different clinical scenarios.